Protective Effect of TNFRSF11A rs7239667 G > C Gene Polymorphism on Coronary Outcome of Kawasaki Disease in Southern Chinese Population

BackgroundThe main symptoms of Kawasaki disease (KD) are inflammatory vasculitis characterized by fever lasting 1–2 weeks, failure to respond to antibiotic treatment, conjunctivitis, redness of the lips and mouth, strawberry tongue, and painless enlargement of the neck lymph nodes. Studies have been shown that tumor necrosis factor (TNF) and TNF receptor family members are abnormally expressed in the acute phase of Kawasaki disease, also revealing that these two play a significant role in the pathogenesis of KD. The purpose of our study is to determine the relationship between TNFRSF11A rs7239667 and the pathogenesis of KD and Coronary artery lesions in KD.Methods and ResultsIn this study, TNFRSF11A (rs7239667) genotyping was performed in 1396 patients with KD and 1673 healthy controls. Our results showed that G > C polymorphism of TNFRSF11A (rs7239667) was not associated with KD susceptibility. In addition, the patients with KD were divided into CAA and NCAA groups according to whether they had coronary artery aneurysm (CAA) or not, and the TNFRSF11A rs7239667 genotyping was performed in the two groups. After gender and age calibration, We found that genotype CC of TNFRSF11A may be a protective factor in KD coronary artery damage (adjusted OR = 0.69 95% CI = 0.49–0.99 P = 0.0429) and is more significant in children with KD ≤ 60 months (adjusted OR = 0.49 95% CI = 0.49–0.93 P = 0.0173).ConclusionOur study suggests that TNFRSF11A rs7239667 G > C polymorphism maybe play a protective gene role for the severity of KD coronary artery injury and is related to age, which has not been previously revealed.

KLF4 Recruits SWI/SNF to Increase Chromatin Accessibility and Reprogram the Endothelial Enhancer Landscape under Laminar Shear Stress

Physiologic laminar shear stress (LSS) induces an endothelial gene expression profile that is vasculo-protective. In this report, we delineate how LSS mediates changes in the epigenetic landscape to promote this beneficial response. We show that under LSS, KLF4 interacts with the SWI/SNF nucleosome remodeling complex to increase accessibility at enhancer sites that promote expression of homeostatic endothelial genes. By combining molecular and computational approaches we discovered enhancers that loop to promoters of known and novel KLF4- and LSS-responsive genes that stabilize endothelial cells and suppress inflammation, such as BMPR2 and DUSP5. By linking enhancers to genes that they regulate under physiologic LSS, our work establishes a foundation for interpreting how non-coding DNA variants in these regions might disrupt protective gene expression to influence vascular disease.

Serotonin signaling by maternal neurons upon stress ensures progeny survival

Germ cells are vulnerable to stress. Therefore, how organisms protect their future progeny from damage in a fluctuating environment is a fundamental question in biology. We show that in Caenorhabditis elegans, serotonin released by maternal neurons during stress ensures the viability and stress resilience of future offspring. Serotonin acts through a signal transduction pathway conserved between C. elegans and mammalian cells to enable the transcription factor HSF1 to alter chromatin in soon-to-be fertilized germ cells by recruiting the histone chaperone FACT, displacing histones, and initiating protective gene expression. Without serotonin release by maternal neurons, FACT is not recruited by HSF1 in germ cells, transcription occurs but is delayed, and progeny of stressed C. elegans mothers fail to complete development. These studies uncover a novel mechanism by which stress sensing by neurons is coupled to transcription response times of germ cells to protect future offspring.

Serotonin signaling by maternal neurons upon stress ensures progeny survival

Germ cells are vulnerable to stress. Therefore, how organisms protect their future progeny from damage in a fluctuating environment is a fundamental question in biology. We show that in Caenorhabditis elegans, serotonin released by maternal neurons during stress ensures the viability and stress tolerance of future offspring by enabling the transcription factor HSF1 to alter chromatin in soon-to-be fertilized germ cells by recruiting the histone chaperone FACT, displacing histones, and initiating protective gene expression. Without maternal serotonin signaling by neurons, FACT is not recruited by HSF1 in germ cells, transcription occurs but is delayed, and progeny of stressed C. elegans mothers fail to complete development. Serotonin acts through a signal transduction pathway conserved between C. elegans and mammalian cells to facilitate HSF1 to recruit FACT. These studies uncover a novel mechanism by which stress sensing by neurons is coupled to transcription response times of germ cells to protect future offspring.

Cellular acidosis triggers human MondoA transcriptional activity by driving mitochondrial ATP production

Human MondoA requires glucose as well as other modulatory signals to function in transcription. One such signal is acidosis, which increases MondoA activity and also drives a protective gene signature in breast cancer. How low pH controls MondoA transcriptional activity is unknown. We found that low pH medium increases mitochondrial ATP (mtATP), which is subsequently exported from the mitochondrial matrix. Mitochondria-bound hexokinase transfers a phosphate from mtATP to cytoplasmic glucose to generate glucose-6-phosphate (G6P), which is an established MondoA activator. The outer mitochondrial membrane localization of MondoA suggests that it is positioned to coordinate the adaptive transcriptional response to a cell’s most abundant energy sources, cytoplasmic glucose and mtATP. In response to acidosis, MondoA shows preferential binding to just two targets, TXNIP and its paralog ARRDC4. Because these transcriptional targets are suppressors of glucose uptake, we propose that MondoA is critical for restoring metabolic homeostasis in response to high energy charge.

Glyphosate Stimulates the Accumulation of N-Compounds, Grain Yield and Seed Vigor in Glyphosate-Resistant Soybean

Glyphosate-resistant (GR) soybean is widely used in agriculture, however, plants exposed to herbicide show physiological changes. This study investigated the effect of treatments with glyphosate on the metabolism of N compounds, crop yield and physiological quality of seeds in GR soybean. The plants were grown in field experiment, located in the city of Selvíria, MS, Brazil. Glyphosate was applied postemergence at V4 crop stage in a dose-response, including four rates (0; 360; 720 and 1440 g e. a. ha-1) with four replicates. Crop yield, physiological and biochemical features were determined. The results revealed previously unreported stimulant effects of glyphosate on GR soybean plants. Glyphosate changed the ureide shape in leaves, but did not change the concentration of total ureides, indicating maintenance of biological nitrogen fixation in plants exposed to herbicide. Amino acids concentration increased in plants submitted to higher doses. GR soybean showed higher crop yield and seed vigor with increased glyphosate doses. The results of this study indicate that glyphosate does not cause stress to the plant; however, it modulates a distinct response in plant development due to the protective gene inserted. This study can serve as a matrix for additional studies in order to seek clarification of responses of resistant/tolerant plants to glyphosate.