| 1. |
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| 2. |
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| 3. |
- Martin, A. V., et al.
(författare)
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Noise-robust coherent diffractive imaging with a single diffraction pattern
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:15, s. 16650-16661
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Tidskriftsartikel (refereegranskat)abstract
- The resolution of single-shot coherent diffractive imaging at X-ray free-electron laser facilities is limited by the low signal-to-noise level of diffraction data at high scattering angles. The iterative reconstruction methods, which phase a continuous diffraction pattern to produce an image, must be able to extract information from these weak signals to obtain the best quality images. Here we show how to modify iterative reconstruction methods to improve tolerance to noise. The method is demonstrated with the hybrid input-output method on both simulated data and single-shot diffraction patterns taken at the Linac Coherent Light Source. (C) 2012 Optical Society of America
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| 4. |
- Barack, Leor, et al.
(författare)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Forskningsöversikt (refereegranskat)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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| 5. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 6. |
- Evilevitch, Alex, et al.
(författare)
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Effects of Salts on Internal DNA Pressure and Mechanical Properties of Phage Capsids.
- 2011
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 405, s. 18-23
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Tidskriftsartikel (refereegranskat)abstract
- Based on atomic force microscopy nanoindentation measurements of phage λ, we previously proposed a minimal model describing the effect of water hydrating DNA that strengthens viral capsids against external deformation at wild-type DNA packing density. Here, we report proof of this model by testing the prediction that DNA hydration forces can be dramatically decreased by addition of multivalent ions (Mg(2+) and Sp(4+)). These results are explained using a DNA hydration model without adjustable parameters. The model also predicts the stiffness of other DNA-filled capsids, which we confirm using bacteriophage ϕ29 and herpes simplex virus type 1 particles.
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| 7. |
- Oehri, Jacqueline, et al.
(författare)
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Vegetation type is an important predictor of the arctic summer land surface energy budget
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Despite the importance of high-latitude surface energy budgets (SEBs) for land-climate interactions in the rapidly changing Arctic, uncertainties in their prediction persist. Here, we harmonize SEB observations across a network of vegetated and glaciated sites at circumpolar scale (1994–2021). Our variance-partitioning analysis identifies vegetation type as an important predictor for SEB-components during Arctic summer (June-August), compared to other SEB-drivers including climate, latitude and permafrost characteristics. Differences among vegetation types can be of similar magnitude as between vegetation and glacier surfaces and are especially high for summer sensible and latent heat fluxes. The timing of SEB-flux summer-regimes (when daily mean values exceed 0 Wm−2) relative to snow-free and -onset dates varies substantially depending on vegetation type, implying vegetation controls on snow-cover and SEB-flux seasonality. Our results indicate complex shifts in surface energy fluxes with land-cover transitions and a lengthening summer season, and highlight the potential for improving future Earth system models via a refined representation of Arctic vegetation types.
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| 8. |
- Tazelaar, Gijs H. P., et al.
(författare)
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Association of NIPA1 repeat expansions with amyotrophic lateral sclerosis in a large international cohort
- 2019
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 74, s. 234.e9-234.e15
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Tidskriftsartikel (refereegranskat)abstract
- NIPA1 (nonimprinted in Prader-Willi/Angelman syndrome 1) mutations are known to cause hereditary spastic paraplegia type 6, a neurodegenerative disease that phenotypically overlaps to some extent with amyotrophic lateral sclerosis (ALS). Previously, a genomewide screen for copy number variants found an association with rare deletions in NIPA1 and ALS, and subsequent genetic analyses revealed that long (or expanded) polyalanine repeats in NIPA1 convey increased ALS susceptibility. We set out to perform a large-scale replication study to further investigate the role of NIPA1 polyalanine expansions with ALS, in which we characterized NIPA1 repeat size in an independent international cohort of 3955 patients with ALS and 2276 unaffected controls and combined our results with previous reports. Meta-analysis on a total of 6245 patients with ALS and 5051 controls showed an overall increased risk of ALS in those with expanded (>8) GCG repeat length (odds ratio = 1.50, p = 3.8×10−5). Together with previous reports, these findings provide evidence for an association of an expanded polyalanine repeat in NIPA1 and ALS.
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| 9. |
- van Rheenen, Wouter, et al.
(författare)
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Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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| 10. |
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| 11. |
- Arp, Hans Peter H., et al.
