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    Autophagy in the context of the cellular membrane-trafficking system: the enigma of Atg9 vesicles.
    Biochem Soc Trans 2017 Nov 17. Epub 2017 Nov 17.
    Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan
    Macroautophagy is an intracellular degradation system that involves the de novo formation of membrane structures called autophagosomes, although the detailed process by which membrane lipids are supplied during autophagosome formation is yet to be elucidated. Macroautophagy is thought to be associated with canonical membrane trafficking, but several mechanistic details are still missing. In this review, the current understanding and potential mechanisms by which membrane trafficking participates in macroautophagy are described, with a focus on the enigma of the membrane protein Atg9, for which the proximal mechanisms determining its movement are disputable, despite its key role in autophagosome formation. Read More

    Transcriptional regulators of redox balance and other homeostatic processes with the potential to alter neurodegenerative disease trajectory.
    Biochem Soc Trans 2017 Nov 17. Epub 2017 Nov 17.
    Edinburgh Medical School, University of Edinburgh, Edinburgh EH16 4TJ, U.K.
    Diverse neurodegenerative diseases share some common aspects to their pathology, with many showing evidence of disruption to the brain's numerous homeostatic processes. As such, imbalanced inflammatory status, glutamate dyshomeostasis, hypometabolism and oxidative stress are implicated in many disorders. That these pathological processes can influence each other both up- and downstream makes for a complicated picture, but means that successfully targeting one area may have an effect on others. Read More

    The devil is in the domain: understanding protein recognition of multiple RNA targets.
    Biochem Soc Trans 2017 Nov 17. Epub 2017 Nov 17.
    Institute of Structural and Molecular Biology, University College London, London WC1E 6XA, U.K.
    RNA regulation provides a finely tuned and highly co-ordinated control of gene expression. Regulation is mediated by hundreds to thousands of multi-functional RNA-binding proteins which often interact with large sets of RNAs. In this brief review, we focus on a recent work that highlights how the proteins use multiple RNA-binding domains to interact selectively with the different RNA targets. Read More

    Distinct RNA-unwinding mechanisms of DEAD-box and DEAH-box RNA helicase proteins in remodeling structured RNAs and RNPs.
    Biochem Soc Trans 2017 Nov 17. Epub 2017 Nov 17.
    Department of Molecular Biosciences and the Institute for Cellular & Molecular Biology, University of Texas at Austin, Austin, TX 78712, U.S.A.
    Structured RNAs and RNA-protein complexes (RNPs) fold through complex pathways that are replete with misfolded traps, and many RNAs and RNPs undergo extensive conformational changes during their functional cycles. These folding steps and conformational transitions are frequently promoted by RNA chaperone proteins, notably by superfamily 2 (SF2) RNA helicase proteins. The two largest families of SF2 helicases, DEAD-box and DEAH-box proteins, share evolutionarily conserved helicase cores, but unwind RNA helices through distinct mechanisms. Read More

    Breaking the scale: how disrupting the karyoplasmic ratio gives cancer cells an advantage for metastatic invasion.
    Biochem Soc Trans 2017 Nov 17. Epub 2017 Nov 17.
    Wellcome Centre for Cell Biology and Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, U.K.
    Nuclear size normally scales with the size of the cell, but in cancer this 'karyoplasmic ratio' is disrupted. This is particularly so in more metastatic tumors where changes in the karyoplasmic ratio are used in both diagnosis and prognosis for several tumor types. However, the direction of nuclear size changes differs for particular tumor types: for example in breast cancer, larger nuclear size correlates with increased metastasis, while for lung cancer smaller nuclear size correlates with increased metastasis. Read More

    Emerging candidate treatment strategies for Hutchinson-Gilford progeria syndrome.
    Biochem Soc Trans 2017 Nov 10. Epub 2017 Nov 10.
    Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden
    Hutchinson-Gilford progeria syndrome (HGPS, progeria) is an extremely rare premature aging disorder affecting children, with a disease incidence of ∼1 in 18 million individuals. HGPS is usually caused by a de novo point mutation in exon 11 of the LMNA gene (c.1824C>T, p. Read More

    SNARE phosphorylation: a control mechanism for insulin-stimulated glucose transport and other regulated exocytic events.
    Biochem Soc Trans 2017 Nov 3. Epub 2017 Nov 3.
    Institute of Molecular Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, U.K.
    Trafficking within eukaryotic cells is a complex and highly regulated process; events such as recycling of plasma membrane receptors, formation of multivesicular bodies, regulated release of hormones and delivery of proteins to membranes all require directionality and specificity. The underpinning processes, including cargo selection, membrane fusion, trafficking flow and timing, are controlled by a variety of molecular mechanisms and engage multiple families of lipids and proteins. Here, we will focus on control of trafficking processes via the action of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family of proteins, in particular their regulation by phosphorylation. Read More

    Biochemical targets of drugs mitigating oxidative stress via redox-independent mechanisms.
    Biochem Soc Trans 2017 Nov 3. Epub 2017 Nov 3.
    Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Humboldtstrasse 46/3, Graz 8010, Austria
    Acute or chronic oxidative stress plays an important role in many pathologies. Two opposite approaches are typically used to prevent the damage induced by reactive oxygen and nitrogen species (RONS), namely treatment either with antioxidants or with weak oxidants that up-regulate endogenous antioxidant mechanisms. This review discusses options for the third pharmacological approach, namely amelioration of oxidative stress by 'redox-inert' compounds, which do not inactivate RONS but either inhibit the basic mechanisms leading to their formation (i. Read More

    Impact of bacterial sRNAs in stress responses.
    Biochem Soc Trans 2017 Nov 3. Epub 2017 Nov 3.
    Department of Cell and Molecular Biology, Uppsala University, Box 596, Uppsala S-75124, Sweden.
    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. Read More

    Combining high-resolution cryo-electron microscopy and mutagenesis to develop cowpea mosaic virus for bionanotechnology.
    Biochem Soc Trans 2017 Nov 3. Epub 2017 Nov 3.
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, U.K.
    Particles of cowpea mosaic virus (CPMV) have enjoyed considerable success as nanoparticles. The development of a system for producing empty virus-like particles (eVLPs) of the virus, which are non-infectious and have the potential to be loaded with heterologous material, has increased the number of possible applications for CPMV-based particles. However, for this potential to be realised, it was essential to demonstrate that eVLPs were accurate surrogates for natural virus particles, and this information was provided by high-resolution cryo-EM studies of eVLPs. Read More

    Regulated intramembrane proteolysis: emergent role in cell signalling pathways.
    Biochem Soc Trans 2017 Oct 27. Epub 2017 Oct 27.
    Signal Transduction Laboratory, School of Biochemistry and Cell Biology, Analytical and Biological Chemistry Research Facility (ABCRF), Western Gateway Building, University College Cork, Cork, Ireland
    Receptor signalling events including those initiated following activation of cytokine and growth factor receptors and the well-characterised death receptors (tumour necrosis factor receptor, type 1, FasR and TRAIL-R1/2) are initiated at the cell surface through the recruitment and formation of intracellular multiprotein signalling complexes that activate divergent signalling pathways. Over the past decade, research studies reveal that many of these receptor-initiated signalling events involve the sequential proteolysis of specific receptors by membrane-bound proteases and the γ-secretase protease complexes. Proteolysis enables the liberation of soluble receptor ectodomains and the generation of intracellular receptor cytoplasmic domain fragments. Read More

    Biomolecular coevolution and its applications: Going from structure prediction toward signaling, epistasis, and function.
    Biochem Soc Trans 2017 Oct 20. Epub 2017 Oct 20.
    Steinbuch Centre for Computing, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany
    Evolution leads to considerable changes in the sequence of biomolecules, while their overall structure and function remain quite conserved. The wealth of genomic sequences, the 'Biological Big Data', modern sequencing techniques provide allows us to investigate biomolecular evolution with unprecedented detail. Sophisticated statistical models can infer residue pair mutations resulting from spatial proximity. Read More

