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  • 151.
    Arabi, Thyba
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Cajal cellernas roll i mag-tarm komplikationer hos patienter med transtyretin amyloidos2017Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 152. Arenz, Stefan
    et al.
    Abdelshahid, Maha
    Sohmen, Daniel
    Payoe, Roshani
    Starosta, Agata L.
    Berninghausen, Otto
    Hauryliuk, Vasili
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). University of Tartu, Institute of Technology, Tartu, Estonia.
    Beckmann, Roland
    Wilson, Daniel N.
    The stringent factor RelA adopts an open conformation on the ribosome to stimulate ppGpp synthesis2016Inngår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 44, nr 13, s. 6471-6481Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Under stress conditions, such as nutrient starvation, deacylated tRNAs bound within the ribosomal A-site are recognized by the stringent factor RelA, which converts ATP and GTP/GDP to (p)ppGpp. The signaling molecules (p) ppGpp globally rewire the cellular transcriptional program and general metabolism, leading to stress adaptation. Despite the additional importance of the stringent response for regulation of bacterial virulence, antibiotic resistance and persistence, structural insight into how the ribosome and deacylated-tRNA stimulate RelA-mediated (p)ppGpp has been lacking. Here, we present a cryo-EM structure of RelA in complex with the Escherichia coli 70S ribosome with an average resolution of 3.7 angstrom and local resolution of 4 to > 10 angstrom for RelA. The structure reveals that RelA adopts a unique 'open' conformation, where the C-terminal domain (CTD) is intertwined around an A/T-like tRNA within the intersubunit cavity of the ribosome and the N-terminal domain (NTD) extends into the solvent. We propose that the open conformation of RelA on the ribosome relieves the autoinhibitory effect of the CTD on the NTD, thus leading to stimulation of (p)ppGpp synthesis by RelA.

  • 153. Arfvidsson, Berndt
    et al.
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Norgren, Lars
    S100B concentrations increase perioperatively in jugular vein blood despite limited metabolic and inflammatory response to clinically uneventful carotid endarterectomy2015Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 53, nr 1, s. 111-117Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Our aim was to test the hypothesis that metabolic and inflammatory responses of the brain perioperatively during carotid endarterectomy (CEA) might affect blood brain barrier (BBB) integrity. Methods: Twenty patients with >70% stenosis of internal carotid artery (ICA) were prospectively included. Surgery was performed under general anaesthesia. Blood was sampled from ipsilateral internal jugular vein and radial artery: just before, during, and after ICA clamping S100B protein, glucose, lactate, 20 amino acids, and key cytokines were analysed. Results: Jugular vein S100B increased during clamping and reperfusion, while a marginal systemic increase was recorded, unrelated to stump pressure during clamping. Glucose increased during clamping in jugular vein blood and even more systemically, while jugular lactate values were higher than systemic values initially. Most amino acids did not differ significantly between jugular vein and systemic levels: glutamic acid and aspartic acid decreased during surgery while asparagine increased. Jugular vein interleukin (IL)-6 showed a transient non-significant increase during clamping and decreased systemically. IL-8 and IL-10 increased over time. Conclusions: Rising jugular vein S100B concentrations indicated reduced BBB integrity, and marginal secondary increase of S100B systemically. Limited ischaemic effects on the brain during cross-clamping, unrelated to S100B concentrations, were confirmed by lower brain glucose levels and higher lactate levels than in systemic blood. The lack of increased jugular vein glutamic acid disproves any major ischaemic brain injury following CEA. The inflammatory response was limited, did not differ greatly between jugular and systemic blood, and was unrelated to S100B.

  • 154.
    Arinell, Karin
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Acute Internal Medicine, Centralsjukhuset, Karlstad, Sweden.
    Blanc, Stéphane
    CNRS UMR 7178, Institut Pluridisciplinaire Hubert Curien, Université de Strasbourg, Strasbourg, France.
    Welinder, Karen Gjesing
    Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark.
    Støen, Ole Gunnar
    Norwegian Institute for Nature Research, Trondheim, Norway.
    Evans, Alina L.
    Department of Forestry and Wildlife Management, Inland Norway University of Applied Sciences, Koppang, Norway.
    Fröbert, Ole
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Physical inactivity and platelet function in humans and brown bears: A comparative study2018Inngår i: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 29, nr 1, s. 87-90Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Physical inactivity increases the risk of thromboembolism. However, good standardized human models on inactivity are in short supply and experimental models are few.

    Our objective was to investigate how standardized bed rest affects platelet aggregation in humans and to investigate if aggregation is altered in a translational model system - the hibernating brown bear (Ursus arctos). We collected blood from (1) healthy male volunteers participating in a 21-day bed rest study in head-down tilt position (-6°) 24 h a day; (2) free-ranging brown bears captured during winter hibernation and again during active state in summer. We analyzed platelet function using multiple electrode platelet aggregometry. In total, 9 healthy male volunteers (age 31.0 ± 6.4 years) and 13 brown bears (7 females and 6 males, age 2.8 ± 0.6 years) were included. In hibernating bears adenosine diphosphate, arachidonic acid, thrombin receptor activating peptide, and collagen impedance aggregometry tests were all halved compared to summer active state. In human volunteers no statistically significant changes were found between baseline and the end of bed rest. In human male volunteers 3 weeks of bed rest did not affect platelet function. In hibernating brown bears platelet aggregation was halved compared to summer and we hypothesize that this is a protective measure to avoid formation of thrombi under periods of low blood flow.

  • 155.
    Armulik, Annika
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Studies on the transmembrane signaling of β1 integrins2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Integrins are heterodimeric cell surface receptors, composed of an α and a β subunit, mainly binding for extracellular matrix proteins. lntegrin subunit β1 can combine with at least 12 a subunits and thus form the biggest subfamily within the integrin family. In this thesis, functional properties of the splice variant β1Β, and the effects of several mutations in the cytoplasmic tail of integrin subunit β1Α were studied. In addition, the border between the transmembrane and cytoplasmic domains of several integrin subunits was determined.

    The β1Β splice variant has been reported to have a dominant negative effect on functions of β1Α integrins. In this study, it was studied if the expression of β1Β had similar negative effects on the αvβ3 integrin functions since the β3 subunit is structurally similar to β1Α. The β1Β subunit was expressed in an integrin β1-deficient cell line and it was found that the presence of β1Β does not interfere with adhesion or signaling of endogenous αvβ3

    The border between the cytoplasmic domain and the C-terminal end of the transmembrane domain of integrin α and β subunits has been unclear. This question was experimentally addressed for integrin subunits β1, β2, α2 and α5. It was found that integrin subunits contain a positively charged lysine, which is embedded in the membrane in the absence of interacting proteins.

