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Search Results: 1 - 10 of 45 matches for " Ottar Rolfsson "
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The human metabolic reconstruction Recon 1 directs hypotheses of novel human metabolic functions
Ottar Rolfsson, Bernhard ? Palsson, Ines Thiele
BMC Systems Biology , 2011, DOI: 10.1186/1752-0509-5-155
Abstract: We used the human metabolic network reconstruction RECON 1 and established constraint-based modelling tools to uncover novel functions associated with human metabolism. Flux variability analysis identified 175 gaps in RECON 1 in the form of blocked reactions. These gaps were unevenly distributed within metabolic pathways but primarily found in the cytosol and often caused by compounds whose metabolic fate, rather than production, is unknown. Using a published algorithm, we computed gap-filling solutions comprised of non-organism specific metabolic reactions capable of bridging the identified gaps. These candidate solutions were found to be dependent upon the reaction environment of the blocked reaction. Importantly, we showed that automatically generated solutions could produce biologically realistic hypotheses of novel human metabolic reactions such as of the fate of iduronic acid following glycan degradation and of N-acetylglutamate in amino acid metabolism.The results demonstrate how metabolic models can be utilised to direct hypotheses of novel metabolic functions in human metabolism; a process that we find is heavily reliant upon manual curation and biochemical insight. The effectiveness of a systems approach for novel biochemical pathway discovery in mammals is demonstrated and steps required to tailor future gap filling algorithms to mammalian metabolic networks are proposed.An in silico model of a genome-scale metabolic network reconstruction is based upon a biochemically, genetically and genomically (BiGG) structured knowledge base [1,2]. It is subject to research that, in many cases, entails predicting an organism's phenotypic response to gene deletions and/or environmental perturbations in silico. These properties have resulted in widespread applications of metabolic models in microbial bioengineering, contextualisation of high-throughput data, and biochemical pathway discovery [2,3]. While the number of microbial genome-scale metabolic networks has incre
RNA Packing Specificity and Folding during Assembly of the Bacteriophage MS2
Ottar Rolfsson,Katerina Toropova,Victoria Morton,Simona Francese,Gabriella Basnak,Gary S. Thompson,Stephen W. Homans,Alison E. Ashcroft,Nicola J. Stonehouse,Neil A. Ranson,Peter G. Stockley
Computational and Mathematical Methods in Medicine , 2008, DOI: 10.1080/17486700802168445
Abstract: Using a combination of biochemistry, mass spectrometry, NMR spectroscopy and cryo-electron microscopy (cryo-EM), we have been able to show that quasi-equivalent conformer switching in the coat protein (CP) of an RNA bacteriophage (MS2) is controlled by a sequence-specific RNA–protein interaction. The RNA component of this complex is an RNA stem-loop encompassing just 19 nts from the phage genomic RNA, which is 3569 nts in length. This binding results in the conversion of a CP dimer from a symmetrical conformation to an asymmetric one. Only when both symmetrical and asymmetrical dimers are present in solution is assembly of the T = 3 phage capsid efficient. This implies that the conformers, we have characterized by NMR correspond to the two distinct quasi-equivalent conformers seen in the 3D structure of the virion. An icosahedrally-averaged single particle cryo-EM reconstruction of the wild-type phage (to ∼9 Å resolution) has revealed icosahedrally ordered density encompassing up to 90% of the single-stranded RNA genome. The RNA is seen with a novel arrangement of two concentric shells, with connections between them along the 5-fold symmetry axes. RNA in the outer shell interacts with each of the 90 CP dimers in the T = 3 capsid and although the density is icosahedrally averaged, there appears to be a different average contact at the different quasi-equivalent protein dimers: precisely the result that would be expected if protein conformer switching is RNA-mediated throughout the assembly pathway. This unprecedented RNA structure provides new constraints for models of viral assembly and we describe experiments aimed at probing these. Together, these results suggest that viral genomic RNA folding is an important factor in efficient assembly, and further suggest that RNAs that could sequester viral CPs but not fold appropriately could act as potent inhibitors of viral assembly.
Eco-Efficiency Assessments as a Tool for Revealing the Environmental Improvement Potential of New Regulations
Ottar Michelsen
Sustainability , 2010, DOI: 10.3390/su2010117
Abstract: Public regulations can result in improved environmental performance of products. In this paper eco-efficiency is used to assess the most likely outcome of potential new regulations. The paper presents a case study of furniture production in Norway where different scenarios for improving the environmental performance of the products are presented. Four regulatory options for imposing environmental improvements are assessed; (1) an introduction of a tax on emissions, (2) an increase of the tax on landfills, (3) an introduction of a tax on raw material consumption, and (4) introduction of take-back legislation.
