| 1. |
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Aili, Daniel, et al.
(författare)
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Synthetic de novo designed polypeptides for control of nanoparticle assembly and biosensing
- 2007
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 35:3, s. 532-534
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Akke, Mikael
(författare)
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Conformational dynamics and thermodynamics of protein-ligand binding studied by NMR relaxation.
- 2012
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Ingår i: Biochemical Society Transactions. - 0300-5127. ; 40:2, s. 419-423
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Tidskriftsartikel (refereegranskat)abstract
- Protein conformational dynamics can be critical for ligand binding in two ways that relate to kinetics and thermodynamics respectively. First, conformational transitions between different substates can control access to the binding site (kinetics). Secondly, differences between free and ligand-bound states in their conformational fluctuations contribute to the entropy of ligand binding (thermodynamics). In the present paper, I focus on the second topic, summarizing our recent results on the role of conformational entropy in ligand binding to Gal3C (the carbohydrate-recognition domain of galectin-3). NMR relaxation experiments provide a unique probe of conformational entropy by characterizing bond-vector fluctuations at atomic resolution. By monitoring differences between the free and ligand-bound states in their backbone and side chain order parameters, we have estimated the contributions from conformational entropy to the free energy of binding. Overall, the conformational entropy of Gal3C increases upon ligand binding, thereby contributing favourably to the binding affinity. Comparisons with the results from isothermal titration calorimetry indicate that the conformational entropy is comparable in magnitude to the enthalpy of binding. Furthermore, there are significant differences in the dynamic response to binding of different ligands, despite the fact that the protein structure is virtually identical in the different protein-ligand complexes. Thus both affinity and specificity of ligand binding to Gal3C appear to depend in part on subtle differences in the conformational fluctuations that reflect the complex interplay between structure, dynamics and ligand interactions.
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| 7. |
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| 8. |
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| 9. |
- Barg, Sebastian, 1969-, et al.
(författare)
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Granule docking and cargo release in pancreatic β-cells
- 2008
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 36:Pt 3, s. 294-299
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
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| 11. |
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| 12. |
- Blom, Anna
(författare)
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Structural and functional studies of complement inhibitor C4b-binding protein.
- 2002
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Ingår i: Biochemical Society Transactions. - 0300-5127. ; 30:Pt 6, s. 978-982
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Tidskriftsartikel (refereegranskat)abstract
- C4b-binding protein (C4BP) is a potent inhibitor of the classical pathway of the complement system. This large plasma glycoprotein consists of seven identical a- chains and a unique b-chain held together by disulphide bridges. Both types of subunits are composed almost exclusively of complement control protein domains (CCPs). Using homology-based computer modelling and mutagenesis of recombinant proteins we have localized binding sites for several ligands of C4BP: complement factor C4b, heparin and vitamin K-dependent anticoagulant protein S (PS). We found that C4b requires CCP1–3 of the a-chain for binding. The interaction is ionic in nature and mediated by a cluster of positively charged amino acids present on the interface between CCP1 and CCP2 of the a-chain. Loss of C4b-binding resulted in a loss of all inhibitory functions of C4BP within the classical pathway of complement. Binding of heparin required CCPs 1–3 of the a-chain, with CCP2 being the most important, as well as the cluster of positively charged amino acids involved in binding of C4b. The interaction between C4BP and PS is of very high affinity and conveyed by a cluster of surface exposed hydrophobic amino acids localized on CCP1 of the b-chain. Furthermore, C4BP is captured on the surface of several pathogens, which may contribute to their serum resistance and pathogenicity. We have localized interaction of C4BP with Neisseria gonorrhoeae, Bordetella pertussis, Streptococcus pyogenes and Escherichia coli to various regions of the a-chain.
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| 13. |
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| 14. |
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| 15. |
- Cenci Nilsson, Angela
(författare)
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Glutamatergic pathways as a target for the treatment of dyskinesias in Parkinson's disease.
