@article{NagyCusumanoAndreattaetal.2019, author = {Nagy, D{\´o}ra and Cusumano, Paola and Andreatta, Gabriele and Martin Anduaga, Ane and Hermann-Luibl, Christiane and Reinhard, Nils and Gesto, Jo{\~a}o and Wegener, Christian and Mazzotta, Gabriella and Rosato, Ezio and Kyriacou, Charalambos P. and Helfrich-F{\"o}rster, Charlotte and Costa, Rodolfo}, title = {Peptidergic signaling from clock neurons regulates reproductive dormancy in Drosophila melanogaster}, series = {PLoS Genetics}, volume = {15}, journal = {PLoS Genetics}, doi = {10.1371/journal.pgen.1008158}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231681}, year = {2019}, abstract = {With the approach of winter, many insects switch to an alternative protective developmental program called diapause. Drosophila melanogaster females overwinter as adults by inducing a reproductive arrest that is characterized by inhibition of ovarian development at previtellogenic stages. The insulin producing cells (IPCs) are key regulators of this process, since they produce and release insulin-like peptides that act as diapause-antagonizing hormones. Here we show that in D. melanogaster two neuropeptides, Pigment Dispersing Factor (PDF) and short Neuropeptide F (sNPF) inhibit reproductive arrest, likely through modulation of the IPCs. In particular, genetic manipulations of the PDF-expressing neurons, which include the sNPF-producing small ventral Lateral Neurons (s-LNvs), modulated the levels of reproductive dormancy, suggesting the involvement of both neuropeptides. We expressed a genetically encoded cAMP sensor in the IPCs and challenged brain explants with synthetic PDF and sNPF. Bath applications of both neuropeptides increased cAMP levels in the IPCs, even more so when they were applied together, suggesting a synergistic effect. Bath application of sNPF additionally increased Ca2+ levels in the IPCs. Our results indicate that PDF and sNPF inhibit reproductive dormancy by maintaining the IPCs in an active state.}, language = {en} } @article{LuBoswellBoswelletal.2018, author = {Lu, Yuan and Boswell, Mikki and Boswell, William and Kneitz, Susanne and Klotz, Barbara and Savage, Markita and Salinas, Raquel and Marks, Rebacca and Regneri, Janine and Postlethwait, John and Warren, Wesley C. and Schartl, Manfred and Walter, Ronald}, title = {Gene expression variation and parental allele inheritance in a Xiphophorus interspecies hybridization model}, series = {PLoS Genetics}, volume = {14}, journal = {PLoS Genetics}, doi = {10.1371/journal.pgen.1007875}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237318}, year = {2018}, abstract = {Understanding the genetic mechanisms underlying segregation of phenotypic variation through successive generations is important for understanding physiological changes and disease risk. Tracing the etiology of variation in gene expression enables identification of genetic interactions, and may uncover molecular mechanisms leading to the phenotypic expression of a trait, especially when utilizing model organisms that have well-defined genetic lineages. There are a plethora of studies that describe relationships between gene expression and genotype, however, the idea that global variations in gene expression are also controlled by genotype remains novel. Despite the identification of loci that control gene expression variation, the global understanding of how genome constitution affects trait variability is unknown. To study this question, we utilized Xiphophorus fish of different, but tractable genetic backgrounds (inbred, F1 interspecies hybrids, and backcross hybrid progeny), and measured each individual's gene expression concurrent with the degrees of inter-individual expression variation. We found, (a) F1 interspecies hybrids exhibited less variability than inbred animals, indicting gene expression variation is not affected by the fraction of heterozygous loci within an individual genome, and (b), that mixing genotypes in backcross populations led to higher levels of gene expression variability, supporting the idea that expression variability is caused by heterogeneity of genotypes of cis or trans loci. In conclusion, heterogeneity of genotype, introduced by inheritance of different alleles, accounts for the largest effects on global phenotypical variability.}, language = {en} } @article{BreitenbachLiangBeyersdorfetal.2019, author = {Breitenbach, Tim and Liang, Chunguang and Beyersdorf, Niklas and Dandekar, Thomas}, title = {Analyzing pharmacological intervention points: A method to calculate external stimuli to switch between steady states in regulatory networks}, series = {PLoS Computational Biology}, volume = {15}, journal = {PLoS Computational Biology}, doi = {10.1371/journal.pcbi.1007075}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220385}, year = {2019}, abstract = {Once biological systems are modeled by regulatory networks, the next step is to include external stimuli, which model the experimental possibilities to affect the activity level of certain network's nodes, in a mathematical framework. Then, this framework can be interpreted as a mathematical optimal control framework such that optimization algorithms can be used to determine external stimuli which cause a desired switch from an initial state of the network to another final state. These external stimuli are the intervention points for the corresponding biological experiment to obtain the desired outcome of the considered experiment. In this work, the model of regulatory networks is extended to controlled regulatory networks. For this purpose, external stimuli are considered which can affect the activity of the network's nodes by activation or inhibition. A method is presented how to calculate a selection of external stimuli which causes a switch between two different steady states of a regulatory network. A software solution based on Jimena and Mathworks Matlab is provided. Furthermore, numerical examples are presented to demonstrate application and scope of the software on networks of 4 nodes, 11 nodes and 36 nodes. Moreover, we analyze the aggregation of platelets and the behavior of a basic T-helper cell protein-protein interaction network and its maturation towards Th0, Th1, Th2, Th17 and Treg cells in accordance with experimental data.