@article{SchartlKneitzVolkoffetal.2019, author = {Schartl, Manfred and Kneitz, Susanne and Volkoff, Helene and Adolfi, Mateus and Schmidt, Cornelia and Fischer, Petra and Minx, Patrick and Tomlinson, Chad and Meyer, Axel and Warren, Wesley C.}, title = {The piranha genome provides molecular insight associated to its unique feeding behavior}, series = {Genome Biology and Evolution}, volume = {11}, journal = {Genome Biology and Evolution}, number = {8}, doi = {10.1093/gbe/evz139}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202218}, pages = {2099-2106}, year = {2019}, abstract = {The piranha enjoys notoriety due to its infamous predatory behavior but much is still not understood about its evolutionary origins and the underlying molecular mechanisms for its unusual feeding biology. We sequenced and assembled the red-bellied piranha (Pygocentrus nattereri) genome to aid future phenotypic and genetic investigations. The assembled draft genome is similar to other related fishes in repeat composition and gene count. Our evaluation of genes under positive selection suggests candidates for adaptations of piranhas' feeding behavior in neural functions, behavior, and regulation of energy metabolism. In the fasted brain, we find genes differentially expressed that are involved in lipid metabolism and appetite regulation as well as genes that may control the aggression/boldness behavior of hungry piranhas. Our first analysis of the piranha genome offers new insight and resources for the study of piranha biology and for feeding motivation and starvation in other organisms.}, language = {en} } @article{PoppRamirezZavalaSchwanfelderetal.2019, author = {Popp, Christina and Ram{\´i}rez-Zavala, Bernardo and Schwanfelder, Sonja and Kr{\"u}ger, Ines and Morschh{\"a}user, Joachim}, title = {Evolution of fluconazole-resistant Candida albicans strains by drug-induced mating competence and parasexual recombination}, series = {mBio}, volume = {10}, journal = {mBio}, number = {1}, doi = {10.1128/mBio.02740-18}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200901}, pages = {e02740-18}, year = {2019}, abstract = {The clonal population structure of Candida albicans suggests that (para)sexual recombination does not play an important role in the lifestyle of this opportunistic fungal pathogen, an assumption that is strengthened by the fact that most C. albicans strains are heterozygous at the mating type locus (MTL) and therefore mating-incompetent. On the other hand, mating might occur within clonal populations and allow the combination of advantageous traits that were acquired by individual cells to adapt to adverse conditions. We have investigated if parasexual recombination may be involved in the evolution of highly drug-resistant strains exhibiting multiple resistance mechanisms against fluconazole, an antifungal drug that is commonly used to treat infections by C. albicans. Growth of strains that were heterozygous for MTL and different fluconazole resistance mutations in the presence of the drug resulted in the emergence of derivatives that had become homozygous for the mutated allele and the mating type locus and exhibited increased drug resistance. When MTLa/a and MTLα/α cells of these strains were mixed in all possible combinations, we could isolate mating products containing the genetic material from both parents. The initial mating products did not exhibit higher drug resistance than their parental strains, but further propagation under selective pressure resulted in the loss of the wild-type alleles and increased fluconazole resistance. Therefore, fluconazole treatment not only selects for resistance mutations but also promotes genomic alterations that confer mating competence, which allows cells in an originally clonal population to exchange individually acquired resistance mechanisms and generate highly drug-resistant progeny.}, language = {en} } @article{SchmidtHaywardCoelhoetal.2019, author = {Schmidt, Thomas S. B. and Hayward, Matthew R. and Coelho, Luiis P. and Li, Simone S. and Costea, Paul I. and Voigt, Anita Y. and Wirbel, Jakob and Maistrenko, Oleksandr M. and Alves, Renato J. C. and Bergsten, Emma and de Beaufort, Carine and Sobhani, Iradj and Heintz-Buschart, Anna and Sunagawa, Shinichi and Zeller, Georg and Wilmes, Paul and Bork, Peer}, title = {Extensive transmission of microbes along the gastrointestinal tract}, series = {eLife}, volume = {8}, journal = {eLife}, doi = {10.7554/eLife.42693}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228954}, pages = {e42693, 1-18}, year = {2019}, abstract = {The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.