| 1. |
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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 3. |
- Abgrall, N., et al.
(författare)
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The large enriched germanium experiment for neutrinoless double beta decay (LEGEND)
- 2017
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Ingår i: AIP Conference Proceedings. - : Author(s). - 1551-7616 .- 0094-243X. ; 1894
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Konferensbidrag (refereegranskat)abstract
- The observation of neutrinoless double-beta decay (0νββ) would show that lepton number is violated, reveal that neu-trinos are Majorana particles, and provide information on neutrino mass. A discovery-capable experiment covering the inverted ordering region, with effective Majorana neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with excellent energy resolution and extremely low backgrounds, at the level of ∼0.1 count /(FWHM·t·yr) in the region of the signal. The current generation 76Ge experiments GERDA and the Majorana Demonstrator, utilizing high purity Germanium detectors with an intrinsic energy resolution of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in the 0νββ signal region of all 0νββ experiments. Building on this success, the LEGEND collaboration has been formed to pursue a tonne-scale 76Ge experiment. The collaboration aims to develop a phased 0νββ experimental program with discovery potential at a half-life approaching or at 1028 years, using existing resources as appropriate to expedite physics results.
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| 4. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 5. |
- Costantini, H., et al.
(författare)
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Recent results of the 14N(p,γ)15O measurement at LUNA
- 2005
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 758:1-4 SPEC. ISS., s. 383C-386C
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Tidskriftsartikel (refereegranskat)abstract
- The 14N(p, γ)15O reaction has been investigated by LUNA at the National Laboratory of Gran Sasso (LNGS) using two different techniques. The first study has been performed using a solid target and detecting the γ-rays coming from the single transitions with a HPGe detector in very close geometry to the target. In a second phase a windowless gas target sorrounded by a nearly 4π BGO summing crystal has been used and the total S-factor has been measured down to Eb = 80 keV. © 2005 Elsevier B.V. All rights reserved.
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| 6. |
- Formicola, A, et al.
(författare)
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Astrophysical S-factor of 14N(p,γ)15O
- 2004
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 591:1-2, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- We report on a new measurement of the 14N(p,γ) 15O capture cross section at Ep=140 to 400 keV using the 400 kV LUNA accelerator facility at the Laboratori Nazionali del Gran Sasso (LNGS). The uncertainties have been reduced with respect to previous measurements and their analysis. We have analyzed the data using the R-matrix method and we find that the ground state transition accounts for about 15% of the total S-factor. The main contribution to the S-factor is given by the transition to the 6.79 MeV state. We find a total S(0)=1.7±0.2 keVb, in agreement with recent extrapolations. The result has important consequences for the solar neutrino spectrum as well as for the age of globular clusters. © 2004 Elsevier B.V. All rights reserved.
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| 7. |
- Imbriani, G., et al.
(författare)
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S-factor of 14N(p,γ)15O at astrophysical energies
- 2005
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 25:3, s. 455-466
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Tidskriftsartikel (refereegranskat)abstract
- The astrophysical S(E) factor of 14N(p,γ)15O has been measured for effective center-of-mass energies between E eff = 119 and 367 keV at the LUNA facility using TiN solid targets and Ge detectors. The data are in good agreement with previous and recent work at overlapping energies. R-matrix analysis reveals that due to the complex level structure of 15O the extrapolated S(0) value is model dependent and calls for additional experimental efforts to reduce the present uncertainty in S(0) to a level of a few percent as required by astrophysical calculations. © Società Italiana di Fisica / Springer-Verlag 2005.
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| 8. |
- Bemmerer, D., et al.
(författare)
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Feasibility of low-energy radiative-capture experiments at the LUNA underground accelerator facility
- 2005
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 24:2, s. 313-319
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Tidskriftsartikel (refereegranskat)abstract
- The LUNA (Laboratory Underground for Nuclear Astrophysics) facility has been designed to study nuclear reactions of astrophysical interest. It is located deep underground in the Gran Sasso National Laboratory, Italy. Two electrostatic accelerators, with 50 and 400 kV maximum voltage, in combination with solid and gas target setups allowed to measure the total cross-sections of the radiative-capture reactions 2H2H(p, γ) 3He3Heand 14N14N(p, γ) 15O15Owithin their relevant Gamow peaks. We report on the gamma background in the Gran Sasso laboratory measured by germanium and bismuth germanate detectors, with and without an incident proton beam. A method to localize the sources of beam-induced background using the Doppler shift of emitted gamma rays is presented. The feasibility of radiative-capture studies at energies of astrophysical interest is discussed for several experimental scenarios. © Società Italiana di Fisica/Springer-Verlag 2005.
