Like-sign dimuon asymmetry of B0 meson and LFV in SU(5) SUSY GUT with S4 flavor symmetry

The like-sign dimuon charge asymmetry of the $B$ meson, which was reported in the D\O Collaboration, is studied in the SU(5) SUSY GUT model with $S_4$ flavor symmetry. Additional CP violating effects from the squark sector are discussed in $B_s-\bar B_s$ mixing process. The predicted like-sign charge asymmetry is in the 2$\sigma$ range of the combined result of D\O and CDF measurements. Since the SUSY contributions in the quark sector affect to the lepton sector because of the SU(5) GUT relation, two predictions are given in the leptonic processes: (i) both ${\rm BR}(\mu \to e \gamma)$ and the electron EDM are close to the present upper bound, (ii) the decay ratios of $\tau$ decays, $\tau \to \mu\gamma$ and $\tau \to e \gamma$, are related to each other via the Cabibbo angle $\lambda_c$: {\rm BR}(\tau \to e\gamma)/{\rm BR}(\tau \to \mu\gamma)\sime \lambda_c^2. These are testable at future experiments.Comment: 33 pages, 4 figures, a footnote and references are adde

Different Pathological Roles of Toll-Like Receptor 9 on Mucosal B Cells and Dendritic Cells in Murine IgA Nephropathy

Although pathogenesis of IgA nephropathy (IgAN) is still obscure, pathological contribution of mucosal immunity including production of nephritogenic IgA and IgA immune complex (IC) has been discussed. We have reported that mucosal toll-like receptor (TLR)-9 is involved in the pathogenesis of human and murine IgAN. However, cell-type expressing TLR9 in mucosa remains unclear. To address this, we nasally challenged cell-specific CpG DNA ((i): dendritic cell: (DC), (ii): B cell, (iii): both), known as ligand for TLR9, to IgAN prone mice and analyzed disease phenotype of each group. After 8 times of the weekly administration, every group showed deterioration of glomerular damage. However, CpG-A-group showed clear extension of mesangial proliferative lesions with increase of serum IgA-IgG2a IC and its glomerular depositions, while CpG-B-group showed extent of glomerular sclerotic lesions with increase of serum and glomerular IgA and M2 macrophage infiltration. Present results indicate that mucosal TLR9 on B cells and DC may differently contribute to the progression of this disease via induction of nephritogenic IgA or IgA-IgG IC, respectively. This picture is suggestive for the pathological difference between child and adult IgAN

B-Cell-Activating Factor Affects the Occurrence of Thyroid Autoimmunity in Chronic Hepatitis C Patients Treated with Interferon Alpha

Chronic hepatitis C (CHC) patients frequently suffer from thyroid disorders during interferon therapy. However, the mechanism remains unclear. In this study, we investigated the association between serum B-cell-activating factor belonging to the TNF family (BAFF) levels and the presence of antithyroid peroxidase antibody (anti-TPO) in CHC patients treated with pegylated interferon alpha and ribavirin combination therapy. Six months after the therapy, anti-TPO antibody was detected in 10 (males, 1; females, 9) of 50 patients. The mean age of these patients was higher than that of the anti-TPO-negative patients (61 yr versus 55 yr). Before treatment, the serum BAFF levels of the anti-TPO-positive patients were higher than those of the anti-TPO-negative patients. After starting therapy, the serum BAFF levels of both the anti-TPO-positive and -negative patient groups were elevated. Our findings suggest that the serum BAFF concentration before therapy can predict the risk of thyroid autoimmunity in elderly female patients with CHC

Pathological Role of Tonsillar B Cells in IgA Nephropathy

Although impaired immune regulation along the mucosa-bone marrow axis has been postulated to play an important role, the pathogenesis of IgA nephropathy (IgAN) is unknown; thus, no disease-specific therapy for this disease exists. The therapeutic efficacy of tonsillectomy or tonsillectomy in combination with steroid pulse therapy for IgAN has been discussed. Although randomized control trials for these therapies are ongoing in Japan, the scientific rationale for these therapies remains obscure. It is now widely accepted that abnormally glycosylated IgA1 and its related immune complex (IC) are probably key molecules for the pathogenesis, and are thus considered possible noninvasive biomarkers for this disease. Emerging evidence indicates that B cells in mucosal infections, particularly in tonsillitis, may produce the nephritogenic IgA. In this paper, we briefly summarize characteristics of the nephritogenic IgA/IgA IC, responsible B cells, and underlying mechanisms. This clinical and experimental information may provide important clues for a therapeutic rationale

