| 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. |
- 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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| 3. |
- 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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| 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. |
- Zheng, TH, et al.
(författare)
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Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
- 2021
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:8, s. 1538-1549
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Tidskriftsartikel (refereegranskat)abstract
- Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.DesignWe conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.ResultsWe demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.ConclusionHEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
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| 6. |
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| 7. |
- Heidegger, A., et al.
(författare)
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Development and inter-laboratory validation of the VISAGE enhanced tool for age estimation from semen using quantitative DNA methylation analysis
- 2022
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Ingår i: Forensic Science International: Genetics. - : Elsevier BV. - 1872-4973. ; 56
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Tidskriftsartikel (refereegranskat)abstract
- The analysis of DNA methylation has become an established method for chronological age estimation. This has triggered interest in the forensic community to develop new methods for age estimation from biological crime scene material. Various assays are available for age estimation from somatic tissues, the majority from blood. Age prediction from semen requires different DNA methylation markers and the only assays currently developed for forensic analysis are based on SNaPshot or pyrosequencing. Here, we describe a new assay using massively parallel sequencing to analyse 13 candidate CpG sites targeted in two multiplex PCRs. The assay has been validated by five consortium laboratories of the VISible Attributes through GEnomics (VISAGE) project within a collaborative exercise and was tested for reproducible quantification of DNA methylation levels and sensitivity with DNA methylation controls. Furthermore, DNA extracts and stains on Whatman FTA cards from two semen samples were used to evaluate concordance and mimic casework samples. Overall, the assay yielded high read depths (> 1000 reads) at all 13 marker positions. The methylation values obtained indicated robust quantification with an average standard deviation of 2.8% at the expected methylation level of 50% across the 13 markers and a good performance with 50 ng DNA input into bisulfite conversion. The absolute difference of quantifications from one participating laboratory to the mean quantifications of concordance and semen stains of remaining laboratories was approximately 1%. These results demonstrated the assay to be robust and suitable for age estimation from semen in forensic investigations. In addition to the 13-marker assay, a more streamlined protocol combining only five age markers in one multiplex PCR was developed. Preliminary results showed no substantial differences in DNA methylation quantification between the two assays, indicating its applicability with the VISAGE age model for semen developed with data from the complete 13-marker tool.
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| 8. |
- 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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| 9. |
- Kuppler, Jonas, et al.
(författare)
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Global gradients in intraspecific variation in vegetative and floral traits are partially associated with climate and species richness
- 2020
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 29:6, s. 992-1007
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Tidskriftsartikel (refereegranskat)abstract
- AimIntraspecific trait variation (ITV) within natural plant communities can be large, influencing local ecological processes and dynamics. Here, we shed light on how ITV in vegetative and floral traits responds to large‐scale abiotic and biotic gradients (i.e., climate and species richness). Specifically, we tested whether associations of ITV with temperature, precipitation and species richness were consistent with any of four hypotheses relating to stress tolerance and competition. Furthermore, we estimated the degree of correlation between ITV in vegetative and floral traits and how they vary along the gradients.LocationGlobal.Time period1975–2016.Major taxa studiedHerbaceous and woody plants.MethodsWe compiled a dataset of 18,401 measurements of the absolute extent of ITV (measured as the coefficient of variation) in nine vegetative and seven floral traits from 2,822 herbaceous and woody species at 2,372 locations.ResultsLarge‐scale associations between ITV and climate were trait specific and more prominent for vegetative traits, especially leaf morphology, than for floral traits. The ITV showed pronounced associations with climate, with lower ITV values in colder areas and higher values in drier areas. The associations of ITV with species richness were inconsistent across traits. Species‐specific associations across gradients were often idiosyncratic, and covariation in ITV was weaker between vegetative and floral traits than within the two trait groups.Main conclusionsOur results show that, depending on the traits considered, ITV either increased or decreased with climate stress and species richness, suggesting that both factors can constrain or enhance ITV, which might foster plant‐population persistence in stressful conditions. Given the species‐specific responses and covariation in ITV, associations can be hard to predict for traits and species not yet studied. We conclude that consideration of ITV can improve our understanding of how plants cope with stressful conditions and environmental change across spatial and biological scales.
