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  • 1. Aili, Daniel
    et al.
    Enander, Karin
    Baltzer, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Liedberg, Bo
    Synthetic de novo designed polypeptides for control of nanoparticle assembly and biosensing2007In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 35, no 3, p. 532-534Article in journal (Refereed)
    Abstract [en]

    This contribution describes how de novo designed synthetic helix–loop–helix polypeptides are utilized tocontrol the assembly of gold nanoparticles and as scaffolds for biosensing. The synthetic polypeptides aredesigned to fold into a four-helix bundle upon dimerization. When immobilized on gold nanoparticles,dimerization and folding occur between peptides on neighbouring particles as an effect of particleaggregation and the folded polypeptides are rigid enough to keep the particles separated at a distancecorresponding to the size of the four-helix bundle. Moreover, peptide dimerization offers a convenientroute to assemble nanoparticles into hybrid multilayers on planar substrates. The drastic change in theresonance conditions of the localized nanoparticle surface plasmon upon particle aggregation is shown tobe useful for optical detection of biomolecular interactions.

  • 2. Barg, Sebastian
    et al.
    Lindqvist, Anders
    Obermüller, Stefanie
    Granule docking and cargo release in pancreatic β-cells2008In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 36, no Pt 3, p. 294-299Article in journal (Refereed)
    Abstract [en]

    Biphasic insulin secretion is required for proper insulin action and is observed not only in vivo, but also in isolated pancreatic islets and even single beta-cells. Late events in the granule life cycle are thought to underlie this temporal pattern. In the last few years, we have therefore combined live cell imaging and electrophysiology to study insulin secretion at the level of individual granules, as they approach the plasma membrane, undergo exocytosis and finally release their insulin cargo. In the present paper, we review evidence for two emerging concepts that affect insulin secretion at the level of individual granules: (i) the existence of specialized sites where granules dock in preparation for exocytosis; and (ii) post-exocytotic regulation of cargo release by the fusion pore.

  • 3. Barragan, A
    et al.
    Spillmann, Dorothe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Carlson, J
    Wahlgren, M
    Role of glycans in Plasmodium falciparum infection1999In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 27, no 4, p. 487-493Article in journal (Refereed)
  • 4. Christakopoulos, Paul
    et al.
    Kekos, D.
    Macris, B.J.
    Bhat, M.K.
    Institute of Food Research, Reading.
    Multiple forms of endo-1,4-β-D-glucanase in the extracellular cellulase system of Fusarium oxysporum1995In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 23, no 4, p. 586S-Article in journal (Refereed)
  • 5.
    Daniel, Chammiran
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
    Öhman, Marie
    Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
    RNA editing and its impact on GABAa receptor function2009In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 37, p. 1399-1403Article in journal (Refereed)
    Abstract [en]

    A-to-I (adenosine-to-inosine) RNA editing catalysed by the ADARs (adenosine deaminases that act on RNA) is a post-transcriptional event that contributes to protein diversity in metazoans. In mammalian neuronal ion channels, editing alters functionally important amino acids and creates receptor subtypes important for the development of the nervous system. The excitatory AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and kainate glutamate receptors, as well as the inhibitory GABAA [GABA (γ-aminobutyric acid) type A] receptor, are subject to A-to-I RNA editing. Editing affects several features of the receptors, including kinetics, subunit assembly and cell-surface expression. Here, we discuss the regulation of editing during brain maturation and the impact of RNA editing on the expression of different receptor subtypes.

  • 6.
    Debatin, K. M.
    et al.
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Beltinger, C.
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Bohler, T.
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Fellenberg, J.
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Friesen, C.
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Fulda, S.
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Herr, I.
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Los, Marek Jan
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Scheuerpflug, C.
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Sieverts, H.
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Stahnke, K.
    GERMAN CANC RES CTR,DIV MOL ONCOL,D-69120 HEIDELBERG,GERMANY.
    Regulation of apoptosis through CD95 (APO-I/Fas) receptor-ligand interaction1997In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 25, no 2, p. 405-410Article in journal (Refereed)
  • 7.
    Dimberg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The glioblastoma vasculature as a target for cancer therapy2014In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 42, p. 1647-1652Article in journal (Refereed)
    Abstract [en]

    Glioblastoma is characterized by microvascular proliferation and a highly abnormal dysfunctional vasculature. The glioblastoma vessels differ significantly from normal brain vessels morphologically, functionally and molecularly. The present review provides a brief overview of the current understanding of the formation, functional abnormalities and specific gene expression of glioblastoma vessels and the consequences of vascular abnormalization for the tumour microenvironment.

  • 8. Doherty, Gary J
    et al.
    Lundmark, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    GRAF1-dependent endocytosis2009In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 37, no 5, p. 1061-1065Article in journal (Refereed)
    Abstract [en]

    The role of endocytosis in controlling a multitude of cell biological events is well established. Molecular and mechanistic characterization of endocytosis has predominantly focused on CME (clathrin-mediated endocytosis), although many other endocytic pathways have been described. it was recently shown that the BAR (Bin/amphiphysin/Rvs) and Rho GAP (GTPase-activating protein) domain-containing protein GRAF1 (GTPase regulator associated with focal adhesion kinase-1) is found on prevalent, pleiomorphic endocytic membranes, and is essential for the major, clathrin-independent endocytic pathway that these membranes mediate. This pathway is characterized by its ability to internalize GPI (glycosylphosphatidylinositol)anchored proteins, bacterial toxins and large amounts of extracellular fluid. These membrane carriers are highly dynamic and associated with the activity of the small G-protein Cdc42 (cell division cycle 42). in the present paper, we review the role of GRAF1 in this CLIC (clathrin-independent carrier)/GEEC (GPI-anchored protein-enriched early endocytic compartment) endocytic pathway and discuss the current understanding regarding how this multidomain protein functions at the interface between membrane sculpting, small G-protein signalling and endocytosis.

  • 9.
    Figueroa, Ricardo A.
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Gudise, Santhosh
    Stockholm University, Faculty of Science, Department of Neurochemistry. Karolinska Institutet, Sweden.
    Hallberg, Einar
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Microtubule-associated nuclear envelope proteins in interphase and mitosis2011In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 39, p. 1786-1789Article in journal (Refereed)
    Abstract [en]

    The LINC (linker of nucleoskeleton and cytoskeleton) complex forms a transcisternal bridge across the NE (nuclear envelope) that connects the cytoskeleton with the nuclear interior. This enables some proteins of the NE to communicate with the centrosome and the microtubule cytoskeleton. The position of the centrosome relative to the NE is of vital importance for many cell functions, such as cell migration and division, and centrosomal dislocation is a frequent phenotype in laminopathic disorders. Also in mitosis, a small group of transmembrane NE proteins associate with microtubules when they concentrate in a specific membrane domain associated with the mitotic spindle. The present review discusses structural and functional aspects of microtubule association with NE proteins and how this association may be maintained over the cell cycle.

  • 10.
    Filatov, D.
    et al.
    Umeå universitet.
    Ingemarson, R.
    Umeå universitet.
    Johansson, E.
    Umeå universitet.
    Rova, Ulrika
    Thelander, L.
    Umeå universitet.
    Mouse ribonucleotide reductase: from genes to proteins1995In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 23, no 4, p. 903-905Article in journal (Refereed)
  • 11. Fischer, Urs
    et al.
    Ikeda, Yoshihisa
    Grebe, Markus
    Institutionen för skoglig genetik och växtfysiologi, Sveriges Lantbruksuniversitet, Umeå.
    Planar polarity of root hair positioning in Arabidopsis2007In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 35, no Pt 1, p. 149-151Article in journal (Refereed)
    Abstract [en]

    The co-ordinated polarity of cells within the plane of a single tissue layer (planar polarity) is intensively studied in animal epithelia but has only recently been systematically analysed in plants. The polar positioning of hairs in the root epidermis of Arabidopsis thaliana provides an easily accessible system for the functional dissection of a plant-specific planar polarity. Recently, mutants originally isolated in genetic screens for defects in root hair morphogenesis and changes in the sensitivity to or the production of the plant hormones auxin and ethylene have identified players that contribute to polar root hair placement. Here, we summarize and discuss recent progress in research on polar root hair positioning from studies in Arabidopsis.

  • 12.
    Gekara, N O
    et al.
    Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
    Weiss, S
    Lipid rafts clustering and signalling by listeriolysin O.2004In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 32, no Pt 5, p. 712-714Article in journal (Refereed)
    Abstract [en]

    Listeriolysin O, the major virulent determinant of Listeria monocytogenes, is known for forming pores on cholesterol-rich membranes. In the present study, we reveal its other facet, rafts clustering. By immunofluorescence microscopy, we show that the glycosylphosphatidylinositol-anchored proteins CD14 and CD24, which normally exhibit uniform distribution on J774 cells, undergo clustering upon treatment with LLO. The non-raft marker transferrin receptor is unaffected by such treatment. Rafts clustering might explain the induction of tyrosine phosphorylation observed on LLO-treated cells.

  • 13.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Kihlström, Erik
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Ståhlbom, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid2003In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 31, no 4, p. 810-814Article in journal (Refereed)
    Abstract [en]

    PLUNC (palate, lung and nasal epithelial clone) is a newly discovered gene that is expressed in the upper respiratory tract and is suggested to be of importance in host defence against bacteria. We have identified two forms of the PLUNC protein in human nasal lavage fluid (NLF) using two-dimensional gel electrophoresis (2-DE) and MS. The apparent molecular masses and isoelectric points of these forms are 24.8 kDa/pI 5.4 and 25.1 kDa/pI 5.5. Notably, the 24.8 kDa/pI 5.4 form of PLUNC is an abundant protein in the 2-DE protein patterns of NLF from healthy subjects. Decreased levels of PLUNC were found in NLF from smokers and workers exposed to reactive epoxy chemicals, indicating that long-term exposure to airway irritants impairs the production of PLUNC in the upper respiratory tract. We have also investigated the presence of lipopolysaccharide (LPS)-binding proteins in NLF. Five proteins were found to adsorb to a LPS-coated surface; two of these proteins correspond to the two PLUNC forms, as judged by 2-DE pattern matching. For comparison, human saliva was found to contain a set of LPS-binding proteins with similar 2-DE spot positions (the same pIs but somewhat lower apparent molecular masses of 20 kDa). These results indicate that PLUNC may be a new marker of airway inflammation and may play a part in the innate immune response, and that human saliva contains yet other members of the family of LPS-binding proteins.

  • 14.
    Gutierrez-de-Teran, Hugo
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Bello, Xabier
    Rodriguez, David
    Characterization of the dynamic events of GPCRs by automated computational simulations2013In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 41, p. 205-212Article in journal (Refereed)
    Abstract [en]

    The recent advances in membrane protein crystallography have provided extremely valuable structural information of the superfamily of GPCRs (G-protein-coupled receptors). This has been particularly true for a few receptors whose structure was solved several times under different biochemical conditions. It follows that the mechanisms of receptor conformational equilibrium and related dynamic events can be explored by computational simulations. In the present article, we summarize our recent understanding of several dynamic features of GPCRs, accomplished through the use of MD (molecular dynamics) simulations. Our pipeline for the MD simulations of GPCRs, implemented in the web service http://gpcr.usc.es, is updated in the present paper and illustrated by recent applications. Special emphasis is put on the A(2A) adenosine receptor, one of the selected cases where crystal structures in several conformations and conditions exist, and on the dimerization process of the CXCR4 (CXC chemokine receptor 4).

  • 15.
    Holmqvist, Erik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Wagner, E. Gerhart H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Impact of bacterial sRNAs in stress responses2017In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 45, p. 1203-1212Article, review/survey (Refereed)
    Abstract [en]

    Bacterial life is harsh and involves numerous environmental and internal challenges that are perceived as stresses. Consequently, adequate responses to survive, cope with, and counteract stress conditions have evolved. In the last few decades, a class of small, non-coding RNAs (sRNAs) has been shown to be involved as key players in stress responses. This review will discuss - primarily from an enterobacterial perspective - selected stress response pathways that involve antisense-type sRNAs. These include themes of how bacteria deal with severe envelope stress, threats of DNA damage, problems with poisoning due to toxic sugar intermediates, issues of iron homeostasis, and nutrient limitation/starvation. The examples discussed highlight how stress relief can be achieved, and how sRNAs act mechanistically in regulatory circuits. For some cases, we will propose scenarios that may suggest why contributions from post-transcriptional control by sRNAs, rather than transcriptional control alone, appear to be a beneficial and universally selected feature.

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  • 16.
    Hubert, Madlen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Umea Univ, Dept Integrat Med Biol, SE-90187 Umea, Sweden.
    Larsson, Elin
    Umea Univ, Dept Integrat Med Biol, SE-90187 Umea, Sweden.
    Lundmark, Richard
    Umea Univ, Dept Integrat Med Biol, SE-90187 Umea, Sweden.
    Keeping in touch with the membrane: protein- and lipid-mediated confinement of caveolae to the cell surface2020In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 48, p. 155-163Article, review/survey (Refereed)
    Abstract [en]

    Caveolae are small Omega-shaped invaginations of the plasma membrane that play important roles in mechanosensing, lipid homeostasis and signaling. Their typical morphology is characterized by a membrane funnel connecting a spherical bulb to the membrane. Membrane funnels (commonly known as necks and pores) are frequently observed as transient states during fusion and fission of membrane vesicles in cells. However, caveolae display atypical dynamics where the membrane funnel can be stabilized over an extended period of time, resulting in cell surface constrained caveolae. In addition, caveolae are also known to undergo flattening as well as short-range cycles of fission and fusion with the membrane, requiring that the membrane funnel closes or opens up, respectively. This mini-review considers the transition between these different states and highlights the role of the protein and lipid components that have been identified to control the balance between surface association and release of caveolae.

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  • 17.
    Hubert, Madlen
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Department of Pharmacy, Uppsala University, BMC P.O. Box 580, SE-751 23 Uppsala, Sweden.
    Larsson, Elin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Lundmark, Richard
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Keeping in touch with the membrane; protein- and lipid-mediated confinement of caveolae to the cell surface2020In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 48, p. 155-163Article, review/survey (Refereed)
    Abstract [en]

    Caveolae are small Omega-shaped invaginations of the plasma membrane that play important roles in mechanosensing, lipid homeostasis and signaling. Their typical morphology is characterized by a membrane funnel connecting a spherical bulb to the membrane. Membrane funnels (commonly known as necks and pores) are frequently observed as transient states during fusion and fission of membrane vesicles in cells. However, caveolae display atypical dynamics where the membrane funnel can be stabilized over an extended period of time, resulting in cell surface constrained caveolae. In addition, caveolae are also known to undergo flattening as well as short-range cycles of fission and fusion with the membrane, requiring that the membrane funnel closes or opens up, respectively. This mini-review considers the transition between these different states and highlights the role of the protein and lipid components that have been identified to control the balance between surface association and release of caveolae.

    Download full text (pdf)
    fulltext
  • 18.
    Hughes, Diarmaid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Tubulekas, I
    Ternary complex-ribosome interaction: its influence on protein synthesis and on growth rate1993In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 21, no 4, p. 851-857Article, review/survey (Other academic)
  • 19.
    Ishizaki, Takahiro
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Hernandez, Sophia
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Paoletta, Martina S.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Instituto de Agrobiotecnología y Biología Molecular (IABIMO), Argentina.
    Sanderson, Theo
    Francis Crick Institute London, United Kingdom.
    Bushell, Ellen
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    CRISPR/Cas9 and genetic screens in malaria parasites: small genomes, big impact2022In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 50, no 3, p. 1069-1079Article, review/survey (Refereed)
    Abstract [en]

    The ∼30 Mb genomes of the Plasmodium parasites that cause malaria each encode ∼5000 genes, but the functions of the majority remain unknown. This is due to a paucity of functional annotation from sequence homology, which is compounded by low genetic tractability compared with many model organisms. In recent years technical breakthroughs have made forward and reverse genome-scale screens in Plasmodium possible. Furthermore, the adaptation of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-Associated protein 9 (CRISPR/Cas9) technology has dramatically improved gene editing efficiency at the single gene level. Here, we review the arrival of genetic screens in malaria parasites to analyse parasite gene function at a genome-scale and their impact on understanding parasite biology. CRISPR/Cas9 screens, which have revolutionised human and model organism research, have not yet been implemented in malaria parasites due to the need for more complex CRISPR/Cas9 gene targeting vector libraries. We therefore introduce the reader to CRISPR-based screens in the related apicomplexan Toxoplasma gondii and discuss how these approaches could be adapted to develop CRISPR/Cas9 based genome-scale genetic screens in malaria parasites. Moreover, since more than half of Plasmodium genes are required for normal asexual blood-stage reproduction, and cannot be targeted using knockout methods, we discuss how CRISPR/Cas9 could be used to scale up conditional gene knockdown approaches to systematically assign function to essential genes.