    Platelet mitochondrial dysfunction and the correlation with human diseases.
    Biochem Soc Trans 2017 Oct 20. Epub 2017 Oct 20.
    Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
    The platelet is considered as an accessible and valuable tool to study mitochondrial function, owing to its greater content of fully functional mitochondria compared with other metabolically active organelles. Different lines of studies have demonstrated that mitochondria in platelets have function far more than thrombogenesis regulation, and beyond hemostasis, platelet mitochondrial dysfunction has also been used for studying mitochondrial-related diseases. In this review, the interplay between platelet mitochondrial dysfunction and oxidative stress, mitochondrial DNA lesions, electron transfer chain impairments, mitochondrial apoptosis and mitophagy has been outlined. Read More

    Oxidative stress and endoplasmic reticulum (ER) stress in the development of neonatal hypoxic-ischaemic brain injury.
    Biochem Soc Trans 2017 Oct 22;45(5):1067-1076. Epub 2017 Sep 22.
    Perinatal Brain Injury Group, Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London SE1 7EH, U.K.
    Birth asphyxia in term neonates affects 1-2/1000 live births and results in the development of hypoxic-ischaemic encephalopathy with devastating life-long consequences. The majority of neuronal cell death occurs with a delay, providing the potential of a treatment window within which to act. Currently, treatment options are limited to therapeutic hypothermia which is not universally successful. Read More

    G-quadruplex unwinding helicases and their function in vivo.
    Biochem Soc Trans 2017 Oct 22;45(5):1173-1182. Epub 2017 Sep 22.
    European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands
    The concept that G-quadruplex (G4) structures can form within DNA or RNA in vitro has been long known and extensively discussed. In recent years, accumulating evidences imply that G-quadruplex structures form in vivo Initially, inefficient regulation of G-quadruplex structures was mainly associated with genome instability. However, due to the location of G-quadruplex motifs and their evolutionary conservation, different cellular functions of these structures have been postulated (e. Read More

    Mass spectrometry techniques for studying the ubiquitin system.
    Biochem Soc Trans 2017 Oct 22;45(5):1137-1148. Epub 2017 Sep 22.
    Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle-upon-Tyne, U.K.
    Post-translational control of proteins through covalent attachment of ubiquitin plays important roles in all eukaryotic cell functions. The ubiquitin system in humans consists of 2 E1, 35 E2 and >600 E3 ubiquitin ligases as well as hundreds of deubiquitylases, which reverse ubiquitin attachment. Moreover, there are hundreds of proteins with ubiquitin-binding domains that bind one of the eight possible polyubiquitin chains. Read More

    Long and small noncoding RNAs during oocyte-to-embryo transition in mammals.
    Biochem Soc Trans 2017 Oct 22;45(5):1117-1124. Epub 2017 Sep 22.
    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic
    Oocyte-to-embryo transition is a process during which an oocyte ovulates, is fertilized, and becomes a developing embryo. It involves the first major genome reprogramming event in life of an organism where gene expression, which gave rise to a differentiated oocyte, is remodeled in order to establish totipotency in blastomeres of an early embryo. This remodeling involves replacement of maternal RNAs with zygotic RNAs through maternal RNA degradation and zygotic genome activation. Read More

    Omega-3 fatty acids and inflammatory processes: from molecules to man.
    Biochem Soc Trans 2017 Oct 12;45(5):1105-1115. Epub 2017 Sep 12.
    Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, IDS Building, MP887 Southampton General Hospital, Tremona Road, Southampton SO16 6YD, U.K.
    Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Read More

    Geometries of vasculature bifurcation can affect the level of trophic damage during formation of a brain ischemic lesion.
    Biochem Soc Trans 2017 Oct 12;45(5):1097-1103. Epub 2017 Sep 12.
    Institute of Cytochemistry and Molecular Pharmacology, 6-th Radial'naya str. 24-14, Moscow 115404, Russia
    Ischemic lesion is a common cause of various diseases in humans. Brain tissue is especially sensitive to this type of damage. A common reason for the appearance of an ischemic area is a stop in blood flow in some branch of the vasculature system. Read More