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| 9. |
- Imbriani, G., et al.
(författare)
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The bottleneck of CNO burning and the age of Globular Clusters
- 2004
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 420:2, s. 625-629
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Tidskriftsartikel (refereegranskat)abstract
- The transition between the Main Sequence and the Red Giant Branch in low mass stars is powered by the onset of CNO burning, whose bottleneck is 14N(p, γ) 15O. The LUNA collaboration has recently improved the low energy measurements of the cross section of this key reaction. We analyse the impact of the revised reaction rate on the estimate of the Globular Cluster ages, as derived from the turnoff luminosity. We found that the age of the oldest Globular Clusters should be increased by about 0.7-1 Gyr with respect to the current estimates.
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| 10. |
- Caciolli, A., et al.
(författare)
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Revision of the 15N(p, γ)16O reaction rate and oxygen abundance in H-burning zones
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 533
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Tidskriftsartikel (refereegranskat)abstract
- Context. The NO cycle takes place in the deepest layer of a H-burning core or shell, when the temperature exceeds T ≈ 30 × 106 K. The O depletion observed in some globular cluster giant stars, always associated with a Na enhancement, may be due to either a deep mixing during the red giant branch (RGB) phase of the star or to the pollution of the primordial gas by an early population of massive asymptotic giant branch (AGB) stars, whose chemical composition was modified by the hot bottom burning. In both cases, the NO cycle is responsible for the O depletion. Aims. The activation of this cycle depends on the rate of the 15N(p, γ)16O reaction. A precise evaluation of this reaction rate at temperatures as low as experienced in H-burning zones in stellar interiors is mandatory to understand the observed O abundances. Methods. We present a new measurement of the 15N(p, γ)16O reaction performed at LUNA covering for the first time the center of mass energy range 70-370 keV, which corresponds to stellar temperatures between 65 × 106 K and 780 × 106 K. This range includes the 15N(p, γ)16O Gamow-peak energy of explosive H-burning taking place in the external layer of a nova and the one of the hot bottom burning (HBB) nucleosynthesis occurring in massive AGB stars. Results. With the present data, we are also able to confirm the result of the previous R-matrix extrapolation. In particular, in the temperature range of astrophysical interest, the new rate is about a factor of 2 smaller than reported in the widely adopted compilation of reaction rates (NACRE or CF88) and the uncertainty is now reduced down to the 10% level. © 2011 ESO.
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| 11. |
- Marta, M., et al.
(författare)
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Precision study of ground state capture in the 14N(p,γ)15O reaction
- 2008
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 78:2
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Tidskriftsartikel (refereegranskat)abstract
- The rate of the hydrogen-burning carbon-nitrogen-oxygen (CNO) cycle is controlled by the slowest process, 14N(p,γ)15O, which proceeds by capture to the ground and several excited states in O15. Previous extrapolations for the ground state contribution disagreed by a factor 2, corresponding to 15% uncertainty in the total astrophysical S factor. At the Laboratory for Underground Nuclear Astrophysics (LUNA) 400 kV accelerator placed deep underground in the Gran Sasso facility in Italy, a new experiment on ground state capture has been carried out at 317.8, 334.4, and 353.3 keV center-of-mass energy. Systematic corrections have been reduced considerably with respect to previous studies by using a Clover detector and by adopting a relative analysis. The previous discrepancy has been resolved, and ground state capture no longer dominates the uncertainty of the total S factor. © 2008 The American Physical Society.
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| 12. |
- Marta, M., et al.
(författare)
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The N14(p,γ)O15 reaction studied with a composite germanium detector
- 2011
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 83:4
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Tidskriftsartikel (refereegranskat)abstract
- The rate of the carbon-nitrogen-oxygen (CNO) cycle of hydrogen burning is controlled by the N14(p,γ)O15 reaction. The reaction proceeds by capture to the ground states and several excited states in O15. In order to obtain a reliable extrapolation of the excitation curve to astrophysical energy, fits in the R-matrix framework are needed. In an energy range that sensitively tests such fits, new cross-section data are reported here for the four major transitions in the N14(p,γ)O15 reaction. The experiment has been performed at the Laboratory for Underground Nuclear Astrophysics (LUNA) 400-kV accelerator placed deep underground in the Gran Sasso facility in Italy. Using a composite germanium detector, summing corrections have been considerably reduced with respect to previous studies. The cross sections for capture to the ground state and to the 5181, 6172, and 6792 keV excited states in O15 have been determined at 359, 380, and 399 keV beam energy. In addition, the branching ratios for the decay of the 278-keV resonance have been remeasured. © 2011 American Physical Society.