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  • 20. Jackson, J B
    et al.
    Lever, T M
    Rydström, J
    Persson, Bengt L.
    Department of Biochemistry and Biotechnology, Royal Institute of Technology .
    Carlenor, E
    Proton-translocating transhydrogenase from photosynthetic bacteria1991In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 19, no 3, p. 573-575Article in journal (Refereed)
  • 21.
    Jin, Yi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Kaluza, David
    Jakobsson, Lars
    VEGF, Notch and TGFβ/BMPs in regulation of sprouting angiogenesis and vascular patterning2014In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 42, no 6, p. 1576-1583Article in journal (Refereed)
    Abstract [en]

    The blood vasculature is constantly adapting to meet the demand from tissue. In so doing, branches may form, reorganize or regress. These complex processes employ integration of multiple signalling cascades, some of them being restricted to endothelial and mural cells and, hence, suitable for targeting of the vasculature. Both genetic and drug targeting experiments have demonstrated the requirement for the vascular endothelial growth factor (VEGF) system, the Delta-like-Notch system and the transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) cascades in vascular development. Although several of these signalling cascades in part converge into common downstream components, they differ in temporal and spatial regulation and expression. For example, the pro-angiogenic VEGFA is secreted by cells in need of oxygen, presented to the basal side of the endothelium, whereas BMP9 and BMP10 are supplied via the bloodstream in constant interaction with the apical side to suppress angiogenesis. Delta-like 4 (DLL4), on the other hand, is provided as an endothelial membrane bound ligand. In the present article, we discuss recent data on the integration of these pathways in the process of sprouting angiogenesis and vascular patterning and malformation.

  • 22.
    Järver, Peter
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Langel, K.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    EL Andaloussi, Samir
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Langel, Ülo
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Applications of cell-penetrating peptides in regulation of gene expression2007In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 35, no Pt 4, p. 770-774Article in journal (Refereed)
    Abstract [en]

    CPPs (cell-penetrating peptides) can be defined as short peptides that are able to efficiently penetrate cellular lipid bilayers. Because of this remarkable feature, they are excellent candidates regarding alterations in gene expression. CPPs have been utilized in in vivo and in vitro experiments as delivery vectors for different bioactive cargoes. This review focuses on the experiments performed in recent years where CPPs have been used as vectors for multiple effectors of gene expression such as oligonucleotides for antisense, siRNA (small interfering RNA) and decoy dsDNA (double-stranded DNA) applications, and as transfection agents for plasmid delivery.

  • 23.
    Karlsson, Hannah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Approaches to augment CAR T-cell therapy by targeting the apoptotic machinery2016In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 44, no 2, p. 371-376Article, review/survey (Refereed)
    Abstract [en]

    Chimaeric antigen receptor (CAR) T-cells have shown impressive results in patients with B-cell leukaemia. Yet, in patients with lymphoma durable responses are still rare and heavy preconditioning required. Apoptosis resistance is considered a hallmark of cancer, often conveyed by a halted apoptosis signalling. Tumours regularly skew the balance of the components of the apoptotic machinery either through up-regulating antiapoptotic proteins or silencing pro-apoptotic ones. Malignant B-cells frequently up-regulate anti-apoptotic B-cell lymphoma 2 (Bcl-2) family proteins leading to therapy resistance. CAR T-cells kill tumour cells via apoptosis induction and their efficacy may be affected by the level of Bcl-2 family proteins. Hence, there is an interesting possibility to increase the effect of CAR T-cell therapy by combining it with apoptosis inhibitor blockade agents. Compounds that inhibit Bcl-2, B-cell lymphoma extra large (Bcl-xL) and Bcl-2-like protein 2 (Bcl-w), can restore execution of apoptosis in tumour cells or sensitize them to other apoptosis-dependent treatments. Hence, there is a great interest to combine such agents with CAR T-cell therapy to potentiate the effect of CAR T-cell killing. This review will focus on the potential of targeting the apoptotic machinery to sensitize tumour cells to CAR T-cell killing.

  • 24.
    Kirsebom, Leif A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    RNase P RNA-mediated catalysis.2002In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 30, no 6, p. 1153-1158Article in journal (Other academic)
    Abstract [en]

    The endoribonuclease RNase P is involved in the processing of tRNA precursors to generate mature 5' termini. The catalytic activity of RNase P is associated with an RNA, RNase P RNA. A specific interaction between the 3' end of the substrate and RNase P RNA, to form an RNase P RNA-substrate complex, is referred to as the '73-294-interaction'. This interaction has an important role for efficient and correct cleavage to occur. Here our understanding of the contribution of the 73-294-interaction and metal ions, with respect to efficient and correct cleavage in RNase P RNA-mediated catalysis, will be discussed.

  • 25.
    Klingstedt, Therése
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biochemistry. Linköping University, The Institute of Technology.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Luminescent conjugated poly- and oligo-thiophenes: optical ligands for spectral assignment of a plethora of protein aggregates2012In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 40, p. 704-710Article in journal (Refereed)
    Abstract [en]

    The deposition of protein aggregates in various parts of our body gives rise to several devastating diseases, and the development of probes for the selective detection of aggregated proteins is crucial to advance our understanding of the pathogenesis underlying these diseases. LCPs (luminescent conjugated polythiophenes) are fluorescent probes that bind selectively to protein aggregates. The conjugated thiophene backbone is flexible and offers a connection between the conformation and the emission properties, hence binding of LCPs gives the molecule a spectral fingerprint. The present review covers the utilization of LCPs to study the heterogeneity of protein aggregates. It emphasizes specifically the introduction of well-defined probes called LCOs (luminescent conjugated oligothiophenes) and reports how these molecules can be used for real-time in vivo imaging of cerebral plaques as well as for spectral discrimination of protein aggregates and detection of early species in the fibrillation pathway of amyloid beta-peptide.

  • 26.
    Koch, Sina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Neuropilin signalling in angiogenesis2012In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 40, p. 20-25Article in journal (Refereed)
    Abstract [en]

    VEGFs (vascular endothelial growth factors) are master regulators of vascular development and of blood and lymphatic vessel function during health and disease in adults. This family of five mammalian ligands acts through three RTKs (receptor tyrosine kinases). In addition, co-receptors such as NRPs (neuropilins) associate with the ligand-receptor signalling complex and modulate the output. Therapeutics to block several of the VEGF signalling components as well as NRP function have been developed with the aim of halting blood vessel formation, angiogenesis, in diseases that involve tissue growth and inflammation, such as cancer. The present review outlines the current understanding of NRPs in relation to blood and lymphatic vessel biology.

