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  • 1.
    Akbaba, Yusuf
    et al.
    Erzurum Tech Univ, Fac Sci, Dept Basic Sci, Erzurum, Turkiye..
    Kaci, Fatma Necmiye
    Erzurum Tech Univ, Fac Sci, Dept Mol Biol & Genet, Erzurum, Turkiye.;St James Univ Hosp, Univ Leeds, Fac Med & Hlth, Leeds, England..
    Arslan, Mehmet Enes
    Erzurum Tech Univ, Fac Sci, Dept Mol Biol & Genet, Erzurum, Turkiye..
    Goksu, Suleyman
    Ataturk Univ, Fac Sci, Dept Chem, Erzurum, Turkiye..
    Mardinoglu, Adil
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London, England.;KTH Royal Inst Technol, Sci Life Lab, SE-17121 Stockholm, Sweden..
    Turkez, Hasan
    Ataturk Univ, Fac Med, Dept Med Biol, Erzurum, Turkiye..
    Novel tetrahydronaphthalen-1-yl-phenethyl ureas: synthesis and dual antibacterial-anticancer activities2024In: Journal of enzyme inhibition and medicinal chemistry (Print), ISSN 1475-6366, E-ISSN 1475-6374, Vol. 39, no 1, article id 2286925Article in journal (Refereed)
    Abstract [en]

    Cancer and antibiotic-resistant bacterial infections are significant global health challenges. The resistance developed in cancer treatments intensifies therapeutic difficulties. In addressing these challenges, this study synthesised a series of N,N '-dialkyl urea derivatives containing methoxy substituents on phenethylamines. Using isocyanate for the efficient synthesis yielded target products 14-18 in 73-76% returns. Subsequently, their antibacterial and anticancer potentials were assessed. Cytotoxicity tests on cancer cell lines, bacterial strains, and a healthy fibroblast line revealed promising outcomes. All derivatives demonstrated robust antibacterial activity, with MIC values ranging from 0.97 to 15.82 mu M. Notably, compounds 14 and 16 were particularly effective against the HeLa cell line, while compounds 14, 15, and 17 showed significant activity against the SH-SY5Y cell line. Importantly, these compounds had reduced toxicity to healthy fibroblast cells than to cancer cells, suggesting their potential as dual-functioning agents targeting both cancer and bacterial infections.

  • 2. Akyuz, Lalehan
    et al.
    Kaya, Murat
    Koc, Behlul
    Mujtaba, Muhammad
    Ilk, Sedef
    Labidi, Jalel
    Salaberria, Asier M.
    Cakmak, Yavuz Selim
    Yildiz, Aysegul
    Diatomite as a novel composite ingredient for chitosan film with enhanced physicochemical properties2017In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 105, p. 1401-1411Article in journal (Refereed)
  • 3.
    Andersson, Christin
    et al.
    KTH, Superseded Departments (pre-2005), Biotechnology.
    Wikman, Maria
    KTH, Superseded Departments (pre-2005), Biotechnology.
    Lövgren-Bengtsson, Karin
    Lundén, Anne
    Ståhl, Stefan
    KTH, Superseded Departments (pre-2005), Biotechnology.
    In vivo and in vitro lipidation of recombinant immunogens for direct iscom incorporation2001In: Journal of Immunological Methods, ISSN 0022-1759, Vol. 255, no 1-2, p. 135-148Article in journal (Refereed)
    Abstract [en]

    We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic tags to improve their capacity to be incorporated into an adjuvant formulation (J. Immunol. Methods 222 (1999) 171; 238 (2000) 181). Here, we have explored the possibility to use in vivo or in vitro lipidation of recombinant immunogens as means to achieve iscom incorporation through hydrophobic interaction. For the in vivo lipidation strategy, a general expression vector was constructed encoding a composite tag consisting of a sequence (lpp) of the major lipoprotein of E. coli, fused to a dual affinity fusion tag to allow efficient recovery by affinity chromatography. Upon expression in E. coli, fatty acids would be linked to the produced gene products. To achieve in vitro lipidation, the target immunogen would be expressed in frame with an N-terminal His6-ABP affinity tag, in which the hexahistidyl tag was utilized to obtain lipidation via a Cu2+-chelating lipid. A 238 amino acid segment ΔSAG1, from the central region of the major surface antigen SAG1 of Toxoplasma gondii, served as model immunogen in this study. The two generated fusion proteins, lpp-His6-ABP-ΔSAG1 and His6-ABP-ΔSAG1, both expressed at high levels (approximately 5 and 100 mg/l, respectively), could be recovered to high purity by ABP-mediated affinity chromatography, and were evaluated in iscom-incorporation experiments. The His6-ABP-ΔSAG1 fusion protein was associated to iscom matrix with pre-incorporated chelating lipid. Both fusion proteins were found in the iscom fractions after analytical ultracentrifugation in a sucrose gradient, indicating successful iscom incorporation/association. Iscom formation was further supported by electron microscopy analysis. In addition, these iscom preparations were demonstrated to induce high-titer antigen-specific antibody responses upon immunization of mice. For this particular target immunogen, ΔSAG1, the induced antibodies demonstrated poor reactivity to the native antigen, although slightly better for the preparation employing the in vitro lipidation strategy, indicating that ΔSAG1 was suboptimally folded or presented. Nevertheless, we believe that the presented strategies offer convenient alternative ways to achieve efficient adjuvant incorporation for recombinant immunogens.

  • 4.
    Antypas, Haris
    et al.
    AIMES - Center for the Advancement of Integrated Medical and Engineering Sciences, Karolinska Institutet, Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Zhang, Tianqi
    AIMES - Center for the Advancement of Integrated Medical and Engineering Sciences, Karolinska Institutet, Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Choong, Ferdinand X.
    AIMES - Center for the Advancement of Integrated Medical and Engineering Sciences, Karolinska Institutet, Sweden; Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Melican, Keira
    AIMES - Center for the Advancement of Integrated Medical and Engineering Sciences, Karolinska Institutet Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Richter-Dahlfors, Agneta
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Dynamic single cell analysis in a proximal-tubule-on-chip reveals heterogeneous epithelial colonization strategies of uropathogenic Escherichia coli under shear stress2023In: FEMS Microbes, E-ISSN 2633-6685, Vol. 4, article id xtad007Article in journal (Refereed)
    Abstract [en]

    The urinary tract is a hydrodynamically challenging microenvironment and uropathogenic Escherichia coli (UPEC) must overcome several physiological challenges in order to adhere and establish a urinary tract infection. Our previous work in vivo revealed a synergy between different UPEC adhesion organelles, which facilitated effective colonization of the renal proximal tubule. To allow highresolution real-time analysis of this colonization behavior, we established a biomimetic proximal-tubule-on-chip (PToC). The PToC allowed for single-cell resolution analysis of the first stages of bacterial interaction with host epithelial cells, under physiological flow. Time-lapse microscopy and single-cell trajectory analysis in the PToC revealed that while the majority of UPEC moved directly through the system, a minority population initiated heterogeneous adhesion, identified as either rolling or bound. Adhesion was predominantly transient andmediated by P pili at the earliest time-points. These bound bacteria initiated a founder populationwhich rapidly divided, leading to 3D microcolonies. Within the first hours, the microcolonies did not express extracellular curli matrix, but rather were dependent on Type 1 fimbriae as the key element in the microcolony structure. Collectively, our results show the application of Organ-on-chip technology to address bacterial adhesion behaviors, demonstrating a well-orchestrated interplay and redundancy between adhesion organelles that enables UPEC to form microcolonies and persist under physiological shear stress.

  • 5.
    Arslan, Mehmet Enes
    et al.
    Erzurum Tech Univ, Fac Sci, Dept Mol Biol & Genet, TR-25050 Erzurum, Turkey..
    Tatar, Arzu
    Ataturk Univ, Fac Med, Dept Otorhinolaryngol, TR-25240 Erzurum, Turkey..
    Yildirim, Ozge Caglar
    Erzurum Tech Univ, Fac Sci, Dept Mol Biol & Genet, TR-25050 Erzurum, Turkey..
    Sahin, Irfan Oguz
    Ondokuz Mayis Univ, Fac Med, Dept Pediat, Pediat Cardiol, TR-55139 Samsun, Turkey..
    Ozdemir, Ozlem
    Erzurum Tech Univ, Fac Sci, Dept Mol Biol & Genet, TR-25050 Erzurum, Turkey..
    Sonmez, Erdal
    Ataturk Univ, Grad Sch Nat & Appl Sci, Dept Nanosci & Nanoengn, Adv Mat Res Lab, TR-25240 Erzurum, Turkey..
    Hacimuftuoglu, Ahmet
    Ataturk Univ, Med Fac, Dept Med Pharmacol, TR-25240 Erzurum, Turkey..
    Acikyildiz, Metin
    Kilis 7 Aralik Univ, Dept Chem, Fac Sci, TR-79000 Kilis, Turkey..
    Geyikoglu, Fatime
    Ataturk Univ, Fac Arts & Sci, Dept Biol, TR-25240 Erzurum, Turkey..
    Mardinoglu, Adil
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH Royal Inst Technol, Sci Life Lab, SE-17121 Stockholm, Sweden.;Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England..
    Turkez, Hasan
    Ataturk Univ, Fac Med, Dept Med Biol, TR-25240 Erzurum, Turkey..
    In Vitro Transcriptome Analysis of Cobalt Boride Nanoparticles on Human Pulmonary Alveolar Cells2022In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 15, no 23, article id 8683Article in journal (Refereed)
    Abstract [en]

    Nanobiotechnology influences many different areas, including the medical, food, energy, clothing, and cosmetics industries. Considering the wide usage of nanomaterials, it is necessary to investigate the toxicity potentials of specific nanosized molecules. Boron-containing nanoparticles (NPs) are attracting much interest from scientists due to their unique physicochemical properties. However, there is limited information concerning the toxicity of boron-containing NPs, including cobalt boride (Co2B) NPs. Therefore, in this study, Co2B NPs were characterized using X-ray crystallography (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX) techniques. Then, we performed 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, and neutral red (NR) assays for assessing cell viability against Co2B NP exposure on cultured human pulmonary alveolar epithelial cells (HPAEpiC). In addition, whole-genome microarray analysis was carried out to reveal the global gene expression differentiation of HPAEpiC cells after Co2B NP application. The cell viability tests unveiled an IC50 value for Co2B NPs of 310.353 mg/L. The results of our microarray analysis displayed 719 gene expression differentiations (FC >= 2) among the analyzed 40,000 genes. The performed visualization and integrated discovery (DAVID) analysis revealed that there were interactions between various gene pathways and administration of the NPs. Based on gene ontology biological processes analysis, we found that the P53 signaling pathway, cell cycle, and cancer-affecting genes were mostly affected by the Co2B NPs. In conclusion, we suggested that Co2B NPs would be a safe and effective nanomolecule for industrial applications, particularly for medical purposes.

  • 6. Ashokkumar, M.
    et al.
    Aralaguppe, S. G.
    Tripathy, S. P.
    Hanna, L. E.
    Neogi, Ujjwal
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Lab Med, Stockholm, Sweden.
    Unique phenotypic characteristics of recently transmitted HIV-1 subtype C envelope glycoprotein gp120: Use of CXCR6 coreceptor by transmitted founder viruses2018In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 92, no 9, article id e00063-18Article in journal (Refereed)
    Abstract [en]

    Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection. In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7- Luc-IRESs-NefΔgp120 to obtain chimeric viruses. Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection. Among the 250 clones tested, 65 chimeric viruses were infectious, and all belonged to HIV-1 subtype C. The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies. Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants. The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection. CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses. The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.

  • 7. Aspholm-Hurtig, Marina
    et al.
    Dailide, Giedrius
    Lahmann, Martina
    Kalia, Awdhesh
    Ilver, Dag
    Roche, Niamh
    Vikström, Susanne
    Sjöström, Rolf
    Lind\’e;n, Sara
    Bäckström, Anna
    Lundberg, Carina
    Arnqvist, Anna
    Mahdavi, Jafar
    Nilsson, Ulf J
    Velapatiño, Billie
    Gilman, Robert H
    Gerhard, Markus
    Alarcon, Teresa
    López-Brea, Manuel
    Nakazawa, Teruko
    Fox, James G
    Correa, Pelayo
    Dominguez-Bello, Maria Gloria
    Perez-Perez, Guillermo I
    Blaser, Martin J
    Normark, Staffan
    Carlstedt, Ingemar
    Oscarson, Stefan
    Teneberg, Susann
    Berg, Douglas E
    Bor\’e;n, Thomas
    Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin2004In: Science, Vol. 305, no 5683, p. 519-522Article in journal (Refereed)
    Abstract [en]

    Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.

