TY - JOUR A1 - Otto, Christoph A1 - Kastner, Carolin A1 - Schmidt, Stefanie A1 - Uttinger, Konstantin A1 - Baluapuri, Apoorva A1 - Denk, Sarah A1 - Rosenfeldt, Mathias T. A1 - Rosenwald, Andreas A1 - Roehrig, Florian A1 - Ade, Carsten P. A1 - Schuelein-Voelk, Christina A1 - Diefenbacher, Markus E. A1 - Germer, Christoph-Thomas A1 - Wolf, Elmar A1 - Eilers, Martin A1 - Wiegering, Armin T1 - RNA polymerase I inhibition induces terminal differentiation, growth arrest, and vulnerability to senolytics in colorectal cancer cells JF - Molecular Oncology N2 - Ribosomal biogenesis and protein synthesis are deregulated in most cancers, suggesting that interfering with translation machinery may hold significant therapeutic potential. Here, we show that loss of the tumor suppressor adenomatous polyposis coli (APC), which constitutes the initiating event in the adenoma carcinoma sequence for colorectal cancer (CRC), induces the expression of RNA polymerase I (RNAPOL1) transcription machinery, and subsequently upregulates ribosomal DNA (rDNA) transcription. Targeting RNAPOL1 with a specific inhibitor, CX5461, disrupts nucleolar integrity, and induces a disbalance of ribosomal proteins. Surprisingly, CX5461-induced growth arrest is irreversible and exhibits features of senescence and terminal differentiation. Mechanistically, CX5461 promotes differentiation in an MYC-interacting zinc-finger protein 1 (MIZ1)- and retinoblastoma protein (Rb)-dependent manner. In addition, the inhibition of RNAPOL1 renders CRC cells vulnerable towards senolytic agents. We validated this therapeutic effect of CX5461 in murine- and patient-derived organoids, and in a xenograft mouse model. These results show that targeting ribosomal biogenesis together with targeting the consecutive, senescent phenotype using approved drugs is a new therapeutic approach, which can rapidly be transferred from bench to bedside. KW - CRC KW - CX5461 KW - MIZ1 KW - MYC KW - ribosome KW - RNAPOL1 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312806 VL - 16 IS - 15 ER - TY - JOUR A1 - Heydarian, Motaharehsadat A1 - Rühl, Eva A1 - Rawal, Ravisha A1 - Kozjak-Pavlovic, Vera T1 - Tissue models for Neisseria gonorrhoeae research — from 2D to 3D JF - Frontiers in Cellular and Infection Microbiology N2 - Neisseria gonorrhoeae is a human-specific pathogen that causes gonorrhea, the second most common sexually transmitted infection worldwide. Disease progression, drug discovery, and basic host-pathogen interactions are studied using different approaches, which rely on models ranging from 2D cell culture to complex 3D tissues and animals. In this review, we discuss the models used in N. gonorrhoeae research. We address both in vivo (animal) and in vitro cell culture models, discussing the pros and cons of each and outlining the recent advancements in the field of three-dimensional tissue models. From simple 2D monoculture to complex advanced 3D tissue models, we provide an overview of the relevant methodology and its application. Finally, we discuss future directions in the exciting field of 3D tissue models and how they can be applied for studying the interaction of N. gonorrhoeae with host cells under conditions closely resembling those found at the native sites of infection. KW - ex vivo KW - biomimetic tissue models KW - Neisseria gonorrhoeae KW - in vivo KW - in vitro Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-263046 SN - 2235-2988 VL - 12 ER - TY - JOUR A1 - Köhler, Franziska A1 - Reese, Lena A1 - Kastner, Carolin A1 - Hendricks, Anne A1 - Müller, Sophie A1 - Lock, Johan F. A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Surgical site infection following single-port appendectomy: a systematic review of the literature and meta-analysis JF - Frontiers in Surgery N2 - Introduction Surgical site infections (SSIs) are one of the most common postoperative complications after appendectomy leading to recurrent surgery, prolonged hospital stay, and the use of antibiotics. Numerous studies and meta-analyses have been published on the effect of open versus conventional laparoscopic appendectomy (CLA) reporting faster postoperative recovery and less postoperative pain for CLA. A development from CLA has been the single-port appendectomy (SPA), associated with a better cosmesis but seemingly having a higher risk of wound infections. The aim of this systematic literature review and meta-analysis is to investigate whether reduced port or SPA alters the ratio of SSIs. Methods Pubmed, Embase, and Cochrane databases were screened for suitable articles. All articles published between January 1, 2002, and March 23, 2022, were included. Articles regarding children below the age of 18 were excluded as well as manuscripts that investigated solemnly open appendectomies. Articles were screened for inclusion criteria by two independent authors. Incidence of SSI was the primary outcome. Duration of operation and length of hospital stay were defined as secondary outcomes. Results A total of 25 studies were found through a database search describing 5484 patients. A total of 2749 patients received SPA and 2735 received CLA. There