  • 27.
    Kolar, Mallappa K.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Regenerative effects of adipose-tissue-derived stem cells for treatment of peripheral nerve injuries2014In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 42, p. 697-701Article in journal (Refereed)
    Abstract [en]

    Peripheral nerve injuries are a common occurrence affecting the nerves found outside the central nervous system. Complete nerve transections necessitate surgical re-anastomosis, and, in cases where there is a significant gap between the two ends of the injured nerve, bridging strategies are required to repair the defect. The current clinical gold standard is the nerve graft, but this has a number of limitations, including donor site morbidity. An active area of research is focused on developing other techniques to replace these grafts, by creating tubular nerve-guidance conduits from natural and synthetic materials, which are often supplemented with biological cues such as growth factors and regenerative cells. In the present short review, we focus on the use of adipose-tissue-derived stem cells and the possible mechanisms through which they may exert a positive influence on peripheral nerve regeneration, thereby enabling more effective nerve repair.

  • 28.
    Kurup, S
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Abramsson, A
    Li, Jin-Ping
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lindahl, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kjellén, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Betsholtz, C
    Gerhardt, H
    Spillmann, Dorothe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Heparan sulphate requirement in platelet-derived growth factor B-mediated pericyte recruitment2006In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 34, no Pt 3, p. 454-455Article in journal (Refereed)
    Abstract [en]

    HS (heparan sulphate) plays a key role in angiogenesis, by interacting with growth factors required in the process. it has been proposed that HS controls the diffusion, and thus the availability, of platelet-derived growth factor B that is needed for pericyte recruitment around newly formed capillaries. The present paper summarizes our studies on the importance of HS structure in this regulatory process.

  • 29.
    Leul, Melakeselam
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Mattsson, Ulrika
    Sellstedt, Anita
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Molecular characterization of uptake hydrogenase in Frankia2005In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 33, no 1, p. 64-66Article in journal (Refereed)
    Abstract [en]

    A molecular characterization of uptake hydrogenase in Fronkia was performed by using two-dimensional gel electrophoresis, matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry, PCR amplification and Southern blotting. A polypeptide of approx. 60 kDa was recognized in Frankia UGL011102, AVCI1 and KBS on the two-dimensional gel by blotting with Ralstonia eutropha (Hox G) antibody. Further analysis by MS resulted in a peptide 'fingerprint', which was similar to the membrane-bound hydrogenase 2 large subunit (HYD2) in Escherichia coli. in addition, a 127 bp PCR fragment could also be amplified from Frankia AVCI1, which gave a 76% similarity with the large subunit of hydrogenase in, e.g., Azotobacter chrococcum, Bradyrhizobium japonicum and Rhizobium leguminosorum. Although immunological similarity between the small subunit of Frankia hydrogenase and that of other organisms has not yet been found, a PCR product of 500 bp could be amplified from the local source of Fronkia, the analysis of which gave 69 and 67% identity with the small subunit of hydrogenases in B. japonicum and R. leguminosorum respectively. A Southern-blot analysis further indicated evidence for the presence of the small hydrogenase subunit in other Fronkia strains, i.e. KBS, Avcl1 and Ccl3.

  • 30.
    Lidholt, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Biosynthesis of glycosaminoglycans in mammalian cells and in bacteria1997In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 25, no 3, p. 866-70Article, book review (Other academic)
  • 31.
    Lindahl, Tomas L.
    et al.
    Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Linköping University, Linköping, Sweden.
    Boknas, Niklas
    Linköping University, Linköping, Sweden; Region Östergötland, Linköping, Sweden..
    Faxalv, Lars
    Linköping University, Linköping, Sweden.
    Caveats in studies of the physiological role of polyphosphates in coagulation2016In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 44, no 1, p. 35-39Article in journal (Refereed)
    Abstract [en]

    Platelet-derived polyphosphates (polyP), stored in dense granule and released upon platelet activation, have been claimed to enhance thrombin activation of coagulation factor XI (FXI) and to activate FXII directly. The latter claim is controversial and principal results leading to these conclusions are probably influenced by methodological problems. It is important to consider that low-grade contact activation is initiated by all surfaces and is greatly amplified by the presence of phospholipids simulating the procoagulant membranes of activated platelets. Thus, proper use of inhibitors of the contact pathway and a careful choice of materials for plates and tubes is important to avoid artefacts. The use of phosphatases used to degrade polyP has an important drawback as it also degrades the secondary activators ADP and ATP, which are released from activated platelets. In addition, the use of positively charged inhibitors, such as polymyxin B, to inhibit polyP in platelet-rich plasma and blood is problematic, as polymyxin B also slows coagulation in the absence of polyP. In conclusion we hope awareness of the above caveats may improve research on the physiological roles of polyP in coagulation.

  • 32.
    Lindahl, Tomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Boknäs, Niklas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Faxälv, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Caveats in studies of the physiological role of polyphosphates in coagulation2016In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 44, p. 35-39Article, review/survey (Refereed)
    Abstract [en]

    Platelet-derived polyphosphates (polyP), stored in dense granule and released upon platelet activation, have been claimed to enhance thrombin activation of coagulation factor XI (FXI) and to activate FXII directly. The latter claim is controversial and principal results leading to these conclusions are probably influenced by methodological problems. It is important to consider that low-grade contact activation is initiated by all surfaces and is greatly amplified by the presence of phospholipids simulating the procoagulant membranes of activated platelets. Thus, proper use of inhibitors of the contact pathway and a careful choice of materials for plates and tubes is important to avoid artefacts. The use of phosphatases used to degrade polyP has an important drawback as it also degrades the secondary activators ADP and ATP, which are released from activated platelets. In addition, the use of positively charged inhibitors, such as polymyxin B, to inhibit polyP in platelet-rich plasma and blood is problematic, as polymyxin B also slows coagulation in the absence of polyP. In conclusion we hope awareness of the above caveats may improve research on the physiological roles of polyP in coagulation. © 2016 Authors; published by Portland Press Limited.

