404 research outputs found
Image Reconstruction in Multi-Channel Model Under Gaussian Noise
The image reconstruction from noisy data is studied. A nonparametric boundary function is estimated from observations in N independent channels in Gaussian white noise. In each channel the image and the background intensities are unknown. They define a non-identifiable nuisance parameter that slows down the typical minimax rate of convergence. The large sample asymptotics of the minimax risk is found and an asymptotically optimal estimator for boundary function is suggested
Structural aspects of translation termination on the ribosome
Translation of genetic information encoded in messenger RNAs into polypeptide sequences is carried out by ribosomes in all organisms. When a full protein is synthesized, a stop codon positioned in the ribosomal A site signals termination of translation and protein release. Translation termination depends on class I release factors. Recently, atomic-resolution crystal structures were determined for bacterial 70S ribosome termination complexes bound with release factors RF1 or RF2. In combination with recent biochemical studies, the structures resolve long-standing questions about translation termination. They bring insights into the mechanisms of recognition of all three stop codons, peptidyl-tRNA hydrolysis, and coordination of stop-codon recognition with peptidyl-tRNA hydrolysis. In this review, the structural aspects of these mechanisms are discussed
Analysis and Design of Simulation Experiments with Linear Approximation Models
There is a necessity in a number of IIASA's researches to deal with analyzing the properties of the computerized versions of complex models. The use of simulation experiments is one of the most successful tools in solving this problem. In this paper, the package of programs for the design and analysis of simulation experiments is described. The package was prepared in the All-Union Institute of Systems Studies in Moscow. It is one of the first attempts in this field, and the authors did not expect to have constructed a very comprehensive variant, but hope that more experience, remarks and critiques will help to improve and extend the package in a most useful and practical way
Mechanism of premature translation termination on a sense codon
Accurate translation termination by release factors (RFs) is critical for the integrity of cellular proteomes. Premature termination on sense codons, for example, results in truncated proteins, whose accumulation could be detrimental to the cell. Nevertheless, some sense codons are prone to triggering premature termination, but the structural basis for this is unclear. To investigate premature termination, we determined a cryo-EM structure of the Escherichia coli 70S ribosome bound with RF1 in response to a UAU (Tyr) sense codon. The structure reveals that RF1 recognizes a UAU codon similarly to a UAG stop codon, suggesting that sense codons induce premature termination because they structurally mimic a stop codon. Hydrophobic interaction between the nucleobase of U3 (the third position of the UAU codon) and conserved Ile 196 in RF1 is important for misreading the UAU codon. Analyses of RNA binding in ribonucleoprotein complexes or by amino acids reveal that Ile-U packing is a frequent protein-RNA binding motif with key functional implications. We discuss parallels with eukaryotic translation termination by the release factor eRF1
Termi-Luc: a versatile assay to monitor full-protein release from ribosomes
Termination of protein biosynthesis is an essential step of gene expression, during which a complete functional protein is released from the ribosome. Premature or inefficient termination results in truncated, non-functional or toxic proteins that may cause disease. Indeed, more than 10% of human genetic diseases are caused by nonsense mutations leading to premature termination. Efficient and sensitive approaches are required to study eukaryotic termination mechanisms and to identify potential therapeutics that modulate termination. Canonical radioactivity-based termination assays are complex, report on a short peptide release, and are incompatible with high-throughput screening. Here we describe a robust and simple in vitro assay to study the kinetics of full-protein release. The assay monitors luminescence upon release of nanoluciferase from a mammalian pre-termination complex. The assay can be used to record time-progress curves of protein release in a high-throughput format, making it optimal for studying release kinetics and for high-throughput screening for small molecules that modulate the efficiency of termination
ΠΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΡΠΈΠ·ΠΈΠΊΠΎ-Ρ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠ²ΠΎΠΉΡΡΠ² Π±ΠΈΠΎΡΠΎΠ²ΠΌΠ΅ΡΡΠΈΠΌΡΡ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΎΠ² ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΈΠΎΠ½Π½ΠΎΠΉ ΠΈΠΌΠΏΠ»Π°Π½ΡΠ°ΡΠΈΠΈ
Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ Π±ΡΠ»ΠΎ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΈΠΎΠ½Π½ΠΎΠΉ ΠΈΠΌΠΏΠ»Π°Π½ΡΠ°ΡΠΈΠΈ ΠΈΠΎΠ½ΠΎΠ² ΡΠ΅ΡΠ΅Π±ΡΠ°, ΡΠΈΠ½ΠΊΠ° ΠΈ ΠΌΠ°Π³Π½ΠΈΡ Ρ ΡΠΊΡΠΏΠΎΠ·ΠΈΡΠΈΠΎΠ½Π½ΡΠΌΠΈ Π΄ΠΎΠ·Π°ΠΌΠΈ 110β^ ΠΈ ΠΈΠΎΠ½/ΡΠΌ^ Π½Π° ΠΏΠΎΠ²Π΅ΡΡ
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