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| 10. |
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| 11. |
- 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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| 12. |
- van Hoek, A. H. A. M., et al.
(författare)
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A quantitative approach towards a better understanding of the dynamics of Salmonella spp. in a pork slaughter-line
- 2012
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Ingår i: International Journal of Food Microbiology. - : Elsevier BV. - 0168-1605 .- 1879-3460. ; 153:1-2, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- Pork contributes significantly to the public health disease burden caused by Salmonella infections. During the slaughter process pig carcasses can become contaminated with Salmonella. Contamination at the slaughter-line is initiated by pigs carrying Salmonella on their skin or in their faeces. Another contamination route could be resident flora present on the slaughter equipment. To unravel the contribution of these two potential sources of Salmonella a quantitative study was conducted. Process equipment (belly openers and carcass splitters), faeces and carcasses (skin and cutting surfaces) along the slaughter-line were sampled at 11 sampling days spanning a period of 4. months.Most samples taken directly after killing were positive for Salmonella. On 96.6% of the skin samples Salmonella was identified, whereas a lower number of animals tested positive in their rectum (62.5%). The prevalence of Salmonella clearly declined on the carcasses at the re-work station, either on the cut section or on the skin of the carcass or both (35.9%). Throughout the sampling period of the slaughter-line the total number of Salmonella per animal was almost 2log lower at the re-work station in comparison to directly after slaughter.Seven different serovars were identified during the study with S. Derby (41%) and S. Typhimurium (29%) as the most prominent types. A recurring S. Rissen contamination of one of the carcass splitters indicated the presence of an endemic 'house flora' in the slaughterhouse studied. On many instances several serotypes per individual sample were found.The enumeration of Salmonella and the genotyping data gave unique insight in the dynamics of transmission of this pathogen in a slaughter-line. The data of the presented study support the hypothesis that resident flora on slaughter equipment was a relevant source for contamination of pork. © 2011 Elsevier B.V.
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| 13. |
- Amati, Matteo, et al.
(författare)
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Near ambient pressure photoelectron spectro-microscopy : From gas-solid interface to operando devices
- 2021
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Ingår i: Journal of Physics D: Applied Physics. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 54:20
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Tidskriftsartikel (refereegranskat)abstract
- Near ambient pressure scanning photoelectron microscopy adds to the widely used photoemission spectroscopy and its chemically selective capability two key features: (1) the possibility to chemically analyse samples in a more realistic gas pressure condition and (2) the capability to investigate a system at the relevant spatial scale. To achieve these goals the approach developed at the ESCA Microscopy beamline at the Elettra Synchrotron facility combines the submicron lateral resolution of a Scanning Photoelectron Microscope with a custom designed Near Ambient Pressure Cell where a gas pressure up to 0.1 mbar can be achieved. In this manuscript a review of experiments performed with this unique setup will be presented to illustrate its potentiality in both fundamental and applicative research such as the oxidation reactivity and gas sensitivity of metal oxides and semiconductors. In particular, the capability to perform operando experiments with this setup opens the possibility to study operating devices and to properly address the real nature of the studied systems, because if microscopy and spectroscopy are simultaneously combined in a single technique it can yield to more conclusive results.
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| 14. |
- 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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| 15. |
- 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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| 16. |
- Desprez-Loustau, Marie-Laure, et al.
(författare)
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From leaf to continent : The multi-scale distribution of an invasive cryptic pathogen complex on oak
- 2018
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Ingår i: Fungal ecology. - : Elsevier BV. - 1754-5048 .- 1878-0083. ; 36, s. 39-50
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Tidskriftsartikel (refereegranskat)abstract
- The spatial distribution and niche differentiation of three closely related species (Erysiphe alphitoides, Erysiphe quercicola and Erysiphe hypophylla) causing oak powdery mildew was studied at scales ranging from the European continent, where they are invasive, to a single leaf. While E. alphitoides was dominant at all scales, E. quercicola and E. hypophylla had restricted geographic, stand and leaf distributions. The large-scale distributions were likely explained by climatic factors and species environmental tolerances, with E. quercicola being more frequent in warmer climates and E. hypophylla in colder climates. The extensive sampling and molecular analyses revealed the cryptic invasion of E. quercicola in nine countries from which it had not previously been recorded. The presence of the three species was also strongly affected by host factors, such as oak species and developmental stage. Segregation patterns between Erysiphe species were observed at the leaf scale, between and within leaf surfaces, suggesting competitive effects.