was no statistical difference in the rate of SSI (P = 0.98). A total of 22 studies including 4699 patients reported the duration of operation (2223 SPA and 2476 CLA). There was a significantly shorter operation time seen in CLA. The length of hospital stay was reported in 23 studies (4735 patients: 2235 SPA and 2500 CLA). A shorter hospital stay was seen in the SPA group (P < 0.00001). Separately performed analysis of randomized controlled trials could not confirm this effect (P = 0.29). Discussion SPA is an equally safe procedure considering SSI compared to CLA and does not lead to an increased risk of SSI. A longer operation time for SPA and a minor difference in the length of stay does lead to the use of SPA in selected patients only. KW - appendicitis KW - appendectomy KW - surgical site infection KW - single-port appendectomy KW - conventional laparoscopic appendectomy KW - wound infection KW - SSI Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276943 SN - 2296-875X VL - 9 ER - TY - JOUR A1 - Sponsler, Douglas A1 - Kallnik, Katharina A1 - Requier, Fabrice A1 - Classen, Alice A1 - Maihoff, A. Fabienne A1 - Sieger, Johanna A1 - Steffan-Dewenter, Ingolf T1 - Floral preferences of mountain bumble bees are constrained by functional traits but flexible through elevation and season JF - Oikos N2 - Patterns of resource use by animals can clarify how ecological communities have assembled in the past, how they currently function and how they are likely to respond to future perturbations. Bumble bees (Hymentoptera: Bombus spp.) and their floral hosts provide a diverse yet tractable system in which to explore resource selection in the context of plant–pollinator networks. Under conditions of resource limitation, the ability of bumble bees species to coexist should depend on dietary niche overlap. In this study, we report patterns and dynamics of floral morphotype preferences in a mountain bumble bee community based on ~13 000 observations of bumble bee floral visits recorded along a 1400 m elevation gradient. We found that bumble bees are highly selective generalists, rarely visiting floral morphotypes at the rates predicted by their relative abundances. Preferences also differed markedly across bumble bee species, and these differences were well-explained by variation in bumble bee tongue length, generating patterns of preference similarity that should be expected to predict competition under conditions of resource limitation. Within species, though, morphotype preferences varied by elevation and season, possibly representing adaptive flexibility in response to the high elevational and seasonal turnover of mountain floral communities. Patterns of resource partitioning among bumble bee communities may determine which species can coexist under the altered distributions of bumble bees and their floral hosts caused by climate and land use change. KW - resource selection KW - coexistence KW - competition KW - foraging KW - niche KW - pollinator Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259653 VL - 2022 IS - 3 ER - TY - JOUR A1 - Martinez-Bengochea, A. L. A1 - Kneitz, S. A1 - Herpin, A. A1 - Nobrega, R. H. A1 - Adolfi, M. C. A1 - Schartl, M. T1 - Sexual development dysgenesis in interspecific hybrids of Medaka fish JF - Scientific Reports N2 - Fish are amongst vertebrates the group with the highest diversity of known sex-determining genes. Particularly, the genus Oryzias is a suitable taxon to understand how different sex determination genetic networks evolved in closely related species. Two closely related species, O. latipes and O. curvinotus, do not only share the same XX/XY sex chromosome system, but also the same male sex-determining gene, dmrt1bY. We performed whole mRNA transcriptomes and morphology analyses of the gonads of hybrids resulting from reciprocal crosses between O. latipes and O. curvinotus. XY male hybrids, presenting meiotic arrest and no production of sperm were sterile, and about 30% of the XY hybrids underwent male-to-female sex reversal. Both XX and XY hybrid females exhibited reduced fertility and developed ovotestis while aging. Transcriptome data showed that male-related genes are upregulated in the XX and XY female hybrids. The transcriptomes of both types of female and of the male gonads are characterized by upregulation of meiosis and germ cell differentiation genes. Differences in the parental species in the downstream pathways of sexual development could explain sex reversal, sterility, and the development of intersex gonads in the hybrids. We hypothesize that male-to-female sex reversal may be connected to a different development time between species at which dmrt1bY expression starts. Our results provide molecular clues for the proximate mechanisms of hybrid incompatibility and Haldane’s rule. KW - sexual development dysgenesis KW - Medaka fish KW - sex-determining genes. Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300295 VL - 12 IS - 1 ER - TY - JOUR A1 - Peters, Birte A1 - Keller, Alexander A1 - Leonhardt, Sara Diana T1 - Diets maintained in a changing world: Does land-use intensification alter wild bee communities by selecting for flexible generalists? JF - Ecology and evolution N2 - Biodiversity loss, as often found in intensively managed agricultural landscapes, correlates with reduced ecosystem functioning, for example, pollination by insects, and with altered plant composition, diversity, and abundance. But how does this change in floral resource diversity and composition relate to occurrence and resource use patterns of trap-nesting solitary bees? To better understand the impact of land-use intensification on communities of trap-nesting solitary bees in managed grasslands, we investigated their pollen foraging, reproductive fitness, and the nutritional quality of larval food along a land-use intensity gradient in Germany. We found bee species diversity to decrease with increasing land-use intensity irrespective of region-specific community compositions and interaction networks. Land use also strongly affected the diversity and composition of pollen collected by bees. Lack of suitable pollen sources likely explains the absence of several bee species at sites of high land-use intensity. The only species present throughout, Osmia bicornis (red mason bee), foraged on largely different pollen sources across sites. In doing so, it maintained a relatively stable, albeit variable nutritional quality of larval diets (i.e., protein to lipid (P:L) ratio). The observed changes in bee–plant pollen interaction patterns indicate that only the flexible generalists, such as O. bicornis, may be able to compensate the strong alterations in floral resource landscapes and to obtain food of sufficient quality through readily shifting to alternative plant sources. In contrast, other, less flexible, bee species disappear. KW - bee decline KW - biodiversity exploratories KW - foraging KW - metabarcoding KW - pollen nutrients KW - solitary bees Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312786 SN - 2045-7758 VL - 12 IS - 5 ER - TY - JOUR A1 - Ziegler, Alice A1 - Meyer, Hanna A1 - Otte, Insa A1 - Peters, Marcell K. A1 - Appelhans, Tim A1 - Behler, Christina A1 - Böhning-Gaese, Katrin A1 - Classen, Alice A1 - Detsch, Florian A1 - Deckert, Jürgen A1 - Eardley, Connal D. A1 - Ferger, Stefan W. A1 - Fischer, Markus A1 - Gebert, Friederike A1 - Haas, Michael A1 - Helbig-Bonitz, Maria A1 - Hemp, Andreas A1 - Hemp, Claudia A1 - Kakengi, Victor A1 - Mayr, Antonia V. A1 - Ngereza, Christine A1 - Reudenbach, Christoph A1 - Röder, Juliane A1 - Rutten, Gemma A1 - Schellenberger Costa, David A1 - Schleuning, Matthias A1 - Ssymank, Axel A1 - Steffan-Dewenter, Ingolf A1 - Tardanico, Joseph A1 - Tschapka, Marco A1 - Vollstädt, Maximilian G. R. A1 - Wöllauer, Stephan A1 - Zhang, Jie A1 - Brandl, Roland A1 - Nauss, Thomas T1 - Potential of airborne LiDAR derived vegetation structure for the prediction of animal species richness at Mount Kilimanjaro JF - Remote Sensing N2 - The monitoring of species and functional diversity is of increasing relevance for the development of strategies for the conservation and management of biodiversity. Therefore, reliable estimates of the performance of monitoring techniques across taxa become important. Using a unique dataset, this study investigates the potential of airborne LiDAR-derived variables characterizing vegetation structure as predictors for animal species richness at the southern slopes of Mount Kilimanjaro. To disentangle the structural LiDAR information from co-factors related to elevational vegetation zones, LiDAR-based models were compared to the predictive power of elevation models. 17 taxa and 4 feeding guilds were modeled and the standardized study design allowed for a comparison across the assemblages. Results show that most taxa (14) and feeding guilds (3) can be predicted best by elevation with normalized RMSE values but only for three of those taxa and two of those feeding guilds the difference to other models is significant. Generally, modeling performances between different models vary only slightly for each assemblage. For the remaining, structural information at most showed little additional contribution to the performance. In summary, LiDAR observations can be used for animal species prediction. However, the effort and cost of aerial surveys are not always in proportion with the prediction quality, especially when the species distribution follows zonal patterns, and elevation information yields similar results. KW - biodiversity KW - species richness KW - LiDAR KW - elevation KW - partial least square regression KW - arthropods KW - birds KW - bats KW - predictive modeling Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262251 SN - 2072-4292 VL - 14 IS - 3 ER - TY - JOUR A1 - Vollmuth, Nadine A1 - Schlicker, Lisa A1 - Guo, Yongxia A1 - Hovhannisyan, Pargev A1 - Janaki-Raman, Sudha A1 - Kurmasheva, Naziia A1 - Schmitz, Werner A1 - Schulze, Almut A1 - Stelzner, Kathrin A1 - Rajeeve, Karthika A1 - Rudel, Thomas T1 - c-Myc plays a key role in IFN-γ-induced persistence of Chlamydia trachomatis JF - eLife N2 - Chlamydia trachomatis (Ctr) can persist over extended times within their host cell and thereby establish chronic infections. One of the major inducers of chlamydial persistence is interferon-gamma (IFN-γ) released by immune cells as a mechanism of immune defence. IFN-γ activates the catabolic depletion of L-tryptophan (Trp) via indoleamine-2,3-dioxygenase (IDO), resulting in persistent Ctr. Here, we show that IFN-γ induces the downregulation of c-Myc, the key regulator of host cell metabolism, in a STAT1-dependent manner. Expression of c-Myc rescued Ctr from IFN-γ-induced persistence in cell lines and human fallopian tube organoids. Trp concentrations control c-Myc levels most likely via the PI3K-GSK3β axis. Unbiased metabolic analysis revealed that Ctr infection reprograms the host cell tricarboxylic acid (TCA) cycle to support pyrimidine biosynthesis. Addition of TCA cycle intermediates or pyrimidine/purine nucleosides to infected cells rescued Ctr from IFN-γ-induced persistence. Thus, our results challenge the longstanding hypothesis of Trp depletion through IDO as the major mechanism of IFN-γ-induced metabolic immune defence and significantly extends the understanding of the role of IFN-γ as a broad modulator of host cell metabolism. KW - Chlamydia trachomatis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301385 VL - 11 ER - TY - JOUR A1 - Ditzel, Pia A1 - König, Sebastian A1 - Musembi, Peter A1 - Peters, Marcell K. T1 - Correlation between coral reef condition and the diversity and abundance of fishes and sea urchins on an East African coral reef JF - Oceans N2 - Coral reefs are one of the most diverse marine ecosystems, providing numerous ecosystem services. This present study investigated the relationship between coral reef condition and the diversity and abundance of fishes, on a heavily fished East African coral reef at Gazi Bay, Kenya. Underwater visual censuses were conducted on thirty 50 × 5 m belt transects to assess the abundance and diversity of fishes. In parallel, a 25-m length of each of the same transects was recorded with photo-quadrats to assess coral community structure and benthic characteristics. For statistical analyses, multi-model inference based on the Akaike Information Criterion was used to evaluate the support for potential predictor variables of coral reef and fish diversity. We found that coral genus richness was negatively correlated with the abundance of macroalgae, whereas coral cover was positively correlated with both the abundance of herbivorous invertebrates (sea urchins) and with fish family richness. Similarly, fish family richness appeared mainly correlated with coral cover and invertebrate abundance, although no correlates of fish abundance could be identified. Coral and fish diversity were very low, but it appears that, contrary to some locations on the same coast, sea urchin abundance was not high enough to be having a negative influence on coral and fish assemblages. Due to increasing threats to coral reefs, it is important to understand the relationship among the components of the coral reef ecosystem on overfished reefs such as that at Gazi Bay. KW - coral reef ecosystem KW - coral reef resilience KW - global warming KW - climate change KW - overfishing KW - indicator species Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284503 SN - 2673-1924 VL - 3 IS - 1 SP - 1 EP - 14 ER - TY - JOUR A1 - Rackevei, Antonia S. A1 - Karnkowska, Anna A1 - Wolf, Matthias T1 - 18S rDNA sequence–structure phylogeny of the Euglenophyceae (Euglenozoa, Euglenida) JF - Journal of Eukaryotic Microbiology N2 - The phylogeny of Euglenophyceae (Euglenozoa, Euglenida) has been discussed for decades with new genera being described in the last few years. In this study, we reconstruct a phylogeny using 18S rDNA sequence and structural data simultaneously. Using homology modeling, individual secondary structures were predicted. Sequence–structure data are encoded and automatically aligned. Here, we present a sequence–structure neighbor‐joining tree of more than 300 taxa classified as Euglenophyceae. Profile neighbor‐joining was used to resolve the basal branching pattern. Neighbor‐joining, maximum parsimony, and maximum likelihood analyses were performed using sequence–structure information for manually chosen subsets. All analyses supported the monophyly of Eutreptiella, Discoplastis, Lepocinclis, Strombomonas, Cryptoglena, Monomorphina, Euglenaria, and Colacium. Well‐supported topologies were generally consistent with previous studies using a combined dataset of genetic markers. Our study supports the simultaneous use of sequence and structural data to reconstruct more accurate and robust trees. The average bootstrap value is significantly higher than the average bootstrap value obtained from sequence‐only analyses, which is promising for resolving relationships between more closely related taxa. KW - euglena KW - euglenids KW - phylogenetics KW - secondary structure Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311896 VL - 70 IS - 2 ER - TY - JOUR A1 - Kerner, Janika M. A1 - Krauss, Jochen A1 - Maihoff, Fabienne A1 - Bofinger, Lukas A1 - Classen, Alice T1 - Alpine butterflies want to fly high: Species and communities shift upwards faster than their host