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Sample records for indole protects rodent

  1. Indole and its alkyl-substituted derivatives protect erythrocyte and DNA against radical-induced oxidation.

    PubMed

    Zhao, Feng; Liu, Zai-Qun

    2009-01-01

    The antioxidant properties of 1,2,3,4-tetra-hydrocarbazole, 6-methoxy-1,2,3,4-tetrahydrocar-bazole (MTC), 2,3-dimethylindole, 5-methoxy-2,3-dimethylindole, and indole were investigated in the case of hemolysis of human erythrocytes and oxidative damage of DNA induced by 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), respectively. The aim of this work was to explore the influence of methoxy, methyl, and cyclohexyl substituents on the antioxidant activities of indole derivatives. These indole derivatives were able to protect erythrocytes and DNA in a concentration-dependent manner. The alkyl-substituted indole can protect erythrocytes and DNA against AAPH-induced oxidation. Especially, the structural features of cyclohexyl and methoxy substituents made MTC the best antioxidant among the indole derivatives used herein. Finally, the interaction between these indole derivatives and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical cation and 2,2'-diphenyl-1-picrylhydrazyl, respectively, provided direct evidence for these indole derivatives to scavenge radicals and emphasized the importance of electron-donating groups for the free radical-scavenging activity of indole derivatives. 2009 Wiley Periodicals, Inc.

  2. Rodent selectivity of piperidine-4-yl-1H-indoles, a series of CC chemokine receptor-3 (CCR3) antagonists: insights from a receptor model.

    PubMed

    Kriegl, Jan M; Martyres, Domnic; Grundl, Marc A; Anderskewitz, Ralf; Dollinger, Horst; Rast, Georg; Schmid, Bernhard; Seither, Peter; Tautermann, Christofer S

    2015-01-15

    Rodent selectivity data of piperidine-4-yl-1H-indoles, a series of CC chemokine receptor-3 (CCR3) antagonists, are presented and discussed as part of an overall optimization effort within this lead compound class. Although attachment of an acidic moiety to the 1-position of the indole led to an overall balanced in vitro profile, in particular reducing inhibition of the hERG channel, potency on the rat and mouse receptor worsened. These findings could be rationalized in the context of a CCR3 homology model.

  3. Telomerase protects adult rodent olfactory ensheathing glia from early senescence.

    PubMed

    Llamusí, María-Beatriz; Rubio, Mari-Paz; Ramón-Cueto, Almudena

    2011-05-01

    Adult olfactory bulb ensheathing glia (OB-OEG) promote the repair of acute, subacute, and chronic spinal cord injuries and autologous transplantation is a feasible approach. There are interspecies differences between adult rodent and primate OB-OEG related to their longevity in culture. Whereas primate OB-OEG exhibit a relatively long life span, under the same culture conditions rodent OB-OEG divide just three to four times, are sensitive to oxidative stress and become senescent after the third week in vitro. Telomerase is a "physiological key regulator" of the life span of normal somatic cells and also has extratelomeric functions such as increased resistance to oxidative stress. To elucidate whether telomerase has a role in the senescence of rodent OB-OEG, we have introduced the catalytic subunit of telomerase mTERT into cultures of these cells by retroviral infection. Native and modified adult rat OB-OEG behaved as telomerase-competent cells as they divided while expressing mTERT but entered senescence once the gene switched off. After ectopic expression of mTERT, OB-OEG resumed division at a nonsenescent rate, expressed p75 and other OEG markers, and exhibited the morphology of nonsenescent OB-OEG. The nonsenescent period of mTERT-OEG lasted 9weeks and then ectopic mTERT switched off and cells entered senescence again. Our results suggest a role of telomerase in early senescence of adult rodent OB-OEG cultures and a protection from oxidative damage. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

  4. Indole-3-carbinol protects against cisplatin-induced acute nephrotoxicity: role of calcitonin gene-related peptide and insulin-like growth factor-1

    PubMed Central

    El-Naga, Reem N.; Mahran, Yasmen F.

    2016-01-01

    Nephrotoxicity associated with the clinical use of the anticancer drug cisplatin is a limiting problem. Thus, searching for new protective measures is required. Indole-3-carbinol is a powerful anti-oxidant, anti-inflammatory and anti-tumor agent. The present study aimed to investigate the potential protective effect of indole-3-carbinol against cisplatin-induced acute nephrotoxicity in rats. Rats were pre-treated with 20 mg/kg indole-3-carbinol orally before giving cisplatin (7 mg/kg). Cisplatin-induced acute nephrotoxicity was demonstrated where relative kidney weight, BUN and serum creatinine were significantly increased. Increased oxidative stress was evident in cisplatin group where GSH and SOD tissue levels were significantly depleted. Also, lipid peroxidation and NOX-1 were increased as compared to the control. Additionally, renal expression of pro-inflammatory mediators was induced by cisplatin. Cisplatin-induced cell death was shown by increased caspase-3 and decreased expression of EGF, IGF-1 and IGF-1 receptor. Nephrotoxicity, oxidative stress, inflammation and apoptotic effects induced by cisplatin were significantly ameliorated by indole-3-carbinol pre-treatment. Besides, the role of CGRP in cisplatin-induced nephrotoxicity was explored. Furthermore, cisplatin cytotoxic activity was significantly enhanced by indole-3-carbinol pre-treatment in vitro. In conclusion, indole-3-carbinol provides protection against cisplatin-induced nephrotoxicity. Also, reduced expression of CGRP may play a role in the pathogenesis of cisplatin-induced renal injury. PMID:27417335

  5. Hantavirus ecology in rodent populations in three protected areas of Argentina.

    PubMed

    Vadell, M V; Bellomo, C; San Martín, A; Padula, P; Gómez Villafañe, I

    2011-10-01

    In this study, we identified hantavirus genotypes and their reservoirs and evaluated the spatial and temporal distribution of the virus in rodent population in three protected areas of Argentina over 3 years (2007-2010). A total of 837 rodents were captured with an effort of 22 117 trap-nights. We detected the genotype Lechiguanas in Oligoryzomys nigripes and O. flavescens and Pergamino in Akodon azarae. There was no correlation between seroprevalence and trap success of the host. The proportion of seropositive males was significantly higher than the proportion of seropositive females. The total length of seropositives was higher than that of seronegatives in each host species. Seropositive individuals were observed in warm months and not in cold months, which suggests an infection cycle. This investigation confirms that protected areas of central east Argentina are places with a variety of sylvan rodents species associated with different hantavirus genotypes where reservoirs are numerically dominant. Although there was more than one known reservoir of hantavirus, only one species had antibodies in each area. This can be explained because the transmission of the virus does need not only the presence of a rodent species but also a threshold density. Longevity of even a small proportion of the host population in cold months may provide a trans-seasonal mechanism for virus persistence. The seroprevalence detected was higher than the one found before in rodent populations of Argentina, and this explains the appearance of human cases in two of these three areas.

  6. Attenuated vaccinia virus-circumsporozoite protein recombinants confer protection against rodent malaria.

    PubMed Central

    Lanar, D E; Tine, J A; de Taisne, C; Seguin, M C; Cox, W I; Winslow, J P; Ware, L A; Kauffman, E B; Gordon, D; Ballou, W R; Paoletti, E; Sadoff, J C

    1996-01-01

    NYVAC-based vaccinia virus recombinants expressing the circumsporozoite protein (CSP) were evaluated in the Plasmodium berghei rodent malaria model system. Immunization of mice with a NYVAC-based CSP recombinant elicited a high level of protection (60 to 100%). Protection did not correlate with CS repeat-specific antibody responses and was abrogated by in vivo CD8+ T-cell depletion. Protection was not enhanced by modification of the subcellular localization of CSP. These results suggest the potential of poxvirus-based vectors for the development of vaccine candidates for human malaria. PMID:8613376

  7. Palladium-catalyzed direct desulfitative C2 arylations of 3-halo-N-protected indoles using (hetero)arenesulfonyl chlorides.

    PubMed

    Hfaiedh, Anoir; Ben Ammar, Hamed; Soulé, Jean-François; Doucet, Henri

    2016-06-07

    The direct arylation of N-protected 3-haloindole derivatives with benzenesulfonyl chlorides as coupling partners using 5 mol% of bis(acetonitrile)dichloropalladium(ii) catalyst and lithium carbonate as a base in 1,4-dioxane was investigated. We demonstrated that both iodo and chloro substituents at the indolyl C3 position act as temporary blocking groups allowing the formation of 2-arylindoles through a direct desulfitative arylation, followed by in situ dehalogenation. While, from 3-bromoindole derivatives, 2-aryl-3-bromoindoles were obtained without debromination, and could be converted into 2,3-diarylindoles through a second palladium coupling. This method allows one to prepare in a few steps a very wide variety of indole derivatives, which are of interest in the synthesis of bioactive molecules.

  8. Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models.

    PubMed

    Salman, Ahmed M; Montoya-Díaz, Eduardo; West, Heather; Lall, Amar; Atcheson, Erwan; Lopez-Camacho, Cesar; Ramesar, Jai; Bauza, Karolis; Collins, Katharine A; Brod, Florian; Reis, Fernando; Pappas, Leontios; González-Cerón, Lilia; Janse, Chris J; Hill, Adrian V S; Khan, Shahid M; Reyes-Sandoval, Arturo

    2017-04-18

    Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation.

  9. A novel regulatory circuit to control indole biosynthesis protects Escherichia coli from nitrosative damages during the anaerobic respiration of nitrate.

    PubMed

    Lai, Yong; Xu, Zeling; Yan, Aixin

    2017-02-01

    Indole is a widely distributed microbial secondary metabolite. It mediates a broad range of physiological processes in both its producing and surrounding species. Yet, indole biosynthesis during the anaerobiosis of bacteria remains largely uncharacterized. Here, we find that while indole production is promoted during fermentation and anaerobic respiration of fumarate and trimethylamine N-oxide in E. coli, its biosynthesis is repressed during anaerobic respiration of nitrate especially during exponential growth. We show that expression of the indole biosynthetic operon tnaCAB is repressed under this condition by the two component systems NarXL and NarPQ in the global regulator FNR dependent manner. During stationary growth phase of nitrate respiration, indole biosynthesis is derepressed. However, cellular indole concentration remains low. We demonstrate that this is due to the rapid conversion of indole into mutagenic indole nitrosative derivatives under this condition. Consistent with this, a supplement of exogenous indole during nitrate respiration causes elevated mutation frequencies in E. coli cells lacking the detoxifying efflux genes mdtEF, and ectopic over-expression of tnaAB genes decreases the fitness of E. coli to this physiological condition. Together, these results suggest that indole production is tuned to the bioenergetics activities of E. coli to facilitate its adaptation and fitness. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  10. Cerium oxide nanoparticles protect rodent lungs from hypobaric hypoxia-induced oxidative stress and inflammation.

    PubMed

    Arya, Aditya; Sethy, Niroj Kumar; Singh, Sushil Kumar; Das, Mainak; Bhargava, Kalpana

    2013-01-01

    Cerium oxide nanoparticles (nanoceria) are effective at quenching reactive oxygen species (ROS) in cell culture and animal models. Although nanoceria reportedly deposit in lungs, their efficacy in conferring lung protection during oxidative stress remains unexplored. Thus, the study evaluated the protective efficacy of nanoceria in rat lung tissue during hypobaric hypoxia. A total of 48 animals were randomly divided into four equal groups (control [C], nanoceria treated [T], hypoxia [H], and nanoceria treated plus hypoxia [T+H]). Animals were injected intraperitoneally with either a dose of 0.5 μg/kg body weight/week of nanoceria (T and T+H groups) or vehicle (C and H groups) for 5 weeks. After the final dose, H and T+H animals were challenged with hypobaric hypoxia, while C and T animals were maintained at normoxia. Lungs were isolated and homogenate was obtained for analysis of ROS, lipid peroxidation, glutathione, protein carbonylation, and 4-hydroxynonenal-adduct formation. Plasma was used for estimating major inflammatory cytokines using enzyme-linked immunosorbent assay. Intact lung tissues were fixed and both transmission electron microscopy and histopathological examinations were carried out separately for detecting internalization of nanoparticles as well as altered lung morphology. Spherical nanoceria of 7-10 nm diameter were synthesized using a microemulsion method, and the lung protective efficacy of the nanoceria evaluated during hypobaric hypoxia. With repeated intraperitoneal injections of low micromole concentration, we successfully localized the nanoceria in rodent lung without any inflammatory response. The lung-deposited nanoceria limited ROS formation, lipid peroxidation, and glutathione oxidation, and prevented oxidative protein modifications like nitration and carbonyl formation during hypobaric hypoxia. We also observed reduced lung inflammation in the nanoceria-injected lungs, supporting the anti-inflammatory properties of nanoceria

  11. Rupatadine Protects against Pulmonary Fibrosis by Attenuating PAF-Mediated Senescence in Rodents

    PubMed Central

    Lv, Xiao-xi; Wang, Xiao-xing; Li, Ke; Wang, Zi-yan; Li, Zhe; Lv, Qi; Fu, Xiao-ming; Hu, Zhuo-Wei

    2013-01-01

    A similar immune response is implicated in the pathogenesis of pulmonary fibrosis and allergic disorders. We investigated the potential therapeutic efficacy and mechanism of rupatadine, a dual antagonist of histamine and platelet-activation factor (PAF), in bleomycin- (BLM-) and silica-induced pulmonary fibrosis. The indicated dosages of rupatadine were administered in rodents with bleomycin or silica-induced pulmonary fibrosis. The tissue injury, fibrosis, inflammatory cells and cytokines, and lung function were examined to evaluate the therapeutic efficacy of rupatadine. The anti-fibrosis effect of rupatadine was compared with an H1 or PAF receptor antagonist, and efforts were made to reveal rupatadine’s anti-fibrotic mechanism. Rupatadine promoted the resolution of pulmonary inflammation and fibrosis in a dose-dependent manner, as indicated by the reductions in inflammation score, collagen deposition and epithelial-mesenchymal transformation, and infiltration or expression of inflammatory cells or cytokines in the fibrotic lung tissue. Thus, rupatadine treatment improved the declined lung function and significantly decreased animal death. Moreover, rupatadine was able not only to attenuate silica-induced silicosis but also to produce a superior therapeutic efficacy compared to pirfenidone, histamine H1 antagonist loratadine, or PAF antagonist CV-3988. The anti-fibrotic action of rupatadine might relate to its attenuation of BLM- or PAF-induced premature senescence because rupatadine treatment protected against the in vivo and in vitro activation of the p53/p21-dependent senescence pathway. Our studies indicate that rupatadine promotes the resolution of pulmonary inflammation and fibrosis by attenuating the PAF-mediated senescence response. Rupatadine holds promise as a novel drug to treat the devastating disease of pulmonary fibrosis. PMID:23869224

  12. Indole-TEMPO conjugates alleviate ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function.

    PubMed

    Bi, Wei; Bi, Yue; Gao, Xiang; Li, Pengfei; Hou, Shanshan; Zhang, Yanrong; Bammert, Cathy; Jockusch, Steffen; Legalley, Thomas D; Michael Gibson, K; Bi, Lanrong

    2017-05-01

    Mitochondrial oxidative damage contributes to a wide range of pathologies including ischemia/reperfusion injury. Accordingly, protecting mitochondria from oxidative damage should possess therapeutic relevance. In the present study, we have designed and synthesized a series of novel indole-TEMPO conjugates that manifested good anti-inflammatory properties in a murine model of xylene-induced ear edema. We have demonstrated that these compounds can protect cells from simulated ischemia/reperfusion (s-I/R)-induced reactive oxygen species (ROS) overproduction and mitochondrial dysfunction. Furthermore, we have demonstrated that indole-TEMPO conjugates can attenuate organ damage induced in rodents via intestinal I/R injury. We therefore propose that the pharmacological profile and mechanism of action of these indole-TEMPO conjugates involve convergent roles, including the ability to decrease free radical production via lipid peroxidation which couples to an associated decrease in ROS-mediated activation of the inflammatory process. We further hypothesize that the protective effects of indole-TEMPO conjugates partially reside in maintaining optimal mitochondrial function.

  13. Gastroprotective mechanisms of indole alkaloids from Himatanthus lancifolius.

    PubMed

    Baggio, Cristiane Hatsuko; De Martini Otofuji, Glaucia; de Souza, Wesley Mauricio; de Moraes Santos, Cid Aimbiré; Torres, Luce Maria Brandao; Rieck, Lia; de Andrade Marques, Maria Consuelo; Mesia-Vela, Sonia

    2005-08-01

    The indole alkaloids mixture (AlkF) obtained from the barks of Himatanthus lancifolius (Muell. Arg.) Woodson was evaluated for gastroprotective properties in rodents. The AlkF potently protected rats from experimentally induced gastric lesions by ethanol (ED (50) = 30 mg/kg, p. o.) and reduced gastric acid hypersecretion induced by pylorus ligature (ED (50) = 82 mg/kg, i. d.). Protective effects of the AlkF in the ethanol and hypersecretion models included increase of GSH levels of gastric mucosa indicating activation of GSH-dependent cytoprotective mechanisms. Also, an increase of the antioxidant capacity as measured through glutathione S-transferase activity was observed in the hypersecretory but not in the ulcerative model. Furthermore, the amount of nitric oxide derivatives (NO (3) + NO (2)) in the forestomach was increased while the amount released into the gastric juice during pylorus ligature was decreased by the AlkF suggesting an alteration of NO-related mechanisms. Reduction of gastric acid hypersecretion induced by pylorus ligature seems to correlate with the blockade of H (+),K (+)-ATPase activity as determined in vitro by the capacity of the AlkF mix to decrease the hydrolysis of ATP by the ATPase isolated from dog gastric mucosa (EC (50) = 212 microg/mL). Cholinergic mechanisms can be excluded since intestinal transit was not modified with doses up to 100 mg/kg ( p. o.). GC-MS investigation of components of the AlkF resulted in the identification of 3 main indole alkaloids, uleine (53 %), its isomer (13 %), demethoxyaspidormine (23.8 %) and traces of at least other five alkaloids. Collectively, the results show the novel gastroprotective properties of the indole AlkF of H. lancifolius through a variety of mechanisms.

  14. Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer's disease in rodent models

    PubMed Central

    Daniels, Michael J. D.; Rivers-Auty, Jack; Schilling, Tom; Spencer, Nicholas G.; Watremez, William; Fasolino, Victoria; Booth, Sophie J.; White, Claire S.; Baldwin, Alex G.; Freeman, Sally; Wong, Raymond; Latta, Clare; Yu, Shi; Jackson, Joshua; Fischer, Nicolas; Koziel, Violette; Pillot, Thierry; Bagnall, James; Allan, Stuart M.; Paszek, Pawel; Galea, James; Harte, Michael K.; Eder, Claudia; Lawrence, Catherine B.; Brough, David

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes. The NLRP3 inflammasome is a multi-protein complex responsible for the processing of the proinflammatory cytokine interleukin-1β and is implicated in many inflammatory diseases. Here we show that several clinically approved and widely used NSAIDs of the fenamate class are effective and selective inhibitors of the NLRP3 inflammasome via inhibition of the volume-regulated anion channel in macrophages, independently of COX enzymes. Flufenamic acid and mefenamic acid are efficacious in NLRP3-dependent rodent models of inflammation in air pouch and peritoneum. We also show therapeutic effects of fenamates using a model of amyloid beta induced memory loss and a transgenic mouse model of Alzheimer's disease. These data suggest that fenamate NSAIDs could be repurposed as NLRP3 inflammasome inhibitors and Alzheimer's disease therapeutics. PMID:27509875

  15. Rodent repellency

    USGS Publications Warehouse

    DeWitt, J.B.; Welch, J.F.; Bellack, E.

    1950-01-01

    In the course of studies involving more than 2,500 chemical repellents, it has been found that certain groups of- compounds containing nitrogen or sulfur are repellent to rats under the , test conditions and it appears probable that some of these compounds might be used for the protection of packaged goods against rodent attacks. Additional tests to determine optimum methods of application will be necessary before final evaluation of these compounds will be possible and extensive field trials will be required to establish the degree of protection which may be afforded by the use of these materials. Pending such final evaluation, it may be assumed that the results,to date offer a means of selecting the most promising types of'materials for further trial....On the basis of the test data, it appears that some amine derivative, such as a salt of some organic, acid, or a complex with trinitrobenzene or with a metallic salt of a dialkyl dithiocarbamic acid might offer promise of protection of packaging materials against rodent attacks....Protection might be obtained through the use of certain 'physical deterrents' such as plastics, waxes or drying oils.

  16. Protection Against Esophageal Cancer in Rodents With Lyophilized Berries: Potential Mechanisms

    PubMed Central

    Stoner, Gary D.; Chen, Tong; Kresty, Laura A.; Aziz, Robeena M.; Reinemann, Tiffany; Nines, Ronald

    2010-01-01

    For several years, our laboratory has been evaluating the ability of lyophilized (freeze-dried) black raspberries (Rubus occidentalis, BRBs), blackberries (R. fructicosus, BBs), and strawberries (Fragaria ananasia, STRWs) to inhibit carcinogen-induced cancer in the rodent esophagus. To assure “standardized” berry preparations for study, each berry type is of the same cultivar, picked at about the same degree of ripeness, washed and frozen within 2–4 h of the time of picking, and freeze-dried under conditions that preserve the components in the berries. Some of the known chemopreventive agents in berries include vitamins A, C, and E and folic acid; calcium and selenium; β-carotene, α-carotene, and lutein; polyphenols such as ellagic acid, ferulic acid, p-coumaric acid, quercetin, and several anthocyanins; and phytosterols such as β-sitosterol, stigmasterol, and kaempferol. In initial bioassays, freeze-dried STRW, BRB, and BB powders were mixed into AIN-76A synthetic diet at concentrations of 5% and 10% and fed to Fischer 344 rats before, during, and after treatment with the esophageal carcinogen N-nitrosomethylbenzylamine (NMBA). At 25 wk of the bioassay, all three berry types were found to inhibit the number of esophageal tumors (papillomas) in NMBA-treated animals by 24–56% relative to NMBA controls. This inhibition correlated with reductions in the formation of the NMBA-induced O6-methylguanine adduct in esophageal DNA, suggesting that the berries influenced the metabolism of NMBA leading to reduced DNA damage. Studies are ongoing to determine the mechanisms by which berries influence NMBA metabolism and DNA adduct formation. BRBs and STRWs were also tested in a postinitiation scheme and were found to inhibit NMBA-induced esophageal tumorigenesis by 31–64% when administered in the diet following treatment of the animals with NMBA. Berries, therefore, inhibit tumor promotion and progression events as well as tumor initiation. In vivo mechanistic

  17. Protection against esophageal cancer in rodents with lyophilized berries: potential mechanisms.

    PubMed

    Stoner, Gary D; Chen, Tong; Kresty, Laura A; Aziz, Robeena M; Reinemann, Tiffany; Nines, Ronald

    2006-01-01

    For several years, our laboratory has been evaluating the ability of lyophilized (freeze-dried) black raspberries (Rubus occidentalis, BRBs), blackberries (R. fructicosus, BBs), and strawberries (Fragaria ananasia, STRWs) to inhibit carcinogen-induced cancer in the rodent esophagus. To assure "standardized" berry preparations for study, each berry type is of the same cultivar, picked at about the same degree of ripeness, washed and frozen within 2-4 h of the time of picking, and freeze-dried under conditions that preserve the components in the berries. Some of the known chemopreventive agents in berries include vitamins A, C, and E and folic acid; calcium and selenium; beta-carotene, alpha-carotene, and lutein; polyphenols such as ellagic acid, ferulic acid, p-coumaric acid, quercetin, and several anthocyanins; and phytosterols such as beta-sitosterol, stigmasterol, and kaempferol. In initial bioassays, freeze-dried STRW, BRB, and BB powders were mixed into AIN-76A synthetic diet at concentrations of 5% and 10% and fed to Fischer 344 rats before, during, and after treatment with the esophageal carcinogen N-nitrosomethylbenzylamine (NMBA). At 25 wk of the bioassay, all three berry types were found to inhibit the number of esophageal tumors (papillomas) in NMBA-treated animals by 24-56% relative to NMBA controls. This inhibition correlated with reductions in the formation of the NMBA-induced O6-methylguanine adduct in esophageal DNA, suggesting that the berries influenced the metabolism of NMBA leading to reduced DNA damage. Studies are ongoing to determine the mechanisms by which berries influence NMBA metabolism and DNA adduct formation. BRBs and STRWs were also tested in a postinitiation scheme and were found to inhibit NMBA-induced esophageal tumorigenesis by 31-64% when administered in the diet following treatment of the animals with NMBA. Berries, therefore, inhibit tumor promotion and progression events as well as tumor initiation. In vivo mechanistic studies

  18. Mild Sensory Stimulation Completely Protects the Adult Rodent Cortex from Ischemic Stroke

    PubMed Central

    Chen-Bee, Cynthia H.; Frostig, Ron D.

    2010-01-01

    Despite progress in reducing ischemic stroke damage, complete protection remains elusive. Here we demonstrate that, after permanent occlusion of a major cortical artery (middle cerebral artery; MCA), single whisker stimulation can induce complete protection of the adult rat cortex, but only if administered within a critical time window. Animals that receive early treatment are histologically and behaviorally equivalent to healthy controls and have normal neuronal function. Protection of the cortex clearly requires reperfusion to the ischemic area despite permanent occlusion. Using blood flow imaging and other techniques we found evidence of reversed blood flow into MCA branches from an alternate arterial source via collateral vessels (inter-arterial connections), a potential mechanism for reperfusion. These findings suggest that the cortex is capable of extensive blood flow reorganization and more importantly that mild sensory stimulation can provide complete protection from impending stroke given early intervention. Such non-invasive, non-pharmacological intervention has clear translational potential. PMID:20585659

  19. Marine Indole Alkaloids

    PubMed Central

    Netz, Natalie; Opatz, Till

    2015-01-01

    Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed. PMID:26287214

  20. Benzo[g]indoles

    NASA Astrophysics Data System (ADS)

    Pozharskii, A. F.; Kachalkina, S. G.; Gulevskaya, A. V.; Filatova, E. A.

    2017-07-01

    The data on the synthesis and properties of benzo[g]indoles accumulated mainly over a period of the past 15-20 years are integrated. Various variants of pyrrole ring and naphthalene nucleus closure are considered. It is demonstrated that, in addition to the expected similarity between benzo[g]indoles and indoles, there are noticeable differences between them as well, especially where the synthesis of the benzoindole system is concerned. Practical applications of benzo[g]indoles are discussed. The bibliography includes 199 references.

  1. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection

    PubMed Central

    Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu

    2016-01-01

    Recent successes with monoclonal antibody cocktails ZMappTM and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs. PMID:27067649

  2. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection.

    PubMed

    Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu

    2016-04-12

    Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab')2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab')2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.

  3. The Respiratory Syncytial Virus G Protein Conserved Domain Induces a Persistent and Protective Antibody Response in Rodents

    PubMed Central

    Nguyen, Thien N.; Power, Ultan F.; Robert, Alain; Haeuw, Jean-François; Helffer, Katia; Perez, Amadeo; Asin, Miguel-Angel; Corvaia, Nathalie; Libon, Christine

    2012-01-01

    Respiratory syncytial virus (RSV) is an important cause of severe upper and lower respiratory disease in infants and in the elderly. There are 2 main RSV subtypes A and B. A recombinant vaccine was designed based on the central domain of the RSV-A attachment G protein which we had previously named G2Na (aa130–230). Here we evaluated immunogenicity, persistence of antibody (Ab) response and protective efficacy induced in rodents by: (i) G2Na fused to DT (Diphtheria toxin) fragments in cotton rats. DT fusion did not potentiate neutralizing Ab responses against RSV-A or cross-reactivity to RSV-B. (ii) G2Nb (aa130–230 of the RSV-B G protein) either fused to, or admixed with G2Na. G2Nb did not induce RSV-B-reactive Ab responses. (iii) G2Na at low doses. Two injections of 3 µg G2Na in Alum were sufficient to induce protective immune responses in mouse lungs, preventing RSV-A and greatly reducing RSV-B infections. In cotton rats, G2Na-induced RSV-reactive Ab and protective immunity against RSV-A challenge that persisted for at least 24 weeks. (iv) injecting RSV primed mice with a single dose of G2Na/Alum or G2Na/PLGA [poly(D,L-lactide-co-glycolide]. Despite the presence of pre-existing RSV-specific Abs, these formulations effectively boosted anti-RSV Ab titres and increased Ab titres persisted for at least 21 weeks. Affinity maturation of these Abs increased from day 28 to day 148. These data indicate that G2Na has potential as a component of an RSV vaccine formulation. PMID:22479601

  4. Protective, restorative, and therapeutic properties of recombinant human IL-1 in rodent models

    SciTech Connect

    Castelli, M.P.; Black, P.L.; Schneider, M.; Pennington, R.; Abe, F.; Talmadge, J.E.

    1988-06-01

    Human rIL-1 alpha and -1 beta are shown to increase significantly the CFU-culture activity in the spleen as well as at other sites after i.v. or i.p. administration. IL-1 can also significantly increase survival and can rescue a number of animals if administered either before or after lethal doses of cyclophosphamide or gamma-irradiation. The protective and reconstitutive activities of the rIL-1 are shown to correlate with increased CFU-culture frequency and total number, as well as increased cellularity in the bone marrow and peripheral blood, suggesting that this is one of their mechanisms of action. The sequence and timing of administration of human rIL-1 is critical for the protection or rescue of animals receiving DNA-damaging agents; maximal activity is achieved when IL-1 is given 20 h before insult or 48 h after alkylating agent administration. Minimal therapeutic activity is observed with IL-1 as a single agent for the treatment of metastatic disease compared with other biologic response modifiers including IFN-gamma.

  5. A non-adjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria1

    PubMed Central

    Abanega Kaba, Stephen; Brando, Clara; Guo, Qin; Mittelholzer, Christian; Raman, Senthilkumar; Tropel, David; Aebi, Ueli; Burkhard, Peter; Ervin Lanar, David

    2015-01-01

    We have designed and produced a prototypic malaria vaccine based on a highly versatile self-assembling polypeptide nanoparticle (SAPN) platform that can repetitively display antigenic epitopes. We used this platform to display a tandem repeat of the B cell immunodominant repeat epitope (DPPPPNPN)2D of the malaria parasite Plasmodium berghei circumsporozoite protein (CSP). Administered in saline, without the need for a heterologous adjuvant, the SAPN construct P4c-Mal conferred a long lived protective immune response to mice with a broad range of genetically distinct immune backgrounds including the H-2b, H-2d and H-2k alleles. Immunized mice produced a CD4+ T cell dependent, high titer, long lasting, high avidity antibody response against the B cell epitope. Mice were protected against an initial challenge of parasites given up to 6 months after the last immunization or for up to 15 months against a second challenge after an initial challenge of parasites had successfully been cleared. Furthermore, we demonstrate that the SAPN platform not only functions to deliver an ordered repetitive array of B cell peptide epitopes but operates as a classical immunological carrier to provide cognate help to the P4c-Mal specific B cells. PMID:19915055

  6. Toxicity assessment of Clostridium difficile toxins in rodent models and protection of vaccination.

    PubMed

    Wang, Su; Rustandi, Richard R; Lancaster, Catherine; Hong, Laura G; Thiriot, David S; Xie, Jinfu; Secore, Susan; Kristopeit, Adam; Wang, Sheng-Ching; Heinrichs, Jon H

    2016-03-04

    Clostridium difficile is the leading cause of hospital-acquired diarrhea, also known as C. difficile associated diarrhea. The two major toxins, toxin A and toxin B are produced by most C. difficile bacteria, but some strains, such as BI/NAP1/027 isolates, produce a third toxin called binary toxin. The precise biological role of binary toxin is not clear but it has been shown to be a cytotoxin for Vero cells. We evaluated the toxicity of these toxins in mice and hamsters and found that binary toxin causes death in both animals similar to toxins A and B. Furthermore, immunization of mice with mutant toxoids of all three toxins provided protection upon challenge with native toxins. These results support the concept that binary toxin contributes to the pathogenicity of C. difficile and provide a method for monitoring the toxicity of binary toxin components in vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Benefits of protective fencing to plant and rodent communities of the western Mojave Desert, California

    NASA Astrophysics Data System (ADS)

    Brooks, Matthew L.

    1995-01-01

    Human disturbance in the western Mojave Desert takes many forms. The most pervasive are livestock grazing and off-highway vehicle use. Over the past few decades several areas within this region have been fenced to preclude human disturbance. These areas provide opportunities to study the impact of human activities in a desert ecosystem. This paper documents the response of plant and small mammal populations to fencing constructed between 1978 and 1979 at the Desert Tortoise Research Natural Area, Kern County, California. Aboveground live annual plant biomass was generally greater inside than outside the fenced plots during April 1990, 1991, and 1992. The alien grass Schismus barbatus was a notable exception, producing more biomass in the unprotected area. Forb biomass was greater than that of alien annual grasses inside the fence during all three years of the study. Outside the fence, forb biomass was significantly higher than that of alien grasses only during spring 1992. Percent cover of perennial shrubs was higher inside the fence than outside, while no significant trend was detected in density. There was als more seed biomass inside the fence; this may have contributed to the greater diversity and density of Merriam's kangaroo rats ( Dipodomys merriami), long-tailed pocket mice ( Chaetodipus formosus), and southern grasshopper mice ( Onychomys torridus) in the protected area. These results show that protection from human disturbance has many benefits, including greater overall community biomass and diversity. The significance and generality of these results can be further tested by studying other exclosures of varying age and configurations in different desert regions of the southwestern United States.

  8. Rodent Control

    ERIC Educational Resources Information Center

    Indian Journal of Adult Education, 1975

    1975-01-01

    Strategies for rodent control in crop fields, threshing yards, and rural residential areas are presented together with an operational plan for implementing a program for rodent control at the national level. Training personnel in rodent control procedures and procedures for educating the public in the necessity for control are covered. (EC)

  9. Rodent Control

    ERIC Educational Resources Information Center

    Indian Journal of Adult Education, 1975

    1975-01-01

    Strategies for rodent control in crop fields, threshing yards, and rural residential areas are presented together with an operational plan for implementing a program for rodent control at the national level. Training personnel in rodent control procedures and procedures for educating the public in the necessity for control are covered. (EC)

  10. Hydroalcoholic extract of Brazilian red propolis exerts protective effects on acetic acid-induced ulcerative colitis in a rodent model.

    PubMed

    Barbosa Bezerra, Gislaine; de Menezes de Souza, Luana; Dos Santos, Adailma Santana; de Almeida, Grace Kelly Melo; Souza, Marília Trindade Santana; Santos, Sandra Lauton; Aparecido Camargo, Enilton; Dos Santos Lima, Bruno; de Souza Araújo, Adriano Antunes; Cardoso, Juliana Cordeiro; Gomes, Silvana Vieira Floresta; Gomes, Margarete Zanardo; de Albuquerque, Ricardo Luiz Cavalcanti

    2017-01-01

    Ulcerative colitis (UC) is a common intestinal inflammatory disease with an etiology that is not well understood. Although the anti-inflammatory and anti-oxidant effects of the hydroalcoholic extract of Brazilian red propolis (HERP) have been reported in various experimental models, its protective effect in models of UC have not been evaluated. The purpose of this study was to investigate the chemopreventive effect of hydroalcoholic extract of Brazilian red propolis (HERP) in acetic acid-induced colitis (AAIC) using a rodent model. The HERP was chemically characterised by HPLC/DAD analyses. Male rats were randomly assigned into four groups: sham, vehicle (with AAIC, treated with vehicle), P10 (with AAIC, treated with 10mg/kg HERP), and P100 (with AAIC, treated with 100mg/kg HERP). Treatments were performed for 7days, and colitis was induced on day seven. Animals were euthanized 24h after colitis induction and body weight, colon length, gross and histological scores, malondialdehyde (MDA) and myeloperoxidase (MPO) concentrations in colon tissue, and the immunohistochemical expression of inducible nitric oxide synthase (iNOS) were assessed. The major compounds found in HERP were liquiritigenin (68.8mg/g), formononetin (54.29mg/g), biochanin A (30.97mg/g), and daidzein (19.90mg/g). Rats treated with 10mg/kg HERP demonstrated significant decreases in MPO concentrations, gross and histological scores of tissue damage, and iNOS expression (p<0.05). Similarly, rats treated with 100mg/kg HERP demonstrated significant decreases in MPO levels (p<0.05) and histological scores of tissue damage (p<0.05). The results of this study indicate that oral administration of HERP attenuates AAIC in rats, which may be due to anti-inflammatory effects related to iNOS inhibition. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Regioselective oxidative arylation of indoles bearing N-alkyl protecting groups: dual C-H functionalization via a concerted metalation-deprotonation mechanism.

    PubMed

    Potavathri, Shathaverdhan; Pereira, Kyle C; Gorelsky, Serge I; Pike, Andrew; LeBris, Alexis P; DeBoef, Brenton

    2010-10-20

    The most direct method for synthesizing 2-arylindoles is oxidative coupling of an arene with an indole. We have shown that both the activity and regioselectivity of this cross-coupling reaction are correlated with the acidity of the medium. This insight has been applied to predict the best conditions for the oxidative cross-coupling of N-alkylindoles, an important class of substrates that has heretofore been incompatible with the harsh conditions required for oxidative cross-coupling. Both experimental and computational data indicate that the mechanism for C-H palladation of both the indoles and simple arenes is best described as concerted metalation-deprotonation, regardless of the substitution on the arene.

  12. Indolent Wegener's granulomatosis.

    PubMed Central

    Macfarlane, D G; Bourne, J T; Dieppe, P A; Easty, D L

    1983-01-01

    Classical Wegener's granulomatosis is a relentlessly progressive and rapidly fatal disease. A pulmonary 'limited form' is associated with a much better prognosis. We report 3 cases of Wegener's granulomatosis which ran a prolonged indolent course despite major manifestations outside the lower respiratory tract and review the literature on survival. Images PMID:6882035

  13. Rituximab In Indolent Lymphomas

    PubMed Central

    Sousou, Tarek; Friedberg, Jonathan

    2010-01-01

    Indolent Non Hodgkin's lymphoma (NHL) comprises a group of incurable, generally slow growing lymphomas highly responsive to initial therapy with a relapsing and progressive course. Rituximab, an anti CD-20 antibody, has had a large impact on treatment of indolent NHL. Its effectiveness as a single agent and in conjunction with known chemotherapy regimens has made it a standard of care in the treatment of NHL. Analysis of data obtained from NHL clinical trials as well as data from the National Cancer Institute indicates that the overall survival of indolent NHL has improved since the discovery of rituximab. Given its effectiveness and tolerability, it is currently being investigated as a maintenance agent with encouraging results. This review summarizes several landmark trials utilizing rituximab as a single agent and in combination with chemotherapy for treatment of NHL. In addition, a review of the studied rituximab maintenance dosing schedules and its impact on NHL will also be presented. Overall, rituximab has changed the landscape for treatment of indolent NHL however additional research is necessary to identify the optimal dosing schedule as well as patients most likely to respond to prolonged rituximab therapy. PMID:20350660

  14. New azepino[4,3-b]indole derivatives as nanomolar selective inhibitors of human butyrylcholinesterase showing protective effects against NMDA-induced neurotoxicity.

    PubMed

    de Candia, Modesto; Zaetta, Giorgia; Denora, Nunzio; Tricarico, Domenico; Majellaro, Maria; Cellamare, Saverio; Altomare, Cosimo D

    2017-01-05

    Several 6-substituted 3,4,5,6-tetrahydroazepino[4,3-b]indol-1(2H)-one (THAI) derivatives were synthesized and evaluated for their activity as cholinesterase (ChE) inhibitors. The most potent inhibitors were identified among 6-(2-phenylethyl)-THAI derivatives, and in particular compounds 12b and 12d proved to be very active against human BChE (IC50 = 13 and 1.8 nM, respectively), with 1000-fold selectivity over AChE. Structure-activity relationships highlighted critical features (e.g., ring fusion [4,3-b], integrity of the lactam CONH function) and favorable physicochemical properties of the 6-(2-phenylethyl) group (i.e., optimal position, size and lipophilicity of phenyl substituents). The effects of a number of compounds against NMDA-induced SH-SY5Y neuronal cell injury were also evaluated. Treatment with 12b increased cell viability in SH-SY5Y cells pretreated with 250 μM NMDA, with significant effects (P < 0.05) at concentrations between 0.5 and 5 μM. These findings suggest that THAI can be used as a scaffold for developing new drug leads for the treatment of Alzheimer-type neurodegeneration syndrome. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. ZrCl4-mediated regio- and chemoselective Friedel-Crafts acylation of indole.

    PubMed

    Guchhait, Sankar K; Kashyap, Maneesh; Kamble, Harshad

    2011-06-03

    An efficient method for regio- and chemoselective Friedel-Crafts acylation of indole using acyl chlorides in the presence of ZrCl(4) has been discovered. It minimizes/eliminates common competing reactions that occur due to high and multiatom-nucleophilic character of indole. In this method, a wide range of aroyl, heteroaroyl alkenoyl, and alkanoyl chlorides undergo smooth acylation with various indoles without NH protection and afford 3-acylindoles in good to high yields.

  16. Peroxynitrite scavenging activity of indole derivatives: interaction of indoles with peroxynitrite.

    PubMed

    Soung, Do Yu; Choi, Hye Rhi; Kim, Ji Young; No, Jae Kyung; Lee, Jee Hyun; Kim, Min Sun; Rhee, Sook Hee; Park, Jin Seng; Kim, Myung Jung; Yang, Ryung; Chung, Hae Young

    2004-01-01

    One of the products of nitrogen-derived free radicals, peroxynitrite (ONOO(-)), is formed by the reaction of superoxide anion (O(2)(*-)) with nitric oxide (NO). ONOO(-) can cause damage to proteins and DNA through nitration. In particular, proteins and their constituent amino acids have been proven to be extremely sensitive to ONOO(-). However, the lack of specific endogenous defense enzymes to protect against ONOO(-) has prompted many researchers to search for endogenous scavengers. We previously found 5-hydroxytryptamine (HT), which is an indole derivative (ID), to be an efficient ONOO(-) scavenger. In the present study, the interaction of several other indoles was further investigated: tryptophan (TRP), 5-hydroxyL-tryptophan (HLT), HT, N-acetyl-5-hydroxytryptamine (AHT), 5-methoxyindole-3-acetate (MIA), 5-methoxytryptamine (MT), and melatonin. The ONOO(-) scavenging activity of ID was assayed by measuring the formation of oxidized dihydrorhodamine-123 (DHR-123). The scavenging efficacy was expressed as the IC(50), denoting the concentration of each indole required to cause 50% inhibition of DHR-123 formation. In a separate in vitro study, the protective effect of IDs against ONOO(-)-induced nitration of bovine serum albumin was investigated. Nitration was quantified using an immunoassay with a monoclonal anti-nitrotyrosine antibody, and a horseradish peroxidase-conjugated anti-mouse secondary antibody from sheep. The results revealed that the inhibitory activities of indoles were as follows: HLT, IC(50) = 0.73 microM; HT, IC(50) = 1.03 microM; and AHT, IC(50) = 0.98 microM), showing relatively strong activities against ONOO(-). Interestingly, TRP, MIA, MT, and melatonin were less effective. Regarding the protection of albumin by IDs, the data showed that the formation of ONOO(-) was inhibited in a dose-dependent manner. Further probing of the mode of the interaction of indoles revealed that the hydroxyl groups in IDs are required for the enhanced scavenging

  17. Dual action of high estradiol doses on MNU-induced prostate neoplasms in a rodent model with high serum testosterone: Protective effect and emergence of unstable epithelial microenvironment.

    PubMed

    Gonçalves, Bianca F; de Campos, Silvana G P; Góes, Rejane M; Scarano, Wellerson R; Taboga, Sebastião R; Vilamaior, Patricia S L

    2017-06-01

    Estrogens are critical players in prostate growth and disease. Estrogen therapy has been the standard treatment for advanced prostate cancer for several decades; however, it has currently been replaced by alternative anti-androgenic therapies. Additionally, studies of its action on prostate biology, resulting from an association between carcinogens and estrogen, at different stages of life are scarce or inconclusive about its protective and beneficial role on induced-carcinogenesis. Thus, the aim of this study was to determine whether estradiol exerts a protective and/or stimulatory role on N-methyl-N-nitrosurea-induced prostate neoplasms. We adopted a rodent model that has been used to study induced-prostate carcinogenesis: the Mongolian gerbil. We investigated the occurrence of neoplasms, karyometric patterns, androgen and estrogen receptors, basal cells, and global methylation status in ventral and dorsolateral prostate tissues. Histopathological analysis showed that estrogen was able to slow tumor growth in both lobes after prolonged treatment. However, a true neoplastic regression was observed only in the dorsolateral prostate. In addition to the protective effects against neoplastic progression, estrogen treatment resulted in an epithelium that exhibited features distinctive from a normal prostate, including increased androgen-insensitive basal cells, high androgens and estrogen receptor positivity, and changes in DNA methylation patterns. Estrogen was able to slow tumor growth, but the epithelium exhibited features distinct from a normal prostatic epithelium, and this unstable microenvironment could trigger lesion recurrence over time. © 2017 Wiley Periodicals, Inc.

  18. Piper umbellatum L.: A medicinal plant with gastric-ulcer protective and ulcer healing effects in experimental rodent models.

    PubMed

    da Silva Junior, Iberê Ferreira; Balogun, Sikiru Olaitan; de Oliveira, Ruberlei Godinho; Damazo, Amílcar Sabino; Martins, Domingos Tabajara de Oliveira

    2016-11-04

    Piper umbellatum L. (Piperaceae) is a shrub found in the Amazon, Savannah and Atlantic Forest region of Brazil. It is widely used in folk medicine in many countries primarily for the treatment of gastric disorders. The aim of this study was to evaluate the gastroprotective and anti-ulcer effects of hydroethanolic extract of P. umbellatum (HEPu) leaves in experimental rodents. In addition, the anti-Helicobacter pylori activity of the extract was assessed. The leaves of P. umbellatum were macerated in 75% (1:3w/v) hydroethanolic solution to obtain HEPu. The gastroprotective and ulcer healing activities of HEPu were evaluated using acidified ethanol (acute) and acetic acid (chronic) gastric ulcer models in rodents. The anti-H. pylori activity was evaluated by in vitro broth microdilution assay using H. pylori cagA(+) and vacA(+) strain. The probable mechanism of action of HEPu was evaluated by determining gastric secretory parameters, antioxidant enzyme (catalase), non-protein sulfhydryl (glutathione) and malondialdehyde levels in gastric tissue, including pro-inflammatory (IL-1β, TNF-a, IL -17, RANTES, IFN-γ and MIP-2) and anti-inflammatory (IL-10) cytokines. HEPu demonstrated potent gastroprotection against acute ulcer induced by acidified ethanol and excellent healing effect of the chronic ulcer induced by acetic acid. The gastroprotective activity in acidified ethanol is partly attributed to the antioxidant mechanisms, while anti-secretory, anti-inflammatory and regeneration of the gastric mucosa are evoked as part of its antiulcer mechanism of action. The gastric ulcer healing of HEPu also involves restoration of the altered cytokines levels to near normal. However, it has no in vitro anti-H. pylori activity. The results of this study showed that HEPu possesses preventive and curative effects in experimental models of gastric ulcers in animals. These effects are partially dependent on antioxidant, antisecretory, anti-inflammatory and mucosa regeneration. It is

  19. Aqueous stem bark extract of Stereospermum kunthianum (Cham, Sandrine Petit) protects against generalized seizures in pentylenetetrazole and electro-convulsive models in rodents.

    PubMed

    Ching, F P; Omogbai, E K I; Otokiti, I O

    2009-07-03

    Stereospermum kunthianum, Cham Sandrine Petit (Bignoniaceae) known in English as pink jacaranda is used in traditional medicine to treat an array of ailments including febrile convulsions in infants and young children by the rural dwellers in Nigeria. This study examined the anticonvulsant activity of its aqueous stem bark extract (100 - 400mg/kg) against maximal electroshock and pentylenetetrazole-induced seizures in rodents. Phenobarbitone and ethosuximide were used as reference anticonvulsant drugs for comparison. Stereospermum kunthianum extract (200 - 400mg/kg, i.p.) remarkably protected (76.9% and 84.6 % respectively) the rats against electroshock-induced seizures. However, the extract (200- 400mg/kg) when administered orally showed a comparatively less effect (33.3% and 55.6% respectively) to the intraperitoneally administered extract in the maximal electroshock test. The extract (100-400mg/kg, i.p.) significantly delayed (p<0.05) the onset of pentylenetetrazole-induced clonic seizures but only slightly prolonged the time of death of the mice. Although the findings in the present study do not provide conclusive evidence, it appears that the aqueous stem bark extract of Stereospermum kunthianum produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain. The results indicate that the aqueous extract possesses anticonvulsant activity in rodents and therefore tend to suggest that the shrub may be used as a natural supplementary remedy in the management, control and/or treatment of childhood convulsions. It can be concluded that the aqueous stem bark extract possesses anticonvulsant activity and therefore lend pharmacological credence to the traditionally claimed use in the treatment of childhood convulsions.

  20. Ultraviolet radiation-induced non-melanoma skin cancer in the Crl:SKH1:hr-BR hairless mouse: augmentation of tumor multiplicity by chlorophyllin and protection by indole-3-carbinol.

    PubMed

    Cope, R B; Loehr, C; Dashwood, R; Kerkvliet, N I

    2006-05-01

    Over 1 million new cases of ultraviolet radiation-induced non-melanoma skin cancers (NMSC) per year now occur in the USA and the incidence of these diseases continues to increase. New preventative strategies are required. The hypothesis tested was that dietary administration of the putative cancer chemopreventatives sodium-copper-chlorophyllin (Chlor) or indole-3-carbinol (I3C) would inhibit UV-induced skin carcinogenesis in the Crl:SKH1:hr-BR hairless mouse. Groups of 20 mice were pre-fed isocaloric/isonutritive 20% corn-oil AIN-76a based diets that contained either Chlor (1.52 g%), I3C (5.08 g%) or no chemopreventative (control) for 2 weeks followed by exposure of their dorsal skin to a 10 week incremental, sub-erythemal, carcinogenic simulated solar UV exposure regime. Feeding was continued for the duration of the experiment. Matched non-UV exposed dietary groups were also included in the experimental design. The diets had no significant (p > 0.05) effect on body weight, feed consumption, cutaneous methanol-extractable UV photoprotective substances or on cutaneous UV-reflective characteristics. By day 180, UV-irradiated mice fed the Chlor had a significantly (p < 0.05) higher tumor multiplicity (33.6 +/- 4.72; mean +/- SEM) than UV-irradiated control animals (22.8 +/- 4.25). UV-irradiated mice fed I3C had a significantly (p < 0.001) lower tumor multiplicity (13.0 +/- 2.42) than that of both the UV-irradiated control and UV-irradiated Chlor-fed mice. The Chlor or I3C diets did not significantly (p > 0.05) affect UV-induced systemic suppression of contact hypersensitivity responses. These results demonstrate augmentation of the UV-induced cutaneous carcinogenic process by dietary chlorophyllin and protection from this carcinogenic process by indole-3-carbinol via mechanisms that do not involve changes in skin optical properties, modulation of photoimmunosuppression or caloric/nutrient effects.

  1. Topiramate protects against glutamate excitotoxicity via activating BDNF/TrkB-dependent ERK pathway in rodent hippocampal neurons.

    PubMed

    Mao, Xiao-Yuan; Cao, Yong-Gang; Ji, Zhong; Zhou, Hong-Hao; Liu, Zhao-Qian; Sun, Hong-Li

    2015-07-03

    Topiramate (TPM) was previously found to have neuroprotection against neuronal injury in epileptic and ischemic models. However, whether TPM protects against glutamate-induced excitotoxicity in hippocampal neurons is elusive. Our present work aimed to evaluate the protective effect of TPM against glutamate toxicity in hippocampal neurons and further figure out the potential molecular mechanisms. The in vitro glutamate excitotoxic model was prepared with 125μM glutamate for 20min. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) analysis and Hoechst 33342 staining were conducted to detect neuronal survival. The protein expressions of brain-derived neurotrophic factor (BDNF), TrkB, mitogen-activated protein kinase (MAPK) cascade (including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK), cyclic AMP response element binding protein (CREB), Bcl-2, Bax and β-actin were detected via Western blot assay. Our results demonstrated that TPM protected hippocampal neurons from glutamate toxicity. Meanwhile, the pretreatment of TPM for 10min significantly prevented the down-regulation of BDNF and the phosphorylation of TrkB. Furthermore, the elevation of phosphorylated EKR expression was significantly inhibited after blockade of TrkB by TrkB IgG, while no alterations of phosphorylated JNK and p38 MAPK were found in the cultured hippocampal neurons. Besides, it was also found that the enhanced phosphorylation of CREB was evidently reversed under excitotoxic conditions after treating with U0126 (the selective inhibitor of ERK). The protein level of Bcl-2 was also observed to be remarkably increased after TPM treatment. In conclusion, these findings implicate that TPM exerts neuroprotective effects against glutamate excitotoxicity in hippocampal neurons and its protection may be modulated through BDNF/TrkB-dependent ERK pathway.

  2. Sulforaphane Protects Rodent Retinas against Ischemia-Reperfusion Injury through the Activation of the Nrf2/HO-1 Antioxidant Pathway

    PubMed Central

    Liu, Ruixing; Brecha, Nicholas C.; Yu, Albert Cheung Hoi; Pu, Mingliang

    2014-01-01

    Retinal ischemia-reperfusion (I/R) injury induces oxidative stress, leukocyte infiltration, and neuronal cell death. Sulforaphane (SF), which can be obtained in cruciferous vegetables such as broccoli, exerts protective effects in response to oxidative stress in various tissues. These effects can be initiated through nuclear factor E2-related factor 2 (Nrf2)-mediated induction of heme oxygenase-1 (HO-1). This investigation was designed to elucidate the neural protective mechanisms of SF in the retinal I/R rat model. Animals were intraperitoneally (i.p.) injected with SF (12.5 mg/kg) or vehicle (corn oil) once a day for 7 consecutive days. Then, retinal I/R was made by elevating the intraocular pressure (IOP) to 130 mmHg for 1 h. To determine if HO-1 was involved in the Nrf2 antioxidant pathway, rats were subjected to protoporphyrin IX zinc (II) (ZnPP, 30 mg/kg, i.p.) treatments at 24 h before retinal ischemia. The neuroprotective effects of SF were assessed by determining the morphology of the retina, counting the infiltrating inflammatory cells and the surviving retinal ganglion cells (RGCs) and amacrine cells, and measuring apoptosis in the retinal layers. The expression of Nrf2 and HO-1 was studied by immunofluorescence analysis and western blotting. I/R induced a marked increase of ROS generation, caused pronounced inflammation, increased the apoptosis of RGCs and amacrine cells and caused the thinning of the inner retinal layer (IRL), and these effects were diminished or abolished by SF pretreatment. Meanwhile, SF pretreatment significantly elevated the nuclear accumulation of Nrf2 and the level of HO-1 expression in the I/R retinas; however, ZnPP reversed the protective effects of SF on I/R retinas. Together, we offer direct evidence that SF had protective effects on I/R retinas, which could be attributed, at least in part, to the activation of the Nrf2/HO-1 antioxidant pathway. PMID:25470382

  3. Baculovirus-vectored multistage Plasmodium vivax vaccine induces both protective and transmission-blocking immunities against transgenic rodent malaria parasites.

    PubMed

    Mizutani, Masanori; Iyori, Mitsuhiro; Blagborough, Andrew M; Fukumoto, Shinya; Funatsu, Tomohiro; Sinden, Robert E; Yoshida, Shigeto

    2014-10-01

    A multistage malaria vaccine targeting the pre-erythrocytic and sexual stages of Plasmodium could effectively protect individuals against infection from mosquito bites and provide transmission-blocking (TB) activity against the sexual stages of the parasite, respectively. This strategy could help prevent malaria infections in individuals and, on a larger scale, prevent malaria transmission in communities of endemicity. Here, we describe the development of a multistage Plasmodium vivax vaccine which simultaneously expresses P. vivax circumsporozoite protein (PvCSP) and P25 (Pvs25) protein of this species as a fusion protein, thereby acting as a pre-erythrocytic vaccine and a TB vaccine, respectively. A new-concept vaccine platform based on the baculovirus dual-expression system (BDES) was evaluated. The BDES-Pvs25-PvCSP vaccine displayed correct folding of the Pvs25-PvCSP fusion protein on the viral envelope and was highly expressed upon transduction of mammalian cells in vitro. This vaccine induced high levels of antibodies to Pvs25 and PvCSP and elicited protective (43%) and TB (82%) efficacies against transgenic P. berghei parasites expressing the corresponding P. vivax antigens in mice. Our data indicate that our BDES, which functions as both a subunit and DNA vaccine, can offer a promising multistage vaccine capable of delivering a potent antimalarial pre-erythrocytic and TB response via a single immunization regimen. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  4. The reno-protective effect of aqueous extract of Carum carvi (black zeera) seeds in streptozotocin induced diabetic nephropathy in rodents.

    PubMed

    Sadiq, Soban; Nagi, Abdul Hannan; Shahzad, Muhammad; Zia, Azam

    2010-11-01

    To assess the effect of aqueous extract of Carum carvi seeds in experimentally induced diabetic nephropathy (DN) in rodents, we studied 48 adult male Wistar rats divided into 4 groups: normal controls (group A), diabetes positive control (group B), and experimental (groups C and D). They received Carum carvi extract as a renoprotective agent. Rats having fasting blood glucose levels over 280 mg/dL were included in this study. Group C rats received STZ (60 mg/kg) and aqueous extract of Carum carvi at 30 mg/kg of body weights. On the other hand group D rats received STZ (60 mg/kg) and aqueous extract of Carum carvi at 60 mg/kg of body weight. Blood samples were collected on the 60 th day, and kidneys were also extracted for examination. The diabetic group rats showed a variable increase in the serum levels of glucose, urea, creatinine, total urinary protein and microalbuminuric levels. Body weight decreased and urine volume increased in the diabetic groups. 30 mg/kg body weight of Carum carvi dose decreased the levels of these parameters in rats. On the other hand, 60 mg/kg body weight of Carum carvi dose significantly decreased the levels of the biochemical parameters. The morphological examination of group C rats showed no changes whereas the rats in group D showed moderate changes. Carum carvi constituents, especially flavonoids and carvone have strong anti-oxidant activity, which provides reno-protection against diabetes and its complications. In conclusion, high dose of Carum carvi aqueous seeds extract (60 mg/kg) showed reno-protection against STZ induced dia-betic nephropathy in rats.

  5. Toxicological evaluation of Terminalia paniculata bark extract and its protective effect against CCl4-induced liver injury in rodents

    PubMed Central

    2013-01-01

    Background Based on the reported antioxidant and anti-inflammatory potential of Terminalia paniculata, the bark aqueous extract (TPW) was investigated against liver damage. Methods Intrinsic cytotoxicity was tested on normal human liver (Chang) cell lines, followed by acute and sub-chronic toxicity studies in mice. TPW was then evaluated against CCl4-induced liver toxicity in rats. Liver enzymes (AST, ALT, and ALP) and antioxidant markers were assessed. The effect of TPW on isolated hepatic cells, post-CCl4 administration, was assessed by isolated mitochondrial membrane staining. The actions of TPW on apoptotic pathway in CCl4-treated Chang cells were also elucidated. Results TPW was found to be safe at all doses tested in both in vitro and in vivo toxicity studies. TPW (400 mg/kg, p.o.) significantly (*p <0.05) improved liver enzyme activity as compared to CCl4. Also, it improved antioxidant status (GSH, GST, MDA and total thiol) and preserved hepatic cell architecture. TPW pre-treatment significantly attenuated the levels of phospho-p53, p53, cleaved caspase-3, phospho-Bad, Bad and cleaved PARP in CCl4-treated Chang cells, improving the viability considerably. Conclusion The findings support a protective role for Terminalia paniculata in pathologies involving oxidative stress. PMID:23742226

  6. A Single Subcutaneous Injection of Cellulose Ethers Administered Long before Infection Confers Sustained Protection against Prion Diseases in Rodents

    PubMed Central

    Oguma, Ayumi; Nishizawa, Keiko; Kawata, Maki; Sakasegawa, Yuji; Doh-ura, Katsumi

    2016-01-01

    Prion diseases are fatal, progressive, neurodegenerative diseases caused by prion accumulation in the brain and lymphoreticular system. Here we report that a single subcutaneous injection of cellulose ethers (CEs), which are commonly used as inactive ingredients in foods and pharmaceuticals, markedly prolonged the lives of mice and hamsters intracerebrally or intraperitoneally infected with the 263K hamster prion. CEs provided sustained protection even when a single injection was given as long as one year before infection. These effects were linked with persistent residues of CEs in various tissues. More effective CEs had less macrophage uptake ratios and hydrophobic modification of CEs abolished the effectiveness. CEs were significantly effective in other prion disease animal models; however, the effects were less remarkable than those observed in the 263K prion-infected animals. The genetic background of the animal model was suggested to influence the effects of CEs. CEs did not modify prion protein expression but inhibited abnormal prion protein formation in vitro and in prion-infected cells. Although the mechanism of CEs in vivo remains to be solved, these findings suggest that they aid in elucidating disease susceptibility and preventing prion diseases. PMID:27973536

  7. Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents.