SUNCT syndrome: The materialization of a headache syndrome
Ottar Sjaastad
Clinical Ophthalmology , 2008,
Abstract: Ottar SjaastadDepartment of Neurology, St. Olav′s Hospital, 7006 Trondheim University Hospitals, Trondheim, NorwayAbstract: Shortlasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome is a rare headache, described by our group in 1989. This overview presents our early studies of SUNCT pathogenesis. Due to the conspicuous ictal, ocular phenomena, ie, conjunctival injection and tearing, our studies started out with ocular parameters: intraocular pressure and corneal indentation pulse amplitudes, both of which showed clear ictal increments, symptomatic side. Beat-to-beat, noninvasive blood pressure measurements during attack showed instant, systolic blood pressure rise and corresponding pulse rate decrease. Carotid body, the principal peripheral chemoreceptor, seemed to function normally. The middle cerebral artery was dilated during attacks, particularly on the symptomatic side. Finally, some viewpoints are added regarding terminology. SUNCT is a workable and accepted term. There does not seem to be any need for another, fictitious term to describe the same clinical picture.Keywords: SUNCT syndrome, intraocular blood flow, intraocular pressure, median artery blood flow, carotid body function, hypothalamic stimulation
Linkage of Osteoporosis to Chromosome 20p12 and Association to BMP2
Unnur Styrkarsdottir,Jean-Baptiste Cazier,Augustine Kong,Ottar Rolfsson,Helene Larsen,Emma Bjarnadottir,Vala D. Johannsdottir,Margret S. Sigurdardottir,Yu Bagger,Claus Christiansen,Inga Reynisdottir,Struan F. A. Grant,Kristjan Jonasson,Michael L. Frigge,Jeffrey R. Gulcher,Gunnar Sigurdsson,Kari Stefansson
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0000069
Abstract: Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 × 10?7), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes.
Linkage of Osteoporosis to Chromosome 20p12 and Association to BMP2
Unnur Styrkarsdottir ,Jean-Baptiste Cazier,Augustine Kong,Ottar Rolfsson,Helene Larsen,Emma Bjarnadottir,Vala D Johannsdottir,Margret S Sigurdardottir,Yu Bagger,Claus Christiansen,Inga Reynisdottir,Struan F. A Grant,Kristjan Jonasson,Michael L Frigge,Jeffrey R Gulcher equal contributor,Gunnar Sigurdsson ,Kari Stefansson equal contributor
PLOS Biology , 2003, DOI: 10.1371/journal.pbio.0000069
Abstract: Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 × 10?7), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes.
Altered motor control patterns in whiplash and chronic neck pain
Astrid Woodhouse, Ottar Vasseljen
BMC Musculoskeletal Disorders , 2008, DOI: 10.1186/1471-2474-9-90
Abstract: Participants (n = 173) were recruited to three groups: 59 patients with persistent WAD, 57 patients with chronic non-traumatic neck pain and 57 asymptomatic volunteers. A 3D motion tracking system (Fastrak) was used to record maximal range of motion in the three cardinal planes of the cervical spine (sagittal, frontal and horizontal), and concurrent motion in the two associated cardinal planes relative to each primary plane were used to express conjunct motion. Joint position error was registered as the difference in head positions before and after cervical rotations.Reduced conjunct motion was found for WAD and chronic neck pain patients compared to asymptomatic subjects. This was most evident during cervical rotation. Reduced conjunct motion was not explained by current pain or by range of motion in the primary plane. Total conjunct motion during primary rotation was 13.9° (95% CI; 12.2–15.6) for the WAD group, 17.9° (95% CI; 16.1–19.6) for the chronic neck pain group and 25.9° (95% CI; 23.7–28.1) for the asymptomatic group. As expected, maximal cervical range of motion was significantly reduced among the WAD patients compared to both control groups. No group differences were found in maximal ROM-variability or joint position error.Altered movement patterns in the cervical spine were found for both pain groups, indicating changes in motor control strategies. The changes were not related to a history of neck trauma, nor to current pain, but more likely due to long-lasting pain. No group differences were found for kinaesthetic sense.Whiplash associated disorders (WAD) have been studied mainly in comparison to asymptomatic subjects and it remains controversial whether WAD represent a diagnostic entity different from chronic neck pain. WAD patients are separated from chronic neck pain merely on the history of trauma [1]. The trauma designation is however not reflected in structural injuries of the cervical spine or the cerebrum [2,3]. Consequently, somatosensory and m
Measuring inequalities in the distribution of health workers: the case of Tanzania
Michael A Munga, Ottar M?stad
Human Resources for Health , 2009, DOI: 10.1186/1478-4491-7-4
