12640
2015
eng
3
10
article
1
2016-01-31
--
--
Hypotonic Activation of the Myo-Inositol Transporter SLC5A3 in HEK293 Cells Probed by Cell Volumetry, Confocal and Super-Resolution Microscopy
Swelling-activated pathways for myo-inositol, one of the most abundant organic osmolytes in mammalian cells, have not yet been identified. The present study explores the SLC5A3 protein as a possible transporter of myo-inositol in hyponically swollen HEK293 cells. To address this issue, we examined the relationship between the hypotonicity-induced changes in plasma membrane permeability to myo-inositol Pino [m/s] and expression/localization of SLC5A3. Pino values were determined by cell volumetry over a wide tonicity range (100–275 mOsm) in myo-inositol-substituted solutions. While being negligible under mild hypotonicity (200–275 mOsm), Pino grew rapidly at osmolalities below 200 mOsm to reach a maximum of ∼3 nm/s at 100–125 mOsm, as indicated by fast cell swelling due to myo-inositol influx. The increase in Pino resulted most likely from the hypotonicity-mediated incorporation of cytosolic SLC5A3 into the plasma membrane, as revealed by confocal fluorescence microscopy of cells expressing EGFP-tagged SLC5A3 and super-resolution imaging of immunostained SLC5A3 by direct stochastic optical reconstruction microscopy (dSTORM). dSTORM in hypotonic cells revealed a surface density of membrane-associated SLC5A3 proteins of 200–2000 localizations/μm2. Assuming SLC5A3 to be the major path for myo-inositol, a turnover rate of 80–800 myo-inositol molecules per second for a single transporter protein was estimated from combined volumetric and dSTORM data. Hypotonic stress also caused a significant upregulation of SLC5A3 gene expression as detected by semiquantitative RT-PCR and Western blot analysis. In summary, our data provide first evidence for swelling-mediated activation of SLC5A3 thus suggesting a functional role of this transporter in hypotonic volume regulation of mammalian cells.
PLoS One
10.1371/journal.pone.0119990
urn:nbn:de:bvb:20-opus-126408
PLoS ONE 10(3): e0119990. doi:10.1371/journal.pone.0119990
Joseph Andronic
Ryo Shirakashi
Simone U. Pickel
Katherine M. Westerling
Teresa Klein
Thorge Holm
Markus Sauer
Vladimir L. Sukhorukov
eng
uncontrolled
electrolytes
eng
uncontrolled
isotonic
eng
uncontrolled
membrane proteins
eng
uncontrolled
cell membranes
eng
uncontrolled
hypotonic
eng
uncontrolled
hypotonic solutions
eng
uncontrolled
tonicity
eng
uncontrolled
permeability
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2015
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12640/Sukhurokov_journal.pone.0119990.pdf
14795
2016
eng
baw146
2016
article
1
2017-05-05
--
--
TBro: visualization and management of de novo transcriptomes
RNA sequencing (RNA-seq) has become a powerful tool to understand molecular mechanisms and/or developmental programs. It provides a fast, reliable and cost-effective method to access sets of expressed elements in a qualitative and quantitative manner. Especially for non-model organisms and in absence of a reference genome, RNA-seq data is used to reconstruct and quantify transcriptomes at the same time. Even SNPs, InDels, and alternative splicing events are predicted directly from the data without having a reference genome at hand. A key challenge, especially for non-computational personnal, is the management of the resulting datasets, consisting of different data types and formats. Here, we present TBro, a flexible de novo transcriptome browser, tackling this challenge. TBro aggregates sequences, their annotation, expression levels as well as differential testing results. It provides an easy-to-use interface to mine the aggregated data and generate publication-ready visualizations. Additionally, it supports users with an intuitive cart system, that helps collecting and analysing biological meaningful sets of transcripts. TBro’s modular architecture allows easy extension of its functionalities in the future. Especially, the integration of new data types such as proteomic quantifications or array-based gene expression data is straightforward. Thus, TBro is a fully featured yet flexible transcriptome browser that supports approaching complex biological questions and enhances collaboration of numerous researchers.
Database
10.1093/database/baw146
urn:nbn:de:bvb:20-opus-147954
Database, 2016, 1–7 doi: 10.1093/database/baw146
Markus J. Ankenbrand
Lorenz Weber
Dirk Becker
Frank Förster
Felix Bemm
eng
uncontrolled
database
Datenverarbeitung; Informatik
open_access
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2016
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14795/Ankenbrand_baw146.pdf
15200
2015
eng
e0126986
5
10
article
1
2017-07-24
--
--
Genome-Wide Association Analyses Point to Candidate Genes for Electric Shock Avoidance in Drosophila melanogaster
Electric shock is a common stimulus for nociception-research and the most widely used reinforcement in aversive associative learning experiments. Yet, nothing is known about the mechanisms it recruits at the periphery. To help fill this gap, we undertook a genome-wide association analysis using 38 inbred Drosophila melanogaster strains, which avoided shock to varying extents. We identified 514 genes whose expression levels and/or sequences covaried with shock avoidance scores. We independently scrutinized 14 of these genes using mutants, validating the effect of 7 of them on shock avoidance. This emphasizes the value of our candidate gene list as a guide for follow-up research. In addition, by integrating our association results with external protein-protein interaction data we obtained a shock avoidance- associated network of 38 genes. Both this network and the original candidate list contained a substantial number of genes that affect mechanosensory bristles, which are hairlike organs distributed across the fly's body. These results may point to a potential role for mechanosensory bristles in shock sensation. Thus, we not only provide a first list of candidate genes for shock avoidance, but also point to an interesting new hypothesis on nociceptive mechanisms.
PLoS ONE
10.1371/journal.pone.0126986
urn:nbn:de:bvb:20-opus-152006
PLoS ONE 10(5): e0126986 (2015). DOI: 10.1371/journal.pone.0126986
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Mirjam Appel
Claus-Jürgen Scholz
Tobias Müller
Marcus Dittrich
Christian König
Marie Bockstaller
Tuba Oguz
Afshin Khalili
Emmanuel Antwi-Adjei
Tamas Schauer
Carla Margulies
Hiromu Tanimoto
Ayse Yarali
eng
uncontrolled
functional analysis
eng
uncontrolled
disruption project
eng
uncontrolled
natural variation
eng
uncontrolled
complex traits
eng
uncontrolled
networks
eng
uncontrolled
behavior
eng
uncontrolled
flies
eng
uncontrolled
temperature
eng
uncontrolled
genetics
eng
uncontrolled
painful
Datenverarbeitung; Informatik
Menschliche Anatomie, Zytologie, Histologie
open_access
Institut für Humangenetik
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/15200/Appel_Plos_One.PDF
28303
2022
eng
10
article
1
--
2022-08-08
--
Nanocellulose composites as smart devices with chassis, light-directed DNA Storage, engineered electronic properties, and chip integration
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.
Frontiers in Bioengineering and Biotechnology
2296-4185
10.3389/fbioe.2022.869111
urn:nbn:de:bvb:20-opus-283033
2022-08-22T06:12:38+00:00
sword
swordwue
attachment; filename=deposit.zip
08c41da1a44f4856a12fdea55a2ce372
Frontiers in Bioengineering and Biotechnology (2022) 10:869111. DOI:10.3389/fbioe.2022.869111
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Elena Bencurova
Sergey Shityakov
Dominik Schaack
Martin Kaltdorf
Edita Sarukhanyan
Alexander Hilgarth
Christin Rath
Sergio Montenegro
Günter Roth
Daniel Lopez
Thomas Dandekar
eng
uncontrolled
nanocellulose
eng
uncontrolled
DNA storage
eng
uncontrolled
light-gated proteins
eng
uncontrolled
single-electron transistors
eng
uncontrolled
protein chip
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Institut für Informatik
Theodor-Boveri-Institut für Biowissenschaften
Import
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28303/DataSheet1.docx
https://opus.bibliothek.uni-wuerzburg.de/files/28303/fbioe-10-869111.pdf
14086
2011
eng
e16931
2
6
article
1
2016-11-25
--
--
Internal Transcribed Spacer 2 (nu ITS2 rRNA) Sequence-Structure Phylogenetics: Towards an Automated Reconstruction of the Green Algal Tree of Life
Background:
Chloroplast-encoded genes (matK and rbcL) have been formally proposed for use in DNA barcoding efforts targeting embryophytes. Extending such a protocol to chlorophytan green algae, though, is fraught with problems including non homology (matK) and heterogeneity that prevents the creation of a universal PCR toolkit (rbcL). Some have advocated the use of the nuclear-encoded, internal transcribed spacer two (ITS2) as an alternative to the traditional chloroplast markers. However, the ITS2 is broadly perceived to be insufficiently conserved or to be confounded by introgression or biparental inheritance patterns, precluding its broad use in phylogenetic reconstruction or as a DNA barcode. A growing body of evidence has shown that simultaneous analysis of nucleotide data with secondary structure information can overcome at least some of the limitations of ITS2. The goal of this investigation was to assess the feasibility of an automated, sequence-structure approach for analysis of IT2 data from a large sampling of phylum Chlorophyta.
Methodology/Principal Findings:
Sequences and secondary structures from 591 chlorophycean, 741 trebouxiophycean and 938 ulvophycean algae, all obtained from the ITS2 Database, were aligned using a sequence structure-specific scoring matrix. Phylogenetic relationships were reconstructed by Profile Neighbor-Joining coupled with a sequence structure-specific, general time reversible substitution model. Results from analyses of the ITS2 data were robust at multiple nodes and showed considerable congruence with results from published phylogenetic analyses.
Conclusions/Significance:
Our observations on the power of automated, sequence-structure analyses of ITS2 to reconstruct phylum-level phylogenies of the green algae validate this approach to assessing diversity for large sets of chlorophytan taxa. Moreover, our results indicate that objections to the use of ITS2 for DNA barcoding should be weighed against the utility of an automated, data analysis approach with demonstrated power to reconstruct evolutionary patterns for highly divergent lineages.
PLoS ONE
10.1371/journal.pone.0016931
urn:nbn:de:bvb:20-opus-140866
PLoS ONE 6(2): e16931. doi:10.1371/journal.pone.0016931
Mark A. Buchheim
Alexander Keller
Christian Koetschan
Frank Förster
Benjamin Merget
Matthias Wolf
eng
uncontrolled
RBCL Gene-sequences
eng
uncontrolled
Colonial volvocales chlorophyta
eng
uncontrolled
26S RDNA Data
eng
uncontrolled
Land plants
eng
uncontrolled
Molecular systematics
eng
uncontrolled
Secondary structure
eng
uncontrolled
Nuclear RDNA
eng
uncontrolled
DNA
eng
uncontrolled
Barcodes
eng
uncontrolled
Dasycladales chlorophyta
eng
uncontrolled
Profile distances
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14086/079_Buchheim_PLOS-ONE.PDF
13065
2012
eng
e50985
12
7
article
1
2016-03-24
--
--
Identification of New Therapeutic Targets by Genome-Wide Analysis of Gene Expression in the Ipsilateral Cortex of Aged Rats after Stroke
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.
PLoS One
10.1371/journal.pone.0050985
urn:nbn:de:bvb:20-opus-130657
PLoS ONE 7(12): e50985. doi:10.1371/journal.pone.0050985
Ana-Maria Buga
Claus Jürgen Scholz
Senthil Kumar
James G. Herndon
Dragos Alexandru
Gabriel Radu Cojocaru
Thomas Dandekar
Aurel Popa-Wagner
eng
uncontrolled
gamma
eng
uncontrolled
corticotropin-releasing hormone
eng
uncontrolled
colony-stimulating factor
eng
uncontrolled
cerebral ischemia
eng
uncontrolled
receptor
eng
uncontrolled
brain
eng
uncontrolled
protein
eng
uncontrolled
inhibitor
eng
uncontrolled
mouse
eng
uncontrolled
differentiation
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13065/journal.pone.0050985.pdf
28986
2022
eng
10
10
article
1
--
2022-09-29
--
Progeria and aging — Omics based comparative analysis
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.
Biomedicines
2227-9059
10.3390/biomedicines10102440
urn:nbn:de:bvb:20-opus-289868
2022-10-27T12:51:25+00:00
sword
swordwue
attachment; filename=deposit.zip
8853dccdf7a5377b3f24f03e236f2b91
Biomedicines (2022) 10:10, 2240. doi:10.3390/biomedicines10102440
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Aylin Caliskan
Samantha A. W. Crouch
Sara Giddins
Thomas Dandekar
Seema Dangwal
eng
uncontrolled
progeria
eng
uncontrolled
aging
eng
uncontrolled
omics
eng
uncontrolled
RNA sequencing
eng
uncontrolled
bioinformatics
eng
uncontrolled
sun exposure
eng
uncontrolled
HGPS
eng
uncontrolled
IGFBP2
eng
uncontrolled
ACKR4
eng
uncontrolled
WNT
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
Medizin und Gesundheit
open_access
Theodor-Boveri-Institut für Biowissenschaften
Import
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28986/biomedicines-10-02440-v3.pdf
18394
2019
eng
24
preprint
1
--
--
--
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
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.
urn:nbn:de:bvb:20-opus-183945
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Thomas Dandekar
eng
uncontrolled
heuristics
eng
uncontrolled
inflation
eng
uncontrolled
cosmology
eng
uncontrolled
crystallization
eng
uncontrolled
crystal growth
eng
uncontrolled
E8 symmetry
eng
uncontrolled
Hurwitz theorem
eng
uncontrolled
evolution
eng
uncontrolled
Lee Smolin
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/18394/Dandekar_Preprint_Crystal_2019.pdf
29858
2023
eng
42
preprint
1
2022-12-22
--
--
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
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.
urn:nbn:de:bvb:20-opus-298580
10.25972/OPUS-29858
publish
true
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Thomas Dandekar
eng
uncontrolled
phase space
eng
uncontrolled
cosmology
eng
uncontrolled
emergent time
eng
uncontrolled
qubit
eng
uncontrolled
phase transition
eng
uncontrolled
bit
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
General Literature
GENERAL
ASTRONOMY AND ASTROPHYSICS (For celestial mechanics, see 70F15)
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/29858/Dandekar_Bioinformatics_Standard_Model_F_Preprint.pdf
28168
2022
eng
7
10
article
1
--
2022-07-06
--
Kinetin ameliorates cisplatin-induced hepatotoxicity and lymphotoxicity via attenuating oxidative damage, cell apoptosis and inflammation in rats
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.
Biomedicines
2227-9059
10.3390/biomedicines10071620
urn:nbn:de:bvb:20-opus-281686
2022-08-03T09:59:49+00:00
sword
swordwue
attachment; filename=deposit.zip
2cd049481715d6ec27e2c2ffe2ac1da4
Biomedicines (2022) 10:7, 1620. doi:10.3390/biomedicines10071620
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Moustafa Fathy
Mostafa A. Darwish
Al-Shaimaa M. Abdelhamid
Gehad M. Alrashedy
Othman Ali Othman
Muhammad Naseem
Thomas Dandekar
Eman M. Othman
eng
uncontrolled
cisplatin
eng
uncontrolled
hepatotoxicity
eng
uncontrolled
lymphotoxicity
eng
uncontrolled
oxidative stress
eng
uncontrolled
AKT
eng
uncontrolled
CD95
eng
uncontrolled
caspase-3
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Import
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28168/biomedicines-10-01620-v3.pdf
28599
2022
eng
16
23
article
1
--
2022-08-14
--
Role of the pangolin in origin of SARS-CoV-2: an evolutionary perspective
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.
International Journal of Molecular Sciences
1422-0067
10.3390/ijms23169115
urn:nbn:de:bvb:20-opus-285995
2022-09-07T15:18:43+00:00
sword
swordwue
attachment; filename=deposit.zip
bca9fa9a8ea25bb6eda7a4a0b168d862
International Journal of Molecular Sciences (2022) 23:16, 9115. doi:10.3390/ijms23169115
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Shishir K. Gupta
Rashmi Minocha
Prithivi Jung Thapa
Mugdha Srivastava
Thomas Dandekar
eng
uncontrolled
COVID-19
eng
uncontrolled
SARS-CoV-2
eng
uncontrolled
origin
eng
uncontrolled
evolution
eng
uncontrolled
intermediate host
eng
uncontrolled
pangolin
eng
uncontrolled
mutation
eng
uncontrolled
recombination
eng
uncontrolled
adaptation
eng
uncontrolled
transmission
eng
uncontrolled
comparative sequence analysis
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Institut für Molekulare Infektionsbiologie
Theodor-Boveri-Institut für Biowissenschaften
Import
Center for Computational and Theoretical Biology
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28599/ijms-23-09115-v2.pdf
17211
2017
eng
1
13
article
1
2018-11-19
--
--
Fiji macro 3D ART VeSElecT: 3D automated reconstruction tool for vesicle structures of electron tomograms
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.