    PubMed

    Backhauss, C; Krieglstein, J

    1992-05-14

    The purpose of the present study was to test whether kava extract and its constituents kawain, dihydrokawain, methysticin, dihydromethysticin and yangonin provide protection against ischemic brain damage. To this end, we used a model of focal cerebral ischemia in mice and rats. Ischemia was induced by microbipolar coagulation of the left middle cerebral artery (MCA). To quantify the size of the lesion in mice, the area of the infarct on the brain surface was assessed planimetrically 48 h after MCA occlusion by transcardial perfusion of carbon black. In the rat model infarct volume was determined 48 h after MCA occlusion by planimetric analysis and subsequent integration of the infarct areas on serial coronal slices. Compounds were administered i.p., except the kava extract, which was administered orally. The effects of the kava extract and its constituents were compared with those produced by the typical anticonvulsant, memantine. The kava extract, methysticin and dihydromethysticin produced effects similar to those of the reference substance memantine. The kava extract (150 mg/kg, 1 h before ischemia) diminished the infarct area (P less than 0.05) in mouse brains and the infarct volume (P less than 0.05) in rat brains. Methysticin, dihydromethysticin (both 10 and 30 mg/kg, 15 min before ischemia) and memantine (20 mg/kg, 30 min before ischemia) significantly reduced the infarct area in mouse brains. All other compounds failed to produce a beneficial effect on the infarct area in mouse brains. In conclusion, the kava extract exhibited neuroprotective activity, which was probably mediated by its constituents methysticin and dihydromethysticin.

  8. Nuclear Factor kB and Inhibitor of kB: Acupuncture Protection Against Acute Focal Cerebral Ischemia in Rodents.

    PubMed

    Huang, Wei; Zhou, Zhongyu; Wan, Bijiang; Chen, Guang; Li, Jia

    2017-02-27

    Context • Acute, focal, cerebral ischemic stroke is a leading cause of morbidity and mortality worldwide. Acupuncture is an emerging alternative therapy for treatment of acute brain ischemia. Nevertheless, the precise mechanism underlying the neuroprotective effects of acupuncture has not been elucidated. Nuclear factor κB (NF-κB) and nuclear factor of κ light polypeptide gene enhancer in B cell inhibitor alpha (IκB-α) are involved in cerebral inflammation. However, the involvement of NF-κB and IκB-α in the protective effects of acupuncture on ischemic tolerance remains unknown. Objective • The study evaluated the hypothesis that acupuncture can exert a neuroprotective action in a rat model of middle cerebral artery occlusion (MCAO). Design • The rats were randomly divided into a normal group (N), a sham model group (SM), an MCAO model group (M), a sham acupuncture group (SA), and an acupuncture group (A). Setting • All of processes of this study were conducted at Hubei University of Chinese Medicine (Hubei Shang, China). Animals • The animals were 100 Sprague-Dawley rats, aged 3 mo. Intervention • Craniotomy and electrocoagulation of the middle cerebral artery were conducted to generate acute, focal, cerebral ischemic models in 3 groups, excluding the N and SM groups. The SM group received a surgical fenestration similar to the M group, but the procedure did not include the coagulation of the exposed artery. In the A group, acupuncture was administered at the acupoints Baihui (GV-20) and Renzhong (GV-26). In the SA group, sham acupuncture was performed at a depth of 5 mm at a position close to the left side of the GV-20 and GV-26 points. The N, M, and SM groups received neither the acupuncture nor the sham acupuncture treatment. Outcome Measures • The study (1) evaluated neurological function using the modified neurological severity score; (2) examined the ultrastructure; (3) assessed the infarct volume; (4) determined levels of serum

  9. The involvement of calcium in the protective and toxic (nonlinear) responses of rodent and human astroglial cells.

    PubMed

    Slamon, N Debbie; Mead, Carole; Morgan, Chris; Mitchell, Andy; Pentreath, Vic W

    2005-01-01

    associated with increased protective capacities) and toxic responses of C6 and 1321N1 cells to different chemical agents are associated with dose-dependent alterations in [Ca(2+)](i).

  10. Chiral N,N'-Dioxide-Scandium(III) Complex-Catalyzed Asymmetric Friedel-Crafts Alkylation Reaction of ortho-Hydroxybenzyl Alcohols with C3-Substituted N-Protected Indoles.

    PubMed

    Zheng, Jianfeng; Lin, Lili; Dai, Li; Yuan, Xiao; Liu, Xiaohua; Feng, Xiaoming

    2016-12-12

    The first Lewis acid catalyzed asymmetric Friedel-Crafts alkylation reaction of ortho-hydroxybenzyl alcohols with C3-substituted indoles is described. A chiral N,N'-dioxide Sc(OTf)3 complex served not only to promote formation of ortho-quinone methides (o-QMs) in situ but also induced the asymmetry of the reaction. This methodology enables a novel activation of ortho-hydroxybenzyl alcohols, thus affording the desired chiral diarylindol-2-ylmethanes in up to 99 % yield and 99 % ee. A range of functional groups were also tolerated under the mild reaction conditions. Moreover, this strategy gives concise access to enantioenriched indole-fused benzoxocines.

  11. Ginseng protects rodent hearts from acute myocardial ischemia-reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism.

    PubMed

    Zhou, Hua; Hou, Shao Zhen; Luo, Pei; Zeng, Bao; Wang, Jing Rong; Wong, Yuen Fan; Jiang, Zhi Hong; Liu, Liang

    2011-05-17

    Ginseng (Panax ginseng C.A. Meyer) is widely used in Asian communities for treating cardiovascular diseases. However, the mechanism by which it protects the myocardium in ischemia-reperfusion (I/R) injury remains unclear. In this study, we aim to investigate whether a standardized ginseng extract (RSE) protects rodent hearts against I/R injury and if glucocorticoid and/or estrogen receptor-mediated activation of Akt and Erk1/2 (the reperfusion injury salvage kinase pathway, RISK) and subsequent nitric oxide (NO) synthesis signaling are involved in this effect. Rats or gene-deleted mice were subjected to 30 min ischemia by occluding the left anterior descending coronary artery and 90 min reperfusion. Infarct size, serum level of creatine kinase (CK), lactate dehydrogenase (LDH), and NO, expression and phosphorylation of glucocorticoid receptor (GR), estrogen receptor (ER), phosphatidylinositol-3 kinase (PI3K), Akt, NO synthase (NOS), extracellular signal-regulated kinase (Erk) 1/2, p38, and c-Jun NH2 terminal kinases (JNK) were examined in rat or mice treated with or without RSE in the absence or presence of pharmacological inhibitors. RSE significantly reduced infarct size in a dose-dependent manner and reduced the incidence of arrhythmia, increased serum NO production, reduced serum activities of creatine kinase and lactate dehydrogenase. The infarct size reduction effect of RSE was abolished by RU468 (an inhibitor of GR), tamoxifen (an inhibitor of ER), LY294002 (an inhibitor of PI3K), Akt inhibitor IV (an inhibitor of Akt protein kinase), U0126 (an inhibitor of Erk1/2) and NG-nitro-l-arginine methyl ester hydrochloride (an inhibitor of NOS), but not actinomycin D (an inhibitor of transcription process). RSE also significantly increased the activation of GR/ER, PI3K-Akt-eNOS cascades and Erk1/2 signaling in rat heart. However, RSE did not markedly reduce infarct size in endothelium NOS(-/-) mice. This differs from its effect in inducible NOS(-/-) and wild type

  12. Immunogenicity and Protective Efficacy of Brugia malayi Heavy Chain Myosin as Homologous DNA, Protein and Heterologous DNA/Protein Prime Boost Vaccine in Rodent Model

    PubMed Central

    Gupta, Jyoti; Pathak, Manisha; Misra, Sweta; Misra-Bhattacharya, Shailja

    2015-01-01

    We earlier demonstrated the immunoprophylactic efficacy of recombinant heavy chain myosin (Bm-Myo) of Brugia malayi (B. malayi) in rodent models. In the current study, further attempts have been made to improve this efficacy by employing alternate approaches such as homologous DNA (pcD-Myo) and heterologous DNA/protein prime boost (pcD-Myo+Bm-Myo) in BALB/c mouse model. The gene bm-myo was cloned in a mammalian expression vector pcDNA 3.1(+) and protein expression was confirmed in mammalian Vero cell line. A significant degree of protection (79.2%±2.32) against L3 challenge in pcD-Myo+Bm-Myo immunized group was observed which was much higher than that exerted by Bm-Myo (66.6%±2.23) and pcD-Myo (41.6%±2.45). In the heterologous immunized group, the percentage of peritoneal leukocytes such as macrophages, neutrophils, B cells and T cells marginally increased and their population augmented further significantly following L3 challenge. pcD-Myo+Bm-Myo immunization elicited robust cellular and humoral immune responses as compared to pcD-Myo and Bm-Myo groups as evidenced by an increased accumulation of CD4+, CD8+ T cells and CD19+ B cells in the mouse spleen and activation of peritoneal macrophages. Though immunized animals produced antigen-specific IgG antibodies and isotypes, sera of mice receiving pcD-Myo+Bm-Myo or Bm-Myo developed much higher antibody levels than other groups and there was profound antibody-dependent cellular adhesion and cytotoxicity (ADCC) to B. malayi infective larvae (L3). pcD-Myo+Bm-Myo as well as Bm-Myo mice generated a mixed T helper cell phenotype as evidenced by the production of both pro-inflammatory (IL-2, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines. Mice receiving pcD-Myo on contrary displayed a polarized pro-inflammatory immune response. The findings suggest that the priming of animals with DNA followed by protein booster generates heightened and mixed pro- and anti-inflammatory immune responses that are capable of providing

  13. Chemiluminescence of indole and its derivatives

    NASA Astrophysics Data System (ADS)

    Vasil'ev, Rostislav F.; Trofimov, A. V.; Tsaplev, Yuri B.

    2010-02-01

    The results of studies on chemiluminescence of indole and its derivatives are critically analyzed. It is shown that chemical transformations of indoles lead, depending on the structure and experimental conditions, to various electronically excited products and emission of light. Many reactions considered are used as a basis for highly sensitive methods for detection of indoles in biology, medicine, ecology and forensics.

  14. Commensal Bacteria-Dependent Indole Production Enhances Epithelial Barrier Function in the Colon

    PubMed Central

    Shimada, Yosuke; Kinoshita, Makoto; Harada, Kazuo; Mizutani, Masafumi; Masahata, Kazunori; Kayama, Hisako; Takeda, Kiyoshi

    2013-01-01

    Microbiota have been shown to have a great influence on functions of intestinal epithelial cells (ECs). The role of indole as a quorum-sensing (QS) molecule mediating intercellular signals in bacteria has been well appreciated. However, it remains unknown whether indole has beneficial effects on maintaining intestinal barriers in vivo. In this study, we analyzed the effect of indole on ECs using a germ free (GF) mouse model. GF mice showed decreased expression of junctional complex molecules in colonic ECs. The feces of specific pathogen-free (SPF) mice contained a high amount of indole; however the amount was significantly decreased in the feces of GF mice by 27-fold. Oral administration of indole-containing capsules resulted in increased expression of both tight junction (TJ)- and adherens junction (AJ)-associated molecules in colonic ECs in GF mice. In accordance with the increased expression of these junctional complex molecules, GF mice given indole-containing capsules showed higher resistance to dextran sodium sulfate (DSS)-induced colitis. A similar protective effect of indole on DSS-induced epithelial damage was also observed in mice bred in SPF conditions. These findings highlight the beneficial role of indole in establishing an epithelial barrier in vivo. PMID:24278294

  15. Evaluation of habitat requirements of small rodents and effectiveness of an ecologically-based management in a hantavirus-endemic natural protected area in Argentina.

    PubMed

    Vadell, María Victoria; García Erize, Francisco; Gómez Villafañe, Isabel Elisa

    2017-01-01

    Hantavirus pulmonary syndrome is a severe cardio pulmonary disease transmitted to humans by sylvan rodents found in natural and rural environments. Disease transmission is closely linked to the ecology of animal reservoirs and abiotic factors such as habitat characteristics, season or climatic conditions. The main goals of this research were: to determine the biotic and abiotic factors affecting richness and abundance of rodent species at different spatial scales, to evaluate different methodologies for studying population of small rodents, and to describe and analyze an ecologically-based rodent management experience in a highly touristic area. A 4-year study of small rodent ecology was conducted between April 2007 and August 2011 in the most relevant habitats of El Palmar National Park, Argentina. Management involved a wide range of control and prevention measures, including poisoning, culling and habitat modification. A total of 172 individuals of 5 species were captured with a trapping effort of 13 860 traps-nights (1.24 individuals/100 traps-nights). Five rodent species were captured, including 2 hantavirus-host species, Oligoryzomys nigripes and Akodon azarae. Oligoryzomys nigripes, host of a hantavirus that is pathogenic in humans, was the most abundant species and the only one found in all the studied habitats. Our results are inconsistent with the dilution effect hypothesis. The present study demonstrates that sylvan rodent species, including the hantavirus-host species, have distinct local habitat selection and temporal variation patterns in abundance, which may influence the risk of human exposure to hantavirus and may have practical implications for disease transmission as well as for reservoir management.

  16. Evidence for Personal Protective Measures to Reduce Human Contact With Blacklegged Ticks and for Environmentally Based Control Methods to Suppress Host-Seeking Blacklegged Ticks and Reduce Infection with Lyme Disease Spirochetes in Tick Vectors and Rodent Reservoirs.

    PubMed

    Eisen, Lars; Dolan, Marc C

    2016-07-20

    In the 1980s, the blacklegged tick, Ixodes scapularis Say, and rodents were recognized as the principal vector and reservoir hosts of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, and deer were incriminated as principal hosts for I. scapularis adults. These realizations led to pioneering studies aiming to reduce the risk for transmission of B. burgdorferi to humans by attacking host-seeking ticks with acaricides, interrupting the enzootic transmission cycle by killing immatures infesting rodent reservoirs by means of acaricide-treated nesting material, or reducing deer abundance to suppress tick numbers. We review the progress over the past three decades in the fields of: 1) prevention of human-tick contact with repellents and permethrin-treated clothing, and 2) suppression of I. scapularis and disruption of enzootic B. burgdorferi transmission with environmentally based control methods. Personal protective measures include synthetic and natural product-based repellents that can be applied to skin and clothing, permethrin sprays for clothing and gear, and permethrin-treated clothing. A wide variety of approaches and products to suppress I. scapularis or disrupt enzootic B. burgdorferi transmission have emerged and been evaluated in field trials. Application of synthetic chemical acaricides is a robust method to suppress host-seeking I. scapularis ticks within a treated area for at least 6-8 wk. Natural product-based acaricides or entomopathogenic fungi have emerged as alternatives to kill host-seeking ticks for homeowners who are unwilling to use synthetic chemical acaricides. However, as compared with synthetic chemical acaricides, these approaches appear less robust in terms of both their killing efficacy and persistence. Use of rodent-targeted topical acaricides represents an alternative for homeowners opposed to open distribution of acaricides to the ground and vegetation on their properties. This host-targeted approach also

  17. Spot indole test: evaluation of four reagents.

    PubMed Central

    Miller, J M; Wright, J W

    1982-01-01

    Kovacs indole reagent, p-dimethylaminobenzaldehyde, Ehrlich indole reagent and p-dimethylaminocinnamaldehyde were used as spot indole reagents to test 359 strains of gram-negative rods growing on 5% sheep blood agar, Trypticase soy agar (BBL Microbiology Systems), and MacConkey agar. The p-dimethylaminocinnamaldehyde reagent was the most sensitive of those tested and provided results that were easiest to interpret. The p-dimethylaminocinnamaldehyde reagent was able to detect providencia alcalifaciens indole production because of the red-violet color unique to that organism. All reagents tested were accurate in detecting indole produced by members of the Enterobacteriaceae family, with the exception of P. alcalifaciens. PMID:7040458

  18. Hydroalcoholic extract from bark of Persea major (Meisn.) L.E. Kopp (Lauraceae) exerts antiulcer effects in rodents by the strengthening of the gastric protective factors.

    PubMed

    Somensi, Lincon Bordignon; Boeing, Thaise; Cury, Benhur Judah; Steimbach, Viviane Miranda Bispo; Niero, Rivaldo; de Souza, Lauro Mera; da Silva, Luisa Mota; de Andrade, Sérgio Faloni

    2017-09-14

    The Persea major (Meisn.) L.E. Kopp (Lauraceae) (botanical synonym: Persea pyrifolia (D. Don) Spreng, Persea pyrifolia Nees and Mart., Persea cordata var. major (Meisn.) Mez and Persea willdenovii Kosterm) is a medicinal plant native in the south of Brazil, where is popularly known as Pau de Andrade, Maçaranduba or Abacate-do-Mato. Its barks are commonly used to prepare an infusion which is administered orally or topically to treat ulcers and wounds, respectively. Thus, this study has been undertaken to contribute to the validation of the popular use of P. major to treat of ulcerative disorders from gastrointestinal system, using different experimental models in rodents. Firstly, ultra-performance liquid chromatography coupled to a mass spectrophotometer has been performed. Next, the potential gastroprotective of hydroalcoholic extract of P. major barks (HEPM) (30-300mg/kg) has been evaluated in ulcer models acute as: ethanol, ethanol/HCl and indomethacin-induced ulcer. The extract (300mg/kg) has been also tested in acetic acid-induced chronic ulcer model. Histological, toxicological, histochemical, oxidative stress and gastric secretion parameters were analyzed. The main compounds found in HEPM were polyphenols as condensed tannins, flavonoids heterosides derivatives from quercetin and kaempferol. HEPM (300mg/kg, p.o) prevented gastric lesions induced by ethanol or indomethacin in rats by 58.98% and 97.48%, respectively, compared to vehicle group (148.00±14.83mm(2) and 12.07±1.61mm(2), respectively). In acetic acid-induced chronic ulcer model the HEPM (300mg/kg, p.o) reduced the ulcer are by 40.58%, compared to vehicle group (127.90±12.04mm(2)). The healing effect was confirmed histologically, by an increase in mucin content and by the reduction in oxidative and inflammatory parameters at the ulcer site. Neither significant effect on gastric acid secretion nor toxicological effects and cytotoxicity were provoked by administration of HEPM. The results allows to

  19. Selective indole-based ECE inhibitors: synthesis and pharmacological evaluation.

    PubMed

    Brands, Michael; Ergüden, Jens-Kerim; Hashimoto, Kentaro; Heimbach, Dirk; Krahn, Thomas; Schröder, Christian; Siegel, Stephan; Stasch, Johannes-Peter; Tsujishita, Hideki; Weigand, Stefan; Yoshida, Nagahiro H

    2006-01-01

    Inhibition of the metalloprotease ECE-1 may be beneficial for the treatment of coronary heart disease, cancer, renal failure, and urological disorders. A novel class of indole-based ECE inhibitors was identified by high throughput screening. Optimization of the original screening lead structure 6 led to highly potent inhibitors such as 11, which bears a bisaryl amide moiety linked to the indole C2 position through an amide group. Docking of 11 into a model structure of ECE revealed a unique binding mode in which the Zn center of the enzyme is not directly addressed by the inhibitor, but key interactions are suggested for the central amide group. Testing of the lead compound 6 in hypertensive Dahl S rats resulted in a decrease in blood pressure after an initial period in which the blood pressure remained unchanged, most probably the result of ET-1 already present. Indole derivative 6 also displays a cardio-protective effect in a mouse model of acute myocardial infarction after oral administration. The more potent chloropyridine derivative 9 antagonizes big-ET-1-induced increase in blood pressure in rats at intravenous administration of 3 mg kg-1. All ECE inhibitors of the indole class showed high selectivity for ECE over related metalloproteases such as NEP and ACE. Therefore, these compounds might have further potential as drugs for the treatment of coronary heart diseases.

  20. Indolent palatal swelling: Catch 22

    PubMed Central

    Sharma, Preeti; Wadhwan, Vijay; Kumar, K. V. Arun; Venkatesh, Arvind; Thapa, Timsy

    2016-01-01

    We present an interesting but intriguing case of an indolent palatal swelling. The lesion was asymptomatic causing little discomfort to the patient and thus was an incidental clinical finding. Provisional diagnosis was a benign, minor salivary gland tumor. Clinical differential diagnoses included benign lymphoepithelial lesion or mucus extravasation phenomenon. Nevertheless, we also considered malignancies such as mucoepidermoid carcinoma, lymphoma, and neoplasm of the maxillary sinus. However, the histopathology revealed a rare clinicopathologic entity prompting immediate treatment of the lesion. PMID:28356700

  1. The glucosinolate breakdown product indole-3-carbinol acts as an auxin antagonist in roots of Arabidopsis thaliana.

    PubMed

    Katz, Ella; Nisani, Sophia; Yadav, Brijesh S; Woldemariam, Melkamu G; Shai, Ben; Obolski, Uri; Ehrlich, Marcelo; Shani, Eilon; Jander, Georg; Chamovitz, Daniel A

    2015-05-01

    The glucosinolate breakdown product indole-3-carbinol functions in cruciferous vegetables as a protective agent against foraging insects. While the toxic and deterrent effects of glucosinolate breakdown on herbivores and pathogens have been studied extensively, the secondary responses that are induced in the plant by indole-3-carbinol remain relatively uninvestigated. Here we examined the hypothesis that indole-3-carbinol plays a role in influencing plant growth and development by manipulating auxin signaling. We show that indole-3-carbinol rapidly and reversibly inhibits root elongation in a dose-dependent manner, and that this inhibition is accompanied by a loss of auxin activity in the root meristem. A direct interaction between indole-3-carbinol and the auxin perception machinery was suggested, as application of indole-3-carbinol rescues auxin-induced root phenotypes. In vitro and yeast-based protein interaction studies showed that indole-3-carbinol perturbs the auxin-dependent interaction of Transport Inhibitor Response (TIR1) with auxin/3-indoleacetic acid (Aux/IAAs) proteins, further supporting the possibility that indole-3-carbinol acts as an auxin antagonist. The results indicate that chemicals whose production is induced by herbivory, such as indole-3-carbinol, function not only to repel herbivores, but also as signaling molecules that directly compete with auxin to fine tune plant growth and development.

  2. Indole signaling and (micro)algal auxins decrease the virulence of Vibrio campbellii, a major pathogen of aquatic organisms.

    PubMed

    Yang, Qian; Pande, Gde Sasmita Julyantoro; Wang, Zheng; Lin, Baochuan; Rubin, Robert A; Vora, Gary J; Defoirdt, Tom

    2017-03-02

    Vibrios belonging to the Harveyi clade are major pathogens of marine vertebrates and invertebrates, causing major losses in wild and cultured organisms. Despite their significant impact, the pathogenicity mechanisms of these bacteria are not yet completely understood. In this study, we investigated the impact of indole signaling on the virulence of Vibrio campbellii. Elevated indole levels significantly decreased motility, biofilm formation, exopolysaccharide production and virulence to crustacean hosts. Indole furthermore inhibited the three-channel quorum sensing system of V. campbellii, a regulatory mechanism that is required for full virulence of the pathogen. Further, indole signaling was found to interact with the stress sigma factor RpoS. Together with our observations that energy-consuming processes (motility and bioluminescence) are downregulated, and microarray-based transcriptomics demonstrating that indole decreases the expression of genes involved in energy and amino acid metabolism, the data suggest that indole is a starvation signal in V. campbellii. Finally, we found that the auxins indole-3-acetic acid and indole-3-acetamide, which are produced by various (micro)algae sharing the aquatic environment with V. campbellii, have a similar effect as observed for indole. Auxins might therefore have a significant impact on the interactions between vibrios, (micro)algae and higher organisms, with major ecological and practical implications. This article is protected by copyright. All rights reserved.

  3. Rodents And Other Gnawers.

    ERIC Educational Resources Information Center

    Naturescope, 1986

    1986-01-01

    Presents information about rodents and lagomorphs, including definitions and the characteristics of these animals. Contains teaching activities such as "Habitats for Hoppers,""Cartoon Gnawers," and "The Great Rodent Expedition." Reproducible handouts for two of the activities are provided. (TW)

  4. Photoinduced charge separation in indole water clusters

    NASA Astrophysics Data System (ADS)

    Sobolewski, Andrzej L.; Domcke, Wolfgang

    2000-10-01

    Ab initio (RHF, MP2, CASSCF and CASPT2) calculations in the ground and the lowest excited singlet states have been performed for indole-water clusters. The calculations reveal a remarkable role of the lowest 1πσ∗ state in the photochemistry of these systems: indole in the 1πσ∗ state ejects an electron into the aqueous environment, leading to the formation of a charge-separated state. The computational results indicate that indole-water clusters are good models for the investigation of the mechanistic details of the electron solvation process occurring upon UV photoexcitation of indole and tryptophan in liquid water.

  5. Indole Alkaloids from Alocasia macrorrhiza.

    PubMed

    Zhu, Ling-Hua; Chen, Cheng; Wang, Hui; Ye, Wen-Cai; Zhou, Guang-Xiong

    2012-01-01

    Five new indole alkaloids, alocasins A-E (3-7), together with known hyrtiosin B (1) and hyrtiosulawesin (2) were isolated from Alocasia macrorrhiza (L.) SCHOTT; their structures were elucidated on the basis of spectroscopic data. Compounds 1-7 were in vitro tested for cytostatic activity on human throat cancer (Hep-2), human hepatocarcinoma (Hep-G2), and human nasopharyngeal carcinoma epithelial (CNE) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method; compounds 2, 3, 6 and 7 showed mild antiproliferative activity against Hep-2 and Hep-G2 whereas compounds 2 and 4 showed gentle antiproliferative activity against CNE.

  6. Rodent Research-1 Validation of Rodent Hardware

    NASA Technical Reports Server (NTRS)

    Globus, Ruth; Beegle, Janet

    2013-01-01

    To achieve novel science objectives, validation of a rodent habitat on ISS will enable - In-flight analyses during long duration spaceflight- Use of genetically altered animals- Application of modern analytical techniques (e.g. genomics, proteomics, and metabolomics)

  7. Halogenated Indole Alkaloids from Marine Invertebrates

    PubMed Central

    Pauletti, Patrícia Mendonça; Cintra, Lucas Silva; Braguine, Caio Guedes; da Silva Filho, Ademar Alves; Silva, Márcio Luís Andrade e; Cunha, Wilson Roberto; Januário, Ana Helena

    2010-01-01

    This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the 13C-NMR spectral data of these selected natural indole alkaloids is also provided. PMID:20559487

  8. Halogenated indole alkaloids from marine invertebrates.

    PubMed

    Pauletti, Patrícia Mendonça; Cintra, Lucas Silva; Braguine, Caio Guedes; da Silva Filho, Ademar Alves; Silva, Márcio Luís Andrade E; Cunha, Wilson Roberto; Januário, Ana Helena

    2010-04-28

    This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the (13)C-NMR spectral data of these selected natural indole alkaloids is also provided.

  9. Gait analysis methods for rodent models of osteoarthritis.

    PubMed

    Jacobs, Brittany Y; Kloefkorn, Heidi E; Allen, Kyle D

    2014-10-01

    Patients with osteoarthritis (OA) primarily seek treatment due to pain and disability, yet the primary endpoints for rodent OA models tend to be histological measures of joint destruction. The discrepancy between clinical and preclinical evaluations is problematic, given that radiographic evidence of OA in humans does not always correlate to the severity of patient-reported symptoms. Recent advances in behavioral analyses have provided new methods to evaluate disease sequelae in rodents. Of particular relevance to rodent OA models are methods to assess rodent gait. While obvious differences exist between quadrupedal and bipedal gait sequences, the gait abnormalities seen in humans and in rodent OA models reflect similar compensatory behaviors that protect an injured limb from loading. The purpose of this review is to describe these compensations and current methods used to assess rodent gait characteristics, while detailing important considerations for the selection of gait analysis methods in rodent OA models.

  10. Gait Analysis Methods for Rodent Models of Osteoarthritis

    PubMed Central

    Jacobs, Brittany Y.; Kloefkorn, Heidi E.; Allen, Kyle D.

    2014-01-01

    Patients with osteoarthritis (OA) primarily seek treatment due to pain and disability, yet the primary endpoints for rodent OA models tend to be histological measures of joint destruction. The discrepancy between clinical and preclinical evaluations is problematic, given that radiographic evidence of OA in humans does not always correlate to the severity of patient-reported symptoms. Recent advances in behavioral analyses have provided new methods to evaluate disease sequelae in rodents. Of particular relevance to rodent OA models are methods to assess rodent gait. While obvious differences exist between quadrupedal and bipedal gait sequences, the gait abnormalities seen in humans and in rodent OA models reflect similar compensatory behaviors that protect an injured limb from loading. The purpose of this review is to describe these compensations and current methods used to assess rodent gait characteristics, while detailing important considerations for the selection of gait analysis methods in rodent OA models. PMID:25160712

  11. Daily Movements and Microhabitat Selection of Hantavirus Reservoirs and Other Sigmodontinae Rodent Species that Inhabit a Protected Natural Area of Argentina.

    PubMed

    Maroli, Malena; Vadell, María Victoria; Iglesias, Ayelén; Padula, Paula Julieta; Gómez Villafañe, Isabel Elisa

    2015-09-01

    Abundance, distribution, movement patterns, and habitat selection of a reservoir species influence the dispersal of zoonotic pathogens, and hence, the risk for humans. Movements and microhabitat use of rodent species, and their potential role in the transmission of hantavirus were studied in Otamendi Natural Reserve, Buenos Aires, Argentina. Movement estimators and qualitative characteristics of rodent paths were determined by means of a spool and line device method. Sampling was conducted during November and December 2011, and March, April, June, October, and December 2012. Forty-six Oxymycterus rufus, 41 Akodon azarae, 10 Scapteromys aquaticus and 5 Oligoryzomys flavescens were captured. Movement patterns and distances varied according to sex, habitat type, reproductive season, and body size among species. O. flavescens, reservoir of the etiologic agent of hantavirus pulmonary syndrome in the region, moved short distances, had the most linear paths and did not share paths with other species. A. azarae had an intermediate linearity index, its movements were longer in the highland grassland than in the lowland marsh and the salty grassland, and larger individuals traveled longer distances. O. rufus had the most tortuous paths and the males moved more during the non-breeding season. S. aquaticus movements were associated with habitat type with longer distances traveled in the lowland marsh than in the salty grassland. Hantavirus antibodies were detected in 20% of A. azarae and were not detected in any other species. Seropositive individuals were captured during the breeding season and 85% of them were males. A. azarae moved randomly and shared paths with all the other species, which could promote hantavirus spillover events.

  12. Pharmacological activation of the pyruvate dehydrogenase complex reduces statin-mediated upregulation of FOXO gene targets and protects against statin myopathy in rodents.

    PubMed

    Mallinson, Joanne E; Constantin-Teodosiu, Dumitru; Glaves, Philip D; Martin, Elizabeth A; Davies, Wendy J; Westwood, F Russell; Sidaway, James E; Greenhaff, Paul L

    2012-12-15

    We previously reported that statin myopathy is associated with impaired carbohydrate (CHO) oxidation in fast-twitch rodent skeletal muscle, which we hypothesised occurred as a result of forkhead box protein O1 (FOXO1) mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) gene transcription. Upregulation of FOXO gene targets known to regulate proteasomal and lysosomal muscle protein breakdown was also evident. We hypothesised that increasing CHO oxidation in vivo, using the pyruvate dehydrogenase complex (PDC) activator, dichloroacetate (DCA), would blunt activation of FOXO gene targets and reduce statin myopathy. Female Wistar Hanover rats were dosed daily for 12 days (oral gavage) with either vehicle (control, 0.5% w/v hydroxypropyl-methylcellulose 0.1% w/v polysorbate-80; n = 9), 88 mg( )kg(-1) day(-1) simvastatin (n = 8), 88 mg( )kg(-1) day(-1) simvastatin + 30 mg kg(-1) day(-1) DCA (n = 9) or 88 mg kg(-1) day(-1) simvastatin + 40 mg kg(-1) day(-1) DCA (n = 9). Compared with control, simvastatin reduced body mass gain and food intake, increased muscle fibre necrosis, plasma creatine kinase levels, muscle PDK4, muscle atrophy F-box (MAFbx) and cathepsin-L mRNA expression, increased PDK4 protein expression, and proteasome and cathepsin-L activity, and reduced muscle PDC activity. Simvastatin with DCA maintained body mass gain and food intake, abrogated the myopathy, decreased muscle PDK4 mRNA and protein, MAFbx and cathepsin-L mRNA, increased activity of PDC and reduced proteasome activity compared with simvastatin. PDC activation abolished statin myopathy in rodent skeletal muscle, which occurred at least in part via inhibition of FOXO-mediated transcription of genes regulating muscle CHO utilisation and protein breakdown.

  13. Indole alkaloids from Geissospermum reticulatum.

    PubMed

    Reina, M; Ruiz-Mesia, W; López-Rodríguez, M; Ruiz-Mesia, L; González-Coloma, A; Martínez-Díaz, R

    2012-05-25

    Ten indole alkaloids were isolated from Geissospermum reticulatum, seven (1-7) from the leaves and three (8-10) from the bark. Seven were aspidospermatan-type alkaloids (1-3, 5-9), including four (5-8) with a 1-oxa-3-cyclopentene group in their molecule, which we named geissospermidine subtype. Compounds 1-3, 5-8, and 10 had not been reported previously as natural products, while 4 and 9 were the known alkaloids O-demethylaspidospermine and flavopereirine. Their structures were determined by spectroscopic techniques including 1D and 2D NMR experiments (COSY, NOESY, HSQC, HMBC). Additionally, X-ray crystallographic analyses of 1, 2, and 6 were performed. Antiparasitic activities of the ethanolic and alkaloidal extracts and of the pure alkaloids were tested against Trypanosoma cruzi and Leishmania infantum. In general, the extracts exhibited selective action and were more active against Leishmania than against Trypanosoma. Alkaloid 4 was also very active against L. infantum.

  14. Gas Chromatographic Analysis of Acidic Indole Auxins in Nicotiana1

    PubMed Central

    Bayer, Margret H.

    1969-01-01

    Acidic indole auxins have been extracted from N. glauca, N. langsdorffii and their 2 tumor-prone 4n- and 2n-hybrids. After purification of the extracts and thin-layer chromatography, acidic indoles were subjected to esterification and gas chromatography. The esters of 4 indole acids were detected and determined: indole-3-acetic acid, indole-3-carboxylic acid, indole-3-propionic acid and indole-3-butyric acid. The indolic nature of fractionated samples was confirmed by spectrophotofluorometry and the physiological significance of the indole esters proven in a biotest. A substantial increase in extractable indole-3-butyric acid in the tumor-prone hybrids suggests an additional pathway of auxin synthesis in these tissues. PMID:5774173

  15. Detoxification of Indole by an Indole-Induced Flavoprotein Oxygenase from Acinetobacter baumannii

    PubMed Central

    Lin, Guang-Huey; Chen, Hao-Ping; Shu, Hung-Yu

    2015-01-01

    Indole, a derivative of the amino acid tryptophan, is a toxic signaling molecule, which can inhibit bacterial growth. To overcome indole-induced toxicity, many bacteria have developed enzymatic defense systems to convert indole to non-toxic, water-insoluble indigo. We previously demonstrated that, like other aromatic compound-degrading bacteria, Acinetobacter baumannii can also convert indole to indigo. However, no work has been published investigating this mechanism. Here, we have shown that the growth of wild-type A. baumannii is severely inhibited in the presence of 3.5 mM indole. However, at lower concentrations, growth is stable, implying that the bacteria may be utilizing a survival mechanism to oxidize indole. To this end, we have identified a flavoprotein oxygenase encoded by the iifC gene of A. baumannii. Further, our results suggest that expressing this recombinant oxygenase protein in Escherichia coli can drive indole oxidation to indigo in vitro. Genome analysis shows that the iif operon is exclusively present in the genomes of A. baumannii and Pseudomonas syringae pv. actinidiae. Quantitative PCR and Western blot analysis also indicate that the iif operon is activated by indole through the AraC-like transcriptional regulator IifR. Taken together, these data suggest that this species of bacteria utilizes a novel indole-detoxification mechanism that is modulated by IifC, a protein that appears to be, at least to some extent, regulated by IifR. PMID:26390211

  16. Evaluation of Two Spot-Indole Reagents

    PubMed Central

    Lowrance, B. L.; Reich, P.; Traub, W. H.

    1969-01-01

    Two spot-indole reagents, p-dimethylaminobenzaldehyde (DMABA) and p-dimethylaminocinnamaldehyde, were evaluated quantitatively. Although fourfold less sensitive, DMABA proved to be more stable and economical. PMID:4894726

  17. A Herbal Composition of Semen Hoveniae, Radix Puerariae, and Fructus Schisandrae Shows Potent Protective Effects on Acute Alcoholic Intoxication in Rodent Models

    PubMed Central

    Xiong, Jie; Guo, Yu; Li, Lu-yi; Hu, Hang; Qu, Xin-lan; Sun, Xi-zhen; Liu, Sheng-hua; Wang, Hui

    2012-01-01

    This study is designed to evaluate the effects of a herbal composition of Semen Hoveniae, Radix Puerariae and Fructus Schisandrae (SRF) against acute alcoholic intoxication. The animals were treated with SRF extract (SRFE) for 14 days, and ethanol was conducted subsequent to the final treatment. The effects of SRFE on righting reflex, inebriety rates, kinetic parameters of blood ethanol and acetaldehyde were determined. In addition; levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the activities of cytochrome P450 2E1 (CYP2E1), selected antioxidative enzymes, and the contents of malonaldehyde (MDA) were measured. SRFE-pretreated rodents exhibited lower rates of intoxication, longer times to loss of righting reflex, and shortened times to recovery of righting reflex than in controls. The peak concentrations and area under the time-concentration curves were lower in the pretreated animals than in controls, which corresponded to higher levels of ADH and ALDH in both gastrointestines and livers of the SRFE-treated animals. The activities of CYP2E1 were lower in SRFE-pretreated animals, which also exhibited higher activities of some antioxidant enzymes and lower hepatic MDA levels. These findings suggest that the anti-inebriation effects of SRFE may involve inhibition of ethanol absorption, promotion of ethanol metabolism, and enhancing hepatic anti-oxidative functions. PMID:23118795

  18. Indole-3-thio­uronium nitrate

    PubMed Central

    Lutz, Martin; Spek, Anthony L.; van der Geer, Erwin P. L.; van Koten, Gerard; Klein Gebbink, Robertus J. M.

    2008-01-01

    In the title compound, C9H10N3S+·NO3 −, the indole ring system and the thiouronium group are nearly perpendicular, with a dihedral angle of 88.62 (6)°. Hydrogen bonding generates two-dimensional networks which are linked to each other via π stacking inter­actions of the indole groups [average inter-planar ring–ring distance of 3.449 (2) Å]. PMID:21200759

  19. Auditing laboratory rodent biosecurity programs.

    PubMed

    Porter, William P; Horn, Mandy J; Cooper, Dale M; Klein, Hilton J

    2013-10-22

    A rodent biosecurity program that includes periodic evaluation of procedures used in an institution's vivarium can be used to ensure that best practices are in place to prevent a microbial pathogen outbreak. As a result of an ongoing comprehensive biosecurity review within their North American and European production facilities, the authors developed a novel biosecurity auditing process and worksheet that could be useful in other animal care and use operations. The authors encourage other institutions to consider initiating similar audits of their biosecurity programs to protect the health of their laboratory animals.

  20. Indoles in edible members of the Cruciferae.

    PubMed

    Wall, M E; Taylor, H; Perera, P; Wani, M C

    1988-01-01

    Antimutagenic fractions from collards yielded indole-3-carboxaldehyde [4] and traces of indole-3-acetonitrile [2]. The compounds had no antimutagenic activity. An analytical procedure for various indoles in plants was developed based on reversed-phase hplc. The indoles studied included the 3-carbinol 1, the acetonitrile 2, the carboxaldehyde 4, the 3-carboxylic acid 5, and the 3-acetic acid 6. Many Cruciferae and non-Cruciferae were analyzed. The latter did not contain measurable quantities of these compounds. In the case of the Cruciferae--with the exception of collards, which consistently indicated the presence of the aldehyde 4--major indole found was the nitrile 2. Although a particularly careful search for the carbinol 1 was conducted, only trace levels were noted. A review of the literature indicates that the content and occurrence of this indole in plants have been heavily overestimated. Because of the low levels found in the Cruciferae, our studies indicate that the role of the compound as a dietary factor may be questionable.

  1. 1-[2-(4-Benzyloxyphenoxy)Ethyl]Imidazole inhibits monoamine oxidase B and protects against neuronal loss and behavioral impairment in rodent models of Parkinson's disease.

    PubMed

    Chung, Jin Yong; Lee, Ji Won; Ryu, Choon Ho; Min, Hye Kyung; Yoon, Yeo Jin; Lim, Mi Jung; Park, Cheol Hyoung

    2015-08-01

    Monoamine oxidase B (MAO-B) is well known as a therapeutic target for Parkinson's disease (PD). MAO-B inhibitors retain antiparkinsonism abilities to improve motor function and prevent neuronal loss by decreasing dopamine metabolism and oxidative stress in the brain. From the study to find novel antiparkinsonism drugs that can inhibit MAO-B activity, neuronal loss, and behavioral deficits in the mouse model of PD, we identified that 1-[2-(4-benzyloxyphenoxy)ethyl]imidazole (BPEI) or safinamide strongly and selectively inhibited MAO-B activities in a dose-dependent manner (IC50 of BPEI and safinamide for MAO-B were 0.016 and 0.0021 µM and for MAO-A were 70.0 and 370 µM, respectively). In ex vivo studies after an administration (30 mg/kg, i.p.) of BPEI or safinamide to normal mice, the MAO-B activity in the brain was reduced by up to 90.6% or 82.4% at 1.0 hr. BPEI (20 mg/kg, i.p.) or safinamide (20 mg/kg, i.p.) significantly reversed the behavioral impairments, dopamine levels in the striatum, and neuronal loss in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice compared with the MPTP-alone-treated group. In the 6-hydroxydopamine-induced PD rat model, behavioral improvement by levodopa sparing activity was observed in the BPEI- or safinamide-treated (20 mg/kg, i.p.) rats. Moreover, BPEI revealed additional curative activities for nonmotor symptoms of PD such as pain, anxiety, epilepsy, and depression in rodent disease models. Therefore, BPEI has broad therapeutic potential for treating motor symptoms via strong and selective inhibitory effects on MAO-B, with additional benefits for comorbid symptoms in PD. © 2015 Wiley Periodicals, Inc.

  2. ESP and ESM1 mediate indol-3-acetonitrile production from indol-3-ylmethyl glucosinolate in Arabidopsis.

    PubMed

    Burow, Meike; Zhang, Zhi-Yong; Ober, James A; Lambrix, Virginia M; Wittstock, Ute; Gershenzon, Jonathan; Kliebenstein, Daniel J

    2008-02-01

    Glucosinolates are plant secondary metabolites that act as direct defenses against insect herbivores and various pathogens. Recent analysis has shown that methionine-derived glucosinolates are hydrolyzed/activated into either nitriles or isothiocyanates depending upon the plants genotype at multiple loci. While it has been hypothesized that tryptophan-derived glucosinolates can be a source of indole-acetonitriles, it has not been explicitly shown if the same proteins control nitrile production from tryptophan-derived glucosinolates as from methionine-derived glucosinolates. In this report, we formally test if the proteins involved in controlling aliphatic glucosinolate hydrolysis during tissue disruption can control production of nitriles during indolic glucosinolate hydrolysis. We show that myrosinase is not sufficient for indol-3-acetonitrile production from indol-3-ylmethyl glucosinolate and requires the presence of functional epithospecifier protein in planta and in vitro to produce significant levels of indol-3-acetonitrile. This reaction is also controlled by the Epithiospecifier modifier 1 gene. Thus, like formation of nitriles from aliphatic glucosinolates, indol-3-acetonitrile production following tissue disruption is controlled by multiple loci raising the potential for complex regulation and fine tuning of indol-3-acetonitrile production from indol-3-ylmethyl glucosinolate.

  3. Indole Alkaloids from Marine Sources as Potential Leads against Infectious Diseases

    PubMed Central

    França, Paulo H. B.; Barbosa, Daniel P.; da Silva, Daniel L.; Ribeiro, Êurica A. N.; Santana, Antônio E. G.; Santos, Bárbara V. O.; Barbosa-Filho, José M.; Quintans, Jullyana S. S.; Barreto, Rosana S. S.; Quintans-Júnior, Lucindo J.; de Araújo-Júnior, João X.

    2014-01-01

    Indole alkaloids comprise a large and complex class of natural products found in a variety of marine sources. Infectious diseases remain a major threat to public health, and in the absence of long-term protective vaccines, the control of these infectious diseases is based on a small number of chemotherapeutic agents. Furthermore, the emerging resistance against these drugs makes it urgently necessary to discover and develop new, safe and, effective anti-infective agents. In this regard, the aim of this review is to highlight indole alkaloids from marine sources which have been shown to demonstrate activity against infectious diseases. PMID:24995289

  4. Activation of the Nrf2/HO-1 Antioxidant Pathway Contributes to the Protective Effects of Lycium Barbarum Polysaccharides in the Rodent Retina after Ischemia-Reperfusion-Induced Damage

    PubMed Central

    Chang, Raymond Chuen-Chung; So, Kwok-Fai; Brecha, Nicholas C.; Pu, Mingliang

    2014-01-01

    Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are protective to retina after ischemia-reperfusion (I/R). The antioxidant response element (ARE)–mediated antioxidant pathway plays an important role in maintaining the redox status of the retina. Heme oxygenase-1 (HO-1), combined with potent AREs in its promoter, is a highly effective therapeutic target for the protection against neurodegenerative diseases, including I/R-induced retinal damage. The aim of our present study was to investigate whether the protective effect of LBP after I/R damage was mediated via activation of the Nrf2/HO-1-antioxidant pathway in the retina. Retinal I/R was induced by an increase in intraocular pressure to 130 mm Hg for 60 minutes. Prior to the induction of ischemia, rats were orally treated with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week. For specific experiments, zinc protoporphyrin (ZnPP, 20 mg/kg), an HO-1 inhibitor, was intraperitoneally administered at 24 h prior to ischemia. The protective effects of LBP were evaluated by quantifying ganglion cell and amacrine cell survival, and by measuring cell apoptosis in the retinal layers. In addition, HO-1 expression was examined using Western blotting and immunofluorescence analyses. Cytosolic and nuclear Nrf2 was measured using immunofluorescent staining. LBP treatment significantly increased Nrf2 nuclear accumulation and HO-1 expression in the retina after I/R injury. Increased apoptosis and a decrease in the number of viable cells were observed in the ganglion cell layer (GCL) and inner nuclear layer (INL) in the I/R retina, which were reversed by LBP treatment. The HO-1 inhibitor, ZnPP, diminished the LBP treatment-induced protective effects in the retina after I/R. Taken together, these results suggested that LBP partially exerted its beneficial neuroprotective effects via the activation of Nrf2 and an increase in HO-1 protein expression. PMID:24400114

  5. Palladium(0)-Catalyzed Heteroarylation of 2- and 3-Indolylzinc Derivatives. An Efficient General Method for the Preparation of (2-Pyridyl)indoles and Their Application to Indole Alkaloid Synthesis.

    PubMed

    Amat, Mercedes; Hadida, Sabine; Pshenichnyi, Grigorii; Bosch, Joan

    1997-05-16

    Palladium(0)-catalyzed coupling of (1-(benzenesulfonyl)-2-indolyl)zinc chloride (1) and (1-(tert-butyldimethylsilyl)-3-indolyl)zinc chloride (6) with diversely substituted (alkyl, methoxy, methoxycarbonyl, nitro, hydroxy) 2-halopyridines gives the corresponding 2- and 3-(2-pyridyl)indoles [4 and 7 (or 8), respectively] in excellent yields. A series of other 3-(heteroaryl)indoles (pyrazinyl, furyl, thienyl, indolyl) have been similarly prepared from 6. The potential of some of these (2-pyridyl)indoles in alkaloid synthesis is demonstrated. Thus, from 2-(2-pyridyl)indole 4b, a new synthetic entry to the indolo[2,3-a]quinolizidine system, involving stereoselective hydrogenation of the pyridine ring with subsequent electrophilic cyclization upon the indole 3-position from an appropriately N(b)-substituted 2-(2-piperidyl)indole, is reported. For this purpose, Pummerer cyclizations have been extensively studied. Whereas the indole-unprotected sulfoxide 17 gives the corresponding indoloquinolizidine 19 in low yield and mainly undergoes an abnormal Pummerer cyclization that ultimately leads to sulfide 18, the N(a)-protected sulfoxides 24a and 24b afford the respective indoloquinolizidines 25a,b in 70% yield. On the other hand, the conversion of 3-(2-pyridyl)indole 8k into tetracyclic ketone 35 by stereoselective hydrogenation, followed by cyclization of the resulting all-cis-3-(2-piperidyl)indole 34, represents a formal synthesis of Strychnos alkaloids with the strychnan skeletal type (tubifoline, tubifolidine, 19,20-dihydroakuammicine). A similar conversion of 8j into nordasycarpidone constitutes a formal synthesis of the alkaloids of the uleine group. Reduction of nordasycarpidone leads to tetracycle 37, an advanced intermediate in a previous synthesis of tubotaiwine, a Strychnos alkaloid with the aspidospermatan skeletal type. Finally, piperidylindole 34 was transformed into tetracycle 41, an ABDE substructure of akuammiline alkaloids, by a sequence involving the

  6. Folic acid and soybean isoflavone combined supplementation protects the post-neural tube closure defects of rodents induced by cyclophosphamide in vivo and in vitro.

    PubMed

    Zhao, Haifeng; Liang, Jiang; Li, Xuemin; Yu, Huanling; Li, Xiuhua; Xiao, Rong

    2010-03-01

    To evaluate the neuroprotective effect of folic acid (FA) and soybean isoflavone (SIF) combined supplementation on the post-neural tube closure of rodents induced by cyclophosphamide (CPA) in vitro and in vivo, pregnant rats were randomly divided into control, model, solo-FA intervention, solo-SIF intervention and co-intervention of FA and SIF groups. Rats in solo-intervention groups and co-intervention group were treated with FA 0.7 mg/kg, SIF 160 mg/kg and FA 0.7 mg/kg+SIF 160 mg/kg at the duration of pregnancy, respectively. On the 13th day of gestation, control rats were given physiological saline and the other four groups were treated with CPA12.5mg/kg. On the 14th day of gestation, three rats selected randomly from every group were executed and the ultrastructure, DNA damage and the proteins expressions of Bcl-2, Bax and P53 on embryo brains were checked. The rest of the rats were executed on the 20th day, the frequency of neural tube closure defects and fetus' development indices were measured. In addition, T-SOD, MDA and NO in serum of the pregnant rats were checked. In vitro, the effect of FA and genistein on the apoptosis was determined. Compared with the model group, the malformation incidence was lower but fetus' development indices were higher in the combination treated group. The combination decreased the damage of CPA, such as damaged nuclear DNA, early apoptotic morphological changes, Bax and P53 expressions on embryo brains and in vivo. Furthermore, T-SOD activity in serum of the pregnant rats increased and the levels of MDA and NO decreased in the combined supplementation group. Our study indicates the neuroprotection of FA and SIF combined administration is superior to solo treatment. Decrease of DNA damage and neuron apoptosis involved in the mechanisms. Furthermore, the up-regulation of Bcl-2 and the down-regulation of Bax and P53 proteins also participate in the effect.

  7. Use of the dog as non-rodent test species in the safety testing schedule associated with the registration of crop and plant protection products (pesticides): present status.

    PubMed

    Box, Rainer J; Spielmann, Horst

    2005-11-01

    The results from a survey of the expert information that is publicly accessible on the use of the dog as test species during the regulatory evaluation of agricultural chemicals and pesticides are reported. Methods that are being used or considered in order to reduce the number of dogs used for this purpose are described. Regulatory evaluation aims at establishing threshold values for safe human exposure; it is based on no-observed-adverse-effect levels (NOELs) determined in animal studies. Current regulations require testing in two species, a rodent species (usually rat or mouse), and a non-rodent species (usually the dog). Subchronic (90-day) and chronic (12-month) repeated-dose feeding studies must be routinely conducted in dogs. This report first focuses on the results from a retrospective study analysing data on 216 pesticides kept on record by the Bundesinstitut für Risikobewertung, BfR (German Federal Institute for Risk Assessment), the competent regulatory authority in Germany. The study was sponsored and coordinated by SET, the German Foundation for the Promotion of Research on Replacement and Complementary Methods to Reduce Animal Testing (Stiftung zur Förderung der Erforschung von Ersatz-und Ergänzungsmethoden zur Einschränkung von Tierversuchen, Mainz) and conducted by the BfR. Since the data submitted for registration of a product is the property of the manufacturer, the study could only proceed with the collaboration of the German Association of Manufacturers of Agricultural Chemicals (Industrieverband Agrar, IVA). To ensure confidentiality, designated codes were used instead of the compounds' proper names when the study was published. The results support two major conclusions. The use of the dog for the testing of pesticides is indeed necessary because the dog has proved to be the most sensitive species for about 15% of the compounds examined. However, chronic studies are only of limited value since they only provide essential information that

  8. Indole-Diterpene Biosynthetic Capability of Epichloë Endophytes as Predicted by ltm Gene Analysis▿

    PubMed Central

    Young, Carolyn A.; Tapper, Brian A.; May, Kimberley; Moon, Christina D.; Schardl, Christopher L.; Scott, Barry

    2009-01-01

    Bioprotective alkaloids produced by Epichloë and closely related asexual Neotyphodium fungal endophytes protect their grass hosts from insect and mammalian herbivory. One class of these compounds, known for antimammalian toxicity, is the indole-diterpenes. The LTM locus of Neotyphodium lolii (Lp19) and Epichloë festuce (Fl1), required for the biosynthesis of the indole-diterpene lolitrem, consists of 10 ltm genes. We have used PCR and Southern analysis to screen a broad taxonomic range of 44 endophyte isolates to determine why indole-diterpenes are present in so few endophyte-grass associations in comparison to that of the other bioprotective alkaloids, which are more widespread among the endophtyes. All 10 ltm genes were present in only three epichloë endophytes. A predominance of the asexual Neotyphodium spp. examined contained 8 of the 10 ltm genes, with only one N. lolii containing the entire LTM locus and the ability to produce lolitrems. Liquid chromatography-tandem mass spectrometry profiles of indole-diterpenes from a subset of endophyte-infected perennial ryegrass showed that endophytes that contained functional genes present in ltm clusters 1 and 2 were capable of producing simple indole-diterpenes such as paspaline, 13-desoxypaxilline, and terpendoles, compounds predicted to be precursors of lolitrem B. Analysis of toxin biosynthesis genes by PCR now enables a diagnostic method to screen endophytes for both beneficial and detrimental alkaloids and can be used as a resource for screening isolates required for forage improvement. PMID:19181837

  9. Enzymic synthesis of 1-O-indol-3-ylacetyl-beta-D-glucose and indol-3-ylacetyl-myo-inositol.

    PubMed Central

    Michalczuk, L; Bandurski, R S

    1982-01-01

    An enzyme fraction from extracts of immature kernels of Zea mays catalyses the formation of 1-O-indol-3-ylacetyl-beta-D-glucose from indol-3-ylacetic acid and UDP-glucose. A second enzyme fraction catalyses the formation of indol-3-ylacetyl-myo-inositol from 1-O-indol-3-ylacetyl-beta-D-glucose and myo-inositol. To our knowledge, this is the first example of hydroxy-group acylation by a 1-O-acyl sugar. The following reaction sequence is proposed: Indol-3-ylacetic acid + UDP-glucose leads to indol-3-ylacetylglucose + UDP (1) Indol-3-ylacetylglucose + myo-inositol leads to indol-3-ylacetyl-myo-inositol + glucose (2) The enzyme catalysing reaction (1) is called UDP-glucose:indol-3-ylacetate glucosyl-transferase (indol-3-ylacetylglucose synthase), and that catalysing reaction (2) is indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (indol-3-ylacetyl-myo-inositol synthase). We further show that indol-3-ylacetylglucose synthase is specific for UDP-glucose and, at the stage of purity tested, the enzyme will use either indol-3-ylacetic acid or naphthalene-1-acetic acid, but not 2.4-dichlorophenoxyacetic acid, as glucose acceptor. The indol-3-ylacetyl-myo-inositol synthase is specific for indol-3-ylacetyl-glucose and will not use naphthalene-1-acetylglucose as substrate, and it is specific for myo-inositol among the alcohol acceptors tested. Thus, of the auxins tested, only indol-3-ylacetic acid forms the myo-inositol ester. PMID:6218801

  10. Development of oxidative stress by cytochrome P450 induction in rodents is selective for barbiturates and related to loss of pyridine nucleotide-dependent protective systems.

    PubMed

    Dostalek, Miroslav; Hardy, Klarissa D; Milne, Ginger L; Morrow, Jason D; Chen, Chi; Gonzalez, Frank J; Gu, Jun; Ding, Xinxin; Johnson, Delinda A; Johnson, Jeffrey A; Martin, Martha V; Guengerich, F Peter

    2008-06-20

    Reactive oxygen species (ROS) and oxidative stress have been considered in a variety of disease models, and cytochrome P450 (P450) enzymes have been suggested to be a source of ROS. Induction of P450s by phenobarbital (PB), beta-naphthoflavone (betaNF), or clofibrate in a mouse model increased ROS parameters in the isolated liver microsomes, but isoniazid treatment did not. However, when F(2)-isoprostanes (F(2)-IsoPs) were measured in tissues and urine, PB showed the strongest effect and betaNF had a measurable but weaker effect. The same trend was seen when an Nfr2-based transgene reporter sensitive to ROS was analyzed in the mice. This pattern had been seen earlier with F(2)-IsoPs both in vitro and in vivo with rats (Dostalek, M., Brooks, J. D., Hardy, K. D., Milne, G. L., Moore, M. M., Sharma, S., Morrow, J. D., and Guengerich, F. P. (2007) Mol. Pharmacol. 72, 1419-1424). One possibility for the general in vitro-in vivo discrepancy in oxidative stress found in both mice and rats is that PB treatment might attenuate protective systems. One potential candidate suggested by an mRNA microarray was nicotinamide N-methyltransferase. PB was found to elevate nicotinamide N-methyltransferase activity 3- to 4-fold in mice and rats and to attenuate levels of NAD(+), NADP(+), NADH, and NADPH in both species (20-40%), due to the enhanced excretion of (N-methyl)nicotinamide. PB also down-regulated glutathione peroxidase and glutathione reductase, which together constitute a key enzymatic system that uses NADPH in protecting against oxidative stress. These multiple effects on the protective systems are proposed to be more important than P450 induction in oxidative stress and emphasize the importance of studying in vivo models.

  11. Chronic stimulation of alpha-2A-adrenoceptors with guanfacine protects rodent prefrontal cortex dendritic spines and cognition from the effects of chronic stress

    PubMed Central

    Hains, Avis Brennan; Yabe, Yoko; Arnsten, Amy F.T.

    2015-01-01

    The prefrontal cortex (PFC) provides top-down regulation of behavior, cognition, and emotion, including spatial working memory. However, these PFC abilities are greatly impaired by exposure to acute or chronic stress. Chronic stress exposure in rats induces atrophy of PFC dendrites and spines that correlates with working memory impairment. As similar PFC grey matter loss appears to occur in mental illness, the mechanisms underlying these changes need to be better understood. Acute stress exposure impairs PFC cognition by activating feedforward cAMP-calcium- K+ channel signaling, which weakens synaptic inputs and reduces PFC neuronal firing. Spine loss with chronic stress has been shown to involve calcium-protein kinase C signaling, but it is not known if inhibiting cAMP signaling would similarly prevent the atrophy induced by repeated stress. The current study examined whether inhibiting cAMP signaling through alpha-2A-adrenoceptor stimulation with chronic guanfacine treatment would protect PFC spines and working memory performance during chronic stress exposure. Guanfacine was selected due to 1) its established effects on cAMP signaling at post-synaptic alpha-2A receptors on spines in PFC, and 2) its increasing clinical use for the treatment of pediatric stress disorders. Daily guanfacine treatment compared to vehicle control was found to prevent dendritic spine loss in layer II/III pyramidal neurons of prelimbic PFC in rats exposed to chronic restraint stress. Guanfacine also protected working memory performance; cognitive performance correlated with dendritic spine density. These findings suggest that chronic guanfacine use may have clinical utility by protecting PFC gray matter from the detrimental effects of stress. PMID:25664335

  12. In vitro protective effects of botryosphaeran, a (1→3;1→6)-β-d-glucan, against mutagens in normal and tumor rodent cells.

