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  • 51.
    Ajaxon, Ingrid
    et al.
    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.
    Mechanical Properties of Brushite Calcium Phosphate Cements2017Inngår i: The World Scientific Encyclopedia of Nanomedicine and Bioengineering II: Bioimplants, Regenerative Medicine, and Nano-Cancer Diagnosis and Phototherapy: Volume 3: Design of Bioactive Materials for Bone Repair and Regeneration / [ed] Shi, D., Singapore: World Scientific Pte Ltd. , 2017Kapittel i bok, del av antologi (Fagfellevurdert)
  • 52.
    Ajaxon, Ingrid
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    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.
    Long-term in vitro degradation of a high-strength brushite cement in water, PBS, and serum solution2015Inngår i: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, artikkel-id 575079Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bone loss and fractures may call for the use of bone substituting materials, such as calcium phosphate cements (CPCs). CPCs can be degradable, and, to determine their limitations in terms of applications, their mechanical as well as chemical properties need to be evaluated over longer periods of time, under physiological conditions. However, there is lack of data on how the in vitro degradation affects high-strength brushite CPCs over longer periods of time, that is, longer than it takes for a bone fracture to heal. This study aimed at evaluating the long-term in vitro degradation properties of a high-strength brushite CPC in three different solutions: water, phosphate buffered saline, and a serum solution. Microcomputed tomography was used to evaluate the degradation nondestructively, complemented with gravimetric analysis. The compressive strength, chemical composition, and microstructure were also evaluated. Major changes from 10 weeks onwards were seen, in terms of formation of a porous outer layer of octacalcium phosphate on the specimens with a concomitant change in phase composition, increased porosity, decrease in object volume, and mechanical properties. This study illustrates the importance of long-term evaluation of similar cement compositions to be able to predict the material’s physical changes over a relevant time frame. 

  • 53.
    Ajaxon, Ingrid
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Öhman Mägi, 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.
    Compressive fatigue properties of an acidic calcium phosphate cement—effect of phase composition2017Inngår i: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 28, nr 3, artikkel-id 41Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Calcium phosphate cements (CPCs) are synthetic bone grafting materials that can be used in fracture stabilization and to fill bone voids after, e.g., bone tumour excision. Currently there are several calcium phosphate-based formulations available, but their use is partly limited by a lack of knowledge of their mechanical properties, in particular their resistance to mechanical loading over longer periods of time. Furthermore, depending on, e.g., setting conditions, the end product of acidic CPCs may be mainly brushite or monetite, which have been found to behave differently under quasi-static loading. The objectives of this study were to evaluate the compressive fatigue properties of acidic CPCs, as well as the effect of phase composition on these properties. Hence, brushite cements stored for different lengths of time and with different amounts of monetite were investigated under quasi-static and dynamic compression. Both storage and brushite-to-monetite phase transformation was found to have a pronounced effect both on quasi-static compressive strength and fatigue performance of the cements, whereby a substantial phase transformation gave rise to a lower mechanical resistance. The brushite cements investigated in this study had the potential to survive 5 million cycles at a maximum compressive stress of 13 MPa. Given the limited amount of published data on fatigue properties of CPCs, this study provides an important insight into the compressive fatigue behaviour of such materials. 

  • 54.
    Akgun, Kocere Kurdé
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Evaluation of Different Extraction- and Analysis Methods for Calprotectin in Feces2012Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    Background Calprotectin is a protein expressed in the cytoplasm inside the neutrophile granulocytes. During inflammatory bowel disease (IBD), the neutrophile granulocytes are involved in a complex interaction at the inflammatory area where they die and release their content into the intestinal lumen. Therefore, calprotectin in stool is a suitable marker for diagnosis and measurement of the disease-activity in patients with IBD. The most commonly used method to detect calprotectin in stool is ELISA, but the process of manual preparation of stool samples is time-consuming.

    Aim The objective of the study was to evaluate an extraction method that could replace manual preparation of fecal samples and to compare different methods for measuring Calprotectin in stool using two ELISA-methods from two manufacturers and one rapidtest.

    Methods For extraction of calprotectin from stool samples we used sample collector tubes from Epitope Diagnostics and fecal preparation kits from Roche. Two different ELISA-kits for measuring calprotectin concentration in stool were compared. Measurements of calprotectin with rapid-test from Epitope Diagnostics were also performed and were compared with the two ELISA kits.

    Results The results indicate a poor correlation between two extraction methods with Sample Collector Tube and Roche preparation kit. The comparison between the two ELISA-kits showed poor correlation. Evaluation of rapid test showed 33% false negative results with a cut-off value at 50 mg/kg.

    Conclusion Evaluation of products from Epitope Diagnostics showed poor correlation with the Bühlmann ELISA and an unreliable rapid test. Therefore, none of evaluated products from Epitope Diagnostics is accurate enough to be used for clinical diagnosis in the laboratory.

  • 55.
    Akhras, Michael S.
    et al.
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Pettersson, Erik
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Diamond, Lisa
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Unemo, Magnus
    Region Örebro län.
    Okamoto, Jennifer
    Dept Bioengn, Stanford Univ, Stanford CA, USA.; Howard Hughes Med Inst, Stanford Univ, Stanford CA, USA.
    Davis, Ronald W.
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA , USA.
    Pourmand, Nader
    Dept Biomol Engn, University of California, Santa Cruz CA, USA.
    The Sequencing Bead Array (SBA), a Next-Generation Digital Suspension Array2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, artikkel-id UNSP e76696Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here we describe the novel Sequencing Bead Array (SBA), a complete assay for molecular diagnostics and typing applications. SBA is a digital suspension array using Next-Generation Sequencing (NGS), to replace conventional optical readout platforms. The technology allows for reducing the number of instruments required in a laboratory setting, where the same NGS instrument could be employed from whole-genome and targeted sequencing to SBA broad-range biomarker detection and genotyping. As proof-of-concept, a model assay was designed that could distinguish ten Human Papillomavirus (HPV) genotypes associated with cervical cancer progression. SBA was used to genotype 20 cervical tumor samples and, when compared with amplicon pyrosequencing, was able to detect two additional co-infections due to increased sensitivity. We also introduce in-house software Sphix, enabling easy accessibility and interpretation of results. The technology offers a multi-parallel, rapid, robust, and scalable system that is readily adaptable for a multitude of microarray diagnostic and typing applications, e. g. genetic signatures, single nucleotide polymorphisms (SNPs), structural variations, and immunoassays. SBA has the potential to dramatically change the way we perform probe-based applications, and allow for a smooth transition towards the technology offered by genomic sequencing.

