Patric Nilsson

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Papers by Patric Nilsson

Mutations E688K and G569R within the NALP3 gene, associated with development of hereditary auto inflammatory disorders

The NALP3 protein plays an important role in activation of inflammasomes upon stimulation by diff... more The NALP3 protein plays an important role in activation of inflammasomes upon stimulation by different ligands. Different mutations in the NALP3 gene are believed to be associated with several inherited auto-inflammatory diseases such as familial cold inflammatory syndrome (FCAS), neonatal onset multisystem inflammatory disorder (NOMID) and muckle-wells syndrome (MWS). In order to express and eventually study the function of the two novel mutations G569R and E688K, they were supposed to be created in the cloned wild type NALP3 gene, sequenced and later expressed in a bacterial host for functional studies. Sequencing results was only obtained for mutation G569R that was re-cloned and expressed in bacterial cells. The expression of this recombinant target protein could not be verified by SDS-PAGE analyses, due to some cellular or mutational problem. Further work on this item should focus on to achieve a verified expression of the desired mutations in both bacterial and mammalian cells...

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Controlling Complexity

Autonomic Computing and other self-managing system initiatives, many strongly based on biological... more Autonomic Computing and other self-managing system initiatives, many strongly based on biological metaphors, are emerging as significant new vision for the design and development of complex computer systems. They offer the promise of controlling complexity through the achievement of selfgovernance (autonomy) and self-management (autonomicity). We consider how complexity is exhibited in the computer industry as a whole, and how the situation is deteriorating, rather than improving. We consider how Autonomous and Autonomic Systems, with their biological inspiration, can provide a framework for tackling complexity and overcoming the problems of its (unavoidable) inherent existence in certain classes of systems.

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The cyclic lemmings

Asynchronous population of Siberian lemmings across the Palaearctic tundra

Oecologia, 1999

Investigation of the implications of nitric oxide on biofilm development

Biofilms are communities of sessile microorganisms attached to a surface and imbedded in a matrix... more Biofilms are communities of sessile microorganisms attached to a surface and imbedded in a matrix of extracellular polysaccharide substances. These communities can be found in diverse aquatic environments, such as in industrial pipes and in humans. By forming microcolony structures, which are highly resistant to adverse physical conditions as well as antimicrobial agents, biofilms are very problematic when associated with e.g. persistent infections. In order to find new ways of controlling biofilm growth, the processes involved in biofilm development must be investigated further. The main interest of this study is the occurrence of void formation inside biofilms. This phenomenon has been observed in several studies and has been correlated to cell death inside the microcolonies. The occurrence of cell death has recently been associated with the presence of nitric oxide in the biofilm. In this study, the implications of nitric oxide accumulation on biofilm development were investigated using an individual-based model. Specifically, the role of nitric oxide in void formation was considered. A large number of simulations were run using different parameter settings in order to determine if nitric oxide could account for the occurrence of void formation observed experimentally. The general predictions made by the model system showed agreement to some experimental data, but not to others. Sloughing, the detachment of chunks of cells from the biofilm, was observed in the majority of simulations. In some cases, the model also predicted the presence of live cells inside the voids, which has been observed experimentally.

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An information fusion approach to controlling complexity in bioinformatics research

Information Fusion (IF) is about combining, or fusing, information from different sources in orde... more Information Fusion (IF) is about combining, or fusing, information from different sources in order to facilitate our understanding of a complex system and thereby provide insights that could not be gained from any of the individual data sources in isolation. We argue in this paper that there is a need for applying an IF approach in bioinformatics research, since the

Evolutionary Search for Improved Path Diagrams

Lecture Notes in Computer Science

A path diagram relates observed, pairwise, variable correlations to a functional structure which ... more A path diagram relates observed, pairwise, variable correlations to a functional structure which describes the hypothesized causal relations between the variables. Here we combine path diagrams, heuristics and evolutionary search into a system which seeks to improve existing gene regulatory models. Our evaluation shows that once a correct model has been identified it receives a lower prediction error compared to

Bud Dormancy as a Bet-Hedging Strategy

The American Naturalist, 1996

ABSTRACT The presence of dormant buds allows grazed plants to compensate for destroyed active mer... more ABSTRACT The presence of dormant buds allows grazed plants to compensate for destroyed active meristems. In this article we present a theoretical analysis of the adaptive significance of bud dormancy when the risk of herbivory varies from year to year. Under constant herbivore pressure, selection tends to favor either plants that have no dormant buds and hence no capacity of compensatory growth due to low risk of herbivory, or those that leave most of their buds in dormancy because of high risk of herbivory. We show that when the risk of herbivory varies from year to year, selection will favor intermediate phenotypes having both dormant and active meristems. The intermediate phenotypes represent bet-hedging strategies that have lower variance of seed production than either of the extreme strategies. We also show that intensive herbivory can favor meristem allocation strategies that allow plants to overcompensate for herbivore damage. Our results suggest that two kinds of herbivores might cause selection pressures favoring compensatory growth: large ungulate herbivores that remove a large proportion of the aboveground parts of the attacked plants and that predictably attack fairly many plants (&gt;50%) each year, and invertebrate herbivores that periodically cause extensive damage during years of mass attacks.

