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

Centre for Discrete Mathematics and Theoretical Computer ScienceNot Every Domain of a Plain Decompressor Contains the Domain of a Prefix-Free One

question about the relation between plain and prefix Kolmogorov complexities (see their paper in DLT 2008 conference proceedings): does the domain of every optimal decompressor contain the domain of some optimal prefix-free decompressor? In this paper we provide a negative answer to this question.

Arts and Science of Digital Mental Health Support

Globally, over 600 million people are affected by mental health-related issues, according to the recent statistics. Similar to the global scenario, these issues are the single source of disease burden in the UK as well. On the bright side, the boom in the mobile application or `app' market and the paradigm shift in the global disease burden has promoted a growing interest for mental health-related apps. This paper critically explores the mobile application for mental health support to understand what apps are available in the market and their merits and capabilities to meet the need of users' demand. This paper also provides a recommendation for future directions

World Order in the Past, Present, and Future

The present article analyzes the world order in the past, present and future as well as the main factors, foundations and ideas underlying the maintaining and change of the international and global order. The first two sections investigate the evolution of the world order starting from the ancient times up to the late twentieth century. The third section analyzes the origin and decline of the world order based on the American hegemony. The authors reveal the contradictions of the current unipolar world and explain in what way globalization has become more profitable for the developing countries but not for the developed ones. In the paper also explains the strengthening belief that the US leading status will inevitably weaken. In this connection we discuss the alternatives of the American strategy and the possibility of the renaissance of the American leadership. The last section presents a factor analysis which allows stating that the world is shifting toward a new balance of power and is likely to become the world without a leader. The new world order will consist of a number of large blocks, coalitions and countries acting within a framework of rules and mutual responsibility. However, the transition to a new world order will take certain time (about two decades). This period, which we denote as the epoch of new coalitions, will involve a reconfiguration of the World System and bring an increasing turbulence and conflict intensity

Global History and Future World Order

The present article analyzes the world order in the past, present and future as well as the main factors, foundations and ideas underlying the maintaining and change of the international and global order. The first two sections investigate the evolution of the world order starting from the ancient times up to the late twentieth century. The third section analyzes the origin and decline of the world order based on the American hegemony. The authors reveal the contradictions of the current unipolar world and explain in what way globalization has become more profitable for the developing countries but not for the developed ones. The authors also explain the strengthening belief that the US leading status will inevitably weaken. In this connection we discuss the alternatives of the American strategy and the possibility of the renaissance of the American leadership. The last section presents a factor analysis which allows stating that the world is shifting toward a new balance of power and is likely to become the world without a leader. The new world order will consist of a number of large blocks, coalitions and countries acting within a framework of rules and mutual responsibility. However, the transition to a new world order will take certain time (about two decades). This period, which we denote as the epoch of new coalitions, will involve a reconfiguration of the World System and bring an increasing turbulence and conflict intensit

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

Региональные вузы и внешняя миграция выпускников: влияние на сферу экономики (на примере Приморского края)

Primorsky krai, a region located in the Far East of Russia, is suffering a deficit with qualified graduates to facilitate the economy processes. There is a gap between the offering of specific staff to advance the economy and ability of local universities to satisfy it. External migration of graduates, so-called “brain drain”, is a deterrent to development of the economy. Approximately 78 percent of the migration flow are the young people under 35. Along the asymmetry of supply and demand due a professional qualification, the tendency of reducing the universities’ graduates leads to a structural imbalance in the labor market. As a result, the region will only partially be able to meet the needs of economy in higher degree employees. Thus, for regional universities is vital to develop educational programs fit the prospective economic spheres, taking the forecast for the economy and the labor market, at least for 5-7 years. The strategic goal for a core regional university is reducing the imbalance in the labor market and providing the economy with specific knowledge and skills. An axial university, or a core regional university, is becoming a research and project center which able transforming the knowledge into a commercial product. It generates a network of partnerships covering the boundaries of the entire economic system of a region.Primorsky krai, una región ubicada en el Lejano Oriente de Rusia, sufre un déficit con graduados calificados para facilitar los procesos económicos. Existe una brecha entre la oferta de personal específico para avanzar en la economía y la capacidad de las universidades locales para satisfacerla. La migración externa de los graduados, llamada "fuga de cerebros", es un elemento disuasorio para el desarrollo de la economía. Aproximadamente el 78 por ciento del flujo migratorio son los jóvenes menores de 35 años. Junto con la asimetría de la oferta y la demanda debido a una calificación profesional, la tendencia a reducir los graduados de las universidades conduce a un desequilibrio estructural en el mercado laboral. Como resultado, la región solo podrá satisfacer parcialmente las necesidades de la economía de los empleados de mayor grado. Por lo tanto, para las universidades regionales es vital desarrollar programas educativos que se ajusten a las esferas económicas prospectivas, tomando el pronóstico para la economía y el mercado laboral, al menos durante 5-7 años. El objetivo estratégico de una universidad regional central es reducir el desequilibrio en el mercado laboral y proporcionar a la economía conocimientos y habilidades específicas. Una universidad axial, o una universidad regional central, se está convirtiendo en un centro de investigación y proyectos que puede transformar el conocimiento en un producto comercial. Genera una red de asociaciones que cubre los límites de todo el sistema económico de una región. Приморский край, регион, расположенный на Дальнем Востоке России, испытывает дефицит квалифицированных выпускников для содействия экономическим процессам. Существует разрыв между предложением конкретных сотрудников для развития экономики и способностью местных университетов ее удовлетворить. Внешняя миграция выпускников, так называемая «утечка мозгов», является сдерживающим фактором для развития экономики. Приблизительно 78 процентов миграционного потока составляют молодые люди в возрасте до 35 лет. Наряду с асимметрией спроса и предложения, обусловленной профессиональной квалификацией, тенденция сокращения числа выпускников университетов приводит к структурному дисбалансу на рынке труда. В результате регион сможет лишь частично удовлетворить потребности экономики в работниках высшей степени. Таким образом, для региональных вузов жизненно важно разработать образовательные программы, подходящие для перспективных сфер экономики, принимая прогноз по экономике и рынку труда, по крайней мере, на 5-7 лет. Стратегической целью основного регионального университета является снижение дисбаланса на рынке труда и обеспечение экономики конкретными знаниями и навыками. Осевой университет, или основной региональный университет, становится исследовательским и проектным центром, способным превращать знания в коммерческий продукт. Он создает сеть партнерских отношений, охватывающих границы всей экономической системы региона

