| 1. |
- Covarrubias, Adrian Suarez, et al.
(författare)
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Structural, biochemical and in vivo investigations of the threonine synthase from Mycobacterium tuberculosis
- 2008
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 381:3, s. 622-633
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Tidskriftsartikel (refereegranskat)abstract
- Threonine biosynthesis is a general feature of prokaryotes, eukaryotic microorganisms, and higher plants. Since mammals lack the appropriate synthetic machinery, instead obtaining the amino acid through their diet, the pathway is a potential focus for the development of novel antibiotics, antifungal agents, and herbicides. Threonine synthase (TS), a pyridoxal-5-phosphate-dependent enzyme, catalyzes the final step in the pathway, in which L-homoserine phosphate and water are converted into threonine and inorganic phosphate. In the present publication, we report structural and functional studies of Mycobacterium tuberculosis TS, the product of the rv1295 (thrC) gene. The structure gives new insights into the catalytic mechanism of TSs in general, specifically by suggesting the direct involvement of the phosphate moiety of the cofactor, rather than the inorganic phosphate product, in transferring a proton from C4' to C-gamma in the formation of the alpha beta-unsaturated aldimine. It further provides a basis for understanding why this enzyme has a higher pH optimum than has been reported elsewhere for TSs and gives rise to the prediction that the equivalent enzyme from Thermus thermophilus will exhibit similar behavior. A deletion of the relevant gene generated a strain of M. tuberculosis that requires threonine for growth, such auxotrophic strains are frequently attenuated in vivo, indicating that TS is a potential drug target in this organism.
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| 2. |
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| 3. |
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| 4. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 5. |
- Eriksson, Martin, 1970, et al.
(författare)
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A phylogenetic approach to detect selection on the target site of the antifouling compound irgarol in tolerant periphyton communities
- 2009
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Ingår i: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 11:8, s. 2065-2077
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Tidskriftsartikel (refereegranskat)abstract
- Using DNA sequence data for phylogenetic assessment of toxicant targets is a new and promising approach to study toxicant-induced selection in communities. Irgarol 1051 is a photosystem (PS) II inhibitor used in antifouling paint. It inhibits photosynthesis through binding to the D1 protein in PS II, which is encoded by the psbA gene found in genomes of chloroplasts, cyanobacteria and cyanophages. psbA mutations that alter the target protein can confer tolerance to PS II inhibitors. We have previously shown that irgarol induces community tolerance in natural marine periphyton communities and suggested a novel tolerance mechanism, involving the amino acid sequence of a turnover-regulating domain of D1, as contributive to this tolerance. Here we use a large number of psbA sequences of known identity to assess the taxonomic affinities of psbA sequences from these differentially tolerant communities, by performing phylogenetic analysis. We show that periphyton communities have high psbA diversity and that this diversity is adversely affected by irgarol. Moreover, we suggest that within tolerant periphyton the novel tolerance mechanism is present among diatoms only, whereas some groups of irgarol-tolerant cyanobacteria seem to have other tolerance mechanisms. However, it proved difficult to identify periphyton psbA haplotypes to the species or genus level, which indicates that the genomic pool of the attached, periphytic life forms is poorly studied and inadequately represented in international sequence databases.
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| 6. |
- Eriksson, Martin, 1970, et al.