    The functional importance of the lysine in integrin transmembrane domains was investigated by mutating this amino acid to leucine in β1Α. The mutation affected cell spreading and tyrosine phosphorylation of the adapter protein CAS. The activation of focal adhesion kinase and tyrosine phosphorylation of paxillin was not affected. Furthermore, the mutation of two tyrosines to phenylalanines in the β1Α cytoplasmic tail was found to reduce the capability of β1Α integrins to mediate cell spreading and migration. Activation of focal adhesion kinase in response to the later β1Α mutant was shown to be impaired as well as tyrosine phosphorylation of adapter proteins paxillin and tensin whereas overall tyrosine phosphorylation of CAS was unaffected. These data suggests the presence of focal adhesion kinase-dependent and -independent pathways for tyrosine phosphorylation of CAS after integrin β1Α-mediated adhesion.

  • 156.
    Arndt, Anton
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Laboratoriet för biomekanik och motorisk kontroll (BMC).
    The evolution of running shoes2012Konferansepaper (Annet vitenskapelig)
  • 157.
    Arndt, Anton
    et al.
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Laboratoriet för biomekanik och motorisk kontroll (BMC).
    Lundgren, Paul
    Liu, Anmin
    Nester, Christopher
    Maiwald, Christian
    Jones, Richard
    Lundberg, Arne
    The effect of a midfoot cut in the outer sole of a shoe on intrinsic foot kinematics during walking.2013Inngår i: Footwear Science, ISSN 1942-4280, Vol. 5, nr 1, s. 63-69Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Modifications in shoe outer soles are frequently made with the intention of altering biomechanics of the foot inside the shoe. These modifications are however, generally based upon intuition with little or no scientific data for support. The purpose of this study was to quantify changes in intrinsic foot segmental kinematics between walking in a neutral shoe and a shoe modified with a clear cut forming a break underneath the midfoot, approximating the Lisfrancs joint.

    Five healthy male subjects participated in the study. Intracortical pins were inserted under sterile conditions and local anaesthetic in nine different bones of the foot and shank. The subjects performed 10 walking trials in both a neutral, standard, flatsoled, flexible walking shoe and in the same shoe with an approximately 1 cm deep cut aligned with the subjects’ Lisfrancs joint. Material tests showed that the cut reduced midfoot shoe bending stiffness by 23% to 38% and torsional stiffness by 23% to 28%. A helical axis approach was applied for calculating the 3D rotations about relevant joints.

    Kinematic trajectories in the sagittal, frontal, and transverse planes were normalised to the stance phase for seven selected joints to compare rotation patterns when wearing the two shoe conditions. Although one out of 21 ranges of motion (ROM) showed a significant difference, there is strong reason to regard this as the result of a type 1 error. Apart from this no differences in ROM occurred between the shoe conditions.

    The low subject number reduced the statistical power of the results. However, the study indicated that outer sole modifications that may be assumed to have clear effects upon foot kinematics, do not necessarily do so.

  • 158.
    Arnqvist, Jennifer
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Optimering av lymfocytfraktionering med AutoMACS Pro för biobankning av hematologiska maligniteter2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 159.
    Aronsson, Anna
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Genetisk modifiering och kloning av coxsackievirus B5 Dalldorf2012Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 160.
    Aronsson, Christopher
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Tunable and modular assembly of polypeptides and polypeptide-hybrid biomaterials2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Biomaterials are materials that are specifically designed to be in contact with biological systems and have for a long time been used in medicine. Examples of biomaterials range from sophisticated prostheses used for replacing outworn body parts to ordinary contact lenses. Currently it is possible to create biomaterials that can e.g. specifically interact with cells or respond to certain stimuli. Peptides, the shorter version of proteins, are excellent molecules for fabrication of such biomaterials. By following and developing design rules it is possible to obtain peptides that can self-assemble into well-defined nanostructures and biomaterials.

    The aim of this thesis is to create ”smart” and tunable biomaterials by molecular self-assembly using dimerizing –helical polypeptides. Two different, but structurally related, polypeptide-systems have been used in this thesis. The EKIV-polypeptide system was developed in this thesis and consists of four 28-residue polypeptides that can be mixed-and-matched to self-assemble into four different coiled coil heterodimers. The dissociation constant of the different heterodimers range from μM to < nM. Due to the large difference in affinities, the polypeptides are prone to thermodynamic social self-sorting. The JR-polypeptide system, on the other hand, consists of several 42-residue de novo designed helix-loop-helix polypeptides that can dimerize into four-helix bundles. In this work, primarily the glutamic acid-rich polypeptide JR2E has been explored as a component in supramolecular materials. Dimerization was induced by exposing the polypeptide to either Zn2+, acidic conditions or the complementary polypeptide JR2K.

    By conjugating JR2E to hyaluronic acid and the EKIV-polypeptides to star-shaped poly(ethylene glycol), respectively, highly tunable hydrogels that can be self-assembled in a modular fashion have been created. In addition, self-assembly of spherical superstructures has been investigated and were obtained by linking two thiol-modified JR2E polypeptides via a disulfide bridge in the loop region. ŒThe thesis also demonstrates that the polypeptides and the polypeptide-hybrids can be used for encapsulation and release of molecules and nanoparticles. In addition, some of the hydrogels have been explored for 3D cell culture. By using supramolecular interactions combined with bio-orthogonal covalent crosslinking reactions, hydrogels were obtained that enabled facile encapsulation of cells that retained high viability.

    The results of the work presented in this thesis show that dimerizing α–helical polypeptides can be used to create modular biomaterials with properties that can be tuned by specific molecular interactions. The modularity and the tunable properties of these smart biomaterials are conceptually very interesting andmake them useful in many emerging biomedical applications, such as 3D cell culture, cell therapy, and drug delivery

    .

  • 161.
    Aronsson, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Local Delivery of Bisphosphonates from FibMat Matrix2008Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    Improving the functionality and reducing revision rates are important driving forces in the development of orthopaedic implants. FibMat is a fibrinogen based matrix developed towards commercialisation by the company Optovent AB. This matrix can be coated on implants and act as a local drug delivery system for bisphosphonates (BPs). BPs are drugs inhibiting bone resorption, and applied with FibMat to improve stability of implants in bone, e.g. when fixing bone fractures. In this thesis, FibMat loaded with BP (FibMat/BP) was coated on stainless-steel screws and titanium screws in order to investigate some technology properties relevant to its clinical applicability. Bone-mimicking materials were used to study scrape-off effect upon insertion. The coagulation properties of fibrinogen as well as the structural properties of BPs were studied after exposure to gamma radiation.

    The screws were coated with FibMat and BP (alendronate and 14C-alendronate) using standard coupling techniques. The total amount and distribution of BP after insertion was measured by liquid scintillation and autoradiography. Coagulation assays were performed in order to determine the coagulation properties of fibrinogen, exposed to doses up to 35 kGy, mixed with thrombin. The structural properties of four different BPs (alendronate, pamidronate, zoledronate and ibandronate), exposed to doses up to 35 kGy were analysed by transmission infrared spectroscopy.

