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  • 251.
    Baranowska Körberg, Izabella
    et al.
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden .
    Sundström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Meadows, Jennifer R. S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Pielberg, Gerli Rosengren
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Gustafson, Ulla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Hedhammar, Ake
    Karlsson, Elinor K.
    Seddon, Jennifer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Soderberg, Arne
    Vila, Carles
    Zhang, Xiaolan
    Akesson, Mikael
    Lindblad-Toh, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Andersson, Goran
    Andersson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    A Simple Repeat Polymorphism in the MITF-M Promoter Is a Key Regulator of White Spotting in Dogs2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 8, s. e104363-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The white spotting locus (S) in dogs is colocalized with the MITF (microphtalmia-associated transcription factor) gene. The phenotypic effects of the four S alleles range from solid colour (S) to extreme white spotting (s(w)). We have investigated four candidate mutations associated with the s(w) allele, a SINE insertion, a SNP at a conserved site and a simple repeat polymorphism all associated with the MITF-M promoter as well as a 12 base pair deletion in exon 1B. The variants associated with white spotting at all four loci were also found among wolves and we conclude that none of these could be a sole causal mutation, at least not for extreme white spotting. We propose that the three canine white spotting alleles are not caused by three independent mutations but represent haplotype effects due to different combinations of causal polymorphisms. The simple repeat polymorphism showed extensive diversity both in dogs and wolves, and allele-sharing was common between wolves and white spotted dogs but was non-existent between solid and spotted dogs as well as between wolves and solid dogs. This finding was unexpected as Solid is assumed to be the wild-type allele. The data indicate that the simple repeat polymorphism has been a target for selection during dog domestication and breed formation. We also evaluated the significance of the three MITF-M associated polymorphisms with a Luciferase assay, and found conclusive evidence that the simple repeat polymorphism affects promoter activity. Three alleles associated with white spotting gave consistently lower promoter activity compared with the allele associated with solid colour. We propose that the simple repeat polymorphism affects cooperativity between transcription factors binding on either flanking sides of the repeat. Thus, both genetic and functional evidence show that the simple repeat polymorphism is a key regulator of white spotting in dogs.

  • 252.
    Barba, Albert
    et al.
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Maazouz, Yassine
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Diez-Escudero, Anna
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Rappe, Katrin
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Espanol, Montserrat
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Montufar, Edgar
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Öhman, Caroline
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Persson, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Fontecha, Pedro
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Manzanares, Maria-Cristina
    Human Anatomy and Embryology Unit, Department of Pathology and Experimental Therapeutics, Universitat de Barcelona.
    Franch, Jordi
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Osteogenesis by foamed and 3D-printed nanostructured calcium phosphate scaffolds: Effect of pore architecture2018Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 79, s. 135-147Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is an urgent need of synthetic bone grafts with enhanced osteogenic capacity. This can be achieved by combining biomaterials with exogenous growth factors, which however can have numerous undesired side effects, but also by tuning the intrinsic biomaterial properties. In a previous study, we showed the synergistic effect of nanostructure and pore architecture of biomimetic calcium deficient hydroxyapatite (CDHA) scaffolds in enhancing osteoinduction, i.e. fostering the differentiation of mesenchymal stem cells to bone forming cells. This was demonstrated by assessing bone formation after implanting the scaffolds intramuscularly. The present study goes one step forward, since it analyzes the effect of the geometrical features of the same CDHA scaffolds, obtained either by 3D-printing or by foaming, on the osteogenic potential and resorption behaviour in a bony environment. After 6 and 12 weeks of intraosseous implantation, both bone formation and material degradation had been drastically affected by the macropore architecture of the scaffolds. Whereas nanostructured CDHA was shown to be highly osteoconductive both in the robocast and foamed scaffolds, a superior osteogenic capacity was observed in the foamed scaffolds, which was associated with their higher intrinsic osteoinductive potential. Moreover, they showed a significantly higher cell-mediated degradation than the robocast constructs, with a simultaneous and progressive replacement of the scaffold by new bone. In conclusion, these results demonstrate that the control of macropore architecture is a crucial parameter in the design of synthetic bone grafts, which allows fostering both material degradation and new bone formation. Statement of Significance 3D-printing technologies open new perspectives for the design of patient-specific bone grafts, since they allow customizing the external shape together with the internal architecture of implants. In this respect, it is important to design the appropriate pore geometry to maximize the bone healing capacity of these implants. The present study analyses the effect of pore architecture of nanostructured hydroxyapatite scaffolds, obtained either by 3D-printing or foaming, on the osteogenic potential and scaffold resorption in an in vivo model. While nanostructured hydroxyapatite showed excellent osteoconductive properties irrespective of pore geometry, we demonstrated that the spherical, concave macropores of foamed scaffolds significantly promoted both material resorption and bone regeneration compared to the 3D-printed scaffolds with orthogonal-patterned struts and therefore prismatic, convex macropores.

  • 253.
    Barbu, Andreea
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Jansson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sandberg, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Quach, My
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Palm, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    The use of hydrogen gas clearance for blood flow measurements in single endogenous and transplanted pancreatic islets2015Inngår i: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 97, s. 124-129Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The blood perfusion of pancreatic islets is regulated independently from that of the exocrine pancreas, and is of importance for multiple aspects of normal islet function, and probably also during impaired glucose tolerance. Single islet blood flow has been difficult to evaluate due to technical limitations. We therefore adapted a hydrogen gas washout technique using microelectrodes to allow such measurements. Platinum micro-electrodes monitored hydrogen gas clearance from individual endogenous and transplanted islets in the pancreas of male Lewis rats and in human and mouse islets implanted under the renal capsule of male athymic mice. Both in the rat endogenous pancreatic islets as well as in the intra-pancreatically transplanted islets, the vascular conductance and blood flow values displayed a highly heterogeneous distribution, varying by factors 6-10 within the same pancreas. The blood flow of human and mouse islet grafts transplanted in athymic mice was approximately 30% lower than that in the surrounding renal parenchyma. The present technique provides unique opportunities to study the islet vascular dysfunction seen after transplantation, but also allows for investigating the effects of genetic and environmental perturbations on islet blood flow at the single islet level in vivo. (C) 2014 The Authors. Published by Elsevier Inc.

  • 254. Barderi, P
    et al.
    Campetella, O
    Frasch, A C
    Santome, JA
    Hellman, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Medicinsk genetik.
    Cazzulo, JJ
    The NADP+ linked glutamate dehydrogenase from Trypanosoma cruzi: sequence, genomic organization and expression1998Inngår i: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 330, nr 2, s. 951-958Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    NADP-linked glutamate dehydrogenase (NADP+-GluDH, EC 1.4.1.4) has been purified to homogeneity from epimastigotes of Trypanosoma cruzi by an improved procedure, and the amino acid sequences of 11 internal peptides obtained by digestion with trypsin, endopeptidase Lys-C, endopeptidase Arg-C or CNBr have been obtained. Using oligonucleotide primers synthesized according to the amino acid sequence of the N-terminus of the mature enzyme and to the nucleotide sequence of a clone corresponding to the C-terminus, obtained by immunological screening of an expression library, two complete open reading frames (TcGluDH1 and TcGluDH2) were isolated and sequenced. The sequences obtained are most similar to that of the NADP+-GluDH of Escherichia coli (70-72% identity), and less similar (50-56%) to those of lower eukaryotes. Using TcGluDH1 as a probe, evidence for the presence of several genes and developmental regulation of the expression of NADP+-GluDH in different parasite stages was obtained. TcGluDH1 encodes an enzymically active protein, since its expression in E. coli resulted in the production of a GluDH activity with kinetic parameters similar to those of the natural enzyme.

  • 255.
    Barnkob, Rune
    et al.
    Tech Univ Denmark, Lyngby, Denmark .
    Iranmanesh, Ida
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.
    Wiklund, Martin
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biomedicinsk fysik och röntgenfysik.
    Bruus, Henrik
    Tech Univ Denmark, Lyngby, Denmark .
    Measuring acoustic energy density in microchannel acoustophoresis using a simple and rapid light-intensity method2012Inngår i: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 12, nr 13, s. 2337-2344Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We present a simple and rapid method for measuring the acoustic energy density in microchannel acoustophoresis based on light-intensity measurements of a suspension of particles. The method relies on the assumption that each particle in the suspension undergoes single-particle acoustophoresis. It is validated by the single-particle tracking method, and we show by proper re-scaling that the re-scaled light intensity plotted versus re-scaled time falls on a universal curve. The method allows for analysis of moderate-resolution images in the concentration range encountered in typical experiments, and it is an attractive alternative to particle tracking and particle image velocimetry for quantifying acoustophoretic performance in microchannels.

  • 256.
    Baroshki, Rojan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Mykofenolsyra och AUC-beräkning för organtransplanterade patienter2015Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 257.
    Barqasho, Babilonia
    et al.
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden .
    Nowak, Piotr
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden; Division of Infectious Diseases, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Abdurahman, Samir
    Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden .
    Walther-Jallow, Lillian
    Center for Infectious Medicine, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden .
    Sönnerborg, Anders
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden; Division of Infectious Diseases, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Implications of the release of high-mobility group box 1 protein from dying cells during human immunodeficiency virus type 1 infection in vitro2010Inngår i: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 91, nr Pt 7, s. 1800-1809Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plasma levels of high-mobility group box 1 protein (HMGB1) are elevated during the course of human immunodeficiency virus type 1 (HIV-1) infection and the molecule has an impact on virus replication. This study investigated the mode of cell death and release of HMGB1 during HIV-1 infection in vitro. MT4 cells and primary CD4(+) T cells were infected with HIV-1 isolates, and HMGB1 release was monitored in relation to cytopathic effects (CPE) and apoptosis. HMGB1 release from cells was analysed by Western blotting. For MT4 cells, an enzyme-linked immunosorbent spot (ELISPOT) assay was adapted to measure the release during necrosis. Lactate dehydrogenase (LDH) activity was quantified using a commercial assay. Flow cytometry was used to determine the level of infection and apoptosis. MT4 cells were > or =90 % infected at 48 h post-infection (p.i.). CPE was first observed at 60 h and correlated with release of HMGB1, LDH activity and caspase-3 (C3) activation. HMGB1 spots were clearly detected by ELISPOT assay at 72 h p.i. Annexin V and C3 staining showed that apoptosis was substantially involved in HIV-1-related cell death. Addition of Z-VAD (a caspase inhibitor) in a single dose at 24 or 40 h p.i. decreased both the number of caspase-positive cells and the release of HMGB1. Infection of primary CD4(+) T cells showed a 22 % (median) infection rate at 96 h. Related CPE corresponded to LDH and HMGB1 release. Both necrosis and apoptosis contributed to HMGB1 liberation during HIV-1-induced cell death and the protein could induce tumour necrosis factor-alpha release from peripheral mononuclear blood cells. These data imply that passive HMGB1 release contributes to the excessive immune activation characteristic of HIV-1 pathogenesis.

