Improvement of acid resistance of Zn-doped dentin by newly generated chemical bonds

Dental caries, the world's most prevalent infectious disease, is caused by the diffusion of hydroxyl ions into tooth structures. To prevent dental caries, the application of fluoride (F) and zinc (Zn) ions to teeth surfaces are potential effective measures. In this study, The ionic influence, especially the chemical bond of F and Zn, on the acid resistance of dentin were investigated by particle induced X-ray / gamma-ray emission, X-ray diffraction, X-ray photoelectron spectroscopy and X-ray absorption spectroscopy. The results showed Zn was distributed in the limited surface layer of dentin without altering its crystal structure. From the Zn K edge extended X-ray absorption fine structure, Zn incorporated into dentin was surrounded by oxygen and demonstrated four-fold coordination. The bond length and chemical state of Zn–O in Zn doped dentin suggested newly generated Zn–O covalent bond, which may improve acid resistance of dentin. This study showed that the atomic and molecular structures, such as the molecular distances and chemical state, influenced acid resistance of teeth, emphasizing the validity of chemical state analysis for understanding properties in biomaterials.Naito K., Kuwahara Y., Yamamoto H., et al. Improvement of acid resistance of Zn-doped dentin by newly generated chemical bonds. Materials and Design, 215, 110412. https://doi.org/10.1016/j.matdes.2022.110412

AIR-COOLED MAGNETIC ALLOY CAVITY FOR J-PARC DOUBLED REP.-RATE SCENARIO

Abstract The upgrade project of the J-PARC MR (Main Ring) based on doubled repetition-rate scenario is in progress to deliver the beam power of 750 kW. The present RF section will be occupied by 9 sets of new magnetic alloy, FT3L, cavities using the direct water cooling scheme. The direct water cooling is the efficient scheme to cool the magnetic alloy core although it requires dedicated high-quality cooling water which does not contain copper oxide and copper ions because copper ions may cause the severe corrosion damage on the magnetic alloy cores. These cavities will be used for the fundamental RF for acceleration which requires high duty operation. The second harmonic RF is necessary to increase the bunch length. This allows to enlarge the beam current because it relaxes the space charge effects during the injection. Thanks to the high impedance FT3L and low duty operation of the second harmonic RF, the power loss in the second harmonic RF system becomes moderate. The air cooled cavity is designed to fit in any locations in the MR where the dedicated high-quality water is not available. This paper reports the design of the second RF system, technical issues to produce the magnetic alloy cores to fit the air cooling, and construction of the system

PERFORMANCE OF MULTI-HARMONIC RF FEEDFORWARD SYSTEM FOR BEAM LOADING COMPENSATION IN THE J-PARC RCS

Abstract The beam loading compensation is a key part for acceleration of high intensity proton beams in the J-PARC RCS. In the wide-band MA-loaded RF cavity, the wake voltage consists of not only the accelerating harmonic component but also the higher harmonics. The higher harmonic components cause the RF bucket distortion. We employ the RF feedforward method to compensate the multi-harmonic beam loading. The full-digital feedforward system is developed, which compensates the first three harmonic components of the beam loading. We present the results of the beam test with a high intensity proton beam (2.5 × 10 13 ppp). The impedance seen by the beam is greatly reduced, the impedance of the fundamental accelerating harmonic is reduced to less than 25 Ω in a full accelerating cycle, while the shunt resistance of the cavity is in the order of 800 Ω. The performance of the feedforward system is promising for achievement of the design beam power, 1 MW, in the future

On the top of ARB N/L type Ca channel blocker leads to less elevation of aldosterone

Synopsis The activation of the renin-angiotensin system (RAS) is one of the unfavourable characteristics of calcium channel blocker (CCB). N type calcium channel is thought to be involved in renin gene transcription and adrenal aldosterone release. Accordingly, N/L type CCB has a possibility of less elevation of plasma aldosterone concentrations (PAC) among CCBs. In a monotherapy study, we had already demonstrated that N/L type CCB leads to less activation of the RAS compared with L type CCB. The objective of this study is to substantiate the hypothesis that at the condition of additive administration on the top of an angiotensin receptor blocker (ARB), still N/L type CCB leads to less elevation of PAC compared with L type one. Subjects were 60 hypertensives administered with valsartan. As an open label study, amlodipine (L type) or cilnidipine (N/L type) were administered on the top of valsartan (ARB) in a cross-over manner. Results were as follows (valsartan + amlodipine compared with valsartan + cilnidipine): systolic blood pressure (SBP)/diastolic blood pressure (DBP) (mmHg): 132 + − 10/76 + − 10 compared with 131 + − 10/77 + − 9, P = 0.95/0.48, plasma renin activity (PRA) (ng/ml·h): 2.41 + − 2.67 compared with 2.00 + − 1.50 P = 0.20, PAC (pg/ml): 77.3 + − 31.0 compared with 67.4 + − 24.8, P < 0.05, urinary albumin excretion (UAE) (mg/gCr): 105.9 + − 216.1 compared with 73.9 + − 122.2, P < 0.05. Thus, PAC at cilnidipine was significantly lower than those at amlodipine in spite of the comparable BP reductions. Besides, UAE was significantly lower at cilnidipine. In conclusion, on the top of the ARB, it is suggested that cilnidipine administration might lead to less elevation of PAC and reduction in UAE compared with amlodipine

Small RNA class transition from siRNA/piRNA to miRNA during pre-implantation mouse development

Recent studies showed that small interfering RNAs (siRNAs) and Piwi-interacting RNA (piRNA) in mammalian germ cells play important roles in retrotransposon silencing and gametogenesis. However, subsequent contribution of those small RNAs to early mammalian development remains poorly understood. We investigated the expression profiles of small RNAs in mouse metaphase II oocytes, 8–16-cell stage embryos, blastocysts and the pluripotent inner cell mass (ICM) using high-throughput pyrosequencing. Here, we show that during pre-implantation development a major small RNA class changes from retrotransposon-derived small RNAs containing siRNAs and piRNAs to zygotically synthesized microRNAs (miRNAs). Some siRNAs and piRNAs are transiently upregulated and directed against specific retrotransposon classes. We also identified miRNAs expression profiles characteristic of the ICM and trophectoderm (TE) cells. Taken together, our current study reveals a major reprogramming of functional small RNAs during early mouse development from oocyte to blastocyst

The history of human populations in the Japanese Archipelago inferred from genome-wide SNP data with a special reference to the Ainu and the Ryukyuan populations

The Japanese Archipelago stretches over 4000 km from north to south, and is the homeland of the three human populations; the Ainu, the Mainland Japanese and the Ryukyuan. The archeological evidence of human residence on this Archipelago goes back to 430 000 years, and various migration routes and root populations have been proposed. Here, we determined close to one million single-nucleotide polymorphisms (SNPs) for the Ainu and the Ryukyuan, and compared these with existing data sets. This is the first report of these genome-wide SNP data. Major findings are: (1) Recent admixture with the Mainland Japanese was observed for more than one third of the Ainu individuals from principal component analysis and frappe analyses; (2) The Ainu population seems to have experienced admixture with another population, and a combination of two types of admixtures is the unique characteristics of this population; (3) The Ainu and the Ryukyuan are tightly clustered with 100% bootstrap probability followed by the Mainland Japanese in the phylogenetic trees of East Eurasian populations. These results clearly support the dual structure model on the Japanese Archipelago populations, though the origins of the Jomon and the Yayoi people still remain to be solved

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target