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  • 33.
    Ljungdahl, Per O
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Amino-acid-induced signalling via the SPS-sensing pathway in yeast.2009In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 37, no Pt 1, p. 242-7Article in journal (Refereed)
    Abstract [en]

    Yeast cells rely on the SPS-sensing pathway to respond to extracellular amino acids. This nutrient-induced signal transduction pathway regulates gene expression by controlling the activity of two redundant transcription factors: Stp1 and Stp2. These factors are synthesized as latent cytoplasmic proteins with N-terminal regulatory domains. Upon induction by extracellular amino acids, the plasma membrane SPS-sensor catalyses an endoproteolytic processing event that cleaves away the regulatory N-terminal domains. The shorter forms of Stp1 and Stp2 efficiently target to the nucleus, where they bind and activate transcription of selected genes encoding a subset of amino acid permeases that function at the plasma membrane to catalyse the transport of amino acids into cells. In the present article, the current understanding of events in the SPS-sensing pathway that enable external amino acids to induce their own uptake are reviewed with a focus on two key issues: (i) the maintenance of Stp1 and Stp2 latency in the absence of amino acid induction; and (ii) the amino-acid-induced SPS-sensor-mediated proteolytic cleavage of Stp1 and Stp2.

  • 34.
    Mannervik, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Runarsdottir, Arna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Kurtovic, Sanela
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Multi-substrate-activity space and quasi-species in enzyme evolution: Ohno's dilemma, promiscuity and functional orthogonality2009In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 37, no Pt 4, p. 740-744Article in journal (Refereed)
    Abstract [en]

    A functional enzyme displays activity with at least one substrate and can be represented by a vector in substrate-activity space. Many enzymes, including GSTs (glutathione transferases), are promiscuous in the sense that they act on alternative substrates, and the corresponding vectors operate in multidimensional space. The direction of the vector is governed by the relative activities of the diverse substrates. Stochastic mutations of already existing enzymes generate populations of variants, and clusters of functionally similar mutants can serve as parents for subsequent generations of enzymes. The proper evolving unit is a functional quasi-species, which may not be identical with the 'best' variant in its generation. The manifestation of the quasi-species is dependent on the substrate matrix used to explore catalytic activities. Multivariate analysis is an approach to identifying quasi-species and to investigate evolutionary trajectories in the directed evolution of enzymes for novel functions.

  • 35.
    Marcos-Torres, Francisco Javier
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Biology. Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín-CSIC, 18011 Granada, Spain.
    Juniar, Linda
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Biology.
    Griese, Julia J.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Biology.
    The molecular mechanisms of the bacterial iron sensor IdeR2023In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, article id BST20221539Article, review/survey (Refereed)
    Abstract [en]

    Life came to depend on iron as a cofactor for many essential enzymatic reactions. However, once the atmosphere was oxygenated, iron became both scarce and toxic. Therefore, complex mechanisms have evolved to scavenge iron from an environment in which it is poorly bioavailable, and to tightly regulate intracellular iron contents. In bacteria, this is typically accomplished with the help of one key regulator, an iron-sensing transcription factor. While Gram-negative bacteria and Gram-positive species with low guanine-cytosine (GC) content generally use Fur (ferric uptake regulator) proteins to regulate iron homeostasis, Gram-positive species with high GC content use the functional homolog IdeR (iron-dependent regulator). IdeR controls the expression of iron acquisition and storage genes, repressing the former, and activating the latter in an iron-dependent manner. In bacterial pathogens such as Corynebacterium diphtheriae and Mycobacterium tuberculosis, IdeR is also involved in virulence, whereas in non-pathogenic species such as Streptomyces, it regulates secondary metabolism as well. Although in recent years the focus of research on IdeR has shifted towards drug development, there is much left to learn about the molecular mechanisms of IdeR. Here, we summarize our current understanding of how this important bacterial transcriptional regulator represses and activates transcription, how it is allosterically activated by iron binding, and how it recognizes its DNA target sites, highlighting the open questions that remain to be addressed.

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  • 36.
    Martijn, Joran
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    From archaeon to eukaryote: the evolutionary dark ages of the eukaryotic cell2013In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 41, p. 451-457Article in journal (Refereed)
    Abstract [en]

    The evolutionary origin of the eukaryotic cell represents an enigmatic, yet largely incomplete, puzzle. Several mutually incompatible scenarios have been proposed to explain how the eukaryotic domain of life could have emerged. To date, convincing evidence for these scenarios in the form of intermediate stages of the proposed eukaryogenesis trajectories is lacking, presenting the emergence of the complex features of the eukaryotic cell as an evolutionary deus ex machina. However, recent advances in the field of phylogenomics have started to lend support for a model that places a cellular fusion event at the basis of the origin of eukaryotes (symbiogenesis), involving the merger of an as yet unknown archaeal lineage that most probably belongs to the recently proposed 'TACK superphylum' (comprising Thaumarchaeota, Aigarchaeota, Crenarchaeota and Korarchaeota) with an alphaproteobacterium (the protomitochondrion). Interestingly, an increasing number of so-called ESPs (eukaryotic signature proteins) is being discovered in recently sequenced archaeal genomes, indicating that the archaeal ancestor of the eukaryotic cell might have been more eukaryotic in nature than presumed previously, and might, for example, have comprised primitive phagocytotic capabilities. In the present paper, we review the evolutionary transition from archaeon to eukaryote, and propose a new model for the emergence of the eukaryotic cell, the 'PhAT (phagocytosing archaeon theory)', which explains the emergence of the cellular and genomic features of eukaryotes in the light of a transiently complex phagocytosing archaeon.

