Refine
Has Fulltext
- yes (142) (remove)
Is part of the Bibliography
- yes (142)
Year of publication
Document Type
- Journal article (121)
- Preprint (9)
- Review (9)
- Conference Proceeding (1)
- Other (1)
- Working Paper (1)
Keywords
- metabolism (8)
- apoptosis (6)
- cosmology (6)
- crystallization (6)
- SARS-CoV-2 (5)
- cytokinins (5)
- qubit (5)
- COVID-19 (4)
- decoherence (4)
- evolution (4)
- regulation (4)
- transcriptome (4)
- Candida albicans (3)
- bioinformatics (3)
- cisplatin (3)
- cytotoxicity (3)
- database (3)
- expression (3)
- identification (3)
- leukemic cells (3)
- molecular docking (3)
- mutation (3)
- systems biology (3)
- virulence (3)
- "-omics" (2)
- Aspergillus fumigatus (2)
- Bioinformatik (2)
- Biology (2)
- Caenorhabditis elegans (2)
- DNA (2)
- DNA storage (2)
- Metabolic pathways (2)
- RNA (2)
- Salmonella-containing vacuole (SCV) (2)
- Staphylococcus aureus (2)
- adaptation (2)
- algorithm (2)
- alignment (2)
- annotation (2)
- cellular signalling networks (2)
- complexity (2)
- dendritic cells (2)
- differentiation (2)
- drug repurposing (2)
- emergent time (2)
- engineering (2)
- infection (2)
- loop quantum gravity (2)
- lung cancer (2)
- machine learning (2)
- metabolic modeling (2)
- modified inflation (2)
- molecular dynamics (2)
- mouse (2)
- oncolytic virus (2)
- oxidative stress (2)
- phase transition (2)
- platelet (2)
- positive selection (2)
- protein folding (2)
- qubit interaction (2)
- recombination (2)
- resistance (2)
- synthetic biology (2)
- transcriptional regulation (2)
- 1st-line treatment (1)
- 3D lung tumor tissue models (1)
- 3D tissue models (1)
- 5-Fluorouracil (1)
- 6-benzylaminopurine (1)
- A2a-R receptor (1)
- ACKR4 (1)
- AIModules (1)
- AKT (1)
- Abstandsmessung (1)
- Aspergillus (1)
- Aspergillus fumigalus (1)
- Axl tyrosine kinase (1)
- B-cell (1)
- BRAF mutation (1)
- Bedeutung (1)
- Beobachter (1)
- Berberine (1)
- Berechnungskomplexität (1)
- Beta-catenin (1)
- Biologie (1)
- Boolean function (1)
- Boolean tree (1)
- C-60 fullerene (1)
- C60 fullerene (1)
- CD95 (1)
- CETCH cycle (1)
- CLAVATA3 (1)
- CLV3p (1)
- CO2-sequestration (1)
- C\(_{60}\) fullerene (1)
- Camponotus floridanus (1)
- Carcinoma cells (1)
- Cell surface proteomics (1)
- Cestode (1)
- Chagas diagnosis (1)
- Chagas disease (1)
- Chagas monitoring (1)
- Chagas real time PCR (1)
- Chlamydia trachomatis (1)
- Computer modelling (1)
- Computer software (1)
- Cushing’s disease (1)
- DLS and AFM measurements (1)
- DNA damage (1)
- Doxorubicin (1)
- E8 symmetry (1)
- EMT (1)
- ERK signaling (1)
- Echinococcosis (1)
- Echinococcus (1)
- Einfluss (1)
- Embryonic induction (1)
- Enterobacteriaceae (1)
- Entscheidung (1)
- Entscheidungen (1)
- Enzyme kinetics (1)
- Enzyme metabolism (1)
- Enzyme regulation (1)
- Enzymes (1)
- Epicardium-derived cells (1)
- Evaluation (1)
- Evolution (1)
- FLS2 receptor (1)
- Fibroblasts (1)
- Fluorouracil (1)
- Functional modules (1)
- Fundamentalkonstante (1)
- GPVI (1)
- Gene expression vectors (1)
- Gödel (1)
- H7N9 influenza virus (1)
- HGPS (1)
- HIV (1)
- HeLa cells (1)
- Host-parasite interaction (1)
- Human atrial stromal cells (1)
- Hurwitz theorem (1)
- Hurwitz-Theorem (1)
- ICEP (1)
- ICP27 (1)
- IGFBP2 (1)
- Insulin (1)
- Integrated network analysis (1)
- Invasion (1)
- IronChip Evaluation Package (1)
- KRAS biomarker signatures (1)
- Ki67 (1)
- Kinase inhibitor (1)
- Klimaneutralität (1)
- Klimapflanzen (1)
- Klimawandel (1)
- Kolmogorov-Komplexität (1)
- Komplex <Algebra> (1)
- Komplexität (1)
- Kosmologie (1)
- LS-MIDA (1)
- Lee Smolin (1)
- MHC I (1)
- MHC II (1)
- MITE (1)
- Matrix (1)
- Metabolic profiles (1)
- Microarray (1)
- Mikroarray (1)
- Milnesium tardigradum (1)
- Multicenter randomized-trial (1)
- Mycoplasma (1)
- Natur (1)
- Nature constants (1)
