TY - JOUR A1 - Korte, Arthur T1 - Der Zusammenhang zwischen Genom und Phänotyp JF - BIOspektrum N2 - Understanding the causal relationship between genotype and phenotype is a major objective in biology. Genome-wide association studies (GWAS) correlate genetic polymorphisms with trait variation and have already identified causative variants for various traits in many different organisms, from humans to plants. Importantly, many adaptive traits, like the regulation of flowering time in plants, are not regulated by distinct genetic effects, but by more sophisticated gene regulatory networks. KW - Genom KW - Phänotyp KW - Genomweite Assoziationstudie (GWAS) Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324231 SN - 0947-0867 VL - 28 IS - 3 ER - TY - JOUR A1 - Peters, Birte A1 - Keller, Alexander A1 - Leonhardt, Sara Diana T1 - Diets maintained in a changing world: Does land-use intensification alter wild bee communities by selecting for flexible generalists? JF - Ecology and evolution N2 - Biodiversity loss, as often found in intensively managed agricultural landscapes, correlates with reduced ecosystem functioning, for example, pollination by insects, and with altered plant composition, diversity, and abundance. But how does this change in floral resource diversity and composition relate to occurrence and resource use patterns of trap-nesting solitary bees? To better understand the impact of land-use intensification on communities of trap-nesting solitary bees in managed grasslands, we investigated their pollen foraging, reproductive fitness, and the nutritional quality of larval food along a land-use intensity gradient in Germany. We found bee species diversity to decrease with increasing land-use intensity irrespective of region-specific community compositions and interaction networks. Land use also strongly affected the diversity and composition of pollen collected by bees. Lack of suitable pollen sources likely explains the absence of several bee species at sites of high land-use intensity. The only species present throughout, Osmia bicornis (red mason bee), foraged on largely different pollen sources across sites. In doing so, it maintained a relatively stable, albeit variable nutritional quality of larval diets (i.e., protein to lipid (P:L) ratio). The observed changes in bee–plant pollen interaction patterns indicate that only the flexible generalists, such as O. bicornis, may be able to compensate the strong alterations in floral resource landscapes and to obtain food of sufficient quality through readily shifting to alternative plant sources. In contrast, other, less flexible, bee species disappear. KW - bee decline KW - biodiversity exploratories KW - foraging KW - metabarcoding KW - pollen nutrients KW - solitary bees Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312786 SN - 2045-7758 VL - 12 IS - 5 ER - TY - JOUR A1 - Dannhäuser, Sven A1 - Mrestani, Achmed A1 - Gundelach, Florian A1 - Pauli, Martin A1 - Komma, Fabian A1 - Kollmannsberger, Philip A1 - Sauer, Markus A1 - Heckmann, Manfred A1 - Paul, Mila M. T1 - Endogenous tagging of Unc-13 reveals nanoscale reorganization at active zones during presynaptic homeostatic potentiation JF - Frontiers in Cellular Neuroscience N2 - Introduction Neurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein meshwork the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release. Methods We employ minos-mediated integration cassette (MiMIC)-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV-3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system. Results and discussion Electrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13\(^{GFSTF}\) 3rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13\(^{GFSTF}\), Bruchpilot, and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13\(^{GFSTF}\) subclusters that move toward the AZ center during PHP with unaltered Unc-13\(^{GFSTF}\) protein levels. KW - active zone KW - Unc-13 KW - MiMIC KW - presynaptic homeostasis KW - nanoarchitecture KW - localization microscopy KW - STORM KW - HDBSCAN Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299440 SN - 1662-5102 VL - 16 ER - TY - JOUR A1 - Gupta, Shishir K. A1 - Osmanoglu, Özge A1 - Minocha, Rashmi A1 - Bandi, Sourish Reddy A1 - Bencurova, Elena A1 - Srivastava, Mugdha