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Sökning: WFRF:(Tryggvason S)

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  • Oblander, S A, et al. (författare)
  • Distinctive functions of membrane type 1 matrix-metalloprotease (MT1-MMP or MMP-14) in lung and submandibular gland development are independent of its role in pro-MMP-2 activation
  • 2005
  • Ingår i: Developmental Biology. - : Elsevier BV. - 1095-564X .- 0012-1606. ; 277:1, s. 255-269
  • Tidskriftsartikel (refereegranskat)abstract
    • Membrane type 1-matrix metalloprotease (MT1-MMP or MMP-14) is a major activator of pro-MMP-2 and is essential for skeletal development. We show here that it is required for branching morphogenesis of the submandibular gland but not the lung. Instead, in the lung, it is essential for postnatal development of alveolar septae. Lung development in Mmp14-/- mice is arrested at the prealveolar stage with compensatory hyperinflation of immature saccules. Mmp2-/- mice lacked comparable defects in the lung and submandibular gland, suggesting that NIT1-MMP acts via mechanisms independent of pro-MMP-2 activation. Since the developmental defects in the lung are first manifest around the time of initial vascularization (E16.5), we investigated the behavior of pulmonary endothelial cells from Mmp14+/+ and Mmp14-/- mice. Endothelial cells from lungs of 1-week-old Mmp14-/- mice show reduced migration and formation of three-dimensional structures on Matrigel. Since pulmonary septal development requires capillary growth, the underlying mechanism of pulmonary hypoplasia in Mmp14-/- mice may be defective angiogenesis, supporting a model in which angiogenesis is a critical rate-limiting step for acquisition of pulmonary parenchymal mass.
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  • Pluddemann, A, et al. (författare)
  • SR-A, MARCO and TLRs differentially recognise selected surface proteins from Neisseria meningitidis: an example of fine specificity in microbial ligand recognition by innate immune receptors
  • 2009
  • Ingår i: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 1:2, s. 153-163
  • Tidskriftsartikel (refereegranskat)abstract
    • Macrophages express various classes of pattern recognition receptors involved in innate immune recognition of artificial, microbial and host-derived ligands. These include the scavenger receptors (SRs), which are important for phagocytosis, and the Toll-like receptors (TLRs) involved in microbe sensing. The class A macrophage scavenger receptor (SR-A) and macrophage receptor with a collagenous structure (MARCO) display similar domain structures and ligand-binding specificity, which has led to the assumption that these two receptors may be functionally redundant. In this study we show that SR-A and MARCO differentially recognise artificial polyanionic ligands as well as surface proteins from the pathogenic bacterium <i>Neisseria meningitidis</i>. We show that, while acetylated low-density lipoprotein (AcLDL) is a strong ligand for SR-A, it is not a ligand for MARCO. Of the neisserial proteins that were SR ligands, some were ligands for both receptors, while other proteins were only recognised by either SR-A or MARCO. We also analysed the potential of these ligands to act as TLR agonists and assessed the requirement for SR-A and MARCO in pro-inflammatory cytokine induction. SR ligation alone did not induce cytokine production; however, for proteins that were both SR and TLR ligands, the SRs were required for full activation of TLR pathways.
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  • Sen Kwek, S, et al. (författare)
  • A systematic approach to the development of a safe live attenuated Zika vaccine
  • 2018
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1031-
  • Tidskriftsartikel (refereegranskat)abstract
    • Zika virus (ZIKV) is a flavivirus that can cause congenital disease and requires development of an effective long-term preventative strategy. A replicative ZIKV vaccine with properties similar to the yellow fever 17D (YF17D) live-attenuated vaccine (LAV) would be advantageous, as a single dose of YF17D produces lifelong immunity. However, a replicative ZIKV vaccine must also be safe from causing persistent organ infections. Here we report an approach to ZIKV LAV development. We identify a ZIKV variant that produces small plaques due to interferon (IFN)-restricted viral propagation and displays attenuated infection of endothelial cells. We show that these properties collectively reduce the risk of organ infections and vertical transmission in a mouse model but remain sufficiently immunogenic to prevent wild-type ZIKV infection. Our findings suggest a strategy for the development of a safe but efficacious ZIKV LAV.
