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  • 51.
    Henriksson, Anna
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Wardle A., David
    Swedish University of Agriculture Sciences, Department of Forest Vegetation Ecology.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Diehl, Sebastian
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Englund, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Strong invaders are strong defenders: implications for the resistance of invaded communities2016Inngår i: Ecology Letters, ISSN 1461-023X, E-ISSN 1461-0248, Vol. 19, nr 4, s. 487-494Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many ecosystems receive a steady stream of non-native species. How biotic resistance develops over time in these ecosystems will depend on how established invaders contribute to subsequent resistance. If invasion success and defence capacity (i.e. contribution to resistance) are correlated, then community resistance should increase as species accumulate. If successful invaders also cause most impact (through replacing native species with low defence capacity) then the effect will be even stronger. If successful invaders instead have weak defence capacity or even facilitative attributes, then resistance should decrease with time, as proposed by the invasional meltdown hypothesis. We analysed 1157 introductions of freshwater fish in Swedish lakes and found that species' invasion success was positively correlated with their defence capacity and impact, suggesting that these communities will develop stronger resistance over time. These insights can be used to identify scenarios where invading species are expected to cause large impact.

  • 52.
    Henriksson, Anna
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Yu, Jun
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Wardle A., David
    Swedish University of Agriculture Sciences, Department of Forest Vegetation Ecology.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Englund, Göran
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Weighted species richness outperforms species richness as predictor of biotic resistance2016Inngår i: Ecology, ISSN 0012-9658, E-ISSN 1939-9170, Vol. 97, nr 1, s. 262-271Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The species richness hypothesis, which predicts that species-rich communities should be better at resisting invasions than species-poor communities, has been empirically tested many times and often poorly supported. In this paper we contrast the species richness hypothesis with four alternative hypotheses with the aim of finding better descriptors of invasion resistance. These alternative hypotheses state that resistance to invasions is determined by abiotic conditions, community saturation (i.e., the number of resident species relative to the maximum number of species that can be supported), presence/absence of key species, or weighted species richness. Weighted species richness is a weighted sum of the number of species, where each species' weight describes its contribution to resistance. We tested these hypotheses using data on the success of 571 introductions of four freshwater fish species into lakes throughout Sweden (i.e., Arctic char (Salvelinus alpinus), tench (Tinca tinca), zander (Sander lucioperca), and whitefish (Coregonus lavaretus)). We found that the weighted species richness best predicted invasion success. The weights describing the contribution of each resident species to community resistance varied considerably in both strength and sign. Positive resistance weights, which indicate that species repel invaders, were as common as negative resistance weights, which indicate facilitative interactions. This result can be contrasted with the implicit assumption of the original species richness hypothesis, that all resident species have negative effects on invader success. We argue that this assumption is unlikely to be true in natural communities, and thus that we expect that weighted species richness is a better predictor of invader success than the actual number of resident species.

  • 53. Hoffman, Daniel E.
    et al.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. SweTree Technologies AB, Umeå, Sweden.
    Bylesjö, Max
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Almac Diagnostics Ltd, Craigavon, UK.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Eriksson, Maria E.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Moritz, Thomas
    Changes in diurnal patterns within the Populus transcriptome and metabolome in response to photoperiod variation2010Inngår i: Plant, Cell and Environment, ISSN 0140-7791, E-ISSN 1365-3040, Vol. 33, nr 8, s. 1298-1313Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Changes in seasonal photoperiod provides an important environmental signal that affects the timing of winter dormancy in perennial, deciduous, temperate tree species, such as hybrid aspen (Populus tremula x Populus tremuloides). In this species, growth cessation, cold acclimation and dormancy are induced in the autumn by the detection of day-length shortening that occurs at a given critical day length. Important components in the detection of such day-length changes are photoreceptors and the circadian clock, and many plant responses at both the gene regulation and metabolite levels are expected to be diurnal. To directly examine this expectation and study components in these events, here we report transcriptomic and metabolomic responses to a change in photoperiod from long to short days in hybrid aspen. We found about 16% of genes represented on the arrays to be diurnally regulated, as assessed by our pre-defined criteria. Furthermore, several of these genes were involved in circadian-associated processes, including photosynthesis and primary and secondary metabolism. Metabolites affected by the change in photoperiod were mostly involved in carbon metabolism. Taken together, we have thus established a molecular catalog of events that precede a response to winter.

  • 54. Idborg, Helena
    et al.
    Oliynyk, Ganna
    Rännar, Stefan
    AcureOmics AB.
    Forshed, Jenny
    Branca, Rui Mamede
    Donten, Magdalena
    Gustafsson, Johanna
    Vikerfors, Anna
    Gunnarsson, Iva
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lehtiö, Janne
    Lundstedt, Torbjörn
    Svenungsson, Elisabet
    Jakobsson, Per-Johan
    Systems biology of SLE: biochemical characterisation of subgroups within SLE for improved diagnosis and treatment2012Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, s. A12-Artikkel i tidsskrift (Annet vitenskapelig)
  • 55. Idborg, Helena
    et al.
    Rannar, Stefan
    Oliynyk, Ganna
    Forshed, Jenny
    Branca, Rui Mamede
    Donten, Magdalena
    Bennett, Kate
    Gustafsson, Johanna
    Vikerfors, Anna
    Truedsson, Lennart
    Nilsson, Bo
    Gunnarsson, Iva
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lehtio, Janne
    Lundstedt, Torbjorn
    Svenungsson, Elisabet
    Jakobsson, Per-Johan
    STRATIFICATION OF SLE PATIENTS FOR IMPROVED DIAGNOSIS AND TREATMENT2013Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, s. A80-A80Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background. Systemic autoimmune diseases (SAIDs) affect about 2% of the population in Western countries. Sufficient diagnostic criteria are lacking due to the heterogeneity within diagnostic categories and apparent overlap regarding symptoms and patterns of autoantibodies between different diagnoses. Systemic lupus erythematosus (SLE) is regarded as a prototype for SAIDs and we hypothesise that subgroups of patients with SLE may have different pathogenesis and should consequently be subject to different treatment strategies.

    Objectives. Our goal is to find new biomarkers to be used for the identification of more homogenous patient populations for clinical trials and to identify sub-groups of patients with high risk of for example cardiovascular events.

    Methods. In this study we have utilised 320 SLE patients from the Karolinska lupus cohort and 320 age and gender matched controls. The SLE cohort was characterised based on clinical, genetic and serological data and combined by multivariate data analysis in a systems biology approach to study possible subgroups. A pilot study was designed to verify and investigate suggested subgroups of SLE. Two main subgroups were defined: One group was defined as having SSA and SSB antibodies and a negative lupus anticoagulant test (LAC), i.e., a “Sjögren-like” group. The other group was defined as being negative for SSA and SSB antibodies but positive in the LAC test.i.e. an “APS-like” group. EDTA-plasma from selected patients in these two groups and controls were analysed using a mass spectrometry (MS) based proteomic and metabolomic approach. Pathway analysis was then performed on the obtained data.

    Results. Our pilot study showed that differences in levels of proteins and metabolites could separate disease groups from population controls. The profile/pattern of involved factors in the complement system supported a division of SLE in two major subgroups, although each individual factor was not significantly different between subgroups. Complement factor 2 (C2) and membrane attack complex (MAC) were analysed in the entire cohort with complementary methods and C2 verifies our results while the levels of MAC did not differ between SLE subgroups. The generated metabolomics data clearly separated SLE patients from controls in both gas chromatography (GC)-MS and liquid chromatography (LC)-MS data. We found for example that tryptophan was lower in the SLE patients compared to controls.

    Conclusions. Our systems biology approach may lead to a better understanding of the disease and its pathogenesis, and assigning patients into subgroups will result in improved diagnosis and better outcome measures of SLE.

  • 56. Jakobsson, P-J
    et al.
    Svenungsson, E.
    Idborg, H.
    Nilsson, P.
    Wheelock, C.
    Gunnarsson, I.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lehtio, J.
    Koistinen, I. S.
    Proteomics and metabolomics in the classification of SLE subsets2014Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr Suppl. 127 Meeting Abstract PP267, s. 95-95Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: Systemic autoimmune diseases (SAIDs) affect about 0.5–1% of Europeans with a remarkable female predominance (80–90%). Present diagnostic entities are vague and rely on fairly old and unspecific criteria that do not use state-of-the-art laboratory parameters. New diagnostic tools and therapeutic/prognostic biomarkers are needed. Systemic lupus erythematosus (SLE) is regarded as a prototype for SAIDs and we hypothesized that subgroups of patients with SLE may have different pathogenesis and should consequently be subject to different treatment strategies. Our aim was to find new biomarkers to be used for the identification of more homogeneous patient populations.

    Method: This study involved 320 SLE patients from the Karolinska lupus cohort and 320 age- and gender-matched controls. Plasma samples were analysed using an antibody Luminex assay with 367 antibodies targeting 281 unique selected proteins. Subsets of the SLE cohort and controls were also analysed for their sphingolipid content, as well as by a metabolomic and mass spectrometry-based proteomic approach.

    Results: The Luminex platform revealed 66 proteins found at higher or lower levels in SLE. Mass spectrometry-based proteomics has shown very promising data for the components of the complement and coagulation cascades. Metabolomics identified patterns of plasma metabolites that separate SLE from controls. Finally, analysis of >30 sphingolipids demonstrated a specific group of these lipids at significantly higher concentrations in SLE compared to controls. Following treatment, these differences were normalized.

    Conclusions: Preliminary data demonstrate the involvement of several distinct biochemical pathways in SLE that can be used for biomarker discovery and a better understanding of the pathophysiological events underlying the disease.

  • 57.
    Jiye, A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Granström, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Marklund, Stefan
    Johansson, Annika
    Stenlund, Hans
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Moritz, Thomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Jiye, A
    Guangji, Wang
    Dynamic modification of blood erythrocytes metabolism based on GC/TOF-MS analysis2006Annet (Annet (populærvitenskap, debatt, mm))
  • 58.
    Jiye, A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Gullberg, Jonas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Johansson, Annika I.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Marklund, Stefan L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Moritz, Thomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Extraction and GC/MS analysis of the human blood plasma metabolome2005Inngår i: ANALYTICAL CHEMISTRY, ISSN 0003-2700, Vol. 77, nr 24, s. 8086-94Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Analysis of the entire set of low molecular weight compounds (LMC), the metabolome, could provide deeper insights into mechanisms of disease and novel markers for diagnosis. In the investigation, we developed an extraction and derivatization protocol, using experimental design theory (design of experiment), for analyzing the human blood plasma metabolome by GC/MS. The protocol was optimized by evaluating the data for more than 500 resolved peaks using multivariate statistical tools including principal component analysis and partial least-squares projections to latent structures (PLS). The performance of five organic solvents (methanol, ethanol, acetonitrile, acetone, chloroform), singly and in combination, was investigated to optimize the LMC extraction. PLS analysis demonstrated that methanol extraction was particularly efficient and highly reproducible. The extraction and derivatization conditions were also optimized. Quantitative data for 32 endogenous compounds showed good precision and linearity. In addition, the determined amounts of eight selected compounds agreed well with analyses by independent methods in accredited laboratories, and most of the compounds could be detected at absolute levels of similar to 0.1 pmol injected, corresponding to plasma concentrations between 0.1 and 1 mu M. The results suggest that the method could be usefully integrated into metabolomic studies for various purposes, e.g., for identifying biological markers related to diseases.

  • 59. Jiye, A
    et al.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Gullberg, Jonas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Moritz, Thomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Marklund, Stefan
    Global analysis of low-molecular-weight compounds in human plasma using GC/TOF-MS2004Inngår i: DRUG METABOLISM REVIEWS, ISSN 0360-2532, Vol. 36, s. 246-246Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    We developed a method for analysis of low-molecular-weight compounds (LMWC) in human plasma involving extraction of metabolites by organic solvents, derivatization of extract and final analysis by GC/TOF-MS. The overall strategy for the development of the method was based on using design-of-experimental (DOE), and data evaluation based on multivariate statistical tools like PCA and PLS. The results showed that the extraction efficiency for different solvents varied, and that methanol was important for high reproducibility. More than 300 compounds could be detected in one analysis. Forty five of them were identified, including amino acids, lipids and free fatty acids, organic acids, carbohydrates and so on. The quantitative data of these metabolites showed, with two exceptions, high precision and good linearity between response and concentration. By using this method it is now possible to analyze plasma samples with high throughput to identify metabolic biomarkers for different kinds of diseases.

  • 60.
    Jonsson, Pär
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bruce, Stephen J
    Moritz, Thomas
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Sjöström, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Plumb, Robert
    Granger, Jennifer
    Maibaum, Elaine
    Nicholson, Jeremy K
    Holmes, Elaine
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Extraction, interpretation and validation of information for comparing samples in metabolic LC/MS data sets2005Inngår i: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 130, nr 5, s. 701-707Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    LC/MS is an analytical technique that, due to its high sensitivity, has become increasingly popular for the generation of metabolic signatures in biological samples and for the building of metabolic data bases. However, to be able to create robust and interpretable ( transparent) multivariate models for the comparison of many samples, the data must fulfil certain specific criteria: (i) that each sample is characterized by the same number of variables, (ii) that each of these variables is represented across all observations, and (iii) that a variable in one sample has the same biological meaning or represents the same metabolite in all other samples. In addition, the obtained models must have the ability to make predictions of, e. g. related and independent samples characterized accordingly to the model samples. This method involves the construction of a representative data set, including automatic peak detection, alignment, setting of retention time windows, summing in the chromatographic dimension and data compression by means of alternating regression, where the relevant metabolic variation is retained for further modelling using multivariate analysis. This approach has the advantage of allowing the comparison of large numbers of samples based on their LC/MS metabolic profiles, but also of creating a means for the interpretation of the investigated biological system. This includes finding relevant systematic patterns among samples, identifying influential variables, verifying the findings in the raw data, and finally using the models for predictions. The presented strategy was here applied to a population study using urine samples from two cohorts, Shanxi (People's Republic of China) and Honolulu ( USA). The results showed that the evaluation of the extracted information data using partial least square discriminant analysis (PLS-DA) provided a robust, predictive and transparent model for the metabolic differences between the two populations. The presented findings suggest that this is a general approach for data handling, analysis, and evaluation of large metabolic LC/MS data sets.

  • 61.
    Jonsson, Pär
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Johansson, Annika I.
    Gullberg, Jonas
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Jiye, A
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Grung, Björn
    Marklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Sjöström, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    High-throughput data analysis for detecting and identifying differences between samples in GC/MS-based metabolomic analyses2005Inngår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 77, nr 17, s. 5635-5642Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In metabolomics, the objective is to identify differences in metabolite profiles between samples. A widely used tool in metabolomics investigations is gas chromatography-mass spectrometry (GC/MS). More than 400 compounds can be detected in a single analysis, if overlapping GC/ MS peaks are deconvoluted. However, the deconvolution process is time-consuming and difficult to automate, and additional processing is needed in order to compare samples. Therefore, there is a need to improve and automate the data processing strategy for data generated in GC/MS-based metabolomics; if not, the processing step will be a major bottleneck for high-throughput analyses. Here we describe a new semiautomated strategy using a hierarchical multivariate curve resolution approach that processes all samples simultaneously. The presented strategy generates (after appropriate treatment, e.g., multivariate analysis) tables of all the detected metabolites that differ in relative concentrations between samples. The processing of 70 samples took similar time to that of the GC/TOFMS analyses of the samples. The strategy has been validated using two different sets of samples: a complex mixture of standard compounds and Arabidopsis samples.

    KeyWords Plus: CHROMATOGRAPHY MASS-SPECTROMETRY; PRINCIPAL COMPONENT ANALYSIS; SYSTEMS BIOLOGY; ARABIDOPSIS-THALIANA; CHEMOMETRIC ANALYSIS; 2-WAY DATA; MS; REGRESSION; RESOLUTION; ALIGNMENT

  • 62.
    Jonsson, Pär
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Sjövik-Johansson, Elin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wuolikainen, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindberg, Johan
    Schuppe-Koistinen, Ina
    Kusano, Miyako
    Sjöström, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Moritz, Thomas
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Predictive metabolite profiling applying hierarchical multivariate curve resolution to GC-MS data: a potential tool for multi-parametric diagnosis2006Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 5, nr 6, s. 1407-1414Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A method for predictive metabolite profiling based on resolution of GC-MS data followed by multivariate data analysis is presented and applied to three different biofluid data sets (rat urine, aspen leaf extracts, and human blood plasma). Hierarchical multivariate curve resolution (H-MCR) was used to simultaneously resolve the GC-MS data into pure profiles, describing the relative metabolite concentrations between samples, for multivariate analysis. Here, we present an extension of the H-MCR method allowing treatment of independent samples according to processing parameters estimated from a set of training samples. Predictions or inclusion of the new samples, based on their metabolite profiles, into an existing model could then be carried out, which is a requirement for a working application within, e.g., clinical diagnosis. Apart from allowing treatment and prediction of independent samples the proposed method also reduces the time for the curve resolution process since only a subset of representative samples have to be processed while the remaining samples can be treated according to the obtained processing parameters. The time required for resolving the 30 training samples in the rat urine example was approximately 13 h, while the treatment of the 30 test samples according to the training parameters required only approximately 30 s per sample (approximately 15 min in total). In addition, the presented results show that the suggested approach works for describing metabolic changes in different biofluids, indicating that this is a general approach for high-throughput predictive metabolite profiling, which could have important applications in areas such as plant functional genomics, drug toxicity, treatment efficacy and early disease diagnosis.

  • 63.
    Jonsson, Pär
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Stenlund, Hans
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Moritz, Thomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Sjöström, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Verheij, Elwin R
    Lindberg, Johan
    Schuppe-Koistinen, Ina
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    A strategy for modelling dynamic responses in metabolic samples characterized by GC/MS2006Inngår i: Metabolomics, Vol. 2, nr 3, s. 135-143Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    A multivariate strategy for studying the metabolic response over time in urinary GC/MS data is presented and exemplified by a study of drug-induced liver toxicity in the rat. The strategy includes the generation of representative data through hierarchical multivariate curve resolution (H-MCR), highlighting the importance of obtaining resolved metabolite profiles for quantification and identification of exogenous (drug related) and endogenous compounds (potential biomarkers) and for allowing reliable comparisons of multiple samples through multivariate projections. Batch modelling was used to monitor and characterize the normal (control) metabolic variation over time as well as to map the dynamic response of the drug treated animals in relation to the control. In this way treatment related metabolic responses over time could be detected and classified as being drug related or being potential biomarkers. In summary the proposed strategy uses the relatively high sensitivity and reproducibility of GC/MS in combination with efficient multivariate curve resolution and data analysis to discover individual markers of drug metabolism and drug toxicity. The presented results imply that the strategy can be of great value in drug toxicity studies for classifying metabolic markers in relation to their dynamic responses as well as for biomarker identification.