(författare)
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The presence, emission and partitioning behavior of polychlorinated biphenyls in waste, leachate and aerosols from Norwegian waste-handling facilities
- 2020
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Ingår i: Science of the Total Environment. - : ELSEVIER. - 0048-9697 .- 1879-1026. ; 715, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Even though production and open use of polychlorinated biphenyls (PCBs) have been phased out in Western industrialised countries since the 1980s, PCBs were still present in waste collected from different waste handling facilities in Norway in 2013. Sums of seven indicator-PCBs (I-PCB7:PCB-28, -52, -101, -118, -138, -153 and -180) were highest in plastic waste (3700 +/- 1800 mu g/kg, n=15), waste electrical and electronic equipment (WEEE) (1300 +/- 400 mu g/kg, n=12) and fine vehicle fluff (1800 = 1400 mu g/kg, n=4) and lowest in glass waste, combustibles, bottom ash and fly ash (0.3 to 65 mu g/kg). Concentrations in leachate water varied from 1.7 to 2900 ng/L, with higher concentrations found at vehicle and WEEE handling facilities. Particles in leachate water exhibited similar PCB sorption properties as solid waste collected on site, with waste-water partitioning coefficients ranging from 10(5)to 10(7) .I-PCB7 in air samples collected at the sites were mostly in the gas phase (100-24000 pg/m(3)), compared to those associated with particles (9-1900 pg/m(3)). In contrast, brominated flame retardants (BFRs) in the same samples were predominantly found associated with particles (e.g. sum of 10 brominated diethyl ethers, Sigma BDE10, associated with particles 77-194,000 pg/m(3)) compared to the gas phase (Sigma DE10 6-473 pg/m(3)). Measured gas-phase I-PCB7 concentrations are less than predicted, assuming waste-air partitioning in equilibrium with predominant waste on site. However, the gas-particle partitioning behavior of PCBs and BFRs could be predicted using an established partitioning model for ambient aerosols. PCB emissions from Norwegian waste handling facilities occurred primarily in the form of atmospheric vapor or leachate particles.
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| 12. |
- Gironella-Torrent, Marta, et al.
(författare)
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Viscoelastic phenotyping of red blood cells
- 2024
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Ingår i: BIOPHYSICAL JOURNAL. - 0006-3495 .- 1542-0086. ; 123:7, s. 770-781
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Tidskriftsartikel (refereegranskat)abstract
- Red blood cells (RBCs) are the simplest cell types with complex dynamical and viscoelastic phenomenology. While the mechanical rigidity and the flickering noise of RBCs have been extensively investigated, an accurate determination of the constitutive equations of the relaxational kinetics is lacking. Here we measure the force relaxation of RBCs under different types of tensional and compressive extension-jump protocols by attaching an optically trapped bead to the RBC membrane. Relaxational kinetics follows linear response from 60 pN (tensional) to similar to 20 pN (compressive) applied forces, exhibiting a triple exponential function with three well-separated timescales over four decades (0.01-100 s). While the fast timescale (tau(F) similar to 0.02(1) s) corresponds to the relaxation of the membrane, the intermediate and slow timescales (tau(I) = 4(1) s; tau(S) = 70(8) s) likely arise from the cortex dynamics and the cytosol viscosity. Relaxation is highly heterogeneous across the RBC population, yet the three relaxation times are correlated, showing dynamical scaling. Finally, we find that glucose depletion and laser illumination of RBCs lead to faster triple exponential kinetics and RBC rigidification. Viscoelastic phenotyping is a promising dynamical biomarker applicable to other cell types and active systems. SIGNIFICANCE This research shows the structured viscoelastic dynamics of red blood cells (RBCs) and highlights the significance of considering multiple timescales for understanding their mechanical behavior. The observed triple exponential relaxation behavior, coupled with the proposed viscoelastic model, provides valuable insights into the underlying processes governing RBC mechanics. Furthermore, our findings regarding the impact of glucose depletion and light illumination on RBC rigidity show how environmental factors affect RBC properties. Our results expand the current knowledge of RBC mechanics and pave the way for future investigations of relaxational phenomena in other cell types.
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| 13. |
- Oen, Amy M. P., et al.
(författare)
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In Situ Measurement of PCB Pore Water Concentration Profiles in Activated Carbon-Amended Sediment Using Passive Samplers
- 2011
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 45:9, s. 4053-4059
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Tidskriftsartikel (refereegranskat)abstract
- Vertical pore water profiles of in situ PCBs were determined in a contaminated mudflat in San Francisco Bay, CA, 30 months after treatment using an activated carbon amendment in the upper layer of the sediment. Pore water concentrations were derived from concentrations of PCBs measured in two passive samplers; polyethylene (PE, 51 mu m thick) and polyoxymethylene (POM, 17 mu m thick) at different sediment depths. To calculate pore water concentrations from PCB contents in the passive samplers, an equilibrium approach and a first-order uptake model were applied, using five performance reference compounds to estimate pore water sampling rates. Vertical pore water profiles showed good agreement among the measurement and calculation methods with variations within a factor of 2, which seems reasonable for in situ measurements. The close agreements of pore water estimates for the two sampler materials (PE and POM) and the two methods used to translate uptake in samplers to pore water concentrations demonstrate the robustness and suitability of the passive sampling approach. The application of passive samplers in the sediment presents a promising method for site monitoring and remedial treatment evaluation of sorbent amendment or capping techniques that result in changes of pore water concentrations in the sediment subsurface.