    PubMed

    Kerche-Silva, Leandra E; Cólus, Ilce M S; Malini, Maressa; Mori, Mateus Prates; Dekker, Robert F H; Barbosa-Dekker, Aneli M

    2017-02-01

    Botryosphaeran (BOT) is an exocellular β-d-glucan (carbohydrate biopolymer) of the (1→3;1→6)-linked type produced by Botryosphaeria rhodina MAMB-05. The cytotoxic, mutagenic, genotoxic, and protective effects of this substance were evaluated in Chinese hamster lung fibroblasts (V79) and rat hepatocarcinoma cells (HTC) by the micronucleus test (MN) and the comet assay. BOT was not genotoxic in either cell line; it decreased the clastogenic effects of doxorubicin, H2O2, and benzo[a]pyrene. These results indicate that BOT may have potential as a therapeutic agent. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Orthopox virus infections in Eurasian wild rodents.

    PubMed

    Kinnunen, Paula M; Henttonen, Heikki; Hoffmann, Bernd; Kallio, Eva R; Korthase, Christian; Laakkonen, Juha; Niemimaa, Jukka; Palva, Airi; Schlegel, Mathias; Ali, Hanan Sheikh; Suominen, Paula; Ulrich, Rainer G; Vaheri, Antti; Vapalahti, Olli

    2011-08-01

    The genus Orthopoxvirus includes variola (smallpox) virus and zoonotic cowpox virus (CPXV). All orthopoxviruses (OPV) are serologically cross-reactive and cross-protective, and after the cessation of smallpox vaccination, CPXV and other OPV infections represent an emerging threat to human health. In this respect CPXV, with its reservoir in asymptomatically infected wild rodents, is of special importance. In Europe, clinical cowpox has been diagnosed in both humans and animals. The main objective of this study was to elucidate the prevalence of OPV infections in wild rodents in different parts of Eurasia and to compare the performance of three real-time polymerase chain reaction (PCR) methods in detecting OPV DNA in wildlife samples. We investigated 962 wild rodents from Northern Europe (Finland), Central Europe (Germany), and Northern Asia (Siberia, Russia) for the presence of OPV antibodies. According to a CPXV antigen-based immunofluorescence assay, animals from 13 of the 17 locations (76%) showed antibodies. Mean seroprevalence was 33% in Finland (variation between locations 0%-69%), 32% in Germany (0%-43%), and 3.2% (0%-15%) in Siberia. We further screened tissue samples from 513 of the rodents for OPV DNA using up to three real-time PCRs. Three rodents from two German and one Finnish location were OPV DNA positive. The amplicons were 96% to 100% identical to available CPXV sequences. Further, we demonstrated OPV infections as far east as the Baikal region and occurring in hamster and two other rodent species, ones previously unnoticed as possible reservoir hosts. Based on serological and PCR findings, Eurasian wild rodents are frequently but nonpersistently infected with OPVs. Results from three real-time PCR methods were highly concordant. This study extends the geographic range and wildlife species diversity in which OPV (or CPXV) viruses are naturally circulating.

  14. The largest fossil rodent

    PubMed Central

    Rinderknecht, Andrés; Blanco, R. Ernesto

    2008-01-01

    The discovery of an exceptionally well-preserved skull permits the description of the new South American fossil species of the rodent, Josephoartigasia monesi sp. nov. (family: Dinomyidae; Rodentia: Hystricognathi: Caviomorpha). This species with estimated body mass of nearly 1000 kg is the largest yet recorded. The skull sheds new light on the anatomy of the extinct giant rodents of the Dinomyidae, which are known mostly from isolated teeth and incomplete mandible remains. The fossil derives from San José Formation, Uruguay, usually assigned to the Pliocene–Pleistocene (4–2 Myr ago), and the proposed palaeoenvironment where this rodent lived was characterized as an estuarine or deltaic system with forest communities. PMID:18198140

  15. The largest fossil rodent.

    PubMed

    Rinderknecht, Andrés; Blanco, R Ernesto

    2008-04-22

    The discovery of an exceptionally well-preserved skull permits the description of the new South American fossil species of the rodent, Josephoartigasia monesi sp. nov. (family: Dinomyidae; Rodentia: Hystricognathi: Caviomorpha). This species with estimated body mass of nearly 1000kg is the largest yet recorded. The skull sheds new light on the anatomy of the extinct giant rodents of the Dinomyidae, which are known mostly from isolated teeth and incomplete mandible remains. The fossil derives from San José Formation, Uruguay, usually assigned to the Pliocene-Pleistocene (4-2Myr ago), and the proposed palaeoenvironment where this rodent lived was characterized as an estuarine or deltaic system with forest communities.

  16. Indoles: Industrial, Agricultural and Over-the-Counter Uses

    NASA Astrophysics Data System (ADS)

    Barden, Timothy C.

    Indole-containing compounds are best known for their medicinal properties in the pharmaceutical industry. Although to a lesser degree, the indole motif none-the-less appears in many significant products across the entire chemical industry. This chapter describes the role that indole plays in a more commodity setting and provides examples illustrating these uses.

  17. Induced production of 1-methoxy-indol-3-ylmethyl glucosinolate by jasmonic acid and methyl jasmonate in sprouts and leaves of pak choi (Brassica rapa ssp. chinensis).

    PubMed

    Wiesner, Melanie; Hanschen, Franziska S; Schreiner, Monika; Glatt, Hansruedi; Zrenner, Rita

    2013-07-18

    Pak choi plants (Brassica rapa ssp. chinensis) were treated with different signaling molecules methyl jasmonate, jasmonic acid, linolenic acid, and methyl salicylate and were analyzed for specific changes in their glucosinolate profile. Glucosinolate levels were quantified using HPLC-DAD-UV, with focus on induction of indole glucosinolates and special emphasis on 1-methoxy-indol-3-ylmethyl glucosinolate. Furthermore, the effects of the different signaling molecules on indole glucosinolate accumulation were analyzed on the level of gene expression using semi-quantitative realtime RT-PCR of selected genes. The treatments with signaling molecules were performed on sprouts and mature leaves to determine ontogenetic differences in glucosinolate accumulation and related gene expression. The highest increase of indole glucosinolate levels, with considerable enhancement of the 1-methoxy-indol-3-ylmethyl glucosinolate content, was achieved with treatments of sprouts and mature leaves with methyl jasmonate and jasmonic acid. This increase was accompanied by increased expression of genes putatively involved in the indole glucosinolate biosynthetic pathway. The high levels of indole glucosinolates enabled the plant to preferentially produce the respective breakdown products after tissue damage. Thus, pak choi plants treated with methyl jasmonate or jasmonic acid, are a valuable tool to analyze the specific protection functions of 1-methoxy-indole-3-carbinole in the plants defense strategy in the future.

  18. Induced Production of 1-Methoxy-indol-3-ylmethyl Glucosinolate by Jasmonic Acid and Methyl Jasmonate in Sprouts and Leaves of Pak Choi (Brassica rapa ssp. chinensis)

    PubMed Central

    Wiesner, Melanie; Hanschen, Franziska S.; Schreiner, Monika; Glatt, Hansruedi; Zrenner, Rita

    2013-01-01

    Pak choi plants (Brassica rapa ssp. chinensis) were treated with different signaling molecules methyl jasmonate, jasmonic acid, linolenic acid, and methyl salicylate and were analyzed for specific changes in their glucosinolate profile. Glucosinolate levels were quantified using HPLC-DAD-UV, with focus on induction of indole glucosinolates and special emphasis on 1-methoxy-indol-3-ylmethyl glucosinolate. Furthermore, the effects of the different signaling molecules on indole glucosinolate accumulation were analyzed on the level of gene expression using semi-quantitative realtime RT-PCR of selected genes. The treatments with signaling molecules were performed on sprouts and mature leaves to determine ontogenetic differences in glucosinolate accumulation and related gene expression. The highest increase of indole glucosinolate levels, with considerable enhancement of the 1-methoxy-indol-3-ylmethyl glucosinolate content, was achieved with treatments of sprouts and mature leaves with methyl jasmonate and jasmonic acid. This increase was accompanied by increased expression of genes putatively involved in the indole glucosinolate biosynthetic pathway. The high levels of indole glucosinolates enabled the plant to preferentially produce the respective breakdown products after tissue damage. Thus, pak choi plants treated with methyl jasmonate or jasmonic acid, are a valuable tool to analyze the specific protection functions of 1-methoxy-indole-3-carbinole in the plants defense strategy in the future. PMID:23873294

  19. New indole alkaloid from Peschiera affinis (Apocynaceae).

    PubMed

    Santos, Allana Kellen L; Machado, Luciana L; Bizerra, Ayla Marcia C; Monte, Francisco José Q; Santiago, Gilvandete M P; Braz-Filho, Raimundo; Lemos, Telma L G

    2012-06-01

    A new indole alkaloid of the pyridocarbazole type, named 6N-hydroxy-olivacine, and two known compounds, 2N-oxide-olivacine and olivacine, were isolated from roots of Peschiera affinis. The structures of the compounds were determined by spectroscopic {IR and extensive NMR (COSY, HMQC, HMBCand NOESY)} and EIMS analysis.

  20. A new indole alkaloid from Alstonia scholaris.

    PubMed

    Jain, Luna; Pandey, M B; Singh, Sarita; Singh, A K; Pandey, V B

    2009-01-01

    A new indole alkaloid, N-formylscholarine, together with picrinine, strictamine and nareline has been isolated from the fruit pods of Alstonia scholaris, and their structures were established by various spectral data. This is the first report of these alkaloids in A. scholaris fruit pods.

  1. The Potential of Indole/Indolylquinoline Compounds in Tau Misfolding Reduction by Enhancement of HSPB1.

    PubMed

    Chang, Kuo-Hsuan; Lin, Chih-Hsin; Chen, Hsuan-Chiang; Huang, Hsin-Yu; Chen, Shu-Ling; Lin, Te-Hsien; Ramesh, Chintakunta; Huang, Chin-Chang; Fung, Hon-Chung; Wu, Yih-Ru; Huang, Hei-Jen; Lee-Chen, Guey-Jen; Hsieh-Li, Hsiu Mei; Yao, Ching-Fa

    2017-01-01

    Neurofibrillary tangles formed from tau misfolding have long been considered one of the pathological hallmarks of Alzheimer's disease (AD). The misfolding of tau in AD correlates with the clinical progression of AD and inhibition or reversal of tau misfolding may protect the affected neurons. We generated 293 and SH-SY5Y cells expressing DsRed-tagged pro-aggregation mutant of repeat domain of tau (ΔK280 tauRD ) to test indole/indolylquinoline derivatives for reducing tau misfolding and neuroprotection. Four of the 10 derivatives tested displayed good misfolding-inhibitory effects on Tet-On 293 cells. Among them, NC009-1 and NC009-7 enhanced heat-shock 27 kDa protein 1 (HSPB1) expression to increase ∆K280 tauRD -DsRed solubility and promoted neurite outgrowth in Tet-On SH-SY5Y cells. Knockdown of HSPB1 resulted in decreased ∆K280 tauRD -DsRed solubility and reduced neurite outgrowth, which were rescued by addition of NC009-1/NC009-7. Treatment with indole/indolylquinoline derivatives also improved neuronal cell viability and neurite outgrowth in mouse hippocampal primary culture under tau cytotoxicity. Our results demonstrate how indole/indolylquinoline derivatives are likely to work in tau misfolding reduction, providing insight into the possible working mechanism of indole and indolylquinoline derivatives in AD treatment. © 2016 John Wiley & Sons Ltd.

  2. Microdialysis in Rodents

    PubMed Central

    Zapata, Agustin; Chefer, Vladimir I.; Shippenberg, Toni S.

    2010-01-01

    Microdialysis is an in vivo sampling technique that permits the quantification of various substances (e.g., neurotransmitters, peptides, electrolytes) in blood and tissue. It is also used to infuse substances into the brain and spinal cord. This unit describes methods for the construction and stereotaxic implantation of microdialysis probes into discrete brain regions of the rat and mouse. Procedures for the conduct of conventional and quantitative microdialysis experiments in the awake and anesthetized rodent are also provided. PMID:19340813

  3. Indole Localization in an Explicit Bilayer Revealed via Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Norman, Kristen

    2005-11-01

    It is well known that the amino-acid tryptophan is particularly stable in the interfacial region of biological membranes, and this preference is a property of the tryptophan side-chain. Analogues of this side-chain, such as indole, strongly localize in the interfacial region, especially near the glycerol moiety of the lipids in the bilayer. Using molecular dynamics calculations, we determine the potential of mean force (PMF) for indoles in the bilayer. We compare the calculated PMF for indole with that of benzene to show that exclusion from the center of the lipid bilayer does not occur in all aromatics, but is strong in indoles. We find three minima in the PMF. Indole is most stabilized near the glycerol moiety. A weaker binding location is found near the choline groups of the lipid molecules. An even weaker binding side is found near the center of the lipid hydrocarbon core. Comparisions between uncharged, weakly charged, and highly charged indoles demonstrate that the exclusion is caused by the charge distribution on the indole rather than the ``lipo-phobic'' effect. High temperature simulations are used to determine the relative contribution of enthalpy and entropy to indole localization. The orientation of indole is found to be largely charge independent and is a strong function of depth within the bilayer. We find good agreement between simulated SCD order parameters for indole and experimentally determined order parameters.

  4. Indoles - A promising scaffold for drug development.

    PubMed

    Sravanthi, T V; Manju, S L

    2016-08-25

    Generally, heterocycles occupy a prominent place in chemistry due to their wide range of applications in the fields of drug design, photochemistry, agrochemicals, dyes and so on. Among them, indole scaffolds have been found in most of the important synthetic drug molecules and paved a faithful way to develop effective targets. Privileged structures bind to multiple receptors with high affinity, thus aiding the development of novel biologically active compounds. Among the indole class of compounds, 2-arylindoles appear to be a most promising lead for drug development. The derivatives of 2-arylindoles exhibits antibacterial, anticancer, anti-oxidants, anti-inflammatory, anti-diabetic, antiviral, antiproliferative, antituberculosis activity, etc. This article would provide a clear knowledge on the wide-ranging biological activities of 2-arylindoles over the past two decades, which would be beneficial for the designing of more potent drug targets in order to compete with the existing drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Obinutuzumab for the treatment of indolent lymphoma.

    PubMed

    Edelmann, Jennifer; Gribben, John G

    2016-08-01

    Obinutuzumab is a humanized, type II anti-CD20 monoclonal antibody designed for strong induction of direct cell death and antibody-dependent cell-mediated cytotoxicity. The Phase III GADOLIN trial tested the clinical efficacy of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy in rituximab-refractory indolent non-Hodgkin lymphoma versus treatment with bendamustine alone. It demonstrated significantly longer progression-free survival for the obinutuzumab-containing regimen in this difficult to treat patient group. Based on the results of this trial, US FDA approval was most recently granted for obinutuzumab in the treatment of follicular lymphoma that has relapsed after or was refractory to a rituximab-containing regimen. This article summarizes the available data on chemistry, pharmacokinetics, clinical efficacy and safety of obinutuzumab in the treatment of indolent non-Hodgkin lymphoma.

  6. Molecular Characterization of Indolent Prostate Cancer

    DTIC Science & Technology

    2016-12-01

    reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of...feature of all human cancers at different stages of disease progression, we hypothesized that RNA and DNA alterations characteristic of indolent...Following review of our progress on the tasks outlined in SOW, we communicated to CDMRP our intention to request EWOF. On October 15th, 2015, this project

  7. New indole alkaloids from Sarcocephalus latifolius.

    PubMed

    Abreu, P; Pereira, A

    2001-01-01

    Phytochemical investigation of the root extract of Sarcocephalus latifolius has led to the isolation of the new indole alkaloids 21-O-methylstrictosamide aglycone and 21-O-ethylstrictosamide aglycone, together with strictosamide, angustine, nauclefine, angustidine, angustoline, 19-O-ethylangustoline, naucleidinal, 19-epi-naucleidinal, quinovic acid-3 beta-O-beta-D-fucopyranoside, quinovic acid-3 beta-O-alpha-L-rhamnopyranoside, scopoletin, and beta-sitosterol. Strictosamide displayed moderate antiplasmodial activity against Plasmodium falciparum.

  8. Motility-indole-lysine-sulfide medium.

    PubMed

    Ederer, G M; Lund, M E; Blazevic, D J; Reller, L B; Mirrett, S

    1975-09-01

    A medium designed for the detection of motility, indole, lysine decarboxylase and deaminase reactions, and H2S production was devised and evaluated. Results, using 157 strains of enteric pathogens, were in agreement with reference methods. When 300 isolates from fecal cultures were screened using this medium, Shigella was easily differentiated from Escherichia and more of the Proteus species, especially P. morganii, could be eliminated from further study.

  9. Unique monoterpenoid indole alkaloids from Alstonia scholaris.

    PubMed

    Cai, Xiang-Hai; Du, Zhi-Zhi; Luo, Xiao-Dong

    2007-04-26

    [structure: see text] A pair of geometrically isomeric monoterpenoid indole alkaloids with a skeleton rearrangement and two additional carbons, named (19,20) E-alstoscholarine (1) and (19,20) Z-alstoscholarine (2), were obtained from the leaf extract of Alstonia scholaris. Their structures were elucidated on the basis of spectroscopic methods and then confirmed by X-ray crystal diffraction. The biogenesis of these compounds was also proposed.

  10. Microwave spectrum and molecular constants of indole

    NASA Astrophysics Data System (ADS)

    Nesvadba, Radim; Studecký, Tomáš; Uhlíková, Tereza; Urban, Štěpán

    2017-09-01

    Every single person has a certain characteristic group of scent molecules. The microwave spectra of the organic compounds of scent could be useful for the identification of people, but a database of spectra of scent molecules needs to be created first. The spectrum of indole, that is among the human scent molecules, was measured in the frequency range of 7.5-19 GHz under the conditions of supersonic expansion in a pulse emission Fourier Transform Microwave Spectrometer (FTMW) with a Fabry-Perot resonator. The high resolution of the spectrometer enables the detection of rotational transitions with hyperfine splitting. A total of 37 new rotational transitions were measured and analyzed using the PGOPHER software to derive the rotational and centrifugal distortion constants, as well as the 14N nuclear quadrupole coupling constants. The molecular constants were determined with approximately two orders of magnitude greater accuracy as compared with some earlier studies of indole. The obtained data and constants of indole are the first step towards the development of a database of the human scent molecules.

  11. Unprecedented Utilization of Pelargonidin and Indole for the Biosynthesis of Plant Indole Alkaloids.

    PubMed

    Warskulat, Anne-Christin; Tatsis, Evangelos C; Dudek, Bettina; Kai, Marco; Lorenz, Sybille; Schneider, Bernd

    2016-02-15

    Nudicaulins are a group of indole alkaloid glycosides responsible for the color of yellow petals of Papaver nudicaule (Iceland poppy). The unique aglycone scaffold of these alkaloids attracted our interest as one of the most unusual flavonoid-indole hybrid structures that occur in nature. Stable isotope labeling experiments with sliced petals identified free indole, but not tryptamine or l-tryptophan, as one of the two key biosynthetic precursors of the nudicaulin aglycone. Pelargonidin was identified as the second key precursor, contributing the polyphenolic unit to the nudicaulin molecule. This finding was inferred from the temporary accumulation of pelargonidin glycosides in the petals during flower bud development and a drop at the point in time when nudicaulin levels start to increase. The precursor-directed incorporation of cyanidin into a new 3'-hydroxynudicaulin strongly supports the hypothesis that anthocyanins are involved in the biosynthesis of nudicaulins.

  12. Unprecedented Utilization of Pelargonidin and Indole for the Biosynthesis of Plant Indole Alkaloids

    PubMed Central

    Warskulat, Anne‐Christin; Tatsis, Evangelos C.; Dudek, Bettina; Kai, Marco; Lorenz, Sybille

    2016-01-01

    Abstract Nudicaulins are a group of indole alkaloid glycosides responsible for the color of yellow petals of Papaver nudicaule (Iceland poppy). The unique aglycone scaffold of these alkaloids attracted our interest as one of the most unusual flavonoid‐indole hybrid structures that occur in nature. Stable isotope labeling experiments with sliced petals identified free indole, but not tryptamine or l‐tryptophan, as one of the two key biosynthetic precursors of the nudicaulin aglycone. Pelargonidin was identified as the second key precursor, contributing the polyphenolic unit to the nudicaulin molecule. This finding was inferred from the temporary accumulation of pelargonidin glycosides in the petals during flower bud development and a drop at the point in time when nudicaulin levels start to increase. The precursor‐directed incorporation of cyanidin into a new 3′‐hydroxynudicaulin strongly supports the hypothesis that anthocyanins are involved in the biosynthesis of nudicaulins. PMID:26670055

  13. Towards a facile and convenient synthesis of highly functionalized indole derivatives based on Multi-Component Reactions

    PubMed Central

    Neochoritis, Constantinos G.; Dömling, Alexander

    2014-01-01

    A library of potentially bioactive compounds through the novel 1H-indole-methyl-isocyanide and MCRs has been described. A flexible and efficient synthesis affording great complexity and diversity is achieved, with moderate to good yields with no need for protection and deprotection steps. PMID:24477767

  14. Rodent models of sleep apnea.

    PubMed

    Davis, Eric M; O'Donnell, Christopher P

    2013-09-15

    Rodent models of sleep apnea have long been used to provide novel insight into the generation and predisposition to apneas as well as to characterize the impact of sleep apnea on cardiovascular, metabolic, and psychological health in humans. Given the significant body of work utilizing rodent models in the field of sleep apnea, the aims of this review are three-fold: first, to review the use of rodents as natural models of sleep apnea; second, to provide an overview of the experimental interventions employed in rodents to simulate sleep apnea; third, to discuss the refinement of rodent models to further our understanding of breathing abnormalities that occur during sleep. Given mounting evidence that sleep apnea impairs cognitive function, reduces quality of life, and exacerbates the course of multiple chronic diseases, rodent models will remain a high priority as a tool to interrogate both the pathophysiology and sequelae of breathing related abnormalities during sleep and to improve approaches to diagnosis and therapy.

  15. Geomagnetic field detection in rodents

    SciTech Connect

    Olcese, J.; Reuss, S.; Semm, P.

    1988-01-01

    In addition to behavioral evidence for the detection of earth-strength magnetic fields (MF) by rodents, recent investigations have revealed that electrophysiological and biochemical responses to MF occur in the pineal organ and retina of rodents. In addition, ferrimagnetic deposits have been identified in the ethmoidal regions of the rodent skull. These findings point to a new sensory phenomenon, which interfaces with many fields of biology, including neuroscience, psychophysics, behavioral ecology, chronobiology and sensory physiology.

  16. Indole-3-acetic acid in plant-microbe interactions.

    PubMed

    Duca, Daiana; Lorv, Janet; Patten, Cheryl L; Rose, David; Glick, Bernard R

    2014-07-01

    Indole-3-acetic acid (IAA) is an important phytohormone with the capacity to control plant development in both beneficial and deleterious ways. The ability to synthesize IAA is an attribute that many bacteria including both plant growth-promoters and phytopathogens possess. There are three main pathways through which IAA is synthesized; the indole-3-pyruvic acid, indole-3-acetamide and indole-3-acetonitrile pathways. This chapter reviews the factors that effect the production of this phytohormone, the role of IAA in bacterial physiology and in plant-microbe interactions including phytostimulation and phytopathogenesis.

  17. Rodent carcinogens: Setting priorities

    SciTech Connect

    Gold, L.S.; Slone, T.H.; Stern, B.R.; Manley, N.B.; Ames, B.N. )

    1992-10-09

    The human diet contains an enormous background of natural chemicals, such as plant pesticides and the products of cooking, that have not been a focus of carcinogenicity testing. A broadened perspective that includes these natural chemicals is necessary. A comparison of possible hazards for 80 daily exposures to rodent carcinogens from a variety of sources is presented, using an index (HERP) that relates human exposure to carcinogenic potency in rodents. A similar ordering would be expected with the use of standard risk assessment methodology for the same human exposure values. Results indicate that, when viewed against the large background of naturally occurring carcinogens in typical portions of common foods, the residues of synthetic pesticides or environmental pollutants rank low. A similar result is obtained in a separate comparison of 32 average daily exposures to natural pesticides and synthetic pesticides residues in the diet. Although the findings do not indicate that these natural dietary carcinogens are important in human cancer, they cast doubt on the relative importance for human cancer of low-dose exposures to synthetic chemicals.

  18. Antitussive indole alkaloids from Kopsia hainanensis.

    PubMed

    Tan, Min-Jia; Yin, Chun; Tang, Chun-Ping; Ke, Chang-Qiang; Lin, Ge; Ye, Yang

    2011-06-01

    Three new indole alkaloids, named kopsihainins A-C (1-3), and two known compounds, kopsinine (4) and methyl demethoxycarbonylchanofruticosinate (5), were isolated from the stems of Kopsia hainanensis. Their structures were determined using extensive spectroscopic methods. The two main constituents 4 and 5 exhibited significant antitussive activity in a citric acid induced guinea pig cough model. The antitussive effect of 4 was demonstrated to interact with the δ-opioid receptor. This is the first report of antitussive effects of aspidofractinine type and chanofruticosinate type alkaloids. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Identification of New Metabolites of Bacterial Transformation of Indole by Gas Chromatography-Mass Spectrometry and High Performance Liquid Chromatography

    PubMed Central

    Arora, Pankaj Kumar

    2014-01-01

    Arthrobacter sp. SPG transformed indole completely in the presence of an additional carbon source. High performance liquid chromatography and gas chromatography-mass spectrometry detected indole-3-acetic acid, indole-3-glyoxylic acid, and indole-3-aldehyde as biotransformation products. This is the first report of the formation of indole-3-acetic acid, indole-3-glyoxylic acid, and indole-3-aldehyde from indole by any bacterium. PMID:25548566

  20. Aquaporins in desert rodent physiology.

    PubMed

    Pannabecker, Thomas L

    2015-08-01

    Desert rodents face a sizeable challenge in maintaining salt and water homeostasis due to their life in an arid environment. A number of their organ systems exhibit functional characteristics that limit water loss above that which occurs in non-desert species under similar conditions. These systems include renal, pulmonary, gastrointestinal, nasal, and skin epithelia. The desert rodent kidney preserves body water by producing a highly concentrated urine that reaches a maximum osmolality nearly three times that of the common laboratory rat. The precise mechanism by which urine is concentrated in any mammal is unknown. Insights into the process may be more apparent in species that produce highly concentrated urine. Aquaporin water channels play a fundamental role in water transport in several desert rodent organ systems. The role of aquaporins in facilitating highly effective water preservation in desert rodents is only beginning to be explored. The organ systems of desert rodents and their associated AQPs are described.

  1. Enzymic synthesis of indol-3-ylacetyl-myo-inositol galactoside.

    PubMed

    Corcuera, L J; Michalczuk, L; Bandurski, R S

    1982-11-01

    Extracts of immature kernels of Zea mays catalysed the synthesis of indol-3-ylacetyl-myo-inositol galactoside from indol-3-ylacetyl-myo-inositol and UDP-galactose. Addition of 2-mercaptoethanol was required for stability of the catalytic activity during dialysis. The enzyme could be fractionated with (NH4)2SO4, and 55% of the activity was recovered in the 30-60%-saturation fraction. The product of the reaction contained radioactivity from UDP-[U-14C]galactose and was identified as indol-3-ylacetyl-myo-inositol galactoside by gas chromatography-mass spectrometry. Therefore a UDP-galactose:indol-3-ylacetyl-myo-inositol galactosyltransferase (indol-3-ylacetyl-myo-inositol galactoside synthase) is present in developing kernels of Zea mays. The description of this enzyme, together with the enzymes described in the accompanying paper [Michalczuk & Bandurski (1982) Biochem. J. 207, 273-281] for the synthesis of indol-3-ylacetylglucose and indol-3-ylacetyl-myo-inositol, now provides mechanisms for the biosynthesis of one-half of the low-molecular-weight esters of indol-3-ylacetic acid in Zea mays.

  2. Antifungal Indole Alkaloids from Winchia calophylla.

    PubMed

    Yang, Mei-Li; Chen, Jia; Sun, Meng; Zhang, Dong-Bo; Gao, Kun

    2016-05-01

    Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl-echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 µM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 µM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 µM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 µM, respectively.

  3. Chemoselective and Enantioselective Oxidation of Indoles Employing Aspartyl Peptide Catalysts

    PubMed Central

    Kolundzic, Filip; Noshi, Mohammad N.; Tjandra, Meiliana; Movassaghi, Mohammad; Miller, Scott J.

    2011-01-01

    Catalytic enantioselective indole oxidation is a process of particular relevance to the chemistry of complex alkaloids, as it has been implicated in their biosynthesis. In the context of synthetic methodology, catalytic enantioselective indole oxidation allows a rapid and biomimetic entry into several classes of alkaloid natural products. Despite this potentially high utility in the total synthesis, reports of catalytic enantioselective indole oxidation remain sparse. Here we report a highly chemoselective catalytic system for the indole oxidation that delivers 3-hydroxy-indolenines with good chemical yields and moderate to high levels of enantio- and diastereoselectivity (up to 95:5 er and up to 92:8 dr. These results represent, to our knowledge, the most selective values yet reported in the literature for catalytic asymmetric indole oxidation). Furthermore, the utility of enantioenriched hydroxy-indolenines in stereospecific rearrangements is demonstrated. PMID:21539386

  4. The gene controlling the indole glucosinolate modifier1 quantitative trait locus alters indole glucosinolate structures and aphid resistance in Arabidopsis.

    PubMed

    Pfalz, Marina; Vogel, Heiko; Kroymann, Juergen

    2009-03-01

    Glucosinolates are defensive secondary compounds that display large structural diversity in Arabidopsis thaliana and related plants. Much attention has been paid to variation in the biosynthesis of Met-derived aliphatic glucosinolates and its ecological consequences, but little is known about the genes that cause qualitative and quantitative differences in Trp-derived indole glucosinolates. We use a combination of quantitative trait locus (QTL) fine-mapping and microarray-based transcript profiling to identify CYP81F2 (At5g57220), encoding a cytochrome P450 monooxygenase, as the gene underlying Indole Glucosinolate Modifier1 (IGM1), a metabolic QTL for the accumulation of two modified indole glucosinolates, 4-hydroxy-indole-3-yl-methyl and 4-methoxy-indole-3-yl-methyl glucosinolate. We verify CYP81F2 function with two SALK T-DNA insertion lines and show that CYP81F2 catalyzes the conversion of indole-3-yl-methyl to 4-hydroxy-indole-3-yl-methyl glucosinolate. We further show that the IGM1 QTL is largely caused by differences in CYP81F2 expression, which results from a combination of cis- and trans-acting expression QTL different from known regulators of indole glucosinolate biosynthesis. Finally, we elucidate a potential function of CYP81F2 in plant-insect interactions and find that CYP81F2 contributes to defense against the green peach aphid (Myzus persicae) but not to resistance against herbivory by larvae from four lepidopteran species.

  5. The allometry of rodent intestines.

    PubMed

    Lovegrove, Barry G

    2010-06-01

    This study examined the allometry of the small intestine, caecum, colon and large intestine of rodents (n = 51) using a phylogenetically informed approach. Strong phylogenetic signal was detected in the data for the caecum, colon and large intestine, but not for the small intestine. Most of the phylogenetic signal could be attributed to clade effects associated with herbivorous versus omnivorous rodents. The herbivorous rodents have longer caecums, colons and large intestines, but their small intestines, with the exception of the desert otomyine rodents, are no different to those of omnivorous rodents. Desert otomyine rodents have significantly shorter small intestines than all other rodents, reflecting a possible habitat effect and providing a partial explanation for the low basal metabolic rates of small desert mammals. However, the desert otomyines do not have shorter colons or large intestines, challenging claims for adaptation to water retention in arid environments. Data for the Arvicolidae revealed significantly larger caecums and colons, and hence longer large intestines, with no compensatory reduction in the length of the small intestine, which may explain how the smallest mammalian herbivores manage to meet the demands of a very high mass-specific metabolic rate. This study provides phylogenetically corrected allometries suitable for future prediction testing.

  6. Oculoscopy in Rabbits and Rodents.

    PubMed

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2015-09-01

    Ophthalmic diseases are common in rabbits and rodents. Fast and definitive diagnosis is imperative for successful treatment of ocular diseases. Ophthalmic examination in rabbits and rodents can be challenging. Oculoscopy offers great magnification for the examination of the ocular structures in such animals, including the evaluation of cornea, anterior eye chamber, limbus, iris, lens, and retina. To date, oculoscopy has been described only sporadically and/or under experimental conditions. This article describes the oculoscopy technique, normal and abnormal ocular findings, and the most common eye disorders diagnosed with the aid of endoscopy in rabbits and rodents.

  7. Astronaut Norman Thagard changes tray in RAHF for rodents

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Astronaut Norman Thagard changes a tray in the research animal holding facility (RAHF) for rodents at the Ames double rack facility aboard the Spacelab 3 science module in the cargo bay of the shuttle Challenger. Lending a hand is payload specialist Lodewijk van den Berg. Both men are wearing protective clothing and surgical masks for this procedure.

  8. Astronaut Norman Thagard changes tray in RAHF for rodents

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Astronaut Norman Thagard changes a tray in the research animal holding facility (RAHF) for rodents at the Ames double rack facility aboard the Spacelab 3 science module in the cargo bay of the shuttle Challenger. Lending a hand is payload specialist Lodewijk van den Berg. Both men are wearing protective clothing and surgical masks for this procedure.

  9. C-2 selective arylation of indoles with heterogeneous nanopalladium and diaryliodonium salts.

    PubMed

    Malmgren, Joel; Nagendiran, Anuja; Tai, Cheuk-Wai; Bäckvall, Jan-E; Olofsson, Berit

    2014-10-13

    A simple and efficient method to prepare synthetically useful 2-arylindoles is presented, using a heterogeneous Pd catalyst and diaryliodonium salts in water under mild conditions. A remarkably low leaching of metal catalyst was observed under the applied conditions. The developed protocol is highly C-2 selective and tolerates structural variations both in the indole and in the diaryliodonium salt. Arylations of both N-H indoles and N-protected indoles with ortho-substituted, electron-rich, electron-deficient, or halogenated diaryliodonium salts were achieved to give the desired products in high to excellent isolated yields within 6 to 15 h at room temperature or 40 °C. © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of Creative Commons Attribution NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

  10. Indole and 7-hydroxyindole diminish Pseudomonas aeruginosa virulence.

    PubMed

    Lee, Jintae; Attila, Can; Cirillo, Suat L G; Cirillo, Jeffrey D; Wood, Thomas K

    2009-01-01

    Indole is an extracellular biofilm signal for Escherichia coli, and many bacterial oxygenases readily convert indole to various oxidized compounds including 7-hydroxyindole (7HI). Here we investigate the impact of indole and 7HI on Pseudomonas aeruginosa PAO1 virulence and quorum sensing (QS)-regulated phenotypes; this strain does not synthesize these compounds but degrades them rapidly. Indole and 7HI both altered extensively gene expression in a manner opposite that of acylhomoserine lactones; the most repressed genes encode the mexGHI-opmD multidrug efflux pump and genes involved in the synthesis of QS-regulated virulence factors including pyocyanin (phz operon), 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) signal (pqs operon), pyochelin (pch operon) and pyoverdine (pvd operon). Corroborating these microarray results, indole and 7HI decreased production of pyocyanin, rhamnolipid, PQS and pyoverdine and enhanced antibiotic resistance. In addition, indole affected the utilization of carbon, nitrogen and phosphorus, and 7HI abolished swarming motility. Furthermore, 7HI reduced pulmonary colonization of P. aeruginosa in guinea pigs and increased clearance in lungs. Hence, indole-related compounds have potential as a novel antivirulence approach for the recalcitrant pathogen P. aeruginosa.

  11. Glucose enhances indolic glucosinolate biosynthesis without reducing primary sulfur assimilation

    PubMed Central

    Miao, Huiying; Cai, Congxi; Wei, Jia; Huang, Jirong; Chang, Jiaqi; Qian, Hongmei; Zhang, Xin; Zhao, Yanting; Sun, Bo; Wang, Bingliang; Wang, Qiaomei

    2016-01-01

    The effect of glucose as a signaling molecule on induction of aliphatic glucosinolate biosynthesis was reported in our former study. Here, we further investigated the regulatory mechanism of indolic glucosinolate biosynthesis by glucose in Arabidopsis. Glucose exerted a positive influence on indolic glucosinolate biosynthesis, which was demonstrated by induced accumulation of indolic glucosinolates and enhanced expression of related genes upon glucose treatment. Genetic analysis revealed that MYB34 and MYB51 were crucial in maintaining the basal indolic glucosinolate accumulation, with MYB34 being pivotal in response to glucose signaling. The increased accumulation of indolic glucosinolates and mRNA levels of MYB34, MYB51, and MYB122 caused by glucose were inhibited in the gin2-1 mutant, suggesting an important role of HXK1 in glucose-mediated induction of indolic glucosinolate biosynthesis. In contrast to what was known on the function of ABI5 in glucose-mediated aliphatic glucosinolate biosynthesis, ABI5 was not required for glucose-induced indolic glucosinolate accumulation. In addition, our results also indicated that glucose-induced glucosinolate accumulation was due to enhanced sulfur assimilation instead of directed sulfur partitioning into glucosinolate biosynthesis. Thus, our data provide new insights into molecular mechanisms underlying glucose-regulated glucosinolate biosynthesis. PMID:27549907

  12. [Evaluation of antimicrobial activity of indol alkaloids].

    PubMed

    Rojas Hernández, N M

    1979-01-01

    In pursuing the study of the antimicrobial properties of alkaloids prepared from Cuban plants the activity of 10 indol alkaloids and 4 semisynthetic variables obtained from three plants--Catharanthus roseus G. Don., Vallesia antillana Wood and Ervatamia coronaria Staph, of the family Apocynaceae--growing in Cuba was assessed in vitro. The alkaloids and the variables used were catharantine, vindoline, vindolinine, perivine, reserpine, tabernaemontanine, tetrahydroalstonine, aparicine, vindolinic acid, reserpic acid and vindolininol. These were faced to 40 bacterial strains from the genera Salmonella, Shigella, Proteus, Escherichia, Pseudomonas, Staphylococcus and Corynebacterium as well as to fungi and yeasts from the genera Aspergillus, kCunnighamella, kCandida and Saccharomyces. The method involving cylindric sections in a double agar layer was applied and lectures were obtained at 24-48 hours of incubation at 25 degrees C for fungi and yeasts and 37 degrees C for bacteria. Inhibition zones are reported in millimeters.

  13. Strongly Acidic Auxin Indole-3-Methanesulfonic Acid

    PubMed Central

    Cohen, Jerry D.; Baldi, Bruce G.; Bialek, Krystyna

    1985-01-01

    A radiochemical synthesis is described for [14C]indole-3-methanesulfonic acid (IMS), a strongly acidic auxin analog. Techniques were developed for fractionation and purification of IMS using normal and reverse phase chromatography. In addition, the utility of both Fourier transform infrared spectrometry and fast atom bombardment mass spectrometry for analysis of IMS has been demonstrated. IMS was shown to be an active auxin, stimulating soybean hypocotyl elongation, bean first internode curvature, and ethylene production. IMS uptake by thin sections of soybean hypocotyl was essentially independent of solution pH and, when applied at a 100 micromolar concentration, IMS exhibited a basipetal polarity in its transport in both corn coleoptile and soybean hypocotyl sections. [14C]IMS should, therefore, be a useful compound to study fundamental processes related to the movement of auxins in plant tissues and organelles. PMID:16664007

  14. Electron attachment to indole and related molecules

    SciTech Connect

    Modelli, Alberto; Jones, Derek; Pshenichnyuk, Stanislav A.

    2013-11-14

    Gas-phase formation of temporary negative ion states via resonance attachment of low-energy (0–6 eV) electrons into vacant molecular orbitals of indoline (I), indene (II), indole (III), 2-methylen-1,3,3-trimethylindoline (IV), and 2,3,3-trimethyl-indolenine (V) was investigated for the first time by electron transmission spectroscopy (ETS). The description of their empty-level structures was supported by density functional theory and Hartree-Fock calculations, using empirically calibrated linear equations to scale the calculated virtual orbital energies. Dissociative electron attachment spectroscopy (DEAS) was used to measure the fragment anion yields generated through dissociative decay channels of the parent molecular anions of compounds I-V, detected with a mass filter as a function of the incident electron energy in the 0–14 eV energy range. The vertical and adiabatic electron affinities were evaluated at the B3LYP/6-31+G(d) level as the anion/neutral total energy difference. The same theoretical method is also used for evaluation of the thermodynamic energy thresholds for production of the negative fragments observed in the DEA spectra. The loss of a hydrogen atom from the parent molecular anion ([M-H]{sup −}) provides the most intense signal in compounds I-IV. The gas-phase DEAS data can provide support for biochemical reaction mechanisms in vivo involving initial hydrogen abstraction from the nitrogen atom of the indole moiety, present in a variety of biologically important molecules.

  15. Production of indole pigments by Candida glabrata.

    PubMed

    Mayser, Peter; Wenzel, Maja; Krämer, Hans-Joachim; Kindler, Bernhard L J; Spiteller, Peter; Haase, Gerhard

    2007-09-01

    When provided as the sole nitrogen source tryptophan induces the production of several indole alkaloids, e.g., pityriacitrin, malasseziaindole, pityriaanhydride and pityriarubin with proven biological activity in the lipophilic yeast Malassezia furfur. So far these pigments seem to have been unique and only produced by highly specialized basidiomycetal yeasts of the genus Malassezia. Having surprisingly observed a brown pigmented Candida glabrata isolate as a contaminant on such a pigment inducing culture plate, we systematically analyzed whether this ascomycetal yeast can also synthesize the respective pigments. Therefore, 30 Candida glabrata strains, including the ex-type strain CBS 138, were cultured for 2 weeks on a pigment-inducing medium containing L-tryptophan. This culture medium along with the resultant biomass was then extracted with ethyl acetate. The extracted pigments were separated into six fractions by column chromatography. Each of these fractions was subjected to thin-layer chromatography (TLC) on silica gel and yielded identical pigment bands comparable to those observed with M. furfur. In the case of strain CBS 138, the individual TLC zones were further purified by HPLC and structural analysis of the pure metabolites was performed by mass spectrometry and proton nuclear magnetic resonance ((1)H-NMR), thereby proving the presence of pityriacitrin, malassezia indole, pityriaanhydride and pityriarubin C. Since lineage divergence of Basidiomycota and Ascomycota occurred approximately 600 million years ago, our findings demonstrate that the complex underlying biochemical pathway has not been exclusively evolved in the highly adapted basidiomycetes yeast M. furfur, but instead seems to be rather fundamental and archaic. Therefore, further investigations on the potential biological properties and the genetic regulation of these metabolites are needed to elucidate their hitherto unknown functions.

  16. Rodent Empathy and Affective Neuroscience

    PubMed Central

    Panksepp, Jules B.; Lahvis, Garet P.

    2011-01-01

    In the past few years, several experimental studies have suggested that empathy occurs in the social lives of rodents. This indicates that rodent behavioral models can be developed in an attempt to elucidate the mechanistic substrates of empathy at levels that have heretofore been unavailable. For example, the finding that mice from certain inbred strains express behavioral and physiological responses to conspecific distress, while others do not, underscores that the genetic underpinnings of empathy are specifiable and that in the future they could be harnessed to develop new therapies for human psychosocial impairments. However, the advent of rodent models of empathy is met at the outset with a number of theoretical and semantic problems that are similar to those previously confronted by studies of empathy in humans. The distinct underlying components of empathy must be differentiated from one another and from lay usage of the term. The primary goal of this paper is to review a set of seminal studies that are directly relevant to developing a concept of empathy in rodents. We first consider some of the psychological phenomena that have been associated with empathy, and within this context, we consider the component processes, or endophenotypes of rodent empathy. We then review a series of recent experimental studies that demonstrate the capability of rodents to detect and respond to the affective state of their social partners. We focus primarily on experiments that examine how rodents share affective experiences of fear, but we also highlight how similar types of experimental paradigms can be utilized to evaluate the possibility that rodents share positive affective experiences. Taken together, these studies were inspired by Jaak Panksepp’s theory that all mammals are capable of felt affective experiences. PMID:21672550

  17. Rodent empathy and affective neuroscience.

    PubMed

    Panksepp, Jules B; Lahvis, Garet P

    2011-10-01

    In the past few years, several experimental studies have suggested that empathy occurs in the social lives of rodents. Thus, rodent behavioral models can now be developed to elucidate the mechanistic substrates of empathy at levels that have heretofore been unavailable. For example, the finding that mice from certain inbred strains express behavioral and physiological responses to conspecific distress, while others do not, underscores that the genetic underpinnings of empathy are specifiable and that they could be harnessed to develop new therapies for human psychosocial impairments. However, the advent of rodent models of empathy is met at the outset with a number of theoretical and semantic problems that are similar to those previously confronted by studies of empathy in humans. The distinct underlying components of empathy must be differentiated from one another and from lay usage of the term. The primary goal of this paper is to review a set of seminal studies that are directly relevant to developing a concept of empathy in rodents. We first consider some of the psychological phenomena that have been associated with empathy, and within this context, we consider the component processes, or endophenotypes of rodent empathy. We then review a series of recent experimental studies that demonstrate the capability of rodents to detect and respond to the affective state of their social partners. We focus primarily on experiments that examine how rodents share affective experiences of fear, but we also highlight how similar types of experimental paradigms can be utilized to evaluate the possibility that rodents share positive affective experiences. Taken together, these studies were inspired by Jaak Panksepp's theory that all mammals are capable of felt affective experiences.

  18. Effectiveness of rodent control and monitoring techniques for a montane rainforest

    USGS Publications Warehouse

    Nelson, Jay T.; Woodworth, Bethany L.; Fancy, Steven G.; Lindsey, Gerald D.; Tweed, Eric J.

    2002-01-01

    Introduced black (Rattus rattus) and Polynesian (R. exulans) rats are damaging to native birds, insects, and plants in island ecosystems. We controlled rodent populations in a montane rainforest on the island of Hawaii to determine feasibility, cost, and effectiveness of ground-based rodent control in a rugged, remote rainforest habitat. Treatment was conducted 1996-99, from January to April each year, using rodenticide bait stations and snap-traps. We monitored rodent numbers in 48-ha treatment and reference areas before, during, and after control. As indexed by presence of rat sign in tracking tunnels or census blocks, rodent control reduced rodent abundance 58-90% each year 1 month after treatment began. There was an influx of rats into the treatment area, as shown by higher than expected numbers of rats snap-trapped on the treatment perimeter. Rodent numbers recovered to approximate pretreatment levels by the beginning of the following treatment year. Coast of equipment and supplies for rodent control for the first year was about \\$7,000 for a 1-km2 grid. After the first year, cost decreased to about \\$2,000 for 1 km2 per year. Rodent control applied continuously for 4 months each year during the breeding season may be effective in protecting nesting forest birds, but will not provide protection to plants and invertebrates vulnerable to predation throughout the year, and it is not likely to protect avian food resources.

  19. Friedel-Crafts Hydroxyalkylation of Indoles Mediated by Trimethylsilyl Trifluoromethanesulfonate.

    PubMed

    Downey, C Wade; Poff, Christopher D; Nizinski, Alissa N

    2015-10-16

    Indoles and N-alkylindoles undergo Friedel-Crafts addition to aldehydes in the presence of trimethylsilyl trifluoromethanesulfonate and a trialkylamine to produce 3-(1-silyloxyalkyl)indoles. Neutralization of the reaction mixture with pyridine followed by deprotection under basic conditions with tetrabutylammonium fluoride provides the 1:1 adduct as the free alcohol. This method prevents spontaneous conversion of the desired products to the thermodynamically favored bisindolyl(aryl)methanes, a process typically observed when indoles are reacted with aldehydes under acidic conditions.

  20. The ethics of rodent control.

    PubMed

    Meerburg, Bastiaan G; Brom, Frans W A; Kijlstra, Aize

    2008-12-01

    Because western societies generally see animals as objects of moral concern, demands have been made on the way they are treated, e.g. during animal experimentation. In the case of rodent pests, however, inhumane control methods are often applied. This inconsistency in the human-animal relationship requires clarification. This paper analyses the criteria that must be met when judging the use of animals during experiments, and investigates whether these can be applied in rodent control. This is important, because, until now, animal welfare has been less of an issue in pest control: effectiveness, hygiene and cost efficiency have been leading principles. Two options are available to solve the inconsistency: the first is to abandon the criteria used in animal experimentation; the second is to apply these criteria to both animal experimentation and rodent control. This latter option implies that rodent control methods should not lead to intense pain or discomfort, and any discomfort should have a short duration and should allow escaped rodents to lead a natural life. Adherence to this option will, however, require a shift in the design of rodent control methods: effectiveness will no longer be the leading principle. It will have to share its position with animal welfare and humaneness.

  1. Translocation of radiolabeled indole-3-acetic acid and indole-3-acetyl-myo-inositol from kernel to shoot of Zea mays L

    NASA Technical Reports Server (NTRS)

    Chisnell, J. R.; Bandurski, R. S.

    1988-01-01

    Either 5-[3H]indole-3-acetic acid (IAA) or 5-[3H]indole-3-acetyl-myo-inositol was applied to the endosperm of kernels of dark-grown Zea mays seedlings. The distribution of total radioactivity, radiolabeled indole-3-acetic acid, and radiolabeled ester conjugated indole-3-acetic acid, in the shoots was then determined. Differences were found in the distribution and chemical form of the radiolabeled indole-3-acetic acid in the shoot depending upon whether 5-[3H]indole-3-acetic acid or 5-[3H]indole-3-acetyl-myo-inositol was applied to the endosperm. We demonstrated that indole-3-acetyl-myo-inositol applied to the endosperm provides both free and ester conjugated indole-3-acetic acid to the mesocotyl and coleoptile. Free indole-3-acetic acid applied to the endosperm supplies some of the indole-3-acetic acid in the mesocotyl but essentially no indole-3-acetic acid to the coleoptile or primary leaves. It is concluded that free IAA from the endosperm is not a source of IAA for the coleoptile. Neither radioactive indole-3-acetyl-myo-inositol nor IAA accumulates in the tip of the coleoptile or the mesocotyl node and thus these studies do not explain how the coleoptile tip controls the amount of IAA in the shoot.

  2. Translocation of radiolabeled indole-3-acetic acid and indole-3-acetyl-myo-inositol from kernel to shoot of Zea mays L

    NASA Technical Reports Server (NTRS)

    Chisnell, J. R.; Bandurski, R. S.

    1988-01-01

    Either 5-[3H]indole-3-acetic acid (IAA) or 5-[3H]indole-3-acetyl-myo-inositol was applied to the endosperm of kernels of dark-grown Zea mays seedlings. The distribution of total radioactivity, radiolabeled indole-3-acetic acid, and radiolabeled ester conjugated indole-3-acetic acid, in the shoots was then determined. Differences were found in the distribution and chemical form of the radiolabeled indole-3-acetic acid in the shoot depending upon whether 5-[3H]indole-3-acetic acid or 5-[3H]indole-3-acetyl-myo-inositol was applied to the endosperm. We demonstrated that indole-3-acetyl-myo-inositol applied to the endosperm provides both free and ester conjugated indole-3-acetic acid to the mesocotyl and coleoptile. Free indole-3-acetic acid applied to the endosperm supplies some of the indole-3-acetic acid in the mesocotyl but essentially no indole-3-acetic acid to the coleoptile or primary leaves. It is concluded that free IAA from the endosperm is not a source of IAA for the coleoptile. Neither radioactive indole-3-acetyl-myo-inositol nor IAA accumulates in the tip of the coleoptile or the mesocotyl node and thus these studies do not explain how the coleoptile tip controls the amount of IAA in the shoot.

  3. Oxidative Furan-to-Indole Rearrangement. Synthesis of 2-(2-Acylvinyl)indoles and Flinderole C Analogues.

    PubMed

    Makarov, Anton S; Merkushev, Anton A; Uchuskin, Maxim G; Trushkov, Igor V

    2016-05-06

    Oxidative rearrangement of 2-(2-aminobenzyl)furans affording 2-(2-acylvinyl)indoles in a stereocontrolled manner in good-to-excellent yields has been developed. Thus, (2-aminobenzyl)furans with electron-releasing alkoxy substituents in the phenyl group form only E-isomers of 2-(2-acylvinyl)indoles. Conversely, substrates without such substituents produce target products as Z-isomers exclusively. A short diastereoselective method for the transformation of the obtained 2-(2-acylvinyl)indoles into antimalarial bisindole alkaloid flinderole A-C analogues has been developed.

  4. Indole-3-Acetic Acid Biosynthesis in Colletotrichum gloeosporioides f. sp. aeschynomene

    PubMed Central

    Robinson, M.; Riov, J.; Sharon, A.

    1998-01-01

    We characterized the biosynthesis of indole-3-acetic acid by the mycoherbicide Colletotrichum gloeosporioides f. sp. aeschynomene. Auxin production was tryptophan dependent. Compounds from the indole-3-acetamide and indole-3-pyruvic acid pathways were detected in culture filtrates. Feeding experiments and in vitro assay confirmed the presence of both pathways. Indole-3-acetamide was the major pathway utilized by the fungus to produce indole-3-acetic acid in culture. PMID:9835603

  5. Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis

    PubMed Central

    Lee, Hyang-Yeol; Yerkes, Nancy; O’Connor, Sarah E.

    2009-01-01

    Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan and tryptamine derived natural product pathways. PMID:20064432

  6. Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis.

    PubMed

    Lee, Hyang-Yeol; Yerkes, Nancy; O'Connor, Sarah E

    2009-12-24

    Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor-directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan- and tryptamine-derived natural product pathways.

  7. Epidemiology, pathology and treatment of non-follicular indolent lymphomas.

    PubMed

    Landgren, Ola; Tilly, Hervé

    2008-01-01

    Non-follicular indolent subtypes of non-Hodgkin lymphoma (NHL), which include chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL) and marginal zone lymphomas (MZL), are a diverse group of disorders with different presenting features, behaviour patterns and treatment outcomes. Current knowledge of these subtypes is largely based on retrospective analyses. A precise diagnosis can be difficult to achieve, and specific diagnostic criteria are needed to more precisely define some of the rarer indolent tumors, such as nodal and splenic MZLs. Although some subtypes of NHL have a prolonged indolent course, with a good prognosis (e.g. SLL), others (e.g. nodal and splenic MZLs) can rapidly evolve into more aggressive subtypes. In asymptomatic patients, treatment may be deferred until the disease progresses and the patient becomes symptomatic. Universally accepted therapeutic guidelines do not exist, however, and carefully designed, prospective clinical studies are needed to further assess optimal therapeutic approaches for these indolent NHLs.

  8. Design and synthesis of hybrid cyclophanes containing thiophene and indole units via Grignard reaction, Fischer indolization and ring-closing metathesis as key steps

    PubMed Central

    2015-01-01

    Summary We demonstrate a new synthetic strategy to cyclophanes containing thiophene and indole moieties via Grignard addition, Fischer indolization and ring-closing metathesis as key steps. PMID:26425209

  9. The copper-catalyzed N-arylation of indoles.

    PubMed

    Antilla, Jon C; Klapars, Artis; Buchwald, Stephen L

    2002-10-02

    A general method for the N-arylation of indoles using catalysts derived from CuI and trans-1,2-cyclohexanediamine (1a), trans-N,N'-dimethyl-1,2-cyclohexanediamine (2a), or N,N'-dimethyl-ethylenediamine (3) is reported. N-Arylindoles can be produced in high yield from the coupling of an aryl iodide or aryl bromide with a variety of indoles.

  10. Serovars of Leptospira isolated from dogs and rodents.

    PubMed

    Suepaul, S M; Carrington, C V F; Campbell, M; Borde, G; Adesiyun, A A

    2010-07-01

    We determined the frequency of isolation of Leptospira from dogs and rodents, the serovars of Leptospira, and the clinical, gross and histological manifestations in dogs with leptospirosis in Trinidad. From dogs, samples of urine, blood and kidney were collected while only kidney and blood samples of trapped rodents were used. Isolates were cultured and serotyped using a panel of 23 international serovars and monoclonal antibodies. The risk factors for leptospirosis were also determined in owned dogs using a standard questionnaire. Of a total of 468 animals investigated for Leptospira, 70 (15.0%) were positive, comprising nine (18.0%) of 50 suspected canine leptospirosis cases, seven (3.4%) of 207 stray dogs and 54 (25.6%) of 211 rodents. The observation that rodents have a statistically (P<0.05, chi2) higher frequency of isolation emphasizes the importance of rodents as reservoirs of leptospirosis in the country. Copenhageni was the predominant serovar found in 100.0% (7/7), 33.3% (2/6) and 68.5% (37/54) of isolates from suspected canine leptospirosis cases, stray dogs and rodents, respectively. Serovars Icterohaemorrhagiae and Canicola, the two serovars present in the commercial vaccines used locally, were detected in one (1.5%) and zero (0.0%) isolates respectively of the 67 tested. Data provided suggest that the apparent vaccine failure may be a consequence of the fact that the predominant serovar (Copenhageni) detected in sick, apparently healthy dogs and in rodents is not contained in the vaccines used locally to protect dogs against canine leptospirosis.

  11. Indole and 7‐hydroxyindole diminish Pseudomonas aeruginosa virulence

    PubMed Central

    Lee, Jintae; Attila, Can; Cirillo, Suat L. G.; Cirillo, Jeffrey D.; Wood, Thomas K.

    2009-01-01

    Summary Indole is an extracellular biofilm signal for Escherichia coli, and many bacterial oxygenases readily convert indole to various oxidized compounds including 7‐hydroxyindole (7HI). Here we investigate the impact of indole and 7HI on Pseudomonas aeruginosa PAO1 virulence and quorum sensing (QS)‐regulated phenotypes; this strain does not synthesize these compounds but degrades them rapidly. Indole and 7HI both altered extensively gene expression in a manner opposite that of acylhomoserine lactones; the most repressed genes encode the mexGHI‐opmD multidrug efflux pump and genes involved in the synthesis of QS‐regulated virulence factors including pyocyanin (phz operon), 2‐heptyl‐3‐hydroxy‐4(1H)‐quinolone (PQS) signal (pqs operon), pyochelin (pch operon) and pyoverdine (pvd operon). Corroborating these microarray results, indole and 7HI decreased production of pyocyanin, rhamnolipid, PQS and pyoverdine and enhanced antibiotic resistance. In addition, indole affected the utilization of carbon, nitrogen and phosphorus, and 7HI abolished swarming motility. Furthermore, 7HI reduced pulmonary colonization of P. aeruginosa in guinea pigs and increased clearance in lungs. Hence, indole‐related compounds have potential as a novel antivirulence approach for the recalcitrant pathogen P. aeruginosa. PMID:21261883

  12. Photoreaction of indole-containing mycotoxins to fluorescent products.

    PubMed

    Maragos, C M

    2009-06-01

    Photochemical reaction of the non-fluorescent mycotoxin cyclopiazonic acid (CPA) to fluorescent products was recently reported. Because CPA contains an indole moiety, believed to contribute to the fluorescence, it was of interest to determine whether the effect might be more generally applicable to indole-containing mycotoxins. Three indole-containing tremorgens (penitrem A, paxilline, verruculogen) that have not previously been reported to be fluorescent were rendered fluorescent by exposure to ultraviolet light in a photoreactor. Naturally fluorescent ergot alkaloids, which also contain an indole-moiety, exhibited a diminished response after exposure. This suggests that the phenomenon may be most useful for detection of indole-containing tremorgens that are non-fluorescent, rather than for the enhancement of materials that are already fluorescent, such as the ergot alkaloids. The extent to which fluorescence enhancement was seen was strongly influenced by the reaction environment, in particular the solvent used and whether cyclodextrins were present. In an HPLC format, placement of the photoreactor post-column allowed for the fluorescence detection of penitrem A, paxilline, and verruculogen. The ability to photoreact indole-containing tremorgens and detect them by fluorescence may open up new avenues for detection of these mycotoxins alone or in combination.

