11 results found
Kontopoulos D-G, van Sebille E, Lange M, et al., 2018, Phytoplankton thermal responses adapt in the absence of hard thermodynamic constraints, Publisher: Cold Spring Harbor Laboratory
<jats:p>To better predict how populations and communities respond to climatic temperature variation, it is necessary to understand how the shape of the response of fitness-related traits to temperature evolves (the thermal performance curve). Currently, there is disagreement about the extent to which the evolution of thermal performance curves is constrained. One school of thought has argued for the prevalence of thermodynamic constraints through enzyme kinetics, whereas another argues that adaptation can - at least partly - overcome such constraints. To shed further light on this debate, we perform a phylogenetic meta-analysis of the thermal performance curve of growth rate of phytoplankton - a globally important functional group -, controlling for potential environmental effects. We find that thermodynamic constraints have a minor influence on the shape of the curve. In particular, we detect a very weak increase of the maximum curve height with the temperature at which the curve peaks, suggesting a weak "hotter-is-better" constraint. Also, instead of a constant thermal sensitivity of growth across species, as might be expected from strong constraints, we detect phylogenetic signal in this as well as all other curve parameters. Our results suggest that phytoplankton thermal performance curves adapt to thermal environments largely in the absence of hard thermodynamic constraints.</jats:p>
Pawar S, Garcia-Carreras B, Sal S, et al., Role of carbon allocation efficiency in the temperature dependence of autotroph growth rate, Proceedings of the National Academy of Sciences, ISSN: 0027-8424
Kumbhar R, Vidal-Eychenié S, Kontopoulos DG, et al., 2018, Recruitment of ubiquitin-activating enzyme UBA1 to DNA by poly(ADP-ribose) promotes ATR signalling, Life Science Alliance, Vol: 1, Pages: e201800096-e201800096, ISSN: 2575-1077
The DNA damage response (DDR) ensures cellular adaptation to genotoxic insults. In the crowded environment of the nucleus, the assembly of productive DDR complexes requires multiple protein modifications. How the apical E1 ubiquitin activation enzyme UBA1 integrates spatially and temporally in the DDR remains elusive. Using a human cell-free system, we show that poly(ADP-ribose) polymerase 1 promotes the recruitment of UBA1 to DNA. We find that the association of UBA1 with poly(ADP-ribosyl)ated protein–DNA complexes is necessary for the phosphorylation replication protein A and checkpoint kinase 1 by the serine/threonine protein kinase ataxia-telangiectasia and RAD3-related, a prototypal response to DNA damage. UBA1 interacts directly with poly(ADP-ribose) via a solvent-accessible and positively charged patch conserved in the Animalia kingdom but not in Fungi. Thus, ubiquitin activation can anchor to poly(ADP-ribose)-seeded protein assemblies, ensuring the formation of functional ataxia-telangiectasia mutated and RAD3-related-signalling complexes.
Kontopoulos DG, García-Carreras B, Sal S, et al., 2018, Use and misuse of temperature normalisation in meta-analyses of thermal responses of biological traits, PeerJ, Vol: 6, ISSN: 2167-8359
There is currently unprecedented interest in quantifying variation in thermal physiologyamong organisms, especially in order to understand and predict the biological impactsof climate change. A key parameter in this quantification of thermal physiologyis the performance or value of a rate, across individuals or species, at a commontemperature (temperature normalisation). An increasingly popular model for fittingthermal performance curves to data—the Sharpe-Schoolfield equation—can yieldstrongly inflated estimates of temperature-normalised rate values. These deviationsoccur whenever a key thermodynamic assumption of the model is violated, i.e., whenthe enzyme governing the performance of the rate is not fully functional at the chosenreference temperature. Using data on 1,758 thermal performance curves across awide range of species, we identify the conditions that exacerbate this inflation. Wethen demonstrate that these biases can compromise tests to detect metabolic coldadaptation, which requires comparison of fitness or rate performance of differentspecies or genotypes at some fixed low temperature. Finally, we suggest alternativemethods for obtaining unbiased estimates of temperature-normalised rate values formeta-analyses of thermal performance across species in climate change impact studies.