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| 17. |
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| 18. |
- 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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| 19. |
- 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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| 20. |
- 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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| 21. |
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| 22. |
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| 23. |
- 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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| 24. |
- 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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| 25. |
- 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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| 26. |
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| 27. |
- Kiwanuka, Elizabeth, 1983-, et al.
(författare)
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Cdc42 and p190RhoGAP activation by CCN2 regulates cell spreading and polarity and induces actin disassembly in migrating keratinocytes
- 2016
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Ingår i: International Wound Journal. - : Wiley. - 1742-4801 .- 1742-481X. ; 13:3, s. 372-381
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Tidskriftsartikel (refereegranskat)abstract
- Cell migration requires spatiotemporal integration of signals that regulate cytoskeletal dynamics. In response to a migration-promoting agent, cells begin to polarise and extend protrusions in the direction of migration. These cytoskeletal rearrangements are orchestrated by a variety of proteins, including focal adhesion kinase (FAK) and the Rho family of GTPases. CCN2, also known as connective tissue growth factor, has emerged as a regulator of cell migration but the mechanism by which CCN2 regulates keratinocyte function is not well understood. In this article, we sought to elucidate the basicmechanism of CCN2-induced cellmigration in human keratinocytes. Immunohistochemical staining was used to demonstrate that treatment with CCN2 induces a migratory phenotype through actin disassembly, spreading of lamellipodia and re-orientation of the Golgi. In vitro assays were used to show that CCN2-induced cell migration is dependent on FAK, RhoA and Cdc42, but independent of Rac1. CCN2-treated keratinocytes displayed increased Cdc42 activity and decreased RhoA activity up to 12 hours post-treatment, with upregulation of p190RhoGAP. An improved understanding of how CCN2 regulates cell migration may establish the foundation for future therapeutics in fibrotic and neoplastic diseases.
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| 28. |
- 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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- 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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- Xavier, Catarina, et al.
(författare)
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Evaluation of the VISAGE basic tool for appearance and ancestry inference using ForenSeq® chemistry on the MiSeq FGx® system
- 2022
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Ingår i: Forensic Science International: Genetics. - : Elsevier BV. - 1872-4973. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of providing investigative leads when conventional DNA identification methods fail to solve a case can be of extreme relevance to law enforcement. Therefore, the forensic genetics community has focused research towards the broadened use of DNA, particularly for prediction of appearance traits, bio-geographical ancestry and age. The VISible Attributes through GEnomics (VISAGE) Consortium expanded the use of DNA phenotyping by developing new molecular and statistical tools for appearance, age and ancestry prediction. The VISAGE basic tool for appearance (EVC) and ancestry (BGA) prediction was initially developed using Ampliseq chemistry, but here is being evaluated using ForenSeq chemistry. The VISAGE basic tool offers a total of 41 EVC and 115 BGA SNPs and thus provides more predictions, i.e., skin color, than achieved with the ForenSeq DNA Signature Prep kit that is based on 24 EVC and 56 BGA SNPs. Five VISAGE laboratories participated in collaborative experiments to provide foreground for developmental validation of the assay. Assessment of assay performance and quality metrics, reproducibility, sensitivity, inhibitor tolerance and species specificity are described. Furthermore, the assay was tested using challenging samples such as mock casework samples and artificially degraded DNA. Two different analysis strategies were applied for this study and output on genotype calls and read depth was compared. Overall, inter-laboratory, inter-method and concordance with publicly available data were analysed and compared. Finally, the results showed a reliable and robust tool, which can be easily applied for laboratories already using a MiSeq FGx with ForenSeq reagents.
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