    The results show that FibMat/BP coating on porous stainless-steel screws is virtually unaffected by insertion into bone materials. The anodised, planar titanium screws are more affected by the insertion process, but an even BP distribution in the cancellous material is indicated. The coagulation assays show that gamma-irradiated fibrinogen has a slower coagulation process compared to non-irradiated fibrinogen and form interrupted network unable to clot. The chemical structures of the BPs seem unaffected by exposure to gamma irradiation. In conclusion, the FibMat/BP is a promising technology for local distribution of BP in conjunction with bone implants.

  • 162.
    Aronsson, Per
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Method Development: Quantitative Determination of Polysorbate 80 in Gammanorm® and Poloxamer 188 in Octagenate® Using Hydrophilic Interaction Liquid Chromatography Coupled with Evaporative Light Scattering Detection2012Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Polysorbate 80 (PS80) and Poloxamer 188 (P188) are non-ionic detergents used as surfactants in the injection fluids Gammanorm® (human immunoglobulin) and Octagenate® (recombinant human factor VIII) respectively.PS80 in Gammanorm® is currently quantified using a spectrophotometric method based on complexation with ammonium cobalt(II)-thiocyanate after a protein precipitation step with ethanol (T-603). Highly questionable performance of T-603 has led to the development of an analysis method based on hydrophilic interaction liquid chromatography (HILIC) with evaporative light scattering detection (ELSD). P188 in Octagenate® is currently quantified using HILIC-ELSD (Q-726), but recent problems with peak broadening, signal saturation and insufficient resolution have caused Q-726 to be placed on hold.The aim of this work was to solve the problems connected with Q-726, an analysis method for the quantitative determination of P188 in Octagenate®, and to develop a new analysis method for the quantitative determination of PS80 in Gammanorm® based on HILIC-ELSD.Optimization of ELSD parameters and increased water content in the mobile phase, proved effective in solving the problems with the analysis of P188. The lack of reproducible ethanol injections without interfering peaks prevented further advancement of the PS80 method development. Good results from analysis of standard injections of PS80 between 1 and 10 ppm in the PS80 method were obtained with good correlation (R2 > 0.99). The obtained results, in combination with a recently published article, describing a quantitative determination of PS80 in therapeutic protein formulations based on HPLC-ELSD, indicates potential for this method and further analysis should be performed to validate whether or not the method development is to be continued.

  • 163.
    Aronsson, Ulrika
    Örebro universitet, Institutionen för hälsovetenskaper.
    Metodutvärdering och mervärde av Treponema pallidum IgM analys vid diagnostik av syfilis2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 164.
    Arponen, Omar
    Högskolan Kristianstad, Fakulteten för naturvetenskap.
    Realtids-PCR för påvisande av plasmidburen ampicillinresistens: Kartläggning av förekomst i vattenisolat från Helge Å, Kristianstad2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    The antibiotic class β-lactams include drugs such as penicillins, cephalosporines, carbapenems and monobactams which mechanism of action is to inhibit cell-wall synthesis. Bacteria have developed several mechanisms to counter β-lactams. Bacteria can defend themselves from antibiotics by releasing enzymes that attack the antibiotic compound itself by hydrolysis, target alteration or redox reactions. Presence of antibiotics can also trigger a downregulation of genes coding for antibiotic binding proteins, as well as upregulation of proteins that serves as channel and pump proteins that ensure no accumulation of antibiotics occurs in the cytosol. The aim with the study was to investigate the presence of three plasmid-mediated genes (blaFOX, blaCIT(CMY-2) and blaMOX) coding for ampicillin resistance (pAmpC) in water isolates sampled from Helge River, Kristianstad. The detection of genes was done according to a previous optimized protocol for Real-Time PCR with SYBR™Green chemistry (duplex blaCIT(CMY-2)/blaMOX and singleplex blaFOX). The method proved not to be robust for multiplex PCR, only the singelplex for the gene blaFOX could produce valid results. 30 of 96 isolates were deemed as positive for the gene, whereas 27 of 79 were considered clinical relevant. Among the 27 isolates, 16 also harbored other genes for resistance (13 blaCTX-M, 2 blaOXA, 1 blaTEM and 1 blaSHV). One isolate carried on three resistancegenes (blaFOX, blaCTX-M och blaTEM). A majority of the positive isolates, 20 out of 27, were sampled near the pumpstation. The findings indicate that Helge river might be a reservoir for dissemination of antibiotic resistance genes.

  • 165. Arsov, S.
    et al.
    Trajceska, L.
    van Oeveren, W.
    Smit, A. J.
    Vidimliski, P. Dzekova
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sikole, A.
    Rakhorst, G.
    Graaff, R.
    The use of a skin age reader to evaluate risk of cvd and mortality in dialysis patients2011Inngår i: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 34, nr 8, s. 606-606Artikkel i tidsskrift (Annet vitenskapelig)
  • 166. Arsov, Stefan
    et al.
    Graaff, Reindert
    van Oeveren, Wim
    Stegmayr, Bernd
    Sikole, Aleksandar
    Rakhorst, Gerhard
    Smit, Andries J.
    Advanced glycation end-products and skin autofluorescence in end-stage renal disease: a review2014Inngår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 52, nr 1, SI, s. 11-20Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality; hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are so-called uremic toxins. These include advanced glycation end-products (AGE). AGE levels are markedly increased in CKD patients not only because of impaired excretion but also because of increased production. AGE formation has initially been described as a non-enzymatic reaction between proteins and glucose in the so-called Maillard reaction, but they are also more rapidly formed during oxidative stress and subsequent formation of reactive carbonyl compounds like (methyl) glyoxal. AGE accumulate in tissue where they cross-link with proteins, e. g., collagen, inducing tissue stiffening of blood vessels and skin. They may also interact with receptor of AGE (RAGE) and other receptors, which lead to activation of intracellular transduction mechanisms resulting in cytokine release and further tissue damage in CKD. The accumulation of AGE in the skin can be measured non-invasively using autofluorescence. The skin autofluorescence is a strong marker of cardiovascular mortality in CKD. The focus of this review is on the role of tissue and plasma AGE, and of skin autofluorescence as a proxy of tissue AGE accumulation, in the increase in cardiovascular disease in end stage renal disease (ESRD). This review will also present the possibility of reducing the AGE accumulation in ESRD patients using the following five methods: 1) use of low AGE peritoneal dialysis solutions; 2) use of advanced hemodialysis techniques; 3) use of AGE reducing drugs; 4) optimizing the nutrition of hemodialysis patients; and 5) renal transplantation.

