STIM/Orai-mediated calcium entry elicits spontaneous TSLP overproduction in epidermal cells of atopic dermatitis mice

Aim: Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease. Thymic stromal lymphopoietin (TSLP) is highly expressed in the epidermis of patients with AD and induces T helper 2 (Th2) immune responses and itching. Although the mechanism underlying the stimulus-induced TSLP production in normal keratinocytes has been intensively studied, whether the production capability of TSLP is naturally enhanced in epidermal cells in AD conditions remains unclear. Previous studies demonstrated that a deficiency of polyunsaturated fatty acid (PUFA) causes AD-like pruritic skin inflammation in special diet-fed hairless mice. The aim of the study was to examine the TSLP production capability of epidermal cells isolated from diet-induced AD mouse model and its mechanism. Methods: Epidermal cells were isolated from normal and AD mice and incubated under unstimulated culture conditions to assess spontaneous TSLP production. Messenger ribonucleic acid (mRNA) and protein levels of TSLP were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: TSLP level was markedly increased in the skin of AD mice. When epidermal cells were isolated from AD mice and cultured without stimulation, Tslp gene expression was upregulated, and a large amount of TSLP protein was extracellularly released. Such TSLP overproduction was not observed in the epidermal cells of normal mice. TSLP overproduction in AD epidermal cells was almost completely inhibited by extracellular calcium chelation, interference with plasma membrane interaction of stromal interaction molecule 1 (STIM1), blockade of the calcium release-activated calcium (CRAC) channels Orai1 and Orai2, or treatment with a PUFA γ-linolenic acid (GLA). Conclusions: Epidermal cells isolated from AD mice can spontaneously produce TSLP through STIM/Orai-mediated calcium entry, and GLA may negatively regulate this TSLP production

Genome-wide association study of semen volume, sperm concentration, testis size, and plasma inhibin B levels

Semen quality is affected by environmental factors, endocrine function abnormalities, and genetic factors. A GWAS recently identified ERBB4 at 2q34 as a genetic locus associated with sperm motility. However, GWASs for human semen volume and sperm concentration have not been conducted. In addition, testis size also reportedly correlates with semen quality, and it is important to identify genes that affect testis size. Reproductive hormones also play an important role in spermatogenesis. To date, genetic loci associated with plasma testosterone, sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels have been identified using GWASs. However, GWASs have not identified any relevant loci for plasma inhibin B levels. We conducted a two-stage GWAS using 811 Japanese men in a discovery stage followed by a replication stage using an additional 721 Japanese men. The results of the discovery and replication stages were combined into a meta-analysis. After setting a suggestive significance threshold for P values < 5 × 10-6　in the discovery stage, we identified ten regions with SNPs (semen volume: one, sperm concentration: three, testes size: two, and inhibin B: four). We selected only the most significant SNP in each region for replication genotyping. Combined discovery and replication results in the meta-analysis showed that the locus 12q21.31 associated with plasma inhibin B levels (rs11116724) had the most significant association (P = 5.7 × 10-8). The LRRIQ1 and TSPAN19 genes are located in the 12q21.31 region. This study provides new susceptibility variants that contribute to plasma inhibin B levels

