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991.
Methods for targeting oncolytic viruses can increase efficacy and accelerate development. Genetic engineering, the predominant method for changing vector tropism, is limited in scope and often represents the bottleneck for vector development. Metabolic incorporation of an unnatural azido sugar, O-GlcNAz, at a specific site on the adenoviral surface allows chemoselective attachment of affibodies for Her2 or EGF receptors. Modification with these high-affinity, high-selectivity proteins is straightforward and readily generalizable, demonstrates minimal impact on virus physiology, and affords significant increases in gene delivery to cancer cells. As a result, this method has significant potential to increase the efficacy of next-generation viral vectors. 相似文献
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O Jara R Acuña IE García J Maripillán V Figueroa JC Sáez R Araya-Secchi CF Lagos T Pérez-Acle VM Berthoud EC Beyer AD Martínez 《Molecular biology of the cell》2012,23(17):3299-3311
To identify motifs involved in oligomerization of the gap junction protein Cx26, we studied individual transmembrane (TM) domains and the full-length protein. Using the TOXCAT assay for interactions of isolated TM α-helices, we found that TM1, a Cx26 pore domain, had a strong propensity to homodimerize. We identified amino acids Val-37-Ala-40 (VVAA) as the TM1 motif required for homodimerization. Two deafness-associated Cx26 mutations localized in this region, Cx26V37I and Cx26A40G, differentially affected dimerization. TM1-V37I dimerized only weakly, whereas TM1-A40G did not dimerize. When the full-length mutants were expressed in HeLa cells, both Cx26V37I and Cx26A40G formed oligomers less efficiently than wild-type Cx26. A Cx26 cysteine substitution mutant, Cx26V37C formed dithiothreitol-sensitive dimers. Substitution mutants of Val-37 formed intercellular channels with reduced function, while mutants of Ala-40 did not form functional gap junction channels. Unlike wild-type Cx26, neither Cx26V37I nor Cx26A40G formed functional hemichannels in low extracellular calcium. Thus the VVAA motif of Cx26 is critical for TM1 dimerization, hexamer formation, and channel function. The differential effects of VVAA mutants on hemichannels and gap junction channels imply that inter-TM interactions can differ in unapposed and docked hemichannels. Moreover, Cx26 oligomerization appears dependent on transient TM1 dimerization as an intermediate step. 相似文献
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A study was made of the effects of foliar spray of bacitracin, chloramphenicol and gibberellic acid on the rhizosphere microflora
of pea seedlings (Pisum sativum L.) infected withVerticillium dahliae. The antibiotics increased fungus and actinomycete counts and reduced the bacterial populations in the rhizosphere. Gibberellic
acid at 10 ppm concentration reduced all three groups of microorganisms while at 100 ppm fungi and actinomycetes increased
slightly. Invariably the rhizosphere effect was as follows: bacteria > fungi > actinomycetes. Foliar sprays also affected
the percentage occurrence of particular genera of fungi in the rhizosphere; for example,Trichoderma spp. were stimulated by all the treatments, the maximum being with 10 ppm gibberellic acid, even though the total fungus
count was reduced. The disease severity was markedly reduced by foliar sprays. 相似文献
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