  • 167. Arsov, Stefan
    et al.
    Trajceska, Lada
    van Oeveren, Wim
    Smit, Andries J
    Dzekova, Pavlina
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sikole, Aleksandar
    Rakhorst, Gerhard
    Graaff, Reindert
    Increase in skin autofluorescence and release of heart-type fatty acid binding protein in plasma predicts mortality of hemodialysis patients2013Inngår i: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 37, nr 7, s. E114-E122Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Advanced glycation end-products (AGEs) are uremic toxins that accumulate progressively in hemodialysis (HD) patients. The aim of this study was to assess the 1-year increase in skin autofluorescence (DAF), a measure of AGEs accumulation and plasma markers, as predictors of mortality in HD patients. One hundred sixty-nine HD patients were enrolled in this study. Skin autofluorescence was measured twice, 1 year apart using an AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands). Besides routine blood chemistry, additional plasma markers including superoxide dismutase, myeloperoxydase, intercellular adhesion molecule 1 (ICAM-1), C-reactive protein (hs-CRP), heart-type fatty acid binding protein (H-FABP), and von Willebrand factor were measured at baseline. The mortality of HD patients was followed for 36 months. Skin autofluorescence values of the HD patients at the two time points were significantly higher (P < 0.001) than those of healthy subjects of the same age. Mean 1-year DAF of HD patients was 0.16 +/- 0.06, which was around seven-to ninefold higher than 1-year DAF in healthy subjects. Multivariate Cox regression showed that age, hypertension, 1-year DAF, hs-CRP, ICAM-1, and H-FABP were independent predictors of overall mortality. Hypertension, 1-year DAF, hs-CRP, and H-FABP were also independent predictors of cardiovascular mortality. One-year DAF and plasma H-FABP, used separately and in combination, are strong predictors of overall and cardiovascular mortality in HD patients.

  • 168.
    Arvidsson, Malin
    et al.
    Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för naturvetenskap och biomedicin.
    Li, Sabina
    Högskolan i Jönköping, Hälsohögskolan, HHJ, Avd. för naturvetenskap och biomedicin.
    Prevalens av Anaplasma phagocytophilum i fästingar avlägsnade från flyttfåglar vid Ottenby fågelstation, Öland2017Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Anaplasma phagocytophilum är en obligat intracellulär bakterie som nyttjar fästingar som vektor för sin spridning till nya värdar. Den kan orsaka fästingfeber hos djur samt human granulocytär anaplasmos. Eftersom bakterien påverkar immunförsvarets celler bidrar den till att infekterade djur och människor lättare blir mottagliga för sekundära infektioner, vilket medför stora konsekvenser inom bland annat fåruppfödning. Syftet med studien var att undersöka prevalens av bakterien A. phagocytophilum i hårda fästingar inom familjen Ixodidae avlägsnade från flyttfåglar vid Ottenby fågelstation på Öland. 1115 fästingar från 4778 fåglar screenades för förekomst av genen Anaplasma-citratsyntas (gltA) med realtids-PCR. Tio fästingar var positiva för bakterien A. phagocytophilum, en prevalens på 0,9 %. Två av dem var fästingar i larvstadiet, sju i nymfstadiet och en med okänt utvecklingsstadium. Larverna blev troligen infekterade av fåglarna de avlägsnades ifrån, då dessa var fästingarnas första värdar. De positiva fästingarna plockades från fåglarna koltrast, rödhake, lövsångare och trädpiplärka. Koltrast visade en signifikant högre prevalens av A. phagocytophilum (4,8 %) än rödhake, den fågelart som bar på flest fästingar. Studiens resultat stöder uppfattningen om att fåglar har en roll i spridningen av fästingburna patogener.

  • 169.
    Asaei, Ava
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Effekten av interleukin-6, interleukin-17 och kombinationen av dessa på inflammatoriskt svar i humana endotelceller2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 170. Asan, Noor Badariah
    et al.
    Noreland, Daniel
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Hassan, Emadeldeen
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap. Department of Electronics and Electrical Communications, Menoufia University, Menouf, Egypt.
    Shah, Syaiful Redzwan Mohd
    Rydberg, Anders
    Blokhuis, Taco J.
    Carlsson, Per-Ola
    Voigt, Thiemo
    Augustine, Robin
    Intra-body microwave communication through adipose tissue2017Inngår i: Healthcare technology letters, E-ISSN 2053-3713, Vol. 4, nr 4, s. 115-121Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The human body can act as a medium for the transmission of electromagnetic waves in the wireless body sensor networks context. However, there are transmission losses in biological tissues due to the presence of water and salts. This Letter focuses on lateral intra-body microwave communication through different biological tissue layers and demonstrates the effect of the tissue thicknesses by comparing signal coupling in the channel. For this work, the authors utilise the R-band frequencies since it overlaps the industrial, scientific and medical radio (ISM) band. The channel model in human tissues is proposed based on electromagnetic simulations, validated using equivalent phantom and ex-vivo measurements. The phantom and ex-vivo measurements are compared with simulation modelling. The results show that electromagnetic communication is feasible in the adipose tissue layer with a low attenuation of approximate to 2 dB per 20 mm for phantom measurements and 4 dB per 20 mm for ex-vivo measurements at 2 GHz. Since the dielectric losses of human adipose tissues are almost half of ex-vivo tissue, an attenuation of around 3 dB per 20 mm is expected. The results show that human adipose tissue can be used as an intra-body communication channel.

  • 171.
    Ashri, Nadia Y.
    et al.
    Najd Consulting Hosp, Riyadh, Saudi Arabia..
    Abdel-Rehim, Mohamed
    Karlstads universitet, Fakulteten för teknik- och naturvetenskap, Avdelningen för kemi och biomedicinsk vetenskap. AstraZeneca R&D Sodertalje, Clin Pharmacol, SE-15185 Sodertalje, Sweden.;AstraZeneca R&D Sodertalje, DMPK, SE-15185 Sodertalje, Sweden.;Karlstad Univ, Dept Chem & Biomed Sci, SE-65188 Karlstad, Sweden.;Stockholm Univ, Dept Analyt Chem, SE-10691 Stockholm, Sweden..
    Sample treatment based on extraction techniques in biological matrices2011Inngår i: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 3, nr 17, s. 2003-2018Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The importance of sample preparation methods as the first stage in bioanalysis is described. In this article, the sample preparation concept and strategies will be discussed, along with the requirements for good sample preparation. The most widely used sample preparation methods in the pharmaceutical industry are presented; for example, the need for same-day rotation of results from large numbers of biological samples in pharmaceutical industry makes high throughput bioanalysis more essential. In this article, high-throughput sample preparation techniques are presented; examples are given of the extraction and concentration of analytes from biological matrices, including protein precipitation, solid-phase extraction, liquid-liquid extraction and microextraction-related techniques. Finally, the potential role of selective extraction methods, including molecular imprinted phases, is considered.

  • 172.
    Asif, Sana
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Ekdahl, Kristina N
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Fromell, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Gustafson, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Barbu, Andreea
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Le Bland, Katarina
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Teramura, Yuji
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Heparinization of cell surfaces with short pepetide-conjugated PEG-lipid regulates thromboinflammation in thransplantation of human MSCs and hepatocytes2016Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 35, s. 194-205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival.