}, subject = {Barrier}, language = {en} } @article{SrivastavaBencurovaGuptaetal.2019, author = {Srivastava, Mugdha and Bencurova, Elena and Gupta, Shishir K. and Weiss, Esther and L{\"o}ffler, J{\"u}rgen and Dandekar, Thomas}, title = {Aspergillus fumigatus challenged by human dendritic cells: metabolic and regulatory pathway responses testify a tight battle}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {9}, journal = {Frontiers in Cellular and Infection Microbiology}, doi = {10.3389/fcimb.2019.00168}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201368}, pages = {168}, year = {2019}, abstract = {Dendritic cells (DCs) are antigen presenting cells which serve as a passage between the innate and the acquired immunity. Aspergillosis is a major lethal condition in immunocompromised patients caused by the adaptable saprophytic fungus Aspergillus fumigatus. The healthy human immune system is capable to ward off A. fumigatus infections however immune-deficient patients are highly vulnerable to invasive aspergillosis. A. fumigatus can persist during infection due to its ability to survive the immune response of human DCs. Therefore, the study of the metabolism specific to the context of infection may allow us to gain insight into the adaptation strategies of both the pathogen and the immune cells. We established a metabolic model of A. fumigatus central metabolism during infection of DCs and calculated the metabolic pathway (elementary modes; EMs). Transcriptome data were used to identify pathways activated when A. fumigatus is challenged with DCs. In particular, amino acid metabolic pathways, alternative carbon metabolic pathways and stress regulating enzymes were found to be active. Metabolic flux modeling identified further active enzymes such as alcohol dehydrogenase, inositol oxygenase and GTP cyclohydrolase participating in different stress responses in A. fumigatus. These were further validated by qRT-PCR from RNA extracted under these different conditions. For DCs, we outlined the activation of metabolic pathways in response to the confrontation with A. fumigatus. We found the fatty acid metabolism plays a crucial role, along with other metabolic changes. The gene expression data and their analysis illuminate additional regulatory pathways activated in the DCs apart from interleukin regulation. In particular, Toll-like receptor signaling, NOD-like receptor signaling and RIG-I-like receptor signaling were active pathways. Moreover, we identified subnetworks and several novel key regulators such as UBC, EGFR, and CUL3 of DCs to be activated in response to A. fumigatus. In conclusion, we analyze the metabolic and regulatory responses of A. fumigatus and DCs when confronted with each other.}, language = {en} } @article{HeibyGoretzkiJohnsonetal.2019, author = {Heiby, Julia C. and Goretzki, Benedikt and Johnson, Christopher M. and Hellmich, Ute A. and Neuweiler, Hannes}, title = {Methionine in a protein hydrophobic core drives tight interactions required for assembly of spider silk}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, doi = {10.1038/s41467-019-12365-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202539}, pages = {4378}, year = {2019}, abstract = {Web spiders connect silk proteins, so-called spidroins, into fibers of extraordinary toughness. The spidroin N-terminal domain (NTD) plays a pivotal role in this process: it polymerizes spidroins through a complex mechanism of dimerization. Here we analyze sequences of spidroin NTDs and find an unusually high content of the amino acid methionine. We simultaneously mutate all methionines present in the hydrophobic core of a spidroin NTD from a nursery web spider's dragline silk to leucine. The mutated NTD is strongly stabilized and folds at the theoretical speed limit. The structure of the mutant is preserved, yet its ability to dimerize is substantially impaired. We find that side chains of core methionines serve to mobilize the fold, which can thereby access various conformations and adapt the association interface for tight binding. Methionine in a hydrophobic core equips a protein with the capacity to dynamically change shape and thus to optimize its function.}, language = {en} } @article{KehrbergerHolzschuh2019, author = {Kehrberger, Sandra and Holzschuh, Andrea}, title = {How does timing of flowering affect competition for pollinators, flower visitation and seed set in an early spring grassland plant?