Yamamoto M

References (56)

Title : Crystal structure of Staphylococcus aureus lipase complex with unsaturated petroselinic acid - Kitadokoro_2024_FEBS.Open.Bio__
Author(s) : Kitadokoro J , Kamitani S , Okuno Y , Hikima T , Yamamoto M , Hirokawa T , Kitadokoro K
Ref : FEBS Open Bio , : , 2024
Abstract : Staphylococcus aureus produces large amounts of toxins and virulence factors. In patients with underlying diseases or compromised immune systems, this bacterium can lead to severe infections and potentially death. In this study, the crystal structure of the complex of S. aureus lipase (SAL), which is involved in the growth of this bacterium, with petroselinic acid (PSA), an inhibitor of unsaturated fatty acids, was determined by X-ray crystallography. Recently, PSA was shown to inhibit S. aureus biofilm formation and the enzymatic activity of SAL. To further characterize the inhibitory mechanism, we determined the half-inhibitory concentration of SAL by PSA and the crystal structure of the complex. The IC(50) of the inhibitory effect of PSA on SAL was 3.4 microm. SAL and PSA inhibitors were co-crystallized, and diffraction data sets were collected to 2.19 A resolution at SPring-8 to determine the crystal structure and elucidate the detailed structural interactions. The results show that the fatty acid moiety of PSA is tightly bound to a hydrophobic pocket extending in two directions around the catalytic residue Ser116. Ser116 was also covalently bonded to the carbon of the unsaturated fatty acid moiety, and an oxyanion hole in SAL stabilized the electrons of the double bond. The difference in inhibitory activity between PSA and ester compounds revealed a structure-activity relationship between SAL and PSA. Additional research is required to further characterize the clinical potential of PSA.
ESTHER : Kitadokoro_2024_FEBS.Open.Bio__
PubMedSearch : Kitadokoro_2024_FEBS.Open.Bio__
PubMedID: 38757397

Title : Maternal DHA intake in mice increased DHA metabolites in the pup brain and ameliorated MeHg-induced behavioral disorder - Oguro_2023_J.Lipid.Res__100458
Author(s) : Oguro A , Fujiyama T , Ishihara Y , Kataoka C , Yamamoto M , Eto K , Komohara Y , Imaoka S , Sakuragi T , Tsuji M , Shibata E , Kotake Y , Yamazaki T
Ref : J Lipid Res , :100458 , 2023
Abstract : Although pregnant women's fish consumption is beneficial for the brain development of the fetus due to the docosahexaenoic acid (DHA) in fish, seafood also contains methylmercury (MeHg), which adversely affects fetal brain development. Epidemiological studies suggest that high DHA levels in pregnant women's sera may protect the fetal brain from MeHg-induced neurotoxicity, but the underlying mechanism is unknown. Our earlier study revealed that DHA and its metabolite 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP) produced by cytochrome P450s (P450s) and soluble epoxide hydrolase (sEH) can suppress MeHg-induced cytotoxicity in mouse primary neuronal cells. In the present study, DHA supplementation to pregnant mice suppressed MeHg-induced impairments of pups' body weight, grip strength, motor function, and short-term memory. DHA supplementation also suppressed MeHg-induced oxidative stress and the decrease in the number of subplate neurons in the cerebral cortex of the pups. DHA supplementation to dams significantly increased the DHA metabolites 19,20- epoxydocosapentaenoic acid (19,20-EDP) and 19,20-DHDP as well as DHA itself in the fetal and infant brains, although the expression levels of P450s and sEH were low in the fetal brain and liver. DHA metabolites were detected in the mouse breast milk and in human umbilical cord blood, indicating the active transfer of DHA metabolites from dams to pups. These results demonstrate that DHA supplementation increased DHA and its metabolites in the mouse pup brain and alleviated the effects of MeHg on fetal brain development. Pregnant women's intake of fish containing high levels of DHA (or DHA supplementation) may help prevent MeHg-induced neurotoxicity in the fetus.
ESTHER : Oguro_2023_J.Lipid.Res__100458
PubMedSearch : Oguro_2023_J.Lipid.Res__100458
PubMedID: 37838304

Title : Residue-Specific Incorporation of the Non-Canonical Amino Acid Norleucine Improves Lipase Activity on Synthetic Polyesters - Haernvall_2022_Front.Bioeng.Biotechnol_10_769830
Author(s) : Haernvall K , Fladischer P , Schoeffmann H , Zitzenbacher S , Pavkov-Keller T , Gruber K , Schick M , Yamamoto M , Kuenkel A , Ribitsch D , Guebitz GM , Wiltschi B
Ref : Front Bioeng Biotechnol , 10 :769830 , 2022
Abstract : Environmentally friendly functionalization and recycling processes for synthetic polymers have recently gained momentum, and enzymes play a central role in these procedures. However, natural enzymes must be engineered to accept synthetic polymers as substrates. To enhance the activity on synthetic polyesters, the canonical amino acid methionine in Thermoanaerobacter thermohydrosulfuricus lipase (TTL) was exchanged by the residue-specific incorporation method for the more hydrophobic non-canonical norleucine (Nle). Strutural modelling of TTL revealed that residues Met-114 and Met-142 are in close vicinity of the active site and their replacement by the norleucine could modulate the catalytic activity of the enzyme. Indeed, hydrolysis of the polyethylene terephthalate model substrate by the Nle variant resulted in significantly higher amounts of release products than the Met variant. A similar trend was observed for an ionic phthalic polyester containing a short alkyl diol (C5). Interestingly, a 50% increased activity was found for TTL [Nle] towards ionic phthalic polyesters containing different ether diols compared to the parent enzyme TTL [Met]. These findings clearly demonstrate the high potential of non-canonical amino acids for enzyme engineering.
ESTHER : Haernvall_2022_Front.Bioeng.Biotechnol_10_769830
PubMedSearch : Haernvall_2022_Front.Bioeng.Biotechnol_10_769830
PubMedID: 35155387
Gene_locus related to this paper: theet-q3ch51

Title : DHA and Its Metabolites Have a Protective Role against Methylmercury-Induced Neurotoxicity in Mouse Primary Neuron and SH-SY5Y Cells - Oguro_2021_Int.J.Mol.Sci_22_
Author(s) : Oguro A , Fujita K , Ishihara Y , Yamamoto M , Yamazaki T
Ref : Int J Mol Sci , 22 : , 2021
Abstract : The consumption of fish now involves a risk of methylmercury (MeHg) exposure but also provides the benefit of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) such as docosahexaenoic acid (DHA). Some epidemiological studies have suggested that the intake of DHA can alleviate the neurotoxicity of MeHg, but the underlying mechanism is not known. Herein, we observed that pretreatment with 0.1-1 microM DHA suppressed MeHg-induced cytotoxicity in human neuroblastoma (SH-SY5Y) cells and mouse primary neuronal cells. These effects of DHA were canceled in the presence of the retinoid X receptor (RXR) antagonist UVI3003. An RXR agonist, bexarotene, suppressed the cytotoxicity of MeHg. DHA also suppressed the MeHg-induced production of reactive oxygen species (ROS) via an induction of antioxidant genes (catalase and SOD1). Pretreatment with DHA did not change the incorporation of MeHg. We showed previously that in the brain, the intake of DHA increased the level of 19,20-DHDP, which is the metabolite produced by cytochrome P450 and soluble epoxide hydrolase from DHA. In the present study, we observed that 19,20-DHDP also suppressed neurotoxicity from MeHg. These results indicate that DHA and its metabolites have a protective role in MeHg-induced neurotoxicity.
ESTHER : Oguro_2021_Int.J.Mol.Sci_22_
PubMedSearch : Oguro_2021_Int.J.Mol.Sci_22_
PubMedID: 33809931

Title : Crystal structure of pathogenic Staphylococcus aureus lipase complex with the anti-obesity drug orlistat - Kitadokoro_2020_Sci.Rep_10_5469
Author(s) : Kitadokoro K , Tanaka M , Hikima T , Okuno Y , Yamamoto M , Kamitani S
Ref : Sci Rep , 10 :5469 , 2020
Abstract : Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important virulence factor and may be a therapeutic target for infectious diseases. Herein, we determined the 3D structure of native SAL, the mutated S116A inactive form, and the inhibitor complex using the anti-obesity drug orlistat to aid in drug development. The determined crystal structures showed a typical alpha/beta hydrolase motif with a dimeric form. Fatty acids bound near the active site in native SAL and inactive S116A mutant structures. We found that orlistat potently inhibits SAL activity, and it covalently bound to the catalytic Ser116 residue. This is the first report detailing orlistat-lipase binding. It provides structure-based information on the production of potent anti-SAL drugs and lipase inhibitors. These results also indicated that orlistat can be repositioned to treat bacterial diseases.
ESTHER : Kitadokoro_2020_Sci.Rep_10_5469
PubMedSearch : Kitadokoro_2020_Sci.Rep_10_5469
PubMedID: 32214208
Gene_locus related to this paper: staau-lipas

Title : Comparisons of Postoperative Complications and Nutritional Status After Proximal Laparoscopic Gastrectomy with Esophagogastrostomy and Double-Tract Reconstruction - Miyauchi_2020_Yonago.Acta.Med_63_335
Author(s) : Miyauchi W , Matsunaga T , Shishido Y , Miyatani K , Hanaki T , Kihara K , Yamamoto M , Tokuyasu N , Takano S , Sakamoto T , Honjo S , Saito H , Fujiwara Y
Ref : Yonago Acta Med , 63 :335 , 2020
Abstract : BACKGROUND: The purpose of this study was to compare postoperative complications and nutritional status between esophagogastrostomy and double-tract reconstruction in patients who underwent laparoscopic proximal gastrectomy, and assess the advantages of both surgical procedures. METHODS: Between 2010 and 2018, 47 cases underwent proximal gastrectomy with esophagogastrostomy (n = 23) or double-tract reconstruction (n = 24) at our institution for the treatment of clinical T1N0 adenocarcinoma located in the upper third of the stomach. Patient clinical characteristics, short-term outcomes, nutrition status, and skeletal muscle index were compared among the two groups. RESULTS: There was no significant difference between esophagogastrostomy and double-tract reconstruction in terms of operation time, blood loss, and length of postoperative hospital stay. Reflux symptoms and anastomotic stenosis were significantly higher in the esophagogastrostomy group compared with the double-tract reconstruction group (P < 0.001 and P = 0.004, respectively). There was no significant difference in anastomotic leakage, surgical site infection, and pancreatic fistula. For the nutritional status, the decrease rate of cholinesterase was significantly higher in the esophagogastrostomy group compared with the double-tract reconstruction group at 6 months (P = 0.008) There was no significant difference in the decrease rate of skeletal muscle mass index at 1 year after surgery. CONCLUSION: Compared with esophagogastrostomy, double-tract reconstruction tends to have better short-term nutritional status and postoperative outcomes in terms of preventing the occurrence of gastroesophageal reflux and anastomosis stenosis. These findings suggest that double-tract reconstruction may be a useful method in laparoscopic proximal gastrectomy.
ESTHER : Miyauchi_2020_Yonago.Acta.Med_63_335
PubMedSearch : Miyauchi_2020_Yonago.Acta.Med_63_335
PubMedID: 33253340

Title : Hemorrhoidectomy for elderly patients aged 75 years or more, before and after studies - Yamamoto_2020_Ann.Med.Surg.(Lond)_55_88
Author(s) : Yamamoto M , Ikeda M , Matsumoto T , Takemoto M , Sumimoto R , Kobayashi T , Ohdan H
Ref : Ann Med Surg (Lond) , 55 :88 , 2020
Abstract : Background: The incidence of hemorrhoids requiring hemorrhoidectomy among the elderly has been increasing. Old age is sometimes considered a contraindication for surgery. The relationship between age and complications of hemorrhoidectomy for elderly patients is not well established. This study aimed to compare the clinicopathological features and postoperative outcomes of hemorrhoidectomy in the elderly (>/=75 years old) and non-elderly patients (<75 years old). Methods: A total of 100 patients who underwent hemorrhoidectomy for hemorrhoids of Goligher classification grades 3 and 4 at our institution between 2014 and 2018 were enrolled. The clinical characteristics were compared between the elderly and non-elderly patients. Pain scores were measured at 6, 12, 24, and 48 h after surgery. The risk factors for postoperative complications were identified. Results: A total of 34 patients were classified as elderly patients. In the elderly group, aspartate aminotransferase levels were higher while the albumin levels and cholinesterase levels were lower and the platelet counts were significantly lower. The blood urea nitrogen levels were higher and estimated glomerular filtration rates and hemoglobin levels were significantly lower in the elderly group. The pain scores significantly decreased at 48 h postoperatively compared to those recorded at 6 h postoperatively in both groups. Multivariate analysis identified Goligher classification grade 4 and high neutrophil to lymphocyte ratio at the indicators of complications. Conclusions: Hemorrhoids due to impairment of liver function and kidney function were dominant in elderly patients. Aging itself was not a risk factor for postoperative complications.
ESTHER : Yamamoto_2020_Ann.Med.Surg.(Lond)_55_88
PubMedSearch : Yamamoto_2020_Ann.Med.Surg.(Lond)_55_88
PubMedID: 32477502