  • 56.
    Akil, Shahnaz
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Discrimination of abnormal ST-deviation patterns from those caused by acute coronary occlusion, using 12-lead electrocardiogram-based computed elctrocardiograpich imaging2012Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
  • 57. Akoachere, Monique
    et al.
    Iozef, Rimma
    Rahlfs, Stefan
    Deponte, Marcel
    Mannervik, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi. Institutionen för biokemi och organisk kemi, Biokemi.
    Creighton, Donald J
    Schirmer, Heiner
    Becker, Katja
    Characterization of the glyoxalases of the malarial parasite Plasmodium falciparum and comparison with their human counterparts.2005Inngår i: Biol Chem, ISSN 1431-6730, Vol. 386, nr 1, s. 41-52Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The glyoxalase system consisting of glyoxalase I (GloI) and glyoxalase II (GloII) constitutes a glutathione-dependent intracellular pathway converting toxic 2-oxoaldehydes, such as methylglyoxal, to the corresponding 2-hydroxyacids. Here we describe a complete glyoxalase system in the malarial parasite Plasmodium falciparum. The biochemical, kinetic and structural properties of cytosolic GloI (cGloI) and two GloIIs (cytosolic GloII named cGloII, and tGloII preceded by a targeting sequence) were directly compared with the respective isofunctional host enzymes. cGloI and cGloII exhibit lower K(m) values and higher catalytic efficiencies (k(cat)/K(m) ) than the human counterparts, pointing to the importance of the system in malarial parasites. A Tyr185Phe mutant of cGloII shows a 2.5-fold increase in K(m) , proving the contribution of Tyr185 to substrate binding. Molecular models suggest very similar active sites/metal binding sites of parasite and host cell enzymes. However, a fourth protein, which has highest similarities to GloI, was found to be unique for malarial parasites; it is likely to act in the apicoplast, and has as yet undefined substrate specificity. Various S-(N-hydroxy-N-arylcarbamoyl)glutathiones tested as P. falciparum Glo inhibitors were active in the lower nanomolar range. The Glo system of Plasmodium will be further evaluated as a target for the development of antimalarial drugs.

  • 58.
    Akula, Ilona
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Hjärtfunktion vid ärftlig transtyretin-amyloidos: Jämförelse av hjärtfrekvensvariabilitet och ekokardiografi mellan två amyloidfibrilltyper2015Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 59.
    Akula, Srinivas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Mohammadamin, Sayran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, s. e96903-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR gamma chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

  • 60.
    Akula, Srinivas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Thorpe, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Boinapally, Vamsi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Granule Associated Serine Proteases of Hematopoietic Cells - An Analysis of Their Appearance and Diversification during Vertebrate Evolution2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 11, artikkel-id e0143091Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Serine proteases are among the most abundant granule constituents of several hematopoietic cell lineages including mast cells, neutrophils, cytotoxic T cells and NK cells. These proteases are stored in their active form in the cytoplasmic granules and in mammals are encoded from four different chromosomal loci: the chymase locus, the met-ase locus, the T cell tryptase and the mast cell tryptase locus. In order to study their appearance during vertebrate evolution we have performed a bioinformatic analysis of related genes and gene loci from a large panel of metazoan animals from sea urchins to placental mammals for three of these loci: the chymase, met-ase and granzyme A/K loci. Genes related to mammalian granzymes A and K were the most well conserved and could be traced as far back to cartilaginous fish. Here, the granzyme A and K genes were found in essentially the same chromosomal location from sharks to humans. However in sharks, no genes clearly identifiable as members of the chymase or met-ase loci were found. A selection of these genes seemed to appear with bony fish, but sometimes in other loci. Genes related to mammalian met-ase locus genes were found in bony fish. Here, the most well conserved member was complement factor D. However, genes distantly related to the neutrophil proteases were also identified in this locus in several bony fish species, indicating that this locus is also old and appeared at the base of bony fish. In fish, a few of the chymase locus-related genes were found in a locus with bordering genes other than the mammalian chymase locus and some were found in the fish met-ase locus. This indicates that a convergent evolution rather than divergent evolution has resulted in chymase locus-related genes in bony fish.

  • 61.
    Al Hwamdeh, Yaseen
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Urinary Stone Diagnosis Non: Contrast Computed Tomography versus Intravenous Urography2015Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
  • 62.
    Al Rabiey, Ahmed
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Detektion av aktin i paraffinsnitt från human vävnad2015Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 63.
    Al-Amin, Abdullah
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gallant, Caroline
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lööf, Sara
    Department of Oncology-Pathology, Karolinska Institutet.
    Lengqvist, Johan
    Department of Medicine, Karolinska Institutet.
    Bacanu, Smarand
    Department of Oncology-Pathology, Karolinska Institutet.
    Nordlund, Pär
    Department of Oncology-Pathology, Karolinska Institutet.
    Landegren, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Sensitive Measurement of Cellular Drug-Target Engagement Using Multiplex Proximity Extension AssaysManuskript (preprint) (Annet vitenskapelig)
  • 64. Al-Anati, Lauy
    et al.
    Viluksela, Matti
    Strid, Anna
    Bergman, Åke
    Andersson, Patrik L
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Stenius, Ulla
    Högberg, Johan
    Hydroxyl metabolite of PCB 180 induces DNA damage signaling and enhances the DNA damaging effect of benzo[a]pyrene2015Inngår i: Chemico-Biological Interactions, ISSN 0009-2797, E-ISSN 1872-7786, Vol. 239, s. 164-173Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) and their hydroxyl metabolites (OH-PCBs) are ubiquitous environmental contaminants in human tissues and blood. The toxicological impact of these metabolites is poorly understood. In this study rats were exposed to ultrapure PCB180 (10-1000 mg/kg bw) for 28 days and induction of genotoxic stress in liver was investigated. DNA damage signaling proteins (pChk1Ser317 and gamma H2AXSer319) were increased dose dependently in female rats. This increase was paralleled by increasing levels of the metabolite 3'-OH-PCB180. pChk1 was the most sensitive marker. In in vitro studies HepG2 cells were exposed to 1 mu M of PCB180 and 3'-OH-PCB180 or the positive control benzo[a]pyrene (BaP, 5 mu M). 3'-OH-PCB180, but not PCB180, induced CYP1A1 mRNA and gamma H2AX. CYP1A1 mRNA induction was seen at 1 h, and gamma H2AX at 3 h. The anti-oxidant N-Acetyl-L-Cysteine (NAC) completely prevented, and 17 beta-estradiol amplified the gamma H2AX induction by 3'-OH-PCB180. As 3'-OH-PCB180 induced CYP1A1, a major BaP-metabolizing and activating enzyme, interactions between 3'-OH-PCB180 and BaP was also studied. The metabolite amplified the DNA damage signaling response to BaP. In conclusion, metabolism of PCB180 to its hydroxyl metabolite and the subsequent induction of CYP1A1 seem important for DNA damage induced by PCB180 in vivo. Amplification of the response with estradiol may explain why DNA damage was only seen in female rats.

  • 65.
    Alarcon, E I
    et al.
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Vulesevic, B
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Argawal, A
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Ross, A
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Bejjani, P
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Podrebarac, J
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Ravichandran, Ranjithkumar
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Suuronen, E J
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Coloured cornea replacements with anti-infective properties: expanding the safe use of silver nanoparticles in regenerative medicine.2016Inngår i: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 8, nr 12, s. 6484-6489Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite the broad anti-microbial and anti-inflammatory properties of silver nanoparticles (AgNPs), their use in bioengineered corneal replacements or bandage contact lenses has been hindered due to their intense yellow coloration. In this communication, we report the development of a new strategy to pre-stabilize and incorporate AgNPs with different colours into collagen matrices for fabrication of corneal implants and lenses, and assessed their in vitro and in vivo activity.

  • 66.
    Al-Asafi, Zainab
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Förekomst av Mycobacterium avium i vattenprover från barns närmiljö: med fokus på badleksaker2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Mykobakterier är grampositiva bakterier som hör till familjen Mycobacteriaceae. Inom släktet Mycobacterium finns det mer än 50 arter av mykobakterier som ger upphov till sjukdomar hos människan, där den viktigaste arten är M. tuberculosis. Icke-tuberkulösa mykobakterier benämns även som miljömykobakterier. En del arter kan leva i miljöer med mycket låga halter av näringsämnen samt i akvatiska miljöer och återfinns i bl.a. vatten, jord, kärr och sumpmarker. Vissa miljömykobakteriearter är patogena och framkallar sjukdomar hos människan och även djur. Oftast är de opportunistiskt patogena, dvs. angriper och infekterar människan vid starkt nedsatt immunförsvar eller kronisk sjukdom.

