TY - JOUR A1 - Schmidt, Sabrina A1 - Reil, Daniela A1 - Jeske, Kathrin A1 - Drewes, Stephan A1 - Rosenfeld, Ulrike A1 - Fischer, Stefan A1 - Spierling, Nastasja G. A1 - Labutin, Anton A1 - Heckel, Gerald A1 - Jacob, Jens A1 - Ulrich, Rainer G. A1 - Imholt, Christian T1 - Spatial and temporal dynamics and molecular evolution of Tula orthohantavirus in German vole populations JF - Viruses / Molecular Diversity Preservation International (MDPI) N2 - Tula orthohantavirus (TULV) is a rodent-borne hantavirus with broad geographical distribution in Europe. Its major reservoir is the common vole (Microtus arvalis), but TULV has also been detected in closely related vole species. Given the large distributional range and high amplitude population dynamics of common voles, this host-pathogen complex presents an ideal system to study the complex mechanisms of pathogen transmission in a wild rodent reservoir. We investigated the dynamics of TULV prevalence and the subsequent potential effects on the molecular evolution of TULV in common voles of the Central evolutionary lineage. Rodents were trapped for three years in four regions of Germany and samples were analyzed for the presence of TULV-reactive antibodies and TULV RNA with subsequent sequence determination. The results show that individual (sex) and population-level factors (abundance) of hosts were significant predictors of local TULV dynamics. At the large geographic scale, different phylogenetic TULV clades and an overall isolation-by-distance pattern in virus sequences were detected, while at the small scale (<4 km) this depended on the study area. In combination with an overall delayed density dependence, our results highlight that frequent, localized bottleneck events for the common vole and TULV do occur and can be offset by local recolonization dynamics. KW - rodents KW - hantavirus KW - monitoring KW - population dynamics KW - common vole KW - field vole KW - water vole KW - phylogeny KW - molecular evolution Y1 - 2021 U6 - https://doi.org/10.3390/v13061132 SN - 1999-4915 VL - 13 IS - 6 PB - MDPI CY - Basel ER - TY - JOUR A1 - Belluardo, Francesco A1 - Scherz, Mark D. A1 - Santos, Barbara A1 - Andreone, Franco A1 - Antonelli, Alexandre A1 - Glaw, Frank A1 - Munoz-Pajares, A. Jesus A1 - Randrianirina, Jasmin E. A1 - Raselimanana, Achille P. A1 - Vences, Miguel A1 - Crottini, Angelica T1 - Molecular taxonomic identification and species-level phylogeny of the narrow-mouthed frogs of the genus Rhombophryne (Anura: Microhylidae: Cophylinae) from Madagascar JF - Systematics and biodiversity N2 - The study of diamond frogs (genus Rhombophryne, endemic to Madagascar) has been historically hampered by the paucity of available specimens, because of their low detectability in the field. Over the last 10 years, 13 new taxa have been described, and 20 named species are currently recognized. Nevertheless, undescribed diversity within the genus is probably large, calling for a revision of the taxonomic identification of published records and an update of the known distribution of each lineage. Here we generate DNA sequences of the mitochondrial 16S rRNA gene of all specimens available to us, revise the genetic data from public databases, and report all deeply divergent mitochondrial lineages of Rhombophryne identifiable from these data. We also generate a multi-locus dataset (including five mitochondrial and eight nuclear markers; 9844 bp) to infer a species-level phylogenetic hypothesis for the diversification of this genus and revise the distribution of each lineage. We recognize a total of 10 candidate species, two of which are identified here for the first time. The genus Rhombophryne is here proposed to be divided into six main species groups, and phylogenetic relationships among some of them are not fully resolved. These frogs are primarily distributed in northern Madagascar, and most species are known from only few localities. A previous record of this genus from the Tsingy de Bemaraha (western Madagascar) is interpreted as probably due to a mislabelling and should not be considered further unless confirmed by new data. By generating this phylogenetic hypothesis and providing an updated distribution of each lineage, our findings will facilitate future species descriptions, pave the way for evolutionary studies, and provide valuable information for the urgent conservation of diamond frogs. KW - amphibians KW - candidate species KW - diamond frogs KW - mitochondrial lineages KW - northern Madagascar KW - species-identification KW - systematics Y1 - 2022 U6 - https://doi.org/10.1080/14772000.2022.2039320 SN - 1477-2000 SN - 1478-0933 VL - 20 IS - 1 SP - 1 EP - 13 PB - Routledge, Taylor & Francis Group CY - Abingdon ER - TY - JOUR A1 - Garbulowski, Mateusz A1 - Smolinska, Karolina A1 - Çabuk, Uğur A1 - Yones, Sara A. A1 - Celli, Ludovica A1 - Yaz, Esma Nur A1 - Barrenas, Fredrik A1 - Diamanti, Klev A1 - Wadelius, Claes A1 - Komorowski, Jan T1 - Machine learning-based analysis of glioma grades reveals co-enrichment JF - Cancers N2 - 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. KW - glioma KW - machine learning KW - batch effect KW - TCGA KW - co-enrichment KW - rough sets Y1 - 2022 U6 - https://doi.org/10.3390/cancers14041014 SN - 2072-6694 VL - 14 IS - 4 PB - MDPI CY - Basel ER - TY - JOUR A1 - Agarwal, Saloni A1 - Hamidizadeh, Mojdeh A1 - Bier, Frank Fabian T1 - Detection of reverse transcriptase LAMP-amplified nucleic acid from oropharyngeal viral swab samples using biotinylated DNA probes through a lateral flow assay JF - Biosensors : open access journal N2 - This study focuses on three key aspects: (a) crude throat swab samples in a viral transport medium (VTM) as templates for RT-LAMP reactions; (b) a biotinylated DNA probe with enhanced specificity for LFA readouts; and (c) a digital semi-quantification of LFA readouts. Throat swab samples from SARS-CoV-2 positive and negative patients were used in their crude (no cleaning or pre-treatment) forms for the RT-LAMP reaction. The samples were heat-inactivated but not treated for any kind of nucleic acid extraction or purification. The RT-LAMP (20 min processing time) product was read out by an LFA approach using two labels: FITC and biotin. FITC was enzymatically incorporated into the RT-LAMP amplicon with the LF-LAMP primer, and biotin was introduced using biotinylated DNA probes, specifically for the amplicon region after RT-LAMP amplification. This assay setup with biotinylated DNA probe-based LFA readouts of the RT-LAMP amplicon was 98.11% sensitive and 96.15% specific. The LFA result was further analysed by a smartphone-based IVD device, wherein the T-line intensity was recorded. The LFA T-line intensity was then correlated with the qRT-PCR Ct value of the positive swab samples. A digital semi-quantification of RT-LAMP-LFA was reported with a correlation coefficient of R2 = 0.702. The overall RT-LAMP-LFA assay time was recorded to be 35 min with a LoD of three RNA copies/µL (Ct-33). With these three advancements, the nucleic acid testing-point of care technique (NAT-POCT) is exemplified as a versatile biosensor platform with great potential and applicability for the detection of pathogens without the need for sample storage, transportation, or pre-processing. KW - RT-LAMP KW - LFA KW - NAAT-LFA KW - semi-quantitative KW - surveillance-based diagnostics Y1 - 2023 U6 - https://doi.org/10.3390/bios13110988 SN - 2079-6374 VL - 13 IS - 11 PB - MDPI CY - Basel ER - TY - JOUR A1 - Numberger, Daniela A1 - Zoccarato, Luca A1 - Woodhouse, Jason Nicholas A1 - Ganzert, Lars A1 - Sauer, Sascha A1 - García Márquez, Jaime Ricardo A1 - Domisch, Sami A1 - Grossart, Hans-Peter A1 - Greenwood, Alex T1 - Urbanization promotes specific bacteria in freshwater microbiomes including potential pathogens JF - The science of the total environment : an international journal for scientific research into the environment and its relationship with man N2 - Freshwater ecosystems are characterized by complex and highly dynamic microbial communities that are strongly structured by their local environment and biota. Accelerating urbanization and growing city populations detrimentally alter freshwater environments. To determine differences in freshwater microbial communities associated with urban-ization, full-length 16S rRNA gene