Title : Combination of Serum Albumin and Cholinesterase Levels as Prognostic Indicator in Patients ith Colorectal Cancer - Yamamoto_2019_Anticancer.Res_39_1085
Author(s) : Yamamoto M , Saito H , Uejima C , Tanio A , Tada Y , Matsunaga T , Sakamoto T , Honjo S , Ashida K , Fujiwara Y
Ref : Anticancer Research , 39 :1085 , 2019
Abstract : BACKGROUND/AIM: Nutritional status is strongly associated with cancer prognosis. The aim of this study was to identify the most useful combination of nutrition-related serum markers for predicting prognosis of patients with colorectal cancer (CRC). PATIENTS AND METHODS: A total of 523 patients who underwent proctocolectomies for CRC at our hospital were enrolled in this study. Serum concentrations of albumin, cholinesterase and total cholesterol, and total peripheral lymphocyte count (TLC) were used as nutrition-related markers. RESULTS: In multivariate analysis of nutrition-related markers, serum albumin and cholinesterase levels were found to be independent prognostic indicators. Cut-off values from receiver operating characteristic analyses were used to sort patients as ChE(High) or ChE(Low) (serum cholinesterase level >/= or <221.5), and as Alb(High) or Alb(Low) (serum albumin level >/= or <3.85). We then sorted them into three groups: ChE(High)/Alb(High) (Group A); ChE(High)/Alb(Low) or ChE(Low)/Alb(High) (Group B); and ChE(Low)/Alb(Low) (Group C). Their 5-year overall survival rates differed significantly (Group A: 81.6%, Group B: 62.1%, Group C: 42.7%, p<0.0001); as did their 5-year disease-specific survival rates (Group A: 90.1%, Group B: 73.8%, Group C: 62.2%, p<0.0001). CONCLUSION: The combination of serum cholinesterase and albumin levels is useful for predicting the prognosis of patients with CRC.
ESTHER : Yamamoto_2019_Anticancer.Res_39_1085
PubMedSearch : Yamamoto_2019_Anticancer.Res_39_1085
PubMedID: 30711999

Title : Complete biosynthetic pathways of ascofuranone and ascochlorin in Acremonium egyptiacum - Araki_2019_Proc.Natl.Acad.Sci.U.S.A_116_8269
Author(s) : Araki Y , Awakawa T , Matsuzaki M , Cho R , Matsuda Y , Hoshino S , Shinohara Y , Yamamoto M , Kido Y , Inaoka DK , Nagamune K , Ito K , Abe I , Kita K
Ref : Proc Natl Acad Sci U S A , 116 :8269 , 2019
Abstract : Ascofuranone (AF) and ascochlorin (AC) are meroterpenoids produced by various filamentous fungi, including Acremonium egyptiacum (synonym: Acremonium sclerotigenum), and exhibit diverse physiological activities. In particular, AF is a promising drug candidate against African trypanosomiasis and a potential anticancer lead compound. These compounds are supposedly biosynthesized through farnesylation of orsellinic acid, but the details have not been established. In this study, we present all of the reactions and responsible genes for AF and AC biosyntheses in A. egyptiacum, identified by heterologous expression, in vitro reconstruction, and gene deletion experiments with the aid of a genome-wide differential expression analysis. Both pathways share the common precursor, ilicicolin A epoxide, which is processed by the membrane-bound terpene cyclase (TPC) AscF in AC biosynthesis. AF biosynthesis branches from the precursor by hydroxylation at C-16 by the P450 monooxygenase AscH, followed by cyclization by a membrane-bound TPC AscI. All genes required for AC biosynthesis (ascABCDEFG) and a transcriptional factor (ascR) form a functional gene cluster, whereas those involved in the late steps of AF biosynthesis (ascHIJ) are present in another distantly located cluster. AF is therefore a rare example of fungal secondary metabolites requiring multilocus biosynthetic clusters, which are likely to be controlled by the single regulator, AscR. Finally, we achieved the selective production of AF in A. egyptiacum by genetically blocking the AC biosynthetic pathway; further manipulation of the strain will lead to the cost-effective mass production required for the clinical use of AF.
ESTHER : Araki_2019_Proc.Natl.Acad.Sci.U.S.A_116_8269
PubMedSearch : Araki_2019_Proc.Natl.Acad.Sci.U.S.A_116_8269
PubMedID: 30952781
Gene_locus related to this paper: acreg-ascc

Title : Enzymatic hydrolysis of PET: functional roles of three Ca(2+) ions bound to a cutinase-like enzyme, Cut190*, and its engineering for improved activity - Oda_2018_Appl.Microbiol.Biotechnol_102_10067
Author(s) : Oda M , Yamagami Y , Inaba S , Oida T , Yamamoto M , Kitajima S , Kawai F
Ref : Applied Microbiology & Biotechnology , 102 :10067 , 2018
Abstract : Cut190 from Saccharomonospora viridis AHK190 (Cut190) is the only cutinase that exhibits inactive (Ca(2+)-free) and active (Ca(2+)-bound) states, although other homologous cutinases always maintain the active states (Ca(2+)-free and bound). The X-ray crystallography of the S176A mutant of Cut190* (Cut190_S226P/R228S) showed that three Ca(2+) ions were bound at sites 1-3 of the mutant. We analyzed the roles of three Ca(2+) ions by mutation and concluded that they play different roles in Cut190* for activation (sites 1 and 3) and structural and thermal stabilization (sites 2 and 3). Based on these analyses, we elucidated the mechanism for the conformational change from the Ca(2+)-free inactive state to the Ca(2+)-bound active state, proposing the novel Ca(2+) effect on structural dynamics of protein. The introduction of a disulfide bond at Asp250 and Glu296 in site 2 remarkably increased the melting temperatures of the mutant enzymes by more than 20-30 degrees C (while Ca(2+)-bound) and 4-14 degrees C (while Ca(2+)-free), indicating that a disulfide bond mimics the Ca(2+) effect. Replacement of surface asparagine and glutamine with aspartic acid, glutamic acid, or histidine increased the melting temperatures. Engineered mutant enzymes were evaluated by an increase in melting temperatures and kinetic values, based on the hydrolysis of poly(butylene succinate-co-adipate) and microfiber polyethylene terephthalate (PET). A combined mutation, Q138A/D250C-E296C/Q123H/N202H, resulted in the highest thermostability, leading to the maximum degradation of PET film (more than 30%; approximately threefold at 70 degrees C, compared with that of Cut190* at 63 degrees C).
ESTHER : Oda_2018_Appl.Microbiol.Biotechnol_102_10067
PubMedSearch : Oda_2018_Appl.Microbiol.Biotechnol_102_10067
PubMedID: 30250976
Gene_locus related to this paper: sacvd-c7mve8

Title : Enzymes as Enhancers for the Biodegradation of Synthetic Polymers in Wastewater - Haernvall_2018_Chembiochem_19_317
Author(s) : Haernvall K , Zitzenbacher S , Biundo A , Yamamoto M , Schick MB , Ribitsch D , Guebitz GM
Ref : Chembiochem , 19 :317 , 2018
Abstract : Synthetic polyesters are today the second-largest class of ingredients in household products and are entering wastewater treatment plants (WWTPs) after product utilization. One approach to improve polymer biodegradation in wastewater would be to complement current processes with polyester-hydrolyzing enzymes and their microbial producers. In this study, the hydrolysis of poly(oxyethylene terephthalate) polymer by hydrolases from wastewater microorganisms was investigated in vitro and under realistic WWTP conditions. An esterase and a cutinase from Pseudomonas pseudoalcaligenes and a lipase from Pseudomonas pelagia were heterologously expressed in Escherichia coli BL21-Gold(DE3) and were purified by a C-terminal His6 tag. The hydrolases were proven to hydrolyze the polymer effectively, which is a prerequisite for further biodegradation. The hydrolases maintained high activity up to 50 % upon lowering the temperature from 28 to 15 degrees C to mimic WWTP conditions. The hydrolases were also not inhibited by the wastewater matrix. Polyester-hydrolyzing enzymes active under WWTP conditions and their microbial producers thus have the potential to improve biological treatment of wastewater rich in synthetic polymers.
ESTHER : Haernvall_2018_Chembiochem_19_317
PubMedSearch : Haernvall_2018_Chembiochem_19_317
PubMedID: 29119717

Title : Treatment of Myasthenia Gravis With High-Dose Cholinesterase Inhibitors and Calcineurin Inhibitors Caused Spontaneous Muscle Cramps in Patients - Masuda_2018_Clin.Neuropharmacol_41_164
Author(s) : Masuda M , Utsumi H , Tanaka S , Maeno A , Yamamoto M , Sugiyama K , Hirano T , Aizawa H
Ref : Clinical Neuropharmacology , 41 :164 , 2018
Abstract : OBJECTIVES: The objective of this study was to investigate the influence of treatment with cholinesterase inhibitors (ChEIs) and calcineurin inhibitors (CNIs) on the occurrence of cramps in myasthenia gravis (MG) patients. METHODS: The frequency and duration of cramp and serum electrolytes were evaluated in 81 patients with MG. The patients were classified using Myasthenia Gravis Foundation of America postintervention status scores based on the treatment and the responsiveness to the treatment. Quantitative MG score, MG activities of daily living score, MG composite score, or MG quality of life 15 score was used to assess the health-related quality of life (QOL). RESULTS: Muscle cramps developed in 44 (54.3%) of 81 MG patients. The scores of MG activities of daily living, MG composite, or MG-QOL 15-item questionnaire in patients with cramp were significantly higher than those in patients without cramps (P = 0.002, P = 0.01, or P = 0.0022, respectively). The serum magnesium concentrations were lower in patients treated with CNI (n = 16) than in those not treated with CNI (n = 65) (P = 0.002). The probability of cramps was significantly higher in patients treated with ChEIs (>/=180 mg/d) in addition to CNI than in patients who were treated with a low dose of ChEIs (<=60 mg/d) without concomitant CNI treatment (P = 0.017). CONCLUSIONS: Our data suggested that treatment with a high dose of ChEI and CNI accelerated the probability of cramps and reduced the QOL in MG patients.
ESTHER : Masuda_2018_Clin.Neuropharmacol_41_164
PubMedSearch : Masuda_2018_Clin.Neuropharmacol_41_164
PubMedID: 30130259

Title : B-Type Natriuretic Peptide and Hemoglobin are Two Major Factors Significantly Associated With Baseline Cerebral Oxygen Saturation Measured Using the INVOS Oximeter in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery - Yamamoto_2018_J.Cardiothorac.Vasc.Anesth_32_187
Author(s) : Yamamoto M , Hayashida M , Kakemizu-Watanabe M , Ando N , Mukaida H , Kawagoe I , Yusuke S , Inada E
Ref : J Cardiothorac Vasc Anesth , 32 :187 , 2018
Abstract : OBJECTIVES: To investigate an association between the preoperative plasma B-type natriuretic peptide (BNP) concentration and cerebral regional saturation (rSO2) measured using the INVOS oximeter (Medtronic, Minneapolis, MN). DESIGN: A retrospective data analysis. SETTING: Single university hospital. PARTICIPANTS: Patients undergoing off-pump coronary artery bypass (OPCAB) surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Associations of variables obtained from preoperative blood laboratory tests and transthoracic echocardiography with baseline rSO2 before induction of general anesthesia were investigated using bivariate and multivariate regression analyses in 330 OPCAB patients. With bivariate analyses, age; body size-related variables such as weight and body surface area; hematologic function-related variables such as blood hemoglobin (Hb) concentration and arterial oxygen saturation; renal function-related variables including estimated glomerular filtration rate, creatinine, and blood urea nitrogen; hepatic function-related variables including cholinesterase, albumin, total bilirubin, and alanine aminotransferase; serum electrolytes including sodium, chloride, and phosphorus; BNP or log-transformed BNP; and 13 transthoracic echocardiography variables such as left ventricular ejection fraction highly significantly correlated with baseline rSO2 (p < 0.0001). However, the multiple regression analysis revealed that only BNP and Hb remained major factors significantly associated with baseline rSO2 (p < 0.0001), while estimated glomerular filtration rate, arterial oxygen saturation, and body surface area remained minor factors (p < 0.05). Baseline rSO2 correlated better with log-transformed BNP than with BNP, indicating that rSO2 correlated with BNP in an exponential fashion. CONCLUSIONS: Preoperative BNP and Hb concentrations were 2 major factors associated with INVOS rSO2 in patients undergoing OPCAB.
ESTHER : Yamamoto_2018_J.Cardiothorac.Vasc.Anesth_32_187
PubMedSearch : Yamamoto_2018_J.Cardiothorac.Vasc.Anesth_32_187
PubMedID: 28778770

Title : Hydrolysis of Ionic Phthalic Acid Based Polyesters by Wastewater Microorganisms and Their Enzymes - Haernvall_2017_Environ.Sci.Technol_51_4596
Author(s) : Haernvall K , Zitzenbacher S , Wallig K , Yamamoto M , Schick MB , Ribitsch D , Guebitz GM
Ref : Environ Sci Technol , 51 :4596 , 2017
Abstract : Water-soluble polyesters are used in a range of applications today and enter wastewater treatment plants after product utilization. However, little is known about extracellular enzymes and aquatic microorganisms involved in polyester biodegradation and mineralization. In this study, structurally different ionic phthalic acid based polyesters (the number-average molecular weights (Mn) 1770 to 10000 g/mol and semi crystalline with crystallinity below 1%) were synthesized in various combinations. Typical wastewater microorganisms like Pseudomonas sp. were chosen for in-silico screening toward polyester hydrolyzing enzymes. Based on the in-silico search, a cutinase from Pseudomonas pseudoalcaligenes (PpCutA) and a putative lipase from Pseudomonas pelagia (PpelaLip) were identified. The enzymes PpCutA and PpelaLip were demonstrated to hydrolyze all structurally different polyesters. Activities on all the polyesters were also confirmed with the strains P. pseudoalcaligenes and P. pelagia. Parameters identified to enhance hydrolysis included increased water solubility and polyester hydrophilicity as well as shorter diol chain lengths. For example, polyesters containing 1,2-ethanediol were hydrolyzed faster than polyesters containing 1,8-octanediol. Interestingly, the same trend was observed in biodegradation experiments. This information is important to gain a better mechanistic understanding of biodegradation processes of polyesters in WWTPs where the extracellular enzymatic hydrolysis seems to be the limiting step.
ESTHER : Haernvall_2017_Environ.Sci.Technol_51_4596
PubMedSearch : Haernvall_2017_Environ.Sci.Technol_51_4596
PubMedID: 28345898
Gene_locus related to this paper: 9gamm-PpelaLip , pseol-e9kjl1