PLoS Computational Biology
10.1371/journal.pcbi.1005317
28056033
urn:nbn:de:bvb:20-opus-172112
PLoS Computational Biology (2017) 13(1):e1005317. https://doi.org/10.1371/journal.pcbi.1005317
true
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Kristin Verena Kaltdorf
Katja Schulze
Frederik Helmprobst
Philip Kollmannsberger
Thomas Dandekar
Christian Stigloher
eng
uncontrolled
Biology
eng
uncontrolled
Vesicles
eng
uncontrolled
Caenorhabditis elegans
eng
uncontrolled
Zebrafish
eng
uncontrolled
Septins
eng
uncontrolled
Synaptic vesicles
eng
uncontrolled
Neuromuscular junctions
eng
uncontrolled
Computer software
eng
uncontrolled
Synapses
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Center for Computational and Theoretical Biology
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17211/Kaltdorf_pcbi.1005317.pdf
12867
2013
eng
14
article
1
2016-03-04
--
--
Jimena: Efficient computing and system state identification for genetic regulatory networks
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.
BMC Bioinformatics
10.1186/1471-2105-14-306
urn:nbn:de:bvb:20-opus-128671
BMC Bioinformatics 2013, 14:306. doi:10.1186/1471-2105-14-306
Stefan Karl
Thomas Dandekar
eng
uncontrolled
Boolean function
eng
uncontrolled
genetic regulatory network
eng
uncontrolled
interpolation
eng
uncontrolled
stable state
eng
uncontrolled
binary decision diagram
eng
uncontrolled
Boolean tree
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12867/011_Karl_Jimena.pdf
12364
2012
eng
97-128
6
article
1
2015-12-21
--
--
Different evolutionary modifications as a guide to rewire two-component systems
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.
Bioinformatics and Biology Insights
PMC3348925
10.4137/BBI.S9356
urn:nbn:de:bvb:20-opus-123647
This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.
Bioinformatics and Biology Insights 2012:6 97–128. doi: 10.4137/BBI.S9356
Beate Krueger
Torben Friedrich
Frank Förster
Jörg Bernhardt
Roy Gross
Thomas Dandekar
eng
uncontrolled
histidine kinase
eng
uncontrolled
connector
eng
uncontrolled
Mycoplasma
eng
uncontrolled
engineering
eng
uncontrolled
promoter
eng
uncontrolled
sensor
eng
uncontrolled
response regulator
eng
uncontrolled
synthetic biology
eng
uncontrolled
sequence alignment
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12364/f_3168-BBI-Different-Evolutionary-Modifications-as-a-Guide-to-Rewire-Two-Componen.pdf_4288.pdf
13602
2015
eng
e0145478
12
10
article
1
2016-07-12
--
--
UPLC-MRM Mass Spectrometry Method for Measurement of the Coagulation Inhibitors Dabigatran and Rivaroxaban in Human Plasma and Its Comparison with Functional Assays
Introduction The fast, precise, and accurate measurement of the new generation of oral anticoagulants such as dabigatran and rivaroxaban in patients' plasma my provide important information in different clinical circumstances such as in the case of suspicion of overdose, when patients switch from existing oral anticoagulant, in patients with hepatic or renal impairment, by concomitant use of interaction drugs, or to assess anticoagulant concentration in patients' blood before major surgery. Methods Here, we describe a quick and precise method to measure the coagulation inhibitors dabigatran and rivaroxaban using ultra-performance liquid chromatography electrospray ionization-tandem mass spectrometry in multiple reactions monitoring (MRM) mode (UPLC-MRM MS). Internal standards (ISs) were added to the sample and after protein precipitation; the sample was separated on a reverse phase column. After ionization of the analytes the ions were detected using electrospray ionization-tandem mass spectrometry. Run time was 2.5 minutes per injection. Ion suppression was characterized by means of post-column infusion. Results The calibration curves of dabigatran and rivaroxaban were linear over the working range between 0.8 and 800 mu g/L (r > 0.99). Limits of detection (LOD) in the plasma matrix were 0.21 mu g/L for dabigatran and 0.34 mu g/L for rivaroxaban, and lower limits of quantification (LLOQ) in the plasma matrix were 0.46 mu g/L for dabigatran and 0.54 mu g/L for rivaroxaban. The intraassay coefficients of variation (CVs) for dabigatran and rivaroxaban were < 4% and 6%; respectively, the interassay CVs were < 6% for dabigatran and < 9% for rivaroxaban. Inaccuracy was < 5% for both substances. The mean recovery was 104.5% (range 83.8-113.0%) for dabigatran and 87.0%(range 73.6-105.4%) for rivaroxaban. No significant ion suppressions were detected at the elution times of dabigatran or rivaroxaban. Both coagulation inhibitors were stable in citrate plasma at -20 degrees C, 4 degrees C and even at RT for at least one week. A method comparison between our UPLC-MRM MS method, the commercially available automated Direct Thrombin Inhibitor assay (DTI assay) for dabigatran measurement from CoaChrom Diagnostica, as well as the automated anti-Xa assay for rivaroxaban measurement from Chromogenix both performed by ACL-TOP showed a high degree of correlation. However, UPLC-MRM MS measurement of dabigatran and rivaroxaban has a much better selectivity than classical functional assays measuring activities of various coagulation factors which are susceptible to interference by other coagulant drugs. Conclusions Overall, we developed and validated a sensitive and specific UPLC-MRM MS assay for the quick and specific measurement of dabigatran and rivaroxaban in human plasma.
PLOS ONE
10.1371/journal.pone.0145478
urn:nbn:de:bvb:20-opus-136023
PLoS ONE 10(12): e0145478. doi:10.1371/ journal.pone.0145478
Joachim Kuhn
Tatjana Gripp
Tobias Flieder
Marcus Dittrich
Doris Hendig
Jessica Busse
Cornelius Knabbe
Ingvild Birschmann
eng
uncontrolled
LC-MS/MS
eng
uncontrolled
validation
eng
uncontrolled
serum
eng
uncontrolled
quantification
eng
uncontrolled
apixaban
eng
uncontrolled
diagnostic accuracy
eng
uncontrolled
performance liquid chromatography
eng
uncontrolled
factor XA inhibitor
eng
uncontrolled
direct oral anticoagulants
eng
uncontrolled
direct thrombin inhibitor
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13602/asset1.pdf
14736
2016
eng
baw041
2016
article
1
2017-04-20
--
--
The drug-minded protein interaction database (DrumPID) for efficient target analysis and drug development
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.