    Två mykobakteriearter vid namn Mykobakterium avium avium och Mykobakterium avium hominissuis tillhör undergruppen Mykobakterium avium komplex (MAC).

    Friska barn mellan 1 och 5 år är en utsatt grupp för MAC-infektioner. När barnen infekteras med MAC, uppstår en lymfkörtelinflammation (lymfadenit) runt halsområdet. Eftersom det inte konstaterats någon MAC-smitta människor emellan, spekuleras det över andra möjliga vägar för MAC-bakterier att nå och infektera vuxna och barn med lymfadenit.  Det antas att MAC infekterar människan via naturen samt dricksvattnet. 

    Syftet med studien var att utveckla en metod för att detektera förekomst av M. avium bakterier i vanligt kranvatten från Öland, Kalmar och Hultsfred, inkuberat i badankor. I syftet ingick också att experimentellt undersöka om M. avium överlever och/ eller anrikar sig i badanksmiljön. De metoder som utvärderades var odling med efterföljande detektion via MALDI-TOF samt triplex q-PCR.  

    Studien utfördes på rena (nya) och smutsiga (använda) badankor innehållande kranvatten från Öland, Kalmar och Hultsfred, där vissa injicerades med kända stammar av M. avium avium och M. avium hominissuis och inkuberades i fem veckor. Från vattnet från respektive badanka extraherades DNA som analyserades med q-PCR. Dessutom gjordes utstryk från vattenproven och odlades på näringsrik agar för att senare, om möjligt, detektera med MALDI-TOF.

    Resultatet av studien med q-PCR visade detektion av bakterierna M. avium avium och M. avium hominissus i samtliga miljöprover. En trolig orsak till detta kan vara att extraktionslösningarna som användes varit kontaminerade. Studien visade dock att mykobakterier överlevde i badanksmiljö.

  • 67.
    Albeer, Merna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Evaluation of ELISA and rapid test for the analysis of fecal Calprotectin2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    ABSTRACT

    Background Calprotectin is a protein found in the cytoplasm of neutrophile granulocytes. In the course of inflammatory bowel disease (IBD), calprotectin is released during chronic inflammation in the gut. Activation of neutrophils during the inflammation is followed by activation and secretion of pro-inflammatory molecules such as calprotectin. Calprotectin is stable in stool up to 7 days and can therefore be used as a non-invasive marker for diagnosis, treatment and measurement of the disease activity in patients with IBD. The most common method for analysis of calprotectin concentration is ELISA. This method is time-consuming and many manufactures have therefore developed rapid tests as a faster alternative for quantification of calprotectin in stool.

    Aim The aim of the study was to evaluate one ELISA and one rapid test from the same manufacture compare the data with the existing ELISA-method used in the laboratory for routine analysis.

    Methods A rapid test (CalFast) and an ELISA method (CalPrest) from Eurospital, were used for analysis of calprotectin in stool. These two methods were compared with known concentrations of calprotectin obtained by the ELISA method from Bühlmann used in the routine work. 

    Results The results showed poor correlation between the rapid test and the ELISA method. Furthermore, the comparison between the two ELISA-methods showed a poor correlation.

    Conclusion Evaluation of the two new methods showed poor correlation with the existing ELISA method from Bühlmann. Evaluation of the rapid test did not show any correlation with the two ELISA methods and the data cannot be trusted. It is difficult to conclude which of the two ELISA methods gives accurate results due to the absence of an international standard.

  • 68.
    Alberti, Esteban
    et al.
    Department of Neurobiology, International Center of Neurological Restoration, CIREN, Havana, Cuba..
    Los, Marek Jan
    Interfaculty Institute for Biochemistry, University of Tübingen, Germany; BioApplications Enterprises, Winnipeg, MB, Canada.
    Garcia, Rocio
    Department of Neurobiology, International Center of Neurological Restoration, CIREN, Havana, Cuba..
    Fraga, JL
    Department of Neurobiology, International Center of Neurological Restoration, CIREN, Havana, Cuba..
    Serrano, T.
    Department of Neurobiology, International Center of Neurological Restoration, CIREN, Havana, Cuba..
    Hernandez, E.
    Department of Neurobiology, International Center of Neurological Restoration, CIREN, Havana, Cuba..
    Klonisch, Thomas
    Department of Human Anatomy and Cell Sciences, and Manitoba Institute of Child Health, Winnipeg, Canada.
    Macías, R.
    Department of Neurobiology, International Center of Neurological Restoration, CIREN, Havana, Cuba..
    Martinez, L.
    Department of Neurobiology, International Center of Neurological Restoration, CIREN, Havana, Cuba..
    Castillo, L.
    Department of Neurobiology, International Center of Neurological Restoration, CIREN, Havana, Cuba..
    de la Cuétara, K.
    Department of Neurobiology, International Center of Neurological Restoration, CIREN, Havana, Cuba.
    Prolonged Survival and expression of neural markers by bone marrow-derived stem cells transplanted into brain lesions2009Inngår i: Medical Science Monitor, ISSN 1234-1010, E-ISSN 1643-3750, Vol. 15, nr 2, s. BR47-BR54Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Bone marrow-derived stem cell transplantation is a potentially viable therapeutic option for the treatment of neurodegenerative disease. MATERIAL/METHODS: We have isolated bone marrow stem cells by standard method. We then evaluated the survival of rats' bone marrow mononuclear cells implanted in rats' brain. The cells were extracted from rats' femurs, and marked for monitoring purposes by adenoviral transduction with Green Fluorescent Protein (GFP). Labeled cells were implanted within the area of rats' striatum lesions that were induced a month earlier employing quinolinic acid-based method. The implants were phenotyped by monitoring CD34; CD38; CD45 and CD90 expression. Bone marrow stromal cells were extracted from rats' femurs and cultivated until monolayer bone marrow stromal cells were obtained. The ability of bone marrow stromal cells to express NGF and GDNF was evaluated by RT-PCR. RESULTS: Implanted cells survived for at least one month after transplantation and dispersed from the area of injection towards corpus callosum and brain cortex. Interestingly, passaged rat bone marrow stromal cells expressed NGF and GDNF mRNA. CONCLUSIONS: The bone marrow cells could be successfully transplanted to the brain either for the purpose of trans-differentiation, or for the expression of desired growth factors.

  • 69.
    Albertsson, Jakob
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Effekt av förbehandling vid detektion av muterat superoxiddismutas-1 protein: Immunohistokemisk detektion av SOD1 aggregat hos G93A transgena möss2016Independent thesis Basic level (professional degree), 180 hpOppgave
  • 70.
    Albertsson, Jakob
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Effekt av förbehandling vid detektion av muterat superoxiddismutas-1 protein: Immunohistokemisk detektion av SOD1 aggregat hos G93A transgena möss2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 71. Albèr, C.
    et al.
    Brandner, B. D.
    Björklund, S.
    Billsten, P.
    Corkery, Robert
    KTH, Skolan för kemivetenskap (CHE), Kemi, Tillämpad fysikalisk kemi.
    Engblom, J.
    Effects of water gradients and use of urea on skin ultrastructure evaluated by confocal Raman microspectroscopy2013Inngår i: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1828, nr 11, s. 2470-2478Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The rather thin outermost layer of the mammalian skin, stratum corneum (SC), is a complex biomembrane which separates the water rich inside of the body from the dry outside. The skin surface can be exposed to rather extreme variations in ambient conditions (e.g. water activity, temperature and pH), with potential effects on the barrier function. Increased understanding of how the barrier is affected by such changes is highly relevant for regulation of transdermal uptake of exogenous chemicals. In the present study we investigate the effect of hydration and the use of a well-known humectant, urea, on skin barrier ultrastructure by means of confocal Raman microspectroscopy. We also perform dynamic vapor sorption (DVS) microbalance measurements to examine the water uptake capacity of SC pretreated with urea. Based on novel Raman images, constructed from 2D spectral maps, we can distinguish large water inclusions within the skin membrane exceeding the size of fully hydrated corneocytes. We show that these inclusions contain water with spectral properties similar to that of bulk water. The results furthermore show that the ambient water activity has an important impact on the formation of these water inclusions as well as on the hydration profile across the membrane. Urea significantly increases the water uptake when present in skin, as compared to skin without urea, and it promotes formation of larger water inclusions in the tissue. The results confirm that urea can be used as a humectant to increase skin hydration.