  13. Indole: An evolutionarily conserved influencer of behavior across kingdoms.

    PubMed

    Tomberlin, Jeffery K; Crippen, Tawni L; Wu, Guoyao; Griffin, Ashleigh S; Wood, Thomas K; Kilner, Rebecca M

    2017-02-01

    Indole is a key environmental cue that is used by many organisms. Based on its biochemistry, we suggest indole is used so universally, and by such different organisms, because it derives from the metabolism of tryptophan, a resource essential for many species yet rare in nature. These properties make it a valuable, environmental cue for resources almost universally important for promoting fitness. We then describe how indole is used to coordinate actions within organisms, to influence the behavior of conspecifics and can even be used to change the behavior of species that belong to other kingdoms. Drawing on the evolutionary framework that has been developed for understanding animal communication, we show how this is diversely achieved by indole acting as a cue, a manipulative signal, and an honest signal, as well as how indole can be used synergistically to amplify information conveyed by other molecules. Clarifying these distinct functions of indole identifies patterns that transcend different kingdoms of organisms. © 2016 WILEY Periodicals, Inc.

  14. Friedel-Crafts Fluoroacetylation of Indoles with Fluorinated Acetic Acids for the Synthesis of Fluoromethyl Indol-3-yl Ketones under Catalyst- and Additive-Free Conditions.

    PubMed

    Yao, Shun-Jiang; Ren, Zhi-Hui; Wang, Yao-Yu; Guan, Zheng-Hui

    2016-05-20

    A simple and efficient protocol for the fluoroacetylation of indoles is reported. The reaction uses fluorinated acetic acids as the fluoroacetylation reagents to synthesize diverse fluoromethyl indol-3-yl ketones in good yields under catalyst- and additive-free conditions. In addition, the only byproduct is water in this transformation. The synthetic utility of this reaction was also demonstrated by the concise synthesis of α-(trifluoromethyl)(indol-3-yl)methanol and indole-3-carboxylic acid.

  15. UV-photoelectron spectroscopy of BN indoles: experimental and computational electronic structure analysis.

    PubMed

    Chrostowska, Anna; Xu, Senmiao; Mazière, Audrey; Boknevitz, Katherine; Li, Bo; Abbey, Eric R; Dargelos, Alain; Graciaa, Alain; Liu, Shih-Yuan

    2014-08-20

    We present a comprehensive electronic structure analysis of two BN isosteres of indole using a combined UV-photoelectron spectroscopy (UV-PES)/computational chemistry approach. Gas-phase He I photoelectron spectra of external BN indole I and fused BN indole II have been recorded, assessed by density functional theory calculations, and compared with natural indole. The first ionization energies of these indoles are natural indole (7.9 eV), external BN indole I (7.9 eV), and fused BN indole II (8.05 eV). The computationally determined molecular dipole moments are in the order: natural indole (2.177 D) > fused BN indole II (1.512 D) > external BN indole I (0.543 D). The λmax in the UV-vis absorption spectra are in the order: fused BN indole II (292 nm) > external BN indole I (282 nm) > natural indole (270 nm). The observed relative electrophilic aromatic substitution reactivity of the investigated indoles with dimethyliminium chloride as the electrophile is as follows: fused BN indole II > natural indole > external BN indole I, and this trend correlates with the π-orbital coefficient at the 3-position. Nucleus-independent chemical shifts calculations show that the introduction of boron into an aromatic 6π-electron system leads to a reduction in aromaticity, presumably due to a stronger bond localization. Trends and conclusions from BN isosteres of simple monocyclic aromatic systems such as benzene and toluene are not necessarily translated to the bicyclic indole core. Thus, electronic structure consequences resulting from BN/CC isosterism will need to be evaluated individually from system to system.

  16. Partial purification and characterization of indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (indoleacetic acid-inositol synthase)

    NASA Technical Reports Server (NTRS)

    Kesy, J. M.; Bandurski, R. S.

    1990-01-01

    A procedure is described for the purification of the enzyme indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (IAA-myo-inositol synthase). This enzyme catalyzes the transfer of indol-3-ylacetate from 1-0-indol-3-ylacetyl-beta-d-glucose to myo-inositol to form indol-3-ylacetyl-myo-inositol and glucose. A hexokinase or glucose oxidase based assay system is described. The enzyme has been purified approximately 16,000-fold, has an isoelectric point of pH 6.1 and yields three catalytically inactive bands upon acrylamide gel electrophoresis of the native protein. The enzyme shows maximum transferase activity with myo-inositol but shows some transferase activity with scyllo-inositol and myo-inosose-2. No transfer of IAA occurs with myo-inositol-d-galactopyranose, cyclohexanol, mannitol, or glycerol as acyl acceptor. The affinity of the enzyme for 1-0-indol-3-ylacetyl-beta-d-glucose is, Km = 30 micromolar, and for myo-inositol is, Km = 4 millimolar. The enzyme does not catalyze the exchange incorporation of glucose into IAA-glucose indicating the reaction mechanism involves binding of IAA glucose to the enzyme with subsequent hydrolytic cleavage of the acyl moiety by the hydroxyl of myo-inositol to form IAA myo-inositol ester.

  17. Partial purification and characterization of indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (indoleacetic acid-inositol synthase)

    NASA Technical Reports Server (NTRS)

    Kesy, J. M.; Bandurski, R. S.

    1990-01-01

    A procedure is described for the purification of the enzyme indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (IAA-myo-inositol synthase). This enzyme catalyzes the transfer of indol-3-ylacetate from 1-0-indol-3-ylacetyl-beta-d-glucose to myo-inositol to form indol-3-ylacetyl-myo-inositol and glucose. A hexokinase or glucose oxidase based assay system is described. The enzyme has been purified approximately 16,000-fold, has an isoelectric point of pH 6.1 and yields three catalytically inactive bands upon acrylamide gel electrophoresis of the native protein. The enzyme shows maximum transferase activity with myo-inositol but shows some transferase activity with scyllo-inositol and myo-inosose-2. No transfer of IAA occurs with myo-inositol-d-galactopyranose, cyclohexanol, mannitol, or glycerol as acyl acceptor. The affinity of the enzyme for 1-0-indol-3-ylacetyl-beta-d-glucose is, Km = 30 micromolar, and for myo-inositol is, Km = 4 millimolar. The enzyme does not catalyze the exchange incorporation of glucose into IAA-glucose indicating the reaction mechanism involves binding of IAA glucose to the enzyme with subsequent hydrolytic cleavage of the acyl moiety by the hydroxyl of myo-inositol to form IAA myo-inositol ester.

  18. Influence of the tryptophan-indole-IFNγ axis on human genital Chlamydia trachomatis infection: role of vaginal co-infections

    PubMed Central

    Aiyar, Ashok; Quayle, Alison J.; Buckner, Lyndsey R.; Sherchand, Shardulendra P.; Chang, Theresa L.; Zea, Arnold H.; Martin, David H.; Belland, Robert J.

    2014-01-01

    The natural history of genital Chlamydia trachomatis infections can vary widely; infections can spontaneously resolve but can also last from months to years, potentially progressing to cause significant pathology. The host and bacterial factors underlying this wide variation are not completely understood, but emphasize the bacterium's capacity to evade/adapt to the genital immune response, and/or exploit local environmental conditions to survive this immune response. IFNγ is considered to be a primary host protective cytokine against endocervical C. trachomatis infections. IFNγ acts by inducing the host enzyme indoleamine 2,3-dioxgenase, which catabolizes tryptophan, thereby depriving the bacterium of this essential amino acid. In vitro studies have revealed that tryptophan deprivation causes Chlamydia to enter a viable but non-infectious growth pattern that is termed a persistent growth form, characterized by a unique morphology and gene expression pattern. Provision of tryptophan can reactivate the bacterium to the normal developmental cycle. There is a significant difference in the capacity of ocular and genital C. trachomatis serovars to counter tryptophan deprivation. The latter uniquely encode a functional tryptophan synthase to synthesize tryptophan via indole salvage, should indole be available in the infection microenvironment. In vitro studies have confirmed the capacity of indole to mitigate the effects of IFNγ; it has been suggested that a perturbed vaginal microbiome may provide a source of indole in vivo. Consistent with this hypothesis, the microbiome associated with bacterial vaginosis includes species that encode a tryptophanase to produce indole. In this review, we discuss the natural history of genital chlamydial infections, morphological and molecular changes imposed by IFNγ on Chlamydia, and finally, the microenvironmental conditions associated with vaginal co-infections that can ameliorate the effects of IFNγ on C. trachomatis. PMID

  19. One-pot N-arylation of indoles directly from N-arylsulfonylindoles via consecutive deprotection and S(N)Ar Reactions with activated Aryl halides.

    PubMed

    Xu, Hui; Fan, Ling-Ling

    2009-03-01

    An efficient one-pot step by step t-BuOK-mediated procedure for the synthesis of N-arylindoles has been developed in moderate to good yields. The protocol involves the consecutive deprotection of N-arylsulfonylindoles as latent indoles and subsequent S(N)Ar reactions with activated aryl halides. This tandem reaction affords an efficient and convenient preparation of N-arylindoles that benefit from prior indoles protection by arylsulfonyl group, and can shorten a reaction sequence and improve synthetic efficiency.

  20. Ruthenium(II)-Catalyzed C-H Activation of Imidamides and Divergent Couplings with Diazo Compounds: Substrate-Controlled Synthesis of Indoles and 3H-Indoles.

    PubMed

    Li, Yunyun; Qi, Zisong; Wang, He; Yang, Xifa; Li, Xingwei

    2016-09-19

    Indoles are an important structural motif that is commonly found in biologically active molecules. In this work, conditions for divergent couplings between imidamides and acceptor-acceptor diazo compounds were developed that afforded NH indoles and 3H-indoles under ruthenium catalysis. The coupling of α-diazoketoesters afforded NH indoles by cleavage of the C(N2 )-C(acyl) bond whereas α-diazomalonates gave 3H-indoles by C-N bond cleavage. This reaction constitutes the first intermolecular coupling of diazo substrates with arenes by ruthenium-catalyzed C-H activation.

  1. Low-Dose Radiotherapy in Indolent Lymphoma

    SciTech Connect

    Rossier, Christine; Schick, Ulrike; Miralbell, Raymond; Mirimanoff, Rene O.; Weber, Damien C.; Ozsahin, Mahmut

    2011-11-01

    Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 months (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.

  2. Guide to Commensal Rodent Control

    DTIC Science & Technology

    1991-12-01

    slaughterhouses. Pigs have been shown to contract trichinosis from infected rat feces in their food. i. Tapeworms - Hymenolepis nana and H. dimanuta...are two of the intestinal parasites transmitted to man by food that has been contaminated with tapeworm - bearing rodent feces. j. Tetanus - The wound

  3. Allometric disparity in rodent evolution

    PubMed Central

    Wilson, Laura A B

    2013-01-01

    In this study, allometric trajectories for 51 rodent species, comprising equal representatives from each of the major clades (Ctenohystrica, Muroidea, Sciuridae), are compared in a multivariate morphospace (=allometric space) to quantify magnitudes of disparity in cranial growth. Variability in allometric trajectory patterns was compared to measures of adult disparity in each clade, and dietary habit among the examined species, which together encapsulated an ecomorphological breadth. Results indicate that the evolution of allometric trajectories in rodents is characterized by different features in sciurids compared with muroids and Ctenohystrica. Sciuridae was found to have a reduced magnitude of inter-trajectory change and growth patterns with less variation in allometric coefficient values among members. In contrast, a greater magnitude of difference between trajectories and an increased variation in allometric coefficient values was evident for both Ctenohystrica and muroids. Ctenohystrica and muroids achieved considerably higher adult disparities than sciurids, suggesting that conservatism in allometric trajectory modification may constrain morphological diversity in rodents. The results provide support for a role of ecology (dietary habit) in the evolution of allometric trajectories in rodents. PMID:23610638

  4. 21 CFR 1250.96 - Rodent control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rodent control. 1250.96 Section 1250.96 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.96 Rodent control. Vessels shall be... of rodent control....

  5. 21 CFR 1250.96 - Rodent control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rodent control. 1250.96 Section 1250.96 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.96 Rodent control. Vessels shall be... of rodent control. ...

  6. 21 CFR 1250.96 - Rodent control.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rodent control. 1250.96 Section 1250.96 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.96 Rodent control. Vessels shall be... of rodent control. ...

  7. 21 CFR 1250.96 - Rodent control.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Rodent control. 1250.96 Section 1250.96 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.96 Rodent control. Vessels shall be... of rodent control. ...

  8. 21 CFR 1250.96 - Rodent control.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Rodent control. 1250.96 Section 1250.96 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.96 Rodent control. Vessels shall be... of rodent control. ...

  9. Rodent Oncology: Diseases, Diagnostics, and Therapeutics.

    PubMed

    Hocker, Samuel E; Eshar, David; Wouda, Raelene M

    2017-01-01

    Cancer incidence in rodent species varies dramatically from a common occurrence in mice and rats to just a limited number of documented cases in chinchillas and degus. This article summarizes common tumors, both benign and malignant, that have been reported to occur in rodents. Outlined are clinical signs, diagnostics, and treatments that have been described for rodents presenting with specific neoplasms.

  10. [Monitoring populations of rodent reservoirs of zoonotic diseases. Projects, aims and results].

    PubMed

    Jacob, J; Ulrich, R G; Freise, J; Schmolz, E

    2014-05-01

    Rodents can harbor and transmit pathogens that can cause severe disease in humans, companion animals and livestock. Such zoonotic pathogens comprise more than two thirds of the currently known human pathogens. The epidemiology of some zoonotic pathogens, such as hantaviruses, can be linked to the population dynamics of the rodent host. In this case, during an outbreak of the rodent host population many human infections may occur. In other rodent-borne zoonotic diseases such phenomena are not known and in many cases the rodent host specificity of a given pathogen is unclear. The monitoring of relevant rodent populations and of the rodent-borne zoonotic pathogens is essential to (1) understand the distribution and epidemiology of pathogens and (2) develop forecasting tools to predict outbreaks of zoonoses. Presently, there are no systematic long-term monitoring programs in place for zoonoses in Germany. Rodent monitoring activities are largely restricted to the plant protection sector, such as for the common vole (Microtus arvalis) and forest-damaging rodents. However, during the last 10-15 years a number of specific research projects have been initiated and run for a few years and Norway rat (Rattus norvegicus) monitoring has been implemented in Hamburg and Lower Saxony. Based on close cooperation of federal and state authorities and research institutions these efforts could be utilized to gain information about the distribution and importance of rodent-borne zoonoses. Nevertheless, for the integration of rodent population dynamics and zoonotic disease patterns and especially for developing predictive models, long-term monitoring is urgently required. To establish a systematic long-term monitoring program, existing networks and cooperation need to be used, additional collaborators (e.g., pest control operators) should be included and synergetic effects of different scientific fields should be utilized.

  11. Synthesis, Characterization, and Evaluation of Difluoropyrido[4,3-b]indoles as Potential Agents for Acetylcholinesterase and Antiamnesic Activity.

    PubMed

    Madaiah, Malavalli; Jayanna, Bidarur K; Manu, Arakere S; Prashanth, Maralekere K; Revanasiddappa, Hosakere D; Veeresh, Bantal

    2017-04-01

    Acetylcholinesterase (AChE) inhibitors are currently the most widely prescribed drugs for Alzheimer's disease. The high potential of indole compounds in medicinal chemistry led us to discover a novel series of fluoroindole compounds. The synthesis and pharmacological analysis of the difluoropyrido[4,3-b]indoles 11-34 are described. Compounds 11-34 were tested for AChE inhibition activity using a rat brain homogenate. Compounds 25-29 display a promising in vitro profile with an IC50 value range of 46-51.6 nM and show significant protective effect on scopolamine-induced amnesia. The present data indicate that compounds 25-29 may represent attractive potent molecules for the treatment of Alzheimer's disease.

  12. Rodent nutrition: digestive comparisons of 4 common rodent species.

    PubMed

    Grant, Kerrin

    2014-09-01

    This article summarizes the literature regarding digestive strategies and captive diets of common rodent pocket pets. A comparison is made between the 2 suborders in which chinchillas, guinea pigs, hamsters, and gerbils occur, highlighting digestive anatomy and dietary adaptations. Recommended captive diets are provided, as well as common nutritionally related health issues that may be presented to veterinary clinics. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Is papillary thyroid microcarcinoma an indolent tumor?

    PubMed Central

    Gao, Xuemei; Zhang, Xiao; Zhang, Yajing; Hua, Wenjuan; Maimaiti, Yusufu; Gao, Zairong

    2016-01-01

    Abstract The increasing detection of papillary thyroid microcarcinoma (PTMC) has created management dilemmas. To clarify the clinical significance of postsurgery stimulated thyroglobulin (ps-Tg) in PTMC who undergo thyroidectomy and radioactive iodine (RAI), we retrospectively reviewed the 358 PTMC patients who were treated with RAI and followed up in our hospital. Those with an excessive anti-Tg antibody, ultrasound-detected residual were excluded, thereby resulting in the inclusion of 280 cases. Their clinical and histopathological information and clinical outcomes were collected and summarized. Tumor stages were classified according to the tumor, node, metastasis (TNM) staging system and the consensus of the European Thyroid Association (ETA) risk stratification system, respectively. Kaplan–Meier curves were constructed to compare the disease-free survival (DFS) rates of different risk-staging systems. By the end of follow-up, none of the patients died of the disease or relapsed. The 8-year DFS rate was 76.9%. Kaplan–Meier curves showed different DFS rates in TNM stages I versus IV, III versus IV, very low risk versus high risk, low risk versus high risk, respectively (P < 0.05), while they were not significantly different in stage I versus stage III, very low risk versus low risk (P > 0.05). Finally, 40 (14.3%) cases got a persistent disease. Five variables (male sex, nonconcurrent benign pathology, initial tumor size >5 mm, lymph node metastasis, and ps-Tg ≥ 10 μg/L) were associated with disease persistence by univariate regression analysis. Ps-Tg ≥ 10 μg/L was the only independent prognostic variable that predicted disease persistence by multivariate regression analysis (odds ratio: 36.057, P = 0.000). Therefore, PTMC with a small size of ≤1 cm does not always act as an indolent tumor. In conclusion, ps-Tg ≥ 10 μg/L is associated with increased odds of disease persistence. ETA risk stratification is more

  14. Indole Localization in Lipid Membranes Revealed by Molecular Simulation

    PubMed Central

    Norman, Kristen E.; Nymeyer, Hugh

    2006-01-01

    It is commonly known that the amino acid residue tryptophan and its side-chain analogs, e.g., indole, are strongly attracted to the interfacial region of lipid bilayers. Phenylalanine and its side-chain analogs, e.g., benzene, do not localize in the interface but are distributed throughout the lipid bilayer. We use molecular dynamics to investigate the details of indole and benzene localization and orientation within a POPC bilayer and the factors that lead to their different properties. We identify three sites in the bilayer at which indole is localized: 1), a site in the interface near the glycerol moiety; 2), a weakly bound site in the interface near the choline moiety; and 3), a weakly bound site in the center of the bilayer's hydrocarbon core. Benzene is localized in the same three positions, but the most stable position is the hydrocarbon core followed by the site near the glycerol moiety. Transfer of indole from water to the hydrocarbon core shows a classic hydrophobic effect. In contrast, interfacial binding is strongly enthalpy driven. We use several different sets of partial charges to investigate the factors that contribute to indole's and benzene's orientational and spatial distribution. Our simulations show that a number of electrostatic interactions appear to contribute to localization, including hydrogen bonding to the lipid carbonyl groups, cation-π interactions, interactions between the indole dipole and the lipid bilayer's strong interfacial electric field, and nonspecific electrostatic stabilization due to a mismatch in the variation of the nonpolar forces and local dielectric with position in the bilayer. PMID:16815896

  15. Novel indole sulfides as potent HIV-1 NNRTIs.

    PubMed

    Brigg, Siobhan; Pribut, Nicole; Basson, Adriaan E; Avgenikos, Moscos; Venter, Reinhardt; Blackie, Margaret A; van Otterlo, Willem A L; Pelly, Stephen C

    2016-03-15

    In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. However, the methyl ether functionality on these compounds, which was crucial for potency, was susceptible to acid promoted indole assisted SN1 substitution. This particular problem did not bode well for an orally bioavailable drug. Here we describe bioisosteric replacement of this problematic functional group, leading to a series of compounds which are potent inhibitors of HIV replication, and are acid stable.

  16. Indole Alkaloids from the Leaves of Nauclea officinalis.

    PubMed

    Fan, Long; Liao, Cheng-Hui; Kang, Qiang-Rong; Zheng, Kai; Jiang, Ying-Chun; He, Zhen-Dan

    2016-07-23

    Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids, paratunamide C (2), paratunamide D (3) and paratunamide A (4). The structures with absolute configurations of the new compounds were identified on the basis of 1D and 2D NMR, HRESIMS, acid hydrolysis and quantum chemical circular dichroism (CD) calculation. According to the structures of isolated indole alkaloids, their plausible biosynthetic pathway was deduced.

  17. New indole alkaloids from the bark of Alstonia scholaris.

    PubMed

    Salim, Angela A; Garson, Mary J; Craik, David J

    2004-09-01

    A new indole alkaloid, akuammiginone (1), and a new glycosidic indole alkaloid, echitamidine-N-oxide 19-O-beta-d-glucopyranoside (2), together with the five known alkaloids, echitaminic acid (3), echitamidine N-oxide (4), N(b)-demethylalstogustine N-oxide (5), akuammicine N-oxide (6), and N(b)-demethylalstogustine (7), were isolated from the trunk bark of Alstonia scholaris collected in Timor, Indonesia. The structures of all compounds were elucidated by spectroscopic methods. This is the first report of compounds 3-5and 7 in A. scholaris. Some NMR assignments of the known compounds were revised.

  18. Paramagnetic nuclear magnetic resonance relaxation and molecular mechanics studies of the chloroperoxidase-indole complex: insights into the mechanism of chloroperoxidase-catalyzed regioselective oxidation of indole.

    PubMed

    Zhang, Rui; He, Qinghao; Chatfield, David; Wang, Xiaotang

    2013-05-28

    To unravel the mechanism of chloroperoxidase (CPO)-catalyzed regioselective oxidation of indole, we studied the structure of the CPO-indole complex using nuclear magnetic resonance (NMR) relaxation measurements and computational techniques. The dissociation constant (KD) of the CPO-indole complex was calculated to be approximately 21 mM. The distances (r) between protons of indole and the heme iron calculated via NMR relaxation measurements and molecular docking revealed that the pyrrole ring of indole is oriented toward the heme with its 2-H pointing directly at the heme iron. Both KD and r values are independent of pH in the range of 3.0-6.5. The stability and structure of the CPO-indole complex are also independent of the concentration of chloride or iodide ion. Molecular docking suggests the formation of a hydrogen bond between the NH group of indole and the carboxyl O of Glu 183 in the binding of indole to CPO. Simulated annealing of the CPO-indole complex using r values from NMR experiments as distance restraints reveals that the van der Waals interactions were much stronger than the Coulomb interactions in the binding of indole to CPO, indicating that the association of indole with CPO is primarily governed by hydrophobic rather than electrostatic interactions. This work provides the first experimental and theoretical evidence of the long-sought mechanism that leads to the "unexpected" regioselectivity of the CPO-catalyzed oxidation of indole. The structure of the CPO-indole complex will serve as a lighthouse in guiding the design of CPO mutants with tailor-made activities for biotechnological applications.

  19. Paramagnetic NMR Relaxation and Molecular Mechanics Studies of Chloroperoxidase-Indole Complex: Insights into the Mechanism of Chloroperoxidase-Catalyzed Regioselective Oxidation of Indole

    PubMed Central

    Zhang, Rui; He, Qinghao; Chatfield, David; Wang, Xiaotang

    2013-01-01

    To unravel the mechanism of CPO-catalyzed regioselective oxidation of indole, the structure of the CPO-indole complex was studied using NMR relaxation measurements and computational techniques. The dissociation constant (KD) of the CPO-indole complex was calculated to be approximately 21 mM. The distances (r) between protons of indole and the heme iron calculated from NMR relaxation measurements and molecular docking revealed that the pyrrole ring of indole is oriented toward the heme with its 2-H pointing directly at the heme iron. Both KD and r values are independent of pH in the range of 3.0–6.5. The stability and structure of the CPO-indole complex are also independent of the concentration of chloride/iodide ion. Molecular docking suggests the formation of a hydrogen bond between the N–H of indole and the carboxyl O of Glu 183 in the binding of indole to CPO. Simulated annealing of the CPO-indole complex using r values from NMR experiments as distance restraints reveals that the van der Waals interactions were much stronger than the Coulomb interactions in indole binding to CPO, indicating that the association of indole with CPO is primarily governed by hydrophobic rather than electrostatic interactions. This work provides the first experimental and theoretical evidence for the long-sought mechanism that leads to the “unexpected” regioselectivity of CPO-catalyzed oxidation of indole. The structure of the CPO-indole complex will serve as a lighthouse in guiding the design of CPO mutants with tailor-made activities for biotechnological applications. PMID:23634952

  20. Rodent models of cerebral ischemia

    SciTech Connect

    Ginsberg, M.D.; Busto, R. )

    1989-12-01

    The use of physiologically regulated, reproducible animal models is crucial to the study of ischemic brain injury--both the mechanisms governing its occurrence and potential therapeutic strategies. Several laboratory rodent species (notably rats and gerbils), which are readily available at relatively low cost, are highly suitable for the investigation of cerebral ischemia and have been widely employed for this purpose. We critically examine and summarize several rodent models of transient global ischemia, resulting in selective neuronal injury within vulnerable brain regions, and focal ischemia, typically giving rise to localized brain infarction. We explore the utility of individual models and emphasize the necessity for meticulous experimental control of those variables that modulate the severity of ischemic brain injury.169 references.

  1. Identifying Rodent Hantavirus Reservoirs, Brazil

    PubMed Central

    Bisordi, Ivani; Levis, Silvana; Garcia, Jorge; Pereira, Luiz E.; Souza, Renato P.; Sugahara, Teresa K.N.; Pini, Noemi; Enria, Delia; Souza, Luiza T.M.

    2004-01-01

    We describe the genetic analysis of samples from hantavirus pulmonary syndrome (HPS) patients from southern and southeastern states of Brazil and rodents captured at the presumed site of infection of these patients. A total of 65 samples that were antibody-positive for Sin Nombre or Laguna Negra virus by enzyme-linked immunosorbent assay were processed by nested reverse transcription–polymerase chain reaction (RT-PCR) by using several primer combinations in the M and S genome segments. PCR products were amplified and sequenced from samples from 11 HPS patient and 7 rodent samples. Phylogenetic analysis of nucleotide sequence differences showed the cocirculation of Araraquara and Juquitiba-like viruses, previously characterized from humans. Our genetic data indicate that Araraquara virus is associated with Bolomys lasiurus (hairy-tailed Bolo mouse) and the Juquitiba-like virus is associated with Oligoryzomys nigripes (black-footed pigmy rice rat). PMID:15663849

  2. Preclinical imaging anesthesia in rodents.

    PubMed

    Vesce, Giancarlo; Micieli, Fabiana; Chiavaccini, Ludovica

    2017-03-01

    Despite the outstanding progress achieved by preclinical imaging science, laboratory animal anesthesia remains quite stationary. Ninety percent of preclinical imaging studies are carried on small rodents (mice and rats) anesthetized by outdated injectable and/or inhalation agents. A need for imaging awake (conscious) animals is questionably registered mainly for brain research, for phMRI and for accomplishing pain and analgesia studies. A need for improving current rodent anesthesia protocols and for enforcing the 3Rs paradigm is sought. Patient monitoring throughout the procedure and recovery phases, as well as vital parameter's data must be recorded in basic consciousness states and during imaging sessions. A multidrug approach is suggested to overcome the limits of monoanesthesia and well-timed physiological data are required to ground findings and to interpret imaging data.

  3. Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.

    PubMed

    Clark, Simon; Cross, Martin L; Smith, Alan; Court, Pinar; Vipond, Julia; Nadian, Allan; Hewinson, R Glyn; Batchelor, Hannah K; Perrie, Yvonne; Williams, Ann; Aldwell, Frank E; Chambers, Mark A

    2008-10-29

    Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery

  4. Metabolic Engineering in Nicotiana benthamiana Reveals Key Enzyme Functions in Arabidopsis Indole Glucosinolate Modification[W

    PubMed Central

    Pfalz, Marina; Mikkelsen, Michael Dalgaard; Bednarek, Paweł; Olsen, Carl Erik; Halkier, Barbara Ann; Kroymann, Juergen

    2011-01-01

    Indole glucosinolates, derived from the amino acid Trp, are plant secondary metabolites that mediate numerous biological interactions between cruciferous plants and their natural enemies, such as herbivorous insects, pathogens, and other pests. While the genes and enzymes involved in the Arabidopsis thaliana core biosynthetic pathway, leading to indol-3-yl-methyl glucosinolate (I3M), have been identified and characterized, the genes and gene products responsible for modification reactions of the indole ring are largely unknown. Here, we combine the analysis of Arabidopsis mutant lines with a bioengineering approach to clarify which genes are involved in the remaining biosynthetic steps in indole glucosinolate modification. We engineered the indole glucosinolate biosynthesis pathway into Nicotiana benthamiana, showing that it is possible to produce indole glucosinolates in a noncruciferous plant. Building upon this setup, we demonstrate that all members of a small gene subfamily of cytochrome P450 monooxygenases, CYP81Fs, are capable of carrying out hydroxylation reactions of the glucosinolate indole ring, leading from I3M to 4-hydroxy-indol-3-yl-methyl and/or 1-hydroxy-indol-3-yl-methyl glucosinolate intermediates, and that these hydroxy intermediates are converted to 4-methoxy-indol-3-yl-methyl and 1-methoxy-indol-3-yl-methyl glucosinolates by either of two family 2 O-methyltransferases, termed indole glucosinolate methyltransferase 1 (IGMT1) and IGMT2. PMID:21317374

  5. Role of Indole Production on Virulence of Vibrio cholerae Using Galleria mellonella Larvae Model.

    PubMed

    Nuidate, Taiyeebah; Tansila, Natta; Saengkerdsub, Suwat; Kongreung, Jetnaphang; Bakkiyaraj, Dhamodharan; Vuddhakul, Varaporn

    2016-09-01

    Cell to cell communication facilitated by chemical signals plays crucial roles in regulating various cellular functions in bacteria. Indole, one such signaling molecule has been demonstrated to control various bacterial phenotypes such as biofilm formation and virulence in diverse bacteria including Vibrio cholerae. The present study explores some key factors involved in indole production and the subsequent pathogenesis of V. cholerae. Indole production was higher at 37 °C than at 30 °C, although the growth at 37 °C was slightly higher. A positive correlation was observed between indole production and biofilm formation in V. cholerae. Maximum indole production was detected at pH 7. There was no significant difference in indole production between clinical and environmental V. cholerae isolates, although indole production in one environmental isolate was significantly different. Both growth and indole production showed relevant changes with differences in salinity. An indole negative mutant strain was constructed using transposon mutagenesis and the direct effect of indole on the virulence of V. cholerae was evaluated using Galleria mellonella larvae model. Comparison to the wild type strain, the mutant significantly reduced the mortality of G. mellonella larvae which regained its virulence after complementation with exogenous indole. A gene involved in indole production and the virulence of V. cholerae was identified.

  6. Control of Breast Tumor Cell Growth by Dietary Indoles

    DTIC Science & Technology

    1997-09-01

    anticarcinogenesis by indole-3-carbinol: detailed in vivo DNA binding dose-response studies after dietary administration with aflatoxin B1 . Carcinogenesis 9, 427-430...lipofectamine (Gibco BRL) mixtures were prepared by mixing 1 Vg of ERE-vit-CAT reporter (-596 to +21 of the Xenopus laevis vitellogenin B1 genomic

  7. Indole alkaloids from the seeds of Centaurea cyanus (Asteraceae).

    PubMed

    Sarker, S D; Laird, A; Nahar, L; Kumarasamy, Y; Jaspars, M

    2001-08-01

    Preparative RP-HPLC analysis of a methanol extract of the seeds of Centaurea cyanus afforded four indole alkaloids: moschamine, cis-moschamine, centcyamine and cis-centcyamine, the latter two being new natural products. Structures of these compounds were elucidated by comprehensive spectroscopic analyses. General toxicity of the isolates was determined by Brine Shrimp Lethality bioassay.

  8. Organocatalytic enantioselective indole alkylations of alpha,beta-unsaturated ketones.

    PubMed

    Chen, Wei; Du, Wei; Yue, Lei; Li, Rui; Wu, Yong; Ding, Li-Sheng; Chen, Ying-Chun

    2007-03-07

    The C3-selective enantioselective Michael-type Friedel-Crafts alkylations of indoles with nonchelating alpha,beta-unsaturated alkyl ketones, catalysed by a chiral primary amine derived from natural cinchonine, were investigated. The reactions, in the presence of 30 mol% catalyst, were smoothly conducted at 0 to -20 degrees C. Moderate to good ee (47-89%) has been achieved.

  9. Palladium-catalyzed direct arylation of indoles with arylsulfonyl hydrazides.

    PubMed

    Liu, Congrong; Ding, Lianghui; Guo, Guang; Liu, Weiwei; Yang, Fu-Lai

    2016-03-14

    A novel method to synthesise 2-arylindoles is demonstrated via direct arylation of indoles with arylsulfonyl hydrazides. Under the optimized reaction conditions, the reaction well tolerates a wide variety of functional groups to afford structurally diverse 2-arylindoles in good to excellent yields at 70 °C.

  10. Palladium-catalyzed direct arylation of indoles with cyclohexanones.

    PubMed

    Chen, Shanping; Liao, Yunfeng; Zhao, Feng; Qi, Hongrui; Liu, Saiwen; Deng, Guo-Jun

    2014-03-21

    A novel palladium catalyzed approach to 3-arylindoles was developed from indoles and cyclohexanones. Various cyclohexanones acted as aryl sources via an alkylation and dehydrogenation sequence using molecular oxygen as the hydrogen acceptor. This method showed good regioselectivity and afforded 3-arylindoles as the sole products.

  11. New indole alkaloids from the roots of Ochrosia acuminata.

    PubMed

    Salim, Angela A; Garson, Mary J; Craik, David J

    2004-10-01

    Two new indole alkaloids, polyneuridine-N-oxide (1) and 17-hydroxy-10-methoxy-yohimbane (2), together with seven known alkaloids were isolated from the roots of Ochrosia acuminata collected in Savu, Indonesia. 9-Methoxyellipticine (3) and ellipticine (4) were responsible for the antitumor activities of the extract. The structures of all compounds were elucidated using MS and NMR methods.

  12. Tenualexin, other phytoalexins and indole glucosinolates from wild cruciferous species.

    PubMed

    Pedras, M Soledade C; Yaya, Estifanos E

    2014-06-01

    In general, the chemodiversity of phytoalexins, elicited metabolites involved in plant defense mechanisms against microbial pathogens, correlates with the biodiversity of their sources. In this work, the phytoalexins produced by four wild cruciferous species (Brassica tournefortii, Crambe abyssinica (crambe), Diplotaxis tenuifolia (sand rocket), and Diplotaxis tenuisiliqua (wall rocket)) were identified and quantified by HPLC with photodioarray and electrospray mass detectors. In addition, the production of indole glucosinolates, biosynthetic precursors of cruciferous phytoalexins, was evaluated. Tenualexin, (=2-(1,4-dimethoxy-1H-indol-3-yl)acetonitrile), the first cruciferous phytoalexin containing two MeO substituents in the indole ring, was isolated from D. tenuisiliqua, synthesized, and evaluated for antifungal activity. The phytoalexins cyclobrassinin and spirobrassinin were detected in B. tournefortii and C. abyssinica, whereas rutalexin and 4-methoxybrassinin were only found in B. tournefortii. D. tenuifolia, and D. tenuisiliqua produced 2-(1H-indol-3-yl)acetonitriles as phytoalexins. Because tenualexin appears to be one of the broad-range antifungals occurring in crucifers, it is suggested that D. tenuisiliqua may have disease resistance traits important to be incorporated in commercial breeding programs.

  13. Diastereoselective Synthesis of Biologically Active Cyclopenta[b]indoles.

    PubMed

    Santos, Marilia S; Fernandes, Daniara C; Rodrigues, Manoel T; Regiani, Thais; Andricopulo, Adriano D; Ruiz, Ana Lúcia T G; Vendramini-Costa, Débora B; de Carvalho, João E; Eberlin, Marcos N; Coelho, Fernando

    2016-08-05

    The cyclopenta[b]indole motif is present in several natural and synthetic biologically active compounds, being directly responsible for the biological effects some of them present. We described herein a three step sequence for the synthesis of cyclopenta[b]indoles with a great structural diversity. The method is based on an oxidative Michael addition of suitable indoles on the double bond of Morita-Baylis-Hillman adducts mediated by a hypervalent iodine reagent (IBX) to form β-ketoesters, which were chemoselectively reduced with NaBH4 in THF to give the corresponding β-hydroxy-esters. The diastereoisomeric mixture was then treated with a catalytic amount of triflic acid (20 mol %) to give cyclopenta[b]indoles with overall yields ranging from 8 to 73% (for 2 steps). The acid-catalyzed cyclization step gave the required heterocycles, via an intramolecular Friedel-Crafts reaction, with high diastereoselectivity, where only the trans product was observed. A mechanistic study monitored by ESI-(+)-MS was also conducted to collect evidence about the mechanism of this reaction. The new molecules herein synthesized were also evaluated against a panel of human cancer cells demonstrating a promising antitumoral profile.

  14. Monoterpenoid indole alkaloids from the bark of Alstonia scholaris.

    PubMed

    Feng, Tao; Cai, Xiang-Hai; Zhao, Pei-Ji; Du, Zhi-Zhi; Li, Wei-Qi; Luo, Xiao-Dong

    2009-11-01

    Six new monoterpenoid indole alkaloids, scholarisines B-G (1- 6), together with 15 known analogues (7- 21), were isolated from the bark of Alstonia scholaris. Their structures were determined by 1D and 2D NMR spectra and MS analyses. The structure of 1 was further supported by the single-crystal X-ray. Georg Thieme Verlag KG Stuttgart, New York.

  15. Indole: An evolutionarily conserved influencer of behavior across kingdoms

    USDA-ARS?s Scientific Manuscript database

    Indole, which is produced from the breakdown of the essential amino acid tryptophan, is a key environmental cue that is used by many organisms. But why is its use so ubiquitous, and how does it function to modulate interactions among such diverse organisms? Here, we review the literature to addres...

  16. Photolysis of Indole-Containing Mycotoxins to Fluorescent Products

    USDA-ARS?s Scientific Manuscript database

    Photochemical reaction of the non-fluorescent mycotoxin cyclopiazonic acid (CPA) to fluorescent products was recently reported. Because CPA contains an indole moiety, believed to contribute to the fluorescence, it was of interest to determine whether the effect might be more generally applicable to ...

  17. Rodent consumption in Khon Kaen Province, Thailand.

    PubMed

    Suwannarong, Kanokwan; Chapman, Robert S

    2014-09-01

    Rodents are important reservoirs of rodent-borne infections worldwide, including Southeast Asia and Northeast Thailand (Isaan), where rodent consumption may be a source of rodent-borne diseases. The behavior of consuming rodents is related to a population's traditions, knowledge, cultural, and household contexts, among other factors. This cross-sectional survey was conducted in Khon Kaen Province, Thailand during November-December 2011. It aimed to elicit information about rodent consumption among residents of this province, and to identify factors associated with rodent consumption there. Multiple logistic regression analysis indicated that male gender, large family size, and use of rainwater as the main source of drinking water were positively associated with reported rodent consumption in this province, while having proper knowledge/attitudes towards animal-borne disease was negatively associated. These results provide evidence-base information for further studies, such as participatory ac- tion research, to further explore how people interact with rodents in different contexts. Further research is also needed to characterize risk of zoonotic diseases in relation to rodent consumption.

  18. Aniline is an inducer, and not a precursor, for indole derivatives in Rubrivivax benzoatilyticus JA2.

    PubMed

    Mujahid, Mohammed; Sasikala, Ch; Ramana, Ch V

    2014-01-01

    Rubrivivax benzoatilyticus JA2 and other anoxygenic photosynthetic bacteria produce indole derivatives when exposed to aniline, a xenobiotic compound. Though this phenomenon has been reported previously, the role of aniline in the production of indoles is still a biochemical riddle. The present study aims at understanding the specific role of aniline (as precursor or stimulator) in the production of indoles and elucidating the biochemical pathway of indoles in aniline-exposed cells by using stable isotope approaches. Metabolic profiling revealed tryptophan accumulation only in aniline exposed cells along with indole 3-acetic acid (IAA) and indole 3-aldehyde (IAld), the two major catabolites of tryptophan. Deuterium labelled aniline feeding studies revealed that aniline is not a precursor of indoles in strain JA2. Further, production of indoles only in aniline-exposed cells suggests that aniline is an indoles stimulator. In addition, production of indoles depended on the presence of a carbon source, and production enhanced when carbon sources were added to the culture. Isotope labelled fumarate feeding identified, fumarate as the precursor of indole, indicating de novo synthesis of indoles. Glyphosate (shikimate pathway inhibitor) inhibited the indoles production, accumulation of tryptophan, IAA and IAld indicating that indoles synthesis in strain JA2 occurs via the de novo shikimate pathway. The up-regulation of anthranilate synthase gene and induction of anthranilate synthase activity correlated well with tryptophan production in strain JA2. Induction of tryptophan aminotransferase and tryptophan 2-monooxygenase activities corroborated well with IAA levels, suggesting that tryptophan catabolism occurs simultaneously in aniline exposed cells. Our study demonstrates that aniline (stress) stimulates tryptophan/indoles synthesis via the shikimate pathway by possibly modulating the metabolic pathway.

  19. Aniline Is an Inducer, and Not a Precursor, for Indole Derivatives in Rubrivivax benzoatilyticus JA2

    PubMed Central

    Mohammed, Mujahid; Ch, Sasikala; Ch, Ramana V.

    2014-01-01

    Rubrivivax benzoatilyticus JA2 and other anoxygenic photosynthetic bacteria produce indole derivatives when exposed to aniline, a xenobiotic compound. Though this phenomenon has been reported previously, the role of aniline in the production of indoles is still a biochemical riddle. The present study aims at understanding the specific role of aniline (as precursor or stimulator) in the production of indoles and elucidating the biochemical pathway of indoles in aniline-exposed cells by using stable isotope approaches. Metabolic profiling revealed tryptophan accumulation only in aniline exposed cells along with indole 3-acetic acid (IAA) and indole 3-aldehyde (IAld), the two major catabolites of tryptophan. Deuterium labelled aniline feeding studies revealed that aniline is not a precursor of indoles in strain JA2. Further, production of indoles only in aniline-exposed cells suggests that aniline is an indoles stimulator. In addition, production of indoles depended on the presence of a carbon source, and production enhanced when carbon sources were added to the culture. Isotope labelled fumarate feeding identified, fumarate as the precursor of indole, indicating de novo synthesis of indoles. Glyphosate (shikimate pathway inhibitor) inhibited the indoles production, accumulation of tryptophan, IAA and IAld indicating that indoles synthesis in strain JA2 occurs via the de novo shikimate pathway. The up-regulation of anthranilate synthase gene and induction of anthranilate synthase activity correlated well with tryptophan production in strain JA2. Induction of tryptophan aminotransferase and tryptophan 2-monooxygenase activities corroborated well with IAA levels, suggesting that tryptophan catabolism occurs simultaneously in aniline exposed cells. Our study demonstrates that aniline (stress) stimulates tryptophan/indoles synthesis via the shikimate pathway by possibly modulating the metabolic pathway. PMID:24533057

  20. Cascade multicomponent synthesis of indoles, pyrazoles, and pyridazinones by functionalization of alkenes.

    PubMed

    Matcha, Kiran; Antonchick, Andrey P

    2014-10-27

    The development of multicomponent reactions for indole synthesis is demanding and has hardly been explored. The present study describes the development of a novel multicomponent, cascade approach for indole synthesis. Various substituted indole derivatives were obtained from simple reagents, such as unfunctionalized alkenes, diazonium salts, and sodium triflinate, by using an established straightforward and regioselective method. The method is based on the radical trifluoromethylation of alkenes as an entry into Fischer indole synthesis. Besides indole synthesis, the application of the multicomponent cascade reaction to the synthesis of pyrazoles and pyridazinones is described. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Synthesis and biological evaluation of novel indole-2-one and 7-aza-2-oxindole derivatives as anti-inflammatory agents

    PubMed Central

    Chen, Gaozhi; Jiang, Lili; Dong, Lili; Wang, Zhe; Xu, Fengli; Ding, Ting; Fu, Lili; Fang, Qilu; Liu, Zhiguo; Shan, Xiaoou; Liang, Guang

    2014-01-01

    Sepsis, a typically acute inflammatory disease, is the biggest cause of death in ICU (intensive care unit). Novel anti-inflammatory alternatives are still in urgent need. In this study, we designed and synthesized 30 indole-2-one and 7-aza-2-oxindole derivatives based on the skeleton of tenidap, and their anti-inflammatory activity was determined by evaluating the inhibitory potency against lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)-α and interleukin (IL)-6 release in RAW264.7 macrophages. Quantitative SAR (structure–activity relationship) analysis revealed that a high molecular polarizability and low lipid/water partition coefficient (ALogP) in indole-2-one are beneficial for anti-inflammatory activity. Moreover, compounds 7i and 8e inhibited the expression of TNF-α, IL-6, COX-2, PGES, and iNOS in LPS-stimulated macrophages, and 7i exhibited a significant protection from LPS-induced septic death in mouse models. These data present a series of new indole-2-one compounds with potential therapeutic effects in acute inflammatory diseases. PMID:25378906

  2. Simultaneous detection and quantification of indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) produced by rhizobacteria from l-tryptophan (Trp) using HPTLC.

    PubMed

    Goswami, Dweipayan; Thakker, Janki N; Dhandhukia, Pinakin C

    2015-03-01

    A simple, quick and reliable method is proposed for the detection and quantitation of indole-3-acetate (IAA) and indole-3-butyrate (IBA), an auxin phytohormone produced by rhizobacteria from l-tryptophan (Trp) metabolism using high performance thin-layer chromatography (HPTLC). Microbial auxin biosynthesis routes involve Trp as a precursor where other than IAA and IBA, products such as indole-3-pyruvate (IPA), indole-3-acetamide (IAM), tryptamine, indole-3-acetonitrile (IAN), indole-3-lactic acid (ILA) and indole-3-acetaldehyde (IAAld) are also produced. In traditional spectrophotometric method, Salkowski reagent develops color by reacting with indolic compounds. The color development is non-specific contributed by several Trp derivatives produced by rhizobacteria rather than IAA only. To overcome this limitation, HPTLC based protocol is developed to precisely detect and quantify IAA and IBA in the range of 100 to 1000ng per spot. This protocol is applicable to detect and quantify IAA and IBA from microbial samples ignoring other Trp derivatives. For microbial samples, the spectrophotometric method gives larger values as compared to HPTLC derived values which may be attributed by total indolic compounds reacting with Salkowski reagent rather than only IAA and/or IBA. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Regio- and chemoselective N-1 acylation of indoles: Pd-catalyzed domino cyclization to afford 1,2-fused tricyclic indole scaffolds.

    PubMed

    Liu, Yongxian; Huang, Yuanqiong; Song, Hongjian; Liu, Yuxiu; Wang, Qingmin

    2015-03-27

    A concise method for the synthesis of 1,2-fused tricyclic indole scaffolds by domino cyclization involving a Pd-catalyzed Sonogashira coupling, indole cyclization, regio- and chemoselective N-1 acylation, and 1,4-Michael addition is reported. This method provides straightforward access to tetrahydro[1,4]diazepino[1,2-a]indole and hexahydro[1,5]diazocino[1,2-a]indole scaffolds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Prospects for biological control of rodent populations*

    PubMed Central

    Wodzicki, Kazimierz

    1973-01-01

    Pathogens and predatory animals are the main agents used for the biological control of rodents. The pathogens that have been used are of the genus Salmonella; none is rodent-specific and all can cause severe infection in man and domestic animals. Furthermore, rodents frequently develop immunity to, and become carriers of, these organisms, and there is little to commend their use, except in lightly populated areas where control is infrequently applied. The relationships of five predator species with their rodent prey have been examined. The monitor lizard, mongoose, and ferret were for different reasons found to be unsatisfactory, and there is not yet sufficient evidence to warrant further releases of the Japanese weasel. Domestic and feral cats control rodents well in some situations but only after some other agent has removed a large part of the rodent population. PMID:4587482

  5. Formation of Volatile Tea Constituent Indole During the Oolong Tea Manufacturing Process.

    PubMed

    Zeng, Lanting; Zhou, Ying; Gui, Jiadong; Fu, Xiumin; Mei, Xin; Zhen, Yunpeng; Ye, Tingxiang; Du, Bing; Dong, Fang; Watanabe, Naoharu; Yang, Ziyin

    2016-06-22

    Indole is a characteristic volatile constituent in oolong tea. Our previous study indicated that indole was mostly accumulated at the turn over stage of oolong tea manufacturing process. However, formation of indole in tea leaves remains unknown. In this study, one tryptophan synthase α-subunit (TSA) and three tryptophan synthase β-subunits (TSBs) from tea leaves were isolated, cloned, sequenced, and functionally characterized. Combination of CsTSA and CsTSB2 recombinant protein produced in Escherichia coli exhibited the ability of transformation from indole-3-glycerol phosphate to indole. CsTSB2 was highly expressed during the turn over process of oolong tea. Continuous mechanical damage, simulating the turn over process, significantly enhanced the expression level of CsTSB2 and amount of indole. These suggested that accumulation of indole in oolong tea was due to the activation of CsTSB2 by continuous wounding stress from the turn over process. Black teas contain much less indole, although wounding stress is also involved in the manufacturing process. Stable isotope labeling indicated that tea leaf cell disruption from the rolling process of black tea did not lead to the conversion of indole, but terminated the synthesis of indole. Our study provided evidence concerning formation of indole in tea leaves for the first time.

  6. Systematic investigation and microbial community profile of indole degradation processes in two aerobic activated sludge systems

    PubMed Central

    Ma, Qiao; Qu, Yuanyuan; Zhang, Xuwang; Liu, Ziyan; Li, Huijie; Zhang, Zhaojing; Wang, Jingwei; Shen, Wenli; Zhou, Jiti

    2015-01-01

    Indole is widely spread in various environmental matrices. Indole degradation by bacteria has been reported previously, whereas its degradation processes driven by aerobic microbial community were as-yet unexplored. Herein, eight sequencing batch bioreactors fed with municipal and coking activated sludges were constructed for aerobic treatment of indole. The whole operation processes contained three stages, i.e. stage I, glucose and indole as carbon sources; stage II, indole as carbon source; and stage III, indole as carbon and nitrogen source. Indole could be completely removed in both systems. Illumina sequencing revealed that alpha diversity was reduced after indole treatment and microbial communities were significantly distinct among the three stages. At genus level, Azorcus and Thauera were dominant species in stage I in both systems, while Alcaligenes, Comamonas and Pseudomonas were the core genera in stage II and III in municipal sludge system, Alcaligenes and Burkholderia in coking sludge system. In addition, four strains belonged to genera Comamonas, Burkholderia and Xenophilus were isolated using indole as sole carbon source. Burkholderia sp. IDO3 could remove 100 mg/L indole completely within 14 h, the highest degradation rate to date. These findings provide novel information and enrich our understanding of indole aerobic degradation processes. PMID:26657581

  7. Isolation of Indole Utilizing Bacteria Arthrobacter sp. and Alcaligenes sp. From Livestock Waste.

    PubMed

    Kim, Minsu; Lee, Jin-Hyung; Kim, Eonmi; Choi, Hyukjae; Kim, Younghoon; Lee, Jintae

    2016-06-01

    Indole is an interspecies and interkingdom signaling molecule widespread in different environmental compartment. Although multifaceted roles of indole in different biological systems have been established, little information is available on the microbial utilization of indole in the context of combating odor emissions from different types of waste. The present study was aimed at identifying novel bacteria capable of utilizing indole as the sole carbon and energy source. From the selective enrichment of swine waste and cattle feces, we identified Gram-positive and Gram-negative bacteria belonging to the genera Arthrobacter and Alcaligenes. Bacteria belonging to the genus Alcaligenes showed higher rates of indole utilization than Arthrobacter. Indole at 1.0 mM for growth was completely utilized by Alcaligenes sp. in 16 h. Both strains produced two intermediates, anthranilic acid and isatin, during aerobic indole metabolism. These isolates were also able to grow on several indole derivatives. Interestingly, an adaptive response in terms of a decrease in cell size was observed in both strains in the presence of indole. The present study will help to explain the degradation of indole by different bacteria and also the pathways through which it is catabolized. Furthermore, these novel bacterial isolates could be potentially useful for the in situ attenuation of odorant indole and its derivatives emitted from different types of livestock waste.

  8. Indoles as therapeutics of interest in medicinal chemistry: Bird's eye view.

    PubMed

    Chadha, Navriti; Silakari, Om

    2017-07-07

    Indoles constitute extensively explored heterocyclic ring systems with wide range of applications in pathophysiological conditions that is, cancer, microbial and viral infections, inflammation, depression, migraine, emesis, hypertension, etc. Presence of indole nucleus in amino acid tryptophan makes it prominent in phytoconstituents such as perfumes, neurotransmitters, auxins (plant hormones), indole alkaloids etc. The interesting molecular architecture of indole makes them suitable candidates for the drug development. This review article provides an overview of the chemistry, biology, and toxicology of indoles focusing on their application as drugs. Our effort is to corroborate the information available on the natural indole alkaloids, indole based FDA approved drugs and clinical trial candidates having diverse therapeutic implementations. This compiled information may serve as a benchmark for the alteration of existing ligands to design novel potent molecules with lesser side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Prediction of rodent carcinogenicity for 30 chemicals

    SciTech Connect

    Ashby, J.

    1996-10-01

    Predictions of carcinogenic activity are made for 30 chemicals currently being assessed for rodent carcinogenicity by the U.S. National Toxicology Program. The predictions are based upon the chemical structure, the anticipated or reported mutagenicity, and the reported sub-chronic toxicity of each chemical. It is predicted that 13 chemicals will be noncarcinogenic to rodents, that 7 will be genotoxic carcinogens, and that 10 may show some evidence of presumed nongenotoxic rodent carcinogenesis. 3 refs., 1 fig.

  10. Tactile learning in rodents: Neurobiology and neuropharmacology.

    PubMed

    Roohbakhsh, Ali; Shamsizadeh, Ali; Arababadi, Mohammad Kazemi; Ayoobi, Fateme; Fatemi, Iman; Allahtavakoli, Mohammad; Mohammad-Zadeh, Mohammad

    2016-02-15

    Animal models of learning and memory have been the subject of considerable research. Rodents such as mice and rats are nocturnal animals with poor vision, and their survival depends on their sense of touch. Recent reports have shown that whisker somatosensation is the main channel through which rodents collect and process environmental information. This review describes tactile learning in rodents from a neurobiological and neuropharmacological perspective, and how this is involved in memory-related processes.

  11. A rapid and specific method for the detection of indole in complex biological samples.

    PubMed

    Darkoh, Charles; Chappell, Cynthia; Gonzales, Christopher; Okhuysen, Pablo

    2015-12-01

    Indole, a bacterial product of tryptophan degradation, has a variety of important applications in the pharmaceutical industry and is a biomarker in biological and clinical specimens. Yet, specific assays to quantitate indole are complex and require expensive equipment and a high level of training. Thus, indole in biological samples is often estimated using the simple and rapid Kovács assay, which nonspecifically detects a variety of commonly occurring indole analogs. We demonstrate here a sensitive, specific, and rapid method for measuring indole in complex biological samples using a specific reaction between unsubstituted indole and hydroxylamine. We compared the hydroxylamine-based indole assay (HIA) to the Kovács assay and confirmed that the two assays are capable of detecting microgram amounts of indole. However, the HIA is specific to indole and does not detect other naturally occurring indole analogs. We further demonstrated the utility of the HIA in measuring indole levels in clinically relevant biological materials, such as fecal samples and bacterial cultures. Mean and median fecal indole concentrations from 53 healthy adults were 2.59 mM and 2.73 mM, respectively, but varied widely (0.30 mM to 6.64 mM) among individuals. We also determined that enterotoxigenic Escherichia coli strain H10407 produces 3.3 ± 0.22 mM indole during a 24-h period in the presence of 5 mM tryptophan. The sensitive and specific HIA should be of value in a variety of settings, such as the evaluation of various clinical samples and the study of indole-producing bacterial species in the gut microbiota. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Evidence-Based Advances in Rodent Medicine.

    PubMed

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2017-09-01

    The number of exotic companion pet rodents seen in veterinary practices is growing very rapidly. According to the American Veterinary Medical Association's surveys, more than 2,093,000 pet rodents were kept in US households in 2007 and in 2012 it was more than 2,349,000 animals. This article summarizes the most important evidence-based knowledge in exotic pet rodents (diagnostics of the hyperadrenocorticism in guinea pigs, pituitary tumors in rats, urolithiasis in guinea pigs, use of itopride as prokinetics, use of deslorelin acetate in rodents, cause of dental disease, and prevention of mammary gland tumors in rats). Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Mycobacteriosis in the rabbit and rodent.

    PubMed

    McClure, Diane E

    2012-01-01

    Spontaneous mycobacteriosis is rare in rabbits and rodents with the exception of the pygmy rabbit, and there are only a handful of reported cases involving other rodents. Mycobacterium avium complex was the most commonly identified organism in reports of spontaneous mycobacteriosis involving rabbits and rodents. The resistance of rabbits and rodents to mycobacterial disease has been useful in understanding the disease in humans and other animals. Preventing or controlling Mycobacterium sp transmission from wildlife to domestic animals will require collaboration between agriculture, wildlife, environmental, and political entities. Understanding the ecology and epidemiology of mycobacteria is needed for better worldwide management of tuberculosis.

  14. Urban resident attitudes toward rodents, rodent control products, and environmental effects

    EPA Science Inventory

    Rodent control in urban areas can result in the inadvertent mortality of non-target species (e.g., bobcats). However, there is little detailed information about rodent control practices of urban residents. Our objective was to evaluate urban rodent control behaviors in two area...

  15. Urban resident attitudes toward rodents, rodent control products, and environmental effects

    EPA Science Inventory

    Rodent control in urban areas can result in the inadvertent mortality of non-target species (e.g., bobcats). However, there is little detailed information about rodent control practices of urban residents. Our objective was to evaluate urban rodent control behaviors in two area...

  16. Indole-3-acetic acid: A widespread physiological code in interactions of fungi with other organisms

    PubMed Central

    Fu, Shih-Feng; Wei, Jyuan-Yu; Chen, Hung-Wei; Liu, Yen-Yu; Lu, Hsueh-Yu; Chou, Jui-Yu

    2015-01-01

    Plants as well as microorganisms, including bacteria and fungi, produce indole-3-acetic acid (IAA). IAA is the most common plant hormone of the auxin class and it regulates various aspects of plant growth and development. Thus, research is underway globally to exploit the potential for developing IAA-producing fungi for promoting plant growth and protection for sustainable agriculture. Phylogenetic evidence suggests that IAA biosynthesis evolved independently in bacteria, microalgae, fungi, and plants. Present studies show that IAA regulates the physiological response and gene expression in these microorganisms. The convergent evolution of IAA production leads to the hypothesis that natural selection might have favored IAA as a widespread physiological code in these microorganisms and their interactions. We summarize recent studies of IAA biosynthetic pathways and discuss the role of IAA in fungal ecology. PMID:26179718

  17. The Miocene rodents of Serbia

    NASA Astrophysics Data System (ADS)

    Markovic, Z.

    2009-04-01

    During the Miocene period a group of shallow lakes was created in depressions at the territory of present-day Serbia. This caused the present wide distribution of lacustrine sediments, which occasionally alternate with the alluvial and marsh sediments. The remains of large mammals are relatively common, while the remains of small mammals used to be known only from two localities - Mala Miliva and Sibnica. The method of sediment sieving, used during the last decade, led to discovery of 6 new localities with remains of fossil vertebrates - Sibnica 1, Vračevići, village Lazarevac, Bele Vode, Brajkovac and Tavnik. Most of the fossil material is represented by osteological and odontological remains of small mammals. The best represented group of small mammals at each of the localities was the rodents. According to the odontological material presence was proven for 35 rodent species from 6 families. MN zonation was determined according to structure of associations. The geological age of fossil-bearing sediments was determined by using the method of correlation with the sites in Europe and Turkey.