  • 173.
    Asif, Sana
    et al.
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB). Uppsala University.
    Fromell, Karin
    Uppsala University.
    Gustafson, Elisabet
    Uppsala University Hospital.
    Barbu, Andreea
    Uppsala University.
    Le Blanc, Katarina
    Karolinska Institutet;Karolinska University Hospital.
    Nilsson, Bo
    Uppsala University.
    Teramura, Yuji
    Uppsala University;The University of Tokyo, Japan.
    Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes2016Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 35, s. 194-205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  • 174.
    Ask, Alexandra
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    REPLICATING THE TUMOUR MICROENVIRONMENT:CHEMOSENSITIVITY TESTING IN FIBROBLAST COCULTURES2017Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 175.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Carlsson, P
    Öberg, Åke
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Pettersson, H
    Törngren, P
    Tibbling, Lita
    Feedback system for control of abdominal compression in oesophageal investigations.1981Inngår i: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 19, nr 4, s. 501-503Artikkel i tidsskrift (Fagfellevurdert)
  • 176.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Edwall, G
    Tibbling, Lita
    Combined pH and pressure measurement device for oesophageal investigations.1981Inngår i: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 19, nr 4, s. 443-446Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A combined pH- and pressure-measurement device for oesophageal investigations has been designed using monocrystalline antimony pH electrodes and perfused polyvinyl catheters. The combined device facilitates pressure measurements simultaneously with pH recording, both distal and proximal to the pH electrode. The device is easier to pass through the nose to the oesophagus than the conventional glass pH electrode. pH and pressure measurements in the oesophagus are therefore simplified and valuable information about the function of the region of the lower oesophageal sphincter is added owing to the simultaneous recording of the two parameters.

  • 177.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Sökjer, H.
    Tibbling, Lita
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Mechanisms affecting lower oesophageal sphincter opening and oesophageal retention: A combined X-ray and manometry study1978Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 13, nr 7, s. 857-861Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Using simultaneous manometry and cineradiography, oesophageal evacuation was studied while contrast medium was infused via a catheter. The distal half of the oesophagus could be filled with contrast medium without triggering peristalsis. The hydrostatic pressure necessary to open the lower oesophageal sphincter (LES) was of approximately the same magnitude as the pressure gradient between oesophagus and LES. No significant relaxation of the LES could be observed at the initiation of swallowing. The LES may be looked upon not only as a sphincter preventing reflux but also as a gate which must be forced open by food.

  • 178.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Tibbling, Lita
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan.
    Clinical evaluation of different fluid-filled systems for oesophageal manometry1979Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 14, nr 1, s. 1-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In a clinical study of oesophageal manometry with fluid-filled catheters, both a non-perfused system and a perfused system with a syringe pump have been compared to a system with a low-compliance perfusion pump, which served as a reference. Significantly lower values of motility amplitudes, motility derivatives, and partly of LES pressures, and a time delay of up to 0.5 sec of the amplitude maximum were obtained with the non-perfused system and the system with a syringe pump in comparison to the low-compliance system. Since the oesophageal function can be erroneously evaluated by use of a non-perfused system or a perfused system with a syringe pump, such systems cannot be recommended for clinical use.

  • 179.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Tibbling, Lita
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Öberg, P.Å.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Bandbreddskrav hos oesophagusmanometriska system.1978Konferansepaper (Fagfellevurdert)
  • 180.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Fysiologisk mätteknik. Linköpings universitet, Tekniska högskolan.
    Öberg, P. Åke
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Tibbling, Lita
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oto-Rhino-Laryngologi. Linköpings universitet, Hälsouniversitetet.
    Static and dynamic characteristics of fluid-filled esophageal manometry systems1977Inngår i: American Journal of Physiology, ISSN 0002-9513, Vol. 233, nr 5, s. E389-E396Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Esophageal manometric systems with water-filled catheters have been characterized by the use of model experiments. The examined parameters have been: catheter dimension, catheter compliance, catheter resistance, pump type, pump compliance, and perfusion flow. Accurate static pressure measurements have been obtained for perfused systems independently of the investigated parameters. The dynamic characteristics vary with catheter diameter and perfusion flow. For catheters with low diameter, a narrow bandwidth is obtained for the investigated perfusion flows. The results have been expressed in terms of an electric model of the measurement system. Perfusion pumps with low compliance are recommended to improve the dynamic properties of the measurement system.

  • 181.
    Ask, Per
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Öberg, Åke
    Linköpings universitet, Institutionen för medicinsk teknik.
    Ödman, S.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Tenland, T.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Skogh, M.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    ECG Electrodes: A Study of Electrical and Mechanical Long-term Properties1979Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 23, nr 2, s. 189-206Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The long-term properties of commercially available ECG-electrodes were studied by investigating the parameters: polarization potential, electrical impedance, adhesion, and skin reactions during a period of 7 days. As expected, the most stable polarization potentials were obtained for Ag/AgCl electrodes. Certain simple disposable electrodes showed large polarization potential variations. The most stable electrode impedance was obtained for disposable electrodes with stable adhesion and equipped with an electrode cup or similar. Unchanged adhesion and mechanical properties during the test period were shown by the disposable electrodes with a large self-adhesive collar.

  • 182.
    Aspelin, Jesper
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Anrikning med Illumina Nextera XT sekvenseringsbibliotek2017Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 183.
    Asper, M.
    et al.
    Charles River Biopharmaceut Serv GmbH, D-51105 Cologne, Germany..
    Hanrieder, T.
    Charles River Biopharmaceut Serv GmbH, D-51105 Cologne, Germany..
    Quellmalz, Arne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Mihranyan, Albert
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Removal of xenotropic murine leukemia virus by nanocellulose based filter paper2015Inngår i: Biologicals (Print), ISSN 1045-1056, E-ISSN 1095-8320, Vol. 43, nr 6, s. 452-456Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The removal of xenotrpic murine leukemia virus (xMuLV) by size-exclusion filter paper composed of 100% naturally derived cellulose was validated. The filter paper was produced using cellulose nanofibers derived from Cladophora sp. algae. The filter paper was characterized using atomic force microscopy, scanning electron microscopy, helium pycnometry, and model tracer (100 nm latex beads and 50 nm gold nanoparticles) retention tests. Following the filtration of xMuLV spiked solutions, LRV >= 5.25 log(10) TCID50 was observed, as limited by the virus titre in the feed solution and sensitivity of the tissue infectivity test. The results of the validation study suggest that the nanocellulose filter paper is useful for removal of endogenous rodent retroviruses and retrovirus-like particles during the production of recombinant proteins.

