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991.
Dr. Monica Varese Dr. Salvador Guardiola Dr. Jesús García Prof. Ernest Giralt 《Chembiochem : a European journal of chemical biology》2019,20(24):2981-2986
Our laboratory has recently identified two nanobodies (small antibodies produced by camelids)—Nb1 and Nb6—that bind efficiently to epithelial growth factor (EGF) and inhibit its ability to activate its receptor (EGFR). Because of the relevance of the EGF/EGFR axis as a target in oncology, these new nanobodies have promising therapeutic potential. This article, however, is focused on another feature of these nanobodies: their distinct thermodynamic signatures. Nb1 binds to EGF through an entropy-driven mechanism whereas Nb6 binds to this factor under enthalpic control. We discuss the advantages and disadvantages of each mechanism in the contexts of traditional medical chemistry (small-molecule drugs) and also of biological drugs. In this latter case, the implications in terms of selectivity are far from being clearly established and further experimental data are required. Their monomeric natures, high stability, and ease of recombinant production make nanobodies ideally suited for thermodynamic studies. Moreover, nanobodies, thanks to their simpler structures in comparison with conventional antibodies, might provide better understanding of the structural basis of the thermodynamic parameters of antigen recognition. 相似文献
992.
Ethan S. Pickerill Rebecca P. Kurtz Aaron Tharp Paula Guerrero Sanz Munni Begum Douglas A. Bernstein 《Yeast (Chichester, England)》2019,36(11):669-677
RNA can be modified in over 100 distinct ways, and these modifications are critical for function. Pseudouridine synthases catalyse pseudouridylation, one of the most prevalent RNA modifications. Pseudouridine synthase 7 modifies a variety of substrates in Saccharomyces cerevisiae including tRNA, rRNA, snRNA, and mRNA, but the substrates for other budding yeast Pus7 homologues are not known. We used CRISPR-mediated genome editing to disrupt Candida albicans PUS7 and find absence leads to defects in rRNA processing and a decrease in cell surface hydrophobicity. Furthermore, C. albicans Pus7 absence causes temperature sensitivity, defects in filamentation, altered sensitivity to antifungal drugs, and decreased virulence in a wax moth model. In addition, we find C. albicans Pus7 modifies tRNA residues, but does not modify a number of other S. cerevisiae Pus7 substrates. Our data suggests C. albicans Pus7 is important for fungal vigour and may play distinct biological roles than those ascribed to S. cerevisiae Pus7. 相似文献
993.
Investigation into time dependent long-term performance of Prefabricated Vertical Drains (PVDs) combined with vacuum consolidation in thick deposits of clay has been extremely limited. Predicting both settlements and excess pore pressures in such cases has become increasingly challenging when time duration is long-term, e.g. several years. In discussing such matter, finding a suitable model to predict the long-term performance is inevitable. Elasto-plastic analysis models such as Cam-Clay cannot predict long-term time-dependent deformational behaviour in soft soils. In this technical note, a Biot type fully-coupled creep-based elastic viscoplastic (EVP) finite element (FE) numerical model has been extended for application in vacuum consolidation. The vacuum consolidation section of the embankment constructed in Ballina, New South Wales, Australia (hereafter referred as Ballina embankment), is analysed using the model through a unit cell analysis and the numerical predictions are compared with field performance monitoring data up to 1200 days (>3 years). The proposed analysis method for PVD combined with vacuum consolidation involving an EVP model is found to be capable of predicting both short-term and long-term deformational behaviours. Predictions are improved when an exponential function is used for the secondary compression index in the EVP model. Comparison has also been carried out at another location in the embankment where the foundation clay thickness was different to check the precision of the methodology and for better understanding of ground settlement behaviour. Details of the analysis methodology and its validation against field performance data are presented in this note. 相似文献
994.
995.
Protection of Metals and Physical Chemistry of Surfaces - The form of elution curves in the linear frontal dynamics of adsorption is studied based on the exact solution of a direct problem. It is... 相似文献
996.