- Naturgesetz (1)
- Natürliche Auslese (1)
- Neuromuscular junctions (1)
- Olea (1)
- Phylogenie (1)
- PknB (1)
- Polymerase chain reaction (1)
- Predictive toxicology (1)
- Prognose (1)
- Proteasen (1)
- Proteine (1)
- Quantenschleifen-Gravitation (1)
- Qubits (1)
- R0 (1)
- RNA secondary structure (1)
- RNA sequencing (1)
- RNA-SEQ (1)
- RNAi (1)
- Receptor kinase (1)
- Salmonella enterica (1)
- Salmonella-containing vacuole (1)
- Sanger sequencing (1)
- Septins (1)
- Shotgun method (1)
- Spumaviren (1)
- Stp (1)
- Strukturanalyse (1)
- Synapses (1)
- Synaptic vesicles (1)
- Synthetic biology (1)
- T-cell (1)
- T-cell epitope (1)
- Tapeworm (1)
- Tissue (1)
- Toxicity (1)
- Transcriptional control (1)
- Trend test (1)
- Trypanosoma (1)
- Trypanosoma cruzi (1)
- UV–Vis (1)
- V1–V9 (1)
- V4 (1)
- V7/V8 (1)
- VASP (1)
- Vasodilatator-stimuliertes Phosphoprotein (1)
- Verschränkung (1)
- Vesicles (1)
- Virtual sequencing (1)
- WNT (1)
- Yolk protein (1)
- Zebrafish (1)
- Zika virus (1)
- abscisic acid (ABA) (1)
- accumulation (1)
- adaption (1)
- agent-based model (1)
- aging (1)
- air-liquid interface (1)
- alveolar fibrosis (1)
- alveolar regeneration (1)
- alzheimer's disease (1)
- alzheimers disease (1)
- animals (1)
- anti-cancer drug-like molecules (1)
- anti-thrombotic therapies (1)
- anticancer activity (1)
- antimicrobial peptides (1)
- antimycotics (1)
- antioxidants (1)
- antiproliferative (1)
- approved drugs (1)
- arabidopsis thaliana (1)
- arabidpsis thaliana (1)
- artificial membrane-permeability (1)
- asthmatic bronchial epithelium (1)
- auxin (1)
- bacterial invasion (1)
- bacterial pathogens (1)
- bacteriology (1)
- beta-lactamase inhibition (1)
- binary decision diagram (1)
- binding pocket (1)
- binding protein (1)
- biofilm formation (1)
- biofuel (1)
- bioinformatics and computational biology (1)
- biological activities (1)
- biomanufacturing (1)
- biomarker (1)
- biomaterial surfaces (1)
- bioreactor culture (1)
- bit (1)
- blood platelets (1)
- boolean in silico models (1)
- boolean modeling (1)
- brain (1)
- caenorhabditis elegans (1)
- calcium (1)
- calcium signaling pathway (1)
- camponotus floridanus (1)
- cancer therapy (1)
- candida genome database (1)
- carboxylation (1)
- carpenter ant (1)
- cascade (1)
- caspase-3 (1)
- cell death (1)
- cell staining (1)
- cell wall (1)
- centrality (1)
- cerebral ischemia (1)
- chemical similarity (1)
- chondrosarcoma (1)
- cluster (1)
- collagen (1)
- colony-stimulating factor (1)
- colorectal cancer (1)
- combinatorial drug predictions (1)
- comparative sequence analysis (1)
- complex networks (1)
- computational (1)
- computational biology and bioinformatics (1)
- computational modelling (1)
- computational prediction (1)
- computational systems biology (1)
- computer modelling (1)
- computer-assisted (1)
- connector (1)
- control group (1)
- control profiles (1)
- controllability (1)
- corticotropin-releasing hormone (1)
- crosstalk (1)
- cryptic (1)
- crystal growth (1)
- culture (1)
- cycle (1)
- cyclic nucleotide signaling (1)
- cytokines (1)
- cytokinin (1)
- cytokinin kinetin (1)
- data mining/methods (1)
- data storage (1)
- decision (1)
- defense and evasion strategies (1)
- defense signaling (1)
- defenses (1)
- design (1)
- deubiquitinases (1)
- differentially expressed genes (1)
- discovery (1)
- disease (1)
- docking (1)
- domain (1)
- doxorubicin (1)
- drosophila (1)
- drug design (1)
- drug release (1)
- drug resistance (1)
- drug-minded protein (1)
- dynamic protein-protein interactions (1)
- early cosmology (1)
- early diagnosis (1)
- efficient intervention points (1)
- elementary body (1)
- elementary modes (1)
- embryonic stem cells (1)
- emergent gravity (1)
- encapsulation (1)
- encephalitis dementia (1)
- entanglement (1)
- enteric pathogens (1)