}, language = {en} } @article{HerpinSchmidtKneitzetal.2019, author = {Herpin, Amaury and Schmidt, Cornelia and Kneitz, Susanne and Gob{\´e}, Clara and Regensburger, Martina and Le Cam, Aur{\´e}lie and Montfort, J{\´e}rome and Adolfi, Mateus C. and Lillesaar, Christina and Wilhelm, Dagmar and Kraeussling, Michael and Mourot, Brigitte and Porcon, B{\´e}atrice and Pannetier, Ma{\"e}lle and Pailhoux, Eric and Ettwiller, Laurence and Dolle, Dirk and Guiguen, Yann and Schartl, Manfred}, title = {A novel evolutionary conserved mechanism of RNA stability regulates synexpression of primordial germ cell-specific genes prior to the sex-determination stage in medaka}, series = {PLoS Biology}, volume = {17}, journal = {PLoS Biology}, doi = {10.1371/journal.pbio.3000185}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320011}, year = {2019}, abstract = {Dmrt1 is a highly conserved transcription factor, which is critically involved in regulation of gonad development of vertebrates. In medaka, a duplicate of dmrt1—acting as master sex-determining gene—has a tightly timely and spatially controlled gonadal expression pattern. In addition to transcriptional regulation, a sequence motif in the 3′ UTR (D3U-box) mediates transcript stability of dmrt1 mRNAs from medaka and other vertebrates. We show here that in medaka, two RNA-binding proteins with antagonizing properties target this D3U-box, promoting either RNA stabilization in germ cells or degradation in the soma. The D3U-box is also conserved in other germ-cell transcripts, making them responsive to the same RNA binding proteins. The evolutionary conservation of the D3U-box motif within dmrt1 genes of metazoans—together with preserved expression patterns of the targeting RNA binding proteins in subsets of germ cells—suggest that this new mechanism for controlling RNA stability is not restricted to fishes but might also apply to other vertebrates.}, language = {en} } @article{MorgensternPeikertLuebbertetal.2021, author = {Morgenstern, Marcel and Peikert, Christian D. and L{\"u}bbert, Philipp and Suppanz, Ida and Klemm, Cinzia and Alka, Oliver and Steiert, Conny and Naumenko, Nataliia and Schendzielorz, Alexander and Melchionda, Laura and M{\"u}hlh{\"a}user, Wignand W. D. and Knapp, Bettina and Busch, Jakob D. and Stiller, Sebastian B. and Dannenmaier, Stefan and Lindau, Caroline and Licheva, Mariya and Eickhorst, Christopher and Galbusera, Riccardo and Zerbes, Ralf M. and Ryan, Michael T. and Kraft, Claudine and Kozjak-Pavlovic, Vera and Drepper, Friedel and Dennerlein, Sven and Oeljeklaus, Silke and Pfanner, Nikolaus and Wiedemann, Nils and Warscheid, Bettina}, title = {Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context}, series = {Cell Metabolism}, volume = {33}, journal = {Cell Metabolism}, doi = {10.1016/j.cmet.2021.11.001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-371114}, pages = {2464-2483}, year = {2021}, abstract = {Mitochondria are key organelles for cellular energetics, metabolism, signaling, and quality control and have been linked to various diseases. Different views exist on the composition of the human mitochondrial proteome. We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). We identified interactors of translocases, respiratory chain, and ATP synthase assembly factors. The abundance of MitoCoP proteins covers six orders of magnitude and amounts to 7\% of the cellular proteome with the chaperones HSP60-HSP10 being the most abundant mitochondrial proteins. MitoCoP dynamics spans three orders of magnitudes, with half-lives from hours to months, and suggests a rapid regulation of biosynthesis and assembly processes. 460 MitoCoP genes are linked to human diseases with a strong prevalence for the central nervous system and metabolism. MitoCoP will provide a high-confidence resource for placing dynamics, functions, and dysfunctions of mitochondria into the cellular context.}, language = {en} } @article{MoreauxMeirelesSonneetal.2022, author = {Moreaux, C{\´e}line and Meireles, Desir{\´e}e A. L. and Sonne, Jesper and Badano, Ernesto I. and Classen, Alice and Gonz{\´a}lez-Chaves, Adrian and Hip{\´o}lito, Juliana and Klein, Alexandra-Maria and Maruyama, Pietro K. and Metzger, Jean Paul and Philpott, Stacy M. and Rahbek, Carsten and Saturni, Fernanda T. and Sritongchuay, Tuanjit and Tscharntke, Teja and Uno, Shinsuke and Vergara, Carlos H. and Viana, Blandina F. and Strange, Niels and Dalsgaard, Bo}, title = {The value of biotic pollination and dense forest for fruit set of Arabica coffee: A global assessment}, series = {Agriculture, Ecosystems \& Environment}, volume = {323}, journal = {Agriculture, Ecosystems \& Environment}, doi = {10.1016/j.agee.2021.107680}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370982}, year = {2022}, abstract = {Animal pollinators are globally threatened by anthropogenic land use change and agricultural intensification. The yield of many food crops is therefore negatively impacted because they benefit from biotic pollination. This is especially the case in the tropics. For instance, fruit set of Coffea arabica has been shown to increase by 10-30\% in plantations with a high richness of bee species, possibly influenced by the availability of surrounding forest habitat. Here, we performed a global literature review to (1) assess how much animal pollination enhances coffee fruit set, and to (2) examine the importance of the amount of forest cover, distance to nearby forest and forest canopy density for bee species richness and coffee fruit set. Using a systematic literature review, we identified eleven case studies with a total of 182 samples where fruit set of C. arabica was assessed. We subsequently gathered forest data for all study sites from satellite imagery. We modelled the effects of open (all forest with a canopy density of ≥25\%), closed (≥50\%) and dense (≥75\%) forests on pollinator richness and fruit set of coffee. Overall, we found that animal pollination increases coffee fruit set by ~18\% on average. In only one of the case studies, regression results indicate a positive effect of dense forest on coffee fruit set, which increased with higher forest cover and shorter distance to the forest. Against expectations, forest cover and distance to open forest were not related to bee species richness and fruit set. In summary, we provide strong empirical support for the notion that animal pollinators increase coffee fruit set. Forest proximity had little overall influence on bee richness and coffee fruit set, except when farms were surrounded by dense tropical forests, potentially because these may provide high-quality habitats for bees pollinating coffee. We, therefore, advocate that more research is done to understand the biodiversity value of dense forest for pollinators, notably assessing the mechanisms underlying the importance of forest for pollinators and their pollination services.}, language = {en} } @article{MaGulbinsEdwardsetal.2017, author = {Ma, Jie and Gulbins, Erich and Edwards, Michael J. and Caldwell, Charles C. and Fraunholz, Martin and Becker, Katrin Anne}, title = {Staphylococcus aureus α-toxin induces inflammatory cytokines via lysosomal acid sphingomyelinase and ceramides}, series = {Cellular Physiology and Biochemistry}, volume = {43}, journal = {Cellular Physiology and Biochemistry}, number = {6}, doi = {10.1159/000484296}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181481}, pages = {2170-2184}, year = {2017}, abstract = {Staphylococcus aureus (S. aureus) infections are a major clinical problem and range from mild skin and soft-tissue infections to severe and even lethal infections such as pneumonia, endocarditis, sepsis, osteomyelitis, and toxic shock syndrome. Toxins that are released from S. aureus mediate many of these effects. Here, we aimed to identify molecular mechanisms how α-toxin, a major S. aureus toxin, induces inflammation. Methods: Macrophages were isolated from the bone marrow of wildtype and acid sphingomyelinase-deficient mice, stimulated with S. aureus α-toxin and activation of the acid sphingomyelinase was quantified. The subcellular formation of ceramides was determined by confocal microscopy. Release of cathepsins from lysosomes, activation of inflammasome proteins and formation of Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α) were analyzed by western blotting, confocal microscopy and ELISA. Results: We demonstrate that S. aureus α-toxin activates the acid sphingomyelinase in ex vivo macrophages and triggers a release of ceramides. Ceramides induced by S. aureus α-toxin localize to lysosomes and mediate a release of cathepsin B and D from lysosomes into the cytoplasm. Cytosolic cathepsin B forms a complex with Nlrc4. Treatment of macrophages with α-toxin induces the formation of IL-1β and TNF-α. These events are reduced or abrogated, respectively, in cells lacking the acid sphingomyelinase and upon treatment of macrophages with amitriptyline, a functional inhibitor of acid sphingomyelinase. Pharmacological inhibition of cathepsin B prevented activation of the inflammasome measured as release of IL-1β, while the formation of TNF-α was independent of cathepsin B. Conclusion: We demonstrate a novel mechanism how bacterial toxins activate the inflammasome and mediate the formation and release of cytokines: S. aureus α-toxin triggers an activation of the acid sphingomyelinase and a release of ceramides resulting in the release of lysosomal cathepsin B and formation of pro-inflammatory cytokines.}, language = {en} } @article{SzklarczykMorrisCooketal.2017, author = {Szklarczyk, Damian and Morris, John H. and Cook, Helen and Kuhn, Michael and Wyder, Stefan and Simonovic, Milan and Santos, Aalberto and Doncheva, Nadezhda T. and Roth, Alexander and Bork, Peer and Jensen, Lars J. and von Mering, Christian}, title = {The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible}, series = {Nucleic Acids Research}, volume = {45}, journal = {Nucleic Acids Research}, number = {D1}, doi = {10.1093/nar/gkw937}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181445}, pages = {D362-D368}, year = {2017}, abstract = {A system-wide understanding of cellular function requires knowledge of all functional interactions between the expressed proteins. The STRING database aims to collect and integrate this information, by consolidating known and predicted protein-protein association data for a large number of organisms. The associations in STRING include direct (physical) interactions, as well as indirect (functional) interactions, as long as both are specific and biologically meaningful. Apart from collecting and reassessing available experimental data on protein-protein interactions, and importing known pathways and protein complexes from curated databases, interaction predictions are derived from the following sources: (i) systematic co-expression analysis, (ii) detection of shared selective signals across genomes, (iii) automated text-mining of the scientific literature and (iv) computational transfer of interaction knowledge between organisms based on gene orthology. In the latest version 10.5 of STRING, the biggest changes are concerned with data dissemination: the web frontend has been completely redesigned to reduce dependency on outdated browser technologies, and the database can now also be queried from inside the popular Cytoscape software framework. Further improvements include automated background analysis of user inputs for functional enrichments, and streamlined download options. The STRING resource is available online, at http://string-db.org/.