scholarly journals Understanding biases in ribosome profiling experiments reveals signatures of translation dynamics in yeast

2015 ◽  
Author(s):  
Jeffrey A Hussmann ◽  
Stephanie Patchett ◽  
Arlen Johnson ◽  
Sara Sawyer ◽  
William H Press
Keyword(s):  
Negative Correlation ◽  
Ribosome Profiling ◽  
Messenger Rnas ◽  
Translation Rate ◽  
Ribosome Density ◽  
Weak Negative Correlation ◽  
Specific Elongation ◽  
Positive Correlations ◽  
Cognate Trna

Ribosome profiling produces snapshots of the locations of actively translating ribosomes on messenger RNAs. These snapshots can be used to make inferences about translation dynamics. Recent ribosome profiling studies in yeast, however, have reached contradictory conclusions regarding the average translation rate of each codon. Some experiments have used cycloheximide (CHX) to stabilize ribosomes before measuring their positions, and these studies all counterintuitively report a weak negative correlation between the translation rate of a codon and the abundance of its cognate tRNA. In contrast, some experiments performed without CHX report strong positive correlations. To explain this contradiction, we identify unexpected patterns in ribosome density downstream of each type of codon in experiments that use CHX. These patterns are evidence that elongation continues to occur in the presence of CHX but with dramatically altered codon-specific elongation rates. The measured positions of ribosomes in these experiments therefore do not reflect the amounts of time ribosomes spend at each position in vivo. These results suggest that conclusions from experiments in yeast using CHX may need reexamination. In particular, we show that in all such experiments, codons decoded by less abundant tRNAs were in fact being translated more slowly before the addition of CHX disrupted these dynamics.

scholarly journals Inferring translational heterogeneity from ribosome profiling data

2019 ◽  
Author(s):  
Pedro do Couto Bordignon ◽  
Sebastian Pechmann
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Biosynthesis ◽  
Ribosome Profiling ◽  
Translation Regulation ◽  
Messenger Rnas ◽  
Translation Elongation ◽  
Cellular Homeostasis ◽  
Ribosome Density ◽  
Experimental Variability ◽  
Underlying Mechanisms

Translation of messenger RNAs into proteins by the ribosome is the most important step of protein biosynthesis. Accordingly, translation is tightly controlled and heavily regulated to maintain cellular homeostasis. Ribosome profiling (Ribo-seq) has revolutionized the study of translation by revealing many of its underlying mechanisms. However, equally many aspects of translation remain mysterious, in part also due to persisting challenges in the interpretation of data obtained from Ribo-seq experiments. Here, we show that some of the variability observed in Ribo-seq data has biological origins and reflects programmed heterogeneity of translation. To systematically identify sequences that are differentially translated (DT) across mRNAs beyond what can be attributed to experimental variability, we performed a comparative analysis of Ribo-seq data from Saccharomyces cerevisiae and derived a consensus ribosome density profile that reflects consistent signals in individual experiments. Remarkably, the thus identified DT sequences link to mechanisms known to regulate translation elongation and are enriched in genes important for protein and organelle biosynthesis. Our results thus highlight examples of translational heterogeneity that are encoded in the genomic sequences and tuned to optimizing cellular homeostasis. More generally, our work highlights the power of Ribo-seq to understand the complexities of translation regulation.

scholarly journals High-throughput inverse toeprinting reveals the complete sequence dependence of ribosome-targeting antibiotics

2018 ◽  
Author(s):  
Britta Seip ◽  
Guénaёl Sacheau ◽  
Denis Dupuy ◽  
C. Axel Innis
Keyword(s):  
High Throughput ◽  
Quantitative Measure ◽  
Complete Sequence ◽  
Ribosome Profiling ◽  
Sequence Specificity ◽  
Messenger Rnas ◽  
Coding Region ◽  
Sequence Dependence

It has recently become clear that various antibiotics block the translation of bacterial proteins in a sequence-specific manner. In order to understand how this specificity contributes to antibiotic potency and select better antimicrobial leads, new high-throughput tools are needed. Here, we present inverse toeprinting, a new method to map the position of ribosomes arrested on messenger RNAs during in vitro translation. Unlike ribosome profiling, our method protects the entire coding region upstream of a stalled ribosome, making it possible to work with transcript libraries that randomly sample the sequence space. We used inverse toeprinting to characterize the pausing landscape of free and drug-bound bacterial ribosomes engaged in translation. We obtained a comprehensive list of arrest motifs that could be validated in vivo, along with a quantitative measure of their pause strength. Thus, our method provides a highly parallel and scalable means to characterize the sequence specificity of translation inhibitors.

