Processing of mutated proinsulin with tetrabasic cleavage sites to bioactive insulin in the non-endocrine cell line, COS-7

AbstractThe amino acid sequence, Arg−4-X−3-Lys/Arg−2-Arg−1 ↓ X+1, is thought to be a consensus processing site for a constitutive secretory pathway in non-endocrine cells. We created a mutant proinsulin DNA with a peptide structure of B chain-Arg-Arg-Lys-Arg-C peptide-Arg-Arg-Lys-Arg-A chain, which compares to the native proinsulin structure of B chain-Arg-Arg-C peptide-Lys-Arg-A chain. When the mutant insulin was expressed in a monkey kidney-derived cell line, COS-7, approximately 60% of the total immunoreactive insulin appeared as mature insulin in the culture medium. This conversion to the mature form was strikingly facilitated by co-expressing the mutant proinsulin with furin, a homologue of the yeast endoprotease, Kex2

サーモグラフィーによる体表面温度の測定

Body Surface Temperature was observed by thermography. The surface temperature of a healthy person's lower limbs, after being cooled in a water bath, increased in parallel with time. Patients with Diabetes Mellitus had different patterns in the rate of increase of the surface temperature. After cold loading, one patient had a 99% recovery ratio of surface temperature, the same level as healthy volunteers (83%, and 88%), as calculated by a picture processing program with the computerized thermotracer. However, the recovery ratio of other patients was poorer, ranging from 56% to under 6% recovery. This measurement of elevation of body temperature is useful for the estimation of peripheral blood flow in patients with lower limbcirculation failure.健常人並びに糖尿病患者を対象にして下肢の体表面温度を測定した｡測定にはサーモグラフィーを用い,得られた画像の数値化にはコンピュータを用いた画像処理システムを利用した｡健常人を用いた実験では,20℃の水を用いた冷水負荷を5分間行うことにより,冷水負荷後,下肢の体表面温度は時間とともに上昇して30分後に良好な回復を得ることができた｡画像処理により28℃以上の体表面温度を呈した下肢の面積を負荷前と比較したところ,回復率は,2名の健常人についてみるとそれぞれ83%,88%であった｡27℃で画像処理を行った場合には回復率は93%となり過大評価される可能性があった｡また,29℃で画像処理を行ったところに,逆に,64%となり過少評価される可能性があり,28℃が最も良い条件であった｡この様な条件下で,糖尿病患者7名について同様に測定を行ったところ,1名は健常人と同じく99%の良好な回復率を呈した｡しかし,他の1名は56%であり,残りの,5名は6%以下であった｡この様に,糖尿病患者では,下肢の体表面温度の冷水負荷後の回復率に顕著な差を認めた｡この差は,糖尿病患者における,末梢循環障害の程度を反映しているものと考えられた｡この様にコンピュータを用いた画像処理システムの応用によりサーモグラフィーの画像は数値化することが出来,測定結果はより客観的に据えることが可能となった｡画像処理されたサーモグラフィーは下肢の循環障害を持つ患者の末梢血流量の評価に有用な測定方法であると考えられた

Ⅱ型喘息(細気管支閉塞型)と気管支肺胞洗浄液の好中球数

Bronchial asthma is classified into three types ; type Ia (Ia-1 and Ia-2), type Ib, and type Ⅱ, by clinical symptoms (clinical diagnosis). Asthma is also classified by clinical findings and examinations (score diagnosis). Both classification systems show that markedly increased proportion of BAL neutrophils and marked decrease in % V25 value are characteristic of type Ⅱ, bronchiolar　obstruction, asthma. However, there are some type Ⅱ asthma patients without BAL neutrophilia. In these patients, age is higher compared to those with BAL enutrophlia. Decrease in FEV1.0% value and decrease in the proportion of BAL lympocytes and serum IgG level, are not so remarkable as decrease in those with BAL neutrophilia. It has been suggested that type Ⅱ asthma with BAL neutrophilia correlates with suppression of humoral and cellular immunity, and same type of astma without BAL neutrophilia is in part caused by aging.気管支喘息は,その臨床症状より,Ia型(Ia-1およびIa-2),Ib型およびⅡ型の3つの病型に分けることができる(臨床分類)｡また,同時に臨床所見および検査により分類することができる(スコアー分類)｡いずれの分類においても,BAL液中の好中球の著増および高度な% V25値の低下がⅡ細気管支閉塞型の特徴的所見である｡しかしながら,BAL液中の好中球の増加をともなわないⅡ型喘息が存在することが明らかにされている｡これらの症例では,BAL液 中好中球増加をともなう症例に比べ平均年齢が高い｡しかし,FEVl.0% 値､BAL液中リンパ球頻度や血清IgG値などは､好中球増加をともなう症例ほどの低下傾向は見られない｡これらの結果はBAL液中好中球増加をともなうⅡ型z喘息の発症機序には､液性および細胞性免疫能の低下が､また､BAL液中好中球増加をともなわないⅡ型喘息では､加齢がある程度関連していることを示 している

