Conservation and implications of eukaryote transcriptional regulatory regions across multiple species

<p>Abstract</p> <p>Background</p> <p>Increasing evidence shows that whole genomes of eukaryotes are almost entirely transcribed into both protein coding genes and an enormous number of non-protein-coding RNAs (ncRNAs). Therefore, revealing the underlying regulatory mechanisms of transcripts becomes imperative. However, for a complete understanding of transcriptional regulatory mechanisms, we need to identify the regions in which they are found. We will call these transcriptional regulation regions, or TRRs, which can be considered functional regions containing a cluster of regulatory elements that cooperatively recruit transcriptional factors for binding and then regulating the expression of transcripts.</p> <p>Results</p> <p>We constructed a hierarchical stochastic language (HSL) model for the identification of core TRRs in yeast based on regulatory cooperation among TRR elements. The HSL model trained based on yeast achieved comparable accuracy in predicting TRRs in other species, e.g., fruit fly, human, and rice, thus demonstrating the conservation of TRRs across species. The HSL model was also used to identify the TRRs of genes, such as p53 or <it>OsALYL1</it>, as well as microRNAs. In addition, the ENCODE regions were examined by HSL, and TRRs were found to pervasively locate in the genomes.</p> <p>Conclusion</p> <p>Our findings indicate that 1) the HSL model can be used to accurately predict core TRRs of transcripts across species and 2) identified core TRRs by HSL are proper candidates for the further scrutiny of specific regulatory elements and mechanisms. Meanwhile, the regulatory activity taking place in the abundant numbers of ncRNAs might account for the ubiquitous presence of TRRs across the genome. In addition, we also found that the TRRs of protein coding genes and ncRNAs are similar in structure, with the latter being more conserved than the former.</p

Integrated Bioinformatic Analysis Reveals TXNRD1 as a Novel Biomarker and Potential Therapeutic Target in Idiopathic Pulmonary Arterial Hypertension

Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening cardiopulmonary disease lacking specific diagnostic markers and targeted therapy, and its mechanism of development remains to be elucidated. The present study aimed to explore novel diagnostic biomarkers and therapeutic targets in IPAH by integrated bioinformatics analysis. Four eligible datasets (GSE117261, GSE15197, GSE53408, GSE48149) was firstly downloaded from GEO database and subsequently integrated by Robust rank aggregation (RRA) method to screen robust differentially expressed genes (DEGs). Then functional annotation of robust DEGs was performed by GO and KEGG enrichment analysis. The protein-protein interaction (PPI) network was constructed followed by using MCODE and CytoHubba plug-in to identify hub genes. Finally, 10 hub genes were screened including ENO1, TALDO1, TXNRD1, SHMT2, IDH1, TKT, PGD, CXCL10, CXCL9, and CCL5. The GSE113439 dataset was used as a validation cohort to appraise these hub genes and TXNRD1 was selected for verification at the protein level. The experiment results confirmed that serum TXNRD1 concentration was lower in IPAH patients and the level of TXNRD1 had great predictive efficiency (AUC:0.795) as well as presents negative correlation with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). Consistently, the expression of TXNRD1 was proved to be inhibited in animal and cellular model of PAH. In addition, GSEA analysis was performed to explore the functions of TXNRD1 and the results revealed that TXNRD1 was closely correlated with mTOR signaling pathway, MYC targets, and unfolded protein response. Finally, knockdown of TXNRD1 was shown to exacerbate proliferative disorder, migration and apoptosis resistance in PASMCs. In conclusion, our study demonstrates that TXNRD1 is a promising candidate biomarker for diagnosis of IPAH and plays an important role in PAH pathogenesis, although further research is necessary

Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

Increasing evidences indicate that reactive oxygen species are the main factor promoting stem cell aging. Recent studies have demonstrated that coenzyme Q10 (CoQ10) plays a positive role in organ and cellular aging. However, the potential for CoQ10 to protect stem cell aging has not been fully evaluated, and the mechanisms of cell senescence inhibited by CoQ10 are still poorly understood. Our previous study had indicated that D-galactose (D-gal) can remarkably induce mesenchymal stem cell (MSC) aging through promoting intracellular ROS generation. In this study, we showed that CoQ10 could significantly inhibit MSC aging induced by D-gal. Moreover, in the CoQ10 group, the expression of p-Akt and p-mTOR was clearly reduced compared with that in the D-gal group. However, after Akt activating by CA-Akt plasmid, the senescence-cell number in the CoQ10 group was significantly higher than that in the control group. These results indicated that CoQ10 could inhibit D-gal-induced MSC aging through the Akt/mTOR signaling