Psoriasis and metabolic syndrome: comorbidity mechanisms

2019 ◽  
Vol 1 (7) ◽  
pp. 34-38
Author(s):  
E. V. Dontsova ◽  
O. Yu. Olisova ◽  
L. S. Kruglova
Keyword(s):  
Metabolic Syndrome ◽  
Negative Correlation ◽  
Inflammatory Cytokine ◽  
Antioxidant Ability ◽  
Weak Correlation ◽  
Strong Negative Correlation ◽  
The Metabolic Syndrome ◽  
Diagnostic Signs ◽  
Weak Negative Correlation ◽  
Correlation Link

Objectives: to study communications of separate components of the metabolic syndrome (MS) and immune and oxidative characteristics of patients with psoriasis in combination with MS. Methods. The research included 312 patients with psoriasis having diagnostic signs of a metabolic syndrome. Biochemical and immunological researches were conducted by means of immunofermental and immunokhemilyuminestsentny analyses. Results. At patients with psoriasis at a combination to MS abdominal obesity, a giperleptinemiya, insulin resistance, high oxidizing potential and hyperactivity of interleukins (ILS) -1β,-6,-8, a factor of a necrosis of tumors an alpha (FNO-α), interferon scale (INF-γ) are noted. the waist circle’ is characteristic direct weak correlation with the pro-inflammatory tsitokina oxidized by lipoproteins of blood (LDL-ok) and with the general oxidizing ability of blood (OOS), weak negative correlation of an indicator - with the general antioxidant ability of blood (OAS) and superoxide dismutase (SOD). The HOMA-IR index has direct correlation link of moderate force with levels of a leptin of blood, LDL-ok, OOS, pro-inflammatory tsitokin, negative correlation of moderate force - with OAS, SOD. At patients with psoriasis with MS direct strong correlation link of level of a leptin of blood with activity of the studied pro-inflammatory cytokine, LDL-ok, OOS moderated is established with the level of insulin in the blood., the HOMA-IR index, strong negative correlation with OAS, SOD. Conclusion. Presence at patients with psoriasis of signs of a metabolic syndrome is followed by increase in activity of immune and inflammatory mechanisms, development of oxidative stress.

DEGRADATION OF MESSENGER RNA IN MAMMALIAN CELLS

1972 ◽  
Vol 71 (2_Suppla) ◽  
pp. S369-S380 ◽  
Author(s):  
Francis T. Kenney ◽  
Kai-Lin Lee ◽  
Charles D. Stiles
Keyword(s):  
Messenger Rna ◽  
Mammalian Cells ◽  
Messenger Rnas ◽  
Tyrosine Transaminase

ABSTRACT Analyses of the response of hydrocortisone-induced tyrosine transaminase in cultured H-35 cells to inhibitors of translation (cycloheximide, puromycin) suggest: (1) that bound ribosomes stabilize messenger RNA in vivo; (2) that messenger is degraded at a rate determined by the rate of translation. Since specific messenger RNAs of mammalian cells are degraded at quite different rates, there may be extensive heterogeneity either in the rate at which ribosomes traverse different messengers or in the number of ribosomes which translate specific messenger RNAs.

Abstract 562: Human Carotid Atherosclerosis Plaque Progression and Vessel Material Stiffness at Follow Up Had Positive Correlation: An in vivo Vessel Stiffness MRI Follow Up Study

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Qingyu Wang ◽  
Dalin Tang ◽  
Gador Canton ◽  
Jian Guo ◽  
Xiaoya Guo ◽  
...  
Keyword(s):  
Negative Correlation ◽  
Material Properties ◽  
Stretch Ratio ◽  
Patient Specific ◽  
Plaque Progression ◽  
Material Stiffness ◽  
Variation Rate ◽  
Vessel Material

