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Droz, Jean-Marie y Emmanuel Wagner. "Grid diagrams and Khovanov homology". Algebraic & Geometric Topology 9, n.º 3 (1 de julio de 2009): 1275–97. http://dx.doi.org/10.2140/agt.2009.9.1275.
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Shin, Moon-Kyun, Hyun-Ah Lee, Jae-Jun Lee, Ki-Nam Song y Gyung-Jin Park. "ICONE15-10366 Optimization of a Nuclear Fuel Spacer Grid Spring Using Homology Constraints". Proceedings of the International Conference on Nuclear Engineering (ICONE) 2007.15 (2007): _ICONE1510. http://dx.doi.org/10.1299/jsmeicone.2007.15._icone1510_186.
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Cavallo, Alberto. "The concordance invariant tau in link grid homology". Algebraic & Geometric Topology 18, n.º 4 (26 de abril de 2018): 1917–51. http://dx.doi.org/10.2140/agt.2018.18.1917.
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Ramyachitra, D. y P. Pradeep Kumar. "Frog leap algorithm for homology modelling in grid environment". International Journal of Grid and Utility Computing 7, n.º 1 (2016): 29. http://dx.doi.org/10.1504/ijguc.2016.073775.
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Shin, M. K., H. A. Lee, J. J. Lee, K. N. Song y G. J. Park. "Optimization of a nuclear fuel spacer grid spring using homology constraints". Nuclear Engineering and Design 238, n.º 10 (octubre de 2008): 2624–34. http://dx.doi.org/10.1016/j.nucengdes.2008.04.003.
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Dey, Subhankar y Hakan Doğa. "A combinatorial description of the knot concordance invariant epsilon". Journal of Knot Theory and Its Ramifications 30, n.º 06 (mayo de 2021): 2150036. http://dx.doi.org/10.1142/s021821652150036x.
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In this paper, we give a combinatorial description of the concordance invariant [Formula: see text] defined by Hom, prove some properties of this invariant using grid homology techniques. We compute the value of [Formula: see text] for [Formula: see text] torus knots and prove that [Formula: see text] if [Formula: see text] is a grid diagram for a positive braid. Furthermore, we show how [Formula: see text] behaves under [Formula: see text]-cabling of negative torus knots.
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Wong, Michael. "Grid diagrams and Manolescu’s unoriented skein exact triangle for knot Floer homology". Algebraic & Geometric Topology 17, n.º 3 (17 de julio de 2017): 1283–321. http://dx.doi.org/10.2140/agt.2017.17.1283.
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Kaczynski, Tomasz, Marian Mrozek y Anik Trahan. "Ideas from Zariski Topology in the Study of Cubical Homology". Canadian Journal of Mathematics 59, n.º 5 (1 de octubre de 2007): 1008–28. http://dx.doi.org/10.4153/cjm-2007-043-3.
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AbstractCubical sets and their homology have been used in dynamical systems as well as in digital imaging. We take a fresh look at this topic, following Zariski ideas from algebraic geometry. The cubical topology is defined to be a topology in ℝd in which a set is closed if and only if it is cubical. This concept is a convenient frame for describing a variety of important features of cubical sets. Separation axioms which, in general, are not satisfied here, characterize exactly those pairs of points which we want to distinguish. The noetherian property guarantees the correctness of the algorithms. Moreover, maps between cubical sets which are continuous and closed with respect to the cubical topology are precisely those for whom the homology map can be defined and computed without grid subdivisions. A combinatorial version of the Vietoris–Begle theorem is derived. This theorem plays the central role in an algorithm computing homology of maps which are continuous with respect to the Euclidean topology.
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Naumann, Robert K., Patricia Preston-Ferrer, Michael Brecht y Andrea Burgalossi. "Structural modularity and grid activity in the medial entorhinal cortex". Journal of Neurophysiology 119, n.º 6 (1 de junio de 2018): 2129–44. http://dx.doi.org/10.1152/jn.00574.2017.
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Following the groundbreaking discovery of grid cells, the medial entorhinal cortex (MEC) has become the focus of intense anatomical, physiological, and computational investigations. Whether and how grid activity maps onto cell types and cortical architecture is still an open question. Fundamental similarities in microcircuits, function, and connectivity suggest a homology between rodent MEC and human posteromedial entorhinal cortex. Both are specialized for spatial processing and display similar cellular organization, consisting of layer 2 pyramidal/calbindin cell patches superimposed on scattered stellate neurons. Recent data indicate the existence of a further nonoverlapping modular system (zinc patches) within the superficial MEC layers. Zinc and calbindin patches have been shown to receive largely segregated inputs from the presubiculum and parasubiculum. Grid cells are also clustered in the MEC, and we discuss possible structure-function schemes on how grid activity could map onto cortical patch systems. We hypothesize that in the superficial layers of the MEC, anatomical location can be predictive of function; thus relating functional properties and neuronal morphologies to the cortical modules will be necessary for resolving how grid activity maps onto cortical architecture. Imaging or cell identification approaches in freely moving animals will be required for testing this hypothesis.
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Maršálek, Roman, Radim Zedka, Erich Zöchmann, Josef Vychodil, Radek Závorka, Golsa Ghiaasi y Jiří Blumenstein. "Persistent Homology Approach for Human Presence Detection from 60 GHz OTFS Transmissions". Sensors 23, n.º 4 (16 de febrero de 2023): 2224. http://dx.doi.org/10.3390/s23042224.
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Orthogonal Time Frequency Space (OTFS) is a new, promising modulation waveform candidate for the next-generation integrated sensing and communication (ISaC) systems, providing environment-awareness capabilities together with high-speed wireless data communications. This paper presents the original results of OTFS-based person monitoring measurements in the 60 GHz millimeter-wave frequency band under realistic conditions, without the assumption of an integer ratio between the actual delays and Doppler shifts of the reflected components and the corresponding resolution of the OTFS grid. As the main contribution of the paper, we propose the use of the persistent homology technique as a method for processing gathered delay-Doppler responses. We highlight the advantages of the persistent homology approach over the standard constant false alarm rate target detector for selected scenarios.
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Oduselu, Gbolahan O., Olayinka O. Ajani y Ezekiel F. Adebiyi. "Molecular docking studies of Amidoxime-containing heterocyclic compounds from Zinc database against homology modelled PfADSL". IOP Conference Series: Earth and Environmental Science 993, n.º 1 (1 de marzo de 2022): 012026. http://dx.doi.org/10.1088/1755-1315/993/1/012026.
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Abstract Malaria remains one of the most infectious life-threatening diseases in the world. The lingering effect of drug resistance by malarial parasites, especially Plasmodium falciparum, has made it essential for the continuous search for novel antimalarial drugs that can act on new protein targets and through new modes of action. Amidoxime functional groups have, in recent years, shown to be good incorporations in heterocyclic backbones due to their vast biological activities. Hence, the antimalarial activities of some amidoxime-containing heterocyclic compounds have been predicted using molecular docking studies to determine the binding affinities and the inhibition constants of the compounds. The amidoxime-containing compounds were downloaded from the ZINC database and docked, using Auto Dock vina, against the active sites of homology modelled Plasmodium falciparumadenylosuccinate lyase (PfADSL) as obtained from the SWISS-MoDeL. The grid box was constructed using 80, 80, and 80, pointing in x, y, and z directions, respectively, with a grid point spacing of 0.375 A. The post-docking analysis, which entails determining the hydrogen bond formed and the bond length between the compounds and the protein target, was carried out using AutoDockTools, LigPlot and PyMOLmolecular viewer. The docking studies showed that the compounds possess binding affinities ranging from -8.6 to- 5.7 kcal/mol, with ZINC2268942 having the lowest binding affinity. The presence of the amidoxime-functional group on the best hit contributed significantly to the hydrogen bonds formed between the compound and the binding sites of PfADSL,which were observed atThr 124D, Ser 125D, Thr 172C, His 173C, Gln 250D, and Ser 299A. The results obtained from the molecular docking studies will be helpful in the development of a potential antimalarial drug that can target PfADSL after careful experimental validation of the target, then in vitro and in vivo screening.
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Fowler, Philip W., Shantenu Jha y Peter V. Coveney. "Grid-based steered thermodynamic integration accelerates the calculation of binding free energies". Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 363, n.º 1833 (20 de julio de 2005): 1999–2015. http://dx.doi.org/10.1098/rsta.2005.1625.
