Genome-Wide Search Links Senescence-Associated Secretory Proteins With Susceptibility for Coronary Artery Disease in Mouse and Human.

Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associated secretory phenotype (SASP). How SASP contributes to atherosclerosis and CAD, however, remains unclear. Here, we integrated RNA-array datasets of senescent human coronary arterial endothelial cells (HCAECs) and aortic smooth muscle cells (HASMCs) as well as genome-wide association data for CAD. We identified 26 genes from HCAECs and 6 genes from HASMCs related to SASP and CAD in both in-house and published datasets. Of which, Cystatin C (CST3), a CAD susceptibility gene, was found to be expressed in both HCAECs and HASMCs, thus, it was prioritized for further investigation. We demonstrated it was significantly elevated in senescent vascular cells, aged arteries, and early atherosclerosis. In vitro experiments showed that CST3 enhances the monocyte-endothelial cell adhesion. Additionally, ligand-receptor pairing analyses revealed two important pathways, COL4A1-ITGA1 and LPL-LRP1 pathways, linked to the critical processes in the development of atherosclerosis, including cell adhesion, inflammation response, extracellular matrix organization, and lipid metabolism. We further demonstrated a reduced monocyte-endothelial cell adhesion following the knockdown of COL4A1 or ITGA1 and a significantly increased expression of COL4A1, ITGA1, and LPL in arterial intima of aged mice and ApoE-/- mice. Our findings demonstrate that vascular cell-derived SASP proteins increase the CAD susceptibility and identify CST3 functionally contributing to atherosclerosis.

Preliminary study on lyrics intelligibility at different pitches in Chinese vocal music.

Background: There is still no clear experimental data on the relationship between the intelligibility of Chinese vocal lyrics and different pitch.Aims/Objective: This study aims at investigating the intelligibility of Chinese sung words at different pitch.Material and methods: A word list is created and sung by eight singers at five different pitches (C5, F4, bB4, bE5, and bA5). The intelligibility of the words is tested by listeners with and without music background.Results: The average intelligibility score in the music-listeners is 84.9% (SD = 9.5%). The score at five pitches (from low to high) is 93%, 91.7%, 89.7%, 83.1%, and 67.1%, respectively. The average score is 77.4% (SD = 10.7%) in the non-music listeners. The average score is 87%, 86%, 79.8%, 76.8%, and 57.5% at five pitches, respectively. The ratio of unidentified sung words is 19.3% (SD, 4.3%) in female singers and 11.9% (SD = 1.5%) in male singers.Conclusions: The intelligibility of Chinese sung words declines gradually with increase in pitch, and the extent of decreases gradually elevating. Generally, the identified ratio of words sung by male singers is higher than that of female singers. The listeners who had no musical background have a lower intelligibility score than those with experience.

mTOR and tau phosphorylated proteins in the hippocampal tissue of rats with type 2 diabetes and Alzheimer's disease.

This study explored the effects of mammalian target of rapamycin (mTOR) on the increased risk of developing Alzheimer's disease (AD) in rats with type 2 diabetes mellitus (T2DM). Male Sprague-Dawley rats were randomly divided into four groups: control, T2DM, AD and T2DM+AD. Changes in the learning and memory abilities of the rats were observed using the Morris water maze. mTOR activity and tau protein hyperphosphorylation in the hippocampus were analyzed by immunohistochemical staining and RT-PCR. The learning and memory abilities of the experimental rats were weakened compared with those of the control group. The T2DM+AD group revealed significant changes over the T2DM and AD groups. Compared with the control, T2DM and AD groups, the mTOR protein and mRNA levels, hyperphosphorylation of tau protein and total tau protein mRNA levels were significantly increased in the T2DM+AD group. T2DM may excessively activate mTOR in the hippocampal tissue by impairing insulin signaling, thereby increasing the extent of tau hyperphosphorylation and promoting the occurrence of AD.

[Anterior cervical discectomy and fusion in the treatment of Hangman's fracture].

OBJECTIVE: To evaluate the efficacies and features of treating Hangman's fracture by anterior cervical discectomy and fusion (ACDF). METHODS: Since June 2005 to December 2008, 36 cases with Hangman's fracture were analyzed with their clinical data including history, symptoms, signs, radiological findings and treatments. According to the classification system designed by Levine and Edwards depending on the radiological manifestations of Hangman's fractures, they were subdivided into type I (n = 9) (conservative therapy), type II (n = 17) and type IIA (n = 10). Conservative therapy was offered to type I in 9 cases, while ACDF with cervical gear protection for 4 weeks after surgery was performed to type II in 17 cases and type IIA in 10 cases. A combination of operation time, days of hospitalization, complications, neurological improvement and fusion rate was assessed. RESULTS: An average follow-up of 15 months (range: 10 - 36) was achieved. No vertebral redisplacement and angulation deformity occurred. Axial pain was relieved in each case. The preoperative neurological deficits in all patients got improvements. No spinal cord injury, vertebral artery injury or cerebrospinal fluid leakage occurred. No complication related to internal fixator was found. Average operative time and hospitalization were similar to those of ACDF for lower cervical spine (98 minutes vs. 9 days). Fusion was achieved within 6 months in all cases. CONCLUSION: ACDF at C2-C3 may be an effective and safe way to treat Hangman's fracture.

Hierarchical structure analysis describing abnormal base composition of genomes.

Abnormal base compositional patterns of genomic DNA sequences are studied in the framework of a hierarchical structure (HS) model originally proposed for the study of fully developed turbulence [She and Lévêque, Phys. Rev. Lett. 72, 336 (1994)]. The HS similarity law is verified over scales between 10(3)bp and 10(5)bp, and the HS parameter beta is proposed to describe the degree of heterogeneity in the base composition patterns. More than one hundred bacteria, archaea, virus, yeast, and human genome sequences have been analyzed and the results show that the HS analysis efficiently captures abnormal base composition patterns, and the parameter beta is a characteristic measure of the genome. Detailed examination of the values of beta reveals an intriguing link to the evolutionary events of genetic material transfer. Finally, a sequence complexity (S) measure is proposed to characterize gradual increase of organizational complexity of the genome during the evolution. The present study raises several interesting issues in the evolutionary history of genomes.