Pilot study of the optimal protocol of low dose step‐up follicle stimulating hormone therapy for infertile women

Purpose: To evaluate the optimized protocol of low dose follicle‐stimulating hormone (FSH) therapy that has a starting dose of 50 IU/62.5 IU with a small increment dose (12.5 IU) for women with World Health Organization (WHO) II ovulatory disorder and unexplained infertility. Methods: Anovulatory women with WHO group II ovulatory disorder (ovulation induction [OI] patients, n = 29), and with an unexplained infertility (ovarian stimulation [OS] patients, n = 21) were enrolled. The protocol of low dose step‐up FSH therapy was optimized for the starting dose as 50 IU (body mass index [BMI] < 20 group) and 62.5 IU (BMI ≥ 20 group) with the increment dose of 12.5 IU. Study outcomes were ovulation, monofollicular development and other variables. Results: In the OIpatients, the ovulation rate was 100% (BMI < 20 group) and 90.9% (BMI ≥ 20 group). Monofollicular development was 80.0% (BMI < 20) and 77.3% (BMI ≥ 20). The pregnancy rate was 60% (3/5 BMI < 20) and 18.2% (4/22 BMI ≥ 20). There was no multiple pregnancy. In the OSpatients, the ovulation rate was 100%. Monofollicular development was 85.7% (BMI < 20) and 76.6% (BMI ≥ 20). No pregnancy was achieved in the OSpatients. Conclusion: Optimized protocol of low dose FSH therapy setting a starting dose 50 IU/62.5 IU by BMI with an increment dose of 12.5 IU was safe and highly effective in WHO group II anovulatory patients. However, this protocol seemed uneffective for patients with unexplained infertility

Reconstruction of precipitating electrons and three-dimensional structure of a pulsating auroral patch from monochromatic auroral images obtained from multiple observation points

In recent years, aurora observation networks using high-sensitivity cameras have been developed in the polar regions. These networks allow dimmer auroras, such as pulsating auroras (PsAs), to be observed with a high signal-to-noise ratio. We reconstructed the horizontal distribution of precipitating electrons using computed tomography with monochromatic PsA images obtained from three observation points. The three-dimensional distribution of the volume emission rate (VER) of the PsA was also reconstructed. The characteristic energy of the reconstructed precipitating electron flux ranged from 6 to 23 keV, and the peak altitude of the reconstructed VER ranged from 90 to 104 km. We evaluated the results using a model aurora and compared the model’s electron density with the observed one. The electron density was reconstructed correctly to some extent, even after a decrease in PsA intensity. These results suggest that the horizontal distribution of precipitating electrons associated with PsAs can be effectively reconstructed from ground-based optical observations

Dysregulated Aire expression and autoimmunity

Deficiency for AIRE/Aire in both humans and mice results in the development of organ-specific autoimmune disease. We tested whether augmented and/or dysregulated AIRE/Aire expression might be also prone to the breakdown of self-tolerance. To define the effect of augmented Aire expression on the development of autoimmunity, antigen-specific clonal deletion and production of clonotypic regulatory T cells (Tregs) in the thymus were examined using mice expressing two additional copies of Aire in a heterozygous state (3xAire-knockin mice: 3xAire-KI). We found that both clonal deletion of autoreactive T cells and production of clonotypic Tregs in the thymus from 3xAire-KI were impaired in a T-cell receptor-transgenic system. Furthermore, 3xAire-KI females showed higher scores of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein than wild-type littermates, suggesting that augmented Aire expression exacerbates organ-specific autoimmunity under disease-prone conditions. In humans, we found that one patient with amyopathic dermatomyositis showed CD3–CD19– cells expressing AIRE in the peripheral blood before the treatment but not during the remission phase treated with immunosuppressive drugs. Thus, not only loss of function of AIRE/Aire but also augmented and/or dysregulated expression of AIRE/Aire should be considered for the pathogenesis of organ-specific autoimmunity. We suggest that further analyses should be pursued to establish a novel link between organ-specific autoimmune disease and dysregulated AIRE expression in clinical settings

Dwarf Novae in the Shortest Orbital Period Regime: I. A New Short Period Dwarf Nova, OT J055717+683226

We report the observation of a new dwarf nova, OT J055717+683226, during its first-ever recorded superoutburst in December 2006. Our observation shows that this object is an SU UMa-type dwarf nova having a very short superhump period of 76.67+/- 0.03 min (0.05324+/-0.00002 d). The next superoutburst was observed in March 2008. The recurrence time of superoutbursts (supercycle) is, hence, estimated to be ~480 d. The supercycle is much shorter than those of WZ Sge-type dwarf novae having supercycles of >~ 10 yr, which are a major population of dwarf novae in the shortest orbital period regime (<~85 min). Using a hierarchical cluster analysis, we identified seven groups of dwarf novae in the shortest orbital period regime. We identified a small group of objects that have short supercycles, small outburst amplitudes, and large superhump period excesses, compared with those of WZ Sge stars. OT J055717+683226 probably belongs to this group.Comment: 14 pages, 11 figures, accepted for publication in PAS

ISAI: Investigating Solar Axion by Iron-57

The existence of the axion is a unique solution for the strong CP problem, and the axion is one of the most promising candidates of the dark matter. Investigating Solar Axion by Iron-57 (ISAI) is being prepared as a complemented table-top experiment to confirm the solar axion scenario. Probing an X-ray emission from the nuclear transitions associated with the axion-nucleon coupling is a leading approach. ISAI searches for the monochromatic 14.4 keV X-ray from the first excited state of 57Fe using a state-of-the-art pixelized silicon detector, dubbed XRPIX, under an extremely low-background environment. We highlight scientific objectives, experimental design and the latest status of ISAI

Structural insights into tetraspanin CD9 function

Umeda, R., Satouh, Y., Takemoto, M. et al. Structural insights into tetraspanin CD9 function. Nat Commun 11, 1606 (2020). https://doi.org/10.1038/s41467-020-15459-

Vitamin B6 Prevents IL-1β Protein Production by Inhibiting NLRP3 Inflammasome Activation

Vitamin B6 includes six water-soluble vitamers: pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN), and their phosphorylated forms. Pyridoxal 5o\u27-phosphate (PLP) is an important cofactor for many metabolic enzymes. Several lines of evidence demonstrate that blood levels of PLP are significantly lower in patients with inflammation than in control subjects and that vitamin B6 has anti-inflammatory effects, with therapeutic potential for a variety of inflammatory diseases. Although one of our group previously demonstrated that PL inhibits the NF-κB pathway, the molecular mechanism by which vitamin B6 suppresses inflammation is not well understood. Here, we showed that both PL and PLP suppressed the expression of cytokine genes in macrophages by inhibiting Toll-like receptor (TLR)-mediated TAK1 phosphorylation and the subsequent NF-κB and JNK activation. Furthermore, PL and PLP abolished NLRP3-dependent caspase-1 processing and the subsequent secretion of mature IL-1β and IL-18 in LPS-primed macrophages. In contrast, PM and PN had little effect on IL-1β production. PLP, but not PL, markedly reduced the production of mitochondrial reactive oxygen species (ROS) in peritoneal macrophages. Importantly, PL and PLP reduced IL-1β production induced by LPS and ATP, or by LPS alone, in mice. Moreover, PL and PLP protected mice from lethal endotoxic shock. Collectively, these findings reveal novel anti-inflammatory activities for vitamin B6 and suggest its potential for preventing inflammatory diseases driven by the NLRP3 inflammasome. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc