Pyrrolysine and Selenocysteine Use Dissimilar Decoding Strategies

Selenocysteine (Sec) and pyrrolysine (Pyl) are known as the 21st and 22nd amino acids in protein. Both are encoded by codons that normally function as stop signals. Sec specification by UGA codons requires the presence of a cis-acting selenocysteine insertion sequence (SECIS) element. Similarly, it is thought that Pyl is inserted by UAG codons with the help of a putative pyrrolysine insertion sequence (PYLIS) element. Herein, we analyzed the occurrence of Pyl-utilizing organisms, Pyl-associated genes, and Pyl-containing proteins. The Pyl trait is restricted to several microbes, and only one organism has both Pyl and Sec. We found that methanogenic archaea that utilize Pyl have few genes that contain in-frame UAG codons, and many of these are followed with nearby UAA or UGA codons. In addition, unambiguous UAG stop signals could not be identified. This bias was not observed in Sec-utilizing organisms and non-Pyl-utilizing archaea, as well as with other stop codons. These observations as well as analyses of the coding potential of UAG codons, overlapping genes, and release factor sequences suggest that UAG is not a typical stop signal in Pyl-utilizing archaea. On the other hand, searches for conserved Pyl-containing proteins revealed only four protein families, including methylamine methyltransferases and transposases. Only methylamine methyltransferases matched the Pyl trait and had conserved Pyl, suggesting that this amino acid is used primarily by these enzymes. These findings are best explained by a model wherein UAG codons may have ambiguous meaning and Pyl insertion can effectively compete with translation termination for UAG codons obviating the need for a specific PYLIS structure. Thus, Sec and Pyl follow dissimilar decoding and evolutionary strategies

Assessment of the Required Changes of Russian Ecological Taxes

Russia is one of the most polluting countries in the world and environmental problem is very important in this country. The forecast of atmospheric emissions was conducted according to various economic development scenarios in Russia using dynamic Dynamic Input-Output Model. The optimistic scenario is realized under hypothesis about oil prices increase and real ruble exchange rate strengthening beginning of the end of 2015, the revival of investment processes, the successful policy of import substitution, and the competent using of instruments of monetary and fiscal policy. The pessimistic scenario is implemented under assumption of negative economic tendency prolongation of the 2014. Future increase of environmental pressure will be expected in optimistic scenario. The improvement of pollution taxes mechanism as a way of government ecological policy is discussed in the article. Keywords: Input-Output Model, environmental pollution, forecast of emission, pollution taxes JEL Classifications: E62, H23, Q32, Q38, Q42, Q

Recode-2: new design, new search tools, and many more genes

'Recoding' is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing. Although only a small proportion of genes utilize recoding in protein synthesis, accurate annotation of ‘recoded’ genes lags far behind annotation of 'standard' genes. In order to address this issue, provide a service to researchers in the field, and offer training data for developers of gene-annotation software, we have gathered together known cases of recoding within the Recode database. Recode-2 is an improved and updated version of the database. It provides access to detailed information on genes known to utilize translational recoding and allows complex search queries, browsing of recoding data and enhanced visualization of annotated sequence elements. At present, the Recode-2 database stores information on approximately 1500 genes that are known to utilize recoding in their expression—a factor of approximately three increase over the previous version of the database. Recode-2 is available at http://recode.ucc.i

A novel-type luciferin from Siberian luminous earthworm Fridericia heliota : structure elucidation by spectral studies and total synthesis

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Wiley-VCH Verlag GmbH & Co for personal use, not for redistribution. The definitive version was published in Angewandte Chemie International Edition 53 (2014): 5566–5568, doi:10.1002/anie.201400529.We report structure elucidation and synthesis of the luciferin from the recently discovered luminous earthworm Fridericia heliota. This luciferin represents a key component of a novel ATP-dependent bioluminescence system. The UV, fluorescence, NMR and HRMS spectral studies were performed on 5 mkg of the isolated substance, and gave four isomeric structures, conforming with spectral data. These isomers were chemically synthesized and one of them was found to produce light in the reaction with a protein extract from Fridericia. The novel luciferin was found to have an unusual deeply modified peptidic nature, implying an unprecedented mechanism of action.We acknowledge support from the Program of the Government of the Russian Federation “Measures to attract leading scientists to Russian educational institutions” (grant no. 11. G34.31.0058), the programs MCB RAS, President of the Russian Federation “Leading science school” (grant 3951.2012.4) and the Russian Foundation for Basic Research (grant 14-03-01015). B.M.S. was supported by a stipend from the Program of the President of the Russian Federation.2015-04-1