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| 14. |
- Persson, Fredrik, et al.
(författare)
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Fluorescence microscopy of nanochannel-confined DNA
- 2011
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Ingår i: Single Molecule Analysis : Methods and Protocols - Methods and Protocols. - Totowa, NJ : Humana Press. - 1064-3745. - 9781617792816 ; 783, s. 159-179
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Bokkapitel (refereegranskat)abstract
- Stretching of DNA in nanoscale confinement allows for direct visualization of the genetic contents of the DNA on the single DNA molecule level. DNA stretched in nanoscale confinement also allows for studies of DNA-protein interactions and DNA polymer physics in confined environments. This chapter describes the basic steps to fabricate the nanostructures, to perform the experiments, and to analyze the data.
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| 15. |
- Sparrevik, Magnus, et al.
(författare)
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Life Cycle Assessment to Evaluate the Environmental Impact of Biochar Implementation in Conservation Agriculture in Zambia
- 2013
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 47:3, s. 1206-1215
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Tidskriftsartikel (refereegranskat)abstract
- Biochar amendment to soil is a potential technology for carbon storage and climate change mitigation. It may, in addition, be a valuable soil fertility enhancer for agricultural purposes in sandy and/or weathered soils. A life cycle assessment including ecological, health and resource impacts has been conducted for field sites in Zambia to evaluate the overall impacts of biochar for agricultural use. The life cycle impacts from conservation farming using cultivation growth basins and precision fertilization with and without biochar addition were in the present study compared to conventional agricultural methods. Three different biochar production methods were evaluated: traditional earth-mound kilns, improved retort kilns, and micro top-lit updraft (TLUD) gasifier stoves. The results confirm that the use of biochar in conservation farming is beneficial for climate change mitigation purposes. However, when including health impacts from particle emissions originating from biochar production, conservation farming plus biochar from earth-mound kilns generally results in a larger negative effect over the whole life cycle than conservation farming without biochar addition. The use of cleaner technologies such as retort kilns or TLUDs can overcome this problem, mainly because fewer particles and less volatile organic compounds, methane and carbon monoxide are emitted. These results emphasize the need for a holistic view on biochar use in agricultural systems. Of special importance is the biochar production technique which has to be evaluated from both environmental/climate, health and social perspectives.
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| 16. |
- Tazelaar, Gijs H.P., et al.
(författare)
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Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis
- 2023
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 122, s. 76-87
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis is a heterogeneous, fatal neurodegenerative disease, characterized by motor neuron loss and in 50% of cases also by cognitive and/or behavioral changes. Mendelian forms of ALS comprise approximately 10-15% of cases. The majority is however considered sporadic, but also with a high contribution of genetic risk factors. To explore the contribution of somatic mutations and/or epigenetic changes to disease risk, we performed whole genome sequencing and methylation analyses using samples from multiple tissues on a cohort of 26 monozygotic twins discordant for ALS, followed by in-depth validation and replication experiments. The results of these analyses implicate several mechanisms in ALS pathophysiology, which include a role for de novo mutations, defects in DNA damage repair and accelerated aging.
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| 17. |
- Toepoel, Mascha, et al.
(författare)
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Haplotype-specific expression of the human PDGFRA gene correlates with the risk of glioblastomas
- 2008
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 123:2, s. 322-329
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Tidskriftsartikel (refereegranskat)abstract
- Aberrant expression of the platelet-derived growth factor a-receptor (PDGFRA) gene has been associated with various diseases, including neural tube defects and gliomas. We have previously identified 5 distinct haplotypes for the PDGFRA promoter region, designated H1, H2 alpha, H2 beta, H2 gamma and H2 delta. Of these haplotypes H1 and H2 alpha: are the most common, whereby H1 drives low and H2 alpha high transcriptional activity in transient transfection assays. Here we have investigated the role of these PDGFRA promoter haplotypes in gliomagenesis at both the genetic and cellular level. In a case-control study on 71 glioblastoma patients, we observed a clear underrepresentation of H1 alleles, with pH1 = 0.141 in patients and pH1 = 0.211 in a combined Western European control group (n = 998, p < ; 0.05). Furthermore, in 3 out of 4 available H1/H2 alpha heterozygous human glioblastoma cell lines, H1-derived mRNA levels were more than 10-fold lower than from H2 alpha, resulting at least in part from haplotype-specific epigenetic differences such as DNA methylation and histone acetylation. Together, these results indicate that PDGFRA promoter haplotypes may predispose to gliomas. We propose a model in which PDGFRA is upregulated in a haplotype-specific manner during neural stem cell differentiation, which affects the pool size of cells that can later undergo gliomagenesis.