    Structure and function of Pif1 helicase.
    Biochem Soc Trans 2017 Oct 12;45(5):1159-1171. Epub 2017 Sep 12.
    Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
    Pif1 family helicases have multiple roles in the maintenance of nuclear and mitochondrial DNA in eukaryotes. Saccharomyces cerevisiae Pif1 is involved in replication through barriers to replication, such as G-quadruplexes and protein blocks, and reduces genetic instability at these sites. Another Pif1 family helicase in S. Read More

    Regulation of the cell cycle and centrosome biology by deubiquitylases.
    Biochem Soc Trans 2017 Oct 12;45(5):1125-1136. Epub 2017 Sep 12.
    Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, U.K.
    Post-translational modification of proteins by ubiquitylation is increasingly recognised as a highly complex code that contributes to the regulation of diverse cellular processes. In humans, a family of almost 100 deubiquitylase enzymes (DUBs) are assigned to six subfamilies and many of these DUBs can remove ubiquitin from proteins to reverse signals. Roles for individual DUBs have been delineated within specific cellular processes, including many that are dysregulated in diseases, particularly cancer. Read More

    Role of conformational change and K-path ligands in controlling cytochrome c oxidase activity.
    Biochem Soc Trans 2017 Oct 24;45(5):1087-1095. Epub 2017 Aug 24.
    Department of Biochemistry and Molecular Biology, Michigan State University, 603 Wilson Rd, East Lansing, MI 48824, U.S.A.
    Given the central role of cytochrome c oxidase (CcO) in health and disease, it is an increasingly important question as to how the activity and efficiency of this key enzyme are regulated to respond to a variety of metabolic states. The present paper summarizes evidence for two modes of regulation of activity: first, by redox-induced conformational changes involving the K-proton uptake path; and secondly, by ligand binding to a conserved site immediately adjacent to the entrance of the K-path that leads to the active site. Both these phenomena highlight the importance of the K-path in control of CcO. Read More

    Visualising pattern recognition receptor signalling.
    Biochem Soc Trans 2017 Oct 24;45(5):1077-1085. Epub 2017 Aug 24.
    Department of Veterinary Medicine, The University of Cambridge, Madingley Road, Cambridge CB3 0ES, U.K.
    Signalling by pattern recognition receptors (PRRs) is critical for protecting the host against pathogens. Disruption of these signalling pathways has been implicated in many diseases ranging from infection susceptibility to cancer and autoimmune disease. Understanding how PRRs signal is of critical importance due to their potential as therapeutic targets to ameliorate symptoms of inflammatory diseases. Read More

    Structure of the Holliday junction: applications beyond recombination.
    Biochem Soc Trans 2017 Oct 24;45(5):1149-1158. Epub 2017 Aug 24.
    Department of Biochemistry and Molecular Biology, Colorado State University, 1870 Campus Delivery, Fort Collins, CO 80523-1870, U.S.A.
    The Holliday junction (HJ) is an essential element in recombination and related mechanisms. The structure of this four-stranded DNA assembly, which is now well-defined alone and in complex with proteins, has led to its applications in areas well outside of molecular recombination, including nanotechnology and biophysics. This minireview explores some interesting recent research on the HJ, as it has been adapted to design regular two- or three-dimensional lattices for crystal engineering, and more complex systems through DNA origami. Read More

    Mitochondrial health maintenance in axons.
    Biochem Soc Trans 2017 Oct 4;45(5):1045-1052. Epub 2017 Aug 4.
    F.M. Kirby Center for Neurobiology, Children's Hospital Boston, Boston, MA 02115, U.S.A.
    Neurons are post-mitotic cells that must function throughout the life of an organism. The high energetic requirements and Ca(2+) spikes of synaptic transmission place a burden on neuronal mitochondria. The removal of older mitochondria and the replenishment of the functional mitochondrial pool in axons with freshly synthesized components are therefore important parts of neuronal maintenance. Read More

