| 1. |
- Patterson, Allison, et al.
(författare)
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Foraging range scales with colony size in high-latitude seabirds
- 2022
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:17, s. 3800-3807
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Tidskriftsartikel (refereegranskat)abstract
- Density-dependent prey depletion around breeding colonies has long been considered an important factor controlling the population dynamics of colonial animals.1, 2, 3, 4 Ashmole proposed that as seabird colony size increases, intraspecific competition leads to declines in reproductive success, as breeding adults must spend more time and energy to find prey farther from the colony.1 Seabird colony size often varies over several orders of magnitude within the same species and can include millions of individuals per colony.5,6 As such, colony size likely plays an important role in determining the individual behavior of its members and how the colony interacts with the surrounding environment.6 Using tracking data from murres (Uria spp.), the world’s most densely breeding seabirds, we show that the distribution of foraging-trip distances scales to colony size0.33 during the chick-rearing stage, consistent with Ashmole’s halo theory.1,2 This pattern occurred across colonies varying in size over three orders of magnitude and distributed throughout the North Atlantic region. The strong relationship between colony size and foraging range means that the foraging areas of some colonial species can be estimated from colony sizes, which is more practical to measure over a large geographic scale. Two-thirds of the North Atlantic murre population breed at the 16 largest colonies; by extrapolating the predicted foraging ranges to sites without tracking data, we show that only two of these large colonies have significant coverage as marine protected areas. Our results are an important example of how theoretical models, in this case, Ashmole’s version of central-place-foraging theory, can be applied to inform conservation and management in colonial breeding species.
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| 2. |
- Timmons, James A., et al.
(författare)
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Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans
- 2010
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 108:6, s. 1487-1496
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Tidskriftsartikel (refereegranskat)abstract
- Timmons JA, Knudsen S, Rankinen T, Koch LG, Sarzynski M, Jensen T, Keller P, Scheele C, Vollaard NB, Nielsen S, Akerstrom T, MacDougald OA, Jansson E, Greenhaff PL, Tarnopolsky MA, van Loon LJ, Pedersen BK, Sundberg CJ, Wahlestedt C, Britton SL, Bouchard C. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 108: 1487-1496, 2010. First published February 4, 2010; doi:10.1152/japplphysiol.01295.2009.-A low maximal oxygen consumption ((V) over dotO(2max)) is a strong risk factor for premature mortality. Supervised endurance exercise training increases (V) over dotO(2max) with a very wide range of effectiveness in humans. Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression profiling to produce a molecular classifier that predicts (V) over dotO(2max) training response. We then hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous (V) over dotO(2max) response. Two independent preintervention RNA expression data sets were generated (n = 41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA expression signature that predicted change in (V) over dotO(2max) (""predictor"" genes). The HERITAGE Family Study (n = 473) was used for genotyping. We discovered a 29-RNA signature that predicted (V) over dotO(2max) training response on a continuous scale; these genes contained similar to 6 new single-nucleotide polymorphisms associated with gains in (V) over dotO(2max) in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., ""reciprocal"" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in (V) over dotO(2max), corresponding to similar to 50% of the estimated genetic variance for (V) over dotO(2max). In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. (V) over dotO(2max) responses to endurance training can be predicted by measuring a similar to 30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans.
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| 3. |
- Balaz, Martina, et al.
(författare)
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Effects of surface adsorption on catalytic activity of heavy meromyosin studied using a fluorescent ATP analogue
- 2007
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 46:24, s. 7233-7251
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Tidskriftsartikel (refereegranskat)abstract
- Biochemical studies in solution and with myosin motor fragments adsorbed to surfaces (in vitro motility assays) are invaluable for elucidation of actomyosin function. However, there is limited understanding of how surface adsorption affects motor properties, e.g., catalytic activity. Here we address this issue by comparing the catalytic activity of heavy meromyosin (HMM) in solution and adsorbed to standard motility assay surfaces [derivatized with trimethylchlorosilane (TMCS)]. For these studies we first characterized the interaction of HMM and actomyosin with the fluorescent ATP analogue adenosine 5'-triphosphate Alexa Fluor 647 2'- (or 3'-) O-(N-(2-aminoethyl)urethane) hexa(triethylammonium) salt (Alexa-ATP). The data suggest that Alexa-ATP is hydrolyzed by HMM in solution at a slightly higher rate than ATP but with a generally similar mechanism. Furthermore, Alexa-ATP is effective as a fuel for HMM-propelled actin filament sliding. The catalytic activity of HMM on TMCS surfaces was studied using (1) Alexa-ATP in total internal reflection fluorescence (TIRF) spectroscopy experiments and (2) Alexa-ATP and ATP in HPLC-aided ATPase measurements. The results support the hypothesis of different HMM configurations on the surface. However, a dominant proportion of the myosin heads were catalytically active, and their average steady-state hydrolysis rate was slightly higher (with Alexa-ATP) or markedly higher (with ATP) on the surface than in solution. The results are discussed in relation to the use of TMCS surfaces and Alexa-ATP for in vitro motility assays and single molecule studies. Furthermore, we propose a novel TIRF microscopy method to accurately determine the surface density of catalytically active myosin motors.