PacBio sequencing was performed in a case study from surface waters and sedi-ments from a wastewater treatment plant, urban and rural lakes in the Berlin-Brandenburg region, Northeast Germany. Water samples exhibited highly habitat specific bacterial communities with multiple genera showing clear urban signatures. We identified potentially harmful bacterial groups associated with environmental parameters specific to urban habitats such as Alistipes, Escherichia/Shigella, Rickettsia and Streptococcus. We demonstrate that urban-ization alters natural microbial communities in lakes and, via simultaneous warming and eutrophication and creates favourable conditions that promote specific bacterial genera including potential pathogens. Our findings are evidence to suggest an increased potential for long-term health risk in urbanized waterbodies, at a time of rapidly expanding global urbanization. The results highlight the urgency for undertaking mitigation measures such as targeted lake restoration projects and sustainable water management efforts. KW - Urbanization KW - Urban waters KW - Wastewater KW - Lakes KW - Microbial community KW - composition KW - Humanization KW - Full-length 16S rRNA PacBio sequencing Y1 - 2022 U6 - https://doi.org/10.1016/j.scitotenv.2022.157321 SN - 0048-9697 SN - 1879-1026 VL - 845 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Zavorka, Libor A1 - Blanco, Andreu A1 - Chaguaceda, Fernando A1 - Cucherousset, Julien A1 - Killen, Shaun S. A1 - Lienart, Camilla A1 - Mathieu-Resuge, Margaux A1 - Nemec, Pavel A1 - Pilecky, Matthias A1 - Scharnweber, Inga Kristin A1 - Twining, Cornelia W. A1 - Kainz, Martin J. T1 - The role of vital dietary biomolecules in eco-evo-devo dynamics JF - Trends in ecology and evolution N2 - The physiological dependence of animals on dietary intake of vitamins, amino acids, and fatty acids is ubiquitous. Sharp differences in the availability of these vital dietary biomolecules among different resources mean that consumers must adopt a range of strategies to meet their physiological needs. We review the emerging work on omega-3 long-chain polyunsaturated fatty acids, focusing predominantly on predator-prey interactions, to illustrate that trade-off between capacities to consume resources rich in vital biomolecules and internal synthesis capacity drives differences in phenotype and fitness of consumers. This can then feedback to impact ecosystem functioning. We outline how focus on vital dietary biomolecules in eco-eco-devo dynamics can improve our understanding of anthropogenic changes across multiple levels of biological organization. Y1 - 2023 U6 - https://doi.org/10.1016/j.tree.2022.08.010 SN - 0169-5347 SN - 1872-8383 VL - 38 IS - 1 SP - 72 EP - 84 PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Grdseloff, Nastasja A1 - Boulday, Gwenola A1 - Roedel, Claudia J. A1 - Otten, Cecile A1 - Vannier, Daphne Raphaelle A1 - Cardoso, Cecile A1 - Faurobert, Eva A1 - Dogra, Deepika A1 - Tournier-Lasserve, Elisabeth A1 - Abdelilah-Seyfried, Salim T1 - Impaired retinoic acid signaling in cerebral cavernous malformations JF - Scientific reports N2 - The capillary-venous pathology cerebral cavernous malformation (CCM) is caused by loss of CCM1/Krev interaction trapped protein 1 (KRIT1), CCM2/MGC4607, or CCM3/PDCD10 in some endothelial cells. Mutations of CCM genes within the brain vasculature can lead to recurrent cerebral hemorrhages. Pharmacological treatment options are urgently needed when lesions are located in deeply-seated and in-operable regions of the central nervous system. Previous pharmacological suppression screens in disease models of CCM led to the discovery that treatment with retinoic acid improved CCM phenotypes. This finding raised a need to investigate the involvement of retinoic acid in CCM and test whether it has a curative effect in preclinical mouse models. Here, we show that components of the retinoic acid synthesis and degradation pathway are transcriptionally misregulated across disease models of CCM. We complemented this analysis by pharmacologically modifying retinoic acid levels in zebrafish and human endothelial cell models of