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Non-syndromic tooth agenesis (or non-syndromic congenitally missing tooth) is one of the most common congenital defects in humans affecting the craniofacial function and appearance. Single nucleotide polymorphisms (SNPs) have been associated with an individual’s susceptibility to these anomalies. The aim of the present study was therefore to investigate the roles of the potentially functional SNPs of BMP2 in the occurrence of tooth agenesis. Overall, four potentially functional SNPs of BMP2 (rs15705, rs235768, rs235769 and rs3178250) were selected, and their associations with the susceptibility of tooth agenesis were evaluated in a case-control study of 335 non-syndromic tooth agenesis cases and 444 healthy controls. The SNPs rs15705 and rs3178250 were found to be associated with an individual’s risk of tooth agenesis (P = 0.046 and P = 0.039, respectively). Both SNPs showed an increased risk of mandibular incisor agenesis (rs15705, AA/AC vs. CC = 1.58, 95% CI = [1.06–2.34], P = 0.024; rs3178250, TT/TC vs. CC = 1.60, 95% CI = [1.08–2.37], P = 0.020). Bioinformatics analysis indicated that these two SNPs located at the 3’-untranslated region (3’-UTR) of BMP2 might alter the binding ability of miR-1273d and miR-4639-5p, respectively, which was confirmed by luciferase activity assays in the 293A and COS7 cell lines (P < 0.001 in 293A and P < 0.01 in COS7 for miR-1273d; and P < 0.001 in both cells for miR-4639-5p). Furthermore, BMP2 mRNA expression decreased after transfecting either miR-1273d or miR-4639-5p into these two cell lines (P < 0.01 in 293A and P < 0.001 in COS7 for miR-1273d, and P < 0.01 in both cell lines for miR-4639-5p). Taken together, our findings indicate that rs15705 and rs317250 are associated with the susceptibility of non-syndromic tooth agenesis by possibly affecting miRNAs and mRNA interaction. [ABSTRACT FROM AUTHOR]

Background and Objective: China has a high burden of cervical cancer (CC) and wide disparities in CC burden exist among different socio-economic regions. In order to reduce these disparities, China’s government launched the National Cervical Cancer Screening Program in Rural Areas (NCCSPRA) in 2009. Understanding the factors associated with underutilization of CC screening among target populations is important to improve the screening participation rate, and a high participation rate is key to achieving the goals of a screening program. However, data on the knowledge of CC among target populations in program areas is lacking in China. This study will investigate the knowledge of CC prevention and control among women in specific project counties to develop a better understanding of factors that might influence CC screening participation in order to improve the implementation of the NCCSPRA. Materials and Methods: A cross-sectional survey was conducted and face-to-face interview questionnaires were completed by 308 women who received CC screening services in 6 project counties of NCCSPRA across different socio-economic regions of China. ANOVA and Chi-square tests were used to compare the knowledge rates and scores across the different subgroups. Logistic regression was conducted to examine factors associated with knowledge level. Results: The overall CC knowledge rate of the target population was only 19.5%. Regional socio-economic level, advice from doctors, age, and educational status were strong predictors of knowledge level of CC screening. Significantly lower knowledge rates and scores were identified in older women (55–64 years old), less educated women (with primary school or illiterate), women in less developed regions and women who did not receive any advice about screening results from doctors. Conclusion: The knowledge of CC screening among women in the project counties of NCCSPRA was found to be very poor. Given the importance of knowledge in encouraging women to participate in screening is key to reducing CC burden in rural women in China, it is urgent that a targeted health promotion intervention is developed and implemented in project counties, especially targeting older women, women with less education and women in less developed regions, and focus on improving their CC knowledge and encouraging them to communicate with health care providers. The health promotion intervention targeting health care providers is also important to improve their knowledge of CC and provide best advice to women. [ABSTRACT FROM AUTHOR]