Title : Polyol Structure Influences Enzymatic Hydrolysis of Bio-Based 2,5-Furandicarboxylic Acid (FDCA) Polyesters - Haernvall_2017_Biotechnol.J_12_
Author(s) : Haernvall K , Zitzenbacher S , Amer H , Zumstein MT , Sander M , McNeill K , Yamamoto M , Schick MB , Ribitsch D , Guebitz GM
Ref : Biotechnol J , 12 : , 2017
Abstract : Polyesters of 2,5-furandicarboxylic acid (FDCA) have gained attention as they can be regarded as the bio-based alternatives to the petroleum-based polyesters of terephthalic acid. However, only little is known about the biodegradation and enzymatic hydrolysis of FDCA-based polyesters. This work aims to investigate the influence of different polyols on enzymatic hydrolysis of FDCA-based polyesters. A series of polyesters containing various polyols are synthesized and analyzed regarding susceptibility to enzymatic hydrolysis by cutinase 1 from Thermobifida cellulosilytica (Thc_Cut1). FDCA-based polyesters' number average molecular weight (Mn ) ranged from 9360-35 800 g mol(-1) according to gel permeation chromatography (GPC) analysis. Differential scanning calorimetry (DSC) analyses show decreasing glass transition temperature (Tg ) with increasing diol chain length. Crystallinity of all polyesters is below 1% except for polyesters containing 1,6-hexanediol, 1,8-octanediol, and 1,12-dodecanediol for which calculated crystallinities are 27, 37, and 30%, respectively. Thc_Cut1 hydrolyzes all tested polyesters with preference for polyesters containing 1,5-pentanediol and 1,9-nonanediol (57.7 +/- 7.5 and 52.8 +/- 4.0% released FDCA). Enzyme activity increases when the linear diol 1,3-propanediol is replaced by the branched analog 1,2-propanediol or ethoxy units are introduced into the polyester chain. The results will contribute to expand the knowledge of microbial biodegradation of FDCA-based polyesters.
ESTHER : Haernvall_2017_Biotechnol.J_12_
PubMedSearch : Haernvall_2017_Biotechnol.J_12_
PubMedID: 28731613
Gene_locus related to this paper: thefu-q6a0i4

Title : Polyol Structure and Ionic Moieties Influence the Hydrolytic Stability and Enzymatic Hydrolysis of Bio-Based 2,5-Furandicarboxylic Acid (FDCA) Copolyesters - Haernvall_2017_Polymers.(Basel)_9_
Author(s) : Haernvall K , Zitzenbacher S , Yamamoto M , Schick MB , Ribitsch D , Guebitz GM
Ref : Polymers (Basel) , 9 : , 2017
Abstract : A series of copolyesters based on furanic acid and sulfonated isophthalic acid with various polyols were synthetized and their susceptibility to enzymatic hydrolysis by cutinase 1 from Thermobifida cellulosilytica (Thc_Cut1) investigated. All copolyesters consisted of 30 mol % 5-sulfoisophthalate units (NaSIP) and 70 mol % 2,5-furandicarboxylic acid (FDCA), while the polyol component was varied, including 1,2-ethanediol, 1,4-butanediol, 1,8-octanediol, diethylene glycol, triethylene glycol, or tetraethylene glycol. The composition of the copolyesters was confirmed by H-NMR and the number average molecular weight (M(n)) was determined by GPC to range from 2630 to 8030 g/mol. A DSC analysis revealed glass-transition temperatures (T(g)) from 84 to 6 degreesC, which were decreasing with increasing diol chain length. The crystallinity was below 1% for all polyesters. The hydrolytic stability increased with the chain length of the alkyl diol unit, while it was generally higher for the ether diol units. Thc_Cut1 was able to hydrolyze all of the copolyesters containing alkyl diols ranging from two to eight carbon chain lengths, while the highest activities were detected for the shorter chain lengths with an amount of 13.6 +/- 0.7 mM FDCA released after 72 h of incubation at 50 degreesC. Faster hydrolysis was observed when replacing an alkyl diol by ether diols, as indicated, e.g., by a fivefold higher release of FDCA for triethylene glycol when compared to 1,8-octanediol. A positive influence of introducing ionic phthalic acid was observed while the enzyme preferentially cleaved ester bonds associated to the non-charged building blocks.
ESTHER : Haernvall_2017_Polymers.(Basel)_9_
PubMedSearch : Haernvall_2017_Polymers.(Basel)_9_
PubMedID: 30965704
Gene_locus related to this paper: thefu-q6a0i4

Title : A new arylesterase from Pseudomonas pseudoalcaligenes can hydrolyze ionic phthalic polyesters - Haernvall_2017_J.Biotechnol_257_70
Author(s) : Haernvall K , Zitzenbacher S , Yamamoto M , Schick MB , Ribitsch D , Guebitz GM
Ref : J Biotechnol , 257 :70 , 2017
Abstract : Extracellular enzymes are assumed to be responsible for the initial and rate limiting step in biodegradation of polymers. Mainly enzymes with aliphatic esters as their natural substrates (e.g. lipase, cutinases) have until now been evaluated for polyester hydrolysis studies. However, the potential of enzymes with aromatic esters as their natural substrates (e.g. arylesterases) have been neglected although many types of polyester today contain aromatic moieties. Consequently, in order to elucidate biodegradation of phthalic polyesters in aquatic systems, a novel arylesterase (PpEst) was investigated related to hydrolysis of ionic phthalic polyesters. The hydrolysis of various ionic phthalic polyesters by PpEst was mechanistically studied. The polyester building blocks (terephthalic acid (TA), 5-sulfoisophthalic acid (NaSIP) and alkyl or ether diols) were systematically varied to investigate the impact on hydrolysis. PpEst effectively hydrolyzed all 14 synthetized ionic phthalic polyesters as indicated by released TA. However, no NaSIP was detected indicating that PpEst has a limited capacity to cleave bonds in close vicinity to the ionic monomer NaSIP. The systematic study indicated that increasing water solubility and hydrophilicity significantly enhanced hydrolysis. A higher release of TA was seen with increasing NaSIP ratio while up to 20 times more TA was released when alkyl diols were replaced by ether diol analogues. In contrast, cyclic and branched diols had a negative effect on hydrolysis when compared to linear diols. PpEst also revealed a linear release of TA over seven days for ether containing polyesters, indicating a very stable enzyme.
ESTHER : Haernvall_2017_J.Biotechnol_257_70
PubMedSearch : Haernvall_2017_J.Biotechnol_257_70
PubMedID: 28237250

Title : Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay - Yamamoto_2016_Antimicrob.Agents.Chemother_60_6532
Author(s) : Yamamoto M , Matsuyama S , Li X , Takeda M , Kawaguchi Y , Inoue JI , Matsuda Z
Ref : Antimicrobial Agents & Chemotherapy , 60 :6532 , 2016
Abstract : Middle East respiratory syndrome (MERS) is an emerging infectious disease associated with a relatively high mortality rate of approximately 40%. MERS is caused by MERS coronavirus (MERS-CoV) infection, and no specific drugs or vaccines are currently available to prevent MERS-CoV infection. MERS-CoV is an enveloped virus, and its envelope protein (S protein) mediates membrane fusion at the plasma membrane or endosomal membrane. Multiple proteolysis by host proteases, such as furin, transmembrane protease serine 2 (TMPRSS2), and cathepsins, causes the S protein to become fusion competent. TMPRSS2, which is localized to the plasma membrane, is a serine protease responsible for the proteolysis of S in the post-receptor-binding stage. Here, we developed a cell-based fusion assay for S in a TMPRSS2-dependent manner using cell lines expressing Renilla luciferase (RL)-based split reporter proteins. S was stably expressed in the effector cells, and the corresponding receptor for S, CD26, was stably coexpressed with TMPRSS2 in the target cells. Membrane fusion between these effector and target cells was quantitatively measured by determining the RL activity. The assay was optimized for a 384-well format, and nafamostat, a serine protease inhibitor, was identified as a potent inhibitor of S-mediated membrane fusion in a screening of about 1,000 drugs approved for use by the U.S. Food and Drug Administration. Nafamostat also blocked MERS-CoV infection in vitro Our assay has the potential to facilitate the discovery of new inhibitors of membrane fusion of MERS-CoV as well as other viruses that rely on the activity of TMPRSS2.
ESTHER : Yamamoto_2016_Antimicrob.Agents.Chemother_60_6532
PubMedSearch : Yamamoto_2016_Antimicrob.Agents.Chemother_60_6532
PubMedID: 27550352

Title : A novel Ca-activated, thermostabilized polyesterase capable of hydrolyzing polyethylene terephthalate from Saccharomonospora viridis AHK190 - Kawai_2014_Appl.Microbiol.Biotechnol_98_10053
Author(s) : Kawai F , Oda M , Tamashiro T , Waku T , Tanaka N , Yamamoto M , Mizushima H , Miyakawa T , Tanokura M
Ref : Applied Microbiology & Biotechnology , 98 :10053 , 2014
Abstract : Only two polyethylene glycol terephthalate (PET)-degrading enzymes have been reported, and their mechanism for the biochemical degradation of PET remains unclear. To identify a novel PET-degrading enzyme, a putative cutinase gene (cut190) was cloned from the thermophile Saccharomonospora viridis AHK190 and expressed in Escherichia coli Rosetta-gami B (DE3). Mutational analysis indicated that substitution of Ser226 with Pro and Arg228 with Ser yielded the highest activity and thermostability. The Ca2+ ion enhanced the enzyme activity and thermostability of the wild-type and mutant Cut190. Circular dichroism suggested that the Ca2+ changes the tertiary structure of the Cut190 (S226P/R228S), which has optimal activity at 65-75 degrees C and pH 6.5-8.0 in the presence of 20 % glycerol. The enzyme was stable over a pH range of 5-9 and at temperatures up to 65 degrees C for 24 h with 40 % activity remaining after incubation for 1 h at 70 degrees C. The Cut190 (S226P/R228S) efficiently hydrolyzed various aliphatic and aliphatic-co-aromatic polyester films. Furthermore, the enzyme degraded the PET film above 60 degrees C. Therefore, Cut190 is the novel-reported PET-degrading enzyme with the potential for industrial applications in polyester degradation, monomer recycling, and PET surface modification. Thus, the Cut190 will be a useful tool to elucidate the molecular mechanisms of the PET degradation, Ca2+ activation, and stabilization.
ESTHER : Kawai_2014_Appl.Microbiol.Biotechnol_98_10053
PubMedSearch : Kawai_2014_Appl.Microbiol.Biotechnol_98_10053
PubMedID: 24929560
Gene_locus related to this paper: sacvd-c7mve8

Title : Complex regulation of secondary metabolism controlling pathogenicity in the phytopathogenic fungus Alternaria alternata - Takaoka_2014_New.Phytol_202_1297
Author(s) : Takaoka S , Kurata M , Harimoto Y , Hatta R , Yamamoto M , Akimitsu K , Tsuge T
Ref : New Phytol , 202 :1297 , 2014
Abstract : The filamentous fungus Alternaria alternata includes seven pathogenic variants (pathotypes), which produce different host-selective toxins and cause disease on different plants. The Japanese pear, strawberry and tangerine pathotypes produce AK-toxin, AF-toxin and ACT-toxin, respectively, which have a common structural moiety, 9,10-epoxy-8-hydroxy-9-methyl-decatrienoic acid (EDA). Here, we identified a new gene, AKT7 (AK-toxin biosynthetic gene 7), from the Japanese pear pathotype, which encodes a cytochrome P450 monooxygenase and functions to limit AK-toxin production. AKT7 homologs were found in the strawberry pathotype, but not the tangerine pathotype. However, the strawberry pathotype homolog appeared to include a premature stop codon. Although the Japanese pear pathotype strain has multiple copies of AKT7, a single-copy disruption resulted in mutants with increased production of AK-toxin and EDA. AKT7 overexpression in the three pathotypes caused marked reductions of toxin and EDA production, suggesting that Akt7 catalyzes a side reaction of EDA or its precursor. AKT7 overexpression caused reduced virulence in these pathotypes. We also found that AKT7 transcripts predominantly include misspliced mRNAs, which have premature stop codons. Our observations suggest that the AK-toxin production required for full virulence is regulated in a complex way by the copy number and intron information content of AKT7.
ESTHER : Takaoka_2014_New.Phytol_202_1297
PubMedSearch : Takaoka_2014_New.Phytol_202_1297
PubMedID: 24611558