  • 8.
    Azadpour, Behnam
    et al.
    Department of Materials Science and Engineering, Sharif University of Technology, Tehran, Iran.
    Aharipour, Nazli
    Department of Materials Science and Engineering, Sharif University of Technology, Tehran, Iran.
    Paryab, Amirhosein
    Department of Materials Science and Engineering, Sharif University of Technology, Tehran, Iran.
    Omid, Hamed
    Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran.
    Abdollahi, Sorosh
    Department of Biomedical Engineering, University of Calgary, Alberta, Canada.
    Madaah Hosseini, Hamidreza
    Department of Materials Science and Engineering, Sharif University of Technology, Tehran, Iran.
    Malek Khachatourian, Adrine
    Department of Materials Science and Engineering, Sharif University of Technology, Tehran, Iran.
    Toprak, Muhammet
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biomedical and X-ray Physics.
    Seifalian, Alexander M.
    Nanotechnology & Regenerative Medicine Commercialisation Centre (NanoRegMed Ltd, Nanoloom Ltd, & Liberum Health Ltd), London BioScience Innovation Centre, London, UK.
    Magnetically-assisted viral transduction (magnetofection) medical applications: An update2023In: Biomaterials Advances, E-ISSN 2772-9508, Vol. 154, article id 213657Article, review/survey (Refereed)
    Abstract [en]

    Gene therapy involves replacing a faulty gene or adding a new gene inside the body's cells to cure disease or improve the body's ability to fight disease. Its popularity is evident from emerging concepts such as CRISPR-based genome editing and epigenetic studies and has been moved to a clinical setting. The strategy for therapeutic gene design includes; suppressing the expression of pathogenic genes, enhancing necessary protein production, and stimulating the immune system, which can be incorporated into both viral and non-viral gene vectors. Although non-viral gene delivery provides a safer platform, it suffers from an inefficient rate of gene transfection, which means a few genes could be successfully transfected and expressed within the cells. Incorporating nucleic acids into the viruses and using these viral vectors to infect cells increases gene transfection efficiency. Consequently, more cells will respond, more genes will be expressed, and sustained and successful gene therapy can be achieved. Combining nanoparticles (NPs) and nucleic acids protects genetic materials from enzymatic degradation. Furthermore, the vectors can be transferred faster, facilitating cell attachment and cellular uptake. Magnetically assisted viral transduction (magnetofection) enhances gene therapy efficiency by mixing magnetic nanoparticles (MNPs) with gene vectors and exerting a magnetic field to guide a significant number of vectors directly onto the cells. This research critically reviews the MNPs and the physiochemical properties needed to assemble an appropriate magnetic viral vector, discussing cellular hurdles and attitudes toward overcoming these barriers to reach clinical gene therapy perspectives. We focus on the studies conducted on the various applications of magnetic viral vectors in cancer therapies, regenerative medicine, tissue engineering, cell sorting, and virus isolation.

  • 9.
    Bachmann, Julie
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Burte, Florence
    Pramana, Setia
    Conte, Ianina
    Brown, Biobele J.
    Orimadegun, Adebola E.
    Ajetunmobi, Wasiu A.
    Afolabi, Nathaniel K.
    Akinkunmi, Francis
    Omokhodion, Samuel
    Akinbami, Felix O.
    Shokunbi, Wuraola A.
    Kampf, Caroline
    Pawitan, Yudi
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sodeinde, Olugbemiro
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Wahlgren, Mats
    Fernandez-Reyes, Delmiro
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Affinity Proteomics Reveals Elevated Muscle Proteins in Plasma of Children with Cerebral Malaria2014In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 10, no 4, p. e1004038-Article in journal (Refereed)
    Abstract [en]

    Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.

  • 10.
    Begum, Neelu
    et al.
    Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England..
    Lee, Sunjae
    Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England..
    Pellon, Aize
    Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England..
    Nasab, Shervin Sadeghi
    Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England..
    Nieslen, Jens
    Chalmers Univ Technol, Dept Biol & Biol Engn, Kemivagen 10, SE-41296 Gothenburg, Sweden.;Biolnnovat Inst, Ole Maaloes Vej 3, DK-2200 Copenhagen N, Denmark..
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Moyes, David
    Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England..
    Shoaie, Saeed
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England..
    Portlock, Theo John
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Integrative functional analysis uncovers metabolic differences between Candida species2022In: Communications Biology, E-ISSN 2399-3642, Vol. 5, no 1, article id 1013Article in journal (Refereed)
    Abstract [en]

    Metabolic differences between Candida species are uncovered using the BioFung database alongside genomic and metabolic analysis. Candida species are a dominant constituent of the human mycobiome and associated with the development of several diseases. Understanding the Candida species metabolism could provide key insights into their ability to cause pathogenesis. Here, we have developed the BioFung database, providing an efficient annotation of protein-encoding genes. Along, with BioFung, using carbohydrate-active enzyme (CAZymes) analysis, we have uncovered core and accessory features across Candida species demonstrating plasticity, adaption to the environment and acquired features. We show a greater importance of amino acid metabolism, as functional analysis revealed that all Candida species can employ amino acid metabolism. However, metabolomics revealed that only a specific cluster of species (AGAu species-C. albicans, C. glabrata and C. auris) utilised amino acid metabolism including arginine, cysteine, and methionine metabolism potentially improving their competitive fitness in pathogenesis. We further identified critical metabolic pathways in the AGAu cluster with biomarkers and anti-fungal target potential in the CAZyme profile, polyamine, choline and fatty acid biosynthesis pathways. This study, combining genomic analysis, and validation with gene expression and metabolomics, highlights the metabolic diversity with AGAu species that underlies their remarkable ability to dominate they mycobiome and cause disease.

  • 11.
    Bernardi, Anna
    et al.
    Univ Milan, Dipartimento Chim Organ & Ind, I-20133 Milan, Italy.;Univ Milan, Ctr Eccellenza CISI, I-20133 Milan, Italy..
    Jimenez-Barbero, Jesus
    CSIC, Ctr Invest Biol, Madrid 28040, Spain..
    Casnati, Alessandro
    Univ Parma, Dipartimento Chim, I-43100 Parma, Italy..
    De Castro, Cristina
    Univ Naples Federico II, Dept Chem Sci, I-80126 Naples, Italy..
    Darbre, Tamis
    Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland..
    Fieschi, Franck
    Inst Biol Struct, F-38027 Grenoble 1, France..
    Finne, Jukka
    Univ Helsinki, Dept Biosci, FI-00014 Helsinki, Finland..
    Funken, Horst
    Univ Dusseldorf, Forschungszentrum Julich, Inst Mol Enzyme Technol, D-42425 Julich, Germany..
    Jaeger, Karl-Erich
    Univ Dusseldorf, Forschungszentrum Julich, Inst Mol Enzyme Technol, D-42425 Julich, Germany..
    Lahmann, Martina
    Bangor Univ, Sch Chem, Bangor LL57 2UW, Gwynedd, Wales..
    Lindhorst, Thisbe K.
    Univ Kiel, Otto Diels Inst Organ Chem, D-24098 Kiel, Germany..
    Marradi, Marco
    CIC BiomaGUNE, Lab GlycoNanotechnol, San Sebastian 20009, Spain.;CIBER BBN, San Sebastian 20009, Spain..
    Messner, Paul
    Univ Nat Resources & Life Sci, NanoGlycobiol Unit, Dept NanoBiotechnol, A-1190 Vienna, Austria..
    Molinaro, Antonio
    Univ Naples Federico II, Dept Chem Sci, I-80126 Naples, Italy..
    Murphy, Paul V.
    Natl Univ Ireland, Sch Chem, Galway, Ireland..
    Nativi, Cristina
    Univ Florence, Dipartimento Chim, I-50019 Sesto Fiorentino, Italy..
    Oscarson, Stefan
    Univ Coll Dublin, UCD Sch Chem & Chem Biol, Ctr Synth & Chem Biol, Dublin 4, Ireland..
    Penades, Soledad
    CIC BiomaGUNE, Lab GlycoNanotechnol, San Sebastian 20009, Spain.;CIBER BBN, San Sebastian 20009, Spain..
    Peri, Francesco
    Univ Milano Bicocca, I-20126 Milan, Italy..
    Pieters, Roland J.
    Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Med Chem & Chem Biol, NL-3508 TB Utrecht, Netherlands..
    Renaudet, Olivier
    Univ Grenoble 1, UMR CNRS 5250, Dept Chim Mol, F-38041 Grenoble, France.;Univ Grenoble 1, ICMG FR 2607, F-38041 Grenoble, France..
    Reymond, Jean-Louis
    Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland..
    Richichi, Barbara
    Univ Florence, Dipartimento Chim, I-50019 Sesto Fiorentino, Italy..
    Rojo, Javier
    Univ Seville, CSIC, Inst Invest Quim, Glycosyst Lab, Seville 41092, Spain..
    Sansone, Francesco
    Univ Parma, Dipartimento Chim, I-43100 Parma, Italy..
    Schaeffer, Christina
    Univ Nat Resources & Life Sci, NanoGlycobiol Unit, Dept NanoBiotechnol, A-1190 Vienna, Austria..
    Turnbull, W. Bruce
    Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England.;Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England..
    Velasco-Torrijos, Trinidad
    Natl Univ Ireland, Dept Chem, Maynooth, Kildare, Ireland..
    Vidal, Sebastien
    Univ Lyon 1, CNRS, Inst Chim & Biochim Mol & Supramol UMR 5246, F-69622 Villeurbanne, France.;Univ Namur FUNDP, Dept Chim, Chim Bioorgan Lab, B-5000 Namur, Belgium..
    Vincent, Stephane
    Wennekes, Tom
    Wageningen Univ, Organ Chem Lab, NL-6703 HB Wageningen, Netherlands..
    Zuilhof, Han
    Wageningen Univ, Organ Chem Lab, NL-6703 HB Wageningen, Netherlands.;King Abdulaziz Univ, Dept Chem & Mat Engn, Jeddah 21413, Saudi Arabia..
    Imberty, Anne
    Univ Grenoble, Ctr Rech Macromol Vegetales CERMAV CNRS, F-38041 Grenoble, France..
    Multivalent glycoconjugates as anti-pathogenic agents2013In: Chemical Society Reviews, ISSN 0306-0012, E-ISSN 1460-4744, Vol. 42, no 11, p. 4709-4727Article, review/survey (Refereed)
    Abstract [en]

    Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein-glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategies.

  • 12. Birse, Kenzie D.
    et al.
    Romas, Laura M.
    Guthrie, Brandon L.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Bosire, Rose
    Kiarie, James
    Farquhar, Carey
    Broliden, Kristina
    Burgener, Adam D.
    Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices2017In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 215, no 4, p. 590-598Article in journal (Refereed)
    Abstract [en]

    Background. Increasing evidence suggests depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with human immunodeficiency virus (HIV-1) infection risk; however, the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital proteome and microbiome to gain mechanistic insights. Methods. Cervicovaginal secretions from 86 Kenyan women, including self-reported DMPA users (n = 23), nonhormonal contraceptive users (n = 63), and women who practice vaginal drying (n = 46), were analyzed using tandem-mass spectrometry. Results. We identified 473 human and 486 bacterial proteins from 18 different genera. Depot medroxyprogesterone acetate use associated with increased hemoglobin and immune activation (HBD, HBB, IL36G), and decreased epithelial repair proteins (TFF3, F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1, MYH9, PLAUR). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. More diverse (H index: 0.71 vs 0.45; P =.009) bacterial communities containing Gardnerella vaginalis associated with vaginal drying, whereas DMPA showed no significant association with community composition or diversity. Conclusions. These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers. Future investigations are needed to confirm their relationship with HIV risk in women.

  • 13.
    Butina, Karen
    et al.
    Department of Neuroscience, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
    Tomac, Ana
    Department of Neuroscience, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
    Choong, Ferdinand X.
    Department of Neuroscience, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
    Shirani, Hamid
    Department of Chemistry, IFM, Linköping University, SE-581 83, Linköping, Sweden.
    Nilsson, K. Peter R.
    Department of Chemistry, IFM, Linköping University, SE-581 83, Linköping, Sweden.
    Löffler, Susanne
    Department of Neuroscience, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
    Richter-Dahlfors, Agneta
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH). Department of Neuroscience, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
    Optotracing for selective fluorescence-based detection, visualization and quantification of live S. aureus in real-time2020In: npj Biofilms and Microbiomes, E-ISSN 2055-5008, Vol. 6, no 1, article id 35Article in journal (Refereed)
    Abstract [en]

    Methods for bacterial detection are needed to advance the infection research and diagnostics. Based on conformation-sensitive fluorescent tracer molecules, optotracing was recently established for dynamic detection and visualization of structural amyloids and polysaccharides in the biofilm matrix of gram-negative bacteria. Here, we extend the use of optotracing for detection of gram-positive bacteria, focussing on the clinically relevant opportunistic human pathogen Staphylococcus aureus. We identify a donor-acceptor-donor-type optotracer, whose binding-induced fluorescence enables real-time detection, quantification, and visualization of S. aureus in monoculture and when mixed with gram-negative Salmonella Enteritidis. An algorithm-based automated high-throughput screen of 1920 S. aureus transposon mutants recognized the cell envelope as the binding target, which was corroborated by super-resolution microscopy of bacterial cells and spectroscopic analysis of purified cell wall components. The binding event was essentially governed by hydrophobic interactions, which permitted custom-designed tuning of the binding selectivity towards S. aureus versus Enterococcus faecalis by appropriate selection of buffer conditions. Collectively this work demonstrates optotracing as an enabling technology relevant for any field of basic and applied research, where visualization and detection of S. aureus is needed.

