@article{StueblerKloftHuisinga2023, author = {St{\"u}bler, Sabine and Kloft, Charlotte and Huisinga, Wilhelm}, title = {Cell-level systems biology model to study inflammatory bowel diseases and their treatment options}, series = {CPT: pharmacometrics \& systems pharmacology}, volume = {12}, journal = {CPT: pharmacometrics \& systems pharmacology}, number = {5}, publisher = {Nature Publ. Group}, address = {London}, issn = {2163-8306}, doi = {10.1002/psp4.12932}, pages = {690 -- 705}, year = {2023}, abstract = {To help understand the complex and therapeutically challenging inflammatory bowel diseases (IBDs), we developed a systems biology model of the intestinal immune system that is able to describe main aspects of IBD and different treatment modalities thereof. The model, including key cell types and processes of the mucosal immune response, compiles a large amount of isolated experimental findings from literature into a larger context and allows for simulations of different inflammation scenarios based on the underlying data and assumptions. In the context of a large and diverse virtual IBD population, we characterized the patients based on their phenotype (in contrast to healthy individuals, they developed persistent inflammation after a trigger event) rather than on a priori assumptions on parameter differences to a healthy individual. This allowed to reproduce the enormous diversity of predispositions known to lead to IBD. Analyzing different treatment effects, the model provides insight into characteristics of individual drug therapy. We illustrate for anti-TNF-alpha therapy, how the model can be used (i) to decide for alternative treatments with best prospects in the case of nonresponse, and (ii) to identify promising combination therapies with other available treatment options.}, language = {en} } @article{NumbergerGanzertZoccaratoetal.2019, author = {Numberger, Daniela and Ganzert, Lars and Zoccarato, Luca and M{\"u}hldorfer, Kristin and Sauer, Sascha and Grossart, Hans-Peter and Greenwood, Alex D.}, title = {Characterization of bacterial communities in wastewater with enhanced taxonomic resolution by full-length 16S rRNA sequencing}, series = {Scientific reports}, volume = {9}, journal = {Scientific reports}, publisher = {Nature Publ. Group}, address = {London}, issn = {2045-2322}, doi = {10.1038/s41598-019-46015-z}, pages = {14}, year = {2019}, abstract = {Wastewater treatment is crucial to environmental hygiene in urban environments. However, wastewater treatment plants (WWTPs) collect chemicals, organic matter, and microorganisms including pathogens and multi-resistant bacteria from various sources which may be potentially released into the environment via WWTP effluent. To better understand microbial dynamics in WWTPs, we characterized and compared the bacterial community of the inflow and effluent of a WWTP in Berlin, Germany using full-length 16S rRNA gene sequences, which allowed for species level determination in many cases and generally resolved bacterial taxa. Significantly distinct bacterial communities were identified in the wastewater inflow and effluent samples. Dominant operational taxonomic units (OTUs) varied both temporally and spatially. Disease associated bacterial groups were efficiently reduced in their relative abundance from the effluent by the WWTP treatment process, except for Legionella and Leptospira species which demonstrated an increase in relative proportion from inflow to effluent. This indicates that WWTPs, while effective against enteric bacteria, may enrich and release other potentially pathogenic bacteria into the environment. The taxonomic resolution of full-length 16S rRNA genes allows for improved characterization of potential pathogenic taxa and other harmful bacteria which is required to reliably assess health risk.