  • 258. Bart, Genevieve
    et al.
    Vico, Nuria Ortega
    Hassinen, Antti
    Pujol, Francois M.
    Deen, Ashik Jawahar
    Ruusala, Aino
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Tammi, Raija H.
    Squire, Anthony
    Heldin, Paraskevi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Kellokumpu, Sakari
    Tammi, Markku I.
    Fluorescence Resonance Energy Transfer (FRET) and Proximity Ligation Assays Reveal Functionally Relevant Homo-and Heteromeric Complexes among Hyaluronan Synthases HAS1, HAS2, and HAS32015Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 290, nr 18, s. 11479-11490Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In vertebrates, hyaluronan is produced in the plasma membrane from cytosolic UDP-sugar substrates by hyaluronan synthase 1-3 (HAS1-3) isoenzymes that transfer N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcUA) in alternative positions in the growing polysaccharide chain during its simultaneous extrusion into the extracellular space. It has been shown that HAS2 immunoprecipitates contain functional HAS2 homomers and also heteromers with HAS3 (Karousou, E., Kamiryo, M., Skandalis, S. S., Ruusala, A., Asteriou, T., Passi, A., Yamashita, H., Hellman, U., Heldin, C. H., and Heldin, P. (2010) The activity of hyaluronan synthase 2 is regulated by dimerization and ubiquitination. J. Biol. Chem. 285, 23647-23654). Here we have systematically screened in live cells, potential interactions among the HAS isoenzymes using fluorescence resonance energy transfer (FRET) and flow cytometric quantification. We show that all HAS isoenzymes form homomeric and also heteromeric complexes with each other. The same complexes were detected both in Golgi apparatus and plasma membrane by using FRET microscopy and the acceptor photobleaching method. Proximity ligation assays with HAS antibodies confirmed the presence of HAS1-HAS2, HAS2-HAS2, and HAS2-HAS3 complexes between endogenously expressed HASs. C-terminal deletions revealed that the enzymes interact mainly via uncharacterized N-terminal 86-amino acid domain(s), but additional binding site(s) probably exist in their C-terminal parts. Of all the homomeric complexes HAS1 had the lowest and HAS3 the highest synthetic activity. Interestingly, HAS1 transfection reduced the synthesis of hyaluronan obtained by HAS2 and HAS3, suggesting functional cooperation between the isoenzymes. These data indicate a general tendency of HAS isoenzymes to form both homomeric and heteromeric complexes with potentially important functional consequences on hyaluronan synthesis.

  • 259.
    Bartonek, Asa
    et al.
    Karolinska Inst, Womens & Childrens Hlth, Motoriklab, Stockholm, Sweden..
    Lidbeck, Cecilia
    Karolinska Inst, Womens & Childrens Hlth, Stockholm, Sweden..
    Hellgren, Kerstin
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Gutierrez-Farewik, Elena
    KTH, Skolan för teknikvetenskap (SCI), Mekanik. KTH, Skolan för teknikvetenskap (SCI), Centra, BioMEx. Karolinska Inst, Womens & Childrens Hlth, Stockholm, Sweden..
    Head and Trunk Movements During Turning Gait in Children with Cerebral Palsy2019Inngår i: Journal of motor behavior, ISSN 0022-2895, E-ISSN 1940-1027, Vol. 51, nr 4, s. 362-370Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thirty children with cerebral palsy (CP) and 22 typical developing (TD) were tested with 3D-gait analysis. At turning, trunk rotation was larger in CP2 (GMFCS II) than in TD and CP1 (GMFCS I), and head flexion was larger in CP3 (GMFCS III) than TD. Maximum head and trunk flexion values during the entire trial were larger in CP3 than in the other groups, and trunk flexion was larger in CP2 than in TD. Trial time increased with GMFCS-level. Less trunk rotation than TD and CP1 reflects spatial insecurity in CP2, which in CP3 is compensated by the walker. The flexed head and trunk in CP3 and trunk in CP2 may reflect deficits in proprioception and sensation requiring visual control of the lower limbs.

  • 260.
    Basic, Vladimir
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Molecular mechanisms mediating development of pulmonary cachexia in COPD2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Cigarette smoking (CS) represents the main causative agent underlying development and progress of COPD. Recently, involvement of CS in the pathogenesis of COPDassociated muscle abnormalities is becoming increasingly evident. Nevertheless, involved triggers and underlying mechanisms remain largely unknown. This study was conceived in order to examine effects of cigarette smoke exposure on skeletal muscle morphology, vascular supply and function. For this purpose, we have specifically designed murine COPD/emphysema model and gastrocnemius muscle was examined, while in vitro experiments were conducted using murine C2C12 skeletal muscle myocytes.

    In addition to the mild emphysematous changes present in the lungs of CS-exposed mice, our results demonstrated evident signs of muscle atrophy reflected by decreased fiber cross-sectional area, profound fiber size variation and reduced body mass. Furthermore, we have observed impairment in terminal myogenesis and lower number of myonuclei in skeletal muscles of CS-exposed animals despite evident activation of muscle repair process. Additionally, our results demonstrate capillary rarefaction in skeletal muscles of CS-exposed animals which was associated with deregulation of hypoxia-angiogenesis signaling, reduced levels of angiogenic factors such as HIF1-α and VEGF and enhanced expression of VHL and its partner proteins PHD2 and Ube2D1. The results of our in-vitro experiments demonstrated that VHL and its ubiquitination machinery can be synergistically regulated by TNF and hypoxia consequentially impairing angiogenic potential of skeletal muscle myocytes. Finally, we have shown that CS elicits chronic ER stress in murine skeletal muscles which is associated with activation of ERAD and apoptotic pathways as mirrored by elevated expression of Usp19, caspase 12 and caspase 3 in skeletal muscles of CSexposed animals. Moreover, molecular and morphological alterations in CS-exposed mice resulted in impairment of muscle function as reflected by their impaired exercise capacity.

    Taken together, from our results it is evident that cigarette smoke exposure elicits set of morphological, vascular and functional changes highly resembling those observed in COPD. Additionally, CS induces wide range of molecular alterations and signaling pathway deregulations suggesting profound effects of cigarette smoke exposure on skeletal muscle cell homeostasis.

  • 261.
    Basic, Vladimir T.
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Jacobsen, Annette
    Charles Sturt University, Sydney NSW, Australien.
    Sirsjö, Allan
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Abdel-Halim, Samy
    Danderyd Hospital, Stockholm, Sweden.
    TNF stimulation induces VHL overexpression and impairs angiogenic potential in skeletal muscle myocytes2014Inngår i: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 34, nr 1, s. 228-236Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Decreased skeletal muscle capillarization is considered to significantly contribute to the development of pulmonary cachexia syndrome (PCS) and progressive muscle wasting in several chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). It is unclear to which extent the concurrent presence of systemic inflammation contributes to decreased skeletal muscle capillarization under these conditions. The present study was designed to examine in vitro the effects of the pro-inflammatory cytokine, tumor necrosis factor (TNF), on the regulation of hypoxia-angiogenesis signal transduction and capillarization in skeletal muscles. For this purpose, fully differentiated C2C12 skeletal muscle myocytes were stimulated with TNF and maintained under normoxic or hypoxic conditions. The expression levels of the putative elements of the hypoxia-angiogenesis signaling cascade were examined using qPCR, western blot analysis and immunofluorescence. Under normoxic conditinos, TNF stimulation increased the protein expression of anti-angiogenic von-Hippel Lindau (VHL), prolyl hydroxylase (PHD)2 and ubiquitin conjugating enzyme 2D1 (Ube2D1), as well as the total ubiquitin content in the skeletal muscle myocytes. By contrast, the expression levels of hypoxia-inducible factor 1‑α (HIF1-α) and those of its transcriptional targets, vascular endothelial growth factor (VEGF)A and glucose transporter 1 (Glut1), were markedly reduced. In addition, hypoxia increased the expression of the VHL transcript and further elevated the VHL protein expression levels in C2C12 myocytes following TNF stimulation. Consequently, an impaired angiogenic potential was observed in the TNF-stimulated myocytes during hypoxia. In conclusion, TNF increases VHL expression and disturbs hypoxia-angiogenesis signal transduction in skeletal muscle myocytes. The current findings provide a mechanism linking systemic inflammation and impaired angiogenesis in skeletal muscle. This is particularly relevant to further understanding the mechanisms mediating muscle wasting and cachexia in patients with chronic inflammatory diseases, such as COPD.

  • 262.
    Basic, Vladimir T.
    et al.
    Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Jacobsen, Annette
    Department of Clinical Medicine, Örebro University, Örebro, Sweden; School of Biomedical Sciences, Charles Sturt University, WaggaWagga, Australia.
    Tadele, Elsa
    Department of Clinical Medicine, Örebro University, Örebro, Sweden; Medical University of Giessen, Molecular Biology and Medicine of the Lung program, Giessen, Germany.
    Banjop- Kharlyngdoh, Joubert
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Sirsjö, Allan
    Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Abdel-Halim, Samy M.
    Division of Respiratory Medicine and Allergology, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Cigarette smoke exposure up-regulates Ubiquitin specific protease 19 in murine skeletal muscles as an adaptive response to prolonged ER stressManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Enhanced protein degradation via ubiquitin proteolytic system (UPS) was demonstrated to play an important role in the pathogenesis of cachexia syndrome and muscle wasting in patients with COPD and animal models of the disease. The role of cigarette smoke (CS) exposure in eliciting these abnormalities remains largely unknown. Usp19 is a member of UPS suggested to be involved in progressive muscle wasting in different catabolic conditions. However, factors regulating Usp19 expression, activity and correlation/s with CS-induced muscle atrophy remainunclear.

