Dilatonic Inflation and SUSY Breaking in String-inspired Supergravity

The theory of inflation will be investigated as well as supersymmetry breaking in the context of supergravity, incorporating the target-space duality and the nonperturbative gaugino condensation in the hidden sector. We found an inflationary trajectory of a dilaton field and a condensate field which breaks supersymmetry at once. The model satisfies the slow-roll condition which solves the eta-problem. When the particle rolls down along the minimized trajectory of the potential V(S,Y) at a duality invariant point of T=1, we can obtain the e-fold value \sim 57. And then the cosmological parameters obtained from our model well match the recent WMAP data combined with other experiments. This observation suggests one to consider the string-inspired supergravity as a fundamental theory of the evolution of the universe as well as the particle theory.Comment: 10 pages, 4 eps figures. Typos and references corrected. Final version to appear in Mod. Phys. Lett.

Preparation and Observation of Fresh-frozen Sections of the Green Fluorescent Protein Transgenic Mouse Head

Hard tissue decalcification can cause variation in the constituent protein characteristics. This paper describes a method of preparating of frozen mouse head sections so as to clearly observe the nature of the constituent proteins. Frozen sections of various green fluorescent protein (GFP) transgenic mouse heads were prepared using the film method developed by Kawamoto and Shimizu. This method made specimen dissection without decalcification possible, wherein GFP was clearly observed in an undamaged state. Conversely, using the same method with decalcification made GFP observation in the transgenic mouse head difficult. This new method is suitable for observing GFP marked cells, enabling us to follow the transplanted GFP marked cells within frozen head sections

Endothelial-mesenchymal transition in human atrial fibrillation

Background: Atrial fibrosis is a hallmark of atrial structural remodeling leading to the persistence of atrial fibrillation. Although fibroblasts play a major role in atrial fibrosis, their source in the adult atrium is unclear. We tested the hypothesis that endothelial cells contribute to fibroblast accumulation through an endothelial-mesenchymal transition in the atrium of patients with atrial fibrillation. Methods and results: The study group consisted of patients with atrial fibrillation and valvular disease or atrial septal defect who underwent left atrial appendectomy during cardiac surgery (n =38). The amount of fibrotic depositions in the left atrium positively correlated with left atrial dimension. Furthermore, snail and S100A4, indicative of endothelial-mesenchymal transition, were quantified in the left atrium using western blot analysis, which showed statistically significant correlations with left atrial dimension. Immunofluorescence assay of the left atrial tissue identified snail and S100A4 being expressed within the endocardium which is composed of CD31+ cells. The snail-positive endocardium also showed the expression of membrane type 1-matrix metalloproteinase. Immunofluorescence multi-labeling experiments identified that heat shock protein 47, prolyl-4-hydroxylase, and procollagen type 1 co-localized with snail and S100A4 within the endothelial cells of the left atrium, indicating the mesenchymal phenotype to produce collagen. Conclusions: In this study, we showed that the endothelial-mesenchymal transition occurs in the atrium of patients with atrial fibrillation. This observation should help in constructing a novel therapeutic approach for preventing atrial structural remodeling. © 2016 Japanese College of Cardiology

Non-missense variants of KCNH2 show better outcomes in type 2 long QT syndrome

AIMS: More than one-third of type 2 long QT syndrome (LQT2) patients carry KCNH2 non-missense variants that can result in haploinsufficiency (HI), leading to mechanistic loss-of-function. However, their clinical phenotypes have not been fully investigated. The remaining two-thirds of patients harbour missense variants, and past studies uncovered that most of these variants cause trafficking deficiency, resulting in different functional changes: either HI or dominant-negative (DN) effects. In this study, we examined the impact of altered molecular mechanisms on clinical outcomes in LQT2 patients. METHODS AND RESULTS: We included 429 LQT2 patients (234 probands) carrying a rare KCNH2 variant from our patient cohort undergoing genetic testing. Non-missense variants showed shorter corrected QT (QTc) and less arrhythmic events (AEs) than missense variants. We found that 40% of missense variants in this study were previously reported as HI or DN. Non-missense and HI-groups had similar phenotypes, while both exhibited shorter QTc and less AEs than the DN-group. Based on previous work, we predicted the functional change of the unreported variants-whether they cause HI or DN via altered functional domains-and stratified them as predicted HI (pHI)- or pDN-group. The pHI-group including non-missense variants exhibited milder phenotypes compared to the pDN-group. Multivariable Cox model showed that the functional change was an independent risk of AEs (P = 0.005). CONCLUSION: Stratification based on molecular biological studies enables us to better predict clinical outcomes in the patients with LQT2