  • 37. McLaughlin, Paul J.
    et al.
    Keegan, Liam P.
    Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics. University of Edinburgh, UK.
    Conflict RNA modification, host-parasite co-evolution, and the origins of DNA and DNA-binding proteins2014In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 42, p. 1159-1167Article in journal (Refereed)
    Abstract [en]

    Nearly 150 different enzymatically modified forms of the four canonical residues in RNA have been identified. For instance, enzymes of the ADAR (adenosine deaminase acting on RNA) family convert adenosine residues into inosine in cellular dsRNAs. Recent findings show that DNA endonuclease V enzymes have undergone an evolutionary transition from cleaving 3' to deoxyinosine in DNA and ssDNA to cleaving 3' to inosine in dsRNA and ssRNA in humans. Recent work on dsRNA-binding domains of ADARs and other proteins also shows that a degree of sequence specificity is achieved by direct readout in the minor groove. However, the level of sequence specificity observed is much less than that of DNA major groove-binding helix-turn-helix proteins. We suggest that the evolution of DNA-binding proteins following the RNA to DNA genome transition represents the major advantage that DNA genomes have over RNA genomes. We propose that a hypothetical RNA modification, a RRAR (ribose reductase acting on genomic dsRNA) produced the first stretches of DNA in RNA genomes. We discuss why this is the most satisfactory explanation for the origin of DNA. The evolution of this RNA modification and later steps to DNA genomes are likely to have been driven by cellular genome co-evolution with viruses and intragenomic parasites. RNA modifications continue to be involved in host-virus conflicts; in vertebrates, edited cellular dsRNAs with inosine-uracil base pairs appear to be recognized as self RNA and to suppress activation of innate immune sensors that detect viral dsRNA.

  • 38.
    Moreira, Catia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Calixto, Ana R.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Richard, John P.
    Department of Chemistry, University at Buffalo, SUNY, Buffalo, New York 14260-3000, U.S.A.
    Kamerlin, Shina Caroline Lynn
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    The role of ligand-gated conformational changes in enzyme catalysis2019In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 47, no 5, p. 1449-1460Article in journal (Refereed)
    Abstract [en]

    Structural and biochemical studies on diverse enzymes have highlighted the importance of ligand-gated conformational changes in enzyme catalysis, where the intrinsic binding energy of the common phosphoryl group of their substrates is used to drive energetically unfavorable conformational changes in catalytic loops, from inactive open to catalytically competent closed conformations. However, computational studies have historically been unable to capture the activating role of these conformational changes. Here, we discuss recent experimental and computational studies, which can remarkably pinpoint the role of ligand-gated conformational changes in enzyme catalysis, even when not modeling the loop dynamics explicitly. Finally, through our joint analyses of these data, we demonstrate how the synergy between theory and experiment is crucial for furthering our understanding of enzyme catalysis

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  • 39. Nedergaard, J
    et al.
    Connolly, E
    Nånberg, Eewa
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Mohell, N
    A possible physiological role of the Na+/Ca2+ exchange mechanism of brown-fat mitochondria in the mediation of alpha 1-adrenergic signals.1984In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 12, no 3, p. 393-396Article in journal (Refereed)
  • 40.
    Nedergaard, Jan
    et al.
    The Wenner-Gren Institute, University of Stockholm, Stockholm, Sweden.
    Connolly, Examonn
    The Wenner-Gren Institute, University of Stockholm, Stockholm, Sweden.
    Nånberg, Eewa
    The Wenner-Gren Institute, University of Stockholm, Stockholm, Sweden.
    Mohell, Nina
    The Wenner-Gren Institute, University of Stockholm, Stockholm, Sweden.
    A possible physiological role of the Na+/Ca2+ exchange mechanism of brown-fat mitochondria in the mediation of alpha-1-adrenergic signals1984In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 12, no 3, p. 393-396Article in journal (Refereed)
  • 41.
    Olivecrona, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Liu, Guoqing
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bengtsson-Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Regulation of lipoprotein lipase1993In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 21, no 2, p. 509-513Article in journal (Refereed)
  • 42.
    Olsson, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Therapeutic vaccination targeting the tumour vasculature2014In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 42, p. 1653-1657Article in journal (Refereed)
    Abstract [en]

    Therapeutic vaccination targeting self-molecules could provide a cost-efficient alternative to monoclonal antibody-based therapies for cancer and various inflammatory diseases. However, development of cancer vaccines targeting self-molecules has proven difficult. One complicating factor is that tumour cells have developed strategies to escape recognition by the immune system. Antigens specifically expressed by the tumour vasculature can therefore provide alternative targets. The present mini-review highlights potential target molecules associated with tumour angiogenesis and the approaches made to direct an immune response against them. Furthermore, the requirements on a vaccine targeting self-molecules, in contrast with those directed against virus or bacteria, are discussed.

  • 43.
    Paracini, Nicolò
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Clifton, Luke A
    Lakey, Jeremy H
    Studying the surfaces of bacteria using neutron scattering: finding new openings for antibiotics.2020In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 48, no 5, p. 2139-2149, article id BST20200320Article in journal (Refereed)
    Abstract [en]

    The use of neutrons as a scattering probe to investigate biological membranes has steadily grown in the past three decades, shedding light on the structure and behaviour of this ubiquitous and fundamental biological barrier. Meanwhile, the rise of antibiotic resistance has catalysed a renewed interest in understanding the mechanisms underlying the dynamics of antibiotics interaction with the bacterial cell envelope. It is widely recognised that the key reason behind the remarkable success of Gram-negative pathogens in developing antibiotic resistance lies in the effectiveness of their outer membrane (OM) in defending the cell from antibacterial compounds. Critical to its function, the highly asymmetric lipid distribution between the inner and outer bilayer leaflets of the OM, adds an extra level of complexity to the study of this crucial defence barrier. Here we review the opportunities offered by neutron scattering techniques, in particular reflectometry, to provide structural information on the interactions of antimicrobials with in vitro models of the OM. The differential sensitivity of neutrons towards hydrogen and deuterium makes them a unique probe to study the structure and behaviour of asymmetric membranes. Molecular-level understanding of the interactions between antimicrobials and the Gram-negative OM provides valuable insights that can aid drug development and broaden our knowledge of this critically important biological barrier.