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| 13. |
- Trautvetter, H P, et al.
(författare)
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Ground state capture in 14N(p,γ)15O studied above the 259 keV resonance at LUNA
- 2008
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 35:1
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Tidskriftsartikel (refereegranskat)abstract
- We report on a new measurement of 14N(p,γ)15O for the ground state capture transition at Ep = 360, 380 and 400 keV, using the 400 kV LUNA accelerator. The true coincidence summing effect - the major source of error in the ground state capture determination - has been significantly reduced by using a Clover-type gamma detector. © 2008 IOP Publishing Ltd.
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| 14. |
- O'Gorman, Eoin J., et al.
(författare)
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Impacts of Warming on the Structure and Functioning of Aquatic Communities : Individual-to Ecosystem-Level Responses
- 2012
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Ingår i: Advances in Ecological Research, Vol 47. - : Elsevier. - 9780123983152 ; , s. 81-176
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Bokkapitel (refereegranskat)abstract
- Environmental warming is predicted to rise dramatically over the next century, yet few studies have investigated its effects in natural, multi-species systems. We present data collated over an 8-year period from a catchment of geothermally heated streams in Iceland, which acts as a natural experiment on the effects of warming across different organisational levels and spatiotemporal scales. Body sizes and population biomasses of individual species responded strongly to temperature, with some providing evidence to support temperature size rules. Macroinvertebrate and meiofaunal community composition also changed dramatically across the thermal gradient. Interactions within the warm streams in particular were characterised by food chains linking algae to snails to the apex predator, brown trout These chains were missing from the colder systems, where snails were replaced by much smaller herbivores and invertebrate omnivores were the top predators. Trout were also subsidised by terrestrial invertebrate prey, which could have an effect analogous to apparent competition within the aquatic prey assemblage. Top-down effects by snails on diatoms were stronger in the warmer streams, which could account for a shallowing of mass-abundance slopes across the community. This may indicate reduced energy transfer efficiency from resources to consumers in the warmer systems and/or a change in predator-prey mass ratios. All the ecosystem process rates investigated increased with temperature, but with differing thermal sensitivities, with important implications for overall ecosystem functioning (e.g. creating potential imbalances in elemental fluxes). Ecosystem respiration rose rapidly with temperature, leading to increased heterotrophy. There were also indications that food web stability may be lower in the warmer streams.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Boström, Henrik, et al.
(författare)
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Explaining multivariate time series forecasts : An application to predicting the Swedish GDP?
- 2020
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Ingår i: CEUR Workshop Proceedings. - : CEUR-WS.
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Konferensbidrag (refereegranskat)abstract
- Various approaches to explaining predictions of black box models have been proposed, including model-agnostic techniques that measure feature importance (or effect) by presenting modified test instances to the underlying black-box model. These modifications rely on choosing feature values from the complete range of observed values. However, when applying machine learning algorithms to the task of forecasting from multivariate time-series, it is suggested that the temporal aspect should be taken into account when analyzing the feature effect. A modification of individual conditional expectation (ICE) plots is proposed, called ICE-T plots, which displays the prediction change for temporally ordered feature values. Results are presented from a case study on predicting the Swedish gross domestic product (GDP) based on a comprehensive set of indicator and prognostic variables. The effect of calculating feature effect with and without temporal constraints is demonstrated, as well as the impact of transformations and forecast horizons on what features are found to have a large effect, and the use of ICE-T plots as a complement to ICE plots.
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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. |
- Dyrskjot, Lars, et al.
(författare)
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Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer : A Prospective Multicentre Validation Study
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:3, s. 461-469
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. Objective: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. Design, setting, and participants: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. Outcome measurements and statistical analysis: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. Results and limitations: The progression score was significantly (p < 0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guerin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p < 0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p < 0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R-2 = 0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/ 750 patients). Conclusions: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Patient summary: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.
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| 26. |
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| 27. |
- Hasselbalch, H., et al.