- 2014
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Ingår i: Biochemical Society Transactions. - 0300-5127. ; 42:2, s. 600-604
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Tidskriftsartikel (refereegranskat)abstract
- PD (Parkinson's disease) is characterized by some typical motor features that are caused by striatal dopamine depletion and respond well to dopamine-replacement therapy with L-dopa. Unfortunately, the majority of PD patients treated with L-dopa develop abnormal involuntary movements (dyskinesias) within a few years. The mechanisms underlying the development of LIDs (L-dopa-induced dyskinesias) involve, on one hand, a presynaptic dysregulation of dopamine release and clearance and, on the other hand, an abnormal postsynaptic response to dopamine in the brain. There is a large amount of evidence that these dopamine-dependent mechanisms are modulated by glutamatergic pathways and glutamate receptors. The present article summarizes the pathophysiological role of glutamatergic pathways in LID and reviews pre-clinical and clinical results obtained using pharmacological modulators of different classes and subtypes of glutamate receptors to treat parkinsonian dyskinesias.
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| 16. |
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| 17. |
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| 18. |
- Daniel, Chammiran, et al.
(författare)
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RNA editing and its impact on GABAa receptor function
- 2009
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Ingår i: Biochemical Society Transactions. - : Biochemical Society. - 0300-5127 .- 1470-8752. ; 37, s. 1399-1403
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 19. |
- De Vinuesa, Amaya García, et al.
(författare)
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Targeting tumour vasculature by inhibiting activin receptor-like kinase (ALK)1 function
- 2016
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Ingår i: Biochemical Society Transactions. - 0300-5127. ; 44:4, s. 1142-1149
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis is a hallmark of cancer and is now a validated therapeutic target in the clinical setting. Despite the initial success, anti-angiogenic compounds impinging on the vascular endothelial growth factor (VEGF) pathway display limited survival benefits in patients and resistance often develops due to activation of alternative pathways. Thus, finding and validating new targets is highly warranted. Activin receptor-like kinase (ALK)1 is a transforming growth factor beta (TGF-β) type I receptor predominantly expressed in actively proliferating endothelial cells (ECs). ALK1 has been shown to play a pivotal role in regulating angiogenesis by binding to bone morphogenetic protein (BMP)9 and 10. Two main pharmacological inhibitors, an ALK1-Fc fusion protein (Dalantercept/ACE-041) and a fully human antibody against the extracellular domain of ALK1 (PF-03446962) are currently under clinical development. Herein, we briefly recapitulate the role of ALK1 in blood vessel formation and the current status of the preclinical and clinical studies on inhibition of ALK1 signalling as an anti-angiogenic strategy. Future directions in terms of new combination regimens will also be presented.
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| 20. |
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| 21. |
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| 22. |
- Dimberg, Anna
(författare)
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The glioblastoma vasculature as a target for cancer therapy
- 2014
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 42, s. 1647-1652
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 23. |
- Doherty, Gary J, et al.
(författare)
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GRAF1-dependent endocytosis
- 2009
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Ingår i: Biochemical Society Transactions. - London : Portland Press. - 0300-5127 .- 1470-8752. ; 37:5, s. 1061-1065
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 24. |
- Duarte, João M.N.
(författare)
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Loss of brain energy metabolism control as a driver for memory impairment upon insulin resistance
- 2023
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Ingår i: Biochemical Society Transactions. - 0300-5127. ; 51:1, s. 287-301
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Forskningsöversikt (refereegranskat)abstract
- The pathophysiological mechanisms intersecting metabolic and neurodegenerative disorders include insulin resistance, which has a strong involvement of environmental factors. Besides central regulation of whole-body homeostasis, insulin in the central nervous system controls molecular signalling that is critical for cognitive performance, namely signalling through pathways that modulate synaptic transmission and plasticity, and metabolism in neurons and astrocytes. This review provides an overview on how insulin signalling in the brain might regulate brain energy metabolism, and further identified molecular mechanisms by which brain insulin resistance might impair synaptic fuelling, and lead to cognitive deterioration.
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| 25. |
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| 26. |
- Fex, Malin, et al.
(författare)
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Lipases in the pancreatic beta-cell: implications for insulin secretion.
