@article{RackeveiBorgesEngstleretal.2022, author = {Rackevei, Antonia S. and Borges, Alyssa and Engstler, Markus and Dandekar, Thomas and Wolf, Matthias}, title = {About the analysis of 18S rDNA sequence data from trypanosomes in barcoding and phylogenetics: tracing a continuation error occurring in the literature}, series = {Biology}, volume = {11}, journal = {Biology}, number = {11}, issn = {2079-7737}, doi = {10.3390/biology11111612}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297562}, year = {2022}, abstract = {The variable regions (V1-V9) of the 18S rDNA are routinely used in barcoding and phylogenetics. In handling these data for trypanosomes, we have noticed a misunderstanding that has apparently taken a life of its own in the literature over the years. In particular, in recent years, when studying the phylogenetic relationship of trypanosomes, the use of V7/V8 was systematically established. However, considering the current numbering system for all other organisms (including other Euglenozoa), V7/V8 was never used. In Maia da Silva et al. [Parasitology 2004, 129, 549-561], V7/V8 was promoted for the first time for trypanosome phylogenetics, and since then, more than 70 publications have replicated this nomenclature and even discussed the benefits of the use of this region in comparison to V4. However, the primers used to amplify the variable region of trypanosomes have actually amplified V4 (concerning the current 18S rDNA numbering system).}, language = {en} } @article{DandekarGramschHoughtonetal.1985, author = {Dandekar, Thomas and Gramsch, Christian and Houghton, Richard A. and Schultz, R{\"u}diger}, title = {Affinity purification of \(\beta\)-endorphin-like material from NG108CC15 cells by means of the monoclonal \(\beta\)-endorphin antibody 3-E7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29896}, year = {1985}, abstract = {No abstract available}, language = {en} } @article{GuptaSrivastavaMinochaetal.2021, author = {Gupta, Shishir K. and Srivastava, Mugdha and Minocha, Rashmi and Akash, Aman and Dangwal, Seema and Dandekar, Thomas}, title = {Alveolar regeneration in COVID-19 patients: a network perspective}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {20}, issn = {1422-0067}, doi = {10.3390/ijms222011279}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284307}, year = {2021}, abstract = {A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.}, language = {en} } @article{DandekarArgos1994, author = {Dandekar, Thomas and Argos, Patrick}, title = {Amiloride-sensitive epithelial Na\(^+\) channel is made of three homologous subunits}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29734}, year = {1994}, abstract = {No abstract available}, language = {en} } @article{BreitenbachHelfrichFoersterDandekar2021, author = {Breitenbach, Tim and Helfrich-F{\"o}rster, Charlotte and Dandekar, Thomas}, title = {An effective model of endogenous clocks and external stimuli determining circadian rhythms}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-95391-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261655}, pages = {16165}, year = {2021}, abstract = {Circadian endogenous clocks of eukaryotic organisms are an established and rapidly developing research field. To investigate and simulate in an effective model the effect of external stimuli on such clocks and their components we developed a software framework for download and simulation. The application is useful to understand the different involved effects in a mathematical simple and effective model. This concerns the effects of Zeitgebers, feedback loops and further modifying components. We start from a known mathematical oscillator model, which is based on experimental molecular findings. This is extended with an effective framework that includes the impact of external stimuli on the circadian oscillations including high dose pharmacological treatment. In particular, the external stimuli framework defines a systematic procedure by input-output-interfaces to couple different oscillators. The framework is validated by providing phase response curves and ranges of entrainment. Furthermore, Aschoffs rule is computationally investigated. It is shown how the external stimuli framework can be used to study biological effects like points of singularity or oscillators integrating different signals at once. The mathematical framework and formalism is generic and allows to study in general the effect of external stimuli on oscillators and other biological processes. For an easy replication of each numerical experiment presented in this work and an easy implementation of the framework the corresponding Mathematica files are fully made available. They can be downloaded at the following link: https://www.biozentrum.uni-wuerzburg.de/bioinfo/computing/circadian/.