}, language = {en} } @article{GarbulowskiSmolinskaCabuketal.2022, author = {Garbulowski, Mateusz and Smolinska, Karolina and {\c{C}}abuk, Uğur and Yones, Sara A. and Celli, Ludovica and Yaz, Esma Nur and Barrenas, Fredrik and Diamanti, Klev and Wadelius, Claes and Komorowski, Jan}, title = {Machine learning-based analysis of glioma grades reveals co-enrichment}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {4}, publisher = {MDPI}, address = {Basel}, issn = {2072-6694}, doi = {10.3390/cancers14041014}, pages = {19}, year = {2022}, abstract = {Simple Summary Gliomas are heterogenous types of cancer, therefore the therapy should be personalized and targeted toward specific pathways. We developed a methodology that corrected strong batch effects from The Cancer Genome Atlas datasets and estimated glioma grade-specific co-enrichment mechanisms using machine learning. Our findings created hypotheses for annotations, e.g., pathways, that should be considered as therapeutic targets. Gliomas develop and grow in the brain and central nervous system. Examining glioma grading processes is valuable for improving therapeutic challenges. One of the most extensive repositories storing transcriptomics data for gliomas is The Cancer Genome Atlas (TCGA). However, such big cohorts should be processed with caution and evaluated thoroughly as they can contain batch and other effects. Furthermore, biological mechanisms of cancer contain interactions among biomarkers. Thus, we applied an interpretable machine learning approach to discover such relationships. This type of transparent learning provides not only good predictability, but also reveals co-predictive mechanisms among features. In this study, we corrected the strong and confounded batch effect in the TCGA glioma data. We further used the corrected datasets to perform comprehensive machine learning analysis applied on single-sample gene set enrichment scores using collections from the Molecular Signature Database. Furthermore, using rule-based classifiers, we displayed networks of co-enrichment related to glioma grades. Moreover, we validated our results using the external glioma cohorts. We believe that utilizing corrected glioma cohorts from TCGA may improve the application and validation of any future studies. Finally, the co-enrichment and survival analysis provided detailed explanations for glioma progression and consequently, it should support the targeted treatment.}, language = {en} } @article{IlicicWoodhouseKarstenetal.2022, author = {Ilicic, Doris and Woodhouse, Jason Nicholas and Karsten, Ulf and Zimmermann, Jonas and Wichard, Thomas and Quartino, Maria Liliana and Campana, Gabriela Laura and Livenets, Alexandra and Van den Wyngaert, Silke and Grossart, Hans-Peter}, title = {Antarctic Glacial Meltwater Impacts the Diversity of Fungal Parasites Associated With Benthic Diatoms in Shallow Coastal Zones}, series = {Frontiers in microbiology}, journal = {Frontiers in microbiology}, number = {13}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1664-302X}, doi = {10.3389/fmicb.2022.805694}, pages = {12}, year = {2022}, abstract = {Aquatic ecosystems are frequently overlooked as fungal habitats, although there is increasing evidence that their diversity and ecological importance are greater than previously considered. Aquatic fungi are critical and abundant components of nutrient cycling and food web dynamics, e.g., exerting top-down control on phytoplankton communities and forming symbioses with many marine microorganisms. However, their relevance for microphytobenthic communities is almost unexplored. In the light of global warming, polar regions face extreme changes in abiotic factors with a severe impact on biodiversity and ecosystem functioning. Therefore, this study aimed to describe, for the first time, fungal diversity in Antarctic benthic habitats along the salinity gradient and to determine the co-occurrence of fungal parasites with their algal hosts, which were dominated by benthic diatoms. Our results reveal that Ascomycota and Chytridiomycota are the most abundant fungal taxa in these habitats. We show that also in Antarctic waters, salinity has a major impact on shaping not just fungal but rather the whole eukaryotic community composition, with a diversity of aquatic fungi increasing as salinity decreases. Moreover, we determined correlations between putative fungal parasites and potential benthic diatom hosts, highlighting the need for further systematic analysis of fungal diversity along with studies on taxonomy and ecological roles of Chytridiomycota.