T細胞活性化によるアセチルコリン受容体の発現抑制機構の検討

T細胞にはムスカリン性およびニコチン性アセチルコリン受容体（mAChRおよびnAChR）が発現している。T細胞のAChRは、細胞傷害性の増強、細胞分裂の促進、細胞内cGMP濃度の上昇などの生理的役割を担っている。本研究では、T細胞の活性化がAChRの遺伝子発現に及ぼす影響および発現調節メカニズムを検討した。マウス脾臓細胞あるいは脾臓細胞から単離したCD4陽性T細胞において、2 日間の抗CD3/CD28抗体刺激は、M1-M5 mAChR mRNAおよびα4、α7、β2 nAChR mRNAの発現を減少させた。この減少作用には、nuclear factor-κBが関与していることが明らかとなった。さらに、2 日間の抗CD3/CD28抗体刺激は、mAChRあるいはnAChRの活性化による細胞内Ca2＋濃度上昇を抑制した。以上の結果より、T細胞の活性化は受容体発現を減少させることによりAChに対する反応性を低下させることが明らかとなった。すなわち、T細胞の活性化は、mAChRおよびnAChRを介した細胞障害性の増強や細胞分裂促進などの生理作用を低下させる可能性が示唆された。Muscarinic and nicotinic acetylcholine receptors（mAChR and nAChR）are expressed in immune cells including T cells. AChR of T cells plays physiological roles such as the enhancement of cytotoxicity, the promotion of cell division, the elevation of intracellular cGMP concentration. In this study, the effect of T cell activation on the expression of AChR and the mechanism of its expression were examined. In CD4-positive T cells or CD4-negative cells isolated from mouse spleen cells, anti-CD3/CD28 antibody stimulation for 2 days reduced the expression of M1-M5 mAChR mRNAs and α4, α7, β 2 nAChR mRNAs. It was revealed that nuclear factor-κB is involved in this decreasing action. Furthermore,stimulation of intracellular Ca2＋ concentration by activation of mAChR or nAChR was suppressed by stimulation with anti-CD3/CD28 antibody for 2 days. From the above results, it was revealed that activation of T cells reduces the reactivity to ACh by decreasing AChR expression. That is, it was suggested that differentiation of T cells may decrease physiological effects such as enhancement of cytotoxicity and promotion of cell division via mAChR and nAChR.論

Kinetic boundary conditions for vapor–gas binary mixture

Using molecular dynamics simulations, the present study investigated the precise characteristics of the binary mixture of condensable gas (vapor) and non-condensable gas (NC gas) molecules creating kinetic boundary conditions (KBCs) at a gas–liquid interface in equilibrium. We counted the molecules utilizing the improved two-boundary method proposed in previous studies by Kobayashi et al. (Heat Mass Trans 52:1851–1859, 2016.doi:10.1007/s00231-015-1700-6). In this study, we employed Ar for the vapor molecules, and Ne for the NC gas molecules. The present method allowed us to count easily the evaporating, condensing, degassing, dissolving, and reflecting molecules in order to investigate the detailed motion of the molecules, and also to evaluate the velocity distribution function of the KBCs at the interface. Our results showed that the evaporation and condensation coefficients for vapor and NC gas molecules decrease with the increase in the molar fraction of the NC gas molecules in the liquid. We also found that the KBCs can be specified as a function of the molar fraction and liquid temperature. Furthermore, we discussed the method to construct the KBCs of vapor and NC gas molecules

Influence of a small amount of noncondensable gas on shock wave generation inside a collapsing vapor bubble

In this paper, the influence of a small amount of noncondensable gas on shock wave generation inside a collapsing vapor bubble is examined by combining numerical analysis of a bubble dynamics equation and of the Boltzmann equation for gas flow inside a bubble. We show the importance of the high Knudsen number in the flow, i.e., the nonequilibrium gas flow, to the temperature field inside the collapsing bubble. We also show that the maximum mean Knudsen number inside the collapsing bubble can be evaluated from the initial Knudsen number and the initial number density ratio of noncondensable gas and vapor molecules. As a result, we conclude that a small amount of noncondensable gas strongly affects the temperature field inside the collapsing bubble, preventing shock wave generation inside the bubble in the final stage of collapse

Differences in initial electrocardiographic findings between ST-elevation myocardial infarction due to left main trunk and left anterior descending artery lesions

