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https://www.readbyqxmd.com/read/28350804/syndecan-1-deficiency-promotes-tumor-growth-in-a-murine-model-of-colitis-induced-colon-carcinoma
#1
Adi Binder Gallimidi, Gabriel Nussbaum, Esther Hermano, Barak Weizman, Amichay Meirovitz, Israel Vlodavsky, Martin Götte, Michael Elkin
Syndecan-1 (Sdc1) is an important member of the cell surface heparan sulfate proteoglycan family, highly expressed by epithelial cells in adult organisms. Sdc1 is involved in the regulation of cell migration, cell-cell and cell-matrix interactions, growth-factor, chemokine and integrin activity, and implicated in inflammatory responses and tumorigenesis. Gastrointestinal tract represents an important anatomic site where loss of Sdc1 expression was reported both in inflammation and malignancy. However, the biological significance of Sdc1 in chronic colitis-associated tumorigenesis has not been elucidated...
2017: PloS One
https://www.readbyqxmd.com/read/28350625/outcome-and-histopathology-of-secondary-penetrating-keratoplasty-graft-failure-managed-by-descemet-membrane-endothelial-keratoplasty
#2
Itay Lavy, Vasilios S Liarakos, Robert M Verdijk, Jack Parker, Thomas M Müller, Marieke Bruinsma, Perry S Binder, Gerrit R J Melles
PURPOSE: To describe the clinical outcome and histopathology of Descemet membrane endothelial keratoplasty (DMEK) performed for secondary graft failure after penetrating keratoplasty (PK). METHODS: A total of 11 eyes from 10 patients who underwent DMEK for secondary PK graft failure at a tertiary referral center were included in this retrospective study. Best-corrected visual acuity, endothelial cell density, and central pachymetry were evaluated before and at regular time intervals up to 36 months after DMEK and complications were recorded; 1 post mortem cornea was available for light microscopy...
March 21, 2017: Cornea
https://www.readbyqxmd.com/read/28346811/improved-soluble-scfv-elisa-screening-approach-for-antibody-discovery-using-phage-display-technology
#3
Mohammad R Tohidkia, Maryam Sepehri, Shirin Khajeh, Jaleh Barar, Yadollah Omidi
Phage display technology (PDT) is a powerful tool for the isolation of recombinant antibody (Ab) fragments. Using PDT, target molecule-specific phage-Ab clones are enriched through the "biopanning" process. The individual specific binders are screened by the monoclonal scFv enzyme-linked immunosorbent assay (ELISA) that may associate with inevitable false-negative results. Thus, in this study, three strategies were investigated for optimization of the scFvs screening using Tomlinson I and J libraries, including (1) optimizing the expression of functional scFvs, (2) improving the sensitivity of ELISA, and (3) preparing different samples containing scFvs...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346423/mob1-yap1-taz-nkx2-1-axis-controls-bronchioalveolar-cell-differentiation-adhesion-and-tumour-formation
#4
K Otsubo, H Goto, M Nishio, K Kawamura, S Yanagi, W Nishie, T Sasaki, T Maehama, H Nishina, K Mimori, T Nakano, H Shimizu, T W Mak, K Nakao, Y Nakanishi, A Suzuki
Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway. These proteins, which coactivate LArge Tumour Suppressor homologue kinases, are also tumour suppressors. To investigate MOB1A/B's roles in normal physiology and lung cancer, we generated doxycycline (Dox)-inducible, bronchioalveolar epithelium-specific, null mutations of MOB1A/B in mice (SPC-rtTA/(tetO)7-Cre/Mob1a(flox/flox)/Mob1b(-/-); termed luMob1DKO mice). Most mutants (70%) receiving Dox in utero (luMob1DKO (E6.5-18.5) mice) died of hypoxia within 1 h post-birth...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28345935/targeting-self-binding-peptides-as-a-novel-strategy-to-regulate-protein-activity-and-function-a-case-study-on-the-proto-oncogene-tyrosine-protein-kinase-c-src
#5
Zhengya Bai, Shasha Hou, Shilei Zhang, Zhongyan Li, Peng Zhou
Previously, we have reported a new biomolecular phenomenon spanning between protein folding and binding, termed as self-binding peptides (SBPs), where a short peptide segment in monomeric protein functions as molecular switch by dynamically binding to/unbinding from its cognate domain in the monomer (Yang C, Zhang S, He P, Wang C, Huang J, Zhou P. Self-binding peptides: folding or binding? J. Chem. Inf. MODEL: 2015, 55: 329-342). Here, we attempt to raise the SBP as a new class of druggable targets to regulate the biological activity and function of proteins...
March 27, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28345854/flexible-p-doped-carbon-cloth-vacuum-sealed-preparation-and-enhanced-na-storage-properties-as-binder-free-anode-for-sodium-ion-batteries
#6
Hong-Yan Lü, Xiao-Hua Zhang, Fang Wan, Dao-Sheng Liu, Chao-Ying Fan, Huan-Mei Xu, Guang Wang, Xing-Long Wu
In this work, a flexible and self-supporting P-doped carbon cloth (FPCC), which is composed of interwoven mesh of hollow microtubules with porous carbon walls, is prepared via a vacuum-sealed doping technology by employing the commercially available cotton cloth as sustainable and scalable raw material. When directly used as binder-free anode for sodium-ion batteries, the as-prepared FPCC delivers superior Na-storage properties in terms of specific capacity up to 242.4 mA h g-1, high initial Coulombic efficiency of ~72 %, excellent rate capabilities (e...
March 27, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28345007/partial-occupancy-binders-identified-by-the-pan-dataset-density-analysis-method-offer-new-chemical-opportunities-and-reveal-cryptic-binding-sites
#7
Nicholas M Pearce, Anthony R Bradley, Tobias Krojer, Brian D Marsden, Charlotte M Deane, Frank von Delft
Crystallographic fragment screening uses low molecular weight compounds to probe the protein surface and although individual protein-fragment interactions are high quality, fragments commonly bind at low occupancy, historically making identification difficult. However, our new Pan-Dataset Density Analysis method readily identifies binders missed by conventional analysis: for fragment screening data of lysine-specific demethylase 4D (KDM4D), the hit rate increased from 0.9% to 10.6%. Previously unidentified fragments reveal multiple binding sites and demonstrate: the versatility of crystallographic fragment screening; that surprisingly large conformational changes are possible in crystals; and that low crystallographic occupancy does not by itself reflect a protein-ligand complex's significance...
May 2017: Structural Dynamics (Melville, N.Y.)
https://www.readbyqxmd.com/read/28342851/site-specific-photocoupling-of-pbpa-mutated-scfv-antibodies-for-use-in-affinity-proteomics
#8
Mattias Brofelth, Lars Wagner Städe, Anna Isinger Ekstrand, Linn Petersson Edfeldt, Rebeka Kovačič, Thorbjørn Terndrup Nielsen, Kim Lambertsen Larsen, Laurent Duroux, Christer Wingren
Recombinant antibody libraries can provide a source of renewable and high-performing binders tailored for use in affinity proteomics. In this context, the process of generating site-specific 1:1 tagging/functionalization and/or orientated surface immobilization of antibodies has, however, proved to be challenging. Hence, novel ways of generating such engineered antibodies for use in affinity proteomics could have a major impact on array performance. In this study, we have further tailored the design of human recombinant scFv antibodies for site-specific photocoupling through the use of an unnatural amino acid (UAA) and the Dock'n'Flash technology...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342691/indenocinnoline-derivatives-as-g-quadruplex-binders-topoisomerase-ii%C3%AE-inhibitors-and-antiproliferative-agents
#9
Grigoris Zoidis, Alice Sosic, Silvia Da Ros, Barbara Gatto, Claudia Sissi, Fausta Palluotto, Angelo Carotti, Marco Catto
DNA intercalating agents are a consolidated therapeutic option in the treatment of tumor diseases. Starting from previous findings in the antiproliferative efficacy of a series of indeno[1,2-c]cinnoline-11-one derivatives, we performed a suitable decoration of this scaffold by means of a simple and straightforward chemistry, aiming to a) enlarge the planar core to a pentacyclic benzo[h]indeno[1,2-c]cinnoline-13-one and b) introduce a basic head tethered through a simple polymethylene chain. In fluorescence melting and fluorescence intercalator displacement assays, these new compounds displayed fair to very good intercalating properties on different nucleic acid strands, with preference for G-quadruplex sequences...
March 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28342427/spectroscopic-studies-of-the-interaction-mechanisms-between-mono-caffeoylquinic-acids-and-transferrin
#10
Yanqing Guan, Jing Dong, Shizhong Chen, Meixian Liu, Daidong Wang, Xiaotian Zhang, Hong Wang, Zongtao Lin
Transferrin (Tf) is an important protein responsible for circulating and transporting iron into cytoplasm. Tf can be taken into cells through endocytosis mediated by Tf receptor, which usually overexpresses in cancer cells. The Tf-Tf receptor pathway opens a possible avenue for novel targeted cancer therapy by utilizing Tf-binding active compounds. Among which, anti-cancer active caffeoylquinic acids (CQAs) were recently found to be promising Tf-binders by our group. For better understanding the anti-cancer activities of CQAs, it is important to unveil the binding mechanisms between CQAs and Tf...
March 7, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28340466/a-flexible-and-disposable-battery-powered-by-bacteria-using-eyeliner-coated-paper-electrodes
#11
Ramya Veerubhotla, Debabrata Das, Debabrata Pradhan
Herein, an environment friendly paper-based biobattery is demonstrated that yields a power of 12.5W/m(3). Whatman filter papers were used not only as support for electrode fabrication but also as separator of the biobattery. To provide electrical conductivity to the paper-based cathode and anode, commercially available eyeliner containing carbon nanoparticles and Fe3O4 was directly employed as conductive ink without any binder. With an instant start-up, the as-fabricated biocompatible electrodes could hold bacteria in an active form at the anode allowing chemical oxidation of organic fuel producing current...
March 9, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28340022/nicotine-content-and-physical-properties-of-large-cigars-and-cigarillos-in-the-united-states
#12
Bartosz Koszowski, Meridith Hill Thanner, Wallace B Pickworth, Kenneth M Taylor, Lynn C Hull, Megan J Schroeder
Introduction: Cigars are combusted tobacco products consisting of filler, binder, and wrapper, which are derived from tobacco. Despite the abundance of literature on the composition of traditional combusted cigarettes, research is limited on the physical and chemical properties of cigars. Therefore, research on cigar properties may be useful to better understand their health impact. Methods: In this study, twenty large cigar and cigarillo products were characterized for physical properties (ie, weight, length, and diameter), filler nicotine content, and tobacco pH...
March 4, 2017: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/28339993/one-year-efficacy-and-safety-of-the-iron-based-phosphate-binder-sucroferric-oxyhydroxide-in-patients-on-peritoneal-dialysis
#13
Jürgen Floege, Adrian C Covic, Markus Ketteler, Johannes Mann, Anjay Rastogi, Bruce Spinowitz, Viatcheslav Rakov, Laura J Lisk, Stuart M Sprague
Background.: Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with sevelamer carbonate (sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and sevelamer in the peritoneal dialysis (PD) patient population. Methods.: The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1...
February 23, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339828/single-session-of-functional-electrical-stimulation-assisted-walking-produces-corticomotor-symmetry-changes-related-to-changes-in-poststroke-walking-mechanics
#14
Jacqueline A Palmer, HaoYuan Hsiao, Tamara Wright, Stuart A Binder-Macleod
Background: Recent research demonstrated that symmetry of corticomotor drive to paretic and nonparetic plantarflexor muscles are related to the biomechanical ankle moment strategy that individuals with chronic stroke used to achieve their greatest walking speeds. Rehabilitation strategies that promote corticomotor balance could potentially improve post-stroke walking mechanics and enhance functional ambulation. Objective: To 1) test the effectiveness of a single session of gait training using functional electrical stimulation (FES) to improve plantarflexor corticomotor symmetry and plantarflexion ankle moment symmetry and 2) determine if changes in corticomotor symmetry relate to changes in ankle moment symmetry within the session...