  • 14.
    de Oliveira, Andressa Souza
    et al.
    Univ Brasilia, Fac Med, Trop Med Ctr, Lab Dev Therapeut Innovat, Campus Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil.;Univ Brasilia, Fac Hlth Sci, Postgrad Program Pharmaceut Sci, Asa Norte, Campus Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil..
    de Oliveira, Jonathas Sales
    Univ Fed Ceara, Specialized Med Mycol Ctr, Dept Pathol & Legal Med, Postgrad Program Med Microbiol, Rua Cel Nunes Melo 1315, BR-60430275 Fortaleza, CE, Brazil..
    Kumar, Rajender
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Silva, Fabiana Brandao Alves
    Univ Brasilia, Fac Med, Postgrad Program Trop Med, Campus Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil..
    Fernandes, Mirele Rodrigues
    Univ Fed Ceara, Specialized Med Mycol Ctr, Dept Pathol & Legal Med, Postgrad Program Med Microbiol, Rua Cel Nunes Melo 1315, BR-60430275 Fortaleza, CE, Brazil..
    Nobre, Feynman Dias
    Univ Fed Ceara, Specialized Med Mycol Ctr, Dept Pathol & Legal Med, Postgrad Program Med Microbiol, Rua Cel Nunes Melo 1315, BR-60430275 Fortaleza, CE, Brazil..
    Costa, Anderson da Cunha
    Univ Fed Ceara, Specialized Med Mycol Ctr, Dept Pathol & Legal Med, Postgrad Program Med Microbiol, Rua Cel Nunes Melo 1315, BR-60430275 Fortaleza, CE, Brazil..
    Albuquerque, Patricia
    Univ Brasilia, Ctr Metropolitano Conjunto, Campus Ceilandia,Lote 01, BR-72220900 Brasilia, DF, Brazil..
    Sidrim, Jose Julio Costa
    Univ Fed Ceara, Specialized Med Mycol Ctr, Dept Pathol & Legal Med, Postgrad Program Med Microbiol, Rua Cel Nunes Melo 1315, BR-60430275 Fortaleza, CE, Brazil..
    Rocha, Marcos Fabio Gadelha
    Univ Fed Ceara, Specialized Med Mycol Ctr, Dept Pathol & Legal Med, Postgrad Program Med Microbiol, Rua Cel Nunes Melo 1315, BR-60430275 Fortaleza, CE, Brazil..
    Santos, Flavia Almeida
    Univ Fed Ceara, Dept Physiol & Pharmacol, Lab Nat Prod, Rua Cel Nunes Melo 1315, BR-60430275 Fortaleza, CE, Brazil..
    Srivastava, Vaibhav
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Romeiro, Luiz Antonio Soares
    Univ Brasilia, Fac Med, Trop Med Ctr, Lab Dev Therapeut Innovat, Campus Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil.;Univ Brasilia, Fac Hlth Sci, Postgrad Program Pharmaceut Sci, Asa Norte, Campus Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil.;Univ Brasilia, Fac Med, Postgrad Program Trop Med, Campus Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil.;Campus Univ Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil..
    Brilhante, Raimunda Samia Nogueira
    Univ Fed Ceara, Specialized Med Mycol Ctr, Dept Pathol & Legal Med, Postgrad Program Med Microbiol, Rua Cel Nunes Melo 1315, BR-60430275 Fortaleza, CE, Brazil.;Rua Coronel Nunes Melo 1315, BR-60420270 Fortaleza, CE, Brazil..
    Antifungal activity of sustainable histone deacetylase inhibitors against planktonic cells and biofilms of Candida spp. and Cryptococcusneoformans2023In: Medical Mycology, ISSN 1369-3786, E-ISSN 1460-2709, Vol. 61, no 8, article id myad073Article in journal (Refereed)
    Abstract [en]

    The limited therapeutic options for fungal infections and the increased incidence of fungal strains resistant to antifungal drugs, especially Candida spp., require the development of new antifungal drugs and strategies. Histone deacetylase inhibitors (HDACi), like vorinostat, have been studied in cancer treatment and have antifungal effects, acting alone or synergistically with classical antifungals. Here we investigated the antifungal activity of two novel sustainable HDACi (LDT compounds) based on vorinostat structure. Molecular docking simulation studies reveal that LDT compounds can bind to Class-I HDACs of Candida albicans, C. tropicalis, and Cryptococcus neoformans, which showed similar binding mode to vorinostat. LDT compounds showed moderate activity when tested alone against fungi but act synergistically with antifungal azoles against Candida spp. They reduced biofilm formation by more than 50% in C. albicans (4 µg/mL), with the main action in fungal filamentation. Cytotoxicity of the LDT compounds against RAW264.7 cells was evaluated and LDT536 demonstrated cytotoxicity only at the concentration of 200 µmol/L, while LDT537 showed IC50 values of 29.12 µmol/L. Our data indicated that these sustainable and inexpensive HDACi have potential antifungal and antibiofilm activities, with better results than vorinostat, although further studies are necessary to better understand the mechanism against fungal cells.

  • 15. Demir, E. S.
    et al.
    Oyardi, O.
    Savage, P. B.
    Altay, Özlem
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Bozkurt-Guzel, C.
    In vitro activity of ceragenins against Burkholderia cepacia complex2022In: Journal of Antibiotics, ISSN 0021-8820, E-ISSN 1881-1469, Vol. 75, no 7, p. 403-409Article in journal (Refereed)
    Abstract [en]

    Burkholderia cepacia complex (Bcc) species are aerobic, Gram-negative and non-fermantative bacilli. Bcc can cause clinical symptoms in patients with cystic fibrosis, ranging from asymptomatic carriage to fatal pneumonia. A pressing need exists for new antimicrobial agents that target Bcc. Ceragenins, CSA-13, CSA-131 and CSA-131 with 5% Pluronic® F127 (CSA-131P), were evaluated against Bcc clinical isolates (n = 42). MICs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1x, 4x MICs of ceragenins and sulfamethoxazole-trimethoprim (SXT), levofloxacin. MIC50/ MIC90 results (mg l−1) of CSA-13, CSA-131 and CSA-131P were determined as 16/64, 16/128 and 16/128, respectively. CSA-13 and CSA-131 showed bactericidal activity. CSA-13 - levofloxacin combination displayed synergistic activity against Bcc. First-generation (CSA-13) and second-generation (CSA-131 and CSA-131P) ceragenins have significant antimicrobial effects on Bcc. The findings of this study demonstrate that combinations of ceragenins with currently marketed antibiotics could be synergistic in vitro against Bcc isolates. These results suggest that combination therapy with conventional antibiotics could be an alternative approach for treating Bcc infections in the future. 

  • 16.
    Drobin, Kimi
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Highly multiplexed antibody suspension bead arrays for plasma protein profiling2013In: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 1023, p. 137-145Article in journal (Refereed)
    Abstract [en]

    Alongside the increasing availability of affinity reagents, antibody microarrays have become a powerful tool to screen for target proteins in complex samples. Applying directly labeled samples onto arrays instead of using sandwich assays offers an approach to facilitate a systematic, high-throughput, and flexible exploration of protein profiles in body fluids such as serum or plasma. As an alternative to planar arrays, a system based on color-coded beads for the creation of antibody arrays in suspension has become available to offer a microtiter plate-based option for screening larger number of samples with variable sets of capture reagents. A procedure was established for analyzing biotinylated samples without the necessity to remove excess labeling substance. We have shown that this assay system allows detecting proteins down into lower pico-molar and higher pg/ml levels with dynamic ranges over three orders of magnitude. Presently, this workflow enables the profiling of 384 samples for up to 384 proteins per assay.

  • 17.
    Eckert, Johannes A.
    et al.
    Karolinska Inst, AIMES Ctr Advancement Integrated Med & Engn Sci, Stockholm, Sweden.;Karolinska Inst, Dept Neurosci, Solnavagen 9, SE-17177 Stockholm, Sweden.;Swiss Fed Inst Technol, Dept Biol, Zurich, Switzerland..
    Rosenberg, Ming
    Karolinska Inst, AIMES Ctr Advancement Integrated Med & Engn Sci, Stockholm, Sweden.;KTH Royal Inst Technol, Stockholm, Sweden.;Karolinska Inst, Dept Neurosci, Solnavagen 9, SE-17177 Stockholm, Sweden..
    Rhen, Mikael
    Karolinska Inst, AIMES Ctr Advancement Integrated Med & Engn Sci, Stockholm, Sweden.;KTH Royal Inst Technol, Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solnavagen 9, SE-17177 Stockholm, Sweden..
    Choong, Ferdinand X.
    Karolinska Inst, AIMES Ctr Advancement Integrated Med & Engn Sci, Stockholm, Sweden.;KTH Royal Inst Technol, Stockholm, Sweden.;Karolinska Inst, Dept Neurosci, Solnavagen 9, SE-17177 Stockholm, Sweden..
    Richter-Dahlfors, Agneta
    KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Karolinska Inst, Dept Neurosci, Solnavagen 9, SE-17177 Stockholm, Sweden..
    An optotracer-based antibiotic susceptibility test specifically targeting the biofilm lifestyle of Salmonella2022In: Biofilm, E-ISSN 2590-2075, Vol. 4, p. 100083-, article id 100083Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance is a medical threat of global dimensions. Proper antimicrobial susceptibility testing (AST) for drug development, patient diagnosis and treatment is crucial to counteract ineffective drug use and resistance development. Despite the important role of bacterial biofilms in chronic and device-associated in-fections, the efficacy of antibiotics is determined using planktonic cultures. To address the need for antibiotics targeting bacteria in the biofilm lifestyle, we here present an optotracing-based biofilm-AST using Salmonella as model. Our non-disruptive method enables real-time recording of the extracellular matrix (ECM) components, providing specific detection of the biofilm lifestyle. Biofilm formation prior to antibiotic challenge can thus be confirmed and pre-treatment data collected. By introducing Kirby-Bauer discs, we performed a broad screen of the effects of antibiotics representing multiple classes, and identified compounds with ECM inhibitory as well as promoting effects. These compounds were further tested in agar-based dose-response biofilm-AST assays. By quantifying the ECM based on the amount of curli, and by visualizing the biofilm size and morphology, we achieved new information directly reflecting the treated biofilm. This verified the efficacy of several antibiotics that were effective in eradicating pre-formed biofilms, and it uncovered intriguing possible resistance mecha-nisms initiated in response to treatments. By providing deeper insights into the resistances and susceptibilities of microbes, expanded use of the biofilm-AST will contribute to more effective treatments of infections and reduced resistance development.

  • 18.
    Engström, Anna
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Antonenka, Uladzimir
    Kadyrov, Abdylat
    Kalmambetova, Gulmira
    Kranzer, Katharina
    Merker, Matthias
    Kabirov, Olim
    Parpieva, Nargiza
    Rajabov, Asliddin
    Sahalchyk, Evgeni
    Sayfudtinov, Zayniddin
    Niemann, Stefan
    Hoffmann, Harald
    Population structure of drug-resistant Mycobacterium tuberculosis in Central Asia2019In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 19, no 1, article id 908Article in journal (Refereed)
    Abstract [en]

    Background: Drug-resistant tuberculosis (TB) is a major public health concern threathing the success of TB control efforts, and this is particularily problematic in Central Asia. Here, we present the first analysis of the population structure of Mycobacterium tuberculosis complex isolates in the Central Asian republics Uzbekistan, Tajikistan, and Kyrgyzstan. Methods: The study set consisted of 607 isolates with 235 from Uzbekistan, 206 from Tajikistan, and 166 from Kyrgyzstan. 24-loci MIRU-VNTR (Mycobacterial Interspersed Repetitive Units - Variable Number of Tandem Repeats) typing and spoligotyping were combined for genotyping. In addition, phenotypic drug suceptibility was performed. Results: The population structure mainly comprises strains of the Beijing lineage (411/607). 349 of the 411 Beijing isolates formed clusters, compared to only 33 of the 196 isolates from other clades. Beijing 94-32 (n = 145) and 100-32 (n = 70) formed the largest clusters. Beijing isolates were more frequently multidrug-resistant, pre-extensively resistant (pre-XDR)- or XDR-TB than other genotypes. Conclusions: Beijing clusters 94-32 and 100-32 are the dominant MTB genotypes in Central Asia. The relative size of 100-32 compared to previous studies in Kazakhstan and its unequal geographic distribution support the hypothesis of its more recent emergence in Central Asia. The data also demonstrate that clonal spread of resistant TB strains, particularly of the Beijing lineage, is a root of the so far uncontroled MDR-TB epidemic in Central Asia.

