Fabrication of nanocone arrays by two step metal assisted chemical etching method

This work develops a novel method for preparing a moth eye structure, which has a sub-wavelength periodical Si nanocone structure on Si (100) substrate, using two-step metal assisted chemical etching (MACE). The 1st and 2nd MACE were respectively performed with the intention to form perpendicular Si nanowire arrays on a Si substrate and sharpening the Si nanowire arrays. We found the inhomogeneous absorption and aggregation of Au particles used as a catalyst for 2nd MACE was important to obtain the nanocone shape. The obtained Si nanocone arrays showed superior anti-reflecting properties especially in wavelength below 600 nm compared to the Si nanowire arrays. A possible mechanism involved in the formation of the nanocone structure by the 2-step MACE is discussed in this paper.This work was supported by KAKENHI Grant Numbers 25790024, 25600048 and15K04602 from the Japan Society for the Promotion of Science (JSPS), Strategic Project to Support the Formation of Research Bases at Private Universities: Matching Fund Subsidy from the Ministry of Education, Culture, Sports, Science and Technology(MEXT), and Kansai University Subsidy for supporting Young Scholars 2013

光と酸素或いは過酸化水素を用いる酸化反応の開発に関する研究

酸化反応は有機合成上有用な反応であるが、従来の手法では毒性の高い重金属酸化剤や原子効率の低い複雑な有機分子が必要であった。一方、分子状酸素や過酸化水素を末端酸化剤とする手法は、原子効率が高く、廃棄物として理論上水のみを排出する、グリーンケミストリーの概念に合致した酸化法である。筆者らは最終酸化剤としての「過酸化水素」ならびに「分子状酸素」を利用した環境負荷低減を指向した酸化反応の開発を行った。その結果、ハロゲンソース存在下、スチレン類の光酸素酸化により、対応するフェナシルハライド類を合成することに成功した。また、光酸素酸化反応の後に単体ヨウ素を触媒とする反応をワンポットで行うことにより、スチレン類からアセトフェノン類を、ベンジルアルコール類からビスインドリルメタン類をそれぞれ合成することに成功した。さらに、単体ヨウ素存在下、酸化剤として過酸化水素或いは分子上酸素を用いることにより、三級アミン類と炭素求核剤の酸化的カップリング反応にも成功した。Oxidation is one of the most important reactions in organic synthesis; however, classical methods require toxic heavymetal reagents or complex organic molecules. On the other hand, oxidation using oxygen or hydrogen peroxide has received muchattention in organic synthesis recently since these reagents are effective oxidants of larger atom efficiency and theoretically produceonly water as the end product. With this perspective, we have studied oxidation using oxygen or hydrogen peroxide as a terminaloxidant. As a result, we found that styrenes can be oxidized to corresponding phenacylhalides under aerobic photo-oxidativeconditions in the presence of halogen sources. We also developed one-pot synthesis of acetophenones and bis-indolylmethanes fromstyrenes and benzylalcohols, which includes aerobic photo-oxidation followed by iodine catalyzed reaction, respectively.Furthermore, we developed a cross-dehydrogenative coupling reaction between tertiary amines and carbon nucleophiles usinghydrogen peroxide or oxygen as a terminal oxidant in the presence of catalytic iodine

光と酸素を活用する簡便な酸化プロセスの開発に関する研究

酸化反応は有機合成における最も重要な柱の一つである。しかしながら、従来の酸化反応は重金属を大量に使用しなければならない、廃棄物が大量に副生するなどの問題点を有しており、いわゆる“グリーンケミストリー”の概念に必ずしもそぐわないものがほとんどであった。一方、最近では安価で原子効率が高い分子状酸素を酸化剤として用いた触媒的酸化反応が報告されている。この方法は適当な触媒を用いた場合に、反応後に副生されるものが理論的に水のみであり、理想の酸化反応として注目を集めている。係る背景において、筆者らは分子状酸素を用いる酸化反応について研究を行い、紫外光照射下（400 nm）でも同様の酸化反応が進行することも見出した。さらに、上記の光酸素酸化反応を連続するエステル化反応へ展開し、芳香環上メチル基から芳香族カルボン酸エステルへの効率的な直接一段階合成法を確立することにも成功した。Oxidation is a very important transformation in organic synthesis; however, hitherto these methods usually involve the use of large quantities of heavy metals, which generate a large amount of waste, and are detrimental to the environment. On the other hand, recently, many researchers have reported catalytic oxidation processes with molecular oxygen, which generate little waste. Molecular oxygen has received a great deal of attention as an ideal oxidant, since it theoretically produces only water as the end product with a certain suitable catalyst is inexpensive and has higher atom efficiency than that of other oxidants.With this perspective, we have studied the oxidation with molecular oxygen, and developed the oxidation of methyl aromatics and alcohols to the corresponding carboxylic groups in the presence of a catalytic amount of bromine sources such as aq. HBr and Br2 under UV irradiation (400 nm). Moreover, in developing the above-mentioned oxidation following esterification, we accomplished efficient direct aerobic photooxidative synthesis of aromatic methyl esters from methyl aromatics

Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart Disease.