Database
10.1093/database/baw041
urn:nbn:de:bvb:20-opus-147369
Database (2016) Vol. 2016: article ID baw041; doi:10.1093/database/baw041
Meik Kunz
Chunguang Liang
Santosh Nilla
Alexander Cecil
Thomas Dandekar
eng
uncontrolled
drug-minded protein
eng
uncontrolled
database
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2016
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14736/097_Dandekar_baw041.pdf
12460
2012
eng
e3806
61
article
1
2016-01-19
--
--
The ITS2 Database
The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable ITS2 sequence, it confined this marker to low-level phylogenetics only. However, the combination of the ITS2 sequence and its highly conserved secondary structure improves the phylogenetic resolution1 and allows phylogenetic inference at multiple taxonomic ranks, including species delimitation.
The ITS2 Database presents an exhaustive dataset of internal transcribed spacer 2 sequences from NCBI GenBank accurately reannotated. Following an annotation by profile Hidden Markov Models (HMMs), the secondary structure of each sequence is predicted. First, it is tested whether a minimum energy based fold (direct fold) results in a correct, four helix conformation. If this is not the case, the structure is predicted by homology modeling. In homology modeling, an already known secondary structure is transferred to another ITS2 sequence, whose secondary structure was not able to fold correctly in a direct fold.
The ITS2 Database is not only a database for storage and retrieval of ITS2 sequence-structures. It also provides several tools to process your own ITS2 sequences, including annotation, structural prediction, motif detection and BLAST search on the combined sequence-structure information. Moreover, it integrates trimmed versions of 4SALE and ProfDistS for multiple sequence-structure alignment calculation and Neighbor Joining tree reconstruction. Together they form a coherent analysis pipeline from an initial set of sequences to a phylogeny based on sequence and secondary structure.
In a nutshell, this workbench simplifies first phylogenetic analyses to only a few mouse-clicks, while additionally providing tools and data for comprehensive large-scale analyses.
Journal of Visual Expression
10.3791/3806
urn:nbn:de:bvb:20-opus-124600
Journal of Visual Expression (61), e3806, doi:10.3791/3806 (2012)
Benjamin Merget
Christian Koetschan
Thomas Hackl
Frank Förster
Thomas Dandekar
Tobias Müller
Jörg Schultz
Matthias Wolf
eng
uncontrolled
homology modeling
eng
uncontrolled
molecular systematics
eng
uncontrolled
internal transcribed spacer 2
eng
uncontrolled
alignment
eng
uncontrolled
genetics
eng
uncontrolled
secondary structure
eng
uncontrolled
ribosomal RNA
eng
uncontrolled
phylogenetic tree
eng
uncontrolled
phylogeny
Datenverarbeitung; Informatik
Chemie und zugeordnete Wissenschaften
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Institut für Pharmazie und Lebensmittelchemie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12460/jove-61-3806.pdf
13190
2012
eng
e1003026
11
8
article
1
2016-04-13
--
--
The Role of Auxin-Cytokinin Antagonism in Plant-Pathogen Interactions
No abstract available.
PLOS Pathogens
10.1371/journal.ppat.1003026
urn:nbn:de:bvb:20-opus-131901
PLoS Pathogens 8(11): e1003026. doi:10.1371/ journal.ppat.1003026
Muhammad Naseem
Thomas Dandekar
eng
uncontrolled
disease
eng
uncontrolled
pseudomas-syringae
eng
uncontrolled
arabidpsis thaliana
eng
uncontrolled
immunity
eng
uncontrolled
organogenesis
eng
uncontrolled
transcription
eng
uncontrolled
resistance
eng
uncontrolled
crosstalk
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13190/Naseem_Antagonism.pdf
24926
2021
eng
9
article
1
--
2021-11-01
--
Topological Analysis of the Carbon-Concentrating CETCH Cycle and a Photorespiratory Bypass Reveals Boosted CO\(_2\)-Sequestration by Plants
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.
Frontiers in Bioengineering and Biotechnology
2296-4185
10.3389/fbioe.2021.708417
urn:nbn:de:bvb:20-opus-249260
2021-11-15T09:24:31+00:00
sword
swordwue
attachment; filename=deposit.zip
7bd3978edec8dca4d12bc010cd57324a
Frontiers in Bioengineering and Biotechnology (2021) 9:708417. doi: 10.3389/fbioe.2021.708417
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Özge Osmanoglu
Mariam Khaled AlSeiari
Hasa Abduljaleel AlKhoori
Shabana Shams
Elena Bencurova
Thomas Dandekar
Muhammad Naseem
eng
uncontrolled
CO2-sequestration
eng
uncontrolled
photorespiration
eng
uncontrolled
elementary modes
eng
uncontrolled
synthetic pathways
eng
uncontrolled
carboxylation
eng
uncontrolled
metabolic modeling
eng
uncontrolled
CETCH cycle
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Import
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24926/fbioe-09-708417.pdf
29976
2022
eng
1
23
article
1
--
--
--
ReCSAI: recursive compressed sensing artificial intelligence for confocal lifetime localization microscopy
Background
Localization-based super-resolution microscopy resolves macromolecular structures down to a few nanometers by computationally reconstructing fluorescent emitter coordinates from diffraction-limited spots. The most commonly used algorithms are based on fitting parametric models of the point spread function (PSF) to a measured photon distribution. These algorithms make assumptions about the symmetry of the PSF and thus, do not work well with irregular, non-linear PSFs that occur for example in confocal lifetime imaging, where a laser is scanned across the sample. An alternative method for reconstructing sparse emitter sets from noisy, diffraction-limited images is compressed sensing, but due to its high computational cost it has not yet been widely adopted. Deep neural network fitters have recently emerged as a new competitive method for localization microscopy. They can learn to fit arbitrary PSFs, but require extensive simulated training data and do not generalize well. A method to efficiently fit the irregular PSFs from confocal lifetime localization microscopy combining the advantages of deep learning and compressed sensing would greatly improve the acquisition speed and throughput of this method.
