The ideas of pseudogap and nanocrystals have applied to mechanism of electrical conduction in silicate glass doped by oxides of transition metals (thick film resistors). Pseudogap is formed near the ...valence band of the glass due to diffusion of dopant atoms into the glass in calcination. Nanocrystals are generated in the glass in melting process and undergo structure transitions at high temperatures. This approach lets to explain the temperature dependence of conductivity of doped silicate glass from liquid helium up to 1100 K.
Eukaryotic mRNAs undergo cotranscriptional 5′-end modification with a 7-methylguanosine cap. In higher eukaryotes, the cap carries additional methylations, such as m6Ama common epitranscriptomic ...mark unique to the mRNA 5′-end. This modification is regulated by the Pcif1 methyltransferase and the FTO demethylase, but its biological function is still unknown. Here, we designed and synthesized a trinucleotide FTO-resistant N6-benzyl analogue of the m6Am-cap–m7GpppBn6AmpG (termed AvantCap) and incorporated it into mRNA using T7 polymerase. mRNAs carrying Bn6Am showed several advantages over typical capped transcripts. The Bn6Am moiety was shown to act as a reversed-phase high-performance liquid chromatography (RP-HPLC) purification handle, allowing the separation of capped and uncapped RNA species, and to produce transcripts with lower dsRNA content than reference caps. In some cultured cells, Bn6Am mRNAs provided higher protein yields than mRNAs carrying Am or m6Am, although the effect was cell-line-dependent. m7GpppBn6AmpG-capped mRNAs encoding reporter proteins administered intravenously to mice provided up to 6-fold higher protein outputs than reference mRNAs, while mRNAs encoding tumor antigens showed superior activity in therapeutic settings as anticancer vaccines. The biochemical characterization suggests several phenomena potentially underlying the biological properties of AvantCap: (i) reduced propensity for unspecific interactions, (ii) involvement in alternative translation initiation, and (iii) subtle differences in mRNA impurity profiles or a combination of these effects. AvantCapped-mRNAs bearing the Bn6Am may pave the way for more potent mRNA-based vaccines and therapeutics and serve as molecular tools to unravel the role of m6Am in mRNA.
Eukaryotic mRNAs undergo cotranscriptional 5'-end modification with a 7-methylguanosine cap. In higher eukaryotes, the cap carries additional methylations, such as
A
─a common epitranscriptomic mark ...unique to the mRNA 5'-end. This modification is regulated by the Pcif1 methyltransferase and the FTO demethylase, but its biological function is still unknown. Here, we designed and synthesized a trinucleotide FTO-resistant
6-benzyl analogue of the
A
-cap-m
Gppp
A
pG (termed
) and incorporated it into mRNA using T7 polymerase. mRNAs carrying
A
showed several advantages over typical capped transcripts. The
A
moiety was shown to act as a reversed-phase high-performance liquid chromatography (RP-HPLC) purification handle, allowing the separation of capped and uncapped RNA species, and to produce transcripts with lower dsRNA content than reference caps. In some cultured cells,
A
mRNAs provided higher protein yields than mRNAs carrying A
or
A
, although the effect was cell-line-dependent. m
Gppp
A
pG-capped mRNAs encoding reporter proteins administered intravenously to mice provided up to 6-fold higher protein outputs than reference mRNAs, while mRNAs encoding tumor antigens showed superior activity in therapeutic settings as anticancer vaccines. The biochemical characterization suggests several phenomena potentially underlying the biological properties of
: (i) reduced propensity for unspecific interactions, (ii) involvement in alternative translation initiation, and (iii) subtle differences in mRNA impurity profiles or a combination of these effects.
mRNAs bearing the
A
may pave the way for more potent mRNA-based vaccines and therapeutics and serve as molecular tools to unravel the role of
A
in mRNA.
Extradiol dioxygenase chemistry is essential for catechol breakdown. The largest natural reservoir of catechols, or 1,2-dihydroxybenzenes, is the plant woody-tissue polymer lignin. ...Vicinal–oxygen–chelate (VOC) dioxygenases make up the largest group of characterized extradiol dioxygenases, and while most are found as part of catabolic pathways degrading a variety of natural and human-made aromatic rings, L-DOPA (l-3,4-dihydroxyphenylalanine) dioxygenase is a VOC enzyme that participates in the biosynthesis of a natural product. All VOC superfamily members shared conserved elements of catalysis, yet despite decades of investigation of VOC enzymes, the relationships between VOC domain architecture and enzymatic function remain complex and poorly understood. Herein, we present evidence that L-DOPA dioxygenase is the representative member of a new topological class of VOC extradiol dioxygenases. Guided by its evolutionary similarity to glyoxylase enzymes, we performed a careful investigation of the Streptomyces lincolnensis L-DOPA dioxygenase (LmbB1) active site through mutagenesis, kinetic, and pH studies. Our results demonstrate that the L-DOPA dioxygenase reaction depends upon an active-site tyrosine and histidine and is remarkably resilient to mutation, even at the iron-ligating residues. Evaluation of the cleavage reaction as a function of pH supports the role of a histidine in acid–base catalysis. The active-site architecture is functionally consistent with the existing knowledge of VOC extradiol dioxygenase catalysis.
Compared to other forms of discrimination, ageism, and specific forms of ageism such as elderspeak are understudied. Despite the fact that the majority of older adults are community-dwelling, much of ...the existing literature on elderspeak focuses on caregiver perceptions on elderspeak occurring in assisted living facilities and nursing homes. The present study analyzed community dwelling older adult’s perceptions of elderspeak using their personal examples of experiences of elderspeak. Results indicated that the majority of participants had negative perceptions of elderspeak that would likely not be influenced by changes in contextual factors such as setting, relationship to the speaker, and gender of the speaker.
The paper presents detailed investigations of dynamic processes occurring in nanostructured Si(Fe) material under the radiation exposure, namely: heating, thermoelastic stress generation, elastic ...disturbances of the surrounding medium similar to weak shock waves, and dislocation generation. The performance calculations are proposed for elastic properties of the nanostructured material with a glance to size effects in nanoparticles.
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