Abstract Background Early discrimination of ST-elevation myocardial infarction (STEMI) due to a left main trunk (LMT) lesion provided by straightforward electrocardiographic criteria is useful for prompt treatment. The purpose of this study is to investigate differences in electrocardiographic findings between STEMI due to lesions of LMT and those of left anterior descending artery (LAD). Methods Initial electrocardiogram (ECG) recordings of 435 patients with analyzable ECGs from a cohort of 940 consecutive STEMI patients were analyzed retrospectively for presence of LMT lesions (LMT, n = 39), proximal (pLAD, n = 224) and distal LAD lesions (dLAD, n = 172). ST-segment deviations in 12 leads were assessed among 3 groups without bundle branch block (n = 17 in LMT, n = 180 in pLAD, and n = 159 in dLAD). Results Magnitudes of ST-segment deviations showed significant differences in leads II, III, aVR aVL, aVF, and V2–V6 across the three groups. This difference suggested two possible characteristic findings in the LMT group, allowing it to be distinguished from the pLAD or dLAD group; (A) larger magnitude of ST-segment depression in lead II than that of ST-segment elevation in lead V2 (47.1% in LMT vs. 0.6% in pLAD vs. 1.3% in dLAD, P < 0.0001), and (B) ST-segment depression in lead V5 (58.8% in LMT vs. 6.7% in pLAD vs. 2.5% in dLAD, P < 0.0001). These findings exhibited superior negative predictive value over conventional ST-segment elevation in lead aVR. Conclusions A large reciprocal ST-segment depression in inferior leads and ST-segment depression in lead V5 are useful ECG findings allowing determination of STEMI due to an LMT lesion

Study of electronic structure of Br-incorporated DNA related molecules

The aim of the present study is to clarify the electronic states of DNA related molecules incorporating a bromine atom. Since cells with DNA incorporating 5-bromouracil (BrU) as a thymine analogue have been known to be highly sensitive to ionizing irradiation, BrU is expected to be pharmacological agents as a sensitizer in radiation therapy. Previously, a radiation-track simulation study proposed a mechanism that hydrated electrons produced by water radiolysis could react with Br-DNA to form damage [1]. A recent EPR study reported that the bromine atom changes the yield of unpaired electrons in the uracil moiety [2]. In order to understand the physicochemical nature of Br-DNA, we investigated the binding energies of inner shell electrons of particular atoms in the DNA molecule using X-ray photoelectron spectroscopy (XPS) and X-ray Absorption Near Edge Structure (XANES) around the energies of C, N, O, P and Br K-absorption edges. Thin film samples of 5-bromo-2’-deoxyuridine-5’-monophosphate (BrdUMP) and thymidine-5’-monophosphate (TMP) were used for the spectroscopies. Obtained results indicate that the photoelectron binding energies, as well as the absorption edge energies, were similar for those sample molecules regardless of binding of a bromine atom. Contrary to the initial expectation, it is concluded that a bromine atom does not significantly contribute to the inner shell or unoccupied states in these molecules. Effect of bromine atom on the valence electronic states should be addressed in future studies.[1] Watanabe and Nikjoo Int. J. Radiat. Biol. 78, 953-66 (2002).[2] Oka et al. Appl. Phys. Lett. 113, 243701 (2018).第3回QST国際シンポジウム「Quantum Life Science

Fe-P-S electrodes for all-solid-state lithium secondary batteries using sulfide-based solid electrolytes

Although lithium-sulfur batteries are expected to be the next-generation high-capacity battery of choices, the sulfur electrodes studied so far contain large amounts (typically 30-60 wt%) of carbon additives, resulting in low energy density. In this study, an Fe-P-S-based material is prepared and characterized for the use as a sulfur electrode with a low content of carbon additives. The electrode material based on Fe-P-S is synthesized by the mechanical milling of FePS3 and elemental sulfur. The ball-milled 70FePS(3)center dot 30S (wt%) electrode comprises FeS2 particles of similar to 30 nm in size and amorphous P-S. The all-solid-state battery operated at 100 degrees C exhibits a reversible capacity of more than 625 mAh g(-1) for 50 cycles at 0.51 mA cm(-2) (similar to 0.1C) in spite of the low carbon content (2 wt%) in the electrode. During the discharge-charge cycle, the sulfur component is confirmed to be both reduced and oxidized, cyclically