plants JF - Ecology N2 - Despite sometimes strong codependencies of insect herbivores and plants, the responses of individual taxa to accelerating climate change are typically studied in isolation. For this reason, biotic interactions that potentially limit species in tracking their preferred climatic niches are ignored. Here, we chose butterflies as a prominent representative of herbivorous insects to investigate the impacts of temperature changes and their larval host plant distributions along a 1.4‐km elevational gradient in the German Alps. Following a sampling protocol of 2009, we revisited 33 grassland plots in 2019 over an entire growing season. We quantified changes in butterfly abundance and richness by repeated transect walks on each plot and disentangled the direct and indirect effects of locally assessed temperature, site management, and larval and adult food resource availability on these patterns. Additionally, we determined elevational range shifts of butterflies and host plants at both the community and species level. Comparing the two sampled years (2009 and 2019), we found a severe decline in butterfly abundance and a clear upward shift of butterflies along the elevational gradient. We detected shifts in the peak of species richness, community composition, and at the species level, whereby mountainous species shifted particularly strongly. In contrast, host plants showed barely any change, neither in connection with species richness nor individual species shifts. Further, temperature and host plant richness were the main drivers of butterfly richness, with change in temperature best explaining the change in richness over time. We concluded that host plants were not yet hindering butterfly species and communities from shifting upwards. However, the mismatch between butterfly and host plant shifts might become a problem for this very close plant–herbivore relationship, especially toward higher elevations, if butterflies fail to adapt to new host plants. Further, our results support the value of conserving traditional extensive pasture use as a promoter of host plant and, hence, butterfly richness. KW - Alps KW - altitudinal gradient KW - global warming KW - grazing KW - Lepidoptera KW - mountain biodiversity KW - plant–herbivore interactions KW - species range shifts KW - upslope shift Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312015 VL - 104 IS - 1 ER - TY - JOUR A1 - Fricke, Ute A1 - Redlich, Sarah A1 - Zhang, Jie A1 - Benjamin, Caryl S. A1 - Englmeier, Jana A1 - Ganuza, Cristina A1 - Haensel, Maria A1 - Riebl, Rebekka A1 - Rojas‐Botero, Sandra A1 - Tobisch, Cynthia A1 - Uhler, Johannes A1 - Uphus, Lars A1 - Steffan‐Dewenter, Ingolf T1 - Earlier flowering of winter oilseed rape compensates for higher pest pressure in warmer climates JF - Journal of Applied Ecology N2 - Global warming can increase insect pest pressure by enhancing reproductive rates. Whether this translates into yield losses depends on phenological synchronisation of pests with their host plants and natural enemies. Simultaneously, landscape composition may mitigate climate effects by shaping the resource availability for pests and their antagonists. Here, we study the combined effects of temperature and landscape composition on pest abundances, larval parasitism, crop damage and yield, while also considering crop phenology, to identify strategies for sustainable management of oilseed rape (OSR) pests under warming climates. In all, 29 winter OSR crop fields were investigated in different climates (defined by multi‐annual mean temperature, MAT) and landscape contexts in Bavaria, Germany. We measured abundances of adult pollen beetles and stem weevil larvae, pollen beetle larval parasitism, bud loss, stem damage and seed yield, and calculated the flowering date from growth stage observations. Landscape parameters (proportion of non‐crop and OSR area, change in OSR area relative to the previous year) were calculated at six spatial scales (0.6–5 km). Pollen beetle abundance increased with MAT but to different degrees depending on the landscape context, that is, increased less strongly when OSR proportions were high (1‐km scale), interannually constant (5‐km scale) or both. In contrast, stem weevil abundance and stem damage did not respond to landscape composition nor MAT. Pollen beetle larval parasitism was overall low, but occasionally exceeded 30% under both low and high MAT and with reduced OSR area (0.6‐km scale). Despite high pollen beetle abundance in warm climates, yields were high when OSR flowered early. Thereby, higher temperatures favoured early flowering. Only among late‐flowering OSR crop fields yield was higher in cooler than warmer climates. Bud loss responded analogously. Landscape composition did not substantially affect bud loss and yield. Synthesis and applications: Earlier flowering of winter OSR compensates for higher pollen beetle abundance in warmer climates, while interannual continuity of OSR area prevents high pollen beetle abundance in the first place. Thus, regional coordination of crop rotation and crop management promoting early flowering may