    Methods: To address these questions, 129 SvJ mice were exposed to cigarette smoke for 6 months and the gastrocnemius muscles were collected. Expression levels of Usp19 as well as pivotal mediators of ER stress response have been studied using PCR, qPCR, western blot and immunofluorescence. Factors regulating muscle Usp19 expression were studied using in-silico analysis of Usp19 promoter as well as by stimulating C2C12 myocytes with different inducers of ER stress including hypoxia, TNF and tunicamycin. Finally, Usp19 expression was depleted in C2C12 myocytes using specific Usp19 siRNA quadriplex and the expression of pivotal myogenic regulators were analyzed.

    Results: Usp19 mRNA expression was enhanced in skeletal muscles of CS-exposed mice. Concurrently, ER stress-associated Caspase 12 and Caspase 3 were activated in the CS-exposed group. Analysis of Usp19 promoter sequence revealed binding sites for ER stress response transcription factors such as HSF, STRE1 and AML1-α. Exposure of C2C12 myocytes to tunicamycin but not hypoxia elevated expression levels of Usp19. TNFstimulation elevated Usp19 protein expression but inhibited its RNA transcription in a dose- and time-dependent manner. Finally, Usp19 overexpression in tunicamycin-treated myocytes was accompanied by reduced expression of myosin heavy chain and tropomyosin and their levels were increased after knocking down Usp19 in C2C12 myocytes.

    Conclusions: In summary, our data demonstrated elevated expression of Usp19 in skeletal muscles of CS-exposed 129 SvJ mice. Moreover, Usp19 overexpression was associated with muscle adaptations to ER stress and suppression of myogenesis. Taken together; our results might provide further insight into molecular mechanisms underlying development and progression of skeletal muscle abnormalities in response to chronic cigarette smoke exposure.

  • 263. Basile, Walter
    et al.
    Sachenkova, Oxana
    Light, Sara
    Elofsson, Arne
    KTH, Centra, SeRC - Swedish e-Science Research Centre.
    High GC content causes orphan proteins to be intrinsically disordered2017Inngår i: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 13, nr 3, artikkel-id e1005375Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    De novo creation of protein coding genes involves the formation of short ORFs from noncoding regions; some of these ORFs might then become fixed in the population These orphan proteins need to, at the bare minimum, not cause serious harm to the organism, meaning that they should for instance not aggregate. Therefore, although the creation of short ORFs could be truly random, the fixation should be subjected to some selective pressure. The selective forces acting on orphan proteins have been elusive, and contradictory results have been reported. In Drosophila young proteins are more disordered than ancient ones, while the opposite trend is present in yeast. To the best of our knowledge no valid explanation for this difference has been proposed. To solve this riddle we studied structural properties and age of proteins in 187 eukaryotic organisms. We find that, with the exception of length, there are only small differences in the properties between proteins of different ages. However, when we take the GC content into account we noted that it could explain the opposite trends observed for orphans in yeast (low GC) and Drosophila (high GC). GC content is correlated with codons coding for disorder promoting amino acids. This leads us to propose that intrinsic disorder is not a strong determining factor for fixation of orphan proteins. Instead these proteins largely resemble random proteins given a particular GC level. During evolution the properties of a protein change faster than the GC level causing the relationship between disorder and GC to gradually weaken.

  • 264.
    Baskaran, Sathishkumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi. Department of IGP, Uppsala University.
    New Molecular Approaches to Glioblastoma Therapy2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Glioblastoma (GBM) is the most common high-grade brain tumor diagnosed in patients who are more than 50 years of age. The standard of care treatment is surgery, followed by radiotherapy and chemotherapy. The median life expectancy of patients is only between 12 to 15 months after receiving current treatment regimes. Hence, identification of new therapeutic compounds and gene targets are highly warranted. This thesis describes four interlinked studies to attain this goal. In study 1, we explored drug combination effects in a material of 41 patient-derived GBM cell (GC) cultures. Synergies between three compounds, pterostilbene, gefitinib, and sertraline, resulted in effective killing of GC and can be predicted by biomarkers. In study 2, we performed a large-scale screening of FDA approved compounds (n=1544) in a larger panel of GCs (n=106). By combining the large-scale drug response data with GCs genomics data, we built a novel computational model to predict the sensitivity of each compound for a given GC. A notable finding was that GCs respond very differently to proteasome inhibitors in both in-vitro and in-vivo. In study 3, we explored new gene targets by RNAi (n=1112) in a panel of GC cells. We found that loss of transcription factor ZBTB16/PLZF inhibits GC cell viability, proliferation, migration, and invasion. These effects were due to downregulation of c-MYC and Cyclin B1 after the treatment. In study 4, we tested the genomic stability of three GCs upon multiple passaging. Using molecular and mathematical analyses, we showed that the GCs undergo both systematic adaptations and sequential clonal takeovers. Such changes tend to affect a broad spectrum of pathways. Therefore, a systematic analysis of cell culture stability will be essential to make use of primary cells for translational oncology.

    Taken together, these studies deepen our knowledge of the weak points of GBM and provide several targets and biomarkers for further investigation. The work in this thesis can potentially facilitate the development of targeted therapies and result in more accurate tools for patient diagnostics and stratification. 

  • 265.
    Bass, Tarek
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Affibody molecules targeting HER3 for cancer therapy2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The development of targeted therapy has contributed tremendously to the treatment of patients with cancer. The use of highly specific affinity proteins to target cancer cells has become a standard in treatment strategies for several different cancers. In light of this, many cancer cell markers are investigated for their potential use in diagnostics and therapy. One such marker is the human epidermal growth factor receptor 3, HER3. It has been established as an important contributor to many cancer types. The function of HER3 is to relay cell growth signals from outside of the cell to the inside. Interfering with- and inhibit- ing the function of HER3 has emerged as an interesting strategy for cancer therapeutics. The studies presented in this thesis aim to target HER3 with small, engineered affinity domain proteins for therapeutic purposes. Monomeric affibody molecules have previously been engineered to bind and inhibit HER3 in vitro. Due to the relatively low expression of HER3, an increase in valency appears promising to strengthen the therapeutic potential. Affibody molecules targeting the receptor were thus linked to form bivalent and bispecific constructs and evaluated both in vitro and in vivo. In the first study of this thesis affibody molecules specific for HER3 and HER2 were fused to an albumin binding domain to form bivalent and bispecific construct. The constructs inhibited ligand-induced receptor phos- phorylation of both HER2 and HER3 more efficiently than monomeric affibody molecules. A second approach to enhance the potential of affibody molecules in tumor targeting is described in the second study, where monomeric HER3-binding affibody molecules were engineered to increase their affinity for HER3. The resulting variants showed a 20-fold in- creased affinity and higher capacity to inhibit cancer cell growth. Combining the findings of the first two studies, the third study describes the evaluation of a HER3-targeting bivalent affibody construct for potential application as a therapeutic. Here, the bivalent construct inhibited cancer cell growth in vitro and was found to slow down tumor growth in mice, while being well tolerated and showing no visible toxicity. The fourth study built upon these findings and compares a very similar bivalent construct to the clinically-investigated HER3-specific monoclonal antibody seribantumab. The affibody construct showed very comparable efficacy with the antibody in terms of decreasing tumor growth rate and ex- tending mouse survival. Collectively, these works describe for the first time the use of alternative affinity protein constructs with therapeutic potential targeting HER3.

  • 266.
    Bass, Tarek
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Evaluating the therapeutic potential of a dimeric HER3-binding affibody construct in comparison with a monoclonal antibody, seribantumab.Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    A number of monoclonal antibodies targeting HER3 are currently under clinical investigation as potential cancer therapeutics. We have earlier generated high affinity (low picomolar) affibody molecules targeting HER3. These are small, 58 amino acid, non-immunoglobulin based scaffold proteins that have proved suitable for tumor targeting applications, previously primarily for molecular imaging purposes. Our high affinity HER3-binding affibody molecule has demonstrated to have anti-proliferative capacity on HER3-positive tumor cells. When formatted as a bivalent construct, in which the two affibody moieties are flanking a small albumin-binding domain (ABD), we have recently demonstrated that tumor growth could be delayed in mice for HER3-positive xenografts. In this study, we have modified the construct further and reduced the size. In a comparative study, we evaluated safety, the capacity to delay tumor growth in mice with BxPC-3 xenografts, and mouse survival. Our novel construct was compared to the HER3-specific monoclonal antibody seribantumab (MM-121), presently in clinical development. They were found to be equally potent in their therapeutic effects and in their safety profile. We conclude that this format of bivalent HER3-binding affibody molecules seems promising for further evaluation as candidate therapeutics for treatment of HER3-overexpressing tumors.

  • 267.
    Bastuk, Manuel
    et al.
    Saarland University, Saarbruecken, Germany.
    Bur, Christian
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad sensorvetenskap. Linköpings universitet, Tekniska högskolan. Saarland University, Saarbruecken, Germany.
    Lloyd Spetz, Anita
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad sensorvetenskap. Linköpings universitet, Tekniska högskolan.
    Andersson, Mike
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad sensorvetenskap. Linköpings universitet, Tekniska högskolan.
    Schütze, Andreas
    Saarland University, Saarbruecken, Germany.
    Gas identification based on bias induced hysteresis of a gas-sensitive SiC field effect transistor2014Inngår i: Journal of Sensors and Sensor Systems, Vol. 3, s. 9-19Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this work dynamic variation of gate bias is used on a gas-sensitive SiC field effect transistor ("GasFET") to optimize its sensitivity and increase its selectivity. Gate bias ramps introduce strong hysteresis in the sensor signal. The shape of this hysteresis is shown to be an appropriate feature both for the discrimination of various gases (ammonia, carbon monoxide, nitrogen monoxide and methane) as well as for different gas concentrations (250 and 500 ppm). The shape is very sensitive to ambient conditions as well as to the bias sweep rate. Thus, the influences of oxygen concentration, relative humidity, sensor temperature and cycle duration, i.e., sweep rate, are investigated and reasons for the observed signal changes, most importantly the existence of at least two different and competing processes taking place simultaneously, are discussed. Furthermore, it is shown that even for very fast cycles, in the range of seconds, the gas-induced shape change in the signal is strong enough to achieve a reliable separation of gases using gate bias cycled operation and linear discriminant analysis (LDA) making this approach suitable for practical application.

