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3,4,5-Trimethoxyphenyl-(6′-O-galloyl)-O- beta-D-glucopyranoside

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PMID

24244495

Abstract

Retrotransposons comprise approximately half of the human genome and contribute to chromatin structure, regulatory motifs, and protein-coding sequences. Since retrotransposon insertions can disrupt functional genetic elements as well as introduce new sequence motifs to a region, they have the potential to affect the function of genes that harbour insertions as well as those nearby. Partly as a result of these effects, the distribution of retrotransposons across the genome is non-uniform and there are observed imbalances in the orientation of insertions with respect to the transcriptional direction of the containing gene. Although some of the factors underlying the observed distributions are understood, much of the variability remains unexplained. Detailed characterization of retrotransposon density in genes could help inform predictions of the functional consequence of de novo as well as polymorphic insertions. In order to characterize the relationship between genes and inserted elements, we have examined the distribution of retrotransposons and their internal motifs within tissue-specific and housekeeping genes. We have identified that the previously established retrotransposon antisense bias decays at a linear rate across genes, resulting in an equal density of sense and antisense retrotransposons near the 3′-UTR. In addition, the decay of antisense bias across genes is less pronounced among tissue-specific genes. Our results provide support for the scenario in which this linear decay in antisense bias is established by natural selection shortly after retrotransposon integration, and that total antisense bias observed is above and beyond any bias introduced by the integration process itself. Finally, we provide an example of a retrotransposon acting as an eQTL on a coincident gene, highlighting one of several possible avenues through which insertions may modulate gene function.

Title

Linear Decay of Retrotransposon Antisense Bias across Genes Is Contingent upon Tissue Specificity

Author

Sara Linker 1 and Dale Hedges 2 , *

Publish date

2013;

PMID

30962241

Abstract

Objective
We sought to explore various correlates of blood pressure (BP) and hypertension, and to identify the most important aggregate combination of correlates for BP in South Asian children.

Design
Cross-sectional study

Setting
Community-based recruitment in two Canadian cities

Participants
South Asian children (n=762) provided a range of physiological, lifestyle and social variables. BP was assessed using an automated device. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and BP were transformed to z-scores using published standards.

Outcome measures
Linear and logistic regression analyses were used to explore associations between the range of variables with BP z-scores and hypertension while stepwise regression was used to identify aggregate factors that provided explanatory capacity for systolic BP (SBP) and diastolic BP (DBP) z-scores.

Results
A range of variables were associated with BP z-score and hypertension in unadjusted analysis. On adjustment for confounders, the association between age (β=?0.054, 95% CI=?0.078 to 0.029), female sex (β=?0.208, 95% CI=?0.350 to -0.067), height (β=0.022, 95% CI=0.011 to 0.033), weight (β=0.047, 95% CI=0.040 to 0.055), BMI z-score (β=0.292, 95% CI=0.249 to 0.336), WC z-score (β=0.273, 95% CI=0.219 to 0.326), WHtR z-score (β=0.289, 95% CI=0.236 to 0.342), heart rate (β=0.016, 95% CI=0.010 to 0.022), child’s perception of body image (β=0.183, 95% CI=0.128 to 0.239) and grip strength (β=0.025, 95% CI=0.007 to 0.043) with SBP z-score remained. In stepwise regression, age, sex, BMI z-score, heart rate and weight accounted for 30% of the variance of SBP z-score, while age, BMI z-score, heart rate and daily fast food intake accounted for 23% of the DBP z-score variance.

Conclusion
Our findings suggest that variables, such as age, sex, height, adiposity and heart rate, provide stronger explanatory capacity to BP variance and hypertension risk than other variables in South Asian children.

KEYWORDS

hypertension, paediatrics, epidemiology

Title

Multifactorial correlates of blood pressure in South Asian children in Canada: a cross-sectional study

Author

Adeleke Fowokan,1 Zubin Punthakee,2 Charlotte Waddell,3 Miriam Rosin,1 Katherine M Morrison,2 Milan Gupta,2 Sumathy Rangarajan,4 Koon Teo,4 and Scott Lear3

Publish date

2019;

PMID

31057556

Abstract

Long non-coding RNAs (lncRNAs) have recently emerged as new regulatory molecules with diverse functions in regulating gene expression and significant roles in the immune response. However, the function of many unknown lncRNAs is still unclear. By studying the regulatory effect of daidzein (DA) on immunity, we identified a novel lncRNA with an immune regulatory function: lncRNA- XLOC_098131. In vivo, DA treatment upregulated the expression of lncRNA- XLOC_098131, FOS, and JUN in chickens and affected the expression of activator protein 1 (AP-1) to regulate MAPK signaling, Toll-like receptor signaling, and related mRNA expression. It also enhanced macrophage activity and increased the numbers of blood neutrophils and mononuclear cells, which can improve the body’s ability to respond to stress and bacterial and viral infections. Furthermore, DA treatment also reduced B lymphocyte apoptosis and promoted the differentiation of B lymphocytes into plasma cells, which in turn resulted in the production of more immunoglobulins and the promotion of antigen presentation. In vitro, using HEK293FT cells, we demonstrated that mir-548s could bind to and decrease the expression of both FOS and lncRNA- XLOC_098131. LncRNA- XLOC_098131 served as a competitive endogenous RNA to stabilize FOS by competitively binding to miR-548s and thereby reducing its inhibitory effect of FOS expression. Therefore, we concluded that the novel lncRNA XLOC_098131 acts as a key regulatory molecule that can regulate the Toll-like receptor signaling pathway and related immune function by serving as a competitive endogenous RNA to stabilize FOS mRNA expression.

KEYWORDS

competitive endogenous RNA, daidzein, immunoglobulins, lymphocytes, miR-548s, MAPK signaling, novel lncRNAs, Toll-like receptor pathway

Title

A Novel lncRNA Regulates the Toll-Like Receptor Signaling Pathway and Related Immune Function by Stabilizing FOS mRNA as a Competitive Endogenous RNA

Author

Hao Fan,1 Zengpeng Lv,1 Liping Gan,1 Chao Ning,2 Zhui Li,1 Minghui Yang,2 Beibei Zhang,1 Bochen Song,1 Guang Li,1 Dazhi Tang,1 Jinxin Gao,1 Shaojia Yan,1 Youli Wang,1 Jianfeng Liu,2 and Yuming Guo1,*

Publish date

2019;