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| 4. |
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| 5. |
- Balaz, Martina, et al.
(författare)
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Protein-surface Interactions and Functional Geometry of Surface-adsorbed Myosin Motor Fragments
- 2009
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Ingår i: Biophysical Journal. - : Biophysical Society. - 0006-3495 .- 1542-0086. ; 96:3 Suppl. 1, s. 495A-495A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Biophysical studies with myosin motor fragments (heavy meromyosin; HMM and subfragment 1; S1) adsorbed to artificial surfaces, are important for elucidation of actomyosin function. In spite of the widespread use of such in vitro motility assays and single molecule studies, little is known about the adsorption geometry and effects of protein-surface interactions on the motor properties. Here, we investigate these factors with focus on HMM using quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) spectroscopy based ATPase assays. In the latter, we monitored the turnover of Alexa-fluor647-ATP (Alexa-ATP) by surface adsorbed HMM. Studies were performed with HMM/S1 adsorbed to model hydrophilic (SiO2) or hydrophobic (trimethyl-chlorosilane [TMCS] - derivatized) surfaces. The results suggest that adsorption of HMM is weakened on SiO2 (but not on TMCS) at high (245 mM) compared to low (65 mM) ionic strengths. The changes in ionic strength were also associated with structural changes in the protein layer according to QCM-D studies. Moreover, the TIRF based ATPase assay suggested a larger fraction of HMM molecules with low catalytic activity on SiO2. These and other TIRF and QCM-D results, suggest that HMM preferentially adsorbs to negatively charged hydrophilic surfaces via the actin-binding region. In contrast, the majority of the HMM molecules seem to adsorb via their C-terminal tail on moderately hydrophobic surfaces. In the latter case the catalytic sites appear to be close to, but not immobilized on the surface. The results with HMM were compared to, and found consistent with, QCM-D and TIRF-data obtained with S1 motor fragments.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Chapman, Mark A., et al.
(författare)
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Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 31:12
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Tidskriftsartikel (refereegranskat)abstract
- To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases, This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important "exercise-responsive" genes that could attenuate metabolic disease.
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| 10. |
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| 11. |
- Echternach, Matthias, et al.
(författare)
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High-Speed Imaging and Electroglottography Measurements of the Open Quotient in Untrained Male Voices' Register Transitions
- 2010
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Ingår i: Journal of Voice. - : Elsevier BV. - 0892-1997 .- 1873-4588. ; 24:6, s. 644-650
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Tidskriftsartikel (refereegranskat)abstract
- Vocal fold oscillation patterns in vocal register transitions are still unclarified. The vocal fold oscillations and the open quotient were analyzed with high-speed digital imaging (HSDI) and electroglottography (EGG) in 18 male untrained subjects singing a glissando from modal to the falsetto register. Results reveal that the open quotient changed with register in both HSDI. and EGG. The in-class correlations for different HSDI and EGG determinations of the open quotient were high. However, we found only weak interclass correlations between both methods. In ID subjects, irregularities of vocal fold vibration occurred during the register transition. Our results confirm previous observations that falsetto register is associated with a higher open quotient compared with modal register. These data suggest furthermore that irregularities typically observed in audio and electroglottographic signals during register transitions are caused by irregularities in vocal fold vibration.
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| 12. |
- Echternach, Matthias, et al.
