scholarly journals Integrated analysis of directly captured microRNA targets reveals the impact of microRNAs on mammalian transcriptome

2019 ◽  
Author(s):  
Glen A. Bjerke ◽  
Rui Yi
Keyword(s):  
Epithelial Cells ◽  
Global Analysis ◽  
Integrated Analysis ◽  
Mrna Levels ◽  
Mrna Targets ◽  
Cancer Cell Adhesion ◽  
Bona Fide ◽  
Highly Correlated ◽  
The Impact ◽  
Mammalian Transcriptome

AbstractMicroRNA (miRNA)-mediated regulation is widespread, relatively mild but functionally important. Despite extensive efforts to identify miRNA targets, it remains unclear how miRNAs bind to mRNA targets globally and how changes in miRNA levels affects the transcriptome. Here we apply an optimized method for simultaneously capturing miRNA and targeted RNA sites to wildtype, miRNA knockout and induced epithelial cells. We find that abundantly expressed miRNAs can bind to thousands of different transcripts and many different miRNAs can regulate the same gene. Although mRNA sites that are bound by miRNAs and also contain matches to seed sequences confer the strongest regulation, ∼50% of miRNAs bind to RNA regions without seed matches. In general, these bindings have little impact on mRNA levels and reflect a scanning activity of miRNAs. In addition, different miRNAs have different preferences to seed matches and 3’end base-pairing. For a single miRNA, the effectiveness of mRNA regulation is highly correlated with the number of captured miRNA:RNA fragments. Notably, elevated miRNA expression effectively represses existing targets with little impact on newly recognized targets. Global analysis of directly captured mRNA targets reveals pathways that are involved in cancer, cell adhesion and signaling pathways are highly regulated by many different miRNAs in epithelial cells. Comparison between experimentally captured and TargetScan predicted targets indicates that our approach is more effective to identify bona fide targets by reducing false positive and negative predictions. This study reveals the global binding landscape and impact of miRNAs on mammalian transcriptome.

scholarly journals Cytokine-Mediated Downregulation of Coxsackievirus-Adenovirus Receptor in Endothelial Cells

2004 ◽  
Vol 78 (15) ◽  
pp. 8047-8058 ◽  
Author(s):  
Theresa Vincent ◽  
Ralf F. Pettersson ◽  
Ronald G. Crystal ◽  
Philip L. Leopold
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cells ◽  
Protein Expression ◽  
Western Blot ◽  
Inflammatory Cytokines ◽  
Cell Physiology ◽  
Mrna Levels ◽  
Cytokine Treatment ◽  
Adenovirus Receptor ◽  
The Impact

ABSTRACT Endothelial cells have the ability to change their complement of cell surface proteins in response to inflammatory cytokines. We hypothesized that the expression of the coxsackievirus-adenovirus receptor (CAR), a viral receptor and putative cell-cell adhesion molecule, may be altered during the response of endothelial cells to inflammation. To test this hypothesis, we evaluated CAR protein and mRNA levels in human umbilical vein endothelial cells after they were exposed to tumor necrosis factor alpha, gamma interferon, or a combination of the two cytokines. Flow cytometric and Western blot analyses indicated that cytokine treatment led to a synergistic decrease in CAR protein expression. A Western blot analysis showed that CAR levels decreased to 16% ± 4% or 1% ± 4% of the CAR protein levels in untreated cells with either 24 or 48 h of cytokine treatment, respectively. Quantitative reverse transcription-PCR demonstrated that the combination treatment caused CAR mRNA levels to decrease to 21% ± 12% or 5% ± 3% of the levels in untreated cells after a 24- or 48-h cytokine treatment, respectively. Reduced CAR expression led to a decrease in adenovirus (Ad) binding of 80% ± 3% (compared with untreated endothelial cells), with a subsequent decrease in Ad-mediated gene transfer that was dependent on the dose and duration of cytokine treatment but not on the dose of Ad. A similar decrease in CAR protein level and susceptibility to Ad infection was observed in human microvascular endothelial cells, while CAR expression on normal human bronchial epithelial cells or A549 lung epithelial cells was less affected by cytokine treatments. Taken together, the data demonstrate that inflammatory cytokines decrease CAR mRNA and protein expression with a concomitant decrease in Ad binding, reflecting the impact of cell physiology on the function of CAR and the potential effect of inflammation on the ability of Ad to transfer genes to endothelial cells.