}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-51916-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202549}, pages = {15593}, year = {2019}, abstract = {Knowledge on how the timing of flowering is related to plant fitness and species interactions is crucial to understand consequences of phenological shifts as they occur under climate change. Early flowering plants may face advantages of low competition for pollinators and disadvantages of low pollinator abundances and unfavourable weather conditions. However, it is unknown how this trade-off changes over the season and how the timing affects reproductive success. On eight grasslands we recorded intra-seasonal changes in pollinators, co-flowering plants, weather conditions, flower visitation rates, floral longevity and seed set of Pulsatilla vulgaris. Although bee abundances and the number of pollinator-suitable hours were low at the beginning of the season, early flowers of P. vulgaris received higher flower visitation rates and estimated total number of bee visits than later flowers, which was positively related to seed set. Flower visitation rates decreased over time and with increasing number of co-flowering plants, which competed with P. vulgaris for pollinators. Low interspecific competition for pollinators seems to be a major driver for early flowering dates. Thus, non-synchronous temporal shifts of co-flowering plants as they may occur under climate warming can be expected to strongly affect plant-pollinator interactions and the fitness of the involved plants.}, language = {en} } @article{HornMitesserHovestadtetal.2019, author = {Horn, Melanie and Mitesser, Oliver and Hovestadt, Thomas and Yoshii, Taishi and Rieger, Dirk and Helfrich-F{\"o}rster, Charlotte}, title = {The circadian clock improves fitness in the fruit fly, Drosophila melanogaster}, series = {Frontiers in Physiology}, volume = {10}, journal = {Frontiers in Physiology}, number = {1374}, issn = {1664-042X}, doi = {10.3389/fphys.2019.01374}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195738}, year = {2019}, abstract = {It is assumed that a properly timed circadian clock enhances fitness, but only few studies have truly demonstrated this in animals. We raised each of the three classical Drosophila period mutants for >50 generations in the laboratory in competition with wildtype flies. The populations were either kept under a conventional 24-h day or under cycles that matched the mutant's natural cycle, i.e., a 19-h day in the case of pers mutants and a 29-h day for perl mutants. The arrhythmic per0 mutants were grown together with wildtype flies under constant light that renders wildtype flies similar arrhythmic as the mutants. In addition, the mutants had to compete with wildtype flies for two summers in two consecutive years under outdoor conditions. We found that wildtype flies quickly outcompeted the mutant flies under the 24-h laboratory day and under outdoor conditions, but perl mutants persisted and even outnumbered the wildtype flies under the 29-h day in the laboratory. In contrast, pers and per0 mutants did not win against wildtype flies under the 19-h day and constant light, respectively. Our results demonstrate that wildtype flies have a clear fitness advantage in terms of fertility and offspring survival over the period mutants and - as revealed for perl mutants - this advantage appears maximal when the endogenous period resonates with the period of the environment. However, the experiments indicate that perl and pers persist at low frequencies in the population even under the 24-h day. This may be a consequence of a certain mating preference of wildtype and heterozygous females for mutant males and time differences in activity patterns between wildtype and mutants.}, language = {en} } @article{DuquePoelmanSteffanDewenter2019, author = {Duque, Laura and Poelman, Erik H. and Steffan-Dewenter, Ingolf}, title = {Plant-mediated effects of ozone on herbivores depend on exposure duration and temperature}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-56234-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202805}, pages = {19891}, year = {2019}, abstract = {Abiotic stress by elevated tropospheric ozone and temperature can alter plants' metabolism, growth, and nutritional value and modify the life cycle of their herbivores. We investigated how the duration of exposure of Sinapis arvensis plants to high ozone and temperature levels affect the life cycle of the large cabbage white, Pieris brassicae. Plants were exposed to ozone-clean (control) or ozone-enriched conditions (120 ppb) for either 1 or 5 days and were afterwards kept in a greenhouse with variable