China
Africa
Explore chapters and articles related to this topic
Antitubulin Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
On addition of a new dimer at the positive end, the catalytic domain of α-tubulin contacts the E-site of the previous β-subunit and becomes ready for hydrolysis. The positive end generally has a minimum GTP cap of one tubulin layer that stabilizes the microtubule structure. When this GTP cap is lost, the protofilaments splay apart and the microtubule rapidly depolymerizes. During, or soon after, polymerization the tubulin subunits hydrolyze their bound GTP and become nonexchangeable. Thus, the microtubule lattice is predominantly composed of GDP–tubulin, with depolymerization characterized by the rapid loss of GDP–tubulin subunits and oligomers from the microtubule positive end. At the negative end, contact is made between the E-site of the new dimer and the catalytic region of the last subunit, and thus no GTP cap should be present. Therefore, a GDP-bound tubulin subunit at the tip of a microtubule will fall off, although a GDP-bound tubulin in the middle of a microtubule will not leave spontaneously. Only a tubulin subunit in the GTP-bound state will add to the microtubule, and hence there is generally a GTP-bound tubulin unit at the tip of a microtubule protecting it from disassembly.
Regulation of C-Reactive Protein, Haptoglobin, and Hemopexin Gene Expression
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Dipak P. Ramji, Riccardo Cortese, Gennaro Ciliberto
Sequence comparison between the CRP β- and γ-sites shows some homology with the consensus binding site of LF-B1/HNF-174 (hereafter referred to as LF-B1; Figure 4A). In gel retardation assays with hepatoma Hep 3B cells, a DNA-protein complex is formed with both the β- and γ-sites, and this complex can be specifically competed with the LF-B1 binding sites from the albumin and α1-antitrypsin promoter (Figure 4B; other data not shown). By cross-competition experiments, it can be shown that LF-B1 interacts with the CRP sites with about ten- to 20-fold less affinity compared to the E-site from the albumin promoter. This is consistent with the observation that the CRP β- and γ-sites deviate substantially from the consensus LF-B1 binding sequence (Figure 4A). For example, the two invariant T-residues at positions 4 and 5 are substituted by two As in the β-site, while there is an insertion of an A residue in the γ-site between the two conserved Gs at positions 2 and 3, respectively.
Current Inhibitors of Dengue Virus
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
J. Jonathan Harburn, G. Stuart Cockerill
A disparate range of host target mechanisms and inhibitors have also been described in the last few years- Lactimidomycin binding to the E site of the host ribosome has been described to be active against DENV2 (EC50 = 0.4 μM) (Carocci and Yang 2016); the inhibition of sterol regulatory element-binding protein S1P has shown activity (EC50 =1.2 μM, DENV2) (Uchida et al. 2016); the possible complicity of host IMPDH in an anti-viral effect (Mazzucco et al. 2015); Heme oxygenase 1 (Tseng et al. 2016) and the HMG-CoA (Soto-Acosta et al. 2017) reductase pathway have received some attention. All of these proposed targets are at an early evaluation stage utilizing biochemical tool inhibitors or inducers.
Social capital components and social support of persons with multiple sclerosis: a systematic review of the literature from 2000 to 2018
Published in Disability and Rehabilitation, 2020
Eleni Koutsogeorgou, Antonio M. Chiesi, Matilde Leonardi
More specifically, data synthesis of pre-defined themes – decided among authors based on the aim of this study – were used for data extraction. Consequently, texts segments were extracted from each included study, providing the following information: (a) author(s); (b) year of publication; (c) journal published; (d) aim(s) of study; (e) site of study; (f) sample size; (g) age of participants; (h) inclusion criteria; (i) method of data collection (including method of recruitment of participants); (j) specific measures/instruments used for assessing social capital components and/or social support; (k) main findings in relation to social capital components and/or social support.
A safe and highly efficient tumor-targeted type I interferon immunotherapy depends on the tumor microenvironment
Published in OncoImmunology, 2018
Anje Cauwels, Sandra Van Lint, Geneviève Garcin, Jennyfer Bultinck, Franciane Paul, Sarah Gerlo, José Van der Heyden, Yann Bordat, Dominiek Catteeuw, Lode De Cauwer, Elke Rogge, Annick Verhee, Gilles Uzé, Jan Tavernier
The mutation Q124R was introduced into the IFNa2 sequence by site-directed mutagenesis using the QuikChange II-E Site-Directed Mutagenesis Kit (Agilent Technologies) and single domain llama VHH antibodies (sdAb) were generated at the VIB Protein Service Facility, as described previously10. Mouse AcTaferons are composed of hIFNa2Q124R9 coupled via a 20xGGS-linker to an N-terminal targeting sdAb. A C-terminal tag is added for easy purification. AcTaferons and immunocytokines (WT mIFNa11 coupled to sdAb) were constructed in pHen6 vectors, large scale productions of His-tagged AcTaferons were performed in E. coli. The bacteria were cultured till stationary phase (OD600 of 0.7–0.8) whereupon IPTG (BioScientific) was added to activate the LacZ promoter. Cell supernatant was collected after overnight culture. The proteins in the periplasmic fraction were released by osmotic shock using a sucrose solution and were purified by immobilized metal ion chromatography (IMAC) on a HiTrap Sepharose resin loaded with Kobalt ions (Clontech, Takara Biotechnology). After binding of the protein, columns were washed with 0.5% EMPIGEN (Calbiochem, Millipore), 0.5% CHAPS (Sigma-Aldrich) and PBS. Imidazole (Merck) was used for elution and removed using PD-10 gel filtration columns (GE Healthcare). Protein concentration was determined using the absorbance at 280 nm and purity was assessed via SDS-PAGE. LPS levels were quantified using Limulus Amebocyte Lysate (LAL) QCL-1000 (Lonza). If still present, LPS was removed using Endotoxin Removal Resin (Thermo Scientific). Biological activities of all products were assessed by a functional assay using the mouse luciferase reporter cell line LL171 against the WHO International mouse IFNα standard Ga02-901-511 as described previously.10
Polymethylmethacrylate cranioplasty using low-cost customised 3D printed moulds for cranial defects – a single Centre experience: technical note
Published in British Journal of Neurosurgery, 2019
Krešimir Saša Đurić, Hrvoje Barić, Ivan Domazet, Petra Barl, Niko Njirić, Goran Mrak
Retrospective review of patients who underwent a 3D PMMA cranioplasty at our Department from October 2015, when the method was first introduced, to January 2018. These data were retrieved: a) patient age; b) patient gender; c) initial diagnosis; d) interval between craniectomy and cranioplasty; e) site of defect; f) size of defect; g) postoperative patient reported aesthetic outcome using a four-point Likert scale (0 = strongly not satisfied to 3 = very satisfied); h) duration of surgery; and i) complications.