scholarly journals An ANP-Balanced Scorecard Methodology to Quantify the Impact of TQM Elements on Organisational Strategic Sustainable Development: Application to an Oil Firm

2020 ◽  
Vol 12 (15) ◽  
pp. 6207
Author(s):  
Carla Andrade Arteaga ◽  
Raúl Rodríguez-Rodríguez ◽  
Juan-José Alfaro-Saiz ◽  
María-José Verdecho
Keyword(s):  
Sustainable Development ◽  
Balanced Scorecard ◽  
Global Analysis ◽  
Building Blocks ◽  
Analytic Network Process ◽  
Management Tool ◽  
Integrated Analysis ◽  
Total Quality ◽  
Strategic Objectives ◽  
The Impact

This paper presents a methodology for quantifying the impact of Total Quality Management TQM elements on organisational strategic sustainable development, integrating within it the well-known strategic management tool of Balanced Scorecard to represent the strategic part of the organisations, and the multi-criteria technique Analytic Network Process (ANP) to identify and quantify the mentioned impact. Additionally, the application of TQM generates directly some organisational improvements—or outputs—which help model a decisional ANP network constituted by all three building blocks—TQM elements, strategic objectives and outputs—and their interrelationships. The application of the methodology to an oil firm carried out by an expert group offered, from a decision-making point of view, meaningful results that were developed following three different analyses: Global analysis, which identified the global weight of each variable; Analysis of Influences, which established sound cause–effect relationships between the variables to identify the elements—TQM and outputs—that are more important to achieve the strategic objectives; and the Integrated analysis, which pointed out which TQM elements should be fostered in order to achieve the most important sustainable strategic objectives. Finally, it is suggested to apply the methodology to other types of size and sector activity organisations, as well as to use other techniques that introduce fuzzy elements.

scholarly journals The impact of acid stress on escherichia coli O157:H7 virulence

2021 ◽  
Author(s):  
Belinda House
Keyword(s):  
Escherichia Coli ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Host Cell ◽  
Virulence Factors ◽  
Acid Stress ◽  
Mrna Levels ◽  
E Coli ◽  
Acid Shock ◽  
The Impact

Escherichia coli 0157:H7 infection is a leading cause of hemorrhagic colitis, and hemolytic uremic syndrome. Many opportunities for acid stress exposure exist for this food and waterborne pathogen, including gastric acid shock. Yet little is known how this affects E.coli 0157:H7 virulence. The effect of various acid stress protocols on E. coli 0157:H7 survival, verotoxin production, and the ability to adhere to host epithelial cells was examined. Brief acid shock alone at pH 3.0 decreased the host cell adhesion capability by a factor of 4.3-4.8, yet when the acid shock was preceded by adaptation at pH 5.0, a 1.6-3.2 fold enhanced adhesion of surviving organisms to epithelial cells relative to unstressed organisms was observed. However, acid stress did not affect verotoxin production. Pretreatment of acid stressed bacteria with erythromycin eliminated the acid-induced adhesion enhancement, suggesting that protein synthesis is a requirement for the enhanced adhesion observed with acid-adapted acid-shocked E.coli 0157:H7. Real time PCR analysis of locus for enterocyte effacement (LEE)-encoded virulence factors, intimin and EspA, revealed no significant upregulation for the acid stress treatments associated with the increased host cell adhesion. On the contrary, elevated mRNA levels for both intimin and EspA were observed for bacteria subjected to brief acid shock alone even though the host-cell adhesion was significatly decreased with these treatments. These results suggest that complex regulation mechanisms for LEE encoded virulence factors exists and that E. coli 0157:H7 virulence can be enhanced after acid stress through increased adhesion to host epithelial cells.

scholarly journals Integrated microRNA and mRNA expression profiling in a rat colon carcinogenesis model: effect of a chemo-protective diet

2011 ◽  
Vol 43 (10) ◽  
pp. 640-654 ◽  
Author(s):  
Manasvi S. Shah ◽  
Scott L. Schwartz ◽  
Chen Zhao ◽  
Laurie A. Davidson ◽  
Beiyan Zhou ◽  
...  
Keyword(s):  
Fish Oil ◽  
Mrna Expression ◽  
Gene Set Enrichment Analysis ◽  
Cumulative Distribution ◽  
Rat Colon ◽  
Saline Control ◽  
Integrated Analysis ◽  
Mrna Levels ◽  
Network Analyses ◽  
The Impact

