| 1. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 2. |
- Bastiat, Guillaume, et al.
(författare)
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Development of Non-Phospholipid Liposomes Containing a High Cholesterol Concentration
- 2007
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 23:14, s. 7695-7699
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Tidskriftsartikel (refereegranskat)abstract
- We present a novel formulation of non-phospholipid liposomes formed from cholesterol and palmitic acid. Despite the fact that these two lipidic species do not form individually fluid bilayers, we show that once mixed together, fluid bilayers can be obtained and, moreover, these can be extruded using classical extrusion processes to form liposomes. The chem. anal. indicates that these liposomes contain 70 mol % cholesterol, a content that is considerably higher that the satn. limit generally reported for phospholipid bilayers. These cholesterol-rich liposomes, formed with mols. that have low toxicity in vivo, display an improved impermeability relative to that of traditional phospholipid liposomes. In addn., because of the presence of palmitic acid, the stability of the liposomes is pH-dependent, and it is possible to trigger the release of encapsulated materials by pH stimuli.
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| 3. |
- Bize, Ariane, et al.
(författare)
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A unique virus release mechanism in the Archaea
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:27, s. 11306-11311
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the infection cycles of viruses infecting cells from Archaea, the third domain of life. Here, we demonstrate that the virions of the archaeal Sulfolobus islandicus rod-shaped virus 2 (SIRV2) are released from the host cell through a mechanism, involving the formation of specific cellular structures. Large pyramidal virus-induced protrusions transect the cell envelope at several positions, rupturing the S-layer; they eventually open out, thus creating large apertures through which virions escape the cell. We also demonstrate that massive degradation of the host chromosomes occurs because of virus infection, and that virion assembly occurs in the cytoplasm. Furthermore, intracellular viral DNA is visualized by flow cytometry. The results show that SIRV2 is a lytic virus, and that the host cell dies as a consequence of elaborated mechanisms orchestrated by the virus. The generation of specific cellular structures for a distinct step of virus life cycle is known in eukaryal virus-host systems but is unprecedented in cells from other domains.
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| 4. |
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| 5. |
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| 6. |
- Engström, Maria, et al.
(författare)
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Working Memory in 8 Kleine-Levin Syndrome Patients : An fMRI Study
- 2009
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Ingår i: SLEEP. - 0161-8105. ; 32:5, s. 681-688
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: The objectives of this study were to investigate possible neuropathology behind the Kleine-Levin Syndrome (KLS), a severe form of hypersomnia with onset during adolescence.Design: Functional magnetic resonance imaging (fMRI) applying a verbal working memory task was used in conjunction with a paper-and-pencil version of the task. Participants: Eight patients with KLS and 12 healthy volunteers participated in the study.Results: The results revealed a pattern of increased thalamic activity and reduced frontal activity (involving the anterior cingulate and adjacent prefrontal cortex) while performing a reading span task.Discussion: This finding may explain the clinical symptoms observed in KLS, in that the thalamus is known to be involved in the control of sleep. Given the increasing access to fMRI, this investigation may aid clinicians in the diagnosis of patients suffering from severe forms of hypersomnia.
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| 7. |
- Grundberg, Elin, et al.
(författare)
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Population genomics in a disease targeted primary cell model
- 2009
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 19:11, s. 1942-1952
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Tidskriftsartikel (refereegranskat)abstract
- The common genetic variants associated with complex traits typically lie in noncoding DNA and may alter gene regulation in a cell type-specific manner. Consequently, the choice of tissue or cell model in the dissection of disease associations is important. We carried out an expression quantitative trait loci (eQTL) study of primary human osteoblasts (HOb) derived from 95 unrelated donors of Swedish origin, each represented by two independently derived primary lines to provide biological replication. We combined our data with publicly available information from a genome-wide association study (GWAS) of bone mineral density (BMD). The top 2000 BMD-associated SNPs (P < approximately 10(-3)) were tested for cis-association of gene expression in HObs and in lymphoblastoid cell lines (LCLs) using publicly available data and showed that HObs have a significantly greater enrichment (threefold) of converging cis-eQTLs as compared to LCLs. The top 10 BMD loci with SNPs showing strong cis-effects on gene expression in HObs (P = 6 x 10(-10) - 7 x 10(-16)) were selected for further validation using a staged design in two cohorts of Caucasian male subjects. All 10 variants were tested in the Swedish MrOS Cohort (n = 3014), providing evidence for two novel BMD loci (SRR and MSH3). These variants were then tested in the Rotterdam Study (n = 2090), yielding converging evidence for BMD association at the 17p13.3 SRR locus (P(combined) = 5.6 x 10(-5)). The cis-regulatory effect was further fine-mapped to the proximal promoter of the SRR gene (rs3744270, r(2) = 0.5, P = 2.6 x 10(-15)). Our results suggest that primary cells relevant to disease phenotypes complement traditional approaches for prioritization and validation of GWAS hits for follow-up studies.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Karlsson Edlund, Patrick, 1975-
(författare)
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Methods and models for 2D and 3D image analysis in microscopy, in particular for the study of muscle cells
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many research questions in biological research lead to numerous microscope images that need to be evaluated. Here digital image cytometry, i.e., quantitative, automated or semi-automated analysis of the images is an important rapidly growing discipline. This thesis presents contributions to that field. The work has been carried out in close cooperation with biomedical research partners, successfully solving real world problems.The world is 3D and modern imaging methods such as confocal microscopy provide 3D images. Hence, a large part of the work has dealt with the development of new and improved methods for quantitative analysis of 3D images, in particular fluorescently labeled skeletal muscle cells.A geometrical model for robust segmentation of skeletal muscle fibers was developed. Images of the multinucleated muscle cells were pre-processed using a novel spatially modulated transform, producing images with reduced complexity and facilitating easy nuclei segmentation. Fibers from several mammalian species were modeled and features were computed based on cell nuclei positions. Features such as myonuclear domain size and nearest neighbor distance, were shown to correlate with body mass, and femur length. Human muscle fibers from young and old males, and females, were related to fiber type and extracted features, where myonuclear domain size variations were shown to increase with age irrespectively of fiber type and gender.A segmentation method for severely clustered point-like signals was developed and applied to images of fluorescent probes, quantifying the amount and location of mitochondrial DNA within cells. A synthetic cell model was developed, to provide a controllable golden standard for performance evaluation of both expert manual and fully automated segmentations. The proposed method matches the correctness achieved by manual quantification.An interactive segmentation procedure was successfully applied to treated testicle sections of boar, showing how a common industrial plastic softener significantly affects testosterone concentrations.
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| 12. |
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| 13. |
- Karlsson, Patrick, et al.
(författare)
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Analysis of Skeletal Fibers in Three Dimensional Images : Methodological considerations
- 2007
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Ingår i: XXXVIth European Muscle Conference of the European Society for Muscle Research. ; , s. 130-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Knowledge of the detailed three dimensional organization of nuclei in skeletal muscle fibers is of fundamental importance for the understanding of the basic mechanisms involved in muscle wasting associated with for example neuromuscular disorders and aging. An ongoing interdisciplinary collaboration between the Centre for Image Analysis (CBA), and the Muscle Research Group (MRG), both at Uppsala University, addresses the issue of spatial distribution of myonuclei using confocal microscopic techniques together with advanced methods for computerized image analysis. Performing quantitative analysis on true three dimensional volume images captured by confocal microscopy gives us the option to perform in-depth statistical analysis of the relationship between neighboring myonuclei. The three dimensional representation enables extraction of a number of features for individual myonuclei, e.g., size and shape of a nucleus, and the myonuclear domain (in which each myonucleus control the gene products). This project investigates data sets from single muscle fibers sampled from mouse, rat, pig, human, horse and rhino to determine the myonuclei arrangement between species with a 100,000 fold difference in body weight. The appropriate image analysis tools needed for gaining the understanding of organization in three dimensional volume images are developed within the project to facilitate the analysis of similarities between species, and unique features within a species. The accumulated understanding of the spatial organization of myonuclei, and the effect of individual myonuclei size, will lead to an increased knowledge of basic mechanisms underlying muscle wasting in various neuromuscular disorders. This knowledge will hopefully lead to new therapeutic strategies that can be evaluated in experimental animal models prior to clinical testing trials in patients.