}, language = {en} } @misc{NumbergerDreierVullioudetal.2019, author = {Numberger, Daniela and Dreier, Carola and Vullioud, Colin and Gabriel, Guelsah and Greenwood, Alex D. and Grossart, Hans-Peter}, title = {Correction: Recovery of influenza A viruses from lake water and sediments by experimental inoculation (vol 14, e0216880, 2019)}, series = {PLoS one}, volume = {14}, journal = {PLoS one}, number = {6}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0218882}, pages = {1}, year = {2019}, language = {en} } @article{NwosuRoeserYangetal.2021, author = {Nwosu, Ebuka Canisius and Roeser, Patricia Angelika and Yang, Sizhong and Ganzert, Lars and Dellwig, Olaf and Pinkerneil, Sylvia and Brauer, Achim and Dittmann, Elke and Wagner, Dirk and Liebner, Susanne}, title = {From water into sediment-tracing freshwater cyanobacteria via DNA analyses}, series = {Microorganisms : open access journal}, volume = {9}, journal = {Microorganisms : open access journal}, number = {8}, publisher = {MDPI}, address = {Basel}, issn = {2076-2607}, doi = {10.3390/microorganisms9081778}, pages = {20}, year = {2021}, abstract = {Sedimentary ancient DNA-based studies have been used to probe centuries of climate and environmental changes and how they affected cyanobacterial assemblages in temperate lakes. Due to cyanobacteria containing potential bloom-forming and toxin-producing taxa, their approximate reconstruction from sediments is crucial, especially in lakes lacking long-term monitoring data. To extend the resolution of sediment record interpretation, we used high-throughput sequencing, amplicon sequence variant (ASV) analysis, and quantitative PCR to compare pelagic cyanobacterial composition to that in sediment traps (collected monthly) and surface sediments in Lake Tiefer See. Cyanobacterial composition, species richness, and evenness was not significantly different among the pelagic depths, sediment traps and surface sediments (p > 0.05), indicating that the cyanobacteria in the sediments reflected the cyanobacterial assemblage in the water column. However, total cyanobacterial abundances (qPCR) decreased from the metalimnion down the water column. The aggregate-forming (Aphanizomenon) and colony-forming taxa (Snowella) showed pronounced sedimentation. In contrast, Planktothrix was only very poorly represented in sediment traps (meta- and hypolimnion) and surface sediments, despite its highest relative abundance at the thermocline (10 m water depth) during periods of lake stratification (May-October). We conclude that this skewed representation in taxonomic abundances reflects taphonomic processes, which should be considered in future DNA-based paleolimnological investigations.}, language = {en} } @article{NwosuRoeserYangetal.2021, author = {Nwosu, Ebuka Canisius and Roeser, Patricia Angelika and Yang, Sizhong and Pinkerneil, Sylvia and Ganzert, Lars and Dittmann, Elke and Brauer, Achim and Wagner, Dirk and Liebner, Susanne}, title = {Species-level spatio-temporal dynamics of cyanobacteria in a hard-water temperate lake in the Southern Baltics}, series = {Frontiers in microbiology}, volume = {12}, journal = {Frontiers in microbiology}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1664-302X}, doi = {10.3389/fmicb.2021.761259}, pages = {17}, year = {2021}, abstract = {Cyanobacteria are important primary producers in temperate freshwater ecosystems. However, studies on the seasonal and spatial distribution of cyanobacteria in deep lakes based on high-throughput DNA sequencing are still rare. In this study, we combined monthly water sampling and monitoring in 2019, amplicon sequence variants analysis (ASVs; a proxy for different species) and quantitative PCR targeting overall cyanobacteria abundance to describe the seasonal and spatial dynamics of cyanobacteria in the deep hard-water oligo-mesotrophic Lake Tiefer See, NE Germany. We observed significant seasonal variation in the cyanobacterial community composition (p < 0.05) in the epi- and metalimnion layers, but not in the hypolimnion. In winter-when the water column is mixed-picocyanobacteria (Synechococcus and Cyanobium) were dominant. With the onset of stratification in late spring, we observed potential niche specialization and coexistence among the cyanobacteria taxa driven mainly by light and nutrient dynamics. Specifically, ASVs assigned to picocyanobacteria and the genus Planktothrix were the main contributors to the formation of deep chlorophyll maxima along a light gradient. While Synechococcus and different Cyanobium ASVs were abundant in the epilimnion up to the base of the euphotic zone from spring to fall, Planktothrix mainly occurred in the metalimnetic layer below the euphotic zone where also overall cyanobacteria abundance was highest in summer. Our data revealed two potentially psychrotolerant (cold-adapted) Cyanobium species that appear to cope well under conditions of lower hypolimnetic water temperature and light as well as increasing sediment-released phosphate in the deeper waters in summer. The potential cold-adapted Cyanobium species were also dominant throughout the water column in fall and winter. Furthermore, Snowella and Microcystis-related ASVs were abundant in the water column during the onset of fall turnover. Altogether, these findings suggest previously unascertained and considerable spatiotemporal changes in the community of cyanobacteria on the species level especially within the genus Cyanobium in deep hard-water temperate lakes.