Epigenetic variation in plant responses to defence hormones

Background and Aims There is currently much speculation about the role of epigenetic variation as a determinant of heritable variation in ecologically important plant traits. However, we still know very little about the phenotypic consequences of epigenetic variation, in particular with regard to more complex traits related to biotic interactions. Methods Here, a test was carried out to determine whether variation in DNA methylation alone can cause heritable variation in plant growth responses to jasmonic acid and salicylic acid, two key hormones involved in induction of plant defences against herbivores and pathogens. In order to be able to ascribe phenotypic differences to epigenetic variation, the hormone responses were studied of epigenetic recombinant inbred lines (epiRILs) of Arabidopsis thaliana - lines that are highly variable at the level of DNA methylation but nearly identical at the level of DNA sequence. Key Results Significant heritable variation was found among epiRILs both in the means of phenotypic traits, including growth rate, and in the degree to which these responded to treatment with jasmonic acid and salicylic acid. Moreover, there was a positive epigenetic correlation between the responses of different epiRILs to the two hormones, suggesting that plant responses to herbivore and pathogen attack may have a similar molecular epigenetic basis. Conclusions This study demonstrates that epigenetic variation alone can cause heritable variation in, and thus potentially microevolution of, plant responses to defence hormones. This suggests that part of the variation of plant defences observed in natural populations may be due to underlying epigenetic, rather than entirely genetic, variatio

Research progress of extracellular vesicles and exosomes derived from mesenchymal stem cells in the treatment of oxidative stress-related diseases

There is growing evidence that mesenchymal stem cell-derived extracellular vesicles and exosomes can significantly improve the curative effect of oxidative stress-related diseases. Mesenchymal stem cell extracellular vesicles and exosomes (MSC-EVs and MSC-Exos) are rich in bioactive molecules and have many biological regulatory functions. In this review, we describe how MSC-EVs and MSC-Exos reduce the related markers of oxidative stress and inflammation in various systemic diseases, and the molecular mechanism of MSC-EVs and MSC-Exos in treating apoptosis and vascular injury induced by oxidative stress. The results of a large number of experimental studies have shown that both local and systemic administration can effectively inhibit the oxidative stress response in diseases and promote the survival and regeneration of damaged parenchymal cells. The mRNA and miRNAs in MSC-EVs and MSC-Exos are the most important bioactive molecules in disease treatment, which can inhibit the apoptosis, necrosis and oxidative stress of lung, heart, kidney, liver, bone, skin and other cells, and promote their survive and regenerate

Bayesian path specific frailty models for multi-state survival data with applications

Multi-state models can be viewed as generalizations of both the standard and competing risks models for survivaldata. Models for multi-state data have been the theme of many recent published works. Motivated by bone marrow transplantdata, we propose a Bayesian model using the gap times between two successive events in a path of events experienced by asubject. Path specific frailties are introduced to capture the dependence structure of the gap times in the paths with two ormore states. Under improper prior distributions for the parameters, we establish propriety of the posterior distribution. Anefficient Gibbs sampling algorithm is developed for drawing samples from the posterior distribution. An extensive simulationstudy is carried out to examine the empirical performance of the proposed approach. A bone marrow transplant data set isanalyzed in detail to further demonstrate the proposed methodology.FAPESPCNPqU.S. NIH #GM 70335 and #CA 7401

Bayesian Design of Noninferiority Trials for Medical Devices Using Historical Data

We develop a new Bayesian approach of sample size determination (SSD) for the design of non-inferiority clinical trials. We extend the fitting and sampling priors of Wang and Gelfand (2002) to Bayesian SSD with a focus on controlling the type I error and power. Historical data are incorporated via a hierarchical modeling approach as well as the power prior approach of Ibrahim and Chen (2000). Various properties of the proposed Bayesian SSD methodology are examined and a simulation-based computational algorithm is developed. The proposed methodology is applied to the design of a non-inferiority medical device clinical trial with historical data from previous trials

Influence of different caregiving styles on fundamental movement skills among children