temperature conditions. When given the choice, P. brassicae butterflies laid 49\% fewer eggs on ozone-exposed than on control plants when the exposure lasted for 5 days, but showed no preference when exposure lasted for 1 day. The caterpillars took longer to hatch on ozone-exposed plants and at lower ambient temperatures. The ozone treatment had a positive effect on the survival of the eggs. Ozone decreased the growth of caterpillars reared at higher temperatures on plants exposed for 5 days, but not on plants exposed for 1 day. Overall, longer exposure of the plants to ozone and higher temperatures affected the life cycle of the herbivore more strongly. With global warming, the indirect impacts of ozone on herbivores are likely to become more common.}, language = {en} } @article{WestermannVenturiniSellinetal.2019, author = {Westermann, Alexander J. and Venturini, Elisa and Sellin, Mikael E. and F{\"o}rstner, Konrad U. and Hardt, Wolf-Dietrich and Vogel, J{\"o}rg}, title = {The major RNA-binding protein ProQ impacts virulence gene expression in Salmonella enterica serovar Typhimurium}, series = {mBio}, volume = {10}, journal = {mBio}, number = {1}, doi = {10.1128/mBio.02504-18}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177722}, pages = {e02504-18}, year = {2019}, abstract = {FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged as a new class of major RNA-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mRNAs from many virulence regions, but its role, if any, in bacterial pathogenesis has not been studied. Here, using a Dual RNA-seq approach to profile ProQ-dependent gene expression changes as Salmonella infects human cells, we reveal dysregulation of bacterial motility, chemotaxis, and virulence genes which is accompanied by altered MAPK (mitogen-activated protein kinase) signaling in the host. Comparison with the other major RNA chaperone in Salmonella, Hfq, reinforces the notion that these two global RNA-binding proteins work in parallel to ensure full virulence. Of newly discovered infection-associated ProQ-bound small noncoding RNAs (sRNAs), we show that the 3′UTR-derived sRNA STnc540 is capable of repressing an infection-induced magnesium transporter mRNA in a ProQ-dependent manner. Together, this comprehensive study uncovers the relevance of ProQ for Salmonella pathogenesis and highlights the importance of RNA-binding proteins in regulating bacterial virulence programs. IMPORTANCE The protein ProQ has recently been discovered as the centerpiece of a previously overlooked "third domain" of small RNA-mediated control of gene expression in bacteria. As in vitro work continues to reveal molecular mechanisms, it is also important to understand how ProQ affects the life cycle of bacterial pathogens as these pathogens infect eukaryotic cells. Here, we have determined how ProQ shapes Salmonella virulence and how the activities of this RNA-binding protein compare with those of Hfq, another central protein in RNA-based gene regulation in this and other bacteria. To this end, we apply global transcriptomics of pathogen and host cells during infection. In doing so, we reveal ProQ-dependent transcript changes in key virulence and host immune pathways. Moreover, we differentiate the roles of ProQ from those of Hfq during infection, for both coding and noncoding transcripts, and provide an important resource for those interested in ProQ-dependent small RNAs in enteric bacteria.}, language = {en} } @article{JaślanDreyerLuetal.2019, author = {Jaślan, Dawid and Dreyer, Ingo and Lu, Jinping and O'Malley, Ronan and Dindas, Julian and Marten, Irene and Hedrich, Rainer}, title = {Voltage-dependent gating of SV channel TPC1 confers vacuole excitability}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, doi = {10.1038/s41467-019-10599-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202029}, pages = {2659}, year = {2019}, abstract = {In contrast to the plasma membrane, the vacuole membrane has not yet been associated with electrical excitation of plants. Here, we show that mesophyll vacuoles from Arabidopsis sense and control the membrane potential essentially via the K\(^+\)-permeable TPC1 and TPK channels. Electrical stimuli elicit transient depolarization of the vacuole membrane that can last for seconds. Electrical excitability is suppressed by increased vacuolar Ca\(^{2+}\) levels. In comparison to wild type, vacuoles from the fou2 mutant, harboring TPC1 channels insensitive to luminal Ca\(^{2+}\), can be excited fully by even weak electrical stimuli. The TPC1-loss-of-function mutant tpc1-2 does not respond to electrical stimulation at all, and the loss of TPK1/TPK3-mediated K\(^{+}\) transport affects the duration of TPC1-dependent membrane depolarization. In combination with mathematical modeling, these results show that the vacuolar K\(^+\)-conducting TPC1 and TPK1/TPK3 channels act in concert to provide for Ca\(^{2+}\)- and voltage-induced electrical excitability to the central organelle of plant cells.