The first preparation of the unstable 1-hydroxy-2,3-dimethylindole, andstructural determination of its air-oxidized product,3-hydroxy-2,3-dimethyl-3H-indole N-oxide

1-Hydroxy-2,3-dimethylindole (1) has been prepared for the first time. Under atmospheric oxygen, 1 was converted rapidly into 3-hydroxy-2,3-dimethyl- 3H-indole N-oxide (2). The structure was deduced, based on its products obtained by the reaction with Ac2O in pyridine and confirmed by X-ray single crystallographic analysis

Effects of Model-Based Iterative Reconstruction in Low-Dose Paranasal Computed Tomography: A Comparison with Filtered Back Projection and Hybrid Iterative Reconstruction

Iterative reconstruction (IR) improves image quality compared with filtered back projection (FBP). This study investigated the usefulness of model-based IR (forward-projected model-based iterative reconstruction solution [FIRST]) in comparison with FBP and hybrid IR (adaptive iterative dose reduction three-dimensional processing [AIDR 3D]) in low-dose paranasal CT. Twenty-four patients with paranasal sinusitis who underwent standard-dose CT (120 kV) and low-dose CT (100 kV) scanning before and after medical treatment were enrolled. Standard-dose CT scans were reconstructed with FBP (FBP120), and low-dose CT scans with FBP (FBP100), AIDR 3D, and FIRST. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in three anatomical structures and effective doses were compared using Mann–Whitney U test. Two radiologists independently evaluated the visibility of 16 anatomical structures, overall image quality, and artifacts. Effective doses in lowdose CT were significantly reduced compared with those in standard-dose CT (0.24 vs 0.43 mSv, p<0.001). FIRST achieved significantly higher SNR (p<0.01, respectively) and CNR (p<0.001, respectively) of evaluated structures and significant improvement in overall image quality (p<0.001), artifacts (p<0.001), and visibility related to muscles (p<0.05) compared to FBP120, FBP100, and AIDR 3D. FIRST allowed radiation-dose reduction, while maintaining objective and subjective image quality in low-dose paranasal CT

Findings from recent studies by the Japan Aerospace Exploration Agency examining musculoskeletal atrophy in space and on Earth

The musculoskeletal system provides the body with correct posture, support, stability, and mobility. It is composed of the bones, muscles, cartilage, tendons, ligaments, joints, and other connective tissues. Without effective countermeasures, prolonged spaceflight under microgravity results in marked muscle and bone atrophy. The molecular and physiological mechanisms of this atrophy under unloaded conditions are gradually being revealed through spaceflight experiments conducted by the Japan Aerospace Exploration Agency using a variety of model organisms, including both aquatic and terrestrial animals, and terrestrial experiments conducted under the Living in Space project of the Japan Ministry of Education, Culture, Sports, Science, and Technology. Increasing our knowledge in this field will lead not only to an understanding of how to prevent muscle and bone atrophy in humans undergoing long-term space voyages but also to an understanding of countermeasures against age-related locomotive syndrome in the elderly

Evidence for increased DNA damage repair in the postmortem brain of the high stress-response group of schizophrenia

BackgroundSchizophrenia (SZ) is a disorder diagnosed by specific symptoms and duration and is highly heterogeneous, clinically and pathologically. Although there are an increasing number of studies on the association between genetic and environmental factors in the development of SZ, the actual distribution of the population with different levels of influence of these factors has not yet been fully elucidated. In this study, we focused on stress as an environmental factor and stratified SZ based on the expression levels of stress-responsive molecules in the postmortem prefrontal cortex.MethodsWe selected the following stress-responsive molecules: interleukin (IL) -1β, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, glucocorticoid receptor, brain-derived neurotrophic factor, synaptophysin, S100 calcium-binding protein B, superoxide dismutase, postsynaptic density protein 95, synuclein, apolipoprotein A1 (ApoA1), ApoA2, and solute carrier family 6 member 4. We performed RNA sequencing in the prefrontal gray matter of 25 SZ cases and 21 healthy controls and conducted a hierarchical cluster analysis of SZ based on the gene expression levels of stress-responsive molecules, which yielded two clusters. After assessing the validity of the clusters, they were designated as the high stress-response SZ group and the low stress-response SZ group, respectively. Ingenuity Pathway Analysis of differentially expressed genes (DEGs) between clusters was performed, and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was conducted on four cases each in the high and low stress-response SZ groups to validate DNA damage.ResultsWe found higher prevalence of family history of SZ in the low stress-response SZ group (0/3 vs. 5/4, p = 0.04). Pathway analysis of DEGs between clusters showed the highest enrichment for DNA double-strand break repair. TUNEL staining showed a trend toward a lower percentage of TUNEL-positive cells in the high stress-response SZ group.ConclusionOur results suggest that there are subgroups of SZ with different degrees of stress impact. Furthermore, the pathophysiology of these subgroups may be associated with DNA damage repair. These results provide new insights into the interactions and heterogeneity between genetic and environmental factors

Pillar[6]arene acts as a biosensor for quantitative detection of a vitamin metabolite in crude biological samples