The p53 tumor suppressor protein plays a critical role in cellular stress and cancer prevention. A number of post-transcriptional regulators, termed microRNAs, are closely connected with the p53-mediated cellular networks. While the molecular interactions among p53 and microRNAs have emerged, a systems-level understanding of the regulatory mechanism and the role of microRNAs-forming feedback loops with the p53 core remains elusive. Here we have identified from literature that there exist three classes of microRNA-mediated feedback loops revolving around p53, all with the nature of positive feedback coincidentally. To explore the relationship between the cellular performance of p53 with the microRNA feedback pathways, we developed a mathematical model of the core p53-MDM2 module coupled with three microRNA-mediated positive feedback loops involving miR-192, miR-34a, and miR-29a. Simulations and bifurcation analysis in relationship to extrinsic noise reproduce the oscillatory behavior of p53 under DNA damage in single cells, and notably show that specific microRNA abrogation can disrupt the wild-type cellular phenotype when the ubiquitous cell-to-cell variability is taken into account. To assess these in silico results we conducted microRNA-perturbation experiments in MCF7 breast cancer cells. Time-lapse microscopy of cell-population behavior in response to DNA double-strand breaks, together with image classification of single-cell phenotypes across a population, confirmed that the cellular p53 oscillations are compromised after miR-192 perturbations, matching well with the model predictions. Our study via modeling in combination with quantitative experiments provides new evidence on the role of microRNA-mediated positive feedback loops in conferring robustness to the system performance of stress-induced response of p53. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the effects of intervention with a combination of nutrients in the amyloid precursor protein-presenilin (APP-PSN) C57BL/6J double transgenic mouse model of Alzheimer’s disease (AD). Methods: A total of 72 2-month-old APP-PSN mice were randomly assigned to three groups. The model group (MG) was fed regular, unsupplemented chow, while the low- and high-dose treatment groups (LG and HG, respectively) were given a combination of nutrients that included phosphatidylserine, blueberry extracts, docosahexaenoic acid, and eicosapentaenoic acid as part of their diet. An additional 24 wild-type littermates that were fed unsupplemented chow served as the negative control group (NG). After 3 and 7 months of treatment, the cognitive performance was assessed with the Morris water maze and the shuttle box escape/avoidance task, and the biochemical parameters and oxidative stress were evaluated in both the blood and brain. Results: An improvement in antioxidant capacity was observed in the treatment groups relative to the MG at 3 months, while superior behavioral test results were observed in the mice of the HG and NG groups. In the MG, pycnosis was detected in neuronal nuclei, and a loss of neurons was observed in the cerebral cortex and the hippocampus. At 7 months, the β-amyloid1–42 peptide accumulation was significantly elevated in the MG but was markedly lower in the mice fed the nutrient combination. The antioxidant capacity and behavioral test scores were also higher in these mice. Conclusions: Early intervention with a combination of nutrients should be considered as a strategy for preventing cognitive decline and other symptoms associated with AD. [ABSTRACT FROM AUTHOR]

Variations in elevation limit the growth and distribution of alpine plants because multiple environmental stresses impact plant growth, including sharp temperature shifts, strong ultraviolet radiation exposure, low oxygen content, etc. Alpine plants have developed special strategies to help survive the harsh environments of high mountains, but the internal mechanisms remain undefined. Kobresia pygmaea, the dominant species of alpine meadows, is widely distributed in the Southeastern Tibet Plateau, Tibet Autonomous Region, China. In this study, we mainly used comparative proteomics analyses to investigate the dynamic protein patterns for K. pygmaea located at four different elevations (4600, 4800, 4950 and 5100 m). A total of 58 differentially expressed proteins were successfully detected and functionally characterized. The proteins were divided into various functional categories, including material and energy metabolism, protein synthesis and degradation, redox process, defense response, photosynthesis, and protein kinase. Our study confirmed that increasing levels of antioxidant and heat shock proteins and the accumulation of primary metabolites, such as proline and abscisic acid, conferred K. pygmaea with tolerance to the alpine environment. In addition, the various methods K. pygmaea used to regulate material and energy metabolism played important roles in the development of tolerance to environmental stress. Our results also showed that the way in which K. pygmaea mediated stomatal characteristics and photosynthetic pigments constitutes an enhanced adaptation to alpine environmental stress. According to these findings, we concluded that K. pygmaea adapted to the high-elevation environment on the Tibetan Plateau by aggressively accumulating abiotic stress-related metabolites and proteins and by the various life events mediated by proteins. Based on the species'lexible physiological and biochemical processes, we surmised that environment change has only a slight impact on K. pygmaea except for possible impacts to populations on vulnerable edges of the species' range. [ABSTRACT FROM AUTHOR]

Most EEG-based brain-computer interface (BCI) paradigms include specific electrode positions. As the structures and activities of the brain vary with each individual, contributing channels should be chosen based on original records of BCIs. Phase measurement is an important approach in EEG analyses, but seldom used for channel selections. In this paper, the phase locking and concentrating value-based recursive feature elimination approach (PLCV-RFE) is proposed to produce robust-EEG channel selections in a P300 speller. The PLCV-RFE, deriving from the phase resetting mechanism, measures the phase relation between EEGs and ranks channels by the recursive strategy. Data recorded from 32 electrodes on 9 subjects are used to evaluate the proposed method. The results show that the PLCV-RFE substantially reduces channel sets and improves recognition accuracies significantly. Moreover, compared with other state-of-the-art feature selection methods (SSNRSF and SVM-RFE), the PLCV-RFE achieves better performance. Thus the phase measurement is available in the channel selection of BCI and it may be an evidence to indirectly support that phase resetting is at least one reason for ERP generations. [ABSTRACT FROM AUTHOR]