Prescription trend and lactic acidosis in patients prescribed metformin before and after the revision of package insert for allowing metformin administration to patients with moderately decreased kidney function based on real-world data from MID-NET® in Japan

IntroductionThis study was conducted to understand the impact of package insert (PI) revision in Japan on 18 June 2019 to allow metformin use for patients with moderately decreased kidney function (30 ≤ estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2).MethodsA new user cohort design was employed to examine the prescription trend and the occurrence of lactic acidosis in patients prescribed metformin before and after PI revision using the Medical Information Database Network (MID-NET®).ResultsFrom 12 May 2016 to 31 March 2020, 5,874 patients (before, n = 4,702; after, n = 1,172) were identified as new metformin users, including 1,145 patients (before, n = 914; after, n = 231) with moderately decreased kidney function. Although no marked changes in metformin prescription were observed before and after PI revision, the daily metformin dose at the first prescription decreased after PI revision. For both before and after PI revision, less than 10 cases of lactic acidosis occurred in all patients prescribed metformin, and no lactic acidosis was observed in patients with moderately decreased kidney function.ConclusionThe results of this study are useful for understanding the safety of metformin use in patients with decreased kidney function and suggest no worse impacts of PI revision in Japan, indicating no further safety concerns on metformin use in patients with moderately decreased kidney function under the situation with careful use and safety monitoring of metformin

Association of glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS): a cross-sectional study

Background While survival of systemic lupus erythematosus (SLE) patients has improved substantially, problems remain in the management of their emotional health. Medium to high-dose glucocorticoid doses are known to worsen emotional health; the effect is unclear among patients receiving relatively low-dose glucocorticoids. This study aims to investigate the association between low glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS). Methods This cross-sectional study drew on data from SLE patients in 10 Japanese institutions. The participants were adult patients with SLE duration of >= 1 year who met LLDAS criteria at the study visit from April 2018 through September 2019. The exposure was the daily glucocorticoid dose (mg oral prednisolone). The outcome was the emotional health score of the lupus patient-reported outcome scale (range: 0 to 100). Multiple linear regression analysis was performed with adjustment for confounders including disease-related damage, activity, and psychotropic drug use. Results Of 192 patients enrolled, 175 were included in the analysis. Their characteristics were as follows: female, 89.7%; median age, 47 years (interquartile range (IQR): 37.0, 61.0). Median glucocorticoid dose was 4.0 mg (IQR 2.0, 5.0), and median emotional health score 79.2 (IQR 58.3, 91.7). Multiple linear regression analysis showed daily glucocorticoid doses to be associated with worse emotional health (beta coefficient = - 2.54 [95% confidence interval - 4.48 to - 0.60], P = 0.01). Conclusions Daily glucocorticoid doses were inversely associated with emotional health among SLE patients in LLDAS. Further studies are needed to determine whether glucocorticoid tapering leads to clinically significant improvements in emotional health

Active Learning Models in Science Classes

研究の第１年次に当たる本年は，理科におけるアクティブラーニング型授業の構造化に向けて，内化と外化の往還を取り入れた授業デザインとその実践に取り組み，具体的実践の蓄積を行った。小学校，中学校，高等学校それぞれで実践を行ったところ，１）学習内容の定着が図られる，２）発展的な内容や未習内容を生徒が主体的に理解することが可能である，３）協働的な学びの場面を加えることで理解の深化が図られる，４）どのような課題に取り組ませるのかといった課題の設定がカギである，５）アクティブラーニングであるか否かを判断するための要素を明らかにする必要がある，などの一定の成果と課題が明らかになった。The purpose of this study is to create active learning models in science classes. As the first-year research, the authors designed the classes which would include a round trip between externalization and internalization, and put them into practice. The designed models were adopted in elementary, junior high and senior high school classes. What have become clear are as the following; 1) Students’ acquisition of the learning contents can be promoted, 2) Students can understand advanced contents proactively, 3) Students’ learning can be deepened by adding collaborative activities, 4) The success or failure to active learning may depend on the quality of the tasks which students work on, 5) It is necessary to clarify the factors to determine active learning