  18. Rodent models for human diseases.

    PubMed

    Vandamme, Thierry F

    2015-07-15

    One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. Except in the case of highly controlled and regulated clinical trials, geneticists and scientists do not use humans for their experimental investigations because of the obvious risk to life. Instead, they use various animal, fungal, bacterial, and plant species as model organisms for their studies. Amongst these model organisms, rodent models are the most used due to the easiness for the experiments and the possibility to modify genetically these model animals. Nevertheless, due to the fact that animal models typically do not contract the same genetic diseases as people, so scientists must alter their genomes to induce human disease states and to know what kind of mutation causes the disease. In this brief review, we will discuss the interests of rodent models that have been developed to simulate human pathologies, focusing in models that employ xenografts and genetic modification. Within the framework of genetically engineered mouse (GEM) models, we will review some of the current genetic strategies for modeling diseases.

  19. Indole-3-propionic acid attenuates neuronal damage and oxidative stress in the ischemic hippocampus.

    PubMed

    Hwang, In Koo; Yoo, Ki-Yeon; Li, Hua; Park, Ok Kyu; Lee, Choong Hyun; Choi, Jung Hoon; Jeong, Young-Gil; Lee, Yun Lyul; Kim, Young-Myeong; Kwon, Young-Guen; Won, Moo-Ho

    2009-07-01

    Tryptophan-derived indole compounds have been widely investigated as antioxidants and as free-radical scavengers. Indole-3-propionic acid (IPA), one of these compounds, is a deamination product of tryptophan. In the present study, we used Mongolian gerbils to investigate IPA's neuroprotective effects against ischemic damage and its antioxidative effects in the hippocampal CA1 region (CA1) after 5 min of transient forebrain ischemia. The repeated oral administration of IPA (10 mg/kg) for 15 days before ischemic surgery protected neurons from ischemic damage. In this group, the percentage of cresyl violet-positive neurons in the CA1 was 56.8% compared with that in the sham group. In the vehicle-treated group, glial fibrillary acidic protein (GFAP)-, S-100-, and vimentin-immunoreactive astrocytes and ionized calcium-binding adapter molecule 1 (Iba-1)- and isolectin B4 (IB4)-immunoreactive microglia were activated 4 days after ischemia/reperfusion, whereas in the IPA-treated ischemic group, GFAP, S-100, Iba-1, and IB4, but not vimentin, immunoreactivity was distinctly lower than that in the vehicle-treated ischemic groups. The administration of IPA significantly decreased the level of 4-hydroxy-2-nonenal, a marker of lipid peroxidation, in ischemic hippocampal homogenates compared with that in the vehicle-treated ischemic groups at various times after ischemia/reperfusion. In addition, immunostaining for 8-hydroxy-2'-deoxyguanosine showed DNA damage in pyramidal neurons in the ischemic CA1 was significantly lower in the IPA-treated ischemic groups than in the vehicle-treated ischemic groups. These results suggest that IPA protects neurons from ischemia-induced neuronal damage by reducing DNA damage and lipid peroxidation.

  20. Is the 2,3-carbon-carbon bond of indole really inert to oxidative cleavage by Oxone?--synthesis of isatoic anhydrides from indoles.

    PubMed

    Nelson, Amber C; Kalinowski, Emily S; Czerniecki, Nikolas J; Jacobson, Taylor L; Grundt, Peter

    2013-11-21

    A recent report has indicated that the oxidizing agent Oxone does not possess the ability to cleave the 2,3-carbon-carbon bond of indole. Work in our laboratory shows that this is not the case. Indole and a variety of aryl ring substituted derivatives readily react to form synthetically important isatoic anhydrides.

  1. Study of 1-deoxy-1-(indol-3-yl)-L-sorbose, 1-deoxy-1-(indol-3-yl)-L-tagatose, and their analogs.

    PubMed

    Lavrenov, Sergey N; Korolev, Alexander M; Reznikova, Marina I; Sosnov, Andrey V; Preobrazhenskaya, Maria N

    2003-01-20

    Alkaline degradation of the ascorbigen 2-C-[(indol-3-yl)methyl]-alpha-L-xylo-hex-3-ulofuranosono-1,4-lactone (1a) led to a mixture of 1-deoxy-1-(indol-3-yl)-L-sorbose (2a) and 1-deoxy-1-(indol-3-yl)-L-tagatose (3a). The mixture of diastereomeric ketoses underwent acetylation and pyranose ring opening under the action of acetic anhydride in pyridine in the presence of 4-dimethylaminopyridine (DMAP) with the formation of a mixture of (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-xylo-hex-1-enitol (4a) and (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-lyxo-hex-1-enitol (5a), which were separated chromatographically. Deacetylation of 4a or 5a afforded cyclised tetrols, tosylation of which in admixture resulted in 1-deoxy-1-(indol-3-yl)-3,5-di-O-tosyl-alpha-L-sorbopyranose (12a) and 1-deoxy-1-(indol-3-yl)-4,5-di-O-tosyl-alpha-L-tagatopyranose (13a). Under alkaline conditions 13a readily formed 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)cyclopenten-2-one (15a) in 90% yield. Similar transformations were performed for N-methyl- and N-methoxyindole derivatives.

  2. The multifaceted roles of the interspecies signalling molecule indole in Agrobacterium tumefaciens.

    PubMed

    Lee, Jin-Hyung; Kim, Yong-Guy; Baek, Kwang-Hyun; Cho, Moo Hwan; Lee, Jintae

    2015-04-01

    Bacteria utilize signal molecules to ensure their survival in environmental niches, and indole is an interspecies and interkingdom signalling molecule, which is widespread in the natural environment. In this study, we sought to identify novel roles of indole in soil-borne bacterium Agrobacterium tumefaciens. Agrobacterium tumefaciens was found not to synthesize indole and to degrade it rapidly. The addition of exogenous indole dose-dependently inhibited A. tumefaciens growth and decreased its motility. Surprisingly, indole markedly increased A. tumefaciens biofilm formation on polystyrene, glass and nylon membrane surfaces and enhanced its antibiotic tolerance. Transcriptional analysis showed that indole markedly up-regulated several biofilm-related (celA, cheA, exoR, phoB, flgE, fliR and motA), stress-related genes (clpB, dnaK, gsp, gyrB, marR and soxR) and efflux genes (emrA, norM, and Atu2551) in A. tumefaciens, which partially explained the increased biofilm formation and antibiotic tolerance. In contrast, the plant auxin indole-3-acetic acid did not affect biofilm formation, antibiotic tolerance or gene expression. Interestingly, indole was found to exhibit several similarities with antibiotics, as it inhibited the growth of non-indole-producing bacteria, whereas these bacteria countered its effects by rapidly degrading indole, and by enhancing biofilm formation and antibiotic tolerance.

  3. A Pd(0)-Mediated Indole (Macro)cyclization Reaction

    PubMed Central

    Breazzano, Steven P.; Poudel, Yam B.; Boger, Dale L.

    2013-01-01

    Herein, we report a systematic study of the Larock indole annulation designed to explore the scope and define the generality of its use in macrocyclization reactions, its use in directly accessing the chloropeptin I versus II DEF ring system as well as key unnatural isomers, its utility for both peptide-derived and more conventional carbon-chain based macrocycles, and its extension to intramolecular cyclizations with formation of common ring sizes. The studies define a powerful method complementary to the Stille or Suzuki cross-coupling reactions for the synthesis of cyclic or macrocyclic ring systems containing an embedded indole, tolerating numerous functional groups and incorporating various (up to 28-membered) ring sizes. As a result of the efforts to expand the usefulness and scope of the reaction, we also disclose a catalytic variant of the reaction along with a powerful Pd2(dba)3 derived catalyst system, and an examination of the factors impacting reactivity and catalysis. PMID:23298368

  4. Regulatory and Functional Aspects of Indolic Metabolism in Plant Systemic Acquired Resistance.

    PubMed

    Stahl, Elia; Bellwon, Patricia; Huber, Stefan; Schlaeppi, Klaus; Bernsdorff, Friederike; Vallat-Michel, Armelle; Mauch, Felix; Zeier, Jürgen

    2016-05-02

    Tryptophan-derived, indolic metabolites possess diverse functions in Arabidopsis innate immunity to microbial pathogen infection. Here, we investigate the functional role and regulatory characteristics of indolic metabolism in Arabidopsis systemic acquired resistance (SAR) triggered by the bacterial pathogen Pseudomonas syringae. Indolic metabolism is broadly activated in both P. syringae-inoculated and distant, non-inoculated leaves. At inoculation sites, camalexin, indol-3-ylmethylamine (I3A), and indole-3-carboxylic acid (ICA) are the major accumulating compounds. Camalexin accumulation is positively affected by MYB122, and the cytochrome P450 genes CYP81F1 and CYP81F2. Local I3A production, by contrast, occurs via indole glucosinolate breakdown by PEN2- dependent and independent pathways. Moreover, exogenous application of the defense hormone salicylic acid stimulates I3A generation at the expense of its precursor indol-3-ylmethylglucosinolate (I3M), and the SAR regulator pipecolic acid primes plants for enhanced P. syringae-induced activation of distinct branches of indolic metabolism. In uninfected systemic tissue, the metabolic response is more specific and associated with enhanced levels of the indolics I3A, ICA, and indole-3-carbaldehyde (ICC). Systemic indole accumulation fully depends on functional CYP79B2/3, PEN2, and MYB34/51/122, and requires functional SAR signaling. Genetic analyses suggest that systemically elevated indoles are dispensable for SAR and associated systemic increases of salicylic acid. However, soil-grown but not hydroponically -cultivated cyp79b2/3 and pen2 plants, both defective in indolic secondary metabolism, exhibit pre-induced immunity, which abrogates their intrinsic ability to induce SAR.

  5. Transport and metabolism of indole-3-acetyl-myo-inositol-galactoside in seedlings of Zea mays

    NASA Technical Reports Server (NTRS)

    Komoszynski, M.; Bandurski, R. S.

    1986-01-01

    Indole-3-acetyl-myo-inositol galactoside labeled with 3H in the indole and 14C in the galactose moieties was applied to kernels of 5 day old germinating seedlings of Zea mays. Indole-3-acetyl-myo-inositol galactoside was not transported into either the shoot or root tissue as the intact molecule but was instead hydrolyzed to yield [3H]indole-3-acetyl-myo-inositol and [3H]indole-3-acetic acid which were then transported to the shoot with little radioactivity going to the root. With certain assumption concerning the equilibration of applied [3H]indole-3-acetyl-myo-inositol-[U-14C]galactose with the endogenous pool, it may be concluded that indole-3-acetyl-myo-inositol galactoside in the endosperm supplies about 2 picomoles per plant per hour of indole-3-acetyl-myo-inositol and 1 picomole per plant per hour of indole-3-acetic acid to the shoot and thus is comparable to indole-3-acetyl-myo-inositol as a source of indole-acetic acid for the shoot. Quantitative estimates of the amount of galactose in the kernels suggest that [3H]indole-3-acetyl-myo-inositol-[14C]galactose is hydrolyzed after the compound leaves the endosperm but before it reaches the shoot. In addition, [3H]indole-3-acetyl-myo-inositol-[14C]galactose supplies appreciable amounts of 14C to the shoot and both 14C and 3H to an uncharacterized insoluble fraction of the endosperm.

  6. Transport and metabolism of indole-3-acetyl-myo-inositol-galactoside in seedlings of Zea mays

    NASA Technical Reports Server (NTRS)

    Komoszynski, M.; Bandurski, R. S.

    1986-01-01

    Indole-3-acetyl-myo-inositol galactoside labeled with 3H in the indole and 14C in the galactose moieties was applied to kernels of 5 day old germinating seedlings of Zea mays. Indole-3-acetyl-myo-inositol galactoside was not transported into either the shoot or root tissue as the intact molecule but was instead hydrolyzed to yield [3H]indole-3-acetyl-myo-inositol and [3H]indole-3-acetic acid which were then transported to the shoot with little radioactivity going to the root. With certain assumption concerning the equilibration of applied [3H]indole-3-acetyl-myo-inositol-[U-14C]galactose with the endogenous pool, it may be concluded that indole-3-acetyl-myo-inositol galactoside in the endosperm supplies about 2 picomoles per plant per hour of indole-3-acetyl-myo-inositol and 1 picomole per plant per hour of indole-3-acetic acid to the shoot and thus is comparable to indole-3-acetyl-myo-inositol as a source of indole-acetic acid for the shoot. Quantitative estimates of the amount of galactose in the kernels suggest that [3H]indole-3-acetyl-myo-inositol-[14C]galactose is hydrolyzed after the compound leaves the endosperm but before it reaches the shoot. In addition, [3H]indole-3-acetyl-myo-inositol-[14C]galactose supplies appreciable amounts of 14C to the shoot and both 14C and 3H to an uncharacterized insoluble fraction of the endosperm.

  7. Hantavirus Prevention: Cleanup of Rodent Contamination

    DTIC Science & Technology

    2008-09-01

    Hantaviruses in the Americas may cause human disease involving the lungs, hence the name " hantavirus pulmonary syndrome" (HPS). Since May 1993, a...humans are also found in other rodents, but the number of cases stemming from these hantaviruses is small when compared to SNV. Hantavirus is shed in... HANTAVIRUS PREVENTION: CLEANUP OF RODENT CONTAMINATION Technical Information Paper 18-001-0306

  8. Rodent-vegetation relationships in southeastern Montana

    Treesearch

    James G. MacCracken; Daniel W. Uresk; Hansen; Richard M.

    1985-01-01

    Plant communities of southeastern Montana were surveyed for rodents over a two year period. Deer mice (Peromyscus maniculatus) were the most abundant rodent species found on the study area. Prairie voles (Microtus ochrogaster), meadow voles (M. pennsylvanicus), sagebrush voles (Lagurus curtatus...

  9. Magnetic field effect on indole exciplexes: a comparative study

    NASA Astrophysics Data System (ADS)

    Sengupta, Tamal; Basu, Samita

    2004-04-01

    A comparative magnetic field effect (MFE) study was done on indole exciplexes with various acceptors, anthracene, pyrene, all-s- trans-1,4-diphenylbuta-1,3-diene and 9-cyanophenanthrene. A surprisingly low magnetic field effect was detected for the 9-cyanophenanthrene exciplexes and was correlated with exciplex geometry. The wavelength dependence of magnetic field effect confirms the presence of single charge-transfer complex for all the exciplexes with 1,2-dimethylindole.

  10. Synthesis of an indole analog of folic acid

    SciTech Connect

    Shengeliya, M.S.; Avramenko, V.G.; Kuleshova, L.N.; Ershova, Yu.A.; Chernov, V.A.; Surorov, N.N.

    1987-06-01

    The authors study the replacement of the p-aminobenzoic acid (PABA) moiety. The authors synthesized an indole analog of folic acid, namely dimethyl N-(5-(2'-amino-4'-oxo-6'-pteridinyl)methylaminoindol-2-yl)glutamate. The physicochemical properties and the chemical shifts in the PMR spectra of the compounds obtained are shown. The examination of the compound for antitumor activity was carried out using rats and mice.

  11. Hybrid Monoterpenoid Indole Alkaloids Obtained as Artifacts from Rauvolfia tetraphylla.

    PubMed

    Gao, Yuan; Zhou, Dong-Sheng; Hai, Ping; Li, Yan; Wang, Fei

    2015-10-01

    Five new hybrid monoterpenoid indole alkaloids bearing an unusual 2,2-dimethyl-4-oxopiperidin-6-yl moiety, namely rauvotetraphyllines F-H (1, 3, 4), 17-epi-rauvotetraphylline F (2) and 21-epi-rauvotetraphylline H (5), were isolated from the aerial parts of Rauvolfia tetraphylla. Their structures were established by extensive spectroscopic analysis. The new alkaloids were evaluated for their cytotoxicity in vitro against five human cancer cell lines.

  12. Monoterpenoid Indole Alkaloids from Inadequately Dried Leaves of Alstonia scholaris.

    PubMed

    Qin, Xu-Jie; Zhao, Yun-Li; Song, Chang-Wei; Wang, Bei; Chen, Ying-Ying; Liu, Lu; Li, Qiong; Li, Dan; Liu, Ya-Ping; Luo, Xiao-Dong

    2015-08-01

    Six new indole alkaloids, named alstoniascholarines L-Q (1-6), together with nineteen known analogues were isolated from the inadequately dried leaves of Alstonia scholaris. Their structures were elucidated on the basis of extensive analysis of spectroscopic data and by comparison of their physical and spectroscopic data with the literature values. In addition, the new alkaloids were tested for their cytotoxic and neurite outgrowth-promoting activities.

  13. Alistonitrine A, a caged monoterpene indole alkaloid from Alstonia scholaris.

    PubMed

    Zhu, Guo-Yuan; Yao, Xiao-Jun; Liu, Liang; Bai, Li-Ping; Jiang, Zhi-Hong

    2014-02-21

    Alistonitrine A, a new monoterpene indole alkaloid incorporating a third nitrogen atom, was isolated from the leaves of Alstonia scholaris and found to possess an unprecedented caged skeleton with a unique 6/5/6/5/5/6 ring system. Its structure and absolute configuration were established by extensive spectroscopic analyses and electron circular dichroism calculations. A plausible biogenetic pathway has been proposed for the biosynthesis of alistonitrine A from picrinine.

  14. Indole and beta-carboline alkaloids from Geissospermum sericeum.

    PubMed

    Steele, Jonathan C P; Veitch, Nigel C; Kite, Geoffrey C; Simmonds, Monique S J; Warhurst, David C

    2002-01-01

    The indole alkaloid geissoschizoline (1) and two new derivatives, geissoschizoline N(4)-oxide (2) and 1,2-dehydrogeissoschizoline (3), were obtained from the bark of Geissospermum sericeum together with the beta-carboline alkaloid flavopereirine (4). The in vitro antiplasmodial activity of these compounds was evaluated in chloroquine-resistant (K1) and chloroquine-sensitive (T9-96) Plasmodium falciparum. Their cytotoxicity was determined in a human (KB) cell line.

  15. Pediatric Rodent Models of Traumatic Brain Injury.

    PubMed

    Semple, Bridgette D; Carlson, Jaclyn; Noble-Haeusslein, Linda J

    2016-01-01

    Due to a high incidence of traumatic brain injury (TBI) in children and adolescents, age-specific studies are necessary to fully understand the long-term consequences of injuries to the immature brain. Preclinical and translational research can help elucidate the vulnerabilities of the developing brain to insult, and provide model systems to formulate and evaluate potential treatments aimed at minimizing the adverse effects of TBI. Several experimental TBI models have therefore been scaled down from adult rodents for use in juvenile animals. The following chapter discusses these adapted models for pediatric TBI, and the importance of age equivalence across species during model development and interpretation. Many neurodevelopmental processes are ongoing throughout childhood and adolescence, such that neuropathological mechanisms secondary to a brain insult, including oxidative stress, metabolic dysfunction and inflammation, may be influenced by the age at the time of insult. The long-term evaluation of clinically relevant functional outcomes is imperative to better understand the persistence and evolution of behavioral deficits over time after injury to the developing brain. Strategies to modify or protect against the chronic consequences of pediatric TBI, by supporting the trajectory of normal brain development, have the potential to improve quality of life for brain-injured children.

  16. Developments of indoles as anti-HIV-1 inhibitors.

    PubMed

    Xu, Hui; Lv, Min

    2009-01-01

    Since the first case of acquired immunodeficiency syndrome (AIDS) was reported in 1981, AIDS has always been a global health threat and the leading cause of deaths due to the rapid emergence of drug-resistance and unwanted metabolic side effects. Every day in 2007 an estimated 6850 people were newly infected with human immunodeficiency virus (HIV). Over the past 28 years the rapid worldwide spread of AIDS has prompted an intense research effort to discover compounds that could effectively inhibit HIV. The development of new, selective and safe inhibitors for the treatment of HIV, therefore, still remains a high priority for medical research. To the best of our knowledge, the indole derivatives have been considered as one class of promising HIV-1 inhibitors, such as delavirdine approved by the Food and Drug Administration (FDA) in 1997 for use in combination with other antiretrovirals in adults with HIV infection. In this review we focus on the synthesis and anti-HIV-1 activity of indole derivatives, in the meantime, the structure-activity relationship (SAR) for some derivatives are also surveyed. It will pave the way for the design of indole derivatives as anti-HIV-1 drugs in the future.

  17. [Populations of harmful rodents on commercial swine-breeding farms and their effect on the technology of swine feeding].

    PubMed

    Bildirev, N; Kesiakova, S

    1983-01-01

    The effect was studied of the swine-feeding technology in five industrial complexes on the population density of the harmful rodents in them. This made it necessary to estimate the population density of the rodents in each productional section of the swine-breeding complexes, and to work out their technologic characteristic on the nutrition principle. It was established that the population density of rodents correlated positively with their access to feeds. In sections where rated, mechanical, and protected feeding was prectised the number of rodents were considerably lower than in sections with unrated feeding of pigs. It is believed that the rat invasion of the buildings in the industrial swine-breeding complexes is a factor that contributes to the rise of populations of harmful rodents, while the vast access to feeds is of greater importance chiefly for their further development.

  18. Synthesis of annulated bis-indoles through Au(i)/Brønsted acid-catalyzed reactions of (1H-indol-3-yl)(aryl)methanols with 2-(arylethynyl)-1H-indoles.

    PubMed

    Inamdar, Suleman M; Gonnade, Rajesh G; Patil, Nitin T

    2017-01-25

    A general method to access annulated bis-indoles from (1H-indol-3-yl)(aryl)methanols and 2-(arylethynyl)-1H-indoles under the catalysis of the Ph3PAuOTf/Brønsted acid binary catalyst system has been developed. The reaction was found to proceed in a highly efficient manner and benefit from easy-to-make starting materials, broad substrate scope and operational simplicity. The potential of this method has also been exemplified for the synthesis of pyrrole-annulated indoles using 2-(phenylethynyl)-1H-indoles and phenyl(1H-pyrrol-2-yl)methanols. Furthermore, the use of a ternary catalyst system, involving PdCl2/Brønsted acid/Ph3PAuOTf catalysts, has been realized for the synthesis of annulated bis-indoles starting directly from 2-(phenylbuta-1,3-diyn-1-yl)aniline and (1H-indol-3-yl)(aryl)methanol. Mechanistically, this reaction is very interesting since the overall process involves three different catalytic cycles catalyzed by three different catalysts in a relay fashion.

  19. The reaction of indole with the aminoacrylate intermediate of Salmonella typhimurium tryptophan synthase: observation of a primary kinetic isotope effect with 3-[(2)H]indole.

    PubMed

    Cash, Michael T; Miles, Edith W; Phillips, Robert S

    2004-12-15

    The bacterial tryptophan synthase alpha(2)beta(2) complex catalyzes the final reactions in the biosynthesis of L-tryptophan. Indole is produced at the active site of the alpha-subunit and is transferred through a 25-30 A tunnel to the beta-active site, where it reacts with an aminoacrylate intermediate. Lane and Kirschner proposed a two-step nucleophilic addition-tautomerization mechanism for the reaction of indole with the aminoacrylate intermediate, based on the absence of an observed kinetic isotope effect (KIE) when 3-[(2)H]indole reacts with the aminoacrylate intermediate. We have now observed a KIE of 1.4-2.0 in the reaction of 3-[(2)H]indole with the aminoacrylate intermediate in the presence of monovalent cations, but not when an alpha-subunit ligand, disodium alpha-glycerophosphate (Na(2)GP), is present. Rapid-scanning stopped flow kinetic studies were performed of the reaction of indole and 3-[(2)H]indole with tryptophan synthase preincubated with L-serine, following the decay of the aminoacrylate intermediate at 350 nm, the formation of the quinonoid intermediate at 476 nm, and the formation of the L-Trp external aldimine at 423 nm. The addition of Na(2)GP dramatically slows the rate of reaction of indole with the alpha-aminoacrylate intermediate. A primary KIE is not observed in the reaction of 3-[(2)H]indole with the aminoacrylate complex of tryptophan synthase in the presence of Na(2)GP, suggesting binding of indole with tryptophan synthase is rate limiting under these conditions. The reaction of 2-methylindole does not show a KIE, either in the presence of Na(+) or Na(2)GP. These results support the previously proposed mechanism for the beta-reaction of tryptophan synthase, but suggest that the rate limiting step in quinonoid intermediate formation from indole and the aminoacrylate intermediate is deprotonation.

  20. Controlling bacterial behavior with indole-containing natural products and derivatives

    PubMed Central

    Melander, Roberta J.; Minvielle, Marine J.; Melander, Christian

    2014-01-01

    Indole has recently been implicated as an important small molecule signal utilized by many bacteria to coordinate various forms of behavior. Indole plays a role in numerous bacterial processes, including: biofilm formation and maintenance, virulence factor production, antibiotic resistance and persister cell formation. Intercepting indole-signaling pathways with appropriately designed small molecules provides a n opportunity to control unwanted bacterial behaviors, and is an attractive anti-virulence therapeutic strategy. In this review, we give an overview of the process controlled by indole signaling, and summarize current efforts to design indole-containing small molecules to intercept these pathways, and detail the synthetic efforts towards accessing indole derived bioactive small molecules. PMID:25267859

  1. Origins of Regioselectivity in the Fischer Indole Synthesis of a Selective Androgen Receptor Modulator.

    PubMed

    Noey, Elizabeth L; Yang, Zhongyue; Li, Yanwei; Yu, Hannah; Richey, Rachel N; Merritt, Jeremy M; Kjell, Douglas P; Houk, K N

    2017-06-02

    The selective androgen receptor modulator, (S)-(7-cyano-4-(pyridin-2-ylmethyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic acid isopropyl ester, LY2452473, is a promising treatment of side effects of prostate cancer therapies. An acid-catalyzed Fischer indolization is a central step in its synthesis. The reaction leads to only one of the two possible indole regioisomers, along with minor decomposition products. Computations show that the formation of the observed indole is most favored energetically, while the potential pathway to the minor isomer leads instead to decomposition products. The disfavored [3,3]-sigmatropic rearrangement, which would produce the unobserved indole product, is destabilized by the electron-withdrawing phthalimide substituent. The most favored [3,3]-sigmatropic rearrangement transition state is bimodal, leading to two reaction intermediates from one transition state, which is confirmed by molecular dynamics simulations. Both intermediates can lead to the observed indole product, albeit through different mechanisms.

  2. Indole-Induced Activities of β-Lactamase and Efflux Pump Confer Ampicillin Resistance in Pseudomonas putida KT2440

    PubMed Central

    Kim, Jisun; Shin, Bora; Park, Chulwoo; Park, Woojun

    2017-01-01

    Indole, which is widespread in microbial communities, has received attention because of its effects on bacterial physiology. Pseudomonas putida and Pseudomonas aeruginosa can acquire ampicillin (Amp) resistance during growth on indole-Amp agar. Transcriptome, mutant, and inhibitor studies have suggested that Amp resistance induced by indole can be attributed to increased gene expression of ttgAB encoding two genes of RND-type multidrug efflux operons and an ampC encoding β-lactamase. Expression, enzyme activities, and mutational analyses indicated that AmpC β-lactamase is important for acquiring Amp resistance of P. putida in the presence of indole. Here, we show, for the first time, that volatile indole increased Amp-resistant cells. Consistent with results of the volatile indole assay, a low concentration of indole in liquid culture promoted growth initially, but led to mutagenesis after indole was depleted, which could not be observed at high indole concentrations. Interestingly, ttgAB and ampC gene expression levels correlate with the concentration of indole, which might explain the low number of Amp-mutated cells in high indole concentrations. The expression levels of genes involved in mutagenesis, namely rpoS, recA, and mutS, were also modulated by indole. Our data indicates that indole reduces Amp-induced heterogeneity by promoting expression of TtgABC or MexAB-OprM efflux pumps and the indole-induced β-lactamase in P. putida and P. aeruginosa. PMID:28352264

  3. Ruthenium-catalyzed direct C3 alkylation of indoles with α,β-unsaturated ketones.

    PubMed

    Li, Shuai-Shuai; Lin, Hui; Zhang, Xiao-Mei; Dong, Lin

    2015-01-28

    In this paper, a simple and highly efficient ruthenium-catalyzed direct C3 alkylation of indoles with various α,β-unsaturated ketones without chelation assistance has been developed. This novel C-H activation methodology exhibits a broad substrate scope such as different substituted indoles, pyrroles, and other azoles. Further synthetic applications of the alkylation products can lead to more attractive 3,4-fused tricyclic indoles.

  4. Rodents: food or pests in Neolithic Orkney

    PubMed Central

    Romaniuk, Andrzej A.; Shepherd, Alexandra N.; Clarke, David V.; Sheridan, Alison J.; Fraser, Sheena; Bartosiewicz, László

    2016-01-01

    Rodents have important effects on contemporary human societies, sometimes providing a source of food but more often as agricultural pests, or as vectors and reservoirs of disease. Skeletal remains of rodents are commonly found in archaeological assemblages from around the world, highlighting their potential importance to ancient human populations. However, there are few studies of the interactions between people and rodents at such sites and most of these are confined to locations where rodents have formed a part of the recent diet. Here we compare the accumulation pattern of rodent remains from four locations within and adjacent to the renowned Neolithic site of Skara Brae, Orkney, showing that those within the settlement itself were the result of deliberate human activity. The accumulation and nature of burnt bones, incorporated over an extended period within deposits of household waste, indicate that rodents were used as a nutritional resource and may have been the subject of early pest control. We, therefore, provide the first evidence for the exploitation or control of rodents by the Neolithic inhabitants of Europe. PMID:27853568

  5. Rodents: food or pests in Neolithic Orkney.

    PubMed

    Romaniuk, Andrzej A; Shepherd, Alexandra N; Clarke, David V; Sheridan, Alison J; Fraser, Sheena; Bartosiewicz, László; Herman, Jeremy S

    2016-10-01

    Rodents have important effects on contemporary human societies, sometimes providing a source of food but more often as agricultural pests, or as vectors and reservoirs of disease. Skeletal remains of rodents are commonly found in archaeological assemblages from around the world, highlighting their potential importance to ancient human populations. However, there are few studies of the interactions between people and rodents at such sites and most of these are confined to locations where rodents have formed a part of the recent diet. Here we compare the accumulation pattern of rodent remains from four locations within and adjacent to the renowned Neolithic site of Skara Brae, Orkney, showing that those within the settlement itself were the result of deliberate human activity. The accumulation and nature of burnt bones, incorporated over an extended period within deposits of household waste, indicate that rodents were used as a nutritional resource and may have been the subject of early pest control. We, therefore, provide the first evidence for the exploitation or control of rodents by the Neolithic inhabitants of Europe.

  6. Modelling flavoenzymatic charge transfer events: development of catalytic indole deuteration strategies.

    PubMed

    Murray, Alexander T; Challinor, Jonathan D; Gulácsy, Christina E; Lujan, Cristina; Hatcher, Lauren E; Pudney, Christopher R; Raithby, Paul R; John, Matthew P; Carbery, David R

    2016-04-12

    The formation and chemistry of flavin-indole charge transfer (CT) complexes has been studied using a model cationic flavin. The ability to form a CT complex is sensitive to indole structure as gauged by spectroscopic, kinetics and crystallographic studies. Single crystals of sufficient quality of a flavin-indole CT complex, suitable for X-ray diffraction, have been grown, allowing solid-state structural analysis. When CT complex formation is conducted in d4-methanol, an efficient and synthetically useful C-3 indole deuteration is observed.

  7. Indole Alkaloids from the Sea Anemone Heteractis aurora and Homarine from Octopus cyanea.

    PubMed

    Shaker, Kamel H; Göhl, Matthias; Müller, Tobias; Seifert, Karlheinz

    2015-11-01

    The two new indole alkaloids 2-amino-1,5-dihydro-5-(1H-indol-3-ylmethyl)-4H-imidazol-4-one (1), 2-amino-5-[(6-bromo-1H-indol-3-yl)methyl]-3,5-dihydro-3-methyl-4H-imidazol-4-one (2), and auramine (3) have been isolated from the sea anemone Heteractis aurora. Both indole alkaloids were synthesized for the confirmation of the structures. Homarine (4), along with uracil (5), hypoxanthine (6), and inosine (7) have been obtained from Octopus cyanea.

  8. Indole is an essential herbivore-induced volatile priming signal in maize

    PubMed Central

    Erb, Matthias; Veyrat, Nathalie; Robert, Christelle A. M.; Xu, Hao; Frey, Monika; Ton, Jurriaan; Turlings, Ted C. J.

    2015-01-01

    Herbivore-induced volatile organic compounds prime non-attacked plant tissues to respond more strongly to subsequent attacks. However, the key volatiles that trigger this primed state remain largely unidentified. In maize, the release of the aromatic compound indole is herbivore-specific and occurs earlier than other induced responses. We therefore hypothesized that indole may be involved in airborne priming. Using indole-deficient mutants and synthetic indole dispensers, we show that herbivore-induced indole enhances the induction of defensive volatiles in neighbouring maize plants in a species-specific manner. Furthermore, the release of indole is essential for priming of mono- and homoterpenes in systemic leaves of attacked plants. Indole exposure markedly increases the herbivore-induced production of the stress hormones jasmonate-isoleucine conjugate and abscisic acid, which represents a likely mechanism for indole-dependent priming. These results demonstrate that indole functions as a rapid and potent aerial priming agent that prepares systemic tissues and neighbouring plants for incoming attacks. PMID:25683900

  9. The mechanism of patulin's cytotoxicity and the antioxidant activity of indole tetramic acids

    SciTech Connect

    Riley, R.T.; Showker, J.L. )

    1991-06-01

    In LLC-PK1 cells exposed to patulin (50 microM), lipid peroxidation, abrupt calcium influx, extensive blebbing, and total LDH release appeared to be serially connected events with each representing a step in the loss of structural integrity of the plasma membrane. The aforementioned patulin-induced events were prevented by concurrent incubation with butylated hydroxytoluene, deferoxamine, and cyclopiazonic acid, a fungal metabolite. Patulin also caused depletion of nonprotein sulfhydryls, increased 86Rb+ efflux, dome collapse, and eventually the loss of cell viability. These events were not prevented by antioxidants, results consistent with the hypothesis that they were also serially connected but occurring parallel to those previously mentioned. The earliest events observed in patulin-treated cells were the decrease in nonprotein sulfhydryls and increase in 86Rb+ efflux (5 min) which occurred before statistically significant alterations in protein-bound sulfhydryls. The increased potassium efflux (86Rb+ efflux) occurred via a pathway distinct from BaCl2, quinine, or tetraethylammonium sensitive potassium channels. This is the first published report of the antioxidant activity of indole tetramic acids (cyclopiazonic acid and cyclopiazonic acid imine). The protective effect of tetramic acids in LLC-PK1 cells was restricted to indole tetramic acids, and their prevention of lipid peroxidation did not involve iron chelation. The results of this study demonstrate that cyclopiazonic acid is a potent inhibitor of azide-insensitive, ATP-dependent, a23187-sensitive calcium uptake by the lysate of LLC-PK1 cells. This result is consistent with the hypothesis that the endoplasmic reticulum calcium transport ATPase is a sensitive target for cyclopiazonic acid in LLC-PK1 cells.

  10. The stadium effect: rodent damage patterns in rice fields explored using giving-up densities.

    PubMed

    Jones, Clare R; Lorica, Ma Renee P; Villegas, James M; Ramal, Angelee F; Horgan, Finbarr G; Singleton, Grant R; Stuart, Alexander M

    2016-12-19

    Rodents are globally important pre-harvest pests of rice. In South-east Asia, rodent damage to growing rice crops is commonly concentrated towards the center of rice fields, away from the field edge resulting in a clear pattern known as the 'stadium effect'. To further understand this behavior of rodent pests and develop recommendations for future research and management, we examined the relation between giving-up densities (GUDs) and damage patterns. In Tanay, Luzon, Philippines, GUD trays containing pieces of coconut in a matrix of sand were placed at four different distances from the field edge to quantify the perceived risk of predation in a rice field pest, Rattus tanezumi. GUDs were recorded during a dry and wet season crop at the reproductive and ripening stages of rice. In addition, assessments of active burrows, tracking tile activity and rodent damage to the rice crop, were conducted in the dry season. GUDs were significantly lower in the center of the rice fields than on the field edges suggesting that rodent damage to rice is greater in the middle of rice fields due to a lower perceived predation risk. Furthermore, this perception of predation risk (or fear) increases towards the field edge and is greatest on the rice bund, where there was no vegetation cover. We discuss the implications for rodent management and rodent damage assessments in rice fields. This is the first documented use of GUDs in a rice agro-ecosystem in Asia, thus we identify the challenges and lessons learned through this process. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Current Assessment of the Effects of Environmental Chemicals on the Mammary Gland in Guideline Rodent Studies by the U.S. Environmental Protection Agency (U.S. EPA), Organisation for Economic Co-operation and Development (OECD), and National Toxicology Program (NTP)

    PubMed Central

    2010-01-01

    Background: Evaluation of the structural and/or functional integrity of the mammary gland (MG) across life stages is integral to the assessment of developmental, reproductive, and carcinogenic risk for environmental chemicals. Objectives: In this commentary I characterize MG assessment recommended in U.S. Environmental Protection Agency, Organisation for Economic Co-operation and Development, and National Toxicology Program guideline toxicology study protocols and identify any information gaps for the evaluation of MG development, structure, and function. Discussion: Several data gaps, issues, and challenges were identified. Current guidelines that include a lactation phase do not provide specific recommendations to record observations on maternal or offspring lactation or nursing behavior. In guideline studies, the assessment of MG toxicity often relies upon indirect, nonspecific, or surrogate end points, and information that could be useful in the interpretation of these data (e.g., mode of action or toxicokinetics) is often unavailable. Most guideline studies designed to assess general organ toxicity do not expose test animals during sensitive stages of MG development; histopathological evaluation of the developing MG is not routinely conducted; and evaluation of MG tissue for both sexes is inconsistently recommended. Conclusions: I propose the following general recommendations to enhance MG assessment in guideline toxicology studies: a) inclusion of more specific criteria for the evaluation of MG end points in guideline language, b) inclusion of histopathological evaluation of MG development (using whole-mount techniques) in existing or new guideline protocols that include offspring with perinatal and/or pubertal treatment, c) incorporation of perinatal exposures into rodent subchronic and carcinogenicity assays, and d) expansion of the histopathological evaluation of male MG tissue. PMID:21118785

  12. Current assessment of the effects of environmental chemicals on the mammary gland in guideline rodent studies by the U.S. Environmental Protection Agency (U.S. EPA), Organisation for Economic Co-operation and Development (OECD), and National Toxicology Program (NTP).

    PubMed

    Makris, Susan L

    2011-08-01

    Evaluation of the structural and/or functional integrity of the mammary gland (MG) across life stages is integral to the assessment of developmental, reproductive, and carcinogenic risk for environmental chemicals. In this commentary I characterize MG assessment recommended in U.S. Environmental Protection Agency, Organisation for Economic Co-operation and Development, and National Toxicology Program guideline toxicology study protocols and identify any information gaps for the evaluation of MG development, structure, and function. Several data gaps, issues, and challenges were identified. Current guidelines that include a lactation phase do not provide specific recommendations to record observations on maternal or offspring lactation or nursing behavior. In guideline studies, the assessment of MG toxicity often relies upon indirect, nonspecific, or surrogate end points, and information that could be useful in the interpretation of these data (e.g., mode of action or toxicokinetics) is often unavailable. Most guideline studies designed to assess general organ toxicity do not expose test animals during sensitive stages of MG development; histopathological evaluation of the developing MG is not routinely conducted; and evaluation of MG tissue for both sexes is inconsistently recommended. I propose the following general recommendations to enhance MG assessment in guideline toxicology studies: a) inclusion of more specific criteria for the evaluation of MG end points in guideline language, b) inclusion of histopathological evaluation of MG development (using whole-mount techniques) in existing or new guideline protocols that include offspring with perinatal and/or pubertal treatment, c) incorporation of perinatal exposures into rodent subchronic and carcinogenicity assays, and d) expansion of the histopathological evaluation of male MG tissue.

  13. In vitro rescue of genital strains of Chlamydia trachomatis from interferon-γ and tryptophan depletion with indole-positive, but not indole-negative Prevotella spp.

    PubMed

    Ziklo, Noa; Huston, Wilhelmina M; Taing, Kuong; Katouli, Mohammad; Timms, Peter

    2016-12-03

    The natural course of sexually transmitted infections caused by Chlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key role in the outcome of C. trachomatis infections. Interferon-gamma (IFN-γ), known for its anti-chlamydial properties, activates the expression of indoleamine 2,3-dioxygenase (IDO1) in epithelial cells, an enzyme that catabolizes the amino acid L- tryptophan into N-formylkynurenine, depleting the host cell's pool of tryptophan. Although C. trachomatis is a tryptophan auxotroph, urogenital strains (but not ocular strains) have been shown in vitro to have the ability to produce tryptophan from indole using the tryptophan synthase (trpBA) gene. It has been suggested that indole producing bacteria from the vaginal microbiota could influence the outcome of Chlamydia infection. We used two in vitro models (treatment with IFN-γ or direct limitation of tryptophan), to study the effects of direct rescue by the addition of exogenous indole, or by the addition of culture supernatant from indole-positive versus indole-negative Prevotella strains, on the growth and infectivity of C. trachomatis. We found that only supernatants from the indole-positive strains, P. intermedia and P. nigrescens, were able to rescue tryptophan-starved C. trachomatis. In addition, we analyzed vaginal secretion samples to determine physiological indole concentrations. In spite of the complexity of vaginal secretions, we demonstrated that for some vaginal specimens with higher indole levels, there was a link to higher recovery of the Chlamydia under tryptophan-starved conditions, lending preliminary support to the critical role of the IFN-γ-tryptophan-indole axis in vivo. Our data provide evidence for the ability of both exogenous indole as well as supernatant from indole producing bacteria such as Prevotella, to rescue genital C. trachomatis from tryptophan starvation. This adds weight to the hypothesis

  14. Can rodents conceive hyperbolic spaces?

    PubMed Central

    Urdapilleta, Eugenio; Troiani, Francesca; Stella, Federico; Treves, Alessandro

    2015-01-01

    The grid cells discovered in the rodent medial entorhinal cortex have been proposed to provide a metric for Euclidean space, possibly even hardwired in the embryo. Yet, one class of models describing the formation of grid unit selectivity is entirely based on developmental self-organization, and as such it predicts that the metric it expresses should reflect the environment to which the animal has adapted. We show that, according to self-organizing models, if raised in a non-Euclidean hyperbolic cage rats should be able to form hyperbolic grids. For a given range of grid spacing relative to the radius of negative curvature of the hyperbolic surface, such grids are predicted to appear as multi-peaked firing maps, in which each peak has seven neighbours instead of the Euclidean six, a prediction that can be tested in experiments. We thus demonstrate that a useful universal neuronal metric, in the sense of a multi-scale ruler and compass that remain unaltered when changing environments, can be extended to other than the standard Euclidean plane. PMID:25948611

  15. Can rodents conceive hyperbolic spaces?

    PubMed

    Urdapilleta, Eugenio; Troiani, Francesca; Stella, Federico; Treves, Alessandro

    2015-06-06

    The grid cells discovered in the rodent medial entorhinal cortex have been proposed to provide a metric for Euclidean space, possibly even hardwired in the embryo. Yet, one class of models describing the formation of grid unit selectivity is entirely based on developmental self-organization, and as such it predicts that the metric it expresses should reflect the environment to which the animal has adapted. We show that, according to self-organizing models, if raised in a non-Euclidean hyperbolic cage rats should be able to form hyperbolic grids. For a given range of grid spacing relative to the radius of negative curvature of the hyperbolic surface, such grids are predicted to appear as multi-peaked firing maps, in which each peak has seven neighbours instead of the Euclidean six, a prediction that can be tested in experiments. We thus demonstrate that a useful universal neuronal metric, in the sense of a multi-scale ruler and compass that remain unaltered when changing environments, can be extended to other than the standard Euclidean plane.

  16. Modeling panic disorder in rodents.

    PubMed

    Moreira, Fabrício A; Gobira, Pedro H; Viana, Thércia G; Vicente, Maria A; Zangrossi, Hélio; Graeff, Frederico G

    2013-10-01

    Panic disorder (PD) is a subtype of anxiety disorder in which the core phenomenon is the spontaneous occurrence of panic attacks. Although studies with laboratory animals have been instrumental for the understanding of its neurobiology and treatment, few review articles have focused on the validity of the currently used animal models for studying this psychopathology. Therefore, the aim of the present paper is to discuss the strengths and limits of these models in terms of face, construct and predictive validity. Based on the hypothesis that panic attacks are related to defensive responses elicited by proximal threat, most animal models measure the escape responses induced by specific stimuli. Some apply electrical or chemical stimulation to brain regions proposed to modulate fear and panic responses, such as the dorsal periaqueductal grey or the medial hypothalamus. Other models focus on the behavioural consequences caused by the exposure of rodents to ultrasound or natural predators. Finally, the elevated T-maze associates a one-way escape response from an open arm with panic attacks. Despite some limitations, animal models are essential for a better understanding of the neurobiology and pharmacology of PD and for discovering more effective treatments.

  17. Emergency and critical care of rodents.

    PubMed

    Hawkins, Michelle G; Graham, Jennifer E

    2007-05-01

    Rodents may be presented on an emergency basis with various conditions causing debilitation and disease. Common causes of emergent presentations include trauma, respiratory disease, dental disease, gastrointestinal disease, reproductive disorders, and urinary tract obstruction. Emergency treatment should always include immediate stabilization of the patient until the patient is able to tolerate diagnostic testing and additional therapeutics. Rodent patients benefit from supportive care, including thermal, fluid, and nutritional support. Administration of cardiopulmonary resuscitation, antibiotics, and analgesics through various routes is also appropriate. This article presents an overview of emergency medicine in rodents, including emergency procedures, handling and restraint, triage and patient assessment, sample collection, and supportive care procedures. The most common emergency presentations for rodents are also discussed.

  18. Unintentional wildlife poisoning and proposals for sustainable management of rodents.

    PubMed

    Coeurdassier, Michael; Riols, Romain; Decors, Anouk; Mionnet, Aymeric; David, Fabienne; Quintaine, Thomas; Truchetet, Denis; Scheifler, Renaud; Giraudoux, Patrick

    2014-04-01

    In Europe, bromadiolone, an anticoagulant rodenticide authorized for plant protection, may be applied intensively in fields to control rodents. The high level of poisoning of wildlife that follows such treatments over large areas has been frequently reported. In France, bromadiolone has been used to control water voles (Arvicola terrestris) since the 1980s. Both regulation and practices of rodent control have evolved during the last 15 years to restrict the quantity of poisoned bait used by farmers. This has led to a drastic reduction of the number of cases of poisoned wildlife reported by the French surveillance network SAGIR. During the autumn and winter 2011, favorable weather conditions and high vole densities led to the staging of several hundreds of Red Kites (Milvus milvus) in the Puy-de-Dôme department (central France). At the same time, intensive treatments with bromadiolone were performed in this area. Although no misuse has been mentioned by the authorities following controls, 28 Red Kites and 16 Common Buzzards (Buteo buteo) were found dead during surveys in November and December 2011. For all these birds, poisoning by bromadiolone as the main cause of death was either confirmed or highly suspected. Other observations suggest a possible impact of bromadiolone on the breeding population of Red Kites in this area during the spring 2011. French regulation of vole control for plant protection is currently under revision, and we believe this event calls for more sustainable management of rodent outbreaks. Based on large-scale experiments undertaken in eastern France, we propose that direct control of voles at low density (with trapping or limited chemical treatments) and mechanical destruction of vole tunnels, mole control, landscape management, and predator fostering be included in future regulation because such practices could help resolve conservation and agricultural issues.

  19. Indole RSK inhibitors. Part 1: discovery and initial SAR.

    PubMed

    Boyer, Stephen J; Burke, Jennifer; Guo, Xin; Kirrane, Thomas M; Snow, Roger J; Zhang, Yunlong; Sarko, Chris; Soleymanzadeh, Lida; Swinamer, Alan; Westbrook, John; Dicapua, Frank; Padyana, Anil; Cogan, Derek; Gao, Amy; Xiong, Zhaoming; Madwed, Jeffrey B; Kashem, Mohammed; Kugler, Stanley; O'Neill, Margaret M

    2012-01-01

    A series of inhibitors for the 90 kDa ribosomal S6 kinase (RSK) based on an 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide scaffold were identified through high throughput screening. An RSK crystal structure and exploratory SAR were used to define the series pharmacophore. Compounds with good cell potency, such as compounds 43, 44, and 55 were identified, and form the basis for subsequent kinase selectivity optimization. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Asymmetric Total Synthesis of the Indole Diterpene Alkaloid Paspaline

    PubMed Central

    Sharpe, Robert J.; Johnson, Jeffrey S.

    2015-01-01

    An enantioselective synthesis of the indole diterpenoid natural product paspaline is disclosed. Critical to this approach was the implementation of stereoselective desymmetrization reactions to assemble key stereocenters of the molecule. The design and execution of these tactics are described in detail, and a thorough analysis of observed outcomes is presented, ultimately providing the title compound in high stereopurity. This synthesis provides a novel template for preparing key stereocenters in this family of molecules, and the reactions developed en route to paspaline present a series of new synthetic disconnections in preparing steroidal natural products. PMID:26398568

  1. Indole alkaloids from the leaves of Philippine Alstonia scholaris.

    PubMed

    Macabeo, Allan Patrick G; Krohn, Karsten; Gehle, Dietmar; Read, Roger W; Brophy, Joseph J; Cordell, Geoffrey A; Franzblau, Scott G; Aguinaldo, Alicia M

    2005-05-01

    The first seco-uleine alkaloids, manilamine (1) (18-hydroxy-19,20-dehydro-7,21-seco-uleine) and N4-methyl angustilobine B (2), were isolated from the (pH 5) alkaloid extract of Philippine Alstonia scholaris leaves together with the known indole alkaloids 19,20-(E)-vallesamine (3), angustilobine B N4-oxide (4), 20(S)-tubotaiwine (5), and 6,7-seco-angustilobine B (6). The structure of the alkaloids was established from MS and NMR experiments.

  2. Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease.

    PubMed

    Bendheim, Paul E; Poeggeler, Burkhard; Neria, Eyal; Ziv, Vivi; Pappolla, Miguel A; Chain, Daniel G

    2002-01-01

    The accumulation of amyloid-beta and concomitant oxidative stress are major pathogenic events in Alzheimer's disease. Indole-3-propionic acid (IPA, OXIGON) is a potent anti-oxidant devoid of pro-oxidant activity. IPA has been demonstrated to be an inhibitor of beta-amyloid fibril formation and to be a potent neuroprotectant against a variety of oxidotoxins. This review will summarize the known properties of IPA and outline the rationale behind its selection as a potential disease-modifying therapy for Alzheimer's disease.

  3. Three new monoterpenoid indole alkaloids from Vinca major.

    PubMed

    Zhang, Zhi-Jun; Du, Ru-Nan; He, Juan; Wu, Xing-De; Li, Yan; Li, Rong-Tao; Zhao, Qin-Shi

    2016-01-01

    Three new monoterpenoid indole alkaloids, 19-hydroxyl-10-methoxy-19, 20-dihydrovinorine (1), 19-O-acetyl-10-methoxy-19, 20-dihydrovinorine (2), and 19, 21α-dihydroxyl-10-methoxy-19, 20-dihydrovinorine (3), along with five known analogues (4-8), were isolated from the whole plants of Vinca major. The new structures were elucidated by extensive NMR and MS analysis and comparison with known compounds. In addition, compounds 1-3 were evaluated for their cytotoxicities against five human cancer cell lines.

  4. Indole alkaloids with new skeleton activating neural stem cells.

    PubMed

    Yang, Xing-Wei; Yang, Cui-Ping; Jiang, Li-Ping; Qin, Xu-Jie; Liu, Ya-Ping; Shen, Qiu-Shuo; Chen, Yong-Bin; Luo, Xiao-Dong

    2014-11-07

    Alstoscholarisines A-E (1-5), five unprecedented monoterpenoid indole alkaloids with 6/5/6/6/6 fused-bridge rings, were isolated from Alstonia scholaris. They promoted adult neuronal stem cells (NSCs) proliferation significantly, in which the most active one (1) functioned from a concentration of 0.1 μg/mL in a dosage-dependent manner. Furthermore, 1 enhanced NSC sphere formation and neurogenic fate commitment through activation of a Wnt signaling pathway and promoted NSC differentiation but did not affect proliferation of neuroblastoma cells.

  5. Biosynthesis and regulation of terpenoid indole alkaloids in Catharanthus roseus

    PubMed Central

    Zhu, Jianhua; Wang, Mingxuan; Wen, Wei; Yu, Rongmin

    2015-01-01

    Catharanthus roseus produces a wide range of terpenoid indole alkaloids (TIA). Many of them, such as vinblastine and vincristine, have significant bioactivity. They are valuable chemotherapy drugs used in combination with other drugs to treat lymphoma and leukemia. The TIA biosynthetic pathway has been investigated for many years, for scientific interest and for their potential in manufacturing applications, to fulfill the market demand. In this review, the progress and perspective of C. roseus TIA biosynthesis and its regulating enzymes are described. In addition, the culture condition, hormones, signaling molecules, precursor feeding on the accumulation of TIA, and gene expression are also evaluated and discussed. PMID:26009689

  6. Rodents as potential couriers for bioterrorism agents.

    PubMed

    Lõhmus, Mare; Janse, Ingmar; van de Goot, Frank; van Rotterdam, Bart J

    2013-09-01

    Many pathogens that can cause major public health, economic, and social damage are relatively easily accessible and could be used as biological weapons. Wildlife is a natural reservoir for many potential bioterrorism agents, and, as history has shown, eliminating a pathogen that has dispersed among wild fauna can be extremely challenging. Since a number of wild rodent species live close to humans, rodents constitute a vector for pathogens to circulate among wildlife, domestic animals, and humans. This article reviews the possible consequences of a deliberate spread of rodentborne pathogens. It is relatively easy to infect wild rodents with certain pathogens or to release infected rodents, and the action would be difficult to trace. Rodents can also function as reservoirs for diseases that have been spread during a bioterrorism attack and cause recurring disease outbreaks. As rats and mice are common in both urban and rural settlements, deliberately released rodentborne infections have the capacity to spread very rapidly. The majority of pathogens that are listed as potential agents of bioterrorism by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases exploit rodents as vectors or reservoirs. In addition to zoonotic diseases, deliberately released rodentborne epizootics can have serious economic consequences for society, for example, in the area of international trade restrictions. The ability to rapidly detect introduced diseases and effectively communicate with the public in crisis situations enables a quick response and is essential for successful and cost-effective disease control.

  7. Attenuation of Carcinogenesis and the Mechanism Underlying by the Influence of Indole-3-carbinol and Its Metabolite 3,3'-Diindolylmethane: A Therapeutic Marvel.

    PubMed

    Maruthanila, V L; Poornima, J; Mirunalini, S

    2014-01-01

    Rising evidence provides credible support towards the potential role of bioactive products derived from cruciferous vegetables such as broccoli, cauliflower, kale, cabbage, brussels sprouts, turnips, kohlrabi, bok choy, and radishes. Many epidemiological studies point out that Brassica vegetable protects humans against cancer since they are rich sources of glucosinolates in addition to possessing a high content of flavonoids, vitamins, and mineral nutrients. Indole-3-carbinol (I3C) belongs to the class of compounds called indole glucosinolate, obtained from cruciferous vegetables, and is well-known for tits anticancer properties. In particular, I3C and its dimeric product, 3,3'-diindolylmethane (DIM), have been generally investigated for their value against a number of human cancers in vitro as well as in vivo. This paper reviews an in-depth study of the anticancer activity and the miscellaneous mechanisms underlying the anticarcinogenicity thereby broadening its therapeutic marvel.

  8. Attenuation of Carcinogenesis and the Mechanism Underlying by the Influence of Indole-3-carbinol and Its Metabolite 3,3′-Diindolylmethane: A Therapeutic Marvel

    PubMed Central

    Maruthanila, V. L.; Poornima, J.; Mirunalini, S.

    2014-01-01

    Rising evidence provides credible support towards the potential role of bioactive products derived from cruciferous vegetables such as broccoli, cauliflower, kale, cabbage, brussels sprouts, turnips, kohlrabi, bok choy, and radishes. Many epidemiological studies point out that Brassica vegetable protects humans against cancer since they are rich sources of glucosinolates in addition to possessing a high content of flavonoids, vitamins, and mineral nutrients. Indole-3-carbinol (I3C) belongs to the class of compounds called indole glucosinolate, obtained from cruciferous vegetables, and is well-known for tits anticancer properties. In particular, I3C and its dimeric product, 3,3′-diindolylmethane (DIM), have been generally investigated for their value against a number of human cancers in vitro as well as in vivo. This paper reviews an in-depth study of the anticancer activity and the miscellaneous mechanisms underlying the anticarcinogenicity thereby broadening its therapeutic marvel. PMID:24982671

  9. Effect of the pasteurization process on the contents of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage.

    PubMed

    Ciska, Ewa; Honke, Joanna

    2012-04-11

    The aim of the study was to investigate the effect of the pasteurization process on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage. Pasteurization was run at a temperature of 80 °C for 5-30 min. Significant changes were only observed in contents of ascorbigen and 3,3'-diindolylmethane. The total content of the compounds analyzed in cabbage pasteurized for 10-30 min was found to be decreased by ca. 20%, and the losses were due to thermal degradation of the predominating ascorbigen. Pasteurization was found not to exert any considerable effect on contents of indole-3-acetonitrile and indole-3-carbinol in cabbage nor did it affect contents of the compounds analyzed in juice.

  10. Rhodium(I)-Catalyzed Benzannulation of Heteroaryl Propargylic Esters: Synthesis of Indoles and Related Heterocycles.

    PubMed

    Li, Xiaoxun; Xie, Haibo; Fu, Xiaoning; Liu, Ji-Tian; Wang, Hao-Yuan; Xi, Bao-Min; Liu, Peng; Xu, Xiufang; Tang, Weiping

    2016-07-18

    A de novo synthesis of a benzene ring allows for the preparation of a diverse range of heterocycles including indoles, benzofurans, benzothiophenes, carbazoles, and dibenzofurans from simple heteroaryl propargylic esters using a unified carbonylative benzannulation strategy. Multiple substituents can be easily introduced to the C4-C7 positions of indoles and related heterocycles.

  11. Enantioselective Friedel-Crafts Alkylation Reactions of 3-Substituted Indoles with Electron-Deficient Alkenes.

    PubMed

    Weng, Jian-Quan; Fan, Ren-Jie; Deng, Qiao-Man; Liu, Ren-Rong; Gao, Jian-Rong; Jia, Yi-Xia

    2016-04-01

    Highly enantioselective Friedel-Crafts C2-alkylation reactions of 3-substituted indoles with α,β-unsaturated esters and nitroalkenes were developed using chiral Lewis acids as catalysts, which afforded chiral indole derivatives bearing C2-benzylic stereogenic centers in good to excellent yields (up to 99%) and enantioselectivities (up to 96% ee).

  12. Stereoselective double Friedel-Crafts alkylation of indoles with divinyl ketones.

    PubMed

    Silvanus, Andrew C; Heffernan, Stephen J; Liptrot, David J; Kociok-Köhn, Gabriele; Andrews, Benjamin I; Carbery, David R

    2009-03-05

    A tandem double Friedel-Crafts reaction of indoles and nonsymmetrical divinyl ketones has been achieved. The tandem reaction forms complex [6-5-7]-tricyclic indoles in excellent yields. The reaction is completely regioselective and offers high levels of syn diastereoselectivity. The reaction is also seen to be sensitive to substrate structure and catalyst.

  13. Biotransformation of indole and its derivatives by a newly isolated Enterobacter sp. M9Z.

    PubMed

    Qu, Yuanyuan; Zhang, Zhaojing; Ma, Qiao; Shen, E; Shen, Wenli; Wang, Jingwei; Cong, Longchao; Li, Duanxing; Liu, Ziyan; Li, Huijie; Zhou, Jiti

    2015-04-01

    In this study, a novel bacterial strain M9Z with the ability of producing indigoids from indole and its derivatives was isolated from activated sludge and identified as Enterobacter sp. according to 16S ribosomal RNA (rRNA) sequence analysis. UV-vis spectrometry and high-performance liquid chromatography-mass spectrometry analysis indicated that the products produced from indole, 5-methylindole, 7-methylindole, and 5-methoxyindole were indigo with different substituent groups, and the possible biotransformation pathways of indole derivatives, i.e., indole(s)-cis-indole-2,3-dihydrodiol(s)-indoxyl(s)-indigoids, were proposed. The conditions of indole transformation and indigo biosynthesis by strain M9Z were optimized, and the maximal indigo yield (68.1 mg/L) was obtained when using 150 mg/L indole, 200 mg/L naphthalene, and 5 g/L yeast extract. The transformation rates of 5-methylindole, 7-methylindole, and 5-methoxyindole by strain M9Z were all close to 100 % under certain conditions, making strain M9Z an efficient indigoid producer. This is the first study of indole biotransformation and indigoid biosynthesis by genus Enterobacter.