}, language = {en} } @article{BoetzlKonleKrauss2019, author = {Boetzl, Fabian A. and Konle, Antonia and Krauss, Jochen}, title = {Aphid cards - useful model for assessing predation rates or bias prone nonsense?}, series = {Journal of Applied Entomology}, volume = {144}, journal = {Journal of Applied Entomology}, number = {1-2}, doi = {10.1111/jen.12692}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204798}, pages = {74-80}, year = {2019}, abstract = {Predation on pest organisms is an essential ecosystem function supporting yields in modern agriculture. However, assessing predation rates is intricate, and they can rarely be linked directly to predator densities or functions. We tested whether sentinel prey aphid cards are useful tools to assess predation rates in the field. Therefore, we looked at aphid cards of different sizes on the ground level as well as within the vegetation. Additionally, by trapping ground-dwelling predators, we examined whether obtained predation rates could be linked to predator densities and traits. Predation rates recorded with aphid cards were independent of aphid card size. However, predation rates on the ground level were three times higher than within the vegetation. We found both predatory carabid activity densities as well as community weighted mean body size to be good predictors for predation rates. Predation rates obtained from aphid cards are stable over card type and related to predator assemblages. Aphid cards, therefore, are a useful, efficient method for rapidly assessing the ecosystem function predation. Their use might especially be recommended for assessments on the ground level and when time and resource limitations rule out more elaborate sentinel prey methods using exclosures with living prey animals.}, language = {en} } @article{SauerJuranekMarksetal.2019, author = {Sauer, Markus and Juranek, Stefan A. and Marks, James and De Magis, Alessio and Kazemier, Hinke G and Hilbig, Daniel and Benhalevy, Daniel and Wang, Xiantao and Hafner, Markus and Paeschke, Katrin}, title = {DHX36 prevents the accumulation of translationally inactive mRNAs with G4-structures in untranslated regions}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, number = {2421}, doi = {10.1038/s41467-019-10432-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227486}, pages = {1-15}, year = {2019}, abstract = {Translation efficiency can be affected by mRNA stability and secondary structures, including G-quadruplex structures (G4s). The highly conserved DEAH-box helicase DHX36/RHAU resolves G4s on DNA and RNA in vitro, however a systems-wide analysis of DHX36 targets and function is lacking. We map globally DHX36 binding to RNA in human cell lines and find it preferentially interacting with G-rich and G4-forming sequences on more than 4500 mRNAs. While DHX36 knockout (KO) results in a significant increase in target mRNA abundance, ribosome occupancy and protein output from these targets decrease, suggesting that they were rendered translationally incompetent. Considering that DHX36 targets, harboring G4s, preferentially localize in stress granules, and that DHX36 KO results in increased SG formation and protein kinase R (PKR/EIF2AK2) phosphorylation, we speculate that DHX36 is involved in resolution of rG4 induced cellular stress.}, language = {en} } @article{WagnerKunzChowdhuryetal.2019, author = {Wagner, Fabienne and Kunz, Tobias C. and Chowdhury, Suvagata R. and Thiede, Bernd and Fraunholz, Martin and Eger, Debora and Kozjak-Pavlovic, Vera}, title = {Armadillo repeat-containing protein 1 is a dual localization protein associated with mitochondrial intermembrane space bridging complex}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0218303}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202670}, pages = {e0218303}, year = {2019}, abstract = {Cristae architecture is important for the function of mitochondria, the organelles that play the central role in many cellular processes. The mitochondrial contact site and cristae organizing system (MICOS) together with the sorting and assembly machinery (SAM) forms the mitochondrial intermembrane space bridging complex (MIB), a large protein