  • 72. Alcocer, Marcos
    et al.
    Rundqvist, Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ber e 1 protein: the versatile major allergen from Brazil nut seeds.2012Inngår i: Biotechnology letters, ISSN 0141-5492, E-ISSN 1573-6776, Vol. 34, nr 4, s. 597-610Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Due mainly to its extremely high content of sulphur amino acids, Ber e 1 protein, the major allergen from Brazil nut, has attracted much scientific and press attention. Ber e 1 was the main target protein in early biotechnology transgenic work, in early processing studies of plant storage proteins, in plant vacuolar targeting studies and as the main protein in early nutritional supplementation experiments. Ber e 1 was also one of the first food allergens to be unintentionally transferred from one plant to another and was involved in the first reported case of systemic allergic reaction caused by a food allergen transferred in semen. In this review, many of the Ber e 1 unique biotechnological and structural functions are discussed with a particular emphasis on its use as model protein for studies of intrinsic allergenicity of food proteins.

  • 73.
    Alexander, Helen K.
    et al.
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba.
    Booy, Evan P.
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada .
    Xiao, Wenyan
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba.
    Ezzati, Peyman
    Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba.
    Baust, Heinrich
    Department of Radiooncology, University of Erlangen, Erlangen, Germany .
    Los, Marek Jan
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada, .
    Selected technologies to control genes and their products for experimental and clinical purposes2007Inngår i: Archivum Immunologiae et Therapiae Experimentalis, ISSN 0004-069X, E-ISSN 1661-4917, Vol. 55, nr 3, s. 139-149Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    "On-demand" regulation of gene expression is a powerful tool to elucidate the functions of proteins and biologically-active RNAs. We describe here three different approaches to the regulation of expression or activity of genes or proteins. Promoter-based regulation of gene expression was among the most rapidly developing techniques in the 1980s and 1990s. Here we provide basic information and also some characteristics of the metallothionein-promoter-based system, the tet-off system, Muristerone-A-regulated expression through the ecdysone response element, RheoSwitch (R), coumermycin/novobiocin-regulated gene expression, chemical dimerizer-based promoter activation systems, the "Dual Drug Control" system, "constitutive androstane receptor"-based regulation of gene expression, and RU486/mifepristone-driven regulation of promoter activity. A large part of the review concentrates on the principles and usage of various RNA interference techniques (RNAi: siRNA, shRNA, and miRNA-based methods). Finally, the last part of the review deals with historically the oldest, but still widely used, methods of temperature-dependent regulation of enzymatic activity or protein stability (temperature-sensitive mutants). Due to space limitations we do not describe in detail but just mention the tet-regulated systems and also fusion-protein-based regulation of protein activity, such as estrogen-receptor fusion proteins. The information provided below is aimed to assist researchers in choosing the most appropriate method for the planned development of experimental systems with regulated expression or activity of studied proteins.

  • 74.
    Alfredsson-Timmins, Jenny
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Kristell, Carolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Henningson, Frida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Lyckman, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Bjerling, Pernilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Reorganization of chromatin is an early response to nitrogen starvation in Schizosaccharomyces pombe2009Inngår i: Chromosoma, ISSN 0009-5915, E-ISSN 1432-0886, Vol. 118, nr 1, s. 99-112Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There are several documented events of changes in subnuclear localization during gene activation. However, there are conflicting data on whether the nuclear periphery is a compartment for gene repression or activation, and whether genes are moved to the pores at the nuclear membrane (NM) or not during gene activation. Nitrogen starvation of fission yeast serves as a good model system for studying gene induction since it causes fast regulation of hundreds of genes. In this study the subnuclear localization of two gene clusters repressed by nitrogen was investigated. During normal growth conditions the gene clusters localized to the nuclear periphery at the opposite side of the nucleus as compared to the spindle pole body (SPB). This constrained localization was dependent on the histone deacetylase Clr3, known to transcriptionally repress genes in these clusters. Already 20 minutes after nitrogen depletion drastic changes in subnuclear localization of the two loci were observed, away from the NM towards the nuclear interior. At least for one of the clusters the movement was clearly transcription dependent. Data presented here illustrates how interconnected events of gene activation and nuclear reorganization are, as well as provides a suggestion of how nuclear organization might be maintained.

  • 75.
    Ali Ghani, Hawraa
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Funktionella studier av VEGFR2-bindande affibody-molekyler kovalent konjugerade till spindelsilke2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Spindelsilke och dess mekaniska egenskaper har länge studerats och är idag väl karaktäriserade. Att utvinna spindelsilke ifrån spindlar är komplicerat, därför har en metod att framställa spindelsilkesprotein (4RepCT) med hjälp av rekombinant DNA-teknik utvecklats. 4RepCT är förenlig med levande celler och kan användas som stödmatris för cellodlingar. Fibronektin, (FN) är ett glykoprotein som finns i det extracellulära matrixen och uppvisar peptider som gynnar celladherens. På genetisk väg kan 4RepCT kopplas med en sådan peptid ifrån FN (FN-4RepCT). Vaskulär endoteltillväxtfaktorreceptor 2 (VEGFR-2) uttrycks på endotelceller och aktiveras av VEGF-tillväxtfaktor. Denna aktivering kan initiera tillväxt av redan existerande blodkärl såsom vid cancersjukdomar. VEGFR-2 är således en attraktiv och lovande måltavla för framtida behandling av cancerpatienter. Under projektet användes transgena celler, 293/KDR som överuttrycker VEGFR-2.

    Syftet med examensarbetet var att undersöka funktionaliteten och bioaktiviteten hos VEGFR-2-bindande affibody-molekyler efter deras konjugering till 4RepCT och FN-4RepCT.

    Alamar Blue och immunokemiska tekniken ELISA användes för att undersöka cellproliferation/viabilitet respektive fosforylering. Cellproliferation av 293/KDR undersöktes i brunnar täckta med först 4RepCT och sedan följt utav affibody molekylerna: Zdimer-4RepCT, Ztetramer-4RepCT, FN-4RepCT, Zdimer-FN-4RepCT, Ztetramer-FN-4RepCT och 4RepCT. För att undersöka fosforyleringseffekten av affibody molekyler på 293/KDRs VEGFR-2 användes ELISA.

    Högst proliferationsvärde erhölls från 293/KDR odlade på Ztetramer-FN-4RepCT. Brunnar täckta först med 4RepCT och sedan Zdimer-FN-4RepCT uppvisade en lägre cellproliferationskapacitet än Ztetramer-FN-4RepCT. VEGFR-2 fosforyleringsresultaten visade att affibody-molekylen Ztetramer-4RepCT har en större effekt på VEGFR-2 jämfört med Zdimer-4RepCT. Slutsatsen drogs att Ztetramer kopplad till 4RepCT med eller utan FN visar en stimulerande effekt på VEGFR-2 fosforylering dock behöver ytterligare studier genomföras.

