33 research outputs found

    Poly(A) binding protein, C-terminally truncated by the hepatitis A virus proteinase 3C, inhibits viral translation

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    Proteolytic cleavage of translation initiation factors is a means to interfere with mRNA circularization and to induce translation arrest during picornaviral replication or apoptosis. It was shown that the regulated cleavages of eukaryotic initiation factor (eIF) 4G and poly(A)-binding protein (PABP) by viral proteinases correlated with early and late arrest of host cap-dependent and viral internal ribosome entry site (IRES)-dependent translation, respectively. Here we show that in contrast to coxsackievirus, eIF4G is not a substrate of proteinase 3C of hepatitis A virus (HAV 3Cpro). However, PABP is cleaved by HAV 3Cpro in vitro and in vivo, separating the N-terminal RNA-binding domain (NTD) of PABP from the C-terminal protein-interaction domain. In vitro, NTD has a dominant negative effect on HAV IRES-dependent translation and an enhanced binding affinity to the RNA structural element pY1 in the 5′ nontranslated region of the HAV RNA that is essential for viral genome replication. The results point to a regulatory role of PABP cleavage in RNA template switching of viral translation to RNA synthesis

    Time-dependent increase in ribosome processivity

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    We created a novel tripartite reporter RNA to separately and simultaneously examine ribosome translation rates at the 5′- and 3′-ends of a large open reading frame (ORF) in vitro in HeLa cell lysates. The construct contained Renilla luciferase (RLuc), β-galactosidase and firefly luciferase (FLuc) ORFs linked in frame and separated by a viral peptide sequence that causes cotranslational scission of emerging peptide chains. The length of the ORF contributed to low ribosome processivity, a low number of initiating ribosomes completing translation of the entire ORF. We observed a time-dependent increase in FLuc production rate that was dependent on a poly(A) tail and poly(A)-binding protein, but was independent of eIF4F function. Stimulation of FLuc production occurred earlier on shorter RNA templates. Cleavage of eIF4G at times after ribosome loading on templates occurred did not cause immediate cessation of 5′-RLuc translation; rather, a delay was observed that shortened when shorter templates were translated. Electron microscopic analysis of polysome structures in translation lysates revealed a time-dependent increase in ribosome packing and contact that correlated with increased processivity on the FLuc ORF. The results suggest that ORF transit combined with PABP function contribute to interactions between ribosomes that increase or sustain processivity on long ORFs

    Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

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    Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

    Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

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    Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

    Foreign Language Teacher Education In Finland And Turkey: A Comparative Glance At Teaching Practice

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    İyi bir öğretmen yetiştirme sistemi kuramsal bilgi ve uygulamayı bir araya getirmelidir ve öğretmenlik uygulaması nitelikliöğretmenler yetiştirmede önemli bir role sahiptir. Türkiye ve Finlandiya’daki İngilizce öğretmeni yetiştirme sistemininöğretmenlik uygulaması kısmını karşılaştırmak ve Türkiye için önerilerde bulunmayı amaçlayan bu çalışma birkarşılaştırmalı eğitim araştırmasıdır. Finlandiya’da öğretmenlik uygulaması dört dönemi kapsarken, Türkiye’de bu süreçsadece iki dönem sürmektedir. Süreleri farklı olsa da her iki ülkede de kısıtlı sorumluluk ile danışman öğretmenin sistemligözetimi altında gözlemler yaparak başlayan öğretmenlik uygulaması süreci kısa öğretim uygulamaları yaparak devam ederve öğretmen adayının sınıf içi sorumluluğunun arttırılarak düzenli ve uzun süreli uygulamalar yapmasıyla sona erer.Finlandiya’da öğretmenlik uygulaması eğitim fakültelerine bağlı uygulama okullarında, Türkiye’de ise belli kriterlerisağlayan herhangi bir okulda yapılmaktadır. İki ülkenin öğretmenlik uygulaması arasındaki önemli farklardan birisi budur.Finlandiya ve Türkiye’de benzer şekilde öğretmenlik uygulamasının dört bileşeni öğretmen adayının kendisi, diğer öğretmenadayları, eğitim fakültesindeki danışman öğretim üyesi ve okuldaki danışman öğretmendir ve her iki ülkede de bu dörtbileşenin arasındaki etkileşimin ve iletişim en iyi şekilde sağlanması gerektiğine vurgu yapılmaktadır.An effective teacher education system should unite theoretical knowledge and practice together and teaching practice hasvital importance in training qualified teachers. This study is a comparative education research, which aims to compare theteaching practice period of foreign language teacher education systems in Finland and Turkey and to offer suggestions forTurkey. While teaching practice period lasts for four terms in Finland, it only lasts for two terms in Turkey. Althoughduration of these periods varies, teaching practice period, which starts with observations under the strict supervision ofcooperating teacher and with limited responsibility, goes on with short teaching performances and finishes with extended andregular teaching performances with high responsibility in two countries. While in Finland, teaching practice is done inpractice schools of education faculties, in Turkey teaching practice is done in any school which meets some criteria. This isone of the most important differences between two countries. In Finland and Turkey, teaching practice period has fourcomponents. These are teacher candidate, other teacher candidates, university supervisor from faculty of education andcooperating teacher from practice school. In both countries, it is emphasized that interaction and communication among thestakeholders need to be ensured

    Serum irisin and adropin levels may be predictors for coronary artery ectasia

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    Background There is strong evidence that oxidative stress and inflammation may contribute to the coronary artery ectasia (CAE) pathophysiology. Recent studies have shown that serum irisin and adropin levels are associated with oxidative stress and inflammation. In the light of this information, we aimed to investigate the possible relationship between serum irisin, adropin levels and CAE. Patients & Methods A total of 50 consecutive patients with CAE and 50 consecutive patients with normal coronary anatomy (NCA) were enrolled into the study. Serum irisin, adropin and other clinical parameters were compared between groups. Results Adropin (p < .001) and irisin (p < .001) levels were lower in the CAE group. Low adropin (p = .014) and irisin (p < .001) levels were detected as an independent risk factor for CAE in multiple regression analysis. Receiver operating characteristic curve analysis showed that serum adropin (p < .001) and irisin (p < .001) leves was significant predictor of CAE. Conclusions The results of this study showed that serum irisin and adropin level was lower in the CAE group than in the NCA group. Irisin and adropin could play a role in the pathogenesis of CAE

    Parameter Optimization Of PI Controller By PSO For Optimal Controlling Of A Buck Converter's Output

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    2017 International Artificial Intelligence and Data Processing Symposium (IDAP) -- SEP 16-17, 2017 -- Malatya, TURKEY -- IEEE Turkey Sect, Anatolian SciThis study focuses on the Buck Converter which is one of the Power Electronic topologies. The output of converter is tried to keep under control. The control is implemented via discrete time PI algorithm. In order to maintain efficiency of control process at high level, the controller parameters of Kp and Ki are optimized with the help of Particle Swarm Optimization (PSO) which is an iterative algorithm. The study is simulated in Matlab-Simulink and the results of control process are discussed.WOS:0004268687000742-s2.0-8503990032
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