complex present in mammalian mitochondria that partakes in the formation and maintenance of cristae. We report here a new subunit of the mammalian MICOS/MIB complex, an armadillo repeat-containing protein 1 (ArmC1). ArmC1 localizes both to cytosol and mitochondria, where it associates with the outer mitochondrial membrane through its carboxy-terminus. ArmC1 interacts with other constituents of the MICOS/MIB complex and its amounts are reduced upon MICOS/MIB complex depletion. Mitochondria lacking ArmC1 do not show defects in cristae structure, respiration or protein content, but appear fragmented and with reduced motility. ArmC1 represents therefore a peripheral MICOS/MIB component that appears to play a role in mitochondrial distribution in the cell.}, language = {en} } @article{WoersdoerferDaldaKernetal.2019, author = {W{\"o}rsd{\"o}rfer, Philipp and Dalda, Nahide and Kern, Anna and Kr{\"u}ger, Sarah and Wagner, Nicole and Kwok, Chee Keong and Henke, Erik and Erg{\"u}n, S{\"u}leyman}, title = {Generation of complex human organoid models including vascular networks by incorporation of mesodermal progenitor cells}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-52204-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202681}, pages = {15663}, year = {2019}, abstract = {Organoids derived from human pluripotent stem cells are interesting models to study mechanisms of morphogenesis and promising platforms for disease modeling and drug screening. However, they mostly remain incomplete as they lack stroma, tissue resident immune cells and in particular vasculature, which create important niches during development and disease. We propose, that the directed incorporation of mesodermal progenitor cells (MPCs) into organoids will overcome the aforementioned limitations. In order to demonstrate the feasibility of the method, we generated complex human tumor as well as neural organoids. We show that the formed blood vessels display a hierarchic organization and mural cells are assembled into the vessel wall. Moreover, we demonstrate a typical blood vessel ultrastructure including endothelial cell-cell junctions, a basement membrane as well as luminal caveolae and microvesicles. We observe a high plasticity in the endothelial network, which expands, while the organoids grow and is responsive to anti-angiogenic compounds and pro-angiogenic conditions such as hypoxia. We show that vessels within tumor organoids connect to host vessels following transplantation. Remarkably, MPCs also deliver Iba1\(^+\) cells that infiltrate the neural tissue in a microglia-like manner.}, language = {en} } @article{MottolaMorschhaeuser2019, author = {Mottola, Austin and Morschh{\"a}user, Joachim}, title = {An intragenic recombination event generates a Snf4-independent form of the essential protein kinase SNF1 in Candida albicans}, series = {mSphere}, volume = {4}, journal = {mSphere}, number = {3}, doi = {10.1128/mSphere.00352-19}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202170}, pages = {e00352-19}, year = {2019}, abstract = {The heterotrimeric protein kinase SNF1 plays a key role in the metabolic adaptation of the pathogenic yeast Candida albicans. It consists of the essential catalytic α-subunit Snf1, the γ-subunit Snf4, and one of the two β-subunits Kis1 and Kis2. Snf4 is required to release the N-terminal catalytic domain of Snf1 from autoinhibition by the C-terminal regulatory domain, and snf4Δ mutants cannot grow on carbon sources other than glucose. In a screen for suppressor mutations that restore growth of a snf4Δ mutant on alternative carbon sources, we isolated a mutant in which six amino acids between the N-terminal kinase domain and the C-terminal regulatory domain of Snf1 were deleted. The deletion was caused by an intragenic recombination event between two 8-bp direct repeats flanking six intervening codons. In contrast to truncated forms of Snf1 that contain only the kinase domain, the Snf4-independent Snf1\(^{Δ311 - 316}\) was fully functional and could replace wild-type Snf1 for normal growth, because it retained the ability to interact with the Kis1 and Kis2 β-subunits via its C-terminal domain. Indeed, the Snf4-independent Snf1\(^{Δ311 - 316}\) still required the β-subunits of the SNF1 complex to perform its functions and did not rescue the growth defects of kis1Δ mutants. Our results demonstrate that a preprogrammed in-frame deletion event within the SNF1 coding region can generate a mutated form of this essential kinase which abolishes autoinhibition and thereby overcomes growth deficiencies caused by a defect in the γ-subunit Snf4.