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The calculation of binding free energies is important in many condensed matter problems. Although formally exact computational methods have the potential to complement, add to, and even compete with experimental approaches, they are difficult to use and extremely time consuming. We describe a Grid-based approach for the calculation of relative binding free energies, which we call Steered Thermodynamic Integration calculations using Molecular Dynamics (STIMD), and its application to Src homology 2 (SH2) protein cell signalling domains. We show that the time taken to compute free energy differences using thermodynamic integration can be significantly reduced: potentially from weeks or months to days of wall-clock time. To be able to perform such accelerated calculations requires the ability to both run concurrently and control in realtime several parallel simulations on a computational Grid. We describe how the RealityGrid computational steering system, in conjunction with a scalable classical MD code, can be used to dramatically reduce the time to achieve a result. This is necessary to improve the adoption of this technique and further allows more detailed investigations into the accuracy and precision of thermodynamic integration. Initial results for the Src SH2 system are presented and compared to a reported experimental value. Finally, we discuss the significance of our approach.
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Vigneshwaran, L. V. y K. G. Lalitha. "In silico evaluation of antidiabetic molecules of the seeds of Swietenia mahagoni Jacq". International Journal of Pharmaceutical and Phytopharmacological Research 6, n.º 1 (17 de abril de 2017): 41. http://dx.doi.org/10.24896/eijppr.2016617.
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Diabetes is a chronic metabolic disorder. WHO has projected that India will have around 57 million persons with diabetes by 2025. Swietenia mahagoni Jacq. (Meliaceae) is a large, deciduous tree whose seeds and bark were used for diabetes traditionally. The in silico hyperglycemic activity of the seeds of Swietenia mahagoni Jacq was studied by using AUTODOCK version 4.2 which reveals the putative binding sites of the compound to target protein. Homology modeling was done using MODELLER for the crystal structure of sodium/glucose co-transporter 2(SGLT2). The putative binding modes of compounds were identified using the search method of Lamarckian Genetic Algorithm (LGA).Atomic affinity and electrostatic potential grid maps were calculated using Auto Grid 4.2. From the fallout, we may scrutinize that for successful docking, intermolecular hydrogen bonding and lipophilic interactions between the ligand and the receptor are very essential. The results evolved with the least binding energy ensures that the Oleanolic showed good inhibitory activity and further work may help to develop the compound as an active therapeutic agent for the treatment of hyperglycemia. Keywords: Diabetes mellitus, Swietenia mahagoni Jacq, Docking, Oleanolic acid.
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Joosten, Robbie P., Jean Salzemann, Vincent Bloch, Heinz Stockinger, Ann-Charlott Berglund, Christophe Blanchet, Erik Bongcam-Rudloff et al. "PDB_REDO: automated re-refinement of X-ray structure models in the PDB". Journal of Applied Crystallography 42, n.º 3 (3 de abril de 2009): 376–84. http://dx.doi.org/10.1107/s0021889809008784.
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Structural biology, homology modelling and rational drug design require accurate three-dimensional macromolecular coordinates. However, the coordinates in the Protein Data Bank (PDB) have not all been obtained using the latest experimental and computational methods. In this study a method is presented for automated re-refinement of existing structure models in the PDB. A large-scale benchmark with 16 807 PDB entries showed that they can be improved in terms of fit to the deposited experimental X-ray data as well as in terms of geometric quality. The re-refinement protocol uses TLS models to describe concerted atom movement. The resulting structure models are made available through the PDB_REDO databank (http://www.cmbi.ru.nl/pdb_redo/). Grid computing techniques were used to overcome the computational requirements of this endeavour.
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Akhtar, Noreen y Ishrat Jabeen. "A 2D-QSAR and Grid-Independent Molecular Descriptor (GRIND) Analysis of Quinoline-Type Inhibitors of Akt2: Exploration of the Binding Mode in the Pleckstrin Homology (PH) Domain". PLOS ONE 11, n.º 12 (30 de diciembre de 2016): e0168806. http://dx.doi.org/10.1371/journal.pone.0168806.
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Zafar, Sadia y Ishrat Jabeen. "GRID-independent molecular descriptor analysis and molecular docking studies to mimic the binding hypothesis of γ-aminobutyric acid transporter 1 (GAT1) inhibitors". PeerJ 7 (31 de enero de 2019): e6283. http://dx.doi.org/10.7717/peerj.6283.
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BackgroundThe γ-aminobutyric acid (GABA) transporter GAT1 is involved in GABA transport across the biological membrane in and out of the synaptic cleft. The efficiency of this Na+coupled GABA transport is regulated by an electrochemical gradient, which is directed inward under normal conditions. However, in certain pathophysiological situations, including strong depolarization or an imbalance in ion homeostasis, the GABA influx into the cytoplasm is increased by re-uptake transport mechanism. This mechanism may lead to extra removal of extracellular GABA which results in numerous neurological disorders such as epilepsy. Thus, small molecule inhibitors of GABA re-uptake may enhance GABA activity at the synaptic clefts.MethodsIn the present study, various GRID-independent molecular descriptor (GRIND) models have been developed to shed light on the 3D structural features of human GAT1 (hGAT1) inhibitors using nipecotic acid and N-diarylalkenyl piperidine analogs. Further, a binding hypothesis has been developed for the selected GAT1 antagonists by molecular docking inside the binding cavity of hGAT1 homology model.ResultsOur results indicate that two hydrogen bond acceptors, one hydrogen bond donor and one hydrophobic region at certain distances from each other play an important role in achieving high inhibitory potency against hGAT1. Our docking results elucidate the importance of the COOH group in hGAT1 antagonists by considering substitution of the COOH group with an isoxazol ring in compound37, which subsequently leads to a three order of magnitude decrease in biological activity of37(IC50= 38 µM) as compared to compound1(IC50= 0.040 µM).DiscussionOur docking results are strengthened by the structure activity relationship of the data series as well as by GRIND models, thus providing a significant structural basis for understanding the binding of antagonists, which may be useful for guiding the design of hGAT1 inhibitors.
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Ridderström, Marianne, Ismael Zamora, Ola Fjellström y Tommy B. Andersson. "Analysis of Selective Regions in the Active Sites of Human Cytochromes P450, 2C8, 2C9, 2C18, and 2C19 Homology Models Using GRID/CPCA". Journal of Medicinal Chemistry 44, n.º 24 (noviembre de 2001): 4072–81. http://dx.doi.org/10.1021/jm0109107.
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Conti, Francesco, Davide Moroni y Maria Antonietta Pascali. "A Topological Machine Learning Pipeline for Classification". Mathematics 10, n.º 17 (27 de agosto de 2022): 3086. http://dx.doi.org/10.3390/math10173086.
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In this work, we develop a pipeline that associates Persistence Diagrams to digital data via the most appropriate filtration for the type of data considered. Using a grid search approach, this pipeline determines optimal representation methods and parameters. The development of such a topological pipeline for Machine Learning involves two crucial steps that strongly affect its performance: firstly, digital data must be represented as an algebraic object with a proper associated filtration in order to compute its topological summary, the Persistence Diagram. Secondly, the persistence diagram must be transformed with suitable representation methods in order to be introduced in a Machine Learning algorithm. We assess the performance of our pipeline, and in parallel, we compare the different representation methods on popular benchmark datasets. This work is a first step toward both an easy and ready-to-use pipeline for data classification using persistent homology and Machine Learning, and to understand the theoretical reasons why, given a dataset and a task to be performed, a pair (filtration, topological representation) is better than another.
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Dowling, L. M., W. G. Crewther y D. A. Parry. "Secondary structure of component 8c-1 of α-keratin. An analysis of the amino acid sequence". Biochemical Journal 236, n.º 3 (15 de junio de 1986): 705–12. http://dx.doi.org/10.1042/bj2360705.