  • 19.
    Ezzamouri, Bouchra
    et al.
    Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.;Kings Coll London, St Johns Inst Dermatol, Unit Populat Based Dermatol, London, England.;Guys & St Thomas NHS Fdn Trust, London, England..
    Rosario, Dorines
    Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England..
    Bidkhori, Gholamreza
    Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.;AIVIVO Ltd, Bioinnovat Ctr, Unit 25, Cambridge Sci Pk, Cambridge, England..
    Lee, Sunjae
    Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England..
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Shoaie, Saeed
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Kings Coll London, Fac Dent Oral & Craniofacial Sci.
    Metabolic modelling of the human gut microbiome in type 2 diabetes patients in response to metformin treatment2023In: NPJ SYSTEMS BIOLOGY AND APPLICATIONS, ISSN 2056-7189, Vol. 9, no 1, article id 2Article in journal (Refereed)
    Abstract [en]

    The human gut microbiome has been associated with several metabolic disorders including type 2 diabetes mellitus. Understanding metabolic changes in the gut microbiome is important to elucidate the role of gut bacteria in regulating host metabolism. Here, we used available metagenomics data from a metformin study, together with genome-scale metabolic modelling of the key bacteria in individual and community-level to investigate the mechanistic role of the gut microbiome in response to metformin. Individual modelling predicted that species that are increased after metformin treatment have higher growth rates in comparison to species that are decreased after metformin treatment. Gut microbial enrichment analysis showed prior to metformin treatment pathways related to the hypoglycemic effect were enriched. Our observations highlight how the key bacterial species after metformin treatment have commensal and competing behavior, and how their cellular metabolism changes due to different nutritional environment. Integrating different diets showed there were specific microbial alterations between different diets. These results show the importance of the nutritional environment and how dietary guidelines may improve drug efficiency through the gut microbiota.

  • 20.
    Fredolini, Claudia
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Dodig-Crnkovic, Tea
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Bendes, Annika
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Dahl, Leo
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Dale, Matilda
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Albrecht, Vincent
    KTH. Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, 171 65, Solna, Sweden.
    Mattsson, Cecilia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Thomas, Cecilia Engel
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Naluai, Asa Torinsson
    Univ Gothenburg, Inst Biomed, Sahlgrenska Acad, S-40530 Gothenburg, Sweden..
    Gisslen, Magnus
    Univ Gothenburg, Sahlgrenska Acad, Dept Infect Dis, S-40530 Gothenburg, Sweden.;Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden.;Publ Hlth Agcy Sweden, S-17165 Solna, Sweden..
    Beck, Olof
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden..
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Univ Hosp, MedTechLabs, BioClinicum, S-17164 Solna, Sweden.
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Proteome profiling of home-sampled dried blood spots reveals proteins of SARS-CoV-2 infections2024In: Communications Medicine, E-ISSN 2730-664X, Vol. 4, no 1, article id 55Article in journal (Refereed)
    Abstract [en]

    Background Self-sampling of dried blood spots (DBS) offers new routes to gather valuable health-related information from the general population. Yet, the utility of using deep proteome profiling from home-sampled DBS to obtain clinically relevant insights about SARS-CoV-2 infections remains largely unexplored.Methods Our study involved 228 individuals from the general Swedish population who used a volumetric DBS sampling device and completed questionnaires at home during spring 2020 and summer 2021. Using multi-analyte COVID-19 serology, we stratified the donors by their response phenotypes, divided them into three study sets, and analyzed 276 proteins by proximity extension assays (PEA). After normalizing the data to account for variances in layman-collected samples, we investigated the association of DBS proteomes with serology and self-reported information.Results Our three studies display highly consistent variance of protein levels and share associations of proteins with sex (e.g., MMP3) and age (e.g., GDF-15). Studying seropositive (IgG+) and seronegative (IgG-) donors from the first pandemic wave reveals a network of proteins reflecting immunity, inflammation, coagulation, and stress response. A comparison of the early-infection phase (IgM+IgG-) with the post-infection phase (IgM-IgG+) indicates several proteins from the respiratory system. In DBS from the later pandemic wave, we find that levels of a virus receptor on B-cells differ between seropositive (IgG+) and seronegative (IgG-) donors.Conclusions Proteome analysis of volumetric self-sampled DBS facilitates precise analysis of clinically relevant proteins, including those secreted into the circulation or found on blood cells, augmenting previous COVID-19 reports with clinical blood collections. Our population surveys support the usefulness of DBS, underscoring the role of timing the sample collection to complement clinical and precision health monitoring initiatives. The COVID-19 pandemic has posed multiple challenges to healthcare systems. A significant gap that remains is a lack of understanding of the impact of SARS-CoV-2 on individuals who did not seek or require hospitalization. To address this, we distribute self-sampling devices to random citizens, aiming to analyze how blood protein levels are affected in people who have had COVID-19 but had no or mild symptoms. Conducting multiple molecular measurements in dried blood, our study confirms clinically known markers and their relationship to infection stages, even if the donors themselves collect the sample. Our work highlights the potential of combining self-sampling with laboratory methods to provide useful information on human health. This convenient patient-centric sampling approach may potentially be useful when studying other diseases. Fredolini et al. present a proteomics analysis of home-sampled dried blood spots taken from the general population in Stockholm during the COVID-19 pandemic. The study provides insights into the molecular effects of SARS-CoV-2 infection in non-hospitalized individuals and demonstrates the compatibility of self-sampled blood spots with proteomics.

  • 21. Hultström, M.
    et al.
    Roxhed, Niclas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Nordquist, L.
    Intradermal insulin delivery: A promising future for diabetes management2014In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 8, no 3, p. 453-457Article in journal (Refereed)
    Abstract [en]

    The incidence of insulinopenic diabetes mellitus is constantly increasing, and in addition, approximately a third of all hyperinsulinemic diabetic patients develop insulinopenia. Optimal glycemic control is essential to minimize the risk for diabetes-induced complications, but the majority of diabetic patients fail to achieve proper long-term glucose levels even in clinical trials, and even more so in clinical practice. Compliance with a treatment regimen is likely to be higher if the procedure is simple, painless, and discreet. Thus, insulin has been suggested for nasal, gastrointestinal, and inhalation therapy, but so far with considerable downsides in effect, side effects, or patient acceptance. The stratum corneum is the main barrier preventing convenient drug administration without the drawbacks of subcutaneous injections. Recently, devices with miniaturized needles have been developed that combine the simplicity and discretion of patch-based treatments, but with the potential of peptide and protein administration. As this review describes, initial comparisons with subcutaneous administration now suggest microneedle patches for active insulin delivery are efficient in maintaining glycemic control. Hollow microneedle technology could also prove to be efficient in systemic as well as local delivery of other macromolecular drugs, such as vaccines.

  • 22. Hunold, A.
    et al.
    Escobedo-Hinojosa, W.
    Potoudis, E.
    Resende, D.
    Farr, T.
    Syrén, Per-Olof
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    Hauer, B.
    Assembly of a Rieske non-heme iron oxygenase multicomponent system from Phenylobacterium immobile E DSM 1986 enables pyrazon cis-dihydroxylation in E. coli2021In: Applied Microbiology and Biotechnology, ISSN 0175-7598, E-ISSN 1432-0614, Vol. 105, no 5, p. 2003-2015Article in journal (Refereed)
    Abstract [en]

    Abstract: Phenylobacterium immobile strain E is a soil bacterium with a striking metabolism relying on xenobiotics, such as the herbicide pyrazon, as sole carbon source instead of more bioavailable molecules. Pyrazon is a heterocyclic aromatic compound of environmental concern and its biodegradation pathway has only been reported in P. immobile. The multicomponent pyrazon oxygenase (PPO), a Rieske non-heme iron oxygenase, incorporates molecular oxygen at the 2,3 position of the pyrazon phenyl moiety as first step of degradation, generating a cis-dihydrodiendiol. The aim of this work was to identify the genes encoding for each one of the PPO components and enable their functional assembly in Escherichia coli. P. immobile strain E genome sequencing revealed genes encoding for RO components, such as ferredoxin-, reductase-, α- and β-subunits of an oxygenase. Though, P. immobile E displays three prominent differences with respect to the ROs currently characterized: (1) an operon-like organization for PPO is absent, (2) all the elements are randomly scattered in its DNA, (3) not only one, but 19 different α-subunits are encoded in its genome. Herein, we report the identification of the PPO components involved in pyrazon cis-dihydroxylation in P. immobile, its appropriate assembly, and its functional reconstitution in E. coli. Our results contributes with the essential missing pieces to complete the overall elucidation of the PPO from P. immobile. Key points: • Phenylobacterium immobile E DSM 1986 harbors the only described pyrazon oxygenase (PPO). • We elucidated the genes encoding for all PPO components. • Heterologous expression of PPO enabled pyrazon dihydroxylation in E. coli JW5510. 

  • 23.
    Ilk, Sedef
    et al.
    Faculty of Ayhan Şahenk Agricultural Sciences and Technologies, Nigde University, Nigde, Turkey;.
    Saglam, Necdet
    Department of Nanotechnology and Nanomedicine, the Institute of Science and Engineering, Hacettepe University, Beytepe, Ankara, Turkey;.
    Özgen, Mustafa
    Department of Plant Production and Technologies, Faculty of Ayhan Şahenk Agricultural Sciences and Technologies, Nigde University, Nigde, Turkey.
    Kaempferol loaded lecithin/chitosan nanoparticles: preparation, characterization, and their potential applications as a sustainable antifungal agent2016In: Artificial Cells, Nanomedicine, and Biotechnology, ISSN 2169-1401, Vol. 45, no 5, p. 907-916Article in journal (Refereed)
  • 24. Ilk, Sedef
    et al.
    Sağlam, Necdet
    Özgen, Mustafa
    Korkusuz, Feza
    Chitosan nanoparticles enhances the anti-quorum sensing activity of kaempferol2017In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 94, p. 653-662Article in journal (Refereed)
  • 25.
    Iseri, Emre
    et al.
    KTH.
    Akay, S.
    van der Wijngaart, Wouter
    KTH.
    Detection of E.coli in a digital assay2018In: 2018 IEEE Micro Electro Mechanical Systems (MEMS), Institute of Electrical and Electronics Engineers (IEEE), 2018, p. 301-303Conference paper (Refereed)
    Abstract [en]

    In this paper, we demonstrate the dipstick-based digitisation and detection of bacterial sample of concentration down to 103 CFU/ml. The significance of this work is that we are able to detect concentrations of bacteria relevant for urinary tract infection (UTI) with minimal handling time and without the need for complicated external equipment.

  • 26.
    Iseri, Emre
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. UTIlizer AB, Stockholm, Sweden.
    Nilsson, Sara
    Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
    van Belkum, Alex
    BaseClear BV, Leiden, the Netherlands.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Özenci, Volkan
    Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden;Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden.
    Performance of an innovative culture-based digital dipstick for detection of bacteriuria2023In: Microbiology Spectrum, E-ISSN 2165-0497Article in journal (Refereed)
    Abstract [en]

    UTI-lizer is a recent digital format for easy-to-use culture-based detection, preliminary identification, and quantification of bacteria in urine at the point of care (PoC). This study aimed to evaluate the diagnostic accuracy of UTI-lizer tests for detection of bacteriuria caused by five common bacterial species: Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Proteus mirabilis, and Staphylococcus saprophyticus. We evaluated the accuracy of UTI-lizer tests by comparing test results of UTI-lizer with those of current standard bacterial culture-based diagnostics in clinical microbiology laboratories in a retrospective and a prospective study. Comparator methods were classical bacterial culture in combination with matrix-assisted laser desorption/ionization-time of flight mass spectrometry mediated bacterial identification. In the retrospective study, we tested 104 urine samples with in-panel microorganisms, plain urethral microbiota, and culture-negative samples. In the prospective study, we used 137 urine samples within 10 hours of their collection at general practitioner clinics. The retrospective study demonstrated 100% sensitivity and specificity in the detection of bacteriuria, and 98.6% sensitivity and 96.8% specificity in identifying primary pathogens with UTI-lizer when compared to clinical standards. S. saprophyticus and E. coli could not be distinguished. The combined nitrite and esterase test predicted the presence of bacteriuria in only 36.5% of cases. The prospective study demonstrated 100% sensitivity and 89.6% specificity in the detection of significant bacteriuria for in-panel microorganisms with a coverage rate of 88.3% (121/137). This study indicates that digital dipsticks are a promising alternative for the detection of the five main pathogens that cause the vast majority of urinary tract infections (UTIs). The results demonstrate that digital dipsticks have the potential to uniquely provide—in primary care or at the point of care—a UTI diagnostic quality on par with that of current gold-standard testing. The ease of testing, rapid test handling time, and time to result as well as simple test equipment make digital dipsticks an attractive solution for decentralized testing for bacteriuria and with that improvement in UTI diagnostics. These results motivate future studies to validate the use of UTI-lizer at the PoC setting.