  • 64.
    Jonsson, Pär
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Stenlund, Hans
    Moritz, Thomas
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Sjöström, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Verheij, Elwin R
    Lindberg, Johan
    Schuppe-Koistinen, Ina
    Antti, Henrik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Modeling of time dependent toxicological responses in urinary GC/MS dataArtikkel i tidsskrift (Fagfellevurdert)
  • 65.
    Karimpour, Masoumeh
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Surowiec, Izabella
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wu, Junfang
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Gouveia-Figueira, Sandra
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Pinto, Rui
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Bioinformatics Infrastructure for Life Sciences, Sweden.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Zivkovic, Angela M.
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Postprandial metabolomics: A pilot mass spectrometry and NMR study of the human plasma metabolome in response to a challenge meal2016Inngår i: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 908, s. 121-131Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The study of postprandial metabolism is relevant for understanding metabolic diseases and characterizing personal responses to diet. We combined three analytical platforms – gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) – to validate a multi-platform approach for characterizing individual variation in the postprandial state. We analyzed the postprandial plasma metabolome by introducing, at three occasions, meal challenges on a usual diet, and 1.5 years later, on a modified background diet. The postprandial response was stable over time and largely independent of the background diet as revealed by all three analytical platforms. Coverage of the metabolome between NMR and GC-MS included more polar metabolites detectable only by NMR and more hydrophobic compounds detected by GC-MS. The variability across three separate testing occasions among the identified metabolites was in the range of 1.1–86% for GC-MS and 0.9–42% for NMR in the fasting state at baseline. For the LC-MS analysis, the coefficients of variation of the detected compounds in the fasting state at baseline were in the range of 2–97% for the positive and 4–69% for the negative mode. Multivariate analysis (MVA) of metabolites detected with GC-MS revealed that for both background diets, levels of postprandial amino acids and sugars increased whereas those of fatty acids decreased at 0.5 h after the meal was consumed, reflecting the expected response to the challenge meal. MVA of NMR data revealed increasing postprandial levels of amino acids and other organic acids together with decreasing levels of acetoacetate and 3-hydroxybutanoic acid, also independent of the background diet. Together these data show that the postprandial response to the same challenge meal was stable even though it was tested 1.5 years apart, and that it was largely independent of background diet. This work demonstrates the efficacy of a multi-platform metabolomics approach followed by multivariate and univariate data analysis for a broad-scale screen of the individual metabolome, particularly for studies using repeated measures to determine dietary response phenotype.

  • 66. Kirwan, Gemma M
    et al.
    Johansson, Erik
    Kleemann, Robert
    Verheij, Elwin R
    Wheelock, Asa M
    Goto, Susumu
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wheelock, Craig E
    Building Multivariate Systems Biology Models2012Inngår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, nr 16, s. 7064-7071Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Systems biology methods using large-scale "omics" data sets face unique challenges: integrating and analyzing near limitless data space, while recognizing and removing systematic variation or noise. Herein we propose a complementary multivariate analysis workflow to both integrate "omics" data from disparate sources and analyze the results for specific and unique sample correlations. This workflow combines principal component analysis (PCA), orthogonal projections to latent structures discriminate analysis (OPLS-DA), orthogonal 2 projections to latent structures (O2PLS), and shared and unique structures (SUS) plots. The workflow is demonstrated using data from a study in which ApoE3Leiden mice were fed an atherogenic diet consisting of increasing cholesterol levels followed by therapeutic intervention (fenofibrate, rosuvastatin, and LXR activator T-0901317). The levels of structural lipids (lipidomics) and free fatty acids in liver were quantified via liquid chromatography-mass spectrometry (LC-MS). The complementary workflow identified diglycerides as key hepatic metabolites affected by dietary cholesterol and drug intervention. Modeling of the three therapeutics for mice fed a high-cholesterol diet further highlighted diglycerides as metabolites of interest in atherogenesis, suggesting a role in eliciting chronic liver inflammation. In particular, O2PLS-based SUS2 plots showed that treatment with T-0901317 or rosuvastatin returned the diglyceride profile in high-cholesterol-fed mice to that of control animals.

  • 67. Kuess, Peter
    et al.
    Andrzejewski, Piotr
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Georg, Petra
    Knoth, Johannes
    Susani, Martin
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Helbich, Thomas H.
    Polanec, Stephan H.
    Georg, Dietmar
    Nyholm, Tufve
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Association between pathology and texture features of multi parametric MRI of the prostate2017Inngår i: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 62, nr 19, s. 7833-7854Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The role of multi-parametric (mp)MRI in the diagnosis and treatment of prostate cancer has increased considerably. An alternative to visual inspection of mpMRI is the evaluation using histogram-based (first order statistics) parameters and textural features (second order statistics). The aims of the present work were to investigate the relationship between benign and malignant sub-volumes of the prostate and textures obtained from mpMR images. The performance of tumor prediction was investigated based on the combination of histogram-based and textural parameters. Subsequently, the relative importance of mpMR images was assessed and the benefit of additional imaging analyzed. Finally, sub-structures based on the PI-RADS classification were investigated as potential regions to automatically detect maligned lesions. Twenty-five patients who received mpMRI prior to radical prostatectomy were included in the study. The imaging protocol included T2, DWI, and DCE. Delineation of tumor regions was performed based on pathological information. First and second order statistics were derived from each structure and for all image modalities. The resulting data were processed with multivariate analysis, using PCA (principal component analysis) and OPLS-DA (orthogonal partial least squares discriminant analysis) for separation of malignant and healthy tissue. PCA showed a clear difference between tumor and healthy regions in the peripheral zone for all investigated images. The predictive ability of the OPLS-DA models increased for all image modalities when first and second order statistics were combined. The predictive value reached a plateau after adding ADC and T2, and did not increase further with the addition of other image information. The present study indicates a distinct difference in the signatures between malign and benign prostate tissue. This is an absolute prerequisite for automatic tumor segmentation, but only the first step in that direction. For the specific identified signature, DCE did not add complementary information to T2 and ADC maps.

  • 68. Kusano, Miyako
    et al.
    Jonsson, Pär
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Fukushima, Atsushi
    Gullberg, Jonas
    Sjöström, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Moritz, Thomas
    Metabolite signature during short-day induced growth cessation in populus2011Inngår i: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 2, artikkel-id 29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The photoperiod is an important environmental signal for plants, and influences a wide range of physiological processes. For woody species in northern latitudes, cessation of growth is induced by short photoperiods. In many plant species, short photoperiods stop elongational growth after a few weeks. It is known that plant daylength detection is mediated by Phytochrome A (PHYA) in the woody hybrid aspen species. However, the mechanism of dormancy involving primary metabolism remains unclear. We studied changes in metabolite profiles in hybrid aspen leaves (young, middle, and mature leaves) during short-day-induced growth cessation, using a combination of gas chromatography–time-of-flight mass spectrometry, and multivariate projection methods. Our results indicate that the metabolite profiles in mature source leaves rapidly change when the photoperiod changes. In contrast, the differences in young sink leaves grown under long and short-day conditions are less distinct. We found short daylength induced growth cessation in aspen was associated with rapid changes in the distribution and levels of diverse primary metabolites. In addition, we conducted metabolite profiling of leaves of PHYA overexpressor (PHYAOX) and those of the control to find the discriminative metabolites between PHYAOX and the control under the short-day conditions. The metabolite changes observed in PHYAOX leaves, together with those in the source leaves, identified possible candidates for the metabolite signature (e.g., 2-oxo-glutarate, spermidine, putrescine, 4-amino-butyrate, and tryptophan) during short-day-induced growth cessation in aspen leaves.

  • 69. Landén Ludvigsson, Maria
    et al.
    Peterson, Gunnel
    Jull, Gwendolen
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Peolsson, Anneli
    Mechanical properties of the trapezius during scapular elevation in people with chronic whiplash associated disorders: A case-control ultrasound speckle tracking analysis2016Inngår i: Manual Therapy, ISSN 1356-689X, E-ISSN 1532-2769, Vol. 21, s. 177-182Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Approximately 50% of people with Whiplash Associated Disorders (WAD) report longstanding symptoms. The upper trapezius is commonly painful yet its mechanical properties are not fully understood.

    Objectives: This study examined the deformation of different depths of the upper trapezius muscle during a scapular elevation task (shoulder shrugging) before and following loaded arm abduction. Design and Methods: A cross-sectional case-control study of 36 people (26 female and 10 male, mean age 38 (SD 11)) with chronic WAD and 36 controls, matched for age and gender. Real-time ultrasound recordings of upper trapezius were taken during both scapular elevation tasks. Post-process speckle tracking analysis was undertaken of three different sections of the upper trapezius muscle (superficial, middle, deep).

    Results: The WAD group had lower deformation of the superficial section of the upper trapezius compared to the control group in both concentric and eccentric phases of scapular elevation (p < 0.05) especially before the loaded arm abduction. After arm abduction, the deformation of the trapezius was reduced in both groups but only significantly in the WAD-group (p = 0.03). Within-group analysis revealed that the control group least engaged the deep section of upper trapezius during the task (p < 0.01).

    Conclusion: This study, measuring mechanical deformation of the upper trapezius during a scapular elevation task indicates that persons with WAD may display different patterns in engagement of the muscle sections than those in the control group. Further research is needed to replicate and understand the reasons for and implications of this possible change in motor strategy within upper trapezius.

