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

Optimizing the economic information transparency level of high-tech enterprises in the post-industrial globalized economy

Purpose: Managerial conditions of economic operation of a high technology enterprise as it integrates into the global economy that is essentially postindustrial and globalized were considered in this article. Design/Methodology/Approach: An inevitable immersion of the enterprise into the well-developed external infosphere, as well as a membrane borderline between the external and the internal infospheres were shown. The enterprise was represented dually – as both a donor and a recipient of information resources. Findings: An interpretation of the content of the infosphere was presented. Multiple causes of the discrete nature of the enterprise’s infosphere implementation were shown. The concept of “informational economic transparency” of an enterprise was introduced, and multiple components determining transparency levels were described. Practical Implications: The influence of transformations of informational economic transparency of an enterprise on external impacts on it from legal relations parties. Positive and negative effect of increases and decreases in the informational economic transparency of the enterprise were highlighted in the context of its influence on the economic counterpart and conflict-studies situations. The understanding of the specialized control object was provided. The optimizability of a level of the transparency in the aspect of target orientation of the enterprise was demonstrated. Originality/Value: A structural prototype to the primary support managerial toolkit in the shape of a DSS, a recommender system, allowing to conduct required feasibility studies of managerial decisions was proposed.peer-reviewe

Unification and convergence of hierarchic structures such as organizational separations and product projects at creation of recommending decision support systems

Studied the problem of integrated self-management of multilevel hierarchic groups and quasi-groups under modern economic conditions, based on intellectual recommending Decision Support Systems (DSS). Split-level stereotypical linear organizational structures and project organizational quasi-structures involved in implementation of separated product projects and project groups have been conceptually unified. Proved that this unification in question engenders, for each management level, a coordinating inter-project managing system that is toponymical identical to the managing system of this level. Demonstrated that relevant management is organically whole and can be viewed as self-management of a general corporate structure. Discovered that hierarchic economical management can be in principle reduced to a finite sequence of bilevel economical managements of general corporate structures, where the order of hierarchy levels descends from the top level to the bottom one. Presented a schematic description of the basic procedural modes of operation of the respective recommending DSS.peer-reviewe

MeV Electron Irradiation of Ion-Implanted Si-SiO2 Structures

The effect of (10–25) MeV electron irradiation on Si‐SiO2 structures implanted with different ions (Ar, Si, O, B, and P) has been investigated by different methods, such as deep‐level transient spectroscopy (DLTS), thermo‐stimulated current (TSCM), Rutherford backscattering (RBS), and soft X‐ray emission spectroscopy (SXES). It has been shown that in double‐treated Si‐SiO2 structures, the defect generation by high‐energy electrons depends significantly on the location of preliminary implanted ions relative to the Si‐SiO2 interface as well as on the type (n‐ or p‐Si) of silicon wafer. SiO2 surface roughness changes, induced by ion implantation and high‐energy electron irradiation of Si‐SiO2 structures, are observed by the atomic force microscopy (AFM). Si nanoclusters in SiO2 of ion‐implanted Si‐SiO2 structures generated by MeV electron irradiation is also discussed

Концепция государственной управленческой доктрины

The thesis about the priority of such a crisis-generating factor as total management imperfection was postulated. As a selected component of management innovating, it was chosen the initiation of the qualification requirements for a management system by the state through the introduction of the State management doctrine. There is the status idea of this management document and the vision of its heading structure and substantive content.En el presente artículo se postula la tesis sobre la prioridad de un factor generador de crisis como la imperfección total de la gestión. Como componente de la gestión innovadora, se ha seleccionado la iniciación por parte del Estado de los requisitos de cualificación para un sistema de gestión a través de la introducción de la doctrina de gestión pública. En el documento se analiza la idea de gestión, la visión de su estructura de dirección y su contenido sustantivo.Постулирован тезис о приоритетности такого кризисообразующего фактора, как тотальное несовершенство управления. В качестве выделенной компоненты управленческого инновирования выбрано инициирование государством цензовых требований к управляющим системам через привнесение Государственной управленческой доктрины. Сформулирована статусная идея этого задающего управленческого документа и изложено ви́дение его рубрикационной структуры, а также содержательного наполнения

