| 1. |
- Ilieva, N., et al.
(författare)
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Are There Folding Pathways in the Functional Stages of Intrinsically Disordered Proteins?
- 2016
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Ingår i: Application Of Mathematics In Technical And Natural Sciences (AMITANS'16). - 9780735414310
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Konferensbidrag (refereegranskat)abstract
- We proceed from the description of protein folding by means of molecular dynamics (MD) simulations with all-atom force fields, with folding pathways interpreted in terms of soliton structures, to identify possible systematic dynamical patterns of self-organisation that govern protein folding process. We perform in silico investigations of the conformational transformations of three different proteins MYC protein (an alpha-helical protein), amylin and indolicidin (IDPs with different length and binding dynamics). We discuss the emergence of soliton-mediated secondary motifs, in the case of IDPs in the context of their functional activity. We hypothesize that soliton-like quasi-ordered conformations appear as an important intermediate stage in this process.
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| 2. |
- Nummela, Aleksi J., et al.
(författare)
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Effects of dexmedetomidine, propofol, sevoflurane and S-ketamine on the human metabolome : A randomised trial using nuclear magnetic resonance spectroscopy
- 2022
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Ingår i: European Journal of Anaesthesiology. - : Wolters Kluwer. - 0265-0215 .- 1365-2346. ; 39:6, s. 521-532
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pharmacometabolomics uses large-scale data capturing methods to uncover drug-induced shifts in the metabolic profile. The specific effects of anaesthetics on the human metabolome are largely unknown.OBJECTIVE: We aimed to discover whether exposure to routinely used anaesthetics have an acute effect on the human metabolic profile.DESIGN: Randomised, open-label, controlled, parallel group, phase IV clinical drug trial.SETTING: The study was conducted at Turku PET Centre, University of Turku, Finland, 2016 to 2017.PARTICIPANTS: One hundred and sixty healthy male volunteers were recruited. The metabolomic data of 159 were evaluable.INTERVENTIONS: Volunteers were randomised to receive a 1-h exposure to equipotent doses (EC50 for verbal command) of dexmedetomidine (1.5 ng ml-1; n = 40), propofol (1.7 μg ml-1; n = 40), sevoflurane (0.9% end-tidal; n = 39), S-ketamine (0.75 μg ml-1; n = 20) or placebo (n = 20).MAIN OUTCOME MEASURES: Metabolite subgroups of apolipoproteins and lipoproteins, cholesterol, glycerides and phospholipids, fatty acids, glycolysis, amino acids, ketone bodies, creatinine and albumin and the inflammatory marker GlycA, were analysed with nuclear magnetic resonance spectroscopy from arterial blood samples collected at baseline, after anaesthetic administration and 70 min postanaesthesia.RESULTS: All metabolite subgroups were affected. Statistically significant changes vs. placebo were observed in 11.0, 41.3, 0.65 and 3.9% of the 155 analytes in the dexmedetomidine, propofol, sevoflurane and S-ketamine groups, respectively. Dexmedetomidine increased glucose, decreased ketone bodies and affected lipoproteins and apolipoproteins. Propofol altered lipoproteins, fatty acids, glycerides and phospholipids and slightly increased inflammatory marker glycoprotein acetylation. Sevoflurane was relatively inert. S-ketamine increased glucose and lactate, whereas branched chain amino acids and tyrosine decreased.CONCLUSION: A 1-h exposure to moderate doses of routinely used anaesthetics led to significant and characteristic alterations in the metabolic profile. Dexmedetomidine-induced alterations mirror α2-adrenoceptor agonism. Propofol emulsion altered the lipid profile. The inertness of sevoflurane might prove useful in vulnerable patients. S-ketamine induced amino acid alterations might be linked to its suggested antidepressive properties.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02624401. URL: https://clinicaltrials.gov/ct2/show/NCT02624401.
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| 3. |
- Alekseev, Anton, et al.
(författare)
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Provenance of classical Hamiltonian time crystals
- 2020
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Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :8
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Tidskriftsartikel (refereegranskat)abstract
- Classical Hamiltonian systems with conserved charges and those with constraints often describe dynamics on a pre-symplectic manifold. Here we show that a pre-symplectic manifold is also the proper stage to describe autonomous energy conserving Hamiltonian time crystals. We explain how the occurrence of a time crystal relates to the wider concept of spontaneously broken symmetries; in the case of a time crystal, the symmetry breaking takes place in a dynamical context. We then analyze in detail two examples of timecrystalline Hamiltonian dynamics. The first example is a piecewise linear closed string, with dynamics determined by a Lie-Poisson bracket and Hamiltonian that relates to membrane stability. We explain how the Lie-Poisson brackets descents to a time-crystalline pre-symplectic bracket, and we show that the Hamiltonian dynamics supports two phases; in one phase we have a time crystal and in the other phase time crystals are absent. The second example is a discrete one dimensional model of a Hamiltonian chain. It is obtained by a reduction from the Q-ball Lagrangian that describes time dependent nontopological solitons. We show that a time crystal appears as a minimum energy domain wall configuration, along the chain.
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| 4. |
- Begun, Alexander, et al.