(författare)
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Circulating hyaluronan in the myelofibrosis/osteomyelosclerosis syndrome and other myeloproliferative disorders
- 1991
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Ingår i: American Journal of Hematology. - 0361-8609 .- 1096-8652. ; 36:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The serum concentration of hyaluronan (HYA) was determined in 59 patients with various myeloproliferative disorders, including 33 patients with idiopathic myelofibrosis. In 18 patients the serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) was measured concomitantly. Raised serum HYA levels were seen in patients with active disease compared with age-matched healthy subjects, whereas no significant difference in serum HYA was seen between patients with stable disease and age-matched controls. Serum HYA concentrations correlated significantly with the leukocyte count (rho = 0.38; P less than 0.02) and with the serum concentration of PIIINP (rho = 0.50; P less than 0.001). During cytotoxic treatment, the serum HYA and PIIINP concentrations decreased in concert with declining leukocyte counts. These findings suggest that clonal expansion is accompanied by a bone marrow stromal reaction similar to the repair processes following injury to soft connective tissues. The relatively modest changes in serum HYA with frequent overlaps between patient categories and healthy subjects imply that the clinical utility of single determinations of serum HYA in the present disease groups is restrained. On the other hand, sequential measurements of HYA may provide a reflection of the myeloproliferative process in individual patients.
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| 28. |
- Huss, Fredrik R.M., et al.
(författare)
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Macroporous gelatine spheres as culture substrate, transplantation vehicle, and biodegradable scaffold for guided regeneration of soft tissues. : In vivo study in nude mice
- 2007
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Ingår i: Journal of Plastic, Reconstructive, and Aesthetic Surgery. - : Elsevier BV. - 1748-6815 .- 1878-0539. ; 60:5, s. 543-555
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Tidskriftsartikel (refereegranskat)abstract
- In the course of development of a new type of filler for the correction of small defects in soft tissues we studied macroporous gelatine spheres as culture substrate, transplantation vehicle, and biodegradable scaffold for guided regeneration of soft tissues in vivo. We injected intradermally in nude mice gelatine spheres that had either been preseeded with human fibroblasts or preadipocytes, or left unseeded. We compared the extent of regenerated tissue with that found after injections of saline or single-cell suspensions of human fibroblasts or preadipocytes. Routine histological examinations and immunohistochemical staining for von Willebrand factor (indicating neoangiogenesis) were made after 7, 21, and 56 days. Injected saline or single-cell suspensions had no effect. However, a quick and thorough tissue regeneration with developing neoangiogenesis was elicited by the gelatine spheres and the effect of spheres preseeded with preadipocytes surpassed the effect of spheres preseeded with fibroblasts, which in turn surpassed the effect of unseeded gelatine spheres. We suggest that minor soft tissue defects such as wrinkles or creases can be corrected by injection of naked macroporous gelatine spheres, whereas larger defects are best corrected by injection of macroporous gelatine spheres preseeded with fibroblasts, or preadipocytes, or both.
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| 29. |
- Junker, Alex, et al.
(författare)
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Human studies of mitochondrial biology demonstrate an overall lack of binary sex differences : A multivariate meta-analysis
- 2022
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Ingår i: FASEB Journal. - 0892-6638. ; 36:2
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondria are maternally inherited organelles that play critical tissue-specific roles, including hormone synthesis and energy production, that influence human development, health, and aging. However, whether mitochondria from women and men exhibit consistent biological differences remains unclear, representing a major gap in knowledge. This meta-analysis systematically examined four domains and six subdomains of mitochondrial biology (total 39 measures), including mitochondrial content, respiratory capacity, reactive oxygen species (ROS) production, morphometry, and mitochondrial DNA copy number. Standardized effect sizes (Hedge's g) of sex differences were computed for each measure using data in 2258 participants (51.5% women) from 50 studies. Only two measures demonstrated aggregate binary sex differences: higher mitochondrial content in women's WAT and isolated leukocyte subpopulations (g = 0.20, χ2 p =.01), and higher ROS production in men's skeletal muscle (g = 0.49, χ2 p <.0001). Sex differences showed weak to no correlation with age or BMI. Studies with small sample sizes tended to overestimate effect sizes (r = −.17, p <.001), and sex differences varied by tissue examined. Our findings point to a wide variability of findings in the literature concerning possible binary sex differences in mitochondrial biology. Studies specifically designed to capture sex- and gender-related differences in mitochondrial biology are needed, including detailed considerations of physical activity and sex hormones.