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| 18. |
- van Mameren, Joost, et al.
(författare)
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Unraveling the structure of DNA during overstretching by using multicolor, single-molecule fluorescence imaging.
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 106:43, s. 18231-6
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Tidskriftsartikel (refereegranskat)abstract
- Single-molecule manipulation studies have revealed that double-stranded DNA undergoes a structural transition when subjected to tension. At forces that depend on the attachment geometry of the DNA (65 pN or 110 pN), it elongates approximately 1.7-fold and its elastic properties change dramatically. The nature of this overstretched DNA has been under debate. In one model, the DNA cooperatively unwinds, while base pairing remains intact. In a competing model, the hydrogen bonds between base pairs break and two single DNA strands are formed, comparable to thermal DNA melting. Here, we resolve the structural basis of DNA overstretching using a combination of fluorescence microscopy, optical tweezers, and microfluidics. In DNA molecules undergoing the transition, we visualize double- and single-stranded segments using specific fluorescent labels. Our data directly demonstrate that overstretching comprises a gradual conversion from double-stranded to single-stranded DNA, irrespective of the attachment geometry. We found that these conversions favorably initiate from nicks or free DNA ends. These discontinuities in the phosphodiester backbone serve as energetically favorable nucleation points for melting. When both DNA strands are intact and no nicks or free ends are present, the overstretching force increases from 65 to 110 pN and melting initiates throughout the molecule, comparable to thermal melting. These results provide unique insights in the thermodynamics of DNA and DNA-protein interactions.
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| 19. |
- Vergouwen, Daphne P. C., et al.
(författare)
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The enigma of sclera-specific autoimmunity in scleritis
- 2024
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 144
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Tidskriftsartikel (refereegranskat)abstract
- Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value.
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| 20. |
- Wenzel, Michaela, 1986, et al.
(författare)
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Control of septum thickness by the curvature of SepF polymers
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:2
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Tidskriftsartikel (refereegranskat)abstract
- Gram-positive bacteria divide by forming a thick cross wall. How the thickness of this septal wall is controlled is unknown. In this type of bacteria, the key cell division protein FtsZ is anchored to the cell membrane by two proteins, FtsA and/or SepF. We have isolated SepF homologs from different bacterial species and found that they all polymerize into large protein rings with diameters varying from 19 to 44 nm. Interestingly, these values correlated well with the thickness of their septa. To test whether ring diameter determines septal thickness, we tried to construct different SepF chimeras with the purpose to manipulate the diameter of the SepF protein ring. This was indeed possible and confirmed that the conserved core domain of SepF regulates ring diameter. Importantly, when SepF chimeras with different diameters were expressed in the bacterial host Bacillus subtilis, the thickness of its septa changed accordingly. These results strongly support a model in which septal thickness is controlled by curved molecular clamps formed by SepF polymers attached to the leading edge of nascent septa. This also implies that the intrinsic shape of a protein polymer can function as a mold to shape the cell wall.
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| 21. |
- Zhang, Xiao-Qun, et al.
(författare)
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Specific expression in mouse mesoderm- and neural crest-derived tissues of a human PDGFRA promoter/lacZ transgene
- 1998
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Ingår i: Mechanisms of Development. - 0925-4773 .- 1872-6356. ; 70:1-2, s. 167-180
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Tidskriftsartikel (refereegranskat)abstract
- The platelet-derived growth factor alpha-receptor (PDGFR-alpha) displays a lineage-specific expression pattern in the mouse embryo and is required for normal development of mesoderm and cephalic neural crest derivatives. The purpose of the present study was to demonstrate the in vivo promoter function of genomic DNA fragments representing the 5'-flanking part of the human PDGFRA gene. 2.2, 0.9 and 0.4 kb PDGFRA promoter fragments, ligated to a lacZ reporter gene, were microinjected into fertilized mouse eggs and transgenic mouse lines were established. The expression patterns were basically similar in the 2.2 and 0.9 kb lines and overlapped grossly the endogenous Pdgfra gene expression pattern. The transgenic line with the highest expression level was chosen for detailed analysis. Expression was, as expected, mainly confined to tissues of mesodermal and neural crest origin. No expression was found in epithelial tissues of endo- or ectodermal origin. The promoter fragments were also active in neuroepithelium and in certain neuronal cell types that did not faithfully express PDGFR-alpha mRNA, while they failed to specify reporter expression in PDGFR-alpha expressing O-2A progenitor cells and other glial elements of the central nervous system. Thus, the isolated human PDGFRA promoter contains most but not all of the regulatory elements that are necessary to establish tissue specific gene expression during development.
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