- 2008
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Ingår i: Biochemical Society Transactions. - 0300-5127. ; 36:Pt 5, s. 885-890
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Tidskriftsartikel (refereegranskat)abstract
- Lipids have been implicated in beta-cell stimulus-secretion coupling. In such a role, lipases in beta-cells would be required to generate lipid coupling factors. We have shown previously that glucose stimulates lipolysis in rodent islets. In addition, lipolysis and diacylglycerol lipase activity in islets are abolished by orlistat, an irreversible lipase inhibitor with a broad specificity for substrates. Moreover, orlistat dose-dependently inhibits glucose- and forskolin-stimulated insulin secretion, while leaving glucose oxidation and the rise in the ATP/ADP ratio intact. In an effort to identify beta-cell lipase(s), we found that HSL (hormone-sensitive lipase), the rate-limiting enzyme for acylglycerol hydrolysis in adipocytes, is expressed in rodent beta-cells. To resolve the role of this lipase, we have created global and beta-cell-specific knockout mice. Although our line of global HSL-knockout mice is moderately glucose-intolerant owing to reduced peripheral insulin sensitivity and exhibits normal islet metabolism and insulin secretion, other HSL-knockout lines have displayed impaired insulin secretion under certain conditions. In contrast, beta-cell-specific HSL-knockout mice, which are less prone to genetic redundancy, are hyperglycaemic, presumably caused by a perturbation of first-phase insulin secretion. Thus studies by us and others demonstrate that lipases, such as HSL, play a regulatory role in beta-cell stimulus-secretion coupling.
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| 27. |
- Figueiredo, Duarte, et al.
(författare)
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Signalling events regulating seed coat development
- 2014
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 42, s. 358-363
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of seeds was a major reason for the rise of angiosperms to ecological dominance. Seeds of angiosperms are composed of three main structures: the embryo, which will give rise to the next generation; the endosperm, a nurturing tissue whose main function is to deliver nutrients from the mother plant to the embryo; and the seed coat (or testa), a tissue that is derived from the maternal integuments and which provides support and protection to the growing embryo. All three seed components need to exchange signals to ensure co-ordinated growth and development. The present review discusses the structure of the seed coat, its interaction with the endosperm, and bidirectional signalling events between endosperm and seed coat that co-ordinate growth of both tissues. Angiosperm seeds are not only of evolutionary significance, but also of major agronomic importance, demanding a thorough understanding of the events governing seed growth and development.
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| 28. |
- Figueroa, Ricardo A., et al.
(författare)
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Microtubule-associated nuclear envelope proteins in interphase and mitosis
- 2011
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 39, s. 1786-1789
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 29. |
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| 30. |
- Fischer, Urs, et al.
(författare)
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Planar polarity of root hair positioning in Arabidopsis
- 2007
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 35:Pt 1, s. 149-151
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 31. |
- Forsberg, Jens, et al.
(författare)
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Redox signalling in chloroplasts and mitochondria: genomic and biochemical evidence for two-component regulatory systems in bioenergetic organelles
- 2001
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Ingår i: Biochemical Society Transactions. - 0300-5127. ; 29:4, s. 403-407
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Tidskriftsartikel (refereegranskat)abstract
- Redox chemistry is central to the primary functions of chloroplasts and mitochondria, that is, to energy conversion in photosynthesis and respiration. However, these bioenergetic organelles always contain very small, specialized genetic systems, relics of their bacterial origin. At huge cost, organellar genomes contain, typically, a mere 0.1% of the genetic information in a eukaryotic cell. There is evidence that chloroplast and mitochondrial genomes encode proteins whose function and biogenesis are particularly tightly governed by electron transfer. We have identified nuclear genes for 'bacterial' histidine sensor kinases and aspartate response regulators that seem to be targeted to chloroplast and mitochondrial membranes. Sequence similarities to cyanobacterial redox signalling components indicate homology and suggest conserved sensory and signalling functions. Two-component redox signalling pathways might be ancient, conserved mechanisms that permit endogenous control over the biogenesis, in situ, of bioenergetic complexes of chloroplasts and mitochondria.
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| 32. |
- Gekara, N O, et al.
(författare)
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Lipid rafts clustering and signalling by listeriolysin O.
- 2004
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 32:Pt 5, s. 712-714
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 33. |
- Ghafouri, Bijar, 1972-, et al.
(författare)
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PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid
- 2003
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 31:4, s. 810-814
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 34. |
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| 35. |
- Gutierrez-de-Teran, Hugo, et al.
(författare)
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Characterization of the dynamic events of GPCRs by automated computational simulations
- 2013
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 41, s. 205-212
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Tidskriftsartikel (refereegranskat)abstract
- 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).
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| 36. |
- Hasan, Kamrul, et al.
(författare)
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Electrochemical communication between microbial cells and electrodes via osmium redox systems.