RATIONALE: Therapies that inhibit CETP (cholesteryl ester transfer protein) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human DNA sequence variants that truncate the CETP gene may provide insight into the efficacy of CETP inhibition. OBJECTIVE: To test whether protein-truncating variants (PTVs) at the CETP gene were associated with plasma lipid levels and CHD. METHODS AND RESULTS: We sequenced the exons of the CETP gene in 58 469 participants from 12 case-control studies (18 817 CHD cases, 39 652 CHD-free controls). We defined PTV as those that lead to a premature stop, disrupt canonical splice sites, or lead to insertions/deletions that shift frame. We also genotyped 1 Japanese-specific PTV in 27561 participants from 3 case-control studies (14 286 CHD cases, 13 275 CHD-free controls). We tested association of CETP PTV carrier status with both plasma lipids and CHD. Among 58 469 participants with CETP gene-sequencing data available, average age was 51.5 years and 43% were women; 1 in 975 participants carried a PTV at the CETP gene. Compared with noncarriers, carriers of PTV at CETP had higher high-density lipoprotein cholesterol (effect size, 22.6 mg/dL; 95% confidence interval, 18-27; P<1.0×10-4), lower low-density lipoprotein cholesterol (-12.2 mg/dL; 95% confidence interval, -23 to -0.98; P=0.033), and lower triglycerides (-6.3%; 95% confidence interval, -12 to -0.22; P=0.043). CETP PTV carrier status was associated with reduced risk for CHD (summary odds ratio, 0.70; 95% confidence interval, 0.54-0.90; P=5.1×10-3). CONCLUSIONS: Compared with noncarriers, carriers of PTV at CETP displayed higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, lower triglycerides, and lower risk for CHD

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

Syngenic grafting of a whole juvenile male gonadal tissue into the adult testes confers successful spermatogenesis in mice

Objective: To examine whether functional spermatozoa can be obtained when a whole male gonadal tissue (testes, epididymides, and fat) isolated from neonatal mice is grafted underneath adult mouse testes. Methods: Neonatal (1-day-old) male gonadal tissue, isolated from enhanced green fluorescent protein (EGFP)-transgenic (Tg) mice (C57BL/6-Tg(ACTB-EGFP)1Osb/J), was inserted deep in the testis of a non-Tg recipient mouse through a tunica albuginea incision. Two months after transplantation, the fluorescent grafted tissues were retrieved from recipient mice. Results: Histological analysis demonstrated that epididymal architecture was well developed and that spermatogenesis in the testis occurred in 30–60% of each seminiferous tubule of all the grafted tissues examined. Interestingly, motile spermatozoa could be successfully retrieved from the portion corresponding to the cauda epididymis in 1 of the 7 transplants obtained. These obtained spermatozoa had transgenes and could support embryonic development when intracytoplasmic sperm injection was performed using frozen-thawed spermatozoa. Conclusion: This present technique will be useful for study in various biological fields including the rescue of Tg lines with lethal postnatal phenotypes and cloned animals that die immediately after birth

Synthesis of 4-Imidazolidinones from Diamides and Ethynyl Benzio- doxolones vis Double Michael Addition: Ethynyl Benziodoxolones as Electrophilic Ynol Synthons

The moiety of 4-imidazolidinone is an important structural motif in organic synthesis and medicinal chemistry. We achieved the efficient synthesis of 4-imidazolidinones from a variety of diamides by double Michael addition, a novel reaction mode for hypervalent alkynyl iodine compounds, and a formal reductive elimination sequence using in situ-generated EBX from TMS-EBX or EBX-MeCN. The highly reactive EBX enabled chemoselective intermolecular N- alkenylation of the sulfonamide moiety and intramolecular cyclization of the amide moiety under mild basic conditions. The reaction diastereoselectively gave cis-2,5-disubstituted 4-imidazolidinones from amino acid-derived diamides. Furthermore, 2-[(2-iodobenzoyloxy)methyl]-4-imidazolidinone was derivatized by solvolysis and Sonogashira coupling. DFT calculations indicated that the double Michael addition mechanism is plausible. Thus, the potential of an unsubstituted EBX reagent for the synthesis of heterocycles from complex molecules and their functionalization with mild nucleophiles was demonstrated