  • 268.
    Basu, Alex
    et al.
    Uppsala University, Sweden.
    Lindh, Jonas
    Uppsala university, Sweden.
    Ålander, Eva
    RISE - Research Institutes of Sweden, Bioekonomi.
    Strömme, Maria
    Uppsala university, Sweden.
    Ferraz, Natalia
    Uppsala university, Sweden.
    On the use of ion-crosslinked nanocellulose hydrogels for wound healing solutions: Physicochemical properties and application-oriented biocompatibility studies2017Inngår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 174, s. 299-308Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Calcium ion-crosslinked nanofibrillated cellulose (NFC) hydrogels were investigated as potential materials for wound healing dressings. The physicochemical properties of the hydrogels were examined by rheology and water retention tests. Skin cells and monocytes were selected for application-oriented biocompatibility studies. The NFC hydrogels presented entangled fibrous networks and solid-like behavior. Water retention tests showed the materialÂŽs potential to maintain a suitable moist environment for different type of wounds. The hydrogels did not affect dermal fibroblasts monolayer cultures upon direct contact, as cell monolayers remained intact after application, incubation and removal of the materials. Inflammatory response studies with blood-derived mononuclear cells revealed the inert nature of the hydrogels in terms of cytokine secretion and reactive oxygen species production. Results highlight the great potential of ion-crosslinked NFC hydrogels for the development of advanced wound dressings, where further functionalization of the material could lead to improved properties towards the healing of specific wound types.

  • 269.
    Basu, Samar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Univ Clermont Auvergne, Fac Pharm, Dept Biochem Mol Biol & Nutr, BP 10448, F-63000 Clermont Ferrand, France..
    Kadiiska, Maria B.
    NIEHS, Immun Inflammat & Dis Lab, NIH, Res Triangle Pk, NC 27709 USA..
    Ozone exposure effect on systemic prostaglandin F-2 alpha in rat plasma and urine may not reveal pulmonary damage through inflammation2017Inngår i: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 126, s. 79-83Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The acute ozone induced lung injury model has been widely used to explore injury and repair processes induced by oxidant overload. The current study evaluated acute ozone exposure effects on prostaglandin F-2 alpha (PGF(2 alpha)) in male Fischer rat plasma and urine with the hypothesis that ozone may induce an inflammatory response in the body that can be measured by the induction of PGF2 alpha. That might then lead to the identification of potential marker for acute lung injury through systemic inflammation. The time and dose-dependent effects of ozone exposure on the plasma and urinary levels of a major PGF(2 alpha) metabolite15-keto-dihydro-PGF(2 alpha) were determined using a radioimmunoassay. No statistically significant differences in the PGF(2 alpha) metabolite were found between the control and the experimental groups at either ozone exposure dose (2 ppm and 5 ppm) or any time point (2 h, 7 h and 16 h) post exposure for plasma and at 7 different post exposure time points (between 2 and 80 h) for urine. It is concluded that acute ozone exposure does not cause changes in plasma and urinary PGF(2 alpha), and therefore their measurement in plasma and urine may not be used to reveal pulmonary inflammation and damage by ozone.

  • 270.
    Batool, Tahira
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fang, Jianping
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. GlycoNovo Technol Co Ltd, Shanghai, Peoples R China..
    Barash, Uri
    Technion, Fac Med, Canc & Vasc Biol Res Ctr Rappaport, Haifa, Israel..
    Moustakas, Aristidis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Vlodavsky, Israel
    Technion, Fac Med, Canc & Vasc Biol Res Ctr Rappaport, Haifa, Israel..
    Li, Jin-Ping
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Overexpression of heparanase attenuated TGF-beta-stimulated signaling in tumor cells2017Inngår i: FEBS Open Bio, E-ISSN 2211-5463, Vol. 7, nr 3, s. 405-413Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Heparan sulfate (HS) mediates the activity of various growth factors including TGF-beta. Heparanase is an endo-glucuronidase that specifically cleaves and modifies HS structure. In this study, we examined the effect of heparanase expression on TGF-beta 1-dependent signaling activities. We found that overexpression of heparanase in human tumor cells (i.e., Fadu pharyngeal carcinoma, MCF7 breast carcinoma) attenuated TGF-beta 1-stimulated Smad phosphorylation and led to a slower cell proliferation. TGF-beta 1-stimulated Akt and Erk phosphorylation was also affected in the heparanase overexpression cells. This effect involved the enzymatic activity of heparanase, as overexpression of mutant inactive heparanase did not affect TGF-beta 1 signaling activity. Analysis of HS isolated from Fadu cells revealed an increase in sulfation of the HS that had a rapid turnover in cells overexpressing heparanase. It appears that the structural alterations of HS affect the ability of TGF-beta 1 to signal via its receptors and elicit a growth response. Given that heparanase expression promotes tumor growth in most cancers, this finding highlights a crosstalk between heparanase, HS, and TGF-beta 1 function in tumorigenesis.

  • 271.
    Batool, Tahira
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fang, Jianping
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Glyconovo Technologies Co., Ltd., TianXiong Road, Shanghai International Medical Zone (SIMZ), Pudong New Area, Shanghai 201318, China.
    Jansson, Viktor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Zhao, Hongxing
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gallant, Caroline J.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Moustakas, Aristidis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Li, Jin-Ping
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Upregulated BMP-Smad signaling activity in the glucuronyl C5-epimerase knock out MEF cells2019Inngår i: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 54, s. 122-129Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Glucuronyl C5-epimerase (Hsepi) catalyzes the conversion of glucuronic acid to iduronic acid in the process of heparan sulfate biosynthesis. Targeted interruption of the gene, Glce,in mice resulted in neonatal lethality with varied defects in organ development. To understand the molecular mechanisms of the phenotypes, we used mouse embryonic fibroblasts (MEF) as a model to examine selected signaling pathways. Our earlier studies found reduced activities of FGF-2, GDNF, but increased activity of sonic hedgehog in the mutant cells. In this study, we focused on the bone morphogenetic protein (BMP) signaling pathway. Western blotting detected substantially elevated endogenous Smad1/5/8 phosphorylation in the Hsepi mutant (KO) MEF cells, which is reverted by re-expression of the enzyme in the KO cells. The mutant cells displayed an enhanced proliferation and elevated alkaline phosphatase activity, marking higher differentiation, when cultured in osteogenic medium. The high level of Smad1/5/8 phosphorylation was also found in primary calvarial cells isolated from the KO mice. Analysis of the genes involved in the BMP signaling pathway revealed upregulation of a number of BMP ligands, but reduced expression of several Smads and BMP antagonist (Grem1) in the KO MEF cells. The results suggest that Hsepi expression modulates BMP signaling activity, which, at least partially, is associated with defected molecular structure of heparan sulfate expressed in the cells.   

  • 272.
    Baudin, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Ökad trombopoes och perifer trombocytaktivering i Hantavirus-infekterade patienter2017Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 273.
    Bauer, Margit
    et al.
    Med Univ Graz, Dept Obstet & Gynecol, Graz, Austria..
    Mazza, Edoardo
    Swiss Fed Inst Technol, Dept Mech & Proc Engn, Zurich, Switzerland..
    Jabareen, Mahmood
    Swiss Fed Inst Technol, Dept Mech & Proc Engn, Zurich, Switzerland..
    Sultan, Leila
    Univ Zurich Hosp, Dept Obstet & Gynecol, CH-8091 Zurich, Switzerland..
    Bajka, Michael
    Univ Zurich Hosp, Dept Obstet & Gynecol, CH-8091 Zurich, Switzerland..
    Lang, Uwe
    Med Univ Graz, Dept Obstet & Gynecol, Graz, Austria..
    Zimmermann, Roland
    Univ Zurich Hosp, Dept Obstet & Gynecol, CH-8091 Zurich, Switzerland..
    Holzapfel, Gerhard A.
    KTH, Skolan för elektro- och systemteknik (EES).
    In Vivo Biomechanical Testing of the Human Uterine Cervix in Pregnancy Using an Aspiration Device2009Inngår i: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 16, nr 3, s. 197A-197AArtikkel i tidsskrift (Annet vitenskapelig)
  • 274.
    Bauer, Sofia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning. Koch Institute for Integrative Cancer Research, M.I.T..
    The in vivo role of Cpt1a and whether a HFD renders ISCs, progenitors or established tumors metabolically reliant on fatty acid oxidation for their maintenance2019Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    The mammalian intestine is made of the small intestine and the colon. The small intestine is arranged into two fundamental structures called villi and crypts. Lgr5+ cells represent the intestinal stem cells (ISCs) and are identified by marker gene Lgr5, which is expressed at the bottom of mouse crypts, i.e. mucosal glands found in the intestinal epithelium. The mammalian intestine is said to respond to signals from the diet. Increased ISC numbers and progenitor proliferation have been associated with the effects of a high-fat diet (HFD) and these cells can, under HFD conditions initiate organoids i.e. small intestine-like structures cultured in vitro. In relation to cancer it has been shown that a HFD acts through the nuclear receptor PPAR-δ in ISCs and progenitors, and that PPAR-δ is also involved in fatty acid oxidation (FAO) as a master transcriptional regulator of the key FAO gene Cpt1a. The aim of this Master’s thesis seeks to assess whether a HFD renders ISCs, progenitors or established tumors metabolically reliant on FAO for their maintenance. Lineage tracing analysis in vivo with the computer software Aperio ImageScope, after βgalactosidase staining experiments contributed to confirm the reduced effects of a HFD in ISCs and progenitors as consequence of Cpt1a loss. The inhibition of FAO through in vitro and in vivo organoid experiments with genotypes APCΔ; P53Δ; Rosa-LSL-ZsGreen; Vil-CreER (APZV) and APCΔ; P53Δ; Cpt1afl/fl; Rosa-LSL-tdTomato; Vil-CreER (APCTV) also showed adverse effects on tumor maintenance. This from the clonogenicity assay after cell/organoid count analysis with the computer software ImageJ. In conclusion from the results obtained, which confirmed the hypothesis in the aims to a large extent Cpt1a could serve as a potential future therapeutic target. However, more experimental trials are needed to ascertain whether Cpt1a is the main contributor to mediate the HFD phenotype, but it is a promising start in the right direction. Increased knowledge of the impacts of diet in health and disease pursues to assist both in the prevention, as well as in the cure of established diseases in patients such as cancer. In the future, it would also be of interest to focus on and confirm whether the effects of the diet on various pathologies is reversible.