Title : Acetylcholine esterase is a regulator of GFAP expression and a target of dichlorvos in astrocytic differentiation of rat glioma C6 cells - Ozawa_2013_Brain.Res_1537_37
Author(s) : Ozawa A , Kadowaki E , Haga Y , Sekiguchi H , Hemmi N , Kaneko T , Maki T , Sakabe K , Hara S , Yamamoto M , Arishima K , Sakaue M
Ref : Brain Research , 1537 :37 , 2013
Abstract : The main target of neurotoxins is neurons because they comprise the main part of neural function, but glial cells may be indirect targets because they support the function of neurons. Among the glial cells, astrocytes in particular act as "nurse cells", regulating neuronal survival and functions. In the present study, to reveal whether a known neurotoxic substance, organophosphate dichlorvos (DDVP), affects the differentiation of astrocytes, we used an astrocyte differentiation model in rat glioma C6 cells. Morphological change and induction of GFAP expression in the differentiating C6 cells were suppressed by DDVP treatment. The known potential targets of DDVP are acetylcholine esterase (AChE), fatty acid amide hydrolase and methyl guanine methyl transferase. Among the specific inhibitors against these enzymes, the AChE inhibitor paraoxon successfully suppressed the cellular morphological changes and the induction of GFAP expression in differentiating C6 cells. These results indicate that DDVP inhibits differentiation in the C6 astrocyte-differentiation model, in which at least AChE inhibition is involved and that AChE is a potent regulator of the differentiation. Furthermore, considering that the main substrate of AChE is ACh, thus, ACh may act as regulators of astrocyte differentiation.
ESTHER : Ozawa_2013_Brain.Res_1537_37
PubMedSearch : Ozawa_2013_Brain.Res_1537_37
PubMedID: 24001591

Title : Host-selective toxins produced by the plant pathogenic fungus Alternaria alternata - Tsuge_2013_FEMS.Microbiol.Rev_37_44
Author(s) : Tsuge T , Harimoto Y , Akimitsu K , Ohtani K , Kodama M , Akagi Y , Egusa M , Yamamoto M , Otani H
Ref : FEMS Microbiology Reviews , 37 :44 , 2013
Abstract : Host-selective toxins (HSTs) produced by fungal plant pathogens are generally low-molecular-weight secondary metabolites with a diverse range of structures that function as effectors controlling pathogenicity or virulence in certain plant-pathogen interactions. There are now seven known diseases caused by Alternaria alternata in which HSTs are responsible for fungal pathogenesis. The pathogens have been defined as pathotypes of A. alternata because of morphological similarity but pathological differences. Chemical structures of HSTs from six pathotypes have been determined. The role of A. alternata HSTs in pathogenesis has been studied extensively, and discovery of the release of HSTs from germinating conidia prior to penetration aids in understanding the early participation of HSTs to induce susceptibility of host cells by suppressing their defence reactions. Many attempts have been made to find the target sites of A. alternata HSTs, and four cellular components, plasma membrane, mitochondrion, chloroplast and a metabolically important enzyme, have been identified as the primary sites of each HST action, leading to elucidation of the molecular mechanisms of HST sensitivity in host plants. Studies of the molecular genetics of HST production have identified supernumerary chromosomes encoding HST gene clusters and have provided new insights into the evolution of A. alternata pathotypes.
ESTHER : Tsuge_2013_FEMS.Microbiol.Rev_37_44
PubMedSearch : Tsuge_2013_FEMS.Microbiol.Rev_37_44
PubMedID: 22846083
Gene_locus related to this paper: altal-aft8 , altal-actt2 , altal-amt4

Title : Optical resolution of n-butyl D- and L-lactates using immobilized lipase catalyst - Ohara_2011_J.Biosci.Bioeng_111_19
Author(s) : Ohara H , Yamamoto M , Onogi A , Hirao K , Kobayashi S
Ref : J Biosci Bioeng , 111 :19 , 2011
Abstract : n-Butyl D- and L-lactates (BuDLa and BuLLa) were incubated with immobilized lipase. (1)H-NMR showed that BuDLa reacted to oligomers, while BuLLa did not react. A mixture containing 90.4% of BuLLa and 9.6% of BuDLa was incubated with the enzyme for 72 h, then distilled. The purity of BuLLa increased to 98.6%.
ESTHER : Ohara_2011_J.Biosci.Bioeng_111_19
PubMedSearch : Ohara_2011_J.Biosci.Bioeng_111_19
PubMedID: 20851671

Title : Comprehensive sequence analysis of 24,783 barley full-length cDNAs derived from 12 clone libraries - Matsumoto_2011_Plant.Physiol_156_20
Author(s) : Matsumoto T , Tanaka T , Sakai H , Amano N , Kanamori H , Kurita K , Kikuta A , Kamiya K , Yamamoto M , Ikawa H , Fujii N , Hori K , Itoh T , Sato K
Ref : Plant Physiol , 156 :20 , 2011
Abstract : Full-length cDNA (FLcDNA) libraries consisting of 172,000 clones were constructed from a two-row malting barley cultivar (Hordeum vulgare 'Haruna Nijo') under normal and stressed conditions. After sequencing the clones from both ends and clustering the sequences, a total of 24,783 complete sequences were produced. By removing duplicates between these and publicly available sequences, 22,651 representative sequences were obtained: 17,773 were novel barley FLcDNAs, and 1,699 were barley specific. Highly conserved genes were found in the barley FLcDNA sequences for 721 of 881 rice (Oryza sativa) trait genes with 50% or greater identity. These FLcDNA resources from our Haruna Nijo cDNA libraries and the full-length sequences of representative clones will improve our understanding of the biological functions of genes in barley, which is the cereal crop with the fourth highest production in the world, and will provide a powerful tool for annotating the barley genome sequences that will become available in the near future.
ESTHER : Matsumoto_2011_Plant.Physiol_156_20
PubMedSearch : Matsumoto_2011_Plant.Physiol_156_20
PubMedID: 21415278
Gene_locus related to this paper: horvd-f2cta8 , horvd-f2cu28 , horvd-f2cu67 , horvd-f2cvb1 , horvd-f2d2e7 , horvd-f2d3b2 , horvd-f2d8w8 , horvd-f2dam1 , horvd-f2db20 , horvd-f2de38 , horvd-f2dey8 , horvd-f2djs2 , horvd-f2dlw1 , horvd-f2dnj9 , horvd-f2dnr0 , horvd-f2dq60 , horvd-f2dr75 , horvd-f2dvh4 , horvd-f2dwx9 , horvd-f2e2j6 , horvd-f2e3n3 , horvd-f2e504 , horvd-f2eb83 , horvd-f2ebk6 , horvd-f2ec44 , horvd-f2ecv3 , horvd-f2ee51 , horvd-f2eji1 , horvu-cp22 , orysa-q2qx94 , horvd-f2dey9 , horvd-f2djx2 , horvd-f2dln9 , horvd-f2dmr7 , horvd-f2dnv4 , horvd-f2drv9 , horvd-f2ds75 , horvd-f2dsx0 , horvd-f2e0a7 , horvd-f2e0u2 , horvd-f2e5v7 , horvd-f2d4p5 , horvd-m0vg59 , horvd-f2cqv0 , horvd-f2e1j3 , horvd-f2d241 , horvd-f2e8z5 , horvd-m0x298 , horvd-m0y280 , horvd-f2djb2 , horvd-f2dq90 , horvv-f2dwm7 , horvv-f2cwp1 , horvv-a0a287g9l8 , horvv-f2dfe3 , horvv-f2db09 , horvv-f2e0h1

Title : Lipase-catalyzed oligomerization and hydrolysis of alkyl lactates: direct evidence in the catalysis mechanism that enantioselection is governed by a deacylation step - Ohara_2010_Biomacromolecules_11_2008
Author(s) : Ohara H , Onogi A , Yamamoto M , Kobayashi S
Ref : Biomacromolecules , 11 :2008 , 2010
Abstract : Lipase-catalyzed oligomerization of alkyl d- and l-lactate monomers (RDLa and RLLa, respectively) was studied for the first time. It has been found that the oligomerization occurs enantioselectively only for d-lactates to give oligomers up to heptamers of lactic acid (LA) in good to high yields by using primary C1 to C8 alkyl groups and sec-butyl group for d-lactate monomers. No reaction happened for all l-lactates in similar conditions. Lipase-catalyzed hydrolysis of alkyl d- and l-lactates was also examined, revealing that the hydrolysis took place for both d- and l-lactates, although l-lactates proceeded a couple of times slower. The hydrolysis results clearly demonstrate that the lipase catalysis mechanism involves an acyl-enzyme intermediate (EM) formation via the acylation step from both d- and l-lactates as a rate-determining step, and the subsequent deacylation step, a nucleophilic attack of water to the EM, takes place to produce free LA. On the other hand, in the oligomerization of d-lactates, the deacylation step, in which a sec-alcohol group of the monomer or of the propagating chain-end attacks to the EM, is only allowed for the sec-d-alcohol group to give a one-LA-unit-elongated oligomer. l-Lactates form the EM; however, the subsequent deacylation reaction with both the sec-l- and sec-d-alcohol groups does not take place, failing in the oligomerization to occur. These results provide with the first direct evidence in the lipase catalysis that the enantioselection is governed by the deacylation step. In the co-oligomerization between l- and d-lactates, the l-isomer retarded the reaction rate of the d-isomer, which was found due to the function of the former as a competitive inhibitor in the acylation step toward the latter.
ESTHER : Ohara_2010_Biomacromolecules_11_2008
PubMedSearch : Ohara_2010_Biomacromolecules_11_2008
PubMedID: 20593895

Title : Epidermal triglyceride levels are correlated with severity of ichthyosis in Dorfman-Chanarin syndrome - Ujihara_2010_J.Dermatol.Sci_57_102
Author(s) : Ujihara M , Nakajima K , Yamamoto M , Teraishi M , Uchida Y , Akiyama M , Shimizu H , Sano S
Ref : J Dermatol Sci , 57 :102 , 2010
Abstract : BACKGROUND: Dorfman-Chanarin syndrome (DCS), also referred to as neutral lipid storage disease with ichthyosis, is a rare autosomal recessive form of nonbullous congenital ichthyosiform erythroderma, characterized by the presence of intracellular lipid droplets in multiorgans. DCS patients often have mutations in CGI-58, which is an activator of adipose triglyceride lipase (ATGL), leading to accumulation of triglycerides (TG). OBJECTIVE: To study whether a patient with DCS demonstrates TG accumulation in the epidermis and to analyze whether TG levels are correlated with skin disease activity. METHODS: Skin specimen from a 62-year-old man with DCS was stained with oil red O, and analyzed on electromicrographs. Sequencing analysis of CGI-58 was performed using the patient's blood cells. The scales from the lesion were subject to lipid analysis by high-performance thin-layer chromatography (HPTLC). RESULTS: The patient demonstrated ichthyoform erythroderma with a distinct seasonal fluctuation: his skin lesions were aggravated in summer but resolved during winter. Epidermis of the lesion showed intracellular lipid droplets. Sequencing analysis revealed a novel missense mutation in the exon 3 of CGI-58 gene. Lipid analysis of the scales from his lesions, compared with those from normal human control, revealed increased levels of triglycerides (TG) but, in turn, decreased levels of free fatty acids, suggesting dysfunction of adipose TG lipase. Notably, the TG levels in the scales from the patient were positively correlated with the severity of ichthyosis. CONCLUSION: These results suggest that TG accumulation by epidermal keratinocytes directly contributes to ichthyosiform phenotype of DCS.
ESTHER : Ujihara_2010_J.Dermatol.Sci_57_102
PubMedSearch : Ujihara_2010_J.Dermatol.Sci_57_102
PubMedID: 20022472

Title : Role of the host-selective ACT-toxin synthesis gene ACTTS2 encoding an enoyl-reductase in pathogenicity of the tangerine pathotype of Alternaria alternata - Ajiro_2010_Phytopathology_100_120
Author(s) : Ajiro N , Miyamoto Y , Masunaka A , Tsuge T , Yamamoto M , Ohtani K , Fukumoto T , Gomi K , Peever TL , Izumi Y , Tada Y , Akimitsu K
Ref : Phytopathology , 100 :120 , 2010
Abstract : ABSTRACT The tangerine pathotype of Alternaria alternata produces host-selective ACT-toxin and causes Alternaria brown spot disease of tangerines and tangerine hybrids. Sequence analysis of a genomic BAC clone identified a previously uncharacterized portion of the ACT-toxin biosynthesis gene cluster (ACTT). A 1,034-bp gene encoding a putative enoyl-reductase was identified by using rapid amplification of cDNA ends and polymerase chain reaction and designated ACTTS2. Genomic Southern blots demonstrated that ACTTS2 is present only in ACT-toxin producers and is carried on a 1.9 Mb conditionally dispensable chromosome by the tangerine pathotype. Targeted gene disruption of ACTTS2 led to a reduction in ACT-toxin production and pathogenicity, and transcriptional knockdown of ACTTS2 using RNA silencing resulted in complete loss of ACT-toxin production and pathogenicity. These results indicate that ACTTS2 is an essential gene for ACT-toxin biosynthesis in the tangerine pathotype of A. alternata and is required for pathogenicity of this fungus.
ESTHER : Ajiro_2010_Phytopathology_100_120
PubMedSearch : Ajiro_2010_Phytopathology_100_120
PubMedID: 20055645
Gene_locus related to this paper: altal-actt2