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The amino acid sequence of component 8c-1 from alpha-keratin was analysed by using secondary-structure prediction techniques, homology search methods, fast Fourier-transform techniques to detect regularities in the linear disposition of amino acids, interaction counts to assess possible modes of chain aggregation and assessment of hydrophilicity distribution. The analyses show the following. The molecule has two lengths of coiled-coil structure, each about 20 nm long, one from residues 56-202 with a discontinuity from about residue 91 to residue 101, and the other from residues 219-366 with discontinuities from about residue 238 to residue 245 and at about residue 306. The acidic and basic residues in the coiled-coil segment between residues 102 and 202 show a 9,4-residue structural period in their linear disposition, whereas between residues 246 and 366 a period of 9.9 residues is observed in the positioning of ionic residues. Acidic and basic residues are out of phase by 180 degrees. Similar repeats occur in corresponding regions of other intermediate-filament proteins. The overall mean values for the repeats are 9.55 residues in the N-terminal region and 9.85 residues in the C-terminal region. The regions at each end of the protein chain (residues 1-55 and 367-412) are not alpha-helical and contain many potential beta-bends. The regions specified in have a significant degree of homology mainly due to a semi-regular disposition of proline and half-cystine residues on a three-residue grid; this is especially apparent in the C-terminal segment, in which short (Pro-Cys-Xaa)n regions occur. The coiled-coil segments of component 8c-1 bear a striking similarity to corresponding segments of other intermediate-filament proteins as regards sequence homology, structural periodicity of ionic residues and secondary/tertiary-structure predictions. The assessments of the probabilities that these homologies occurred by chance indicate that there are two populations of keratin filament proteins. The non-coiled-coil regions at each end of the chain are less hydrophilic than the coiled-coil regions. Ionic interactions between the heptad regions of components 8c-1 and 7c from the microfibrils of alpha-keratin are optimized when a coiled-coil structure is formed with the heptad regions of the constituent chains both parallel and in register.
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Autin, L., W. H. Lee, M. A. Miteva, K. Mertens, K. P. Radtke y B. O. Villoutreix. "Molecular Models of the Procoagulant Intrinsic Tenase Complex." Blood 104, n.º 11 (16 de noviembre de 2004): 1723. http://dx.doi.org/10.1182/blood.v104.11.1723.1723.
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Abstract Formation of the intrinsic tenase-complex, is an essential event in the procoagulant reactions that lead to clot formation. The tenase-complex is formed when the activated serine protease, factor IXa (FIXa), and its cofactor factor VIIIa (FVIIIa) assemble on the phospholipid surface of activated platelets in the presence of calcium ions to proteolytically convert the zymogen factor X (FX) into its active form FXa. The physiological relevance of the tenase complex is evident in hemophilia A or B patients, who present with bleeding disorders due to quantitative and/or qualitative deficiencies of FVIII or FIX. In this work we present preliminary models of the FVIIIa-FIXa-FX complex that were generated based on the published X-ray structures of FIXa (PNAS1995; 92:9796–800.), factor Va (PNAS2004; 101:8918–23.), factor Xa (PNAS1995; 95:6630–5.) and the FVIII homology model (Blood2002; 99:1215–23.). In a first step we developed new, refined, theoretical models of FVIIIa and FX zymogen via homology modeling, inter-domain docking/simulation and new loop simulation algorithms. This was followed by Pseudo-Brownian protein-protein docking in internal coordinates between FVIIIa and FIXa and between FIXa and FX with internal coordinate mechanics (Proteins2003; 52:113–7.). Flexibility of the molecules was partially accounted for by the use of a soft interaction energy function precalculated on a grid. Several models of the tenase-complex were selected based on structural criteria and agreement with known experimental data such as site directed mutagenesis, naturally occurring FVIII and FIX mutations reported in hemophilia, and overall location of the membrane plane with regard to the enzyme active site and peptide studies. These 3D models of the tenase-complex will be useful tools to guide future site directed mutagenesis and drug design studies aimed at improving functionality and half-life of FVIII and FIX and will contribute a better understanding of the role of the tenase-complex in the blood coagulation cascade.
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Lisi, Simonetta, Ilaria Mazzon y Kristin White. "Diverse Domains of THREAD/DIAP1 Are Required to Inhibit Apoptosis Induced by REAPER and HID in Drosophila". Genetics 154, n.º 2 (1 de febrero de 2000): 669–78. http://dx.doi.org/10.1093/genetics/154.2.669.
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Abstract Significant amounts of apoptosis take place during Drosophila development. The proapoptotic genes reaper (rpr), grim, and head involution defective (hid) are required for virtually all embryonic apoptosis. The proteins encoded by these genes share a short region of homology at their amino termini. The Drosophila IAP homolog THREAD/DIAP1 (TH/DIAP1), encoded by the thread (th) gene, negatively regulates apoptosis during development. It has been proposed that RPR, GRIM, and HID induce apoptosis by binding and inactivating TH/DIAP1. The region of homology between the three proapoptotic proteins has been proposed to bind to the conserved BIR2 domain of TH/DIAP1. Here, we present an analysis of loss-of-function and gain-of-function alleles of th, which indicates that additional domains of TH/DIAP1 are necessary for its ability to inhibit death induced by RPR, GRIM, and HID. In addition, that analysis of loss-of-function mutations demonstrates that th is necessary to block apoptosis very early in embryonic development. This may reflect a requirement to block maternally provided RPR and HID, or it may indicate another function of the TH/DIAP1 protein.
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Hu, Zhongbo, Xiaomiao Li, David Ostrov y William Slayton. "Screening Small Molecule Inhibitors of VLA-5 to Block the Interaction Between Acute Lymphoblastic Leukemia with Ph+ and Their Microenvironment." Blood 116, n.º 21 (19 de noviembre de 2010): 1027. http://dx.doi.org/10.1182/blood.v116.21.1027.1027.
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Abstract Abstract 1027 Integrin VLA-5 (α5β1, CD49e/CD29) plays an important role in hematopoietic cells functioning as well as in promoting tumor angiogenesis and tumor metastasis. Molecules targeting VLA-5 can be rapidly developed into anti-inflammatory and anti-tumor pharmaceuticals. VLA-5 is highly expressed on Ph+ leukemia cells and VLA-5 inhibitory antibodies can significantly inhibit the adhesion of Ph+ leukemia cells to human fibronectin. We generated an atomic homology model of VLA-5 based on the crystal structure of the extracellular segment of integrin αVβ3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence and utilized this structure-based approach to identify VLA-5 binding drug-like small molecules. We selected the Arg-Gly-Asp binding residues and the epitopes of VLA-5 antibody as the target for small molecule binding using SPHERE_SELECT in DOCK6. The grid-based scoring system was used for scoring with the non-bonded force field energy function. The 100 highest scoring small molecules were assayed in an in vitro adhesion assay using leukemia cell lines and solid phase assay. This approach identified several leading small-molecule compounds, V10, V20, V37 and L4. Their IC50 are respectively 22.5μM, 23.7μM, 32.0μM and 28.9μM. These compounds can inhibit the adhesion of VLA-5 expressing Philadelphia chromosome positive leukemia to both human fibronectin and bone marrow stromal cells. Compounds V10 and V20 also significantly inhibited the growth of Ph+ leukemia cells. These compounds can enhance the effect of imatinib and dasatinib to kill Ph+ leukemia cells when cultured contacting with bone marrow stromal cells. We are currently testing the synergistic effect of these compounds with tyrosine kinase inhibitors to treat the Ph+ acute lymphoblastic leukemia in NOD/SCID animal model. Disclosures: No relevant conflicts of interest to declare.
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Zimmermann, Katja C., Jean-Ehrland Ricci, Nathalie M. Droin y Douglas R. Green. "The role of ARK in stress-induced apoptosis in Drosophila cells". Journal of Cell Biology 156, n.º 6 (11 de marzo de 2002): 1077–87. http://dx.doi.org/10.1083/jcb.20112068.
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The molecular mechanisms of apoptosis are highly conserved throughout evolution. The homologs of genes essential for apoptosis in Caenorhabditis elegans and Drosophila melanogaster have been shown to be important for apoptosis in mammalian systems. Although a homologue for CED-4/apoptotic protease-activating factor (Apaf)-1 has been described in Drosophila, its exact function and the role of the mitochondrial pathway in its activation remain unclear. Here, we used the technique of RNA interference to dissect apoptotic signaling pathways in Drosophila cells. Inhibition of the Drosophila CED-4/Apaf-1–related killer (ARK) homologue resulted in pronounced inhibition of stress-induced apoptosis, whereas loss of ARK did not protect the cells from Reaper- or Grim-induced cell death. Reduction of DIAP1 induced rapid apoptosis in these cells, whereas the inhibition of DIAP2 expression did not but resulted in increased sensitivity to stress-induced apoptosis; apoptosis in both cases was prevented by inhibition of ARK expression. Cells in which cytochrome c expression was decreased underwent apoptosis induced by stress stimuli, Reaper or Grim. These results demonstrate the central role of ARK in stress-induced apoptosis, which appears to act independently of cytochrome c. Apoptosis induced by Reaper or Grim can proceed via a distinct pathway, independent of ARK.
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Jonsson, Jakob. "Certain Homology Cycles of the Independence Complex of Grids". Discrete & Computational Geometry 43, n.º 4 (3 de septiembre de 2009): 927–50. http://dx.doi.org/10.1007/s00454-009-9224-9.