CCM, and in acute and chronic mouse models of CCM. Our pharmacological intervention studies in CCM2-depleted human umbilical vein endothelial cells (HUVECs) and krit1 mutant zebrafish showed positive effects when retinoic acid levels were increased. However, therapeutic approaches to prevent the development of vascular lesions in adult chronic murine models of CCM were drug regiment-sensitive, possibly due to adverse developmental effects of this hormone. A treatment with high doses of retinoic acid even worsened CCM lesions in an adult chronic murine model of CCM. This study provides evidence that retinoic acid signaling is impaired in the CCM pathophysiology and suggests that modification of retinoic acid levels can alleviate CCM phenotypes. KW - Developmental biology KW - Molecular medicine Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-31905-0 SN - 2045-2322 VL - 13 IS - 1 PB - Nature Portfolio CY - Berlin ER - TY - JOUR A1 - Stübler, Sabine A1 - Kloft, Charlotte A1 - Huisinga, Wilhelm T1 - Cell-level systems biology model to study inflammatory bowel diseases and their treatment options JF - CPT: pharmacometrics & systems pharmacology N2 - 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. Y1 - 2023 U6 - https://doi.org/10.1002/psp4.12932 SN - 2163-8306 VL - 12 IS - 5 SP - 690 EP - 705 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Derežanin, Lorena A1 - Blažytė, Asta A1 - Dobrynin, Pavel A1 - Duchêne, David A. A1 - Grau, José Horacio A1 - Jeon, Sungwon A1 - Kliver, Sergei A1 - Koepfli, Klaus-Peter A1 - Meneghini, Dorina A1 - Preick, Michaela A1 - Tomarovsky, Andrey A1 - Totikov, Azamat A1 - Fickel, Jörns A1 - Förster, Daniel W. T1 - Multiple types of genomic variation contribute to adaptive traits in the mustelid subfamily Guloninae JF - Molecular ecology N2 - Species of the mustelid subfamily Guloninae inhabit diverse habitats on multiple continents, and occupy a variety of ecological niches. They differ in feeding ecologies, reproductive strategies and morphological adaptations. To identify candidate loci associated with adaptations to their respective environments, we generated a de novo assembly of the tayra (Eira barbara), the earliest diverging species in the subfamily, and compared this with the genomes available for the wolverine (Gulo gulo) and the sable (Martes zibellina). Our comparative genomic analyses included searching for signs of positive selection, examining changes in gene family sizes and searching for species-specific structural variants. Among candidate loci associated with phenotypic traits, we observed many related to diet, body condition and reproduction. For example, for the tayra, which has an atypical gulonine reproductive strategy of aseasonal breeding, we observed species-specific changes in many pregnancy-related genes. For the wolverine, a circumpolar hypercarnivore that must cope with seasonal food scarcity, we observed many changes in genes associated with diet and body condition. All types of genomic variation examined (single nucleotide polymorphisms, gene family expansions, structural variants) contributed substantially to the identification of candidate loci. This argues strongly for consideration of variation other than single nucleotide polymorphisms in comparative genomics studies aiming to identify loci of adaptive significance. KW - adaptation KW - gene family evolution KW - genomics KW - mustelids KW - positive KW - selection KW - structural variation Y1 - 2022 U6 - https://doi.org/10.1111/mec.16443 SN - 0962-1083 SN - 1365-294X N1 - Corrigendum: Molecular ecology, Volume 32, Issue 3, Pages 752, February 2023 VL - 31 IS - 10 SP - 2898 EP - 2919 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Abdelilah-Seyfried, Salim A1 - Iruela-Arispe, M. Luisa A1 - Penninger, Josef M. A1 - Tournier-Lasserve, Elisabeth A1 - Vikkula, Miikka A1 - Cleaver, Ondine T1 - Recalibrating vascular malformations and mechanotransduction by pharmacological intervention JF - Journal of clinical investigation Y1 - 2022 U6 - https://doi.org/10.1172/JCI160227 SN - 0021-9738 SN - 1558-8238 VL - 132 IS - 8 PB - American Society for Clinical Investigation CY - Ann Arbor ER -