  • 70.
    Larsson, Nirina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Lundström, Susanna
    Pinto, Rui
    Rankin, Greg
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Karimpour, Masoumeh
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Pourazar, Jamshid
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Behndig, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Wheelock, Craig
    Nording, Malin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lipid mediator profiles differ between lung compartments in asthmatic and healthy humans2014Inngår i: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 43, nr 2, s. 453-463Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Oxylipins are oxidised fatty acids that can exert lipid mediator functions in inflammation, and several oxylipins derived from arachidonic acid are linked to asthma. This study quantified oxylipin profiles in different regions of the lung to obtain a broad-scale characterisation of the allergic asthmatic inflammation in relation to healthy individuals. Bronchoalveolar lavage fluid (BALF), bronchial wash fluid and endobronchial mucosal biopsies were collected from 16 healthy and 16 mildly allergic asthmatic individuals. Inflammatory cell counts, immunohistochemical staining and oxylipin profiling were performed. Univariate and multivariate statistics were employed to evaluate compartment-dependent and diagnosis-dependent oxylipin profiles in relation to other measured parameters. Multivariate modelling showed significantly different bronchial wash fluid and BALF oxylipin profiles in both groups ((RY)-Y-2[cum]=0.822 and Q(2)[cum]=0.759). Total oxylipin concentrations and five individual oxylipins, primarily from the lipoxygenase (LOX) pathway of arachidonic and linoleic acid, were elevated in bronchial wash fluid from asthmatics compared to that from healthy controls, supported by immunohistochemical staining of 15-LOX-1 in the bronchial epithelium. No difference between the groups was found among BALF oxylipins. In conclusion, bronchial wash fluid and BALF contain distinct oxylipin profiles, which may have ramifications for the study of respiratory diseases. Specific protocols for sampling proximal and distal airways separately should be employed for lipid mediator studies.

  • 71.
    Lundstedt, Torbjörn
    et al.
    AcurePharma AB, Uppsala, Sweden.
    Hedenström, Mattias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Soeria-Atmadja, D
    Division of Toxicology, National Food Administration, Uppsala, Sweden.
    Hammerling, U
    Division of Toxicology, National Food Administration, Uppsala, Sweden.
    Gabrielsson, Jon
    AcureOmics AB, Umeå, Sweden.
    Olsson, J
    KPL Good Food Practice AB, Uppsala, Sweden.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Dynamic modelling of time series data in nutritional metabonomics: A powerful complement to randomized clinical trials in functional food studies2010Inngår i: Chemometrics and Intelligent Laboratory Systems, ISSN 0169-7439, E-ISSN 1873-3239, Vol. 104, nr 1, s. 112-120Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Functional foods are foods or dietary ingredients that provide a health benefit beyond basic nutrition. A new legislation, known as the Nutrition and Health Claims Regulation, defines the legal framework for such claims within the European Union. Any claim about the nutritional or physiological effects of a product must be scientifically demonstrated. In this study, we have focused on the exploration of metabonomics as a complementary profiling technology to establish monitoring/data analysis procedures of randomized nutritional trials. More specifically, a combined intake of soybean and grapefruit in a human intervention study was analyzed with respect to both pharmacological and physiological effects. Resulting multivariate models showed a diet-induced decrease of lactate, cholesterols and triglycerides. The most drastically elevated metabolite, myo-inositol, was found to accompany a marked reduction of triglyceride levels. Suggestively, this is due to the biotransformation of myo-inositol to phosphatidylinositol, which results in a decrease of available precursors to form triglycerides. Strong inter-subject variation was present that required special attention. Dynamic modelling of collected time series data that provided the opportunity to identify slow, medium or fast responders as well as groups of subjects showing different response profiles, was also highlighted in the study. The applied strategy of time series data has proven to be a powerful complement to randomized nutritional studies adopting a clinical trial design.

  • 72.
    Lundstedt, Torbjörn
    et al.
    AcureOmics AB.
    Moritz, Tomas
    Madsen, Rasmus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lundstedt-Enkel, Katrin
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Endogenous metabolic profiling as a tool in drug discovery2010Inngår i: Abstract book for the 7th annual global conference on Neuroprotection and Neuroregeneration 2010, Stockholm, Sweden, Ingenta Connect , 2010Konferansepaper (Annet vitenskapelig)
  • 73. Lundstedt, Torbjörn
    et al.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Eriksson, Lennart
    Gottfries, Johan
    Editorial2006Inngår i: Journal of Chemometrics, Vol. 20, nr 8-10, s. 323-324Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    No Abstract

  • 74. Lundstedt-Enkel, Katrin
    et al.
    Tysklind, Mats
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Schüller, Peter
    Asplund, Lillemor
    Eriksson, Ulla
    Häggberg, Lisbeth
    Odsjö, Tjelvar
    Hjelmberg, Mats
    Olsson, Mats
    Örberg, Jan
    A Statistical Resampling Method To Calculate Biomagnification Factors Exemplified with Organochlorine Data from Herring (Clupea harengus) Muscle and Guillemot (Uria aalge) Egg from the Baltic Sea2005Inngår i: ENVIRONMENTAL SCIENCE & TECHNOLOGY, ISSN 0013-936X, Vol. 39, nr 21, s. 8395-8402Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A novel method for calculating biomagnification factors is presented and demonstrated using contaminant concentration data from the Swedish national monitoring program regarding organochlorine contaminants (OCs) in herring (Clupea harengus) muscle and guillemot (Uria aalge) egg, sampled from 1996 to 1999 from the Baltic Sea. With this randomly sampled ratios (RSR) method, biomagnification factors (BMFRSR) were generated and denoted with standard deviation (0) as a measure of the variation. The BMFRSR were calculated by randomly selecting one guillemot egg out of a total of 29 and one herring out of a total of 74, and the ratio was determined between the concentration of a given OC in that egg and the concentration of the same OC in that herring. With the resampling technique, this was performed 50 000 times for any given OC, and from this new distribution of ratios, BMFRSR for each OC were calculated and given as geometric mean (GM) with GM standard deviation (GMSD) range, arithmetic mean (AM) with AMSD range, and minimum (BMFMIN) as well as maximum (BMFMAX) biomagnification factors. The 14 analyzed OCs were p,p'DDT and its metabolites p,p'DDE and p,p'DDD, polychlorinated biphenyls (PCB congeners: CB28, CB52, CB101, CB118, CB138, CB153, and CB180), hexachlorocyclohexane isomers (alpha-, beta-, and gamma HCH), and hexachlorobenzene (HCB). Multivariate data analysis (MVDA) methods, including principal components analysis (PCA), partial least squares regression (PLS), and PLS discriminant analyses (PLS-DA), were first used to extract information from the complex biological and chemical data generated from each individual animal. MVDA were used to model similarities/dissimilarities regarding species (PCA, PLS-DA), sample years (PLS), and sample location (PLS-DA) to give a deeper understanding of the data that the BMF modeling was based upon. Contaminants that biomagnify, that had BMFRSR significantly higher than one, were p,p'DDE, CB118, HCB, CB138, CB180, CB153, beta HCH, and CB28. The contaminants that did not biomagnify were p,p'DDT, p,p'DDD, alpha HCH, CB101, and CB52. Eventual biomagnification for gamma HCH could not be determined. The BMFRSR for OCs present in herring muscle and guillemot egg showed a broad span with large variations for each contaminant. To be able to make reliable calculations of BMFs for different contaminants, we emphasize the importance of using data based upon large numbers of, as well as well-defined, individuals.

  • 75.
    Löfstedt, Tommy
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Ahnlund, Olof
    Peolsson, Michael
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Dynamic ultrasound imaging: a multivariate approach for the analysis and comparison of time-dependent musculoskeletal movements2012Inngår i: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 12, nr 1, s. 29-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Muscle functions are generally assumed to affect a wide variety of conditions and activities, including pain, ischemic and neurological disorders, exercise and injury. It is therefore very desirable to obtain more information on musculoskeletal contributions to and activity during clinical processes such as the treatment of muscle injuries, post-surgery evaluations, and the monitoring of progressive degeneration in neuromuscular disorders.The spatial image resolution achievable with ultrasound systems has improved tremendously in the last few years and it is nowadays possible to study skeletal muscles in real-time during activity. However, ultrasound imaging has an inherent problem that makes it difficult to compare different measurement series or image sequences from two or more subjects. Due to physiological differences between different subjects, the ultrasound sequences will be visually different -- partly because of variation in probe placement and partly because of the difficulty of perfectly reproducing any given movement. METHODS: Ultrasound images of the biceps and calf of a single subject were transformed to achieve congruence and then efficiently compressed and stacked to facilitate analysis using a multivariate method known as O2PLS. O2PLS identifies related and unrelated variation in and between two sets of data such that different phases of the studied movements can be analysed. The methodology was used to study the dynamics of the Achilles tendon and the calf and also the Biceps brachii and upper arm. The movements of these parts of the body are both of interest in clinical orthopaedic research. RESULTS: This study extends the novel method of multivariate analysis of congruent images (MACI) to facilitate comparisons between two series of ultrasound images. This increases its potential range of medical applications and its utility for detecting, visualising and quantifying the dynamics and functions of skeletal muscle. CONCLUSIONS: The most important results of this study are that MACI with O2PLS is able to consistently extract meaningful variability from pairs of ultrasound sequences. The MACI method with O2PLS is a powerful tool with great potential for visualising and comparing dynamics between movements. It has many potential clinical applications in the study of muscle injuries, post-surgery evaluations and evaluations of rehabilitation, and the assessment of athletic training interventions.

  • 76.
    Löfstedt, Tommy
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Eriksson, Lennart
    Gunilla Wormbs, Gunilla
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bi-modal OnPLS2012Inngår i: Journal of Chemometrics, ISSN 0886-9383, E-ISSN 1099-128X, Vol. 26, nr 6, s. 236-245Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This paper presents an extension to the recently published OnPLS data analysis method. Bi-modal OnPLS allows for arbitrary block relationships in both columns and rows and is able to extract orthogonal variation in both columns and rows without bias towards any particular direction or matrix: the method is fully symmetric with regard to both rows and columns.

    Bi-modal OnPLS extracts a minimal number of globally predictive score vectors that exhibit maximal covariance and correlation in the column space and a corresponding set of predictive loading vectors that exhibit maximal correlation in the row space. The method also extracts orthogonal variation (i.e. variation that is not related to all other matrices) in both columns and rows. The method was applied to two synthetic datasets and one real data set regarding sensory information and consumer likings of dairy products. It was shown that Bi-modal OnPLS greatly improves the intercorrelations between both loadings and scores while still finding the correct variation. This facilitates interpretation of the predictive components and makes it possible to study the orthogonal variation in the data.

  • 77.
    Löfstedt, Tommy
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Hanafi, Mohamed
    Unité de Recherches "Sensometrics and Chemometrics", ONIRIS, Site de la Géraudière, BP 82 225 Nantes 44322 Cedex 03, France.
    Mazerolles, Gérard
    INRA-UMR 1083 SPO, INRA, 2 Place Viala, 34060 Montpellier, France.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    OnPLS path modelling2012Inngår i: Chemometrics and Intelligent Laboratory Systems, ISSN 0169-7439, E-ISSN 1873-3239, Vol. 118, s. 139-149Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OnPLS was recently presented as a general extension of O2PLS to the multiblock case. OnPLS is equivalent to O2PLS in the case of two matrices, but generalises symmetrically to cases with more than two matrices, i.e. without giving preference to any one of the matrices.

    This article presents a straight-forward extension to this method and thereby also introduces the OPLS framework to the field of PLS path modelling. Path modelling links a number of data blocks to each other, thereby establishing a set of paths along which information is considered to flow between blocks, representing for instance a known time sequence, an assumed causality order, or some other chosen organising principle. Compared to existing methods for path analysis, OnPLS path modelling extracts a minimum number of predictive components that are maximally covarying with maximised correlation. This is a significant contribution to path modelling, because other methods may yield score vectors with variation that obstructs the interpretation. The method achieves this by extracting a set of "orthogonal" components that capture local phenomena orthogonal to the variation shared with all the connected blocks.

    Two applications will be used to illustrate the method. The first is based on a simulated dataset that show how the interpretation is improved by removing orthogonal variation and the second on a real data process for monitoring of protein structure changes during cheese ripening by analysing infrared data.

  • 78.
    Löfstedt, Tommy
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Hanafi, Mohamed
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Multiblock and Path Modeling with OnPLS2013Inngår i: New Perspectives in Partial Least Squares and Related Methods (Part IV) / [ed] Herve Abdi, Wynne W. Chin, Vincenzo Esposito Vinzi, Giorgio Russolillo, Laura Trinchera, Springer Science+Business Media B.V., 2013, 56, , s. 209-220s. 209-220Konferansepaper (Fagfellevurdert)
    Abstract [en]

    OnPLS was recently proposed as a general extension of O2PLS for applications in multiblock and path model analysis. OnPLS is very similar to O2PLS in the case with two matrices, but generalizes symmetrically to cases with more than two matrices without giving preference to any matrix.

    OnPLS extracts a minimal number of globally joint components that exhibit maximal covariance and correlation. A number of locally joint components are also extracted. These are shared between some matrices, but not between all. These components are also maximally covarying with maximal correlation. The variation that remains after the joint and locally joint variation has been extracted is unique to a particular matrix. This unique variation is orthogonal to all other matrices and captures phenomena specific in its matrix.

    The method's utility has been demonstrated by its application to synthetic datasets with very good results in terms of its ability to decompose the matrices. It has been shown that OnPLS affords a reduced number of globally joint components and increased intercorrelations of scores, and that it greatly facilitates interpretation of the models. Preliminary results in the application on real data has also given positive results. The results are similar to previous results using other multiblock and path model methods, but afford an increased interpretability because of the locally joint and unique components.

  • 79.
    Löfstedt, Tommy
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Hoffman, Daniel
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Global, local and unique decompositions in OnPLS for multiblock data analysis2013Inngår i: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 791, s. 13-24Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background OnPLS is an extension of O2PLS that decomposes a set of matrices, in either multiblock or path model analysis, such that each matrix consists of two parts: a globally joint part containing variation shared with all other connected matrices, and another containing unique or locally joint variation, i.e. variation that is specific to a particular matrix or shared with some, but not all, other connected matrices.

    Results A further extension of OnPLS suggested here decomposes the non-globally joint parts into locally joint and unique parts, using the OnPLS method to first find and extract a globally joint model, and then applying OnPLS recursively to subsets of matrices containing the non-globally joint variation remaining after the globally joint variation has been extracted. This results in a set of locally joint models. The variation that is left after the globally joint and locally joint variation has been extracted is not related (by definition) to the other matrices and thus represents the strictly unique variation specific to each matrix. The method's utility is demonstrated by its application to both a simulated data set and a real data set acquired from metabolomic, proteomic and transcriptomic profiling of three genotypes of hybrid aspen.

    Conclusions The results show that OnPLS can successfully decompose each matrix into global, local and unique models, resulting in lower numbers of globally joint components and higher intercorrelations of scores. OnPLS also increases the interpretability of models of connected matrices, because of the locally joint and unique models it generates.

  • 80.
    Löfstedt, Tommy
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    OnPLS—a novel multiblock method for the modelling of predictive and orthogonal variation2011Inngår i: Journal of Chemometrics, ISSN 0886-9383, E-ISSN 1099-128X, Vol. 25, nr 8, s. 441-455Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This paper presents a new multiblock analysis method called OnPLS, a general extension of O2PLS to the multiblock case. The proposed method is equivalent to O2PLS in cases involving only two matrices, but generalises to cases involving more than two matrices without giving preference to any particular matrix: the method is fully symmetric. OnPLS extracts a minimal number of globally predictive components that exhibit maximal covariance and correlation. Furthermore, the method can be used to study orthogonal variation, i.e. local phenomena captured in the data that are specific to individual combinations of matrices or to individual matrices. The method's utility was demonstrated by its application to three synthetic data sets. It was shown that OnPLS affords a reduced number of globally predictive components and increased intercorrelations of scores, and that it greatly facilitates interpretation of the predictive model.

  • 81.
    Madsen, Rasmus
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Banday, Viqar Showkat
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Moritz, Thomas
    Umeå Plant Science Center, Department of Forest Genetics and Plant Physiology, Swedish University of Agriculture Sciences, Umeå, Sweden.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lejon, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Altered metabolic signature in Pre-Diabetic NOD Mice2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 4, s. e35445-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Altered metabolism proceeding seroconversion in children progressing to Type 1 diabetes has previously been demonstrated. We tested the hypothesis that non-obese diabetic (NOD) mice show a similarly altered metabolic profile compared to C57BL/6 mice. Blood samples from NOD and C57BL/6 female mice was collected at 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 13 and 15 weeks and the metabolite content was analyzed using GC-MS. Based on the data of 89 identified metabolites OPLS-DA analysis was employed to determine the most discriminative metabolites. In silico analysis of potential involved metabolic enzymes was performed using the dbSNP data base. Already at 0 weeks NOD mice displayed a unique metabolic signature compared to C57BL/6. A shift in the metabolism was observed for both strains the first weeks of life, a pattern that stabilized after 5 weeks of age. Multivariate analysis revealed the most discriminative metabolites, which included inosine and glutamic acid. In silico analysis of the genes in the involved metabolic pathways revealed several SNPs in either regulatory or coding regions, some in previously defined insulin dependent diabetes (Idd) regions. Our result shows that NOD mice display an altered metabolic profile that is partly resembling the previously observation made in children progressing to Type 1 diabetes. The level of glutamic acid was one of the most discriminative metabolites in addition to several metabolites in the TCA cycle and nucleic acid components. The in silico analysis indicated that the genes responsible for this reside within previously defined Idd regions.

  • 82.
    Madsen, Rasmus Kirkegaard
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lundstedt, Torbjörn
    Department of Medicinal Chemistry, BMC, Uppsala University, SE-75123 Uppsala, Sweden.
    Gabrielsson, Jon
    AcureOmics, Tvistevägen 48, SE-90736 Umeå, Sweden.
    Sennbro, Carl-Johan
    Active Biotech Research, Scheelevägen 22, SE-22007 Lund, Sweden.
    Alenius, Gerd-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Moritz, Thomas
    Umeå Plant Science Center, Swedish University of Agricultural Sciences, SE-90183 Umeå, Sweden.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Diagnostic properties of metabolic perturbations in rheumatoid arthritis2011Inngår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 13, nr 1, s. R19-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: The aim of the study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. METHODS: We compared the metabolic profile of patients with RA with those of healthy controls and patients with psoriatic arthritis (PsoA). The metabolites were measured using two different chromatography-mass spectrometry platforms, thereby giving a broad overview of serum metabolites. The metabolic profiles of patient and control groups were compared using multivariate statistical analysis. The findings were validated in a follow-up study of RA patients and healthy volunteers. RESULTS: RA patients were diagnosed with a sensitivity of 93 % and a specificity of 70 % in a validation study using detection of 52 metabolites. Patients with RA or PsoA could be distinguished with a sensitivity of 90 % and a specificity of 94 %. Glyceric acid, D-ribofuranoise and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased when compared with healthy controls. CONCLUSIONS: Metabolite profiling (metabolomics) is a potentially useful technique for diagnosing RA. The predictive value was irrespective of the presence of antibodies against cyclic citrullinated peptides (ACPA).

  • 83.
    Madsen, Rasmus Kirkegaard
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lundstedt, Torbjörn
    AcureOmics AB, Tvistevägen 48, 907 36 Umeå, Sweden.
    Moritz, Thomas
    Umeå Plant Science Center, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, SE-90183 Umeå, Sweden.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Metabolic responses to change in disease activity during tumor necrosis factor inhibition in patients with rheumatoid arthritis2012Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 11, nr 7, s. 3796-3804Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Assessment of disease activity in patients with rheumatoid arthritis (RA) is of importance in the evaluation of treatment. The most important measure of disease activity is the Disease Activity Score counted in 28 joints (DAS28). In this study, we evaluated whether metabolic profiling could complement current measures of disease activity. Fifty-six patients, in two separate studies, were followed for two years after commencing anti-TNF therapy. DAS28 was assessed, and metabolic profiles were recorded at defined time points. Correlations between metabolic profile and DAS28 scores were analyzed using multivariate statistics. The metabolic responses to lowering DAS28 scores varied in different patients but could predict DAS28 scores at the individual and subgroup level models. The erythrocyte sedimentation rate (ESR) component in DAS28 was most correlated to the metabolite data, pointing to inflammation as the primary effect driving metabolic profile changes. Patients with RA had differing metabolic response to changes in DAS28 following anti-TNF therapy. This suggests that discovery of new metabolic biomarkers for disease activity will derive from studies at the individual and subgroup level. Increased inflammation, measured as ESR, was the main common effect seen in metabolic profiles from periods associated with high DAS28.

  • 84.
    Madsen, Rasmus
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lundstedt, Torbjörn
    AcureOmics AB.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Chemometrics in metabolomics - a review in human disease diagnosis2010Inngår i: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 659, nr 1-2, s. 23-33Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Metabolomics is a post genomic research field concerned with developing methods for analysis of low molecular weight compounds in biological systems, such as cells, organs or organisms. Analyzing metabolic differences between unperturbed and perturbed systems, such as healthy volunteers and patients with a disease, can lead to insights into the underlying pathology. In metabolomics analysis, large amounts of data are routinely produced in order to characterize samples. The use of multivariate data analysis techniques and chemometrics is a commonly used strategy for obtaining reliable results. Metabolomics have been applied in different fields such as disease diagnosis, toxicology, plant science and pharmaceutical and environmental research. In this review we take a closer look at the chemometric methods used and the available results within the field of disease diagnosis. We will first present some current strategies for performing metabolomics studies, especially regarding disease diagnosis. The main focus will be on data analysis strategies and validation of multivariate models, since there are many pitfalls in this regard. Further, we highlight the most interesting metabolomics publications and discuss these in detail; additional studies are mentioned as a reference for the interested reader. A general trend is an increased focus on biological interpretation rather than merely the ability to classify samples. In the conclusions, the general trends and some recommendations for improving metabolomics data analysis are provided.

  • 85.
    Marcinowska, Renata
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wolf-Watz, Hans
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Mortiz, Thomas
    Surowiec, Izabella
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Optimization of a sample preparation method for the metabolomic analysis of clinically relevant bacteria2011Inngår i: Journal of Microbiological Methods, ISSN 0167-7012, E-ISSN 1872-8359, Vol. 87, nr 1, s. 24-31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Metabolomics, or metabolite profiling, is an approach that is increasingly used to study the metabolism of diverse organisms, elucidate biological processes and/or find characteristic biomarkers of physiological states. Here, we describe the optimization of a method for global metabolomic analysis of bacterial cultures, with the following steps. Cells are grown to log-phase, starting from an overnight culture and bacterial concentrations are monitored by measuring the optical density of the cultures at 600nm. At an appropriate density they are harvested by centrifugation, washed three times with NaCl solution and metabolites are extracted using methanol and a bead-mill. Dried extracts are methoxymated and derivatized with methyltrimethylsilyltrifluoroacetamide (MSTFA) then analyzed using gas chromatography coupled to time-of-flight mass spectrometry (GC-MS/TOF). Finally, patterns in the acquired data are examined by multivariate data modeling. This method enabled us to obtain reproducible metabolite profiles of Yersinia pseudotuberculosis, with about 25% compound identification, based on comparison with entries in available GC-MS libraries. To assess the potential utility of the method for comparative analysis of other bacterial species we analyzed cultures of Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli and methicillin-sensitive Staphylococcus aureus (MSSA). Multivariate analysis of the acquired data showed that it was possible to differentiate the species according to their metabolic profiles. Our results show that the presented procedure can be used for metabolomic analysis of a wide range of bacterial species of clinical interest.

  • 86. Moore, John P.
    et al.
    Zhang, Song-Lei
    Nieuwoudt, Helene
    Divol, Benoit
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bauer, Florian F.
    A Multivariate Approach Using Attenuated Total Reflectance Mid-infrared Spectroscopy To Measure the Surface Mannoproteins and beta-Glucans of Yeast Cell Walls during Wine Fermentations2015Inngår i: Journal of Agricultural and Food Chemistry, ISSN 0021-8561, E-ISSN 1520-5118, Vol. 63, nr 45, s. 10054-10063Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Yeast cells possess a cell wall comprising primarily glycoproteins, mannans, and glucan polymers. Several yeast phenotypes relevant for fermentation, wine processing, and wine quality are correlated with cell wall properties. To investigate the effect of wine fermentation on cell wall composition, a study was performed using mid-infrared (MIR) spectroscopy coupled with multivariate methods (i.e., PCA and OPLS-DA). A total of 40 yeast strains were evaluated, including Saccharomyces strains (laboratory and industrial) and non-Saccharomyces species. Cells were fermented in both synthetic MS300 and Chardonnay grape must to stationery phase, processed, and scanned in the MIR spectrum. PCA of the fingerprint spectral region showed distinct separation of Saccharomyces strains from non-Saccharomyces species; furthermore, industrial wine yeast strains separated from laboratory strains. PCA loading plots and the use of OPLS-DA to the data sets suggested that industrial strains were enriched with cell wall proteins (e.g., mannoproteins), whereas laboratory strains were composed mainly of mannan and glucan polymers.

  • 87.
    Nording, Malin Linder
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Yang, Jun
    Georgi, Katrin
    Karbowski, Christine Hegedus
    German, J. Bruce
    Weiss, Robert H.
    Hogg, Ronald J.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Hammock, Bruce D.
    Zivkovic, Angela M.
    Individual Variation in Lipidomic Profiles of Healthy Subjects in Response to Omega-3 Fatty Acids2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, s. e76575-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Conflicting findings in both interventional and observational studies have resulted in a lack of consensus on the benefits of omega 3 fatty acids in reducing disease risk. This may be due to individual variability in response. We used a multi-platform lipidomic approach to investigate both the consistent and inconsistent responses of individuals comprehensively to a defined omega 3 intervention. Methods: The lipidomic profile including fatty acids, lipid classes, lipoprotein distribution, and oxylipins was examined multi- and uni-variately in 12 healthy subjects pre vs. post six weeks of omega 3 fatty acids (1.9 g/d eicosapentaenoic acid [EPA] and 1.5 g/d docosahexaenoic acid [DHA]). Results: Total lipidomic and oxylipin profiles were significantly different pre vs. post treatment across all subjects (p=0.00007 and p=0.00002 respectively). There was a strong correlation between oxylipin profiles and EPA and DHA incorporated into different lipid classes (r(2)=0.93). However, strikingly divergent responses among individuals were also observed. Both omega 3 and omega 6 fatty acid metabolites displayed a large degree of variation among the subjects. For example, in half of the subjects, two arachidonic acid cyclooxygenase products, prostaglandin E-2 (PGE(2)) and thromboxane B2 (TXB2), and a lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) significantly decreased post intervention, whereas in the other half they either did not change or increased. The EPA lipoxygenase metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) varied among subjects from an 82% decrease to a 5,000% increase. Conclusions: Our results show that certain defined responses to omega 3 fatty acid intervention were consistent across all subjects. However, there was also a high degree of inter-individual variability in certain aspects of lipid metabolism. This lipidomic based phenotyping approach demonstrated that individual responsiveness to omega 3 fatty acids is highly variable and measurable, and could be used as a means to assess the effectiveness of omega 3 interventions in modifying disease risk and determining metabolic phenotype.

  • 88.
    Obudulu, Ogonna
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bygdell, Joakim
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Sundberg, Bjorn
    Moritz, Thomas
    Hvidsten, Torgeir R.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. 5 Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Norway.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wingsle, Gunnar
    Quantitative proteomics reveals protein profiles underlying major transitions in aspen wood development2016Inngår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 17, artikkel-id 119Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Wood development is of outstanding interest both to basic research and industry due to the associated cellulose and lignin biomass production. Efforts to elucidate wood formation (which is essential for numerous aspects of both pure and applied plant science) have been made using transcriptomic analyses and/or low-resolution sampling. However, transcriptomic data do not correlate perfectly with levels of expressed proteins due to effects of post-translational modifications and variations in turnover rates. In addition, high-resolution analysis is needed to characterize key transitions. In order to identify protein profiles across the developmental region of wood formation, an in-depth and tissue specific sampling was performed. Results: We examined protein profiles, using an ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry system, in high-resolution tangential sections spanning all wood development zones in Populus tremula from undifferentiated cambium to mature phloem and xylem, including cell expansion and cell death zones. In total, we analyzed 482 sections, 20-160 mu m thick, from four 47-year-old trees growing wild in Sweden. We obtained high quality expression profiles for 3,082 proteins exhibiting consistency across the replicates, considering that the trees were growing in an uncontrolled environment. A combination of Principal Component Analysis (PCA), Orthogonal Projections to Latent Structures (OPLS) modeling and an enhanced stepwise linear modeling approach identified several major transitions in global protein expression profiles, pinpointing (for example) locations of the cambial division leading to phloem and xylem cells, and secondary cell wall formation zones. We also identified key proteins and associated pathways underlying these developmental landmarks. For example, many of the lignocellulosic related proteins were upregulated in the expansion to the early developmental xylem zone, and for laccases with a rapid decrease in early xylem zones. We observed upregulation of two forms of xylem cysteine protease (Potri.002G005700.1 and Potri.005G256000.2; Pt-XCP2.1) in early xylem and their downregulation in late maturing xylem. Our data also show that Pt-KOR1.3 (Potri.003G151700.2) exhibits an expression pattern that supports the hypothesis put forward in previous studies that this is a key xyloglucanase involved in cellulose biosynthesis in primary cell walls and reduction of cellulose crystallinity in secondary walls. Conclusion: Our novel multivariate approach highlights important processes and provides confirmatory insights into the molecular foundations of wood development.

  • 89.
    Obudulu, Ogonna
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, 90183 Umeå, Sweden.
    Mähler, Niklas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Faculty of Chemistry, Biotechnology and Food Science, Norwegian, University of Life Sciences, 1432 Ås, Norway.
    Skotare, Tomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Bygdell, Joakim
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Abreu, Ilka N.
    Ahnlund, Maria
    Latha Gandla, Madhavi
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Petterle, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Moritz, Thomas
    Hvidsten, Torgeir R.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Faculty of Chemistry, Biotechnology and Food Science, Norwegian, University of Life Sciences, 1432 Ås, Norway.
    Jönsson, Leif J.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wingsle, Gunnar
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Tuominen, Hannele
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees2018Inngår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 19, artikkel-id 11Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32–38 kDa proteins that are involved in membrane trafficking. A systems approach was taken to elucidate function of SCAMPs in wood formation of Populus trees. Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3;Potri.019G104000).

    Results: The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls. This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines. Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition. The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type. Several of these were related to secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis.

    Conclusions: Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems. Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport. The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.

  • 90. Orikiiriza, Judy
    et al.
    Surowiec, Izabella
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindquist, Elisabeth
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Bonde, Mari
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Magambo, Jimmy
    Muhinda, Charles
    Bergström, Sven
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Normark, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar. Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria2017Inngår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 13, nr 4, artikkel-id 41Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Several studies have observed serum lipid changes during malaria infection in humans. All of them were focused at analysis of lipoproteins, not specific lipid molecules. The aim of our study was to identify novel patterns of lipid species in malaria infected patients using lipidomics profiling, to enhance diagnosis of malaria and to evaluate biochemical pathways activated during parasite infection.

    Methods: Using a multivariate characterization approach, 60 samples were representatively selected, 20 from each category (mild, severe and controls) of the 690 study participants between age of 0.5–6 years. Lipids from patient’s plasma were extracted with chloroform/methanol mixture and subjected to lipid profiling with application of the LCMS-QTOF method.

    Results: We observed a structured plasma lipid response among the malaria-infected patients as compared to healthy controls, demonstrated by higher levels of a majority of plasma lipids with the exception of even-chain length lysophosphatidylcholines and triglycerides with lower mass and higher saturation of the fatty acid chains. An inverse lipid profile relationship was observed when plasma lipids were correlated to parasitaemia.

    Conclusions: This study demonstrates how mapping the full physiological lipid response in plasma from malaria-infected individuals can be used to understand biochemical processes during infection. It also gives insights to how the levels of these molecules relate to acute immune responses.

  • 91. Peolsson, A.
    et al.
    Peolsson, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Jull, G.
    Löfstedt, Tommy
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    O'Leary, S.
    Preliminary evaluation of dorsal muscle activity during resisted cervical extension in patients with longstanding pain and disability following anterior cervical decompression and fusion surgery2015Inngår i: Physiotherapy, ISSN 0031-9406, E-ISSN 1873-1465, Vol. 101, nr 1, s. 69-74Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives To compare mechanical activity (deformation and deformation rate) of the dorsal neck muscles between individuals with longstanding symptoms after anterior cervical decompression and fusion (ACDF) surgery and healthy controls.

    Design Preliminary cross-sectional study.

    Setting Neurosurgery clinic.

    Participants Ten individuals {mean age 60 [standard deviation (SD) 7.111 who had undergone ACDF surgery 10 to 13 years previously and 10 healthy age- and sex-matched controls.

    Main outcomes Mechanical activity of the different layers of dorsal neck muscles, measured at the C4 segment using ultrasonography (speckle tracking analysis) during a standardised, resisted cervical extension task.

    Results A significant group x muscle interaction was found for muscle deformation (P<0.03) but not for deformation rate (P>0.79). The ACDF group showed significantly less deformation of the semispinalis capitis muscle during the extension task compared with the control group [mean 3.12 (SD 2.06) and 6.64 (SD 4.17), respectively; mean difference 3.34 (95% confidence interval 0.54 to 7.21)].

    Conclusions As the semispinalis capitis muscle is a powerful neck extensor, the finding of altered activation following ACDF surgery lends support to the inclusion of exercise to train neck muscle performance in the management of these patients.

  • 92.
    Peolsson, A.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Medical and Health Sciences, Physiotherapy, Linköping University, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Sweden.
    Peterson, G.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Altered mechanical deformation of the trapezius and multifidus muscles registered with ultrasonography in women with chronic whiplash-associated disorders2016Inngår i: Manual Therapy, ISSN 1356-689X, E-ISSN 1532-2769, Vol. 25, s. e58-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The deformation and deformation rate of the dorsal neck muscle layers in individuals with chronic whiplash associated disorders (WAD) is rarely evaluated, and the mechanical behaviour during dynamic neck extension remains to be investigated.

    Purpose: To compare the deformation and deformation rate of dorsal neck muscles (trapezius, splenius capitis, semispinalis capitis and cervicis, and multifidus) in women with chronic WAD compared with healthy controls during a dynamic resisted neck extension.

    Methods: Nine women with chronic grade 2 and 3 WAD (mean age 38 years, standard deviation [SD] 11.3) and nine age- and gender-matched healthy controls (mean age 38 years, SD 11.6) participated in this cross-sectional, controlled study. Ultrasonography movies and post-process speckle tracking were used to investigate real-time mechanical dorsal neck muscle behaviour at the C4 segmental level during a low-loaded dynamic standardized neck extension. Deformation (longitudinal shortening and elongation) and deformation rate (speed of deformation) were calculated during the entire exercise sequence.

    Results: There were significant differences between the WAD and control groups in total deformation for the trapezius (p < 0.04) and multifidus (p < 0.03). The WAD group showed more shortening in the deformation pattern during the concentric contraction phase in the trapezius muscle, and during both the concentric and eccentric phase in the multifidus muscle compared to healthy controls. There were no other significant differences between groups either in deformation or deformation rate.

    Conclusion: There were altered mechanical deformations of the trapezius and multifidus muscles, with preliminary evidence for overuse in individuals with WAD compared to healthy controls. The findings must be interpreted with caution due to the small sample size.

    Implications: An ultrasound investigation made it possible to non-invasively capture multi-layered muscles in real time, adding new information of value for clinical practice of patients with WAD, which may impact future rehabilitation.

  • 93. Peolsson, Anneli
    et al.
    Löfstedt, Tommy
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Peolsson, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Ultrasound imaging with speckle tracking of cervical muscle deformation and deformation rate: isometric contraction of patients after anterior cervical decompression and fusion for cervical disc disease and controls2012Inngår i: Manual Therapy, ISSN 1356-689X, E-ISSN 1532-2769, Vol. 17, nr 6, s. 519-525Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is currently a lack of information regarding neck muscle activity during specific exercises. The purpose of the present study was to investigate deformation and deformation rate in different layers of dorsal and ventral neck muscles during isometric neck muscle contraction in individuals after anterior cervical decompression and fusion and in healthy controls. This study included 10 individuals (mean age 60 years; SD 7.1) with a verified, long-standing neck disorder and 10 healthy, age- and sex-matched controls. Ultrasonography and post-process speckle tracking analysis was used to investigate the degree and the rate of neck muscles motions at the C4 segmental level during sub-maximal, isometric resistance of the head in a seated position. None of the analyses performed showed significant differences between groups (p > 0.05). In the dorsal muscles, both groups exhibited a higher deformation rate in the multifidus than in the trapezius, splenius, and semispinalis capitis (p ≤ 0.01). In the neck disorder group, the multifidus also showed a higher deformation rate compared to the semispinalis cervicis (p = 0.02). In the ventral muscles of patients with neck disorders, the longus colli had a higher deformation rate than the sternocleidomastoid (p = 0.02). Among the healthy controls, the multifidus showed a higher degree of deformation (p = 0.02) than the trapezius. In conclusion, our results showed no significant differences between the two groups in mechanical neck muscle activation. Larger studies with different exercises, preferably with a standardized measure of resistance, are needed to investigate whether patients and controls show differences in deformation and deformation rates in neck muscles.