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Lidjan, Edin y Ðordje Baralic. "Homology of polyomino tilings on flat surfaces". Applicable Analysis and Discrete Mathematics, n.º 00 (2021): 31. http://dx.doi.org/10.2298/aadm210307031l.
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The homology group of a tiling introduced by M. Reid is studied for certain topological tilings. As in the planar case, for finite square grids on topological surfaces, the method of homology groups, namely the non-triviality of some specific element in the group allows a ?coloring proof? of impossibility of a tiling. Several results about the non-existence of polyomino tilings on certain square-tiled surfaces are proved in the paper.
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Choe, Seungho y Sheela Ramanna. "Cubical Homology-Based Machine Learning: An Application in Image Classification". Axioms 11, n.º 3 (3 de marzo de 2022): 112. http://dx.doi.org/10.3390/axioms11030112.
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Persistent homology is a powerful tool in topological data analysis (TDA) to compute, study, and encode efficiently multi-scale topological features and is being increasingly used in digital image classification. The topological features represent a number of connected components, cycles, and voids that describe the shape of data. Persistent homology extracts the birth and death of these topological features through a filtration process. The lifespan of these features can be represented using persistent diagrams (topological signatures). Cubical homology is a more efficient method for extracting topological features from a 2D image and uses a collection of cubes to compute the homology, which fits the digital image structure of grids. In this research, we propose a cubical homology-based algorithm for extracting topological features from 2D images to generate their topological signatures. Additionally, we propose a novel score measure, which measures the significance of each of the sub-simplices in terms of persistence. In addition, gray-level co-occurrence matrix (GLCM) and contrast limited adapting histogram equalization (CLAHE) are used as supplementary methods for extracting features. Supervised machine learning models are trained on selected image datasets to study the efficacy of the extracted topological features. Among the eight tested models with six published image datasets of varying pixel sizes, classes, and distributions, our experiments demonstrate that cubical homology-based machine learning with the deep residual network (ResNet 1D) and Light Gradient Boosting Machine (lightGBM) shows promise with the extracted topological features.
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MEIK, JESSE M., A. MICHELLE LAWING y JESSICA A. WATSON. "Use of scalation landmarks in geometric morphometrics of squamate reptiles: a comment on homology". Zootaxa 4816, n.º 3 (17 de julio de 2020): 397–400. http://dx.doi.org/10.11646/zootaxa.4816.3.12.
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Geometric morphometrics (GM) is a powerful analytical approach for evaluating phenotypic variation relevant to taxonomy and systematics, and as with any statistical methodology, requires adherence to fundamental assumptions for inferences to be strictly valid. An important consideration for GM is how landmark configurations, which represent sets of anatomical loci for evaluating shape variation through Cartesian coordinates, relate to underlying homology (Zelditch et al. 1995; Polly 2008). Perhaps more so than with traditional morphometrics, anatomical homology is a crucial assumption for GM because of the mathematical and biological interpretations associated with shape change depicted by deformation grids, such as the thin plate spline (Klingenberg 2008; Zelditch et al. 2012). GM approaches are often used to analyze shapes or outlines of structures, which are not necessarily related to common ancestry, and in this respect GM approaches that use linear semi-landmarks and related methods are particularly amenable to evaluating primary homology, or raw similarity between structures (De Pinna 1991; Palci & Lee 2019). This relaxed interpretation of homology that focuses more on recognizable and repeatable landmarks is defensible so long as authors are clear regarding the purpose of the analyses and in defining their landmark configurations (Palci & Lee 2019). Secondary homology, or similarity due to common ancestry, can also be represented with GM methods and is often assumed to be reflected in fixed Type 1 (juxtaposition of tissues) or Type 2 (self-evident geometry) landmarks (Bookstein 1991).
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Friedrich, Markus. "Deep Conservation of Hid-Like RHG Gene Family Homologs in Winged Insects Revealed by “Taxon Hopping” BLAST". Insects 12, n.º 11 (21 de octubre de 2021): 957. http://dx.doi.org/10.3390/insects12110957.
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Together with sickle (skl), the Drosophila paralogs reaper (rpr), head involution defective (hid), and grim (RHG) control a critical switch in the induction of programmed cell death. RHG homologs have been identified in other dipteran and lepidopteran species but not beyond. Revisiting this issue with a “taxon hopping” BLAST search strategy in current genome and transcriptome resources, I detected high confidence RHG homologs in Coleoptera, Hymenoptera, Hemiptera, and Dictyoptera. Analyses of gene structure and protein sequence conservation revealed aconserved splicing pattern and highly conserved amino acid residues at both the N- and C-terminal ends that identify hid as the most ancestrally organized RHG gene family member in Drosophila. hid-like RHG homologs were also detected in mosquitoes, redefining their michelob_x (mx) genes as an expansion of derived RHG homologs. Only singleton homologs were detected in the large majority of other insect clades. Lepidopteran RHG homologs, however, stand out by producing an evolutionarily-derived splice isoform, identified in previous work, in addition to the newly detected hid-like isoform. Exceptional sequence diversification of select RHG homologs at the family- and genus-level explain their previous elusiveness in important insect genome model species like the red flour beetle Tribolium castaneum and the pea aphid Acyrthosiphon pisum. Combined, these findings expand the minimal age of the RHG gene family by about 100 million years and open new avenues for molecular cell death studies in insects.
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Abelleira, A., A. Picoaga, J. P. Mansilla y O. Aguin. "Detection of Bursaphelenchus Xylophilus, Causal Agent of Pine Wilt Disease on Pinus pinaster in Northwestern Spain". Plant Disease 95, n.º 6 (junio de 2011): 776. http://dx.doi.org/10.1094/pdis-12-10-0902.
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The pine wood nematode, Bursaphelenchus xylophilus (Steiner & Buhrer) Nickle, a quarantine organism, causes serious damage to pines worldwide. In Europe, it was first detected in Portugal in 1999 (3) and the pathogen was thought to be restricted to this area. However, in 2008, B. xylophilus was isolated from a single tree in the Cáceres Region (Extremadura) of Spain, bordering Portugal (2). The region of Galicia has approximately 383,632 ha of Pinus pinaster Aiton that constitutes more than 40% of the surface of Spain. Since 1999, we have analyzed 5,155 samples to monitor the presence of the pathogen. In 2008, a Spanish national contingency plan established three delimiting sampling areas, including a high risk area 20 km from the border with Portugal (2 × 2 km grid), a medium risk area 80 km wide (4 × 4), and another area covering the whole region (8 × 8). The plan required collecting samples from symptomatic trees. In 2010, in the high risk area, 307 sites were surveyed in coniferous forests. At each site, wood chip samples were collected from five pine trees. The collected wood chips were then incubated for 15 days in the lab and nematodes were extracted by Baermann's funnel method. B. xylophilus was detected from a decayed mass of P. pinaster from the As Neves Municipality (Pontevedra, Galicia). Affected specimens showed typical symptoms associated with pine wilt, including needle discoloration and death of branches. B. xylophilus was identified by morphological and molecular methods. Morphological characteristics included high lips, constricted heads, and short stylets with reduced basal knobs. Females had rounded tails, some with a short mucro, and flat vulva, while males had spicules curved with a cucullus. Measurements of these nematodes (10 females: body length = 720.99 ± 123.87 μm, a = 41.07 ± 5.83, b = 9.22 ± 3.44, c = 26.57 ± 4.13, V = 73.2, stylet length = 14.91 ± 1.65 μm; 10 males: body length = 576.4 ± 88.16 μm, a = 38.12 ± 5.36, b = 7.83 ± 0.39, c = 23.07 ± 2.59, stylet length = 14.63 ± 1.95 μm, spicules length = 22.5 ± 2.21 μm) were similar to the isolates found in Portugal described by Penas et al.(4) and smaller than described by Mota et al. (3). Molecular diagnosis was done following the protocols recommended by the EPPO (1): (i) Amplification of satellite DNA of B. xylophilus by PCR obtaining fragments of 160, 320, and 480 bp; (ii) PCR amplification of a region of 77 bp satellite DNA of B. xylophilus by Taqman Real Time; and (iii) PCR-restriction fragment length polymorphism of the internal transcribed spacer (ITS) region of Bursaphelenchus spp. nrDNA obtaining the restriction pattern for B. xylophilus. The ITS product amplified by PCR was also sequenced, showing a 99% homology with the sequences of B. xylophilus deposited in GenBank. A sequence of this nematode was submitted to GenBank database and assigned the number HQ646254. On the basis of these diagnostic characteristics, we have confirmed that B. xylophilus is now present in Galicia (northwestern Spain), which is one of the most productive and important region of Spain for forestry. References: (1) EPPO Bull. 39:344, 2009. (2) EPPO Rep. Serv. 3:2010/051, 2010. (3) M. M. Mota et al. Nematology 1:727, 1999. (4) A. C. Penas et al. J. Nematol. Morphol. Syst. 10:137, 2008.
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Ragno, Rino, Silvia Simeoni, Dante Rotili, Antonella Caroli, Giorgia Botta, Gerald Brosch, Silvio Massa y Antonello Mai. "Class II-selective histone deacetylase inhibitors. Part 2: Alignment-independent GRIND 3-D QSAR, homology and docking studies". European Journal of Medicinal Chemistry 43, n.º 3 (marzo de 2008): 621–32. http://dx.doi.org/10.1016/j.ejmech.2007.05.004.
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Li, Bian, Yucheng T. Yang, John A. Capra y Mark B. Gerstein. "Predicting changes in protein thermodynamic stability upon point mutation with deep 3D convolutional neural networks". PLOS Computational Biology 16, n.º 11 (30 de noviembre de 2020): e1008291. http://dx.doi.org/10.1371/journal.pcbi.1008291.
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Predicting mutation-induced changes in protein thermodynamic stability (ΔΔG) is of great interest in protein engineering, variant interpretation, and protein biophysics. We introduce ThermoNet, a deep, 3D-convolutional neural network (3D-CNN) designed for structure-based prediction of ΔΔGs upon point mutation. To leverage the image-processing power inherent in CNNs, we treat protein structures as if they were multi-channel 3D images. In particular, the inputs to ThermoNet are uniformly constructed as multi-channel voxel grids based on biophysical properties derived from raw atom coordinates. We train and evaluate ThermoNet with a curated data set that accounts for protein homology and is balanced with direct and reverse mutations; this provides a framework for addressing biases that have likely influenced many previous ΔΔG prediction methods. ThermoNet demonstrates performance comparable to the best available methods on the widely used Ssym test set. In addition, ThermoNet accurately predicts the effects of both stabilizing and destabilizing mutations, while most other methods exhibit a strong bias towards predicting destabilization. We further show that homology between Ssym and widely used training sets like S2648 and VariBench has likely led to overestimated performance in previous studies. Finally, we demonstrate the practical utility of ThermoNet in predicting the ΔΔGs for two clinically relevant proteins, p53 and myoglobin, and for pathogenic and benign missense variants from ClinVar. Overall, our results suggest that 3D-CNNs can model the complex, non-linear interactions perturbed by mutations, directly from biophysical properties of atoms.
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Sen, S. y A. Mangalam. "Flux tube model in the solar atmosphere". Proceedings of the International Astronomical Union 13, S340 (febrero de 2018): 55–56. http://dx.doi.org/10.1017/s1743921318001096.
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AbstractWe construct two classes of the magnetohydrostatic equilibria of the axisymmetric flux tubes with twisted magnetic fields in the stratified solar atmosphere that span from the photosphere to the transition region. We built the models by incorporating specific forms of the gas pressure and poloidal current in the Grad-Shafranov equation. This model gives both closed and open field structure of the flux tube. The other open field model we construct is based on the self-similar formulation, where we have incorporated specific forms of the gas pressure, poloidal current and two different shape functions. We study the homology of the parameter space that is consistent with the solar atmosphere and find that the estimation of the magnetic structure inside the flux tubes is consistent with the observation and simulation results of the magnetic bright points.
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Fan, Chengcheng y Douglas C. Rees. "Crystal structure of the Escherichia coli transcription termination factor Rho". Acta Crystallographica Section F Structural Biology Communications 76, n.º 9 (20 de agosto de 2020): 398–405. http://dx.doi.org/10.1107/s2053230x20010572.
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During the crystal structure analysis of an ATP-binding cassette (ABC) transporter overexpressed in Escherichia coli, a contaminant protein was crystallized. The identity of the contaminant was revealed by mass spectrometry to be the Escherichia coli transcription terminator factor Rho, structures of which had been previously determined in different conformational states. Although Rho was present at only ∼1% of the target protein (a bacterial homolog of the eukaryotic ABC transporter of mitochondria from Novosphingobium aromaticivorans; NaAtm1), it preferentially crystallized in space group C2 as thin plates that diffracted to 3.30 Å resolution. The structure of Rho in this crystal form exhibits a hexameric open-ring staircase conformation with bound ATP; this characteristic structure was also observed on electron-microscopy grids of the NaAtm1 preparation.
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Marangon, Mattia, Stéphane Jacobs y Scott H. Frey. "Evidence for context sensitivity of grasp representations in human parietal and premotor cortices". Journal of Neurophysiology 105, n.º 5 (mayo de 2011): 2536–46. http://dx.doi.org/10.1152/jn.00796.2010.
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Grasp-related responses in neurons of the macaque rostral inferior parietal lobule [PF/PFG and the anterior intraparietal area (AIP)] are modulated by task context. Event-related functional MRI was used to determine whether this is true in putative homologs of the human cortex, the rostral inferior parietal lobule (rIPL) and the anterior intraparietal sulcus (aIPS). Fifteen healthy, right-handed adults were required to select prospectively the most comfortable way to grasp a horizontally oriented handle using the cued hand (left or right). In the “no-rotation” condition, the task was simply to grasp the handle, whereas in the “rotation” condition, the goal was to plan to grasp and rotate it into a vertical orientation with the cued end (medial or lateral) pointing downward. In both conditions, participants remained still and indicated their grip preferences by pressing foot pedals. As in overt grasping, participants' grip preferences were significantly influenced by anticipation of the demands associated with handle rotation. Activity within the aIPS and rIPL increased bilaterally in both the rotation and no-rotation conditions. Importantly, these responses were significantly greater in the rotation vs. no-rotation condition. Similar context effects were detected in the presupplementary motor area, caudal intraparietal sulcus/superior parietal lobule, and bilateral dorsal and left ventral premotor cortices. Grasp representations within the rIPL and aIPS are sensitive to predicted task demands and play a role in context-sensitive grip selection. Moreover, the findings provide additional evidence that areas involved in the sensorimotor control of grasp also contribute to feedforward planning.
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Carapeti, Melina, Ricardo C. T. Aguiar, John M. Goldman y Nicholas C. P. Cross. "A Novel Fusion Between MOZ and the Nuclear Receptor Coactivator TIF2 in Acute Myeloid Leukemia". Blood 91, n.º 9 (1 de mayo de 1998): 3127–33. http://dx.doi.org/10.1182/blood.v91.9.3127.
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Abstract Chromosomal abnormalities of band 8p11 are associated with a distinct subtype of acute myeloid leukemia with French-American-British M4/5 morphology and prominent erythrophagocytosis by the blast cells. This subtype is usually associated with the t(8;16)(p11;p13), a translocation that has recently been shown to result in a fusion between the MOZ and CBP genes. We have cloned the inv(8)(p11q13), an abnormality associated with the same leukemia phenotype, and found a novel fusion between MOZ and the nuclear receptor transcriptional coactivatorTIF2/GRIP-1/NCoA-2. This gene has not previously been implicated in the pathogenesis of leukemia or other malignancies. MOZ-TIF2 retains the histone acetyltransferase homology domains of both proteins and also the CBP binding domain of TIF2. We speculate that the apparently identical leukemia cell phenotype observed in cases with the t(8;16) and the inv(8) arises by recruitment of CBP by MOZ-TIF2, resulting in modulation of the transcriptional activity of target genes by a mechanism involving abnormal histone acetylation.
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Carapeti, Melina, Ricardo C. T. Aguiar, John M. Goldman y Nicholas C. P. Cross. "A Novel Fusion Between MOZ and the Nuclear Receptor Coactivator TIF2 in Acute Myeloid Leukemia". Blood 91, n.º 9 (1 de mayo de 1998): 3127–33. http://dx.doi.org/10.1182/blood.v91.9.3127.3127_3127_3133.