A1 - Dandekar, Thomas T1 - Genome-wide scan for potential CD4+ T-cell vaccine candidates in Candida auris by exploiting reverse vaccinology and evolutionary information JF - Frontiers in Medicine N2 - Candida auris is a globally emerging fungal pathogen responsible for causing nosocomial outbreaks in healthcare associated settings. It is known to cause infection in all age groups and exhibits multi-drug resistance with high potential for horizontal transmission. Because of this reason combined with limited therapeutic choices available, C. auris infection has been acknowledged as a potential risk for causing a future pandemic, and thus seeking a promising strategy for its treatment is imperative. Here, we combined evolutionary information with reverse vaccinology approach to identify novel epitopes for vaccine design that could elicit CD4+ T-cell responses against C. auris. To this end, we extensively scanned the family of proteins encoded by C. auris genome. In addition, a pathogen may acquire substitutions in epitopes over a period of time which could cause its escape from the immune response thus rendering the vaccine ineffective. To lower this possibility in our design, we eliminated all rapidly evolving genes of C. auris with positive selection. We further employed highly conserved regions of multiple C. auris strains and identified two immunogenic and antigenic T-cell epitopes that could generate the most effective immune response against C. auris. The antigenicity scores of our predicted vaccine candidates were calculated as 0.85 and 1.88 where 0.5 is the threshold for prediction of fungal antigenic sequences. Based on our results, we conclude that our vaccine candidates have the potential to be successfully employed for the treatment of C. auris infection. However, in vivo experiments are imperative to further demonstrate the efficacy of our design. KW - T-cell epitope KW - epitope prediction KW - positive selection KW - evolution KW - immune-informatics Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-293953 SN - 2296-858X VL - 9 ER - TY - JOUR A1 - Schilcher, Felix A1 - Hilsmann, Lioba A1 - Ankenbrand, Markus J. A1 - Krischke, Markus A1 - Mueller, Martin J. A1 - Steffan-Dewenter, Ingolf A1 - Scheiner, Ricarda T1 - Honeybees are buffered against undernourishment during larval stages JF - Frontiers in Insect Science N2 - The negative impact of juvenile undernourishment on adult behavior has been well reported for vertebrates, but relatively little is known about invertebrates. In honeybees, nutrition has long been known to affect task performance and timing of behavioral transitions. Whether and how a dietary restriction during larval development affects the task performance of adult honeybees is largely unknown. We raised honeybees in-vitro, varying the amount of a standardized diet (150 µl, 160 µl, 180 µl in total). Emerging adults were marked and inserted into established colonies. Behavioral performance of nurse bees and foragers was investigated and physiological factors known to be involved in the regulation of social organization were quantified. Surprisingly, adult honeybees raised under different feeding regimes did not differ in any of the behaviors observed. No differences were observed in physiological parameters apart from weight. Honeybees were lighter when undernourished (150 µl), while they were heavier under the overfed treatment (180 µl) compared to the control group raised under a normal diet (160 µl). These data suggest that dietary restrictions during larval development do not affect task performance or physiology in this social insect despite producing clear effects on adult weight. We speculate that possible effects of larval undernourishment might be compensated during the early period of adult life. KW - nutrition KW - juvenile hormone KW - nurse bees KW - foragers KW - triglycerides KW - undernourishment KW - task allocation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304646 SN - 2673-8600 VL - 2 ER - TY - JOUR A1 - Vedder, Daniel A1 - Lens, Luc A1 - Martin, Claudia A. A1 - Pellikka, Petri A1 - Adhikari, Hari A1 - Heiskanen, Janne A1 - Engler, Jan O. A1 - Sarmento Cabral, Juliano T1 - Hybridization may aid evolutionary rescue of an endangered East African passerine JF - Evolutionary