  • 27.
    Iyengar, Sharath Narayana
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. Karolinska Inst, AIMES Ctr Adv Integrated Med & Engn Sci, S-17165 Stockholm, Sweden.;KTH Royal Inst Technol, S-17165 Stockholm, Sweden..
    Dietvorst, Jiri
    Univ Autonoma Barcelona, Inst Microelect Barcelona IMB CNM, CSIC, Barcelona 08193, Spain..
    Ferrer-Vilanova, Amparo
    Univ Autonoma Barcelona, Inst Microelect Barcelona IMB CNM, CSIC, Barcelona 08193, Spain..
    Guirado, Gonzalo
    Univ Autonoma Barcelona, Dept Quim, Barcelona 08193, Spain..
    Munoz-Berbel, Xavier
    Univ Autonoma Barcelona, Inst Microelect Barcelona IMB CNM, CSIC, Barcelona 08193, Spain..
    Russom, Aman
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology. KTH Royal Inst Technol, Div Nanobiotechnol, Dept Prot Sci, Sci Life Lab, S-17165 Stockholm, Sweden.;Karolinska Inst, AIMES Ctr Adv Integrated Med & Engn Sci, S-17165 Stockholm, Sweden.;KTH Royal Inst Technol, S-17165 Stockholm, Sweden..
    Toward Rapid Detection of Viable Bacteria in Whole Blood for Early Sepsis Diagnostics and Susceptibility Testing2021In: ACS Sensors, E-ISSN 2379-3694, Vol. 6, no 9, p. 3357-3366Article in journal (Refereed)
    Abstract [en]

    Sepsis is a serious bloodstream infection where the immunity of the host body is compromised, leading to organ failure and death of the patient. In early sepsis, the concentration of bacteria is very low and the time of diagnosis is very critical since mortality increases exponentially with every hour after infection. Common culture-based methods fail in fast bacteria determination, while recent rapid diagnostic methods are expensive and prone to false positives. In this work, we present a sepsis kit for fast detection of bacteria in whole blood, here achieved by combining selective cell lysis and a sensitive colorimetric approach detecting as low as 10(3) CFU/mL bacteria in less than 5 h. Homemade selective cell lysis buffer (combination of saponin and sodium cholate) allows fast processing of whole blood in 5 min while maintaining bacteria alive (100% viability). After filtration, retained bacteria on filter paper are incubated under constant illumination with the electrochromic precursors, i.e., ferricyanide and ferric ammonium citrate. Viable bacteria metabolically reduce iron(III) complexes, initiating a photocatalytic cascade toward Prussian blue formation. As a proof of concept, we combine this method with antibiotic susceptibility testing to determine the minimum inhibitory concentration (MIC) using two antibiotics (ampicillin and gentamicin). Although this kit is used to demonstrate its applicability to sepsis, this approach is expected to impact other key sectors such as hygiene evaluation, microbial contaminated food/beverage, or UTI, among others.

  • 28.
    Ju, Han
    et al.
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, Jinan 250012, Shandong, Peoples R China..
    Natarajan Arul, Murugan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Theoretical Chemistry and Biology.
    Hou, Lingxin
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, Jinan 250012, Shandong, Peoples R China..
    Li, Ping
    Shandong Univ Tradit Chinese Med, Coll Pharm, Jinan 250355, Peoples R China..
    Guizzo, Laura
    Univ Padua, Dept Mol Med, I-35121 Padua, Italy..
    Zhang, Ying
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, Jinan 250012, Shandong, Peoples R China..
    Bertagnin, Chiara
    Univ Padua, Dept Mol Med, I-35121 Padua, Italy..
    Kong, Xiujie
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, Jinan 250012, Shandong, Peoples R China..
    Kang, Dongwei
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, Jinan 250012, Shandong, Peoples R China..
    Jia, Ruifang
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, Jinan 250012, Shandong, Peoples R China..
    Ma, Xiuli
    Shandong Acad Agr Sci, Inst Poultry Sci, Jinan 250100, Shandong, Peoples R China..
    Du, Ruikun
    Shandong Univ Tradit Chinese Med, Coll Pharm, Jinan 250355, Peoples R China..
    Poongavanam, Vasanthanathan
    Univ Southern Denmark, Dept Phys Chem & Pharm, DK-5230 Odense M, Denmark..
    Loregian, Arianna
    Univ Padua, Dept Mol Med, I-35121 Padua, Italy..
    Huang, Bing
    Shandong Acad Agr Sci, Inst Poultry Sci, Jinan 250100, Shandong, Peoples R China..
    Liu, Xinyong
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, Jinan 250012, Shandong, Peoples R China..
    Zhan, Peng
    Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, Jinan 250012, Shandong, Peoples R China..
    Identification of C5-NH2 Modified Oseltamivir Derivatives as Novel Influenza Neuraminidase Inhibitors with Highly Improved Antiviral Activities and Favorable Druggability2021In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 64, no 24, p. 17992-18009Article in journal (Refereed)
    Abstract [en]

    Our previous efforts have proved that modifications targeting the 150-cavity of influenza neuraminidase can achievemore potent and more selective inhibitors. In this work, foursubseries of C5-NH2modified oseltamivir derivatives weredesigned and synthesized to explore every region inside the 150-cavity. Among them, compound23dwas exceptionally potentagainst the whole panel of Group-1 NAs with IC50values rangingfrom 0.26 to 0.73 nM, being 15 & minus;53 times better than oseltamivircarboxylate (OSC) and 7 & minus;11 times better than zanamivir. Incellular assays,23dshowed more potent or equipotent antiviralactivities against corresponding virus strains compared to OSCwith no cytotoxicity. Furthermore,23dexhibited high metabolicstability in human liver microsomes (HLM) and low inhibitoryeffect on main cytochrome P450 enzymes. Notably,23ddisplayed favorable druggability in vivo and potent antiviral efficacy in the embryonated egg model and mice model. Overall,23dappears to be a promising candidate for the treatment of influenza virus infection.

  • 29. Koivula, R. W.
    et al.
    Atabaki-Pasdar, N.
    Giordano, G. N.
    White, T.
    Adamski, J.
    Bell, J. D.
    Beulens, J.
    Brage, S.
    Brunak, S.
    De Masi, F.
    Dermitzakis, E. T.
    Forgie, I. M.
    Frost, G.
    Hansen, T.
    Hansen, T. H.
    Hattersley, A.
    Kokkola, T.
    Kurbasic, A.
    Laakso, M.
    Mari, A.
    McDonald, T. J.
    Pedersen, O.
    Rutters, F.
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Teare, H. J. A.
    Thomas, E. L.
    Vinuela, A.
    Mahajan, A.
    McCarthy, M. I.
    Ruetten, H.
    Walker, M.
    Pearson, E.
    Pavo, I.
    Franks, P. W.
    Consortium, for the IMI DIRECT
    The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study2020In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 63, no 4, p. 744-756Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). Methods: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. Results: The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. Conclusions/interpretation: These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.

  • 30. Komen, Job
    et al.
    Wolbers, Floor
    Franke, Henk R.
    Andersson-Svahn, Helene
    KTH, School of Biotechnology (BIO), Proteomics.
    Vermes, Istvan
    van den Berg, Albert
    Viability analysis and apoptosis induction of breast cancer cells in a microfluidic device: effect of cytostatic drugs2008In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 10, no 5, p. 727-737Article in journal (Refereed)
    Abstract [en]

    Breast cancer is the leading cause of cancer deaths among non-smoking women worldwide. At the moment the treatment regime is such that patients receive different chemotherapeutic and/or hormonal treatments dependent on the hormone receptor status, the menopausal status and age. However, in vitro sensitivity testing of tumor biopsies could rationalize and improve the choice of chemo-and hormone therapy. Lab-on-a-Chip devices, using microfluidic techniques, make detailed cellular analysis possible using fewer cells, enabling working with a patients' own cells and performing chemo-and hormone sensitivity testing in an ex vivo setting. This article describes the development of two microfluidic devices made in poly(dimethylsiloxane) PDMS) to validate the cell culture properties and analyze the chemosensitivity of MCF-7 cells (estrogen receptor positive human breast cancer cells) in response to the drug staurosporine (SSP). In both cases, cell viability was assessed using the life-stain Calcein-AM (CAAM) and the death dye propidium iodide (PI). MCF-7 cells could be statically cultured for up to 7 days in the microfluidic chip. A 30 min flow with SSP and a subsequent 24 h static incubation in the incubator induced apoptosis in MCF-7 cells, as shown by a disappearance of the aggregate-like morphology, a decrease in CAAM staining and an increase in PI staining. This work provides valuable leads to develop a microfluidic chip to test the chemosensitivity of tumor cells in response to therapeutics and in this way improve cancer treatment towards personalized medicine.

  • 31.
    Kretschmer, Manuel
    et al.
    KTH.
    Ceña-Diez, R.
    Butnarasu, C.
    Silveira, V.
    Dobryden, I.
    Visentin, S.
    Berglund, Per
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology.
    Sönnerborg, A.
    Lieleg, O
    Crouzier, Thomas
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Yan, Hongji
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Synthetic Mucin Gels with Self-Healing Properties Augment Lubricity and Inhibit HIV-1 and HSV-2 Transmission2022In: Advanced Science, ISSN 2198-3844, Vol. 9, no 32, p. 2203898-Article in journal (Refereed)
    Abstract [en]

    Mucus is a self-healing gel that lubricates the moist epithelium and provides protection against viruses by binding to viruses smaller than the gel’s mesh size and removing them from the mucosal surface by active mucus turnover. As the primary nonaqueous components of mucus (≈0.2%–5%, wt/v), mucins are critical to this function because the dense arrangement of mucin glycans allows multivalence of binding. Following nature’s example, bovine submaxillary mucins (BSMs) are assembled into “mucus-like” gels (5%, wt/v) by dynamic covalent crosslinking reactions. The gels exhibit transient liquefaction under high shear strain and immediate self-healing behavior. This study shows that these material properties are essential to provide lubricity. The gels efficiently reduce human immunodeficiency virus type 1 (HIV-1) and genital herpes virus type 2 (HSV-2) infectivity for various types of cells. In contrast, simple mucin solutions, which lack the structural makeup, inhibit HIV-1 significantly less and do not inhibit HSV-2. Mechanistically, the prophylaxis of HIV-1 infection by BSM gels is found to be that the gels trap HIV-1 by binding to the envelope glycoprotein gp120 and suppress cytokine production during viral exposure. Therefore, the authors believe the gels are promising for further development as personal lubricants that can limit viral transmission.

  • 32.
    La Rosa, Sabina Leanti
    et al.
    Norwegian Univ Life Sci, Fac Biosci, N-1433 As, Norway..
    Ostrowski, Matthew P.
    Univ Michigan, Dept Microbiol & Immunol, Med Sch, Ann Arbor, MI 48109 USA..
    de Leon, Arturo Vera-Ponce
    Norwegian Univ Life Sci, Fac Chem Biotechnol & Food Sci, N-1433 As, Norway..
    McKee, Lauren S.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Larsbrink, Johan
    Chalmers Univ Technol, Dept Biol & Biol Engn, Div Ind Biotechnol, S-41296 Gothenburg, Sweden..
    Eijsink, Vincent G.
    Norwegian Univ Life Sci, Fac Chem Biotechnol & Food Sci, N-1433 As, Norway..
    Lowe, Elisabeth C.
    Newcastle Univ, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England..
    Martens, Eric C.
    Univ Michigan, Dept Microbiol & Immunol, Med Sch, Ann Arbor, MI 48109 USA..
    Pope, Phillip B.
    Norwegian Univ Life Sci, Fac Biosci, N-1433 As, Norway.;Norwegian Univ Life Sci, Fac Chem Biotechnol & Food Sci, N-1433 As, Norway..
    Glycan processing in gut microbiomes2022In: Current Opinion in Microbiology, ISSN 1369-5274, E-ISSN 1879-0364, Vol. 67, p. 102143-, article id 102143Article, review/survey (Refereed)
    Abstract [en]

    Microbiomes and their enzymes process many of the nutrients accessible in the gastrointestinal tract of bilaterians and play an essential role in host health and nutrition. In this review, we describe recent insights into nutrient processing in microbiomes across three exemplary yet contrasting gastrointestinal ecosystems (humans, ruminants and insects), with focus on bacterial mechanisms for the utilization of common and atypical dietary glycans as well as host-derived mucus glycans. In parallel, we discuss findings from multi-omic studies that have provided new perspectives on understanding glycan-dependent interactions and the complex food-webs of microbial populations in their natural habitat. Using key examples, we emphasize how increasing understanding of glycan processing by gut microbiomes can provide critical insights to assist 'microbiome reprogramming', a growing field that seeks to leverage diet to improve animal growth and host health.