}, language = {en} } @article{KehrbergerHolzschuh2019, author = {Kehrberger, Sandra and Holzschuh, Andrea}, title = {Warmer temperatures advance flowering in a spring plant more strongly than emergence of two solitary spring bee species}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0218824}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201165}, pages = {e0218824}, year = {2019}, abstract = {Climate warming has the potential to disrupt plant-pollinator interactions or to increase competition of co-flowering plants for pollinators, due to species-specific phenological responses to temperature. However, studies focusing on the effect of temperature on solitary bee emergence and the flowering onset of their food plants under natural conditions are still rare. We studied the effect of temperature on the phenology of the two spring bees Osmia cornuta and Osmia bicornis, by placing bee cocoons on eleven grasslands differing in mean site temperature. On seven grasslands, we additionally studied the effect of temperature on the phenology of the red-list plant Pulsatilla vulgaris, which was the first flowering plant, and of co-flowering plants with later flowering. With a warming of 0.1°C, the abundance-weighted mean emergence of O. cornuta males advanced by 0.4 days. Females of both species did not shift their emergence. Warmer temperatures advanced the abundance-weighted mean flowering of P. vulgaris by 1.3 days per 0.1°C increase, but did not shift flowering onset of co-flowering plants. Competition for pollinators between P. vulgaris and co-flowering plants does not increase within the studied temperature range. We demonstrate that temperature advances plant flowering more strongly than bee emergence suggesting an increased risk of pollinator limitation for the first flowers of P. vulgaris.}, language = {en} } @article{ElHawarySayedMohammedetal.2019, author = {El-Hawary, Seham S. and Sayed, Ahmed M. and Mohammed, Rabab and Hassan, Hossam M. and Rateb, Mostafa E. and Amin, Elham and Mohammed, Tarek A. and El-Mesery, Mohamed and Bin Muhsinah, Abdullatif and Alsayari, Abdulrhman and Wajant, Harald and Anany, Mohamed A. and Abdelmohsen, Usama Ramadan}, title = {Bioactive brominated oxindole alkaloids from the Red Sea sponge Callyspongia siphonella}, series = {Marine Drugs}, volume = {17}, journal = {Marine Drugs}, number = {8}, doi = {10.3390/md17080465}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201485}, pages = {465}, year = {2019}, abstract = {In the present study, LC-HRESIMS-assisted dereplication along with bioactivity-guided isolation led to targeting two brominated oxindole alkaloids (compounds 1 and 2) which probably play a key role in the previously reported antibacterial, antibiofilm, and cytotoxicity of Callyspongia siphonella crude extracts. Both metabolites showed potent antibacterial activity against Gram-positive bacteria, Staphylococcus aureus (minimum inhibitory concentration (MIC) = 8 and 4 µg/mL) and Bacillus subtilis (MIC = 16 and 4 µg/mL), respectively. Furthermore, they displayed moderate biofilm inhibitory activity in Pseudomonas aeruginosa (49.32\% and 41.76\% inhibition, respectively), and moderate in vitro antitrypanosomal activity (13.47 and 10.27 µM, respectively). In addition, they revealed a strong cytotoxic effect toward different human cancer cell lines, supposedly through induction of necrosis. This study sheds light on the possible role of these metabolites (compounds 1 and 2) in keeping fouling organisms away from the sponge outer surface, and the possible applications of these defensive molecules in the development of new anti-infective agents.}, language = {en} } @article{AkhoonGuptaTiwarietal.2019, author = {Akhoon, Bashir A. and Gupta, Shishir K. and Tiwari, Sudeep and Rathor, Laxmi and Pant, Aakanksha and Singh, Nivedita and Gupta, Shailendra K. and Dandekar, Thomas and Pandey, Rakesh}, title = {C. elegans protein interaction network analysis probes RNAi validated pro-longevity effect of nhr-6, a human homolog of tumor suppressor Nr4a1}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-51649-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202666}, pages = {15711}, year = {2019}, abstract = {Protein-protein interaction (PPI) studies are gaining momentum these days due to the plethora of various high-throughput experimental methods available for detecting PPIs. Proteins create complexes and networks by functioning in harmony with other proteins and here in silico network biology hold the promise to reveal new functionality of genes as it is very