Концепция организации и функционирования интегрированной электронной инфосферы отчётности по результатам научно-исследовательских работ

This article addresses the problem of fragmentation and inaccessibility of research results at various hierarchical levels: in world community, state, industries, corporations, enterprises, etc. in terms of information donors and recipients. It shows the negative consequences of the current information and management situation due to inaccessibility, distortion and incoherence of relevant information, the goal of rationalizing the use of cumulatively accumulated knowledge resources and the components of the formed methodology of rational synergetic integration of local specialized infospheres. This document presents the transition to the global electronic market of results of the performed research and introduction of procedures of mutual ordering of results of research. Furthermore, in the results it proposes to enter a unified description of knowledge. Also, it proposes to position the results of research as objects of intellectual property in order to fix the property rights in relation to them and to evaluate the value characteristics. In addition, the article shows the applicability of a single Infosphere for the examination of the proposed research projects in terms of their relevance and resource intensity. The paper reasons the expediency of the subsequent distribution of the formulated provisions in the field of scientific publications as a whole (including scientific publications on the rights of printed works of all kinds) and the final transition to the knowledge base of civilization. Additionally, it introduces a scheme of information of an open contractual alliance, identifies the most problematic project tasks and gives a list of conceived but not implemented similar projects.Este artículo aborda el problema de la fragmentación e inaccesibilidad de los resultados de las investigaciones en varios niveles jerárquicos: a nivel mundial, a nivel estatal, en las industrias, en las empresas, etc., en términos de donantes y receptores de información. El documento muestra las consecuencias negativas de la situación actual de la información y su gestión debido a su inaccesibilidad, su distorsión, su incoherencia y al objetivo de racionalizar el uso de los recursos acumulados de conocimientos y los componentes de la metodología formada de integración sinérgica racional de las esferas locales especializadas. Este documento presenta la transición al mercado electrónico global de los resultados de la investigación realizada y la introducción de procedimientos de ordenamiento mutuo de los resultados de las investigaciones. Además, en los resultados propone introducir una descripción unificada de los conocimientos. Asimismo, propone posicionar los resultados de las investigaciones como objetos de propiedad intelectual para fijar los derechos en relación a ellos y evaluar las características de valor. Además, el artículo muestra la aplicabilidad de una sola infoesfera para el examen de los proyectos de investigación propuestos en términos de su relevancia e intensidad de recursos. El documento explica la conveniencia de la posterior distribución de las disposiciones formuladas en el ámbito de las publicaciones científicas en su conjunto (incluyendo aquellas sobre los derechos de las obras impresas de cualquier tipo) y la transición final a la base de conocimientos de la civilización. Además, introduce un esquema de información de una alianza contractual abierta, identifica las tareas más problemáticas de los proyectos y proporciona una lista de proyectos similares concebidos, pero no implementados.Este artigo aborda o problema da fragmentação e inacessibilidade dos resultados da investigação a vários níveis hierárquicos: a nível global, a nível estatal, nas indústrias, nas empresas, etc., em termos de doadores e receptores de informação. O documento mostra as conseqüências negativas da situação atual da informação e sua gestão devido a sua inacessibilidade, sua distorção, sua incoerência e o objetivo de racionalizar o uso de recursos de conhecimento acumulados e os componentes da metodologia formada de integração sinérgica racional de esferas locais especializadas. Este documento apresenta a transição para um mercado electrónico global para os resultados da investigação realizada e a introdução de procedimentos para a gestão mútua dos resultados da investigação. Além disso, propõe nos resultados a introdução de uma descrição unificada dos conhecimentos. Propõe igualmente posicionar os resultados da investigação como objectos de propriedade intelectual, a fim de estabelecer direitos em relação aos mesmos e avaliar as características do valor. Além disso, o artigo mostra a aplicabilidade de uma única infosfera para o exame dos projectos de investigação propostos em termos da sua relevância e intensidade de recursos. O documento explica a conveniência da posterior distribuição das disposições formuladas no campo das publicações científicas como um todo (incluindo as relativas aos direitos das obras impressas de qualquer tipo) e a transição final para a base de conhecimento da civilização. Além disso, introduz um sistema de informação de uma aliança contratual aberta, identifica as tarefas de projecto mais problemáticas e fornece uma lista de projectos semelhantes concebidos mas não executados.Выделена проблема разрозненности и труднодоступности результатов научно-исследовательских работ на различных иерархических уровнях: на уровнях мирового сообщества, государства, отраслей, корпораций, предприятий и т.д. в части информационных доноров и реципиентов. Показаны негативные последствия сложившейся информационно-управленческой ситуации, обусловленные недоступностью, искажённостью и несвязанностью соответствующих сведений. Декларирована цель рационализации использования кумулятивно накапливаемых ресурсов знаний. Предложено использование компонент формируемой методологии рациональной синергетической интеграции локальных специализированных инфосфер. Обоснован переход к глобальному электронному рынку результатов выполненных НИР и введение процедур взаимной упорядоченности результатов НИР. Для результатов НИР предложено вводить унифицированное описание знаний. В рамках него - позиционировать результаты НИР как объекты интеллектуальной собственности, фиксировать права собственности в отношении них и оценивать стоимостные характеристики. Показана применимость единой инфосферы для проведения экспертиз проектов предлагаемых НИР в части их актуальности и ресурсоёмкости. Аргументирована целесообразность последующего распространения сформулированных положений на область научных изданий в целом (в том числе, включая научные публикации на правах печатных работ всех видов) и конечный переход к базе знаний цивилизации. Введена схема информационного открытого договорного альянса. Выделены наиболее проблемные проектные задачи. Приведён перечень задуманных, но не реализованных сходственных проектов