Results
Here we introduce ReCSAI, a compressed sensing neural network to reconstruct localizations for confocal dSTORM, together with a simulation tool to generate training data. We implemented and compared different artificial network architectures, aiming to combine the advantages of compressed sensing and deep learning. We found that a U-Net with a recursive structure inspired by iterative compressed sensing showed the best results on realistic simulated datasets with noise, as well as on real experimentally measured confocal lifetime scanning data. Adding a trainable wavelet denoising layer as prior step further improved the reconstruction quality.
Conclusions
Our deep learning approach can reach a similar reconstruction accuracy for confocal dSTORM as frame binning with traditional fitting without requiring the acquisition of multiple frames. In addition, our work offers generic insights on the reconstruction of sparse measurements from noisy experimental data by combining compressed sensing and deep learning. We provide the trained networks, the code for network training and inference as well as the simulation tool as python code and Jupyter notebooks for easy reproducibility.
BMC Bioinformatics
10.1186/s12859-022-05071-5
urn:nbn:de:bvb:20-opus-299768
@articleReinhard.2022, author = Reinhard, Sebastian and Helmerich, Dominic A. and Boras, Dominik and Sauer, Markus and Kollmannsberger, Philip, year = 2022, title = ReCSAI: recursive compressed sensing artificial intelligence for confocal lifetime localization microscopy, pages = 530, volume = 23, number = 1, journal = BMC bioinformatics, doi = 10.1186/s12859-022-05071-5,
md5:51dbe1911f74602c49d709e9348a34bc
2023-01-18T06:58:02+00:00
/tmp/phps7SBw9
bibtex
63c7987a66ef32.21172452
BMC Bioinformatics 2022, 23(1):530. DOI: 10.1186/s12859-022-05071-5
835102)
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Sebastian Reinhard
Dominic A. Helmerich
Dominik Boras
Markus Sauer
Philip Kollmannsberger
eng
uncontrolled
compressed sensing
eng
uncontrolled
AI
eng
uncontrolled
SMLM
eng
uncontrolled
FLIMbee
eng
uncontrolled
dSTORM
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
OpenAIRE
Center for Computational and Theoretical Biology
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/29976/BMC_Reinhard.pdf
24059
2021
eng
9
article
1
--
2021-06-15
--
Computational Enzyme Engineering Pipelines for Optimized Production of Renewable Chemicals
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.
Frontiers in Bioengineering and Biotechnology
2296-4185
10.3389/fbioe.2021.673005
urn:nbn:de:bvb:20-opus-240598
2021-06-29T06:09:09+00:00
sword
swordwue
attachment; filename=deposit.zip
93686d71cb99f070f341283ca508168e
Frontiers in Bioengineering and Biotechnology (2021) 9:673005. doi: 10.3389/fbioe.2021.673005
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Marc Scherer
Sarel J. Fleishman
Patrik R. Jones
Thomas Dandekar
Elena Bencurova
eng
uncontrolled
computational
eng
uncontrolled
enzyme
eng
uncontrolled
engineering
eng
uncontrolled
design
eng
uncontrolled
biomanufacturing
eng
uncontrolled
biofuel
eng
uncontrolled
microbes
eng
uncontrolled
metabolism
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Import
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24059/fbioe-09-673005.pdf
5610
2010
eng
article
1
2012-02-24
--
--
A high-level 3D visualization API for Java and ImageJ
Background: Current imaging methods such as Magnetic Resonance Imaging (MRI), Confocal microscopy, Electron Microscopy (EM) or Selective Plane Illumination Microscopy (SPIM) yield three-dimensional (3D) data sets in need of appropriate computational methods for their analysis. The reconstruction, segmentation and registration are best approached from the 3D representation of the data set. Results: Here we present a platform-independent framework based on Java and Java 3D for accelerated rendering of biological images. Our framework is seamlessly integrated into ImageJ, a free image processing package with a vast collection of community-developed biological image analysis tools. Our framework enriches the ImageJ software libraries with methods that greatly reduce the complexity of developing image analysis tools in an interactive 3D visualization environment. In particular, we provide high-level access to volume rendering, volume editing, surface extraction, and image annotation. The ability to rely on a library that removes the low-level details enables concentrating software development efforts on the algorithm implementation parts. Conclusions: Our framework enables biomedical image software development to be built with 3D visualization capabilities with very little effort. We offer the source code and convenient binary packages along with extensive documentation at http://3dviewer.neurofly.de.
urn:nbn:de:bvb:20-opus-67851
6785
BMC BIOINFORMATICS (2010) 11, DOI: 10.1186/1471-2105-11-274
Benjamin Schmid
Johannes Schindelin
Albert Cardona
Martin Longair
Martin Heisenberg
deu
swd
Visualisierung
deu
swd
Java 3D
eng
uncontrolled
ImageJ
eng
uncontrolled
framework
Datenverarbeitung; Informatik
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5610/Schmid_1471_2105_11_274.pdf
13444
2012
eng
e45682
9
7
article
1
2016-06-06
--
--
Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state
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.