  14. Nanoparticle Based Contrast Enhancement for Discriminating Indolent From Aggressive Prostate Cancer

    DTIC Science & Technology

    2016-06-01

    AWARD NUMBER: W81XWH-15-1-0102 TITLE: Nanoparticle -Based Contrast Enhancement for Discriminating Indolent From Aggressive Prostate Cancer...2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Nanoparticle -Based Contrast Enhancement for Discriminating Indolent From Aggressive Prostate Cancer 5b...followed through watchful waiting or active surveillance management. Specifically, we aim to image metallic and polymer nanoparticles as they

  15. Intermolecular decarboxylative direct C-3 arylation of indoles with benzoic acids.

    PubMed

    Cornella, Josep; Lu, Pengfei; Larrosa, Igor

    2009-12-03

    A palladium catalyzed C-H activation of indoles and a silver catalyzed decarboxylative C-C activation of ortho substituted benzoic acids are synergistically combined to synthesize indoles arylated exclusively in the C-3 position. This novel decarboxylative C-H arylation methodology is compatible with electron-donating and -withdrawing substituents in both coupling partners.

  16. Yuehchukene, a Novel Anti-implantation Indole Alkaloid from Murraya paniculata.

    PubMed

    Kong, Y C; Ng, K H; Wat, K H; Wong, A; Saxena, I F; Cheng, K F; But, P P; Chang, H T

    1985-08-01

    Yuehchukene, 11beta-(3'-indolyl-7,9alpha,9beta-trimethyl-5beta,8,9,10beta-tetrahydroindano-[2,3- B]indole, a novel dimeric indole alkaloid from the roots of MURRAY A PANICULATA has potent anti-implantation activity in rats at 3 mg/kg P. O. dosing on pregnancy day 2.

  17. Pityriacitrin -- an ultraviolet-absorbing indole alkaloid from the yeast Malassezia furfur.

    PubMed

    Mayser, Peter; Schäfer, Ute; Krämer, Hans-Joachim; Irlinger, Bernhard; Steglich, Wolfgang

    2002-05-01

    As the main nitrogen source in Malassezia furfur, tryptophan induces the formation of fluorochromes and pigments, which make the yeast less sensitive to UV light. To detect a chemical UV filter, M. furfur (CBS 1878) was incubated at 30 degrees C for 14 days on a pigment-inducing medium and agar extracts were purified by column chromatography, preparative TLC and HPLC. Structural analysis of the pure metabolites was performed by mass spectroscopy and NMR. A yellow compound eluting from the column with 64% acetonitrile was found to be a potential UV filter because of its broad UV absorption (lambda(max) 389, 315, 289, 212 nm). It was an indole derivative (C(20)H(13)N(3)O; pityriacitrin) which had recently been shown to be a potent UV filter in bacteria. Its UV protective properties were confirmed in a yeast model and also in humans. Pityriasis versicolor induced by Malassezia yeasts is characterized by depigmented skin areas showing reduced melanin synthesis but no increased UV sensitivity. This UV protection might be explained by the presence of pityriacitrin which is produced by M. furfur.

  18. Rhodium-Catalyzed NH-Indole-Directed C-H Carbonylation with Carbon Monoxide: Synthesis of 6H-Isoindolo[2,1-a]indol-6-ones.

    PubMed

    Huang, Qiufeng; Han, Qingshuai; Fu, Shurong; Yao, Zizhu; Su, Lv; Zhang, Xiaofeng; Lin, Shen; Xiang, Shengchang

    2016-12-16

    An efficient synthesis of 6H-isoindolo[2,1-a]indol-6-ones through rhodium-catalyzed NH-indole-directed C-H carbonylation of 2-arylindoles with carbon monoxide has been developed. Preliminary mechanistic studies revealed that this reaction proceeds via N-H bond cleavage and subsequent C-H bond cleavage. Reaction monitoring via ESI-MS was used to support the formation of five-membered rhodacycle species in the catalytic cycle.

  19. 5-Meth-oxy-1-[(5-meth-oxy-1H-indol-2-yl)meth-yl]-1H-indole.

    PubMed

    Attia, Mohamed I; El-Brollosy, Nasser R; Ghabbour, Hazem A; Arshad, Suhana; Fun, Hoong-Kun

    2012-04-01

    In the title compound, C(19)H(18)N(2)O(2), the two indole ring systems are essentially planar [maximum deviation = 0.015 (2) Å in both indole ring systems] and make a dihedral angle of 72.17 (7)° with each other. In the crystal, the mol-ecules are linked into a zigzag chain along the a axis via N-H⋯O hydrogen bonds.

  20. Systemic endotoxin levels in chronic indolent periodontal infections

    PubMed Central

    Ebersole, J. L.; Stevens, J.; Steffen, M. J.; Dawson, D.; Novak, M. J.

    2014-01-01

    Background and Objective: Periodontal disease has been linked with an increased risk of various systemic diseases. A plausible biologic explanation for this link includes the opportunity for oral pathogens to translocate to the circulation as a result of breakdown in integrity of the oral epithelium. This study refined a methodology used to detect endotoxin activity in the serum of subjects with indolent periodontal infections. Material and Methods: The QCL® Kinetic Chromogenic Assay (Cambrex) is a kinetic measure of endotoxin activity. Sera from 211 pregnant women with periodontitis enrolled in the Obstetrics and Periodontal Therapy Trial were used to develop the assay further and to evaluate the detection of endotoxin activity that might accompany a low-level bacteremia in chronic periodontitis. Results: We optimized the system to increase the sensitivity and reproducibility of the assay. The refined system was able to detect endotoxin activity in serum at > 0.0125 EU/mL. At baseline (13–16 wk of gestation), 35.5% of the women were positive for endotoxin activity (1.62 ± 2.21; range: 0.38–15 EU/mL). Conclusion: This report describes a sensitive measure of endotoxin activity in serum. The procedure allowed us to document levels of this microbial virulence factor in serum of individuals with indolent infections such as periodontal disease. PMID:20465752

  1. Synthesis and Biological Evaluation of Aminonaphthols Incorporated Indole Derivatives

    PubMed Central

    Anand Raghunath, Saundane; Nandibeoor Mathada, Kirankumar

    2014-01-01

    An efficient one pot condensation of naphthols (1), 2,5-disubstituted indole-3-carboxaldehydes (2), and secondary amines (3) has been achieved using dichloromethane as a solvent, stirring at room temperature. Some of the new [(disubstituted amino)(5-substituted 2-phenyl-1H-indol-3-yl)methyl]naphthalene-ols (4) derivatives were prepared in good yields. The significant features of this method are simple work-up procedure, inexpensive nontoxic solvent, shorter reaction times, and excellent product yields. The structures of newly synthesized compounds (4a–r) are confirmed by their elemental analysis, FTIR, 1H and 13C NMR, and mass spectral data. These compounds were screened for their in vitro antioxidant, antimicrobial, antitubercular, and anticancer activities. Among the synthesized compounds (4a–r), the compound 4e exhibited highest activity for radical scavenging and ferric ions reducing antioxidant power activities; compounds 4b, 4h, and 4k showed good metal chelating activity. Compounds 4n and 4q showed excellent antimicrobial activities with MIC value 08 µg/mL against tested strains. Compounds 4h, 4k, 4n, and 4q exhibited promising antitubercular activity with MIC value 12.5 µg/mL. Compounds 4k and 4q exhibited 100% cell lysis at concentration 10 µg/mL against MDA-MB-231 (human adenocarcinoma mammary gland) cell lines. PMID:25383220

  2. Indole based Tubulin Polymerization Inhibitors: An Update on Recent Developments.

    PubMed

    Sunil, Dhanya; Kamath, Pooja R

    2016-01-01

    The exploration of cancer microenvironment and its physiology have exposed a number of potential molecular targets for selective therapeutic intervention by anti-cancer agents. Microtubules are basic cell components formed by polymerization of αβ heterodimers which play a pivotal role in cellular functions as well as cell division. Drugs that can control the microtubule assembly either by hindering tubulin polymerization or by obstructing microtubule disassembly are of great importance in anti-cancer therapy. Diverse classes of naturally occurring as well as synthetic and semi-synthetic compounds with an indole nucleus induce microtubule polymerization and depolymerization and thereby change tubulin dynamics. Rapid development of several novel tubulin polymerization inhibitors has been observed over the past few years and some of them have associated vascular disrupting properties too. The present review starts with the structure, function and importance of microtubules in a eukaryotic cell. The well characterized tubulin binding domains and the corresponding inhibitors including their mechanism of action is also a part of this article. The report mainly focuses on the brief synthetic methodology with the relevant SAR studies of different indole derived molecules that have been reported in the past few years as potential inhibitors of tubulin polymerization is discussed. This review will provide the up-to-date evidence-base for synthetic chemists as well as biologists to design and synthesize new active molecules to inhibit tubulin polymerization.

  3. A new indole glycoside from the seeds of Raphanus sativus.

    PubMed

    Jin, Hong-Guang; Ko, Hae Ju; Chowdhury, Md Anisuzzaman; Lee, Dong-Sung; Woo, Eun-Rhan

    2016-06-01

    A new indole glycoside, β-D-glucopyranosyl 2-(methylthio)-1H-indole-3-carboxylate, named raphanuside A (1), as well as eight known compounds, β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (2), (3-O-sinapoyl)-β-D-fructofuranosyl-(2 → 1)-α-D-glucopyranoside (3), (3-O-sinapoyl)-β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (4), (3,4-O-disinapoyl)-β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (5), isorhamnetin 3,4'-di-O-β-D-glucoside (6), isorhamnetin 3-O-β-D-glucoside-7-O-α-L-rhamnoside (7), isorhamnetin 3-O-β-D-glucoside (8) and 3'-O-methyl-(-)-epicatechin 7-O-β-D-glucoside (9) were isolated from the seeds of Raphanus sativus. Furthermore, compounds 1-3 and 6-9, were isolated from this plant for the first time. The structures of compounds 1-9 were identified using 1D and 2D NMR, including (1)H-(1)H COSY, HSQC, HMBC and NOESY spectroscopic analyses. The inhibitory activity of these isolated compounds against interleukin-6 (IL-6) production in TNF-α stimulated MG-63 cells was also examined.

  4. A multi-component domino reaction for the direct access to polyfunctionalized indoles via intermolecular allylic esterification and indolation†

    PubMed Central

    Jiang, Bo; Yi, Mian-Shuai; Shi, Feng; Pindi, Suresh; McDowell, Patrick

    2013-01-01

    A novel multi-component reaction for the synthesis of polyfunctionalized indoles and bis-indoles has been established. The reaction pathways were controlled by varying enamines with different substitution patterns to give polyfunctionalized indoles and bis-indoles selectively. The reaction proceeds at a fast speed within 15–30 min with water as the major byproduct, which makes work-up convenient. PMID:22038299

  5. FeCl3-mediated Friedel-Crafts hydroarylation with electrophilic N-acetyl indoles for the synthesis of benzofuroindolines.

    PubMed

    Beaud, Rodolphe; Guillot, Régis; Kouklovsky, Cyrille; Vincent, Guillaume

    2012-12-07

    IRONic electrophilic indoles! The C3-regioselective hydroarylation of N-acetyl indoles with aromatic nucleophiles mediated by FeCl(3) features a rare example of the electrophilic reactivity of the indole core in a Friedel-Crafts reaction. This indole umpolung allows us straightforward access to the tetracyclic benzofuroindoline motif found in the natural product diazonamide A, which is a potent antitumor agent. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Arabidopsis cytochrome P450s that catalyze the first step of tryptophan-dependent indole-3-acetic acid biosynthesis

    PubMed Central

    Hull, Anna K.; Vij, Rekha; Celenza, John L.

    2000-01-01

    Plants synthesize numerous secondary metabolites that are used as developmental signals or as defense against pathogens. Tryptophan (Trp)-derived secondary metabolites include camalexin, indole glucosinolates, and indole-3-acetic acid (IAA); however, the steps in their synthesis from Trp or its precursors remain unclear. We have identified two Arabidopsis cytochrome P450s (CYP79B2 and CYP79B3) that can convert Trp to indole-3-acetaldoxime (IAOx), a precursor to IAA and indole glucosinolates. PMID:10681464

  7. Application of Fischer Indolization under Green Conditions using Deep Eutectic Solvents.

    PubMed

    Kotha, Sambasivarao; Chakkapalli, Chandravathi

    2017-04-05

    Indole and its derivatives captured the attention of organic chemists due to their applications in medicinal chemistry. The examples covered here are intricate polycyclic indole derivatives and these include: azapolyquinanes, cyclophanes, spirocycles and other heterocycles. We found that deep eutectic mixture such as L-(+)-tartaric acid (TA) and dimethyl urea (DMU) is useful to prepare complex unnatural indole derivatives. These conditions from time to time produced indole derivatives which are not possible by conventional methods. Various substrates containing multiple carbonyl groups were shown to undergo Fischer indolization (FI) in deep eutectic mixtures and thus expand its scope to a higher level. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Four new minor brominated indole related alkaloids with antibacterial activities from Laurencia similis.

    PubMed

    Li, Mei-Chen; Sun, Wen-Shuang; Cheng, Wei; Liu, Dong; Liang, Hong; Zhang, Qing-Ying; Lin, Wen-Han

    2016-08-01

    Four new minor brominated indole related alkaloids (one indoles, 1, one 1,3-dihydro-indole-2-one, 2, one carbazole, 3, and one 2-carbonylamino-benzoate, 4) were isolated and identified from Laurencia similis by extensive chromatographic and spectrometric methods. Among them, 1 and 2 were the first example of naturally occurring indole with 3-benzyl group and 1,3-dihydro-indole-2-one with 2-isopropylidene group, respectively, whereas 3 and 4 were the first carbazole alkaloids and 2-carbonylamino-benzoate, respectively, isolated from the genus Laurencia. Moreover, 1 showed the most potent antibacterial activity against seven bacterial strains with MIC values ranging from 2 to 8μg/mL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines

    PubMed Central

    Xu, Kun; Gilles, Thomas; Breit, Bernhard

    2015-01-01

    The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue. PMID:26137886

  10. Pd-Catalyzed Cyclocarbonylation of 2-(2-Bromoaryl)indoles with CO as a C1 Source: Selective Access to 6 H-Isoindolo[2,1-a]indol-6-ones and Indeno[1,2-b]indol-10(5 H)-ones.

    PubMed

    Guo, Shenghai; Tao, Li; Wang, Fang; Fan, Xuesen

    2016-11-07

    A highly efficient and regioselective synthetic route to 6 H-isoindolo[2,1-a]indol-6-ones and indeno[1,2-b]indol-10(5 H)-ones through the Pd-catalyzed cyclocarbonylation of 2-(2-bromoaryl)indoles under atmospheric CO pressure has been achieved. Notably, the regioselectivity of the reaction was exclusively dependent on the structural characteristics of the indole substrates. With N-unsubstituted indoles as the starting materials, the reaction afforded 6H-isoindolo[2,1-a]indol-6-ones in good-to-excellent yields. On the other hand, with N-substituted indoles as the substrates, the reaction gave indeno[1,2-b]indol-10(5 H)-ones in a highly regioselective manner.

  11. Simultaneous extraction and HPLC determination of 3-indole butyric acid and 3-indole acetic acid in pea plant by using ionic liquid-modified silica as sorbent.

    PubMed

    Sheikhian, Leila; Bina, Sedigheh

    2016-01-15

    In this study, ionic liquid-modified silica was used as sorbent for simultaneous extraction and preconcentration of 3-indole butyric acid and 3-indole acetic acid in pea plants. The effect of some parameters such as pH and ionic strength of sample solution, amount of sorbent, flow rate of aqueous sample solution and eluent solution, concentration of eluent solution, and temperature were studied for each hormone solution. Percent extraction of 3-indole butyric acid and 3-indole acetic acid was strongly affected by pH of aqueous sample solution. Ionic strength of aqueous phase and temperature showed no serious effects on extraction efficiency of studied plant hormones. Obtained breakthrough volume was 200mL for each of studied hormones. Preconcentration factor for spectroscopic and chromatographic determination of studied hormones was 100 and 4.0×10(3) respectively. Each solid sorbent phase was reusable for almost 10 times of extraction/stripping procedure. Relative standard deviations of extraction/stripping processes of 3-indole butyric acid and 3-indole acetic acid were 2.79% and 3.66% respectively. The calculated limit of detections for IBA and IAA were 9.1×10(-2)mgL(-1) and 1.6×10(-1)mgL(-1) respectively.

  12. Effect of boiling on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage.

    PubMed

    Ciska, Ewa; Verkerk, Ruud; Honke, Joanna

    2009-03-25

    The aim of the study was to investigate the effect of the boiling process on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage. The cabbage was boiled for 5 to 60 min. Boiling resulted in a decrease of the total content of the compounds analysed. The changes were mainly caused by leaching of ascorbigen predominating in cabbage into cooking water and by its thermal hydrolysis. Ascorbigen losses resulting from thermal hydrolysis accounted for 30% after 10 min of boiling and for 90% after 60 min of boiling. One of the ascorbigen breakdown products was indole 3 carbinol; the decrease in ascorbigen content was accompanied by a drastic increase in the content of 3,3'-diindolylmethane, a condensation product of indole-3-carbinol. After 40 and 50 min of boiling, the total content of 3,3'-diindolylmethane in cabbage and cooking water was approximately 0.2 micromol/100 g and was 6-fold higher than that in uncooked cabbage. 3,3'-Diindolylmethane synthesis proceeded within the plant tissue. After 10 min of boiling, the content of free indole-3-carbinol and indole-3-acetonitrile stabilized at the level of about 80% as compared to the uncooked cabbage.

  13. Indole production promotes Escherichia coli mixed-culture growth with Pseudomonas aeruginosa by inhibiting quorum signaling.

    PubMed

    Chu, Weihua; Zere, Tesfalem R; Weber, Mary M; Wood, Thomas K; Whiteley, Marvin; Hidalgo-Romano, Benjamin; Valenzuela, Ernesto; McLean, Robert J C

    2012-01-01

    Indole production by Escherichia coli, discovered in the early 20th century, has been used as a diagnostic marker for distinguishing E. coli from other enteric bacteria. By using transcriptional profiling and competition studies with defined mutants, we show that cyclic AMP (cAMP)-regulated indole formation is a major factor that enables E. coli growth in mixed biofilm and planktonic populations with Pseudomonas aeruginosa. Mutants deficient in cAMP production (cyaA) or the cAMP receptor gene (crp), as well as indole production (tnaA), were not competitive in coculture with P. aeruginosa but could be restored to wild-type competitiveness by supplementation with a physiologically relevant indole concentration. E. coli sdiA mutants, which lacked the receptor for both indole and N-acyl-homoserine lactones (AHLs), showed no change in competitive fitness, suggesting that indole acted directly on P. aeruginosa. An E. coli tnaA mutant strain regained wild-type competiveness if grown with P. aeruginosa AHL synthase (rhlI and rhlI lasI) mutants. In contrast to the wild type, P. aeruginosa AHL synthase mutants were unable to degrade indole. Indole produced during mixed-culture growth inhibited pyocyanin production and other AHL-regulated virulence factors in P. aeruginosa. Mixed-culture growth with P. aeruginosa stimulated indole formation in E. coli cpdA, which is unable to regulate cAMP levels, suggesting the potential for mixed-culture gene activation via cAMP. These findings illustrate how indole, an early described feature of E. coli central metabolism, can play a significant role in mixed-culture survival by inhibiting quorum-regulated competition factors in P. aeruginosa.

  14. Population cycles in small rodents.

    PubMed

    Krebs, C J; Gaines, M S; Keller, B L; Myers, J H; Tamarin, R H

    1973-01-05

    We conclude that population fluctuations in Microtus in southern Indiana are produced by a syndrome of changes in birth and death rates similar to that found in other species of voles and lemmings. The mechanisms which cause the changes in birth and death rates are demolished by fencing the population so that no dispersal can occur. Dispersal thus seems critical for population regulation in Microtus. Because most dispersal occurs during the increase phase of the population cycle and there is little dispersal during the decline phase, dispersal is not directly related to population density. Hence the quality of dispersing animals must be important, and we have found one case of increased dispersal tendency by one genotype. The failure of population regulation of Microtus in enclosed areas requires an explanation by any hypothesis attempting to explain population cycles in small rodents. It might be suggested that the fence changed the predation pressure on the enclosed populations. However, the fence was only 2 feet (0.6 meter) high and did not stop the entrance of foxes, weasels, shrews, or avian predators. A striking feature was that the habitat in the enclosures quickly recovered from complete devastation by the start of the spring growing season. Obviously the habitat and food quality were sufficient to support Microtus populations of abnormally high densities, and recovery of the habitat was sufficiently quick that the introduction of new animals to these enclosed areas resulted in another population explosion. Finally, hypotheses of population regulation by social stress must account for the finding that Microtus can exist at densities several times greater than normal without "stress" taking an obvious toll. We hypothesize that the prevention of dispersal changes the quality of the populations in the enclosures in comparison to those outside the fence. Voles forced to remain in an overcrowded fenced population do not suffer high mortality rates and continue

  15. Transport of the two natural auxins, indole-3-butyric acid and indole-3-acetic acid, in Arabidopsis

    NASA Technical Reports Server (NTRS)

    Rashotte, Aaron M.; Poupart, Julie; Waddell, Candace S.; Muday, Gloria K.; Brown, C. S. (Principal Investigator)

    2003-01-01

    Polar transport of the natural auxin indole-3-acetic acid (IAA) is important in a number of plant developmental processes. However, few studies have investigated the polar transport of other endogenous auxins, such as indole-3-butyric acid (IBA), in Arabidopsis. This study details the similarities and differences between IBA and IAA transport in several tissues of Arabidopsis. In the inflorescence axis, no significant IBA movement was detected, whereas IAA is transported in a basipetal direction from the meristem tip. In young seedlings, both IBA and IAA were transported only in a basipetal direction in the hypocotyl. In roots, both auxins moved in two distinct polarities and in specific tissues. The kinetics of IBA and IAA transport appear similar, with transport rates of 8 to 10 mm per hour. In addition, IBA transport, like IAA transport, is saturable at high concentrations of auxin, suggesting that IBA transport is protein mediated. Interestingly, IAA efflux inhibitors and mutations in genes encoding putative IAA transport proteins reduce IAA transport but do not alter IBA movement, suggesting that different auxin transport protein complexes are likely to mediate IBA and IAA transport. Finally, the physiological effects of IBA and IAA on hypocotyl elongation under several light conditions were examined and analyzed in the context of the differences in IBA and IAA transport. Together, these results present a detailed picture of IBA transport and provide the basis for a better understanding of the transport of these two endogenous auxins.

  16. Transport of the two natural auxins, indole-3-butyric acid and indole-3-acetic acid, in Arabidopsis

    NASA Technical Reports Server (NTRS)

    Rashotte, Aaron M.; Poupart, Julie; Waddell, Candace S.; Muday, Gloria K.; Brown, C. S. (Principal Investigator)

    2003-01-01

    Polar transport of the natural auxin indole-3-acetic acid (IAA) is important in a number of plant developmental processes. However, few studies have investigated the polar transport of other endogenous auxins, such as indole-3-butyric acid (IBA), in Arabidopsis. This study details the similarities and differences between IBA and IAA transport in several tissues of Arabidopsis. In the inflorescence axis, no significant IBA movement was detected, whereas IAA is transported in a basipetal direction from the meristem tip. In young seedlings, both IBA and IAA were transported only in a basipetal direction in the hypocotyl. In roots, both auxins moved in two distinct polarities and in specific tissues. The kinetics of IBA and IAA transport appear similar, with transport rates of 8 to 10 mm per hour. In addition, IBA transport, like IAA transport, is saturable at high concentrations of auxin, suggesting that IBA transport is protein mediated. Interestingly, IAA efflux inhibitors and mutations in genes encoding putative IAA transport proteins reduce IAA transport but do not alter IBA movement, suggesting that different auxin transport protein complexes are likely to mediate IBA and IAA transport. Finally, the physiological effects of IBA and IAA on hypocotyl elongation under several light conditions were examined and analyzed in the context of the differences in IBA and IAA transport. Together, these results present a detailed picture of IBA transport and provide the basis for a better understanding of the transport of these two endogenous auxins.

  17. Indole-3-butyric acid induces lateral root formation via peroxisome-derived indole-3-acetic acid and nitric oxide.

    PubMed

    Schlicht, Markus; Ludwig-Müller, Jutta; Burbach, Christian; Volkmann, Dieter; Baluska, Frantisek

    2013-10-01

    Controlled plant growth requires regulation through a variety of signaling molecules, including steroids, peptides, radicals of oxygen and nitrogen, as well as the 'classical' phytohormone groups. Auxin is critical for the control of plant growth and also orchestrates many developmental processes, such as the formation of new roots. It modulates root architecture both slowly, through actions at the transcriptional level and, more rapidly, by mechanisms targeting primarily plasma membrane sensory systems and intracellular signaling pathways. The latter reactions use several second messengers, including Ca(2+) , nitric oxide (NO) and reactive oxygen species (ROS). Here, we investigated the different roles of two auxins, the major auxin indole-3-acetic acid (IAA) and another endogenous auxin indole-3-butyric acid (IBA), in the lateral root formation process of Arabidopsis and maize. This was mainly analyzed by different types of fluorescence microscopy and inhibitors of NO production. This study revealed that peroxisomal IBA to IAA conversion is followed by peroxisomal NO, which is important for IBA-induced lateral root formation. We conclude that peroxisomal NO emerges as a new player in auxin-induced root organogenesis. In particular, the spatially and temporally coordinated release of NO and IAA from peroxisomes is behind the strong promotion of lateral root formation via IBA. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  18. Behavioral and mechanistic insight into rodent empathy.

    PubMed

    Sivaselvachandran, Sivaani; Acland, Erinn L; Abdallah, Salsabil; Martin, Loren J

    2016-06-14

    Empathy is a psychological construct that allows individuals to understand and share the emotions of others. The ability to share emotional states relies on basic social mechanisms, such as mimicry and emotional contagion, which are considered building blocks for empathy. Mimicking another's emotional or physical state is essential for successful social interactions and is found in a number of animal species. For the current review we focus on emotional state sharing in rodents, a core feature of empathy that is often measured using pain and fear as proxies; we also discuss prosociality in rodents. The evidence for empathy in rodents shows that rats and mice consistently imitate arousal states and behaviors of conspecifics and will even sacrifice personal gain to relieve the distress of a conspecific. These behaviors support basic processes that are crucial for the survival of individual animals and give us insight into the neural mechanisms that govern empathy-related behaviors.

  19. Endoparasites of Wild Rodents in Southeastern Iran

    PubMed Central

    Nateghpour, Mehdi; Motevalli-Haghi, Afsaneh; Akbarzadeh, Kamran; Akhavan, Amir Ahmad; Mohebali, Mehdi; Mobedi, Iraj; Farivar, Leila

    2015-01-01

    Background: This study was aimed to collect wild rodents for endoparasites determination in some parts of Sistan and Baluchistan Province, southeastern Iran nearby Pakistan and Afghanistan countries. Methods: A total of 100 wild rodents were captured alive with cage traps. Various samples were collected from blood and feces, also impression smear prepared from different organs. The samples were prepared by formalin-ether or stained with Giemsa, after that were examined under microscope. Results: All the caught rodents (47 Tatera indica, 44 Meriones hurriana, 5 Gerbilus nanus and 4 Meriones libycus) were studied for endoparasites emphasizing to their zoonotic aspects. Endoparasites including Spirurida, Hymenolepis diminuta, Hymenolepis nana feraterna, Trichuris trichiura, Skerjabino taenia, Trichostrongylus spp, Entamoeba muris, Chilomastix mesnili and Leishmania spp were parasitologically identified. Conclusion: Among 9 genera or species of the identified parasites at least 5 of them have zoonotic and public health importance. PMID:26114139

  20. The MAM rodent model of schizophrenia

    PubMed Central

    Lodge, Daniel J.

    2013-01-01

    Rodent models of human disease are essential to obtain a better understanding of disease pathology, the mechanism of action underlying conventional treatments, as well as for the generation of novel therapeutic approaches. There are a number of rodent models of schizophrenia based on either genetic manipulations, acute or sub-chronic drug administration, or developmental disturbances. The prenatal methylazoxymethanol acetate (MAM) rodent model is a developmental disruption model gaining increased attention because it displays a number of histological, neurophysiological and behavioral deficits analogous to those observed in schizophrenia patients. This unit describes the procedures required to safely induce the MAM phenotype in rats. In addition, we describe a simple behavioral procedure, amphetamine-induced hyper-locomotion, which can be utilized to verify the MAM phenotype. PMID:23559309

  1. Brönsted Acid-Catalyzed One-Pot Synthesis of Indoles from o-Aminobenzyl Alcohols and Furans

    PubMed Central

    Kuznetsov, Alexey; Makarov, Anton; Rubtsov, Alexandr E.; Butin, Alexander V.; Gevorgyan, Vladimir

    2013-01-01

    Brönsted acid-catalyzed one-pot synthesis of indoles from o-aminobenzyl alcohols and furans has been developed. This method operates via the in situ formation of aminobenzylfuran, followed by its recyclization into the indole core. The method proved to be efficient for substrates possessing different functional groups, including -OMe, -CO2Cy, and -Br. The resulting indoles can easily be transformed into diverse scaffolds, including 2,3- and 1,2-fused indoles, and indole possessing an α,β-unsaturated ketone moiety at the C-2 position. PMID:24255969

  2. [Application of genetic diversity in the researches on rodents].

    PubMed

    Liu, Zhu; Yang, Chun-Wen; Xu, Yan-Chun; Jin, Zhi-Min; Ma, Jian-Zhang

    2014-02-01

    Genetic diversity is the base of the species diversity and ecosystem diversity, and also the foundation for biological evolution and species differentiation. Furthermore, genetic diversity is important evidence for evaluation of biological resources of nature. The genetic diversity data from a wide variety of rodents have many complex applications. We summarized the application of rodent prevention, the origin and differentiation including evolutionary history of rodents, the potential adaptation of rodents, the dynamics of population and regulatory mechanisms, and the conservation biology of rodents. Researches in the future should focus on the systematic study on the relationships between population dynamics and genetic diversity, and long-term monitoring of genetic diversity of rodents.

  3. General Approach to the Total Synthesis of 9-Methoxy Substituted Indole Alkaloids: Synthesis of Mitragynine, as well as 9-Methoxygeissoschizol and 9-Methoxy-Nb-methylgeissoschizol

    PubMed Central

    Ma, Jun; Yin, Wenyuan; Zhou, Hao; Liao, Xuebin; Cook, James M.

    2009-01-01

    Herein the full details of the synthesis of the 9-methoxy-substituted Corynanthe indole alkaloids mitragynine (1), 9-methoxygeissoschizol (3) and 9-methoxy-Nb-methylgeissoschizol (4) are described. Initially an efficient synthetic route to the optically active 4-methoxytryptophan ethyl ester 20 on a multigram scale was developed via a Mori-Ban-Hegedus indole synthesis. The ethyl ester of (D)-4-methoxytryptophan 20 was obtained with a radical-mediated regioselective bromination of indoline 12 serving as a key step. Alternatively, the key 4-methoxytryptophan intermediate 22 could be synthesized by the Larock heteroannulation of aryl iodide 10b with the internal alkyne 21a. The use of the Boc protected aniline 10b was crucial to the success of this heteroannulation. The α,β-unsaturated ester 6 was synthesized via the Pictet-Spengler reaction as the pivotal step. This was followed by a Ni(COD)2 mediated cyclization to set up the stereocenter at C-15. The benzyloxy group in 31 was removed to provide the intermediate ester 5. This chiral tetracyclic ester 5 was employed to accomplish the first total synthesis of 9-methoxygeissoschizol (3) and 9-methoxy-Nb-methylgeisso-schizol (4) as well as the opioid agonistic indole alkaloid mitragynine (1). PMID:19046119

  4. Synthesis of tricyclic indole-2-carboxylic [correction of caboxylic] acids as potent NMDA-glycine antagonists.

    PubMed

    Katayama, S; Ae, N; Nagata, R

    2001-05-18

    The practical synthesis of a series of tricyclic indole-2-carboxylic acids, 7-chloro-3-arylaminocarbonylmethyl-1,3,4,5-tetrahydrobenz[cd]indole-2-carboxylic acids, as a new class of potent NMDA-glycine antagonists is described. The synthetic route to the key intermediate 12a comprises a regioselective iodination of 4-chloro-2-nitrotoluene, modified Reissert indole synthesis, Jeffery's Heck-type reaction with allyl alcohol, Wittig-Horner-Emmons reaction, and iodination at the indole C-3 position. The key step in the route is an intramolecular cyclization of 12a to give the tricyclic indole structure. Two methods of cyclization, (1) an intramolecular radical cyclization of 12a and (2) a sequence of intramolecular Heck reaction of 12a followed by a 1,4-reduction, were performed. The resulting tricyclic indole diester 13a was selectively hydrolyzed to afford the desired tricyclic indole monocarboxylic acid 16 on a multihundred gram scale without any chromatographic purifications. Optical resolution of 16 to (-)-isomer 17 and (+)-isomer 18 was carried out, and the resulting isomers were derivatized, respectively. Evaluation of the optically active derivatives for affinity to the NMDA-glycine binding site using the radio ligand binding assay with [(3)H]-5,7-dichlorokynurenic acid revealed that the derivatives of (-)-isomer 17 were more potent than the others and that especially substituted anilide (-)-isomer 24 (K(i) = 0.8 nM) showed high affinity.

  5. Asymmetric distribution of glucose and indole-3-acetyl-myo-inositol in geostimulated Zea mays seedlings

    NASA Technical Reports Server (NTRS)

    Momonoki, Y. S.; Bandurski, R. S. (Principal Investigator)

    1988-01-01

    Indole-3-acetyl-myo-inositol occurs in both the kernel and vegetative shoot of germinating Zea mays seedlings. The effect of a gravitational stimulus on the transport of [3H]-5-indole-3-acetyl-myo-inositol and [U-14C]-D-glucose from the kernel to the seedling shoot was studied. Both labeled glucose and labeled indole-3-acetyl-myo-inositol become asymmetrically distributed in the mesocotyl cortex of the shoot with more radioactivity occurring in the bottom half of a horizontally placed seedling. Asymmetric distribution of [3H]indole-3-acetic acid, derived from the applied [3H]indole-3-acetyl-myo-inositol, occurred more rapidly than distribution of total 3H-radioactivity. These findings demonstrate that the gravitational stimulus can induce an asymmetric distribution of substances being transported from kernel to shoot. They also indicate that, in addition to the transport asymmetry, gravity affects the steady state amount of indole-3-acetic acid derived from indole-3-acetyl-myo-inositol.

  6. Asymmetric distribution of glucose and indole-3-acetyl-myo-inositol in geostimulated Zea mays seedlings

    NASA Technical Reports Server (NTRS)

    Momonoki, Y. S.; Bandurski, R. S. (Principal Investigator)

    1988-01-01

    Indole-3-acetyl-myo-inositol occurs in both the kernel and vegetative shoot of germinating Zea mays seedlings. The effect of a gravitational stimulus on the transport of [3H]-5-indole-3-acetyl-myo-inositol and [U-14C]-D-glucose from the kernel to the seedling shoot was studied. Both labeled glucose and labeled indole-3-acetyl-myo-inositol become asymmetrically distributed in the mesocotyl cortex of the shoot with more radioactivity occurring in the bottom half of a horizontally placed seedling. Asymmetric distribution of [3H]indole-3-acetic acid, derived from the applied [3H]indole-3-acetyl-myo-inositol, occurred more rapidly than distribution of total 3H-radioactivity. These findings demonstrate that the gravitational stimulus can induce an asymmetric distribution of substances being transported from kernel to shoot. They also indicate that, in addition to the transport asymmetry, gravity affects the steady state amount of indole-3-acetic acid derived from indole-3-acetyl-myo-inositol.

  7. Indole production provides limited benefit to Escherichia coli during co-culture with Enterococcus faecalis.

    PubMed

    Pringle, Shelly L; Palmer, Kelli L; McLean, Robert J C

    2017-01-01

    Escherichia coli lives in the gastrointestinal tract and elsewhere, where it coexists within a mixed population. Indole production enables E. coli to grow with other gram-negative bacteria as indole inhibits N-acyl-homoserine lactone (AHL) quorum regulation. We investigated whether E. coli indole production enhanced competition with gram-positive Enterococcus faecalis, wherein quorum signaling is mediated by small peptides. During planktonic co-culture with E. faecalis, the fitness and population density of E. coli tnaA mutants (unable to produce indole) equaled or surpassed that of E. coli wt. During biofilm growth, the fitness of both populations of E. coli stabilized around 100 %, whereas the fitness of E. faecalis declined over time to 85-90 %, suggesting that biofilm and planktonic populations have different competition strategies. Media supplementation with indole removed the competitive advantage of E. coli tnaA in planktonic populations but enhanced it in biofilm populations. E. coli wt and tnaA showed similar growth in Luria-Bertani (LB) broth. However, E. coli growth was inhibited in the presence of filter-sterilized spent LB from E. faecalis, with inhibition being enhanced by indole. Similarly, there was also an inhibition of E. faecalis growth by proteinaceous components (likely bacteriocins) from spent culture media from both E. coli strains. We conclude that E. coli indole production is not a universal competition strategy, but rather works against gram-negative, AHL-producing bacteria.

  8. Genomic hallmarks of localized, non-indolent prostate cancer.

    PubMed

    Fraser, Michael; Sabelnykova, Veronica Y; Yamaguchi, Takafumi N; Heisler, Lawrence E; Livingstone, Julie; Huang, Vincent; Shiah, Yu-Jia; Yousif, Fouad; Lin, Xihui; Masella, Andre P; Fox, Natalie S; Xie, Michael; Prokopec, Stephenie D; Berlin, Alejandro; Lalonde, Emilie; Ahmed, Musaddeque; Trudel, Dominique; Luo, Xuemei; Beck, Timothy A; Meng, Alice; Zhang, Junyan; D'Costa, Alister; Denroche, Robert E; Kong, Haiying; Espiritu, Shadrielle Melijah G; Chua, Melvin L K; Wong, Ada; Chong, Taryne; Sam, Michelle; Johns, Jeremy; Timms, Lee; Buchner, Nicholas B; Orain, Michèle; Picard, Valérie; Hovington, Helène; Murison, Alexander; Kron, Ken; Harding, Nicholas J; P'ng, Christine; Houlahan, Kathleen E; Chu, Kenneth C; Lo, Bryan; Nguyen, Francis; Li, Constance H; Sun, Ren X; de Borja, Richard; Cooper, Christopher I; Hopkins, Julia F; Govind, Shaylan K; Fung, Clement; Waggott, Daryl; Green, Jeffrey; Haider, Syed; Chan-Seng-Yue, Michelle A; Jung, Esther; Wang, Zhiyuan; Bergeron, Alain; Dal Pra, Alan; Lacombe, Louis; Collins, Colin C; Sahinalp, Cenk; Lupien, Mathieu; Fleshner, Neil E; He, Housheng H; Fradet, Yves; Tetu, Bernard; van der Kwast, Theodorus; McPherson, John D; Bristow, Robert G; Boutros, Paul C

    2017-01-19

    Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.

  9. 2-(1H-Indol-3-yl)acetohydrazide

    PubMed Central

    Sidra, Lala Rukh; Khan, Islam Ullah; Yar, Muhammad; Simpson, Jim

    2012-01-01

    In the title compound C10H11N3O, the mean plane of the indole ring system (r.m.s. deviation 0.0131 Å) subtends a dihedral angle of 87.27 (5)° to the almost planar acetohydrazide substituent (r.m.s. deviation 0.0291 Å). In the crystal, bifurcated N—H⋯(O,N) and N—H⋯N hydrogen bonds involving the pyrrole N–H grouping combine to form zigzag chains along a. Additional N—H⋯O contacts from the hydrazide N–H group augmented by C—H⋯π inter­actions link the mol­ecules into chains along the a axis. The overall effect of these contacts is a three-dimensional network structure with mol­ecules stacked along the b-axis direction. PMID:23284462

  10. 2-(1H-Indol-3-yl)acetohydrazide.

    PubMed

    Sidra, Lala Rukh; Khan, Islam Ullah; Yar, Muhammad; Simpson, Jim

    2012-11-01

    In the title compound C(10)H(11)N(3)O, the mean plane of the indole ring system (r.m.s. deviation 0.0131 Å) subtends a dihedral angle of 87.27 (5)° to the almost planar acetohydrazide substituent (r.m.s. deviation 0.0291 Å). In the crystal, bifurcated N-H⋯(O,N) and N-H⋯N hydrogen bonds involving the pyrrole N-H grouping combine to form zigzag chains along a. Additional N-H⋯O contacts from the hydrazide N-H group augmented by C-H⋯π inter-actions link the mol-ecules into chains along the a axis. The overall effect of these contacts is a three-dimensional network structure with mol-ecules stacked along the b-axis direction.

  11. Biogenetically inspired synthesis and skeletal diversification of indole alkaloids

    NASA Astrophysics Data System (ADS)

    Mizoguchi, Haruki; Oikawa, Hideaki; Oguri, Hiroki

    2014-01-01

    To access architecturally complex natural products, chemists usually devise a customized synthetic strategy for constructing a single target skeleton. In contrast, biosynthetic assembly lines often employ divergent intramolecular cyclizations of a polyunsaturated common intermediate to produce diverse arrays of scaffolds. With the aim of integrating such biogenetic strategies, we show the development of an artificial divergent assembly line generating unprecedented numbers of scaffold variations of terpenoid indole alkaloids. This approach not only allows practical access to multipotent intermediates, but also enables systematic diversification of skeletal, stereochemical and functional group properties without structural simplification of naturally occurring alkaloids. Three distinct modes of [4+2] cyclizations and two types of redox-mediated annulations provided divergent access to five skeletally distinct scaffolds involving iboga-, aspidosperma-, andranginine- and ngouniensine-type skeletons and a non-natural variant within six to nine steps from tryptamine. The efficiency of our approach was demonstrated by successful total syntheses of (±)-vincadifformine, (±)-andranginine and (-)-catharanthine.

  12. The Rhazinilam-Leuconoxine-Mersicarpine Triad of Monoterpenoid Indole Alkaloids.

    PubMed

    Pfaffenbach, Magnus; Gaich, Tanja

    The rhazinilam-leuconoxine-mersicarpine triad of monoterpenoid indole alkaloids comprises a variety of diverse natural products with unprecedented structural features and intriguing biological activities. This subfamily of Aspidosperma alkaloids has drawn significant attention from the synthetic community which is reflected by over 20 syntheses within the last 5years. Numerous transformations and strategies have been developed to access the different key structural motifs such as the tetrahydroindolizine, α,β-unsaturated carbinolamide, diaza[5.5.6.6]fenestrane, and tetrahydro-2H-azepine frameworks. The present contribution comprehensively covers the abundant literature on this natural product class up to the end of May 2016, providing a detailed account of the formal and total syntheses which is complemented by an overview of their biosynthesis, spectroscopy, and pharmacology. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Studies on organic indole-3-aldehyde single crystals

    NASA Astrophysics Data System (ADS)

    Haja Hameed, A. S.; Ravi, G.; Dhanasekaran, R.; Ramasamy, P.

    Indole-3-aldehyde (IA) is a new organic nonlinear material for which its solubility in methanol and acetone was found out using the apparatus fabricated by the authors. In order to get the good-quality crystals, methods of evaporation of solvent at room temperature and slow cooling of saturated solution at boiling temperature were adopted. Simulated lattice parameter values were found out using experimentally known " d" values. The etching and mechanical strength studies on different planes of the crystal were carried out. Decomposition temperature, weight loss and different functional bond frequencies associated with the crystal were also found out from differential thermal analysis (DTA), thermo-gravimetric analysis (TGA) and Fourier transform infra-red (FTIR) spectroscopic analysis, respectively.

  14. Response of patients with indolent systemic mastocytosis to tamoxifen citrate.

    PubMed

    Butterfield, Joseph H; Chen, Dong

    2016-01-01

    We examined whether tamoxifen citrate at 20mg/day for 1 year had a beneficial effect on laboratory findings, bone marrow mastocytosis, common clinical symptoms, or quality-of-life assessment for 5 women and 2 men with indolent systemic mastocytosis. Tamoxifen was well tolerated. We found significant reductions in the platelet count, serum alkaline phosphatase, and 24-h urinary excretion of N-methylhistamine and significant increases in serum lactate dehydrogenase and (excluding 2 patients taking aspirin) in 24-h urinary excretion of 11β-prostaglandin F2α. Overall, no change occurred in percent involvement of bone marrow by mastocytosis. Symptom scores were mild and did not change during the treatment. The 36-Item Short Form Health Survey scores for quality of life physical and mental components showed no marked changes. Tamoxifen, an older, nonhematotoxic medication, has limited activity in systemic mastocytosis at the dosage used in this study.

  15. Understanding arid environments using fossil rodent middens

    USGS Publications Warehouse

    Pearson, S.; Betancourt, J.L.

    2002-01-01

    American rodent middens have made a more dramatic contribution to understanding past environments and the development of ecological theory than Australian rodent middens. This relates to differences in the natural environment, the landscape histories, the scale and scientific approaches of the researchers. The comparison demonstrates: the power of synoptic perspectives; the value of thorough macrofossil identification in midden analysis and its potential advance in Australia where pollen has dominated analyses, the value of herbaria and reference collections; the potential of environmental databases; the importance of scientific history and 'critical research mass' and; finally, the opportunistic nature of palaeoecological research. ?? 2002 Elsevier Science Ltd.

  16. Kinetic mechanism of indole-3-glycerol phosphate synthase.

    PubMed

    Schlee, Sandra; Dietrich, Susanne; Kurćon, Tomasz; Delaney, Pamela; Goodey, Nina M; Sterner, Reinhard

    2013-01-08

    The (βα)(8)-barrel enzyme indole-3-glycerol phosphate synthase (IGPS) catalyzes the multistep transformation of 1-(o-carboxyphenylamino)-1-deoxyribulose 5-phosphate (CdRP) into indole-3-glycerol phosphate (IGP) in tryptophan biosynthesis. Mutagenesis data and crystal structure analysis of IGPS from Sulfolobus solfataricus (sIGPS) allowed for the formulation of a plausible chemical mechanism of the reaction, and molecular dynamics simulations suggested that flexibility of active site loops might be important for catalysis. Here we developed a method that uses extrinsic fluorophores attached to active site loops to connect the kinetic mechanism of sIGPS to structure and conformational motions. Specifically, we elucidated the kinetic mechanism of sIGPS and correlated individual steps in the mechanism to conformational motions of flexible loops. Pre-steady-state kinetic measurements of CdRP to IGP conversion monitoring changes in intrinsic tryptophan and IGP fluorescence provided a minimal three-step kinetic model in which fast substrate binding and chemical transformation are followed by slow product release. The role of sIGPS loop conformational motion during substrate binding and catalysis was examined via variants that were covalently labeled with fluorescent dyes at the N-terminal extension of the enzyme and mobile active site loop β1α1. Analysis of kinetic data monitoring dye fluorescence revealed a conformational change that follows substrate binding, suggesting an induced-fit-type binding mechanism for the substrate CdRP. Global fitting of all kinetic results obtained with wild-type sIGPS and the labeled variants was best accommodated by a four-step kinetic model. In this model, both the binding of CdRP and its on-enzyme conversion to IGP are accompanied by conformational transitions. The liberation of the product from the active site is the rate-limiting step of the overall reaction. Our results confirm the importance of flexible active loops for substrate

  17. Phase I trial of nelarabine in indolent leukemias.

    PubMed

    Gandhi, Varsha; Tam, Constantine; O'Brien, Susan; Jewell, Roxanne C; Rodriguez, Carlos O; Lerner, Susan; Plunkett, William; Keating, Michael J

    2008-03-01

    To test whether nelarabine is an effective agent for indolent leukemias and to evaluate whether there is a relationship between cellular pharmacokinetics of the analog triphosphate and clinical responses. Thirty-five patients with relapsed/refractory leukemias (n = 24, B-cell chronic lymphocytic leukemia and n = 11, T-cell prolymphocytic leukemia) were entered onto three different protocols. For schedule A, patient received nelarabine daily for 5 days, whereas for schedule B, nelarabine was administered on days 1, 3, and 5. Schedule C was similar to schedule B except that fludarabine was also infused. Plasma and cellular pharmacokinetics were studied during the first cycle. Responses were achieved in 20%, 15%, and 63% of patients receiving schedule A, B, and C, respectively. Histologic category, number of prior therapies, and fludarabine refractoriness did not influence the response rate. The most common nonhematologic toxicity was peripheral neuropathy. Grade 4 neutropenia and thrombocytopenia complicated 23% and 26% of courses respectively, and were significantly more frequent among patients with pre-existing marrow failure. Pharmacokinetics of plasma nelarabine and arabinosylguanine (ara-G) and of cellular ara-G triphosphate (ara-GTP) were similar in the two groups of diagnoses, and the elimination of ara-GTP from leukemia cells was slow (median, > 24 hours). The median peak intracellular concentrations of ara-GTP were significantly different (P = .0003) between responders (440 micromol/L; range, 35 to 1,438 micromol/L; n = 10) and nonresponders (50 micromol/L; range, 22 to 178 micromol/L; n = 15). Nelarabine is an effective regimen against indolent leukemias, and combining it with fludarabine was most promising. Determination of tumor cell ara-GTP levels may provide a predictive test for response to nelarabine.

  18. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    PubMed

    Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

    2017-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT2a,b,c and NEα2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT2a,c receptors as compared to MDMA.

  19. Anthranilate deteriorates the structure of Pseudomonas aeruginosa biofilms and antagonizes the biofilm-enhancing indole effect.

    PubMed

    Kim, Soo-Kyoung; Park, Ha-Young; Lee, Joon-Hee

    2015-04-01

    Anthranilate and indole are alternative degradation products of tryptophan, depending on the bacterial species. While indole enhances the biofilm formation of Pseudomonas aeruginosa, we found that anthranilate, the tryptophan degradation product of P. aeruginosa, had an opposite effect on P. aeruginosa biofilm formation, in which anthranilate deteriorated the mushroom structure of biofilm. The anthranilate effect on biofilm formation was differentially exerted depending on the developmental stage and the presence of shear force. Anthranilate slightly accelerated the initial attachment of P. aeruginosa at the early stage of biofilm development and appeared to build more biofilm without shear force. But anthranilate weakened the biofilm structure in the late stage, deteriorating the mushroom structure of biofilms with shear force to make a flat biofilm. To investigate the interplay of anthranilate with indole in biofilm formation, biofilms were cotreated with anthranilate and indole, and the results showed that anthranilate antagonized the biofilm-enhancing effect of indole. Anthranilate was able to deteriorate the preformed biofilm. The effect of anthranilate and indole on biofilm formation was quorum sensing independent. AntR, a regulator of anthranilate-degrading metabolism was synergistically activated by cotreatment with anthranilate and indole, suggesting that indole might enhance biofilm formation by facilitating the degradation of anthranilate. Anthranilate slightly but significantly affected the cyclic diguaniylate (c-di-GMP) level and transcription of major extracellular polysaccharide (Psl, Pel, and alginate) operons. These results suggest that anthranilate may be a promising antibiofilm agent and antagonize the effect of indole on P. aeruginosa biofilm formation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genome-wide analyses

    PubMed Central

    2012-01-01

    Background Many Gram-positive and Gram-negative bacteria produce large quantities of indole as an intercellular signal in microbial communities. Indole demonstrated to affect gene expression in Escherichia coli as an intra-species signaling molecule. In contrast to E. coli, Salmonella does not produce indole because it does not harbor tnaA, which encodes the enzyme responsible for tryptophan metabolism. Our previous study demonstrated that E. coli-conditioned medium and indole induce expression of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium for inter-species communication; however, the global effect of indole on genes in Salmonella remains unknown. Results To understand the complete picture of genes regulated by indole, we performed DNA microarray analysis of genes in the S. enterica serovar Typhimurium strain ATCC 14028s affected by indole. Predicted Salmonella phenotypes affected by indole based on the microarray data were also examined in this study. Indole induced expression of genes related to efflux-mediated multidrug resistance, including ramA and acrAB, and repressed those related to host cell invasion encoded in the Salmonella pathogenicity island 1, and flagella production. Reduction of invasive activity and motility of Salmonella by indole was also observed phenotypically. Conclusion Our results suggest that indole is an important signaling molecule for inter-species communication to control drug resistance and virulence of S. enterica. PMID:22632036

  1. Carbon catabolite repression-independent and pH-dependent production of indoles by Rubrivivax benzoatilyticus JA2.

    PubMed

    Mujahid, Md; Sasikala, Ch; Ramana, Ch V

    2013-10-01

    Rubrivivax benzoatilyticus JA2 produces indole derivatives (indoles) from aniline, anthranilate or L-tryptophan. Glucose repressed indole production in R. benzoatilyticus JA2, while malate had no effect. Growth of R. benzoatilyticus JA2 on glucose resulted in decrease in culture pH (6.4) compared with malate (8.4). Growth of R. benzoatilyticus JA2 on sugar carbon sources decreased culture pH (6.4-6.6) and indole production. Further, culture pH of 6.4 repressed the indole production, and pH 8.4 promoted the production irrespective of carbon sources used for growth. Moreover, correlation between indole production and culture pH was observed, where acidic pH inhibited indole production, while alkaline pH promoted the production, suggesting the role of pH in indole production. Tryptophan-catabolizing enzyme activities are significantly high in malate-grown cultures (pH 8.4) compared with that of the glucose (pH 6.4)-grown cultures and corroborated well with indole production, indicating their role in indole production. These results confirm that indole production in R. benzoatilyticus JA2 is pH dependent rather than carbon catabolite repression.

  2. Highly active modulators of indole signaling alter pathogenic behaviors in Gram-negative and Gram-positive bacteria.

    PubMed

    Minvielle, Marine J; Eguren, Kristen; Melander, Christian

    2013-12-16

    Indole is a universal signal that regulates various bacterial behaviors, such as biofilm formation and antibiotic resistance. To generate mechanistic probes of indole signaling and control indole-mediated pathogenic phenotypes in both Gram-positive and Gram-negative bacteria, we have investigated the use of desformylflustrabromine (dFBr) derivatives to generate highly active indole mimetics. We have developed non-microbicidal dFBr derivatives that are 27-2000 times more active than indole in modulating biofilm formation, motility, acid resistance, and antibiotic resistance. The activity of these analogues parallels indole, because they are dependent on temperature, the enzyme tryptophanase TnaA, and the transcriptional regulator SdiA. This investigation demonstrates that molecules based on the dFBr scaffold can alter pathogenic behaviors by mimicking indole-signaling pathways.

  3. One-Pot Multicatalytic Approaches for the Synthesis of Cyclohepta[b]indoles, Indolotropones, and Tetrahydrocarbazoles.

    PubMed

    Mishra, Uttam K; Yadav, Sonu; Ramasastry, S S V

    2017-07-07

    Diversity oriented one-pot synthesis of cyclohepta[b]indoles, indolotropones, and tetrahydrocarbazoles (THCs) have been reported. Readily accessible 3-(2-aminophenyl)-5-hexenyn-3-ols under a one-pot trimetallic orthogonal catalysis furnish tetrahydrocyclohepta[b]indoles, and a one-pot quadruple reaction sequence of the enynols generates dihydrocyclohepta[b]indoles and indolotropones. During this study, formation of THCs was realized to be a reason for the yield loss in certain cases, this observation led to the development of a one-pot bimetallic approach for the synthesis of 1,3-disubstituted THCs.

  4. Palladium-catalyzed direct C2 arylation of N-substituted indoles with 1-aryltriazenes.

    PubMed

    Liu, Can; Miao, Tao; Zhang, Lei; Li, Pinhua; Zhang, Yicheng; Wang, Lei

    2014-09-01

    A novel and efficient palladium-catalyzed C2 arylation of N-substituted indoles with 1-aryltriazenes for the synthesis of 2-arylindoles was developed. In the presence of BF3⋅OEt2 and palladium(II) acetate (Pd(OAc)2), N-substituted indoles reacted with 1-aryltriazenes in N,N-dimethylacetamide (DMAC) to afford the corresponding aryl-indole-type products in good to excellent yields. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Discovery and optimization of indole and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-II).

    PubMed

    Sessions, E Hampton; Chowdhury, Sarwat; Yin, Yan; Pocas, Jennifer R; Grant, Wayne; Schröter, Thomas; Lin, Li; Ruiz, Claudia; Cameron, Michael D; LoGrasso, Philip; Bannister, Thomas D; Feng, Yangbo

    2011-12-01

    Therapeutic interventions with Rho kinase (ROCK) inhibitors may effectively treat several disorders such as hypertension, stroke, cancer, and glaucoma. Herein we disclose the optimization and biological evaluation of potent novel ROCK inhibitors based on substituted indole and 7-azaindole core scaffolds. Substitutions on the indole C3 position and on the indole NH and/or amide NH positions all yielded potent and selective ROCK inhibitors (25, 42, and 50). Improvement of aqueous solubility and tailoring of in vitro and in vivo DMPK properties could be achieved through these substitutions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Optimization of novel indole-2-carboxamide inhibitors of neurotropic alphavirus replication.

    PubMed

    Sindac, Janice A; Barraza, Scott J; Dobry, Craig J; Xiang, Jianming; Blakely, Pennelope K; Irani, David N; Keep, Richard F; Miller, David J; Larsen, Scott D

    2013-11-27

    Neurotropic alphaviruses, which include western equine encephalitis virus (WEEV) and Fort Morgan virus, are mosquito-borne pathogens that infect the central nervous system causing acute and potentially fatal encephalitis. We previously reported a novel series of indole-2-carboxamides as alphavirus replication inhibitors, one of which conferred protection against neuroadapted Sindbis virus infection in mice. We describe here further development of this series, resulting in 10-fold improvement in potency in a WEEV replicon assay and up to 40-fold increases in half-lives in mouse liver microsomes. Using a rhodamine123 uptake assay in MDR1-MDCKII cells, we were able to identify structural modifications that markedly reduce recognition by P-glycoprotein, the key efflux transporter at the blood-brain barrier. In a preliminary mouse PK study, we were able to demonstrate that two new analogues could achieve higher and/or longer plasma drug exposures than our previous lead and that one compound achieved measurable drug levels in the brain.

  7. Object Recognition Memory and the Rodent Hippocampus

    ERIC Educational Resources Information Center

    Broadbent, Nicola J.; Gaskin, Stephane; Squire, Larry R.; Clark, Robert E.

    2010-01-01

    In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR…

  8. Options for Dealing With Rodent Infestations

    EPA Pesticide Factsheets

    After removing sources of food and water and shelter, your next options are rodent traps and poisons (rodenticides). Rat or mouse traps may be lethal (snap traps) or live (cage-type), and poison baits must be placed in tamper-resistant bait stations.

  9. Rodent Depredation -- A Direct Seeding Problem

    Treesearch

    O. Gordon Langdon; William P. LeGrande

    1965-01-01

    Foresters have known for a long time that seed-eating rodents, birds, and insects must be circumvented before direct seeding can be successful. Advances have been made in reducing losses in the direct seeding of pine by the use of chemical repellents, and in several areas of the South recommended concentrations have been satisfactory. Direct seeding is now on an...

  10. Object Recognition Memory and the Rodent Hippocampus

    ERIC Educational Resources Information Center

    Broadbent, Nicola J.; Gaskin, Stephane; Squire, Larry R.; Clark, Robert E.

    2010-01-01

    In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR…

  11. Conjunctival lymphoid follicles in new world rodents.

    PubMed

    Astley, Roger A; Chodosh, James; Caire, William; Wilson, Gregory M

    2007-09-01

    We report for the first time, the detection of conjunctival lymphoid follicles (CLF) in the eyes of New World rodents. CLF were found in 7 of the 15 species examined, 6 of the 10 genera, and in at least one individual in four families of rodents. These follicles are dense collections of leukocytes in the conjunctival substantia propria with a thinned overlying epithelium lacking in goblet cells. Although the precise location of CLF within the conjunctiva varied from species to species, all CLF were found in the fornix of the conjunctival sac. In general, size and complexity of CLF varied with the size of the eye; the larger the eye, the larger and more complex the CLF. Our findings also reveal that some species of New World rodents, like the majority of Old World rodents examined in this and previous studies might lack CLF. However, until larger samples are examined, this is difficult to state with certainty. Consequently, the presence/absence of CLF at this point might not be informative for phylogenetic comparisons. Our findings also suggest the deer mouse, Peromyscus maniculatus, might serve as a useful model species for studying ocular infections and immunology of the eye.

