Pedalitin from Isodon japonica, an inactivation of soybean lipoxygenase-1

Pedalitin, isolated from the aerial part of Rabdosia japonica (Labiatae), inhibited soybean lipoxygenase-1 (EC 1.13.11.12, Type I) with an IC50 of 152.5 M. The progress curves for an enzyme reaction, pedalitin inactivate the lipoxygenase-1 in a time dependent, irreversible manner, exhibiting kinetics with a kinact/KI of 59.6 ± 10 mM-1min-1. In the pseudoperoxidase activity, pedalitin is very slowly oxidized by the soybean lipoxygenase-1 catalyzed decomposition of lipid hydroperoxides

Genome-wide association analysis provides insights into the genetic basis of photosynthetic responses to low-temperature stress in spring barley

Low-temperature stress (LTS) is among the major abiotic stresses affecting the geographical distribution and productivity of the most important crops. Understanding the genetic basis of photosynthetic variation under cold stress is necessary for developing more climate-resilient barley cultivars. To that end, we investigated the ability of chlorophyll fluorescence parameters (FVFM, and FVF0) to respond to changes in the maximum quantum yield of Photosystem II photochemistry as an indicator of photosynthetic energy. A panel of 96 barley spring cultivars from different breeding zones of Canada was evaluated for chlorophyll fluorescence-related traits under cold acclimation and freeze shock stresses at different times. Genome-wide association studies (GWAS) were performed using a mixed linear model (MLM). We identified three major and putative genomic regions harboring 52 significant quantitative trait nucleotides (QTNs) on chromosomes 1H, 3H, and 6H for low-temperature tolerance. Functional annotation indicated several QTNs were either within the known or close to genes that play important roles in the photosynthetic metabolites such as abscisic acid (ABA) signaling, hydrolase activity, protein kinase, and transduction of environmental signal transduction at the posttranslational modification levels. These outcomes revealed that barley plants modified their gene expression profile in response to decreasing temperatures resulting in physiological and biochemical modifications. Cold tolerance could influence a long-term adaption of barley in many parts of the world. Since the degree and frequency of LTS vary considerably among production sites. Hence, these results could shed light on potential approaches for improving barley productivity under low-temperature stress

The Role of Optical Coherence Tomography in Coronary Intervention

Optical coherence tomography (OCT) is an optical analog of intravascular ultrasound (IVUS) that can be used to examine the coronary arteries and has 10-fold higher resolution than IVUS. Based on polarization properties, OCT can differentiate tissue characteristics (fibrous, calcified, or lipid-rich plaque) and identify thin-cap fibroatheroma. Because of the strong attenuation of light by blood, OCT systems required the removal of blood during OCT examinations. A recently developed frequency-domain OCT system has a faster frame rate and pullback speed, making the OCT procedure more user-friendly and not requiring proximal balloon occlusion. During percutaneous coronary intervention (PCI), OCT can provide detailed information (dissection, tissue prolapse, thrombi, and incomplete stent apposition [ISA]). At follow-up examinations after stent implantation, stent strut coverage and ISA can be assessed. Several OCT studies have demonstrated delayed neointimal coverage following drug-eluting stent (DES) implantation vs. bare metal stent (BMS) placement. While newer DESs promote more favorable vascular healing, the clinical implications remain unknown. Recent OCT studies have provided insights into restenotic tissue characteristics; DES restenotic morphologies differ from those with BMSs. OCT is a novel, promising imaging modality; with more in-depth assessments of its use, it may impact clinical outcomes in patients with symptomatic coronary artery disease

Polycystic Kidney Disease in the Medaka (Oryzias latipes) pc Mutant Caused by a Mutation in the Gli-Similar3 (glis3) Gene

Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients

Fundamental electron-transfer and proton-coupled electron-transfer properties of Ru(iv)-oxo complexes

Isolation and characterisation of Ru-IV(O) complexes were accomplished to investigate their fundamental electron transfer (ET) and proton-coupled ET (PCET) properties. Reorganisation energies (lambda) in electron transfer (ET) and proton-coupled ET (PCET) from electron donors to the isolated Ru-IV(O) complexes have been determined for the first time to be in the range of 1.70-1.88 eV (ET) and 1.20-1.26 eV (PCET). It was suggested that the reduction of the lambda values of PCET in comparison with those of ET should be due to the smaller structural change in PCET than that in ET on the basis of DFT calculations on 1 and 1e(-)-reduced 1 in the absence and presence of TFA, respectively. In addition, the smaller lambda values for the Ru-IV(O) complexes than those reported for Fe-IV(O) and Mn-IV(O) complexes should be due to the lack of participation of d(sigma) orbitals in the ET and PCET reactions. This is the first example to evaluate fundamental ET and PCET properties of Ru-IV(O) complexes leading to further understanding of their reactivity in oxidation reactions