PLoS One
10.1371/journal.pone.0045682
urn:nbn:de:bvb:20-opus-134447
PLoS ONE 7(9): e45682. doi:10.1371/journal.pone.0045682
Elham Schokraie
Uwe Warnken
Agnes Hotz-Wagenblatt
Markus A. Grohme
Steffen Hengherr
Frank Förster
Ralph O. Schill
Marcus Frohme
Thomas Dandekar
Martina Schnölzer
eng
uncontrolled
life-span regulation
eng
uncontrolled
genes
eng
uncontrolled
Yolk protein
eng
uncontrolled
water stress
eng
uncontrolled
expression
eng
uncontrolled
tolerance
eng
uncontrolled
richtersius coronifer
eng
uncontrolled
superoxide-dismutase
eng
uncontrolled
caenorhabditis elegans
eng
uncontrolled
arabidopsis thaliana
eng
uncontrolled
vitellogenin
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13444/Schokraie_PLoSOne.pdf
13611
2015
eng
1407
6
article
1
2016-07-13
--
--
Recombinant Bivalent Fusion Protein rVE Induces CD4+ and CD8+ T-Cell Mediated Memory Immune Response for Protection Against Yersinia enterocolitica Infection
Studies investigating the correlates of immune protection against Yersinia infection have established that both humoral and cell mediated immune responses are required for the comprehensive protection. In our previous study, we established that the bivalent fusion protein (rVE) comprising immunologically active regions of Y pestis LcrV (100-270 aa) and YopE (50-213 aa) proteins conferred complete passive and active protection against lethal Y enterocolitica 8081 challenge. In the present study, cohort of BALB/c mice immunized with rVE or its component proteins rV, rE were assessed for cell mediated immune responses and memory immune protection against Y enterocolitica 8081 rVE immunization resulted in extensive proliferation of both CD4 and CD8 T cell subsets; significantly high antibody titer with balanced IgG1: IgG2a/IgG2b isotypes (1:1 ratio) and up regulation of both Th1 (INF-\(\alpha\), IFN-\(\gamma\), IL 2, and IL 12) and Th2 (IL 4) cytokines. On the other hand, rV immunization resulted in Th2 biased IgG response (11:1 ratio) and proliferation of CD4+ T-cell; rE group of mice exhibited considerably lower serum antibody titer with predominant Th1 response (1:3 ratio) and CD8+ T-cell proliferation. Comprehensive protection with superior survival (100%) was observed among rVE immunized mice when compared to the significantly lower survival rates among rE (37.5%) and rV (25%) groups when IP challenged with Y enterocolitica 8081 after 120 days of immunization. Findings in this and our earlier studies define the bivalent fusion protein rVE as a potent candidate vaccine molecule with the capability to concurrently stimulate humoral and cell mediated immune responses and a proof of concept for developing efficient subunit vaccines against Gram negative facultative intracellular bacterial pathogens.
Frontiers in Microbiology
10.3389/fmicb.2015.01407
urn:nbn:de:bvb:20-opus-136114
Frontiers in Microbiology 6:1407. doi:10.3389/fmicb.2015.01407
Amit K. Singh
Joseph J. Kingston
Shishir K. Gupta
Harsh V. Batra
eng
uncontrolled
I-tasser
eng
uncontrolled
Yersinia enterocolitica
eng
uncontrolled
memory immune responses
eng
uncontrolled
cytokine profiling
eng
uncontrolled
CD8+T cells
eng
uncontrolled
CD4+T cells
eng
uncontrolled
recombinant protein rVE
eng
uncontrolled
resistance
eng
uncontrolled
pneumonic plague
eng
uncontrolled
pestis infection
eng
uncontrolled
nonhuman-primates
eng
uncontrolled
III secretion
eng
uncontrolled
V-antigen
eng
uncontrolled
mice
eng
uncontrolled
vaccine
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13611/fmicb-06-01407.pdf
13132
2012
eng
e34796
4
7
article
1
2016-04-05
--
--
A Critical Evaluation of Network and Pathway-Based Classifiers for Outcome Prediction in Breast Cancer
Recently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically constructed by aggregating the expression levels of several genes. The secondary data sources are employed to guide this aggregation. Although many studies claim that these approaches improve classification performance over single genes classifiers, the gain in performance is difficult to assess. This stems mainly from the fact that different breast cancer data sets and validation procedures are employed to assess the performance. Here we address these issues by employing a large cohort of six breast cancer data sets as benchmark set and by performing an unbiased evaluation of the classification accuracies of the different approaches. Contrary to previous claims, we find that composite feature classifiers do not outperform simple single genes classifiers. We investigate the effect of (1) the number of selected features; (2) the specific gene set from which features are selected; (3) the size of the training set and (4) the heterogeneity of the data set on the performance of composite feature and single genes classifiers. Strikingly, we find that randomization of secondary data sources, which destroys all biological information in these sources, does not result in a deterioration in performance of composite feature classifiers. Finally, we show that when a proper correction for gene set size is performed, the stability of single genes sets is similar to the stability of composite feature sets. Based on these results there is currently no reason to prefer prognostic classifiers based on composite features over single genes classifiers for predicting outcome in breast cancer.