    Consequences of RNA oxidation on protein synthesis rate and fidelity: implications for the pathophysiology of neuropsychiatric disorders.
    Biochem Soc Trans 2017 Oct 4;45(5):1053-1066. Epub 2017 Aug 4.
    Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX 78249, U.S.A.
    Unlike DNA, oxidative damage to RNA has received little attention presumably due to the assumed transient nature of RNA. However, RNAs including mRNA can persist for several hours to days in certain tissues and are demonstrated to sustain greater oxidative damage than DNA. Because neuronal cells in the brain are continuously exposed to reactive oxygen species due to a high oxygen consumption rate, it is not surprising that neuronal RNA oxidation is observed as a common feature at an early stage in a series of neurodegenerative disorders. Read More

    Deciphering the regulation of metabolism with dynamic optimization: an overview of recent advances.
    Biochem Soc Trans 2017 Jul 28. Epub 2017 Jul 28.
    Research Group Medical Systems Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.
    Understanding optimality principles shaping the evolution of regulatory networks controlling metabolism is crucial for deriving a holistic picture of how metabolism is integrated into key cellular processes such as growth, adaptation and pathogenicity. While in the past the focus of research in pathway regulation was mainly based on stationary states, more recently dynamic optimization has proved to be an ideal tool to decipher regulatory strategies for metabolic pathways in response to environmental cues. In this short review, we summarize recent advances in the elucidation of optimal regulatory strategies and identification of optimal control points in metabolic pathways. Read More

    Interaction of misfolded proteins and mitochondria in neurodegenerative disorders.
    Biochem Soc Trans 2017 Jul 21. Epub 2017 Jul 21.
    Institute of Cell Biophysics Russian Academy of Sciences, Pushchino 142290, Russia.
    The number of the people affected by neurodegenerative disorders is growing dramatically due to the ageing of population. The major neurodegenerative diseases share some common pathological features including the involvement of mitochondria in the mechanism of pathology and misfolding and the accumulation of abnormally aggregated proteins. Neurotoxicity of aggregated β-amyloid, tau, α-synuclein and huntingtin is linked to the effects of these proteins on mitochondria. Read More

    Identification of optimal strategies for state transition of complex biological networks.
    Biochem Soc Trans 2017 Jul 21. Epub 2017 Jul 21.
    Simulation and Optimal Processes Group, Institute of Automation and Systems Engineering, Ilmenau University of Technology, Ilmenau 98684, Germany
    Complex biological networks typically contain numerous parameters, and determining feasible strategies for state transition by parameter perturbation is not a trivial task. In the present study, based on dynamical and structural analyses of the biological network, we optimized strategies for controlling variables in a two-node gene regulatory network and a T-cell large granular lymphocyte signaling network associated with blood cancer by using an efficient dynamic optimization method. Optimization revealed the critical value for each decision variable to steer the system from an undesired state into a desired attractor. Read More

    Nutritional modulation of metabolic inflammation.
    Biochem Soc Trans 2017 08 14;45(4):979-985. Epub 2017 Jul 14.
    Nutrigenomics Research Group, Conway Institute of Biomedical and Biomolecular Research, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland
    Metabolic inflammation is a very topical area of research, wherein aberrations in metabolic and inflammatory pathways probably contribute to atherosclerosis, insulin resistance (IR) and type 2 diabetes. Metabolic insults arising from obesity promote inflammation, which in turn impedes insulin signalling and reverse cholesterol transport (RCT). Key cells in the process are metabolically activated macrophages, which up-regulate both pro- and anti-inflammatory pathways in response to lipid spillover from adipocytes. Read More