contribute to sustainable pest management in OSR under current and future climatic conditions. KW - canola KW - climate‐smart pest management KW - crop rotation KW - global warming KW - oilseed rape KW - pollen beetle KW - seed yield KW - stem weevil Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312562 VL - 60 IS - 2 SP - 365 EP - 375 ER - TY - JOUR A1 - Graus, Dorothea A1 - Li, Kunkun A1 - Rathje, Jan M. A1 - Ding, Meiqi A1 - Krischke, Markus A1 - Müller, Martin J. A1 - Cuin, Tracey Ann A1 - Al‐Rasheid, Khaled A. S. A1 - Scherzer, Sönke A1 - Marten, Irene A1 - Konrad, Kai R. A1 - Hedrich, Rainer T1 - Tobacco leaf tissue rapidly detoxifies direct salt loads without activation of calcium and SOS signaling JF - New Phytologist N2 - Salt stress is a major abiotic stress, responsible for declining agricultural productivity. Roots are regarded as hubs for salt detoxification, however, leaf salt concentrations may exceed those of roots. How mature leaves manage acute sodium chloride (NaCl) stress is mostly unknown. To analyze the mechanisms for NaCl redistribution in leaves, salt was infiltrated into intact tobacco leaves. It initiated pronounced osmotically‐driven leaf movements. Leaf downward movement caused by hydro‐passive turgor loss reached a maximum within 2 h. Salt‐driven cellular water release was accompanied by a transient change in membrane depolarization but not an increase in cytosolic calcium ion (Ca\(^{2+}\)) level. Nonetheless, only half an hour later, the leaves had completely regained turgor. This recovery phase was characterized by an increase in mesophyll cell plasma membrane hydrogen ion (H\(^{+}\)) pumping, a salt uptake‐dependent cytosolic alkalization, and a return of the apoplast osmolality to pre‐stress levels. Although, transcript numbers of abscisic acid‐ and Salt Overly Sensitive pathway elements remained unchanged, salt adaptation depended on the vacuolar H\(^{+}\)/Na\(^{+}\)‐exchanger NHX1. Altogether, tobacco leaves can detoxify sodium ions (Na\(^{+}\)) rapidly even under massive salt loads, based on pre‐established posttranslational settings and NHX1 cation/H+ antiport activity. Unlike roots, signaling and processing of salt stress in tobacco leaves does not depend on Ca\(^{2+}\) signaling. KW - calcium signaling KW - cytosolic pH KW - leaf response KW - NaCl transport KW - NHX1 KW - osmotic effects KW - Salt Overly Sensitive pathway KW - salt stress Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312152 VL - 237 IS - 1 SP - 217 EP - 231 ER - TY - JOUR A1 - Diebold, Mathias A1 - Schönemann, Lars A1 - Eilers, Martin A1 - Sotriffer, Christoph A1 - Schindelin, Hermann T1 - Crystal structure of a covalently linked Aurora-A-MYCN complex JF - Acta Crystallographica N2 - Formation of the Aurora-A–MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be `undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A–MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development and screening campaigns. To overcome the challenges that a ternary system composed of Aurora-A, MYCN and a small molecule entails, a covalently cross-linked construct of the Aurora-A–MYCN complex was designed, expressed and characterized, thus enabling screening and design campaigns to identify selective binders. KW - MYCNv KW - neuroblastoma cell KW - proteasome system Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-318855 VL - D79 SP - 1 EP - 9 ER - TY - JOUR A1 - Kaltdorf, Martin A1 - Breitenbach, Tim A1 - Karl, Stefan A1 - Fuchs, Maximilian A1 - Kessie, David Komla A1 - Psota, Eric A1 - Prelog, Martina A1 - Sarukhanyan, Edita A1 - Ebert, Regina A1 - Jakob, Franz A1 - Dandekar, Gudrun A1 - Naseem, Muhammad A1 - Liang, Chunguang A1 - Dandekar, Thomas T1 - Software JimenaE allows efficient dynamic simulations of Boolean networks, centrality and system state analysis JF - Scientific Reports N2 - The signal modelling framework JimenaE simulates dynamically Boolean networks. In contrast to SQUAD, there is systematic and not just heuristic calculation of all system states. These specific features are not present in CellNetAnalyzer and BoolNet. JimenaE is an expert extension of Jimena, with new optimized code, network conversion into different formats, rapid convergence both for system state calculation as well as for all three network centralities. It allows higher accuracy in determining network states and allows to dissect networks and identification of network control type and amount for each protein with high accuracy. Biological examples demonstrate this: (i) High plasticity of mesenchymal stromal cells for differentiation into chondrocytes, osteoblasts and adipocytes and differentiation-specific network control focusses on wnt-, TGF-beta and PPAR-gamma signaling. JimenaE allows to study individual proteins, removal or adding interactions (or autocrine loops) and accurately quantifies effects as well as number of system states. (ii) Dynamical modelling of cell–cell interactions of plant Arapidopsis thaliana against Pseudomonas syringae DC3000: We analyze for the first time the pathogen perspective and its interaction with the host. We next provide a