  • 184.
    Asplund, Annika
    et al.
    Takara Bio Europe AB, Gothenburg, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Andersson, Christian X.
    Takara Bio Europe AB, Gothenburg, Sweden.
    Küppers-Munther, Barbara
    Takara Bio Europe AB, Gothenburg, Sweden.
    A novel maintenance medium extends the life-span and enables long term applications for both human primary hepatocytes and human pluripotent stem cell derived hepatocytes in conventional 2D cultures2017Konferansepaper (Fagfellevurdert)
  • 185.
    Assadi, Ghazaleh
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden .
    Vesterlund, Liselotte
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Mazzurana, Luca
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Cordeddu, Lina
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Schepis, Danika
    Rheumatology unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden .
    Mjösberg, Jenny
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden .
    Ruhrmann, Sabrina
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fabbri, Alessia
    Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy .
    Vukojevic, Vladana
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden .
    Percipalle, Piergiorgio
    Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
    Salomons, Florian A.
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
    Laurencikiene, Jurga
    Lipid laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Törkvist, Leif
    Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden .
    Halfvarson, Jonas
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    D'Amato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain .
    Functional Analyses of the Crohn's Disease Risk Gene LACC12016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 12, artikkel-id e0168276Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression.

    Methods: We implemented Western blot, quantitative real-time PCR, immunofluorescence microscopy, and flow cytometry analyses to investigate fatty acid metabolism-immune nexus (FAMIN; the LACC1 encoded protein) expression in subcellular compartments, cell lines and relevant human tissues. Gene-set enrichment analyses were performed to initially investigate modulatory mechanisms of LACC1 expression. A small-interference RNA knockdown in vitro model system was used to study the effect of FAMIN depletion on peroxisome function.

    Results: FAMIN expression was detected in macrophage-differentiated THP-1 cells and several human tissues, being highest in neutrophils, monocytes/macrophages, myeloid and plasmacytoid dendritic cells among peripheral blood cells. Subcellular co-localization was exclusively confined to peroxisomes, with some additional positivity for organelle endomembrane structures. LACC1 co-expression signatures were enriched for genes involved in peroxisome proliferator-activated receptors (PPAR) signaling pathways, and PPAR ligands downregulated FAMIN expression in in vitro model systems.

    Conclusion: FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events. However, the precise molecular mechanisms through which FAMIN exerts its biological effects in immune cells remain to be elucidated.

  • 186. Assi, Nada
    et al.
    Fages, Anne
    Vineis, Paolo
    Chadeau-Hyam, Marc
    Stepien, Magdalena
    Duarte-Salles, Talita
    Byrnes, Graham
    Boumaza, Houda
    Knueppel, Sven
    Kuehn, Tilman
    Palli, Domenico
    Bamia, Christina
    Boshuizen, Hendriek
    Bonet, Catalina
    Overvad, Kim
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Travis, Ruth
    Gunter, Marc J.
    Lund, Eiliv
    Dossus, Laure
    Elena-Herrmann, Benedicte
    Riboli, Elio
    Jenab, Mazda
    Viallon, Vivian
    Ferrari, Pietro
    A statistical framework to model the meeting-in-the-middle principle using metabolomic data: application to hepatocellular carcinoma in the EPIC study2015Inngår i: Mutagenesis, ISSN 0267-8357, E-ISSN 1464-3804, Vol. 30, nr 6, s. 743-753Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Metabolomics is a potentially powerful tool for identification of biomarkers associated with lifestyle exposures and risk of various diseases. This is the rationale of the 'meeting-in-the-middle' concept, for which an analytical framework was developed in this study. In a nested case-control study on hepatocellular carcinoma (HCC) within the European Prospective Investigation into Cancer and nutrition (EPIC), serum H-1 nuclear magnetic resonance (NMR) spectra (800 MHz) were acquired for 114 cases and 222 matched controls. Through partial least square (PLS) analysis, 21 lifestyle variables (the 'predictors', including information on diet, anthropometry and clinical characteristics) were linked to a set of 285 metabolic variables (the 'responses'). The three resulting scores were related to HCC risk by means of conditional logistic regressions. The first PLS factor was not associated with HCC risk. The second PLS metabolomic factor was positively associated with tyrosine and glucose, and was related to a significantly increased HCC risk with OR = 1.11 (95% CI: 1.02, 1.22, P = 0.02) for a 1SD change in the responses score, and a similar association was found for the corresponding lifestyle component of the factor. The third PLS lifestyle factor was associated with lifetime alcohol consumption, hepatitis and smoking, and had negative loadings on vegetables intake. Its metabolomic counterpart displayed positive loadings on ethanol, glutamate and phenylalanine. These factors were positively and statistically significantly associated with HCC risk, with 1.37 (1.05, 1.79, P = 0.02) and 1.22 (1.04, 1.44, P = 0.01), respectively. Evidence of mediation was found in both the second and third PLS factors, where the metabolomic signals mediated the relation between the lifestyle component and HCC outcome. This study devised a way to bridge lifestyle variables to HCC risk through NMR metabolomics data. This implementation of the 'meeting-in-the-middle' approach finds natural applications in settings characterised by high-dimensional data, increasingly frequent in the omics generation.

  • 187.
    Ataei, Shakila
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Optimering av analysmetoden hos koldioxid-isotop-analysatorn, Picarro-G2131-i2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Marine bacteria are microscopically visible organisms that can survive in most of the marine environments. Their function is to decompose dead organic matter, and thus contribute to the carbon cycle in the oceans. They utilizes dissolved organic matter in the oceans and produce carbon dioxide through respiration. This carbon dioxide can be measured with modern instruments to determine the primary production of the ecosystem and determine what carbon sources are responsible for the energy flow in the ecosystem. During this study, the possibility, advisability and the sensitivity of measuring bacterial respiration with the carbon dioxide isotope analyzer Picarro-G2131-i was examined. Further, the method was developed. For the experiment, two species of proteorhodopsin containing marine bacteria Polaribacter sp. strain MED152 and Dokdonia sp. strain MED134 were used. Growth and respiration of the bacteria were studied in nutrient rich medium. To test the Picarro-instrument is sensitivity, the respiration of both bacterial species was performed in respectively dilution series. In addition, the growth and respiration of MED134 in nutrient-poor conditions in light and darkness condition was compared. To study the impact of light on the growth of bacteria. No significant difference was found between MED134´s growth and respiration in light and dark. The method could be improved by modification such as changing pump, shorten tubes, remove a safety bottle and use a refefence bottle.

     

    Conclusion

    The carbon dioxide isotope analyzer Picarro-G2131-i is a sensitive instrument and can detect both the 12CO2 and 13CO2. According to the growth experiment, the bacteria grow very rapidly in nutrient rich medium. For comparing bacterial growth in light and dark, the correct light intensity and sufficient nutrient must be used.

  • 188.
    Ataei, Tahereh
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Förekomst av penicillinkänslighet hos blododlingsisolat av Staphylococcus aureus2014Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Staphylococcus aureus is the most clinically important Staphylococcus species and is associated with high mortality in patients with positive blood cultures. S. aureus bacteria may cause a variety of disease manifestations ranging from minor skin infections to life-threatening conditions such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome (TSS) and sepsis. This microorganism belonging to the gram positive cocci may also be part of the normal flora. In Sweden, penicillinase-stable penicillins are the primary alternatives to treat S. aureus infection. Mutations in genes encoding the penicillin binding proteins (PBP2) in the bacteria which lead to a lower affinity for the  beta-lactam antibiotics define  methicillin resistant S. aureus (MRSA) which is a significant global health problem. Other resistance mechanisms of S. aureus are present, and one of these is penicillinase production which is associated with resistance to penicillin G. In order to detect penicillinase production in S. aureus, there are several methods but the European guidelines recommend disc diffusion and the clover-leaf test for follow-up if the zone diameter for benzylpenicillin (PcG) is 26 mm or more. There are no modern Swedish studies on the prevalence of S. aureus susceptible to PcG and this has recently attained interest from infectious disease physicans. Thus, the purpose of this study was to investigate the frequency of S. aureus susceptible to PcG from blood cultures isolated during 2012 from the Kalmar county.    Disc diffusion testing showed that 32% of 90 unique isolates tested had an inhibition zone diameter of PcG that was ≥ 26 mm in diameter. All of these isolates were confirmed as PcG sensitive with clover-leaf test. Internal controls showed little variation and external control isolates showed full agreement with the results obtained from a Danish study, suggesting that PcG zone diameter of ≥ 26 mm in combination with cloverleaf test can be used to detect penicillin susceptibility of S. aureus.    In conclusion, this study shows that nearly 1 /3 of the blood culture isolates of S. aureus from Kalmar are sensitive to benzylpenicillin.

  • 189.
    Atikuzzaman, Mohammad
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Sanz, Libia
    Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.
    Pla, Davinia
    Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.
    Alvarez-Rodriguez, Manuel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Rubér, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Wright, Dominic
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Calvete, Juan J.
    Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Selection for higher fertility reflects in the seminal fluid proteome of modern domestic chicken2017Inngår i: Comparative Biochemistry and Physiology - Part D: Genomics and Proteomics, ISSN 1744-117X, E-ISSN 1878-0407, Vol. 21, s. 27-40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The high egg-laying capacity of the modern domestic chicken (i.e. White Leghorn, WL) has arisen from the low egg-laying ancestor Red Junglefowl (RJF) via continuous trait selection and breeding. To investigate whether this long-term selection impacted the seminal fluid (SF)-proteome, 2DE electrophoresis-based proteomic analyses and immunoassays were conducted to map SF-proteins/cytokines in RJF, WL and a 9th generation Advanced Intercross Line (AIL) of RJF/WL-L13, including individual SF (n = 4, from each RJF, WL and AIL groups) and pools of the SF from 15 males of each group, analyzed by 2DE to determine their degree of intra-group (AIL, WL, and RJF) variability using Principal Component Analysis (PCA); respectively an inter-breed comparative analysis of intergroup fold change of specific SF protein spots intensity between breeds. The PCA clearly highlighted a clear intra-group similarity among individual roosters as well as a clear inter-group variability (e.g. between RJF, WL and AIL) validating the use of pools to minimize confounding individual variation. Protein expression varied considerably for processes related to sperm motility, nutrition, transport and survival in the female, including signaling towards immunomodulation. The major conserved SF-proteins were serum albumin and ovotransferrin. Aspartate aminotransferase, annexin A5, arginosuccinate synthase, glutathione S-transferase 2 and l-lactate dehydrogenase-A were RJF-specific. Glyceraldehyde-3-phosphate dehydrogenase appeared specific to the WL-SF while angiotensin-converting enzyme, γ-enolase, coagulation factor IX, fibrinogen α-chain, hemoglobin subunit α-D, lysozyme C, phosphoglycerate kinase, Src-substrate protein p85, tubulins and thioredoxin were AIL-specific. The RJF-SF contained fewer immune system process proteins and lower amounts of the anti-inflammatory/immunomodulatory TGF-β2 compared to WL and AIL, which had low levels- or lacked pro-inflammatory CXCL10 compared to RJF. The seminal fluid proteome differs between ancestor and modern chicken, with a clear enrichment of proteins and peptides related to immune-modulation for sperm survival in the female and fertility.

  • 190.
    Attevall, Janine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Genetic investigation of rare microdeletions and microduplications with distinct clinical features2018Independent thesis Advanced level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [en]

    Chromosomal microduplications and microdeletions represent the largest significant fraction of Copy Number Variants (CNV) and some can cause developmental delay and intellectual disability. The relatively common microdeletions and microduplications syndromes are well known but there are clinical cases with unique microduplications/-deletions that have not been studied sufficiently. The aim of this study was to verify positive SNP-microarray results during the genetic investigation of four patients with different unique microduplications or microduplications with metaphase-FISH. Since sodium heparin tubes contain the existing test material for these patients, a validation of RNA extraction was also made to verify if blood taken in these tubes can be used for further gene expression analysis.

    Blood samples and amniotic fluid were analyzed with SNP-microarray and verified with metaphase-FISH. RNA was extracted from blood taken in EDTA and sodium heparin tubes from five different individuals. Gene expression analysis with RT-qPCR were performed as a control for the RNA extraction using the genes ISPD and GUSB.

    FISH-analysis could detect the chromosomal rearrangements in all patients and investigation of the parents showed that these rearrangements were de novo. These results contribute to a better understanding of these unique aberrations and the patients´ phenotypes. There was no significant difference in RNA quality between sodium heparin and EDTA tubes. However RT-qPCR showed lower efficiency for both target gene (ISPD) and reference gene (GUSB) in RNA samples extracted from sodium heparin tubes. Blood samples in sodium heparin tubes should therefore not be used for RNA-analysis in further investigations.

  • 191.
    Attwood, Misty M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Krishnan, Arunkumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Pivotti, Valentina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Yazdi, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Almén, Markus Sällman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Topology based identification and comprehensive classification of four-transmembrane helix containing proteins (4TMs) in the human genome2016Inngår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 17, artikkel-id 268Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Membrane proteins are key components in a large spectrum of diverse functions and thus account for the major proportion of the drug-targeted portion of the genome. From a structural perspective, the a-helical transmembrane proteins can be categorized into major groups based on the number of transmembrane helices and these groups are often associated with specific functions. When compared to the well-characterized seven-transmembrane containing proteins (7TM), other TM groups are less explored and in particular the 4TM group. In this study, we identify the complete 4TM complement from the latest release of the human genome and assess the 4TM structure group as a whole. We functionally characterize this dataset and evaluate the resulting groups and ubiquitous functions, and furthermore describe disease and drug target involvement.