  12. Rodent Cage Allocation | Center for Cancer Research

    Cancer.gov

    CCR Animal Cage Allocation Principles - 2017 Rodent cage allocations for each principal investigator (PI) are based on: Animal study design and justification BSC Recommendations Package for new tenure track or tenured investigator Average cage usage in previous fiscal years Note: The allocations largely reflect PI requirements for standard mouse caging.

  13. Methods for measuring populations of arboreal rodents.

    Treesearch

    Andrew B. Carey; Brian L. Biswell; Joseph W. Witt

    1991-01-01

    Three arboreal rodents are sensitive indicators of forest ecosystem function in the Pacific Northwest. The northern flying squirrel (Glaucomys sabrinus) is mycophagous, cavity-nesting, and a major prey of the spotted owl (Strix occidentalis). The red tree vole (Phenacomys longicaudus) is restricted to trees...

  14. Synthesis of Benzofurans and Indoles from Terminal Alkynes and Iodoaromatics Catalyzed by Recyclable Palladium Nanoparticles Immobilized on Siliceous Mesocellular Foam.

    PubMed

    Bruneau, Alexandre; Gustafson, Karl P J; Yuan, Ning; Tai, Cheuk-Wai; Persson, Ingmar; Zou, Xiaodong; Bäckvall, Jan-E

    2017-07-23

    Herein, we report on the utilization of a heterogeneous catalyst, consisting of Pd nanoparticles supported on a siliceous mesocellular foam (Pd(0) -AmP-MCF), for the synthesis of heterocycles. Reaction of o-iodophenols and protected o-iodoanilines with acetylenes in the presence of a Pd nanocatalyst produced 2-substituted benzofurans and indoles, respectively. In general, the catalytic protocol afforded the desired products in good to excellent yields under mild reaction conditions without the addition of ligands. Moreover, the structure of the reported Pd nanocatalyst was further elucidated with extended X-ray absorption fine-structure spectroscopy, and it was proven that the catalyst could be recycled multiple times without significant loss of activity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Growth of Brassica juncea under chromium stress: influence of siderophores and indole 3 acetic acid producing rhizosphere bacteria.

    PubMed

    Rajkumar, M; Lee, Kui Jae; Lee, Wang Hyu; Banu, J Rajesh

    2005-10-01

    Plant growth promoting rhizobacterial (PGPR) strains A3 and S32 have been shown to promote the growth of Brassica juncea under chromium stress which has been related to the microbial production of siderophores and indole 3 acetic acid (IAA). The aim of the present study is to evaluate the importance of siderophores and IAA producing PGPR on the growth of Brassica juncea under chromium stress. The production of IAA and siderophores were observed in the strains A3 and S32, respectively. Both PGPR strains promote the growth of Brassica juncea under chromium stress. The maximum growth was observed in plants inoculated with siderophores producing strain 32. Both the bacterial inoculum did not influence the uptake of chromium by plants. The present observation showed that PGPR isolates A3 and S32 are capable of protecting the plants against the inhibitory effects of chromium by producing the siderophores and IAA.

  16. Ethylene-enhanced catabolism of ( sup 14 C)indole-3-acetic acid to indole-3-carboxylic acid in citrus leaf tissues. [Citrus sinensis

    SciTech Connect

    Sagee, O.; Riov, J.; Goren, J. )

    1990-01-01

    Exogenous ({sup 14}C)indole-3-acetic acid (IAA) is conjugated in citrus (Citrus sinensis) leaf tissues to one major substance which has been identified as indole-3-acetylaspartic acid (IAAsp). Ethylene pretreatment enhanced the catabolism of ({sup 14}C)IAA to indole-3-carboxylic acid (ICA), which accumulated as glucose esters (ICGlu). Increased formation of ICGlu by ethylene was accompanied by a concomitant decrease in IAAsp formation. IAAsp and ICGlu were identified by combined gas chromatography-mass spectrometry. Formation of ICGlu was dependent on the concentration of ethylene and the duration of the ethylene pretreatment. It is suggested that the catabolism of IAA to ICA may be one of the mechanisms by which ethylene endogenous IAA levels.

  17. Arenavirus Diversity and Phylogeography of Mastomys natalensis Rodents, Nigeria

    PubMed Central

    Obadare, Adeoba; Oyeyiola, Akinlabi; Igbokwe, Joseph; Fasogbon, Ayobami; Igbahenah, Felix; Ortsega, Daniel; Asogun, Danny; Umeh, Prince; Vakkai, Innocent; Abejegah, Chukwuyem; Pahlman, Meike; Becker-Ziaja, Beate; Günther, Stephan; Fichet-Calvet, Elisabeth

    2016-01-01

    Mastomys natalensis rodents are natural hosts for Lassa virus (LASV). Detection of LASV in 2 mitochondrial phylogroups of the rodent near the Niger and Benue Rivers in Nigeria underlines the potential for LASV emergence in fresh phylogroups of this rodent. A Mobala-like sequence was also detected in eastern Nigeria. PMID:26982388

  18. Arenavirus Diversity and Phylogeography of Mastomys natalensis Rodents, Nigeria.

    PubMed

    Olayemi, Ayodeji; Obadare, Adeoba; Oyeyiola, Akinlabi; Igbokwe, Joseph; Fasogbon, Ayobami; Igbahenah, Felix; Ortsega, Daniel; Asogun, Danny; Umeh, Prince; Vakkai, Innocent; Abejegah, Chukwuyem; Pahlman, Meike; Becker-Ziaja, Beate; Günther, Stephan; Fichet-Calvet, Elisabeth

    2016-04-01

    Mastomys natalensis rodents are natural hosts for Lassa virus (LASV). Detection of LASV in 2 mitochondrial phylogroups of the rodent near the Niger and Benue Rivers in Nigeria underlines the potential for LASV emergence in fresh phylogroups of this rodent. A Mobala-like sequence was also detected in eastern Nigeria.

  19. 7 CFR 58.147 - Insect and rodent control program.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Insect and rodent control program. 58.147 Section 58... Service 1 Operations and Operating Procedures § 58.147 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control...

  20. 20 CFR 654.415 - Insect and rodent control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Insect and rodent control. 654.415 Section 654.415 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR SPECIAL... Insect and rodent control. Housing and facilities shall be free of insects, rodents, and other vermin....

  1. 7 CFR 58.147 - Insect and rodent control program.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Insect and rodent control program. 58.147 Section 58... Service 1 Operations and Operating Procedures § 58.147 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control...

  2. 20 CFR 654.415 - Insect and rodent control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Insect and rodent control. 654.415 Section 654.415 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR SPECIAL... Insect and rodent control. Housing and facilities shall be free of insects, rodents, and other vermin....

  3. 7 CFR 58.247 - Insect and rodent control program.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Insect and rodent control program. 58.247 Section 58... Service 1 Operations and Operating Procedures § 58.247 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control program...

  4. 7 CFR 58.147 - Insect and rodent control program.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Insect and rodent control program. 58.147 Section 58... Service 1 Operations and Operating Procedures § 58.147 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control...

  5. 7 CFR 58.147 - Insect and rodent control program.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Insect and rodent control program. 58.147 Section 58... Service 1 Operations and Operating Procedures § 58.147 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control...

  6. 20 CFR 654.415 - Insect and rodent control.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Insect and rodent control. 654.415 Section 654.415 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR SPECIAL... Insect and rodent control. Housing and facilities shall be free of insects, rodents, and other vermin....

  7. 7 CFR 58.247 - Insect and rodent control program.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Insect and rodent control program. 58.247 Section 58... Service 1 Operations and Operating Procedures § 58.247 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control program...

  8. 7 CFR 58.247 - Insect and rodent control program.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Insect and rodent control program. 58.247 Section 58... Service 1 Operations and Operating Procedures § 58.247 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control program...

  9. 7 CFR 58.247 - Insect and rodent control program.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Insect and rodent control program. 58.247 Section 58... Service 1 Operations and Operating Procedures § 58.247 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control program...

  10. 20 CFR 654.415 - Insect and rodent control.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Insect and rodent control. 654.415 Section 654.415 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR SPECIAL... Insect and rodent control. Housing and facilities shall be free of insects, rodents, and other vermin....

  11. 7 CFR 58.147 - Insect and rodent control program.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Insect and rodent control program. 58.147 Section 58... Service 1 Operations and Operating Procedures § 58.147 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control...

  12. 20 CFR 654.415 - Insect and rodent control.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Insect and rodent control. 654.415 Section 654.415 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR SPECIAL... Insect and rodent control. Housing and facilities shall be free of insects, rodents, and other vermin....

  13. Novel indole-3-sulfonamides as potent HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs)

    SciTech Connect

    Zhao, Zhijian; Wolkenberg, Scott E.; Lu, Meiqing; Munshi, Vandna; Moyer, Gregory; Feng, Meizhen; Carella, Anthony V.; Ecto, Linda T.; Gabryelski, Lori J.; Lai, Ming-Tain; Prasad, Sridar G.; Yan, Youwei; McGaughey, Georgia B.; Miller, Michael D.; Lindsley, Craig W.; Hartman, George D.; Vacca, Joseph P.; Williams, Theresa M.

    2008-09-29

    This Letter describes the design, synthesis, and biological evaluation of novel 3-indole sulfonamides as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) with balanced profiles against common HIV RT mutants K103N and Y181C.

  14. Biological matching of chemical reactivity: pairing indole nucleophilicity with electrophilic isoprenoids.

    PubMed

    Walsh, Christopher T

    2014-12-19

    The indole side chain of tryptophan has latent nucleophilic reactivity at both N1 and all six (nonbridgehead) carbons, which is not generally manifested in post-translational reactions of proteins. On the other hand, all seven positions can be prenylated by the primary metabolite Δ(2)-isopentenyl diphosphate by dimethyallyl transferase (DMATs) family members as initial steps in biosynthetic pathways to bioactive fungal alkaloids including ergots and tremorgens. These are formulated as regioselective capture of isopentenyl allylic cationic transition states by the indole side chain as a nucleophile. The balance of regiospecificity and promiscuity among these indole prenyltransferases continues to raise questions about possible Cope and azaCope rearrangements of nascent products. In addition to these two electron reaction manifolds, there is evidence for one electron reaction manifolds in indole ring biosynthetic functionalization.

  15. An in vitro system from maize seedlings for tryptophan-independent indole-3-acetic acid biosynthesis

    SciTech Connect

    Oestin, A.; Ilic, N.; Cohen, J.D.

    1999-01-01

    The enzymatic synthesis of indole-3-acetic acid (IAA) from indole by an in vitro preparation from maize (Zea mays L.) that does not use tryptophan (Trp) as an intermediate is described. Light-grown seedlings of normal maize and the maize mutant orange pericarp were shown to contain the necessary enzymes to convert [{sup 14}C]indole to IAA. The reaction was not inhibited by unlabeled Trp and neither [{sup 14}C]Trp nor [{sup 14}C]serine substituted for [{sup 14}C]indole in this in vitro system. The reaction had a pH optimum greater than 8.0, required a reducing environment, and had an oxidation potential near that of ascorbate. The results obtained with this in vitro enzyme preparation provide strong, additional evidence for the presence of a Trp-independent IAA biosynthesis pathway in plants.

  16. Theoretical Reactivity Study of Indol-4-Ones and Their Correlation with Antifungal Activity.

    PubMed

    Zermeño-Macías, María de Los Ángeles; González-Chávez, Marco Martín; Méndez, Francisco; González-Chávez, Rodolfo; Richaud, Arlette

    2017-03-08

    Chemical reactivity descriptors of indol-4-ones obtained via density functional theory (DFT) and hard-soft acid-base (HSAB) principle were calculated to prove their contribution in antifungal activity [...].

  17. Iridium-catalyzed hydrogen transfer: synthesis of substituted benzofurans, benzothiophenes, and indoles from benzyl alcohols.

    PubMed

    Anxionnat, Bruno; Gomez Pardo, Domingo; Ricci, Gino; Rossen, Kai; Cossy, Janine

    2013-08-02

    An iridium-catalyzed hydrogen transfer has been developed in the presence of p-benzoquinone, allowing the synthesis of a diversity of substituted benzofurans, benzothiophenes, and indoles from substituted benzylic alcohols.

  18. Indole is an inter-species biofilm signal mediated by SdiA

    PubMed Central

    Lee, Jintae; Jayaraman, Arul; Wood, Thomas K

    2007-01-01

    Background As a stationary phase signal, indole is secreted in large quantities into rich medium by Escherichia coli and has been shown to control several genes (e.g., astD, tnaB, gabT), multi-drug exporters, and the pathogenicity island of E. coli; however, its impact on biofilm formation has not been well-studied. Results Through a series of global transcriptome analyses, confocal microscopy, isogenic mutants, and dual-species biofilms, we show here that indole is a non-toxic signal that controls E. coli biofilms by repressing motility, inducing the sensor of the quorum sensing signal autoinducer-1 (SdiA), and influencing acid resistance (e.g., hdeABD, gadABCEX). Isogenic mutants showed these associated proteins are directly related to biofilm formation (e.g., the sdiA mutation increased biofilm formation 50-fold), and SdiA-mediated transcription was shown to be influenced by indole. The reduction in motility due to indole addition results in the biofilm architecture changing from scattered towers to flat colonies. Additionally, there are 12-fold more E. coli cells in dual-species biofilms grown in the presence of Pseudomonas cells engineered to express toluene o-monooxygenase (TOM, which converts indole to an insoluble indigoid) than in biofilms with pseudomonads that do not express TOM due to a 22-fold reduction in extracellular indole. Also, indole stimulates biofilm formation in pseudomonads. Further evidence that the indole effects are mediated by SdiA and homoserine lactone quorum sensing is that the addition of N-butyryl-, N-hexanoyl-, and N-octanoyl-L-homoserine lactones repress E. coli biofilm formation in the wild-type strain but not with the sdiA mutant. Conclusion Indole is an interspecies signal that decreases E. coli biofilms through SdiA and increases those of pseudomonads. Indole may be manipulated to control biofilm formation by oxygenases of bacteria that do not synthesize it in a dual-species biofilm. Furthermore, E. coli changes its biofilm in

  19. Indole is an inter-species biofilm signal mediated by SdiA.

    PubMed

    Lee, Jintae; Jayaraman, Arul; Wood, Thomas K

    2007-05-18

    As a stationary phase signal, indole is secreted in large quantities into rich medium by Escherichia coli and has been shown to control several genes (e.g., astD, tnaB, gabT), multi-drug exporters, and the pathogenicity island of E. coli; however, its impact on biofilm formation has not been well-studied. Through a series of global transcriptome analyses, confocal microscopy, isogenic mutants, and dual-species biofilms, we show here that indole is a non-toxic signal that controls E. coli biofilms by repressing motility, inducing the sensor of the quorum sensing signal autoinducer-1 (SdiA), and influencing acid resistance (e.g., hdeABD, gadABCEX). Isogenic mutants showed these associated proteins are directly related to biofilm formation (e.g., the sdiA mutation increased biofilm formation 50-fold), and SdiA-mediated transcription was shown to be influenced by indole. The reduction in motility due to indole addition results in the biofilm architecture changing from scattered towers to flat colonies. Additionally, there are 12-fold more E. coli cells in dual-species biofilms grown in the presence of Pseudomonas cells engineered to express toluene o-monooxygenase (TOM, which converts indole to an insoluble indigoid) than in biofilms with pseudomonads that do not express TOM due to a 22-fold reduction in extracellular indole. Also, indole stimulates biofilm formation in pseudomonads. Further evidence that the indole effects are mediated by SdiA and homoserine lactone quorum sensing is that the addition of N-butyryl-, N-hexanoyl-, and N-octanoyl-L-homoserine lactones repress E. coli biofilm formation in the wild-type strain but not with the sdiA mutant. Indole is an interspecies signal that decreases E. coli biofilms through SdiA and increases those of pseudomonads. Indole may be manipulated to control biofilm formation by oxygenases of bacteria that do not synthesize it in a dual-species biofilm. Furthermore, E. coli changes its biofilm in response to signals it cannot

  20. FeCl3·6H2O-catalyzed alkenylation of indoles with aldehydes.

    PubMed

    Yang, Qin; Wang, Liandi; Guo, Tenglong; Yu, Zhengkun

    2012-09-21

    FeCl(3)·6H(2)O-catalyzed efficient C3-alkenylation of indoles was realized through the condensation of aldehydes and indole derivatives in the presence of 2 equiv of ethanol at ambient temperature, forming 3-vinylindoles in up to 93% yields. Ethanol promoted formation of the desired products. An obvious solvent effect was observed, and bisindoles were identified as the reaction intermediates.

  1. Enantioselective one-pot synthesis of 2-amino-4-(indol-3-yl)-4H-chromenes.

    PubMed

    Chen, Weiliang; Cai, Yunfei; Fu, Xuan; Liu, Xiaohua; Lin, Lili; Feng, Xiaoming

    2011-09-16

    An enantioselective one-pot synthesis of 2-amino-4-(indol-3-yl)-4H-chromenes via a Knoevenagel/Pinner/Friedel-Crafts reaction of salicylaldehyde, malononitrile, and indole is presented. Moderate to good yields (up to 89%) and high enantioselectivities (up to 90% ee) were obtained with an N,N'-dioxide-Zn(II) complex as the catalyst. This strategy provides an efficient and convenient method to access enantiomerically enriched 2-amino-4H-chromene derivatives.

  2. A Scalable Method for Regioselective 3-Acylation of 2-Substituted Indoles under Basic Conditions.

    PubMed

    Johansson, Henrik; Urruticoechea, Andoni; Larsen, Inna; Sejer Pedersen, Daniel

    2015-01-02

    Privileged structures such as 2-arylindoles are recurrent molecular scaffolds in bioactive molecules. We here present an operationally simple, high yielding and scalable method for regioselective 3-acylation of 2-substituted indoles under basic conditions using functionalized acid chlorides. The method shows good tolerance to both electron-withdrawing and donating substituents on the indole scaffold and gives ready access to a variety of functionalized 3-acylindole building blocks suited for further derivatization.

  3. Discovery of nonsteroidal glucocorticoid receptor ligands based on 6-indole-1,2,3,4-tetrahydroquinolines.

    PubMed

    Roach, Steven L; Higuchi, Robert I; Adams, Mark E; Liu, Yan; Karanewsky, Donald S; Marschke, Keith B; Mais, Dale E; Miner, Jeffrey N; Zhi, Lin

    2008-06-15

    A series of nonsteroidal glucocorticoid receptor (GR) ligands based on a 6-indole-1,2,3,4-tetrahydroquinoline scaffold are reported. Structure-activity relationship (SAR) of the pendent indole group identified compound 20 exhibiting good GR binding affinity (K(i)=1.5nM) and 100- to 1000-fold selectivity over MR, PR, and AR while showing activity in an E-selectin repression assay.

  4. A facile means for the identification of indolic compounds from plant tissues.

    PubMed

    Yu, Peng; Hegeman, Adrian D; Cohen, Jerry D

    2014-09-01

    The bulk of indole-3-acetic acid (IAA) in plants is found in the form of conjugated molecules, yet past research on identifying these compounds has largely relied on methods that were both laborious and inefficient. Using recent advances in analytical instrumentation, we have developed a simple yet powerful liquid chromatography-mass spectrometry (LC-MS)-based method for the facile characterization of the small IAA conjugate profile of plants. The method uses the well-known quinolinium ion (m/z 130.0651) generated in MS processes as a signature with high mass accuracy that can be used to screen plant extracts for indolic compounds, including IAA conjugates. We reinvestigated Glycine max (soybean) for its indoles and found indole-3-acetyl-trytophan (IA-Trp) in addition to the already known indole-3-acetyl-aspartic acid (IA-Asp) and indole-3-acetyl-glutamic acid (IA-Glu) conjugates. Surprisingly, several organic acid conjugates of tryptophan were also discovered, many of which have not been reported in planta before. These compounds may have important physiological roles in tryptophan metabolism, which in turn can affect human nutrition. We also demonstrated the general applicability of this method by identifying indolic compounds in different plant tissues of diverse phylogenetic origins. It involves minimal sample preparation but can work in conjunction with sample enrichment techniques. This method enables quick screening of IAA conjugates in both previously characterized as well as uncharacterized species, and facilitates the identification of indolic compounds in general. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  5. Synthesis of Pyrido[1,2-a]indole Malonates and Amines through Aryne Annulation

    PubMed Central

    Rogness, Donald C.; Markina, Nataliya A.; Waldo, Jesse P.; Larock, Richard C.

    2012-01-01

    Pyrido[1,2-a]indoles are known as medicinally and pharmaceutically important compounds, but there is a lack of efficient methods for their synthesis. We report a convenient and efficient route to these privileged structures starting from easily accessible 2-substituted pyridines and aryne precursors. A small library of compounds has been synthesized utilizing the developed method, affording variously substituted pyrido[1,2-a]indoles in moderate to good yields. PMID:22356459

  6. An Efficient, Microwave-Assisted, One-Pot Synthesis of Indoles Under Sonogashira Conditions

    PubMed Central

    Chen, Yu; Markina, Nataliya A.; Larock, Richard C.

    2009-01-01

    A microwave-assisted, one-pot, three-component coupling reaction for the synthesis of indoles has been developed. The reaction is carried out in two steps under standard Sonogashira coupling conditions from an N-substituted/N,N-disubstituted 2-iodoaniline and a terminal alkyne, followed by the addition of acetonitrile and an aryl iodide. A variety of polysubstituted indoles have been prepared in moderate to excellent yields using the present method. PMID:20160894

  7. Hydroxy-Directed Enantioselective Hydroxyalkylation in the Carbocyclic Ring of Indoles.

    PubMed

    Montesinos-Magraner, Marc; Vila, Carlos; Blay, Gonzalo; Fernández, Isabel; Muñoz, M Carmen; Pedro, José R

    2017-04-07

    A Cinchona-derived squaramide catalyzes the reaction between hydroxyindoles and isatins leading to enantioenriched indoles substituted in the carbocyclic ring. The reaction proceeds efficiently with differently substituted isatins, yielding the desired products with excellent regioselectivity, good yields, and high enantiocontrol. Moreover, every position of the carbocyclic ring of the indole can be functionalized by using the appropriate starting hydroxyindole. The OH group was removed smoothly upon hydrogenolysis of the corresponding triflate.

  8. Novel synthetic bis-indolic derivatives with antistaphylococcal activity, including against MRSA and VISA strains.

    PubMed

    Caspar, Yvan; Jeanty, Matthieu; Blu, Jérôme; Burchak, Olga; Le Pihive, Emmanuelle; Maigre, Laure; Schneider, Dominique; Jolivalt, Claude; Paris, Jean-Marc; Hequet, Arnaud; Minassian, Frédéric; Denis, Jean-Noël; Maurin, Max

    2015-01-01

    We report the synthesis, antibacterial activity and toxicity of 24 bis-indolic derivatives obtained during the development of new ways of synthesis of marine bis-indole alkaloids from the spongotine, topsentin and hamacanthin classes. Innovative ways of synthesis and further structural optimizations led to bis-indoles presenting either the 1-(1H-indol-3'-yl)-1,2-diaminoethane unit or the 1-(1H-indol-3-yl)ethanamine unit. MIC determination was performed for reference and clinical strains of Staphylococcus aureus and CoNS species. MBC, time-kill kinetics, solubility, hydrophobicity index, plasma protein-binding and cytotoxicity assays were performed for lead compounds. Inhibition of the S. aureus NorA efflux pump was also tested for bis-indoles with no antistaphylococcal activity. Lead compounds were active against both S. aureus and CoNS species, with MICs between 1 and 4 mg/L. Importantly, the same MICs were found for MRSA and vancomycin-intermediate S. aureus strains. Early concentration-dependent bactericidal activity was observed for lead derivatives. Compounds with no intrinsic antibacterial activity could inhibit the S. aureus NorA efflux pump, which is involved in resistance to fluoroquinolones. At 0.5 mg/L, the most effective compound led to an 8-fold reduction of the ciprofloxacin MIC for the SA-1199B S. aureus strain, which overexpresses NorA. However, the bis-indole compounds displayed a high hydrophobicity index and high plasma protein binding, which significantly reduced antibacterial activity. We have synthesized and characterized novel bis-indole derivatives as promising candidates for the development of new antistaphylococcal treatments, with preserved activity against MDR S. aureus strains. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Indole-3-acetic acid: a potential new photosensitizer for photodynamic therapy of acne vulgaris.

    PubMed

    Na, Jung-Im; Kim, So-Young; Kim, Jeong-Hye; Youn, Sang-Woong; Huh, Chang-Hun; Park, Kyoung-Chan

    2011-03-01

    ALA (5-aminolevulinic acid) photodynamic therapy (PDT) is a new treatment option for acne. However, it needs a relatively long incubation period and adverse effects are common. Indole-3-acetic acid (IAA) is not toxic by itself but produces free radicals with ultraviolet B. In this study we examined the potential of IAA as a photosensitizer for acne treatment. Free radical formation was measured after visible light irradiation of IAA. Antimicrobial effect was evaluated by assessing growth suppression of Propionibacterium acnes and Staphylococcus aureus after IAA PDT. To evaluate the histological changes, skin biopsies were performed on nude mice skin after IAA PDT. To evaluate the clinical efficacy of IAA PDT, 14 acne patients were treated with the following IAA PDT regimen: three times each with a 15 minutes incubation period and a 2-week interval. The number of inflammatory lesions and the amount of sebum secretion were then assessed. IAA produced free radicals with green light irradiation. Importantly, IAA lost its photosensitizing ability after exposure to certain amount of light. This implies IAA PDT would not require post-procedure photo-protection. The growth of P. acnes and S. aureus were significantly suppressed with IAA PDT. In addition, IAA PDT treated skin showed destruction of follicular ostia epithelium. Interestingly, there was no significant difference between a 4 hours and a 30 minutes incubation, which means that longer absorption time is not necessary for IAA PDT. In the clinical study, inflammatory lesions and sebum secretion were significantly reduced. The procedure was painless and no adverse effect was observed. Photo-protection was not performed and there were no further phototoxic responses. IAA PDT has therapeutic effects on acne via its antimicrobial activities, its sebum-reducing effect and through relieving follicular occlusion. It is a very simple and safe treatment option for acne. Copyright © 2011 Wiley-Liss, Inc.

  10. Transport and Metabolism of Indole-3-Acetyl-myo-Inositol-Galactoside in Seedlings of Zea mays1

    PubMed Central

    Komoszynski, Michal; Bandurski, Robert S.

    1986-01-01

    Indole-3-acetyl-myo-inositol galactoside labeled with 3H in the indole and 14C in the galactose moieties was applied to kernels of 5 day old germinating seedlings of Zea mays. Indole-3-acetyl-myo-inositol galactoside was not transported into either the shoot or root tissue as the intact molecule but was instead hydrolyzed to yield [3H]indole-3-acetyl-myo-inositol and [3H]indole-3-acetic acid which were then transported to the shoot with little radioactivity going to the root. With certain assumptions concerning the equilibration of applied [3H]indole-3-acetyl-myo-inositol-[U-14C]galactose with the endogenous pool, it may be concluded that indole-3-acetyl-myo-inositol galactoside in the endosperm supplies about 2 picomoles per plant per hour of indole-3-acetyl-myo-inositol and 1 picomole per plant per hour of indole-3-acetic acid to the shoot and thus is comparable to indole-3-acetyl-myo-inositol as a source of indole-acetic acid for the shoot. Quantitative estimates of the amount of galactose in the kernels suggest that [3H]indole-3-acetyl-myo-inositol-[14C] galactose is hydrolyzed after the compound leaves the endosperm but before it reaches the shoot. In addition, [3H]indole-3-acetyl-myo-inositol-[14C]galactose supplies appreciable amounts of 14C to the shoot and both 14C and 3H to an uncharacterized insoluble fraction of the endosperm. PMID:11539040

  11. [Content of indole alkaloids and bufadienolides contained in toad medicines].

    PubMed

    Qu, Ting; Gao, Hui-Min; Chen, Liang-Mian; Wang, Zhi-Min; Zhang, Qi-Wei; Cheng, Yi-Yu

    2012-10-01

    To kinds of establish a HPLC method for determining contents of indole alkaloids and bufadienolides contained in toad medicines, and analyze two kinds of components contained in toad venom, toad skin and toad periostracum. As for alkaloids, Nucleosil C18 column was adopted with acetonitrile and water containing 0.5% potassium dihydrogen phosphate (6: 94, adjust pH to 3.2 with phosphate acid) as the mobile phase. The flow rate was 0.8 mL x min(-1), the detection wavelength was 275 nm, and the column temperature was 30 degrees C. As for bufadienolides, Alltima C18 column was adopted with acetonitrile and water containing 0.3% acetic acid (B) as the mobile phase. The gradient process was as follows: a linear gradient from 28% to 54% acetonitrile in the first 15 min, then kept at 54% for additional 20 min. The flow rate was 0.6 mL x min(-1), the detection wavelength was 296 nm, and the column temperature was 30 degrees C. The linear ranges were 0.079 6-0.796 microg for serotonin, 0.097 2-1.945 microg for N-methylserotonin, 0.074 4-0.744 microg for N,N-dimethylserotonin, 0.103-2.05 microg for N,N,N-trimethylserotonin, and 0.067 2-0.672 microg for bufothionine, respectively. The average recoveries of serotonin and N-methylserotonin were 98.6% and 91.3%, respectively. The linear ranges of gamabufotalin, bufotalin, bufalin, cinobufagin and resibufogenin were 0.004 83-0.614, 0.007 9-1.006, 0.007 95-1.016, 0.009 7-1.24 and 0.009 6-1.22 microg, respectively, and their average recoveries were 101.6%, 102.5%, 101.0%, 99.1% and 98.9%, respectively. Toad venom has the highest contents of indole alkaloids and bufadienolides, followed by toad skin, and toad periostracum showed the lowest contents and even no detection result.

  12. Indole hydroxylation by bacterial cytochrome P450 BM-3 and modulation of activity by cumene hydroperoxide.

    PubMed

    Li, Qing-Shan; Ogawa, Jun; Schmid, Rolf D; Shimizu, Sakayu

    2005-02-01

    Cytochrome P450 BM-3 from Bacillus megaterium catalyzed NADPH-supported indole hydroxylation under alkaline conditions with homotropic cooperativity toward indole. The activity was also found with the support of H2O2, tert-butyl hydroperoxide (tBuOOH), or cumene hydroperoxide (CuOOH). Enhanced activity and heterotropic cooperativity were observed in CuOOH-supported hydroxylation, and both the Hill coefficient and substrate concentration required for half-maximal activity in the CuOOH-supported reaction were much lower than those in the H2O2-, tBuOOH-, or NADPH-supported reactions. CuOOH greatly enhanced NADPH consumption and indole hydroxylation in the NADPH-supported reaction. However, when CuOOH was replaced by tBuOOH or H2O2, heterotropic cooperativity was not observed. Spectral studies also confirmed that CuOOH stimulated indole binding to P450 BM-3. Interestingly, a mutant enzyme with enhanced indole-hydroxylation activity, F87V (Phe87 was replaced by Val), lost homotropic cooperativity towards indole and heterotropic cooperativity towards CuOOH, indicating that the active-site structure affects the cooperativities.

  13. Molecular basis of indole production catalyzed by tryptophanase in the genus Prevotella.

    PubMed

    Sasaki-Imamura, Takako; Yoshida, Yasuo; Suwabe, Kyosuke; Yoshimura, Fuminobu; Kato, Hirohisa

    2011-09-01

    Indole is most commonly known as a diagnostic marker and a malodorous chemorepellent. More recently, it has been recognized that indole also functions as an extracellular signaling molecule that controls bacterial physiology and virulence. The gene (tnaA) for tryptophanase, which produces indole, ammonia, and pyruvate via β-elimination of L-tryptophan, was cloned from Prevotella intermedia ATCC 25611 and recombinant TnaA was purified and enzymatically characterized. Analysis by reverse transcriptase-mediated PCR showed that the gene was not cotranscribed with flanking genes in P. intermedia. The results of gel-filtration chromatography suggested that P. intermedia TnaA forms homodimers, unlike other reported TnaA proteins. Recombinant TnaA exhibited a K(m) of 0.23 ± 0.01 mM and k(cat) of 0.45 ± 0.01 s(-1). Of 22 Prevotella species tested, detectable levels of indole were present in the culture supernatants of six, including P. intermedia. Southern hybridization showed that tnaA-positive signals were present in the genomic DNA from the six indole-producing strains, but not the other 16 strains tested. The indole-producing strains, with the exception of Prevotella micans, formed a phylogenetic cluster based on trees constructed using 16S rRNA gene sequences, which suggested that tnaA in P. micans might have been transferred from other Prevotella species relatively recently.

  14. Interactions of Indole Derivatives with β-Cyclodextrin: A Quantitative Structure-Property Relationship Study

    PubMed Central

    Šoškić, Milan; Porobić, Ivana

    2016-01-01

    Retention factors for 31 indole derivatives, most of them with auxin activity, were determined by high-performance liquid chromatography, using bonded β-cyclodextrin as a stationary phase. A three-parameter QSPR (quantitative structure-property relationship) model, based on physico-chemical and structural descriptors was derived, which accounted for about 98% variations in the retention factors. The model suggests that the indole nucleus occupies the relatively apolar cavity of β-cyclodextrin while the carboxyl group of the indole -3-carboxylic acids makes hydrogen bonds with the hydroxyl groups of β-cyclodextrin. The length and flexibility of the side chain containing carboxyl group strongly affect the binding of these compounds to β-cyclodextrin. Non-acidic derivatives, unlike the indole-3-carboxylic acids, are poorly retained on the column. A reasonably well correlation was found between the retention factors of the indole-3-acetic acids and their relative binding affinities for human serum albumin, a carrier protein in the blood plasma. A less satisfactory correlation was obtained when the retention factors of the indole derivatives were compared with their affinities for auxin-binding protein 1, a plant auxin receptor. PMID:27124734

  15. The cytidine repressor participates in the regulatory pathway of indole in Pantoea agglomerans.

    PubMed

    Jia, Mengqi; Yu, Xuemei; Jiang, Jing; Li, Zihua; Feng, Yongjun

    2017-09-01

    Indole, an important signal molecule in both intraspecies and interspecies, regulates a variety of bacterial behaviors, but its regulatory mechanism is still unknown. Pantoea agglomerans YS19, a preponderant endophytic bacterium isolated from rice, does not produce indole, yet it senses exogenous indole. In this study, a mutant of YS19-Rp(r) whose target gene expression was downregulated by indole was selected through mTn5 transposon mutagenesis. Using the TAIL-PCR technique, the mutation gene was identified as a cytR homologue, which encodes a cytidine repressor (CytR) protein, a bacterial transcription factor involved in a complex regulation scheme. The negative regulation of indole in cytR, which is equivalent to the mutation in cytR, promotes the expression of a downstream gene deoC, which encodes the key enzyme deoxyribose-phosphate aldolase in participating in pentose metabolism. We found that DeoC is one of the regulatory proteins of P. agglomerans that is involved in counteracting starvation. Furthermore, the expression of deoC was induced by starvation conditions, accompanied by a decrease in cytR expression. This finding suggests that the indole signal and the mutation of cytR relieve inhibition of CytR in the transcription of deoC, facilitating better adaptation of the bacterium to the adverse conditions of the environment. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  16. [Aerosol deposition in nasal passages of burrowing and ground rodents when breathing dust-laden air].

    PubMed

    Moshkin, M P; Petrovskiĭ, D V; Akulov, A E; Romashchenko, A V; Gerlinskaia, L A; Muchnaia, M I; Ganimedov, V L; Sadovskiĭ, A S; Savelov, A A; Koptiug, I V; Troitskiĭ, S Iu; Bukhtiiarov, V I; Kolchanov, N A; Sagdeev, R Z; Fomin, V M

    2014-01-01

    In subterranean rodents, which dig down the passages with frontal teeth, adaptation to the underground mode of life presumes forming of mechanisms that provide protection against inhaling dust particles of different size when digging. One of such mechanisms can be specific pattern of air flow organization in the nasal cavity. To test this assumption, comparative study of geometry and aerodynamics of nasal passages has been conducted with regard to typical representative of subterranean rodents, the mole vole, and a representative of ground rodents, the house mouse. Numerical modeling of air flows and deposition of micro- and nanoparticle aerosols indicates that sedimentation of model particles over the whole surface of nasal cavity is higher in mole vole than in house mouse. On the contrary, particles deposition on the surface of olfactory epithelium turns out to be substantially less in the burrowing rodent as compared to the ground one. Adaptive significance of the latter observation has been substantiated by experimental study on the uptake ofnanoparticles of hydrated manganese oxide MnO x (H2O)x and Mn ions from nasal cavity into brain. It has been shown with use of magnetic resonance tomography method that there is no difference between studied species with respect to intake of particles or ions by olfactory bulb when they are introduced intranasally. Meanwhile, when inhaling nanoparticle aerosol of MnCl2, deposition of Mn in mouse's olfactory bulbs surpasses markedly that in vole's bulbs. Thereby, the morphology of nasal passages as a factor determining the aerodynamics of upper respiratory tract ensures for burrowing rodents more efficient protection of both lungs and brain against inhaled aerosols than for ground ones.

  17. Ivermectin as a Rodent Feed-Through Insecticide for Control of Immature Sand Flies (Diptera: Psychodidae)

    DTIC Science & Technology

    2008-01-01

    humidity and is protected from extreme temperatures . Adult sand flies live in close proximity to sources of blood (from the rodents living within the... temperature for 7 days and then were stored at 270uC until used. In each experiment, the body weight and daily food intake of hamsters in the 4 diet groups were...LN, Mamigonova RI, Sabatov EA. 1983. Use of D-20 aerosol insecticide smoke pots in controlling burrow sandflies . Med Parazitol Parazit Bolezni 4:78

  18. Indole alkaloids synthesis via a selective cyclization of aminocyclopropanes.

    PubMed

    De Simone, Filippo; Waser, Jérôme

    2012-01-01

    The continuous progress in medicinal chemistry requires more versatile synthetic strategies for the generation of large libraries of active compounds and their analogues. As a result, the research for new effective cyclization and cycloaddition reactions is an essential task in organic chemistry. In 2008 we developed the first catalytic formal homo-Nazarov reaction starting from activated cyclopropanes. Herein we report the extension of the catalytic formal homo-Nazarov cyclization to aminocyclopropanes. Highly diastereoselective cyclizations were obtained via an acyliminium intermediate generated through opening of the cyclopropane. An excellent control over the regioselectivity of either the C-C or C-N cyclization in the case of free indoles as nucleophilic partners was achieved. The utility of the developed methodology was demonstrated by the generation of the polycyclic scaffolds of Aspidosperma and Gonioma natural products starting from a common intermediate. Based on this method, a formal total synthesis of the alkaloid aspidospermidine and the total synthesis of the alkaloid goniomitine are presented. Finally, the scope and limitations of our methodology are discussed on an extended range of vinyl-cyclopropyl ketones with cyclic or acyclic carbamates, as well as ethers as donor groups on the cyclopropane.

  19. Metabolic regulation of the plant hormone indole-3-acetic acid

    SciTech Connect

    Jerry D. Cohen

    2009-11-01

    The phytohormone indole-3-acetic acid (IAA, auxin) is important for many aspects of plant growth, development and responses to the environment yet the routes to is biosynthesis and mechanisms for regulation of IAA levels remain important research questions. A critical issue concerning the biosynthesis if IAA in plants is that redundant pathways for IAA biosynthesis exist in plants. We showed that these redundant pathways and their relative contribution to net IAA production are under both developmental and environmental control. We worked on three fundamental problems related to how plants get their IAA: 1) An in vitro biochemical approach was used to define the tryptophan dependent pathway to IAA using maize endosperm, where relatively large amounts of IAA are produced over a short developmental period. Both a stable isotope dilution and a protein MS approach were used to identify intermediates and enzymes in the reactions. 2) We developed an in vitro system for analysis of tryptophan-independent IAA biosynthesis in maize seedlings and we used a metabolite profiling approach to isolate intermediates in this reaction. 3) Arabidopsis contains a small family of genes that encode potential indolepyruvate decarboxylase enzymes. We cloned these genes and studied plants that are mutant in these genes and that over-express each member in the family in terms of the level and route of IAA biosynthesis. Together, these allowed further development of a comprehensive picture of the pathways and regulatory components that are involved in IAA homeostasis in higher plants.

  20. Indolent anti-Hu-associated paraneoplastic sensory neuropathy.

    PubMed

    Graus, F; Bonaventura, I; Uchuya, M; Valls-Solé, J; Reñé, R; Leger, J M; Tolosa, E; Delattre, J Y

    1994-12-01

    Paraneoplastic sensory neuropathy (PSN) usually runs a subacute progressive course, leaving the patient with severe sensory dysfunction in weeks to months. We describe five patients with PSN, high titers of anti-Hu antibodies (type 1 antineuronal nuclear autoantibodies), and an indolent clinical course. The patients had a median age of 55 years (range, 41 to 72). Four had small-cell (3) or undifferentiated large-cell (1) lung cancer. Patients presented with mild, asymmetric sensory symptoms; in two, the neuropathy was predominant in the arms. Two patients also had a visceral neuropathy causing gastrointestinal dysfunction. The PSN was stable or progressed very slowly without treatment for a median of 18 months (range, 5 to 32) and remained so after treatment with immunoglobulins (1 patient), chemotherapy (3), or both therapies (1). All patients were ambulatory, leading an independent life up until the time of the last visit or until death from the tumor (2 patients). The median follow-up was 36 months (range, 22 to 52). A paraneoplastic origin should be considered in patients with mild, very slowly progressive sensory neuropathies.

  1. Synthesis of indole analogs as potent β-glucuronidase inhibitors.

    PubMed

    Baharudin, Mohd Syukri; Taha, Muhammad; Imran, Syahrul; Ismail, Nor Hadiani; Rahim, Fazal; Javid, Muhammad Tariq; Khan, Khalid Mohammed; Ali, Muhammad

    2017-06-01

    Natural products are the main source of motivation to design and synthesize new molecules for drug development. Designing new molecules against β-glucuronidase inhibitory is utmost essential. In this study indole analogs (1-35) were synthesized, characterized using various spectroscopic techniques including (1)H NMR and EI-MS and evaluated for their β-glucuronidase inhibitory activity. Most compounds were identified as potent inhibitors for the enzyme with IC50 values ranging between 0.50 and 53.40μM, with reference to standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Structure-activity relationship had been also established. The results obtained from docking studies for the most active compound 10 showed that hydrogen bond donor features as well as hydrogen bonding with (Oε1) of nucleophilic residue Glu540 is believed to be the most importance interaction in the inhibition activity. It was also observed that hydroxyl at fourth position of benzylidene ring acts as a hydrogen bond donor and interacts with hydroxyl (OH) on the side chain of catalysis residue Tyr508. The enzyme-ligand complexed were being stabilized through electrostatic π-anion interaction with acid-base catalyst Glu451 (3.96Å) and thus preventing Glu451 from functioning as proton donor residue. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Saddle-Shaped Cyclic Indole Tetramers: 3D Electroactive Molecules.

    PubMed

    Ruiz, Constanza; Monge, Ángeles; Gutiérrez-Puebla, Enrique; Alkorta, Ibon; Elguero, José; Navarrete, Juan T López; Ruiz Delgado, M Carmen; Gómez-Lor, Berta

    2016-07-18

    We present a joint theoretical and experimental study of a series of cyclic indole tetramers aimed at understanding the fundamental electronic properties of this 3D platform and evaluating its potential in the construction of new semiconductors. To this end, we combined absorption and Raman spectroscopy, cyclic voltammetry, and spectroelectrochemistry with DFT calculations. Our results suggest that this platform can be easily and reversibly oxidized. Additionally, it has a HOMO that matches very well with the workfunction of gold, therefore charge injection from a gold electrode is expected to occur without significant barriers. Interestingly, the cyclic tetraindoles allow for good electron delocalization in spite of their saddle-shaped structures. The steric constraints introduced by N-substitution significantly inhibits ring inversion of the central cyclooctatetraene unit, whereas it only barely affects the optical and electrochemical properties (a slightly higher oxidation potential and a blueshifted absorption upon alkylation are observed). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Obinutuzumab for relapsed or refractory indolent non-Hodgkin's lymphomas.

    PubMed

    Gabellier, Ludovic; Cartron, Guillaume

    2016-04-01

    The use of anti-CD20 monoclonal antibodies (mAbs), such as rituximab, in CD20-positive B-cell malignancies has dramatically improved the outcome of chronic lymphoid leukemia and non-Hodgkin's lymphomas (NHL). However, the occurrence of relapse and development of rituximab-refractory disease highlight the need to develop novel anti-CD20 mAbs, with improved mechanisms of action. Obinutuzumab is the first humanized type II glycoengineered anti-CD20 mAb. In vitro and in vivo data suggested several differences compared with rituximab, including a low level of complement-dependent cytotoxicity and an increased direct nonapoptotic cell death. Moreover, the glycoengineered Fc-linked nonfucosylated oligosaccharide enhanced the Fc-Fcγ receptor (FcγR) IIIa interaction, resulting in improved antibody-dependent cellular cytotoxicity and phagocytosis. Preclinical models suggested that these differences translate into superior survival in murine lymphoma models. Phase I/II trials in monotherapy in relapsed or refractory B-cell NHL demonstrated that obinutuzumab has an acceptable safety profile, infusion-related reactions being the most common adverse event. In rituximab-refractory indolent NHL, the recent randomized phase III GADOLIN study demonstrated an improved median progression-free survival for patients treated with obinutuzumab plus bendamustine rather than bendamustine alone. Further trials are ongoing to determine the role of obinutuzumab as a first-line agent in the treatment of follicular lymphoma.

  4. Molecular epidemiology of paramyxoviruses in Zambian wild rodents and shrews.

    PubMed

    Sasaki, Michihito; Muleya, Walter; Ishii, Akihiro; Orba, Yasuko; Hang'ombe, Bernard M; Mweene, Aaron S; Moonga, Ladslav; Thomas, Yuka; Kimura, Takashi; Sawa, Hirofumi

    2014-02-01

    Rodents and shrews are known to harbour various viruses. Paramyxoviruses have been isolated from Asian and Australian rodents, but little is known about them in African rodents. Recently, previously unknown paramyxovirus sequences were found in South African rodents. To date, there have been no reports related to the presence and prevalence of paramyxoviruses in shrews. We found a high prevalence of paramyxoviruses in wild rodents and shrews from Zambia. Semi-nested reverse transcription-PCR assays were used to detect paramyxovirus RNA in 21 % (96/462) of specimens analysed. Phylogenetic analysis revealed that these viruses were novel paramyxoviruses and could be classified as morbillivirus- and henipavirus-related viruses, and previously identified rodent paramyxovirus-related viruses. Our findings suggest the circulation of previously unknown paramyxoviruses in African rodents and shrews, and provide new information regarding the geographical distribution and genetic diversity of paramyxoviruses.

  5. Metal-free catalyzed oxidative trimerization of indoles by using TEMPO in air: a biomimetic approach to 2-(1H-indol-3-yl)-2,3'-biindolin-3-ones.

    PubMed

    Qin, Wen-Bing; Chang, Qiong; Bao, Yun-Hong; Wang, Ning; Chen, Zheng-Wang; Liu, Liang-Xian

    2012-11-28

    A simple, convenient and efficient metal-free catalyzed oxidative trimeric reaction of indoles toward a variety of 2-(1H-indol-3-yl)-2,3'-biindolin-3-one derivatives in moderate to excellent yields has been developed. This transformation proceeds via a tandem oxidative homocoupling reaction by using TEMPO in air as an environmentally benign oxidant. This methodology provides an alternative approach for the direct generation of all-carbon quaternary centers at the C3 position of indoles.

  6. Bats and Rodents Shape Mammalian Retroviral Phylogeny.

    PubMed

    Cui, Jie; Tachedjian, Gilda; Wang, Lin-Fa

    2015-11-09

    Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general.

  7. Rodent models of TDP-43: Recent advances

    PubMed Central

    Tsao, William; Jeong, Yun Ha; Lin, Sophie; Ling, Jonathan; Price, Donald L.; Chiang, Po-Min; Wong, Philip C.

    2013-01-01

    Recently, missense mutations in the gene TARDBP encoding TDP-43 have been linked to familial ALS. The discovery of genes encoding these RNA binding proteins, such as TDP-43 and FUS/TLS, raised the notion that altered RNA metabolism is a major factor underlying the pathogenesis of ALS. To begin to unravel how mutations in TDP-43 cause dysfunction and death of motor neurons, investigators have employed both gain- and loss-of-function studies in rodent model systems. Here, we will summarize major findings from the initial sets of TDP-43 transgenic and knockout rodent models, identify their limitations, and point to future directions toward clarification of disease mechanism(s) and testing of therapeutic strategies that ultimately may lead to novel therapy for this devastating disease. PMID:22608070

  8. REVIEW: GENETIC MANIPULATION OF THE RODENT PLACENTA

    PubMed Central

    Renaud, Stephen J.; Rumi, M.A. Karim; Soares, Michael J.

    2011-01-01

    The principal role of the placenta is the maintenance of pregnancy and promotion of fetal growth and viability. The use of transgenic rodents has greatly enhanced our understanding of placental development and function. However, embryonic lethality is often a confounding variable in determining whether a genetic modification adversely affected placental development. In these cases, it is beneficial to specifically manipulate the placental genome. The purpose of this review is to summarize available methodologies for specific genetic modification of the rodent placenta. By restricting genetic alterations to the trophoblast lineage, it is possible to gain a deeper understanding of placental development that perhaps will lead to gene-targeted therapies to rescue irregular placentation in transgenic animals or in women at high-risk for placenta-associated pregnancy complications. PMID:21256588

  9. Learning in the Rodent Motor Cortex.

    PubMed

    Peters, Andrew J; Liu, Haixin; Komiyama, Takaki

    2017-03-31

    The motor cortex is far from a stable conduit for motor commands and instead undergoes significant changes during learning. An understanding of motor cortex plasticity has been advanced greatly using rodents as experimental animals. Two major focuses of this research have been on the connectivity and activity of the motor cortex. The motor cortex exhibits structural changes in response to learning, and substantial evidence has implicated the local formation and maintenance of new synapses as crucial substrates of motor learning. This synaptic reorganization translates into changes in spiking activity, which appear to result in a modification and refinement of the relationship between motor cortical activity and movement. This review presents the progress that has been made using rodents to establish the motor cortex as an adaptive structure that supports motor learning. Expected final online publication date for the Annual Review of Neuroscience Volume 40 is July 8, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  10. Cage allocation designs for rodent carcinogenicity experiments

    PubMed Central

    Herzberg, Agnes M.; Lagakos, Stephen W.

    1991-01-01

    Cage allocation designs for rodent carcinogenicity experiments are discussed and presented with the goal of avoiding dosage group biases related to cage location. Considerations in selecting a cage design are first discussed in general terms. Specific designs are presented for use in experiments involving three, four, and five dose groups and with one, four, and five rodents per cage. Priorities for balancing treatment groups include horizontal position on shelf and shelf of rack, nearest neighbor balance, and male–female balance. It is proposed that these balance criteria be considered together with practical issues, such as the ability to accurately conform to a design and to determine a sensible and efficient design for each experiment. PMID:17539183

  11. Cage allocation designs for rodent carcinogenicity experiments.

    PubMed Central

    Herzberg, A M; Lagakos, S W

    1992-01-01

    Cage allocation designs for rodent carcinogenicity experiments are discussed and presented with the goal of avoiding dosage group biases related to cage location. Considerations in selecting a cage design are first discussed in general terms. Specific designs are presented for use in experiments involving three, four, and five dose groups and with one, four, and five rodents per cage. Priorities for balancing treatment groups include horizontal position on shelf and shelf of rack, nearest neighbor balance, and male-female balance. It is proposed that these balance criteria be considered together with practical issues, such as the ability to accurately conform to a design and to determine a sensible and efficient design for each experiment. PMID:1295494

  12. Rodent reservoirs of future zoonotic diseases.

    PubMed

    Han, Barbara A; Schmidt, John Paul; Bowden, Sarah E; Drake, John M

    2015-06-02

    The increasing frequency of zoonotic disease events underscores a need to develop forecasting tools toward a more preemptive approach to outbreak investigation. We apply machine learning to data describing the traits and zoonotic pathogen diversity of the most speciose group of mammals, the rodents, which also comprise a disproportionate number of zoonotic disease reservoirs. Our models predict reservoir status in this group with over 90% accuracy, identifying species with high probabilities of harboring undiscovered zoonotic pathogens based on trait profiles that may serve as rules of thumb to distinguish reservoirs from nonreservoir species. Key predictors of zoonotic reservoirs include biogeographical properties, such as range size, as well as intrinsic host traits associated with lifetime reproductive output. Predicted hotspots of novel rodent reservoir diversity occur in the Middle East and Central Asia and the Midwestern United States.

  13. Genetic detection of hantaviruses in rodents, Albania.

    PubMed

    Papa, Anna; Rogozi, Elton; Velo, Enkelejda; Papadimitriou, Evangelia; Bino, Silvia

    2016-08-01

    In order to have a first insight into the epidemiology of hantaviruses in Albania, 263 small mammals (248 rodents, 15 insectivores) were captured in 352 locations in 29 districts and tested for hantavirus infection. Dobrava-Belgrade virus (DOBV) was detected in 10 of 148 (6.7%) Apodemus flavicollis rodents. DOBV-positive A. flavicollis were detected in six districts (Diber, Korce, Kolonje, Librazhd, Pogradec, and Vlore). The obtained nucleotide sequences were highly similar to each other and to DOBV sequences from northwestern Greece. Understanding the epidemiology of hantaviruses and identifying the endemic foci enables the public health strategies to minimize the risk of human infection. J. Med. Virol. 88:1309-1313, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Anaplasma phagocytophilum from Rodents and Sheep, China

    PubMed Central

    Zhan, Lin; Jiang, Jia-Fu; Zhang, Xiao-Ai; Liu, Yun-Xi; Wu, Xiao-Ming; Zhang, Wen-Yi; Zhang, Pan-He; Bian, Chang-Ling; Dumler, J. Stephen; Yang, Hong; Zuo, Shu-Qing; Chu, Chen-Yi; Liu, Wei; Richardus, Jan H.; Habbema, J. Dik F.

    2010-01-01

    To characterize the strains of Anaplasma phagocytophilum in wild and domestic animals in China, we isolated the organism from rodents and sheep in northeastern China. We isolated 3 strains (2 from rodents and 1 from sick sheep) through propagation in BALB/c mice and then cell culture in HL60 cells. The 3 isolates were identified by Wright-Giemsa staining, immunofluorescence, and electronic microscopy and were characterized by sequence analyses of the 16S rRNA gene, partial citrate synthase gene, major surface protein 4 gene, and heat shock protein gene. The multiple sequences of the 3 isolates were identical to each other but different from all known strains from other countries. The public health and veterinary relevance of the isolates deserves further investigation. PMID:20409364

  15. MRI of neuronal plasticity in rodent models.

    PubMed

    Pelled, Galit

    2011-01-01

    Modifications in the behavior and architecture of neuronal networks are well documented to occur in association with learning and memory, as well as following injury. These plasticity mechanisms are crucial to ensure adequate processing of stimuli, and they also dictate the degree of recovery following peripheral or central nervous system injury. Nevertheless, the underlying neuronal mechanisms that determine the degree of plasticity of neuronal pathways are not fully understood. Recent developments in animal-dedicated magnetic resonance imaging (MRI) scanners and related hardware afford a high spatial and temporal resolution, making functional MRI and manganese-enhanced MRI emerging tools for studying reorganization of neuronal pathways in rodent models. Many of the observed changes in neuronal functions in rodent's brains following injury discussed here agree with clinical human fMRI findings. This demonstrates that animal model imaging can have a significant clinical impact in the neuronal plasticity and rehabilitation arenas.

  16. Leptospira interrogans in Rodents from Cape Verde.

    PubMed

    Plata-Luis, Josué; Foronda, Pilar; Martín-Alonso, Aaron; Feliu, Carlos; Alves, Joana; Gil, Horacio; Valladares, Basilio

    2016-11-01

    Leptospirosis is an important worldwide zoonotic disease that can infect both animals and humans. In most cases, leptospirosis is a nonspecific self-limiting illness, but some patients can develop a severe form with a high mortality. This study was carried out in Santiago Island, Cape Verde, in 2012-2013. A total of 62 wild rodents (Rattus rattus and Mus domesticus) were analyzed. The lipL32 gene, present only in pathogenic Leptospira spp., was amplified by PCR, and 16 samples were positive (25.8%). In both rodent species, Leptospira interrogans was identified. The results show the presence of pathogenic Leptospira in the three localities analyzed in Santiago. The presence of L. interrogans demonstrates a serious health risk for the population, since this species has been associated with the most severe form of leptospirosis, the Weil's disease in humans, a severe infection with jaundice, renal failure, and hemorrhage.

  17. Bats and Rodents Shape Mammalian Retroviral Phylogeny

    PubMed Central

    Cui, Jie; Tachedjian, Gilda; Wang, Lin-Fa

    2015-01-01

    Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general. PMID:26548564

  18. The rodent malaria lactate dehydrogenase assay provides a high throughput solution for in vivo vaccine studies.

    PubMed

    Otsuki, Hitoshi; Yokouchi, Yuki; Iyoku, Natsumi; Tachibana, Mayumi; Tsuboi, Takafumi; Torii, Motomi

    2015-08-01

    Rodent malaria is a useful model for evaluating the efficacy of malaria vaccine candidates; however, labor-intensive microscopic parasite counting hampers the use of an in vivo parasite challenge in high-throughput screening. The measurement of malaria parasite lactate dehydrogenase (pLDH) activity, which is commonly used in the in vitro growth inhibition assay of Plasmodium falciparum, may be the cheapest and simplest alternative to microscopic parasite counting. However, the pLDH assay has not been applied in the in vivo rodent malaria model. Here, we showed that the pLDH assay is reliable and accurately determines parasitemia in the rodent malaria model. pLDH activity measured using a chromogenic substrate reflects the parasite number in the blood; it allows fast and easy assessment using a conventional microplate reader. To validate this approach, we synthesized recombinant PyMSP1-19 protein (rPyMSP1-19) using a wheat germ cell-free protein synthesis system and immunized mice with rPyMSP1-19. The antisera showed specific reactivity on the surface of the Plasmodium yoelii merozoite and immunized mice were protected against a lethal P. yoelii 17 XL challenge. The pLDH assay quickly and easily demonstrated a significant reduction of the parasite numbers in the immunized mice. Accordingly, the pLDH assay proved to be an efficient alternative to rodent malaria parasite counting, and may therefore accelerate in vivo vaccine candidate screening.

  19. Chemotherapy of Rodent Malaria. Part 1

    DTIC Science & Technology

    1987-10-01

    50,000) 88 3.4 Cytoplasmic polyhedrosis virus in Anopheles stephensi. Cytoplasmic polyhedrosis viruses (CPV) are identified by the production of...microsporidia or viruses , the presence of CPV was detected. Since this virus interferes radically with the transmission of rodent malaria, it was...80 28. SPN strain 83 29. P.y.niqeriensis NIG strain 86 30. P.y.yoelii 17X strain 87 3.4 Cytoplasmic polyhedrosis virus in A.stephensi 89 4

  20. Evidence for Novel Hepaciviruses in Rodents

    PubMed Central

    Drexler, Jan Felix; Corman, Victor Max; Müller, Marcel Alexander; Lukashev, Alexander N.; Gmyl, Anatoly; Coutard, Bruno; Adam, Alexander; Ritz, Daniel; Leijten, Lonneke M.; van Riel, Debby; Kallies, Rene; Klose, Stefan M.; Gloza-Rausch, Florian; Binger, Tabea; Annan, Augustina; Adu-Sarkodie, Yaw; Oppong, Samuel; Bourgarel, Mathieu; Rupp, Daniel; Hoffmann, Bernd; Schlegel, Mathias; Kümmerer, Beate M.; Krüger, Detlev H.; Schmidt-Chanasit, Jonas; Setién, Alvaro Aguilar; Cottontail, Veronika M.; Hemachudha, Thiravat; Wacharapluesadee, Supaporn; Osterrieder, Klaus; Bartenschlager, Ralf; Matthee, Sonja; Beer, Martin; Kuiken, Thijs; Reusken, Chantal; Leroy, Eric M.; Ulrich, Rainer G.; Drosten, Christian

    2013-01-01

    Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species); and sera from 2,939 bats (51 species). Three highly divergent rodent hepacivirus clades were detected in 27 (1.8%) of 1,465 European bank voles (Myodes glareolus) and 10 (1.9%) of 518 South African four-striped mice (Rhabdomys pumilio). Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study. 210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats. The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together. Five full genomes were sequenced, representing all viral lineages. Salient genome features and distance criteria supported classification of all viruses as hepaciviruses. Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively. Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus. Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%). Our data enable new hypotheses regarding HCV evolution and encourage efforts to

  1. Spontaneous Type 2 Diabetic Rodent Models

    PubMed Central

    Wang, Yang-wei; Sun, Guang-dong; Sun, Jing; Liu, Shu-jun; Wang, Ji; Xu, Xiao-hong; Miao, Li-ning

    2013-01-01

    Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes. PMID:23671868

  2. Geometric Morphometrics of Rodent Sperm Head Shape

    PubMed Central

    Varea Sánchez, María; Bastir, Markus; Roldan, Eduardo R. S.