difficult and laborious to carry out experimental high-throughput genetic screens in living organisms. We demonstrate this approach by computationally screening C. elegans conserved homologs of already reported human tumor suppressor and aging associated genes. We select by this nhr-6, vab-3 and gst-23 as predicted longevity genes for RNAi screen. The RNAi results demonstrated the pro-longevity effect of these genes. Nuclear hormone receptor nhr-6 RNAi inhibition resulted in a C. elegans phenotype of 23.46\% lifespan reduction. Moreover, we show that nhr-6 regulates oxidative stress resistance in worms and does not affect the feeding behavior of worms. These findings imply the potential of nhr-6 as a common therapeutic target for aging and cancer ailments, stressing the power of in silico PPI network analysis coupled with RNAi screens to describe gene function.}, language = {en} } @article{ReuterJaeckelsKneitzetal.2019, author = {Reuter, Isabel and J{\"a}ckels, Jana and Kneitz, Susanne and Kuper, Jochen and Lesch, Klaus-Peter and Lillesaar, Christina}, title = {Fgf3 is crucial for the generation of monoaminergic cerebrospinal fluid contacting cells in zebrafish}, series = {Biology Open}, volume = {8}, journal = {Biology Open}, doi = {10.1242/bio.040683}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200749}, pages = {bio040683}, year = {2019}, abstract = {In most vertebrates, including zebrafish, the hypothalamic serotonergic cerebrospinal fluid-contacting (CSF-c) cells constitute a prominent population. In contrast to the hindbrain serotonergic neurons, little is known about the development and function of these cells. Here, we identify fibroblast growth factor (Fgf)3 as the main Fgf ligand controlling the ontogeny of serotonergic CSF-c cells. We show that fgf3 positively regulates the number of serotonergic CSF-c cells, as well as a subset of dopaminergic and neuroendocrine cells in the posterior hypothalamus via control of proliferation and cell survival. Further, expression of the ETS-domain transcription factor etv5b is downregulated after fgf3 impairment. Previous findings identified etv5b as critical for the proliferation of serotonergic progenitors in the hypothalamus, and therefore we now suggest that Fgf3 acts via etv5b during early development to ultimately control the number of mature serotonergic CSF-c cells. Moreover, our analysis of the developing hypothalamic transcriptome shows that the expression of fgf3 is upregulated upon fgf3 loss-of-function, suggesting activation of a self-compensatory mechanism. Together, these results highlight Fgf3 in a novel context as part of a signalling pathway of critical importance for hypothalamic development.}, language = {en} } @article{vonCollenbergSchmittRuelickeetal.2019, author = {von Collenberg, Cora R. and Schmitt, Dominique and R{\"u}licke, Thomas and Sendtner, Michael and Blum, Robert and Buchner, Erich}, title = {An essential role of the mouse synapse-associated protein Syap1 in circuits for spontaneous motor activity and rotarod balance}, series = {Biology Open}, volume = {8}, journal = {Biology Open}, doi = {10.1242/bio.042366}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201986}, pages = {bio042366}, year = {2019}, abstract = {Synapse-associated protein 1 (Syap1) is the mammalian homologue of synapse-associated protein of 47 kDa (Sap47) in Drosophila. Genetic deletion of Sap47 leads to deficiencies in short-term plasticity and associative memory processing in flies. In mice, Syap1 is prominently expressed in the nervous system, but its function is still unclear. We have generated Syap1 knockout mice and tested motor behaviour and memory. These mice are viable and fertile but display distinct deficiencies in motor behaviour. Locomotor activity specifically appears to be reduced in early phases when voluntary movement is initiated. On the rotarod, a more demanding motor test involving control by sensory feedback, Syap1-deficient mice dramatically fail to adapt to accelerated speed or to a change in rotation direction. Syap1 is highly expressed in cerebellar Purkinje cells and cerebellar nuclei. Thus, this distinct motor phenotype could be due to a so-far unknown function of Syap1 in cerebellar sensorimotor control. The observed motor defects are highly specific since other tests in the modified SHIRPA exam, as well as cognitive tasks like novel object recognition, Pavlovian fear conditioning, anxiety-like behaviour in open field dark-light transition and elevated plus maze do not appear to be affected in Syap1 knockout mice.}, language = {en} }