}, language = {en} } @article{AlnusaireSayedElmaidomyetal.2021, author = {Alnusaire, Taghreed S. and Sayed, Ahmed M. and Elmaidomy, Abeer H. and Al-Sanea, Mohammad M. and Albogami, Sarah and Albqmi, Mha and Alowaiesh, Bassam F. and Mostafa, Ehab M. and Musa, Arafa and Youssif, Khayrya A. and Refaat, Hesham and Othman, Eman M. and Dandekar, Thomas and Alaaeldin, Eman and Ghoneim, Mohammed M. and Abdelmohsen, Usama Ramadan}, title = {An in vitro and in silico study of the enhanced antiproliferative and pro-oxidant potential of Olea europaea L. cv. Arbosana leaf extract via elastic nanovesicles (spanlastics)}, series = {Antioxidants}, volume = {10}, journal = {Antioxidants}, number = {12}, issn = {2076-3921}, doi = {10.3390/antiox10121860}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250064}, year = {2021}, abstract = {The olive tree is a venerable Mediterranean plant and often used in traditional medicine. The main aim of the present study was to evaluate the effect of Olea europaea L. cv. Arbosana leaf extract (OLE) and its encapsulation within a spanlastic dosage form on the improvement of its pro-oxidant and antiproliferative activity against HepG-2, MCF-7, and Caco-2 human cancer cell lines. The LC-HRESIMS-assisted metabolomic profile of OLE putatively annotated 20 major metabolites and showed considerable in vitro antiproliferative activity against HepG-2, MCF-7, and Caco-2 cell lines with IC\(_{50}\) values of 9.2 ± 0.8, 7.1 ± 0.9, and 6.5 ± 0.7 µg/mL, respectively. The encapsulation of OLE within a (spanlastic) nanocarrier system, using a spraying method and Span 40 and Tween 80 (4:1 molar ratio), was successfully carried out (size 41 ± 2.4 nm, zeta potential 13.6 ± 2.5, and EE 61.43 ± 2.03\%). OLE showed enhanced thermal stability, and an improved in vitro antiproliferative effect against HepG-2, MCF-7, and Caco-2 (IC\(_{50}\) 3.6 ± 0.2, 2.3 ± 0.1, and 1.8 ± 0.1 µg/mL, respectively) in comparison to the unprocessed extract. Both preparations were found to exhibit pro-oxidant potential inside the cancer cells, through the potential inhibitory activity of OLE against glutathione reductase and superoxide dismutase (IC\(_{50}\) 1.18 ± 0.12 and 2.33 ± 0.19 µg/mL, respectively). These inhibitory activities were proposed via a comprehensive in silico study to be linked to the presence of certain compounds in OLE. Consequently, we assume that formulating such a herbal extract within a suitable nanocarrier would be a promising improvement of its therapeutic potential.}, language = {en} } @article{LiPradaDaminelietal.2021, author = {Li, Kunkun and Prada, Juan and Damineli, Daniel S. C. and Liese, Anja and Romeis, Tina and Dandekar, Thomas and Feij{\´o}, Jos{\´e} A. and Hedrich, Rainer and Konrad, Kai Robert}, title = {An optimized genetically encoded dual reporter for simultaneous ratio imaging of Ca\(^{2+}\) and H\(^{+}\) reveals new insights into ion signaling in plants}, series = {New Phytologist}, volume = {230}, journal = {New Phytologist}, number = {6}, doi = {10.1111/nph.17202}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239847}, pages = {2292 -- 2310}, year = {2021}, abstract = {Whereas the role of calcium ions (Ca\(^{2+}\)) in plant signaling is well studied, the physiological significance of pH-changes remains largely undefined. Here we developed CapHensor, an optimized dual-reporter for simultaneous Ca\(^{2+}\) and pH ratio-imaging and studied signaling events in pollen tubes (PTs), guard cells (GCs), and mesophyll cells (MCs). Monitoring spatio-temporal relationships between membrane voltage, Ca\(^{2+}\)- and pH-dynamics revealed interconnections previously not described. In tobacco PTs, we demonstrated Ca\(^{2+}\)-dynamics lag behind pH-dynamics during oscillatory growth, and pH correlates more with growth than Ca\(^{2+}\). In GCs, we demonstrated abscisic acid (ABA) to initiate stomatal closure via rapid cytosolic alkalization followed by Ca2+ elevation. Preventing the alkalization blocked GC ABA-responses and even opened stomata in the presence of ABA, disclosing an important pH-dependent GC signaling node. In MCs, a flg22-induced membrane depolarization preceded Ca2+-increases and cytosolic acidification by c. 2 min, suggesting a Ca\(^{2+}\)/pH-independent early pathogen signaling step. Imaging Ca2+ and pH resolved similar cytosol and nuclear signals and demonstrated flg22, but not ABA and hydrogen peroxide to initiate rapid membrane voltage-, Ca\(^{2+}\)- and pH-responses. We propose close interrelation in Ca\(^{2+}\)- and pH-signaling that is cell type- and stimulus-specific and the pH having crucial roles in regulating PT growth and stomata movement.