  • 33.
    Lee, Sunjae
    et al.
    Kings Coll London, Ctr Host Microbial Interact, Guys Campus, London, England..
    Arefaine, Bethlehem
    Fdn Liver Res, Inst Hepatol, London, England..
    Witherden, Elizabeth
    Kings Coll London, Ctr Host Microbial Interact, Guys Campus, London, England..
    Begum, Neelu
    Kings Coll London, Ctr Host Microbial Interact, Guys Campus, London, England..
    Harzandi, Azadeh
    Kings Coll London, Ctr Host Microbial Interact, Guys Campus, London, England..
    Zamalloa, Ane
    Kings Coll Hosp London, Inst Liver Studies, London, England..
    Corcoran, Eleanor
    Kings Coll Hosp NHS Fdn Trust, Dept Crit Care, London, England..
    Smith, John
    Kings Coll Hosp NHS Fdn Trust, Dept Crit Care, London, England..
    Williams, Roger
    Fdn Liver Res, Inst Hepatol, London, England.;Kings Coll London, Sch Immunol & Microbial Sci, London, England..
    Chokshi, Shilpa
    Fdn Liver Res, Inst Hepatol, London, England.;Kings Coll London, Sch Immunol & Microbial Sci, London, England..
    Proctor, Gordon
    Kings Coll London, Ctr Host Microbial Interact, Guys Campus, London, England..
    Mardinoglu, Adil
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Kings Coll London, Ctr Host Microbial Interact, Guys Campus, London, England..
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Shoaie, Saeed
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. Kings Coll London, Ctr Host Microbial Interact, Guys Campus, London, England..
    Patel, Vishal C.
    Fdn Liver Res, Inst Hepatol, London, England.;Kings Coll Hosp London, Inst Liver Studies, London, England.;Kings Coll London, Sch Immunol & Microbial Sci, London, England..
    In-depth shotgun metagenomic analysis of the gut microbiome identifies striking variations in microbial community structure based on severity and stage of cirrhosis2021In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 75, p. S222-S223Article in journal (Other academic)
  • 34. Li, Linlin
    et al.
    Victoria, Joseph
    Kapoor, Amit
    Blinkova, Olga
    Wang, Chunlin
    Babrzadeh, Farbod
    Stanford Genome Technology Center, Stanford University, United States .
    Mason, Carl J.
    Pandey, Prativa
    Triki, Hinda
    Bahri, Olfa
    Oderinde, Bamidele Soji
    Baba, Marycelin Mandu
    Bukbuk, David Nadeba
    Besser, John M.
    Bartkus, Joanne M.
    Delwart, Eric L.
    A Novel Picornavirus Associated with Gastroenteritis2009In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 83, no 22, p. 12002-12006Article in journal (Refereed)
    Abstract [en]

    A novel picornavirus genome was sequenced, showing 42.6%, 35.2%, and 44.6% of deduced amino acid identities corresponding to the P1, P2, and P3 regions, respectively, of the Aichi virus. Divergent strains of this new virus, which we named salivirus, were detected in 18 stool samples from Nigeria, Tunisia, Nepal, and the United States. A statistical association was seen between virus shedding and unexplained cases of gastroenteritis in Nepal (P = 0.0056). Viruses with approximately 90% nucleotide similarity, named klassevirus, were also recently reported in three cases of unexplained diarrhea from the United States and Australia and in sewage from Spain, reflecting a global distribution and supporting a pathogenic role for this new group of picornaviruses.

  • 35.
    Martín-Rodríguez, A. J.
    et al.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Villion, K.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Yilmaz Turan, Secil
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Vilaplana, Francisco
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Sjöling, Å.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Römling, U.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Regulation of colony morphology and biofilm formation in Shewanella algae2021In: Microbial Biotechnology, ISSN 1751-7907, E-ISSN 1751-7915, Vol. 14, no 3, p. 1183-1200Article in journal (Refereed)
    Abstract [en]

    Bacterial colony morphology can reflect different physiological stages such as virulence or biofilm formation. In this work we used transposon mutagenesis to identify genes that alter colony morphology and cause differential Congo Red (CR) and Brilliant Blue G (BBG) binding in Shewanella algae, a marine indigenous bacterium and occasional human pathogen. Microscopic analysis of colonies formed by the wild-type strain S. algae CECT 5071 and three transposon integration mutants representing the diversity of colony morphotypes showed production of biofilm extracellular polymeric substances (EPS) and distinctive morphological alterations. Electrophoretic and chemical analyses of extracted EPS showed differential patterns between strains, although the targets of CR and BBG binding remain to be identified. Galactose and galactosamine were the preponderant sugars in the colony biofilm EPS of S. algae. Surface-associated biofilm formation of transposon integration mutants was not directly correlated with a distinct colony morphotype. The hybrid sensor histidine kinase BarA abrogated surface-associated biofilm formation. Ectopic expression of the kinase and mutants in the phosphorelay cascade partially recovered biofilm formation. Altogether, this work provides the basic analysis to subsequently address the complex and intertwined networks regulating colony morphology and biofilm formation in this poorly understood species.

  • 36.
    Moonens, Kristof
    et al.
    VIB, Struct Biol Res Ctr, Struct & Mol Microbiol, Pl Laan 2, B-1050 Brussels, Belgium.;Vrije Univ Brussel, Struct Biol Brussels, Pl Laan 2, B-1050 Brussels, Belgium..
    Gideonsson, Paer
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Subedi, Suresh
    VIB, Struct Biol Res Ctr, Struct & Mol Microbiol, Pl Laan 2, B-1050 Brussels, Belgium.;Vrije Univ Brussel, Struct Biol Brussels, Pl Laan 2, B-1050 Brussels, Belgium..
    Bugaytsova, Jeanna
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Romao, Ema
    Vrije Univ Brussel, Cellular & Mol Immunol, Pl Laan 2, B-1050 Brussels, Belgium..
    Mendez, Melissa
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Norden, Jenny
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Fallah, Mahsa
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Rakhimova, Lena
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Shevtsova, Anna
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Lahmann, Martina
    Bangor Univ, Sch Chem, Deiniol Rd, Bangor LL57 2UW, Gwynedd, Wales..
    Castaldo, Gaetano
    VIB, Struct Biol Res Ctr, Struct & Mol Microbiol, Pl Laan 2, B-1050 Brussels, Belgium.;Vrije Univ Brussel, Struct Biol Brussels, Pl Laan 2, B-1050 Brussels, Belgium..
    Brannstrom, Kristoffer
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Coppens, Fanny
    VIB, Struct Biol Res Ctr, Struct & Mol Microbiol, Pl Laan 2, B-1050 Brussels, Belgium.;Vrije Univ Brussel, Struct Biol Brussels, Pl Laan 2, B-1050 Brussels, Belgium..
    Lo, Alvin W.
    VIB, Struct Biol Res Ctr, Struct & Mol Microbiol, Pl Laan 2, B-1050 Brussels, Belgium.;Vrije Univ Brussel, Struct Biol Brussels, Pl Laan 2, B-1050 Brussels, Belgium..
    Ny, Tor
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Solnick, Jay V.
    Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA.;Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA.;Univ Calif Davis, Sch Med, Dept Med, Sacramento, CA 95817 USA.;Univ Calif Davis, Sch Med, Dept Microbiol & Immunol, Sacramento, CA 95817 USA..
    Vandenbussche, Guy
    Univ Libre Bruxelles, Struct & Funct Biol Membranes, B-1050 Brussels, Belgium..
    Oscarson, Stefan
    Univ Coll Dublin, Sch Chem, Ctr Synth & Chem Biol, Dublin 4, Ireland..
    Hammarstrom, Lennart
    Karolinska Univ Hosp, Karolinska Inst, Div Clin Immunol, S-14186 Huddinge, Sweden..
    Arnqvist, Anna
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Berg, Douglas E.
    Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA..
    Muyldermans, Serge
    Vrije Univ Brussel, Cellular & Mol Immunol, Pl Laan 2, B-1050 Brussels, Belgium..
    Boren, Thomas
    Umeå Univ, Dept Med Biochem & Biophys, SE-90187 Umeå, Sweden..
    Remaut, Han
    VIB, Struct Biol Res Ctr, Struct & Mol Microbiol, Pl Laan 2, B-1050 Brussels, Belgium.;Vrije Univ Brussel, Struct Biol Brussels, Pl Laan 2, B-1050 Brussels, Belgium..
    Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori2016In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 19, no 1, p. 55-66Article in journal (Refereed)
    Abstract [en]

    The Helicobacter pylori adhesin BabA binds mucosal ABO/Le b blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Le(b) binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.

  • 37.
    Moyo, Sikhulile
    et al.
    Botswana Harvard Health Partnership, Gaborone, Botswana; Harvard T.H. Chan School of Public Health, Boston, MA, USA.
    Ramogola-Masire, Doreen
    Faculty of Medicine, University of Botswana, Gaborone, Botswana.
    Moraka, Natasha O.
    Botswana Harvard Health Partnership, Gaborone, Botswana.
    Tawe, Leabaneng
    Faculty of Medicine, University of Botswana, Gaborone, Botswana.
    Noubary, Farzad
    Department of Health Sciences, Northeastern University, Boston, MA, USA.
    Motsumi, Kesego
    Botswana Harvard Health Partnership, Gaborone, Botswana.
    Manowe, Godiraone
    Botswana Harvard Health Partnership, Gaborone, Botswana.
    Zuze, Boitumelo
    Botswana Harvard Health Partnership, Gaborone, Botswana.
    Radibe, Botshelo
    Botswana Harvard Health Partnership, Gaborone, Botswana.
    Hungwe, Faith
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH). Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Department of Biochemistry and Chemistry, Stockholm University, Stockholm, Sweden.
    Mohammed, Terence
    Botswana Harvard Health Partnership, Gaborone, Botswana.
    Maphorisa, Comfort
    Botswana Harvard Health Partnership, Gaborone, Botswana.
    Shapiro, Roger
    Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Kirstein, 3Rd Floor, 330 Brookline Avenue, Boston, MA, 02215, USA, Kirstein, 3Rd Floor, 330 Brookline Avenue; Harvard Medical School, Boston, MA, USA.
    Gaseitsiwe, Simani
    Botswana Harvard Health Partnership, Gaborone, Botswana; Harvard T.H. Chan School of Public Health, Boston, MA, USA.
    Luckett, Rebecca
    Botswana Harvard Health Partnership, Gaborone, Botswana; Faculty of Medicine, University of Botswana, Gaborone, Botswana; Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Kirstein, 3Rd Floor, 330 Brookline Avenue, Boston, MA, 02215, USA, Kirstein, 3Rd Floor, 330 Brookline Avenue; Harvard Medical School, Boston, MA, USA.
    Comparison of the AmpFire® Multiplex HPV Assay to the Xpert® HPV Assay for detection of human papillomavirus and cervical disease in women with human immunodeficiency virus: a pragmatic performance evaluation2023In: Infectious Agents and Cancer, E-ISSN 1750-9378, Vol. 18, no 1, article id 29Article in journal (Refereed)
    Abstract [en]

    Background: Low- and middle-income countries (LMICs) account for nearly 85% of the global cervical cancer burden, yet have the least access to high-performance screening. International guidelines recommend human papillomavirus testing (HPV) as primary screening, yet implementation is inhibited by the cost of HPV testing. Atila AmpFire® HPV Assay (AmpFire) is both affordable and easy to use, and offers individual genotyping. The objective of this study was to compare the performance of the AmpFire HPV assay to the Xpert® HPV assay in detection of both HPV and clinically significant cervical disease. Methods: We utilized stored cervical specimens from a prospective cohort study of women living with human immunodeficiency virus (HIV) in Botswana conducted from May to July 2018. Positive and negative percent agreement was calculated for the AmpFire and Xpert assays, as was detection of high-grade cervical dysplasia. Results: 63 stored cervical specimens had detectable DNA after thawing and were included in the analysis. The positive percent agreement was 91.2% (95%CI 76.3–98.1) and negative percent agreement was 79.3% (95% CI 60.3–92.0). Six cases positive by AmpFire but negative by Xpert were HPV genotypes 35, 52 (n = 2), 58, 68, and co-infection with HPV 45 and 68. Both Xpert and AmpFire assays detected HPV in all 10 samples of women who had high-grade cervical dysplasia. Conclusions: The AmpFire HPV assay demonstrated excellent analytic performance in both detection of HPV and clinically significant cervical disease. AmpFire HPV is a promising option to increase access to affordable, type-specific HPV screening for cervical cancer in LMICs.

  • 38.
    Ndegwa, Nelson
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Ploner, Alexander
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Andersson, Anders F.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Zagai, Ulrika
    Andreasson, Anna
    Vieth, Michael
    Talley, Nicholas J.
    Agreus, Lars
    Ye, Weimin
    Gastric Microbiota in a Low-Helicobacter pylori Prevalence General Population and Their Associations With Gastric Lesions2020In: Clinical and Translational Gastroenterology, E-ISSN 2155-384X, Vol. 11Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:Non-Helicobacter pylori microbiota might account for some cases with unexplained chronic gastritis that may in a minority eventually progress to gastric cancer through the Correa cascade. We characterized gastric microbiota by describing the normal stomach, compared it with early precancerous lesions and other disease states, and assessed whether H. pylori status affects bacterial diversity.METHODS:In a population-based study of those with and without gastrointestinal symptoms, cytology brush samples were collected during endoscopy from 316 individuals. Mucosal status was classified as normal mucosa (171), nonatrophic H. pylori gastritis (33), atrophic gastritis (12), or antral chemical gastritis (61). The 16S rRNA gene sequencing and analysis were performed to characterize the microbiota.RESULTS:Microbiota in atrophic gastritis and nonatrophic H. pylori gastritis stomachs were dysbiotic and differed from those in the normal stomach (P = 0.001). The normal stomach had the highest microbial diversity, followed by antral chemical gastritis. The atrophic gastritis and chronic H. pylori gastritis groups had the lowest diversity, a difference that was statistically significant (P = 0.01). Besides H. pylori, non-H. pylori bacteria accounted for group differences. Microbial network analysis showed that the normal group network was most highly connected, whereas the H. pylori gastritis group had the lowest connection. We found an increasing positive co-occurrence of oral bacteria in the stomach because samples deviated from the normal network, some of which were pathogens. The H. pylori-negative group had the highest microbial diversity (Shannon index) compared with the H. pylori-positive group (P = 0.001).DISCUSSION:In this low-H. pylori prevalence general population, the gastric mucosal microbiota of the normal stomach differed significantly from those with nonatrophic or atrophic gastritis. There was an increasing abundance of pathogenic bacteria from the normal state to early precancerous states.

  • 39.
    Norström, Anna
    KTH, School of Biotechnology (BIO).
    A comparative study of six hydroponic wastewater treatment plants.2005In: Vatten, ISSN 0042-2886, no 2, p. 95-104Article in journal (Other academic)
    Abstract [en]

    During the last two decades, wastewater treatment in systems combining conventional biological processes andhydroponics has been tried at several locations. In this article, six different systems are described and theirtreatment results compared. Five systems were found in literature, and the sixth system was constructed andoperated by the microbiology group at KTH. These systems can be divided into three subgroups: i) demonstrationsystems with small inflow and long hydraulic retention time (HRT), ii) pilot systems with small to moderateinflow and moderate HRT, iii) full scale systems with large inflow and short HRT. In general, removalof organic matter seems to be most efficient in systems resembling an active sludge process. Systems with longHRT appears over-dimensioned as long as the volume is not simultaneously used for treatment and production.Nitrogen was efficiently removed through conventional biological processes, whereas phosphorus removalthrough mainly sedimentation and adsorption in the systems was not very efficient. Nutrient removal bymeans of up-take through plant growth has not contributed significantly in any of the described treatmentsystems. None of the treatment plants have had the primary objective of biomass production. Hence, potentialremoval and recycling of nutrients through a productive system still remains to be answered.

  • 40.
    Norström, Anna
    et al.
    KTH, School of Biotechnology (BIO).
    Dalhammar, Gunnel
    KTH, School of Biotechnology (BIO).
    Lee, Natuschka
    Investigation of the microbial composition in the hydroponic step of a treatment system for domestic wastewater with fluorescent in situ hybridization (FISH).In: Ecological Engineering: The Journal of Ecotechnology, ISSN 0925-8574, E-ISSN 1872-6992Article in journal (Other academic)
  • 41.
    Norström, Anna
    et al.
    KTH, School of Biotechnology (BIO).
    La Cour Jansen, Jes
    Dalhammar, Gunnel
    KTH, School of Biotechnology (BIO).
    Energy savings versus year‐round production in a small hydroponic system for wastewater treatment.In: Water Science and Technology, ISSN 0273-1223, E-ISSN 1996-9732Article in journal (Other academic)
  • 42.
    Pellon, Aize
    et al.
    Kings Coll London, Fac Dent, Ctr Host Microbiome Interact, Oral & Craniofacial Sci, London, England..
    Begum, Neelu
    Kings Coll London, Fac Dent, Ctr Host Microbiome Interact, Oral & Craniofacial Sci, London, England..
    Sadeghi Nasab, Shervin Dokht
    Kings Coll London, Fac Dent, Ctr Host Microbiome Interact, Oral & Craniofacial Sci, London, England..
    Harzandi, Azadeh
    Kings Coll London, Fac Dent, Ctr Host Microbiome Interact, Oral & Craniofacial Sci, London, England..
    Shoaie, Saeed
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. Kings Coll London, Fac Dent, Ctr Host Microbiome Interact, Oral & Craniofacial Sci, London, England..
    Moyes, David L.
    Kings Coll London, Fac Dent, Ctr Host Microbiome Interact, Oral & Craniofacial Sci, London, England..
    Role of Cellular Metabolism during Candida-Host Interactions2022In: Pathogens, E-ISSN 2076-0817, Vol. 11, no 2, article id 184Article in journal (Refereed)
    Abstract [en]

    Microscopic fungi are widely present in the environment and, more importantly, are also an essential part of the human healthy mycobiota. However, many species can become pathogenic under certain circumstances, with Candida spp. being the most clinically relevant fungi. In recent years, the importance of metabolism and nutrient availability for fungi-host interactions have been highlighted. Upon activation, immune and other host cells reshape their metabolism to fulfil the energy-demanding process of generating an immune response. This includes macrophage upregulation of glucose uptake and processing via aerobic glycolysis. On the other side, Candida modulates its metabolic pathways to adapt to the usually hostile environment in the host, such as the lumen of phagolysosomes. Further understanding on metabolic interactions between host and fungal cells would potentially lead to novel/enhanced antifungal therapies to fight these infections. Therefore, this review paper focuses on how cellular metabolism, of both host cells and Candida, and the nutritional environment impact on the interplay between host and fungal cells.

  • 43. Pinitkiatisakul, S.
    et al.
    Mattsson, J.G.
    Wikman, Maria
    KTH, School of Biotechnology (BIO).
    Friedman, Mikaela
    KTH, School of Biotechnology (BIO).
    Bengtsson, K.L.
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO).
    Lundén, Anne
    Immunisation of mice against neosporosis with recombinant NcSRS2 iscoms2005In: Veterinary parasitology, ISSN 0304-4017, E-ISSN 1873-2550, Vol. 129, no 1-2, p. 25-34Article in journal (Refereed)
    Abstract [en]

    The coccidian parasite Neospora caninum is an intracellular protozoan, causing abortion in cattle in many countries around the world. In this study, the protective potential of the major N. caninum surface antigen NcSRS2, expressed in Escherichia coli and formulated into immunostimulating complexes (iscoms), was investigated in an experimental mouse model. The recombinant protein was specially designed for binding to iscoms via biotin-streptavidin interaction. Two groups of 10 BALB/c mice were immunised twice, on days 0 and 28 with iscoms containing either the recombinant NcSRS2 (NcSRS2 iscoms) or similar iscoms with NcSRS2 substituted by an unrelated recombinant malaria peptide (M5) as a control (M5 iscoms). A third group of 10 age-matched BALB/c mice served as an uninfected control group. Immunisation with recombinant NcSRS2 iscoms resulted in production of substantial antibody titres against N. caninum antigen, while the mice immunised with M5 iscoms produced only very low levels of antibodies reacting with N. caninum antigen. After challenge infection with N. caninum tachyzoites on day 69, mice immunised with NcSRS2 iscoms showed only mild and transient symptoms, whereas the group immunised with M5 iscoms showed clinical symptoms until the end of the experiment at 31 days post inoculation. A competitive PCR assay detecting Nc5-repeats was applied to evaluate the level of parasite DNA in the brain. The amount of Nc5-repeats in the group vaccinated with NcSRS2 iscoms was significantly lower than in the control group given M5 iscoms. In conclusion, it was found that the recombinant NcSRS2 iscoms induced specific antibodies to native NcSRS2 and immunity sufficient to reduce the proliferation of N. caninum in the brains of immunised mice.

  • 44.
    Poux, Candice
    et al.
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    Dondalska, Aleksandra
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    Bergenstråhle, Joseph
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Pålsson, Sandra
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    Contreras, Vanessa
    CEA, Inst Biol Francois Jacob, UMR1184, IDMIT Dept,DRF, Fontenay Aux Roses, France.
    Arasa, Claudia
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    Järver, Peter
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    Albert, Jan
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden.
    Busse, David
    Imperial Coll London, Dept Infect Dis, London, England.
    LeGrand, Roger
    CEA, Inst Biol Francois Jacob, UMR1184, IDMIT Dept,DRF, Fontenay Aux Roses, France.
    Lundeberg, Joakim
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Tregoning, John
    Imperial Coll London, Dept Infect Dis, London, England.
    Spetz, Anna-Lena
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    A Single-Stranded Oligonucleotide Inhibits Toll-Like Receptor 3 Activation and Reduces Influenza A (H1N1) Infection2019In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 10, article id 10.3389/fimmu.2019.02161Article in journal (Refereed)
    Abstract [en]

    The initiation of an immune response is dependent on the activation and maturation of dendritic cells after sensing pathogen associated molecular patterns by pattern recognition receptors. However, the response needs to be balanced as excessive pro-inflammatory cytokine production in response to viral or stress-induced pattern recognition receptor signaling has been associated with severe influenza A virus (IAV) infection. Here, we use an inhibitor of Toll-like receptor (TLR)3, a single-stranded oligonucleotide (ssON) with the capacity to inhibit certain endocytic routes, or a TLR3 agonist (synthetic double-stranded RNA PolyI:C), to evaluate modulation of innate responses during H1N1 IAV infection. Since IAV utilizes cellular endocytic machinery for viral entry, we also assessed ssON's capacity to affect IAV infection. We first show that IAV infected human monocyte-derived dendritic cells (MoDC) were unable to up-regulate the co-stimulatory molecules CD80 and CD86 required for T cell activation. Exogenous TLR3 stimulation did not overcome the IAV-mediated inhibition of co-stimulatory molecule expression in MoDC. However, TLR3 stimulation using PolyI:C led to an augmented pro-inflammatory cytokine response. We reveal that ssON effectively inhibited PolyI:C-mediated pro-inflammatory cytokine production in MoDC, notably, ssON treatment maintained an interferon response induced by IAV infection. Accordingly, RNAseq analyses revealed robust up-regulation of interferon-stimulated genes in IAV cultures treated with ssON. We next measured reduced IAV production in MoDC treated with ssON and found a length requirement for its anti-viral activity, which overlapped with its capacity to inhibit uptake of PolyI:C. Hence, in cases wherein an overreacting TLR3 activation contributes to IAV pathogenesis, ssON can reduce this signaling pathway. Furthermore, concomitant treatment with ssON and IAV infection in mice resulted in maintained weight and reduced viral load in the lungs. Therefore, extracellular ssON provides a mechanism for immune regulation of TLR3-mediated responses and suppression of IAV infection in vitro and in vivo in mice.

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  • 45.
    Roswall, Josefine
    et al.
    Hallands Hosp Halmstad, Dept Pediat, Halmstad, Sweden.;Univ Gothenburg, Gothenburg Pediat Growth Res Ctr, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden..
    Olsson, Lisa M.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden..
    Kovatcheva-Datchary, Petia
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden.;Univ Wurzburg, Inst Mol Infect Biol, Wurzburg, Germany..
    Nilsson, Staffan
    Chalmers Tekniska Hgsk, Dept Math Sci, Gothenburg, Sweden.;Univ Gothenburg, Inst Biomed, Dept Lab Med, Gothenburg, Sweden..
    Tremaroli, Valentina
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden..
    Simon, Marie-Christine
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden..
    Kiilerich, Pia
    Univ Copenhagen, Dept Biol, Lab Genom & Mol Biomed, Copenhagen, Denmark.;Statens Serum Inst, Artillerivej 5, DK-2300 Copenhagen S, Denmark..
    Akrami, Rozita
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden..
    Kramer, Manuela
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden..
    Uhlén, Mathias
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Gummesson, Anders
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Clin Genet & Genom, Reg Vastra Gotaland, Gothenburg, Sweden..
    Kristiansen, Karsten
    Univ Copenhagen, Dept Biol, Lab Genom & Mol Biomed, Copenhagen, Denmark.;BGI Shenzhen, Shenzhen, Peoples R China..
    Dahlgren, Jovanna
    Univ Gothenburg, Gothenburg Pediat Growth Res Ctr, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Pediat, Reg Vastra Gotaland, Gothenburg, Sweden..
    Backhed, Fredrik
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab,Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Clin Physiol, Reg Vastra Gotaland, Gothenburg, Sweden.;Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark..
    Developmental trajectory of the healthy human gut microbiota during the first 5 years of life2021In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 29, no 5, p. 765-776.e3Article in journal (Refereed)
    Abstract [en]

    The gut is inhabited by a densely populated ecosystem, the gut microbiota, that is established at birth. However, the succession by which different bacteria are incorporated into the gut microbiota is still relatively unknown. Here, we analyze the microbiota from 471 Swedish children followed from birth to 5 years of age, collecting samples after 4 and 12 months and at 3 and 5 years of age as well as from their mothers at birth using 16S rRNA gene profiling. We also compare their microbiota to an adult Swedish population. Genera follow 4 different colonization patterns during establishment where Methanobrevibacter and Christensenellaceae colonize late and do not reached adult levels at 5 years. These late colonizers correlate with increased alpha diversity in both children and adults. By following the children through age-specific community types, we observe that children have individual dynamics in the gut microbiota development trajectory.

  • 46.
    Sinha, Suvadip
    et al.
    Indian Inst Sci Educ & Res Kolkata, Ctr Excellence Space Sci India, Mohanpur 741246, W Bengal, India..
    Gupta, Om
    Indian Inst Sci Educ & Res Kolkata, Ctr Excellence Space Sci India, Mohanpur 741246, W Bengal, India.;Indian Inst Sci Educ & Res Kolkata, Dept Phys Sci, Mohanpur 741246, W Bengal, India..
    Singh, Vishal
    Indian Inst Sci Educ & Res Kolkata, Ctr Excellence Space Sci India, Mohanpur 741246, W Bengal, India.;Indian Inst Sci Educ & Res Kolkata, Dept Phys Sci, Mohanpur 741246, W Bengal, India..
    Lekshmi, B.
    Indian Inst Sci Educ & Res Kolkata, Ctr Excellence Space Sci India, Mohanpur 741246, W Bengal, India.;Max Planck Inst Solar Syst Res, D-37077 Gottingen, Germany..
    Nandy, Dibyendu
    Indian Inst Sci Educ & Res Kolkata, Ctr Excellence Space Sci India, Mohanpur 741246, W Bengal, India.;Indian Inst Sci Educ & Res Kolkata, Dept Phys Sci, Mohanpur 741246, W Bengal, India..
    Mitra, Dhrubaditya
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA. Stockholm Univ, Hannes Alfvens Vag 12, S-10691 Stockholm, Sweden..
    Chatterjee, Saikat
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Information Science and Engineering.
    Bhattacharya, Sourangshu
    Indian Inst Technol, Kharagpur, W Bengal, India..
    Chatterjee, Saptarshi
    Indian Inst Technol, Kharagpur, W Bengal, India..
    Srivastava, Nandita
    Indian Inst Sci Educ & Res Kolkata, Ctr Excellence Space Sci India, Mohanpur 741246, W Bengal, India.;Udaipur Solar Observ, Phys Res Lab, POB 198,Badi Rd, Udaipur 313001, Rajasthan, India..
    Brandenburg, Axel
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA. Stockholm Univ, Hannes Alfvens Vag 12, S-10691 Stockholm, Sweden.;Stockholm Univ, Oskar Klein Ctr, Dept Astron, AlbaNova, SE-10691 Stockholm, Sweden..
    Pal, Sanchita
    Indian Inst Sci Educ & Res Kolkata, Ctr Excellence Space Sci India, Mohanpur 741246, W Bengal, India.;Univ Helsinki, Dept Phys, POB 64, FI-00014 Helsinki, Finland..
    A Comparative Analysis of Machine-learning Models for Solar Flare Forecasting: Identifying High-performing Active Region Flare Indicators2022In: Astrophysical Journal, ISSN 0004-637X, E-ISSN 1538-4357, Vol. 935, no 1, article id 45Article in journal (Refereed)
    Abstract [en]

    Solar flares create adverse space weather impacting space- and Earth-based technologies. However, the difficulty of forecasting flares, and by extension severe space weather, is accentuated by the lack of any unique flare trigger or a single physical pathway. Studies indicate that multiple physical properties contribute to active region flare potential, compounding the challenge. Recent developments in machine learning (ML) have enabled analysis of higher-dimensional data leading to increasingly better flare forecasting techniques. However, consensus on high-performing flare predictors remains elusive. In the most comprehensive study to date, we conduct a comparative analysis of four popular ML techniques (k nearest neighbors, logistic regression, random forest classifier, and support vector machine) by training these on magnetic parameters obtained from the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory for the entirety of solar cycle 24. We demonstrate that the logistic regression and support vector machine algorithms perform extremely well in forecasting active region flaring potential. The logistic regression algorithm returns the highest true skill score of 0.967 +/- 0.018, possibly the highest classification performance achieved with any strictly parametric study. From a comparative assessment, we establish that magnetic properties like total current helicity, total vertical current density, total unsigned flux, R_VALUE, and total absolute twist are the top-performing flare indicators. We also introduce and analyze two new performance metrics, namely, severe and clear space weather indicators. Our analysis constrains the most successful ML algorithms and identifies physical parameters that contribute most to active region flare productivity.

  • 47.
    Steiner, Svava E.
    et al.
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Choong, F. X.
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Antypas, Haris
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Morado-Urbina, C. E.
    Department for Physiology and Pharmacology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Schulz, Anette
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Farinotti, Alex Bersellini
    Department for Physiology and Pharmacology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bas, Duygu B.
    Department for Physiology and Pharmacology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Svensson, Camilla I.
    Department for Physiology and Pharmacology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Richter-Dahlfors, Agneta
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Melican, Keira
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    UPEC kidney infection triggers neuro-immune communication leading to modulation of local renal inflammation by splenic IFNγ2021In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 17, no 5, article id e1009553Article in journal (Refereed)
    Abstract [en]

    Bacterial infection results in a veritable cascade of host responses, both local and systemic. To study the initial stages of host-pathogen interaction in living tissue we use spatially-temporally controlled in vivo models. Using this approach, we show here that within 4 h of a uropathogenic Escherichia coli (UPEC) infection in the kidney, an IFNγ response is triggered in the spleen. This rapid infection-mediated inter-organ communication was found to be transmitted via nerve signalling. Bacterial expression of the toxin α-hemolysin directly and indirectly activated sensory neurons, which were identified in the basement membrane of renal tubules. Nerve activation was transmitted via the splenic nerve, inducing upregulation of IFNγ in the marginal zones of the spleen that led to increasing concentrations of IFNγ in the circulation. We found that IFNγ modulated the inflammatory signalling generated by renal epithelia cells in response to UPEC infection. This demonstrates a new concept in the host response to kidney infection; the role of nerves in sensing infection and rapidly triggering a systemic response which can modulate inflammation at the site of infection. The interplay between the nervous and immune systems is an exciting, developing field with the appealing prospect of non-pharmaceutical interventions. Our study identifies an important role for systemic neuro-immune communication in modulating inflammation during the very first hours of a local bacterial infection in vivo.

  • 48.
    Wang, Huan
    et al.
    Huazhong Univ Life Sci & Technol, Coll Life Sci & Technol, Adv Biomat & Tissue Engn Ctr, Wuhan, Peoples R China..
    Fan, Yanmiao
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    Yang, Qiaoli
    Huazhong Univ Life Sci & Technol, Coll Life Sci & Technol, Adv Biomat & Tissue Engn Ctr, Wuhan, Peoples R China..
    Sun, Xiaoyu
    Huazhong Univ Life Sci & Technol, Coll Life Sci & Technol, Adv Biomat & Tissue Engn Ctr, Wuhan, Peoples R China..
    Liu, Hao
    Huazhong Univ Life Sci & Technol, Coll Life Sci & Technol, Adv Biomat & Tissue Engn Ctr, Wuhan, Peoples R China..
    Chen, Wei
    Huazhong Univ Life Sci & Technol, Coll Life Sci & Technol, Adv Biomat & Tissue Engn Ctr, Wuhan, Peoples R China..
    Aziz, Ayesha
    Huazhong Univ Life Sci & Technol, Coll Life Sci & Technol, Adv Biomat & Tissue Engn Ctr, Wuhan, Peoples R China..
    Wang, Shenqi
    Huazhong Univ Life Sci & Technol, Coll Life Sci & Technol, Adv Biomat & Tissue Engn Ctr, Wuhan, Peoples R China..
    Boosting the Electrochemical Performance of PI-5-CA/C-SWCNT Nanohybrid for Sensitive Detection of E. coli O157:H7 From the Real Sample2022In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 10, article id 843859Article in journal (Refereed)
    Abstract [en]

    Redox activity is an important indicator for evaluating electrochemical biosensors. In this work, we have successfully polymerized indole-5-carboxylic acid into poly-5-carboxyindole nanomaterials (PI-5-CA), using its superior redox activity, and introduced carboxylated single-walled carbon nanotubes (C-SWCNTs) to synthesize a composite material. Finally, a synthesized composite material was used for the modification of the glass carbon electrode to fabricate the PI-5-CA/C-SWCNTs/GCE-based immunosensor and was successfully applied for the sensitive detection of E. coli O157:H7. The fabricated immunosensor exhibited an outstanding electrocatalytic activity toward the detection of E. coli O157:H7 with a remarkably lowest limit of detection (2.5 CFU/ml, LOD = 3 SD/k, n = 3) and has a wide linear range from 2.98x10(1) to 2.98x10(7) CFU/ml. Inspired from the excellent results, the fabricated electrode was applied for the detection of bacteria from real samples (water samples) with a good recovery rate (98.13-107.69%) as well as an excellent stability and specificity. Owing to its simple preparation, excellent performance, and detection time within 30 min, our proposed immunosensor will open a new horizon in different fields for the sensitive detection of bacteria from real samples.

  • 49.
    Weibull, Emilie
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Antypas, Haris
    Kjall, Peter
    Brauner, Annelie
    Andersson-Svahn, Helene
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Richter-Dahlfors, Agneta
    Bacterial Nanoscale Cultures for Phenotypic Multiplexed Antibiotic Susceptibility Testing2014In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 52, no 9, p. 3310-3317Article in journal (Refereed)
    Abstract [en]

    An optimal antimicrobial drug regimen is the key to successful clinical outcomes of bacterial infections. To direct the choice of antibiotic, access to fast and precise antibiotic susceptibility profiling of the infecting bacteria is critical. We have developed a high-throughput nanowell antibiotic susceptibility testing (AST) device for direct, multiplexed analysis. By processing in real time the optical recordings of nanoscale cultures of reference and clinical uropathogenic Escherichia coli strains with a mathematical algorithm, the time point when growth shifts from lag phase to early logarithmic phase (T-lag) was identified for each of the several hundreds of cultures tested. Based on T-lag, the MIC could be defined within 4 h. Heatmap presentation of data from this high-throughput analysis allowed multiple resistance patterns to be differentiated at a glance. With a possibility to enhance multiplexing capacity, this device serves as a high-throughput diagnostic tool that rapidly aids clinicians in prescribing the optimal antibiotic therapy.

  • 50.
    Wennstam, Lisa
    KTH, School of Architecture and the Built Environment (ABE), Urban Planning and Environment, Urban and Regional Studies.
    Inte bara hus som hus: Ett underlag till diskussion kring ett lämpligt innehåll i en samtida arkitekturpolitik i Lidköpings kommun2022Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In 2018, in the midst of a global environmental crisis, a national increase in social gaps and segregation, the Swedish government accepted a new national architectural policy, Politik för Gestaltad livsmiljö (Policy for Designed Living Environment). The policy is situated in a market economy and conveys different strategies for sustainable development. They range from social sustainability theories of inclusion and accessibility, down to resource management, local craftsmanship and recycling of building materials. The policy is a result of a changing understanding of architecture, architectural politics, the architect and his or her role, or as theorists Kaminer and Kossak would argue, roles.

    This Master’s degree project in Sustainable Urban Planning and Design explores and puts forth what could be a relevant content in an architectural policy in Lidköping municipality. It is the result of a document study containing the Swedish national architectural policy, local interpretations of it by 12 municipalities across Sweden and Lidköping municipality’s City plan. As well as a questionnaire and an extended dialogue in the shape of a design workshop with six teenagers in Lidköping about the future of their town. This project aims to aid the development of local interpretations of the Swedish national policy, and, act as a base for discussion on the topic of architecture politics in Sweden.

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