In-hospital electrical muscle stimulation for patients early after heart failure decompensation: results from a prospective randomised controlled pilot trial.

BACKGROUND Electrical muscle stimulation (EMS) is being evaluated as a possible alternative to exercise training to improve functional capacity in severely deconditioned patients with heart failure (HF). However, there is insufficient data on delayed effects of EMS starting early after decompensation. The aim of this study was to determine the impact of a short inpatient EMS intervention in severely deconditioned patients with HF on functional capacity and quality of life (QoL) over a follow-up period of 1 month. METHODS This is a prospective randomised sham-controlled pilot study. 45 patients hospitalised for decompensated systolic HF (58% men, mean age 66.4±10.2 years) were randomised to EMS (n=22) or sham stimulation (n=23) of lower limbs starting within 3 days after admission. The intervention included 7-10 sessions lasting from 30 to 90 min. The 6-minute walking test distance (6-MWTD), Duke Activity Status Index (DASI) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were evaluated at baseline, discharge and after 1 month. RESULTS All patients completed the programme with good EMS tolerance. 37 patients were included in the final analysis. At discharge, 6-MWTD improved from 206,1±61,3 to 299.5±91 m, DASI from 12.1±5.6 to 18.3±7.2 and MLHFQ from 55.6±8.5 to 34.2±9 with EMS compared with smaller improvements in the sham group (p<0.05 for all). One month after discharge, improvements in the EMS group remained significant for MLHFQ (p=0.004) and DASI (p=0.042) and statistically non-significant for 6-MWTD compared with the sham group. CONCLUSIONS Short-term in-hospital EMS leads to improvements in functional capacity and QoL in selected patients early after HF decompensation that are retained over 1 month after discharge and therefore may serve as initial intervention to improve physical capacity or as a bridge to further conventional exercise training. Larger studies are required to evaluate individual responses to an early initiation of EMS in decompensated HF as well as long-term effects

Glycyl-tRNA synthetase specifically binds to the poliovirus IRES to activate translation initiation

Adaptation to the host cell environment to efficiently take-over the host cell's machinery is crucial in particular for small RNA viruses like picornaviruses that come with only small RNA genomes and replicate exclusively in the cytosol. Their Internal Ribosome Entry Site (IRES) elements are specific RNA structures that facilitate the 5′ end-independent internal initiation of translation both under normal conditions and when the cap-dependent host protein synthesis is shut-down in infected cells. A longstanding issue is which host factors play a major role in this internal initiation. Here, we show that the functionally most important domain V of the poliovirus IRES uses tRNAGly anticodon stem–loop mimicry to recruit glycyl-tRNA synthetase (GARS) to the apical part of domain V, adjacent to the binding site of the key initiation factor eIF4G. The binding of GARS promotes the accommodation of the initiation region of the IRES in the mRNA binding site of the ribosome, thereby greatly enhancing the activity of the IRES at the step of the 48S initiation complex formation. Moonlighting functions of GARS that may be additionally needed for other events of the virus–host cell interaction are discussed