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  • Agnarsson, Björn, 1977, et al. (författare)
  • Rutile TiO 2 thin films grown by reactive high power impulse magnetron sputtering
  • 2013
  • Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 545, s. 445-450
  • Tidskriftsartikel (refereegranskat)abstract
    • Thin TiO 2 films were grown on Si(001) substrates by reactive dc magnetron sputtering (dcMS) and high power impulse magnetron sputtering (HiPIMS) at temperatures ranging from 300 to 700 C.Optical and structural properties of films were compared both before and after post-annealing using scanning electron microscopy, low angle X-ray reflection (XRR), grazing inc idence X-ray diffractometry and spectroscopic ellipsometry.Both dcMS- and HiPIMS-grown films reveal polycrystalline rutile TiO 2 , even prior to post-annealing.The HiPIMS-grown films exhibit significantly larger grains compared to that of dcMC-grown films, approaching 100% of the film thickness for films grown at 700 C.In addition, the XRR surface roughness of HiPIMS-grown films was significantly lower than that of dcMS-grown films over the whole temperature range 300-700 C.Dispersion curves could only be obtained for the HiPIMS-grown films, which were shown to have a refractive index in the range of 2.7-2.85 at 500 nm.The results show that thin, rutile TiO 2 films, with high refractive index, can be obtained by HiPIMS at relatively low growth temperatures, without post-annealing.Furthermore, these films are smoother and show better optical characteristics than their dcMS-grown counterparts.© 2013 Elsevier B.V.All rights reserved.
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  • Gross, O, et al. (författare)
  • Stem cell therapy for Alport syndrome: the hope beyond the hype
  • 2009
  • Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 24:3, s. 731-734
  • Tidskriftsartikel (refereegranskat)
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  • Leosson, K., et al. (författare)
  • Comparing resonant photon tunneling via cavity modes and Tamm plasmon polariton modes in metal-coated Bragg mirrors
  • 2012
  • Ingår i: Optics Letters. - 0146-9592 .- 1539-4794. ; 37:19, s. 4026-4028
  • Tidskriftsartikel (refereegranskat)abstract
    • Resonant photon tunneling was investigated experimentally in multilayer structures containing a high-contrast (TiO2/SiO2) Bragg mirror capped with a semitransparent gold film. Transmission via a fundamental cavity resonance was compared with transmission via the Tamm plasmon polariton resonance that appears at the interface between a metal film and a one-dimensional photonic bandgap structure. The Tamm-plasmon-mediated transmission exhibits a smaller dependence on the angle and polarization of the incident light for similar values of peak transmission, resonance wavelength, and finesse. Implications for transparent electrical contacts based on resonant tunneling structures are discussed.
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  • Shayestehaminzadeh, S., et al. (författare)
  • Ultra-thin poly-crystalline TiN films grown by HiPIMS on MgO(100) - In-situ resistance study of the initial stage of growth
  • 2013
  • Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 549, s. 199-203
  • Tidskriftsartikel (refereegranskat)abstract
    • The growth of ultra-thin TiN films on single-crystalline MgO(100) substrates by high power impulse magnetron sputtering (HiPIMS) was studied for growth temperatures ranging from 35 degrees C to 600 degrees C. X-ray analysis showed that the films had a textured poly-crystalline structure. Films grown by dc magnetron sputtering (dcMS) were epitaxial at the higher growth temperatures. In-situ resistance measurements, during growth, revealed the coalescence thickness and film continuity thickness. The film grown by HiPIMS at room temperature coalesced at 1.2 +/- 0.1 nm and became structurally continuous at 2.67 +/- 0.15 nm. At 600 degrees C, the coalescence and continuity thicknesses decreased to 0.56 +/- 0.05 nm and 0.82 +/- 0.05 nm, respectively. X-ray reflectivity measurements revealed that the growth rate of the films was roughly constant for all growth temperatures. The film density increased slightly with growth temperature up to 5.3 g/cm(3) at 600 degrees C and the surface roughness of the films decreased from 1 nm to 0.3 nm while the growth temperature increased from 35 degrees C to 600 degrees C. Grazing incident X-ray diffraction measurements showed the presence of [111], [200] and [220] crystallites at all growth temperatures. The smallest [200] and [220] grain sizes appeared at 100 degrees C while the [200] grain size increased by increasing the growth temperature.