Applications N2 - Abstract Introgressive hybridization is a process that enables gene flow across species barriers through the backcrossing of hybrids into a parent population. This may make genetic material, potentially including relevant environmental adaptations, rapidly available in a gene pool. Consequently, it has been postulated to be an important mechanism for enabling evolutionary rescue, that is the recovery of threatened populations through rapid evolutionary adaptation to novel environments. However, predicting the likelihood of such evolutionary rescue for individual species remains challenging. Here, we use the example of Zosterops silvanus, an endangered East African highland bird species suffering from severe habitat loss and fragmentation, to investigate whether hybridization with its congener Zosterops flavilateralis might enable evolutionary rescue of its Taita Hills population. To do so, we employ an empirically parameterized individual‐based model to simulate the species' behaviour, physiology and genetics. We test the population's response to different assumptions of mating behaviour and multiple scenarios of habitat change. We show that as long as hybridization does take place, evolutionary rescue of Z. silvanus is likely. Intermediate hybridization rates enable the greatest long‐term population growth, due to trade‐offs between adaptive and maladaptive introgressed alleles. Habitat change did not have a strong effect on population growth rates, as Z. silvanus is a strong disperser and landscape configuration is therefore not the limiting factor for hybridization. Our results show that targeted gene flow may be a promising avenue to help accelerate the adaptation of endangered species to novel environments, and demonstrate how to combine empirical research and mechanistic modelling to deliver species‐specific predictions for conservation planning. KW - evolutionary rescue KW - habitat change KW - individual‐based model KW - introgressive hybridization KW - Taita Hills KW - Zosterops silvanus Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287264 VL - 15 IS - 7 ER - TY - THES A1 - Anwar, Ammarah T1 - Natural variation of gene regulatory networks in \(Arabidopsis\) \(thaliana\) T1 - Natürliche Variation genregulatorischer Netzwerke in \(Arabidopsis\) \(thaliana\) N2 - Understanding the causal relationship between genotype and phenotype is a major objective in biology. The main interest is in understanding trait architecture and identifying loci contributing to the respective traits. Genome-wide association mapping (GWAS) is one tool to elucidate these relationships and has been successfully used in many different species. However, most studies concentrate on marginal marker effects and ignore epistatic and gene-environment interactions. These interactions are problematic to account for, but are likely to make major contributions to many phenotypes that are not regulated by independent genetic effects, but by more sophisticated gene-regulatory networks. Further complication arises from the fact that these networks vary in different natural accessions. However, understanding the differences of gene regulatory networks and gene-gene interactions is crucial to conceive trait architecture and predict phenotypes. The basic subject of this study – using data from the Arabidopsis 1001 Genomes Project – is the analysis of pre-mature stop codons. These have been incurred in nearly one-third of the ~ 30k genes. A gene-gene interaction network of the co-occurrence of stop codons has been built and the over and under representation of different pairs has been statistically analyzed. To further classify the significant over and under- represented gene-gene interactions in terms of molecular function of the encoded proteins, gene ontology terms (GO-SLIM) have been applied. Furthermore, co- expression analysis specifies gene clusters that co-occur over different genetic and phenotypic backgrounds. To link these patterns to evolutionary constrains, spatial location of the respective alleles have been analyzed as well. The latter shows clear patterns for certain gene pairs that indicate differential selection. N2 - Das Verständnis des kausalen Zusammenhangs zwischen Genotyp und Phänotyp ist ein wichtiges Ziel in der