}, language = {en} } @article{RheeChoiKimetal.2017, author = {Rhee, Jae-Sung and Choi, Beom-Soon and Kim, Jaebum and Kim, Bo-Mi and Lee, Young-Mi and Kim, Il-Chan and Kanamori, Akira and Choi, Ik-Young and Schartl, Manfred and Lee, Jae-Seong}, title = {Diversity, distribution, and significance of transposable elements in the genome of the only selfing hermaphroditic vertebrate Kryptolebias marmoratus}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/srep40121}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181329}, year = {2017}, abstract = {The Kryptolebias marmoratus is unique because it is the only selffertilizing hermaphroditic vertebrate, known to date. It primarily reproduces by internal self-fertilization in a mixed ovary/testis gonad. Here, we report on a high-quality genome assembly for the K. marmoratus South Korea (SK) strain highlighting the diversity and distribution of transposable elements (TEs). We find that K. marmoratus genome maintains number and composition of TEs. This can be an important genomic attribute promoting genome recombination in this selfing fish, while, in addition to a mixed mating strategy, it may also represent a mechanism contributing to the evolutionary adaptation to ecological pressure of the species. Future work should help clarify this point further once genomic information is gathered for other taxa of the family Rivulidae that do not self-fertilize. We provide a valuable genome resource that highlights the potential impact of TEs on the genome evolution of a fish species with an uncommon life cycle.}, language = {en} } @article{MannucciDangHuberetal.2021, author = {Mannucci, Ilaria and Dang, Nghi D. P. and Huber, Hannes and Murry, Jaclyn B. and Abramson, Jeff and Althoff, Thorsten and Banka, Siddharth and Baynam, Gareth and Bearden, David and Beleza-Meireles, Ana and Benke, Paul J. and Berland, Siren and Bierhals, Tatjana and Bilan, Frederic and Bindoff, Laurence A. and Braathen, Geir Julius and Busk, {\O}yvind L. and Chenbhanich, Jirat and Denecke, Jonas and Escobar, Luis F. and Estes, Caroline and Fleischer, Julie and Groepper, Daniel and Haaxma, Charlotte A. and Hempel, Maja and Holler-Managan, Yolanda and Houge, Gunnar and Jackson, Adam and Kellogg, Laura and Keren, Boris and Kiraly-Borri, Catherine and Kraus, Cornelia and Kubisch, Christian and Le Guyader, Gwenael and Ljungblad, Ulf W. and Brenman, Leslie Manace and Martinez-Agosto, Julian A. and Might, Matthew and Miller, David T. and Minks, Kelly Q. and Moghaddam, Billur and Nava, Caroline and Nelson, Stanley F. and Parant, John M. and Prescott, Trine and Rajabi, Farrah and Randrianaivo, Hanitra and Reiter, Simone F. and Schuurs-Hoeijmakers, Janneke and Shieh, Perry B. and Slavotinek, Anne and Smithson, Sarah and Stegmann, Alexander P. A. and Tomczak, Kinga and Tveten, Kristian and Wang, Jun and Whitlock, Jordan H. and Zweier, Christiane and McWalter, Kirsty and Juusola, Jane and Quintero-Rivera, Fabiola and Fischer, Utz and Yeo, Nan Cher and Kreienkamp, Hans-J{\"u}rgen and Lessel, Davor}, title = {Genotype-phenotype correlations and novel molecular insights into the DHX30-associated neurodevelopmental disorders}, series = {Genome Medicine}, volume = {13}, journal = {Genome Medicine}, doi = {10.1186/s13073-021-00900-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-306477}, year = {2021}, abstract = {Background We aimed to define the clinical and variant spectrum and to provide novel molecular insights into the DHX30-associated neurodevelopmental disorder. Methods Clinical and genetic data from affected individuals were collected through Facebook-based family support group, GeneMatcher, and our network of collaborators. We investigated the impact of novel missense variants with respect to ATPase and helicase activity, stress granule (SG) formation, global translation, and their effect on embryonic development in zebrafish. SG formation was additionally analyzed in CRISPR/Cas9-mediated DHX30-deficient HEK293T and zebrafish models, along with in vivo behavioral assays. Results We identified 25 previously unreported individuals, ten of whom carry novel variants, two of which are recurrent, and provide evidence of gonadal mosaicism in one family. All 19 individuals harboring heterozygous missense variants within helicase core motifs (HCMs) have global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities. These variants impair the ATPase and helicase activity of DHX30, trigger SG formation, interfere with global translation, and cause developmental defects in a zebrafish model. Notably, 4 individuals harboring heterozygous variants resulting either in haploinsufficiency or truncated proteins presented with a milder clinical course, similar to an individual harboring a de novo mosaic HCM missense variant. Functionally, we established DHX30 as an ATP-dependent RNA helicase and as an evolutionary conserved factor in SG assembly. Based on the clinical course, the variant location, and type we establish two distinct clinical subtypes. DHX30 loss-of-function variants cause a milder phenotype whereas a severe phenotype is caused by HCM missense variants that, in addition to the loss of ATPase and helicase activity, lead to a detrimental gain-of-function with respect to SG formation. Behavioral characterization of dhx30-deficient zebrafish revealed altered sleep-wake activity and social interaction, partially resembling the human phenotype. Conclusions Our study highlights the usefulness of social media to define novel Mendelian disorders and exemplifies how functional analyses accompanied by clinical and genetic findings can define clinically distinct subtypes for ultra-rare disorders. Such approaches require close interdisciplinary collaboration between families/legal representatives of the affected individuals, clinicians, molecular genetics diagnostic laboratories, and research laboratories.