Plant Compensatory Growth: Herbivory or Competition?

Oikos, 1996

... Johannes Jaremo, Patric Nilsson, and Juha Tuomi ... Paige and Whitham (1987) showed that this... more

Plant Adaptations to Herbivory: Mutualistic versus Antagonistic Coevolution

Oikos, 1999

... Johannes Jaremo , Juha Tuomi2, Patric Nilsson&#x27; and Tommy Lennartsson3. ... responses... more

Asynchronous population dynamics of Siberian lemmings across the Palaearctic tundra

Oecologia, 1999

The synchrony of Siberian lemming (Lemmus sibiricus L.) population dynamics was investigated duri... more The synchrony of Siberian lemming (Lemmus sibiricus L.) population dynamics was investigated during a ship-borne expedition along the Palaearctic tundra coast in the summer of 1994. On 12 sites along the coast from the Kola Peninsula to Wrangel Island, relative densities of lemmings were recorded using a standardised snap-trapping programme. The phase position of the lemming cycle in each of the studied populations was determined based on current density estimates, signs of previous density and the age profile of each population (ageing based on eye lens mass). In addition, dendrochronological methods were used to determine when the last peak in the density of microtine populations occurred at each site. The examined lemming populations were in different phases of the lemming cycle. Some populations were in the peak phase, as indicated by high current densities, an age profile in which older individuals were well represented, and signs of high previous density (abundant old lemming faeces). Other populations were in the decline phase, as reflected in a moderate current density, a predominance of older individuals and signs of high previous density. Populations in the low phase had an extremely low current density and showed signs of high previous density, while populations in the increase phase had a moderate current density, a predominance of younger individuals and showed signs of low previous density. The results of phase determinations based on dendrochronological methods support the findings based on lemming demography. Recent Russian studies carried out on some of the sites also agreed with our phase determination results. Thus, on a regional scale (across the whole Palaearctic tundra), the population dynamics of Siberian lemmings can be considered asynchronous. However, sites situated adjacent to each other were often phase synchronous, suggesting a more fine-grained pattern of dynamics with synchrony over distances as long as 1000 km or so, e.g. the Yamal and Taymyr Peninsulas.

Seed Dormancy and Frequency Dependent Selection Due to Sib Competition: the Effect of Age Specific Gene Expression

Journal of Theoretical Biology, 1996

We analyse the evolution of postponed seed germination in temporally and spatially homogenous hab... more We analyse the evolution of postponed seed germination in temporally and spatially homogenous habitats under the assumption that sibling seedlings compete because of clumped seed dispersal. The seed germination trait is assumed to be affected by two sets of autosomal genes. One set controls a germination factor that is expressed in young individuals, i.e. this factor determines the embryo's propensity to delay germination. The other set of genes controls a germination factor that is expressed in the seed coat, which, because this is maternal tissue, represents an adult trait.The two germination factors together determine the probability of a seed germinating as a function of time. The corresponding probability density function of germination times represents a seed's germination strategy. We investigate the evolutionary stability of such strategies by introducing rare mutant modifier alleles that give rise to small deviations with respect to germination strategies.The analysis shows that the coevolution of the two sets of genes leads to a joint ESS which is such that the embryonal trait favours a faster germination regime than does the adult one. We suggest that this joint ESS is best seen as a result of conflicting selection pressures acting upon genes with age-specific expression, rather than as a conflict between parents and their offspring.

A Dilemma of Plant Defences: Is it Really Worth Killing the Herbivore?

Journal of Theoretical Biology, 1994

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Does seed dormancy benefit the mother plant by reducing sib competition?

Evolutionary Ecology, 1994

Seed dormancy has been considered, almost without exception, as a bet-hedging strategy in a tempo... more Seed dormancy has been considered, almost without exception, as a bet-hedging strategy in a temporally varying environment. However, in this paper we show that seed dormancy can improve the reproductive success of the mother plant when competition between sibling seedlings and adult plants is intense even if the environment is temporally invariable. We allow a cohort of sibling seeds to germinate simultaneously in the same patch and assume a density dependent survival and fecundity of seedlings. In the model, the mother plant is assumed to control the germination behaviour of the seeds, e.g. by enclosing the seeds in coats of different hardiness. When sib competition is intense, a postponed germination of her seeds can increase the reproductive success of the mother plant up to four times, measured in terms of the number of grandchildren. Consequently, our results suggest that postponed germination may function as a mechanism that alters local interactions in viscous plant populations with limited dispersal.

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Plant Compensatory Responses: Bud Dormancy as an Adaptation to Herbivory

Ecology, 1994

... We have specifically focused on bud dormancy and, following Paige and Whitham (1987) andPaige... more

Kinetics of the AHL Regulatory System in a Model Biofilm System: How Many Bacteria Constitute a “Quorum”?