Abstract: We plotted Lorenz and concentration curves to illustrate graphically the distribution of the total health workforce and the cadre-specific (skill mix) distributions. Alternative indicators of health care needs were illustrated by concentration curves. Inequalities were measured by calculating Gini and concentration indices.There are significant inequalities in the distribution of health workers per capita. Overall, the population quintile with the fewest health workers per capita accounts for only 8% of all health workers, while the quintile with the most health workers accounts for 46%. Inequality is perceptible across both urban and rural districts. Skill mix inequalities are also large. Districts with a small share of the health workforce (relative to their population levels have an even smaller share of highly trained medical personnel. A small share of highly trained personnel is compensated by a larger share of clinical officers (a middle-level cadre) but not by a larger share of untrained health workers. Clinical officers are relatively equally distributed. Distributional inequalities tend to be more pronounced when under-five deaths are used as an indicator of health care needs. Conversely, if health care needs are measured by HIV prevalence, the distributional inequalities appear to decline.The measure of inequality in the distribution of the health workforce may depend strongly on the underlying measure of health care needs. In cases of a non-uniform distribution of health care needs across geographical areas, other measures of health care needs than population levels may have to be developed in order to ensure a more meaningful measurement of distributional inequalities of the health workforce.During the last few years, much attention has been paid to the general shortage of health workers in low-income countries, [1,2] and to the crucial importance of reducing it to attain the Millennium Development Goals [3-5]. In addition to the general shortage of hea
Measles on the Edge: Coastal Heterogeneities and Infection Dynamics
Nita Bharti, Yingcun Xia, Ottar N. Bjornstad, Bryan T. Grenfell
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001941
Abstract: Mathematical models can help elucidate the spatio-temporal dynamics of epidemics as well as the impact of control measures. The gravity model for directly transmitted diseases is currently one of the most parsimonious models for spatial epidemic spread. This model uses distance-weighted, population size-dependent coupling to estimate host movement and disease incidence in metapopulations. The model captures overall measles dynamics in terms of underlying human movement in pre-vaccination England and Wales (previously established). In spatial models, edges often present a special challenge. Therefore, to test the model's robustness, we analyzed gravity model incidence predictions for coastal cities in England and Wales. Results show that, although predictions are accurate for inland towns, they significantly underestimate coastal persistence. We examine incidence, outbreak seasonality, and public transportation records, to show that the model's inaccuracies stem from an underestimation of total contacts per individual along the coast. We rescue this predicted ‘edge effect’ by increasing coastal contacts to approximate the number of per capita inland contacts. These results illustrate the impact of ‘edge effects’ on epidemic metapopulations in general and illustrate directions for the refinement of spatiotemporal epidemic models.
The decentralisation-centralisation dilemma: recruitment and distribution of health workers in remote districts of Tanzania
Michael A Munga, Nils Songstad, Astrid Blystad, Ottar M?stad
BMC International Health and Human Rights , 2009, DOI: 10.1186/1472-698x-9-9
Abstract: An exploratory qualitative study was conducted among informants recruited from five underserved, remote districts of mainland Tanzania. Additional informants were recruited from the central government, the NGO sector, international organisations and academia. A comparison of decentralised and the reinstated centralised systems was carried out in order to draw lessons necessary for improving recruitment, distribution and retention of health workers.The study has shown that recruitment of health workers under a decentralised arrangement has not only been characterised by complex bureaucratic procedures, but by severe delays and sometimes failure to get the required health workers. The study also revealed that recruitment of highly skilled health workers under decentralised arrangements may be both very difficult and expensive. Decentralised recruitment was perceived to be more effective in improving retention of the lower cadre health workers within the districts. In contrast, the centralised arrangement was perceived to be more effective both in recruiting qualified staff and balancing their distribution across districts, but poor in ensuring the retention of employees.A combination of centralised and decentralised recruitment represents a promising hybrid form of health sector organisation in managing human resources by bringing the benefits of two worlds together. In order to ensure that the potential benefits of the two approaches are effectively integrated, careful balancing defining the local-central relationships in the management of human resources needs to be worked out.Recruiting and retaining highly qualified health workers in remotely located areas presents an enormous challenge both in developed and developing countries. In both, the urban areas are generally perceived as more attractive because they are relatively more developed, and offer better working and living conditions to the workers, their families and relatives. Urban areas also seem to offer a
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