(författare)
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Perturbation Measurements in Untrained Male Voices' Transitions From Modal to Falsetto Register
- 2011
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Ingår i: Journal of Voice. - : Elsevier BV. - 0892-1997 .- 1873-4588. ; 25:6, s. 663-669
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Voice periodicity during transitions from modal to falsetto register still remains an unclarified question. Method. We examined the acoustic and electroglottographic signals of 20 healthy untrained male voices' transitions from modal to falsetto register on the vowels /a, e, i, o, u, and ae/. Results. In addition to discontinuities in fundamental frequency (F0), an independent increase of jitter, relative average perturbation, and shimmer was observed during and apparently caused by the register transition. In falsetto, the jitter was higher than in the modal register. The contact quotient derived from the electroglottographic signal tended to be lower for higher than for lower F0. Conclusion. Register transitions are associated with increase of perturbation.
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| 13. |
- Emanuelsson, Eric B., et al.
(författare)
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MRI characterization of skeletal muscle size and fatty infiltration in long--term trained and untrained individuals
- 2022
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 54:9, s. 389-389
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated body composition measures in highly trained and untrained individuals using whole--body magnetic resonance imaging (MRI). Additionally, correlations between these measures and skeletal muscle gene expression were performed. Thirty-six individuals were included: endurance-trained males (ME, n = 8) and females (FE, n = 7), strength-trained males (MS, n = 7), and untrained control males (MC, n = 8) and females (FC, n = 6). MRI scans were performed, and resting M. vastus lateralis (VL) biopsies were subjected to RNA sequencing. Liver fat fraction, visceral adipose tissue volume (VAT), total body fat, and total lean tissue were measured from MRI data. Additionally, cross-sectional area (CSA) and fat signal fraction (FSF) were calculated from Mm. pectoralis, M. erector spinae and M. multifidus combined, Mm. quadriceps, and Mm. triceps surae (TS). Liver fat fraction, VAT, and total body fat relative to body weight were lower in ME and FE compared with corresponding controls. MS had a larger CSA across all four muscle groups and lower FSF in all muscles apart from TS compared with MC. ME had a lower FSF across all muscle groups and a larger CSA in all muscles except TS than MC. FE athletes showed a higher CSA in Mm. pectoralis and Mm. quadriceps and a lower CSA in TS than FC with no CSA differences found in the back muscles investigated. Surprisingly, the only difference in FSF between FE and FC was found in Mm. pectoralis. Lastly, correlations between VL gene expression and VL CSA as well as FSF showed that genes positively correlated with CSA revealed an enrichment of the oxidative phosphorylation and thermogenesis pathways, while the genes positively correlated with FSF showed significant enrichment of the spliceosome pathway. Although limited differences were found with training in females, our study suggests that both regular endurance and resistance training are useful in maintaining muscle mass, reducing adipose tissue deposits, and reducing muscle fat content in males.
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| 14. |
- Emanuelsson, Eric B., et al.
(författare)
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Remodeling of the human skeletal muscle proteome found after long-term endurance training but not after strength training
- 2024
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- Exercise training has tremendous systemic tissue-specific health benefits, but the molecular adaptations to long-term exercise training are not completely understood. We investigated the skeletal muscle proteome of highly endurance-trained, strength-trained, and untrained individuals and performed exercise- and sex-specific analyses. Of the 6,000+ proteins identified, >650 were differentially expressed in endurance-trained individuals compared with controls. Strikingly, 92% of the shared proteins with higher expression in both the male and female endurance groups were known mitochondrial. In contrast to the findings in endurance-trained individuals, minimal differences were found in strength-trained individuals and between females and males. Lastly, a co-expression network and comparative literature analysis revealed key proteins and pathways related to the health benefits of exercise, which were primarily related to differences in mitochondrial proteins. This network is available as an interactive database resource where investigators can correlate clinical data with global gene and protein expression data for hypothesis generation.
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| 15. |
- Faulwetter, Jennifer L, et al.