- enterica serovar Typhimurium (1)
- enzyme (1)
- epithelial cell culture (1)
- epitope mapping (1)
- epitope prediction (1)
- error (1)
- error-transfer (1)
- eugenol (1)
- evolutionary (1)
- exome (1)
- explainability of machine learning (1)
- expressed sequence tag (1)
- extracellular matrix (1)
- facultatively intracellular pathogens (1)
- feature analysis (1)
- feature selection (1)
- fine-tuning (1)
- flg22 (1)
- fluorescence recovery after photobleaching (1)
- flux balance analysis (1)
- format (1)
- fostamatinib (1)
- free energy (1)
- functional modules (1)
- fungal pathogens (1)
- fungicide (1)
- gamma (1)
- gene expression (1)
- gene ontology (1)
- genes (1)
- genetic regulatory network (1)
- genetic variation (1)
- genetics (1)
- genome browser (1)
- genus Aspergillus (1)
- guard cells (1)
- heart (1)
- hepatotoxicity (1)
- heuristics (1)
- histidine kinase (1)
- homology modeling (1)
- host-pathogen adaption (1)
- host-pathogen interaction (1)
- human (1)
- human immune system (1)
- human immunodeficiency virus (1)
- human pathogenic fungi (1)
- human xenografted mouse models (1)
- humans (1)
- image processing (1)
- imaging (1)
- immune system (1)
- immune-informatics (1)
- immunity (1)
- immunological cross-talk (1)
- immunotherapies (1)
- in silico simulation (1)
- in vitro (1)
- in vitro models (1)
- in vivo toxicity (1)
- in-vitro (1)
- infected-cell protein (1)
- infection biology (1)
- infection spread (1)
- inflammation (1)
- inflation (1)
- inhibitor (1)
- interaction (1)
- interaction map (1)
- interaction networks (1)
- interactome (1)
- intermediate host (1)
- internal transcribed spacer 2 (1)
- interolog (1)
- interpolation (1)
- interspecies comparison (1)
- invasion (1)
- invasiveness (1)
- ion signaling (1)
- isotopolog profiling (1)
- kinase signaling (1)
- kinetin (1)
- lactate dehydrogenase (1)
- lethality rate (1)
- life-span regulation (1)
- light-gated proteins (1)
- lncRNAs (1)
- lymphocytes (1)
- lymphotoxicity (1)
- mammalian system (1)
- meaning (1)
- messenger RNA (1)
- meta-data (1)
- meta-transcriptome (1)
- metabolic flux (1)
- metabolic modelling (1)
- metabolic pathways (1)
- metabolomic profiling (1)
- miRNAs (1)
- microRNAs (1)
- microRNA–target interaction (1)
- microarray (1)
- microbes (1)
- model reduction (1)
- modeling (1)
- models (1)
- modular tumor tissue models (1)
- modulatory effects (1)
- molecular cloning (1)
- molecular dynamics simulation (1)
- molecular evolution (1)
- molecular modeling (1)
- molecular systematics (1)
- mortality (1)
- mosquito (1)
- mouse model (1)
- multiverse (1)
- myocardial infarction (1)
- myocardium (1)
- nanocarrier (1)
- nanocellulose (1)
- nanocomplex (1)
- natural language processing (1)
- natural processing (1)
- neisseria meningitidis (1)
- network (1)
- network analysis (1)
- network biology (1)
- network inference (1)
- network simulation (1)
- neuraminidase (1)
- neutrophils (1)
- next generation sequencing (1)
- nitric oxide (1)
- non-invasive biomarkers (1)
- noncovalent complex (1)
- noncovalent nanocomplex (1)
- nucleic acid motifs (1)
- observer (1)
- olive (1)
- omics (1)
- on-a-chip (1)
- optimal drug combination (1)
- optimal drug targeting (1)
- optimal pharmacological modulation (1)
- optimal treatment strategies (1)
- optogenetics (1)
- organogenesis (1)
- origin (1)
- pH (1)
- pangolin (1)
- parasite (1)
- pathogen-host interaction (PHI) (1)
- pathogenesis (1)
- pathogenicity (1)
- pathways (1)
- patient data (1)
- permeability (1)
- pharmacology (1)
- phase space (1)
- phosphoproteome (1)
- phosphorylation (1)
- photodynamic chemotherapy (1)
- photorespiration (1)
- phylogenetic analysis (1)
- phylogenetic tree (1)
- phylogenetics (1)
- phylogeny (1)
- phytohormones (1)
- plant hormones (1)
- plant system (1)
- pollen tube (1)
- population coverage (1)
- potential role (1)
- principal (1)
- pro-oxidant (1)
- progeria (1)
- promoter (1)
- protease; Indinavir; lead expansion; docking; pharmacophore (1)
- protein (1)
- protein analysis (1)
- protein chip (1)
- protein familiy (1)
- protein interaction database (1)
- protein-protein interaction (1)
- protein-protein interaction network (1)
- proteins (1)
- proteome (1)
- pseudomas-syringae (1)
- pulmonary drug-delivery (1)
- pyrazolo[3,4-d]pyrimidine (1)
- quantum computing (1)
- radiation (1)
- rational drug design (1)
- re-annotation (1)
- receptor (1)
- reconstructed human epidermis (1)
- regulatory networks (1)
- relA (1)
- reliability (1)
- reproductive toxicity (1)
- respiratory syncytial virus (1)
- response regulator (1)
- reticulate body (1)
- ribosomal RNA (1)
- riboswitch (1)
- richtersius coronifer (1)
- scaffold search (1)
- secondary structure (1)
- selection (1)
- sensor (1)
- sequence (1)
- sequence alignment (1)
- shoot apical meristem (1)
- signaling (1)
- signaling network (1)
- signaling pathway (1)
- signalling (1)
- signalling pathways (1)
- silico model (1)
- simulation (1)
- single cell analysis (1)
- single-electron transistors (1)
- sky kinases (1)
- software (1)
- somatic mutations (1)
- spanlastic (1)
- splicing factors (1)
- stable state (1)
- stable-isotope (1)
- stem cell niche (1)
- stem-cell-triggered immunity (1)
- stemness (1)
- stratification (1)
- stringent response (1)
- structure (1)
- structure-activity relationship (1)
- sun exposure (1)
- superoxide-dismutase (1)
- synaptic vesicles (1)
- synergistic effect (1)
- synthetic pathways (1)
- system inference (1)
- tardigrada (1)
- target (1)
- targeted combination therapy (1)
- targeted therapy (1)
- targets (1)
- therapeutic strategy (1)
- thrombosis (1)
- tolerance (1)
- tools overview (1)
- transcription (1)
- translation (1)
- transmission (1)
- transport studies (1)
- tumors (1)
- type 1 (1)
- unified theories (1)
- uptake (1)
- variable regions (1)
- variants (1)
- vesicle-based barrier (1)
- virulenceregulatory evolution (1)
- viruses (1)
- vitellogenin (1)
- water stress (1)
- wrong labelling (1)
- xanthurenic acid (1)
- yeast U3 localization (1)
- yvcK/glmR operon (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (138)
- Lehrstuhl für Tissue Engineering und Regenerative Medizin (7)
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (6)
- Institut für Molekulare Infektionsbiologie (5)
- Center for Computational and Theoretical Biology (4)
- Institut für Experimentelle Biomedizin (4)
- Institut für Pharmakologie und Toxikologie (4)
- Institut für Virologie und Immunbiologie (4)
- Kinderklinik und Poliklinik (3)
- Institut für Humangenetik (2)
Sonstige beteiligte Institutionen
EU-Project number / Contract (GA) number
- 031A408B (1)
- CoG 721016–HERPES (1)
- ESF-ZDEX 4.0 (1)
Fungal microorganisms frequently lead to life-threatening infections. Within this group of pathogens, the commensal Candida albicans and the filamentous fungus Aspergillus fumigatus are by far the most important causes of invasive mycoses in Europe. A key capability for host invasion and immune response evasion are specific molecular interactions between the fungal pathogen and its human host. Experimentally validated knowledge about these crucial interactions is rare in literature and even specialized host pathogen databases mainly focus on bacterial and viral interactions whereas information on fungi is still sparse. To establish large-scale host fungi interaction networks on a systems biology scale, we develop an extended inference approach based on protein orthology and data on gene functions. Using human and yeast intraspecies networks as template, we derive a large network of pathogen host interactions (PHI). Rigorous filtering and refinement steps based on cellular localization and pathogenicity information of predicted interactors yield a primary scaffold of fungi human and fungi mouse interaction networks. Specific enrichment of known pathogenicity-relevant genes indicates the biological relevance of the predicted PHI. A detailed inspection of functionally relevant subnetworks reveals novel host fungal interaction candidates such as the Candida virulence factor PLB1 and the anti-fungal host protein APP. Our results demonstrate the applicability of interolog-based prediction methods for host fungi interactions and underline the importance of filtering and refinement steps to attain biologically more relevant interactions. This integrated network framework can serve as a basis for future analyses of high-throughput host fungi transcriptome and proteome data.
Control of genetic regulatory networks is challenging to define and quantify. Previous control centrality metrics, which aim to capture the ability of individual nodes to control the system, have been found to suffer from plausibility and applicability problems. Here we present a new approach to control centrality based on network convergence behaviour, implemented as an extension of our genetic regulatory network simulation framework Jimena (http://stefan-karl.de/jimena). We distinguish three types of network control, and show how these mathematical concepts correspond to experimentally verified node functions and signalling pathways in immunity and cell differentiation: Total control centrality quantifies the impact of node mutations and identifies potential pharmacological targets such as genes involved in oncogenesis (e.g. zinc finger protein GLI2 or bone morphogenetic proteins in chondrocytes). Dynamic control centrality describes relaying functions as observed in signalling cascades (e.g. src kinase or Jak/Stat pathways). Value control centrality measures the direct influence of the value of the node on the network (e.g. Indian hedgehog as an essential regulator of proliferation in chondrocytes). Surveying random scale-free networks and biological networks, we find that control of the network resides in few high degree driver nodes and networks can be controlled best if they are sparsely connected.
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.
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.
Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen S. aureus. Genome-scale gene expression data of S. aureus strain NewHG (sigB\(^+\)) elucidated their effect on physiological functions. Moreover, metabolic modelling from these data inferred metabolic adaptations. We compared wild-type to deletion strains lacking pknB, stp or both. Ser/Thr phosphorylation of target proteins by PknB switched amino acid catabolism off and gluconeogenesis on to provide the cell with sufficient components. We revealed a significant impact of PknB and Stp on peptidoglycan, nucleotide and aromatic amino acid synthesis, as well as catabolism involving aspartate transaminase. Moreover, pyrimidine synthesis was dramatically impaired by stp deletion but only slightly by functional loss of PknB. In double knockouts, higher activity concerned genes involved in peptidoglycan, purine and aromatic amino acid synthesis from glucose but lower activity of pyrimidine synthesis from glucose compared to the wild type. A second transcriptome dataset from S. aureus NCTC 8325 (sigB\(^−\)) validated the predictions. For this metabolic adaptation, PknB was found to interact with CdaA and the yvcK/glmR regulon. The involved GlmR structure and the GlmS riboswitch were modelled. Furthermore, PknB phosphorylation lowered the expression of many virulence factors, and the study shed light on S. aureus infection processes.
Conventional anticancer chemotherapy is limited because of severe side effects as well as a quickly evolving multidrug resistance of the tumor cells. To address this problem, we have explored a C\(_{60}\) fullerene-based nanosized system as a carrier for anticancer drugs for an optimized drug delivery to leukemic cells.Here, we studied the physicochemical properties and anticancer activity of C\(_{60}\) fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin. C\(_{60}\)-Doxorubicin complexes in a ratio 1:1 and 2:1 were characterized with UV/Vis spectrometry, dynamic light scattering, and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The obtained analytical data indicated that the 140-nm complexes were stable and could be used for biological applications. In leukemic cell lines (CCRF-CEM, Jurkat, THP1 and Molt-16), the nanocomplexes revealed 3.5 higher cytotoxic potential in comparison with the free drug in a range of nanomolar concentrations. Also, the intracellular drug's level evidenced C\(_{60}\) fullerene considerable nanocarrier function.The results of this study indicated that C\(_{60}\) fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells.
Aspergillus is an important fungal genus containing economically important species, as well as pathogenic species of animals and plants. Using eighteen fungal species of the genus Aspergillus, we conducted a comprehensive investigation of conserved genes and their evolution. This also allows us to investigate the selection pressure driving the adaptive evolution in the pathogenic species A. fumigatus. Among single-copy orthologs (SCOs) for A. fumigatus and the closely related species A. fischeri, we identified 122 versus 50 positively selected genes (PSGs), respectively. Moreover, twenty conserved genes of unknown function were established to be positively selected and thus important for adaption. A. fumigatus PSGs interacting with human host proteins show over-representation of adaptive, symbiosis-related, immunomodulatory and virulence-related pathways, such as the TGF-β pathway, insulin receptor signaling, IL1 pathway and interfering with phagosomal GTPase signaling. Additionally, among the virulence factor coding genes, secretory and membrane protein-coding genes in multi-copy gene families, 212 genes underwent positive selection and also suggest increased adaptation, such as fungal immune evasion mechanisms (aspf2), siderophore biosynthesis (sidD), fumarylalanine production (sidE), stress tolerance (atfA) and thermotolerance (sodA). These genes presumably contribute to host adaptation strategies. Genes for the biosynthesis of gliotoxin are shared among all the close relatives of A. fumigatus as an ancient defense mechanism. Positive selection plays a crucial role in the adaptive evolution of A. fumigatus. The genome-wide profile of PSGs provides valuable targets for further research on the mechanisms of immune evasion, antimycotic targeting and understanding fundamental virulence processes.
Aspergillus fumigatus is a saprophytic, cosmopolitan fungus that attacks patients with a weak immune system. A rational solution against fungal infection aims to manipulate fungal metabolism or to block enzymes essential for Aspergillus survival. Here we discuss and compare different bioinformatics approaches to analyze possible targeting strategies on fungal-unique pathways. For instance, phylogenetic analysis reveals fungal targets, while domain analysis allows us to spot minor differences in protein composition between the host and fungi. Moreover, protein networks between host and fungi can be systematically compared by looking at orthologs and exploiting information from host–pathogen interaction databases. Further data—such as knowledge of a three-dimensional structure, gene expression data, or information from calculated metabolic fluxes—refine the search and rapidly put a focus on the best targets for antimycotics. We analyzed several of the best targets for application to structure-based drug design. Finally, we discuss general advantages and limitations in identification of unique fungal pathways and protein targets when applying bioinformatics tools.
Synergy of chemo- and photodynamic therapies with C\(_{60}\) Fullerene-Doxorubicin nanocomplex
(2019)
A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C\(_{60}\) fullerene (C\(_{60}\)) were applied in 1:1 and 2:1 molar ratio, exploiting C\(_{60}\) both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox’s nuclear and C\(_{60}\)'s extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox's antiproliferative activity and C\(_{60}\)'s photoinduced pro-oxidant activity. When cells were treated with 2:1 C\(_{60}\)-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C\(_{60}\)-Dox enabled a nanomolar concentration of Dox and C\(_{60}\) to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC\(_{50}\) 16, 9 and 7 × 10\(^3\)-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C\(_{60}\)'s photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C\(_{60}\)-mediated Dox delivery and C\(_{60}\) photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C\(_{60}\)-Dox nanoformulation provides a promising synergetic approach for cancer treatment.