@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}
}
@unpublished{Dandekar2019,
  author    = {Dandekar, Thomas},
  title     = {Biological heuristics applied to cosmology suggests a condensation nucleus as start of our universe and inflation cosmology replaced by a period of rapid Weiss domain-like crystal growth},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-183945},
  pages     = {24},
  year      = {2019},
  abstract  = {Cosmology often uses intricate formulas and mathematics to derive new theories and concepts. We do something different in this paper: We look at biological processes and derive from these heuristics so that the revised cosmology agrees with astronomical observations but does also agree with standard biological observations. We show that we then have to replace any type of singularity at the start of the universe by a condensation nucleus and that the very early period of the universe usually assumed to be inflation has to be replaced by a period of rapid crystal growth as in Weiss magnetization domains. Impressively, these minor modifications agree well with astronomical observations including removing the strong inflation perturbations which were never observed in the recent BICEP2 experiments. Furthermore, looking at biological principles suggests that such a new theory with a condensation nucleus at start and a first rapid phase of magnetization-like growth of the ordered, physical laws obeying lattice we live in is in fact the only convincing theory of the early phases of our universe that also is compatible with current observations. We show in detail in the following that such a process of crystal creation, breaking of new crystal seeds and ultimate evaporation of the present crystal readily leads over several generations to an evolution and selection of better, more stable and more self-organizing crystals. Moreover, this explains the "fine-tuning" question why our universe is fine-tuned to favor life: Our Universe is so self-organizing to have enough offspring and the detailed physics involved is at the same time highly favorable for all self-organizing processes including life. This biological theory contrasts with current standard inflation cosmologies. The latter do not perform well in explaining any phenomena of sophisticated structure creation or self-organization. As proteins can only thermodynamically fold by increasing the entropy in the solution around them we suggest for cosmology a condensation nucleus for a universe can form only in a "chaotic ocean" of string-soup or quantum foam if the entropy outside of the nucleus rapidly increases. We derive an interaction potential for 1 to n-dimensional strings or quantum-foams and show that they allow only 1D, 2D, 4D or octonion interactions. The latter is the richest structure and agrees to the E8 symmetry fundamental to particle physics and also compatible with the ten dimensional string theory E8 which is part of the M-theory. Interestingly, any other interactions of other dimensionality can be ruled out using Hurwitz compositional theorem. Crystallization explains also extremely well why we have only one macroscopic reality and where the worldlines of alternative trajectories exist: They are in other planes of the crystal and for energy reasons they crystallize mostly at the same time, yielding a beautiful and stable crystal. This explains decoherence and allows to determine the size of Planck´s quantum h (very small as separation of crystal layers by energy is extremely strong). Ultimate dissolution of real crystals suggests an explanation for dark energy agreeing with estimates for the "big rip". The halo distribution of dark matter favoring galaxy formation is readily explained by a crystal seed starting with unit cells made of normal and dark matter. That we have only matter and not antimatter can be explained as there may be right handed mattercrystals and left-handed antimatter crystals. Similarly, real crystals are never perfect and we argue that exactly such irregularities allow formation of galaxies, clusters and superclusters. Finally, heuristics from genetics suggest to look for a systems perspective to derive correct vacuum and Higgs Boson energies.},
  language  = {en}
}
@article{KunzLiangNillaetal.2016,
  author    = {Kunz, Meik and Liang, Chunguang and Nilla, Santosh and Cecil, Alexander and Dandekar, Thomas},
  title     = {The drug-minded protein interaction database (DrumPID) for efficient target analysis and drug development},
  series = {Database},
  volume    = {2016},
  journal   = {Database},
  doi       = {10.1093/database/baw041},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147369},
  pages     = {baw041},
  year      = {2016},
  abstract  = {The drug-minded protein interaction database (DrumPID) has been designed to provide fast, tailored information on drugs and their protein networks including indications, protein targets and side-targets. Starting queries include compound, target and protein interactions and organism-specific protein families. Furthermore, drug name, chemical structures and their SMILES notation, affected proteins (potential drug targets), organisms as well as diseases can be queried including various combinations and refinement of searches. Drugs and protein interactions are analyzed in detail with reference to protein structures and catalytic domains, related compound structures as well as potential targets in other organisms. DrumPID considers drug functionality, compound similarity, target structure, interactome analysis and organismic range for a compound, useful for drug development, predicting drug side-effects and structure-activity relationships.},
  language  = {en}
}
@article{KaltdorfSrivastavaGuptaetal.2016,
  author    = {Kaltdorf, Martin and Srivastava, Mugdha and Gupta, Shishir K. and Liang, Chunguang and Binder, Jasmin and Dietl, Anna-Maria and Meir, Zohar and Haas, Hubertus and Osherov, Nir and Krappmann, Sven and Dandekar, Thomas},
  title     = {Systematic Identification of Anti-Fungal Drug Targets by a Metabolic Network Approach},
  series = {Frontiers in Molecular Bioscience},
  volume    = {3},
  journal   = {Frontiers in Molecular Bioscience},
  doi       = {10.3389/fmolb.2016.00022},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147396},
  pages     = {22},
  year      = {2016},
  abstract  = {New antimycotic drugs are challenging to find, as potential target proteins may have close human orthologs. We here focus on identifying metabolic targets that are critical for fungal growth and have minimal similarity to targets among human proteins. We compare and combine here: (I) direct metabolic network modeling using elementary mode analysis and flux estimates approximations using expression data, (II) targeting metabolic genes by transcriptome analysis of condition-specific highly expressed enzymes, and (III) analysis of enzyme structure, enzyme interconnectedness ("hubs"), and identification of pathogen-specific enzymes using orthology relations. We have identified 64 targets including metabolic enzymes involved in vitamin synthesis, lipid, and amino acid biosynthesis including 18 targets validated from the literature, two validated and five currently examined in own genetic experiments, and 38 further promising novel target proteins which are non-orthologous to human proteins, involved in metabolism and are highly ranked drug targets from these pipelines.},
  language  = {en}
}
@article{ShityakovDandekarFoerster2015,
  author    = {Shityakov, Sergey and Dandekar, Thomas and F{\"o}rster, Carola},
  title     = {Gene expression profiles and protein-protein interaction network analysis in AIDS patients with HIV-associated encephalitis and dementia},
  series = {HIV/AIDS: Research and Palliative Care},
  volume    = {7},
  journal   = {HIV/AIDS: Research and Palliative Care},
  doi       = {10.2147/HIV.S88438},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149494},
  pages     = {265-276},
  year      = {2015},
  abstract  = {Central nervous system dysfunction is an important cause of morbidity and mortality in patients with human immunodeficiency virus type 1 (HIV-1) infection and acquired immunodeficiency virus syndrome (AIDS). Patients with AIDS are usually affected by HIV-associated encephalitis (HIVE) with viral replication limited to cells of monocyte origin. To examine the molecular mechanisms underlying HIVE-induced dementia, the GSE4755 Affymetrix data were obtained from the Gene Expression Omnibus database and the differentially expressed genes (DEGs) between the samples from AIDS patients with and without apparent features of HIVE-induced dementia were identified. In addition, protein-protein interaction networks were constructed by mapping DEGs into protein-protein interaction data to identify the pathways that these DEGs are involved in. The results revealed that the expression of 1,528 DEGs is mainly involved in the immune response, regulation of cell proliferation, cellular response to inflammation, signal transduction, and viral replication cycle. Heat-shock protein alpha, class A member 1 (HSP90AA1), and fibronectin 1 were detected as hub nodes with degree values >130. In conclusion, the results indicate that HSP90A and fibronectin 1 play important roles in HIVE pathogenesis.},
  language  = {en}
}
@article{WolfKuonenDandekaretal.2015,
  author    = {Wolf, Beat and Kuonen, Pierre and Dandekar, Thomas and Atlan, David},
  title     = {DNAseq workflow in a diagnostic context and an example of a user friendly implementation},
  series = {BioMed Research International},
  journal   = {BioMed Research International},
  number    = {403497},
  doi       = {10.1155/2015/403497},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144527},
  year      = {2015},
  abstract  = {Over recent years next generation sequencing (NGS) technologies evolved from costly tools used by very few, to a much more accessible and economically viable technology. Through this recently gained popularity, its use-cases expanded from research environments into clinical settings. But the technical know-how and infrastructure required to analyze the data remain an obstacle for a wider adoption of this technology, especially in smaller laboratories. We present GensearchNGS, a commercial DNAseq software suite distributed by Phenosystems SA. The focus of GensearchNGS is the optimal usage of already existing infrastructure, while keeping its use simple. This is achieved through the integration of existing tools in a comprehensive software environment, as well as custom algorithms developed with the restrictions of limited infrastructures in mind. This includes the possibility to connect multiple computers to speed up computing intensive parts of the analysis such as sequence alignments. We present a typical DNAseq workflow for NGS data analysis and the approach GensearchNGS takes to implement it. The presented workflow goes from raw data quality control to the final variant report. This includes features such as gene panels and the integration of online databases, like Ensembl for annotations or Cafe Variome for variant sharing.},
  language  = {en}
}
@article{OthmanNaseemAwadetal.2016,
  author    = {Othman, Eman M. and Naseem, Muhammed and Awad, Eman and Dandekar, Thomas and Stopper, Helga},
  title     = {The Plant Hormone Cytokinin Confers Protection against Oxidative Stress in Mammalian Cells},
  series = {PLoS One},
  volume    = {11},
  journal   = {PLoS One},
  number    = {12},
  doi       = {10.1371/journal.pone.0168386},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147983},
  pages     = {e0168386},
  year      = {2016},
  abstract  = {Modulating key dynamics of plant growth and development, the effects of the plant hormone cytokinin on animal cells gained much attention recently. Most previous studies on cytokinin effects on mammalian cells have been conducted with elevated cytokinin concentration (in the μM range). However, to examine physiologically relevant dose effects of cytokinins on animal cells, we systematically analyzed the impact of kinetin in cultured cells at low and high concentrations (1nM-10μM) and examined cytotoxic and genotoxic conditions. We furthermore measured the intrinsic antioxidant activity of kinetin in a cell-free system using the Ferric Reducing Antioxidant Power assay and in cells using the dihydroethidium staining method. Monitoring viability, we looked at kinetin effects in mammalian cells such as HL60 cells, HaCaT human keratinocyte cells, NRK rat epithelial kidney cells and human peripheral lymphocytes. Kinetin manifests no antioxidant activity in the cell free system and high doses of kinetin (500 nM and higher) reduce cell viability and mediate DNA damage in vitro. In contrast, low doses (concentrations up to 100 nM) of kinetin confer protection in cells against oxidative stress. Moreover, our results show that pretreatment of the cells with kinetin significantly reduces 4-nitroquinoline 1-oxide mediated reactive oxygen species production. Also, pretreatment with kinetin retains cellular GSH levels when they are also treated with the GSH-depleting agent patulin. Our results explicitly show that low kinetin doses reduce apoptosis and protect cells from oxidative stress mediated cell death. Future studies on the interaction between cytokinins and human cellular pathway targets will be intriguing.},
  language  = {en}
}
@article{KunzWolfSchulzeetal.2016,
  author    = {Kunz, Meik and Wolf, Beat and Schulze, Harald and Atlan, David and Walles, Thorsten and Walles, Heike and Dandekar, Thomas},
  title     = {Non-Coding RNAs in Lung Cancer: Contribution of Bioinformatics Analysis to the Development of Non-Invasive Diagnostic Tools},
  series = {Genes},
  volume    = {8},
  journal   = {Genes},
  number    = {1},
  doi       = {10.3390/genes8010008},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147990},
  pages     = {8},
  year      = {2016},
  abstract  = {Lung cancer is currently the leading cause of cancer related mortality due to late diagnosis and limited treatment intervention. Non-coding RNAs are not translated into proteins and have emerged as fundamental regulators of gene expression. Recent studies reported that microRNAs and long non-coding RNAs are involved in lung cancer development and progression. Moreover, they appear as new promising non-invasive biomarkers for early lung cancer diagnosis. Here, we highlight their potential as biomarker in lung cancer and present how bioinformatics can contribute to the development of non-invasive diagnostic tools. For this, we discuss several bioinformatics algorithms and software tools for a comprehensive understanding and functional characterization of microRNAs and long non-coding RNAs.},
  language  = {en}
}
@article{CecilRikanovicOhlsenetal.2011,
  author    = {Cecil, Alexander and Rikanovic, Carina and Ohlsen, Knut and Liang, Chunguang and Bernhardt, Jorg and Oelschlaeger, Tobias A. and Gulder, Tanja and Bringmann, Gerd and Holzgrabe, Ulrike and Unger, Matthias and Dandekar, Thomas},
  title     = {Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus, Staphylococcus epidermidis and human cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68802},
  year      = {2011},
  abstract  = {Background: Xenobiotics represent an environmental stress and as such are a source for antibiotics, including the isoquinoline (IQ) compound IQ-143. Here, we demonstrate the utility of complementary analysis of both host and pathogen datasets in assessing bacterial adaptation to IQ-143, a synthetic analog of the novel type N,C-coupled naphthyl-isoquinoline alkaloid ancisheynine. Results: Metabolite measurements, gene expression data and functional assays were combined with metabolic modeling to assess the effects of IQ-143 on Staphylococcus aureus, Staphylococcus epidermidis and human cell lines, as a potential paradigm for novel antibiotics. Genome annotation and PCR validation identified novel enzymes in the primary metabolism of staphylococci. Gene expression response analysis and metabolic modeling demonstrated the adaptation of enzymes to IQ-143, including those not affected by significant gene expression changes. At lower concentrations, IQ-143 was bacteriostatic, and at higher concentrations bactericidal, while the analysis suggested that the mode of action was a direct interference in nucleotide and energy metabolism. Experiments in human cell lines supported the conclusions from pathway modeling and found that IQ-143 had low cytotoxicity. Conclusions: The data suggest that IQ-143 is a promising lead compound for antibiotic therapy against staphylococci. The combination of gene expression and metabolite analyses with in silico modeling of metabolite pathways allowed us to study metabolic adaptations in detail and can be used for the evaluation of metabolic effects of other xenobiotics.},
  subject      = {Staphylococcus aureus},
  language  = {en}
}
@article{WangorschButtMarketal.2011,
  author    = {Wangorsch, Gaby and Butt, Elke and Mark, Regina and Hubertus, Katharina and Geiger, J{\"o}rg and Dandekar, Thomas and Dittrich, Marcus},
  title     = {Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69145},
  year      = {2011},
  abstract  = {Background: Hemostasis is a critical and active function of the blood mediated by platelets. Therefore, the prevention of pathological platelet aggregation is of great importance as well as of pharmaceutical and medical interest. Endogenous platelet inhibition is predominantly based on cyclic nucleotides (cAMP, cGMP) elevation and subsequent cyclic nucleotide-dependent protein kinase (PKA, PKG) activation. In turn, platelet phosphodiesterases (PDEs) and protein phosphatases counterbalance their activity. This main inhibitory pathway in human platelets is crucial for countervailing unwanted platelet activation. Consequently, the regulators of cyclic nucleotide signaling are of particular interest to pharmacology and therapeutics of atherothrombosis. Modeling of pharmacodynamics allows understanding this intricate signaling and supports the precise description of these pivotal targets for pharmacological modulation. Results: We modeled dynamically concentration-dependent responses of pathway effectors (inhibitors, activators, drug combinations) to cyclic nucleotide signaling as well as to downstream signaling events and verified resulting model predictions by experimental data. Experiments with various cAMP affecting compounds including antiplatelet drugs and their combinations revealed a high fidelity, fine-tuned cAMP signaling in platelets without crosstalk to the cGMP pathway. The model and the data provide evidence for two independent feedback loops: PKA, which is activated by elevated cAMP levels in the platelet, subsequently inhibits adenylyl cyclase (AC) but as well activates PDE3. By multi-experiment fitting, we established a comprehensive dynamic model with one predictive, optimized and validated set of parameters. Different pharmacological conditions (inhibition, activation, drug combinations, permanent and transient perturbations) are successfully tested and simulated, including statistical validation and sensitivity analysis. Downstream cyclic nucleotide signaling events target different phosphorylation sites for cAMP- and cGMP-dependent protein kinases (PKA, PKG) in the vasodilator-stimulated phosphoprotein (VASP). VASP phosphorylation as well as cAMP levels resulting from different drug strengths and combined stimulants were quantitatively modeled. These predictions were again experimentally validated. High sensitivity of the signaling pathway at low concentrations is involved in a fine-tuned balance as well as stable activation of this inhibitory cyclic nucleotide pathway. Conclusions: On the basis of experimental data, literature mining and database screening we established a dynamic in silico model of cyclic nucleotide signaling and probed its signaling sensitivity. Thoroughly validated, it successfully predicts drug combination effects on platelet function, including synergism, antagonism and regulatory loops.},
  subject      = {Vasodilatator-stimuliertes Phosphoprotein},
  language  = {en}
}
@article{BeisserGrohmeKopkaetal.2012,
  author    = {Beisser, Daniela and Grohme, Markus A. and Kopka, Joachim and Frohme, Marcus and Schill, Ralph O. and Hengherr, Steffen and Dandekar, Thomas and Klau, Gunnar W. and Dittrich, Marcus and M{\"u}ller, Tobias},
  title     = {Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75241},
  year      = {2012},
  abstract  = {Background: Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun) to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade Milnesium tardigradum were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress. Results: In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites) and 4,378 edges (reactions). Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module) of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurablemetabolism (e.g. glycolysis and amino acid anabolism) during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from monosaccharides as carbon and energy source during rehydration. Conclusions: The functional module identifies relationships among changed metabolites (e.g. spermidine) and reactions and provides first insights into important altered metabolic pathways. With sparse and diverse data available, the presented integrated metabolite network approach is suitable to integrate all existing data and analyse it in a combined manner.},
  subject      = {Milnesium tardigradum},
  language  = {en}
}
@article{ShityakovDandekar2010,
  author    = {Shityakov, Sergey and Dandekar, Thomas},
  title     = {Lead expansion and virtual screening of Indinavir derivate HIV-1 protease inhibitors using pharmacophoric - shape similarity scoring function},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67824},
  year      = {2010},
  abstract  = {Indinavir (Crivaxan®) is a potent inhibitor of the HIV (human immunodeficiency virus) protease. This enzyme has an important role in viral replication and is considered to be very attractive target for new antiretroviral drugs. However, it becomes less effective due to highly resistant new viral strains of HIV, which have multiple mutations in their proteases. For this reason, we used a lead expansion method to create a new set of compounds with a new mode of action to protease binding site. 1300 compounds chemically diverse from the initial hit were generated and screened to determine their ability to interact with protease and establish their QSAR properties. Further computational analyses revealed one unique compound with different protease binding ability from the initial hit and its role for possible new class of protease inhibitors is discussed in this report.},
  subject      = {Proteasen},
  language  = {en}
}
@article{KellerFoersterMuelleretal.2010,
  author    = {Keller, Alexander and Foerster, Frank and Mueller, Tobias and Dandekar, Thomas and Schultz, Joerg and Wolf, Matthias},
  title     = {Including RNA secondary structures improves accuracy and robustness in reconstruction of phylogenetic trees},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67832},
  year      = {2010},
  abstract  = {Background: In several studies, secondary structures of ribosomal genes have been used to improve the quality of phylogenetic reconstructions. An extensive evaluation of the benefits of secondary structure, however, is lacking. Results: This is the first study to counter this deficiency. We inspected the accuracy and robustness of phylogenetics with individual secondary structures by simulation experiments for artificial tree topologies with up to 18 taxa and for divergency levels in the range of typical phylogenetic studies. We chose the internal transcribed spacer 2 of the ribosomal cistron as an exemplary marker region. Simulation integrated the coevolution process of sequences with secondary structures. Additionally, the phylogenetic power of marker size duplication was investigated and compared with sequence and sequence-structure reconstruction methods. The results clearly show that accuracy and robustness of Neighbor Joining trees are largely improved by structural information in contrast to sequence only data, whereas a doubled marker size only accounts for robustness. Conclusions: Individual secondary structures of ribosomal RNA sequences provide a valuable gain of information content that is useful for phylogenetics. Thus, the usage of ITS2 sequence together with secondary structure for taxonomic inferences is recommended. Other reconstruction methods as maximum likelihood, bayesian inference or maximum parsimony may equally profit from secondary structure inclusion. Reviewers: This article was reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber) and Eugene V. Koonin. Open peer review: Reviewed by Shamil Sunyaev, Andrea Tanzer (nominated by Frank Eisenhaber) and Eugene V. Koonin. For the full reviews, please go to the Reviewers' comments section.},
  subject      = {Phylogenie},
  language  = {en}
}
@article{VainshteinSanchezBrazmaetal.2010,
  author    = {Vainshtein, Yevhen and Sanchez, Mayka and Brazma, Alvis and Hentze, Matthias W. and Dandekar, Thomas and Muckenthaler, Martina U.},
  title     = {The IronChip evaluation package: a package of perl modules for robust analysis of custom microarrays},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67869},
  year      = {2010},
  abstract  = {Background: Gene expression studies greatly contribute to our understanding of complex relationships in gene regulatory networks. However, the complexity of array design, production and manipulations are limiting factors, affecting data quality. The use of customized DNA microarrays improves overall data quality in many situations, however, only if for these specifically designed microarrays analysis tools are available. Results: The IronChip Evaluation Package (ICEP) is a collection of Perl utilities and an easy to use data evaluation pipeline for the analysis of microarray data with a focus on data quality of custom-designed microarrays. The package has been developed for the statistical and bioinformatical analysis of the custom cDNA microarray IronChip but can be easily adapted for other cDNA or oligonucleotide-based designed microarray platforms. ICEP uses decision tree-based algorithms to assign quality flags and performs robust analysis based on chip design properties regarding multiple repetitions, ratio cut-off, background and negative controls. Conclusions: ICEP is a stand-alone Windows application to obtain optimal data quality from custom-designed microarrays and is freely available here (see "Additional Files" section) and at: http://www.alice-dsl.net/evgeniy. vainshtein/ICEP/},
  subject      = {Microarray},
  language  = {en}
}
@article{FriedrichRahmannWeigeletal.2010,
  author    = {Friedrich, Torben and Rahmann, Sven and Weigel, Wilfried and Rabsch, Wolfgang and Fruth, Angelika and Ron, Eliora and Gunzer, Florian and Dandekar, Thomas and Hacker, Joerg and Mueller, Tobias and Dobrindt, Ulrich},
  title     = {High-throughput microarray technology in diagnostics of enterobacteria based on genome-wide probe selection and regression analysis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67936},
  year      = {2010},
  abstract  = {The Enterobacteriaceae comprise a large number of clinically relevant species with several individual subspecies. Overlapping virulence-associated gene pools and the high overall genome plasticity often interferes with correct enterobacterial strain typing and risk assessment. Array technology offers a fast, reproducible and standardisable means for bacterial typing and thus provides many advantages for bacterial diagnostics, risk assessment and surveillance. The development of highly discriminative broad-range microbial diagnostic microarrays remains a challenge, because of marked genome plasticity of many bacterial pathogens. Results: We developed a DNA microarray for strain typing and detection of major antimicrobial resistance genes of clinically relevant enterobacteria. For this purpose, we applied a global genome-wide probe selection strategy on 32 available complete enterobacterial genomes combined with a regression model for pathogen classification. The discriminative power of the probe set was further tested in silico on 15 additional complete enterobacterial genome sequences. DNA microarrays based on the selected probes were used to type 92 clinical enterobacterial isolates. Phenotypic tests confirmed the array-based typing results and corroborate that the selected probes allowed correct typing and prediction of major antibiotic resistances of clinically relevant Enterobacteriaceae, including the subspecies level, e.g. the reliable distinction of different E. coli pathotypes. Conclusions: Our results demonstrate that the global probe selection approach based on longest common factor statistics as well as the design of a DNA microarray with a restricted set of discriminative probes enables robust discrimination of different enterobacterial variants and represents a proof of concept that can be adopted for diagnostics of a wide range of microbial pathogens. Our approach circumvents misclassifications arising from the application of virulence markers, which are highly affected by horizontal gene transfer. Moreover, a broad range of pathogens have been covered by an efficient probe set size enabling the design of high-throughput diagnostics.},
  subject      = {Mikroarray},
  language  = {en}
}
@article{DandekarFieselmannFischeretal.2014,
  author    = {Dandekar, Thomas and Fieselmann, Astrid and Fischer, Eva and Popp, Jasmin and Hensel, Michael and Noster, Janina},
  title     = {Salmonella—how a metabolic generalist adopts an intracellular lifestyle during infection},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {4},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  number    = {191},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2014.00191},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120686},
  year      = {2014},