(författare)
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Community-Level Analysis of psbA Gene Sequences and Irgarol Tolerance in Marine Periphyton
- 2009
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Ingår i: Applied and Environmental Microbiology. - Washington, D.C. : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 75:4, s. 897-906
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Tidskriftsartikel (refereegranskat)abstract
- This study analyzes psbA gene sequences, predicted D1 protein sequences, species relative abundance, and pollution-induced community tolerance in marine periphyton communities exposed to the antifouling compound Irgarol 1051. The mechanism of action of Irgarol is the inhibition of photosynthetic electron transport at photosystem II by binding to the D1 protein. The metagenome of the communities was used to produce clone libraries containing fragments of the psbA gene encoding the D1 protein. Community tolerance was quantified with a short-term test for the inhibition of photosynthesis. The communities were established in a continuous flow of natural seawater through microcosms with or without added Irgarol. The selection pressure from Irgarol resulted in an altered species composition and an inducted community tolerance to Irgarol. Moreover, there was a very high diversity in the psbA gene sequences in the periphyton, and the composition of psbA and D1 fragments within the communities was dramatically altered by increased Irgarol exposure. Even though tolerance to this type of compound in land plants often depends on a single amino acid substitution (Ser(264)-> Gly) in the D1 protein, this was not the case for marine periphyton species. Instead, the tolerance mechanism likely involves increased degradation of D1. When we compared sequences from low and high Irgarol exposure, differences in nonconserved amino acids were found only in the so-called PEST region of D1, which is involved in regulating its degradation. Our results suggest that environmental contamination with Irgarol has led to selection for high-turnover D1 proteins in marine periphyton communities at the west coast of Sweden.
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| 7. |
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| 8. |
- Evilevitch, Alex, et al.
(författare)
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Effects of salt concentrations and bending energy on the extent of ejection of phage genomes
- 2008
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Ingår i: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 94:3, s. 1110-1120
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Tidskriftsartikel (refereegranskat)abstract
- Recent work has shown that pressures inside dsDNA phage capsids can be as high as many tens of atmospheres; it is this pressure that is responsible for initiation of the delivery of phage genomes to host cells. The forces driving ejection of the genome have been shown to decrease monotonically as ejection proceeds, and hence to be strongly dependent on the genome length. Here we investigate the effects of ambient salts on the pressures inside phage-l, for the cases of mono-, di-, and tetravalent cations, and measure how the extent of ejection against a fixed osmotic pressure (mimicking the bacterial cytoplasm) varies with cation concentration. We find, for example, that the ejection fraction is halved in 30 mM Mg21 and is decreased by a factor of 10 upon addition of 1 mM spermine. These effects are calculated from a simple model of genome packaging, using DNA-DNA repulsion energies as determined independently from x-ray diffraction measurements on bulk DNA solutions. By comparing the measured ejection fractions with values implied from the bulk DNA solution data, we predict that the bending energy makes the d- spacings inside the capsid larger than those for bulk DNA at the same osmotic pressure.
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| 9. |
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| 10. |
- Günther, Juliane, et al.
(författare)
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Assessment of the immune capacity of mammary epithelial cells : comparison with mammary tissue after challenge with Escherichia coli
- 2009
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Ingår i: Veterinary research (Print). - Les Ulis Cedex A, France : EDP Sciences. - 0928-4249 .- 1297-9716. ; 40:4
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Tidskriftsartikel (refereegranskat)abstract
- We examined the repertoire and extent of inflammation dependent gene regulation in a bovine mammary epithelial cell (MEC) model, to better understand the contribution of the MEC in the immune defence of the udder. We challenged primary cultures of MEC from cows with heat inactivated Escherichia coli pathogens and used Affymetrix DNA-microarrays to profile challenge related alterations in their transcriptome. Compared to acute mastitis, the most prominently activated genes comprise those encoding chemokines, interleukins, beta-defensins, serum amyloid A and haptoglobin. Hence, the MEC exert sentinel as well as effector functions of innate immune defence. E. coli stimulated a larger fraction of genes (30%) in the MEC belonging to the functional category Inflammatory Response than we recorded with the same microarrays during acute mastitis in the udder (17%). This observation underscores the exquisite immune capacity of MEC. To more closely examine the adequacy of immunological regulation in MEC, we compared the inflammation dependent regulation of factors contributing to the complement system between the udder versus the MEC. In the MEC we observed only up regulation of several complement factor-encoding genes. Mastitis, in contrast, in the udder strongly down regulates such genes encoding factors contributing to both, the classical pathway of complement activation and the Membrane Attack Complex, while the expression of factors contributing to the alternative pathway may be enhanced. This functionally polarized regulation of the complex complement pathway is not reflected in the MEC models.