Cyclic Naphthalene Diimide with a Ferrocene Moiety as a Redox-Active Tetraplex-DNA Ligand

Cyclic naphthalene diimides (cNDIs), with a ferrocene moiety (cFNDs) and different linker lengths between the ferrocene and cNDI moieties, were designed and synthesized as redox‐active, tetraplex‐DNA ligands. Intramolecular stacking was observed between ferrocene and the NDI planes, which could affect the binding properties for G‐quadruplexes. Interestingly, the circular dichroism spectrum of one of these compounds clearly shows new Cotton effects around 320–380 and 240 nm, which can be considered a direct evidence of intramolecular stacking of ferrocene and the NDI. Regarding recognition of hybrid G‐quadruplexes, the less rigid structures (longer linkers) show higher binding affinity (106 M−1 order of magnitude). All new compounds show higher selectivity for G4 during electrochemical detection than noncyclic FND derivatives, which further identifies the redox‐active potentiality of the cFNDs. Two of the three compounds tested even show preferential inhibition of cell growth in cancer cells over normal cells in a low concentration range, highlighting the potential for bioapplications of these cFNDs

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

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens\u27 antibacterial susceptibility

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010.The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents.Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S.aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S.pneumoniae were 1.1% and 0.0%, respectively. Among H.influenzae, 17.6% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be β-lactamase-non-producing ABPC-resistant and 11.0% to be β-lactamase-producing ABPC-resistant strains. Extended spectrum β-lactamase-producing K.pneumoniae and multi-drug resistant P.aeruginosa with metallo β-lactamase were 2.9% and 0.6%, respectively.Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis

Research Activities on Venus Atmosphere Balloon Observation Mission

This presentation was part of the session : Probe Missions to the Giant Planets, Titan and VenusSixth International Planetary Probe WorkshopA feasibility study of the small Venus entry capsule and the scientific observation by the water-vapor balloon are described in this paper. Though Venus is the nearest planet to the Earth, it is still filled with mysteries and surprises. The atmosphere observation under the thick cloud on the venusian surface is of great scientific interests. Because a super-pressure type of the balloon can travel long time a wide area by strong winds on the Venus, it is considered to be of prime candidate for the atmosphere observations. A water-vapor super-pressure balloon is advantageous to obtain buoyancy force in the hot Venus atmosphere. At the entry to the Venus, the liquid-phase water is adhered to a number of the water-absorption films layered inside of the outer sealing film. The heat required for the water vaporization is supplied from the ambient environment during the ascending phase. Recently, IC chips, batteries, and solar arrays that function under the high-temperature environment ranging 180 to 220 ?C have been developed and been in practical use. By use of solar arrays, the electric power is supplied to the onboard instruments without any extra cooling system, which enables long-term observation. Then the target altitude is determined to be from 35 to 37 km considering the operation range of the high-temperature electronics. A small entry capsule with the 20m-long water-vapor balloon accommodated in it is separated from a 150kg small spacecraft and carries out direct entry from the interplanetary transfer orbit at the velocity of 11.5 km/s. The capsule releases the balloon at the appropriate altitude after passing through the aerodynamic heating corridor. Total weight of the capsule is about 30 kg containing balloon and observation instruments with weight of 10kg.Japan Aerospace Exploration Agency ; Institute of Space and Astronautical Scienc

Education and Research in Japan's Construction Industry

The paper reports some general observations and specific examples on technological innovation in Japan's construction industry. Educational background and scientific contribution of contractor-based researchers is addressed. With regard to university education, the difference between the disciplines of civil engineering and architecture and the relationship between university graduates and industry are discussed. With regard to research, the reasons that justify the existence of research-and-development (R&D) capabilities are given. The contribution of R&D efforts from general contractors to the advancement of technical knowledge in the form of papers and presentations is discussed. The organization of a specific technical research institute is shown as an example. The construction industry in Japan offers positive work conditions and is innovative rather than reactive to market demands. It is apparent that much could be gained by U.S. professionals by more closely monitoring Japanese technical output. R&D collaboration between U.S. and Japanese contractors should also be pursued