PurposeThis study investigated the influence of parenting and grandparenting caregiving styles on fundamental motor skills (FMS) of preschool children.MethodA total of 1,326 preschool children (698 boys, 628 girls) aged 4–6 years were recruited from the kindergartens of Jinhua City, China. Locomotor skills (LM), ball skills (BS), and total fundamental movement skills (TS) of children were assessed by the Test of Gross Motor Development-3rd edition (TGMD-3).ResultsThere were 978 children in parenting and 348 children in grandparenting caregiving styles. The LM, BS and TS scores of children were considerably (p < 0.001) increased with age (irrespective of sex or caregiving style). For the sex comparisons, BS scores of boys were significantly higher than girls (p < 0.001), while LM and TS scores were not different between boys and girls. For the caregiving style comparison, parenting is superior to grandparenting in developing of children's FMS. Parenting boys of 4-, 5-, and 6-years old showed better BS compared to age-matched parenting girls, whereas boys of 5-years old in grandparenting only showed better BS compared to same-age grandparenting girls (p < 0.05). Furthermore, parenting boys of 6-years reported higher LM (p < 0.01), BS (p < 0.001), and TS (p < 0.001) scores compared to grandparenting boys, but girls' FMS at all ages were not significantly different between the caregiving styles.ConclusionParenting caregiving style is positively associated with proper development of FMS among children. Girl children with poor FMS in grandparenting may need a special care or intervention programs to promote their FMS

Bayesian gamma frailty models for survival data with semi-competing risks and treatment switching

Motivated from a colorectal cancer study, we propose a class of frailty semi-competing risks survival models to account for the dependence between disease progression time, survival time, and treatment switching. Properties of the proposed models are examined and an efficient Gibbs sampling algorithm using the collapsed Gibbs technique is developed. A Bayesian procedure for assessing the treatment effect is also proposed. The Deviance Information Criterion (DIC) with an appropriate deviance function and Logarithm of the Pseudomarginal Likelihood (LPML) are constructed for model comparison. A simulation study is conducted to examine the empirical performance of DIC and LPML and as well as the posterior estimates. The proposed method is further applied to analyze data from a colorectal cancer study

Clinical characterization and proteomic profiling of lean nonalcoholic fatty liver disease

IntroductionObesity has been historically associated with nonalcoholic fatty liver disease (NAFLD), but it can also occur in lean individuals. However, limited data is available on this special group. To investigate the clinical and proteomic characteristics of lean subjects with NAFLD, and to identify potential clinical variables and plasma proteins for diagnosing NAFLD in lean individuals, we collected clinical data from a large cohort of 2,236 subjects.MethodsDiagnosis of NAFLD relied on detecting pronounced hepatic steatosis through abdominal ultrasonography. Participants were categorized into four groups based on body mass index: overweight NAFLD, overweight control, lean NAFLD, and lean control. Plasma proteomic profiling was performed on samples from 20 subjects in each group. The lean NAFLD group was compared to both lean healthy and obese NAFLD groups across all data.Results and discussionThe results indicated that the lean NAFLD group exhibited intermediate metabolic profiles, falling between those of the lean healthy and overweight NAFLD groups. Proteomic profiling of plasma in lean subjects with or without NAFLD revealed 45 statistically significant changes in proteins, of which 37 showed high diagnostic value (AUC > 0.7) for lean NAFLD. These potential biomarkers primarily involved lipid metabolism, the immune and complement systems, and platelet degranulation. Furthermore, AFM, GSN, CFH, HGFAC, MMP2, and MMP9 have been previously associated with NAFLD or NAFLD-related factors such as liver damage, insulin resistance, metabolic syndromes, and extracellular homeostasis. Overall, lean individuals with NAFLD exhibit distinct clinical profiles compared to overweight individuals with NAFLD. Despite having worse metabolic profiles than their healthy counterparts, lean NAFLD patients generally experience milder systemic metabolic disturbances compared to obese NAFLD patients. Additionally, the plasma proteomic profile is significantly altered in lean NAFLD, highlighting the potential of differentially expressed proteins as valuable biomarkers or therapeutic targets for diagnosing and treating NAFLD in this population

Exosomes and exosome composite scaffolds in periodontal tissue engineering

Promoting complete periodontal regeneration of damaged periodontal tissues, including dental cementum, periodontal ligament, and alveolar bone, is one of the challenges in the treatment of periodontitis. Therefore, it is urgent to explore new treatment strategies for periodontitis. Exosomes generated from stem cells are now a promising alternative to stem cell therapy, with therapeutic results comparable to those of their blast cells. It has great potential in regulating immune function, inflammation, microbiota, and tissue regeneration and has shown good effects in periodontal tissue regeneration. In addition, periodontal tissue engineering combines exosomes with biomaterial scaffolds to maximize the therapeutic advantages of exosomes. Therefore, this article reviews the progress, challenges, and prospects of exosome and exosome-loaded composite scaffolds in periodontal regeneration