We have recently demonstrated that nutritional bioactives (fish oil and pectin) modulate microRNA molecular switches in the colon. Since integrated analysis of microRNA and mRNA expression at an early stage of colon cancer development is lacking, in this study, four computational approaches were utilized to test the hypothesis that microRNAs and their posttranscriptionally regulated mRNA targets, i.e., both total mRNAs and actively translated mRNA transcripts, are differentially modulated by carcinogen and diet treatment. Sprague-Dawley rats were fed diets containing corn oil ± fish oil with pectin ± cellulose and injected with azoxymethane or saline (control). Colonic mucosa was assayed at an early time of cancer progression, and global gene set enrichment analysis was used to obtain those microRNAs significantly enriched by the change in expression of their putative target genes. In addition, cumulative distribution function plots and functional network analyses were used to evaluate the impact of diet and carcinogen combination on mRNA levels induced via microRNA alterations. Finally, linear discriminant analysis was used to identify the best single-, two-, and three-microRNA combinations for classifying dietary effects and colon tumor development. We demonstrate that polysomal profiling is tightly related to microRNA changes when compared with total mRNA profiling. In addition, diet and carcinogen exposure modulated a number of microRNAs (miR-16, miR-19b, miR-21, miR26b, miR27b, miR-93, and miR-203) linked to canonical oncogenic signaling pathways. Complementary gene expression analyses showed that oncogenic PTK2B, PDE4B, and TCF4 were suppressed by the chemoprotective diet at both the mRNA and protein levels.

scholarly journals Integrated analysis of directly captured microRNA targets reveals the impact of microRNAs on mammalian transcriptome

RNA ◽  
2020 ◽  
Vol 26 (3) ◽  
pp. 306-323 ◽  
Author(s):  
Glen A. Bjerke ◽  
Rui Yi
Keyword(s):  
Integrated Analysis ◽  
Microrna Targets ◽  
The Impact ◽  
Mammalian Transcriptome

scholarly journals Global analysis of somatic structural genomic alterations and their impact on gene expression in diverse human cancers

2016 ◽  
Vol 113 (48) ◽  
pp. 13768-13773 ◽  
Author(s):  
Babak Alaei-Mahabadi ◽  
Joydeep Bhadury ◽  
Joakim W. Karlsson ◽  
Jonas A. Nilsson ◽  
Erik Larsson
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Global Analysis ◽  
Gene Copy ◽  
Structural Basis ◽  
Whole Genome Sequencing Data ◽  
Mrna Levels ◽  
Gene Fusions ◽  
Structural Genomic ◽  
The Impact

Tumor genomes are mosaics of somatic structural variants (SVs) that may contribute to the activation of oncogenes or inactivation of tumor suppressors, for example, by altering gene copy number amplitude. However, there are multiple other ways in which SVs can modulate transcription, but the general impact of such events on tumor transcriptional output has not been systematically determined. Here we use whole-genome sequencing data to map SVs across 600 tumors and 18 cancers, and investigate the relationship between SVs, copy number alterations (CNAs), and mRNA expression. We find that 34% of CNA breakpoints can be clarified structurally and that most amplifications are due to tandem duplications. We observe frequent swapping of strong and weak promoters in the context of gene fusions, and find that this has a measurable global impact on mRNA levels. Interestingly, several long noncoding RNAs were strongly activated by this mechanism. Additionally, SVs were confirmed in telomere reverse transcriptase (TERT) upstream regions in several cancers, associated with elevatedTERTmRNA levels. We also highlight high-confidence gene fusions supported by both genomic and transcriptomic evidence, including a previously undescribed paired box 8 (PAX8)–nuclear factor, erythroid 2 like 2 (NFE2L2) fusion in thyroid carcinoma. In summary, we combine SV, CNA, and expression data to provide insights into the structural basis of CNAs as well as the impact of SVs on gene expression in tumors.

scholarly journals The impact of acid stress on escherichia coli O157:H7 virulence

2021 ◽  
Author(s):  
Belinda House
Keyword(s):  
Escherichia Coli ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Host Cell ◽  
Virulence Factors ◽  
Acid Stress ◽  
Mrna Levels ◽  
E Coli ◽  
Acid Shock ◽  
The Impact