Biologie. Das Hauptinteresse liegt darin, die Merkmalsarchitektur zu verstehen und Loci zu identifizieren, die zu den jeweiligen Merkmalen beitragen. Genome-wide association mapping (GWAS) ist ein Werkzeug, um diese Zusammenhänge aufzuklären und wurde erfolgreich in vielen verschiedenen Arten eingesetzt. Die meisten Studien konzentrieren sich jedoch auf marginale Markereffekte und ignorieren epistatische und Gen-Umwelt-Interaktionen. Diese Wechselwirkungen sind problematisch zu erklären, werden aber wahrscheinlich einen wichtigen Beitrag zu vielen Phänotypen leisten, die nicht durch unabhängige genetische Effekte, sondern durch ausgefeiltere genregulatorische Netzwerke reguliert werden. Eine weitere Komplikation ergibt sich aus der Tatsache, dass sich diese Netzwerke in verschiedenen natürlichen Akzessionen unterscheiden. Das Verständnis der Unterschiede zwischen genregulatorischen Netzwerken und Gen-Gen- Interaktionen ist jedoch entscheidend, um die Merkmalsarchitektur zu konzipieren und Phänotypen vorherzusagen. Das grundlegende Thema dieser Studie – unter Verwendung von Daten aus dem Arabidopsis 1001 Genomes Project – ist die Analyse von vorzeitigen Stop-Codons. Diese sind in fast einem Drittel der ~ 30k-Gene aufgetreten. Ein Gen-Gen- Interaktionsnetzwerk des gleichzeitigen Auftretens von Stop-Codons wurde aufgebaut und die Über- und Unterrepräsentation verschiedener Paare wurde statistisch analysiert. Um die signifikante über- und unterrepräsentierte Gen-Gen-Interaktion in Bezug auf den biologischen Prozess der kodierten Proteine weiter zu klassifizieren, wurden genonkologische Begriffe (GO-SLIM) verwendet. Darüber hinaus spezifiziert die Koexpressionsanalyse Gencluster, die über verschiedene genetische und phänotypische Hintergründe hinweg gleichzeitig auftreten. Um diese Muster mit evolutionären Einschränkungen in Verbindung zu bringen, wurde auch die räumliche Lage der jeweiligen Allele analysiert. Letzteres zeigt klare Muster für bestimmte Genepaare, die auf eine differentielle Selektion hinweisen. KW - Arabidopsis thaliana KW - Co-occurrence matrix KW - co-expression coefficient KW - gene expression networks KW - non-sense mutations KW - phenotype KW - local adaptation KW - variations in genome KW - Ackerschmalwand Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-291549 ER - TY - JOUR A1 - Reinhard, Sebastian A1 - Helmerich, Dominic A. A1 - Boras, Dominik A1 - Sauer, Markus A1 - Kollmannsberger, Philip T1 - ReCSAI: recursive compressed sensing artificial intelligence for confocal lifetime localization microscopy JF - BMC Bioinformatics N2 - Background Localization-based super-resolution microscopy resolves macromolecular structures down to a few nanometers by computationally reconstructing fluorescent emitter coordinates from diffraction-limited spots. The most commonly used algorithms are based on fitting parametric models of the point spread function (PSF) to a measured photon distribution. These algorithms make assumptions about the symmetry of the PSF and thus, do not work well with irregular, non-linear PSFs that occur for example in confocal lifetime imaging, where a laser is scanned across the sample. An alternative method for reconstructing sparse emitter sets from noisy, diffraction-limited images is compressed sensing, but due to its high computational cost it has not yet been widely adopted. Deep neural network fitters have recently emerged as a new competitive method for localization microscopy. They can learn to fit arbitrary PSFs, but require extensive simulated training data and do not generalize well. A method to efficiently fit the irregular PSFs from confocal lifetime localization microscopy combining the advantages of deep learning and compressed sensing would greatly improve the acquisition speed and throughput of this method. Results Here we introduce ReCSAI, a compressed sensing neural network to reconstruct localizations for confocal dSTORM, together with a simulation tool to generate training data. We implemented and compared different artificial network architectures, aiming to combine the advantages of compressed sensing and deep learning. We found that a U-Net with a recursive structure inspired by iterative compressed sensing showed the best results on realistic simulated datasets with