  • 76.
    Ali, Iman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Pan Genera Detection-​test, a new bacterial detection systems for durability extension of platelets2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Platelets are blood cells that important for transfusion and blood coagulation. Patients will get transfusion with manufactured platelets if they have platelet disorder or extensive blood loss. Platelets isolated from 5 buffy-coats by different ways at a blood center are usable for about 5 days. The sustainability of platelets could be extended by various methods. The previously used method in Gävle BLC was the bacterial culture method using aerobic and anaerobic bottles, which took 5 days to receive an answer. Therefore, this project used Pan Genera Detection (PGD) test as an alternative method to extend the sustainability of platelets. The PGD ​​Test is a rapid method that only takes about 30 minutes. This study showed that PGD the test yielded good results to reduced costs compared with the old method. The durability was extended by 36 h and the analysis runs in routine now at Gävle blood center.

    Finally, this project has shown that PGD-test is a cheaper, faster and safer approach for patient health compared to the old method, the bacterial culture method.

  • 77.
    Ali, Jalal
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Fluorescerande Chlamydia trachomatis-mCherry för analys av nya antimikrobiella substanser2016Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 78. Ali, Raja Hashim
    et al.
    Muhammad, Sayyed Auwn
    Khan, Mehmood Alam
    Arvestad, Lars
    Stockholms universitet, Naturvetenskapliga fakulteten, Numerisk analys och datalogi (NADA). Stockholms universitet, Science for Life Laboratory (SciLifeLab). Swedish e-Science Research Center, Sweden .
    Quantitative synteny scoring improves homology inference and partitioning of gene families2013Inngår i: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 14, nr Suppl,15, s. S12-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Clustering sequences into families has long been an important step in characterization of genes and proteins. There are many algorithms developed for this purpose, most of which are based on either direct similarity between gene pairs or some sort of network structure, where weights on edges of constructed graphs are based on similarity. However, conserved synteny is an important signal that can help distinguish homology and it has not been utilized to its fullest potential.

    Results

    Here, we present GenFamClust, a pipeline that combines the network properties of sequence similarity and synteny to assess homology relationship and merge known homologs into groups of gene families. GenFamClust identifies homologs in a more informed and accurate manner as compared to similarity based approaches. We tested our method against the Neighborhood Correlation method on two diverse datasets consisting of fully sequenced genomes of eukaryotes and synthetic data.

    Conclusions

    The results obtained from both datasets confirm that synteny helps determine homology and GenFamClust improves on Neighborhood Correlation method. The accuracy as well as the definition of synteny scores is the most valuable contribution of GenFamClust.

  • 79.
    Alikhani, Nyosha
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    The Mitochondrial Peptidasome, PreP, relation to Alzheimer Disease2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Amyloid-β (Aβ) is the toxic peptide implicated in the pathogenesis of Alzheimer Disease (AD). Accumulation of Aβ has been shown in brain mitochondria from AD patients and AD mice models. The occurrence of Aβ in the mitochondrial matrix leads to free radical generation and apoptosis in neurons.

    In our studies, Aβ was found in brain mitochondria of living patients with plaque pathology. Extracellular Aβ was taken up by neuroblastoma cells and was found in the mitochondria. Moreover, we showed that Aβ40 and Aβ42 are transported into mitochondria via the Translocase of the Outer Membrane, the TOM machinery.

    We have identified the mitochondrial Aβ-degrading protease hPreP, in human brain mitochondrial matrix. PreP is a metalloprotease, originally identified as presequence protease, but was also shown to degrade other unstructured peptides including Aβ. Immunoinactivation of PreP in human brain mitochondria revealed PreP to be the protease responsible for Aβ degradation in mitochondria.

    Also, we have investigated if genetic variation in the gene encoding hPreP is associated with AD by genotyping 19 single nucleotide polymorphisms (SNPs) in the Swedish population. The study did not show a genetic association between any of the genotyped SNPs and the risk to AD. However, the biochemical analysis of four SNPs selected on the basis of their location within a structural homology model of hPreP revealed a decreased activity compared to wildtype.

    Interestingly, the activity of PreP in human brain mitochondrial matrix in AD individuals was significantly lower compared to non-dement aged-matched controls. These findings were also confirmed in brain mitochondrial matrix of AD mouse models. These results suggest that a decreased PreP activity may contribute to Aβ aggregation and accumulation inside mitochondria leading to neuronal death in AD. In summary, our findings show that the degradation of Aβ by hPreP may be of importance in the pathology of AD.

  • 80.
    Al-Khalili, Lubna
    et al.
    KTH, Skolan för bioteknologi (BIO), Industriell bioteknologi.
    de Castro Barbosa, T.
    Östling, J.
    Massart, J.
    Katayama, M.
    Nyström, A. -C
    Oscarsson, J.
    Zierath, J. R.
    Profiling of human myotubes reveals an intrinsic proteomic signature associated with type 2 diabetes2014Inngår i: Translational Proteomics, ISSN 2212-9634, Vol. 2, nr 1, s. 25-38Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The development of insulin resistance and type 2 diabetes (T2D) involves a complex array of metabolic defects in skeletal muscle. An in vitro cell culture system excludes the acute effects of external systemic factors existing in vivo. Thus, we aimed to determine whether intrinsic differences in the protein profile exist in cultured myotubes derived from T2D versus normal glucose tolerant (NGT) healthy people. Applying two dimensional difference gel electrophoresis technology (2-D DIGE), the abundance of 47 proteins differed in myotubes derived from T2D patients versus NGT donors. Proteins involved in fatty acid and amino acid metabolism, TCA cycle, mitochondrial function, mRNA processing, DNA repair and cell survival showed higher abundance, while proteins associated with redox signaling (PARK7; Parkinson disease 7), glutathione metabolism (glutathione S-transferase, GST, isoforms T1, P1 and M2), and protein dynamics (heat shock protein, HSP, isoform B1 and 90A) showed reduced abundance in myotubes derived from T2D versus NGT donors. Consistent with our proteome analysis results, the level of total glutathione was reduced in myotubes obtained from T2D versus NGT donors. Taken together, our data provide evidence for intrinsic differences in the profile of proteins involved in energy metabolism, cellular oxidative stress, protein dynamics and gene regulation in myotubes derived from T2D patients. These differences thereby suggest a genetic or epigenetic influence on protein content level, which can be further investigated to understand the molecular underpinnings of T2D progression and lead to new therapeutic approaches.

  • 81. Allabwani, Haifaa
    Verification of Bordetella pertussis and Bordetella holmesii withreal-time PCR2017Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
    Abstract [en]

    Bordetella pertussis causes whooping cough, which is a very dangerous disease especially for children. A correct diagnose is very important. Bordetella pertussis usually misidentifies with Bordetella holmesii by routine polymerase chain reaction.The aim of the study is to evaluate a target sequence that can verify a Bordetella pertussis infection and distinguish it from other Bordetella species, in specific Bordetella holmesii.The target sequences' sensitivities were tested on the control bacterial strains. Sixty-five clinical samples were analyzed with real-time PCR.The study concludes that both IS481 and ptxA target sequences are highly specific to detect B. pertussis, while both ho_IS1001 and IS481 are specific to detect B. holmesii. Pa_IS1001 is specific to detect B. parapertussis. Culturing is less sensitive to detect Bordetella infection than real-time PCR.