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| 11. |
- Hacklin, Fredrik, et al.
(författare)
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Core rigidities in the innovation process : a structured benchmark on knowledge management challenges
- 2009
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Ingår i: International Journal of Technology Management. - 0267-5730 .- 1741-5276. ; 45:3-4, s. 244-266
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Konferensbidrag (refereegranskat)abstract
- A changing industrial and technological environment implies a need for a diligent acquisition of dynamic capabilities. While tackling exogenous discontinuities is imperative for success, the problem often lies in the firms' internal processes, where existing core competences might deteriorate to core rigidities. The presented contribution is two-fold: first, a conceptual framework for assessing knowledge-related rigidities along the innovation process is introduced, which is derived from the stage-gate model for new product development. The innovation process is evaluated within cases of four industry firms, with emphasis on identifying problem areas, core rigidities and resulting challenges along the entire way from idea to market launch. Secondly, the challenges are clustered, providing a basis for deriving optimisation approaches, as well as summarised and compared across the cases. In all phases of the innovation process, the benchmark with other firms seems to ease the process of creating awareness on rigidities and to provide a basis for managerial improvement.
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| 12. |
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| 13. |
- King, Martin D., et al.
(författare)
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Oxidation of oleic acid at the air-water interface and its potential effects on cloud critical supersaturations
- 2009
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 11:35, s. 7699-7707
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Tidskriftsartikel (refereegranskat)abstract
- The oxidation of organic films on cloud condensation nuclei has the potential to affect climate and precipitation events. In this work we present a study of the oxidation of a monolayer of deuterated oleic acid (cis-9-octadecenoic acid) at the air-water interface by ozone to determine if oxidation removes the organic film or replaces it with a product film. A range of different aqueous sub-phases were studied. The surface excess of deuterated material was followed by neutron reflection whilst the surface pressure was followed using a Wilhelmy plate. The neutron reflection data reveal that approximately half the organic material remains at the air-water interface following the oxidation of oleic acid by ozone, thus cleavage of the double bond by ozone creates one surface active species and one species that partitions to the bulk (or gas) phase. The most probable products, produced with a yield of similar to(87 +/- 14)%, are nonanoic acid, which remains at the interface, and azelaic acid (nonanedioic acid), which dissolves into the bulk solution. We also report a surface bimolecular rate constant for the reaction between ozone and oleic acid of (7.3 +/- 0.9) x 10(-11) cm(2) molecule s(-1). The rate constant and product yield are not affected by the solution sub-phase. An uptake coefficient of ozone on the oleic acid monolayer of similar to 4 x 10(-6) is estimated from our results. A simple Kohler analysis demonstrates that the oxidation of oleic acid by ozone on an atmospheric aerosol will lower the critical supersaturation needed for cloud droplet formation. We calculate an atmospheric chemical lifetime of oleic acid of 1.3 hours, significantly longer than laboratory studies on pure oleic acid particles suggest, but more consistent with field studies reporting oleic acid present in aged atmospheric aerosol.
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| 14. |
- Martin, Adrian, et al.
(författare)
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An architecture for robotic hardware-in-the-loop simulation
- 2006
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Ingår i: 2006 IEEE International Conference on Mechatronics and Automation, ICMA, Luoyang, China, 25-28 June 2006. - Piscataway, NJ : IEEE Communications Society. - 1424404665 - 9781424404667 ; , s. 2162-2167
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Konferensbidrag (refereegranskat)abstract
- Hardware-in-the-loop simulation is an increasingly popular engineering tool for its effectiveness in maintaining a balance between the two competing demands of: a) well designed and thoroughly tested systems, and b) reduced development time and costs to remain competitive. This paper proposes an architecture for applying hardware-in-the-loop simulation techniques to the design and testing of robot manipulators. Potential benefits of this architecture include allowing concurrent development of hardware and control system components and providing a reusable platform for reconfigurable manipulators through a generic and modular structure. An implementation of this architecture in the preliminary phases of development is presented here to demonstrate how these benefits can be realized. © 2006 IEEE.
