Revisiting Flavor and CP Violation in Supersymmetric SU(5) with Right-Handed Neutrinos

We revisit the minimal supersymmetric SU(5) grand unified theory with three right-handed neutrinos in which universality conditions for soft-supersymmetry breaking parameters are imposed at an input scale above the unification scale. If the Majorana masses for the neutrinos are around $10^{15}$ GeV, large mixing angles and phases in the neutrino sector lead to flavor-violation and CP-violation in the right-handed down squark and left-handed slepton sectors. Since the observed Higgs boson mass and the proton decay constraints indicate sfermions have masses larger than a few TeV, flavor and CP constraints are less restrictive. We explore the constraints on models with a universal soft-supersymmetry breaking input parameters coming from proton stability, electric dipole moments, $\mu\to e\gamma$ decays, and the Higgs mass observed at the LHC. Regions compatible with all constraints can be found if non-zero A-terms are taken.Comment: 28 pages, 4 figures, version accepted PR

キイロショウジョウバエ由来のチオレドキシン還元酵素のC未端テトラペプチド配列は、ヒト肺由来のチオレドキシン還元酵素では酸化還元活性を示さない

The isozymes of mammalian thioredoxin reductase (TrxR) contain the penultimate selenocysteineresidue (SeCys) in the redox-active C-terminal tetrapeptide, -Gly-Cys-SeCys-Gly (end). Amutant form of the mammalian enzyme TrxR-X498C in which SeCys is replaced with Cys showsa dramatically decreased catalytic activity, suggesting that SeCys residue plays an integral role inthe catalysis. In contrast, TrxR of the fruit fly, Drosophila melanogaster, has no selenium in the corresponding C-terminal redox sequence, which instead of SeCys has flanking serine residues in the terminal sequence, -Ser-Cys-Cys-Ser (end). Because the catalytic activity of Dm-TrxR is comparable to that of the mammalian selenoenzyme, we introduced the serine residues at the corresponding positions of the recombinant TrxR-X498C and mimicked the redox center of the fruit fly TrxR. However, the catalysis remained as low as the Cys mutant of the selenoenzyme, suggesting that the additional structural features are still required for the tetrapeptide to function as a redox center. MOPAC calculation suggested that the complete motif might involve the hexapeptide sequence, which includes a proline residue, -Pro-X-Ser-Cys-Cys-Ser (end). The proline-containing motif is conserved among other insect TrxRs such as those of honeybee and fruit fly.ほ乳類チオレドキシン還元酵素はＣ末端配列-Gly-Cys-SeCys-Gly（end）の後ろから２番目にセレノシステイン（SeCys）残基を持つ．SeCys をシステインに変換すると酵素の活性は大きく低下するので，SeCys 残基が触媒活性に必須であることが分かる．これに対してキイロショウジョウバエのチオレドキシン還元酵素（Dm-TrxR）のＣ末端配列にはセレンが含まれず，システイン残基の対が２つのセリンに挟まれた配列-Ser-Cys-Cys-Ser (end）を持つ．それでも Dm-TrxR はほ乳類のセレン含有酵素と同程度の触媒能を示す．われわれはヒト肺チオレドキシン還元酵素に Dm-TrxR のＣ末端テトラペプチド配列を導入してその効果を調べた．しかし，酵素活性はまったく上昇せず，Dm-TrxR のＣ末端のテトラペプチド配列-Ser-Cys-Cys-Ser だけでは Cys 残基のチオール基を活性化する効果はなかった．そこで，分子軌道計算 MOPAC を用いて酸化還元機能を担うためのＣ末端配列モチーフを探索した．その結果，テトラペプチドにさらに２つ先のプロリンまでを含めた Pro-X-Ser-Cys-Cys-Ser（end）により初めて酸化還元モチーフとして機能する可能性が示唆された．Pro を含むこの配列モチーフはミツバチや蚊などほかの昆虫の TrxR でも保存されてい

Fabrication of C₆₀ field-effect transistors with polyimide and Ba_0.4Sr_0.6Ti_0.96O₃ gate insulators

Flexible C60 field-effect transistor (FET) device has been fabricated with polyimide gate insulator on the poly(ethylene terephthalate) substrate, and n-channel normally-off FET properties are observed in this FET device. The field-effect mobility, ?, is estimated to be ~10-2 cm2 V-1 s-1 at 300 K. Furthermore, the C60 FET has been fabricated with high dielectric Ba0.4Sr0.6Ti0.96O3 (BST) gate insulator, showing n-channel properties; the ? value is estimated to be ~10-4 cm2 V-1 s-1 at 300 K. The FET device operates at very low gate voltage, VG, and low drain-source voltage, VDS. Thus these C60 FET devices possess flexibility and low-voltage operation characteristic of polyimide and BST gate insulators, respectively.</p

Impact of extracellular matrix on engraftment and maturation of pluripotent stem cell-derived cardiomyocytes in a rat myocardial infarct model

Pluripotent stem cell-derived cardiomyocytes show great promise in regenerating the heart after myocardial infarction; however, several uncertainties exist that must be addressed before clinical trials. One practical issue is graft survival following transplantation. Although a pro-survival cocktail with Matrigel has been shown to enhance graft survival, the use of Matrigel may not be clinically feasible. The purpose of this study was to test whether a hyaluronan-based hydrogel, HyStem, could be a substitute for Matrigel. Human induced pluripotent stem cell-derived cardiomyocytes diluted with HyStem alone, HyStem plus pro-survival factors, or a pro-survival cocktail with Matrigel (PSC/MG), were transplanted into a rat model of acute myocardial infarction. Histological analysis at 4 weeks post transplantation revealed that, among the three groups, recipients of PSC/MG showed the largest graft size. Additionally, the grafted cardiomyocytes in the recipients of PSC/MG had a more matured phenotype compared to those in the other two groups. These findings suggest that further studies will be required to enhance not only graft size, but also the maturation of grafted cardiomyocytes.ArticleScientific reports 7(1) : 8630-(2017)journal articl