  • 275.
    Baumann, Martin J.
    KTH, Skolan för bioteknologi (BIO).
    Xyloglucan-active enzymes: properties, structures and applications2007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [sv]

    Cellulosabaserade material är världens rikligast förekommande förnyelsebara råvara. Växters cellväggar är naturliga kompositmaterial där den kristallina cellulosan är inbäddad i en väv av hemicellulosa, strukturproteiner och lignin. Xyloglukaner är en viktig hemicellulosagrupp som omger och korslänkar den kristallina cellulosan i cellväggarna. I denna avhandling undersöks undersöks sambanden mellan struktur och funktion hos olika xyloglukan-aktiva enzymer.

    En modell för effektiv enzymatisk omvandling av biomassa ges av cellulosomen hos den anaeroba prokaryota organismen Clostridium thermocellum. Cellulosomen är ett proteinkomplex med hög molmassa och flera olika enzymaktiviteter, bl.a. det inverterande xyloglukan-endohydrolaset CtXGH74A. Proteinstrukturen för CtXGH74A har lösts i komplex med xyloglukanoligosackarider, som stabliliserar vissa loopar/slingor som är oordnade i apostrukturen. Ytterligare detaljerade kinetiska och produktananalyser har genomförts för att entydigt visa att CtXGH74A är ett endoxyloglukanas vars slutliga nedbrytningsprodukt är Glc4-baserade xyloglukanoligosackarider.

    Som jämförelse innehåller glykosidhydrolasfamilj 16 (GH16) såväl hydrolytiska endoxyloglukanaser som xyloglukantransglykosylaser (XETs) från växter. För att utreda vad som bestämmer förhållandet mellan transglykosylering och hydrolys i xyloglukanaktiva enzymer från familj GH 16 jämfördes struktur och kinetik hos ett strikt transglykosylas, PttXET16-34 från hybridasp, med ett nära besläktat hydrolytiskt enzym, NXG1 från krasse. I NXG1 identifierades en viktig förlängningsloop, som vid trunkering gav ett muterat enzym med högre transglykosyleringshastighet och minskad hydrolytisk aktivitet. Kinetikstudierna genomfördes med hjälp av nyutvecklade känsliga provmetoder med väldefinerade XGO:er och ett antal kromogena XGO-arylglykosider.

    En detaljerad förståelse av enzymologin inom GH16 möjliggjorde utvecklingen av en ny kemoenzymatisk metod för biomimetisk fiberytmodifiering med hjälp av PttXET16-34s translgykosyleringsaktivitet. Aminoalditolderivat av xyloglukanoligosackarider användes som nyckelintermediärer för att introducera ny kemisk funktionalitet hos xyloglukan, såsom kromoforer, reaktiva grupper, proteinligander och initiatorer för polymeriseringsreaktioner. Tekniken innebär ett nytt och mångsidigt verktyg för fiberytmodifiering.

  • 276.
    Baumann, Martina
    et al.
    Univ Nat Resources & Appl Life Sci, Dept Biotechnol, Vienna, Austria.
    Höppner, Marc P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Meier, Michael
    Univ Nat Resources & Appl Life Sci, Dept Biotechnol, Vienna, Austria.
    Pontiller, Jens
    Univ Nat Resources & Appl Life Sci, Dept Biotechnol, Vienna, Austria.
    Ernst, Wolfgang
    Univ Nat Resources & Appl Life Sci, Dept Biotechnol, Vienna, Austria.
    Grabherr, Reingard
    Univ Nat Resources & Appl Life Sci, Dept Biotechnol, Vienna, Austria.
    Mauceli, Evan
    Broad Inst, Cambridge, MA USA.
    Grabherr, Manfred G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Broad Inst, Cambridge, MA USA.
    Artificially designed promoters: understanding the role of spatial features and canonical binding sites in transcription2012Inngår i: Bioengineered Bugs, ISSN 1949-1018, E-ISSN 1949-1026, Vol. 3, nr 2, s. 120-123Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The promoter is a key element in gene transcription and regulation. We previously reported that artificial sequences rich in the dinucleotide CpG are sufficient to drive expression in vitro in mammalian cell lines, without requiring canonical binding sites for transcription factor proteins. Here, we report that introducing a promoter organization that alternates in CpGs and regions rich in A and T further increases expression strength, as well as how insertion of specific binding sites makes such sequences respond to induced levels of the transcription factor NFκB. Our findings further contribute to the mechanistic understanding of promoters, as well as how these sequences might be shaped by evolutionary pressure in living organisms.

  • 277.
    Baumgarten, Thomas
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Schlegel, Susan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Wagner, Samuel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Löw, Mirjam
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Eriksson, Jonas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Bonde, Ida
    Herrgård, Markus J.
    Heipieper, Hermann J.
    Nørholm, Morten H. H.
    Slotboom, Dirk Jan
    de Gier, Jan-Willem
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Isolation and characterization of the E. coli membrane protein production strain Mutant56(DE3)2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikkel-id 45089Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Membrane protein production is usually toxic to E. coli. However, using genetic screens strains can be isolated in which the toxicity of membrane protein production is reduced, thereby improving production yields. Best known examples are the C41(DE3) and C43(DE3) strains, which are both derived from the T7 RNA polymerase (P)-based BL21(DE3) protein production strain. In C41(DE3) and C43(DE3) mutations lowering t7rnap expression levels result in strongly reduced T7 RNAP accumulation levels. As a consequence membrane protein production stress is alleviated in the C41(DE3) and C43(DE3) strains, thereby increasing membrane protein yields. Here, we isolated Mutant56(DE3) from BL21(DE3) using a genetic screen designed to isolate BL21(DE3)-derived strains with mutations alleviating membrane protein production stress other than the ones in C41(DE3) and C43(DE3). The defining mutation of Mutant56(DE3) changes one amino acid in its T7 RNAP, which weakens the binding of the T7 RNAP to the T7 promoter governing target gene expression rather than lowering T7 RNAP levels. For most membrane proteins tested yields in Mutant56(DE3) were considerably higher than in C41(DE3) and C43(DE3). Thus, the isolation of Mutant56(DE3) shows that the evolution of BL21(DE3) can be promoted towards further enhanced membrane protein production.

  • 278.
    Beaussant Törne, Karin
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Khan, Fareed Ashraf
    Örnberg, A.
    Weissenrieder, Jonas
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Zn-Mg and Zn-Ag degradation mechanism under biologically relevant conditionsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Zinc alloys form a promising new class of biodegradable metals that combine suitable mechanical properties with the favorable degradation properties of pure zinc. However, the current understanding of the influence of alloying elements on the corrosion of zinc alloys, in biologically relevant media, is limited. We studied the degradation of three alloys, Zn 4 wt% Ag, Zn 0.5 wt% Mg and Zn 3 wt% Mg by in situ electrochemical impedance spectroscopy (EIS). After exposure for 1h or 30 days the samples were characterized by infrared spectroscopy and scanning electron microscopy (SEM). The presence of secondary phases in the alloy microstructure induced selective corrosion and increased degradation rate. An increase in surface inhomogeneity was evident by EIS analysis both at short (hours) as well as long immersion times (days). The microgalvanic corrosion of the Zn-Ag alloy resulted in enrichment of the AgZn3 phase at the sample surface. The enrichment of Ag and potential release of AgZn3 particles may result in complications during the tissue regeneration. The Zn-Mg alloy surface was depleted of the Mg-rich phase after 8-12 days. The selective dissolution caused local precipitation of2corrosion products and a thicker corrosion layer with larger pore size consistent with increased corrosion rate.

  • 279.
    Beaussant Törne, Karin
    et al.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Örnberg, A.
    Weissenrieder, Jonas
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik.
    Characterization of the Protective Layer Formed on Zinc in Whole BloodManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The advantageous degradation properties of zinc in a biological environment are related to the presence of a protective corrosion layer composed of both organic and inorganic components. However, the mechanisms governing its formation and how the organic species influence its properties have not been established. Here we study the protective layer formation during anodic polarization in whole blood by in situ electrochemical impedance spectroscopy (EIS) as well as infrared spectroscopy and scanning electron microscopy. Simulated body fluid (m-SBF) was used as a reference media to discern the influence of the organic species present in whole blood. Protective zinc phosphate layers form on the Zn surface in both solutions, but of different nature and through diverse mechanisms. In m-SBF the passivating thin film formation occur already at open circuit potential, reducing the corrosion current compared to exposure in whole blood by a factor of 103. The high corrosion current in whole blood can be explained by a process including rapid protein adsorption preventing the initial formation of a protective phosphate layer. EIS analysis detected an inductive arc in whole blood at low overpotentials, before the onset of protective film formation, indicating the presence of adsorbed Zn2ions. The coverage of Zn ions approach 100% of the active surface at 110 mV. At this critical surface coverage a reaction between the adsorbed Zn ions and PO42- takes place which results in formation of a protective, porous, film of ~1 μm thickness. The inorganic component of the protective film formed in whole blood was characterized as Zn(PO4)2(OH)2·3H2O.