    Post-transcriptional control of gene expression following stress: the role of RNA-binding proteins.
    Biochem Soc Trans 2017 08 14;45(4):1007-14. Epub 2017 Jul 14.
    Medical Research Council Toxicology Unit, Lancaster Rd, Leicester LE1 9HN, U.K.
    The ability of mammalian cells to modulate global protein synthesis in response to cellular stress is essential for cell survival. While control of protein synthesis is mediated by the regulation of eukaryotic initiation and elongation factors, RNA-binding proteins (RBPs) provide a crucial additional layer to post-transcriptional regulation. RBPs bind specific RNA through conserved RNA-binding domains and ensure that the information contained within the genome and transcribed in the form of RNA is exported to the cytoplasm, chemically modified, and translated prior to folding into a functional protein. Read More

    RNA search engines empower the bacterial intranet.
    Biochem Soc Trans 2017 08 14;45(4):987-997. Epub 2017 Jul 14.
    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, U.K.
    RNA acts not only as an information bearer in the biogenesis of proteins from genes, but also as a regulator that participates in the control of gene expression. In bacteria, small RNA molecules (sRNAs) play controlling roles in numerous processes and help to orchestrate complex regulatory networks. Such processes include cell growth and development, response to stress and metabolic change, transcription termination, cell-to-cell communication, and the launching of programmes for host invasion. Read More

    How tetraspanins shape endothelial and leukocyte nano-architecture during inflammation.
    Biochem Soc Trans 2017 08 14;45(4):999-1006. Epub 2017 Jul 14.
    nAnostic Institute, Centre for Nanotechnology, Heisenbergstrasse 11, 48149 Münster, Germany
    Tetraspanins are ubiquitous membrane proteins that induce local membrane curvature and hence co-ordinate cell-to-cell contacts. This review highlights their role in inflammation, which requires control of the nano-architecture of attachment sites between endothelial cells and leukocytes. The active role of endothelial cells in preparing for transmigration of leukocytes and determining the severity of an inflammation is often underscored. Read More

    P-Rex1 and P-Rex2 RacGEFs and cancer.
    Biochem Soc Trans 2017 08 14;45(4):963-77. Epub 2017 Jul 14.
    Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, 23 Innovation Walk, Clayton, VIC 3800, Australia
    Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger (P-Rex) proteins are RacGEFs that are synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and Gβγ subunits of G-protein-coupled receptors. P-Rex1 and P-Rex2 share similar amino acid sequence homology, domain structure, and catalytic function. Recent evidence suggests that both P-Rex proteins may play oncogenic roles in human cancers. Read More

    Regulation of the trafficking and the function of the metalloprotease ADAM10 by tetraspanins.
    Biochem Soc Trans 2017 08 7;45(4):937-44. Epub 2017 Jul 7.
    Inserm, U935, F-94807 Villejuif, France
    By interacting directly with partner proteins and with one another, tetraspanins organize a network of interactions referred to as the tetraspanin web. ADAM10 (A Disintegrin And Metalloprotease 10), an essential membrane-anchored metalloprotease that cleaves off the ectodomain of a large variety of cell surface proteins including cytokines, adhesion molecules, the precursor of the β-amyloid peptide APP or Notch, has emerged as a major component of the tetraspanin web. Recent studies have shown that ADAM10 associates directly with all members (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17 and Tspan33) of a subgroup of tetraspanins having eight cysteines in the large extracellular domain and referred to as TspanC8. Read More

    Resource allocation in living organisms.
    Biochem Soc Trans 2017 08 7;45(4):945-952. Epub 2017 Jul 7.
    MaIAGE, INRA, Université Paris-Saclay, Jouy-en-Josas 78350, France
    Quantitative prediction of resource allocation for living systems has been an intensive area of research in the field of biology. Resource allocation was initially investigated in higher organisms by using empirical mathematical models based on mass distribution. A challenge is now to go a step further by reconciling the cellular scale to the individual scale. Read More

