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"Colenso, Michael"
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New Anglicisms in Russian
The radical changes in Russian life during the last decade of the twentieth century – the sudden increased exposure to Western influence, and the introduction of large numbers of new institutions, habits and concepts – have led to the inundation of the Russian language with neologisms, in particular Anglicisms, due to the global use of English. These neologisms relate in particular to the ideology of democratic change in Russia, in the economy and its management, social problems, scientific and technological progress, education and culture, law and order, international and inter-ethnic relations.
Many well-established words in the Russian lexicon are loan words from
Book Chapter
Evolutionary analyses reveal independent origins of gene repertoires and structural motifs associated to fast inactivation in calcium-selective TRPV channels
Essential for calcium homeostasis, TRPV5 and TRPV6 are calcium-selective channels belonging to the transient receptor potential (TRP) gene family. In this study, we investigated the evolutionary history of these channels to add an evolutionary context to the already available physiological information. Phylogenetic analyses revealed that paralogs found in mammals, sauropsids, amphibians, and chondrichthyes, are the product of independent duplication events in the ancestor of each group. Within amniotes, we identified a traceable signature of three amino acids located at the amino-terminal intracellular region. The signature correlates with both the duplication events and the phenotype of fast inactivation observed in mammalian TRPV6 channels. Electrophysiological recordings and mutagenesis revealed that the signature sequence modulates the phenotype of fast inactivation in all clades of vertebrates but reptiles. A transcriptome analysis showed a change in tissue expression from gills, in marine vertebrates, to kidneys in terrestrial vertebrates. Our results highlight a cytoplasmatic structural triad composed by the Helix-Loop-Helix domain, the S2-S3 linker, and the TRP domain helix that is important on modulating the activity of calcium-selective TRPV channels.
Journal Article
Tautomer-specific deacylation and Ω-loop flexibility explain carbapenem-hydrolyzing, broad-spectrum activity of the KPC-2 β-lactamase
KPC-2 (Klebsiella pneumoniae carbapenemase-2) is a globally disseminated serine-β-lactamase (SBL) responsible for extensive β-lactam antibiotic resistance in Gram-negative pathogens. SBLs inactivate β-lactams via a mechanism involving a hydrolytically labile covalent acyl-enzyme intermediate. Carbapenems, the most potent β-lactams, evade activity of many SBLs by forming long-lived inhibitory acyl-enzymes; however, carbapenemases such as KPC-2 efficiently catalyze deacylation of carbapenem-derived acyl-enzymes. We present high-resolution (1.25-1.4 Å) crystal structures of KPC-2 acyl-enzymes with representative penicillins (ampicillin), cephalosporins (cefalothin) and carbapenems (imipenem, meropenem and ertapenem), obtained utilizing an isosteric deacylation-deficient mutant (E166Q). Mobility of the Ω-loop (residues 165—170) negatively correlates with antibiotic turnover rates (k) cat), highlighting the role of this region in positioning catalytic residues for efficient hydrolysis of different β-lactams. Carbapenem-derived acyl-enzyme structures reveal predominance of the Δ1-(2R) imine tautomer, except for the imipenem acyl-enzyme, which is present in dual occupancy in both Δ1-(2R) and (2S) configurations. Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations of deacylation of the KPC-2:meropenem acyl-enzyme, using an adaptive string method (ASM), show that the Δ1-(2R) isomer has a 7 kcal/mol higher barrier for the (rate-determining) formation of the tetrahedral deacylation intermediate than the Δ2 tautomer. The simulations identify tautomer-specific differences in hydrogen bonding networks involving the carbapenem C-3 carboxylate and the deacylating water, that, together with stabilization by protonated N-4 of accumulating negative charge during oxyanion formation, accelerate deacylation of the Δ2-enamine acyl-enzyme compared to the Δ1-imine. Taken together, our data show how the flexible Ω-loop helps confer broad spectrum activity upon KPC-2, while carbapenemase activity stems from efficient deacylation of the Δ2-enamine acyl-enzyme tautomer. Differentiation of the barriers associated with deacylation of these subtly different β-lactam isomers further identifies ASM as a sensitive method for calculation of reaction energetics that can accurately model turnover and, potentially, predict the impact of substrate modifications or point mutations upon activity.Competing Interest StatementThe authors have declared no competing interest.
Paper
Evolutionary analyses reveal independent origins of gene repertoires and structural motifs associated to fast inactivation in calcium-selective TRPV channels
Important for calcium homeostasis, TRPV5 and TRPV6 are calcium-selective channels belonging to the transient receptor potential (TRP) gene family. In this study, we investigated the evolutionary history of these channels to add an evolutionary context to the already available physiological information. Phylogenetic analyses revealed that paralogs found in mammals, sauropsids, amphibians, and chondrichthyans, are the product of independent duplication events in the ancestor of each group. Within amniotes, we identified a traceable signature of three amino acids located at the amino-terminal intracellular region (HLH domain). The signature correlates well with both the duplication events and the phenotype of fast inactivation observed in mammalian TRPV6 channels. Electrophysiological recordings and mutagenesis suggest that calcium-induced fast inactivation represents an evolutionary innovation that emerged independently after gene duplication.
Paper