A study of the influence of soft particle size and concentration on strength and strain properties of ceramic composites

In the paper a theoretical study of the influence of particle distribution of soft inclusions-agglomerates in a ceramic composite sample on its strength and deformation characteristics was carried out. A movable cellular automaton method was used to simulate a uniaxial compression test of two-dimensional rectangle composite samples. It was found that the average size of inclusions agglomerate-while maintaining the volume fraction of the particles of the soft phase has little effect on the strength and deformation properties of the simulated samples. The simulation results can help to understand the mechanical properties of such objects within any generalized model

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

Differential Expression of CHL1 Gene during Development of Major Human Cancers

CHL1 gene (also known as CALL) on 3p26.3 encodes a one-pass trans-membrane cell adhesion molecule (CAM). Previously CAMs of this type, including L1, were shown to be involved in cancer growth and metastasis.We used Clontech Cancer Profiling Arrays (19 different types of cancers, 395 samples) to analyze expression of the CHL1 gene. The results were further validated by RT-qPCR for breast, renal and lung cancer. Cancer Profiling Arrays revealed differential expression of the gene: down-regulation/silencing in a majority of primary tumors and up-regulation associated with invasive/metastatic growth. Frequent down-regulation (>40% of cases) was detected in 11 types of cancer (breast, kidney, rectum, colon, thyroid, stomach, skin, small intestine, bladder, vulva and pancreatic cancer) and frequent up-regulation (>40% of cases)--in 5 types (lung, ovary, uterus, liver and trachea) of cancer. Using real-time quantitative PCR (RT-qPCR) we found that CHL1 expression was decreased in 61% of breast, 60% of lung, 87% of clear cell and 89% papillary renal cancer specimens (P<0.03 for all the cases). There was a higher frequency of CHL1 mRNA decrease in lung squamous cell carcinoma compared to adenocarcinoma (81% vs. 38%, P = 0.02) without association with tumor progression.Our results suggested that CHL1 is involved in the development of different human cancers. Initially, during the primary tumor growth CHL1 could act as a putative tumor suppressor and is silenced to facilitate in situ tumor growth for 11 cancer types. We also suggested that re-expression of the gene on the edge of tumor mass might promote local invasive growth and enable further metastatic spread in ovary, colon and breast cancer. Our data also supported the role of CHL1 as a potentially novel specific biomarker in the early pathogenesis of two major histological types of renal cancer