Evaluating Clinical Genome Sequence Analysis by Watson for Genomics

Background: Oncologists increasingly rely on clinical genome sequencing to pursue effective, molecularly targeted therapies. This study assesses the validity and utility of the artificial intelligence Watson for Genomics (WfG) for analyzing clinical sequencing results.Methods: This study identified patients with solid tumors who participated in in-house genome sequencing projects at a single cancer specialty hospital between April 2013 and October 2016. Targeted genome sequencing results of these patients' tumors, previously analyzed by multidisciplinary specialists at the hospital, were reanalyzed by WfG. This study measures the concordance between the two evaluations.Results: In 198 patients, in-house genome sequencing detected 785 gene mutations, 40 amplifications, and 22 fusions after eliminating single nucleotide polymorphisms. Breast cancer (n = 40) was the most frequent diagnosis in this analysis, followed by gastric cancer (n = 31), and lung cancer (n = 30). Frequently detected single nucleotide variants were found in TP53 (n = 107), BRCA2 (n = 24), and NOTCH2 (n = 23). MYC (n = 10) was the most frequently detected gene amplification, followed by ERBB2 (n = 9) and CCND1 (n = 6). Concordant pathogenic classifications (i.e., pathogenic, benign, or variant of unknown significance) between in-house specialists and WfG included 705 mutations (89.8%; 95% CI, 87.5%−91.8%), 39 amplifications (97.5%; 95% CI, 86.8–99.9%), and 17 fusions (77.3%; 95% CI, 54.6–92.2%). After about 12 months, reanalysis using a more recent version of WfG demonstrated a better concordance rate of 94.5% (95% CI, 92.7–96.0%) for gene mutations. Across the 249 gene alterations determined to be pathogenic by both methods, including mutations, amplifications, and fusions, WfG covered 84.6% (88 of 104) of all targeted therapies that experts proposed and offered an additional 225 therapeutic options.Conclusions: WfG was able to scour large volumes of data from scientific studies and databases to analyze in-house clinical genome sequencing results and demonstrated the potential for application to clinical practice; however, we must train WfG in clinical trial settings

当科における基底細胞癌の統計的観察

皮膚に発生する悪性腫瘍のうち比較的高頻度に見られる基底細胞癌(BCC)について統計的観察をおこなった.1990年1月から2001年5月までの11年5ヶ月間に川崎医科大学附属病院形成外科において治療した基底細胞癌の48患者49症例を対象として年齢・部位・臨床および組織分類・切除範囲・切除後の再建方法・再発の有無などについて若干の文献的考察をふまえて検討した.男女比は1.3 : 1,年齢は13～98歳(平均63.4歳),初診までの期間は平均3.6年であった.腫瘍の長径は4～100mm(平均15.1mm)であった.部位は顔面が最も多く眼窩部が19例(38%),鼻部が13例(26%)を占めており,いわゆる胎生期顔裂線に一致する傾向にあった.臨床分類は結節型・結節潰瘍型の2型で85%を占め,組織型ではsolid typeが75%を占めた.腫瘍辺縁からの切除距離は5mmが最多で18例(42%),次いで3mmが8例(19%)などであった.眼周囲19例に限ると切除辺縁は3～5mmが11例,3mm以下が8例であったがいずれも再発は見られなかった.再建方法は局所皮弁が最多で33例(67%)続いて単純縫縮が8例(16%),植皮が6例(12%),遊離皮弁が2例(4%)であった.再発例は頭部,顔面発症の2例であった.Basal cell carcinoma (BCC) is one of the most frequent malignant skin tumors and is often seen on the face. This study aims to analyze the tumor diameter, site, patient\u27s age, surgical treatment and so on. This study analyzed 49 cases of basal cell carcinoma (BCC) which were treated at the Department of plastic and Reconstructive Surgery at Kawasaki Medical School Hospital from January 1990 to May 2001. The patients were between (13-98) years old, average was 63.4 years. The male to female ratio was 1.3 : 1 respectively. The average duration between the onset of BCC and the patient\u27s initial visit was 3.6 years. Tumor diameter ranged from 4 mm to 100 mm (average was 15.1mm). Almost all tumors occurred on the face (especially on the so-called "facial cleft") except one case which occurred on the left knee. Eighty-five percent of clinical types of tumor were nodular and nodulo-ulcerative. Seventy-five percent of histological types were solid. Surgical excision was performed in all cases and skin defects were closed by local flaps (67%), simpleclosure (16%) and other methods. The surgical margin was less than 5 mm in 81.6% of the cases. There were 2 recurrent cases. One was a case of Xcroderma pigmentosum on the face (ulcus tereblans, solid type) and the other was case of BCC on the temporal region (nodular, keratotic type). In accordance with previous results, we suggest further detailed classification and analysis of surgical margins

A Genome-Wide Association Study Identified AFF1 as a Susceptibility Locus for Systemic Lupus Eyrthematosus in Japanese

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10−9, odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4+ and CD19+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset