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| 2. |
- Ahmad, Shafqat, et al.
(författare)
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Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome : A Multi-Cohort Nontargeted Metabolomics Observational and Mendelian Randomization Study
- 2022
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 71:2, s. 329-339
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.
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| 3. |
- Larsson, Karl-Johan, 1985, et al.
(författare)
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Rib Cortical Bone Fracture Risk as a Function of Age and Rib Strain: Updated Injury Prediction Using Finite Element Human Body Models
- 2021
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate vehicle occupant injury risk, finite element human body models (HBMs) can be used in vehicle crash simulations. HBMs can predict tissue loading levels, and the risk for fracture can be estimated based on a tissue-based risk curve. A probabilistic framework utilizing an age-adjusted rib strain-based risk function was proposed in 2012. However, the risk function was based on tests from only twelve human subjects. Further, the age adjustment was based on previous literature postulating a 5.1% decrease in failure strain for femur bone material per decade of aging. The primary aim of this study was to develop a new strain-based rib fracture risk function using material test data spanning a wide range of ages. A second aim was to update the probabilistic framework with the new risk function and compare the probabilistic risk predictions from HBM simulations to both previous HBM probabilistic risk predictions and to approximate real-world rib fracture outcomes. Tensile test data of human rib cortical bone from 58 individuals spanning 17–99 years of ages was used. Survival analysis with accelerated failure time was used to model the failure strain and age-dependent decrease for the tissue-based risk function. Stochastic HBM simulations with varied impact conditions and restraint system settings were performed and probabilistic rib fracture risks were calculated. In the resulting fracture risk function, sex was not a significant covariate—but a stronger age-dependent decrease than previously assumed for human rib cortical bone was evident, corresponding to a 12% decrease in failure strain per decade of aging. The main effect of this difference is a lowered risk prediction for younger individuals than that predicted in previous risk functions. For the stochastic analysis, the previous risk curve overestimated the approximate real-world rib fracture risk for 30-year-old occupants; the new risk function reduces the overestimation. Moreover, the new function can be used as a direct replacement of the previous one within the 2012 probabilistic framework.
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| 4. |
- Larsson, Mikael, 1982, et al.
(författare)
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Effect of ethanol on the water permeability of controlled release films composed of ethyl cellulose and hydroxypropyl cellulose
- 2010
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Ingår i: European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier BV. - 1873-3441 .- 0939-6411. ; 76:3, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- The robustness of controlled release formulations when co-ingested with alcohol is a current concern expressed by regulatory authorities, especially with regard to dose dumping. One such controlled release formulation commonly used is film coating composed of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC). The aim of this study was to investigate how the presence of ethanol in the dissolution medium affects the water permeability of such films. Film samples were prepared in various EC–HPC compositions, and the effect of different ethanol concentrations in the dissolution medium on the permeability was studied using a modified Ussing chamber and tritiated water. It was found that the effect of ethanol on the film permeability varied depending on the composition of the films. The results were interpreted in terms of swelling of the EC in the films, where the swelling increased with increasing ethanol concentration. Thus, for films with low HPC content (non-interconnected pores), the water permeability of the films increased with increasing ethanol concentration as the diffusion through the ethyl cellulose increased due to swelling. However, for films with higher HPC content (having interconnected pores through the films), the permeability decreased, likely due to the swelling of the ethyl cellulose blocking the pores. The interpretation of the results was supported by dynamic mechanic analysis and SEM analysis.
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| 5. |
- Larsson, Mikael, 1982, et al.
(författare)
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Novel nanostructured microfibrillated cellulose–hydroxypropyl methylcellulose films with large one-dimensional swelling and tunable permeability
- 2012
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 88:2, s. 763-771
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Tidskriftsartikel (refereegranskat)abstract
- Microfibrillated cellulose (MFC) films containing the water soluble and pharmaceutically approved polymer hydroxypropyl methylcellulose (HPMC) exhibited an unexpected decrease in permeability and excellent one-dimensional swelling properties above a threshold in HPMC content. It is proposed that the observed material characteristics derive from the influence of HPMC on the aggregation behavior of MFC in such a way that above a critical HPMC content the films are created through self assembly into a layered structure, composed of low swelling layers with swellable inter layer regions. The suggested structures were supported by high resolution microscopy. The findings should hold potential for direct applications, but even more as a concept for future material design.
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| 6. |
- Nilsson, R. Henrik, 1976, et al.
(författare)
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A comprehensive, automatically updated fungal ITS sequence dataset for reference-based chimera control in environmental sequencing efforts
- 2015
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Ingår i: Microbes and Environments. - 1342-6311 .- 1347-4405. ; 30:2, s. 145-150
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear ribosomal internal transcribed spacer (ITS) region is the most commonly chosen genetic marker for the molecular identification of fungi in environmental sequencing and molecular ecology studies. Several analytical issues complicate such efforts, one of which is the formation of chimeric—artificially joined—DNA sequences during PCR amplification or sequence assembly. Several software tools are currently available for chimera detection, but rely to various degrees on the presence of a chimera-free reference dataset for optimal performance. However, no such dataset is available for use with the fungal ITS region. This study introduces a comprehensive, automatically updated reference dataset for fungal ITS sequences based on the UNITE database for the molecular identification of fungi. This dataset supports chimera detection throughout the fungal kingdom and for full-length ITS sequences as well as partial (ITS1 or ITS2 only) datasets. The performance of the dataset on a large set of artificial chimeras was above 99.5%, and we subsequently used the dataset to remove nearly 1,000 compromised fungal ITS sequences from public circulation. The dataset is available at http://unite.ut.ee/repository.php and is subject to web-based third-party curation.
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| 7. |
- Nilsson, R. Henrik, 1976, et al.
(författare)
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Improving ITS sequence data for identification of plant pathogenic fungi
- 2014
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Ingår i: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 67:1, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- Plant pathogenic fungi are a large and diverse assemblage of eukaryotes with substantial impacts on natural ecosystems and human endeavours. These taxa often have complex and poorly understood life cycles, lack observable, discriminatory morphological characters, and may not be amenable to in vitro culturing. As a result, species identification is frequently difficult. Molecular (DNA sequence) data have emerged as crucial information for the taxonomic identification of plant pathogenic fungi, with the nuclear ribosomal internal transcribed spacer (ITS) region being the most popular marker. However, international nucleotide sequence databases are accumulating numerous sequences of compromised or low-resolution taxonomic annotations and substandard technical quality, making their use in the molecular identification of plant pathogenic fungi problematic. Here we report on a concerted effort to identify high-quality reference sequences for various plant pathogenic fungi and to re-annotate incorrectly or insufficiently annotated public ITS sequences from these fungal lineages. A third objective was to enrich the sequences with geographical and ecological metadata. The results – a total of 31,954 changes – are incorporated in and made available through the UNITE database for molecular identification of fungi (http://unite.ut.ee), including standalone FASTA files of sequence data for local BLAST searches, use in the next-generation sequencing analysis platforms QIIME and mothur, and related applications. The present initiative is just a beginning to cover the wide spectrum of plant pathogenic fungi, and we invite all researchers with pertinent expertise to join the annotation effort.
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| 8. |
- Berglund, Fanny, 1988, et al.
(författare)
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Identification of 76 novel B1 metallo-beta-lactamases through large-scale screening of genomic and metagenomic data
- 2017
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 5:1, s. 134-134
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metallo-beta-lactamases are bacterial enzymes that provide resistance to carbapenems, the most potent class of antibiotics. These enzymes are commonly encoded on mobile genetic elements, which, together with their broad substrate spectrum and lack of clinically useful inhibitors, make them a particularly problematic class of antibiotic resistance determinants. We hypothesized that there is a large and unexplored reservoir of unknown metallo-beta-lactamases, some of which may spread to pathogens, thereby threatening public health. The aim of this study was to identify novel metallo-beta-lactamases of class B1, the most clinically important subclass of these enzymes. Results: Based on a new computational method using an optimized hidden Markov model, we analyzed over 10,000 bacterial genomes and plasmids together with more than 5 terabases of metagenomic data to identify novel metallo-beta-lactamase genes. In total, 76 novel genes were predicted, forming 59 previously undescribed metallo-beta-lactamase gene families. The ability to hydrolyze imipenem in an Escherichia coli host was experimentally confirmed for 18 of the 21 tested genes. Two of the novel B1 metallo-beta-lactamase genes contained atypical zinc-binding motifs in their active sites, which were previously undescribed for metallo-beta-lactamases. Phylogenetic analysis showed that B1 metallo-beta-lactamases could be divided into five major groups based on their evolutionary origin. Our results also show that, except for one, all of the previously characterized mobile B1 beta-lactamases are likely to have originated from chromosomal genes present in Shewanella spp. and other Proteobacterial species. Conclusions: This study more than doubles the number of known B1 metallo-beta-lactamases. The findings have further elucidated the diversity and evolutionary history of this important class of antibiotic resistance genes and prepare us for some of the challenges that may be faced in clinics in the future.
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| 9. |
- Bergsten, Eva L., 1969-, et al.
(författare)
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Effects of relocation to activity-based workplaces on perceived productivity : importance of change-oriented leadership
- 2021
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Ingår i: Applied Ergonomics. - : Elsevier. - 0003-6870 .- 1872-9126. ; 93, s. 10-16
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Tidskriftsartikel (refereegranskat)abstract
- Activity-based workplaces (ABWs) are becoming popular in Western countries and were implemented at four office sites of a large Swedish government agency. A fifth office was used as a control group. The study aim was to examine the effects of relocation to ABW on perceived productivity among employees and to determine if perceived change-oriented leadership behavior prior to relocation moderates potential effects. Data were collected three months prior to relocation, and three and 12 months after. 407 respondents were included in linear mixed regression models. Perceived productivity decreased significantly after relocation compared to the control group and these effects persisted 12 months after the relocation. However, the decrease in perceived productivity was significantly smaller among employees perceiving high change-oriented leadership before relocation. Our results point out the importance of a change-oriented leadership behavior during the implementation to avoid productivity loss among employees when implementing ABWs.
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