  • 94. Peolsson, Anneli
    et al.
    Peterson, Gunnel
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Multivariate analysis of ultrasound-recorded dorsal strain sequences: Investigation of dynamic neck extensions in women with chronic whiplash associated disorders2016Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, artikkel-id 30415Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Whiplash Associated Disorders (WAD) refers to the multifaceted and chronic burden that is common after a whiplash injury. Tools to assist in the diagnosis of WAD and an increased understanding of neck muscle behaviour are needed. We examined the multilayer dorsal neck muscle behaviour in nine women with chronic WAD versus healthy controls during the entire sequence of a dynamic low-loaded neck extension exercise, which was recorded using real-time ultrasound movies with high frame rates. Principal component analysis and orthogonal partial least squares were used to analyse mechanical muscle strain (deformation in elongation and shortening). The WAD group showed more shortening during the neck extension phase in the trapezius muscle and during both the neck extension and the return to neutral phase in the multifidus muscle. For the first time, a novel non-invasive method is presented that is capable of detecting altered dorsal muscle strain in women with WAD during an entire exercise sequence. This method may be a breakthrough for the future diagnosis and treatment of WAD.

  • 95. Peolsson, Michael
    et al.
    Löfstedt, Tommy
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Vogt, Susanna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Stenlund, Hans
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Arndt, Anton
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Modelling human musculoskeletal functional movements using ultrasound imaging2010Inngår i: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 10, nr 9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: A widespread and fundamental assumption in the health sciences is that muscle functions are related to a wide variety of conditions, for example pain, ischemic and neurological disorder, exercise and injury. It is therefore highly desirable to study musculoskeletal contributions in clinical applications such as the treatment of muscle injuries, post-surgery evaluations, monitoring of progressive degeneration in neuromuscular disorders, and so on.The spatial image resolution in ultrasound systems has improved tremendously in the last few years and nowadays provides detailed information about tissue characteristics. It is now possible to study skeletal muscles in real-time during activity.

    METHODS: The ultrasound images are transformed to be congruent and are effectively compressed and stacked in order to be analysed with multivariate techniques. The method is applied to a relevant clinical orthopaedic research field, namely to describe the dynamics in the Achilles tendon and the calf during real-time movements.

    RESULTS: This study introduces a novel method to medical applications that can be used to examine ultrasound image sequences and to detect, visualise and quantify skeletal muscle dynamics and functions.

    CONCLUSIONS: This new objective method is a powerful tool to use when visualising tissue activity and dynamics of musculoskeletal ultrasound registrations.

  • 96.
    Peterson, Gunnel
    et al.
    Eskilstuna, Sweden; Linköping, Sweden.
    Dedering, Åsa
    Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden.
    Andersson, Erika
    Linköping, Sweden.
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Peolsson, Michael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wallman, Thorne
    Eskilstuna, Sweden; Uppsala, Swe.
    Peolsson, Anneli
    Linköping, Sweden.
    Altered ventral neck muscle deformation for individuals with whiplash associated disorder compared to healthy controls: A case-control ultrasound study2015Inngår i: Manual Therapy, ISSN 1356-689X, E-ISSN 1532-2769, Vol. 20, nr 2, s. 319-327Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous studies have shown altered neck muscle function in individuals with chronic whiplash associated disorder (WAD). However, we lack real-time investigations with non-invasive methods that can distinguish between the different ventral neck muscle layers. This study investigated deformations and deformation rates in the sternocleidomastoid (SCM), longus capitis (Lcap), and longus colli (Lco) muscles with real-time ultrasonography. Twenty-six individuals with WAD were compared with 26 controls, matched for age and sex. Ultrasound imaging of the SCM, Lcap, and Lco were recorded during 10 repetitive arm elevations. The first and tenth arm elevations were post-process analyzed with speckle tracking. There were few significant differences in the deformations or deformation rates in the SCM, Lcap, and Lco between the WAD and control group. In controls, deformations and deformation rates showed linear positive relationships between SCM/Lcap, SCM/Lco, and Lcap/Lco which increased from the first arm elevation (R-2 = 0.14-0.70); to the tenth arm elevation (R-2 = 0.51-0.71). The WAD group showed similar or weaker linear relationship (R-2 < 0.19) during the tenth compared to the first (R-2 < 0.44) arm elevation except for deformations in Lcap/Lco (R-2 = 0.13-0.57). This result indicated that deformations and deformation rates in one muscle were correlated by similar deformations and deformation rates in other neck muscles in the control group, but this interplay between muscles was not found in the WAD group. (C) 2014 Elsevier Ltd. All rights reserved.

  • 97. Peterson, Gunnel
    et al.
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Peterson, Simon
    Dedering, Åsa
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wallman, Thorne
    Peolsson, Anneli
    Changes in dorsal neck muscle function in individuals with chronic whiplash-associated disorders: a real-time ultrasound case-control study2016Inngår i: Ultrasound in Medicine and Biology, ISSN 0301-5629, E-ISSN 1879-291X, Vol. 42, nr 5, s. 1090-1102Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Impaired neck muscle function leads to disability in individuals with chronic whiplash-associated disorder (WAD), but diagnostic tools are lacking. In this study, deformations and deformation rates were investigated in five dorsal neck muscles during 10 arm elevations by ultrasonography with speckle tracking analyses. Forty individuals with chronic WAD (28 women and 12 men, mean age = 37 y) and 40 healthy controls matched for age and sex were included. The WAD group had higher deformation rates in the multifidus muscle during the first (p < 0.04) and 10th (only women, p < 0.01) arm elevations compared with the control group. Linear relationships between the neck muscles for deformation rate (controls: R-2 = 0.24-0.82, WAD: R-2 = 0.05-0.74) and deformation of the deepest muscles (controls: R-2 = 0.61-0.32, WAD: R-2 = 0.15-0.01) were stronger for women in the control group versus women with WAD, indicating there is altered interplay between dorsal neck muscles in chronic WAD. 

  • 98. Peterson, Gunnel
    et al.
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Falla, Deborah
    Dedering, Åsa
    Wallman, Thorne
    Peolsson, Anneli
    Novel insights into the interplay between ventral neck muscles in individuals with whiplash-associated disorders2015Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, artikkel-id 15289Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic whiplash-associated disorder (WAD) is common after whiplash injury, with considerable personal, social, and economic burden. Despite decades of research, factors responsible for continuing pain and disability are largely unknown, and diagnostic tools are lacking. Here, we report a novel model of mechanical ventral neck muscle function recorded from non-invasive, real-time, ultrasound measurements. We calculated the deformation area and deformation rate in 23 individuals with persistent WAD and compared them to 23 sex-and age-matched controls. Multivariate statistics were used to analyse interactions between ventral neck muscles, revealing different interplay between muscles in individuals with WAD and healthy controls. Although the cause and effect relation cannot be established from this data, for the first time, we reveal a novel method capable of detecting different neck muscle interplay in people with WAD. This non-invasive method stands to make a major breakthrough in the assessment and diagnosis of people following a whiplash trauma.

  • 99. Peterson, Gunnel
    et al.
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Peolsson, Anneli
    Neck-specific exercise improves impaired interactions between ventral neck muscles in chronic whiplash: A randomized controlled ultrasound study2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 9649Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic pain and disability is common in whiplash-associated disorders (WAD), leading to personal suffering, sick leave, and social cost. The cervical spine is heavily dependent on muscular support and whiplash injury can cause damage to the neck muscles, but diagnostic tools to measure neck muscle impairment and evaluate exercise interventions are lacking. Therefore, the present study investigated ventral neck muscle interactions in 26 individuals with chronic WAD randomized to neck-specific exercise (NSE) or remaining on a waiting list (WL) in 3 months. We performed real-time, non-invasive ultrasound measurements with speckle tracking analysis and calculated the deformation area and deformation rate in three ventral neck muscles. Multivariate statistics were used to analyse interactions between the muscles. After 3 months of NSE, significant improvements were observed in neck muscle interactions and pain intensity in the NSE group compared to the WL group. Thus, this study demonstrates that non-invasive ultrasound can be a diagnostic tool for muscle impairment and used to evaluate exercise interventions in WAD and stands to make a breakthrough for better management in chronic WAD.

  • 100. Peterson, Gunnel
    et al.
    O'Leary, Shaun
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Moodie, Katherine
    Tucker, Kylie
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Peolsson, Anneli
    Ultrasound imaging of dorsal neck muscles with speckle tracking analyses: the relationship between muscle deformation and force2019Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikkel-id 13688Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The development of methods of non-invasive measurement of neck muscle function remains a priority in the clinical sciences. In this study, dorsal neck muscle deformation vs time curves (deformation area) were evaluated against incremental force, recorded from non-invasive real-time ultrasound measurement. The results revealed subject-specific moderate to strong linear or non-linear relationships between deformation and force. Test-retest variability showed strong reliability for all five neck muscles summed together and fair to good reliability for the five muscles evaluated separately. Multivariate statistics were used to analyse the interactions between the dorsal neck muscles during different percentages of maximal voluntary contraction (MVC). Low force (10-20% MVC) was related to muscle shortening; higher force (40-80% MVC) showed combination of shortening and elongation deformation in the muscle interactions. The muscle interactions during isometric MVC test were subject-specific, with different combinations and deformations of the five neck muscles. Force >= 40% MVC were associated with a forward movement of the cervical spine that affected the ultrasound measurement of the dorsal neck muscles. Ultrasound with speckle-tracking analyses may be best used to detect low levels (<40% MVC) of neck muscle activity.

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