Title : ACTTS3 encoding a polyketide synthase is essential for the biosynthesis of ACT-toxin and pathogenicity in the tangerine pathotype of Alternaria alternata - Miyamoto_2010_Mol.Plant.Microbe.Interact_23_406
Author(s) : Miyamoto Y , Masunaka A , Tsuge T , Yamamoto M , Ohtani K , Fukumoto T , Gomi K , Peever TL , Tada Y , Ichimura K , Akimitsu K
Ref : Mol Plant Microbe Interact , 23 :406 , 2010
Abstract : The tangerine pathotype of Alternaria alternata produces host-selective ACT-toxin and causes Alternaria brown spot disease of tangerine and tangerine hybrids. Sequence analysis of a genomic BAC clone identified part of the ACT-toxin TOX (ACTT) gene cluster, and knockout experiments have implicated several open reading frames (ORF) contained within the cluster in the biosynthesis of ACT-toxin. One of the ORF, designated ACTTS3, encoding a putative polyketide synthase, was isolated by rapid amplification of cDNA ends and genomic/reverse transcription-polymerase chain reactions using the specific primers designed from the BAC sequences. The 7,374-bp ORF encodes a polyketide synthase with putative beta-ketoacyl synthase, acyltransferase, methyltransferase, beta-ketoacyl reductase, and phosphopantetheine attachment site domains. Genomic Southern blots demonstrated that ACTTS3 is present on the smallest chromosome in the tangerine pathotype of A. alternata, and the presence of ACTTS3 is highly correlated with ACT-toxin production and pathogenicity. Targeted gene disruption of two copies of ACTTS3 led to a complete loss of ACT-toxin production and pathogenicity. These results indicate that ACTTS3 is an essential gene for ACT-toxin biosynthesis in the tangerine pathotype of A. alternata and is required for pathogenicity of this fungus.
ESTHER : Miyamoto_2010_Mol.Plant.Microbe.Interact_23_406
PubMedSearch : Miyamoto_2010_Mol.Plant.Microbe.Interact_23_406
PubMedID: 20192828
Gene_locus related to this paper: altal-actt2

Title : Function of genes encoding acyl-CoA synthetase and enoyl-CoA hydratase for host-selective act-toxin biosynthesis in the tangerine pathotype of Alternaria alternata - Miyamoto_2009_Phytopathology_99_369
Author(s) : Miyamoto Y , Ishii Y , Honda A , Masunaka A , Tsuge T , Yamamoto M , Ohtani K , Fukumoto T , Gomi K , Peever TL , Akimitsu K
Ref : Phytopathology , 99 :369 , 2009
Abstract : The tangerine pathotype of Alternaria alternata produces host-selective ACT-toxin and causes Alternaria brown spot disease. Sequence analysis of a genomic cosmid clone identified a part of the ACTT gene cluster and implicated two genes, ACTT5 encoding an acyl-CoA synthetase and ACTT6 encoding an enoyl-CoA hydratase, in the biosynthesis of ACT-toxin. Genomic Southern blots demonstrated that both genes were present in tangerine pathotype isolates producing ACT-toxin and also in Japanese pear pathotype isolates producing AK-toxin and strawberry pathotype isolates producing AF-toxin. ACT-, AK-, and AF-toxins from these three pathotypes share a common 9,10-epoxy-8-hydroxy-9-methyl-decatrienoic acid moiety. Targeted gene disruption of two copies of ACTT5 significantly reduced ACT-toxin production and virulence. Targeted gene disruption of two copies of ACTT6 led to complete loss of ACT-toxin production and pathogenicity and a putative decatrienoic acid intermediate in ACT-toxin biosynthesis accumulated in mycelial mats. These results indicate that ACTT5 and ACTT6 are essential genes in ACT-toxin biosynthesis in the tangerine pathotype of A. alternata and both are required for full virulence of this fungus.
ESTHER : Miyamoto_2009_Phytopathology_99_369
PubMedSearch : Miyamoto_2009_Phytopathology_99_369
PubMedID: 19271978
Gene_locus related to this paper: altal-actt2

Title : The Rice Annotation Project Database (RAP-DB): 2008 update - Tanaka_2008_Nucleic.Acids.Res_36_D1028
Author(s) : Tanaka T , Antonio BA , Kikuchi S , Matsumoto T , Nagamura Y , Numa H , Sakai H , Wu J , Itoh T , Sasaki T , Aono R , Fujii Y , Habara T , Harada E , Kanno M , Kawahara Y , Kawashima H , Kubooka H , Matsuya A , Nakaoka H , Saichi N , Sanbonmatsu R , Sato Y , Shinso Y , Suzuki M , Takeda J , Tanino M , Todokoro F , Yamaguchi K , Yamamoto N , Yamasaki C , Imanishi T , Okido T , Tada M , Ikeo K , Tateno Y , Gojobori T , Lin YC , Wei FJ , Hsing YI , Zhao Q , Han B , Kramer MR , McCombie RW , Lonsdale D , O'Donovan CC , Whitfield EJ , Apweiler R , Koyanagi KO , Khurana JP , Raghuvanshi S , Singh NK , Tyagi AK , Haberer G , Fujisawa M , Hosokawa S , Ito Y , Ikawa H , Shibata M , Yamamoto M , Bruskiewich RM , Hoen DR , Bureau TE , Namiki N , Ohyanagi H , Sakai Y , Nobushima S , Sakata K , Barrero RA , Souvorov A , Smith-White B , Tatusova T , An S , An G , S OO , Fuks G , Messing J , Christie KR , Lieberherr D , Kim H , Zuccolo A , Wing RA , Nobuta K , Green PJ , Lu C , Meyers BC , Chaparro C , Piegu B , Panaud O , Echeverria M
Ref : Nucleic Acids Research , 36 :D1028 , 2008
Abstract : The Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of the sequence, and other genomics information that could be useful for comprehensive understanding of the rice biology. Since the last publication of the RAP-DB, the IRGSP genome has been revised and reassembled. In addition, a large number of rice-expressed sequence tags have been released, and functional genomics resources have been produced worldwide. Thus, we have thoroughly updated our genome annotation by manual curation of all the functional descriptions of rice genes. The latest version of the RAP-DB contains a variety of annotation data as follows: clone positions, structures and functions of 31 439 genes validated by cDNAs, RNA genes detected by massively parallel signature sequencing (MPSS) technology and sequence similarity, flanking sequences of mutant lines, transposable elements, etc. Other annotation data such as Gnomon can be displayed along with those of RAP for comparison. We have also developed a new keyword search system to allow the user to access useful information. The RAP-DB is available at: http://rapdb.dna.affrc.go.jp/ and http://rapdb.lab.nig.ac.jp/.
ESTHER : Tanaka_2008_Nucleic.Acids.Res_36_D1028
PubMedSearch : Tanaka_2008_Nucleic.Acids.Res_36_D1028
PubMedID: 18089549
Gene_locus related to this paper: orysa-Q9FW17 , orysa-Q0JK71 , orysa-B9EWJ8 , orysa-Q5N7L1 , orysa-pir7a , orysa-q2qyj1 , orysj-q6yse8 , orysa-q6yzk1 , orysa-Q8S0U8 , orysa-q33aq0 , orysa-Q0J0A4 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-b9fi05 , orysj-b9fkb0 , orysj-cgep , orysj-q0djj0 , orysj-q0dud7 , orysj-q0jaf0 , orysj-q0jga1 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q0iq98 , orysj-b9gbs4 , orysj-b9gbs1 , orysj-pla4 , orysj-pla1

Title : Functional analysis of a multicopy host-selective ACT-toxin biosynthesis gene in the tangerine pathotype of Alternaria alternata using RNA silencing - Miyamoto_2008_Mol.Plant.Microbe.Interact_21_1591
Author(s) : Miyamoto Y , Masunaka A , Tsuge T , Yamamoto M , Ohtani K , Fukumoto T , Gomi K , Peever TL , Akimitsu K
Ref : Mol Plant Microbe Interact , 21 :1591 , 2008
Abstract : Alternaria brown spot, caused by the tangerine pathotype of Alternaria alternata, is a serious disease of commercially important tangerines and their hybrids. The pathogen produces host-selective ACT toxin, and several genes (named ACTT) responsible for ACT-toxin biosynthesis have been identified. These genes have many paralogs, which are clustered on a small, conditionally dispensable chromosome, making it difficult to disrupt entire functional copies of ACTT genes using homologous recombination-mediated gene disruption. To overcome this problem, we attempted to use RNA silencing, which has never been employed in Alternaria spp., to knock down the functional copies of one ACTT gene with a single silencing event. ACTT2, which encodes a putative hydrolase and is present in multiple copies in the genome, was silenced by transforming the fungus with a plasmid construct expressing hairpin ACTT2 RNAs. The ACTT2 RNA-silenced transformant (S-7-24-2) completely lost ACTT2 transcripts and ACT-toxin production as well as pathogenicity. These results indicated that RNA silencing may be a useful technique for studying the role of ACTT genes responsible for host-selective toxin biosynthesis in A. alternata. Further, this technique may be broadly applicable to the analysis of many genes present in multiple copies in fungal genomes that are difficult to analyze using recombination-mediated knockdowns.
ESTHER : Miyamoto_2008_Mol.Plant.Microbe.Interact_21_1591
PubMedSearch : Miyamoto_2008_Mol.Plant.Microbe.Interact_21_1591
PubMedID: 18986255
Gene_locus related to this paper: altal-aft8 , altal-actt2

Title : Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana - Itoh_2007_Genome.Res_17_175
Author(s) : Itoh T , Tanaka T , Barrero RA , Yamasaki C , Fujii Y , Hilton PB , Antonio BA , Aono H , Apweiler R , Bruskiewich R , Bureau T , Burr F , Costa de Oliveira A , Fuks G , Habara T , Haberer G , Han B , Harada E , Hiraki AT , Hirochika H , Hoen D , Hokari H , Hosokawa S , Hsing YI , Ikawa H , Ikeo K , Imanishi T , Ito Y , Jaiswal P , Kanno M , Kawahara Y , Kawamura T , Kawashima H , Khurana JP , Kikuchi S , Komatsu S , Koyanagi KO , Kubooka H , Lieberherr D , Lin YC , Lonsdale D , Matsumoto T , Matsuya A , McCombie WR , Messing J , Miyao A , Mulder N , Nagamura Y , Nam J , Namiki N , Numa H , Nurimoto S , O'Donovan C , Ohyanagi H , Okido T , Oota S , Osato N , Palmer LE , Quetier F , Raghuvanshi S , Saichi N , Sakai H , Sakai Y , Sakata K , Sakurai T , Sato F , Sato Y , Schoof H , Seki M , Shibata M , Shimizu Y , Shinozaki K , Shinso Y , Singh NK , Smith-White B , Takeda J , Tanino M , Tatusova T , Thongjuea S , Todokoro F , Tsugane M , Tyagi AK , Vanavichit A , Wang A , Wing RA , Yamaguchi K , Yamamoto M , Yamamoto N , Yu Y , Zhang H , Zhao Q , Higo K , Burr B , Gojobori T , Sasaki T
Ref : Genome Res , 17 :175 , 2007
Abstract : We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is approximately 32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene.
ESTHER : Itoh_2007_Genome.Res_17_175
PubMedSearch : Itoh_2007_Genome.Res_17_175
PubMedID: 17210932
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9FYP7 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-cbp3 , orysa-cbpx , orysa-Q6YSZ8 , orysa-Q9FW17 , orysa-Q84QZ6 , orysa-Q0JK71 , orysa-B9EWJ8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q658B2 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-pir7a , orysa-q2qnj4 , orysa-q2qyj1 , orysa-q2r077 , orysa-Q4VWY7 , orysa-q5smv5 , orysa-q5z901 , orysa-Q5ZBI5 , orysa-q6atz0 , orysa-q6i5q3 , orysa-q6j657 , orysa-q6k4q2 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q8LQS5 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8W3C6 , orysa-Q9LHX5 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q69j38 , orysa-q69y21 , orysa-q75hy1 , orysa-q75hy2 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q652g4 , orysa-q688m8 , orysa-Q6H8G1 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-b9fi05 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q0jga1 , orysj-q0jhi5 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q0iq98 , orysj-b9gbs4 , orysj-b9gbs1

Title : Expression profiles of genes encoded by the supernumerary chromosome controlling AM-toxin biosynthesis and pathogenicity in the apple pathotype of Alternaria alternata - Harimoto_2007_Mol.Plant.Microbe.Interact_20_1463
Author(s) : Harimoto Y , Hatta R , Kodama M , Yamamoto M , Otani H , Tsuge T
Ref : Mol Plant Microbe Interact , 20 :1463 , 2007
Abstract : The apple pathotype of Alternaria alternata produces host-specific AM-toxin and causes Alternaria blotch of apple. Previously, we cloned two genes, AMT1 and AMT2, required for AM-toxin biosynthesis and found that these genes are encoded by small, supernumerary chromosomes of <1.8 Mb in the apple pathotype strains. Here, we performed expressed sequence tag analysis of the 1.4-Mb chromosome encoding AMT genes in strain IFO8984. A cDNA library was constructed using RNA from AM-toxin-producing cultures. A total of 40,980 clones were screened with the 1.4-Mb chromosome probe, and 196 clones encoded by the chromosome were isolated. Sequence analyses of these clones identified 80 unigenes, including AMT1 and AMT2, and revealed that the functions of 43 (54%) genes are unknown. The expression levels of the 80 genes in AM-toxin-producing and nonproducing cultures were analyzed by real-time quantitative polymerase chain reaction (PCR). Most of the genes were found to be expressed in both cultures at markedly lower levels than the translation elongation factor 1-alpha gene used as an internal control. Comparison of the expression levels of these genes between two cultures showed that 21 genes, including AMT1 and AMT2, were upregulated (>10-fold) in AM-toxin-producing cultures. Two of the upregulated genes were newly identified to be involved in AM-toxin biosynthesis by the gene disruption experiments and were named AMT3 and AMT4. Thus, the genes upregulated in AM-toxin-producing cultures contain ideal candidates for novel AM-toxin biosynthetic genes.
ESTHER : Harimoto_2007_Mol.Plant.Microbe.Interact_20_1463
PubMedSearch : Harimoto_2007_Mol.Plant.Microbe.Interact_20_1463
PubMedID: 17990954
Gene_locus related to this paper: altal-amt4