  abstract  = {The human-pathogenic bacterium Salmonella enterica adjusts and adapts to different environments while attempting colonization. In the course of infection nutrient availabilities change drastically. New techniques, "-omics" data and subsequent integration by systems biology improve our understanding of these changes. We review changes in metabolism focusing on amino acid and carbohydrate metabolism. Furthermore, the adaptation process is associated with the activation of genes of the Salmonella pathogenicity islands (SPIs). Anti-infective strategies have to take these insights into account and include metabolic and other strategies. Salmonella infections will remain a challenge for infection biology.},
  language  = {en}
}
@article{WirthGlushakovaScheuermayeretal.2014,
  author    = {Wirth, Christine C. and Glushakova, Svetlana and Scheuermayer, Matthias and Repnik, Urska and Garg, Swatl and Schaack, Dominik and Kachman, Marika M. and Weißbach, Tim and Zimmerberg, Joshua and Dandekar, Thomas and Griffiths, Gareth and Chitnis, Chetan E. and Singh, Shallja and Fischer, Rainer and Pradel, Gabriele},
  title     = {Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes},
  series = {Cellular Microbiology},
  volume    = {16},
  journal   = {Cellular Microbiology},
  number    = {5},
  doi       = {10.1111/cmi.12288},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120895},
  pages     = {709-33},
  year      = {2014},
  abstract  = {Egress of malaria parasites from the host cell requires the concerted rupture of its enveloping membranes. Hence, we investigated the role of the plasmodial perforin-like protein PPLP2 in the egress of Plasmodium falciparum from erythrocytes. PPLP2 is expressed in blood stage schizonts and mature gametocytes. The protein localizes in vesicular structures, which in activated gametocytes discharge PPLP2 in a calcium-dependent manner. PPLP2 comprises a MACPF domain and recombinant PPLP2 has haemolytic activities towards erythrocytes. PPLP2-deficient [PPLP2(-)] merozoites show normal egress dynamics during the erythrocytic replication cycle, but activated PPLP2(-) gametocytes were unable to leave erythrocytes and stayed trapped within these cells. While the parasitophorous vacuole membrane ruptured normally, the activated PPLP2(-) gametocytes were unable to permeabilize the erythrocyte membrane and to release the erythrocyte cytoplasm. In consequence, transmission of PPLP2(-) parasites to the Anopheles vector was reduced. Pore-forming equinatoxin II rescued both PPLP2(-) gametocyte exflagellation and parasite transmission. The pore sealant Tetronic 90R4, on the other hand, caused trapping of activated wild-type gametocytes within the enveloping erythrocytes, thus mimicking the PPLP2(-) loss-of-function phenotype. We propose that the haemolytic activity of PPLP2 is essential for gametocyte egress due to permeabilization of the erythrocyte membrane and depletion of the erythrocyte cytoplasm.},
  language  = {en}
}
@article{KruegerFriedrichFoersteretal.2012,
  author    = {Krueger, Beate and Friedrich, Torben and F{\"o}rster, Frank and Bernhardt, J{\"o}rg and Gross, Roy and Dandekar, Thomas},
  title     = {Different evolutionary modifications as a guide to rewire two-component systems},
  series = {Bioinformatics and Biology Insights},
  volume    = {6},
  journal   = {Bioinformatics and Biology Insights},
  doi       = {10.4137/BBI.S9356},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123647},
  pages     = {97-128},
  year      = {2012},
  abstract  = {Two-component systems (TCS) are short signalling pathways generally occurring in prokaryotes. They frequently regulate prokaryotic stimulus responses and thus are also of interest for engineering in biotechnology and synthetic biology. The aim of this study is to better understand and describe rewiring of TCS while investigating different evolutionary scenarios. Based on large-scale screens of TCS in different organisms, this study gives detailed data, concrete alignments, and structure analysis on three general modification scenarios, where TCS were rewired for new responses and functions: (i) exchanges in the sequence within single TCS domains, (ii) exchange of whole TCS domains; (iii) addition of new components modulating TCS function. As a result, the replacement of stimulus and promotor cassettes to rewire TCS is well defined exploiting the alignments given here. The diverged TCS examples are non-trivial and the design is challenging. Designed connector proteins may also be useful to modify TCS in selected cases.},
  language  = {en}
}
@article{FoersterBeisserGrohmeetal.2012,
  author    = {F{\"o}rster, Frank and Beisser, Daniela and Grohme, Markus A. and Liang, Chunguang and Mali, Brahim and Siegl, Alexander Matthias and Engelmann, Julia C. and Shkumatov, Alexander V. and Schokraie, Elham and M{\"u}ller, Tobias and Schn{\"o}lzer, Martina and Schill, Ralph O. and Frohme, Marcus and Dandekar, Thomas},
  title     = {Transcriptome analysis in tardigrade species reveals specific molecular pathways for stress adaptations},
  series = {Bioinformatics and biology insights},
  volume    = {6},
  journal   = {Bioinformatics and biology insights},
  doi       = {10.4137/BBI.S9150},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123089},
  pages     = {69-96},
  year      = {2012},
  abstract  = {Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade \(Milnesium\) \(tardigradum\) were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from \(Hypsibius\) \(dujardini\), revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for \(M.\) \(tardigradum\) are different from typical motifs known from higher animals. \(M.\) \(tardigradum\) and \(H.\) \(dujardini\) protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of \(M.\) \(tardigradum\). These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and \(M.\) \(tardigradum\) in particular so highly stress resistant.},
  language  = {en}
}
@article{DandekarFieselmannPoppetal.2012,
  author    = {Dandekar, Thomas and Fieselmann, Astrid and Popp, Jasmin and Hensel, Michael},
  title     = {Salmonella enterica: a surprisingly well-adapted intracellular lifestyle},
  series = {Frontiers in Microbiology},
  journal   = {Frontiers in Microbiology},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123135},
  year      = {2012},
  abstract  = {The infectious intracellular lifestyle of Salmonella enterica relies on the adaptation to nutritional conditions within the Salmonella-containing vacuole (SCV) in host cells. We summarize latest results on metabolic requirements for Salmonella during infection. This includes intracellular phenotypes of mutant strains based on metabolic modeling and experimental tests, isotopolog profiling using (13)C-compounds in intracellular Salmonella, and complementation of metabolic defects for attenuated mutant strains towards a comprehensive understanding of the metabolic requirements of the intracellular lifestyle of Salmonella. Helpful for this are also genomic comparisons. We outline further recent studies and which analyses of intracellular phenotypes and improved metabolic simulations were done and comment on technical required steps as well as progress involved in the iterative refinement of metabolic flux models, analyses of mutant phenotypes, and isotopolog analyses. Salmonella lifestyle is well-adapted to the SCV and its specific metabolic requirements. Salmonella metabolism adapts rapidly to SCV conditions, the metabolic generalist Salmonella is quite successful in host infection.},
  language  = {en}
}
@article{GuptaKupperRatzkaetal.2015,
  author    = {Gupta, Shishir K. and Kupper, Maria and Ratzka, Carolin and Feldhaar, Heike and Vilcinskas, Andreas and Gross, Roy and Dandekar, Thomas and F{\"o}rster, Frank},
  title     = {Scrutinizing the immune defence inventory of Camponotus floridanus applying total transcriptome sequencing},
  series = {BMC Genomics},
  volume    = {16},
  journal   = {BMC Genomics},
  number    = {540},
  doi       = {10.1186/s12864-015-1748-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125279},
  year      = {2015},
  abstract  = {Background Defence mechanisms of organisms are shaped by their lifestyle, environment and pathogen pressure. Carpenter ants are social insects which live in huge colonies comprising genetically closely related individuals in high densities within nests. This lifestyle potentially facilitates the rapid spread of pathogens between individuals. In concert with their innate immune system, social insects may apply external immune defences to manipulate the microbial community among individuals and within nests. Additionally, carpenter ants carry a mutualistic intracellular and obligate endosymbiotic bacterium, possibly maintained and regulated by the innate immune system. Thus, different selective forces could shape internal immune defences of Camponotus floridanus. Results The immune gene repertoire of C. floridanus was investigated by re-evaluating its genome sequence combined with a full transcriptome analysis of immune challenged and control animals using Illumina sequencing. The genome was re-annotated by mapping transcriptome reads and masking repeats. A total of 978 protein sequences were characterised further by annotating functional domains, leading to a change in their original annotation regarding function and domain composition in about 8 \% of all proteins. Based on homology analysis with key components of major immune pathways of insects, the C. floridanus immune-related genes were compared to those of Drosophila melanogaster, Apis mellifera, and other hymenoptera. This analysis revealed that overall the immune system of carpenter ants comprises many components found in these insects. In addition, several C. floridanus specific genes of yet unknown functions but which are strongly induced after immune challenge were discovered. In contrast to solitary insects like Drosophila or the hymenopteran Nasonia vitripennis, the number of genes encoding pattern recognition receptors specific for bacterial peptidoglycan (PGN) and a variety of known antimicrobial peptide (AMP) genes is lower in C. floridanus. The comparative analysis of gene expression post immune-challenge in different developmental stages of C. floridanus suggests a stronger induction of immune gene expression in larvae in comparison to adults. Conclusions The comparison of the immune system of C. floridanus with that of other insects revealed the presence of a broad immune repertoire. However, the relatively low number of PGN recognition proteins and AMPs, the identification of Camponotus specific putative immune genes, and stage specific differences in immune gene regulation reflects Camponotus specific evolution including adaptations to its lifestyle.},
  language  = {en}
}
@article{NaseemKunzDandekar2014,
  author    = {Naseem, Muhammad and Kunz, Meik and Dandekar, Thomas},
  title     = {Probing the unknowns in cytokinin-mediated immune defense in Arabidopsis with systems biology approaches},
  series = {Bioinformatics and Biology Insights},
  volume    = {8},
  journal   = {Bioinformatics and Biology Insights},
  issn      = {1177-9322},
  doi       = {10.4137/bbi.s13462},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120199},
  pages     = {35-44},
  year      = {2014},
  abstract  = {Plant hormones involving salicylic acid (SA), jasmonic acid (JA), ethylene (Et), and auxin, gibberellins, and abscisic acid (ABA) are known to regulate host immune responses. However, plant hormone cytokinin has the potential to modulate defense signaling including SA and JA. It promotes plant pathogen and herbivore resistance; underlying mechanisms are still unknown. Using systems biology approaches, we unravel hub points of immune interaction mediated by cytokinin signaling in Arabidopsis. High-confidence Arabidopsis protein-protein interactions (PPI) are coupled to changes in cytokinin-mediated gene expression. Nodes of the cellular interactome that are enriched in immune functions also reconstitute sub-networks. Topological analyses and their specific immunological relevance lead to the identification of functional hubs in cellular interactome. We discuss our identified immune hubs in light of an emerging model of cytokinin-mediated immune defense against pathogen infection in plants.},
  language  = {en}
}
@article{NaseemSrivastavaDandekar2014,
  author    = {Naseem, Muhammad and Srivastava, Mugdha and Dandekar, Thomas},
  title     = {Stem-cell-triggered immunity safeguards cytokinin enriched plant shoot apexes from pathogen infection},
  series = {Frontiers in Plant Science},
  volume    = {5},
  journal   = {Frontiers in Plant Science},
  issn      = {1664-462X},
  doi       = {10.3389/fpls.2014.00588},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118247},
  pages     = {588},
  year      = {2014},
  abstract  = {Intricate mechanisms discriminate between friends and foes in plants. Plant organs deploy overlapping and distinct protection strategies. Despite vulnerability to a plethora of pathogens, the growing tips of plants grow bacteria free. The shoot apical meristem (SAM) is among three stem cells niches, a self-renewable reservoir for the future organogenesis of leaf, stem, and flowers. How plants safeguard this high value growth target from infections was not known until now. Recent reports find the stem cell secreted 12-amino acid peptide CLV3p (CLAVATA3 peptide) is perceived by FLS2 (FLAGELLIN SENSING 2) receptor and activates the transcription of immunity and defense marker genes. No infection in the SAM of wild type plants and bacterial infection in clv3 and fls2 mutants illustrate this natural protection against infections. Cytokinins (CKs) are enriched in the SAM and regulate meristem activities by their involvement in stem cell signaling networks. Auxin mediates plant susceptibility to pathogen infections while CKs boost plant immunity. Here, in addition to the stem-cell-triggered immunity we also highlight a potential link between CK signaling and CLV3p mediated immune response in the SAM.},
  language  = {en}
}
@article{AhmedZeeshanHuberetal.2014,
  author    = {Ahmed, Zeeshan and Zeeshan, Saman and Huber, Claudia and Hensel, Michael and Schomburg, Dietmar and M{\"u}nch, Richard and Eylert, Eva and Eisenreich, Wolfgang and Dandekar, Thomas},
  title     = {'Isotopo' a database application for facile analysis and management of mass isotopomer data},
  series = {Database},
  volume    = {2014},
  journal   = {Database},
  number    = {bau077},
  doi       = {10.1093/database/bau077},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120102},
  year      = {2014},
  abstract  = {The composition of stable-isotope labelled isotopologues/isotopomers in metabolic products can be measured by mass spectrometry and supports the analysis of pathways and fluxes. As a prerequisite, the original mass spectra have to be processed, managed and stored to rapidly calculate, analyse and compare isotopomer enrichments to study, for instance, bacterial metabolism in infection. For such applications, we provide here the database application 'Isotopo'. This software package includes (i) a database to store and process isotopomer data, (ii) a parser to upload and translate different data formats for such data and (iii) an improved application to process and convert signal intensities from mass spectra of \(^{13}C\)-labelled metabolites such as tertbutyldimethylsilyl-derivatives of amino acids. Relative mass intensities and isotopomer distributions are calculated applying a partial least square method with iterative refinement for high precision data. The data output includes formats such as graphs for overall enrichments in amino acids. The package is user-friendly for easy and robust data management of multiple experiments.},
  language  = {en}
}
@article{NaseemDandekar2012,
  author    = {Naseem, Muhammad and Dandekar, Thomas},
  title     = {The Role of Auxin-Cytokinin Antagonism in Plant-Pathogen Interactions},
  series = {PLOS Pathogens},
  volume    = {8},
  journal   = {PLOS Pathogens},
  number    = {11},
  doi       = {10.1371/journal.ppat.1003026},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131901},
  pages     = {e1003026},
  year      = {2012},
  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{BugaScholzKumaretal.2012,
  author    = {Buga, Ana-Maria and Scholz, Claus J{\"u}rgen and Kumar, Senthil and Herndon, James G. and Alexandru, Dragos and Cojocaru, Gabriel Radu and Dandekar, Thomas and Popa-Wagner, Aurel},
  title     = {Identification of New Therapeutic Targets by Genome-Wide Analysis of Gene Expression in the Ipsilateral Cortex of Aged Rats after Stroke},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {12},
  doi       = {10.1371/journal.pone.0050985},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130657},
  pages     = {e50985},
  year      = {2012},
  abstract  = {Background: Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions. Methodology/Principal Findings: We employed the Affymetrix platform to analyze the whole-gene transcriptome following temporary ligation of the middle cerebral artery in aged and young rats. The correspondence, heat map, and dendrogram analyses independently suggest a differential, age-group-specific behaviour of major gene clusters after stroke. Overall, the pattern of gene expression strongly suggests that the response of the aged rat brain is qualitatively rather than quantitatively different from the young, i.e. the total number of regulated genes is comparable in the two age groups, but the aged rats had great difficulty in mounting a timely response to stroke. Our study indicates that four genes related to neuropathic syndrome, stress, anxiety disorders and depression (Acvr1c, Cort, Htr2b and Pnoc) may have impaired response to stroke in aged rats. New therapeutic options in aged rats may also include Calcrl, Cyp11b1, Prcp, Cebpa, Cfd, Gpnmb, Fcgr2b, Fcgr3a, Tnfrsf26, Adam 17 and Mmp14. An unexpected target is the enzyme 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 in aged rats, a key enzyme in the cholesterol synthesis pathway. Post-stroke axonal growth was compromised in both age groups. Conclusion/Significance: We suggest that a multi-stage, multimodal treatment in aged animals may be more likely to produce positive results. Such a therapeutic approach should be focused on tissue restoration but should also address other aspects of patient post-stroke therapy such as neuropathic syndrome, stress, anxiety disorders, depression, neurotransmission and blood pressure.},
  language  = {en}
}
@article{KarlDandekar2013,
  author    = {Karl, Stefan and Dandekar, Thomas},
  title     = {Jimena: Efficient computing and system state identification for genetic regulatory networks},
  series = {BMC Bioinformatics},
  volume    = {14},
  journal   = {BMC Bioinformatics},
  doi       = {10.1186/1471-2105-14-306},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128671},
  year      = {2013},
  abstract  = {Background: Boolean networks capture switching behavior of many naturally occurring regulatory networks. For semi-quantitative modeling, interpolation between ON and OFF states is necessary. The high degree polynomial interpolation of Boolean genetic regulatory networks (GRNs) in cellular processes such as apoptosis or proliferation allows for the modeling of a wider range of node interactions than continuous activator-inhibitor models, but suffers from scaling problems for networks which contain nodes with more than ~10 inputs. Many GRNs from literature or new gene expression experiments exceed those limitations and a new approach was developed. Results: (i) As a part of our new GRN simulation framework Jimena we introduce and setup Boolean-tree-based data structures; (ii) corresponding algorithms greatly expedite the calculation of the polynomial interpolation in almost all cases, thereby expanding the range of networks which can be simulated by this model in reasonable time. (iii) Stable states for discrete models are efficiently counted and identified using binary decision diagrams. As application example, we show how system states can now be sampled efficiently in small up to large scale hormone disease networks (Arabidopsis thaliana development and immunity, pathogen Pseudomonas syringae and modulation by cytokinins and plant hormones). Conclusions: Jimena simulates currently available GRNs about 10-100 times faster than the previous implementation of the polynomial interpolation model and even greater gains are achieved for large scale-free networks. This speed-up also facilitates a much more thorough sampling of continuous state spaces which may lead to the identification of new stable states. Mutants of large networks can be constructed and analyzed very quickly enabling new insights into network robustness and behavior.},
  language  = {en}
}
@article{PachelMathesBayeretal.2013,
  author    = {Pachel, Christina and Mathes, Denise and Bayer, Barbara and Dienesch, Charlotte and Wangorsch, Gaby and Heitzmann, Wolfram and Lang, Isabell and Ardehali, Hossein and Ertl, Georg and Dandekar, Thomas and Wajant, Harald and Frantz, Stefan},
  title     = {Exogenous Administration of a Recombinant Variant of TWEAK Impairs Healing after Myocardial Infarction by Aggravation of Inflammation},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {11},
  doi       = {10.1371/journal.pone.0078938},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129889},
  pages     = {e78938},
  year      = {2013},
  abstract  = {Background: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factorinducible 14 (Fn14) are upregulated after myocardial infarction (MI) in both humans and mice. They modulate inflammation and the extracellular matrix, and could therefore be important for healing and remodeling after MI. However, the function of TWEAK after MI remains poorly defined. Methods and results: Following ligation of the left coronary artery, mice were injected twice per week with a recombinant human serum albumin conjugated variant of TWEAK (HSA-Flag-TWEAK), mimicking the activity of soluble TWEAK. Treatment with HSA-Flag-TWEAK resulted in significantly increased mortality in comparison to the placebo group due to myocardial rupture. Infarct size, extracellular matrix remodeling, and apoptosis rates were not different after MI. However, HSA-Flag-TWEAK treatment increased infiltration of proinflammatory cells into the myocardium. Accordingly, depletion of neutrophils prevented cardiac ruptures without modulating all-cause mortality. Conclusion: Treatment of mice with HSA-Flag-TWEAK induces myocardial healing defects after experimental MI. This is mediated by an exaggerated neutrophil infiltration into the myocardium.},
  language  = {en}
}
@unpublished{Dandekar2007,
  author    = {Dandekar, Thomas},
  title     = {Some general system properties of a living observer and the environment he explores},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33537},
  year      = {2007},
  abstract  = {In a nice assay published in Nature in 1993 the physicist Richard God III started from a human observer and made a number of witty conclusions about our future prospects giving estimates for the existence of the Berlin Wall, the human race and all the rest of the universe. In the same spirit, we derive implications for "the meaning of life, the universe and all the rest" from few principles. Adams´ absurd answer "42" tells the lesson "garbage in / garbage out" - or suggests that the question is non calculable. We show that experience of "meaning" and to decide fundamental questions which can not be decided by formal systems imply central properties of life: Ever higher levels of internal representation of the world and an escalating tendency to become more complex. An observer, "collecting observations" and three measures for complexity are examined. A theory on living systems is derived focussing on their internal representation of information. Living systems are more complex than Kolmogorov complexity ("life is NOT simple") and overcome decision limits (G{\"o}del theorem) for formal systems as illustrated for cell cycle. Only a world with very fine tuned environments allows life. Such a world is itself rather complex and hence excessive large in its space of different states - a living observer has thus a high probability to reside in a complex and fine tuned universe.},
  subject      = {Komplex <Algebra>},
  language  = {en}
}
@article{Dandekar1986,
  author    = {Dandekar, Thomas},
  title     = {Offenlegungsschrift ({\"u}ber einen Biosensor)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31683},
  year      = {1986},
  abstract  = {No abstract available},
  language  = {de}
}
@misc{Dandekar1990,
  author    = {Dandekar, Thomas},
  title     = {Hefezellen - ein gutes Modell f{\"u}r h{\"o}here Zellen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29726},
  year      = {1990},
  abstract  = {No abstract available},
  language  = {de}
}
@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{DandekarRibesTollervey1989,
  author    = {Dandekar, Thomas and Ribes, V. and Tollervey, David},
  title     = {Schizosaccharomyces pombe U4 small nuclear RNA closely resembles vertebrate U4 and is required for growth},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29771},
  year      = {1989},
  abstract  = {No abstract available},
  language  = {en}
}
@misc{Dandekar1991,
  author    = {Dandekar, Thomas},
  title     = {Yeast U3 localization and correct sequence (snR17a) and promotor activity (snR17b) identified by homology search},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29781},
  year      = {1991},
  abstract  = {No abstract available},
  language  = {en}
}
@article{DandekarSibbald1990,
  author    = {Dandekar, Thomas and Sibbald, Peter R.},
  title     = {Trans-splicing of pre-mRNA is predicted to occur in a wide range of organisms including vertebrates},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29798},
  year      = {1990},
  abstract  = {No abstract available},
  language  = {en}
}
@article{SchultzMetznerDandekaretal.1986,
  author    = {Schultz, R{\"u}diger and Metzner, Katharina and Dandekar, Thomas and Gramsch, Christian},
  title     = {Opiates induce long-term increases in prodynorphin derived peptide levels in the guinea-pig myenteric plexus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29809},
  year      = {1986},
  abstract  = {No abstract available},
  language  = {en}
}
@article{DandekarTollervey1991,
  author    = {Dandekar, Thomas and Tollervey, D.},
  title     = {Thirty-three nucleotides of 5' flanking sequence including the TATA box are necessary and sufficient for efficient U2 snRNA transcription in Schizosaccharomycespombe},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29959},
  year      = {1991},
  abstract  = {No abstract available},
  language  = {en}
}
@misc{DandekarArgos1992,
  author    = {Dandekar, Thomas and Argos, Patrick},
  title     = {A novel heterodimeric cysteine protease is required for interleukin 1ß processing in monocytes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29986},
  year      = {1992},
  abstract  = {No abstract available},
  language  = {en}
}
@article{DandekarTollervey1992,
  author    = {Dandekar, Thomas and Tollervey, David},
  title     = {Mutational analysis of Schizosaccharomyces pombe U4 snRNA by plasmid exchange},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29969},
  year      = {1992},
  abstract  = {No abstract available},
  language  = {en}
}
@inproceedings{DandekarArgos1993,
  author    = {Dandekar, Thomas and Argos, P.},
  title     = {Genetic algorithms as a new tool to study protein stability},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29990},
  year      = {1993},
  abstract  = {No abstract available},
  language  = {en}
}
@article{DandekarStripeckeGrayetal.1991,
  author    = {Dandekar, Thomas and Stripecke, Renata and Gray, Nicola K. and Goossen, Britta and Constable, Anne and Johansson, Hans E. and Hentze, Matthias W.},
  title     = {Identification of a novel iron-responsive element in murine and human erythroid \(\delta\)-aminolevulinic acid synthase mRNA},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29929},
  year      = {1991},
  abstract  = {No abstract available},
  language  = {en}
}
@misc{DandekarArgos1993,
  author    = {Dandekar, Thomas and Argos, P.},
  title     = {Drug assay using antibody mimics made by molecular imprinting},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30003},
  year      = {1993},
  abstract  = {No abstract available},
  language  = {en}
}
@article{DandekarArgos1992,
  author    = {Dandekar, Thomas and Argos, P.},
  title     = {Potential of genetic algorithms in protein folding and protein engineering simulations},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29974},
  year      = {1992},
  abstract  = {No abstract available},
  language  = {de}
}
@misc{DandekarArgos1992,
  author    = {Dandekar, Thomas and Argos, Patrick},
  title     = {Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29814},
  year      = {1992},
  abstract  = {No abstract available},
  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{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}
}
@misc{DandekarArgos1994,
  author    = {Dandekar, Thomas and Argos, P.},
  title     = {Three-dimensional structure of the 67k N-terminal Fragment of E.coli DNA Topoisomerase I},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29836},
  year      = {1994},
  abstract  = {No abstract available},
  language  = {en}
}
@article{DandekarArgos1994,
  author    = {Dandekar, Thomas and Argos, P.},
  title     = {Folding the main chain of small proteins with the genetic algorithm},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29847},
  year      = {1994},
  abstract  = {No abstract available},
  language  = {de}
}
@article{DandekarTollervey1993,
  author    = {Dandekar, Thomas and Tollervey, David},
  title     = {Identification and functional analysis of a novel yeast small nucleolar RNA},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29850},
  year      = {1993},
  abstract  = {No abstract available},
  language  = {en}
}