It is hypothesized that artery stiffness may be associated with plaque progression. However, in vivo vessel material stiffness follow-up data is lacking in the literature. In vivo 3D multi-contrast and Cine magnetic resonance imaging (MRI) carotid plaque data were acquired from 8 patients with follow-up (18 months) with written informed consent obtained. Cine MRI and 3D thin-layer models were used to determine parameter values of the Mooney-Rivlin models for the 81slices from 16 plaques (2 scans/patient) using our established iterative procedures. Effective Young’s Modulus (YM) values for stretch ratio [1.0,1.3] were calculated for each slice for analysis. Stress-stretch ratio curves from Mooney-Rivlin models for the 16 plaques and 81 slices are given in Fig. 1. Average YM value of the 81 slices was 411kPa. Slice YM values varied from 70 kPa (softest) to 1284 kPa (stiffest), a 1734% difference. Average slice YM values by vessel varied from 109 kPa (softest) to 922 kPa (stiffest), a 746% difference. Location-wise, the maximum slice YM variation rate within a vessel was 306% (139 kPa vs. 564 kPa). Average slice YM variation rate within a vessel for the 16 vessels was 134%. Average variation of YM values from baseline (T1) to follow up (T2) for all patients was 61.0%. The range of the variation of YM values was [-28.4%, 215%]. For progression study, YM increase (YMI=YM T2 -TM T1 ) showed negative correlation with plaque progression measured by wall thickness increase (WTI), (r= -0.6802, p=0.0634). YM T2 showed strong negative correlation with WTI (r= -0.7764, p=0.0235). Correlation between YM T1 and WTI was not significant (r= -0.4353, p= 0.2811). Conclusion In vivo carotid vessel material properties have large variations from patient to patient, along the vessel segment within a patient, and from baseline to follow up. Use of patient-specific, location specific and time-specific material properties could potentially improve the accuracy of model stress/strain calculations.

scholarly journals Repatriation turnover revisited: A focus on South African multinational enterprises

2018 ◽  
Vol 21 (1) ◽  
Author(s):  
Christiaan J. Naude ◽  
A. Johan Vogel
Keyword(s):  
South African ◽  
Quantitative Study ◽  
Negative Correlation ◽  
Multinational Enterprises ◽  
Multinational Enterprise ◽  
First Year ◽  
Turnover Rates ◽  
Expatriate Managers ◽  
Positive Correlations ◽  
Spearman’S Correlation

Background: The topic of repatriation turnover as a major source of concern for repatriates and their multinational enterprise has been covered extensively in the literature over the years, with the literature showing that between 15% and 38% of repatriated expatriates leave the employment of their multinational enterprise within the first year after repatriation. However, no such study has focused on the repatriation of South African expatriates. Aim: The primary aim of this study was to determine if there is a correlation between the repatriation practices of South African multinational enterprises and their repatriation turnover rates. The secondary aim of the study was to determine why repatriated employees leave the employment of South African multinational enterprises. Method: This quantitative study surveyed 41 expatriate managers of South African multinational enterprises, with the Mann-Whitney U test and Spearman’s correlation coefficient being used to test for correlations between the repatriation practices of South African multinational enterprises and their repatriation turnover rates. Results: The results revealed positive correlations between appointing a mentor to an expatriate to assist with the repatriation process, conducting an orientation programme prior to repatriation and supporting the expatriate with various initiatives during repatriation and lower repatriation turnover rates. Meanwhile a negative correlation was found between when a multinational enterprise starts with an orientation programme prior to repatriation and repatriation turnover rates. Conclusion: These findings provide valuable insights for South African multinational enterprises into practices they can employ to reduce their repatriation turnover rates.

scholarly journals The Influence of Prescribed Fire, Habitat, and Weather on Amblyomma americanum (Ixodida: Ixodidae) in West-Central Illinois, USA

Insects ◽  
2018 ◽  
Vol 9 (2) ◽  
pp. 36 ◽  
Author(s):  
Mary Gilliam ◽  
Will Rechkemmer ◽  
Kenneth McCravy ◽  
Seán Jenkins
Keyword(s):  
Leaf Litter ◽  
Negative Correlation ◽  
Coarse Woody Debris ◽  
Woody Debris ◽  
Life Stage ◽  
Amblyomma Americanum ◽  
Sample Period ◽  
Bare Ground ◽  
Tick Abundance ◽  
Weak Negative Correlation

The distribution of Amblyomma americanum (L.) is changing and reports of tick-borne disease transmitted by A. americanum are increasing in the USA. We used flagging to collect ticks, surveyed vegetation and collected weather data in 2015 and 2016. A. americanum dominated collections in both years (97%). Ticks did not differ among burn treatments; however, tick abundance differed between years among total, adult, and larval ticks. Habitat variables showed a weak negative correlation to total ticks in respect to: Shannon diversity index, percent bare ground, perennial cover, and coarse woody debris. Nymphal ticks showed a weak negative correlation to percent bare ground and fewer adults were collected in areas with more leaf litter and coarse woody debris. Conversely, we found larvae more often in areas with more total cover, biennials, vines, shrubs, and leaf litter, suggesting habitat is important for this life stage. We compared weather variables to tick presence and found, in 2015, temperature, precipitation, humidity, and sample period influenced tick collection and were life stage specific. In 2016, temperature, precipitation, humidity, wind, and sample period influenced tick collection and were also life stage specific. These results indicate that spring burns in an oak woodland do not reduce ticks; other variables such as habitat and weather are more influential on tick abundance or presence at different life stages.

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