}, language = {en} } @article{MaasBrandlHussainetal.2021, author = {Maas, Bea and Brandl, Manuela and Hussain, Raja Imran and Frank, Thomas and Zulka, Klaus Peter and Rabl, Dominik and Walcher, Ronnie and Moser, Dietmar}, title = {Functional traits driving pollinator and predator responses to newly established grassland strips in agricultural landscapes}, series = {Journal of Applied Ecology}, volume = {58}, journal = {Journal of Applied Ecology}, doi = {10.1111/1365-2664.13892}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369992}, pages = {1728-1737}, year = {2021}, abstract = {Agricultural biodiversity and associated ecosystem functions are declining at alarming rates due to widespread land use intensification. They can only be maintained through targeted landscape management that supports species with different habitat preferences, dispersal capacities and other functional traits that determine their survival. However, we need better understanding whether short-term measures can already improve functional diversity in European agroecosystems. We investigated spatio-temporal responses of bees (solitary bees, bumblebees and honey bees), hoverflies, carabid beetles and spiders to newly established grassland strips in Lower Austria over 3 years, and along a distance gradient to old grasslands. Specifically, we asked if new grasslands, compared to old grasslands and cereal fields, serve as temporal dispersal habitat or corridor, and how species-specific traits affect dispersal patterns. Using a trait-based functional diversity approach, we investigated year and distance effects for nine selected key traits per taxon (e.g. body size, feeding guild and habitat preferences). Our results show that the functional diversity of predators and pollinators (i.e. functional richness and evenness), as well as community-weighted means of selected key traits in new grasslands significantly differed from adjacent cereal fields, but only slowly adjusted to adjacent old grasslands. These effects significantly decreased with increasing distance to old grasslands for carabids and spiders, but not for mobile bees and hoverflies. Synthesis and applications. Over 3 years, newly established grassland strips supported larger sized and actively foraging/hunting species in the agricultural landscape. Adjacent crops likely benefit from such measures through enhanced functional diversity and related ecosystem services. However, our results also suggest that 3-year period is too short to enhance the occurrence of pollinators and epigeic predators in new grasslands. Agri-environment measures need to be complemented by the conservation of permanent habitats to effectively maintain species and functional diversity. Our findings should be acknowledged by European policy and agricultural decision makers for the design of more effective agri-environment schemes, taking into account trait-dependent species responses to land use change.}, language = {en} } @article{LuBierbachOrmannsetal.2021, author = {Lu, Yuan and Bierbach, David and Ormanns, Jenny and Warren, Wesley C. and Walter, Ronald B. and Schartl, Manfred}, title = {Fixation of allelic gene expression landscapes and expression bias pattern shape the transcriptome of the clonal Amazon molly}, series = {Genome Research}, volume = {31}, journal = {Genome Research}, doi = {10.1101/gr.268870.120}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369578}, pages = {372-379}, year = {2021}, abstract = {The Amazon molly is a unique clonal fish species that originated from an interspecies hybrid between Poecilia species P. mexicana and P. latipinna. It reproduces by gynogenesis, which eliminates paternal genomic contribution to offspring. An earlier study showed that Amazon molly shows biallelic expression for a large portion of the genome, leading to two main questions: (1) Are the allelic expression patterns from the initial hybridization event stabilized or changed during establishment of the asexual species and its further evolution? (2) Is allelic expression biased toward one parental allele a stochastic or adaptive process? To answer these questions, the allelic expression of P. formosa siblings was assessed to investigate intra- and inter-cohort allelic expression variability. For comparison, interspecies hybrids between P. mexicana and P. latipinna were produced in the laboratory to represent the P. formosa ancestor. We have identified inter-cohort and intra-cohort variation in parental allelic expression. The existence of inter-cohort divergence suggests functional P. formosa allelic expression patterns do not simply reflect the atavistic situation of the first interspecies hybrid but potentially result from long-term selection of transcriptional fitness. In addition, clonal fish show a transcriptional trend representing minimal intra-clonal variability in allelic expression patterns compared to the corresponding hybrids. The intra-clonal similarity in gene expression translates to sophisticated genetic functional regulation at the individuum level. These findings suggest the parental alleles inherited by P. formosa form tightly regulated genetic networks that lead to a stable transcriptomic landscape within clonal individuals.}, language = {en} } @article{LozaValdesMayerKassoufetal.2021, author = {Loza-Valdes, Angel and Mayer, Alexander E and Kassouf, Toufic and Trujillo-Viera, Jonathan and Schmitz, Werner and Dziaczkowski, Filip and Leitges, Michael and Schlosser, Andreas and Sumara, Grzegorz}, title = {A phosphoproteomic approach reveals that PKD3 controls PKA-mediated glucose and tyrosine metabolism}, series = {Life Science Alliance}, volume = {4}, journal = {Life Science Alliance}, doi = {10.26508/lsa.202000863}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369560}, year = {2021}, abstract = {Members of the protein kinase D (PKD) family (PKD1, 2, and 3) integrate hormonal and nutritional inputs to regulate complex cellular metabolism. Despite the fact that a number of functions have been annotated to particular PKDs, their molecular targets are relatively poorly explored. PKD3 promotes insulin sensitivity and suppresses lipogenesis in the liver of animals fed a high-fat diet. However, its substrates are largely unknown. Here we applied proteomic approaches to determine PKD3 targets. We identified more than 300 putative targets of PKD3. Furthermore, biochemical analysis revealed that PKD3 regulates cAMP-dependent PKA activity, a master regulator of the hepatic response to glucagon and fasting. PKA regulates glucose, lipid, and amino acid metabolism in the liver, by targeting key enzymes in the respective processes. Among them the PKA targets phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine. Consistently, we showed that PKD3 is activated by glucagon and promotes glucose and tyrosine levels in hepatocytes. Therefore, our data indicate that PKD3 might play a role in the hepatic response to glucagon.}, language = {en} } @article{LiKuhnZukowskaKasprzyketal.2021, author = {Li, Yuanyue and Kuhn, Michael and Zukowska-Kasprzyk, Joanna and Hennrich, Marco L. and Kastritis, Panagiotis L. and O'Reilly, Francis J. and Phapale, Prasad and Beck, Martin and Gavin, Anne-Claude and Bork, Peer}, title = {Coupling proteomics and metabolomics for the unsupervised identification of protein-metabolite interactions in Chaetomium thermophilum}, series = {PLOS ONE}, volume = {16}, journal = {PLOS ONE}, doi = {10.1371/journal.pone.0254429}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-364299}, year = {2021}, abstract = {Protein-metabolite interactions play an important role in the cell's metabolism and many methods have been developed to screen them in vitro. However, few methods can be applied at a large scale and not alter biological state. Here we describe a proteometabolomic approach, using chromatography to generate cell fractions which are then analyzed with mass spectrometry for both protein and metabolite identification. Integrating the proteomic and metabolomic analyses makes it possible to identify protein-bound metabolites. Applying the concept to the thermophilic fungus Chaetomium thermophilum, we predict 461 likely protein-metabolite interactions, most of them novel. As a proof of principle, we experimentally validate a predicted interaction between the ribosome and isopentenyl adenine.}, language = {en} } @article{LiZhangFanetal.2021, author = {Li, Ming and Zhang, Rui and Fan, Guangyi and Xu, Wenteng and Zhou, Qian and Wang, Lei and Li, Wensheng and Pang, Zunfang and Yu, Mengjun and Liu, Qun and Liu, Xin and Schartl, Manfred and Chen, Songlin}, title = {Reconstruction of the Origin of a Neo-Y Sex Chromosome and Its Evolution in the Spotted Knifejaw, Oplegnathus punctatus}, series = {Molecular Biology and Evolution}, volume = {38}, journal = {Molecular Biology and Evolution}, doi = {10.1093/molbev/msab056}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-364215}, pages = {2615-2626}, year = {2021}, abstract = {Sex chromosomes are a peculiar constituent of the genome because the evolutionary forces that fix the primary sex-determining gene cause genic degeneration and accumulation of junk DNA in the heterogametic partner. One of the most spectacular phenomena in sex chromosome evolution is the occurrence of neo-Y chromosomes, which lead to X1X2Y sex-determining systems. Such neo-sex chromosomes are critical for understanding the processes of sex chromosome evolution because they rejuvenate their total gene content. We assembled the male and female genomes at the chromosome level of the spotted knifejaw (Oplegnathus punctatus), which has a cytogenetically recognized neo-Y chromosome. The full assembly and annotation of all three sex chromosomes allowed us to reconstruct their evolutionary history. Contrary to other neo-Y chromosomes, the fusion to X2 is quite ancient, estimated at 48 Ma. Despite its old age and being even older in the X1 homologous region which carries a huge inversion that occurred as early as 55-48 Ma, genetic degeneration of the neo-Y appears to be only moderate. Transcriptomic analysis showed that sex chromosomes harbor 87 genes, which may serve important functions in the testis. The accumulation of such male-beneficial genes, a large inversion on the X1 homologous region and fusion to X2 appear to be the main drivers of neo-Y evolution in the spotted knifejaw. The availability of high-quality assemblies of the neo-Y and both X chromosomes make this fish an ideal model for a better understanding of the variability of sex determination mechanisms and of sex chromosome evolution.}, language = {en} } @article{LetunicBork2021, author = {Letunic, Ivica and Bork, Peer}, title = {Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation}, series = {Nucleic Acids Research}, volume = {49}, journal = {Nucleic Acids Research}, doi = {10.1093/nar/gkab301}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363803}, pages = {W293-W296}, year = {2021}, abstract = {The Interactive Tree Of Life (https://itol.embl.de) is an online tool for the display, manipulation and annotation of phylogenetic and other trees. It is freely available and open to everyone. iTOL version 5 introduces a completely new tree display engine, together with numerous new features. For example, a new dataset type has been added (MEME motifs), while annotation options have been expanded for several existing ones. Node metadata display options have been extended and now also support non-numerical categorical values, as well as multiple values per node. Direct manual annotation is now available, providing a set of basic drawing and labeling tools, allowing users to draw shapes, labels and other features by hand directly onto the trees. Support for tree and dataset scales has been extended, providing fine control over line and label styles. Unrooted tree displays can now use the equal-daylight algorithm, proving a much greater display clarity. The user account system has been streamlined and expanded with new navigation options and currently handles >1 million trees from >70 000 individual users.}, language = {en} } @article{LehmannJorgensenFratzetal.2021, author = {Lehmann, Julian and J{\o}rgensen, Morten E. and Fratz, Stefanie and M{\"u}ller, Heike M. and Kusch, Jana and Scherzer, S{\"o}nke and Navarro-Retamal, Carlos and Mayer, Dominik and B{\"o}hm, Jennifer and Konrad, Kai R. and Terpitz, Ulrich and Dreyer, Ingo and Mueller, Thomas D. and Sauer, Markus and Hedrich, Rainer and Geiger, Dietmar and Maierhofer, Tobias}, title = {Acidosis-induced activation of anion channel SLAH3 in the flooding-related stress response of Arabidopsis}, series = {Current Biology}, volume = {31}, journal = {Current Biology}, doi = {10.1016/j.cub.2021.06.018}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363320}, pages = {3575-3585}, year = {2021}, abstract = {Plants, as sessile organisms, gained the ability to sense and respond to biotic and abiotic stressors to survive severe changes in their environments. The change in our climate comes with extreme dry periods but also episodes of flooding. The latter stress condition causes anaerobiosis-triggered cytosolic acidosis and impairs plant function. The molecular mechanism that enables plant cells to sense acidity and convey this signal via membrane depolarization was previously unknown. Here, we show that acidosis-induced anion efflux from Arabidopsis (Arabidopsis thaliana) roots is dependent on the S-type anion channel AtSLAH3. Heterologous expression of SLAH3 in Xenopus oocytes revealed that the anion channel is directly activated by a small, physiological drop in cytosolic pH. Acidosis-triggered activation of SLAH3 is mediated by protonation of histidine 330 and 454. Super-resolution microscopy analysis showed that the increase in cellular proton concentration switches SLAH3 from an electrically silent channel dimer into its active monomeric form. Our results show that, upon acidification, protons directly switch SLAH3 to its open configuration, bypassing kinase-dependent activation. Moreover, under flooding conditions, the stress response of Arabidopsis wild-type (WT) plants was significantly higher compared to SLAH3 loss-of-function mutants. Our genetic evidence of SLAH3 pH sensor function may guide the development of crop varieties with improved stress tolerance.}, language = {en} } @article{LeProvostThieleWestphaletal.2021, author = {Le Provost, Ga{\"e}tane and Thiele, Jan and Westphal, Catrin and Penone, Caterina and Allan, Eric and Neyret, Margot and van der Plas, Fons and Ayasse, Manfred and Bardgett, Richard D. and Birkhofer, Klaus and Boch, Steffen and Bonkowski, Michael and Buscot, Francois and Feldhaar, Heike and Gaulton, Rachel and Goldmann, Kezia and Gossner, Martin M. and Klaus, Valentin H. and Kleinebecker, Till and Krauss, Jochen and Renner, Swen and Scherreiks, Pascal and Sikorski, Johannes and Baulechner, Dennis and Bl{\"u}thgen, Nico and Bolliger, Ralph and B{\"o}rschig, Carmen and Busch, Verena and Chist{\´e}, Melanie and Fiore-Donno, Anna Maria and Fischer, Markus and Arndt, Hartmut and Hoelzel, Norbert and John, Katharina and Jung, Kirsten and Lange, Markus and Marzini, Carlo and Overmann, J{\"o}rg and Paŝalić, Esther and Perović, David J. and Prati, Daniel and Sch{\"a}fer, Deborah and Sch{\"o}ning, Ingo and Schrumpf, Marion and Sonnemann, Ilja and Steffan-Dewenter, Ingolf and Tschapka, Marco and T{\"u}rke, Manfred and Vogt, Juliane and Wehner, Katja and Weiner, Christiane and Weisser, Wolfgang and Wells, Konstans and Werner, Michael and Wolters, Volkmar and Wubet, Tesfaye and Wurst, Susanne and Zaitsev, Andrey S. and Manning, Peter}, title = {Contrasting responses of above- and belowground diversity to multiple components of land-use intensity}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, doi = {10.1038/s41467-021-23931-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-371552}, year = {2021}, abstract = {Land-use intensification is a major driver of biodiversity loss. However, understanding how different components of land use drive biodiversity loss requires the investigation of multiple trophic levels across spatial scales. Using data from 150 agricultural grasslands in central Europe, we assess the influence of multiple components of local- and landscape-level land use on more than 4,000 above- and belowground taxa, spanning 20 trophic groups. Plot-level land-use intensity is strongly and negatively associated with aboveground trophic groups, but positively or not associated with belowground trophic groups. Meanwhile, both above- and belowground trophic groups respond to landscape-level land use, but to different drivers: aboveground diversity of grasslands is promoted by diverse surrounding land-cover, while belowground diversity is positively related to a high permanent forest cover in the surrounding landscape. These results highlight a role of landscape-level land use in shaping belowground communities, and suggest that revised agroecosystem management strategies are needed to conserve whole-ecosystem biodiversity.