Escherichia coli 0157:H7 infection is a leading cause of hemorrhagic colitis, and hemolytic uremic syndrome. Many opportunities for acid stress exposure exist for this food and waterborne pathogen, including gastric acid shock. Yet little is known how this affects E.coli 0157:H7 virulence. The effect of various acid stress protocols on E. coli 0157:H7 survival, verotoxin production, and the ability to adhere to host epithelial cells was examined. Brief acid shock alone at pH 3.0 decreased the host cell adhesion capability by a factor of 4.3-4.8, yet when the acid shock was preceded by adaptation at pH 5.0, a 1.6-3.2 fold enhanced adhesion of surviving organisms to epithelial cells relative to unstressed organisms was observed. However, acid stress did not affect verotoxin production. Pretreatment of acid stressed bacteria with erythromycin eliminated the acid-induced adhesion enhancement, suggesting that protein synthesis is a requirement for the enhanced adhesion observed with acid-adapted acid-shocked E.coli 0157:H7. Real time PCR analysis of locus for enterocyte effacement (LEE)-encoded virulence factors, intimin and EspA, revealed no significant upregulation for the acid stress treatments associated with the increased host cell adhesion. On the contrary, elevated mRNA levels for both intimin and EspA were observed for bacteria subjected to brief acid shock alone even though the host-cell adhesion was significatly decreased with these treatments. These results suggest that complex regulation mechanisms for LEE encoded virulence factors exists and that E. coli 0157:H7 virulence can be enhanced after acid stress through increased adhesion to host epithelial cells.

scholarly journals A global analysis of the impact of COVID-19 stay-at-home restrictions on crime

2021 ◽  
Author(s):  
Amy E. Nivette ◽  
Renee Zahnow ◽  
Raul Aguilar ◽  
Andri Ahven ◽  
Shai Amram ◽  
...  
Keyword(s):  
Public Space ◽  
Global Analysis ◽  
Sudden Change ◽  
Interrupted Time Series ◽  
Urban Crime ◽  
Substantial Variation ◽  
Different Types ◽  
Time Series Analyses ◽  
The Impact ◽  
At Home

AbstractThe stay-at-home restrictions to control the spread of COVID-19 led to unparalleled sudden change in daily life, but it is unclear how they affected urban crime globally. We collected data on daily counts of crime in 27 cities across 23 countries in the Americas, Europe, the Middle East and Asia. We conducted interrupted time series analyses to assess the impact of stay-at-home restrictions on different types of crime in each city. Our findings show that the stay-at-home policies were associated with a considerable drop in urban crime, but with substantial variation across cities and types of crime. Meta-regression results showed that more stringent restrictions over movement in public space were predictive of larger declines in crime.

scholarly journals Global analysis of the Sivers functions at NLO+NNLL in QCD

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
Miguel G. Echevarria ◽  
Zhong-Bo Kang ◽  
John Terry
Keyword(s):  
Pair Production ◽  
Global Analysis ◽  
Vector Boson ◽  
Lepton Pair ◽  
Transverse Spin ◽  
Dglap Evolution ◽  
Spin Asymmetries ◽  
Lepton Pair Production ◽  
Asymmetry Data ◽  
The Impact

Abstract We perform global fit to the quark Sivers function within the transverse momentum dependent (TMD) factorization formalism in QCD. We simultaneously fit Sivers asymmetry data from Semi-Inclusive Deep Inelastic Scattering (SIDIS) at COMPASS, HERMES, and JLab, from Drell-Yan lepton pair production at COMPASS, and from W/Z boson at RHIC. This extraction is performed at next-to-leading order (NLO) and next-to-next-to leading logarithmic (NNLL) accuracy. We find excellent agreement between our extracted asymmetry and the experimental data for SIDIS and Drell-Yan lepton pair production, while tension arises when trying to describe the spin asymmetries of W/Z bosons at RHIC. We carefully assess the situation, and we study in details the impact of the RHIC data and their implications through different ways of performing the fit. In addition, we find that the quality of the description of W/Z vector boson asymmetry data could be strongly sensitive to the DGLAP evolution of Qiu-Sterman function, besides the usual TMD evolution. We present discussion on this and the implications for measurements of the transverse-spin asymmetries at the future Electron Ion Collider.

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