Dr. Shukun Li Dr. Yamei Liu Ruirui Xing Prof. Dr. Xuehai Yan 《Chembiochem : a European journal of chemical biology》2019,20(4):555-560
Peptide self-assembly, inspired by the naturally occurring fabrication principle, remains the most attractive in constructing fluorescent nanoagents towards bioimaging. However, the noncovalent interactions that drive peptide self-assembly are usually susceptible to the complex physiological environment; thus leading to disassembly and dysfunction of fluorescent nanoagents. Herein, a covalently crosslinked assembly strategy for fabrication of stable peptide-based nanoparticles with adjustable emission is introduced. In the process of cationic diphenylalanine peptide (H-Phe-Phe-NH2 ⋅ HCl) self-assembly, glutaraldehyde is used as a crosslinker and the resulting product of the Schiff base reaction can be fluorescent. More importantly, the emission wavelength can be readily tuned by controlling the covalent reaction time. It has been demonstrated that the nanoparticles are stable, even after intracellular uptake, and can be used for sustainable multicolor fluorescent imaging. The strategy with integrating peptide self-assembly and covalent crosslinking could be promising for the design and engineering of functional fluorescent nanoparticles with robust physiological stability and adjustable emission towards improved bioimaging applications. 相似文献
997.
998.
André Campaniço Dr. Marta P. Carrasco Dr. Mathew Njoroge Ronnett Seldon Prof. Kelly Chibale Dr. João Perdigão Prof. Isabel Portugal Prof. Digby F. Warner Prof. Rui Moreira Prof. Francisca Lopes 《ChemMedChem》2019,14(16):1537-1546
Herein we report the screening of a small library of aurones and their isosteric counterparts, azaaurones and N-acetylazaaurones, against Mycobacterium tuberculosis. Aurones were found to be inactive at 20 μm , whereas azaaurones and N-acetylazaaurones emerged as the most potent compounds, with nine derivatives displaying MIC99 values ranging from 0.4 to 2.0 μm . In addition, several N-acetylazaaurones were found to be active against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical M. tuberculosis isolates. The antimycobacterial mechanism of action of these compounds remains to be determined; however, a preliminary mechanistic study confirmed that they do not inhibit the mycobacterial cytochrome bc1 complex. Additionally, microsomal metabolic stability and metabolite identification studies revealed that N-acetylazaaurones are deacetylated to their azaaurone counterparts. Overall, these results demonstrate that azaaurones and their N-acetyl counterparts represent a new entry in the toolbox of chemotypes capable of inhibiting M. tuberculosis growth. 相似文献
999.
T. A. Tsyganova D. S. Shevchenko O. S. Magomedova O. V. Rakhimova 《Glass Physics and Chemistry》2019,45(4):298-301
The results of studying the structural parameters and strength characteristics of a bioactive membrane are presented. The membrane was obtained based on high-silica glass via modification with silicon polyoxomolybdate. The membrane strength characteristics were simulated under conditions of the maximum pressure of a vacuum water-jet pump of 300 kPa. 相似文献
1000.
Subha Balakrishnan Varun Prasath Padmanabhan Ravichandran Kulandaivelu T.S. Sankara Narayanan Nellaiappan Suresh Sagadevan Suriati Paiman Faruq Mohammad Hamad A. Al-Lohedan Prasanna Kumar Obulapuram Won Chun Oh 《Ceramics International》2021,47(4):5061-5070
Hydroxyapatite (HAP) is the naturally occurring mineral form of calcium apatite and the most studied material as a bone substituent. Considering HAP's inherent properties, this study explored changes in HAP's characteristics from doping with other metals such as Fe. To form pure HAP and Fe-HAP with different amounts of Fe, we used the hydrothermal approach, and the composites that formed were thoroughly analyzed for their crystallinity, surface bonding, morphology, magnetic behavior, mechanical strength, biocompatibility, hemocompatibility, and in vitro cytotoxicity. The powder XRD studies confirmed the samples' crystallinity, and the lowest crystalline size was 19.7 nm in 10Fe-HAP. The FTIR analysis confirmed the formation of HAP by the hydroxyl, phosphate, and carbonate groups. The FESEM demonstrated that the morphology of the pure HAP was rod-shaped, which transformed into spheres after Fe doping. The EDS analysis confirmed the successful formation of HAP and Fe-HAP composites. The magnetic studies indicated the diamagnetic behavior of the pure HAP, while the Fe-doped HAPs had a superparamagnetic nature with saturation magnetizations (Ms) of 2Fe-HAP, 4Fe-HAP, and 10Fe-HAP at 0.0062, 0.0092, and 0.029 emu/g respectively. Assessment of the mechanical properties, biocompatibility, hemocompatibility, and cytotoxicity indicated that the Fe-doped HAPs were superior to the pure HAP, and among the Fe-HAPs, the 10Fe-HAP) had the highest amount of Fe and the best characteristics. The studies also indicated that Ca2+ interactions influenced the cells via HAP doping with that of Fe, equally increasing the physicochemical and biological properties. 相似文献