Yokonolide B, a Novel Inhibitor of Auxin Action, Blocks Degradation of AUX/IAA Factors

Yokonolide B (YkB; also known as A82548A), a spiroketal-macrolide, was isolated from Streptomyces diastatochromogenes B59 in a screen for inhibitors of beta-glucoronidase expression under the control of an auxin-responsive promoter in Arabidopsis. YkB inhibits the expression of auxin-inducible genes as shown using native and synthetic auxin promoters as well as using expression profiling of 8300 Arabidopsis gene probes but does not affect expression of an abscisic acid- and a gibberellin A3-inducible gene. The mechanism of action of YkB is to block AUX/IAA protein degradation; however, YkB is not a general proteasome inhibitor. YkB blocks auxin-dependent cell division and auxin-regulated epinastic growth mediated by auxin-binding protein 1. Gain of function mutants such as shy2-2, slr1, and axr2-1 encoding AUX/IAA transcriptional repressors and loss of function mutants encoding components of the ubiquitin-proteolytic pathway such as axr1-3 and tir1-1, which display increased AUX/IAAs protein stability, are less sensitive to YkB, although axr1 and tir1 mutants were sensitive to MG132, a general proteasome inhibitor, consistent with a site of action downstream of AXR1 and TIR. YkB-treated seedlings displayed similar phenotypes as dominant AUX/IAA mutants. Taken together, these results indicate that YkB acts to block AUX/IAA protein degradation upstream of AXR and TIR, links a shared element upstream of AUX/IAA protein stability to auxin-induced cell division/elongation and to auxin-binding protein 1, and provides a new tool to dissect auxin signal transduction

インフルエンザ カンセンショウ ニ ガッペイ シタ キュウセイ チュウスイエン ノ 2 ショウニ レイ

症例1は6歳女児.インフルエンザ感染症初日に発熱しオセルタミビルを開始.第3病日,右下腹部に限局した圧痛が出現.腹部造影CTで糞石を認め急性虫垂炎と診断.保存的に加療し炎症反応と腹痛は改善した.症例2は5歳女児.第1病日に発熱と腹痛を認め,第3病日に鼻咽腔迅速検査でインフルエンザB型と診断しザナミビル吸入を開始.触診で右下腹部に反跳痛を認め,腹部単純CTで虫垂壁の肥厚と糞石を確認.急性虫垂炎の併発と診断し,第4病日に虫垂切除術を施行.切除虫垂に膿瘍を認め腹腔ドレーンを留置.第5病日に解熱し経過は順調であった.インフルエンザに伴う腹痛では感染に付随する腹痛と断定せず急性虫垂炎の可能性も考慮し腹部CTなどの画像検査を行うことが肝要である.We report herein two pediatric cases of influenza virus infection associated with acute appendicitis. Patient 1 was a 6-year-old girl. She presented to hospital with a high fever and received oral administration of oseltamivir phosphate. On the third day from the onset, tenderness developed in the right lower area at McBurney\u27s point. Abdominal enhanced computed tomography( CT) showed intestinal fecalith, and acute appendicitis was subsequently diagnosed. Antibiotic therapy was performed, and abdominal pain and inflammation data improved. Patient 2 was a 5-year-old girl. On the first day, abdominal pain developed. On the third day from the onset, influenza type B was diagnosed using rapid antigen testing of the nasal mucosa, and inhalation therapy was started with zanamivir. Rebound tenderness was seen in the lower right abdomen. Abdominal CT showed both hypertrophy of the appendix wall and intestinal fecalith, and influenza infection associated with acute appendicitis was subsequently diagnosed. On the fourth day, appendectomy was performed. Drainage treatment was required to prevent peri-appendicitis abscess. On the fifth day, the patient defervesced and, as for the progress, was favorable. When encountering influenza infection associated with abdominal pain, performing abdominal CT is important

External genitalia formation: role of fibroblast growth factor, retinoic acid signaling, and distal urethral epithelium

The process of fetal external genitalia development might be divided into two processes. The first process accomplishes the initial outgrowth of the anlage, genital tubercle (GT). Previous analysis suggests that the distal urethral epithelium (DUE) of the GT, the Fgf8-expressing region, regulates the outgrowth of the GT. The second process eventually generates the sexually dimorphic development of the external genitalia, which is dependent on the action of steroid hormones. Several key genes, for example, RARs, RXRs, RALDH2, and CYP26, were dynamically expressed during GT development. The teratogenic dose of RA at 9.0 d.p.c. induced a drastic malformation of the urethral plate during GT formation, but did not show gross abnormalities in its outgrowth. In RA-treated embryos, Fgf8 expression was still detected in the distal GT regions. Possible regulatory roles of the FGF and RA signaling systems in external genitalia formation are discussed