}, language = {en} } @article{SrivastavaBencurovaGuptaetal.2019, author = {Srivastava, Mugdha and Bencurova, Elena and Gupta, Shishir K. and Weiss, Esther and L{\"o}ffler, J{\"u}rgen and Dandekar, Thomas}, title = {Aspergillus fumigatus challenged by human dendritic cells: metabolic and regulatory pathway responses testify a tight battle}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {9}, journal = {Frontiers in Cellular and Infection Microbiology}, doi = {10.3389/fcimb.2019.00168}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201368}, pages = {168}, year = {2019}, abstract = {Dendritic cells (DCs) are antigen presenting cells which serve as a passage between the innate and the acquired immunity. Aspergillosis is a major lethal condition in immunocompromised patients caused by the adaptable saprophytic fungus Aspergillus fumigatus. The healthy human immune system is capable to ward off A. fumigatus infections however immune-deficient patients are highly vulnerable to invasive aspergillosis. A. fumigatus can persist during infection due to its ability to survive the immune response of human DCs. Therefore, the study of the metabolism specific to the context of infection may allow us to gain insight into the adaptation strategies of both the pathogen and the immune cells. We established a metabolic model of A. fumigatus central metabolism during infection of DCs and calculated the metabolic pathway (elementary modes; EMs). Transcriptome data were used to identify pathways activated when A. fumigatus is challenged with DCs. In particular, amino acid metabolic pathways, alternative carbon metabolic pathways and stress regulating enzymes were found to be active. Metabolic flux modeling identified further active enzymes such as alcohol dehydrogenase, inositol oxygenase and GTP cyclohydrolase participating in different stress responses in A. fumigatus. These were further validated by qRT-PCR from RNA extracted under these different conditions. For DCs, we outlined the activation of metabolic pathways in response to the confrontation with A. fumigatus. We found the fatty acid metabolism plays a crucial role, along with other metabolic changes. The gene expression data and their analysis illuminate additional regulatory pathways activated in the DCs apart from interleukin regulation. In particular, Toll-like receptor signaling, NOD-like receptor signaling and RIG-I-like receptor signaling were active pathways. Moreover, we identified subnetworks and several novel key regulators such as UBC, EGFR, and CUL3 of DCs to be activated in response to A. fumigatus. In conclusion, we analyze the metabolic and regulatory responses of A. fumigatus and DCs when confronted with each other.}, language = {en} } @article{GuptaSrivastavaOsmanogluetal.2021, author = {Gupta, Shishir K. and Srivastava, Mugdha and Osmanoglu, {\"O}zge and Xu, Zhuofei and Brakhage, Axel A. and Dandekar, Thomas}, title = {Aspergillus fumigatus versus genus Aspergillus: conservation, adaptive evolution and specific virulence genes}, series = {Microorganisms}, volume = {9}, journal = {Microorganisms}, number = {10}, issn = {2076-2607}, doi = {10.3390/microorganisms9102014}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246318}, year = {2021}, abstract = {Aspergillus is an important fungal genus containing economically important species, as well as pathogenic species of animals and plants. Using eighteen fungal species of the genus Aspergillus, we conducted a comprehensive investigation of conserved genes and their evolution. This also allows us to investigate the selection pressure driving the adaptive evolution in the pathogenic species A. fumigatus. Among single-copy orthologs (SCOs) for A. fumigatus and the closely related species A. fischeri, we identified 122 versus 50 positively selected genes (PSGs), respectively. Moreover, twenty conserved genes of unknown function were established to be positively selected and thus important for adaption. A. fumigatus PSGs interacting with human host proteins show over-representation of adaptive, symbiosis-related, immunomodulatory and virulence-related pathways, such as the TGF-β pathway, insulin receptor signaling, IL1 pathway and interfering with phagosomal GTPase signaling. Additionally, among the virulence factor coding genes, secretory and membrane protein-coding genes in multi-copy gene families, 212 genes underwent positive selection and also suggest increased adaptation, such as fungal immune evasion mechanisms (aspf2), siderophore biosynthesis (sidD), fumarylalanine production (sidE), stress tolerance (atfA) and thermotolerance (sodA). These genes presumably contribute to host adaptation strategies. Genes for the biosynthesis of gliotoxin are shared among all the close relatives of A. fumigatus as an ancient defense mechanism. Positive selection plays a crucial role in the adaptive evolution of A. fumigatus. The genome-wide profile of PSGs provides valuable targets for further research on the mechanisms of immune evasion, antimycotic targeting and understanding fundamental virulence processes.}, language = {en} } @article{KaltdorfTheissMarkertetal.2018, author = {Kaltdorf, Kristin Verena and Theiss, Maria and Markert, Sebastian Matthias and Zhen, Mei and Dandekar, Thomas and Stigloher, Christian and Kollmannsberger, Philipp}, title = {Automated classification of synaptic vesicles in electron tomograms of C. elegans using machine learning}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0205348}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176831}, pages = {e0205348}, year = {2018}, abstract = {Synaptic vesicles (SVs) are a key component of neuronal signaling and fulfil different roles depending on their composition. In electron micrograms of neurites, two types of vesicles can be distinguished by morphological criteria, the classical "clear core" vesicles (CCV) and the typically larger "dense core" vesicles (DCV), with differences in electron density due to their diverse cargos. Compared to CCVs, the precise function of DCVs is less defined. DCVs are known to store neuropeptides, which function as neuronal messengers and modulators [1]. In C. elegans, they play a role in locomotion, dauer formation, egg-laying, and mechano- and chemosensation [2]. Another type of DCVs, also referred to as granulated vesicles, are known to transport Bassoon, Piccolo and further constituents of the presynaptic density in the center of the active zone (AZ), and therefore are important for synaptogenesis [3]. To better understand the role of different types of SVs, we present here a new automated approach to classify vesicles. We combine machine learning with an extension of our previously developed vesicle segmentation workflow, the ImageJ macro 3D ART VeSElecT. With that we reliably distinguish CCVs and DCVs in electron tomograms of C. elegans NMJs using image-based features. Analysis of the underlying ground truth data shows an increased fraction of DCVs as well as a higher mean distance between DCVs and AZs in dauer larvae compared to young adult hermaphrodites. Our machine learning based tools are adaptable and can be applied to study properties of different synaptic vesicle pools in electron tomograms of diverse model organisms.}, language = {en} } @article{AkhoonGuptaTiwarietal.2019, author = {Akhoon, Bashir A. and Gupta, Shishir K. and Tiwari, Sudeep and Rathor, Laxmi and Pant, Aakanksha and Singh, Nivedita and Gupta, Shailendra K. and Dandekar, Thomas and Pandey, Rakesh}, title = {C. elegans protein interaction network analysis probes RNAi validated pro-longevity effect of nhr-6, a human homolog of tumor suppressor Nr4a1}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-51649-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202666}, pages = {15711}, year = {2019}, abstract = {Protein-protein interaction (PPI) studies are gaining momentum these days due to the plethora of various high-throughput experimental methods available for detecting PPIs. Proteins create complexes and networks by functioning in harmony with other proteins and here in silico network biology hold the promise to reveal new functionality of genes as it is very difficult and laborious to carry out experimental high-throughput genetic screens in living organisms. We demonstrate this approach by computationally screening C. elegans conserved homologs of already reported human tumor suppressor and aging associated genes. We select by this nhr-6, vab-3 and gst-23 as predicted longevity genes for RNAi screen. The RNAi results demonstrated the pro-longevity effect of these genes. Nuclear hormone receptor nhr-6 RNAi inhibition resulted in a C. elegans phenotype of 23.46\% lifespan reduction. Moreover, we show that nhr-6 regulates oxidative stress resistance in worms and does not affect the feeding behavior of worms. These findings imply the potential of nhr-6 as a common therapeutic target for aging and cancer ailments, stressing the power of in silico PPI network analysis coupled with RNAi screens to describe gene function.}, language = {en} } @article{GrebinykPrylutskaBuchelnikovetal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Buchelnikov, Anatoliy and Tverdokhleb, Nina and Grebinyk, Sergii and Evstigneev, Maxim and Matyshevska, Olga and Cherepanov, Vsevolod and Prylutskyy, Yuriy and Yashchuk, Valeriy and Naumovets, Anton and Ritter, Uwe and Dandekar, Thomas and Frohme, Marcus}, title = {C60 fullerene as an effective nanoplatform of alkaloid Berberine delivery into leukemic cells}, series = {Pharmaceutics}, volume = {11}, journal = {Pharmaceutics}, number = {11}, issn = {1999-4923}, doi = {10.3390/pharmaceutics11110586}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193216}, pages = {586}, year = {2019}, abstract = {A herbal alkaloid Berberine (Ber), used for centuries in Ayurvedic, Chinese, Middle-Eastern, and native American folk medicines, is nowadays proved to function as a safe anticancer agent. Yet, its poor water solubility, stability, and bioavailability hinder clinical application. In this study, we have explored a nanosized carbon nanoparticle—C60 fullerene (C60)—for optimized Ber delivery into leukemic cells. Water dispersions of noncovalent C60-Ber nanocomplexes in the 1:2, 1:1, and 2:1 molar ratios were prepared. UV-Vis spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM) evidenced a complexation of the Ber cation with the negatively charged C60 molecule. The computer simulation showed that π-stacking dominates in Ber and C\(_{60}\) binding in an aqueous solution. Complexation with C\(_{60}\) was found to promote Ber intracellular uptake. By increasing C\(_{60}\) concentration, the C\(_{60}\)-Ber nanocomplexes exhibited higher antiproliferative potential towards CCRF-CEM cells, in accordance with the following order: free Ber < 1:2 < 1:1 < 2:1 (the most toxic). The activation of caspase 3/7 and accumulation in the sub-G1 phase of CCRF-CEM cells treated with C\(_{60}\)-Ber nanocomplexes evidenced apoptosis induction. Thus, this study indicates that the fast and easy noncovalent complexation of alkaloid Ber with C\(_{60}\) improved its in vitro efficiency against cancer cells.}, language = {en} } @article{KannKunzHansenetal.2020, author = {Kann, Simone and Kunz, Meik and Hansen, Jessica and Sievertsen, J{\"u}rgen and Crespo, Jose J. and Loperena, Aristides and Arriens, Sandra and Dandekar, Thomas}, title = {Chagas disease: detection of Trypanosoma cruzi by a new, high-specific real time PCR}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {5}, issn = {2077-0383}, doi = {10.3390/jcm9051517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205746}, year = {2020}, abstract = {Background: Chagas disease (CD) is a major burden in Latin America, expanding also to non-endemic countries. A gold standard to detect the CD causing pathogen Trypanosoma cruzi is currently not available. Existing real time polymerase chain reactions (RT-PCRs) lack sensitivity and/or specificity. We present a new, highly specific RT-PCR for the diagnosis and monitoring of CD. Material and Methods: We analyzed 352 serum samples from Indigenous people living in high endemic CD areas of Colombia using three leading RT-PCRs (k-DNA-, TCZ-, 18S rRNA-PCR), the newly developed one (NDO-PCR), a Rapid Test/enzyme-linked immuno sorbent assay (ELISA), and immunofluorescence. Eighty-seven PCR-products were verified by sequence analysis after plasmid vector preparation. Results: The NDO-PCR showed the highest sensitivity (92.3\%), specificity (100\%), and accuracy (94.3\%) for T. cruzi detection in the 87 sequenced samples. Sensitivities and specificities of the kDNA-PCR were 89.2\%/22.7\%, 20.5\%/100\% for TCZ-PCR, and 1.5\%/100\% for the 18S rRNA-PCR. The kDNA-PCR revealed a 77.3\% false positive rate, mostly due to cross-reactions with T. rangeli (NDO-PCR 0\%). TCZ- and 18S rRNA-PCR showed a false negative rate of 79.5\% and 98.5\% (NDO-PCR 7.7\%), respectively. Conclusions: The NDO-PCR demonstrated the highest specificity, sensitivity, and accuracy compared to leading PCRs. Together with serologic tests, it can be considered as a reliable tool for CD detection and can improve CD management significantly.}, language = {en} } @article{AbdelLatifFathyAnwaretal.2022, author = {Abdel-Latif, Rania and Fathy, Moustafa and Anwar, Hend Ali and Naseem, Muhammad and Dandekar, Thomas and Othman, Eman M.