  • 82.
    Allardyce, Benjamin J.
    et al.
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Rajkhowa, Rangam
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Dilley, Rodney J.
    Univ Western Australia, Sch Surg, Ear Sci Inst Australia, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Surg, Ear Sci Ctr, Nedlands, WA 6009, Australia..
    Xie, Zhigang
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Campbell, Luke
    Univ Melbourne, Dept Otolaryngol, Melbourne, Vic 3010, Australia..
    Keating, Adrian
    Univ Western Australia, Sch Mech & Chem Engn, Nedlands, WA 6009, Australia..
    Atlas, Marcus D.
    Univ Western Australia, Sch Surg, Ear Sci Inst Australia, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Surg, Ear Sci Ctr, Nedlands, WA 6009, Australia..
    von Unge, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Akershus Univ Hosp, Dept ENT, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Wang, Xungai
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Comparative acoustic performance and mechanical properties of silk membranes for the repair of chronic tympanic membrane perforations2016Inngår i: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 64, s. 65-74Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The acoustic and mechanical properties of silk membranes of different thicknesses were tested to determine their suitability as a repair material for tympanic membrane perforations. Membranes of different thickness (10-100 mu m) were tested to determine their frequency response and their resistance to pressure loads in a simulated ear canal model. Their mechanical rigidity to pressure loads was confirmed by tensile testing. These membranes were tested alongside animal cartilage, currently the strongest available myringoplasty graft as well as paper, which is commonly used for simpler procedures. Silk membranes showed resonant frequencies within the human hearing range and a higher vibrational amplitude than cartilage, suggesting that silk may offer good acoustic energy transfer characteristics. Silk membranes were also highly resistant to simulated pressure changes in the middle ear, suggesting they can resist retraction, a common cause of graft failure resulting from chronic negative pressures in the middle ear. Part of this strength can be explained by the substantially higher modulus of silk films compared with cartilage. This allows for the production of films that are much thinner than cartilage, with superior acoustic properties, but that still provide the same level of mechanical support as thicker cartilage. Together, these in vitro results suggest that silk membranes may provide good hearing outcomes while offering similar levels of mechanical support to the reconstructed middle ear.

  • 83.
    Ally Lalloo, Arshad
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Mapping the Role of ATP Binding and Hydrolysis of ClpB Domain in Francisella tularensis2017Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 84.
    Al-Masaraa, Nahil
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Terpenmetabolism i Artemisia annua: rekombinant produktion och karaktärisering av seskviterpensyntaser.2015Independent thesis Basic level (degree of Bachelor), 180 hpOppgave
    Abstract [sv]

    Malaria är en tropisk sjukdom som orsakas av encelliga organismer, protozoer från Plasmodium släktet. Varje år drabbas ungefär en halv miljard människor av malaria och cirka en miljon av dessa dör. Okomplicerad malaria är en mild form av malaria som enligt WHO rekommendationer ska behandlas med artemisinin baserad kombinationsterapi (ACT). Artemisinin produceras naturligt i låg mängd från växten Artemisia annua. Trots att medicinen har visat sig effektiv mot malaria med färre biverkningar är den höga kostnaden en nackdel. Forskning pågår för att hitta nya syntetiska vägar för framställning av artemisinin i växten genom att studera terpenmetabolism och vilka aktiva enzymer det finns som har en avgörande roll i utbytet av artemisinin i växten. Syftet med denna studie var att med hjälp av genteknik och molekylärbiologiska metoder producera och identifiera två rekombinanta enzymer, seskviterpensyntaser från A. annua. Experimentet inleddes med att transformera klonade T-DNA (AaTS-1 och AaTS-2) som kodar för seskviterpensyntaser från A. annua med hjälp av Agrobacterium tumefaciens vartefter transienta transkriptionen av generna som finns i en binär vektor initierades i blad från växten Nicotiana benthamiana genom infiltration. Totalt RNA extraherades från växten och översattes till cDNA för att sedan studera förhållandet av transient uttryck i bladen med qPCR. Enzymerna extraherades från bladen och inkuberades med farnesyldifosfat övernatt och produkten identifierades följande dag med gaskromatografi-masspektrofotometri (GC-MS). Resultatet blev att inget genuttryck av AaTS-1 och AaTS-2 kunde detekteras i bladen. Resultat från GC-MS visade att ingen proteinprodukt genererades. De negativa resultaten berodde främst på brist av resultat som verifierar att plasmiderna var konstruerade med selektionsgenerna, men även på grund av en icke effektiv transformation, orsakad av bakteriecellklumpar som förhindrade infiltreringsmedium att nå inre delarna av bladen.    

  • 85. Almeflo, Sandra
    The effect of shifting host plants on growth of butterfly larvae of Polygonia c-album.2014Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 86.
    Almeros, Isak
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Bindning av Adenovirus typ 40 till kommensala grampositiva och gramnegativa bakterier2013Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 87.
    Alrifaiy, Ahmed
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Luleå University of Technology.
    Bitaraf, Nazanin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Luleå University of Technology.
    Druzin, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Lindahl, Olof
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Luleå University of Technology.
    Ramser, K
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Luleå University of Technology.
    Hypoxia on a chip: a novel approach for patch-clamp studies in a microfluidic system with full oxygen control2013Inngår i: World Congress on Medical Physics and Biomedical Engineering May 26-31, 2012, Beijing, China / [ed] Mian Long, Springer Berlin/Heidelberg, 2013, s. 313-316Konferansepaper (Fagfellevurdert)
    Abstract [en]

    A new approach to perform patch-clamp experiments on living cells under controlled anoxic and normoxic conditions was developed and tested. To provide an optimal control over the oxygen content and the biochemical environment a patch-clamp recording micropipette was integrated within an oxygen tight poly-methyl methacrylate (PMMA) based microchip. The oxygen content within the microfluidic chamber surrounding patch-clamp micropipette was maintained at 0.5-1.5 % by a continuous flow of artificial extracellular solution purged with nitrogen. The nerve and glial cells acutely obtained from the male rat brain were trapped by the optical tweezers and steered towards the patch-clamp micropipette through the channels of the microchip in order to achieve a close contact between the pipette and the cellular membrane. The patch-clamp recordings revealed that optical tweezers did not affect the electrophysiological properties of the tested cells suggesting that optical trapping is a safe and non-traumatizing method to manipulate living cells in the microfluidic system. Thus, our approach of combining optical tweezers and a gas-tight microfluidic chamber may be applied in various electrophysiological investigations of single cells were optimal control of the experimental conditions and the sample in a closed environment are necessary.

  • 88. Alrifaiy, Ahmed
    et al.
    Borg, Johan
    Lindahl, Olof A.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Department of Computer Science, Electrical and Space Engineering, Luleå University of Technology; CMTF, Centre for Biomedical Engineering and Physics, Luleå and Umeå, Sweden; Department of Engineering Sciences and Mathematics, Luleå University of Technology.
    Ramser, Kerstin
    A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy-first investigations of single biological cells2015Inngår i: Biomedical engineering online, ISSN 1475-925X, E-ISSN 1475-925X, Vol. 14, artikkel-id 36Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O-2 to an anoxic value of 0.0-0.5% O-2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 +/- 1 s and a fully developed deoxygenated spectrum was observed after 298 +/- 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 +/- 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 +/- 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 +/- 0.412 M Omega and 889.7 +/- 1.74 M Omega respectively.