With the sequencing of genomes from many organisms now complete and the development of high-throughput sequencing, life science research has entered the functional post-genome era. Therefore, deciphering the function of genes and how they interact is in greater demand. To study an unknown gene, the basic methods are either overexpression or gene knockout by creating transgenic plants, and gene construction is usually the first step. Although traditional cloning techniques using restriction enzymes or a site-specific recombination system (Gateway or Clontech cloning technology) are highly useful for efficiently transferring DNA fragments into destination plasmids, the process is time consuming and expensive. To facilitate the procedure of gene construction, we designed a TA-based cloning system in which only one step was needed to subclone a DNA fragment into vectors. Such a cloning system was developed from the pGreen binary vector, which has a minimal size and facilitates construction manipulation, combined with the negative selection marker gene ccdB, which has the advantages of eliminating the self-ligation background and directly enabling high-efficiency TA cloning technology. We previously developed a set of transient and stable transformation vectors for constitutive gene expression, gene silencing, protein tagging, subcellular localization analysis and promoter activity detection. Our results show that such a system is highly efficient and serves as a high-throughput platform for transient or stable transformation in plants for functional genome research. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinase-1 (MMP-1) plays an important role during the destruction of periodontal tissue. Although multiple studies had focused on the association between MMP-1 g.-1607dupG and periodontitis susceptibility, the results remained inconclusive. The purpose of this meta-analysis was to explore its role in the development of periodontitis. Methods: Retrieved studies from Pubmed, Web of Science, Medline and Google Scholar Search regarding MMP-1 g.-1607dupG and periodontitis susceptibility were included into the final analysis with definite selection and exclusion criteria. Overall and stratified analyses based on disease type, severity, ethnicity and smoking status were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between MMP-1 g.-1607dupG and periodontitis susceptibility, while Q test and Egger’s test were adopted respectively to assess heterogeneity among studies and publication bias. Results: A total of 1580 periodontitis cases and 1386 controls in 11 case-control studies were included in the meta-analysis. The pooled results showed significant association between periodontitis susceptibility and MMP-1 g.-1607dupG polymorphism in homozygote (2G/2G versus 1G/1G, OR = 1.50, 95% CI = 1.02–2.20) and dominant model analysis (2G/2G+2G/1G versus 1G/1G, OR = 1.28, 95% CI = 1.04–1.57). For subgroups by type of periodontitis, increased risk of chronic periodontitis was observed on heterozygote (2G/1G versus 1G/1G, OR = 2.01, 95% CI = 1.58–2.56) and dominant model (OR = 1.27, 95% CI = 1.03–1.57). Furthermore, similar association was also detected in severe chronic periodontitis (2G/2G versus 1G/1G, OR = 2.15, 95% CI = 1.35–3.43; 2G/2G+2G/1G versus 1G/1G, OR = 1.64, 95% CI = 1.12–2.39; 2G/2G versus 2G/1G+1G/1G, OR = 1.86, 95% CI = 1.31–2.64). Conclusions: Our meta-analysis demonstrated that MMP-1 g.-1607dupG polymorphism was associated with chronic periodontitis, especially the severity of the disease condition. [ABSTRACT FROM AUTHOR]

Background: A recent genome-wide association study has identified a new genetic variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese population, but it is unknown whether this newly identified variant is associated with colorectal cancer in other populations, including the Chinese population. Methods: We examined the associations between rs7758229 and colorectal cancer risk among 1,147 cases and 1,203 controls matched by age and sex. Logistic regression model was used to assess the associations. Results: No significant association was found between rs7758229 and colorectal cancer risk (OR = 0.95, 95%CI  = 0.84–1.09, P = 0.463). Similar results were observed in the stratification of tumor location (OR  = 0.94, 95%CI = 0.80–1.11, P = 0.481 for colon cancer, and OR  = 0.96, 95%CI  = 0.82–1.13, P = 0.621 for rectum cancer). Conclusions: Our findings did not support an association between rs7758229 in 6q26-q27 and the risk of colorectal cancer in a Chinese population. [ABSTRACT FROM AUTHOR]

Purpose:miRNAs can regulate the biological processes, including differentiation, proliferation and apoptosis. DICER and DROSHA are two members of RNase III family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study, we hypothesized that genetic variations of the DICER and DROSHA genes were associated with the bladder cancer risk. Experimental Design:We performed a case-control study of 685 bladder cancer cases and 730 controls to investigate the association between the seven functional SNPs of DICER and DROSHA genes and bladder cancer risk. We then evaluated the functionality of the important SNPs. Results:We found that rs10719T>C polymorphism located in 3’ untranslated region (UTR) of DROSHA gene was associated with the increased risk of bladder cancer. Stratified analysis suggested that rs10719TC/CC genotype can increase risk of bladder cancer among male patients (Adjusted OR = 1.34, 95% CI = 1.05-1.70, P = 0.018), and ever smokers (1.56, 1.14-2.14, 0.006), compared with TT genotype. Furthermore, DROSHA rs10719T>C polymorphism was predicted to regulate the binding activity of hsa-miR-27a/b. Luciferase reported gene assay confirmed that rs10719 T to G substitution disrupted the binding site for hsa-miR-27b, resulting the increased levels of DROSHA protein. Conclusions:Taken together, these findings suggested that DROSHA rs10719T>C polymorphism may be associated with bladder cancer risk in a Chinese population, and hsa-miR-27b can influence the expression of DROSHA protein by binding with 3’UTR. [ABSTRACT FROM AUTHOR]