}, language = {en} } @article{ZoccaratoSherMikietal.2022, author = {Zoccarato, Luca and Sher, Daniel and Miki, Takeshi and Segre, Daniel and Grossart, Hans-Peter}, title = {A comparative whole-genome approach identifies bacterial traits for marine microbial interactions}, series = {Communications biology}, volume = {5}, journal = {Communications biology}, number = {1}, publisher = {Springer Nature}, address = {Berlin}, issn = {2399-3642}, doi = {10.1038/s42003-022-03184-4}, pages = {13}, year = {2022}, abstract = {Luca Zoccarato, Daniel Sher et al. leverage publicly available bacterial genomes from marine and other environments to examine traits underlying microbial interactions. Their results provide a valuable resource to investigate clusters of functional and linked traits to better understand marine bacteria community assembly and dynamics. Microbial interactions shape the structure and function of microbial communities with profound consequences for biogeochemical cycles and ecosystem health. Yet, most interaction mechanisms are studied only in model systems and their prevalence is unknown. To systematically explore the functional and interaction potential of sequenced marine bacteria, we developed a trait-based approach, and applied it to 473 complete genomes (248 genera), representing a substantial fraction of marine microbial communities. We identified genome functional clusters (GFCs) which group bacterial taxa with common ecology and life history. Most GFCs revealed unique combinations of interaction traits, including the production of siderophores (10\% of genomes), phytohormones (3-8\%) and different B vitamins (57-70\%). Specific GFCs, comprising Alpha- and Gammaproteobacteria, displayed more interaction traits than expected by chance, and are thus predicted to preferentially interact synergistically and/or antagonistically with bacteria and phytoplankton. Linked trait clusters (LTCs) identify traits that may have evolved to act together (e.g., secretion systems, nitrogen metabolism regulation and B vitamin transporters), providing testable hypotheses for complex mechanisms of microbial interactions. Our approach translates multidimensional genomic information into an atlas of marine bacteria and their putative functions, relevant for understanding the fundamental rules that govern community assembly and dynamics.}, language = {en} } @article{HartmannHasenkampMayeretal.2015, author = {Hartmann, Stefanie and Hasenkamp, Natascha and Mayer, Jens and Michaux, Johan and Morand, Serge and Mazzoni, Camila J. and Roca, Alfred L. and Greenwood, Alex D.}, title = {Endogenous murine leukemia retroviral variation across wild European and inbred strains of house mouse}, series = {BMC genomics}, volume = {16}, journal = {BMC genomics}, publisher = {BioMed Central}, address = {London}, issn = {1471-2164}, doi = {10.1186/s12864-015-1766-z}, pages = {13}, year = {2015}, abstract = {Background: Endogenous murine leukemia retroviruses (MLVs) are high copy number proviral elements difficult to comprehensively characterize using standard low throughput sequencing approaches. However, high throughput approaches generate data that is challenging to process, interpret and present. Results: Next generation sequencing (NGS) data was generated for MLVs from two wild caught Mus musculus domesticus (from mainland France and Corsica) and for inbred laboratory mouse strains C3H, LP/J and SJL. Sequence reads were grouped using a novel sequence clustering approach as applied to retroviral sequences. A Markov cluster algorithm was employed, and the sequence reads were queried for matches to specific xenotropic (Xmv), polytropic (Pmv) and modified polytropic (Mpmv) viral reference sequences. Conclusions: Various MLV subtypes were more widespread than expected among the mice, which may be due to the higher coverage of NGS, or to the presence of similar sequence across many different proviral loci. The results did not correlate with variation in the major MLV receptor Xpr1, which can restrict exogenous MLVs, suggesting that endogenous MLV distribution may reflect gene flow more than past resistance to infection.