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  • Tryggvason, S. H., et al. (författare)
  • A meta-analysis of expression signatures in glomerular disease
  • 2013
  • Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 84:3, s. 591-599
  • Tidskriftsartikel (refereegranskat)abstract
    • Glomerular diseases represent major diagnostic and therapeutic challenges with classification of these diseases largely relying on clinical and histological findings. Elucidation of molecular mechanisms of progressive glomerular disease could facilitate quicker development. High-throughput expression profiling reveals all genes and proteins expressed in tissue and cell samples. These methods are very appropriate for glomerular disease as pure glomeruli can be obtained from kidney biopsies. To date, proteome profiling data are only available for normal glomeruli, but more robust transcriptome methods have been applied to many mouse model and a few human glomerular diseases. Here, we have carried out a meta-analysis of currently available glomerular expression data in normal and diseased glomeruli from mice, rats, and humans using a standardized protocol. The results suggest a potential for glomerular transcriptomics in identifying pathogenic pathways, disease monitoring, and the feasibility to use animal models to study human glomerular disease. We also found that currently there are no specific consensus biomarkers or pathways among different disease data sets, indicating there are likely disease-specific mechanisms and expression profiles. Thus, further transcriptomics and proteomics analysis, especially that of dynamic changes in the diseases, may lead to novel diagnostics tools and specific pharmacologic therapies.
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  • Beltcheva, O, et al. (författare)
  • Sp1 specifically binds to an evolutionarily conserved DNA segment within a region necessary for podocyte-specific expression of nephrin
  • 2010
  • Ingår i: Nephron. Experimental nephrology. - : S. Karger AG. - 1660-2129. ; 114:1, s. E15-E22
  • Tidskriftsartikel (refereegranskat)abstract
    • We have analyzed a conserved 237-bp segment located in a 1.9-kb upstream region of the nephrin gene, previously shown to contain kidney specific enhancer element(s). Electromobility shift assay was used to identify a 20-nucleotide region specifically recognized and bound by protein factors in nuclear extracts from immortalized podocyte and human embryonic kidney cell lines. The region was further narrowed down by competition assays to a stretch of 6 consecutive guanines, which are conserved at this location in multiple species. Introduction of mutations in this sequence abolished all protein binding activity whereas mutations in the flanking nucleotides did not. By means of gel supershift and chromatin immunoprecipitation assays we have shown that the protein factor from podocyte nuclear extracts able to recognize and bind the target sequence is the Sp1 zinc-finger protein.
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  • Domogatskaya, A, et al. (författare)
  • Functional diversity of laminins
  • 2012
  • Ingår i: Annual review of cell and developmental biology. - : Annual Reviews. - 1530-8995 .- 1081-0706. ; 28, s. 523-553
  • Tidskriftsartikel (refereegranskat)abstract
    • Laminins are a large family of conserved, multidomain trimeric basement membrane proteins that contribute to the structure of extracellular matrix and influence the behavior of associated cells, such as adhesion, differentiation, migration, phenotype stability, and resistance to anoikis. In lower organisms such as Hydra there is only one isoform of laminin, but higher organisms have at least 16 trimeric isoforms with varying degrees of cell/tissue specificity. In vitro protein and cell culture studies, gene manipulation in animals, and laminin gene mutations in human diseases have provided insight into the specific functions of some laminins, but the biological roles of many isoforms are still largely unexplored, mainly owing to difficulties in isolating them in pure form from tissues or cells. In this review, we elucidate the evolution of laminins, describe their molecular complexity, and explore the current knowledge of their diversity and functional aspects, including laminin-mediated signaling via membrane receptors, in vitro cell biology, and involvement in various tissues gained from animal model and human disease studies. The potential use of laminins in cell biology research and biotechnology is discussed.