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| 30. |
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| 31. |
- Junker, Johan P E, 1980-, et al.
(författare)
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Mechanical tension stimulates the transdifferentiation of fibroblasts into myofibroblasts in human burn scars
- 2008
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Ingår i: Burns : journal of the International Society for Burn Injuries. - : Elsevier BV. - 1879-1409. ; 34:7, s. 942-6
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Tidskriftsartikel (refereegranskat)abstract
- Scar formation as a result of burn wounds leads to contraction of the formed granulation tissue, which causes both aesthetic and functional impairment for the patient. Currently, the main treatment methods focus on stretching to prevent tissue contraction. The myofibroblasts play a key role in the contraction of granulation tissue during scar formation, but their presence should normally decrease after wound re-epithelialization. In hypertrophic scars the myofibroblasts persist and is believed to cause further hypertrophy. Previous studies have shown that mechanical tension leads to increased myofibroblast numbers in granulation tissue. In order to evaluate the effect mechanical tension as a result of stretching has on the number of myofibroblasts in burn wound scars, an in vitro model was used. This model used human burn scar biopsies which were stretched and examined after 1 and 6 days to evaluate the effect on the number of myofibroblasts. The stretching caused an increase in the number of myofibroblasts after mechanical stimulation. This indicates that mechanical stimulation using stretching induces fibroblast to myofibroblast transdifferentiation, thus underlining the importance of further investigations of optimal methods of this regime for treating burn scars.
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| 32. |
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| 33. |
- Junker, Robert R., et al.
(författare)
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Covariation and phenotypic integration in chemical communication displays : Biosynthetic constraints and eco-evolutionary implications
- 2018
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 220:3, s. 739-749
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Tidskriftsartikel (refereegranskat)abstract
- Chemical communication is ubiquitous. The identification of conserved structural elements in visual and acoustic communication is well established, but comparable information on chemical communication displays (CCDs) is lacking. We assessed the phenotypic integration of CCDs in a meta-analysis to characterize patterns of covariation in CCDs and identified functional or biosynthetically constrained modules. Poorly integrated plant CCDs (i.e. low covariation between scent compounds) support the notion that plants often utilize one or few key compounds to repel antagonists or to attract pollinators and enemies of herbivores. Animal CCDs (mostly insect pheromones) were usually more integrated than those of plants (i.e. stronger covariation), suggesting that animals communicate via fixed proportions among compounds. Both plant and animal CCDs were composed of modules, which are groups of strongly covarying compounds. Biosynthetic similarity of compounds revealed biosynthetic constraints in the covariation patterns of plant CCDs. We provide a novel perspective on chemical communication and a basis for future investigations on structural properties of CCDs. This will facilitate identifying modules and biosynthetic constraints that may affect the outcome of selection and thus provide a predictive framework for evolutionary trajectories of CCDs in plants and animals.
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| 34. |
- Karlsson, Lisa K, et al.
(författare)
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Human Dermal Fibroblasts : A Potential Cell Source for Endothelialization of Vascular Grafts
- 2009
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Ingår i: Annals of Vascular Surgery. - : Elsevier BV. - 0890-5096 .- 1615-5947. ; 23:5, s. 663-674
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently, there has been an intense ongoing search for suitable cell sources for vascular tissue engineering. Previous studies report that cells with multilineage potential have been found within the connective stroma of the skin. In line with this, preliminary data from our group suggest that human dermal fibroblasts have the capacity to alter their phenotype into an endothelial cell-like phenotype in vitro. As a first step in using these cells in vascular tissue engineering, we investigated their ability to form an endothelial cell-like layer on a scaffold in vitro. Furthermore, we studied the possibility of seeding dermal fibroblasts on a scaffold and later commencing with induction toward an endothelial cell-like phenotype. METHODS: Cells cultured in either normal fibroblast medium or endothelial induction medium were seeded on a gelatin-based scaffold. To study the organization of cells, routine staining was performed. Differentiation was confirmed by Western blotting and immunohistochemistry with antibodies directed toward molecules commonly used to identify endothelial cells. RESULTS AND CONCLUSION: Our data support that human dermal fibroblasts differentiated toward endothelial cell-like cells prior to seeding showed histological resemblance to mature endothelial cells, while fibroblasts seeded and later induced into endothelial differentiation grew in multilayer. However, expression of various surface molecules indicative of an endothelial phenotype was seen using both techniques. In conclusion, the results presented in this study indicate that human dermal fibroblasts differentiated toward an endothelial cell-like phenotype may be a novel cell source for endothelialization of vascular grafts.