(författare)
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On topology and knotty entanglement in protein folding
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- We investigate aspects of topology in protein folding. For this we numerically simulate the temperature driven folding and unfolding of the slipknotted archaeal virus protein AFV3-109. Due to knottiness the (un)folding is a topological process, it engages the entire backbone in a collective fashion. Accordingly we introduce a topological approach to model the process. Our simulations reveal that the (un)folding of AFV3-109 slipknot proceeds through a folding intermediate that has the topology of a trefoil knot. We observe that the final slipknot causes a slight swelling of the folded AFV3-109 structure. We disclose the relative stability of the strands and helices during both the folding and unfolding processes. We confirm results from previous studies that pointed out that it can be very demanding to simulate the formation of knotty self-entanglement, and we explain how the problems are circumvented: The slipknotted AFV3-109 protein is a very slow folder with a topologically demanding pathway, which needs to be properly accounted for in a simulation description. When we either increase the relative stiffness of bending, or when we decrease the speed of ambient cooling, the rate of slipknot formation rapidly increases.
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| 5. |
- Begun, Alexander, et al.
(författare)
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Protein tertiary structure and the myoglobin phase diagram
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- We develop an effective theory approach to investigate the phase properties of globular proteins. Instead of interactions between individual atoms or localized interaction centers, the approach builds directly on the tertiary structure of a protein. As an example we construct the phase diagram of (apo) myoglobin with temperature (T) and acidity (pH) as the thermodynamical variables. We describe how myoglobin unfolds from the native folded state to a random coil when temperature and acidity increase. We confirm the presence of two molten globule folding intermediates, and we predict an abrupt transition between the two when acidity changes. When temperature further increases we find that the abrupt transition line between the two molten globule states terminates at a tricritical point, where the helical structures fade away. Our results also suggest that the ligand entry and exit is driven by large scale collective motions that destabilize the myoglobin F-helix.
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| 6. |
- Chen, Si, et al.
(författare)
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On Ramachandran angles, closed strings and knots in protein structure
- 2016
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Ingår i: Journal of Physics D. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 49:31
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Tidskriftsartikel (refereegranskat)abstract
- The Ramachandran angles (phi, psi) of a protein backbone form the vertices of a piecewise geodesic curve on the surface of a torus. When the ends of the curve are connected to each other similarly, by a geodesic, the result is a closed string that in general wraps around the torus a number of times both in the meridional and the longitudinal directions. The two wrapping numbers are global characteristics of the protein structure. A statistical analysis of the wrapping numbers in terms of crystallographic x-ray structures in the protein data bank (PDB) reveals that proteins have no net chirality in the phi direction but in the psi direction, proteins prefer to display chirality. A comparison between the wrapping numbers and the concept of folding index discloses a non-linearity in their relationship. Thus these three integer valued invariants can be used in tandem, to scrutinize and classify the global loop structure of individual PDB proteins, in terms of the overall fold topology.
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| 7. |
- Chernodub, M. N., et al.
(författare)
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Baryon number violation and a new electroweak interaction
- 2009
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Ingår i: Physical Review D. - 1550-7998. ; 79:7, s. 077901-
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Tidskriftsartikel (refereegranskat)abstract
- We introduce a new supercurrent in the electroweak sector of the standard model. Its interaction with the hypergauge field influences the mass of the Z boson but has no effect on the W-+/- boson masses. In the leptonic sector it affects the numerical value of the vector and axial coupling constants between neutral currents and the Z boson, and a comparison with experimental values yields an upper bound to the strength of the coupling between the supercurrent and the hypergauge field. In the baryonic sector the supercurrent gives a new contribution to the anomaly equation for baryon number current. As a consequence it may have an effect on baryogenesis.
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| 8. |
- Chernodub, M.N., et al.
(författare)
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Elastic Energy and Phase Structure in a Continuous Spin Ising Chain with Applications to the Protein Folding Problem
- 2011
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Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics. - 1539-3755 .- 1550-2376. ; 83:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a numerical Monte Carlo analysis of a continuos spin Ising chain that can describe the statistical proterties of folded proteins. We find that depending on the value of the Metropolis temperature, the model displays the three known nontrivial phases of polymers: At low temperatures the model is in a collapsed phase, at medium temperatures it is in a random walk phase, and at high temperatures it enters the self-avoiding random walk phase. By investigating the temperature dependence of the specific energy we confirm that the transition between the collapsed phase and the random walk phase is a phase transition, while the random walk phase and self-avoiding random walk phase are separated from each other by a cross-over transition. We also compare the predictions of the model to a phenomenological elastic energy formula, proposed by Huang and Lei to describe folded proteins.
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| 9. |
- Chernodub, M. N., et al.
(författare)
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Embedding Brans-Dicke gravity into electroweak theory
- 2008
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 77:12, s. 127902-
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Tidskriftsartikel (refereegranskat)abstract
- We argue that a version of the four dimensional Brans-Dicke theory can be embedded in the standard flat spacetime electroweak theory. The embedding involves a change of variables that separates the isospin from the hypercharge in the electroweak theory.
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| 10. |
- Chernodub, M. N., et al.
(författare)
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Non-abelian supercurrents and de Sitter ground state in electroweak theory
- 2008
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Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :12, s. 014-
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Tidskriftsartikel (refereegranskat)abstract
- We show that gauge symmetry breaking in the Weinberg-Salam model can be implemented by a mere change of variables and without any explicit gauge fixing. The change of variables entails the concept of supercurrent which has been widely employed in the study of superconductivity. It also introduces a separation between the isospin and the hypercharge, suggesting that our new variables describe a strongly coupled regime of the electroweak theory. We discuss the description of various embedded topological defects in terms of these variables. We also propose that in terms of our variables the Weinberg-Salam model can be interpreted in terms of a gravity theory with the modulus of Higgs field as dilaton and the de Sitter space as the ground state.
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