- 2012
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Ingår i: Biochemical Society Transactions. - 0300-5127. ; 40:6, s. 1330-1335
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Tidskriftsartikel (refereegranskat)abstract
- Electrochemical communication between micro-organisms and electrodes is the integral and fundamental part of BESs (bioelectrochemical systems). The immobilization of bacterial cells on the electrode and ensuring efficient electron transfer to the electrode via a mediator are decisive features of mediated electrochemical biosensors. Notably, mediator-based systems are essential to extract electrons from the non-exoelectrogens, a major group of microbes in Nature. The advantage of using polymeric mediators over diffusible mediators led to the design of osmium redox polymers. Their successful use in enzyme-based biosensors and BFCs (biofuel cells) paved the way for exploring their use in microbial BESs. The present mini-review focuses on osmium-bound redox systems used to date in microbial BESs and their role in shuttling electrons from viable microbial cells to electrodes.
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| 37. |
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| 38. |
- Holm, Cecilia
(författare)
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Molecular mechanisms regulating hormone-sensitive lipase and lipolysis.
- 2003
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Ingår i: Biochemical Society Transactions. - 0300-5127. ; 31:Pt 6, s. 1120-1124
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Tidskriftsartikel (refereegranskat)abstract
- HSL (hormone-sensitive lipase) is a key enzyme in the mobilization of fatty acids from acylglycerols in adipocytes as well as non-adipocytes. In adipocytes, catecholamines stimulate lipolysis mainly through PKA (protein kinase A)-mediated phosphorylation of HSL and perilipin, a protein coating the lipid droplet. The anti-lipolytic action of insulin is mediated mainly via lowered cAMP levels, accomplished through activation of phosphodiesterase 3B. Phosphorylation of HSL by PKA occurs at three sites, the serines 563, 659 and 660, both in vitro and in primary rat adipocytes. Phosphorylation of Ser-659 and -660 is required for in vitro activation as well as translocation from the cytosol to the lipid droplet, whereas the role of the third PKA site remains elusive. Adipocytes isolated from homozygous HSL-null mice, generated in our laboratory, exhibit completely blunted catecholamine-induced glycerol release and reduced fatty acid release, suggesting the presence of additional, although not necessarily hormone-activatable, triacylglycerol lipase(s). Basal hyperinsulinaemia, release of exaggerated amounts of insulin during glucose challenges and retarded glucose disposal during insulin tolerance tests suggest that HSL-null mice are insulin resistant. Liver, adipose tissue and skeletal muscle appear all to be sites of impaired insulin sensitivity in HSL-null mice.
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| 39. |
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| 40. |
- Holmqvist, Erik, 1977-, et al.
(författare)
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Impact of bacterial sRNAs in stress responses
- 2017
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 45, s. 1203-1212
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Forskningsöversikt (refereegranskat)abstract
- 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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| 41. |
- Hubert, Madlen, et al.
(författare)
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Keeping in touch with the membrane; protein- and lipid-mediated confinement of caveolae to the cell surface
- 2020
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Ingår i: Biochemical Society Transactions. - : PORTLAND PRESS LTD. - 0300-5127 .- 1470-8752. ; 48, s. 155-163
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Forskningsöversikt (refereegranskat)abstract
- 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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| 42. |
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| 43. |
- Hunt, MC, et al.
(författare)
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Lipid regulation of gene expression
- 1999
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Ingår i: Biochemical Society transactions. - : Portland Press Ltd.. - 0300-5127 .- 1470-8752. ; 27:4, s. 378-382
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Tidskriftsartikel (refereegranskat)
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| 44. |
- Ishizaki, Takahiro, et al.
(författare)
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CRISPR/Cas9 and genetic screens in malaria parasites : small genomes, big impact
- 2022
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Ingår i: Biochemical Society Transactions. - : Portland Press. - 0300-5127 .- 1470-8752. ; 50:3, s. 1069-1079
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Forskningsöversikt (refereegranskat)abstract
- 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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| 45. |
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| 46. |
- Jin, Yi, et al.
(författare)
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VEGF, Notch and TGFβ/BMPs in regulation of sprouting angiogenesis and vascular patterning
- 2014
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 42:6, s. 1576-1583
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 47. |
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| 48. |
- Järver, Peter, et al.
(författare)
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Applications of cell-penetrating peptides in regulation of gene expression
- 2007
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 35:Pt 4, s. 770-774
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 49. |
- Karlsson, Hannah, 1979-
(författare)
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Approaches to augment CAR T-cell therapy by targeting the apoptotic machinery
- 2016
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 44:2, s. 371-376
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 50. |
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