Effects of Titanium Micro-Nanopermeable Structures on Osteogenic Differentiation

To evaluate the effects of different Ti surface micro-nanopermeable structures on osteoblast proliferation and differentiation and explore related mechanisms, hybrid technology of sandblast, acid etching, and hydrothermal (HT) was used to form the micro-nanopermeable surface of Ti. Scanning electron microscopy (SEM), surface profiler, and contact angle meter were utilized to assess the surface morphology, roughness, and hydrophilicity. MTT, SEM, alkaline phosphatase (ALP) activity assay, and real-time PCR were performed to investigate proliferation, adhesion and spreading, and differentiation of MC3T3-E1 cells grown on polished Ti (control), sandblast + acid etching- (SLA-) treated Ti, and SLA + HT-treated Ti. MAPK signal pathway activity was evaluated by Western blotting. The results showed that SLA + HT could result in not only formation of microscale groove containing submicroscale and nanoscale porous structures in Ti samples but also rough and hydrophilic surface. SLA + HT treatment has the best effects on cell adhesion and spreading. Significantly increased levels of ALP activity and osteogenic genes including Alp, Ocn, Opn, Runx2, and Bsp, as well as p38 but not ERK phosphorylation, were found in the SLA + HT group. In conclusion, sandblast, acid etching, and hydrothermal treatment on Ti regulates osteoblast differentiation, while activation of the MAPK p38 signaling pathway served as the mechanism

Optimizing the Composition Design of Cement-Based Expanded-Polystyrene (EPS) Exterior Wall Based on Thermal Insulation and Flame Retardance

The use of thermal insulated decorative panel materials with low thermal conductivity and high flame retardance is a key step toward energy-saving buildings. However, traditional thermal insulation materials are always highly conductive and inflammable, which restricts their application for new buildings. This study aims to prepare the non-combustible, cement-based EPS mixtures with thermal conductivity lower than 0.045 and density less than 140 kg/m3 and characterize it with mechanical, thermal, and flame retardant properties. The effect of particle size, Silica coated and content of EPS on the physical, mechanical, thermal, and combustion performance are conducted in this paper. The comprehensive indoor tests including density, water absorbing, softening coefficient, compressive strength, tensile strength, moisture susceptibility, thermal conductivity, and scanning electron microscopy (SEM) along with combustion performance are reported to evaluate the effects of several variables on the investigated cement-based nonflammable EPS (CEPS)mixtures. The results show that small and gradation EPS particles significantly improve the comprehensive performance of mixtures. In addition, Silica coated ESP significantly improve the flame retardance of mixtures while reduce the mechanical characteristics slightly. These results contribute to the selection of appropriate materials to enhance the thermal insulation, flame retardance and mechanical properties of CEPS

Left ventricular long-axis ultrasound strain (GLS) is an ideal indicator for patients with anti-hypertension treatment

Background Primary hypertension is one of the most well-known risk factors for cardiovascular disease. Currently, there is still no ideal indicator for left ventricular end-diastolic pressure. Methods 73 hypertension patients and 37 healthy people were enrolled in this study. Each member was examined with conventional echocardiography including multiple indicators such as Peak mitral valve flow velocity (E, A), E/A, left atrial volume index (LAVl), tissue Doppler (PW-TDI) peak velocities during early and late diastolic mitral valve flow (e ‘), E/e ‘, and GLS. We have collected clinical data from all enrolled members. The above cardiac ultrasound indicators were obtained before the antihypertensive treatment, one month and three months after treatment. Results Left ventricular end-diastolic pressure (LVEDP) was positively correlated and negatively correlated with GLS (r = 0.638, P < .01) and E/e’ (r = −0.578, P < .05), respectively. The hypertensives had lower e’ value and higher values of GLS, E/e’, and LAVI than the control group (P < .05). GLS and E/e’ were significantly lower in hypertension group than those in the Control group after one month and three months of treatment (P < .05). The improvement rate of GLS was significantly higher than those in the improvement rate of e’, E/e’, LAVI after treatment (p < .05). Conclusion The GLS improvement rate was significantly higher than those of e’, E/e’ after one and three-month treatment. Therefore, GLS might be a potential ideal index for patients with anti-hypertension treatment. The results obtained in this study provide useful information for further study