    Lnc-ing inflammation to disease.
    Biochem Soc Trans 2017 08 7;45(4):953-62. Epub 2017 Jul 7.
    Division of Chemical Systems & Synthetic Biology, Institute for Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town 7925, South Africa
    Termed 'master gene regulators' long ncRNAs (lncRNAs) have emerged as the true vanguard of the 'noncoding revolution'. Functioning at a molecular level, in most if not all cellular processes, lncRNAs exert their effects systemically. Thus, it is not surprising that lncRNAs have emerged as important players in human pathophysiology. Read More

    The sweet tooth of the circadian clock.
    Biochem Soc Trans 2017 08 3;45(4):871-884. Epub 2017 Jul 3.
    Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, CT, U.S.A.
    The endogenous circadian clock is a key regulator of daily metabolic processes. On the other hand, circadian clocks in a broad range of tissues can be tuned by extrinsic and intrinsic metabolic cues. The bidirectional interaction between circadian clocks and metabolism involves both transcriptional and post-translational mechanisms. Read More

    Design starch: stochastic modeling of starch granule biogenesis.
    Biochem Soc Trans 2017 08 3;45(4):885-893. Epub 2017 Jul 3.
    Institute of Quantitative and Theoretical Biology, Heinrich-Heine University, Düsseldorf 40225, Germany.
    Starch is the most widespread and abundant storage carbohydrate in plants and the main source of carbohydrate in the human diet. Owing to its remarkable properties and commercial applications, starch is still of growing interest. Its unique granular structure made of intercalated layers of amylopectin and amylose has been unraveled thanks to recent progress in microscopic imaging, but the origin of such periodicity is still under debate. Read More

    Exercise protects from cancer through regulation of immune function and inflammation.
    Biochem Soc Trans 2017 08 3;45(4):905-11. Epub 2017 Jul 3.
    Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Rigshospitalet, Faculty of Health Science, University of Copenhagen, Rigshospitalet 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
    Exercise training has been extensively studied in cancer settings as part of prevention or rehabilitation strategies, yet emerging evidence suggests that exercise training can also directly affect tumor-specific outcomes. The underlying mechanisms for this exercise-dependent cancer protection are just starting to be elucidated. To this end, evasion of immune surveillance and tumor-associated inflammation are established as hallmarks of cancer, and exercise may target cancer incidence and progression through regulation of these mechanisms. Read More

    Targeting the hepatocyte growth factor/Met pathway in cancer.
    Biochem Soc Trans 2017 08 3;45(4):855-870. Epub 2017 Jul 3.
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A.
    Hepatocyte growth factor (HGF)-induced activation of its cell surface receptor, the Met tyrosine kinase, drives mitogenesis, motogenesis and morphogenesis in a wide spectrum of target cell types and embryologic, developmental and homeostatic contexts. Typical paracrine HGF/Met signaling is regulated by HGF activation at target cell surfaces, HGF binding-induced receptor activation, internalization and degradation. Despite these controls, HGF/Met signaling contributes to oncogenesis, tumor angiogenesis and invasiveness, and tumor metastasis in many types of cancer, leading to the rapid growth of pathway-targeted anticancer drug development programs. Read More

    Functions of long non-coding RNAs in human disease and their conservation in Drosophila development.
    Biochem Soc Trans 2017 08 3;45(4):895-904. Epub 2017 Jul 3.
    Brighton and Sussex Medical School, Medical Research Building, University of Sussex, Falmer, Brighton BN1 9PS, U.K.
    Genomic analysis has found that the transcriptome in both humans and Drosophila melanogaster features large numbers of long non-coding RNA transcripts (lncRNAs). This recently discovered class of RNAs regulates gene expression in diverse ways and has been involved in a large variety of important biological functions. Importantly, an increasing number of lncRNAs have also been associated with a range of human diseases, including cancer. Read More