The microbiome and rise of early-onset cancers: knowledge gaps and research opportunities

ABSTRACTAccumulating evidence indicates an alarming increase in the incidence of early-onset cancers, which are diagnosed among adults under 50 years of age, in the colorectum, esophagus, extrahepatic bile duct, gallbladder, liver, stomach, pancreas, as well as the bone marrow (multiple myeloma), breast, head and neck, kidney, prostate, thyroid, and uterine corpus (endometrium). While the early-onset cancer studies have encompassed research on the wide variety of organs, this article focuses on research on digestive system cancers. While a minority of early-onset cancers in the digestive system are associated with cancer-predisposing high penetrance germline genetic variants, the majority of those cancers are sporadic and multifactorial. Although potential etiological roles of diets, lifestyle, environment, and the microbiome from early life to adulthood (i.e. in one’s life course) have been hypothesized, exact contribution of each of these factors remains uncertain. Diets, lifestyle patterns, and environmental exposures have been shown to alter the oral and intestinal microbiome. To address the rising trend of early-onset cancers, transdisciplinary research approaches including lifecourse epidemiology and molecular pathological epidemiology frameworks, nutritional and environmental sciences, multi-omics technologies, etc. are needed. We review current evidence and discuss emerging research opportunities, which can improve our understanding of their etiologies and help us design better strategies for prevention and treatment to reduce the cancer burden in populations

Direct and highly productive conversion of cyanobacteria Arthrospira platensis to ethanol with CaCl2 addition

Background: The cyanobacterium Arthrospira platensis shows promise as a carbohydrate feedstock for biofuel production. The glycogen accumulated in A. platensis can be extracted by lysozyme-degrading the peptidoglycan layer of the bacterial cell walls. The extracted glycogen can be converted to ethanol through hydrolysis by amylolytic enzymes and fermentation by the yeast Saccharomyces cerevisiae. Thus, in the presence of lysozyme, a recombinant yeast expressing α-amylase and glucoamylase can convert A. platensis directly to ethanol, which would simplify the procedure for ethanol production. However, the ethanol titer and productivity in this process are lower than in ethanol production from cyanobacteria and green algae in previous reports. Results: To increase the ethanol titer, a high concentration of A. platensis biomass was employed as the carbon source for the ethanol production using a recombinant amylase-expressing yeast. The addition of lysozyme to the fermentation medium increased the ethanol titer, but not the ethanol productivity. The addition of CaCl2 increased both the ethanol titer and productivity by causing the delamination of polysaccharide layer on the cell surface of A. platensis. In the presence of lysozyme and CaCl2, ethanol titer, yield, and productivity improved to 48 g L−1, 93% of theoretical yield, and 1.0 g L−1 h−1 from A. platensis, corresponding to 90 g L−1 of glycogen. Conclusions: We developed an ethanol conversion process using a recombinant amylase-expressing yeast from A. platensis with a high titer, yield, and productivity by adding both lysozyme and CaCl2. The direct and highly productive conversion process from A. platensis via yeast fermentation could be applied to multiple industrial bulk chemicals

Correlations of post-implant regional dosimetric parameters at 24 hours and one month, with clinical results of low-dose-rate brachytherapy for localized prostate cancer