PLoS One
10.1371/journal.pone.0034796
urn:nbn:de:bvb:20-opus-131323
PLoS ONE 7(4): e34796. doi:10.1371/journal.pone.0034796
Christine Staiger
Sidney Cadot
Raul Kooter
Marcus Dittrich
Tobias Müller
Gunnar W. Klau
Lodewyk F. A. Wessels
eng
uncontrolled
modules
eng
uncontrolled
protein-interaction networks
eng
uncontrolled
expression signature
eng
uncontrolled
classification
eng
uncontrolled
set
eng
uncontrolled
metastasis
eng
uncontrolled
stability
eng
uncontrolled
survival
eng
uncontrolled
database
eng
uncontrolled
markers
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13132/Staiger_PlosOne.pdf
5611
2010
eng
article
1
2012-02-24
--
--
The IronChip evaluation package: a package of perl modules for robust analysis of custom microarrays
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/
urn:nbn:de:bvb:20-opus-67869
6786
BMC BIOINFORMATICS (2010) 11, DOI: 10.1186/1471-2105-11-112
Yevhen Vainshtein
Mayka Sanchez
Alvis Brazma
Matthias W. Hentze
Thomas Dandekar
Martina U. Muckenthaler
deu
swd
Microarray
deu
uncontrolled
ICEP
eng
uncontrolled
IronChip Evaluation Package
Datenverarbeitung; Informatik
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5611/Dandekar_1471_2105_11_112.pdf
12641
2015
eng
18
8
article
1
2016-01-31
--
--
Identification of divergent WH2 motifs by HMM-HMM alignments
Background
The actin cytoskeleton is a hallmark of eukaryotic cells. Its regulation as well as its interaction with other proteins is carefully orchestrated by actin interaction domains. One of the key players is the WH2 motif, which enables binding to actin monomers and filaments and is involved in the regulation of actin nucleation. Contrasting conserved domains, the identification of this motif in protein sequences is challenging, as it is short and poorly conserved.
Findings
To identify divergent members, we combined Hidden-Markov-Model (HMM) to HMM alignments with orthology predictions. Thereby, we identified nearly 500 proteins containing so far not annotated WH2 motifs. This included shootin-1, an actin binding protein involved in neuron polarization. Among others, WH2 motifs of ‘proximal to raf’ (ptr)-orthologs, which are described in the literature, but not annotated in genome databases, were identified.
Conclusion
In summary, we increased the number of WH2 motif containing proteins substantially. This identification of candidate regions for actin interaction could steer their experimental characterization. Furthermore, the approach outlined here can easily be adapted to the identification of divergent members of further domain families.
BMC Research Notes
10.1186/s13104-015-0981-7
urn:nbn:de:bvb:20-opus-126413
BMC Research Notes (2015) 8:18. DOI 10.1186/s13104-015-0981-7
Clemens Leonard Weiß
Jörg Schultz
eng
uncontrolled
WH2 domain
eng
uncontrolled
spire
eng
uncontrolled
shootin-1
eng
uncontrolled
actin nucleation
eng
uncontrolled
HHblits
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2015
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12641/Schultz_10.1186_s13104-015-0981-7.pdf
6201
2010
eng
article
1
2012-10-11
--
--
Towards Performance Measurement and Metrics Based Analysis of PLA Applications
This article is about a measurement analysis based approach to help software practitioners in managing the additional level complexities and variabilities in software product line applications. The architecture of the proposed approach i.e. ZAC is designed and implemented to perform preprocessesed source code analysis, calculate traditional and product line metrics and visualize results in two and three dimensional diagrams. Experiments using real time data sets are performed which concluded with the results that the ZAC can be very helpful for the software practitioners in understanding the overall structure and complexity of product line applications. Moreover the obtained results prove strong positive correlation between calculated traditional and product line measures.
urn:nbn:de:bvb:20-opus-68188
6818
In: International Journal of Software Engineering & Applications (IJSEA) (2010) 1, 3, 66-80, DOI: 10.5121/ijsea.2010.1305
Ahmed Zeeshan
deu
swd
Programmierbare logische Anordnung
eng
uncontrolled
Analysis
eng
uncontrolled
Measurement
eng
uncontrolled
Software product lines
eng
uncontrolled
Variability
Datenverarbeitung; Informatik
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6201/Zeeshan043_0710ijsea5.pdf
12375
2012
eng
287-302
6
article
1
2015-12-22
--
--
Analyzing Thiol-Dependent Redox Networks in the Presence of Methylene Blue and Other Antimalarial Agents with RT-PCR-Supported in silico Modeling
BACKGROUND: In the face of growing resistance in malaria parasites to drugs, pharmacological combination therapies are important. There is accumulating evidence that methylene blue (MB) is an effective drug against malaria. Here we explore the biological effects of both MB alone and in combination therapy using modeling and experimental data.
RESULTS: We built a model of the central metabolic pathways in P. falciparum. Metabolic flux modes and their changes under MB were calculated by integrating experimental data (RT-PCR data on mRNAs for redox enzymes) as constraints and results from the YANA software package for metabolic pathway calculations. Several different lines of MB attack on Plasmodium redox defense were identified by analysis of the network effects. Next, chloroquine resistance based on pfmdr/and pfcrt transporters, as well as pyrimethamine/sulfadoxine resistance (by mutations in DHF/DHPS), were modeled in silico. Further modeling shows that MB has a favorable synergism on antimalarial network effects with these commonly used antimalarial drugs.
CONCLUSIONS: Theoretical and experimental results support that methylene blue should, because of its resistance-breaking potential, be further tested as a key component in drug combination therapy efforts in holoendemic areas.
Bioinformatics and Biology Insights
10.4137/BBI.S10193
PMC3516044
urn:nbn:de:bvb:20-opus-123751
This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.
Bioinformatics and Biology Insights 2012:6 287–302. doi: 10.4137/BBI.S10193
J. Zirkel
A. Cecil
F. Schäfer
S. Rahlfs
A. Ouedraogo
K. Xiao
S. Sawadogo
B. Coulibaly
K. Becker
T. Dandekar
eng
uncontrolled
methylene blue
eng
uncontrolled
malaria
eng
uncontrolled
elementary mode analysis
eng
uncontrolled
drug
eng
uncontrolled
resistance
eng
uncontrolled
combination therapy
eng
uncontrolled
pathway
eng
uncontrolled
metabolic flux
Datenverarbeitung; Informatik
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12375/f_3443-BBI-Analyzing-Thiol-Dependent-Redox-Networks-in-the-Presence-of-Methylene-.pdf_4656.pdf