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| 15. |
- Martin, Adrian, et al.
(författare)
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Analysis of robotic hardware-in-the-loop simulation architecture
- 2007
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Ingår i: IEEE International Conference on Intelligent Robots and Systems, IROS, San Diego, USA, 29 October-2 November 2007. - Piscataway, NJ : IEEE Communications Society. - 1424409128 - 9781424409129 ; , s. 46-51
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Konferensbidrag (refereegranskat)abstract
- An architecture for Robotic Hardware-in-the-Loop Simulation (RHILS) has been proposed as a design and simulation tool for serial-link robot manipulators [1]. This paper evaluates the RHILS platform's capabilities when applied to the simulation of the 5-d.o.f. CRS CataLyst-5 industrial manipulator from Thermo Fisher Scientific Inc. The results demonstrate that the RHILS platform is able to accurately simulate the robot even under extreme operating conditions, and the platform shows significant potential as a design tool for both the robot and its control unit. ©2007 IEEE.
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| 16. |
- Martin, Adrian, et al.
(författare)
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Control AD Libitum : An approach to real-time construction of control systems for unstructured robotic teams
- 2009
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Ingår i: Proceedings of the IASTED International Conference on Robotics and Applications, RA, Cambridge, USA, 2-4 November 2009. - 9780889868137 ; , s. 383-390
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Konferensbidrag (refereegranskat)abstract
- Developers of mobile robot teams face many challenges that will only continue to grow with the complexity of their applications. As the applications evolve it will become impractical to design custom hardware for each problem and begin each control system from scratch. A new approach to control system design is necessary to overcome these challenges. Control ad libitum is an approach that forms a division between the functionality of the control system and specific hardware components, allowing the system to adapt to changing hardware and simplifying the process of adding functionality to the control system. The philosophy of control ad libitum is presented here along with the "Host, Avatar, Agent" (HAA) control architecture designed following this approach. The HAA architecture provides a flexible structure using a distributed processing network that allows modular and incremental construction of control systems. Current progress on an implementation of the HAA architecture for exploration, mapping, and object collection applications shows promising merit from both design and functionality perspectives.
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| 17. |
- Martin, Adrian, et al.
(författare)
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Design and development of robotic hardware-in-the-loop simulation
- 2006
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Ingår i: 9th International Conference on Control, Automation, Robotics and Vision, ICARCV, Singapore, Singapore, 5-8 December 2006. - Piscataway, NJ : IEEE Communications Society. - 1424403421 - 9781424403424
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Konferensbidrag (refereegranskat)abstract
- This paper details the design and development of a robotic hardware-in-the-loop simulation platform that can be used for rapid-prototyping industrial manipulators. The architecture of the proposed platform has been presented in [1]. Potential benefits of such a platform include allowing concurrent development of hardware and control system components and providing a reusable platform for reconfigurable manipulators through a generic and modular structure. Some preliminary tests on the platform have also been discussed in the paper. © 2006 IEEE.
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| 18. |
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| 19. |
- Martin, Adrian, et al.
(författare)
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Dynamic load emulation for robotic hardware-in-the-loop simulation platforms
- 2008
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Ingår i: IEEE International Symposium on Industrial Electronics, ISIE, Cambridge, UK, 30 June-2 July 2008. - Piscataway, NJ : IEEE Communications Society. - 1424416655 - 9781424416653 ; , s. 2207-2212
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Konferensbidrag (refereegranskat)abstract
- There is a growing interest in using hardware-in-theloop simulations for test, design, and development of robot manipulators. A major challenge, however, is how to emulate the nonlinear and coupled dynamic loads on the joint hardware modules in real time. This paper details such a load emulation mechanism, and discusses its application to an industrial robot manipulator. © 2008 IEEE.
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| 20. |
- Ozsahin, Hulya, et al.
(författare)
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Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation.