Purpose : To evaluate the correlations of post-implant regional dosimetrics at 24 hours (24 h) and 1 month after implant procedures, with clinical outcomes of low-dose-rate (LDR) brachytherapy for localized prostate cancer. Material and methods : Between January 2008 and December 2014, 130 consecutive patients treated for localized prostate cancer, receiving definitive iodine-125 ( 125 I) brachytherapy treatment were retrospectively analyzed. All patients underwent post-implant CT imaging for dosimetric analysis at 24 h and 1 month after implantation procedure. Prostate contours were divided into quadrants: anterior-superior (ASQ), posterior-superior (PSQ), anterior-inferior (AIQ), and posterior-inferior (PIQ). Predictive factors and cut-off values of biochemical failure-free survival (BFFS) and toxicities of LDR brachytherapy were analyzed. Results : The median follow-up time was 69.5 months. Seven patients (5.4%) had biochemical failure. The 3-year and 5-year BFFS rates were 96.7% and 93.1%, respectively. On multivariate analysis, prostate-specific antigen and Gleason score were significant prognostic factors for biochemical failure. D 90 (the minimal dose received by 90% of the volume) of PSQ and PIQ at 24 h, and D 90 of PSQ at 1 month were also significant factors. The cut-off values of PSQ D 90 were 145 Gy at 24 h and 160 Gy at 1 month. D 90 of the whole prostate was not significant at 24 h and at 1 month. D 90 of PSQ at 1 month was a significant factor for rectal hemorrhage. Conclusions : Post-implant D 90 of PSQ is significantly associated with BFFS for localized prostate cancer not only at 1 month, but also at 24 hours. D 90 of PSQ at 1 month is also a significant factor for rectal hemorrhage

Cell-surface display technology and metabolic engineering of Saccharomyces cerevisiae for enhancing xylitol production from woody biomass

International audienceXylitol is a major commodity chemical widely used in both the food and pharmaceutical industries. Although the worldwide demand for xylitol is constantly growing, its industrial production from purified D-xylose involves a costly and polluting catalytic hydrogenation process. Biotechnological production of xylitol from biomass is a promising strategy to establish an environmentally friendly sustainable conversion process. In this study, xylitol was produced from woody Kraft pulp (KP) by using an engineered strain of Saccharomyces cerevisiae (YPH499-XR-BGL-XYL-XYN) expressing cytosolic xylose reductase (XR), along with beta-D-glucosidase (BGL), xylosidase (XYL) and xylanase (XYN) enzymes co-displayed on the cell surface. All these enzymes contributed to the consolidated bioprocessing of KP to xylitol with a yield of 2.3 g L-1 (28% conversion) after 96 hours, along with a significantly reduced amount of commercial enzymes required for pre-treatment (commercial hemicellulase cocktail (CHC), [CHC] = 0.02 g-DW per g). Further improvement of the cell surface display of XYL and XYN was obtained by using a SED1 "SSS" cassette, containing the coding sequences of the SED1 promoter, the SED1 secretion signal, and the SED1 anchoring domain, to generate the improved strain YPH499-XR-BGL-XYLsss-XYNsss. This improved strain showed a significantly enhanced xylitol production capacity reaching a yield of 3.7 g L-1 (44% conversion) after 96 hours. The cellulosic content of KP residues was also significantly increased, from 78% to 87% after 96 hours of fermentation, and nanofibrillation of KP residues was observed by scanning electron microscopy. Pre-treatment and fermentation were successfully performed as a proof of concept to further scale up bio-refinery industrial production of xylitol from lignocellulose

Engineering of a novel cellulose-adherent cellulolytic Saccharomyces cerevisiae for cellulosic biofuel production

CITATION: Liu, Z., et al. 2016. Engineering of a novel cellulose-adherent cellulolytic Saccharomyces cerevisiae for cellulosic biofuel production. Scientific Reports, 6:24550, doi:10.1038/srep24550.The original publication is available at http://www.nature.com/srepCellulosic biofuel is the subject of increasing attention. The main obstacle toward its economic feasibility is the recalcitrance of lignocellulose requiring large amount of enzyme to break. Several engineered yeast strains have been developed with cellulolytic activities to reduce the need for enzyme addition, but exhibiting limited effect. Here, we report the successful engineering of a cellulose-adherent Saccharomyces cerevisiae displaying four different synergistic cellulases on the cell surface. The cellulase-displaying yeast strain exhibited clear cell-to-cellulose adhesion and a “tearing” cellulose degradation pattern; the adhesion ability correlated with enhanced surface area and roughness of the target cellulose fibers, resulting in higher hydrolysis efficiency. The engineered yeast directly produced ethanol from rice straw despite a more than 40% decrease in the required enzyme dosage for high-density fermentation. Thus, improved cell-to-cellulose interactions provided a novel strategy for increasing cellulose hydrolysis, suggesting a mechanism for promoting the feasibility of cellulosic biofuel production.https://www.nature.com/articles/srep24550Publisher's versio

Positive Regulation of Steroidogenic Acute Regulatory Protein Gene Expression through the Interaction between Dlx and GATA-4 for Testicular Steroidogenesis

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