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  • Geberhiwot, T, et al. (författare)
  • Laminin-8 (alpha4beta1gamma1) is synthesized by lymphoid cells, promotes lymphocyte migration and costimulates T cell proliferation
  • 2001
  • Ingår i: Journal of cell science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 114:2Pt 2, s. 423-433
  • Tidskriftsartikel (refereegranskat)abstract
    • Laminins are a growing family of large heterotrimeric proteins with cell adhesive and signalling functions. They are major components of basement membranes and are found in many organs, including the vasculature and other compartments of bone marrow, thymus, lymph nodes and spleen. However, expression, recognition and use of laminin isoforms by lymphoid cells are poorly understood. In the present study, lymphoid T cells (Jurkat) were found to synthesize laminin alpha4, beta1 and gamma1 mRNAs and polypeptides and to assemble the chains into laminin-8. Lymphoblastoid B (NAD-20) cells, lymphoid NK (NKL) cells and blood lymphocytes also contained laminin-8 and, after cell permeabilization, practically all blood lymphocytes reacted with mAbs to laminin beta1 and gamma1 chains. Following stimulation, blood lymphocytes secreted laminin-8, and this laminin isoform, but not laminin-10/11(alpha5beta1gamma1/alpha5beta2gamma1), promoted chemokine-induced migration of the cells. In an activation-dependent manner, purified blood CD4 T cells adhered to immobilized laminin-8 and laminin-10/11 by using alpha6beta1 integrin, but minimally to laminin-1 (alpha1beta1gamma1). Accordingly, laminin-8 and laminin-10/11, but not laminin-1, strongly costimulated proliferation of the T cells via the same integrin. Thus, lymphoid cells are able to synthesize and secrete complete laminin molecules. In addition, synthesis of laminin-8 and recognition of laminin-8 and -10/11 by lymphocytes indicate relevance of these laminin isoforms in lymphocyte physiology.
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  • Hanifpour, Fatemeh, et al. (författare)
  • Investigation into the mechanism of electrochemical nitrogen reduction reaction to ammonia using niobium oxynitride thin-film catalysts
  • 2022
  • Ingår i: Electrochimica Acta. - : Elsevier. - 0013-4686 .- 1873-3859. ; 403
  • Tidskriftsartikel (refereegranskat)abstract
    • Niobium oxynitride (NbOxNy) thin films with varying combined non-metal vs. metal stoichiometries ( x + y ) and N/O stoichiometric ratios (y/x) are investigated for their ability to catalyze the nitrogen re-duction reaction and ammonia synthesis at ambient conditions. Electrochemical impedance spectroscopy and ammonia measurements show stark differences both in nitrogen vs. argon media on each surface and on the surfaces in the series when the combined stoichiometry of N + O vs. Nb increases. Surface stability checks at fixed intervals during the experiments and surface characterization after the experiments us -ing X-ray diffraction reveal the least changes occurred to the surface with the highest N + O stoichiometry. Based on these observations, an ammonia synthesis mechanism is proposed. Isotope labeling experiments on the most promising surface of the series, however, show no sign of catalytically produced ammonia, possibly due to the lack of stability of the surface to endure through the ammonia production cycle. 
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  • Hanifpour, Fatemeh, et al. (författare)
  • Operando quantification of ammonia produced from computationally-derived transition metal nitride electro-catalysts
  • 2022
  • Ingår i: Journal of Catalysis. - : Elsevier. - 0021-9517 .- 1090-2694. ; 413, s. 956-967
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrochemical reduction of dinitrogen to ammonia is investigated in a micro-reactor flow-cell using thin films of VN, CrN, NbN and ZrN. Chronoamperometry loops are used for ammonia production analysis. Operando ammonia quantification is accomplished in a flow injection analyzer. Results show the effect of presence/absence of N-2(g) within both the electrochemical characterization and ammonia production for ZrN. However, no ammonia is detected from studies on CrN. VN and NbN are inactivated upon reacting their N atoms of the surface top layer(s). Results obtained from ammonia measurements, electrochemical impedance spectroscopy analysis, surface stability checks, and surface characterization using X-ray reflectivity, reveal certain trends indicating catalytic behavior for ZrN. However, the concentration of produced ammonia is below the detection limit of the methods devised to analyze the samples from isotope labeling experiments. The onset of ammonia production on ZrN appears to be in close agreement with that predicted previously by computational studies.
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