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  • 44. Parmryd, Ingela
    et al.
    Dallner, G
    Organization of isoprenoid biosynthesis1996In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 24, no 3, p. 677-682Article, review/survey (Refereed)
  • 45. RENGER, G
    et al.
    BITTNER, T
    Messinger, Johannes
    Max Volmer Institut für Biophysikalische und Physikalische Chemie, Technischen Universität, Berlin, Germany.
    STRUCTURE-FUNCTION-RELATIONSHIPS IN PHOTOSYNTHETIC WATER OXIDATION1994In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 22, no 2, p. 318-322Article in journal (Refereed)
  • 46.
    Rodriguez, Alejandro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bjerling, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The links between chromatin spatial organization and biological function2013In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 41, no 6, p. 1634-1639Article in journal (Refereed)
    Abstract [en]

    During the last few years, there has been a rapid increase in our knowledge of how chromatin is organized inside the nucleus. Techniques such as FISH (fluorescence in situ hybridization) have proved that chromosomes organize themselves in so-called CTs (chromosome territories). In addition, newly developed 3C (chromatin conformation capture) techniques have revealed that certain chromosomal regions tend to interact with adjacent regions on either the same chromosome or adjacent chromosomes, and also that regions in close proximity are replicated simultaneously. Furthermore, transcriptionally repressed or active areas occupy different nuclear compartments. Another new technique, named DamID (DNA adenine methyltransferase identification), has strengthened the notion that transcriptionally repressed genes are often found in close association with the nuclear membrane, whereas transcriptionally active regions are found in the more central regions of the nucleus. However, in response to various stimuli, transcriptionally repressed regions are known to relocalize from the nuclear lamina to the interior of the nucleus, leading to a concomitant up-regulation of otherwise silenced genes. Taken together, these insights are of great interest for the relationship between chromosomal spatial organization and genome function. In the present article, we review recent advances in this field with a focus on mammalian cells and the eukaryotic model organism Schizosaccharomyces pombe.

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  • 47.
    SAINI, S
    et al.
    ; .
    TURNER, APF
    Cranfield University, UK.
    BIOSENSORS IN ORGANIC PHASES1991In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 19, no 1, p. 28-31Article in journal (Refereed)
    Abstract [en]

    n/a

  • 48.
    Shabalina, Irina G.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Nedergaard, Jan
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Mitochondrial ('mild') uncoupling and ROS production: physiologically relevant or not?2011In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 39, p. 1305-1309Article in journal (Refereed)
    Abstract [en]

    During the last decade, the possibility that 'mild' uncoupling could be protective against oxidative damage by diminishing ROS (reactive oxygen species) production has attracted much interest. In the present paper, we briefly examine the evidence for this possibility. It is only ROS production from succinate under reverse electron-flow conditions that is sensitive to membrane potential fluctuations, and so only this type of ROS production could be affected; however, the conditions under which succinate-supported ROS production is observed include succinate concentrations that are supraphysiological. Any decrease in membrane potential, even 'mild uncoupling', must necessarily lead to large increases in respiration, i.e. it must be markedly thermogenic. Mitochondria within cells are normally ATP-producing and thus already have a diminished membrane potential, and treatment of cells, organs or animals with small amounts of artificial uncoupler does not seem to have beneficial effects that are explainable via reduced ROS production. Although it has been suggested that members of the uncoupling protein family (UCP1, UCP2 and UCP3) may mediate a mild uncoupling, present evidence does not unequivocally support such an effect, e.g. the absence of the truly uncoupling protein UCP1 is not associated with increased oxidative damage. Thus present evidence does not support mild uncoupling as a physiologically relevant alleviator of oxidative damage.

  • 49. Shah, D S
    et al.
    Thomas, M B
    Phillips, S
    Cisneros, David A.
    Biotechnology Center, Dresden University of Technology, Tatzberg 49, 01307 Dresden, Germany‡Biotechnology Center, Dresden University of Technology, Tatzberg 49, 01307 Dresden, Germany‡Biotechnology Center, Dresden University of Technology, Tatzberg 49, 01307 Dresden, Germany.
    Le Brun, A P
    Holt, S A
    Lakey, J H
    Self-assembling layers created by membrane proteins on gold2007In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 35, no 3, p. 522-526Article in journal (Refereed)
    Abstract [en]

    Membrane systems are based on several types of organization. First, amphiphilic lipids are able to create monolayer and bilayer structures which may be flat, vesicular or micellar. Into these structures membrane proteins can be inserted which use the membrane to provide signals for lateral and orientational organization. Furthermore, the proteins are the product of highly specific self-assembly otherwise known as folding, which mostly places individual atoms at precise places in three dimensions. These structures all have dimensions in the nanoscale, except for the size of membrane planes which may extend for millimetres in large liposomes or centimetres on planar surfaces such as monolayers at the air/water interface. Membrane systems can be assembled on to surfaces to create supported bilayers and these have uses in biosensors and in electrical measurements using modified ion channels. The supported systems also allow for measurements using spectroscopy, surface plasmon resonance and atomic force microscopy. By combining the roles of lipids and proteins, highly ordered and specific structures can be self-assembled in aqueous solution at the nanoscale.

  • 50.
    Svensson, Marcus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sköld, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Fälth, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Svenningsson, P.
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Neuropeptidomics: expanding proteomics downwards.2007In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 35, no 3, p. 588-593Article in journal (Refereed)
    Abstract [en]

    Biological function is mainly carried out by a dynamic population of proteins and peptides which may be used as markers for disease diagnosis, prognosis and as a guide for effective treatment. The study of proteins is called proteomics and it is generally performed by two-dimensional gel electrophoresis and mass spectrometric methods. However, gel-based proteomics is methodologically restricted from the low mass region, which includes important endogenous peptides. The study of endogenous peptides, peptidomics, is complicated by protein fragments produced post-mortem during conventional sample handling. Nanoflow liquid chromatography and MS, together with improved methods for sample preparation, have been used to semi-quantitatively monitor endogenous peptides in brain tissue. When rapidly heat-denatured brain tissue was analysed, these methods enabled simultaneous detection of hundreds of peptides and the identification of several endogenous peptides not previously described in the literature. In an application of the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model for Parkinson's disease, the expression of the small protein PEP-19 was compared with controls. The levels were found to be significantly decreased in the striatum of MPTP-treated animals.

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