004 Datenverarbeitung; Informatik
Refine
Has Fulltext
- yes (29)
Is part of the Bibliography
- yes (29)
Year of publication
Document Type
- Journal article (27)
- Preprint (2)
Language
- English (29)
Keywords
- database (3)
- resistance (3)
- cosmology (2)
- engineering (2)
- evolution (2)
- genetics (2)
- 26S RDNA Data (1)
- ACKR4 (1)
- AI (1)
- AKT (1)
- Analysis (1)
- Barcodes (1)
- Biology (1)
- Boolean function (1)
- Boolean tree (1)
- CD4+T cells (1)
- CD8+T cells (1)
- CD95 (1)
- CETCH cycle (1)
- CO2-sequestration (1)
- COVID-19 (1)
- Caenorhabditis elegans (1)
- Colonial volvocales chlorophyta (1)
- Computer software (1)
- DNA (1)
- DNA storage (1)
- Dasycladales chlorophyta (1)
- E8 symmetry (1)
- FLIMbee (1)
- HGPS (1)
- HHblits (1)
- Hurwitz theorem (1)
- I-tasser (1)
- ICEP (1)
- IGFBP2 (1)
- III secretion (1)
- ImageJ (1)
- IronChip Evaluation Package (1)
- Java 3D (1)
- LC-MS/MS (1)
- Land plants (1)
- Lee Smolin (1)
- Measurement (1)
- Microarray (1)
- Molecular systematics (1)
- Mycoplasma (1)
- Neuromuscular junctions (1)
- Nuclear RDNA (1)
- Profile distances (1)
- Programmierbare logische Anordnung (1)
- RBCL Gene-sequences (1)
- RNA sequencing (1)
- SARS-CoV-2 (1)
- SMLM (1)
- Secondary structure (1)
- Septins (1)
- Software product lines (1)
- Synapses (1)
- Synaptic vesicles (1)
- V-antigen (1)
- Variability (1)
- Vesicles (1)
- Visualisierung (1)
- WH2 domain (1)
- WNT (1)
- Yersinia enterocolitica (1)
- Yolk protein (1)
- Zebrafish (1)
- actin nucleation (1)
- adaptation (1)
- aging (1)
- alignment (1)
- apixaban (1)
- arabidopsis thaliana (1)
- arabidpsis thaliana (1)
- behavior (1)
- binary decision diagram (1)
- biofuel (1)
- bioinformatics (1)
- biomanufacturing (1)
- bit (1)
- brain (1)
- caenorhabditis elegans (1)
- carboxylation (1)
- caspase-3 (1)
- cell membranes (1)
- cerebral ischemia (1)
- cisplatin (1)
- classification (1)
- colony-stimulating factor (1)
- combination therapy (1)
- comparative sequence analysis (1)
- complex traits (1)
- compressed sensing (1)
- computational (1)
- connector (1)
- corticotropin-releasing hormone (1)
- crosstalk (1)
- crystal growth (1)
- crystallization (1)
- cytokine profiling (1)
- dSTORM (1)
- design (1)
- diagnostic accuracy (1)
- differentiation (1)
- direct oral anticoagulants (1)
- direct thrombin inhibitor (1)
- disease (1)
- disruption project (1)
- drug (1)
- drug-minded protein (1)
- electrolytes (1)
- elementary mode analysis (1)
- elementary modes (1)
- emergent time (1)
- enzyme (1)
- expression (1)
- expression signature (1)
- factor XA inhibitor (1)
- flies (1)
- framework (1)
- functional analysis (1)
- gamma (1)
- genes (1)
- genetic regulatory network (1)
- hepatotoxicity (1)
- heuristics (1)
- histidine kinase (1)
- homology modeling (1)
- hypotonic (1)
- hypotonic solutions (1)
- immunity (1)
- inflation (1)
- inhibitor (1)
- intermediate host (1)
- internal transcribed spacer 2 (1)
- interpolation (1)
- isotonic (1)
- life-span regulation (1)
- light-gated proteins (1)
- lymphotoxicity (1)
- malaria (1)
- markers (1)
- membrane proteins (1)
- memory immune responses (1)
- metabolic flux (1)
- metabolic modeling (1)
- metabolism (1)
- metastasis (1)
- methylene blue (1)
- mice (1)
- microbes (1)
- modules (1)
- molecular systematics (1)
- mouse (1)
- mutation (1)
- nanocellulose (1)
- natural variation (1)
- networks (1)
- nonhuman-primates (1)
- omics (1)
- organogenesis (1)
- origin (1)
- oxidative stress (1)
- painful (1)
- pangolin (1)
- pathway (1)
- performance liquid chromatography (1)
- permeability (1)
- pestis infection (1)
- phase space (1)
- phase transition (1)
- photorespiration (1)
- phylogenetic tree (1)
- phylogeny (1)
- pneumonic plague (1)
- progeria (1)
- promoter (1)
- protein (1)
- protein chip (1)
- protein-interaction networks (1)
- pseudomas-syringae (1)
- quantification (1)
- qubit (1)
- receptor (1)
- recombinant protein rVE (1)
- recombination (1)
- response regulator (1)
- ribosomal RNA (1)
- richtersius coronifer (1)
- secondary structure (1)
- sensor (1)
- sequence alignment (1)
- serum (1)
- set (1)
- shootin-1 (1)
- single-electron transistors (1)
- spire (1)
- stability (1)
- stable state (1)
- sun exposure (1)
- superoxide-dismutase (1)
- survival (1)
- synthetic biology (1)
- synthetic pathways (1)
- temperature (1)
- tolerance (1)
- tonicity (1)
- transcription (1)
- transmission (1)
- vaccine (1)
- validation (1)
- vitellogenin (1)
- water stress (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (29) (remove)
EU-Project number / Contract (GA) number
- 835102) (1)
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.
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.
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.
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.
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.
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.
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.
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.
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.