detailed analysis on how plant hormonal regulation stimulates specific proteins and who and which protein has which type and amount of network control including a detailed heatmap of the A.thaliana response distinguishing between two states of the immune response. (iii) In an immune response network of dendritic cells confronted with Aspergillus fumigatus, JimenaE calculates now accurately the specific values for centralities and protein-specific network control including chemokine and pattern recognition receptors. KW - cellular signalling networks KW - computer modelling Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313303 VL - 13 ER - TY - JOUR A1 - Aupperle-Lellbach, Heike A1 - Heidrich, Daniela A1 - Kehl, Alexandra A1 - Conrad, David A1 - Brockmann, Maria A1 - Törner, Katrin A1 - Beitzinger, Christoph A1 - Müller, Tobias T1 - KITLG copy number germline variations in schnauzer breeds and their relevance in digital squamous cell carcinoma in black giant schnauzers JF - Veterinary Sciences N2 - Copy number variations (CNVs) of the KITLG gene seem to be involved in the oncogenesis of digital squamous cell carcinoma (dSCC). The aims of this study were (1) to investigate KITLG CNV in giant (GS), standard (SS), and miniature (MS) schnauzers and (2) to compare KITLG CNV between black GS with and without dSCC. Blood samples from black GS (22 with and 17 without dSCC), black SS (18 with and 4 without dSSC; 5 unknown), and 50 MS (unknown dSSC status and coat colour) were analysed by digital droplet PCR. The results are that (1) most dogs had a copy number (CN) value > 4 (range 2.5–7.6) with no significant differences between GS, SS, and MS, and (2) the CN value in black GS with dSCC was significantly higher than in those without dSCC (p = 0.02). CN values > 5.8 indicate a significantly increased risk for dSCC, while CN values < 4.7 suggest a reduced risk for dSCC (grey area: 4.7–5.8). Diagnostic testing for KITLG CNV may sensitise owners to the individual risk of their black GS for dSCC. Further studies should investigate the relevance of KITLG CNV in SS and the protective effects in MS, who rarely suffer from dSCC. KW - tumour KW - toe KW - miniature schnauzer KW - standard schnauzer KW - CNV KW - ddPCR KW - breed predisposition Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-303913 SN - 2306-7381 VL - 10 IS - 2 ER - TY - JOUR A1 - de Paz, Víctor A1 - Asís, Josep D. A1 - Holzschuh, Andrea A1 - Baños-Picón, Laura T1 - Effects of traditional orchard abandonment and landscape context on the beneficial arthropod community in a Mediterranean agroecosystem JF - Insects N2 - Agricultural abandonment is one of the main land-use changes in Europe, and its consequences on biodiversity are context- and taxa-dependent. While several studies have worked on this topic, few have focused on traditional orchards, especially in different landscapes and under a Mediterranean climate. In this context, we aimed to determine the effects of almond orchard abandonment on the communities of three groups of beneficial arthropods and the role of the landscape context in modulating these effects. Between February and September 2019, four samplings were carried out in twelve almond orchards (three abandoned and three traditional (active orchards under traditional agricultural management) located in simple landscapes as well as three abandoned and three traditional in complex landscapes). Abandoned and traditional almond orchards harbor different arthropod communities and diversity metrics that are strongly conditioned by seasonality. Abandoned orchards can favor pollinators and natural enemies, providing alternative resources in simple landscapes. However, the role that abandoned orchards play in simple landscapes disappears as the percentage of semi-natural habitats in the landscape increases. Our results show that landscape simplification, through the loss of semi-natural habitats, has negative consequences on arthropod biodiversity, even in traditional farming landscapes with small fields and high crop diversity. KW - abandonment KW - traditional almond orchard KW - spider KW - parasitoid KW - bee KW - landscape complexity Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311190 SN - 2075-4450 VL - 14 IS - 3 ER - TY - JOUR A1 - Wersebeckmann, Vera A1 - Biegerl, Carolin A1 - Leyer, Ilona A1 - Mody, Karsten T1 - Orthopteran diversity in steep slope vineyards: the role of vineyard type and vegetation management JF - Insects N2 - The abandonment of traditional agricultural practices and subsequent succession are major threats to many open-adapted species and species-rich ecosystems. Viticulture on steep slopes has recently suffered from strong declines due to insufficient profitability, thus increasing the area of fallow land considerably. Changing cultivation systems from vertically oriented to modern vineyard terraces offers an opportunity to maintain management economically viable and thus reduces further abandonment. Hillside parallel terraces favor mechanization, and their embankments offer large undisturbed areas that could provide valuable habitats. We investigated the effects of