Level Anticrossing of Impurity States in Semiconductor Nanocrystals

The size dependence of the quantized energies of elementary excitations is an essential feature of quantum nanostructures, underlying most of their applications in science and technology. Here we report on a fundamental property of impurity states in semiconductor nanocrystals that appears to have been overlooked—the anticrossing of energy levels exhibiting different size dependencies. We show that this property is inherent to the energy spectra of charge carriers whose spatial motion is simultaneously affected by the Coulomb potential of the impurity ion and the confining potential of the nanocrystal. The coupling of impurity states, which leads to the anticrossing, can be induced by interactions with elementary excitations residing inside the nanocrystal or an external electromagnetic field. We formulate physical conditions that allow a straightforward interpretation of level anticrossings in the nanocrystal energy spectrum and an accurate estimation of the states\u27 coupling strength

AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation.

In addition to acting as template for protein synthesis, messenger RNA (mRNA) often contains sensory sequence elements that regulate this process1,2. Here we report a new mechanism that limits the number of complete protein molecules that can be synthesized from a single mRNA molecule of the human AMD1 gene encoding adenosylmethionine decarboxylase 1 (AdoMetDC). A small proportion of ribosomes translating AMD1 mRNA stochastically read through the stop codon of the main coding region. These readthrough ribosomes then stall close to the next in-frame stop codon, eventually forming a ribosome queue, the length of which is proportional to the number of AdoMetDC molecules that were synthesized from the same AMD1 mRNA. Once the entire spacer region between the two stop codons is filled with queueing ribosomes, the queue impinges upon the main AMD1 coding region halting its translation. Phylogenetic analysis suggests that this mechanism is highly conserved in vertebrates and existed in their common ancestor. We propose that this mechanism is used to count and limit the number of protein molecules that can be synthesized from a single mRNA template. It could serve to safeguard from dysregulated translation that may occur owing to errors in transcription or mRNA damage

SelenoDB 1.0 : a database of selenoprotein genes, proteins and SECIS elements

Selenoproteins are a diverse group of proteins usually misidentified and misannotated in sequence databases. The presence of an in-frame UGA (stop) codon in the coding sequence of selenoprotein genes precludes their identification and correct annotation. The in-frame UGA codons are recoded to cotranslationally incorporate selenocysteine, a rare selenium-containing amino acid. The development of ad hoc experimental and, more recently, computational approaches have allowed the efficient identification and characterization of the selenoproteomes of a growing number of species. Today, dozens of selenoprotein families have been described and more are being discovered in recently sequenced species, but the correct genomic annotation is not available for the majority of these genes. SelenoDB is a long-term project that aims to provide, through the collaborative effort of experimental and computational researchers, automatic and manually curated annotations of selenoprotein genes, proteins and SECIS elements. Version 1.0 of the database includes an initial set of eukaryotic genomic annotations, with special emphasis on the human selenoproteome, for immediate inspection by selenium researchers or incorporation into more general databases. SelenoDB is freely available at http://www.selenodb.org

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Quantum exceptional group G_2 and its semisimple conjugacy classes

We construct quantization of semisimple conjugacy classes of the exceptional group G = G2 along with and by means of their representations on highest weight modules over the quantum group Uq(g). With every point t of a fixed maximal torus we associate a highest weight module Mt over Uq(g) and realize the quantized polynomial algebra of the class of t by linear operators on Mt . Quantizations corresponding to points of the same orbit of the Weyl group are isomorphic