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Chromosomal abnormalities of band 8p11 are associated with a distinct subtype of acute myeloid leukemia with French-American-British M4/5 morphology and prominent erythrophagocytosis by the blast cells. This subtype is usually associated with the t(8;16)(p11;p13), a translocation that has recently been shown to result in a fusion between the MOZ and CBP genes. We have cloned the inv(8)(p11q13), an abnormality associated with the same leukemia phenotype, and found a novel fusion between MOZ and the nuclear receptor transcriptional coactivatorTIF2/GRIP-1/NCoA-2. This gene has not previously been implicated in the pathogenesis of leukemia or other malignancies. MOZ-TIF2 retains the histone acetyltransferase homology domains of both proteins and also the CBP binding domain of TIF2. We speculate that the apparently identical leukemia cell phenotype observed in cases with the t(8;16) and the inv(8) arises by recruitment of CBP by MOZ-TIF2, resulting in modulation of the transcriptional activity of target genes by a mechanism involving abnormal histone acetylation.
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MACEDA MENDEZ, ADOLFO. "MATEMÁTICA DIFUSA Y COMPLEJOS CÚBICOS". Revista de Matemática: Teoría y Aplicaciones 24, n.º 2 (18 de julio de 2017): 201. http://dx.doi.org/10.15517/rmta.v24i2.29872.
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La matemática difusa generaliza los conceptos tradicionales de la matemática utilizando los llamados conjuntos difusos, lo que permite modelar y estudiar de manera más apropiada fenómenos caracterizados por su imprecisión. Estas generalizaciones incluyen conceptos de álgebra, análisis y topología, entre otros. Por otra parte, los complejos cúbicos tienen aplicaciones al procesamiento de imágenes digitales y al estudio de los sistemas dinámicos, pero en la literatura actual no hay una extensión de sus propiedades utilizando conjuntos difusos. En este documento se propone una generalización del concepto de complejo cúbico y de algunas de sus características, tales como realización poliédrica, conexidad, componente conexa y agujero, utilizando conjuntos difusos. Se definen los árboles superior e inferior de un complejo cúbico difuso, los cuales proporcionan información sobre la manera en la que están relacionados sus extremos regionales. También se definen los grupos de homología de estos complejos cúbicos difusos y se demuestra que el rango del 0-grupo de homología de un nivel dado es igual al número de máximos regionales de dicho nivel. Por último, se muestra cómo se le puede asociar un complejo cúbico difuso a una imagen digital bidimensional en tonos de gris para estudiar algunas de sus propiedades topológicas.
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Colussi, Paul A., Leonie M. Quinn, David C. S. Huang, Michelle Coombe, Stuart H. Read, Helena Richardson y Sharad Kumar. "Debcl, a Proapoptotic Bcl-2 Homologue, Is a Component of the Drosophila melanogaster Cell Death Machinery". Journal of Cell Biology 148, n.º 4 (21 de febrero de 2000): 703–14. http://dx.doi.org/10.1083/jcb.148.4.703.
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Bcl-2 family of proteins are key regulators of apoptosis. Both proapoptotic and antiapoptotic members of this family are found in mammalian cells, but no such proteins have been described in insects. Here, we report the identification and characterization of Debcl, the first Bcl-2 homologue in Drosophila melanogaster. Structurally, Debcl is similar to Bax-like proapoptotic Bcl-2 family members. Ectopic expression of Debcl in cultured cells and in transgenic flies causes apoptosis, which is inhibited by coexpression of the baculovirus caspase inhibitor P35, indicating that Debcl is a proapoptotic protein that functions in a caspase-dependent manner. debcl expression correlates with developmental cell death in specific Drosophila tissues. We also show that debcl genetically interacts with diap1 and dark, and that debcl-mediated apoptosis is not affected by gene dosage of rpr, hid, and grim. Biochemically, Debcl can interact with several mammalian and viral prosurvival Bcl-2 family members, but not with the proapoptotic members, suggesting that it may regulate apoptosis by antagonizing prosurvival Bcl-2 proteins. RNA interference studies indicate that Debcl is required for developmental apoptosis in Drosophila embryos. These results suggest that the main components of the mammalian apoptosis machinery are conserved in insects.
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Husain, Kazim, Krystal Villalobos-Ayala, Valentina Laverde, Oscar A. Vazquez, Bradley Miller, Samra Kazim, George Blanck et al. "Apigenin Targets MicroRNA-155, Enhances SHIP-1 Expression, and Augments Anti-Tumor Responses in Pancreatic Cancer". Cancers 14, n.º 15 (25 de julio de 2022): 3613. http://dx.doi.org/10.3390/cancers14153613.
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Pancreatic cancer (PC) is a deadly disease with a grim prognosis. Pancreatic tumor derived factors (TDF) contribute to the induction of an immunosuppressive tumor microenvironment (TME) that impedes the effectiveness of immunotherapy. PC-induced microRNA-155 (miRNA-155) represses expression of Src homology 2 (SH2) domain-containing Inositol 5′-phosphatase-1 (SHIP-1), a regulator of myeloid cell development and function, thus impacting anti-tumor immunity. We recently reported that the bioflavonoid apigenin (API) increased SHIP-1 expression which correlated with the expansion of tumoricidal macrophages (TAM) and improved anti-tumor immune responses in the TME of mice with PC. We now show that API transcriptionally regulates SHIP-1 expression via the suppression of miRNA-155, impacting anti-tumor immune responses in the bone marrow (BM) and TME of mice with PC. We discovered that API reduced miRNA-155 in the PC milieu, which induced SHIP-1 expression. This promoted the restoration of myelopoiesis and increased anti-tumor immune responses in the TME of heterotopic, orthotopic and transgenic SHIP-1 knockout preclinical mouse models of PC. Our results suggest that manipulating SHIP-1 through miR-155 may assist in augmenting anti-tumor immune responses and aid in the therapeutic intervention of PC.
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Jaiswal, Amit. "AtTRB1–3 Mediates Structural Changes in AtPOT1b to Hold ssDNA". ISRN Structural Biology 2014 (16 de febrero de 2014): 1–16. http://dx.doi.org/10.1155/2014/827201.
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POT from Arabidopsis thaliana is a member of shelterin complex and belongs to Telo_bind protein family. Three homologs are reported, namely, AtPOT1a, AtPOT1b, and AtPOT1c, where AtPOT1b is involved in genomic stability and chromosome end protection by providing necessary grip to G-rich region of telomeric DNA for telomerase assembly. Telomeric binding factors (TRB1–3) physically interact with POT with no known functionality. In this work attempt has been made to elucidate the reason behind the interaction by analyzing molecular docking interaction between AtPOT1b and AtTRB1–3, which yielded potential residues, which could play essential role in structural modification. 3 ns molecular simulation helped to look into structural stability and conformational dynamics portraying domain movements. AtTRB’s interaction with AtPOT1b provoked structural changes in AtPOT1b, thereby increasing the affinity for single strand DNA (ssDNA) as compared to double strand DNA (dsDNA). Although the obtained results require experimental evidence they can act as a guide in tracing the functions in other organisms. The information provided in this paper would be helpful in understanding functions of TRB1–3 with respect to genomic stability.
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Feng, Ying, Yan Zhang, Zhiqing Lin, Xiaolei Ye, Xue Lin, Lixiu Lv, Yi Lin, Shenfei Sun, Yun Qi y Xinhua Lin. "Chromatin remodeler Dmp18 regulates apoptosis by controlling H2Av incorporation in Drosophila imaginal disc development". PLOS Genetics 18, n.º 9 (27 de septiembre de 2022): e1010395. http://dx.doi.org/10.1371/journal.pgen.1010395.
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Programmed Cell Death (PCD) or apoptosis is a highly conserved biological process and plays essential roles both in the development and stress context. In Drosophila, expression of pro-apoptotic genes, including reaper (rpr), head involution defective (hid), grim, and sickle (skl), is sufficient to induce cell death. Here, we demonstrate that the chromatin remodeler Dmp18, the homolog of mammalian Znhit1, plays a crucial role in regulating apoptosis in eye and wing development. We showed that loss of Dmp18 disrupted eye and wing development, up-regulated transcription of pro-apoptotic genes, and induced apoptosis. Inhibition of apoptosis suppressed the eye defects caused by Dmp18 deletion. Furthermore, loss of Dmp18 disrupted H2Av incorporation into chromatin, promoted H3K4me3, but reduced H3K27me3 modifications on the TSS regions of pro-apoptotic genes. These results indicate that Dmp18 negatively regulates apoptosis by mediating H2Av incorporation and histone H3 modifications at pro-apoptotic gene loci for transcriptional regulation. Our study uncovers the role of Dmp18 in regulating apoptosis in Drosophila eye and wing development and provides insights into chromatin remodeling regulating apoptosis at the epigenetic levels.