The Carboxyl-Terminal Domain of TraR, a Streptomyces HutC Family Repressor, Functions in Oligomerization▿

Efficient conjugative transfer of the Streptomyces plasmid pSN22 is accomplished by regulated expression of the tra operon genes, traA, traB, and spdB. The TraR protein is the central transcriptional repressor regulating the expression of the tra operon and itself and is classified as a member of the HutC subfamily in the helix-turn-helix (HTH) GntR protein family. Sequence information predicts that the N-terminal domain (NTD) of TraR, containing an HTH motif, functions in binding of DNA to the cis element; however, the function of the C-terminal region remains obscure, like that for many other GntR family proteins. Here we demonstrate the domain structure of the TraR protein and explain the role of the C-terminal domain (CTD). The TraR protein can be divided into two structural domains, the NTD of M1 to R95 and the CTD of Y96 to E246, revealed by limited proteolysis. Domain expression experiments revealed that both domains retained their function. An in vitro pull-down assay using recombinant TraR proteins revealed that TraR oligomerization depended on the CTD. A bacterial two-hybrid system interaction assay revealed that the minimum region necessary for this binding is R95 to P151. A mutant TraR protein in which Leu121 was replaced by His exhibited a loss of both oligomerization ability and repressor function. An in vitro cross-linking assay revealed preferential tetramer formation by TraR and the minimum CTD. These results indicate that the C-terminal R95-to-P151 region of TraR functions to form an oligomer, preferentially a tetramer, that is essential for the repressor function of TraR

Complex Formation by the mrpABCDEFG Gene Products, Which Constitute a Principal Na+/H+ Antiporter in Bacillus subtilis▿

The Bacillus subtilis Mrp (also referred to as Sha) is a particularly unusual Na+/H+ antiporter encoded by mrpABCDEFG. Using His tagging of Mrp proteins, we showed complex formation by the mrpABCDEFG gene products by pull-down and blue native polyacrylamide gel electrophoresis analyses. This is the first molecular evidence that the Mrp is a multicomponent antiporter in the cation-proton antiporter 3 family

A novel technique for ligation of the cephalic vein reduces hemorrhaging during a two-in-one insertion of dual cardiac device leads

The cutdown technique for the cephalic vein is a common access route for transvenous cardiac device leads (TVLs), and sometimes one cephalic vein can accomodate two TVLs. We examined a novel ligation technique to balance the hemostasis and lead maneuverability for this two-in-one insertion. A total of 22 patients scheduled for cardiac device implantations with two or more leads were enrolled. The ipsilateral cephalic vein was identified for inserting the TVLs with a cutdown. If two TVLs could be introduced into one cephalic vein, hemostasis was established by ligating the venous wall between the TVLs. We measured the amount of hemorrhaging per minute and the operators assessed the lead maneuverability before and after the ligation. We successfully implanted cardiac devices in 15 patients (68%) with this novel method, whereas only one TVL could be introduced via the cephalic vein in 7 patients. As for the successful patients, hemorrhaging from the gap was significantly reduced (5.6 ± 7.3 to 0.41 ± 0.36g/min, p = 0.016) after the novel ligation. The lead maneuverability was well maintained so there was no difficulty placing the leads into the cardiac chambers in all cases. No major complications were observed. In the present study, the novel ligation method provided significant hemostasis as well as a preserved maneuverability. It could be an optional choice for insertion of multiple TVLs. Keywords: Cephalic vein, Cutdown, Hemostasis, Implantable defibrillator, Pacemake