Dysbindin Regulates the Transcriptional Level of Myristoylated Alanine-Rich Protein Kinase C Substrate via the Interaction with NF-YB in Mice Brain

BACKGROUND: An accumulating body of evidence suggests that Dtnbp1 (Dysbindin) is a key susceptibility gene for schizophrenia. Using the yeast-two-hybrid screening system, we examined the candidate proteins interacting with Dysbindin and revealed one of these candidates to be the transcription factor NF-YB. METHODS: We employed an immunoprecipitation (IP) assay to demonstrate the Dysbindin-NF-YB interaction. DNA chips were used to screen for altered expression of genes in cells in which Dysbindin or NF-YB was down regulated, while Chromatin IP and Reporter assays were used to confirm the involvement of these genes in transcription of Myristoylated alanine-rich protein kinase C substrate (MARCKS). The sdy mutant mice with a deletion in Dysbindin, which exhibit behavioral abnormalities, and wild-type DBA2J mice were used to investigate MARCKS expression. RESULTS: We revealed an interaction between Dysbindin and NF-YB. DNA chips showed that MARCKS expression was increased in both Dysbindin knockdown cells and NF-YB knockdown cells, and Chromatin IP revealed interaction of these proteins at the MARCKS promoter region. Reporter assay results suggested functional involvement of the interaction between Dysbindin and NF-YB in MARCKS transcription levels, via the CCAAT motif which is a NF-YB binding sequence. MARCKS expression was increased in sdy mutant mice when compared to wild-type mice. CONCLUSIONS: These findings suggest that abnormal expression of MARCKS via dysfunction of Dysbindin might cause impairment of neural transmission and abnormal synaptogenesis. Our results should provide new insights into the mechanisms of neuronal development and the pathogenesis of schizophrenia

Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo

Accumulating evidence suggests that human pluripotent stem cell-derived cardiomyocytes can affect “heart regeneration”, replacing injured cardiac scar tissue with concomitant electrical integration. However, electrically coupled graft cardiomyocytes were found to innately induce transient post-transplant ventricular tachycardia in recent large animal model transplantation studies. We hypothesised that these phenomena were derived from alterations in the grafted cardiomyocyte characteristics. In vitro experiments showed that human embryonic stem cell-derived cardiomyocytes (hESC-CMs) contain nodal-like cardiomyocytes that spontaneously contract faster than working-type cardiomyocytes. When transplanted into athymic rat hearts, proliferative capacity was lower for nodal-like than working-type cardiomyocytes with grafted cardiomyocytes eventually comprising only relatively matured ventricular cardiomyocytes. RNA-sequencing of engrafted hESC-CMs confirmed the increased expression of matured ventricular cardiomyocyte-related genes, and simultaneous decreased expression of nodal cardiomyocyte-related genes. Temporal engraftment of electrical excitable nodal-like cardiomyocytes may thus explain the transient incidence of post-transplant ventricular tachycardia, although further large animal model studies will be required to control post-transplant arrhythmia

Outcomes after stepwise ablation for persistent atrial fibrillation in patients with heart failure

AbstractBackgroundThere is limited data regarding the outcomes after stepwise ablation for persistent atrial fibrillation (AF) in patients with heart failure (HF).Methods and resultsPatients without structural heart disease undergoing stepwise ablation for persistent AF (continuous AF≤1 year) were studied (n=108; age, 61±10 years) and 32 patients had a history of HF. The HF patients were further grouped on the basis of left ventricular ejection fraction (LVEF)≤45% (n=15) and >45% (n=17). During a median follow-up period of 2.2 years, repeated ablations were necessary in 65 patients. The proportion of patients that were arrhythmia free 1 year after the last ablation was 67% in patients with LVEF≤45%, 86% in LVEF>45%, and 91% in no HF (p=0.0009). In patients with LVEF≤45%, the AF burden was reduced to less than one paroxysmal episode per month, and patients with and without recurrences both showed significant increases in LVEF over the follow-up period (38±7% to 60±10% and 37±6% to 53±10%, respectively).ConclusionsHF patients with LVEF≤45% had lower chances to remain free from arrhythmias after stepwise ablation for persistent AF than those with LVEF>45%. Nevertheless, LVEF also improved in patients with recurrences, reflecting the observed reduction in AF burden and emphasizing the benefits of ablation

生殖補助医療を行っている患者において卵胞液中のキスペプチン濃度は卵成熟および性腺ホルモン値と関連している

Purpose: To assess the kisspeptin concentrations in follicular fluid and their relationship with clinical outcomes during assisted reproductive technology. Methods: Thirty-nine patients who were aged 24-40 years and underwent oocyte retrieval for in vitro fertilization/intracytoplasmic sperm injection participated in this study. In 65 follicular fluid samples that had been obtained from 30 patients and their blood samples, the kisspeptin levels were measured in order to investigate the correlations with their gonadal hormone levels. Venous blood samples were collected from 14 patients to investigate their plasma kisspeptin levels across different phases of assisted reproductive technology. Results: The follicular fluid kisspeptin level was significantly higher than that of the plasma level and was positively associated with the follicular fluid estradiol concentration and with the serum estradiol and number of mature oocytes. In the plasma, the maximum concentration of kisspeptin was observed on the day of ovum pick-up and on the day of embryo transfer during ovarian stimulation for assisted reproductive technology. Conclusion: Kisspeptin was present in the follicular fluid and the plasma kisspeptin concentration was affected by ovarian stimulation. Kisspeptin appears to affect oocyte maturation and ovulation