  • 280. Bello, M. A.
    et al.
    Ruiz-León, Y.
    Sandoval-Sierra, J. V.
    Rezinciuc, Svetlana
    KTH, Skolan för bioteknologi (BIO), Glykovetenskap.
    Diéguez-Uribeondo, J.
    Scanning electron microscopy (SEM) protocols for problematic plant, oomycete, and fungal samples2017Inngår i: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, Vol. 2017, nr 120, artikkel-id e55031Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Common problems in the processing of biological samples for observations with the scanning electron microscope (SEM) include cell collapse, treatment of samples from wet microenvironments and cell destruction. Using young floral tissues, oomycete cysts, and fungi spores (Agaricalesas examples, specific protocols to process delicate samples are described here that overcome some of the main challenges in sample treatment for image capture under the SEM. Floral meristems fixed with FAA (Formalin-Acetic-Alcohol) and processed with the Critical Point Dryer (CPD) did not display collapsed cellular walls or distorted organs. These results are crucial for the reconstruction of floral development. A similar CPD-based treatment of samples from wet microenvironments, such as the glutaraldehyde-fixed oomycete cysts, is optimal to test the differential growth of diagnostic characteristics (e.g., the cyst spines) on different types of substrates. Destruction of nurse cells attached to fungi spores was avoided after rehydration, dehydration, and the CPD treatment, an important step for further functional studies of these cells. The protocols detailed here represent low-cost and rapid alternatives for the acquisition of good-quality images to reconstruct growth processes and to study diagnostic characteristics.

  • 281.
    Benderix, Ylva
    et al.
    Växjö universitet, Fakulteten för humaniora och samhällsvetenskap, Institutionen för pedagogik.
    Almqvist, Ann-Mari
    Andersson, Åsa
    Bengtsson, Elisabeth
    Björk, Maria
    Birgersson, Petra
    Bramhagen, Ann-Cathrin
    Bredlöv, Britt
    Broberg, Malin
    Danielsson, Pernilla
    Drevenhorn, Eva
    Edwinsson-Månsson, Marie
    Ervander Grandinsson, Inger
    Falk, Ann-Charlotte
    Forsner, Maria
    Gelander, RS
    Gothefors, Leif
    Gånemo, Agneta
    Barn med neuropsykiatriskt funktionshinder2009Inngår i: PEDIATRISK OMVÅRDNAD / [ed] Inger Hallström & Tom Lindberg, Stockholm: LIBER , 2009, s. 309-315Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 282. Bengtsson, Erik
    et al.
    Nerjovaj, Pashtrik
    Wangefjord, Sakarias
    Nodin, Björn
    Eberhard, Jakob
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Borgquist, Signe
    Jirström, Karin
    HMG-CoA reductase expression in primary colorectal cancer correlates with favourable clinicopathological characteristics and an improved clinical outcome2014Inngår i: Diagnostic Pathology, ISSN 1746-1596, E-ISSN 1746-1596, Vol. 9, nr 1, s. 78-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: An association between tumor-specific HMG-CoA reductase (HMGCR) expression and good prognosis has previously been demonstrated in breast and ovarian cancer. In this study, the expression, clinicopathological correlates and prognostic value of HMGCR expression in colorectal cancer was examined. Findings: Immunohistochemical expression of HMGCR was assessed in tissue microarrays with primary tumours from 557 incident cases of colorectal cancer in the Malmo Diet and Cancer Study. Pearson's Chi Square test was applied to explore the associations between HMGCR expression and clinicopathological factors and other investigative biomarkers. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the relationship between HMGCR expression and cancer-specific survival (CSS) according to negative vs positive HMGCR expression. A total number of 535 (96.0%) tumours were suitable for analysis, of which 61 (11.4%) were HMGCR negative. Positive cytoplasmic HMGCR expression was associated with distant metastasis-free disease at diagnosis (p = 0.002), lack of vascular invasion (p = 0.043), microsatellite-instability (p = 0.033), expression of cyclin D1 (p = <0.001) and p21 (p = <0.001). Positive HMGCR expression was significantly associated with a prolonged CSS in unadjusted Cox regression analysis in the entire cohort (HR = 1.79; 95% CI 1.20-2.66) and in Stage III-IV disease (HR = 1.71; 95% CI 1.09-2.68), but not after adjustment for established clinicopathological parameters. Conclusions: Findings from this prospective cohort study demonstrate that HMGCR is differentially expressed in colorectal cancer and that positive expression is associated with favourable tumour characteristics and a prolonged survival in unadjusted analysis. The utility of HMGCR as a predictor of response to neoadjuvant or adjuvant statin treatment in colorectal cancer merits further study. Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2115647072103464.

  • 283.
    Bengtsson, Katarina
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Ytors Fysik och Kemi. Linköpings universitet, Tekniska fakulteten. LunaMicro AB, Linköping, Sweden.
    Christoffersson, Jonas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teknisk biologi. Linköpings universitet, Tekniska fakulteten.
    Mandenius, Carl-Fredrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teknisk biologi. Linköpings universitet, Tekniska fakulteten.
    Robinson, Nathaniel D
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Ytors Fysik och Kemi. Linköpings universitet, Tekniska fakulteten. LunaMicro AB, Linköping, Sweden.
    A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices2018Inngår i: Microfluidics and Nanofluidics, ISSN 1613-4982, E-ISSN 1613-4990, Vol. 22, nr 3, artikkel-id 27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent advances in microfluidic devices put a high demand on small, robust and reliable pumps suitable for high-throughput applications. Here we demonstrate a compact, low-cost, directly attachable (clip-on) electroosmotic pump that couples with standard Luer connectors on a microfluidic device. The pump is easy to make and consists of a porous polycarbonate membrane and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) electrodes. The soft electrode and membrane materials make it possible to incorporate the pump into a standard syringe filter holder, which in turn can be attached to commercial chips. The pump is less than half the size of the microscope slide used for many commercial lab-on-a-chip devices, meaning that these pumps can be used to control fluid flow in individual reactors in highly parallelized chemistry and biology experiments. Flow rates at various electric current and device dimensions are reported. We demonstrate the feasibility and safety of the pump for biological experiments by exposing endothelial cells to oscillating shear stress (up to 5 dyn/cm2) and by controlling the movement of both micro- and macroparticles, generating steady or oscillatory flow rates up to ± 400 μL/min.

  • 284.
    Bengtsson, Rebecca
    Högskolan Kristianstad, Sektionen för lärande och miljö.
    Jämförelse av automatiskt beräknade ejektionsfraktion (EF) ochmaximal volym vid diastole i vänster kammare (EDV) vid myokardscintigrafi och ultraljud.2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Hjärtats storlek och funktion är avgörande för att ställa diagnos och prognos vid kardiella sjukdomar. För bestämning av dessa parametrar finns olika metoder att använda sig av. I denna studie har vi försökt visa korrelation och överensstämmelse mellan 3-dimensionell ekokardiografi (RT3DE) och myokardscintigrafi (SPECT). Då 25 patienter var remitterade för arbetsdelen av myokardscintigrafin undersöktes de även med RT3DE. Av dessa exkluderades 7 patienter antingen för att bildkvaliteten var för dålig för automatiska beräkningar, eller för att programvaran inte klarade av att göra trovärdiga beräkningar även då bildkvaliteten var god. De återstående 18 patienter (ålder 62 ± 11 år, 9 kvinnor) ingick i jämförelserna. Vänsterkammarens ejektionsfraktion (EF) och end diastoliska volym (EDV) beräknades automatiskt utan manuell justering av konturerna med RT3DE och jämfördes med erhållna värden från SPECT. Resultaten för EDV mätt med SPECT och RT3DE blev 83 ± 59 ml (37-291 ml) respektive 118 ± 32 ml (75-186 ml). Pearsons korrelationskoefficient mellan SPECT och RT3DE var r = 0,78 (P < 0,002). Beräkning av överensstämmelsen mellan metoderna ger bias som är medelvärdet av skillnaden vilket blev 35 ± 40 ml (P < 0,001). Motsvarande resultat för EF beräknat med SPECT och RT3DE blev 62 ± 13 % (36-83 %) respektive 54 ± 8 % (36-71 %). Pearsons korrelationskoefficient mellan metoderna var r = 0,59 (P = 0,009). Biasvärdet blev -7 ± 11 % (P = 0,004) för EF. Spridningen mellan metoderna var stor och några tydliga trender kunde inte ses. Med en trendlinje i differensdiagrammet visualiserades att felet växte med storleken på värdena för EF. De stora variationerna mellan metoderna ökar vikten av utbildning och erfarenhet vid bedömning av enskilda resultat oavsett undersökning.

  • 285. Bengtsson-Palme, Johan
    et al.
    Hammaren, Rickard
    Pal, Chandan
    Ostman, Marcus
    Björlenius, Berndt
    KTH, Skolan för bioteknologi (BIO), Industriell bioteknologi.
    Flach, Carl-Fredrik
    Fick, Jerker
    Kristiansson, Erik
    Tysklind, Mats
    Larsson, D. G. Joakim
    Elucidating selection processes for antibiotic resisitance in sewage treatment plants using metagenomics2016Inngår i: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 572, s. 697-712Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sewage treatment plants (STPs) have repeatedly been suggested as hotspots for the emergence and dissemination of antibiotic-resistant bacteria. A critical question still unanswered is if selection pressures within STPs, caused by residual antibiotics or other co-selective agents, are sufficient to specifically promote resistance. To address this, we employed shotgun metagenomic sequencing of samples from different steps of the treatment process in three Swedish STPs. In parallel, concentrations of selected antibiotics, biocides and metals were analyzed. We found that concentrations of tetracycline and ciprofloxacin in the influent were above predicted concentrations for resistance selection, however, there was no consistent enrichment of resistance genes to any particular class of antibiotics in the STPs, neither for biocide and metal resistance genes. The most substantial change of the bacterial communities compared to human feces occurred already in the sewage pipes, manifested by a strong shift from obligate to facultative anaerobes. Through the treatment process, resistance genes against antibiotics, biocides and metals were not reduced to the same extent as fecal bacteria. The OXA-48 gene was consistently enriched in surplus and digested sludge. We find this worrying as OXA-48, still rare in Swedish clinical isolates, provides resistance to carbapenems, one of our most critically important classes of antibiotics. Taken together, metagenomics analyses did not provide clear support for specific antibiotic resistance selection. However, stronger selective forces affecting gross taxonomic composition, and with that resistance gene abundances, limit interpretability. Comprehensive analyses of resistant/non-resistant strains within relevant species are therefore warranted. 