ビタミン代謝物を迅速定量できる超分子バイオセンサーを開発. 京都大学プレスリリース. 2020-12-09.Metabolic syndrome is associated with obesity, hypertension, and dyslipidemia, and increased cardiovascular risk. Therefore, quick and accurate measurements of specific metabolites are critical for diagnosis; however, detection methods are limited. Here we describe the synthesis of pillar[n]arenes to target 1-methylnicotinamide (1-MNA), which is one metabolite of vitamin B3 (nicotinamide) produced by the cancer-associated nicotinamide N-methyltransferase (NNMT). We found that water-soluble pillar[5]arene (P5A) forms host–guest complexes with both 1-MNA and nicotinamide, and water-soluble pillar[6]arene (P6A) selectively binds to 1-MNA at the micromolar level. P6A can be used as a “turn-off sensor” by photoinduced electron transfer (detection limit is 4.38 × 10−6 M). In our cell-free reaction, P6A is used to quantitatively monitor the activity of NNMT. Moreover, studies using NNMT-deficient mice reveal that P6A exclusively binds to 1-MNA in crude urinary samples. Our findings demonstrate that P6A can be used as a biosensor to quantify 1-MNA in crude biological samples

Deep sequencing reveals as-yet-undiscovered small RNAs in Escherichia coli

<p>Abstract</p> <p>Background</p> <p>In <it>Escherichia coli</it>, approximately 100 regulatory small RNAs (sRNAs) have been identified experimentally and many more have been predicted by various methods. To provide a comprehensive overview of sRNAs, we analysed the low-molecular-weight RNAs (< 200 nt) of <it>E. coli </it>with deep sequencing, because the regulatory RNAs in bacteria are usually 50-200 nt in length.</p> <p>Results</p> <p>We discovered 229 novel candidate sRNAs (≥ 50 nt) with computational or experimental evidence of transcription initiation. Among them, the expression of seven intergenic sRNAs and three <it>cis</it>-antisense sRNAs was detected by northern blot analysis. Interestingly, five novel sRNAs are expressed from prophage regions and we note that these sRNAs have several specific characteristics. Furthermore, we conducted an evolutionary conservation analysis of the candidate sRNAs and summarised the data among closely related bacterial strains.</p> <p>Conclusions</p> <p>This comprehensive screen for <it>E. coli </it>sRNAs using a deep sequencing approach has shown that many as-yet-undiscovered sRNAs are potentially encoded in the <it>E. coli </it>genome. We constructed the <it>Escherichia coli </it>Small RNA Browser (ECSBrowser; <url>http://rna.iab.keio.ac.jp/</url>), which integrates the data for previously identified sRNAs and the novel sRNAs found in this study.</p

60歳以上の造血器悪性腫瘍に対して施行した臍帯血移植の3例

(症例1)68歳男性.2002年12月に発症したmantle cell lymphoma,clinical stage III A.CHOP療法,rituximab-CHOP療法により完全寛解となった.治療中に直腸癌が認められたため手術を施行した.その後頚部再発をきたし,化学療法,放射線局所照射を行ったが寛解には到らず,2004年4月に,膀帯血移植を施行した.Day19に生着,day28に完全キメラを確認した.Day44に頚部再発を認め,FK506中止し,腫瘍は縮小となったが再び増大し,化学療法を施行中である.(症例2)62歳男性.2002年7月に発症した.myelodysplastic syndrome (MDS) refractory anemia with excess of blasts(RAEB).Acute myeloblastic leukemia(AML)への進展を認めたため2004年5月に膀帯血移植を施行した.Day31に生着,day28に完全キメラを確認した.現在完全寛解を維持している.(症例3)60歳女性.2004年6月に発症したMDS(RAEB in transformation).早々にAMLへ移行したため,PS1で2004年8月に臍帯血移植を施行した.Day78に生着,day28に完全キメラを確認した.Day61に皮膚stage3・grade IIのacute graft versus host diseaseが出現したが,predonisolone 0.5mg/kg開始し速やかに消退した.現在完全寛解を維持している.最近施行されるようになってきた高齢者に対する造血幹細胞移植は,患者の高齢化に伴い健常な同胞ドナー候補を探すことが困難であり,また病勢によっては骨髄バンクからドナー候補を探す時間的な余裕がないことなどが問題となっている.一方,膀帯血移植は当初は小児領域で施行されていたが,最近では主に成人に対して施行されるようになっている.今回60歳以上の高齢者の造血器悪性腫瘍3例に対して臍帯血移植を施行し,その経過,合併症について検討した.高齢者の造血器悪性腫瘍に対して移植を考慮する場合に同胞に適するドナーがいない場合,非血縁骨髄移植のみならず,今後は臍帯血移植も選択肢の一つとして考慮し得るということが示された.Allogenic stem cell transplantation is now done not only for younger but also for elderly patients. It is very difficult for elderly patients to find healthy, suitable related donors, and in many cases there is not enough time to find unrelated bone marrow donors due to disease status. Cord blood transplantation was originally done for pediatric patients, but is now done for more adult patients than pediatric patients. We performed cord blood transplantation for 3 patients over 60 years old with hematological malignancies. We report their clinical courses and complications. If there are no suitable related donors for elderly patients, it is possible to choose not only unrelated bone marrow transplantation, but also cord blood transplantation