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Wang, Na, Xianli Wang, Changgeng Yang, Xiaojie Zhao, Yuxi Zhang, Tianzi Wang y Songlin Chen. "Molecular cloning and multifunctional characterization of GRIM-19 (gene associated with retinoid-interferon-induced mortality 19) homologue from turbot (Scophthalmus maximus)". Developmental & Comparative Immunology 43, n.º 1 (marzo de 2014): 96–105. http://dx.doi.org/10.1016/j.dci.2013.11.004.
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Horvath, Martin P., Evan W. George, Quang T. Tran, Kody Baumgardner, Gabe Zharov, Sarah Lee, Hassan Sharifzadeh et al. "Structure of the lutein-binding domain of human StARD3 at 1.74 Å resolution and model of a complex with lutein". Acta Crystallographica Section F Structural Biology Communications 72, n.º 8 (27 de julio de 2016): 609–18. http://dx.doi.org/10.1107/s2053230x16010694.
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A crystal structure of the lutein-binding domain of human StARD3 (StAR-related lipid-transfer protein 3; also known as MLN64) has been refined to 1.74 Å resolution. A previous structure of the same protein determined to 2.2 Å resolution highlighted homology with StARD1 and shared cholesterol-binding character. StARD3 has since been recognized as a carotenoid-binding protein in the primate retina, where its biochemical function of binding lutein with specificity appears to be well suited to recruit this photoprotective molecule. The current and previous structures correspond closely to each other (r.m.s.d. of 0.25 Å), especially in terms of the helix-grip fold constructed around a solvent-filled cavity. Regions of interest were defined with alternate conformations in the current higher-resolution structure, including Arg351 found within the cavity and Ω1, a loop of four residues found just outside the cavity entrance. Models of the complex with lutein generated by rigid-body docking indicate that one of the ionone rings must protrude outside the cavity, and this insight has implications for molecular interactions with transport proteins and enzymes that act on lutein. Interestingly, models with the ∊-ionone ring characteristic of lutein pointing towards the bottom of the cavity were associated with fewer steric clashes, suggesting that steric complementarity and ligand asymmetry may play a role in discriminating lutein from the other ocular carotenoids zeaxanthin andmeso-zeaxanthin, which only have β-ionone rings.
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Chibunichev, A. G., A. P. Makarov y E. V. Poliakova. "USING AN LOW-COST STEREO CAMERA FOR AUTONOMOUS NAVIGATION OF MOBILE ROBOT". ISPRS - International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences XLIII-B1-2020 (6 de agosto de 2020): 423–27. http://dx.doi.org/10.5194/isprs-archives-xliii-b1-2020-423-2020.
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Abstract. The paper considers the possibility of using low-cost stereo cameras for autonomous robot navigation. An low-cost stereo camera with a focal length of 5 mm and a photo base of 6 cm was chosen for the research. Experimental studies have shown that the accuracy of determining the coordinates of object points from a pair of images obtained by such a stereo camera is sufficient for organizing autonomous navigation of the robot. In order to improve the reliability and accuracy of determining the trajectory of the robot, this paper proposes to use two stereo cameras. One is directed forward by the robot's movement, and the other is directed at the nadir. Thus, the trajectory is determined twice, independently of each other. Moreover, each case has its own algorithm for finding the homologue points. In the first case, a sparse point cloud is constructed for each stereo pair based on the selection of interesting points and their identification based on the comparison of descriptors. In addition, blunder detection of points identification are realized based on the analysis of the values of the relative orientation equations using the fundamental matrix. In the second case, when the stereo camera is pointed at the nadir, the usual method of correlation is used in the nodes of the grid specified at one image. Experimental studies have shown sufficient efficiency of autonomous navigation of mobile robot based on the use of two stereo cameras.
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Tong, Junsen, Mohammad Kawsar Manik y Young Jun Im. "Structural basis of sterol recognition and nonvesicular transport by lipid transfer proteins anchored at membrane contact sites". Proceedings of the National Academy of Sciences 115, n.º 5 (16 de enero de 2018): E856—E865. http://dx.doi.org/10.1073/pnas.1719709115.
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Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs. Here, we determined the crystal structures of the yeast Lam6 pleckstrin homology (PH)-like domain and the SDs of Lam2 and Lam4 in the apo form and in complex with ergosterol. The Lam6 PH-like domain displays a unique PH domain fold with a conserved N-terminal α-helix. The Lam6 PH-like domain lacks the basic surface for phosphoinositide binding, but contains hydrophobic patches on its surface, which are critical for targeting to endoplasmic reticulum (ER)–mitochondrial contacts. Structures of the LAM SDs display a helix-grip fold with a hydrophobic cavity and a flexible Ω1-loop as a lid. Ergosterol is bound to the pocket in a head-down orientation, with its hydrophobic acyl group located in the tunnel entrance. The Ω1-loop in an open conformation is essential for ergosterol binding by direct hydrophobic interaction. Structural comparison suggested that the sterol binding mode of the Lam2 SD2 is likely conserved among the sterol transfer proteins of the StARkin superfamily. Structural models of full-length Lam2 correlated with the sterol transport function at the membrane contact sites.
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Borges, Rafael Junqueira, Kathrin Meindl, Josep Triviño, Massimo Sammito, Ana Medina, Claudia Millán, Martin Alcorlo, Juan A. Hermoso, Marcos Roberto de Mattos Fontes y Isabel Usón. "SEQUENCE SLIDER: expanding polyalanine fragments for phasing with multiple side-chain hypotheses". Acta Crystallographica Section D Structural Biology 76, n.º 3 (25 de febrero de 2020): 221–37. http://dx.doi.org/10.1107/s2059798320000339.
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Fragment-based molecular-replacement methods can solve a macromolecular structure quasi-ab initio. ARCIMBOLDO, using a common secondary-structure or tertiary-structure template or a library of folds, locates these with Phaser and reveals the rest of the structure by density modification and autotracing in SHELXE. The latter stage is challenging when dealing with diffraction data at lower resolution, low solvent content, high β-sheet composition or situations in which the initial fragments represent a low fraction of the total scattering or where their accuracy is low. SEQUENCE SLIDER aims to overcome these complications by extending the initial polyalanine fragment with side chains in a multisolution framework. Its use is illustrated on test cases and previously unknown structures. The selection and order of fragments to be extended follows the decrease in log-likelihood gain (LLG) calculated with Phaser upon the omission of each single fragment. When the starting substructure is derived from a remote homolog, sequence assignment to fragments is restricted by the original alignment. Otherwise, the secondary-structure prediction is matched to that found in fragments and traces. Sequence hypotheses are trialled in a brute-force approach through side-chain building and refinement. Scoring the refined models through their LLG in Phaser may allow discrimination of the correct sequence or filter the best partial structures for further density modification and autotracing. The default limits for the number of models to pursue are hardware dependent. In its most economic implementation, suitable for a single laptop, the main-chain trace is extended as polyserine rather than trialling models with different sequence assignments, which requires a grid or multicore machine. SEQUENCE SLIDER has been instrumental in solving two novel structures: that of MltC from 2.7 Å resolution data and that of a pneumococcal lipoprotein with 638 residues and 35% solvent content.
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Wang, Kai, Nan Lyu, Hongjuan Diao, Shujuan Jin, Tao Zeng, Yaoqi Zhou y Ruibo Wu. "GM-DockZn: a geometry matching-based docking algorithm for zinc proteins". Bioinformatics 36, n.º 13 (5 de mayo de 2020): 4004–11. http://dx.doi.org/10.1093/bioinformatics/btaa292.
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Abstract Motivation Molecular docking is a widely used technique for large-scale virtual screening of the interactions between small-molecule ligands and their target proteins. However, docking methods often perform poorly for metalloproteins due to additional complexity from the three-way interactions among amino-acid residues, metal ions and ligands. This is a significant problem because zinc proteins alone comprise about 10% of all available protein structures in the protein databank. Here, we developed GM-DockZn that is dedicated for ligand docking to zinc proteins. Unlike the existing docking methods developed specifically for zinc proteins, GM-DockZn samples ligand conformations directly using a geometric grid around the ideal zinc-coordination positions of seven discovered coordination motifs, which were found from the survey of known zinc proteins complexed with a single ligand. Results GM-DockZn has the best performance in sampling near-native poses with correct coordination atoms and numbers within the top 50 and top 10 predictions when compared to several state-of-the-art techniques. This is true not only for a non-redundant dataset of zinc proteins but also for a homolog set of different ligand and zinc-coordination systems for the same zinc proteins. Similar superior performance of GM-DockZn for near-native-pose sampling was also observed for docking to apo-structures and cross-docking between different ligand complex structures of the same protein. The highest success rate for sampling nearest near-native poses within top 5 and top 1 was achieved by combining GM-DockZn for conformational sampling with GOLD for ranking. The proposed geometry-based sampling technique will be useful for ligand docking to other metalloproteins. Availability and implementation GM-DockZn is freely available at www.qmclab.com/ for academic users. Supplementary information Supplementary data are available at Bioinformatics online.