}, language = {en} } @article{NumbergerDreierVullioudetal.2019, author = {Numberger, Daniela and Dreier, Carole and Vullioud, Colin and Gabriel, G{\"u}lsah and Greenwood, Alex D. and Grossart, Hans-Peter}, title = {Recovery of influenza a viruses from lake water and sediments by experimental inoculation}, series = {PLoS one}, volume = {14}, journal = {PLoS one}, number = {5}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0216880}, pages = {13}, year = {2019}, abstract = {Influenza A viruses (IAV) are zoonotic pathogens relevant to human, domestic animal and wildlife health. Many avian IAVs are transmitted among waterfowl via a faecal-oral-route. Therefore, environmental water where waterfowl congregate may play an important role in the ecology and epidemiology of avian IAV. Water and sediment may sustain and transmit virus among individuals or species. It is unclear at what concentrations waterborne viruses are infectious or remain detectable. To address this, we performed lake water and sediment dilution experiments with varying concentrations or infectious doses of four IAV strains from seal, turkey, duck and gull. To test for infectivity of the IAV strains in a concentration dependent manner, we applied cultivation to specific pathogen free (SPF) embryonated chicken eggs and Madin-Darby Canine Kidney (MDCK) cells. IAV recovery was more effective from embryonated chicken eggs than MDCK cells for freshwater lake dilutions, whereas, MDCK cells were more effective for viral recovery from sediment samples. Low infectious dose (1 PFU/200 mu L) was sufficient in most cases to detect and recover IAV from lake water dilutions. Sediment required higher initial infectious doses (>= 100 PFU/200 mu L).}, language = {en} } @article{ReilRosenfeldImholtetal.2017, author = {Reil, Daniela and Rosenfeld, Ulrike and Imholt, Christian and Schmidt, Sabrina and Ulrich, Rainer G. and Eccard, Jana and Jacob, Jens}, title = {Puumala hantavirus infections in bank vole populations}, series = {BMC ecology}, volume = {17}, journal = {BMC ecology}, publisher = {BioMed Central}, address = {London}, issn = {1472-6785}, doi = {10.1186/s12898-017-0118-z}, pages = {13}, year = {2017}, abstract = {Background In Europe, bank voles (Myodes glareolus) are widely distributed and can transmit Puumala virus (PUUV) to humans, which causes a mild to moderate form of haemorrhagic fever with renal syndrome, called nephropathia epidemica. Uncovering the link between host and virus dynamics can help to prevent human PUUV infections in the future. Bank voles were live trapped three times a year in 2010-2013 in three woodland plots in each of four regions in Germany. Bank vole population density was estimated and blood samples collected to detect PUUV specific antibodies. Results We demonstrated that fluctuation of PUUV seroprevalence is dependent not only on multi-annual but also on seasonal dynamics of rodent host abundance. Moreover, PUUV infection might affect host fitness, because seropositive individuals survived better from spring to summer than uninfected bank voles. Individual space use was independent of PUUV infections. Conclusions Our study provides robust estimations of relevant patterns and processes of the dynamics of PUUV and its rodent host in Central Europe, which are highly important for the future development of predictive models for human hantavirus infection risk}, language = {en} } @article{WitzelAbuRishaAlbersetal.2019, author = {Witzel, Katja and Abu Risha, Marua and Albers, Philip and B{\"o}rnke, Frederik and Hanschen, Franziska S.