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| 14. |
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| 15. |
- Karlsson, Patrick, et al.
(författare)
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Correction in 3D Confocal Images
- 2008
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Ingår i: Proceedings of the 2008 Symposium on Image Analysis. ; , s. 31-34
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 16. |
- Liu, Jing-Xia, et al.
(författare)
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Myonuclear domain size and myosin isoform expression in muscle fibres from mammals representing a 100 000-fold difference in body size
- 2009
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 94:1, s. 117-129
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Tidskriftsartikel (refereegranskat)abstract
- This comparative study of myonuclear domain (MND) size in mammalian species representing a 100 000-fold difference in body mass, ranging from 25 g to 2500 kg, was undertaken to improve our understanding of myonuclear organization in skeletal muscle fibres. Myonuclear domain size was calculated from three-dimensional reconstructions in a total of 235 single muscle fibre segments at a fixed sarcomere length. Irrespective of species, the largest MND size was observed in muscle fibres expressing fast myosin heavy chain (MyHC) isoforms, but in the two smallest mammalian species studied (mouse and rat), MND size was not larger in the fast-twitch fibres expressing the IIA MyHC isofom than in the slow-twitch type I fibres. In the larger mammals, the type I fibres always had the smallest average MND size, but contrary to mouse and rat muscles, type IIA fibres had lower mitochondrial enzyme activities than type I fibres. Myonuclear domain size was highly dependent on body mass in the two muscle fibre types expressed in all species, i.e. types I and IIA. Myonuclear domain size increased in muscle fibres expressing both the β/slow (type I; r= 0.84, P < 0.001) and the fast IIA MyHC isoform (r= 0.90; P < 0.001). Thus, MND size scales with body size and is highly dependent on muscle fibre type, independent of species. However, myosin isoform expression is not the sole protein determining MND size, and other protein systems, such as mitochondrial proteins, may be equally or more important determinants of MND size.
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| 17. |
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| 18. |
- Nyblom, Per, 1976-
(författare)
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Dynamic Abstraction for Interleaved Task Planning and Execution
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is often beneficial for an autonomous agent that operates in a complex environment to make use of different types of mathematical models to keep track of unobservable parts of the world or to perform prediction, planning and other types of reasoning. Since a model is always a simplification of something else, there always exists a tradeoff between the model’s accuracy and feasibility when it is used within a certain application due to the limited available computational resources. Currently, this tradeoff is to a large extent balanced by humans for model construction in general and for autonomous agents in particular. This thesis investigates different solutions where such agents are more responsible for balancing the tradeoff for models themselves in the context of interleaved task planning and plan execution. The necessary components for an autonomous agent that performs its abstractions and constructs planning models dynamically during task planning and execution are investigated and a method called DARE is developed that is a template for handling the possible situations that can occur such as the rise of unsuitable abstractions and need for dynamic construction of abstraction levels. Implementations of DARE are presented in two case studies where both a fully and partially observable stochastic domain are used, motivated by research with Unmanned Aircraft Systems. The case studies also demonstrate possible ways to perform dynamic abstraction and problem model construction in practice.