Title : Donepezil in the treatment of musical hallucinations - Ukai_2007_Psychiatry.Clin.Neurosci_61_190
Author(s) : Ukai S , Yamamoto M , Tanaka M , Shinosaki K , Takeda M
Ref : Psychiatry Clin Neurosci , 61 :190 , 2007
Abstract : Musical hallucinations (MH) typically occur among elderly individuals and are associated with hearing impairment. The authors describe a patient with features of typical MH who was successfully treated with donepezil, a cholinesterase inhibitor, as a combination therapy and who has not shown any subsequent cognitive decline for approximately 5 years. The efficacy of donepezil in this patient indicates that age-dependent dysfunction of cholinergic neurons might be related to the development of MH.
ESTHER : Ukai_2007_Psychiatry.Clin.Neurosci_61_190
PubMedSearch : Ukai_2007_Psychiatry.Clin.Neurosci_61_190
PubMedID: 17362438

Title : Muscarinic cationic current in gastrointestinal smooth muscles: signal transduction and role in contraction - Unno_2006_Auton.Autacoid.Pharmacol_26_203
Author(s) : Unno T , Matsuyama H , Okamoto H , Sakamoto T , Yamamoto M , Tanahashi Y , Yan HD , Komori S
Ref : Auton Autacoid Pharmacol , 26 :203 , 2006
Abstract : 1 The muscarinic receptor plays a key role in the parasympathetic nervous control of various peripheral tissues including gastrointestinal tract. The neurotransmitter acetylcholine, via activating muscarinic receptors that exist in smooth muscle, produces its contraction. 2 There is the opening of cationic channels as an underlying mechanism. The opening of cationic channels results in influxes of Ca2+ via the channels into the cell and also via voltage-dependent Ca2+ channels which secondarily opened in response to the depolarization, providing an amount of Ca2+ for activation of the contractile proteins. 3 Electrophysiological and pharmacological studies have shown that the cationic channels as well as muscarinic receptors exist in many visceral smooth muscle cells. However, the activation mechanisms of the cationic channels are still unclear. 4 In this article, we summarize the current knowledge of the muscarinic receptor-operated cationic channels, focusing on the receptor subtype, G protein and other signalling molecules that are involved in activation of these channels and on the molecular characteristics of the channel. This will improve strategies aimed at developing new selective pharmacological agents and understanding the activation mechanism and functions of these channels in physiological systems.
ESTHER : Unno_2006_Auton.Autacoid.Pharmacol_26_203
PubMedSearch : Unno_2006_Auton.Autacoid.Pharmacol_26_203
PubMedID: 16879487

Title : Structural analysis of cosmid clone pcAFT-2 carrying AFT10-1 encoding an acyl-CoA dehydrogenase involved in AF-toxin production in the strawberry pathotype of Alternaria alternata - Ruswandi_2005_J.Gen.Plant.Pathol_71_107
Author(s) : Ruswandi S , Kitani K , Akimitsu K , Tsuge T , Shiraishi T , Yamamoto M
Ref : Journal of General Plant Pathology , 71 :107 , 2005
Abstract : The strawberry pathotype of Alternaria alternata produces the host-specific AF-toxin and causes black spot of strawberry. The genes in the toxin gene cluster are currently being identified and characterized. In this study, a genomic cosmid clone, pcAFT-2, was structurally characterized. This cosmid contains AFT homologs, which were found to be involved in AF-toxin biosynthesis. These homologs were designated AFTR-2 and AFT3-2. Four new open reading frames (ORFs) (AFT9-1, AFT10-1, AFT11-1, AFT12-1) and two transposon-like sequences (TLS-S4, TLS-S5) were also identified. These ORFs were shown to encode for polyketide synthase, acyl-CoA dehydrogenase, P450 monooxygenase, and an oxidoreductase, respectively. Transcripts of all the ORFs were detected. DNA gel blot analysis detected homologs of these four ORFs only in the tangerine, strawberry, and Japanese pear pathotypes, which share a common 9,10-epoxy-8-hydroxy-9-methyl-decatrienoic acid moiety in their toxin structure. Targeting of AFT10-1, which encodes an acyl-CoA dehydrogenase, produced single- and double-copy mutants with highly reduced numbers of lesions on host leaves concomitant with reduced toxin production, confirming its role in pathogenicity. Thus, AFT10-1 exists in multiple copies in the genome of Alternaria alternata; and based on the presence of homologs in the tangerine and Japanese pear pathotypes, it is involved in the formation of the 9,10-epoxy-8-hydroxy-9-methyl-decatrienoic acid moiety of the toxin molecule.
ESTHER : Ruswandi_2005_J.Gen.Plant.Pathol_71_107
PubMedSearch : Ruswandi_2005_J.Gen.Plant.Pathol_71_107
PubMedID:
Gene_locus related to this paper: altal-aft8

Title : Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 mice - Goldring_2004_Hepatology_39_1267
Author(s) : Goldring CE , Kitteringham NR , Elsby R , Randle LE , Clement YN , Williams DP , McMahon M , Hayes JD , Itoh K , Yamamoto M , Park BK
Ref : Hepatology , 39 :1267 , 2004
Abstract : The transcription factor NF-E2-related factor 2 (Nrf2) plays an essential role in the mammalian response to chemical and oxidative stress through induction of hepatic phase II detoxification enzymes and regulation of glutathione (GSH). Enhanced liver damage in Nrf2-deficient mice treated with acetaminophen suggests a critical role for Nrf2; however, direct evidence for Nrf2 activation following acetaminophen exposure was previously lacking. We show that acetaminophen can initiate nuclear translocation of Nrf2 in vivo, with maximum levels reached after 1 hour, in a dose dependent manner, at doses below those causing overt liver damage. Furthermore, Nrf2 was shown to be functionally active, as assessed by the induction of epoxide hydrolase, heme oxygenase-1, and glutamate cysteine ligase gene expression. Increased nuclear Nrf2 was found to be associated with depletion of hepatic GSH. Activation of Nrf2 is considered to involve dissociation from a cytoplasmic inhibitor, Kelch-like ECH-associated protein 1 (Keap1), through a redox-sensitive mechanism involving either GSH depletion or direct chemical interaction through Michael addition. To investigate acetaminophen-induced Nrf2 activation we compared the actions of 2 other GSH depleters, diethyl maleate (DEM) and buthionine sulphoximine (BSO), only 1 of which (DEM) can function as a Michael acceptor. For each compound, greater than 60% depletion of GSH was achieved; however, in the case of BSO, this depletion did not cause nuclear translocation of Nrf2. In conclusion, GSH depletion alone is insufficient for Nrf2 activation: a more direct interaction is required, possibly involving chemical modification of Nrf2 or Keap1, which is facilitated by the prior loss of GSH.
ESTHER : Goldring_2004_Hepatology_39_1267
PubMedSearch : Goldring_2004_Hepatology_39_1267
PubMedID: 15122755

Title : Efficacy of long-term dietary restriction of total calories, fat, iron, and protein in patients with chronic hepatitis C virus - Iwasa_2004_Nutrition_20_368
Author(s) : Iwasa M , Iwata K , Kaito M , Ikoma J , Yamamoto M , Takeo M , Kuroda M , Fujita N , Kobayashi Y , Adachi Y
Ref : Nutrition , 20 :368 , 2004
Abstract : OBJECTIVES: A diet restrictive in total calories, fat, iron, and protein intake reduces serum alanine aminotransferase levels in patients with long-term hepatitis C virus infection. However, whether long-term dietary therapy causes adverse effects such as malnutrition and anemia due to a shortage of energy intake is not clear. We evaluated the balance of energy intake and changes in physical and hematologic indices of nutrition after a long-term dietary therapy.
METHODS: Twenty-two patients with long-term hepatitis C virus infection that did not respond to or who were able or unwilling to take interferon therapy were enrolled in this study. Our prescriptions included 7 mg/d or less of iron, 30 kcal. kg(-1). d(-1) of energy, 1.1 to 1.2 g. kg(-1). d(-1) of protein, and a fat energy fraction of 20%. Patients were followed for 24 mo.
RESULTS: Mean body fat percentage was 24.6% at entry and was significantly reduced after the diet prescription. Mean serum ferritin decreased significantly from 376 ng/mL at entry to 141 ng/mL after 24 mo. Mean serum alanine aminotransferase levels decreased significantly from 66 to 49 IU/L. Mean levels of hemoglobin, serum albumin, and cholinesterase did not change significantly during the follow-up period.
CONCLUSIONS: These results suggest that restriction of energy, fat, iron, and protein intakes is safely tolerated, so its long-term use should be recommended to patients with long-term infection with hepatitis C virus.
ESTHER : Iwasa_2004_Nutrition_20_368
PubMedSearch : Iwasa_2004_Nutrition_20_368
PubMedID: 15043853

Title : Treatment of typical Charles Bonnet syndrome with donepezil - Ukai_2004_Int.Clin.Psychopharmacol_19_355
Author(s) : Ukai S , Yamamoto M , Tanaka M , Takeda M
Ref : Int Clin Psychopharmacol , 19 :355 , 2004
Abstract : Charles Bonnet syndrome (CBS) is characterized by the presence of complex visual hallucinations in psychologically normal people. Although visual hallucinations in the elderly are often associated with dementia with Lewy body (DLB), Alzheimer's disease and delirium, they are excluded from the diagnosis of typical CBS, as are cognitive or psychiatric disturbances, sleep disorders and focal neurological lesions. Here, we describe a patient with typical CBS, who responded to donepezil, a cholinesterase inhibitor, and has not shown any symptoms suggestive of Alzheimer's disease or DLB for approximately the past 40 months. However, follow-up examination of her clinical symptoms is necessary for a definite exclusion of Alzheimer's disease and DLB. The effectiveness of donepezil indicates that the patient's visual hallucinations might be related to dysfunction of cholinergic neurones, although she did not exhibit any cognitive decline, or morphological and physiological brain pathology. Because donepezil has fewer adverse effects than anticonvulsants and neuroleptic drugs, it may be a safer option for the treatment of CBS in the elderly.
ESTHER : Ukai_2004_Int.Clin.Psychopharmacol_19_355
PubMedSearch : Ukai_2004_Int.Clin.Psychopharmacol_19_355
PubMedID: 15486523

Title : Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in Caenorhabditis elegans - Inoue_2004_Proc.Natl.Acad.Sci.U.S.A_101_13233
Author(s) : Inoue T , Sugimoto A , Suzuki Y , Yamamoto M , Tsujimoto M , Inoue K , Aoki J , Arai H
Ref : Proc Natl Acad Sci U S A , 101 :13233 , 2004
Abstract : Type II platelet-activating factor-acetylhydrolase [PAF-AH (II)] is an N-myristoylated enzyme that contains a lipase/esterase catalytic motif and selectively hydrolyzes the sn-2 acetyl ester of PAF and other short-chain acyl groups attached to phosphoglycerides. However, the physiological role of this enzyme remains to be elucidated. PAF-AH (II) is conserved in a variety of species ranging from a simple multicellular organism, Caenorhabditis elegans, to mammals. C. elegans possesses two homologous PAF-AH (II) genes, named paf-1 and paf-2. In this study, we generated these two loss-of-function mutants to elucidate the in vivo PAF-AH (II) function. Surprisingly, mutants of paf-2, a major isoform of C. elegans PAF-AH (II)s, exhibits gross defects in epithelial sheet formation, resulting in unsuccessful subsequent morphogenesis with complete penetrance. Moreover, paf-2 RNA interference worms show a variable abnormal morphology, including ectopic protrusions and a lumpy shape at the late embryonic and early larval stages due to epithelial organization defects. Consistent with these phenotypes, PAF-AH (II) is predominantly expressed in epithelial cells of C. elegans. This study demonstrates that PAF-AH (II) is essential for epithelial morphogenesis.
ESTHER : Inoue_2004_Proc.Natl.Acad.Sci.U.S.A_101_13233
PubMedSearch : Inoue_2004_Proc.Natl.Acad.Sci.U.S.A_101_13233
PubMedID: 15340150
Gene_locus related to this paper: caeel-pafa , caeel-W03G9.6