Journal of Molecular Biology, 2001

Acylated homoserine lactones (AHLs) regulate a wide variety of phenotypes in Gram-negative bacter... more Acylated homoserine lactones (AHLs) regulate a wide variety of phenotypes in Gram-negative bacteria. Most research suggests that AHL-mediated phenotypes are not expressed in populations until late logarithmic phase or stationary phase. Here, we model how the concentration of AHLs inside bacterial cells and in a bio®lm changes over time as a function of population growth rate, diffusion of AHLs and the rate of autoinduction. Our theoretical results show that the concentration of AHLs inside a single bacterium (and by implication induction of a phenotype) has a non-trivial behaviour over time, and often exhibits a rapid increase early in population growth. This rapid increase is followed by a plateau, followed by another rise in the concentration of AHLs, to a second plateau. High concentrations of AHLs inside the bacterial cell early in population growth are positively affected by slow diffusion rates out of the cell and the bio®lm, slow bacterial growth rates and fast autoinduction. In contrast, fast growth rates, slow autoinduction rates and high diffusion rates result in a high concentration plateau in stationary phase. More generally, the density-dependent nature of AHL regulation can be viewed as a trade-off between factors that dilute intracellular concentrations of AHLs (diffusion out of the cell, cell division), and those that increase concentrations (a slowing or restriction of diffusion or growth, or autoinduction). These results suggest that expression of AHLmediated phenotypes can occur at relatively low cell densities and low external/environmental AHL concentrations.

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On the Ecology and Evolution of seed and Bud Dormancy

This thesis considers the ecological and evolutionary significance of seed and bud dormancy. Firs... more This thesis considers the ecological and evolutionary significance of seed and bud dormancy. First, I present theoretical support to the idea that seed dormancy may evolve as a strategy to reduce sib competition in temporally homogeneous environments. In this thesis, I also analyze two different processes that may give rise to parent-offspring conflicts in angiosperms, viz. seed germination and seed provisioning. In either case, I use a single fitness function for a single individual, whereas in earlier contributions fitness for parents and offspring are given distinct definitions. I show that there exists an ESS, and that this ESS is best seen as a compromise between conflicting selection pressures acting upon genes with age-specific expression rather than as a conflcit between parents and offspring. Second, I outline a theoretical framework for the evolution of bud dormancy as an adaptation to a predictable risk of being damaged. The presence of dormant buds/latent meristems enables plants to compensate their meristem losses following damage by the regrowth of secondary and tertiary shoots. I show that intensive and predictable herbivory may select for compensatory growth in plants. An interesting result of the present thesis is that the shape of compensatory responses in relation to meristem loss differs between qualitatively between plants adapted to single grazing episode and plants adapted to repeated grazing events. Finally, I present empirical evidence for an evolutionary history of overcompensation in the herb Gentianella campestris (Gentianaceae). BY overcompensation, I undestand the fact that damaged plants produce more fruits and seeds than do undamaged plants.

Toward Quantifying the Thymic Dysfunctional State in Mouse Models of Inflammatory Bowel Disease

Inflammatory Bowel Diseases, 2013

Inflammatory bowel disease is characterized by a number of immunological alterations, not the lea... more Inflammatory bowel disease is characterized by a number of immunological alterations, not the least in the T-cell compartment. Numerous animal models of colitis have revealed aberrant thymocyte dynamics associated with skewed thymocyte development. The recent advancements in quantitative methods have proposed critical kinetic alterations in the thymocyte development during the progression of colitis. This review focuses on the aberrant thymocyte dynamics in Gαi2-deficient mice as this mouse model provides most quantitative data of the thymocyte development associated with colitis. Herein, we discuss several dynamic changes during the progression of colitis and propose a hypothesis for the underlying causes for the skewed proportions of the thymocyte populations seen in the Gαi2-deficient mice and in other mouse models of colitis.

Luminescence control in the marine bacterium Vibrio fischeri: an analysis of the dynamics of lux regulation

Journal of Molecular Biology, 2000

A mathematical model has been developed based on the fundamental properties of the control system... more A mathematical model has been developed based on the fundamental properties of the control system formed by the lux genes and their products in Vibrio ®scheri. The model clearly demonstrates how the components of this system work together to create two, stable metabolic states corresponding to the expression of the luminescent and non-luminescent phenotypes. It is demonstrated how the cell can ``switch'' between these steady states due to changes in parameters describing metabolic processes and the extracellular concentration of the signal molecule N-3-oxohexanoyl-L-homoserine lactone. In addition, it is shown how these parameters in¯uence how sensitive the switch mechanism is to cellular LuxR and N-3-oxohexanoyl-L-homoserine lactone and complex concentration. While these properties could lead to the collective phenomenon known as quorum sensing, the model also predicts that under certain metabolic circumstances, basal expression of the lux genes could cause a cell to luminesce in the absence of extracellular signal molecule. Finally, the model developed in this study provides a basis for analysing the impact of other levels of control upon lux regulation.

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Using individual-based Network modeling for evaluating interventions aimed to prevent and control Pneumococcal transmission

BMC Infectious Diseases

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