(författare)
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Microbial processes influencing performance of treatment wetlands : A review
- 2009
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Ingår i: ECOLOGICAL ENGINEERING. - : Elsevier BV. - 0925-8574. ; 35:6, s. 987-1004
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Tidskriftsartikel (refereegranskat)abstract
- This review summarizes the microbial mechanisms responsible for removal of carbon, nitrogen. and sulfur compounds in treatment wetlands (TWs) and identifies, categorizes and compares various techniques, from plate count to more modern genomic methods used to elucidate these mechanisms. Removal of a particular pollutant is typically associated with a specific microbial functional group, therefore employment of design and operational methodologies that enhance the activity of that group will better optimize performance. Redox condition is a manipulable parameter that can be used to optimize growth of a targeted functional group, therefore factors influencing the TW redox condition and its influence on organic carbon removal mechanisms are emphasized. Environmental factors influencing growth and activity of N and S cycling microbes (including temperature, pH, salinity, plant species selection and availability of organic carbon and/or inhibiting substances) are discussed with particular attention to factors that might be manipulated. This information is used to offer design and operational methodologies that might enhance growth of a desirable microbial functional group and project what additional microbially-focused research is required to better optimize TW performance.
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| 16. |
- Mijwel, Sara, et al.
(författare)
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Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.
- 2018
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Ingår i: The FASEB Journal. - 0892-6638 .- 1530-6860. ; 32:10, s. 5495-5505
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Tidskriftsartikel (refereegranskat)abstract
- Exercise has been suggested to ameliorate the detrimental effects of chemotherapy on skeletal muscle. The aim of this study was to compare the effects of different exercise regimens with usual care on skeletal muscle morphology and mitochondrial markers in patients being treated with chemotherapy for breast cancer. Specifically, we compared moderate-intensity aerobic training combined with high-intensity interval training (AT-HIIT) and resistance training combined with high-intensity interval training (RT-HIIT) with usual care (UC). Resting skeletal muscle biopsies were obtained pre- and postintervention from 23 randomly selected women from the OptiTrain breast cancer trial who underwent RT-HIIT, AT-HIIT, or UC for 16 wk. Over the intervention, citrate synthase activity, muscle fiber cross-sectional area, capillaries per fiber, and myosin heavy chain isoform type I were reduced in UC, whereas RT-HIIT and AT-HIIT were able to counteract these declines. AT-HIIT promoted up-regulation of the electron transport chain protein levels vs. UC. RT-HIIT favored satellite cell count vs. UC and AT-HIIT. There was a significant association between change in citrate synthase activity and self-reported fatigue. AT-HIIT and RT-HIIT maintained or improved markers of skeletal muscle function compared with the declines found in the UC group, indicating a sustained trainability in addition to the preservation of skeletal muscle structural and metabolic characteristics during chemotherapy. These findings highlight the importance of supervised exercise programs for patients with breast cancer during chemotherapy.-Mijwel, S., Cardinale, D. A., Norrbom, J., Chapman, M., Ivarsson, N., Wengström, Y., Sundberg, C. J., Rundqvist, H. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Månsson, Alf, et al.
(författare)
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Self-organization of motor-propelled cytoskeletal filaments at topographically defined borders.
- 2012
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Ingår i: Journal of Biomedicine and Biotechnology. - : Hindawi Limited. - 1110-7243 .- 1110-7251. ; 2012, s. Article ID: 647265-
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Tidskriftsartikel (refereegranskat)abstract
- Self-organization phenomena are of critical importance in living organisms and of great interest to exploit in nanotechnology. Here we describe in vitro self-organization of molecular motor-propelled actin filaments, manifested as a tendency of the filaments to accumulate in high density close to topographically defined edges on nano- and microstructured surfaces. We hypothesized that this "edge-tracing" effect either (1) results from increased motor density along the guiding edges or (2) is a direct consequence of the asymmetric constraints on stochastic changes in filament sliding direction imposed by the edges. The latter hypothesis is well captured by a model explicitly defining the constraints of motility on structured surfaces in combination with Monte-Carlo simulations [cf. Nitta et al. (2006)] of filament sliding. In support of hypothesis 2 we found that the model reproduced the edge tracing effect without the need to assume increased motor density at the edges. We then used model simulations to elucidate mechanistic details. The results are discussed in relation to nanotechnological applications and future experiments to test model predictions.
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| 28. |
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| 29. |
- Neiman, Daniel, et al.