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Jacobs, Stéphane, Claudia Danielmeier y Scott H. Frey. "Human Anterior Intraparietal and Ventral Premotor Cortices Support Representations of Grasping with the Hand or a Novel Tool". Journal of Cognitive Neuroscience 22, n.º 11 (noviembre de 2010): 2594–608. http://dx.doi.org/10.1162/jocn.2009.21372.
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Humans display a remarkable capacity to use tools instead of their biological effectors. Yet, little is known about the mechanisms that support these behaviors. Here, participants learned to grasp objects, appearing in a variety of orientations, with a novel, handheld mechanical tool. Following training, psychophysical functions relating grip preferences (i.e., pronated vs. supinated) to stimulus orientations indicate a reliance on distinct, effector-specific internal representations when planning grasping actions on the basis of the tool versus the hands. Accompanying fMRI data show that grip planning in both hand and tool conditions was associated with similar increases in activity within the same regions of the anterior intraparietal and caudal ventral premotor cortices, a putative homologue of the macaque anterior intraparietal–ventral premotor (area F5) “grasp circuit.” These findings suggest that tool use is supported by effector-specific representations of grasping with the tool that are functionally independent of previously existing representations of the hand and yet occur within the same parieto-frontal regions involved in manual prehension. These levels of representation are critical for accurate planning and execution of actions in a manner that is sensitive to the respective properties of these effectors. These effector-specific representations likely coexist with effector-independent representations. The latter were recently reported in macaque F5 [Umiltà, M. A., Escola, L., Intskirveli, I., Grammont, F., Rochat, M., Caruana, F., et al. When pliers become fingers in the monkey motor system. Proceedings of the National Academy of Sciences, U.S.A., 105, 2209–2213, 2008] and appear to be established by tool use training through modification of existing representations of grasping with the hand. These more abstract levels of representation may facilitate the transfer of skills between hand and tool.
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Liu, Wenli, Yueqin Liu, Ruihong Wang, Cuiling Li, Chuxia Deng y Griffin P. Rodgers. "Olfactomedin 4 Is Essential for Superoxide Production and Sensitizes Oxidative Stress-Induced Apoptosis in Neutrophils." Blood 114, n.º 22 (20 de noviembre de 2009): 1356. http://dx.doi.org/10.1182/blood.v114.22.1356.1356.
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Abstract Abstract 1356 Poster Board I-378 Introduction Olfactomedin 4 (OLFM4), also called hGC-1, GW112 and pDP4, was first identified and specifically expressed in hematopoietic myeloid cells. OLFM4 expression in myeloid cells is regulated by transcription factors, PU1 and NF-κB. It has significant homology in its C-terminal domain with other olfactomedin-related proteins. OLFM4 encodes a 510 amino acid N-linked glycoprotein. The exact biological function of OLFM4, especially in neutrophils, is currently undefined. To characterize the in vivo function of OLFM4, we generated OLFM4 deficient mice (OLFM4-/-) and investigated its potential role in neutrophil functioins. Results 1) In this study, we showed that OLFM4 is a secreted glycoprotein and is also localized in the mitochondria, cytoplasm and cell membrane fractions of neutrophils. We demonstrated that OLFM4 interacts with GRIM-19 (Genes associated with Retinoid-IFN-induced Mortality-19), an apoptosis related protein, in the neutrophil mitochondria using co-immuoprecipitation assay. GRIM-19 is a subunit of complex I of mitochondrial respiratory chain and is essential for maintenance of mitochondrial membrane potential. Our result suggests that OLFM4 appears to be a novel component of complex I of mitochondrial respiratory chain and may be involved in regulation of mitochondrial membrane potential. 2) Mice heterozygous (OLFM4+/-) and homozygous (OLFM4-/-) for the null mutation in OLFM4 appeared to have normal development, fertility, and viability relative to wild-type (WT) mice. Whole blood analysis, differential leukocyte counts, blood chemistry and bone marrow smears were normal in OLFM4-/- mice, suggesting that OLFM4 is not essential for normal development and hematopoiesis in mice. 3) In response to LPS, fMLP and E.coli bacteria challenge, neutrophils from OLFM4-/- mice showed significantly reduced superoxide (O2−) and hydrogen peroxide (H2O2) production compared with WT mice. These results suggest that OLFM4 is an essential component to mediate O2− and H2O2 production in the neutrophil mitochondria under inflammation stimuli. 4) Exogenous H2O2 induced neutrophil apoptosis in a time and dose dependent manner in WT mice, but this induction of apoptosis was significantly reduced in OLFM4-/- mice. This result suggests that OLFM4 sensitizes and mediates H2O2-induced apoptosis in neutrophils. 5) Furthermore, we demonstrated that H2O2-stimulated mitochondrial membrane permeability reduction and caspase-3 and caspase-9 activation were inhibited in the neutrophils of OLFM4-/- mice. This result confirmed our hypothesis that OLFM4 may be involved in maintenance of mitochondrial membrane potential and suggests that OLFM4 may have opposite role as GRIM-19. 6) Moreover, Bax association with mitochondria and the cytoplasmic translocation of Omi/HtrA2 and Smac/DIABLO in response to H2O2 were inhibited in the neutrophils of OLFM4-/- mice. Conclusion Our results suggest: 1) OLFM4 has multiple subcellular localizations including mitochondria, cytoplasm, and cell membrane in neutrophils. The interaction of OLFM4 with GRIM-19 in the mitochondria suggests that OLFM4 is novel component of complex I of mitochondrial respiratory chain in the mitochondria of neutrophils, 2) OLFM4 is a novel mitochondrial molecule that is essential for O2− and H2O2 production in the neutrophils in the presence of inflammation stimuli, 3) Loss of OLFM4 in neutrophils does not trigger spontaneous apoptosis. However, OLFM4 sensitizes oxidative stress-induced apoptosis in mouse neutrophils. OLFM4 is involved in the regulation of mitochondria membrane potential and sensitizes cytoplasmic translocation of Omi/HtrA2 and Smac/DIABLO and caspases-3 and caspase-9 mediated apoptosis in the presence of oxidative stress. Disclosures No relevant conflicts of interest to declare.
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Gibbs, Elizabeth M., Jackie L. McCourt, Kara M. Shin, Katherine G. Hammond, Jamie L. Marshall y Rachelle H. Crosbie. "Loss of sarcospan exacerbates pathology in mdx mice, but does not affect utrophin amelioration of disease". Human Molecular Genetics 30, n.º 3-4 (11 de enero de 2021): 149–59. http://dx.doi.org/10.1093/hmg/ddaa264.
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Abstract The dystrophin–glycoprotein complex (DGC) is a membrane adhesion complex that provides structural stability at the sarcolemma by linking the myocyte’s internal cytoskeleton and external extracellular matrix. In Duchenne muscular dystrophy (DMD), the absence of dystrophin leads to the loss of the DGC at the sarcolemma, resulting in sarcolemmal instability and progressive muscle damage. Utrophin (UTRN), an autosomal homolog of dystrophin, is upregulated in dystrophic muscle and partially compensates for the loss of dystrophin in muscle from patients with DMD. Here, we examine the interaction between Utr and sarcospan (SSPN), a small transmembrane protein that is a core component of both UTRN–glycoprotein complex (UGC) and DGC. We show that additional loss of SSPN causes an earlier onset of disease in dystrophin-deficient mdx mice by reducing the expression of the UGC at the sarcolemma. In order to further evaluate the role of SSPN in maintaining therapeutic levels of Utr at the sarcolemma, we tested the effect of Utr transgenic overexpression in mdx mice lacking SSPN (mdx:SSPN −/−:Utr-Tg). We found that overexpression of Utr restored SSPN to the sarcolemma in mdx muscle but that the ablation of SSPN in mdx muscle reduced Utr at the membrane. Nevertheless, Utr overexpression reduced central nucleation and improved grip strength in both lines. These findings demonstrate that high levels of Utr transgenic overexpression ameliorate the mdx phenotype independently of SSPN expression but that loss of SSPN may impair Utr-based mechanisms that rely on lower levels of Utr protein.