  • 286.
    Bentley, Katie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi. Harvard Med Sch, Beth Israel Deaconess Med Ctr, Computat Biol Lab, Boston, MA USA..
    Chakravartula, Shilpa
    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Computat Biol Lab, Boston, MA USA..
    The temporal basis of angiogenesis2017Inngår i: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 372, nr 1720, s. 1-11, artikkel-id 20150522Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The process of new blood vessel growth (angiogenesis) is highly dynamic, involving complex coordination of multiple cell types. Though the process must carefully unfold over time to generate functional, well-adapted branching networks, we seldom hear about the time-based properties of angiogenesis, despite timing being central to other areas of biology. Here, we present a novel, time-based formulation of endothelial cell behaviour during angiogenesis and discuss a flurry of our recent, integrated in silico/in vivo studies, put in context to the wider literature, which demonstrate that tissue conditions can locally adapt the timing of collective cell behaviours/decisions to grow different vascular network architectures. A growing array of seemingly unrelated 'temporal regulators' have recently been uncovered, including tissue derived factors (e.g. semaphorins or the high levels of VEGF found in cancer) and cellular processes (e.g. asymmetric cell division or filopodia extension) that act to alter the speed of cellular decisions to migrate. We will argue that 'temporal adaptation' provides a novel account of organ/disease-specific vascular morphology and reveals 'timing' as a new target for therapeutics. We therefore propose and explain a conceptual shift towards a 'temporal adaptation' perspective in vascular biology, and indeed other areas of biology where timing remains elusive. This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'.

  • 287.
    Berg, Cecilia
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hedrum, A
    Holmberg, A
    Pontén, F
    Uhlén, M
    Lundeberg, J
    Direct solid-phase sequence analysis of the human p53 gene by use of multiplex polymerase chain reaction and alpha-thiotriphosphate nucleotides.1995Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 41, nr 10, s. 1461-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Among the candidate cancer-prognostic genes is the p53 tumor suppressor gene, which, when mutated, plays an important role in the development of many types of cancers. To facilitate robust large-scale DNA analysis of microdissected tumor biopsies, we describe a multiplex/nested PCR approach for a simultaneous outer amplification of exons 4-9 of the human p53 gene with parallel amplification of the HLA-DQB1 locus, involving a total of 14 primers. This approach reduces the required number of cells for analysis and avoids any variation in the amplifications of the individual p53 exons during the common outer amplification step. The HLA sequencing allows sample identification because the DQB1 locus is highly polymorphic and is thereby patient-specific. The p53 and HLA amplicons are analyzed by solid-phase sequencing in a semiautomated format. To improve the DNA sequence quality, we used 2'-deoxyribonucleoside 5'-O-1-thiotriphosphates in the sequencing reactions.

  • 288.
    Berg, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Visualisering av mikroorganismer i hårfolliklar från patienter med follikulit2012Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 289. Berg, Kirsti
    et al.
    Ericsson, Madelene
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Lindgren, Mikael
    Gustafsson, Håkan
    A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 3, s. e90964-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: An electron paramagnetic resonance (EPR) technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies. Materials and Methods: Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K) using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CPN) with known spin concentration. Results: The absolute spin concentration could be quantified with a precision and accuracy better than +/- 10 mu M (k = 1). The spin concentration of samples stored at -80 degrees C could be reproduced after 6 months of storage well within the same error estimate. Conclusion: The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time.

  • 290.
    Berg, Mari
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Utvärdering av Sysmex UF-5000 för snabb antibiotikaresistens­bestämning av bakterier2018Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 291. Bergander, L
    et al.
    Wahlström, Niklas
    Södertörns högskola, Avdelning Naturvetenskap. Karolinska Institutet.
    Alsberg, T
    Bergman, Jan
    Södertörns högskola, Avdelning Naturvetenskap. Karolinska Institutet.
    Rannug, A
    Rannug, U
    Characterization of in vitro metabolites of the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b] carbazole by liquid chromatography-mass spectrometry and NMR.2003Inngår i: Drug Metabolism And Disposition, ISSN 0090-9556, E-ISSN 1521-009X, Vol. 31, nr 2, s. 233-241Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The tryptophan photoproduct 6-formylindolo[3,2-b] carbazole (FICZ) exhibits the highest aryl hydrocarbon receptor (AhR) binding affinity reported so far. In different cells, in vitro, both extracts of UV-irradiated tryptophan and the synthesized pure compound FICZ induce a rapid and transient expression of AhR-regulated genes. The transient induction suggests that the biotransformation gene battery induced by AhR activation takes part in a metabolic degradation of the ligand, whereby a low steady-state level is regained. The down-regulation of AhR-regulated gene expression was previously shown to be dependent on cytochrome P450 1A1 (CYP1A1). Metabolism of FICZ generates five major metabolites, which appeared as three peaks (M1-M3) in the high performance liquid chromatography. The aim of the present study was to use rat liver S9 from Aroclor-pretreated rats to produce large enough quantities of FICZ metabolites for structure characterization and to determine their product precursor relationship. NMR analysis of large combined fractions of the metabolites indicated that M3 and M2 contained 2 isomers, respectively. By means of liquid chromatography-mass spectrometry (negative ion electrospray mode) and NMR spectroscopy (by H-1-NMR, correlation spectroscopy, and nuclear Overhauser effect spectroscopy techniques) five metabolites of FICZ were identified, and their structures were elucidated. The molecular weights of the two M3 isomers were 300 and both M2 and M1 compounds demonstrated molecular weights of 316, corresponding to addition of one (M3) and of two oxygen (M2 and M1), respectively. The structures were assigned as 2- and 8-hydroxy (M3), 2,10- and 4,8-dihydroxy (M2) and 2,8-dihydroxy derivatives of indolo[3,2-b] carbazole-6-carboxaldehyde (6-formylindolo[ 3,2-b] carbazole).

  • 292.
    Bergendahl, Christina
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Tibell, Lena
    Department of Biomedicine and Surgery, Linköping .
    Boosting complex learning by strategic assessment and course design2005Inngår i: Journal of Chemical Education, ISSN 0021-9584, E-ISSN 1938-1328, Vol. 82, nr 4, s. 645-651Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Learning quality depends on the assessment methods used, as well as other factors. By choosing adequate assessments and involving students in the process of learning, students can gain a deeper understanding of the content and its context while developing related skills. In this study we describe a practical university-level biochemistry course that focuses on understanding protein separation and analysis techniques and especially on their application. The course was designed to examine the effects of a strategic use of differentassessment methods and an analysis of the resulting outcomes. We used quantitative as well as qualitative methods, including a simplified variant of the Bloom taxonomy, statistical methods, principle component analysis, inquires, and interviews. We conclude that astrategic choice of assessments and instructional design can be used to achieve morecomplex learning. We did not find any single teaching or assessment method to be clearly the best for enhancing higher-order thinking or achieving all learning objectives; rather a combination of different methods (i.e., a strategic choice) seems the best approach.

  • 293.
    Bergfors, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Evaluation of Microsatellite Instability Analysis as a Diagnostic Tool to Identify Lynch Syndrome in Endometrial Cancer Patients2014Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Hereditary endometrial cancer (EC) is a Lynch syndrome (LS) related cancer variant and 2-10% of all EC are hereditary. The aim of this study was to develop a method for analysis of microsatellite instability (MSI) as such analysis would assist in identifying potential LS patients with EC at an early state of their disease, before a possible second cancer is developed in another organ.

    Twenty-six patients with adenocarcinoma in the endometrium, diagnosed at Uppsala University Hospital in Sweden between 1993 and 2012, were included in the study. Seven of these patients were also diagnosed with LS and the rest were sporadic EC. DNA was extracted from the patients’ formalin-fixed and paraffin-embedded tissues. The extracted DNA was subjected to a multiplex PCR with fluorescently labelled primers and then analysed by using capillary electrophoresis.

    Of the sporadic EC, 26% was MSI-High, which correlates well with published data. Of the LS patients, 83% was MSI-High. The outcome of this project resulted in that MSI analysis is now a validated and established method used in the process of identifying potential LS among patients with EC.