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| 35. |
- Kiwanuka, Elizabeth, et al.
(författare)
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CCN2 is transiently expressed by keratinocytes during re-epithelialization and regulates keratinocyte migration in vitro by the ras-MEK-ERK signaling pathway
- 2013
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 185:2, s. E109-E119
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Tidskriftsartikel (refereegranskat)abstract
- Background: CCN2 (previously known as connective tissue growth factor) is a multifunctional matricellular protein that has numerous effects on cell life and cell interactions with the connective tissue. Although the importance of CCN2 for the fibrotic process in wound healing has been well studied, the involvement of CCN2 in keratinocyte function has not yet been explored. Therefore, the aim of the present study was to investigate the role of CCN2 in the epidermis during wound healing. Materials and methods: Immunohistochemistry was done on sections from full-thickness porcine wounds. The effect of CCN2 on the migration of cultured human keratinocytes exposed to scratch wounds, the effect on phosphorylation of extracellular signal-related kinases (ERK), and the effect of adding inhibitors to the ERK/ mitogen-activated protein kinase pathway to human keratinocytes were studied. Results: The CCN2 protein was transiently expressed in vivo at the leading keratinocyte edge during re-epithelialization of full-thickness porcine wounds. In vitro, exogenous addition of CCN2 to human keratinocyte cultures regulated keratinocyte migration and resulted in phosphorylation of ERK. The addition of inhibitors of ERK/mitogen-activated protein kinase counteracted the effect of CCN2 on migration. Conclusions: CCN2 was transiently expressed at the leading keratinocyte edge in vivo. The biologic importance of this was supported in vitro, because CCN2 regulated human keratinocyte migration through activation of the Ras-mitogen-activated protein kinase kinase-ERK signal transduction pathway.
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| 36. |
- Kiwanuka, Elizabeth, et al.
(författare)
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CCN2 promotes keratinocyte adhesion and migration via integrin alpha 5 beta 1
- 2013
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 319:19, s. 2938-2946
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Tidskriftsartikel (refereegranskat)abstract
- Background: CCN2, (a.k.a. connective tissue growth factor and CTGF) has emerged as a regulator of cell migration. While the importance of CCN2 for the fibrotic process in wound healing has been well studied, the effect of CCN2 on keratinocyte function is not well understood. In this study, we investigated the mechanism behind CCN2-driven keratinocyte adhesion and migration. Materials and methods: Adhesion assays were performed by coating wells with 10 mu g/ml fibronectin (FN) or phosphate-buffered saline (PBS). Keratinocytes were seeded in the presence or absence of 200 ng/ml CCN2, 5 mmol/l ethylenediaminetetraacetic acid, 10 mmol/l cations, 500 mu l arginine-glycine-aspartic acid (RGD), 500 mu M arginine-glycine-glutamate-serine (RGES), and 10 mu g/ml anti-integrin blocking antibodies. Migration studies were performed using a modified Boyden chamber assay. Quantitative PCR was used to study the effect of CCN2 on integrin subunit mRNA expression. To block intracellular pathways, keratinocytes were pretreated with 20 mu M PD98059 (MEN-1 inhibitor) or 20 mu M PF573228 (FAN inhibitor) for 60 min prior the addition of CCN2. Western blot was used to measure CCN2, p-ERK1/2, and ERK1/2. Results: CCN2 enhanced keratinocyte adhesion to fibronectin via integrin alpha 5 beta 1. The addition of anti-integrin alpha 5 beta 1 antibodies reduced CCN2-mediated keratinocyte migration. In addition, CCN2 regulated mRNA and protein expression of integrin subunits alpha 5 and beta 1 CCN2 activated the FAK-MAPK signaling pathway, and pretreatment with MEK1-specific inhibitor PD98059 markedly reduced CCN2-induced keratinocyte migration. Conclusions: Our results demonstrate that CCN2 enhances keratinocyte adhesion and migration through integrin alpha 5 beta 1 and activation of the FAK-MAPK signaling cascade.
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| 37. |
- Kiwanuka, Elizabeth, et al.
