| 1. |
- Bally, Marta, 1981, et al.
(författare)
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Interaction of virions with membrane glycolipids
- 2012
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Ingår i: Physical Biology. - : IOP Publishing. - 1478-3967 .- 1478-3975. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Cellular membranes contain various lipids including glycolipids (GLs). The hydrophilic head groups of GLs extend from the membrane into the aqueous environment outside the cell where they act as recognition sites for specific interactions. The first steps of interaction of virions with cells often include contacts with GLs. To clarify the details of such contacts, we have used the total internal reflection fluorescence microscopy to explore the interaction of individual unlabelled virus-like particles (or, more specifically, norovirus protein capsids), which are firmly bound to a lipid bilayer, and fluorescent vesicles containing glycosphingolipids (these lipids form a subclass of GLs). The corresponding binding kinetics were earlier found to be kinetically limited, while the detachment kinetics were logarithmic over a wide range of time. Here, the detachment rate is observed to dramatically decrease with increasing concentration of glycosphingolipids from 1% to 8%. This effect has been analytically explained by using a generic model describing the statistics of bonds in the contact area between a virion and a lipid membrane. Among other factors, the model takes the formation of GL domains into account. Our analysis indicates that in the system under consideration, such domains, if present, have a characteristic size smaller than the contact area between the vesicle and the virus-like particle.
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| 2. |
- Gerlee, Philip, 1980, et al.
(författare)
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The evolution of carrying capacity in constrained and expanding tumour cell populations
- 2015
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Ingår i: Physical Biology. - : IOP Publishing. - 1478-3967 .- 1478-3975. ; 12:5, s. artikel nr 056001-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer cells are known to modify their micro-environment such that it can sustain a larger population, or, in ecological terms, they construct a niche which increases the carrying capacity of the population. It has however been argued that niche construction, which benefits all cells in the tumour, would be selected against since cheaters could reap the benefits without paying the cost. We have investigated the impact of niche specificity on tumour evolution using an individual based model of breast tumour growth, in which the carrying capacity of each cell consists of two components: an intrinsic, subclone-specific part and a contribution from all neighbouring cells. Analysis of the model shows that the ability of a mutant to invade a resident population depends strongly on the specificity. When specificity is low selection is mostly on growth rate, while high specificity shifts selection towards increased carrying capacity. Further, we show that the long-term evolution of the system can be predicted using adaptive dynamics. By comparing the results from a spatially structured versus well-mixed population we show that spatial structure restores selection for carrying capacity even at zero specificity, which poses a solution to the niche construction dilemma. Lastly, we show that an expanding population exhibits spatially variable selection pressure, where cells at the leading edge exhibit higher growth rate and lower carrying capacity than those at the centre of the tumour.
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| 3. |
- Werner, Maria, et al.
(författare)
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A computational study of lambda-lac mutants
- 2009
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Ingår i: PHYS BIOL. - : IOP Publishing. - 1478-3967. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- We present a comprehensive, computational study of the properties of bacteriophage lambda mutants designed by Atsumi and Little (2006 Proc. Natl. Acad. Sci. 103 4558-63). These phages underwent a genetic reconstruction where Cro was replaced by a dimeric form of the Lac repressor. To clarify the theoretical characteristics of these mutants, we built a detailed thermodynamic model. The mutants all have a different genetic wiring than the wild-type. lambda One group lacks regulation of P-RM by the lytic protein. These mutants only exhibit the lysogenic equilibrium, with no transiently active P-R. The other group lacks the negative feedback from CI. In this group, we identify a handful of bi-stable mutants, although the majority only exhibit the lysogenic equilibrium. The experimental identification of functional phages differs from our predictions. From a theoretical perspective, there is no reason why only 4 out of 900 mutants should be functional. The differences between theory and experiment can be explained in two ways. Either, the view of the lambda phage as a bi-stable system needs to be revised, or the mutants have in fact not undergone a modular replacement, as intended by Atsumi and Little, but constitute instead a wider systemic change.
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| 4. |
- Zhdanov, Vladimir, 1952, et al.
(författare)
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Kinetics of enzymatic reactions in lipid membranes containing domains
- 2015
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Ingår i: Physical Biology. - : IOP Publishing. - 1478-3967 .- 1478-3975. ; 12:2, s. art. no. 026003-
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Tidskriftsartikel (refereegranskat)abstract
- An appreciable part of enzymes operating in vivo is associated with lipid membranes. The function of such enzymes can be influenced by the presence of domains containing proteins and/or composed of different lipids. The corresponding experimental model-system studies can be performed under well controlled conditions, e.g., on a planar supported lipid bilayer or surface-immobilized vesicles. To clarify what may happen in such systems, we propose general kinetic equations describing the enzyme-catalyzed substrate conversion occurring via the Michaelis-Menten (MM) mechanism on a membrane with domains which do not directly participate in reaction. For two generic situations when a relatively slow reaction takes place primarily in or outside domains, we take substrate saturation and lateral substrate-substrate interactions at domains into account and scrutinize the dependence of the reaction rate on the average substrate coverage. With increasing coverage, depending on the details, the reaction rate reaches saturation via an inflection point or monotonously as in the conventional MM case. In addition, we show analytically the types of reaction kinetics occurring primarily at domain boundaries. In the physically interesting situation when the domain growth is fast on the reaction time scale, the latter kinetics are far from conventional. The opposite situation when the reaction is fast and controlled by diffusion has been studied by using the Monte Carlo technique. The corresponding results indicate that the dependence of the reaction kinetics on the domain size may be weak.
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| 5. |
- Gao, Chen-Yi, et al.
(författare)
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DCA for genome-wide epistasis analysis : the statistical genetics perspective
- 2019
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Ingår i: Physical Biology. - : IOP PUBLISHING LTD. - 1478-3967 .- 1478-3975. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Direct coupling analysis (DCA) is a now widely used method to leverage statistical information from many similar biological systems to draw meaningful conclusions on each system separately. DCA has been applied with great success to sequences of homologous proteins, and also more recently to whole-genome population-wide sequencing data. We here argue that the use of DCA on the genome scale is contingent on fundamental issues of population genetics. DCA can be expected to yield meaningful results when a population is in the quasi-linkage equilibrium (QLE) phase studied by Kimura and others, but not, for instance, in a phase of clonal competition. We discuss how the exponential (Potts model) distributions emerge in QLE, and compare couplings to correlations obtained in a study of about 3000 genomes of the human pathogen Streptococcus pneumoniae.
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| 6. |
- Aurell, Erik, 1961-, et al.
(författare)
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The bulk and the tail of minimal absent words in genome sequences
- 2016
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Ingår i: Physical Biology. - : Institute of Physics (IOP). - 1478-3967 .- 1478-3975. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Minimal absent words (MAW) of a genomic sequence are subsequences that are absent themselves but the subwords of which are all present in the sequence. The characteristic distribution of genomic MAWs as a function of their length has been observed to be qualitatively similar for all living organisms, the bulk being rather short, and only relatively few being long. It has been an open issue whether the reason behind this phenomenon is statistical or reflects a biological mechanism, and what biological information is contained in absent words. % In this work we demonstrate that the bulk can be described by a probabilistic model of sampling words from random sequences, while the tail of long MAWs is of biological origin. We introduce the novel concept of a core of a minimal absent word, which are sequences present in the genome and closest to a given MAW. We show that in bacteria and yeast the cores of the longest MAWs, which exist in two or more copies, are located in highly conserved regions the most prominent example being ribosomal RNAs (rRNAs). We also show that while the distribution of the cores of long MAWs is roughly uniform over these genomes on a coarse-grained level, on a more detailed level it is strongly enhanced in 3' untranslated regions (UTRs) and, to a lesser extent, also in 5' UTRs. This indicates that MAWs and associated MAW cores correspond to fine-tuned evolutionary relationships, and suggest that they can be more widely used as markers for genomic complexity.
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| 7. |
- Eriksson, Anders, 1975, et al.
(författare)
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Gene-history correlation and population structure.
- 2004
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Ingår i: Physical biology. - : IOP Publishing. - 1478-3967 .- 1478-3975. ; 1:3-4, s. 220-8
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Tidskriftsartikel (refereegranskat)abstract
- Correlation of gene histories in the human genome determines the patterns of genetic variation (haplotype structure) and is crucial to understanding genetic factors in common diseases. We derive closed analytical expressions for the correlation of gene histories in established demographic models for genetic evolution and show how to extend the analysis to more realistic (but more complicated) models of demographic structure. We identify two contributions to the correlation of gene histories in divergent populations: linkage disequilibrium, and differences in the demographic history of individuals in the sample. These two factors contribute to correlations at different length scales: the former at small, and the latter at large scales. We show that recent mixing events in divergent populations limit the range of correlations and compare our findings to empirical results on the correlation of gene histories in the human genome.
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| 8. |
- Hintze, Arend, Professor, et al.
(författare)
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Punishment in public goods games leads to meta-stable phase transitions and hysteresis
- 2015
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Ingår i: Physical Biology. - : Institute of Physics Publishing. - 1478-3967 .- 1478-3975. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of cooperation has been a perennial problem in evolutionary biology because cooperation can be undermined by selfish cheaters who gain an advantage in the short run, while compromising the long-term viability of the population. Evolutionary game theory has shown that under certain conditions, cooperation nonetheless evolves stably, for example if players have the opportunity to punish cheaters that benefit from a public good yet refuse to pay into the common pool. However, punishment has remained enigmatic because it is costly and difficult to maintain. On the other hand, cooperation emerges naturally in the public goods game if the synergy of the public good (the factor multiplying the public good investment) is sufficiently high. In terms of this synergy parameter, the transition from defection to cooperation can be viewed as a phase transition with the synergy as the critical parameter. We show here that punishment reduces the critical value at which cooperation occurs, but also creates the possibility of meta-stable phase transitions, where populations can 'tunnel' into the cooperating phase below the critical value. At the same time, cooperating populations are unstable even above the critical value, because a group of defectors that are large enough can 'nucleate' such a transition. We study the mean-field theoretical predictions via agent-based simulations of finite populations using an evolutionary approach where the decisions to cooperate or to punish are encoded genetically in terms of evolvable probabilities. We recover the theoretical predictions and demonstrate that the population shows hysteresis, as expected in systems that exhibit super-heating and super-cooling. We conclude that punishment can stabilize populations of cooperators below the critical point, but it is a two-edged sword: it can also stabilize defectors above the critical point. © 2015 IOP Publishing Ltd.
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| 9. |
- Jo, Junghyo, et al.
(författare)
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The fractal spatial distribution of pancreatic islets in three dimensions : a self-avoiding growth model
- 2013
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Ingår i: Physical Biology. - : Institute of Physics Publishing (IOPP). - 1478-3967 .- 1478-3975. ; 10:3, s. 036009-
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Tidskriftsartikel (refereegranskat)abstract
- The islets of Langerhans, responsible for controlling blood glucose levels, are dispersed within the pancreas. A universal power law governing the fractal spatial distribution of islets in two-dimensional pancreatic sections has been reported. However, the fractal geometry in the actual three-dimensional pancreas volume, and the developmental process that gives rise to such a self-similar structure, has not been investigated. Here, we examined the three-dimensional spatial distribution of islets in intact mouse pancreata using optical projection tomography and found a power law with a fractal dimension of 2.1. Furthermore, based on two-dimensional pancreatic sections of human autopsies, we found that the distribution of human islets also follows a universal power law with a fractal dimension of 1.5 in adult pancreata, which agrees with the value previously reported in smaller mammalian pancreas sections. Finally, we developed a self-avoiding growth model for the development of the islet distribution and found that the fractal nature of the spatial islet distribution may be associated with the self-avoidance in the branching process of vascularization in the pancreas.
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| 10. |
- Zakrisson, Johan, et al.
(författare)
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Tethered cells in fluid flows : beyond the Stokes’ drag force approach
- 2015
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Ingår i: Physical Biology. - : IOP Publishing. - 1478-3967 .- 1478-3975. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Simulations of tethered cells in viscous sub-layers are frequently performed using the Stokes' drag force, but without taking into account contributions from surface corrections, lift forces, buoyancy, the Basset force, the cells' finite inertia, or added mass. In this work, we investigate to what extent such contributions, under a variety of hydrodynamic conditions, influence the force at the anchor point of a tethered cell and the survival probability of a bacterium that is attached to a host by either a slip or a catch bond via a tether with a few different biomechanical properties. We show that a consequence of not including some of these contributions is that the force to which a bond is exposed can be significantly underestimated; in general by similar to 32-46%, where the influence of the surface corrections dominate ( the parallel and normal correction coefficients contribute similar to 5-8 or similar to 23-26%, respectively). The Basset force is a major contributor, up to 20%, for larger cells and shear rates. The lift force and inertia contribute when cells with radii >3 mu m have shear rates>2000 s(-1). Buoyancy contributes significantly for cells with radii > 3 mu m for shear rates<10 s(-1). Since the lifetime of a bond depends strongly on the force, both the level of approximation and the biomechanical model of the tether significantly affect the survival probability of tethered bacteria. For a cell attached by a FimH-mannose bond and an extendable tether with a shear rate of 3000 s(-1), neglecting the surface correction coefficients or the Basset force can imply that the survival probability is overestimated by more than an order of magnitude. This work thus shows that in order to quantitatively assess bacterial attachment forces and survival probabilities, both the fluid forces and the tether properties need to be modeled accurately.
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