  • 294.
    Berggren, Kevin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Metodvalidering av IGF-1 med ECLIA på Cobas e601 system2019Independent thesis Advanced level (professional degree), 10 poäng / 15 hpOppgave
  • 295.
    Bergkvist, Liza
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Amyloid-β and lysozyme proteotoxicity in Drosophila: Beneficial effects of lysozyme and serum amyloid P component in models of Alzheimer’s disease and lysozyme amyloidosis2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In the work presented this thesis, two different conditions that are classified as protein misfolding diseases: Alzheimer's disease and lysozyme amyloidosis and proteins that could have a beneficial effect in these diseases, have been studied using Drosophila melanogaster, commonly known as the fruit fly. The fruit fly has been used for over 100 years to study and better understand fundamental biological processes. Although the fruit fly, unlike humans, is an invertebrate, many of its central biological mechanisms are very similar to ours. The first transgenic flies were designed in the early 1980s, and since then, the fruit fly has been one of the most widely used model organisms in studies on the effects of over-expressed human proteins in a biological system; one can regard the fly as a living, biological test tube. For  most proteins, it is necessary that they fold into a three-dimensional structure to function properly. But sometimes the folding goes wrong; this may be due to mutations that make the protein unstable and subject to misfolding. A misfolded protein molecule can then aggregate with other misfolded proteins. In Alzheimer's disease, which is the most common form of dementia, protein aggregates are present in the brains of patients. These aggregates are composed of the amyloid-β (Aβ) peptide, a small peptide of around 42 amino acids which is cleaved from the larger, membrane-bound, protein AβPP by two different enzymes, BACE1 and γ-secretase. In the first part of this thesis, two different fly models for Alzheimer’s disease were used: the Aβ fly model, which directly expresses the Aβ peptide, and the AβPP-BACE1 fly model, in which all the components necessary to produce the Aβ peptide in the fly are expressed in the fly central nervous system (CNS). The two different fly models were compared and the results show that a significantly smaller amount of the Aβ peptide is needed to achieve the same, or an even greater, toxic effect in the AβPP-BACE1 model compared to the Aβ model. In the second part of the thesis, these two fly models for Alzheimer’s disease were again used, but now to investigate whether lysozyme, a protein involved in our innate immune system, can counteract the toxic effect of Aβ generated in the fly models. And indeed, lysozyme is able to save the flies from Aβ-induced toxicity. Aβ and lysozyme were found to interact with each other in vivo. The second misfolding disease studied in this thesis is lysozyme amyloidosis. It is a rare, dominantly inherited amyloid disease in which mutant variants of lysozyme give rise to aggregates, weighing up to several kilograms, that accumulate around the kidneys and liver, eventually leading to organ failure. In the third part of this thesis, a fly model for lysozyme amyloidosis was used to study the effect of co-expressing the serum amyloid P component (SAP), a protein that is part of all protein aggregates found within this disease class. SAP is able to rescue the toxicity induced by expressing the mutant variant of lysozyme, F57I, in the fly's CNS. To further investigate how SAP was able to do this, double-expressing lysozyme flies, which exhibit stronger disease phenotypes than those of the single-expressing lysozyme flies previously studied, were used in the fourth part of this thesis. SAP was observed to reduce F57I toxicity and promote F57I to form aggregates with more distinct amyloid characteristics. In conclusion, the work included in this thesis demonstrates that: i) Aβ generated from AβPP processing in the fly CNS results in higher proteotoxicity compared with direct expression of Aβ from the transgene, ii) lysozyme can prevent Aβ proteotoxicity in Drosophila and could thus be a potential therapeutic molecule to treat Alzheimer’s disease and iii) in a Drosophila model of lysozyme amyloidosis, SAP can prevent toxicity from the disease-associated lysozyme variant F57I and promote formation of aggregated lysozyme morphotypes with amyloid properties; this is important to take into account when a reduced level of SAP is considered as a treatment strategy for lysozyme amyloidosis.

  • 296.
    Bergkvist, Liza
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Sandin, Linnea
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Brorsson, Ann-Christin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    A beta PP processing results in greater toxicity per amount of A beta(1-42) than individually expressed and secreted A beta(1-42) in Drosophila melanogaster2016Inngår i: BIOLOGY OPEN, ISSN 2046-6390, Vol. 5, nr 8, s. 1030-1039Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aggregation of the amyloid-beta (A beta) peptide into fibrillar deposits has long been considered the key neuropathological hallmark of Alzheimers disease (AD). A beta peptides are generated from proteolytic processing of the transmembrane A beta precursor protein (A beta PP) via sequential proteolysis through the beta-secretase activity of beta-site A beta PP-cleaving enzyme (BACE1) and by the intramembranous enzyme gamma-secretase. For over a decade, Drosophila melanogaster has been used as a model organism to study AD, and two different approaches have been developed to investigate the toxicity caused by AD-associated gene products in vivo. In one model, the A beta peptide is directly over-expressed fused to a signal peptide, allowing secretion of the peptide into the extracellular space. In the other model, human A beta PP is co-expressed with human BACE1, resulting in production of the A beta peptide through the processing of A beta PP by BACE1 and by endogenous fly gamma-secretase. Here, we performed a parallel study of flies that expressed the A beta(1-42) peptide alone or that co-expressed A beta PP and BACE1. Toxic effects (assessed by eye phenotype, longevity and locomotor assays) and levels of the A beta(1-42), A beta(1-40) and A beta(1-38) peptides were examined. Our data reveal that the toxic effect per amount of detected A beta(1-42) peptide was higher in the flies co-expressing A beta PP and BACE1 than in the A beta(1-42)-expressing flies, and that the co-existence of A beta(1-42) and A beta(1-40) in the flies co-expressing A beta PP and BACE1 could be of significant importance to the neurotoxic effect detected in these flies. Thus, the toxicity detected in these two fly models seems to have different modes of action and is highly dependent on how and where the peptide is generated rather than on the actual level of the A beta(1-42) peptide in the flies. This is important knowledge that needs to be taken into consideration when using Drosophila models to investigate disease mechanisms or therapeutic strategies in AD research.

  • 297.
    Berglin, Lena
    Högskolan i Borås, Institutionen Textilhögskolan.
    Interactive Textile Structures: Creating Multifunctional Textiles based on Smart Materials2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Textiles of today are materials with applications in almost all our activities. We wear clothes all the time and we are surrounded with textiles in almost all our environments. The integration of multifunctional values in such a common material has become a special area of interest in recent years. Smart Textile represents the next generation of textiles anticipated for use in several fashion, furnishing and technical textile applications. The term smart is used to refer to materials that sense and respond in a pre-defined manner to environmental stimuli. The degree of smartness varies and it is possible to enhance the intelligence further by combining these materials with a controlling unit, for example a microprocessor. As an interdisciplinary area Smart Textile includes design spaces from several areas; the textile design space, the information technology design space and the design space of material science. This thesis addresses how Smart Textiles affect the textile design space; how the introduction of smart materials and information technology affects the creation of future textile products. The aim is to explore the convergence between textiles, smart materials and information technology and to contribute to providing a basis for future research in this area. The research method is based on a series of interlinked experiments designed through the research questions and the research objects. The experiments are separated into two different sections: interactive textile structures and health monitoring. The result is a series of basic methods for how interactive textile structures are created and a general system for health monitoring. Furthermore the result consists of a new design space, advanced textile design. In advanced textile design the focus is set on the relation between the different natures of a textile object: its physical structure and its structure in the context of design and use.

  • 298.
    Berglund, Anna-Karin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Dual Targeting of Proteins to Mitochondria and Chloroplasts2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The vast majority of mitochondrial and chloroplastic proteins are nuclear encoded, synthesized in the cytosol and imported into the respective organelle using an N-terminal extension, the targeting peptide (TP). After import into the organelle, the TP is cleaved off and degraded by the Presequence protease (PreP). The import process is thought to be highly specific, however there is a group of proteins that are localised to both mitochondria and chloroplasts, using an ambiguous, dual targeting peptide (dTP). The aim of this thesis was to investigate targeting properties of dTPs. Analysis of the amino acid content of all currently known dually targeted proteins revealed that the dTPs are enriched in hydroxylated, hydrophobic and positively charged residues, lacking acidic residues, whereas the content of serine, arginine and proline is intermediary in comparison to the mitochondrial and chloroplastic TPs. dTPs do not form amphiphilic a-helices, characteristic of the mitochondrial TPs, but the helical structure can be induced in membrane mimetic environment, as revealed by spectroscopic studies of a dTP of an aminoacyl- tRNA-synthetase (aaRS). In vitro and in vivo import experiments of fusion constructs containing N-terminal truncations of seven aaRS-dTPs coupled to green fluorescent protein (GFP) demonstrated different organisation of targeting determinants showing that the N-terminal portion of dTPs was crucial for import into both organelles or at least one organelle for different constructs. In addition, studies of targeting capacity of the TPs of PreP homologues from plant, mammal and yeast (AtPreP, hPreP and Mop112) showed species dependent intra-mitochondrial localisation of the coupled GFP and demonstrated functional complementation of an intermembrane space located Mop112 with a matrix located AtPreP. The studies presented here contribute to understanding of the intracellular and intra-mitochondrial sorting process of proteins in the eukaryotic cell.

  • 299. Berglund, Elias
    The effects of probiotics on sleep and fatty acids2014Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [en]

    Probiotics are dietary supplements that contain bacteria that are potentially beneficial for the intestinal flora. The positive effects of probiotics are however not limited to the intestine. The use of probiotics is becoming more and more common and therefore needs to be studied more closely.The purpose of this study is to see how healthy individuals, in the age between 18 and 28 years old and with a BMI between 20 and 25, respond to the probiotic LactiPlus (also called FF8).Blood samples were collected before and after the subjects have eaten a standardized meal. The subject´s glucometabolic responses to food, sleep patterns and their fatty acid profile was analyzed in relation to the probiotic composition.Due to difficulties including study subjects, three subject completed the participation in the study. The three study subjects had similar sleeping habits, one had slightly higher fruit intake, the word and number memory were similar, but it was not possible to relate any data to the use of probiotics. It can be summarized that inclusion additional study subjects is needed.

  • 300.
    Berglund, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Pollard, Katherine S.
    Webster, Matthew T.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Hotspots of biased nucleotide substitutions in human genes2009Inngår i: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 7, nr 1, s. e26-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genes that have experienced accelerated evolutionary rates on the human lineage during recent evolution are candidates for involvement in human-specific adaptations. To determine the forces that cause increased evolutionary rates in certain genes, we analyzed alignments of 10,238 human genes to their orthologues in chimpanzee and macaque. Using a likelihood ratio test, we identified protein-coding sequences with an accelerated rate of base substitutions along the human lineage. Exons evolving at a fast rate in humans have a significant tendency to contain clusters of AT-to-GC (weak-to-strong) biased substitutions. This pattern is also observed in noncoding sequence flanking rapidly evolving exons. Accelerated exons occur in regions with elevated male recombination rates and exhibit an excess of nonsynonymous substitutions relative to the genomic average. We next analyzed genes with significantly elevated ratios of nonsynonymous to synonymous rates of base substitution (dN/dS) along the human lineage, and those with an excess of amino acid replacement substitutions relative to human polymorphism. These genes also show evidence of clusters of weak-to-strong biased substitutions. These findings indicate that a recombination-associated process, such as biased gene conversion (BGC), is driving fixation of GC alleles in the human genome. This process can lead to accelerated evolution in coding sequences and excess amino acid replacement substitutions, thereby generating significant results for tests of positive selection.

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