Title : Dissection of the host range of the fungal plant pathogen Alternaria alternata by modification of secondary metabolism - Ito_2004_Mol.Microbiol_52_399
Author(s) : Ito K , Tanaka T , Hatta R , Yamamoto M , Akimitsu K , Tsuge T
Ref : Molecular Microbiology , 52 :399 , 2004
Abstract : The filamentous fungus Alternaria alternata contains seven pathogenic variants (pathotypes), which produce different host-specific toxins and cause diseases on different plants. The strawberry pathotype produces host-specific AF-toxin and causes Alternaria black spot of strawberry. This pathotype is also pathogenic to Japanese pear cultivars susceptible to the Japanese pear pathotype that produces AK-toxin. The strawberry pathotype produces two related molecular species, AF-toxins I and II: toxin I is toxic to both strawberry and pear, and toxin II is toxic only to pear. Previously, we isolated a cosmid clone pcAFT-1 from the strawberry pathotype that contains three genes involved in AF-toxin biosynthesis. Here, we have identified a new gene, designated AFTS1, from pcAFT-1. AFTS1 encodes a protein with similarity to enzymes of the aldo-ketoreductase superfamily. Targeted mutation of AFTS1 diminished the host range of the strawberry pathotype: Delta aftS1 mutants were pathogenic to pear, but not to strawberry, as is the Japanese pear pathotype. These mutants were found to produce AF-toxin II, but not AF-toxin I. These data represent a novel example of how the host range of a plant pathogenic fungus can be restricted by modification of secondary metabolism.
ESTHER : Ito_2004_Mol.Microbiol_52_399
PubMedSearch : Ito_2004_Mol.Microbiol_52_399
PubMedID: 15066029
Gene_locus related to this paper: altal-aft8 , altal-amt4

Title : Roles of Nrf2 in activation of antioxidant enzyme genes via antioxidant responsive elements -
Author(s) : Ishii T , Itoh K , Yamamoto M
Ref : Methods Enzymol , 348 :182 , 2002
PubMedID: 11885271

Title : Cloning and sequencing of an intracellular D(-)-3-hydroxybutyrate oligomer hydrolase from Acidovorax sp. strain SA1 and purification of the enzyme - Sugiyama_2002_Curr.Microbiol_45_123
Author(s) : Sugiyama A , Shiraki M , Kobayashi T , Morikawa G , Yamamoto M , Yamaoka M , Saito T
Ref : Curr Microbiol , 45 :123 , 2002
Abstract : The gene of an intracellular D(-)-3-hydroxybutyrate oligomer hydrolase (i3HBOH) was cloned and sequenced from a poly(3-hydroxybutyrate) (PHB)-degrading bacterium, Acidovorax sp. strain SA1. The i3HBOH gene has 876 nucleotides corresponding to the deduced sequence of 292 amino acids. In this amino acid sequence, the general lipase box sequence (G-X(1)-S-X(2)-G) was found, whose serine residue was determined to the active sites serine by site-directed mutagenesis. An i3HBOH was purified to electrophoretical homogeneity from SA1. The molecular mass of the purified enzyme was estimated to be 32 kDa by SDS-PAGE. The N-terminal amino acid sequence of the purified enzyme corresponded to the deduced N-terminal amino acid sequence in the cloned i3HBOH gene. This is the first cloning and sequencing of an intracellular D(-)-3-hydroxybutyrate oligomer hydrolase gene to date.
ESTHER : Sugiyama_2002_Curr.Microbiol_45_123
PubMedSearch : Sugiyama_2002_Curr.Microbiol_45_123
PubMedID: 12070691

Title : A conditionally dispensable chromosome controls host-specific pathogenicity in the fungal plant pathogen Alternaria alternata - Hatta_2002_Genetics_161_59
Author(s) : Hatta R , Ito K , Hosaki Y , Tanaka T , Tanaka A , Yamamoto M , Akimitsu K , Tsuge T
Ref : Genetics , 161 :59 , 2002
Abstract : The filamentous fungus Alternaria alternata contains seven pathogenic variants (pathotypes), which produce host-specific toxins and cause diseases on different plants. Previously, the gene cluster involved in host-specific AK-toxin biosynthesis of the Japanese pear pathotype was isolated, and four genes, named AKT genes, were identified. The AKT homologs were also found in the strawberry and tangerine pathotypes, which produce AF-toxin and ACT-toxin, respectively. This result is consistent with the fact that the toxins of these pathotypes share a common 9,10-epoxy-8-hydroxy-9-methyl-decatrienoic acid structural moiety. In this study, three of the AKT homologs (AFT1-1, AFTR-1, and AFT3-1) were isolated on a single cosmid clone from strain NAF8 of the strawberry pathotype. In NAF8, all of the AKT homologs were present in multiple copies on a 1.05-Mb chromosome. Transformation-mediated targeting of AFT1-1 and AFT3-1 in NAF8 produced AF-toxin-minus, nonpathogenic mutants. All of the mutants lacked the 1.05-Mb chromosome encoding the AFT genes. This chromosome was not essential for saprophytic growth of this pathogen. Thus, we propose that a conditionally dispensable chromosome controls host-specific pathogenicity of this pathogen.
ESTHER : Hatta_2002_Genetics_161_59
PubMedSearch : Hatta_2002_Genetics_161_59
PubMedID: 12019223
Gene_locus related to this paper: altal-aft8

Title : Role of transcription factor Nrf2 in the induction of hepatic phase 2 and antioxidative enzymes in vivo by the cancer chemoprotective agent, 3H-1, 2-dimethiole-3-thione - Kwak_2001_Mol.Med_7_135
Author(s) : Kwak MK , Itoh K , Yamamoto M , Sutter TR , Kensler TW
Ref : Mol Med , 7 :135 , 2001
Abstract : BACKGROUND: The induction of phase 2 enzymes by dithiolethiones such as oltipraz is an effective means for achieving protection against environmental carcinogens in animals and humans. Transcriptional control of the expression of at least some of these protective enzymes is mediated through the antioxidant response element (ARE) found in the upstream regulatory region of many phase 2 genes. The transcription factor Nrf2, which binds to the ARE, appears to be essential for the induction of proto-typical phase 2 enzymes such as glutathione S-transferase (GST) Ya, Yp, and NAD(P)H: quinone reductase (NQO1) in vivo. MATERIALS AND
METHODS: In the present study, 3H-1,2-dithiole-3-thione (D3T) was used as a potent model inducer whose effects on gene expression and chemopreventive efficacy have been extensively characterized in the rat. Over a dozen putative D3T-inducible genes were examined in wild-type and nrf2-disrupted mice by Northern blot hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis to elucidate whether loss of Nrf2 function also affects the induction of a broader representation of phase 2 and antioxidative enzymes. The effects of D3T on hepatic Nrf2 expression and localization were also examined in vivo by Northern blot hybridization, electromobility shift assay, and Western blot analysis.
RESULTS: Specific activities of hepatic GST and NQO1 were increased by D3T in wild-type mice and were largely blunted in the nrf2-deficient mice. However, changes in levels of RNA transcripts following D3T treatment of nrf2-disrupted mice were multidirectional, dependent upon the particular gene examined. Although elevation of mRNAs for GST Ya, NQO1, microsomal epoxide hydrolase and gamma-glutamylcysteine synthetase regulatory chain were blocked in the mutant mice, elevation of GST Yp mRNA was largely unimpeded. Increases in levels of mRNA for the heavy and light chains of ferritin were only seen in the nrf2-disrupted mice. Transcript levels of UDP-glucuronyl-transferase 1A6, heme oxygenase-1, maganese superoxide dismutase, which were inducible in the wild-type mice, actually decreased in the mutant mice, whereas levels of mRNA for GST Yc, aflatoxin B1 aldehyde reductase and catalase decreased following D3T treatment in the mutant mice in the absence of any inductive effect by D3T in the wild-type mice. In wild-type mice, treatment with D3T lead to 3-fold increases in hepatic Nrf2 mRNA levels within several hours following dosing as assessed by Northern blot and RT-PCR analyses. Gel shift analyses with oligonucleotide probes for human NQO1 ARE, murine GST Ya ARE, and erythroid transcription factor (NF-E2) binding site showed increased intensity of binding with nuclear extracts prepared from livers of D3T-treated mice compared to vehicle-treated controls. Antibody to Nrf2 supershifted the DNA binding bands of these nuclear extracts. Moreover, immunoblot analysis indicated accumulation of Nrf2 in extracts prepared from hepatic nuclei of D3T-treated mice at the same time points.
CONCLUSIONS: Nrf2 plays a central role in the regulation of constitutive and inducible expression of multiple phase 2 and antioxidative enzymes by chemoprotective dithiolethiones in vivo, although patterns of response vary among different genes. Knowledge of the factors controlling the specificity of actions of enzyme inducers will be exceedingly helpful in the design and isolation of more efficient and selective chemoprotective agents.
ESTHER : Kwak_2001_Mol.Med_7_135
PubMedSearch : Kwak_2001_Mol.Med_7_135
PubMedID: 11471548

Title : Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice - Ramos-Gomez_2001_Proc.Natl.Acad.Sci.U.S.A_98_3410
Author(s) : Ramos-Gomez M , Kwak MK , Dolan PM , Itoh K , Yamamoto M , Talalay P , Kensler TW
Ref : Proc Natl Acad Sci U S A , 98 :3410 , 2001
Abstract : Induction of phase 2 enzymes, which neutralize reactive electrophiles and act as indirect antioxidants, appears to be an effective means for achieving protection against a variety of carcinogens in animals and humans. Transcriptional control of the expression of these enzymes is mediated, at least in part, through the antioxidant response element (ARE) found in the regulatory regions of their genes. The transcription factor Nrf2, which binds to the ARE, appears to be essential for the induction of prototypical phase 2 enzymes such as glutathione S-transferases (GSTs) and NAD(P)H:quinone oxidoreductase (NQO1). Constitutive hepatic and gastric activities of GST and NQO1 were reduced by 50-80% in nrf2-deficient mice compared with wild-type mice. Moreover, the 2- to 5-fold induction of these enzymes in wild-type mice by the chemoprotective agent oltipraz, which is currently in clinical trials, was almost completely abrogated in the nrf2-deficient mice. In parallel with the enzymatic changes, nrf2-deficient mice had a significantly higher burden of gastric neoplasia after treatment with benzo[a]pyrene than did wild-type mice. Oltipraz significantly reduced multiplicity of gastric neoplasia in wild-type mice by 55%, but had no effect on tumor burden in nrf2-deficient mice. Thus, Nrf2 plays a central role in the regulation of constitutive and inducible expression of phase 2 enzymes in vivo and dramatically influences susceptibility to carcinogenesis. Moreover, the total loss of anticarcinogenic efficacy of oltipraz in the nrf2-disrupted mice highlights the prime importance of elevated phase 2 gene expression in chemoprotection by this and similar enzyme inducers.
ESTHER : Ramos-Gomez_2001_Proc.Natl.Acad.Sci.U.S.A_98_3410
PubMedSearch : Ramos-Gomez_2001_Proc.Natl.Acad.Sci.U.S.A_98_3410
PubMedID: 11248092

Title : Distribution and Characterization of AKT Homologs in the Tangerine Pathotype of Alternaria alternata - Masunaka_2000_Phytopathology_90_762
Author(s) : Masunaka A , Tanaka A , Tsuge T , Peever TL , Timmer LW , Yamamoto M , Yamamoto H , Akimitsu K
Ref : Phytopathology , 90 :762 , 2000
Abstract : ABSTRACT The tangerine pathotype of Alternaria alternata produces a host-selective toxin (HST), known as ACT-toxin, and causes Alternaria brown spot disease of citrus. The structure of ACT-toxin is closely related to AK- and AF-toxins, which are HSTs produced by the Japanese pear and strawberry pathotypes of A. alternata, respectively. AC-, AK-, and AF-toxins are chemically similar and share a 9,10-epoxy-8-hydroxy-9-methyl-decatrienoic acid moiety. Two genes controlling AK-toxin biosynthesis (AKT1 and AKT2) were recently cloned from the Japanese pear pathotype of A. alternata. Portions of these genes were used as heterologous probes in Southern blots, that detected homologs in 13 isolates of A. alternata tangerine pathotype from Minneola tangelo in Florida. Partial sequencing of the homologs in one of these isolates demonstrated high sequence similarity to AKT1 (89.8%) and to AKT2 (90.7%). AKT homologs were not detected in nine isolates of A. alternata from rough lemon, six isolates of nonpathogenic A. alternata, and one isolate of A. citri that causes citrus black rot. The presence of homologs in the Minneola isolates and not in the rough lemon isolates, nonpathogens or black rot isolates, correlates perfectly to pathogenicity on Iyo tangerine and ACT-toxin production. Functionality of the homologs was demonstrated by detection of transcripts using reverse transcription-polymerase chain reaction (RT-PCR) in total RNA of the tangerine pathotype of A. alternata. The high sequence similarity of AKT and AKT homologs in the tangerine patho-type, combined with the structural similarity of AK-toxin and ACT-toxin, may indicate that these homologs are involved in the biosynthesis of the decatrienoic acid moiety of ACT-toxin.
ESTHER : Masunaka_2000_Phytopathology_90_762
PubMedSearch : Masunaka_2000_Phytopathology_90_762
PubMedID: 18944496
Gene_locus related to this paper: altal-actt2