  • 89. Alrifaiy, Ahmed
    et al.
    Lindahl, Olof A
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Ramser, Kerstin
    Polymer-based microfluidic devices for pharmacy, biology and tissue engineering2012Inngår i: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 4, nr 3, s. 1349-1398Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    This paper reviews microfluidic technologies with emphasis on applications in the fields of pharmacy, biology, and tissue engineering. Design and fabrication of microfluidic systems are discussed with respect to specific biological concerns, such as biocompatibility and cell viability. Recent applications and developments on genetic analysis, cell culture, cell manipulation, biosensors, pathogen detection systems, diagnostic devices, high-throughput screening and biomaterial synthesis for tissue engineering are presented. The pros and cons of materials like polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA), polystyrene (PS), polycarbonate (PC), cyclic olefin copolymer (COC), glass, and silicon are discussed in terms of biocompatibility and fabrication aspects. Microfluidic devices are widely used in life sciences. Here, commercialization and research trends of microfluidics as new, easy to use, and cost-effective measurement tools at the cell/tissue level are critically reviewed.

  • 90.
    Alrifaiy, Ahmed
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Ramser, Kerstin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    How to integrate a micropipette into a closed microfluidic system: absorption spectra of an optically trapped erythrocyte2011Inngår i: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 2, nr 8, s. 2299-2306Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We present a new concept of integrating a micropipette within a closed microfluidic system equipped with optical tweezers and a UV-Vis spectrometer. A single red blood cell (RBC) was optically trapped and steered in three dimensions towards a micropipette that was integrated in the microfluidic system. Different oxygenation states of the RBC, triggered by altering the oxygen content in the microchannels through a pump system, were optically monitored by a UV-Vis spectrometer. The built setup is aimed to act as a multifunctional system where the biochemical content and the electrophysiological reaction of a single cell can be monitored simultaneously. The system can be used for other applications like single cell sorting, in vitro fertilization or electrophysiological experiments with precise environmental control of the gas-, and chemical content. 

  • 91. Alsaadi, Hani
    A new High Sensitive Functional Nephelometrical Assay for Assaying C- reactive protein in Serum Based on Phosphocholine Interaction2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Abstract

    C-reactive protein (CRP) is able to bind phosphocholine in the presence of calcium ions. According to a previous functional property of CRP, we tried to develop an affordable and cheap high sensitive nephelometric CRP assay using soy oil.

    Serum samples were measured by Nephelometer BNII (Siemens), by mixing the serum with diluted soy oil emulsion (Intralipid

    ®

    20%) and Tris-calcium buffer (PH 7.5). The measurement took place after 12 min incubation time at 37°C by measuring the agglutination between CRP and phosphocholine. Results from our automated functional assay were compared with results obtained using an immunoturbidimetric CRP assay.

    Results showed a good correlation coefficient for method comparison between functional nephelometric CRP assay and immunoturbidimetric CRP assay, r = 0.895, significance level p <0.0001. The limit of detection for the functional nephelometric CRP assay was 0.1 mg/L. However, the within run % CV values for the functional assay were 6.1 % (20 mg/L), 4.7 % (50 mg/L) and 4.5 % (100 mg/L). The between-run % CV values were 17.6 % (20 mg/L), 18.8 % (50 mg/L), and 11.3 % (100 mg/L).

    The new functional nephelometric CRP assay enables high sensitive CRP measurement in serum in the range of 0.1 mg/L to 300 mg/L. The functional assay could be used for veterinary analysis due to the ability to measure CRP according to the functional properties, not the morphological properties which depend on specific antibodies.

  • 92.
    Alstermark, Bror
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Hultborn, H
    University of Copenhagen Department of Neuroscience and Pharmacology Copenhagen N. Denmark.
    Jankowska, E
    Sahlgrenska Academy, University of Gothenburg Department of Physiology Gothenburg Sweden.
    Pettersson, L-G
    Sahlgrenska Academy, University of Gothenburg Department of Physiology Gothenburg Sweden.
    Anders Lundberg (1920-2009).2010Inngår i: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 200, nr 3-4, s. 193-195Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    Anders Lundberg was one of the founding editorial board members for EBR when it began its life in 1976 under the editorship of John Eccles. He was also one of the most prolific contributors to the journal with a total of 49 papers, including a series of 16 on the topic of “integration in descending motor pathways controlling the forelimb in the cat”. He continued as an editor of the journal until volume 16 when he persuaded his younger colleague Hans Hultborn to take his place. Hans is one of the authors of the obituary. –John Rothwell

  • 93.
    Alsén, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Immunohistochemical evaluation of antibodies for staining of mouse spinal cord and mouse neuronal cells2013Independent thesis Basic level (university diploma), 10 poäng / 15 hpOppgave
  • 94. Altai, M.
    et al.
    Westerlund, Kristina
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Velletta, J.
    Honarvar, H.
    Orlova, A.
    Eriksson Karlström, Amelie
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Tolmachev, V.
    Comparative evaluation of Lu-177-HP2 and In-111-HP2, secondary agents for affibody-based PNA-mediated radionuclide pretargeting2016Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, s. S237-S237Artikkel i tidsskrift (Fagfellevurdert)
  • 95.
    Altai, Mohamed
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Honarvar, Hadis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Wållberg, Helena
    Strand, Joanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Varasteh, Zohreh
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Rosestedt, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Dunås, Finn
    Sandström, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för medicinsk strålfysik.
    Löfblom, John
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Ståhl, Stefan
    Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with 188Re2014Inngår i: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 87, s. 519-528Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of 188Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all 188Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The 188Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of 188Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental 188Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of 188Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.

  • 96.
    Altai, Mohamed
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Westerlund, Kristina
    KTH Royal Inst Technol, Div Prot Technol, Sch Biotechnol, Stockholm, Sweden..
    Velletta, Justin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Mitran, Bogdan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Honarvar, Hadis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Eriksson Karlström, Amelie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Evaluation of affibody molecule-based PNA-mediated radionuclide pretargeting: Development of an optimized conjugation protocol and 177Lu labeling2017Inngår i: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 54, s. 1-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: We have previously developed a pretargeting approach for affibody-mediated cancer therapy based on PNA-PNA hybridization. In this article we have further developed this approach by optimizing the production of the primary agent, Z(HER2.342)-SR-HP1, and labeling the secondary agent, HP2, with the therapeutic radionuclide Lu-177. We also studied the biodistribution profile of Lu-177-HP2 in mice, and evaluated pretargeting with Lu-177-HP2 in vitro and in vivo.

    Methods: The biodistribution profile of Lu-177-HP2 was evaluated in NMRI mice and compared to the previously studied In-111-HP2. Pretargeting using Lu-177-HP2 was studied in vitro using the HER2-expressing cell lines BT-474 and SKOV-3, and in vivo in mice bearing SKOV-3 xenografts.

    Results and conclusion: Using an optimized production protocol for Z(HER2:342)-SR-HP1 the ligation time was reduced from 15 h to 30 min, and the yield increased from 45% to 70%. Lu-177-labeled HP2 binds specifically in vitro to BT474 and SKOV-3 cells pre-treated with Z(HER2:342)-SR-HP1.Lu-177-HP2 was shown to have a more rapid blood clearance compared to In-111-HP2 in NMRI mice, and the measured radioactivity in blood was 0.22 +/- 0.1 and 0.68 +/- 0.07%ID/g for Lu-177- and In-111-HP2, respectively, at 1 h p.i. In contrast, no significant difference in kidney uptake was observed (4.47 +/- 1.17 and 3.94 +/- 0.58%ID/g for Lu-177- and In-111-HP2, respectively, at I h p.i.). Co-injection with either Gelofusine or lysine significantly reduced the kidney uptake for Lu-177-HP2 (1.0 +/- 0.1 and 1.6 +/- 0.2, respectively, vs. 2.97 +/- 0.87%ID/g in controls at 4 h p.i.). Lu-177-HP2 accumulated in SKOV-3 xenografts in BALB/C nu/nu mice when administered after injection of Z(HER2:342)-SR-HP1. Without pre-injection of Z(HER2:342)-SR-HP1, the uptake of Lu-177-HP2 was about 90-fold lower in tumor (0.23 +/- 0.08 vs. 20.7 +/- 3.5%ID/g). The tumor-to-kidney radioactivity accumulation ratio was almost 5-fold higher in the group of mice pre-injected with Z(HER2:342)-SR-HP1. In conclusion, (177)LuHP2 was shown to be a promising secondary agent for affibody-mediated tumor pretargeting in vivo.

  • 97.
    Altun, O.
    et al.
    Division of Clinical Microbiology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Infectious Diseases, Örebro University, Örebro, Sweden.
    Almuhayawi, M.
    Division of Clinical Microbiology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Microbiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia.
    Strålin, K.
    Department of Infectious Diseases, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Özenci, V.
    Division of Clinical Microbiology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Rapid identification of Streptococcus pneumoniae in blood cultures by using the ImmuLex, Slidex and Wellcogen latex agglutination tests and the BinaxNOW antigen test2016Inngår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, nr 4, s. 579-585Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rapid identification of Streptococcus pneumoniae in blood culture (BC) bottles is important for early directed antimicrobial therapy in pneumococcal bacteraemia. We evaluated a new latex agglutination (LA) test on BC bottles, the ImmuLex™ S. pneumoniae Omni (Statens Serum Institut, Denmark), and compared the performance with the Slidex® pneumo-Kit (bioMérieux, France) and the Wellcogen™ S. pneumoniae (Remel, UK) LA tests, as well as the BinaxNOW® S. pneumoniae (Alere, USA) antigen test. The four tests were directly applied on 358 positive BC bottles with Gram-positive cocci in pairs or chains and on 15 negative bottles. Valid test results were recorded in all cases for ImmuLex and BinaxNOW and in 88.5 % (330/373) and 94.1 % (351/373) of cases for Slidex and Wellcogen, respectively. Based on bottles positive for S. pneumoniae by conventional methods, the sensitivity of ImmuLex was 99.6 %, similar to the other tests (range, 99.6-100 %). Based on bottles positive for non-pneumococcal pathogens, the specificity of ImmuLex was 82.6 %, in comparison to 97.6 % for Slidex (p < 0.01) and 85.4 % for Wellcogen (p = ns). The BinaxNOW test had a lower specificity (64.1 %) than any LA test (p < 0.01). On BC bottles positive for α-haemolytic streptococci, ImmuLex was positive in 12/67 (17.9 %) cases, Slidex in 2/59 (3.4 %) cases, Wellcogen in 11/64 (17.2 %) cases and BinaxNOW in 25/67 (37.3 %) cases. In conclusion, the ImmuLex test provides a valid and sensitive technique for the rapid detection of S. pneumoniae in BC bottles, similar to the other compared methods. However, the specificity was sub-optimal, since the test may cross-react with other Gram-positive bacteria.

  • 98. Alvarez, Francisco J.
    et al.
    Ryman, Kicki
    Hooijmaijers, Cornelis
    KTH, Skolan för bioteknologi (BIO), Glykovetenskap.
    Bulone, Vincent
    KTH, Skolan för bioteknologi (BIO), Glykovetenskap.
    Ljungdahl, Per O.
    Diverse Nitrogen Sources in Seminal Fluid Act in Synergy To Induce Filamentous Growth of Candida albicans2015Inngår i: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 81, nr 8, s. 2770-2780Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The pathogenic fungus Candida albicans is the leading cause of vulvovaginal candidiasis (VVC). VVC represents a major quality- of-life issue for women during their reproductive years, a stage of life where the vaginal epithelium is subject to periodic hormonally induced changes associated with menstruation and concomitant exposure to serum as well as potential intermittent contact with seminal fluid. Seminal fluid potently triggers Candida albicans to switch from yeastlike to filamentous modes of growth, a developmental response tightly linked to virulence. Conversely, vaginal fluid inhibits filamentation. Here, we used artificial formulations of seminal and vaginal fluids that faithfully mimic genuine fluids to assess the contribution of individual components within these fluids to filamentation. The high levels of albumin, amino acids, and N-acetylglucosamine in seminal fluid act synergistically as potent inducers of filamentous growth, even at atmospheric levels of CO2 and reduced temperatures (30 degrees C). Using a simplified in vitro model that mimics the natural introduction of seminal fluid into the vulvovaginal environment, a pulse of artificial seminal fluid (ASF) was found to exert an enduring potential to overcome the inhibitory efficacy of artificial vaginal fluid (AVF) on filamentation. These findings suggest that a transient but substantial change in the nutrient levels within the vulvovaginal environment during unprotected coitus can induce resident C. albicans cells to engage developmental programs associated with virulent growth.

  • 99.
    Alvarez, Laura
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Aliashkevich, Alena
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    de Pedro, Miguel A.
    Cava, Felipe
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Bacterial secretion of D-arginine controls environmental microbial biodiversity2018Inngår i: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 12, nr 2, s. 438-450Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bacteria face tough competition in polymicrobial communities. To persist in a specific niche, many species produce toxic extracellular effectors to interfere with the growth of nearby microbes. These effectors include the recently reported non-canonical D-amino acids (NCDAAs). In Vibrio cholerae, the causative agent of cholera, NCDAAs control cell wall integrity in stationary phase. Here, an analysis of the composition of the extracellular medium of V. cholerae revealed the unprecedented presence of D-Arg. Compared with other D-amino acids, D-Arg displayed higher potency and broader toxicity in terms of the number of bacterial species affected. Tolerance to D-Arg was associated with mutations in the phosphate transport and chaperone systems, whereas D-Met lethality was suppressed by mutations in cell wall determinants. These observations suggest that NCDAAs target different cellular processes. Finally, even though virtually all Vibrio species are tolerant to D-Arg, only a few can produce this D-amino acid. Indeed, we demonstrate that D-Arg may function as part of a cooperative strategy in vibrio communities to protect non-producing members from competing bacteria. Because NCDAA production is widespread in bacteria, we anticipate that D-Arg is a relevant modulator of microbial subpopulations in diverse ecosystems.

  • 100.
    Alvarez, Laura
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Espaillat, Akbar
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Hermoso, Juan A.
    de Pedro, Miguel A.
    Cava, Felipe
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Peptidoglycan Remodeling by the Coordinated Action of Multispecific Enzymes2014Inngår i: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 20, nr 3, s. 190-198Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The peptidoglycan (PG) cell wall constitutes the main defense barrier of bacteria against environmental insults and acts as communication interface. The biochemistry of this macromolecule has been well characterized throughout the years but recent discoveries have unveiled its chemical plasticity under environmental stresses. Non-canonical D-amino acids (NCDAA) are produced and released to the extracellular media by diverse bacteria. Such molecules govern cell wall adaptation to challenging environments through their incorporation into the polymer, a widespread capability among bacteria that reveals the inherent catalytic plasticity of the enzymes involved in the cell wall metabolism. Here, we analyze the recent structural and biochemical characterization of Bsr, a new family of broad spectrum racemases able to generate a wide range of NCDAA. We also discuss the necessity of a coordinated action of PG multispecific enzymes to generate adequate levels of modification in the murein sacculus. Finally, we also highlight how this catalytic plasticity of NCDAA-incorporating enzymes has allowed the development of new revolutionary methodologies for the study of PG modes of growth and in vivo dynamics.

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