    Results: We classified 373 proteins, which represents similar to 7 % of the human membrane proteome, and includes 69 more proteins than our previous estimate. We have characterized the 4TM dataset based on functional, structural, and/or evolutionary similarities. Proteins that are involved in transport activity constitute 37 % of the dataset, 23 % are receptor-related, and 13 % have enzymatic functions. Intriguingly, proteins involved in transport are more than double the 15 % of transporters in the entire human membrane proteome, which might suggest that the 4TM topological architecture is more favored for transporting molecules over other functions. Moreover, we found an interesting exception to the ubiquitous intracellular N- and C-termini localization that is found throughout the entire membrane proteome and 4TM dataset in the neurotransmitter gated ion channel families. Overall, we estimate that 58 % of the dataset has a known association to disease conditions with 19 % of the genes possibly involved in different types of cancer.

    Conclusions: We provide here the most robust and updated classification of the 4TM complement of the human genome as a platform to further understand the characteristics of 4TM functions and to explore pharmacological opportunities.

  • 192. Augestad, Ingrid Lovise
    et al.
    Nyman, Axel Karl Gottfrid
    Costa, Alex Ignatius
    Barnett, Susan Carol
    Sandvig, Axel
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Haberg, Asta Kristine
    Sandvig, Ioanna
    Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat2017Inngår i: Neurochemical Research, ISSN 0364-3190, E-ISSN 1573-6903, Vol. 42, nr 6, s. 1599-1609Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Effective transplant-mediated repair of ischemic brain lesions entails extensive tissue remodeling, especially in the ischemic core. Neural stem cells (NSCs) are promising reparative candidates for stroke induced lesions, however, their survival and integration with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a 60-min middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging. Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.

  • 193.
    Augustine, Robin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets elektronik.
    Kurup, Dhanesh G.
    Amrita Univ, Amrita Sch Engn, Dept Elect & Commun, Amrita Vishwa Vidyapeetham, Bangaluru, India..
    Redzwan, Syaiful
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets elektronik.
    Mathur, Parul
    Amrita Univ, Amrita Sch Engn, Dept Elect & Commun, Amrita Vishwa Vidyapeetham, Bangaluru, India..
    Raman, Sujith
    Bharathiar Univ, Dept Elect & Instrumentat, Coimbatore, Tamil Nadu, India..
    Lee, Doojin
    GIST, Dept Med Syst Engn, Gwangju, South Korea..
    Kim, Kangwook
    GIST, Dept Med Syst Engn, Gwangju, South Korea..
    Microwave reflectivity analysis of bone mineral density using ultra wide band antenna2017Inngår i: Microwave and optical technology letters (Print), ISSN 0895-2477, E-ISSN 1098-2760, Vol. 59, nr 1, s. 21-26Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this paper, an approach to analyze the bone mineral density (BMD) based on microwave reflectivity is presented The proposed method enables us to overcome the health risks associated with diagnostic techniques such as X-rays for repeated study of the rate of mineralization in the case of fractures or de-mineralization in the case of osteoporosis. The proposed method is used to demonstrate the application of microwaves for continuous observation of skull healing process during post-cranial surgery period. The proposed technique can be a potential clinical model in future for extracting target characteristics such as bone deposition thickness and other cranial defects. Based on the conclusions of wideband measured data and signal processing techniques, we propose to design the Transceiver using ultra-wideband (UWB) pulsed technology.

  • 194.
    Augustsson Sjögren, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Characterisation of aptamers selected for binding to Yersinia pestis virulence protein LcrV2011Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 195.
    Aulin, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi.
    Extracellular Matrix Based Materials for Tissue Engineering2010Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition.

    The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.

  • 196.
    Awadalla, Mohamed
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Homology Models of Human Retinoic Acid Hydroxylase CYP26A1 and CYP26B1: Molecular Dynamics Refinement and Evaluation of Statins Docking2012Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
  • 197.
    Awdalla, Mohamed
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Homology Models of Human Retinoic Acid Hydroxylase CYP26A1 and CYP26B1: Molecular Dynamics Refinement and Evaluation of Statins Docking2012Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
  • 198.
    Axner, Ove
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Andersson, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Björnham, Oscar
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Castelain, Mickaël
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Klinth, Jeanna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Koutris, Efstratios
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Schedin, Staffan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Assessing bacterial adhesion on an individual adhesin and single pili level using optical tweezers 2011Inngår i: Bacterial adhesion: chemistry, biology and physics / [ed] D. Line and A. Goldman, Berlin: Springer Berlin/Heidelberg, 2011, s. 301-313Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Optical tweezers (OT) are a technique that, by focused laser light, can both manipulate micrometer sized objects and measure minute forces (in the pN range) in biological systems. The technique is therefore suitable for assessment of bacterial adhesion on an individual adhesin-receptor and single attachment organelle (pili) level. This chapter summarizes the use of OT for assessment of adhesion mechanisms of both non-piliated and piliated bacteria. The latter include the important helix-like pili expressed by uropathogenic Escherichia coli (UPEC), which have shown to have unique and intricate biomechanical properties. It is conjectured that the large flexibility of this type of pili allows for a redistribution of an external shear force among several pili, thereby extending the adhesion lifetime of bacteria. Systems with helix-like adhesion organelles may therefore act as dynamic biomechanical machineries, enhancing the ability of bacteria to withstand high shear forces originating from rinsing flows such as in the urinary tract. This implies that pili constitute an important virulence factor and a possible target for future anti-microbial drugs.

  • 199. Aymara, Tagyzade
    Molecular expression of receptive stage endometriumin healthy women and women with endometriosis2017Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [en]

    Endometriosis affects about 10-15% of women in their reproductive age, which increases the risk for infertility. The molecular expression profile of receptive endometrium of women with endometriosis may differ from that of receptive endometrium of healthy women. Thus, the objective of this study was to examine the molecular expression in endometrium of women with endometriosis and compare it with the endometrium from healthy women collected during receptive phase.Endometrium was collected during receptive phase from women with endometriosis (n=4) and from healthy women with proven fertility (n=8). Paraformaldehyde fixed and paraffin embedded tissues were sectioned and the differential protein expression of SOX17, ezrin, WT1 and SLPI were studied by use of immunohistochemistry, and analysed under light microscopy for staining intensity and area. Mann-Whitney U-test was performed to find differences in protein staining.We found that protein expression of SOX17 was confined to endometrial glands. The expression of ezrin present in glands was significantly higher in endometrium from women with endometriosis (p<0.01). There were no differences between the two groups in the expression of SOX17 or WT1. We could not find any detectable levels of SLP1 in the endometrial sections. Thus, we conclude that the endometrium of women with endometriosis have differential expression of ezrin.

  • 200.
    Ayoglu, Burcu
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Affinity Arrays for Profiling Proteins and Autoantibody Repertoires2014Doktoravhandling, med artikler (Annet vitenskapelig)
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