Kontopoulos D-G, Kontopoulou T, Ho H-C, et al., 2017, Towards a theoretically informed policy against a rakghoul plague outbreak, The Medical Journal of Australia, Vol: 207, Pages: 490-494
Kontopoulos D-G, García-Carreras B, Sal S, et al., 2017, Use and misuse of temperature normalisation in meta-analyses of thermal responses of biological traits
<jats:p>There is currently unprecedented interest in quantifying variation in thermal physiology among organisms in order to understand and predict the biological impacts of climate change. A key parameter in this quantification of thermal physiology is the performance or value of a trait, across individuals or species, at a common temperature (temperature normalisation). An increasingly popular model for fitting thermal performance curves to data – the Sharpe-Schoolfield equation – can yield strongly inflated estimates of temperature-normalised trait values. These deviations occur whenever a key thermodynamic assumption of the model is violated, i.e. when the enzyme governing the performance of the trait is not fully functional at the chosen reference temperature. Using data on 1,758 thermal performance curves across a wide range of species, we identify the conditions that exacerbate this inflation. We then demonstrate that these biases can compromise tests to detect metabolic cold adaptation, which requires comparison of fitness or trait performance of different species or genotypes at some fixed low temperature. Finally, we suggest alternative methods for obtaining unbiased estimates of temperature-normalised trait values for meta-analyses of thermal performance across species in climate change impact studies.</jats:p>
Kontopoulos DG, Vlachakis D, Tsiliki G, et al., 2016, Structuprint: a scalable and extensible tool for two-dimensional representation of protein surfaces, BMC Structural Biology, Vol: 16, ISSN: 1472-6807
BackgroundThe term "molecular cartography" encompasses a family of computational methods for two-dimensional transformation of protein structures and analysis of their physicochemical properties. The underlying algorithms comprise multiple manual steps, whereas the few existing implementations typically restrict the user to a very limited set of molecular descriptors.ResultsWe present Structuprint, a free standalone software that fully automates the rendering of protein surface maps, given - at the very least - a directory with a PDB file and an amino acid property. The tool comes with a default database of 328 descriptors, which can be extended or substituted by user-provided ones. The core algorithm comprises the generation of a mould of the protein surface, which is subsequently converted to asphere and mapped to two dimensions, using the Miller cylindrical projection. Structuprint is partly optimized for multicore computers, making the rendering of animations of entire molecular dynamics simulations feasible.ConclusionsStructuprint is an efficient application, implementing a molecular cartography algorithm for protein surfaces. According to the results of a benchmark, its memory requirements and execution time are reasonable, allowing it to run even on low-end personal computers. We believe that it will be of use - primarily but not exclusively - to structural biologists and computational biochemists.
Kontopoulou T, Kontopoulos DG, Vaidakis E, et al., 2015, Adult Kawasaki disease in a European patient: a case report and review of the literature, Journal of Medical Case Reports, Vol: 9, ISSN: 1752-1947
IntroductionKawasaki disease is an acute necrotising vasculitis of the medium- and small-sized vessels, occurring mainly in Japanese and Korean babies and children, aged 6 months to 5 years. Its main complication is damage of coronary arteries, which has the potential to be fatal. Here we report a rare case of Kawasaki disease that occurred in a 20-year-old Greek adult.Case presentationA 20-year-old Greek man presented with high fever, appetite loss, nausea and vomiting, headache and significant malaise. He had an erythema of the palms and strikingly red lips and conjunctiva. As he did not respond to broad-spectrum antibiotics and after having excluded other possible diagnoses, the diagnosis of Kawasaki disease was set. He was treated with intravenous immunoglobulin and oral aspirin on the 10th day since the onset of the illness. His clinico-laboratory response was excellent and no coronary artery aneurysms were detected in coronary artery computed tomography performed 1 month later.ConclusionsThis report of an adult case of European Kawasaki disease may be of benefit to physicians of various specialties, including primary care doctors, hospital internists, intensivists and cardiologists. It demonstrates that a case of prolonged fever, unresponsive to antibiotics, in the absence of other diagnoses may be an incident of Kawasaki disease. It is worth stressing that such a diagnosis should be considered, even if the patient is adult and not of Asian lineage.
Vlachakis D, Kontopoulos DG, Kossida S, 2013, Space constrained homology modelling: The paradigm of the RNA-dependent RNA polymerase of dengue (Type II) virus, Computational and Mathematical Methods in Medicine, Vol: 2013, ISSN: 1748-670X
Protein structure is more conserved than sequence in nature. In this direction we developed a novel methodology that significantly improves conventional homology modelling when sequence identity is low, by taking into consideration 3D structural features of the template, such as size and shape. Herein, our new homology modelling approach was applied to the homology modelling of the RNA-dependent RNA polymerase (RdRp) of dengue (type II) virus. The RdRp of dengue was chosen due to the low sequence similarity shared between the dengue virus polymerase and the available templates, while purposely avoiding to use the actual X-ray structure that is available for the dengue RdRp. The novel approach takes advantage of 3D space corresponding to protein shape and size by creating a 3D scaffold of the template structure. The dengue polymerase model built by the novel approach exhibited all features of RNA-dependent RNA polymerases and was almost identical to the X-ray structure of the dengue RdRp, as opposed to the model built by conventional homology modelling. Therefore, we propose that the space-aided homology modelling approach can be of a more general use to homology modelling of enzymes sharing low sequence similarity with the template structures. © 2013 Dimitrios Vlachakis et al.
Kontopoulos D-G, Glykos NM, 2013, Pinda: A Web service for detection and analysis of intraspecies gene duplication events, COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE, Vol: 111, Pages: 711-714, ISSN: 0169-2607
Vlachakis D, Tsiliki G, Kondos D, et al., 2013, Applied bioinformatics in the structural, post-genomic era, Farm animal proteomics 2013, Editors: Almeida, Eckersall, Bencurova, Dolinska, Mlynarcik, Vincova, Bhide, Publisher: Wageningen Academic Publishers, Pages: 23-25
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