Title : Effects of natural and synthetic auxins on the gravitropic growth habit of roots in two auxin-resistant mutants of Arabidopsis, axr1 and axr4: evidence for defects in the auxin influx mechanism of axr4 - Yamamoto_1999_J.Plant.Res_112_391
Author(s) : Yamamoto M , Yamamoto KT
Ref : J Plant Res , 112 :391 , 1999
Abstract : The partially agravitropic growth habit of roots of an auxin-resistant mutant of Arabidopsis thaliana, axr4, was restored by the addition of 30-300 nM 1-naphthaleneacetic acid (NAA) to the growth medium. Neither indole 3-acetic acid (IAA) nor 2,4-dichlorophenoxyacetic acid (2,4-D) showed such an effect. Growth of axr4 roots was resistant to IAA and 2,4-D, but not at all to NAA. The differential effects of the three auxins suggest that the defects of axr4 result from a lower auxin influx into its cells. The partially agravitropic growth habit of axr1 roots, which was less severe than that of axr4 roots, was only slightly affected by the three auxins in the growth medium at concentrations up to 300 nM; growth of axr1 roots was resistant to all three of the auxins. These results suggest that the lesion of axrl mutants is different from that of axr4.
ESTHER : Yamamoto_1999_J.Plant.Res_112_391
PubMedSearch : Yamamoto_1999_J.Plant.Res_112_391
PubMedID: 11543173

Title : Insertional mutagenesis and cloning of the genes required for biosynthesis of the host-specific AK-toxin in the Japanese pear pathotype of Alternaria alternata - Tanaka_1999_Mol.Plant.Microbe.Interact_12_691
Author(s) : Tanaka A , Shiotani H , Yamamoto M , Tsuge T
Ref : Mol Plant Microbe Interact , 12 :691 , 1999
Abstract : The Japanese pear pathotype of Alternaria alternata causes black spot of Japanese pear by producing a host-specific toxin known as AK-toxin. Restriction enzyme-mediated integration (REMI) mutagenesis was used to tag genes required for toxin biosynthesis. Protoplasts of a wild-type strain were treated with a linearized plasmid along with the restriction enzyme used to linearize the plasmid. Of 984 REMI transformants recovered, three produced no detectable AK-toxin and lost pathogenicity on pear leaves. Genomic DNA flanking the integrated plasmid was recovered from one of the mutants. With the recovered DNA used as a probe, a cosmid clone of the wild-type strain was isolated. Structural and functional analyses of an 8.0-kb region corresponding to the tagged site indicated the presence of two genes. One, designated AKT1, encodes a member of the class of carboxyl-activating enzymes. The other, AKT2, encodes a protein of unknown function. The essential roles of these two genes in both AK-toxin production and pathogenicity were confirmed by transformation-mediated gene disruption experiments. DNA gel blot analysis detected AKT1 and AKT2 homologues not only in the Japanese pear pathotype strains but also in strains from the tangerine and strawberry pathotypes. The host-specific toxins of these two pathotypes are similar in structure to AK-toxin. Homologues were not detected in other pathotypes or in non-pathogenic strains of A. alternata, suggesting acquisition of AKT1 and AKT2 by horizontal transfer.
ESTHER : Tanaka_1999_Mol.Plant.Microbe.Interact_12_691
PubMedSearch : Tanaka_1999_Mol.Plant.Microbe.Interact_12_691
PubMedID: 10432635

Title : A novel nonsense mutation in exon 1 and a transition in intron 3 of the lipoprotein lipase gene - Nakamura_1996_J.Atheroscler.Thromb_3_17
Author(s) : Nakamura T , Suehiro T , Yasuoka N , Yamamoto M , Ito H , Yamano T , Hashimoto K
Ref : J Atheroscler Thromb , 3 :17 , 1996
Abstract : We examined the lipoprotein lipase (LPL) gene by single strand conformation polymorphism (SSCP) and by restriction fragment length polymorphism (RFLP) analysis in 106 patients with hypertriglyceridemia to screen for novel mutations and to study the contribution of LPL genetic defects in hypertriglyceridemia. We found a single incidence of a homozygous novel nonsense mutation (216G-->A; -14Tryptophan-->stop codon) in exon 1 and 6 cases heterozygous for a single transition (C-->T) at six bp upstream from splicing acceptor site of intron 3. These mutations were not found in 105 normolipidemic controls. The proband homozygous for the nonsense mutation in exon 1, a 74 year old woman, had mild hyperchylomicronemia and her post-heparin plasma showed no LPL protein. However, four heterozygous among family members did not demonstrate hypertriglyceridemia. The frequency of heterozygosity for the C-->T transition in intron 3 was significantly different from that in normolipidemic controls. Therefore, it was suggested that the mutation is involved in hypertriglyceridemia. All of the heterozygotes were men with 4 patients having impaired glucose tolerance or diabetes mellitus. These observations suggest that this polymorphism in intron 3 combined with other as yet undefined factors may be related to hypertriglyceridemia.
ESTHER : Nakamura_1996_J.Atheroscler.Thromb_3_17
PubMedSearch : Nakamura_1996_J.Atheroscler.Thromb_3_17
PubMedID: 9225235

Title : Effects of (-)-S-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4,5]decane L-tartrate monohydrate (YM796), a novel muscarinic agonist, on disturbance of passive avoidance learning behavior in drug-treated and senescence-accelerated mice - Suzuki_1995_J.Pharmacol.Exp.Ther_275_728
Author(s) : Suzuki M , Yamaguchi T , Ozawa Y , Ohyama M , Yamamoto M
Ref : Journal of Pharmacology & Experimental Therapeutics , 275 :728 , 1995
Abstract : Effects of YM796 (-)-S-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4,5]decane L-tartrate monohydrate; a novel muscarinic agonist, were observed on disturbance of passive avoidance learning behavior in drug- (protein synthesis inhibitor and anticholinergic drugs) treated and senescence-accelerated mice in comparison with those of a muscarinic agonist (AF102B) and acetylcholinesterase inhibitors (E2020 (1-benzyl-4-[(5,6-dimethoxy-1-indanone-2-yl) methyl] piperidene hydrochloride), NIK247 [9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)-quinoline monohydrate hydrochloride], THA (9-amino-1,2,3,4-tetrahydroacridine) and physostigmine). All tested drugs administered before training significantly prolonged the shortened latency of step-through induced by the protein synthesis inhibitor cycloheximide (150 mg/kg s.c.). This shortened latency was also significantly prolonged when YM796 was administered immediately after training, but not when administered before the test trial. The ameliorating effect of YM796 on the impairment in learning behavior by cycloheximide was significantly suppressed by pirenzepine (0.1 micrograms/mouse i.c.v.). When administered before training, all test drugs prolonged the shortened latency of step-through induced by treatment with the anticholinergic drugs [scopolamine (1 mg/kg s.c.) and hemicholinium-3 (0.3 microgram/mouse i.c.v.)], suggesting that they ameliorated the impairment of learning behavior. This shortened latency in scopolamine-treated mice was also significantly prolonged by YM796, AF102B, E2020, NIK247 and physostigmine when administered immediately after training, but not when administered before the test trial. The pharmacological actions of YM796 administered immediately after training and before the test trial in hemicholinium-3-treated mice were similar to those in scopolamine-treated mice.
ESTHER : Suzuki_1995_J.Pharmacol.Exp.Ther_275_728
PubMedSearch : Suzuki_1995_J.Pharmacol.Exp.Ther_275_728
PubMedID: 7473160

Title : Effect of YM796, a novel muscarinic agonist, on the impairment of passive avoidance response in senescence-accelerated mice - Suzuki_1995_Pharmacol.Biochem.Behav_51_623
Author(s) : Suzuki M , Yamaguchi T , Ozawa Y , Iwai A , Yamamoto M
Ref : Pharmacology, Biochemistry & Behavior , 51 :623 , 1995
Abstract : We compared the effects of YM796 [(-)-S-2,8-dimethyl-3-methylene-1-oxa-8- azaspiro[4,5]-decane L-tartrate monohydrate], a novel muscarinic agonist, on passive avoidance response with those of the cholinomimetics AF102B [(+/-)-cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine hydrochloride] and NIK247 [9-amino-2,3,5,6,7,8-hexahydro1H-cyclopenta(b)- quinoline monohydrate hydrochloride] in senescence-accelerated mice. SAMP8@YAN (SAM-P/8, senescence-accelerated-prone substrain) showed an age-dependent shortening in the latency of step-through when compared with SAMR1/YAN (SAM-R/1, senescence-accelerated-resistant substrain). The shortened latency of step-through in SAMP8@YAN was prolonged by administration of YM796 (0.3 and 1 mg/kg, PO), AF102B (3 and 10 mg/kg PO), and NIK247 (30 mg/kg, PO) in a bell-shaped manner. In contrast, amitriptyline (10, 30, and 50 mg/kg, PO), with cholinolytic properties, had no effect on this shortened latency of step-through. These results suggest that YM796, AF102B, and NIK247 ameliorated the disturbance of learning behavior, presumably due to facilitation of the central cholinergic system in SAMP8@YAN mice and that SAMP8@YAN may be an appropriate age-dependent model of amnesia for evaluating pharmacological actions of drugs.
ESTHER : Suzuki_1995_Pharmacol.Biochem.Behav_51_623
PubMedSearch : Suzuki_1995_Pharmacol.Biochem.Behav_51_623
PubMedID: 7675834

Title : Schizosaccharomyces pombe sxa1+ and sxa2+ encode putative proteases involved in the mating response -
Author(s) : Imai Y , Yamamoto M
Ref : Molecular & Cellular Biology , 12 :1827 , 1992
PubMedID: 1549128
Gene_locus related to this paper: schpo-sxa2

Title : Purification and structural analysis of hippocampal cholinergic neurostimulating peptide - Ojika_1992_Brain.Res_572_164
Author(s) : Ojika K , Kojima S , Ueki Y , Fukushima N , Hayashi K , Yamamoto M
Ref : Brain Research , 572 :164 , 1992
Abstract : Hippocampal soluble fraction stimulates acetylcholine (AcCho) synthesis of medial septal nuclei in explant culture system. This stimulating activity was purified from 10-12-day-old rat hippocampus. During purification, the activity was separated into two fractions and a previously unreported peptide was purified from one fraction. The structure of this novel peptide is acetyl-Ala-Ala-Asp-Ile-Ser-Gln-Trp-Ala-Gly-Pro-Leu and we designated it as hippocampal cholinergic neurostimulating peptide (HCNP). Synthesized HCNP and de-acetylated HCNP (free-HCNP) stimulated AcCho synthesis of medial septal nuclei culture, in a dose-dependent manner, but not cultures of corpus striatum or anterior spinal cord. Mean half-maximal concentrations of HCNP and free-HCNP in AcCho synthesis of medial septal nuclei culture were 1.0 +/- 0.3 x 10(-10) M and 1.0 +/- 0.6 x 10(-11) M, respectively. Affinity purified polyclonal antibody to the free-HCNP neutralized the activity of crude hippocampal extract, as well as synthetic HCNP and free-HCNP. These observations suggested that HCNP was present in the hippocampal extract and was involved in development of specific cholinergic neuron in central nervous system.
ESTHER : Ojika_1992_Brain.Res_572_164
PubMedSearch : Ojika_1992_Brain.Res_572_164
PubMedID: 1611510

Title : ADP-ribosylation of the rho\/rac proteins induces growth inhibition, neurite outgrowth and acetylcholine esterase in cultured PC-12 cells - Nishiki_1990_Biochem.Biophys.Res.Commun_167_265
Author(s) : Nishiki T , Narumiya S , Morii N , Yamamoto M , Fujiwara M , Kamata Y , Sakaguchi G , Kozaki S
Ref : Biochemical & Biophysical Research Communications , 167 :265 , 1990
Abstract : Botulinum ADP-ribosyltransferase C3 (C3 exoenzyme) was purified to homogeneity and added to cultured rat pheochromocytoma PC-12 cells. Incubation with this exoenzyme caused inhibition of cell growth and induced neurites as well as acetylcholine esterase in these cells. These changes were dependent on the amount of the enzyme added to the culture, which correlated with the in situ ADP-ribosylation of the rho/rac proteins in the cells. Preincubation with a specific anti-C3 exoenzyme monoclonal antibody inhibited both the ADP-ribosyltransferase activity and the neurite-inducing activity of the enzyme preparation. These results suggest that C3 exoenzyme affected the cellular function of the rho/rac proteins by ADP-ribosylation to induce these changes in the cells.
ESTHER : Nishiki_1990_Biochem.Biophys.Res.Commun_167_265
PubMedSearch : Nishiki_1990_Biochem.Biophys.Res.Commun_167_265
PubMedID: 2106882

Title : Combined effects of succinylcholine and calcium on membrane-bound acetylcholinesterase activity - Wakamatsu_1987_J.Anesth_1_15
Author(s) : Wakamatsu M , Shimonaka H , Yamamoto M , Kawai K , Nozawa Y
Ref : J Anesth , 1 :15 , 1987
Abstract : The effects of succinylcholine and calcium (Ca2+), alone and together, on membrane-bound acetylcholinesterase ("true-type" cholinesterase) were examined using human erythrocyte ghosts to elucidate the combined pharmacological activity of succinylcholine and calcium in in vivo system. Succinylcholine inhibited the acetylcholinesterase by a mixed style. Calcium alone exhibited an inhibitory effect on the enzyme, but a biphasic effect together with succinylcholine: marked restoration of the enzyme activity at calcium concentrations lower than 6 mM and depression at its higher concentrations. It is suggested that calcium induces a conformational change of the enzyme protein leading to the altered binding capacity of succinylcholine. In anesthetic practice, therefore, the use of calcium may not be indicated for the treatment of SCh phase II block.
ESTHER : Wakamatsu_1987_J.Anesth_1_15
PubMedSearch : Wakamatsu_1987_J.Anesth_1_15
PubMedID: 15237300