    Functional interfaces between TICAM-2/TRAM and TICAM-1/TRIF in TLR4 signaling.
    Biochem Soc Trans 2017 08 19;45(4):929-935. Epub 2017 Jun 19.
    Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
    Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS), produces pro-inflammatory cytokines and type I interferons, and associates with a trigger of endotoxin shock. TLR4 is interacted with a TIR domain-containing adaptor molecule-2 (TICAM-2)/TRAM [TRIF (TIR domain-containing adaptor-inducing interferon-β)-related adaptor molecule] via its Toll-interleukin-1 receptor homology (TIR) domain. TICAM-2 acts as a scaffold protein and activates TIR domain-containing adaptor molecule-1 (TICAM-1)/TRIF. Read More

    Targeting the Ras palmitoylation/depalmitoylation cycle in cancer.
    Biochem Soc Trans 2017 08 19;45(4):913-921. Epub 2017 Jun 19.
    Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4
    The Ras proteins are well-known drivers of many cancers and thus represent attractive targets for the development of anticancer therapeutics. Inhibitors that disrupt the association of the Ras proteins with membranes by blocking the addition of the farnesyl lipid moiety to the Ras C-terminus failed in clinical trials. Here, we explore the possibility of targeting a second lipid modification, S-acylation, commonly referred to as palmitoylation, as a strategy to disrupt the membrane interaction of specific Ras isoforms. Read More

    Structure and function of DHHC protein S-acyltransferases.
    Biochem Soc Trans 2017 08 19;45(4):923-8. Epub 2017 Jun 19.
    Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, U.S.A.
    It has been estimated that 10% of the human genome encodes proteins that are fatty acylated at cysteine residues. The vast majority of these proteins are modified by members of the DHHC protein family, which carry out their enzymatic function on the cytoplasmic face of cell membranes. The biomedical importance of DHHC proteins is underscored by their association with human disease; unique and essential roles for DHHC proteins have been uncovered using DHHC-deficient mouse models. Read More

    Role of ESCRT component HD-PTP/PTPN23 in cancer.
    Biochem Soc Trans 2017 Jun;45(3):845-854
    Department of Biochemistry, McGill University, Montréal, Québec, Canada H3G 1Y6
    Sustained cellular signalling originated from the receptors located at the plasma membrane is widely associated with cancer susceptibility. Endosomal sorting and degradation of the cell surface receptors is therefore crucial to preventing chronic downstream signalling and tumorigenesis. Since the Endosomal Sorting Complexes Required for Transport (ESCRT) controls these processes, ESCRT components were proposed to act as tumour suppressor genes. Read More

    Fundamental principles of vascular network topology.
    Biochem Soc Trans 2017 Jun;45(3):839-844
    Mathematical Modelling and Statistical Analysis, Institute of Cytochemistry and Molecular Pharmacology, Moscow, Russia.
    The vascular system is arguably the most important biological system in many organisms. Although the general principles of its architecture are simple, the growth of blood vessels occurs under extreme physical conditions. Optimization is an important aspect of the development of computational models of the vascular branching structures. Read More

    Let there be light: how to use photoswitchable cross-linker to reprogram proteins.
    Biochem Soc Trans 2017 Jun;45(3):831-837
    Experimental Molecular Biophysics, Department of Physics, Freie Universität Berlin, Berlin 14195, Germany
    Azobenzene is a photo-isomerizing molecule whose end-to-end distance changes upon external illumination. When combined with site-specific reactive groups, it can be used as molecular tweezers to remote-control the structure and function of protein targets. The present study gives a brief overview over the rational design strategies that use an azobenzene-based photoswitchable cross-linker to engineer ON/OFF switches into functional proteins or to reprogram proteins for novel functions. Read More

    Mitochondrial cytochrome c oxidase: catalysis, coupling and controversies.
    Biochem Soc Trans 2017 Jun;45(3):813-829
    Glynn Laboratory of Bioenergetics, Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, U.K.
    Mitochondrial cytochrome c oxidase is a member of a diverse superfamily of haem-copper oxidases. Its mechanism of oxygen reduction is reviewed in terms of the cycle of catalytic intermediates and their likely chemical structures. This reaction cycle is coupled to the translocation of protons across the inner mitochondrial membrane in which it is located. Read More

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