(författare)
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Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells
- 2020
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed that unmethylated insulin promoter fragments in plasma derive exclusively from β cells, reflect their recent demise, and can be used to assess β cell damage in type 1 diabetes. Herein we describe an ultrasensitive assay for detection of a β cell–specific DNA methylation signature, by simultaneous assessment of 6 DNA methylation markers, that identifies β cell DNA in mixtures containing as little as 0.03% β cell DNA (less than 1 β cell genome equivalent). Based on this assay, plasma from nondiabetic individuals (N = 218, aged 4–78 years) contained on average only 1 β cell genome equivalent/mL. As expected, cell-free DNA (cfDNA) from β cells was significantly elevated in islet transplant recipients shortly after transplantation. We also detected β cell cfDNA in a patient with KATP congenital hyperinsulinism, in which substantial β cell turnover is thought to occur. Strikingly, in contrast to previous reports, we observed no elevation of β cell–derived cfDNA in autoantibody-positive subjects at risk for type 1 diabetes (N = 32), individuals with recent-onset type 1 diabetes (<4 months, N = 92), or those with long-standing disease (>4 months, N = 38). We discuss the utility of sensitive β cell cfDNA analysis and potential explanations for the lack of a β cell cfDNA signal in type 1 diabetes.
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| 30. |
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| 31. |
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| 32. |
- Reitzner, Stefan M., et al.
(författare)
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Molecular profiling of high-level athlete skeletal muscle after acute endurance or resistance exercise : A systems biology approach
- 2024
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Ingår i: Molecular Metabolism. - : Elsevier GmbH. - 2212-8778. ; 79
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Long-term high-level exercise training leads to improvements in physical performance and multi-tissue adaptation following changes in molecular pathways. While skeletal muscle baseline differences between exercise-trained and untrained individuals have been previously investigated, it remains unclear how training history influences human multi-omics responses to acute exercise. Methods: We recruited and extensively characterized 24 individuals categorized as endurance athletes with >15 years of training history, strength athletes or control subjects. Timeseries skeletal muscle biopsies were taken from M. vastus lateralis at three time-points after endurance or resistance exercise was performed and multi-omics molecular analysis performed. Results: Our analyses revealed distinct activation differences of molecular processes such as fatty- and amino acid metabolism and transcription factors such as HIF1A and the MYF-family. We show that endurance athletes have an increased abundance of carnitine-derivates while strength athletes increase specific phospholipid metabolites compared to control subjects. Additionally, for the first time, we show the metabolite sorbitol to be substantially increased with acute exercise. On transcriptional level, we show that acute resistance exercise stimulates more gene expression than acute endurance exercise. This follows a specific pattern, with endurance athletes uniquely down-regulating pathways related to mitochondria, translation and ribosomes. Finally, both forms of exercise training specialize in diverging transcriptional directions, differentiating themselves from the transcriptome of the untrained control group. Conclusions: We identify a “transcriptional specialization effect” by transcriptional narrowing and intensification, and molecular specialization effects on metabolomic level Additionally, we performed multi-omics network and cluster analysis, providing a novel resource of skeletal muscle transcriptomic and metabolomic profiling in highly trained and untrained individuals.
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| 33. |
- Roach, Melissa, et al.
(författare)
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Fructokinase is required for carbon partitioning to cellulose in aspen wood
- 2012
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Ingår i: The Plant Journal. - 0960-7412 .- 1365-313X. ; 70:6, s. 967-977
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Tidskriftsartikel (refereegranskat)abstract
- Sucrose is the main transported form of carbon in several plant species, including Populus species. Sucrose metabolism in developing wood has therefore a central role in carbon partitioning to stem biomass. Half of the sucrose-derived carbon is in the form of fructose, but metabolism of fructose has received little attention as a factor in carbon partitioning to walls of wood cells. We show that RNAi-mediated reduction of FRK2 activity in developing wood of hybrid aspen (Populus tremula × tremuloides) led to the accumulation of soluble neutral sugars and a decrease in hexose phosphates and UDP-glucose, indicating that carbon flux to cell-wall polysaccharide precursors is decreased. Reduced FRK2 activity also led to thinner fiber cell walls with a reduction in the proportion of cellulose. No pleiotropic effects on stem height or diameter were observed. The results establish a central role for FRK2 activity in carbon flux to wood cellulose.
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| 34. |
- Roghanian, Ali, et al.
(författare)
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Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo.
- 2015
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 27:4, s. 473-488
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of action by engaging the immune system. Unfortunately, cures rarely occur and patients display intrinsic or acquired resistance. Here, we demonstrate the therapeutic potential of targeting human (h) FcγRIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. FcγRIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFcγRIIB-transgenic (Tg) mice, FcγRIIB-blocking antibodies effectively deleted target cells in combination with rituximab, and other therapeutic antibodies, from resistance-prone stromal compartments. Similar efficacy was seen in primary human tumor xenografts, including with cells from patients with relapsed/refractory disease. These data support the further development of hFcγRIIB antibodies for clinical assessment.