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 111:1, s. 439-45
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Tidskriftsartikel (refereegranskat)abstract
- Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS patients who received transplants between 1979 and 2001 who survived at least 2 years following hematopoietic stem-cell transplantation (HSCT). Events included chronic graft-versus-host disease (cGVHD), autoimmunity, infections, and sequelae of before or after HSCT complications. Three patients (3%) died 2.1 to 21 years following HSCT. Overall 7-year event-free survival rate was 75%. It was lower in recipients of mismatched related donors, also in relation with an older age at HSCT and disease severity. The most striking finding was the observation of cGVHD-independent autoimmunity in 20% of patients strongly associated with a mixed/split chimerism status (P < .001), suggesting that residual-host lymphocytes can mediate autoimmune disease despite the coexistence of donor lymphocytes. Infectious complications (6%) related to splenectomy were also significant and may warrant a more restrictive approach to performing splenectomy in WAS patients. Overall, this study provides the basis for a prospective, standardized, and more in-depth detailed analysis of chimerism and events in long-term follow-up of WAS patients who receive transplants to design better-adapted therapeutic strategies.
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| 21. |
- Peacock, Christopher S, et al.
(författare)
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Comparative genomic analysis of three Leishmania species that cause diverse human disease.
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:7, s. 839-847
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Tidskriftsartikel (refereegranskat)abstract
- Leishmania parasites cause a broad spectrum of clinical disease. Here we report the sequencing of the genomes of two species of Leishmania: Leishmania infantum and Leishmania braziliensis. The comparison of these sequences with the published genome of Leishmania major reveals marked conservation of synteny and identifies only 200 genes with a differential distribution between the three species. L. braziliensis, contrary to Leishmania species examined so far, possesses components of a putative RNA-mediated interference pathway, telomere-associated transposable elements and spliced leader–associated SLACS retrotransposons. We show that pseudogene formation and gene loss are the principal forces shaping the different genomes. Genes that are differentially distributed between the species encode proteins implicated in host-pathogen interactions and parasite survival in the macrophage.
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| 22. |
- Piliponsky, Adrian M., et al.
(författare)
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Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis
- 2008
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 14:4, s. 392-398
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis is a complex, incompletely understood and often fatal disorder, typically accompanied by hypotension, that is considered to represent a dysregulated host response to infection. Neurotensin (NT) is a 13-amino-acid peptide that, among its multiple effects, induces hypotension. We find that intraperitoneal and plasma concentrations of NT are increased in mice after severe cecal ligation and puncture (CLP), a model of sepsis, and that mice treated with a pharmacological antagonist of NT, or NT-deficient mice, show reduced mortality during severe CLP. In mice, mast cells can degrade NT and reduce NT-induced hypotension and CLP-associated mortality, and optimal expression of these effects requires mast cell expression of neurotensin receptor 1 and neurolysin. These findings show that NT contributes to sepsis-related mortality in mice during severe CLP and that mast cells can lower NT concentrations, and suggest that mast cell-dependent reduction in NT levels contributes to the ability of mast cells to enhance survival after CLP.
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| 23. |
- Qazi, S. Junaid S., et al.
(författare)
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Use of wide-angle X-ray diffraction to measure shape and size of dispersed colloidal particles
- 2009
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 338:1, s. 105-110
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory X-ray diffraction is used to investigate the size and shape of dispersed plate-like and spherical colloidal particles. Analysis of the wide-angle diffraction data provides information about the size and shape of crystals from the width of the Bragg peaks according to the Debye-Scherrer formula. The measurements, data analysis, and evaluation are discussed. It is shown that X-ray diffraction with conventional laboratory equipment on dispersed particles is feasible as a tool to determine both particle size and shape. Data for two samples - gold colloids and nickel (II) hydroxide particles are presented. The advantages and limitations of the method are discussed. X-ray diffraction measurements that are made in combination with dynamic light scattering can be used to estimate the thickness of stabilizing layers of polymers. (C) 2009 Elsevier Inc. All rights reserved.
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