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| 19. |
- Pettersson, Per Olof, 1976-
(författare)
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Sampling-based Path Planning for an Autonomous Helicopter
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many of the applications that have been proposed for future small unmanned aerial vehicles (UAVs) are at low altitude in areas with many obstacles. A vital component for successful navigation in such environments is a path planner that can find collision free paths for the UAV.Two popular path planning algorithms are the probabilistic roadmap algorithm (PRM) and the rapidly-exploring random tree algorithm (RRT).Adaptations of these algorithms to an unmanned autonomous helicopter are presented in this thesis, together with a number of extensions for handling constraints at different stages of the planning process.The result of this work is twofold:First, the described planners and extensions have been implemented and integrated into the software architecture of a UAV. A number of flight tests with these algorithms have been performed on a physical helicopter and the results from some of them are presented in this thesis.Second, an empirical study has been conducted, comparing the performance of the different algorithms and extensions in this planning domain. It is shown that with the environment known in advance, the PRM algorithm generally performs better than the RRT algorithm due to its precompiled roadmaps, but that the latter is also usable as long as the environment is not too complex. The study also shows that simple geometric constraints can be added in the runtime phase of the PRM algorithm, without a big impact on performance. It is also shown that postponing the motion constraints to the runtime phase can improve the performance of the planner in some cases.
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| 20. |
- Turner, Pernilla, et al.
(författare)
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A novel variant of Thermotoga neapolitana beta-glucosidase B is an efficient catalyst for the synthesis of alkyl glucosides by transglycosylation
- 2007
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 130:1, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- Alkyl glycosides are surfactants with good biodegradability and low toxicity, attractive to produce by an enzymatic method to get a well-defined product. In this paper, we report a novel thermostable variant of a family 3 β-glucosidase to be an efficient catalyst in alkyl-glucoside forming reactions using transglycosylation with hexanol or octanol as the acceptor molecule. The enzyme has an apparent optimum for hydrolysis at 90 °C, which coincides with its unfolding temperature. The total activity is lower at lower temperature (60 °C), but the ratio of alcoholysis/hydrolysis is slightly more favourable. This ratio is however more heavily influenced by the water content and the pH. Optimal reaction conditions for hexyl glucoside synthesis from p-nitrophenyl-β-glucopyranoside were a water/hexanol two-phase system containing 16% (v/v) water, pH 5.8, and a temperature of 60 °C. Under these conditions, the total initial reaction rate was 153 μmol min−1 mg−1 and the alcoholysis/hydrolysis ratio was 5.1. Comparing with alcoholysis/hydrolysis ratios of other β-glycosidases, TnBgl3B can be considered to be a very promising catalyst for alkyl glucoside production.
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| 21. |
- Wählby, Carolina, 1974-, et al.
(författare)
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Finding cells, finding molecules, finding patterns
- 2006
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Ingår i: Advances in Data Mining. ; , s. 15-24
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Konferensbidrag (refereegranskat)abstract
- Many modern molecular labeling techniques result in bright point signals. Signals from molecules that are detected directly inside a cell can be captured by fluorescence microscopy. Signals representing different types of molecules may be randomly distributed in the cells or show systematic patterns indicating that the corresponding molecules have specific, non-random localizations and functions in the cell. Assessing this information requires high speed robust image segmentation followed by signal detection, and finally pattern analysis. We present and discuss this type of methods and show an example of how the distribution of different variants of mitochondrial DNA can be analyzed.
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| 22. |
- Wählby, Carolina, et al.
(författare)
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Finding cells, finding molecules, finding patterns
- 2008
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Ingår i: International Journal of Signal and Imaging Systems Engineering. - 1748-0698. ; 1:1, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- Many modern molecular labelling techniques result in bright point signals. Signals from molecules that are detected directly inside a cell can be captured by fluorescence microscopy. Signals representing different types of molecules may be randomly distributed in the cells or show systematic patterns, indicating that the corresponding molecules have specific, non-random localisations and functions in the cell. Assessing this information requires high speed robust image segmentation followed by signal detection, and finally, pattern analysis. We present and discuss these types of methods and show an example of how the distribution of different variants of mitochondrial DNA can be analysed.
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