noise, as well as on real experimentally measured confocal lifetime scanning data. Adding a trainable wavelet denoising layer as prior step further improved the reconstruction quality. Conclusions Our deep learning approach can reach a similar reconstruction accuracy for confocal dSTORM as frame binning with traditional fitting without requiring the acquisition of multiple frames. In addition, our work offers generic insights on the reconstruction of sparse measurements from noisy experimental data by combining compressed sensing and deep learning. We provide the trained networks, the code for network training and inference as well as the simulation tool as python code and Jupyter notebooks for easy reproducibility. KW - compressed sensing KW - AI KW - SMLM KW - FLIMbee KW - dSTORM Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299768 VL - 23 IS - 1 ER - TY - JOUR A1 - Gupta, Shishir K. A1 - Minocha, Rashmi A1 - Thapa, Prithivi Jung A1 - Srivastava, Mugdha A1 - Dandekar, Thomas T1 - Role of the pangolin in origin of SARS-CoV-2: an evolutionary perspective JF - International Journal of Molecular Sciences N2 - After the recent emergence of SARS-CoV-2 infection, unanswered questions remain related to its evolutionary history, path of transmission or divergence and role of recombination. There is emerging evidence on amino acid substitutions occurring in key residues of the receptor-binding domain of the spike glycoprotein in coronavirus isolates from bat and pangolins. In this article, we summarize our current knowledge on the origin of SARS-CoV-2. We also analyze the host ACE2-interacting residues of the receptor-binding domain of spike glycoprotein in SARS-CoV-2 isolates from bats, and compare it to pangolin SARS-CoV-2 isolates collected from Guangdong province (GD Pangolin-CoV) and Guangxi autonomous regions (GX Pangolin-CoV) of South China. Based on our comparative analysis, we support the view that the Guangdong Pangolins are the intermediate hosts that adapted the SARS-CoV-2 and represented a significant evolutionary link in the path of transmission of SARS-CoV-2 virus. We also discuss the role of intermediate hosts in the origin of Omicron. KW - COVID-19 KW - SARS-CoV-2 KW - origin KW - evolution KW - intermediate host KW - pangolin KW - mutation KW - recombination KW - adaptation KW - transmission KW - comparative sequence analysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285995 SN - 1422-0067 VL - 23 IS - 16 ER - TY - JOUR A1 - Berger, Nathalie A1 - Demolombe, Vincent A1 - Hem, Sonia A1 - Rofidal, Valérie A1 - Steinmann, Laura A1 - Krouk, Gabriel A1 - Crabos, Amandine A1 - Nacry, Philippe A1 - Verdoucq, Lionel A1 - Santoni, Véronique T1 - Root membrane ubiquitinome under short-term osmotic stress JF - International Journal of Molecular Sciences N2 - Osmotic stress can be detrimental to plants, whose survival relies heavily on proteomic plasticity. Protein ubiquitination is a central post-translational modification in osmotic-mediated stress. In this study, we used the K-Ɛ-GG antibody enrichment method integrated with high-resolution mass spectrometry to compile a list of 719 ubiquitinated lysine (K-Ub) residues from 450 Arabidopsis root membrane proteins (58% of which are transmembrane proteins), thereby adding to the database of ubiquitinated substrates in plants. Although no ubiquitin (Ub) motifs could be identified, the presence of acidic residues close to K-Ub was revealed. Our ubiquitinome analysis pointed to a broad role of ubiquitination in the internalization and sorting of cargo proteins. Moreover, the simultaneous proteome and ubiquitinome quantification showed that ubiquitination is mostly not involved in membrane protein degradation in response to short osmotic treatment but that it is putatively involved in protein internalization, as described for the aquaporin PIP2;1. Our in silico analysis of ubiquitinated proteins shows that two E2 Ub-conjugating enzymes, UBC32 and UBC34, putatively target membrane proteins under osmotic stress. Finally, we revealed a positive role for UBC32 and UBC34 in primary root growth under osmotic stress. KW - aquaporin KW - mass spectrometry KW - osmotic stress KW - ubiquitination Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284003 SN - 1422-0067 VL - 23 IS - 4 ER -