@unpublished{Dandekar2023, author = {Dandekar, Thomas}, title = {Analysing the phase space of the standard model and its basic four forces from a qubit phase transition perspective: implications for large-scale structure generation and early cosmological events}, doi = {10.25972/OPUS-29858}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-298580}, pages = {42}, year = {2023}, abstract = {The phase space for the standard model of the basic four forces for n quanta includes all possible ensemble combinations of their quantum states m, a total of n**m states. Neighbor states reach according to transition possibilities (S-matrix) with emergent time from entropic ensemble gradients. We replace the "big bang" by a condensation event (interacting qubits become decoherent) and inflation by a crystallization event - the crystal unit cell guarantees same symmetries everywhere. Interacting qubits solidify and form a rapidly growing domain where the n**m states become separated ensemble states, rising long-range forces stop ultimately further growth. After that very early events, standard cosmology with the hot fireball model takes over. Our theory agrees well with lack of inflation traces in cosmic background measurements, large-scale structure of voids and filaments, supercluster formation, galaxy formation, dominance of matter and life-friendliness. We prove qubit interactions to be 1,2,4 or 8 dimensional (agrees with E8 symmetry of our universe). Repulsive forces at ultrashort distances result from quantization, long-range forces limit crystal growth. Crystals come and go in the qubit ocean. This selects for the ability to lay seeds for new crystals, for self-organization and life-friendliness. We give energy estimates for free qubits vs bound qubits, misplacements in the qubit crystal and entropy increase during qubit decoherence / crystal formation. Scalar fields for color interaction and gravity derive from the permeating qubit-interaction field. Hence, vacuum energy gets low only inside the qubit crystal. Condensed mathematics may advantageously model free / bound qubits in phase space.}, language = {en} } @article{BencurovaShityakovSchaacketal.2022, author = {Bencurova, Elena and Shityakov, Sergey and Schaack, Dominik and Kaltdorf, Martin and Sarukhanyan, Edita and Hilgarth, Alexander and Rath, Christin and Montenegro, Sergio and Roth, G{\"u}nter and Lopez, Daniel and Dandekar, Thomas}, title = {Nanocellulose composites as smart devices with chassis, light-directed DNA Storage, engineered electronic properties, and chip integration}, series = {Frontiers in Bioengineering and Biotechnology}, volume = {10}, journal = {Frontiers in Bioengineering and Biotechnology}, issn = {2296-4185}, doi = {10.3389/fbioe.2022.869111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283033}, year = {2022}, abstract = {The rapid development of green and sustainable materials opens up new possibilities in the field of applied research. Such materials include nanocellulose composites that can integrate many components into composites and provide a good chassis for smart devices. In our study, we evaluate four approaches for turning a nanocellulose composite into an information storage or processing device: 1) nanocellulose can be a suitable carrier material and protect information stored in DNA. 2) Nucleotide-processing enzymes (polymerase and exonuclease) can be controlled by light after fusing them with light-gating domains; nucleotide substrate specificity can be changed by mutation or pH change (read-in and read-out of the information). 3) Semiconductors and electronic capabilities can be achieved: we show that nanocellulose is rendered electronic by iodine treatment replacing silicon including microstructures. Nanocellulose semiconductor properties are measured, and the resulting potential including single-electron transistors (SET) and their properties are modeled. Electric current can also be transported by DNA through G-quadruplex DNA molecules; these as well as classical silicon semiconductors can easily be integrated into the nanocellulose composite. 4) To elaborate upon miniaturization and integration for a smart nanocellulose chip device, we demonstrate pH-sensitive dyes in nanocellulose, nanopore creation, and kinase micropatterning on bacterial membranes as well as digital PCR micro-wells. Future application potential includes nano-3D printing and fast molecular processors (e.g., SETs) integrated with DNA storage and conventional electronics. This would also lead to environment-friendly nanocellulose chips for information processing as well as smart nanocellulose composites for biomedical applications and nano-factories.}, language = {en} } @article{CaliskanCrouchGiddinsetal.2022, author = {Caliskan, Aylin and Crouch, Samantha A. W. and Giddins, Sara and Dandekar, Thomas and Dangwal, Seema}, title = {Progeria and aging — Omics based comparative analysis}, series = {Biomedicines}, volume = {10}, journal = {Biomedicines}, number = {10}, issn = {2227-9059}, doi = {10.3390/biomedicines10102440}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-289868}, year = {2022}, abstract = {Since ancient times aging has also been regarded as a disease, and humankind has always strived to extend the natural lifespan. Analyzing the genes involved in aging and disease allows for finding important indicators and biological markers for pathologies and possible therapeutic targets. An example of the use of omics technologies is the research regarding aging and the rare and fatal premature aging syndrome progeria (Hutchinson-Gilford progeria syndrome, HGPS). In our study, we focused on the in silico analysis of differentially expressed genes (DEGs) in progeria and aging, using a publicly available RNA-Seq dataset (GEO dataset GSE113957) and a variety of bioinformatics tools. Despite the GSE113957 RNA-Seq dataset being well-known and frequently analyzed, the RNA-Seq data shared by Fleischer et al. is far from exhausted and reusing and repurposing the data still reveals new insights. By analyzing the literature citing the use of the dataset and subsequently conducting a comparative analysis comparing the RNA-Seq data analyses of different subsets of the dataset (healthy children, nonagenarians and progeria patients), we identified several genes involved in both natural aging and progeria (KRT8, KRT18, ACKR4, CCL2, UCP2, ADAMTS15, ACTN4P1, WNT16, IGFBP2). Further analyzing these genes and the pathways involved indicated their possible roles in aging, suggesting the need for further in vitro and in vivo research. In this paper, we (1) compare "normal aging" (nonagenarians vs. healthy children) and progeria (HGPS patients vs. healthy children), (2) enlist genes possibly involved in both the natural aging process and progeria, including the first mention of IGFBP2 in progeria, (3) predict miRNAs and interactomes for WNT16 (hsa-mir-181a-5p), UCP2 (hsa-mir-26a-5p and hsa-mir-124-3p), and IGFBP2 (hsa-mir-124-3p, hsa-mir-126-3p, and hsa-mir-27b-3p), (4) demonstrate the compatibility of well-established R packages for RNA-Seq analysis for researchers interested but not yet familiar with this kind of analysis, and (5) present comparative proteomics analyses to show an association between our RNA-Seq data analyses and corresponding changes in protein expression.}, language = {en} } @article{GuptaMinochaThapaetal.2022, author = {Gupta, Shishir K. and Minocha, Rashmi and Thapa, Prithivi Jung and Srivastava, Mugdha and Dandekar, Thomas}, title = {Role of the pangolin in origin of SARS-CoV-2: an evolutionary perspective}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {16}, issn = {1422-0067}, doi = {10.3390/ijms23169115}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285995}, year = {2022}, abstract = {After the recent emergence of SARS-CoV-2 infection, unanswered questions remain related to its evolutionary history, path of transmission or divergence and role of recombination. There is emerging evidence on amino acid substitutions occurring in key residues of the receptor-binding domain of the spike glycoprotein in coronavirus isolates from bat and pangolins. In this article, we summarize our current knowledge on the origin of SARS-CoV-2. We also analyze the host ACE2-interacting residues of the receptor-binding domain of spike glycoprotein in SARS-CoV-2 isolates from bats, and compare it to pangolin SARS-CoV-2 isolates collected from Guangdong province (GD Pangolin-CoV) and Guangxi autonomous regions (GX Pangolin-CoV) of South China. Based on our comparative analysis, we support the view that the Guangdong Pangolins are the intermediate hosts that adapted the SARS-CoV-2 and represented a significant evolutionary link in the path of transmission of SARS-CoV-2 virus. We also discuss the role of intermediate hosts in the origin of Omicron.}, language = {en} } @article{FathyDarwishAbdelhamidetal.2022, author = {Fathy, Moustafa and Darwish, Mostafa A. and Abdelhamid, Al-Shaimaa M. and Alrashedy, Gehad M. and Othman, Othman Ali and Naseem, Muhammad and Dandekar, Thomas and Othman, Eman M.}, title = {Kinetin ameliorates cisplatin-induced hepatotoxicity and lymphotoxicity via attenuating oxidative damage, cell apoptosis and inflammation in rats}, series = {Biomedicines}, volume = {10}, journal = {Biomedicines}, number = {7}, issn = {2227-9059}, doi = {10.3390/biomedicines10071620}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281686}, year = {2022}, abstract = {Though several previous studies reported the in vitro and in vivo antioxidant effect of kinetin (Kn), details on its action in cisplatin-induced toxicity are still scarce. In this study we evaluated, for the first time, the effects of kinetin in cisplatin (cp)- induced liver and lymphocyte toxicity in rats. Wistar male albino rats were divided into nine groups: (i) the control (C), (ii) groups 2,3 and 4, which received 0.25, 0.5 and 1 mg/kg kinetin for 10 days; (iii) the cisplatin (cp) group, which received a single intraperitoneal injection of CP (7.0 mg/kg); and (iv) groups 6, 7, 8 and 9, which received, for 10 days, 0.25, 0.5 and 1 mg/kg kinetin or 200 mg/kg vitamin C, respectively, and Cp on the fourth day. CP-injected rats showed a significant impairment in biochemical, oxidative stress and inflammatory parameters in hepatic tissue and lymphocytes. PCR showed a profound increase in caspase-3, and a significant decline in AKT gene expression. Intriguingly, Kn treatment restored the biochemical, redox status and inflammatory parameters. Hepatic AKT and caspase-3 expression as well as CD95 levels in lymphocytes were also restored. In conclusion, Kn mitigated oxidative imbalance, inflammation and apoptosis in CP-induced liver and lymphocyte toxicity; therefore, it can be considered as a promising therapy.}, 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} } @article{OsmanogluKhaledAlSeiariAlKhoorietal.2021, author = {Osmanoglu, {\"O}zge and Khaled AlSeiari, Mariam and AlKhoori, Hasa Abduljaleel and Shams, Shabana and Bencurova, Elena and Dandekar, Thomas and Naseem, Muhammad}, title = {Topological Analysis of the Carbon-Concentrating CETCH Cycle and a Photorespiratory Bypass Reveals Boosted CO\(_2\)-Sequestration by Plants}, series = {Frontiers in Bioengineering and Biotechnology}, volume = {9}, journal = {Frontiers in Bioengineering and Biotechnology}, issn = {2296-4185}, doi = {10.3389/fbioe.2021.708417}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249260}, year = {2021}, abstract = {Synthetically designed alternative photorespiratory pathways increase the biomass of tobacco and rice plants. Likewise, some in planta-tested synthetic carbon-concentrating cycles (CCCs) hold promise to increase plant biomass while diminishing atmospheric carbon dioxide burden. Taking these individual contributions into account, we hypothesize that the integration of bypasses and CCCs will further increase plant productivity. To test this in silico, we reconstructed a metabolic model by integrating photorespiration and photosynthesis with the synthetically designed alternative pathway 3 (AP3) enzymes and transporters. We calculated fluxes of the native plant system and those of AP3 combined with the inhibition of the glycolate/glycerate transporter by using the YANAsquare package. The activity values corresponding to each enzyme in photosynthesis, photorespiration, and for synthetically designed alternative pathways were estimated. Next, we modeled the effect of the crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA cycle (CETCH), which is a set of natural and synthetically designed enzymes that fix CO₂ manifold more than the native Calvin-Benson-Bassham (CBB) cycle. We compared estimated fluxes across various pathways in the native model and under an introduced CETCH cycle. Moreover, we combined CETCH and AP3-w/plgg1RNAi, and calculated the fluxes. We anticipate higher carbon dioxide-harvesting potential in plants with an AP3 bypass and CETCH-AP3 combination. We discuss the in vivo implementation of these strategies for the improvement of C3 plants and in natural high carbon harvesters.}, 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{KaltdorfSchulzeHelmprobstetal.2017, author = {Kaltdorf, Kristin Verena and Schulze, Katja and Helmprobst, Frederik and Kollmannsberger, Philip and Dandekar, Thomas and Stigloher, Christian}, title = {Fiji macro 3D ART VeSElecT: 3D automated reconstruction tool for vesicle structures of electron tomograms}, series = {PLoS Computational Biology}, volume = {13}, journal = {PLoS Computational Biology}, number = {1}, doi = {10.1371/journal.pcbi.1005317}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172112}, year = {2017}, abstract = {Automatic image reconstruction is critical to cope with steadily increasing data from advanced microscopy. We describe here the Fiji macro 3D ART VeSElecT which we developed to study synaptic vesicles in electron tomograms. We apply this tool to quantify vesicle properties (i) in embryonic Danio rerio 4 and 8 days past fertilization (dpf) and (ii) to compare Caenorhabditis elegans N2 neuromuscular junctions (NMJ) wild-type and its septin mutant (unc-59(e261)). We demonstrate development-specific and mutant-specific changes in synaptic vesicle pools in both models. We confirm the functionality of our macro by applying our 3D ART VeSElecT on zebrafish NMJ showing smaller vesicles in 8 dpf embryos then 4 dpf, which was validated by manual reconstruction of the vesicle pool. Furthermore, we analyze the impact of C. elegans septin mutant unc-59(e261) on vesicle pool formation and vesicle size. Automated vesicle registration and characterization was implemented in Fiji as two macros (registration and measurement). This flexible arrangement allows in particular reducing false positives by an optional manual revision step. Preprocessing and contrast enhancement work on image-stacks of 1nm/pixel in x and y direction. Semi-automated cell selection was integrated. 3D ART VeSElecT removes interfering components, detects vesicles by 3D segmentation and calculates vesicle volume and diameter (spherical approximation, inner/outer diameter). Results are collected in color using the RoiManager plugin including the possibility of manual removal of non-matching confounder vesicles. Detailed evaluation considered performance (detected vesicles) and specificity (true vesicles) as well as precision and recall. We furthermore show gain in segmentation and morphological filtering compared to learning based methods and a large time gain compared to manual segmentation. 3D ART VeSElecT shows small error rates and its speed gain can be up to 68 times faster in comparison to manual annotation. Both automatic and semi-automatic modes are explained including a tutorial.}, 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} }