}, language = {en} } @article{LarrieuCabanettesCourbaudetal.2021, author = {Larrieu, Laurent and Cabanettes, Alain and Courbaud, Benoit and Goulard, Michel and Heintz, Wilfried and Koz{\´a}k, Daniel and Kraus, Daniel and Lachat, Thibault and Ladet, Sylvie and M{\"u}ller, J{\"o}rg and Paillet, Yoan and Schuck, Andreas and Stillhard, Jonas and Svoboda, Miroslav}, title = {Co-occurrence patterns of tree-related microhabitats: A method to simplify routine monitoring}, series = {Ecological Indicators}, volume = {127}, journal = {Ecological Indicators}, doi = {10.1016/j.ecolind.2021.107757}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363158}, year = {2021}, abstract = {A Tree-related Microhabitat (TreM) is a distinct, well-delineated morphological singularity occurring on living or standing dead trees, which constitutes a crucial substrate or life site for various species. TreMs are widely recognized as key features for biodiversity. Current TreM typology identifies 47 TreM types according to their morphology and their associated taxa. In order to provide a range of resolutions and make the typology more user-friendly, these 47 TreM types have been pooled into 15 groups and seven forms. Depending on the accuracy required and the time available, a user can now choose to describe TreMs at resolution levels corresponding to type, group or form. Another way to more easily record TreMs during routine management work would be to use co-occurrence patterns to reduce the number of observed TreMs required. Based on a large international TreM database (2052 plots; 70,958 individual trees; 78 tree species), we evaluated both the significance and the magnitude of TreM co-occurrence on living trees for 11 TreM groups. We highlighted 33 significant co-occurrences for broadleaves and nine for conifers. Bark loss, rot hole, crack and polypore had the highest number of positive co-occurrences (N = 8) with other TreMs on broadleaves; bark loss (N = 4) had the highest number for conifers. We found mutually exclusive occurrences only for conifers: Exposed Heartwood excluded both dendrotelm and sap run. Among the four variables we tested for their positive contribution to significant co-occurrences, tree diameter at breast height was the most consistent. Based on our results and practical considerations, we selected three TreM groups for broadleaves, and nine for conifers, and formed useful short lists to reduce the number of TreM groups to assess during routine forest management work in the field. In addition, detecting potential similarities or associations between TreMs has potential theoretical value, e.g. it may help researchers identify common factors favouring TreM formation or help managers select trees with multiple TreMs as candidates for retention.}, language = {en} } @article{KuhlGuiguenHoehneetal.2021, author = {Kuhl, Heiner and Guiguen, Yann and H{\"o}hne, Christin and Kreuz, Eva and Du, Kang and Klopp, Christophe and Lopez-Roques,, C{\´e}line and Yebra-Pimentel, Elena Santidrian and Ciorpac, Mitica and Gessner, J{\"o}rn and Holostenco, Daniela and Kleiner, Wibke and Kohlmann, Klaus and Lamatsch, Dunja K. and Prokopov, Dmitry and Bestin, Anastasia and Bonpunt, Emmanuel and Debeuf, Bastien and Haffray, Pierrick and Morvezen, Romain and Patrice, Pierre and Suciu, Radu and Dirks, Ron and Wuertz, Sven and Kloas, Werner and Schartl, Manfred and St{\"o}ck, Matthias}, title = {A 180 Myr-old female-specific genome region in sturgeon reveals the oldest known vertebrate sex determining system with undifferentiated sex chromosomes}, series = {Philosophical Transactions of the Royal Society B}, volume = {376}, journal = {Philosophical Transactions of the Royal Society B}, doi = {10.1098/rstb.2020.0089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363050}, year = {2021}, abstract = {Several hypotheses explain the prevalence of undifferentiated sex chromosomes in poikilothermic vertebrates. Turnovers change the master sex determination gene, the sex chromosome or the sex determination system (e.g. XY to WZ). Jumping master genes stay main triggers but translocate to other chromosomes. Occasional recombination (e.g. in sex-reversed females) prevents sex chromosome degeneration. Recent research has uncovered conserved heteromorphic or even homomorphic sex chromosomes in several clades of non-avian and non-mammalian vertebrates. Sex determination in sturgeons (Acipenseridae) has been a long-standing basic biological question, linked to economical demands by the caviar-producing aquaculture. Here, we report the discovery of a sex-specific sequence from sterlet (Acipenser ruthenus). Using chromosome-scale assemblies and pool-sequencing, we first identified an approximately 16 kb female-specific region. We developed a PCR-genotyping test, yielding female-specific products in six species, spanning the entire phylogeny with the most divergent extant lineages (A. sturio, A. oxyrinchus versus A. ruthenus, Huso huso), stemming from an ancient tetraploidization. Similar results were obtained in two octoploid species (A. gueldenstaedtii, A. baerii). Conservation of a female-specific sequence for a long period, representing 180 Myr of sturgeon evolution, and across at least one polyploidization event, raises many interesting biological questions. We discuss a conserved undifferentiated sex chromosome system with a ZZ/ZW-mode of sex determination and potential alternatives. This article is part of the theme issue 'Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)'.}, language = {en} }