}, title = {Identification and Characterization of Three Epithiospecifier Protein Isoforms in Brassica oleracea}, series = {Frontiers in plant science}, volume = {10}, journal = {Frontiers in plant science}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-462X}, doi = {10.3389/fpls.2019.01552}, pages = {14}, year = {2019}, abstract = {Glucosinolates present in Brassicaceae play a major role in herbivory defense. Upon tissue disruption, glucosinolates come into contact with myrosinase, which initiates their breakdown to biologically active compounds. Among these, the formation of epithionitriles is triggered by the presence of epithiospecifier protein (ESP) and a terminal double bond in the glucosinolate side chain. One ESP gene is characterized in the model plant Arabidopsis thaliana (AtESP; At1g54040.2). However, Brassica species underwent genome triplication since their divergence from the Arabidopsis lineage. This indicates the presence of multiple ESP isoforms in Brassica crops that are currently poorly characterized. We identified three B. oleracea ESPs, specifically BoESP1 (LOC106296341), BoESP2 (LOC106306810), and BoESP3 (LOC106325105) based on in silico genome analysis. Transcript and protein abundance were assessed in shoots and roots of four B. oleracea vegetables, namely broccoli, kohlrabi, white, and red cabbage, because these genotypes showed a differential pattern for the formation of glucosinolate hydrolysis products as well for their ESP activity. BoESP1 and BoESP2 were expressed mainly in shoots, while BoESP3 was abundant in roots. Biochemical characterization of heterologous expressed BoESP isoforms revealed different substrate specificities towards seven glucosinolates: all isoforms showed epithiospecifier activity on alkenyl glucosinolates, but not on non-alkenyl glucosinolates. The pH-value differently affected BoESP activity: while BoESP1 and BoESP2 activities were optimal at pH 6-7, BoESP3 activity remained relatively stable from pH 4 to 7. In order test their potential for the in vivo modification of glucosinolate breakdown, the three isoforms were expressed in A. thaliana Hi-0, which lacks AtESP expression, and analyzed for the effect on their respective hydrolysis products. The BoESPs altered the hydrolysis of allyl glucosinolate in the A. thaliana transformants to release 1-cyano-2,3-epithiopropane and reduced formation of the corresponding 3-butenenitrile and allyl isothiocyanate. Plants expressing BoESP2 showed the highest percentage of released epithionitriles. Given these results, we propose a model for isoform-specific roles of B. oleracea ESPs in glucosinolate breakdown.}, language = {en} } @article{GorinScherzKorostetal.2021, author = {Gorin, Vladislav A. and Scherz, Mark D. and Korost, Dmitry V. and Poyarkov, Nikolay A.}, title = {Consequences of parallel miniaturisation in Microhylinae (Anura, Microhylidae), with the description of a new genus of diminutive South East Asian frogs}, series = {Zoosystematics and evolution : Mitteilungen aus dem Museum f{\"u}r Naturkunde in Berlin}, volume = {97}, journal = {Zoosystematics and evolution : Mitteilungen aus dem Museum f{\"u}r Naturkunde in Berlin}, number = {1}, publisher = {Pensoft Publishers}, address = {Sofia}, issn = {1860-0743}, doi = {10.3897/zse.97.57968}, pages = {21 -- 54}, year = {2021}, abstract = {The genus Microhyla Tschudi, 1838 includes 52 species and is one of the most diverse genera of the family Microhylidae, being the most species-rich taxon of the Asian subfamily Microhylinae. The recent, rapid description of numerous new species of Microhyla with complex phylogenetic relationships has made the taxonomy of the group especially challenging. Several recent phylogenetic studies suggested paraphyly of Microhyla with respect to Glyphoglossus Gunther, 1869, and revealed three major phylogenetic lineages of mid-Eocene origin within this assemblage. However, comprehensive works assessing morphological variation among and within these lineages are absent. In the present study we investigate the generic taxonomy of Microhyla-Glyphoglossus assemblage based on a new phylogeny including 57 species, comparative morphological analysis of skeletons from cleared-and-stained specimens for 23 species, and detailed descriptions of generalized osteology based on volume-rendered micro-CT scans for five speciesal-together representing all major lineages within the group. The results confirm three highly divergent and well-supported clades that correspond with external and osteological morphological characteristics, as well as respective geographic distribution. Accordingly, acknowledging ancient divergence between these lineages and their significant morphological differentiation, we propose to consider these three lineages as distinct genera: Microhyla sensu stricto, Glyphoglossus, and a newly described genus, Nanohyla gen. nov.}, language = {en} }