February 23, 2017: Physical Therapy
https://www.readbyqxmd.com/read/28339199/structure-based-discovery-of-new-antagonist-and-biased-agonist-chemotypes-for-the-kappa-opioid-receptor
#15
Zhong Zheng, Xi-Ping Huang, Thomas J Mangano, Rodger Zou, Xin Chen, Saheem Zaidi, Bryan L Roth, Raymond C Stevens, Vsevolod Katritch
The ongoing epidemics of opioid overdose raises an urgent need for effective anti-addiction therapies and addiction-free painkillers. The κ-opioid receptor (KOR) has emerged as a promising target for both indications, raising demand for new chemotypes of KOR antagonists, as well as G-protein-biased agonists. We employed the crystal structure of the KOR-JDTic complex and ligand-optimized structural templates to perform virtual screening of available compound libraries for new KOR ligands. The prospective virtual screening campaign yielded a high 32% hit rate, identifying novel fragment-like and lead-like chemotypes of KOR ligands...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28337327/discovery-of-potent-selective-and-structurally-novel-dot1l-inhibitors-by-a-fragment-linking-approach
#16
Henrik Möbitz, Rainer Machauer, Philipp Holzer, Andrea Vaupel, Frédéric Stauffer, Christian Ragot, Giorgio Caravatti, Clemens Scheufler, Cesar Fernandez, Ulrich Hommel, Ralph Tiedt, Kim S Beyer, Chao Chen, Hugh Zhu, Christoph Gaul
Misdirected catalytic activity of histone methyltransferase Dot1L is believed to be causative for a subset of highly aggressive acute leukemias. Targeting the catalytic domain of Dot1L represents a potential therapeutic approach for these leukemias. In the context of a comprehensive Dot1L hit finding strategy, a knowledge-based virtual screen of the Dot1L SAM binding pocket led to the discovery of 2, a non-nucleoside fragment mimicking key interactions of SAM bound to Dot1L. Fragment linking of 2 and 3, an induced back pocket binder identified in earlier studies, followed by careful ligand optimization led to the identification of 7, a highly potent, selective and structurally novel Dot1L inhibitor...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337160/the-association-between-self-reported-difficulties-in-emotion-regulation-and-heart-rate-variability-the-salient-role-of-not-accepting-negative-emotions
#17
Endre Visted, Lin Sørensen, Berge Osnes, Julie L Svendsen, Per-Einar Binder, Elisabeth Schanche
Difficulties in emotion regulation are associated with development and maintenance of psychopathology. Typically, features of emotion regulation are assessed with self-report questionnaires. Heart rate variability (HRV) is an objective measure proposed as an index of emotional regulation capacity. A limited number of studies have shown that self-reported difficulties in emotion regulation are associated with HRV. However, results from prior studies are inconclusive, and an ecological validation of the association has not yet been tested...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28336958/from-rabbit-antibody-repertoires-to-rabbit-monoclonal-antibodies
#18
REVIEW
Justus Weber, Haiyong Peng, Christoph Rader
In this review, we explain why and how rabbit monoclonal antibodies have become outstanding reagents for laboratory research and increasingly for diagnostic and therapeutic applications. Starting with the unique ontogeny of rabbit B cells that affords highly distinctive antibody repertoires rich in in vivo pruned binders of high diversity, affinity and specificity, we describe the generation of rabbit monoclonal antibodies by hybridoma technology, phage display and alternative methods, along with an account of successful humanization strategies...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336932/tmeff2-is-expressed-in-differentiating-oligodendrocytes-but-dispensable-for-their-differentiation-in-vivo
#19
Hao Huang, Peng Teng, Ruyi Mei, Aifen Yang, Zunyi Zhang, Xiaofeng Zhao, Mengsheng Qiu
Myelin elaborated by oligodendrocytes (OLs) in the central nervous system (CNS) is required for saltatory conduction of action potentials along neuronal axons. We found that TMEFF2, a transmembrane protein with EGF-like and two follistatin-like domains, is selectively expressed in differentiating/myelinating OLs. Previous studies showed that TMEFF2 is capable of binding to PDGFA, which plays important roles in the proliferation, migration and differentiation of oligodendrocyte progenitor cells (OPCs). However, molecular and genetic analysis revealed that Tmeff2 is a weak binder of PDGFA, and not required for OL differentiation and myelin gene expression in vivo...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336878/ag-nanoparticles-modified-3d-graphene-foam-for-binder-free-electrodes-of-electrochemical-sensors
#20
Tao Han, Jianli Jin, Congxu Wang, Youyi Sun, Yinghe Zhang, Yaqing Liu
Ag nanoparticles-modified 3D graphene foam was synthesized through a one-step in-situ approach and then directly applied as the electrode of an electrochemical sensor. The composite foam electrode exhibited electrocatalytic activity towards Hg(II) oxidation with high limit of detection and sensitivity of 0.11 μM and 8.0 μA/μM, respectively. Moreover, the composite foam electrode for the sensor exhibited high cycling stability, long-term durability and reproducibility. These results were attributed to the unique porous structure of the composite foam electrode, which enabled the surface of Ag nanoparticles modified reduced graphene oxide (Ag NPs modified rGO) foam to become highly accessible to the metal ion and provided more void volume for the reaction with metal ion...
February 16, 2017: Nanomaterials
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