(författare)
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Comparison of Healing Parameters in Porcine Full-Thickness Wounds Transplanted with Skin Micrografts, Split-Thickness Skin Grafts, and Cultured Keratinocytes
- 2011
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Ingår i: Journal of the American College of Surgeons. - : Ovid Technologies (Wolters Kluwer Health). - 1072-7515 .- 1879-1190. ; 213:6, s. 728-735
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transplantation of skin micrografts (MGs), split-thickness skin grafts (STSGs), or cultured autologous keratinocytes (CKs) enhances the healing of large full-thickness wounds. This study compares these methods in a porcine wound model, investigating the utility of micrograft transplantation in skin restoration. STUDY DESIGN: Full-thickness wounds were created on Yorkshire pigs and assigned to one of the following treatment groups: MGs, STSGs, CKs, wet nontransplanted, or dry nontransplanted. Dry wounds were covered with gauze and the other groups' wounds were enclosed in a polyurethane chamber containing saline. Biopsies were collected 6, 12, and 18 days after wounding. Quantitative and qualitative wound healing parameters including macroscopic scar appearance, wound contraction, neoepidermal maturation, rete ridge formation, granulation tissue thickness and width, and scar tissue formation were studied. RESULTS: Transplanted wounds scored lower on the Vancouver Scar Scale compared with nontransplanted wounds, indicating a better healing outcome. All transplanted wounds exhibited significantly lower contraction compared with nontransplanted wounds. Wounds transplanted with either MGs, STSGs, or CKs showed a significant increase in re-epithelialization compared with nontransplanted wounds. Wounds transplanted with MGs or STSGs exhibited improved epidermal healing compared with nongrafted wounds. Furthermore, transplantation with STSGs or MGs led to less scar tissue formation compared with the nontransplanted wounds. No significant impact on scar formation was observed after transplantation of CKs. CONCLUSIONS: Qualitative and quantitative measurements collected from full-thickness porcine wounds show that transplantation of MGs improve wound healing parameters and is comparable to treatment with STSGs.
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| 38. |
- Kiwanuka, Elizabeth, et al.
(författare)
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Connective tissue growth factor enhances keratinocyte adhesion to fibronectin and promotes migration through integrin alpha5/beta1
- 2012
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Ingår i: Journal of the American College of Surgeons. - : Ovid Technologies (Wolters Kluwer Health). - 1072-7515 .- 1879-1190. ; 215:3, s. S81-S82
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: We have previously shown that connective tissue growth factor (CTGF) promotes keratinocyte migration during re-epithelialization. In this study, we investigated whether the CTGF-driven migration involved integrin alpha-5/beta-1 - the principal ligand for fibronectin (FN).Methods: Adhesions assays were performed by coating wells with 10 ug/mL FN or phosphate buffered saline (PBS). Keratinocytes were seeded in the presence or absence of 200 ng/mL CTGF, 5 mmol/L EDTA, 10 mmol/L Mg2+, 10 ug/mL anti-integrin alpha-5/beta-1-blocking antibody. Chemotaxsis assays were performed using a modified Boyden chamber. Keratinocytes were pre-incubated with alpha-5/beta-1-antibodies or mouse-IgG for 30 minute, and migration in the absence or presence of 200 ng/mL CTGF was measured. Cells were stained and absorbance was measured at 570 nm. A value of 1 was assigned to untreated cells.Results: Cell adhesion increased 1.5 ± 0.3 folds in wells coated with FN compared to PBS. CTGF enhanced cell adhesion 2.1 ± 0.3 folds, while EDTA reduced CTGF mediated cell adhesion to baseline (1.1 ± 0.2). The addition of the divalent cation Mg2+ restored CTGF-induced adhesion, indicating involvement of integrins. Integrin alpha-5/beta-1-blocking antibodies reversed CTGF-enhanced binding (1.1 ± 0.2). Consistent with the cell adhesion data, CTGF-induced migration was reduced to 1.5 ± 0.3 by anti-integrin alpha-5/beta-1 antibodies compared to the 2.0 ± 0.6 fold increase seen with 200 ng/mL CTGF.
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| 39. |
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| 40. |
- Kunst, Anton E, et al.
(författare)
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Occupational class and ischemic heart disease mortality in the United States and 11 European countries.
- 1999
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Ingår i: American Journal of Public Health. - 0090-0036 .- 1541-0048. ; 89, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Twelve countries were compared with respect to occupational class differences in ischemic heart disease mortality in order to identify factors that are associated with smaller or larger mortality differences. METHODS: Data on mortality by occupational class among men aged 30 to 64 years were obtained from national longitudinal or cross-sectional studies for the 1980s. A common occupational class scheme was applied to most countries. Potential effects of the main data problems were evaluated quantitatively. RESULTS: A north-south contrast existed within Europe. In England and Wales, Ireland, and Nordic countries, manual classes had higher mortality rates than nonmanual classes. In France, Switzerland, and Mediterranean countries, manual classes had mortality rates as low as, or lower than, those among nonmanual classes. Compared with Northern Europe, mortality differences in the United States were smaller (among men aged 30-44 years) or about as large (among men aged 45-64 years). CONCLUSIONS: The results underline the highly variable nature of socioeconomic inequalities in ischemic heart disease mortality. These inequalities appear to be highly sensitive to social gradients in behavioral risk factors. These risk factor gradients are determined by cultural as well as socioeconomic developments.
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| 41. |
- Nielsen, M. A., et al.
(författare)
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Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogenesis in patients with rheumatoid arthritis
- 2023
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 52:1, s. 33-41
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Galectin-3 (Gal-3) has been suggested as a proinflammatory mediator in rheumatoid arthritis (RA). We aimed to study clinical and pathogenic aspects of Gal-3 in RA. Method: Plasma samples from healthy controls (n = 48) and patients with newly diagnosed, early RA were assayed for soluble Gal-3. In patients with chronic RA (n = 18), Gal-3 was measured in both plasma and synovial fluid. Synovial fluid mononuclear cells were used to purify fibroblast-like synoviocytes (FLSs) and osteoclasts. Monocultures of FLSs and autologous co-cultures of FLSs and peripheral blood mononuclear cells were established and co-incubated with a Gal-3 inhibitor. Results: Patients with early and chronic RA had persistently increased plasma levels of Gal-3 compared with controls. However, changes in plasma Gal-3 at the level of individuals were associated with long-term disease activity. In seropositive early RA patients, all patients with decreasing plasma Gal-3 from 0 to 3 months had low disease activity after 2 years (p < 0.05). Gal-3 levels in synovial fluid were markedly elevated. In vitro, co-incubation with a Gal-3 inhibitor (GB1107, 10 µM) led to a significant reduction in both interleukin-1β and tumour necrosis factor-α secretion from FLS monocultures (both p < 0.05) and decreased monocyte-derived osteoclastogenesis compared with controls (both p < 0.05). Conclusions: Our findings underscore the role of Gal-3 regarding disease activity and tissue destruction in RA. An initial decrease in plasma Gal-3 levels predicted decreased long-term disease activity. Correspondingly, a Gal-3 inhibitor decreased the activity of inflammatory FLSs and osteoclastogenesis in patients with RA.
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| 42. |
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| 43. |
- Sommar, Pehr, et al.
(författare)
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Engineering three-dimensional cartilage- and bone-like tissues using human dermal fibroblasts and macroporous gelatine microcarriers
- 2010
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Ingår i: Journal of plastic, reconstructive & aesthetic surgery : JPRAS. - : Elsevier BV. - 1878-0539 .- 1748-6815. ; 63:6, s. 1036-1046
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Tidskriftsartikel (refereegranskat)abstract
- The creation of tissue-engineered cartilage and bone, using cells from an easily available source seeded on a suitable biomaterial, may have a vast impact on regenerative medicine. While various types of adult stem cells have shown promising results, their use is accompanied by difficulties associated with harvest and culture. The proposed inherent plasticity of dermally derived human fibroblasts may render them useful in tissue-engineering applications. In the present study, human dermal fibroblasts cultured on macroporous gelatine microcarriers encapsulated in platelet-rich plasma into three-dimensional constructs were differentiated towards chondrogenic and osteogenic phenotypes using specific induction media. The effect of flow-induced shear stress on osteogenic differentiation of fibroblasts was also evaluated. The generated tissue constructs were analysed after 4, 8 and 12 weeks using routine and immunohistochemical stainings as well as an enzyme activity assay. The chondrogenic-induced tissue constructs were composed of glycosaminoglycan-rich extracellular matrix, which stained positive for aggrecan. The osteogenic-induced tissue constructs were composed of mineralised extracellular matrix containing osteocalcin and osteonectin, with cells showing an increased alkaline phosphatase activity. Increased osteogenic differentiation was seen when applying flow-induced shear stress to the culture. Un-induced fibroblast controls did not form cartilage- or bone-like tissues. Our findings suggest that primary human dermal fibroblasts can be used to form cartilage- and bone-like tissues in vitro when cultured in specific induction media.
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