Biology subjects

Osmanoglu, O.

Publications and source records attributed to Osmanoglu, O..

3 recordsLinked to original sources

bioRxiv2021

How biological cells including platelets and megakaryocytes decide complex problems fast but risky

Short AbstractMathematical decision processes are accurate but sometimes take very long time or simply do not happen. Decisions in biology happen fast and driven by evolution, optimizing survival chances. This results in stochastic decisions with on average good adaptation to the environment but an inherent risk of individual errors e.g. developing cancer during cell regeneration. We calculate and show in platelets and megakaryocytes how cellular decision processes increases risk for errors and inflammation. Short cut solutions adapted from nature improve computer strategies for protein folding and network decision processes. Complex problems are not always solved in foreseeable time, instead the fast solutions in biology speed up errors everywhere including biochemical aging of blood vessels, misfolded proteins, mis-programmed cells, cancer and heart failure. One sentence abstractWe investigate in biological networks how complex decision problems are mastered not by an accurate but unforeseeable long mathematical search but rather pragmatic and fast, with an inherent risk of error, a basis for inflammation and cancer.

bioinformatics↗

bioRxiv2021

cGMP signaling: probing antagonistic cyclic nucleotide platelet signals by modeling and experiment

BackgroundThe cyclic nucleotides cAMP and cGMP inhibit platelet activation. ResultsWe extended an older model and systematically integrated drugs as external stimuli. Data driven modeling allowed us to design models that provide a quantitative output for quantitative input information. This relies on condensed information about involved regulation and modeling of pharmacological interventions by systematic optimization methods. By multi-experiment fitting, we validated our model optimizing the parameters of the model. In addition, we show how the output of the developed cGMP model can be used as input for a modular model of VASP phosphorylation and for the activity of cAMP and cGMP pathways in platelets. ConclusionsWe present a model for cGMP signaling and VASP phosphorylation, that allows to estimate drug action on any of the inhibitory cyclic nucleotide pathways (cGMP, cAMP) and has been validated by experimental data.

systems biology↗

bioRxiv2020

Aspergillus fumigatus versus Genus Aspergillus: Conservation, adaptive evolution and specific virulence genes

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 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 clearly 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-{beta} pathway, insulin receptor signaling, IL1 pathway and interfering with phagosomal of 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 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, for antimycotic targeting and understanding fundamental processes of virulence.

bioinformatics↗