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| 35. |
- Snoeijs-Leijonmalm, Pauline, 1956-, et al.
(författare)
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Unexpected fish and squid in the central Arctic deep scattering layer
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- The retreating ice cover of the Central Arctic Ocean (CAO) fuels speculations on future fisheries. However, very little is known about the existence of harvestable fish stocks in this 3.3 million-square kilometer ecosystem around the North Pole. Crossing the Eurasian Basin, we documented an uninterrupted 3170-kilometer-long deep scattering layer (DSL) with zooplankton and small fish in the Atlantic water layer at 100- to 500-meter depth. Diel vertical migration of this central Arctic DSL was lacking most of the year when daily light variation was absent. Unexpectedly, the DSL also contained low abundances of Atlantic cod, along with lanternfish, armhook squid, and Arctic endemic ice cod. The Atlantic cod originated from Norwegian spawning grounds and had lived in Arctic water temperature for up to 6 years. The potential fish abundance was far below commercially sustainable levels and is expected to remain so because of the low productivity of the CAO.
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| 36. |
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| 37. |
- Sundberg, Mark, et al.
(författare)
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Actin filament guidance on a chip: Toward high-throughput assays and lab-on-a-chip applications
- 2006
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 22:17, s. 7286-7295
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Tidskriftsartikel (refereegranskat)abstract
- Biological molecular motors that are constrained so that function is effectively limited to predefined nanosized tracks may be used as molecular shuttles in nanotechnological applications. For these applications and in high-throughput functional assays (e. g., drug screening), it is important that the motors propel their cytoskeletal filaments unidirectionally along the tracks with a minimal number of escape events. We here analyze the requirements for achieving this for actin filaments that are propelled by myosin II motor fragments (heavy meromyosin; HMM). First, we tested the guidance of HMM-propelled actin filaments along chemically defined borders. Here, trimethylchlorosilane (TMCS)-derivatized areas with high-quality HMM function were surrounded by SiO2 domains where HMM did not bind actin. Guidance along the TMCS-SiO2 border was almost 100% for filament approach angles between 0 and 20 degrees but only about 10% at approach angles near 90 degrees. A model (Clemmens, J.; Hess, H.; Lipscomb, R.; Hanein, Y.; Bohringer, K. F.; Matzke, C. M.; Bachand, G. D.; Bunker, B. C.; Vogel, V. Langmuir 2003, 19, 10967-10974) accounted for essential aspects of the data and also correctly predicted a more efficient guidance of actin filaments than previously shown for kinesin- propelled microtubules. Despite the efficient guidance at low approach angles, nanosized (< 700 nm wide) TMCS tracks surrounded by SiO2 were not effective in guiding actin filaments. Neither was there complete guidance along nanosized tracks that were surrounded by topographical barriers (walls and roof partially covering the track) unless there was also chemically based selectivity between the tracks and surroundings. In the latter case, with dually defined tracks, there was close to 100% guidance. A combined experimental and theoretical analysis, using tracks of the latter type, suggested that a track width of less than about 200-300 nm is sufficient at a high HMM surface density to achieve unidirectional sliding of actin filaments. In accord with these results, we demonstrate the long- term trapping of actin filaments on a closed-loop track (width < 250 nm). The results are discussed in relation to lab-on-a-chip applications and nanotechnology-assisted assays of actomyosin function.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Sundberg, Mark, et al.