vineyard abandonment, different vineyard management types (vertically oriented vs. terraced), and local parameters on Orthoptera diversity in 45 study sites along the Upper Middle Rhine Valley in Germany. Our results show that woody structures and vineyard abandonment reduced Orthoptera diversity at the local and landscape scale due to decreased habitat quality, especially for open-adapted species. In contrast, open inter-rows of actively managed vineyard types supported heat-adapted Caelifera species. On terrace embankments, extensive management and taller vegetation benefited Ensifera species, while short and mulched vegetation in vertically oriented vineyards favored the dominance of one single Caelifera species. Our results highlight the significance of maintaining viticultural management on steep slopes for the preservation of both open-adapted Orthoptera species and the cultural landscape. KW - abandonment KW - alternating management KW - biodiversity conservation KW - grasshopper KW - insect conservation KW - succession KW - traditional land use KW - vineyard terrace Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304891 SN - 2075-4450 VL - 14 IS - 1 ER - TY - JOUR A1 - Dong, Meng A1 - Böpple, Kathrin A1 - Thiel, Julia A1 - Winkler, Bernd A1 - Liang, Chunguang A1 - Schueler, Julia A1 - Davies, Emma J. A1 - Barry, Simon T. A1 - Metsalu, Tauno A1 - Mürdter, Thomas E. A1 - Sauer, Georg A1 - Ott, German A1 - Schwab, Matthias A1 - Aulitzky, Walter E. T1 - Perfusion air culture of precision-cut tumor slices: an ex vivo system to evaluate individual drug response under controlled culture conditions JF - Cells N2 - Precision-cut tumor slices (PCTS) maintain tissue heterogeneity concerning different cell types and preserve the tumor microenvironment (TME). Typically, PCTS are cultured statically on a filter support at an air–liquid interface, which gives rise to intra-slice gradients during culture. To overcome this problem, we developed a perfusion air culture (PAC) system that can provide a continuous and controlled oxygen medium, and drug supply. This makes it an adaptable ex vivo system for evaluating drug responses in a tissue-specific microenvironment. PCTS from mouse xenografts (MCF-7, H1437) and primary human ovarian tumors (primary OV) cultured in the PAC system maintained the morphology, proliferation, and TME for more than 7 days, and no intra-slice gradients were observed. Cultured PCTS were analyzed for DNA damage, apoptosis, and transcriptional biomarkers for the cellular stress response. For the primary OV slices, cisplatin treatment induced a diverse increase in the cleavage of caspase-3 and PD-L1 expression, indicating a heterogeneous response to drug treatment between patients. Immune cells were preserved throughout the culturing period, indicating that immune therapy can be analyzed. The novel PAC system is suitable for assessing individual drug responses and can thus be used as a preclinical model to predict in vivo therapy responses. KW - precision-cut tumor slices KW - perfusion culture KW - tumor microenvironment KW - ovarian tumor KW - individual drug responses KW - mouse xenografts KW - preclinical model KW - personalized medicine Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311030 SN - 2073-4409 VL - 12 IS - 5 ER - TY - JOUR A1 - Cerezo-Echevarria, Argiñe A1 - Kehl, Alexandra A1 - Beitzinger, Christoph A1 - Müller, Tobias A1 - Klopfleisch, Robert A1 - Aupperle-Lellbach, Heike T1 - Evaluating the histologic grade of digital squamous cell carcinomas in dogs and copy number variation of KIT Ligand — a correlation study JF - Veterinary Sciences N2 - Dark-haired dogs are predisposed to the development of digital squamous cell carcinoma (DSCC). This may potentially suggest an underlying genetic predisposition not yet completely elucidated. Some authors have suggested a potential correlation between the number of copies KIT Ligand (KITLG) and the predisposition of dogs to DSCC, containing a higher number of copies in those affected by the neoplasm. In this study, the aim was to evaluate a potential correlation between the number of copies of the KITLG and the histological grade of malignancy in dogs with DSCC. For this, 72 paraffin-embedded DSCCs with paired whole blood samples of 70 different dogs were included and grouped according to their haircoat color as follow: Group 0/unknown haircoat color (n = 11); Group 1.a/black non-Schnauzers (n = 15); group 1.b/black Schnauzers (n = 33); group 1.c/black and tan dogs (n = 7); group 2/tan animals (n = 4). The DSCCs were histologically graded. Additionally, KITLG Copy Number Variation (CNV) was determined by ddPCR. A significant correlation was observed between KITLG copy number and the histological grade and score value. This finding may suggest a possible factor for the development of canine DSCC, thus potentially having an impact on personalized veterinary oncological strategies and breeding programs. KW - canine KW - cancer KW - toe KW - grading KW - haircoat KW - color KW - genetics KW - gene Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304824 SN - 2306-7381 VL - 10 IS - 2 ER -