}, title = {Cisplatin-induced reproductive toxicity and oxidative stress: ameliorative effect of kinetin}, series = {Antioxidants}, volume = {11}, journal = {Antioxidants}, number = {5}, issn = {2076-3921}, doi = {10.3390/antiox11050863}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271223}, year = {2022}, abstract = {Cisplatin is a commonly used chemotherapeutic agent; however, its potential side effects, including gonadotoxicity and infertility, are a critical problem. Oxidative stress has been implicated in the pathogenesis of cisplatin-induced testicular dysfunction. We investigated whether kinetin use at different concentrations could alleviate gonadal injury associated with cisplatin treatment, with an exploration of the involvement of its antioxidant capacity. Kinetin was administered in different doses of 0.25, 0.5, and 1 mg/kg, alone or along with cisplatin for 10 days. Cisplatin toxicity was induced via a single IP dose of 7 mg/kg on day four. In a dose-dependent manner, concomitant administration of kinetin with cisplatin significantly restored testicular oxidative stress parameters, corrected the distorted sperm quality parameters and histopathological changes, enhanced levels of serum testosterone and testicular StAR protein expression, as well as reduced the up-regulation of testicular TNF-α, IL-1β, Il-6, and caspase-3, caused by cisplatin. It is worth noting that the testicular protective effect of the highest kinetin dose was comparable/more potent and significantly higher than the effects of vitamin C and the lowest kinetin dose, respectively. Overall, these data indicate that kinetin may offer a promising approach for alleviating cisplatin-induced reproductive toxicity and organ damage, via ameliorating oxidative stress and reducing inflammation and apoptosis.}, language = {en} } @article{DandekarTollervey1989, author = {Dandekar, Thomas and Tollervey, David}, title = {Cloning of Schizosaccharomyces pombe genes encoding the U1,U2,U3 and U4 snRNAs}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29919}, year = {1989}, abstract = {No abstract available}, language = {en} } @article{SchokraieWarnkenHotzWagenblattetal.2012, author = {Schokraie, Elham and Warnken, Uwe and Hotz-Wagenblatt, Agnes and Grohme, Markus A. and Hengherr, Steffen and F{\"o}rster, Frank and Schill, Ralph O. and Frohme, Marcus and Dandekar, Thomas and Schn{\"o}lzer, Martina}, title = {Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {9}, doi = {10.1371/journal.pone.0045682}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134447}, pages = {e45682}, year = {2012}, abstract = {Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state.}, language = {en} } @article{BalkenholKaltdorfMammadovaBachetal.2020, author = {Balkenhol, Johannes and Kaltdorf, Kristin V. and Mammadova-Bach, Elmina and Braun, Attila and Nieswandt, Bernhard and Dittrich, Marcus and Dandekar, Thomas}, title = {Comparison of the central human and mouse platelet signaling cascade by systems biological analysis}, series = {BMC Genomics}, volume = {21}, journal = {BMC Genomics}, doi = {10.1186/s12864-020-07215-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230377}, year = {2020}, abstract = {Background Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). Results The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81\%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. Conclusions Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.}, language = {en} } @article{GrebinykPrylutskaGrebinyketal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Grebinyk, Sergii and Prylutskyy, Yuriy and Ritter, Uwe and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {Complexation with C\(_{60}\) fullerene increases doxorubicin efficiency against leukemic cells in vitro}, series = {Nanoscale Research Letters}, volume = {14}, journal = {Nanoscale Research Letters}, number = {61}, doi = {10.1186/s11671-019-2894-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228257}, year = {2019}, abstract = {Conventional anticancer chemotherapy is limited because of severe side effects as well as a quickly evolving multidrug resistance of the tumor cells. To address this problem, we have explored a C\(_{60}\) fullerene-based nanosized system as a carrier for anticancer drugs for an optimized drug delivery to leukemic cells.Here, we studied the physicochemical properties and anticancer activity of C\(_{60}\) fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin. C\(_{60}\)-Doxorubicin complexes in a ratio 1:1 and 2:1 were characterized with UV/Vis spectrometry, dynamic light scattering, and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The obtained analytical data indicated that the 140-nm complexes were stable and could be used for biological applications. In leukemic cell lines (CCRF-CEM, Jurkat, THP1 and Molt-16), the nanocomplexes revealed 3.5 higher cytotoxic potential in comparison with the free drug in a range of nanomolar concentrations. Also, the intracellular drug's level evidenced C\(_{60}\) fullerene considerable nanocarrier function.The results of this study indicated that C\(_{60}\) fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells.}, language = {en} } @article{YangRajeeveRudeletal.2019, author = {Yang, Manli and Rajeeve, Karthika and Rudel, Thomas and Dandekar, Thomas}, title = {Comprehensive Flux Modeling of Chlamydia trachomatis Proteome and qRT-PCR Data Indicate Biphasic Metabolic Differences Between Elementary Bodies and Reticulate Bodies During Infection}, series = {Frontiers in Microbiology}, volume = {10}, journal = {Frontiers in Microbiology}, number = {2350}, issn = {1664-302X}, doi = {10.3389/fmicb.2019.02350}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189434}, year = {2019}, abstract = {Metabolic adaptation to the host cell is important for obligate intracellular pathogens such as Chlamydia trachomatis (Ct). Here we infer the flux differences for Ct from proteome and qRT-PCR data by comprehensive pathway modeling. We compare the comparatively inert infectious elementary body (EB) and the active replicative reticulate body (RB) systematically using a genome-scale metabolic model with 321 metabolites and 277 reactions. This did yield 84 extreme pathways based on a published proteomics dataset at three different time points of infection. Validation of predictions was done by quantitative RT-PCR of enzyme mRNA expression at three time points. Ct's major active pathways are glycolysis, gluconeogenesis, glycerol-phospholipid (GPL) biosynthesis (support from host acetyl-CoA) and pentose phosphate pathway (PPP), while its incomplete TCA and fatty acid biosynthesis are less active. The modeled metabolic pathways are much more active in RB than in EB. Our in silico model suggests that EB and RB utilize folate to generate NAD(P)H using independent pathways. The only low metabolic flux inferred for EB involves mainly carbohydrate metabolism. RB utilizes energy -rich compounds to generate ATP in nucleic acid metabolism. Validation data for the modeling include proteomics experiments (model basis) as well as qRT-PCR confirmation of selected metabolic enzyme mRNA expression differences. The metabolic modeling is made fully available here. Its detailed insights and models on Ct metabolic adaptations during infection are a useful modeling basis for future studies.}, language = {en} } @article{SchererFleishmanJonesetal.2021, author = {Scherer, Marc and Fleishman, Sarel J. and Jones, Patrik R. and Dandekar, Thomas and Bencurova, Elena}, title = {Computational Enzyme Engineering Pipelines for Optimized Production of Renewable Chemicals}, series = {Frontiers in Bioengineering and Biotechnology}, volume = {9}, journal = {Frontiers in Bioengineering and Biotechnology}, issn = {2296-4185}, doi = {10.3389/fbioe.2021.673005}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240598}, year = {2021}, abstract = {To enable a sustainable supply of chemicals, novel biotechnological solutions are required that replace the reliance on fossil resources. One potential solution is to utilize tailored biosynthetic modules for the metabolic conversion of CO2 or organic waste to chemicals and fuel by microorganisms. Currently, it is challenging to commercialize biotechnological processes for renewable chemical biomanufacturing because of a lack of highly active and specific biocatalysts. As experimental methods to engineer biocatalysts are time- and cost-intensive, it is important to establish efficient and reliable computational tools that can speed up the identification or optimization of selective, highly active, and stable enzyme variants for utilization in the biotechnological industry. Here, we review and suggest combinations of effective state-of-the-art software and online tools available for computational enzyme engineering pipelines to optimize metabolic pathways for the biosynthesis of renewable chemicals. Using examples relevant for biotechnology, we explain the underlying principles of enzyme engineering and design and illuminate future directions for automated optimization of biocatalysts for the assembly of synthetic metabolic pathways.}, language = {en} }