Eukaryotic translation initiation machinery can operate in a prokaryotic-like mode without eIF2

Unlike prokaryotes, a specialized eukaryotic initiation factor 2 (eIF2), in the form of the ternary complex eIF2*GTP*Met-tRNAiMet is utilized to deliver the initiator tRNA to the ribosome within all eukaryotic cells1. Phosphorylation of eIF2 is known to be central to the global regulation of protein synthesis under stress conditions and infection2. Another distinctive feature of eukaryotic translation is scanning of mRNA 5'-leaders, whose origin in evolution may be relevant to the appearance of eIF2 in eukaryotes. Translation initiation on the hepatitis C virus (HCV) internal ribosome entry site (IRES) occurs without scanning3,4. Whether these unique features of the HCV IRES account for the formation of the final 80S initiation complex is unknown. Here we show that the HCV IRES-directed translation can occur without either eIF2 or its GTPase activating protein eIF5. In addition to the general eIF2- and eIF5-dependent pathway of 80S complex assembly, the HCV IRES makes use of a prokaryotic-like pathway which involves eIF5B, the analogue of bacterial IF25,6, instead of eIF2. This switch from a eukaryotic-like mode of AUG selection to a "bacterial" one occurs when eIF2 is inactivated by phosphorylation, a way with which host cells counteract infection. The relative resistance of HCV IRES-directed translation to eIF2 phosphorylation may represent one more line of defense used by this virus against host antiviral responses and can contribute to the well known resistance of HCV to interferon based therapy

Classification of bad pixels of the Hawaii-2RG detector of the ASTROnomical NearInfraRed CAMera

ASTRONIRCAM is an infrared camera-spectrograph installed at the 2.5-meter telescope of the CMO SAI. The instrument is equipped with the HAWAII-2RG array. A bad pixels classification of the ASTRONIRCAM detector is proposed. The classification is based on histograms of the difference of consecutive non-destructive readouts of a flat field. Bad pixels are classified into 5 groups: hot (saturated on the first readout), warm (the signal accumulation rate is above the mean value by more than 5 standard deviations), cold (the rate is under the mean value by more than 5 standard deviations), dead (no signal accumulation), and inverse (having a negative signal accumulation in the first readouts). Normal pixels of the ASTRONIRCAM detector account for 99.6% of the total. We investigated the dependence between the amount of bad pixels and the number of cooldown cycles of the instrument. While hot pixels remain the same, the bad pixels of other types may migrate between groups. The number of pixels in each group stays roughly constant. We found that the mean and variance of the bad pixels amount in each group and the transitions between groups do not differ noticeably between normal or slow cooldowns.Comment: 11 pages, 7 Figures, 3 table

Assessment of News Items Objectivity in Mass Media of Countries with Intelligence Systems: the Brexit Case

The role of mass media in society keeps the problem of manipulative influence distinction and the contiguous phenomena, chief among which is objectivity and authenticity of news items, current. The research provides a detailed study of the information broadcasting mechanisms in the media area, defines the problems, impeding an impersonal reproduction and disclosure of information, clarifies the verification methods, and gives their topology. In this research, we examined how the mass media of different countries presented the same event to the public. The publications of four mass media, concerning such an event as the withdrawal of the United Kingdom from the European Union (Brexit), have been determined as an object of the analysis. The chosen mass media refer to the countries, which are not the direct participants of that process: Russia, the USA, and Ukraine. D. Brewer’s criteria were used to define the objectivity of the news items. A relative sentiment of the news, which became the objective analysis basis, has been identified using linguistic rate with Eureka Engine intelligence system. The obtained results predominantly confirmed the hypothesis, that the mass media of different countries would represent the process of the UK withdrawal from the EU according to the country’s policy and interpret the facts in their favor. All the four mass media demonstrate the partiality when broadcasting the current situation in the matter of Brexit. The concepts being the semantic kernel elements of mass media publications have emotional coloring. The sentiment analysis of the publications resulted in the conclusion that only one of the four mass media gave a neutral assessment of the Brexit situation. The other three held to the political stance of their edition or government. The research results indicate that the problem of mass media objectivity remains relevant. The correctional impact on public opinion through mass media is extremely high. Therefore, forming the personal attitude toward the situation or event should occur with using several verifications methods and mass media sources at once

The 5′ untranslated region of Apaf-1 mRNA directs translation under apoptosis conditions via a 5′ end-dependent scanning mechanism

AbstractWe have previously shown that translation driven by the 5′ UTR of Apaf-1 mRNA is relatively efficient in the absence of m7G-cap, but no IRES is involved. Nevertheless, it may be speculated that a “silent” IRES is activated under apoptosis conditions. Here, we show that translation of the mRNA with the Apaf-1 5′ UTR is relatively resistant to apoptosis induced by etoposide when eIF4E is sequestered by 4E-BP and eIF4G is partially cleaved. However, translation under these conditions remains governed by 5′ end-dependent scanning. We hypothesize that the observed phenomenon is based on the intrinsic low cap-dependence of the Apaf-1 5′ UTR

Insights into the mechanisms of eukaryotic translation gained with ribosome profiling

The development of Ribosome Profiling (RiboSeq) has revolutionized functional genomics. RiboSeq is based on capturing and sequencing of the mRNA fragments enclosed within the translating ribosome and it thereby provides a â snapshotâ of ribosome positions at the transcriptome wide level. Although the method is predominantly used for analysis of differential gene expression and discovery of novel translated ORFs, the RiboSeq data can also be a rich source of information about molecular mechanisms of polypeptide synthesis and translational control. This review will focus on how recent findings made with RiboSeq have revealed important details of the molecular mechanisms of translation in eukaryotes. These include mRNA translation sensitivity to drugs affecting translation initiation and elongation, the roles of upstream ORFs in response to stress, the dynamics of elongation and termination as well as details of intrinsic ribosome behavior on the mRNA after translation termination. As the RiboSeq method is still at a relatively early stage we will also discuss the implications of RiboSeq artifacts on data interpretation