(författare)
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Selective spatial localization of actomyosin motor function by chemical surface patterning
- 2006
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 22:17, s. 7302-7312
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Tidskriftsartikel (refereegranskat)abstract
- We have previously described the efficient guidance and unidirectional sliding of actin filaments along nanosized tracks with adsorbed heavy meromyosin (HMM; myosin II motor fragment). In those experiments, the tracks were functionalized with trimethylchlorosilane (TMCS) by chemical vapor deposition (CVD) and surrounded by hydrophilic areas. Here we first show, using in vitro motility assays on nonpatterned and micropatterned surfaces, that the quality of HMM function on CVD-TMCS is equivalent to that on standard nitrocellulose substrates. We further examine the influences of physical properties of different surfaces (glass, SiO2, and TMCS) and chemical properties of the buffer solution on motility. With the presence of methylcellulose in the assay solution, there was HMM-induced actin filament sliding on both glass/SiO2 and on TMCS, but the velocity was higher on TMCS. This difference in velocity increased with decreasing contact angles of the glass and SiO2 surfaces in the range of 20-67 degrees (advancing contact angles for water droplets). The corresponding contact angle of CVD-TMCS was 81 degrees. In the absence of methylcellulose, there was high-quality motility on TMCS but no motility on glass/SiO2. This observation was independent of the contact angle of the glass/SiO2 surfaces and of HMM incubation concentrations (30-150 mu g mL(-1)) and ionic strengths of the assay solution (20-50 mM). Complete motility selectivity between TMCS and SiO2 was observed for both nonpatterned and for micro- and nanopatterned surfaces. Spectrophotometric analysis of HMM depletion during incubation, K/EDTA ATPase measurements, and total internal reflection fluorescence spectroscopy of HMM binding showed only minor differences in HMM surface densities between TMCS and SiO2/glass. Thus, the motility contrast between the two surface chemistries seems to be attributable to different modes of HMM binding with the hindrance of actin binding on SiO2/glass.
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| 42. |
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| 43. |
- Vikhorev, Petr, et al.
(författare)
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Diffusion dynamics of motor driven transport: gradient production and self-organization of surfaces.
- 2008
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 24:23, s. 13509-13517
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between cytoskeletal filaments (e.g., actin filaments) and molecular motors (e.g., myosin) is the basis for many aspects of cell motility and organization of the cell interior. In the in vitro motility assay (IVMA), cytoskeletal filaments are observed while being propelled by molecular motors adsorbed to artificial surfaces (e.g., in studies of motor function). Here we integrate ideas that cytoskeletal filaments may be used as nanoscale templates in nanopatterning with a novel approach for the production of surface gradients of biomolecules and nanoscale topographical features. The production of such gradients is challenging but of increasing interest (e.g., in cell biology). First, we show that myosin-induced actin filament sliding in the IVMA can be approximately described as persistent random motion with a diffusion coefficient D) given by a relationship analogous to the Einstein equation (D = kT/gamma). In this relationship, the thermal energy (kT) and the drag coefficient (gamma) are substituted by a parameter related to the free-energy transduction by actomyosin and the actomyosin dissociation rate constant, respectively. We then demonstrate how the persistent random motion of actin filaments can be exploited in conceptually novel methods for the production of actin filament density gradients of predictable shapes. Because of regularly spaced binding sites (e.g., lysines and cysteines) the actin filaments act as suitable nanoscale scaffolds for other biomolecules (tested for fibronectin) or nanoparticles. This forms the basis for secondary chemical and topographical gradients with implications for cell biological studies and biosensing.
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| 44. |
- Yusup, Shuayib, et al.
(författare)
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Smoke promotes germination of peatland bryophyte spores
- 2023
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Ingår i: Journal of Experimental Botany. - : Oxford University Press. - 0022-0957 .- 1460-2431. ; 74:1, s. 251-264
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Tidskriftsartikel (refereegranskat)abstract
- Northern peatlands are globally important carbon stores. With increasing fire frequency, the re-establishment of bryophytes becomes crucial for their carbon sequestration. Smoke-responsive germination is a common trait of seeds in fire-prone ecosystems but has not been demonstrated in bryophytes. To investigate the potential role of smoke in post-fire peatland recovery, we tested the germination of spores of 15 bryophyte species after treatment with smoke-water. The smoke responsiveness of spores with different laboratory storage times and burial depths/age (3-200 years) was subsequently tested. Smoke increased the germination percentage for 10 of the species and the germination speed for four of these. Smoke responsiveness increased along the fire frequency gradient from open expanse to forest margin, consistent with the theory that this selects for the maintenance of fire-adapted traits. Smoke enhanced the germinability of 1-year but not 4-year laboratory-stored spores, and considerably increased the germinability of spores naturally buried in peat for up to similar to 200 years. The effect of fire may be overlooked in non-fire-prone ecosystems, such as those in which wetland bryophytes dominate. Our study reveals a mechanism by which an increase in fire frequency may lead to shifts in species dominance, which may affect long-term carbon sequestration in peatlands.
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