    2013-01-01

    Mammalian spermatozoa, particularly those of rodent species, are extremely complex cells and differ greatly in form and dimensions. Thus, characterization of sperm size and, particularly, sperm shape represents a major challenge. No consensus exists on a method to objectively assess size and shape of spermatozoa. In this study we apply the principles of geometric morphometrics to analyze rodent sperm head morphology and compare them with two traditional morphometry methods, that is, measurements of linear dimensions and dimensions-derived parameters calculated using formulae employed in sperm morphometry assessments. Our results show that geometric morphometrics clearly identifies shape differences among rodent spermatozoa. It is also capable of discriminating between size and shape and to analyze these two variables separately. Thus, it provides an accurate method to assess sperm head shape. Furthermore, it can identify which sperm morphology traits differ between species, such as the protrusion or retraction of the base of the head, the orientation and relative position of the site of flagellum insertion, the degree of curvature of the hook, and other distinct anatomical features and appendices. We envisage that the use of geometric morphometrics may have a major impact on future studies focused on the characterization of sperm head formation, diversity of sperm head shape among species (and underlying evolutionary forces), the effects of reprotoxicants on changes in cell shape, and phenotyping of genetically-modified individuals. PMID:24312234

  3. Rodent models for compulsive alcohol intake

    PubMed Central

    Hopf, F. Woodward; Lesscher, Heidi M.B.

    2014-01-01

    Continued seeking and drinking of alcohol despite adverse legal, health, economic, and societal consequences is a central hallmark of human alcohol use disorders. This compulsive drive for alcohol, defined by resistance to adverse and deleterious consequences, represents a major challenge when attempting to treat alcoholism clinically. Thus, there has long been interest in developing pre-clinical rodent models for the compulsive drug use that characterizes drug addiction. Here, we review recent studies that have attempted to model compulsive aspects of alcohol and cocaine intake in rodents, and consider technical and conceptual issues that need to be addressed when trying to recapitulate compulsive aspects of human addiction. Aversion-resistant alcohol intake has been examined by pairing intake or seeking with the bitter tastant quinine or with footshock, and exciting recent work has used these models to identify neuroadaptations in the amygdala, cortex, and striatal regions that promote compulsive intake. Thus, rodent models do seem to reflect important aspects of compulsive drives that sustain human addiction, and will likely provide critical insights into the molecular and circuit underpinnings of aversion-resistant intake as well as novel therapeutic interventions for compulsive aspects of addiction. PMID:24731992

  4. Synthesis and Fluorescence Properties of Novel indol-3yl-thiazolo[3,2-a][1,3,5]triazines and indole-3-carbaldehyde Schiff Bases.

    PubMed

    Sravanthi, T V; Manju, S L

    2015-11-01

    Novel photoactive 4-(4-chlorophenyl)-2-(1H-indol-3-yl)-6-substituted phenyl-2H-thiazolo[3,2-a][1,3,5]triazines were synthesized by the conjugate addition of ammonia to the indole-3-carbaldehyde Schiff bases followed by the condensation with 4-chlorobenzaldehyde. All the synthesized compounds were characterized by FT-IR, NMR, mass spectra and elemental analyses. Their antioxidant property, electrochemical and photophysical properties in different organic solvents were investigated. Comparative discussion on the photophysical properties of indole-3-carbaldehyde Schiff bases and 4-(4-chlorophenyl)-2-(1H-indol-3-yl)-6-substituted phenyl-2H-thiazolo[3,2-a][1,3,5]triazines has been described. The fluorescence quantum yield of Schiff bases (Φf = 0.66-0.70 in DMSO) found to be interestingly higher. High fluorescence quantum yield, large molar extinction coefficient, high stokes shift and smaller optical band gap positioning these new derivatives as an efficient metal free organic fluorescent and semiconductor material. Graphical Abstract ᅟ.

  5. Effects of Gibberellic Acid on Endogenous Indole-3-Acetic Acid and Indoleacetyl Aspartic Acid Levels in a Dwarf Pea 1

    PubMed Central

    Law, David M.; Hamilton, Robert H.

    1984-01-01

    Two-week-old dwarf peas (Pisum sativum cv Little Marvel) were sprayed with gibberellic acid (GA3), and after 3 or 4 days the upper stem and young leaf samples were analyzed for indole-3-acetic acid (IAA) and indole-3-acetyl aspartic acid by an isotope dilution high performance liquid chromatography method. GA3 increased IAA levels as much as 8-fold and decreased indole-3-acetyl aspartic acid levels. PMID:16663587

  6. Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity.

    PubMed

    Frost, Jennifer M; Dart, Michael J; Tietje, Karin R; Garrison, Tiffany R; Grayson, George K; Daza, Anthony V; El-Kouhen, Odile F; Yao, Betty B; Hsieh, Gin C; Pai, Madhavi; Zhu, Chang Z; Chandran, Prasant; Meyer, Michael D

    2010-01-14

    Several 3-acylindoles with high affinity for the CB(2) cannabinoid receptor and selectivity over the CB(1) receptor have been prepared. A variety of 3-acyl substituents were investigated, and the tetramethylcyclopropyl group was found to lead to high affinity CB(2) agonists (5, 16). Substitution at the N1-indole position was then examined. A series of aminoalkylindoles was prepared and several substituted aminoethyl derivatives were active (23-27, 5) at the CB(2) receptor. A study of N1 nonaromatic side chain variants provided potent agonists at the CB(2) receptor (16, 35-41, 44-47, 49-54, and 57-58). Several polar side chains (alcohols, oxazolidinone) were well-tolerated for CB(2) receptor activity (41, 50), while others (amide, acid) led to weaker or inactive compounds (55 and 56). N1 aromatic side chains also afforded several high affinity CB(2) receptor agonists (61, 63, 65, and 69) but were generally less potent in an in vitro CB(2) functional assay than were nonaromatic side chain analogues.

  7. The diazo route to diazonamide A. Studies on the indole bis-oxazole fragment.

    PubMed

    Davies, James R; Kane, Peter D; Moody, Christopher J

    2005-09-02

    [structure: see text] Various approaches to the indole bis-oxazole fragment of the marine secondary metabolite diazonamide A are described, all of which feature dirhodium(II)-catalyzed reactions of diazocarbonyl compounds in key steps. Thus, 3-bromophenylacetaldehyde is converted into an alpha-diazo-beta-ketoester, dirhodium(II)-catalyzed reaction of which with N-Boc-valinamide resulted in N-H insertion of the intermediate rhodium carbene to give a ketoamide that readily underwent cyclodehydration to give (S)-2-(1-tert-butoxycarbonylamino)-2-methylpropyl]-5-(3-bromobenzyl)oxazole-4-carboxamide, after ammonolysis of the initially formed ester. This aryl bromide was then coupled to a 3-formyl-indole-4-boronate under Pd catalysis to give the expected biaryl. Subsequent conversion of the aldehyde group into a second alpha-diazo-beta-ketoester gave a substrate for an intramolecular carbene N-H insertion, although attempts to effect this cyclization were unsuccessful. A second approach to an indole bis-oxazole involved an intermolecular rhodium carbene N-H insertion, followed by oxazole formation to give (S)-2-[1-tert-(butoxycarbonylamino)-2-methylpropyl]-5-methyloxazole-4-carboxamide. A further N-H insertion of this carboxmide with the rhodium carbene derived from ethyl 2-diazo-3-[1-(2-nitrobenzenesulfonyl)indol-3-yl]-3-oxopropanoate gave a ketoamide, cyclodehydration of which gave the desired indole bis-oxazole. Finally, the boronate formed from 4-bromotryptamine was coupled to another diazocarbonyl-derived oxazole to give the corresponding biaryl, deprotection and cyclization of which produced a macrocyclic indole-oxazole derivative. Subsequent oxidation and cyclodehydration incorporated the second oxazole and gave the macrocyclic indole bis-oxazole.

  8. Naturally occurring marine brominated indoles are aryl hydrocarbon receptor ligands/agonists.

    PubMed

    DeGroot, Danica E; Franks, Diana G; Higa, Tatsuo; Tanaka, Junichi; Hahn, Mark E; Denison, Michael S

    2015-06-15

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the toxic and biological effects of structurally diverse chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of a larger effort to identify the full spectrum of chemicals that can bind to and activate the AhR, we have examined the ability of several naturally occurring marine-derived brominated indoles and brominated (methylthio)indoles (collectively referred to as brominated indoles) to bind to the AhR and stimulate AhR-dependent gene expression. Incubation of mouse, rat, and guinea pig recombinant cell lines containing a stably transfected AhR-responsive luciferase reporter gene with eight brominated indoles revealed that all compounds stimulated luciferase reporter gene activity, although some species-specific differences were observed. All compounds induced significantly more luciferase activity when incubated with cells for 4 h as compared to 24 h, demonstrating that these compounds are transient activators of the AhR signaling pathway. Three of the brominated indoles induced CYP1A1 mRNA in human HepG2 cells in vitro and Cyp1a mRNA in zebrafish embryos in vivo. The identification of the brominated indoles as direct ligands and activators/agonists of the AhR was confirmed by their ability to compete with [(3)H]TCDD for binding to the AhR and to stimulate AhR transformation and DNA binding in vitro. Taken together, these results indicate that marine-derived brominated indoles are members of a new class of naturally occurring AhR agonists.

  9. Isolation and characterization of esters of indole-3-acetic acid from the liquid endosperm of the horse chestnut (Aesculus species)

    NASA Technical Reports Server (NTRS)

    Domagalski, W.; Schulze, A.; Bandurski, R. S.

    1987-01-01

    Esters of indole-3-acetic acid were extracted and purified from the liquid endosperm of immature fruits of various species of the horse chestnut (Aesculus parviflora, A. baumanni, A. pavia rubra, and A. pavia humulis). The liquid endosperm contained, at least 12 chromatographically distinct esters. One of these compounds was purified and characterized as an ester of indole-3-acetic acid and myo-inositol. A second compound was found to be an ester of indole-3-acetic acid and the disaccharide rutinose (glucosyl-rhamnose). A third compound was partially characterized as an ester of indole-3-acetic acid and a desoxyaminohexose.

  10. A new methodology for functionalization at the 3-position of indoles by a combination of boron Lewis acid with nitriles.

    PubMed

    Mizoi, Kenta; Mashima, Yu; Kawashima, Yuya; Takahashi, Masato; Mimori, Seisuke; Hosokawa, Masakiyo; Murakami, Yasuoki; Hamana, Hiroshi

    2015-01-01

    We discovered that a reagent comprising a combination of PhBCl2 and nitriles was useful for syntheses of both 3-acylindoles and 1-(1H-indol-3-yl)alkylamine from indoles. The reaction proceeded selectively at the 3-position of indoles providing 3-acylindoles in moderate to high yields on treatment with the above reagent. Furthermore, the reaction provided the corresponding amine products in moderate to high yields after the intermediate imine was reduced by NaBH3CN. These reactions proceeded under mild conditions and are applicable to the formation of indoles functionalized at the 3-position.

  11. Isolation and characterization of esters of indole-3-acetic acid from the liquid endosperm of the horse chestnut (Aesculus species)

    NASA Technical Reports Server (NTRS)

    Domagalski, W.; Schulze, A.; Bandurski, R. S.

    1987-01-01

    Esters of indole-3-acetic acid were extracted and purified from the liquid endosperm of immature fruits of various species of the horse chestnut (Aesculus parviflora, A. baumanni, A. pavia rubra, and A. pavia humulis). The liquid endosperm contained, at least 12 chromatographically distinct esters. One of these compounds was purified and characterized as an ester of indole-3-acetic acid and myo-inositol. A second compound was found to be an ester of indole-3-acetic acid and the disaccharide rutinose (glucosyl-rhamnose). A third compound was partially characterized as an ester of indole-3-acetic acid and a desoxyaminohexose.

  12. Indole-Induced Reversion of Intrinsic Multiantibiotic Resistance in Lysobacter enzymogenes.

    PubMed

    Han, Yong; Wang, Yan; Yu, Yameng; Chen, Haotong; Shen, Yuemao; Du, Liangcheng

    2017-09-01

    Lysobacter species are a group of environmental bacteria that are emerging as a new source of antibiotics. One characteristic of Lysobacter is intrinsic resistance to multiple antibiotics, which had not been studied. To understand the resistance mechanism, we tested the effect of blocking two-component regulatory systems (TCSs) on the antibiotic resistance of Lysobacter enzymogenes, a prolific producer of antibiotics. Upon treatment with LED209, an inhibitor of the widespread TCS QseC/QseB, L. enzymogenes produced a large amount of an unknown metabolite that was barely detectable in the untreated culture. Subsequent structural elucidation by nuclear magnetic resonance (NMR) unexpectedly revealed that the metabolite was indole. Indole production was also markedly induced by adrenaline, a known modulator of QseC/QseB. Next, we identified two TCS genes, L. enzymogenesqseC (Le-qseC) and Le-qseB, in L. enzymogenes and found that mutations of Le-qseC and Le-qseB also led to a dramatic increase in indole production. We then chemically synthesized a fluorescent indole probe that could label the cells. While the Le-qseB (cytoplasmic response regulator) mutant was clearly labeled by the probe, the Le-qseC (membrane sensor) mutant was not labeled. It was reported previously that indole can enhance antibiotic resistance in bacteria. Therefore, we tested if the dramatic increase in the level of indole production in L. enzymogenes upon blocking of Le-qseC and Le-qseB would lead to enhanced antibiotic resistance. Surprisingly, we found that indole caused the intrinsically multiantibiotic-resistant bacterium L. enzymogenes to become susceptible. Point mutations at conserved amino acids in Le-QseC also led to antibiotic susceptibility. Because indole is known as an interspecies signal, these findings may have implications.IMPORTANCE The environmental bacterium Lysobacter is a new source of antibiotic compounds and exhibits intrinsic antibiotic resistance. Here, we found that the

  13. Proton-transfer mediated quenching of pyrene/indole charge-transfer states in isooctane solutions.

    PubMed

    Altamirano, Marcela S; Bohorquez, María del Valle; Previtali, Carlos M; Chesta, Carlos A

    2008-01-31

    The fluorescence quenching of pyrene (Py) by a series of N-methyl and N-H substituted indoles was studied in isooctane at 298 K. The fluorescence quenching rate constants were evaluated by mean of steady-state and time-resolved measurements. In all cases, the quenching process involves a charge-transfer (CT) mechanism. The I(o)/I and tau(o)/tau Stern-Volmer plots obtained for the N-H indoles show a very unusual upward deviation with increasing concentration of the quenchers. This behavior is attributed to the self-quenching of the CT intermediates by the free indoles in solution. The efficiency of quenching of the polyaromatic by the N-H indoles increases abruptly in the presence of small amount of added pyridine (or propanol). A detailed analysis of the experimental data obtained in the presence of pyridine provides unambiguous evidence that the self-quenching process involves proton transfer from the CT states to indoles.

  14. Enhanced Photoreduction of Nitro-aromatic Compounds by Hydrated Electrons Derived from Indole on Natural Montmorillonite.

    PubMed

    Tian, Haoting; Guo, Yong; Pan, Bo; Gu, Cheng; Li, Hui; Boyd, Stephen A

    2015-07-07

    A new photoreduction pathway for nitro-aromatic compounds (NACs) and the underlying degradation mechanism are described. 1,3-Dinitrobenzene was reduced to 3-nitroaniline by the widely distributed aromatic molecule indole; the reaction is facilitated by montmorillonite clay mineral under both simulated and natural sunlight irradiation. The novel chemical reaction is strongly affected by the type of exchangeable cation present on montmorillonite. The photoreduction reaction is initiated by the adsorption of 1,3-dinitrobenzene and indole in clay interlayers. Under light irradiation, the excited indole molecule generates a hydrated electron and the indole radical cation. The structural negative charge of montmorillonite plausibly stabilizes the radical cation hence preventing charge recombination. This promotes the release of reactive hydrated electrons for further reductive reactions. Similar results were observed for the photoreduction of nitrobenzene. In situ irradiation time-resolved electron paramagnetic resonance and Fourier transform infrared spectroscopies provided direct evidence for the generation of hydrated electrons and the indole radical cations, which supported the proposed degradation mechanism. In the photoreduction process, the role of clay mineral is to both enhance the generation of hydrated electrons and to provide a constrained reaction environment in the galley regions, which increases the probability of contact between NACs and hydrated electrons.

  15. Synthesis of 4-aminophenyl substituted indole derivatives for the instrumental analysis and molecular docking evaluation studies

    NASA Astrophysics Data System (ADS)

    Singh, Navneet; Kumar, Keshav

    2017-07-01

    The Indole has been known to maintain celebrity status since so many decades and has been a centre point at the spectrum of pharmacological research. The present work stimulates an idea of generating a pool of library of lead compounds. The data collected can be used for the mapping of biologically active compounds. The reported derivatives of 4-aminophenyl substituted Indole were prepared by the methods of Fischer Indole synthesis and Vilsemeier reaction followed by screening for instrumental analysis and molecular docking studies. The synthesized compounds 4-(1-(2-phenylhydrazono)ethyl)aniline, 1, 4-(1H-indol-2-yl)aniline, 2 and 2-(4-aminophenyl)-1H-indole-3-carbaldehyde, 3 were found to have remarkable yield and instrumental data analysis and also showed remarkable docked characteristic. The molecular docking studies revealed that ligand (amino acids) of comp. 1, 2 and 3 had been docked successfully on the binding site of the 3JUS protein selected from PDB with H bonding. The molecular docking data showed that compound 1, would possess remarkable biological activity and compd. 2 and 3 would possess mild to moderate biological activity. Thus this research work paves the way to synthesize new derivatives and thus to develop new compounds in future with accurate prediction.

  16. Novel Biologically Potent Diorganosilicon(IV) Complexes of Indole-2,3-Dione Derivatives

    PubMed Central

    Nagpal, Pooja

    2005-01-01

    The aim of the present study is to synthesize some novel ecofriendly fungicides and bactericides of indole-2,3-dione derivatives, having important pharmacodynamic significance. The ligands used in the present account are derived by the condensation of 1,3-dihydro-3-[2-(phenyl)-2-oxoethylidene]-2H-indol-2- one, 1,3-dihydro-3-[2-(4-nitrophenyl)-2-oxoethylidene]-2H-indol-2-one and 1,3-dihydro-3-[2-(4-nitro-3-methylphenyl)- 2-oxoethylidene]-2H-indol-2-one with hydrazinecarboxamide and hydrazinecarbothioamide. These imines, on interaction with diorganosilicon(IV) chlorides, yield complexes having Si–O or Si–S and Si←N bonds. The structure of these compounds have been elucidated by elemental microanalyses and spectral [(UV), (IR), 1H, 13C and 29Si NMR)] studies which unerringly point to a trigonal bipyramidal and octahedral geometries for unimolar and bimolar reactions, respectively. The potency of the synthesized compounds have been assessed by growth inhibiting potential of the complexes against variety of fungal and bacterial strains and male albino rats. The results of these biological studies have been compared with the standard fungicide, Bavistin. The studies demonstrate that, 1,3-dihydro-3-[2-(4-nitrophenyl)-2-oxoethylidene]-2H-indol-2-onehydrazincarbothioamide and its diphenylsilicon(IV) complexes have comparable antimicrobial activity and are less toxic to male albino rats than Bavistin. PMID:18365103

  17. Indole affects the formation of multicellular aggregate structures in Pantoea agglomerans YS19.

    PubMed

    Yu, Xuemei; Jiang, Jing; Liang, Chen; Zhang, Xiao; Wang, Jieru; Shen, Delong; Feng, Yongjun

    2016-01-01

    Pantoea agglomerans YS19 is an endophytic diazotrophic bacterium isolated from rice. As well as having the ability to form a biofilm, as do most bacteria, it is characterized by the formation of a unique multicellular aggregate structure called symplasmata. Indole is traditionally known as a metabolite of the amino acid tryptophan, which, however, has recently been shown to participate in various regulations of bacterial physiological processes, including stress resistance, quorum sensing and biofilm formation. Here, an indole signal was found to promote symplasmata formation, yet inhibit biofilm formation, indicating different regulatory pathways of indole in the construction of the two structures. However, symplasmata showed almost an equivalent stress-resistant capability, as compared with biofilms, for YS19 to confront acids, heavy metals (Cu(2+)), and UV treatments. Moreover, indole was tested to show a promoting effect on exopolysaccharides (EPS) production and an inhibition effect on the expression of an outer membrane protein OmpW. These results provide evidence for understanding the regulatory mechanisms of indole on such multicellular aggregates.

  18. Management of Indolent Lymphoma: Where Are We Now and Where Are We Going

    PubMed Central

    Lunning, Matthew; Vose, Julie M.

    2013-01-01

    Summary Indolent lymphoma comprises a unique and challenging subset of non-Hodgkin lymphoma (NHL). While definitions of indolence will vary, the most common indolent NHL subtypes include follicular lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma. Patients with indolent NHL (iNHL) excluding those with rare localized presentations are often met with an incurable but highly treatable NHL. In the rituximab era, response rates are approaching 90% with rituximab plus chemotherapy and time to next treatment are beginning to be measured in years. As a result of a prolonged natural history, we are encountering a gridlock of novel regimens and agents that appropriately fill peer-reviewed journals. In this review, we tackle a spectrum of topics in the management of indolent lymphoma including the initial approach to the newly diagnosed patient, approaches to first cytotoxic chemotherapy, maintenance and consolidation techniques, as well as highlight promising treatments on the horizon in iNHL. Clinicians continue to face tough choices in the management of iNHL. Through well-thought out clinical trials and peer-reviewed vetting of data we will continue to determine how to best manage the clinical continuum that is iNHL. PMID:23063143

  19. Relationship between structures of substituted indolic compounds and their degradation by marine anaerobic microorganisms.

    PubMed

    Gu, Ji-Dong; Fan, Yanzhen; Shi, Hanchang

    2002-01-01

    Degradation of selected indolic compounds including indole, 1-methylindole, 2-methylindole, and 3-methylindole was assessed under methanogenic and sulfate-reducing conditions using the serum-bottle anaerobic technique and marine sediment from Victoria Harbour, Hong Kong as an inoculum. Our results showed that indole degradation was achieved in 28 days by a methanogenic consortium and 35 days by a sulfate-reducing consortium. During degradation under both conditions, two intermediates were isolated, purified and identified as oxindole and isatin (indole-2,3-dione) suggesting that both methanogenic and sulfate-reducing bacteria use an identical degradation pathway. Degradation processes followed two steps of oxidation accomplished by hydroxylation and then dehydrogenation at 2- and then 3-position sequentially prior to the cleavage of the pyrrole ring between 2- and 3-positions. However, none of 1-methylindole or 2-methylindole was degraded under any conditions. 3-Methylindole (3-methyl-1H-indole, skatole) was transformed under methanogenic conditions and mineralized only under sulfate-reducing conditions. It is clear that methyl substitution on 1- or 2-position inhibits the initial attack by hydroxylation enzymes making them more persistent in the environment and posing longer toxic impact.

  20. White light generation by carbonyl based indole derivatives due to proton transfer: an efficient fluorescence sensor.

    PubMed

    Singla, Nidhi; Bhadram, Venkata Srinu; Narayana, Chandrabhas; Chowdhury, Papia

    2013-04-04

    The motivation of the present work is to understand the optical, chemical, and electrical aspects of the proton transfer mechanism of indole (I) and some carbonyl based indole derivatives: indole-3-carboxaldehyde (I3C) and indole-7-carboxaldehyde (I7C) for both powder form and their liquid solution. Structural information for indole derivatives (isolated molecule and in solution) is obtained with density functional theory (DFT) and time dependent DFT (TD-DFT) methods. Calculated transition energies are used to generate UV-vis, FTIR, Raman, and NMR spectra which are later verified with the experimental spectra. The occurrence of different conformers [cis (N(c)), trans (N(t)), and zwitterion (Z*)] have been interpreted by Mulliken charge, natural bond orbital (NBO) analysis, and polarization versus electric field (P-E loop) studies. (1)H and (13)C NMR and molecular vibrational frequencies of the fundamental modes established the stability of Nc due to the presence of intramolecular hydrogen bonding (IHB) in the ground state (S0). Computed/experimental UV-vis absorption/emission studies reveal the creation of new species: zwitterion (Z*) and anion (A*) in the excited state (S1) due to excited state intramolecular and intermolecular proton transfer (ESI(ra)PT and ESI(er)PT). Increased electrical conductivity (σ(ac)) with temperature and increased ferroelectric polarization at higher field verifies proton conduction in I7C.

  1. Aniline-induced tryptophan production and identification of indole derivatives from three purple bacteria.

    PubMed

    Mujahid, Md; Sasikala, Ch; Ramana, Ch V

    2010-10-01

    Growth on aniline by three purple non-sulfur bacteria (Rhodospirillum rubrum ATCC 11170, Rhodobacter sphaeroides DSM 158, and Rubrivivax benzoatiliticus JA2) as nitrogen, or carbon source could not be demonstrated. However in its presence, production of indole derivatives was observed with all the strains tested. At least 14 chromatographically (HPLC) distinct peaks were observed at the absorption maxima of 275-280 nm from aniline induced cultures. Five major indoles were identified based on HPLC and LC-MS/MS analysis. While tryptophan was the major common metabolite for all the three aniline induced cultures, production of indole-3-acetic acid was observed with Rvi. benzoatilyticus JA2 alone, while indole-3-aldehyde was identified from Rvi. benzoatilyticus JA2 and Rba. sphaeroides DSM 158. Indole-3-ethanol was identified only from Rsp. rubrum ATCC 1170 and anthranilic acid was identified from Rba. sphaeroides DSM 158.

  2. Motility-indole-lysine medium for presumptive identification of enteric pathogens of Enterobacteriaceae.

    PubMed

    Reller, L B; Mirrett, S

    1975-09-01

    Detection of lysine decarboxylase activity is a useful supplement to reactions on triple sugar-iron (TSI) and urea agars in the initial examination of suspected pathogenic isolates from fecal cultures. Owing to the added value of motility and indole production in the differentiation of enteric pathogens, we prepared and evaluated a motility-indole-lysine (MIL) medium. The following 890 organisms were tested: 264 Shigella, 2 Edwardsiella, 182 Salmonella enteritidis, 235 S. typhi, 3 Arizona, 32 Yersinia enterocolitica, and 172 other members of the family Enterobacteriaceae. With few exceptions the MIL medium gave the same results as the standard motility, indole, and lysine decarboxylase (Moeller) test media. All discrepancies were with the indole reaction, which was weak in 2 of 67 strains of Escherichia coli and falsely negative in 6 of 32 strains of Y. enterocolitica. When both TSI agar and lysine-iron agar (LIA) slants are used in the evaluation isolates from fecal cultures, detection of H2S is duplicated. Both LIA and MIL medium detect lysine decarboxylase and deaminase activity equally well. Because of its ability to detect motility and indole production, the MIL medium is more useful than LIA when used with TSI agar. The combination of TSI agar, MIL medium, and urea agar enables reliable initial recognition of enteric pathogens of the Enterobacteriaceae.

  3. Dissimilation of Tryptophan and Related Indolic Compounds by Ruminal Microorganisms In Vitro1

    PubMed Central

    Yokoyama, M. T.; Carlson, J. R.

    1974-01-01

    Intraruminal doses of L-tryptophan cause acute pulmonary edema and emphysema in cattle. The D and L isomers of tryptophan and 22 related indolic compounds were incubated with ruminal microorganisms in vitro. Incubation of L-[U-benzene ring-14C]tryptophan with ruminal microorganisms for 24 h resulted in 39% of the added radioactivity being incorporated into skatole, 7% into indole, and 4% into indoleacetate (IAA). D-Tryptophan was not degraded to any of these metabolites. The major pathway of skatole formation from L-tryptophan appeared to be by the decarboxylation of IAA. Incubation of [2-14C]IAA with ruminal microorganisms for 24 h resulted in 38% incorporation into skatole. L-[5-Hydroxy]tryptophan was degraded to 5-hydroxyskatole and 5-hydroxyindole, whereas 5-hydroxyindoleacetate was degraded to only 5-hydroxyskatole. Incubation of indolepyruvate, indolelactate, and indolealdehyde with ruminal microorganisms resulted in the formation of both skatole and indole. Under similar conditions, indoleacetaldehyde was converted to IAA and tryptophol. The addition of increasing concentrations of glucose (0 to 110 mM) reduced the formation of both skatole and indole from L-tryptophan and resulted in the accumulation of IAA. Antibiotics reduced the degradation of L-tryptophan to skatole and indole, with kanamycin and neomycin particularly effective in reducing the decarboxylation of IAA to skatole. PMID:4545142

  4. Crystal structures of four indole derivatives as possible cannabinoid allosteric antagonists

    PubMed Central

    Kerr, Jamie R.; Trembleau, Laurent; Storey, John M. D.; Wardell, James L.; Harrison, William T. A.

    2015-01-01

    The crystal structures of four indole derivatives with various substituents at the 2-, 3- and 5-positions of the ring system are described, namely, ethyl 3-(5-chloro-2-phenyl-1H-indol-3-yl)-3-phenyl­propano­ate, C25H22ClNO2, (I), 2-bromo-3-(2-nitro-1-phenyl­eth­yl)-1H-indole, C16H13BrN2O2, (II), 5-meth­oxy-3-(2-nitro-1-phenyl­eth­yl)-2-phenyl-1H-indole, C23H20N2O3, (III), and 5-chloro-3-(2-nitro-1-phenyl­eth­yl)-2-phenyl-1H-indole, C22H17ClN2O2, (IV). The dominant inter­molecular inter­action in each case is an N—H⋯O hydrogen bond, which generates either chains or inversion dimers. Weak C—H⋯O, C—H⋯π and π–π inter­actions occur in these structures but there is no consistent pattern amongst them. Two of these compounds act as modest enhancers of CB1 cannabanoid signalling and two are inactive. PMID:26090143

  5. Mechanisms and Therapeutic Implications of Cell Death Induction by Indole Compounds

    PubMed Central

    Ahmad, Aamir; Sakr, Wael A.; Rahman, KM Wahidur

    2011-01-01

    Indole compounds, obtained from cruciferous vegetables, are well-known for their anti-cancer properties. In particular, indole-3-carbinol (I3C) and its dimeric product, 3,3′-diindolylmethane (DIM), have been widely investigated for their effectiveness against a number of human cancers in vitro as well as in vivo. These compounds are effective inducers of apoptosis and the accumulating evidence documenting their ability to modulate multiple cellular signaling pathways is a testimony to their pleiotropic behavior. Here we attempt to update current understanding on the various mechanisms that are responsible for the apoptosis-inducing effects by these compounds. The significance of apoptosis-induction as a desirable attribute of anti-cancer agents such as indole compounds cannot be overstated. However, an equally intriguing property of these compounds is their ability to sensitize cancer cells to standard chemotherapeutic agents. Such chemosensitizing effects of indole compounds can potentially have major clinical implications because these non-toxic compounds can reduce the toxicity and drug-resistance associated with available chemotherapies. Combinational therapy is increasingly being realized to be better than single agent therapy and, through this review article, we aim to provide a rationale behind combination of natural compounds such as indoles with conventional therapeutics. PMID:24212940

  6. Rodents and risk in the Mekong Delta of Vietnam: seroprevalence of selected zoonotic viruses in rodents and humans.

    PubMed

    Van Cuong, Nguyen; Carrique-Mas, Juan; Vo Be, Hien; An, Nguyen Ngoc; Tue, Ngo Tri; Anh, Nguyet Lam; Anh, Pham Hong; Phuc, Nguyen The; Baker, Stephen; Voutilainen, Liina; Jääskeläinen, Anne; Huhtamo, Eili; Utriainen, Mira; Sironen, Tarja; Vaheri, Antti; Henttonen, Heikki; Vapalahti, Olli; Chaval, Yannick; Morand, Serge; Bryant, Juliet E

    2015-01-01

    In the Mekong Delta in southern Vietnam, rats are commonly traded in wet markets and sold live for food consumption. We investigated seroprevalence to selected groups of rodent-borne viruses among human populations with high levels of animal exposure and among co-located rodent populations. The indirect fluorescence antibody test (IFAT) was used to determine seropositivity to representative reference strains of hantaviruses (Dobrava virus [DOBV], Seoul virus [SEOV]), cowpox virus, arenaviruses (lymphocytic choriomeningitis virus [LCMV]), flaviviruses (tick-borne encephalitis virus [TBEV]), and rodent parechoviruses (Ljungan virus), using sera from 245 humans living in Dong Thap Province and 275 rodents representing the five common rodent species sold in wet markets and present in peridomestic and farm settings. Combined seropositivity to DOBV and SEOV among the rodents and humans was 6.9% (19/275) and 3.7% (9/245), respectively; 1.1% (3/275) and 4.5% (11/245) to cowpox virus; 5.4% (15/275) and 47.3% (116/245) for TBEV; and exposure to Ljungan virus was 18.8% (46/245) in humans, but 0% in rodents. Very little seroreactivity was observed to LCMV in either rodents (1/275, 0.4%) or humans (2/245, 0.8%). Molecular screening of rodent liver tissues using consensus primers for flaviviruses did not yield any amplicons, whereas molecular screening of rodent lung tissues for hantavirus yielded one hantavirus sequence (SEOV). In summary, these results indicate low to moderate levels of endemic hantavirus circulation, possible circulation of a flavivirus in rodent reservoirs, and the first available data on human exposures to parechoviruses in Vietnam. Although the current evidence suggests only limited exposure of humans to known rodent-borne diseases, further research is warranted to assess public health implications of the rodent trade.

  7. Leptospira and Rodents in Cambodia: Environmental Determinants of Infection

    PubMed Central

    Ivanova, Svilena; Herbreteau, Vincent; Blasdell, Kim; Chaval, Yannick; Buchy, Philippe; Guillard, Bertrand; Morand, Serge

    2012-01-01

    We investigated infection of rodents and shrews by Leptospira spp. in two localities of Cambodia (Veal Renh, Kaev Seima) and in four types of habitat (forests, non-flooded lands, lowland rain-fed paddy fields, houses) during the wet and the dry seasons. Habitat preference was common, and rodent and shrew species were found only in houses or in rain-fed paddy fields or in forests. Among 649 small mammals trapped belonging to 12 rodent species and 1 shrew species, 71 of 642 animals tested were carriers of Leptospira according to the 16S ribosomal RNA marker used. Rodent infection was higher in low-slope locations, corresponding to rain-fed paddy fields, especially in the rainy season and in Kaev Seima. Rodents (Rattus exulans) and shrews (Suncus murinus) inhabiting households showed significantly low levels of infections, whereas rodents living in and near to forests (shrubby wasteland, orchards) showed high levels of infection. PMID:22665613

  8. Bartonella infection in rodents and their flea ectoparasites: an overview.

    PubMed

    Gutiérrez, Ricardo; Krasnov, Boris; Morick, Danny; Gottlieb, Yuval; Khokhlova, Irina S; Harrus, Shimon

    2015-01-01

    Epidemiological studies worldwide have reported a high prevalence and a great diversity of Bartonella species, both in rodents and their flea parasites. The interaction among Bartonella, wild rodents, and fleas reflects a high degree of adaptation among these organisms. Vertical and horizontal efficient Bartonella transmission pathways within flea communities and from fleas to rodents have been documented in competence studies, suggesting that fleas are key players in the transmission of Bartonella to rodents. Exploration of the ecological traits of rodents and their fleas may shed light on the mechanisms used by bartonellae to become established in these organisms. The present review explores the interrelations within the Bartonella-rodent-flea system. The role of the latter two components is emphasized.

  9. Expectations for transgenic rodent cancer bioassay models.

    PubMed

    Ashby, J

    2001-01-01

    The results of the present study have advanced dramatically the database on transgenic mouse abbreviated carcinogenicity bioassay models. As such, it will provide a secure foundation for future evaluations of these assays and for their eventual validation as models for the prediction of possible human carcinogens. Based upon the results derived from the present study, it is suggested that 5 areas require discussion as a prelude to the further evaluation of existing models and the future evaluation of new models. First, there is the need to agree a standard list of calibration chemicals to be studied and to derive agreement on optimal bioassay group sizes, statistical methods, and exposure periods. Second, general agreement must be reached regarding the classes/types of known rodent carcinogens so that it is acceptable for the new models to find negative, by implication, those rodent carcinogens considered not to pose a carcinogenic hazard to humans. Third, current understanding of mechanisms of carcinogenesis should be integrated into the evaluation of new bioassay models. Fourth, any changes made to the standard rodent carcinogenicity bioassay protocol will require compromises being made, and these should be commonly owned between interested parties in order to reduce the number of regional/agency-specific carcinogenicity testing schemes. Fifth, a mechanism needs to be developed by which assays can be adopted or rejected for use in the routine bioassay of chemicals. In the absence of such initiatives the increasing number of new bioassay models will come to exist along side of the standard 2-species bioassay, and this may potentially lead to confusion regarding the true future role of these assays.

  10. Retinal image quality in the rodent eye.

    PubMed

    Artal, P; Herreros de Tejada, P; Muñoz Tedó, C; Green, D G

    1998-01-01

    Many rodents do not see well. For a target to be resolved by a rat or a mouse, it must subtend a visual angle of a degree or more. It is commonly assumed that this poor spatial resolving capacity is due to neural rather than optical limitations, but the quality of the retinal image has not been well characterized in these animals. We have modified a double-pass apparatus, initially designed for the human eye, so it could be used with rodents to measure the modulation transfer function (MTF) of the eye's optics. That is, the double-pass retinal image of a monochromatic (lambda = 632.8 nm) point source was digitized with a CCD camera. From these double-pass measurements, the single-pass MTF was computed under a variety of conditions of focus and with different pupil sizes. Even with the eye in best focus, the image quality in both rats and mice is exceedingly poor. With a 1-mm pupil, for example, the MTF in the rat had an upper limit of about 2.5 cycles/deg, rather than the 28 cycles/deg one would obtain if the eye were a diffraction-limited system. These images are about 10 times worse than the comparable retinal images in the human eye. Using our measurements of the optics and the published behavioral and electrophysiological contrast sensitivity functions (CSFs) of rats, we have calculated the CSF that the rat would have if it had perfect rather than poor optics. We find, interestingly, that diffraction-limited optics would produce only slight improvement overall. That is, in spite of retinal images which are of very low quality, the upper limit of visual resolution in rodents is neurally determined. Rats and mice seem to have eyes in which the optics and retina/brain are well matched.

  11. Euthanasia using gaseous agents in laboratory rodents.

    PubMed

    Valentim, A M; Guedes, S R; Pereira, A M; Antunes, L M

    2016-08-01

    Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously. Nevertheless, its aversive potential has been criticized in terms of animal welfare. The data available regarding the use of carbon dioxide (CO2), inhaled anaesthetics (such as isoflurane, sevoflurane, halothane and enflurane), as well as carbon monoxide and inert gases are discussed throughout this review. Euthanasia of fetuses and neonates is also addressed. A table listing currently available information to ease access to data regarding euthanasia techniques using gaseous agents in laboratory rodents was compiled. Regarding better animal welfare, there is currently insufficient evidence to advocate banning or replacing CO2 in the euthanasia of rodents; however, there are hints that alternative gases are more humane. The exposure to a volatile anaesthetic gas before loss of consciousness has been proposed by some scientific studies to minimize distress; however, the impact of such a measure is not clear. Areas of inconsistency within the euthanasia literature have been highlighted recently and stem from insufficient knowledge, especially regarding the advantages of the administration of isoflurane or sevoflurane over CO2, or other methods, before loss of consciousness. Alternative methods to minimize distress may include the development of techniques aimed at inducing death in the home cage of animals. Scientific outcomes have to be considered before choosing the most suitable euthanasia method to obtain the best results and accomplish the 3Rs (replacement, reduction and refinement).

  12. Klebsiella oxytoca: opportunistic infections in laboratory rodents.

    PubMed

    Bleich, Andre; Kirsch, Petra; Sahly, Hany; Fahey, Jim; Smoczek, Anna; Hedrich, Hans-Jürgen; Sundberg, John P

    2008-07-01

    Opportunistic pathogens have become increasingly relevant as the causative agents of clinical disease and pathological lesions in laboratory animals. This study was conducted to evaluate the role of Klebsiella oxytoca as an opportunistic pathogen in laboratory rodents. Therefore, K. oxytoca-induced lesions were studied from 2004 to early 2006 in naturally infected rodent colonies maintained at The Jackson Laboratory (TJL), Bar Harbor, USA, the Animal Research Centre (Tierforschungszentrum, TFZ) of the University of Ulm, Germany and the Central Animal Facility (ZTM) of the Hannover Medical School, Germany. K. oxytoca infections were observed in substrains of C3H/HeJ mice, which carry the Tlr4(Lps-d) allele; in LEW.1AR1-iddm rats, the latter being prone to diabetes mellitus; in immunodeficient NMRI-Foxn1(nu) mice; and in mole voles, Ellobius lutescens. The main lesions observed were severe suppurative otitis media, urogenital tract infections and pneumonia. Bacteriological examination revealed K. oxytoca as monocultures in all cases. Clonality analysis performed on strains isolated at the ZTM and TFZ (serotyping, pulse field gel electrophoresis [PFGE], enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction, sequencing of 16S rRNA and rpoB genes) revealed that the majority of bacteria belonged to two clones, one in each facility, expressing the capsule type K55 (ZTM) or K72 (TFZ). Two strains, one isolated at the ZTM and one at the TFZ, showed different PFGE and ERIC pattern than all other isolates and both expressed capsule type K35. In conclusion, K. oxytoca is an opportunistic pathogen capable of inducing pathological lesions in different rodent species.

  13. The chemical synthesis of 1-O-(indol-3′-ylacetyl)-β-d-glucopyranose. The higher activity of the glucoside in comparison with exogenous indol-3-ylacetic acid in plant-section elongation tests

    PubMed Central

    Keglević, D.; Pokorny, M.

    1969-01-01

    1. The synthesis of 1-O-(indol-3′-ylacetyl)-β-d-glucopyranose via the fully benzylated 1-O-(indol-3′-ylacetyl)-d-glucopyranose is described. The configuration of the free ester glucoside was confirmed by complete hydrolysis with β-glucosidase and by the n.m.r. spectrum of the tetra-acetyl derivative. 2. The growth-promoting effect of the glucoside in Avena coleoptile- and pea stem-section tests distinctly exceeds the responses stimulated by equimolar amounts of indol-3-ylacetic acid or equimolar mixtures of indol-3-ylacetic acid and glucose at all concentrations investigated. Time-sequence experiments revealed that the sections stimulated by the glucoside exhibit a markedly greater rate of elongation than those promoted by indol-3-ylacetic acid. 3. 1-O-(Indol-3′-ylacetyl)-β-d-glucopyranose was isolated from intact Avena coleoptiles. 4. According to the results, the conjugation of indol-3-ylacetic acid with glucose could not be considered merely as a detoxication mechanism for indol-3-ylacetic acid in plant tissues. PMID:5343792

  14. Evaluating effects of EPO in rodent behavioral assays related to depression.

    PubMed

    Duman, Catharine H; Newton, Samuel S

    2013-01-01

    The cytokine erythropoietin (EPO) is an important regulator of hematopoesis and has well-known tissue protective properties. Neurotrophic action is implicated as mechanistically important in the treatment of depression, and neurotrophic actions of EPO suggest potential therapeutic utility of an EPO-like mechanism in depressive disorder. Rodent behavioral models that are responsive to clinically used antidepressants as well as to neurotrophic compounds can be used to assess potential antidepressant properties of EPO and EPO-like compounds. Rodent models described here are the forced-swim test (FST), a hyponeophagia test and the novel object recognition test. Each of these models provides different information and relevance to depression and each can be tested with EPO and similar compounds.

  15. Indole derivatives from a marine sponge-derived yeast as DPPH radical scavengers.

    PubMed

    Sugiyama, Yasumasa; Ito, Yuki; Suzuki, Motofumi; Hirota, Akira

    2009-11-01

    Two new indole derivatives (3, 4) and three known compounds (1, 2, 5) were isolated as radical scavengers from the culture filtrate of a marine sponge-derived yeast. Their structures were determined to be tyrosol (1), tryptophol (2), 2-(1H-indol-3-yl)ethyl 2-hydroxypropanoate (3), 2-(1H-indol-3-yl)ethyl 5-hydroxypentanoate (4), and cyclo(L-Pro-L-Tyr) (5) on the basis of their spectroscopic data. The absolute configurations of compounds 3 and 5 were determined by chiral HPLC analysis combined with synthesis and Marfey's method, respectively. Each obtained compound was evaluated for DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, and all compounds exhibited weak activities.

  16. Peculiarity of methoxy group-substituted phenylhydrazones in Fischer indole synthesis.

    PubMed

    Murakami, Yasuoki

    2012-01-01

    We found that the Fischer indole synthesis of ethyl pyruvate 2-methoxyphenylhydrazone (5) with HCl/EtOH gave an abnormal product, ethyl 6-chloroindole-2-carboxylate (7), as the main product, with a smaller amount of ethyl 7-methoxyindole-2-carboxylate (6) as the normal product. This abnormal reaction was the result of a cyclization on the side with the substituent (methoxy group) of a benzene ring on phenylhydrazone, which was not previously observed. In this initial investigation, we focused on 1) the application of the above-mentioned abnormal Fischer indole synthesis, 2) the details of this reaction of phenylhydrazone with other kinds of substituents, 3) the mechanism of the first step of the Fischer indole synthesis, 4) the abnormal reaction in methoxydiphenylhydrazones, and 5) a synthetic device to avoid an abnormal reaction. The results of these studies are summarized herein.

  17. Isolation of Indole-3-Acetyl Amino Acids using Polyvinylpolypyrrolidone Chromatography 1

    PubMed Central

    Percival, Frank W.

    1986-01-01

    Amino acid conjugates of IAA can be chromatographed on polyvinylpolypyrrolidone (PVPP) using either acidic methanol or aqueous buffers as eluents. In the aqueous system, elution of the compounds is pH-dependent, and the pattern obtained suggests that hydrophobic interactions contribute substantially to the chromatographic behavior of IAA peptides on PVPP. Purification of soybean seed extracts by PVPP chromatography produced fractions containing indole-3-acetylaspartate and indole-3-acetylglutamate, based on chromatographic and mass spectral analysis, as well as three other indolic compounds, tentatively identified as N-acyl tryptophan derivatives. PVPP chromatography provides an effective preliminary purification of IAA peptides from plant extracts prior to their separation by other techniques such as high performance liquid chromatography. PMID:16664594

  18. Indolent T-lymphblastic proliferation: report of a case involving the upper aerodigestive tract

    PubMed Central

    Yang, Fang; Liu, Tengfei; Zhao, Haiyan; Hu, Zhiyan; Xiao, Liwei; Liu, Yanping; Wang, Xiaoyan; Li, Zuguo

    2014-01-01

    T-lymphoblastic lymphoma (T-LBP) is a high-grade malignant lymphoma, which possesses the characteristic of high metastasis and high mortality without treatment. We are presenting a special T-lymphoblastic proliferation involving in the oropharynx, nasopharynx, sinus and trachea in a patient with local involved about 15-years without systemic dissemination. The immunophenotype of this case was similar to T-LBP. The proliferous cells were positive for terminal deoxynucleotidyl transferase (TdT), CD3, and appeared co-expression CD4 and CD8. No clonal rearrangements of TCRγ and/or TCRβ gene were detected. Indolent T-lymphoblastic proliferations rarely occurred or unusually could not be diagnosed, combing with the relevant literature and clinically indolent manifestation, we interpreted this case as indolent T-lymphoblastic proliferation (iT-LBPs). So far, the mechanism of the T-lymphoblastic proliferations is still uncertain and requires further study. PMID:25337290

  19. Experimental and computational study on the molecular energetics of indoline and indole.

    PubMed

    da Silva, Manuel A V Ribeiro; Cabral, Joana I T A; Gomes, José R B

    2008-11-27

    Static bomb calorimetry, Calvet microcalorimetry and the Knudsen effusion technique were used to determine the standard molar enthalpy of formation in the gas phase, at T = 298.15 K, of the indole and indoline heterocyclic compounds. The values obtained were 164.3 +/- 1.3 kJ x mol(-1) and 120.0 +/- 2.9 kJ x mol(-1), respectively. Several different computational approaches and different working reactions were used to estimate the gas-phase enthalpies of formation for indole and indoline. The computational approaches support the experimental results reported. The calculations were further extended to the determination of other properties such as bond dissociation enthalpies, gas-phase acidities, proton and electron affinities and ionization energies. The agreement between theoretical and experimental data for indole is very good supporting the data calculated for indoline.

  20. Weak inter­actions in the crystal structures of two indole derivatives

    PubMed Central

    Kerr, Jamie R.; Trembleau, Laurent; Storey, John M. D.; Wardell, James L.; Harrison, William T. A.

    2016-01-01

    We describe the syntheses and crystal structures of two indole derivatives, namely a second monoclinic polymorph of ethyl 5-chloro-1H-indole-2-carboxyl­ate C11H10ClNO2, (I), and ethyl 5-chloro-3-iodo-1H-indole-2-carboxyl­ate, C11H9ClINO2, (II). In their crystal structures, both compounds form inversion dimers linked by pairs of N—H⋯O hydrogen bonds, which generate R 2 2(10) loops. The dimers are linked into double chains in (I) and sheets in (II) by a variety of weak inter­actions, including π–π stacking, C—I⋯π, C—Cl—π inter­actions and I⋯Cl halogen bonds. PMID:27555941

  1. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles

    PubMed Central

    Hubbard, Troy D.; Murray, Iain A.; Bisson, William H.; Lahoti, Tejas S.; Gowda, Krishne; Amin, Shantu G.; Patterson, Andrew D.; Perdew, Gary H.

    2015-01-01

    Ligand activation of the aryl hydrocarbon (AHR) has profound effects upon the immunological status of the gastrointestinal tract, establishing and maintaining signaling networks, which facilitate host-microbe homeostasis at the mucosal interface. However, the identity of the ligand(s) responsible for such AHR-mediated activation within the gut remains to be firmly established. Here, we combine in vitro ligand binding, quantitative gene expression, protein-DNA interaction and ligand structure activity analyses together with in silico modeling of the AHR ligand binding domain to identify indole, a microbial tryptophan metabolite, as a human-AHR selective agonist. Human AHR, acting as a host indole receptor may exhibit a unique bimolecular (2:1) binding stoichiometry not observed with typical AHR ligands. Such bimolecular indole-mediated activation of the human AHR within the gastrointestinal tract may provide a foundation for inter-kingdom signaling between the enteric microflora and the immune system to promote commensalism within the gut. PMID:26235394

  2. Indole Compounds Related to Auxins and Goitrogens of Woad (Isatis tinctoria L.) 1

    PubMed Central

    Elliott, Malcolm C.; Stowe, Bruce B.

    1971-01-01

    Five conspicuous indole derivatives are present in leaves and other tissues of woad (Isatis tinctoria L.). They were identified as tryptophan, isatan B, glucobrassicin, neoglucobrassicin, and glucobrassicin-1-sulfonate. The latter three indole glucosinolates are present at levels of at least 260, 69, and 200 milligrams per kilogram fresh weight and were isolated as crystalline salts. Comparison of physical and chemical properties, particularly NMR spectral analysis, confirms that the 1-methoxyglucobrassicin structure suggested for neoglucobrassicin is correct, whereas further evidence for the even more unusual sulfonation of the ring nitrogen in glucobrassicin-1-sulfonate was obtained. Glucobrassicin-1-sulfonate has an enzymic degradation pattern identical to that of glucobrassicin. As it too releases thiocyanate, it must be added to the list of known plant goitrogens. These studies and the techniques described establish woad as exceptionally suitable higher plant material for metabolic studies of indoles related to goitrogens and auxins. PMID:16657624

  3. Gustatory and homeostatic functions of the rodent parabrachial nucleus.

    PubMed

    de Araujo, Ivan E

    2009-07-01

    Previous studies demonstrate that lesions to the rodent parabrachial nucleus (PBN) disrupt the formation of gustatory-postingestive associations, while preserving gustatory and viscerosensory functions. This suggests that the rodent PBN functions essentially as an integrative circuit, supporting the conditioning of tastants to postingestive factors. In the case of primates, however, anatomical studies have failed to demonstrate gustatory projections from medullary nuclei to PBN. It should therefore be inferred that the primate PBN lacks the associative functions assigned to its rodent counterpart. Moreover, the ability of rodent midbrain dopaminergic systems to respond to the activation of palatable tastants depends on the integrity of the gustatory PBN. However, recent studies demonstrate that caloric palatable compounds do not require taste signaling to produce elevated brain dopamine levels. This raises the possibility that, in rodents, PBN neurons are important for the detection of postingestive effects of nutrients that occur independently of gustatory input. If confirmed, such function would assign non-associative roles to the rodent PBN, approximating its functional organization to its primate counterpart. We are currently testing this possibility by monitoring the behavioral responses to caloric glucose solutions in sweet-blind mice having sustained bilateral lesions to the PBN. Preliminary results indicate that the rodent PBN regulates nutrient intake even when no gustatory inputs are involved. This favors the assignment of non-gustatory, homeostatic functions to the rodent PBN during feeding, a concept that brings an additional perspective on the rodent versus primate functional discrepancy associated with the anatomy of this pontine nucleus.

  4. Naturally-Occurring Marine Brominated Indoles are Aryl Hydrocarbon Receptor Ligands/Agonists

    PubMed Central

    DeGroot, Danica E.; Franks, Diana G.; Higa, Tatsuo; Tanaka, Junichi; Hahn, Mark E.; Denison, Michael S.

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the toxic and biological effects of structurally diverse chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of a larger effort to identify the full spectrum of chemicals that can bind to and activate the AhR, we have examined the ability of several naturally-occurring marine-derived brominated indoles and brominated (methylthio)indoles (collectively referred to as “brominated indoles”) to bind to the AhR and stimulate AhR-dependent gene expression. Incubation of mouse, rat and guinea pig recombinant cell lines containing a stably transfected AhR-responsive luciferase reporter gene with eight brominated indoles revealed that all compounds stimulated luciferase reporter gene activity, although some species-specific differences were observed. All compounds induced significantly more luciferase activity when incubated with cells for 4 h as compared to 24 h, demonstrating that these compounds are transient activators of the AhR signaling pathway. Three of the brominated indoles induced CYP1A1 mRNA in human HepG2 cells in vitro and Cyp1a mRNA in zebrafish embryos in vivo. The identification of the brominated indoles as direct ligands and activators/agonists of the AhR was confirmed by their ability to compete with [3H]TCDD for binding to the AhR and to stimulate AhR transformation and DNA binding in vitro. Taken together, these marine-derived brominated indoles are members of a new class of naturally-occurring AhR agonists. PMID:26001051

  5. Observation of exclusively π-stacked heterodimer of indole and hexafluorobenzene in the gas phase

    NASA Astrophysics Data System (ADS)

    Kumar, Sumit; Das, Aloke

    2013-09-01

    In this study, the structure of the indole . . . hexafluorobenzene dimer has been investigated in the gas phase by using resonant two photon ionzation (R2PI) and IR-UV double resonance spectroscopy combined with quantum chemistry calculations. We have confirmed the presence of exclusively π-stacked structure of the dimer from both experimental and theoretical IR spectra in the N-H stretching region. Observation of a single stable structure of the dimer has also been verified through 3D potential energy surface scan of the π-stacked dimer by varying the parallel displacement of the hexafluorobenzene unit simultaneously along the major and minor axes of the indole moiety. π-stacking interaction is present very often between the tryptophan and phenylalanine residues in proteins. But this interaction has not been observed earlier in the gas phase experiment by studying indole . . . benzene dimer because the N-H group of indole predominately directs towards the N-H . . . π hydrogen bonded T-shaped structure. The chosen molecular systems in this study not only rule out the possibility of the formation of the N-H . . . π bound T-shaped dimer but also enable the determination of the structure by probing the N-H group. The π-stacked indole . . . hexafluorobenzene dimer has a unique structure where the center of the hexafluorobenznene ring is aligned with the center of the shared bond of the indole ring. Our work provides useful insight in designing unnatural proteins having strong π-stacking interaction between the tryptophan and phenylalanine residues.

  6. Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

    PubMed Central

    Mortén, Magnus; Hennum, Martin

    2015-01-01

    Summary In this letter, we report a novel synthesis of ethyl quinoline-3-carboxylates from reactions between a series of indoles and halodiazoacetates. The formation of the quinoline structure is probably the result of a cyclopropanation at the 2- and 3-positions of the indole followed by ring-opening of the cyclopropane and elimination of H–X. PMID:26664614

  7. Indole synthesis from N-allenyl-2-iodoanilines under mild conditions mediated by samarium(II) diiodide.

    PubMed

    Iwasaki, Hiroki; Suzuki, Kenji; Yamane, Mitsunari; Yoshida, Shohei; Kojima, Naoto; Ozeki, Minoru; Yamashita, Masayuki

    2014-09-21

    A novel method for indole skeleton synthesis under mild conditions mediated by samarium(ii) diiodide has been developed. The reaction of N-allenyl-2-iodoaniline derivatives with SmI2 in the presence of HMPA and i-PrOH at 0 °C afforded indole derivatives in high yields.

  8. Metal-free transannulation reaction of indoles with nitrostyrenes: a simple practical synthesis of 3-substituted 2-quinolones†

    PubMed Central

    Aksenov, Alexander V.; Smirnov, Alexander N.; Aksenov, Nicolai A.; Aksenova, Inna V.; Frolova, Liliya V.; Kornienko, Alexander; Magedov, Igor V.; Rubin, Michael

    2016-01-01

    3-Substituted 2-quinolones are obtained via a novel, metal-free transannulation reaction of 2-substituted indoles with 2-nitroalkenes in polyphosphoric acid. The reaction can be used in conjunction with the Fisher indole synthesis offering a practical three-component heteroannulation methodology to produce 2-quinolones from arylhydrazines, 2-nitroalkenes and acetophenone. PMID:23999797

  9. Indole derivatives produced by the fungus Colletotrichum acutatum causing lime anthracnose and postbloom fruit drop of citrus.

    PubMed

    Chung, Kuang Ren; Shilts, Turksen; Ertürk, Umran; Timmer, L W; Ueng, Peter P

    2003-09-12

    Postbloom fruit drop (PFD) of citrus and Key lime anthracnose (KLA) are caused by Colletotrichum acutatum. Both fungal isolates can infect flower petals, induce young fruit abscission and result in severe yield loss on many citrus cultivars. Previous studies revealed that infection of citrus flowers by C. acutatum caused higher levels of indole-3-acetic acid (IAA), which could be synthesized from the host plant and/or the fungal pathogen. The ability for IAA production by C. acutatum isolates was investigated. Similar to many microorganisms, the production of indole compounds in the medium by C. acutatum was dependent solely on the presence of tryptophan (Trp). In total, 14 PFD and KLA fungal isolates were tested, and revealed that they all were capable of utilizing Trp as a precursor to synthesize IAA and other indole derivatives. High-performance liquid chromatography analysis and chromogenic stains after a fluorescence thin-layer chromatography separation unambiguously identified IAA, tryptophol (TOL), indole-acetaldehyde, indole-acetamide (IAM), indole-pyruvic acid, and indole-lactic acid (ILA) from cultures supplemented with Trp. The data suggest that C. acutatum may synthesize IAA using various pathways. Interestingly, increasing Trp concentrations drastically increased the levels of TOL and ILA, but not IAA and IAM. The ability of C. acutatum to produce IAA and related indole compounds may in part contribute to the increased IAA levels in citrus flowers after infection.

  10. Metal-free transannulation reaction of indoles with nitrostyrenes: a simple practical synthesis of 3-substituted 2-quinolones.

    PubMed

    Aksenov, Alexander V; Smirnov, Alexander N; Aksenov, Nicolai A; Aksenova, Inna V; Frolova, Liliya V; Kornienko, Alexander; Magedov, Igor V; Rubin, Michael

    2013-10-18

    3-Substituted 2-quinolones are obtained via a novel, metal-free transannulation reaction of 2-substituted indoles with 2-nitroalkenes in polyphosphoric acid. The reaction can be used in conjunction with the Fisher indole synthesis offering a practical three-component heteroannulation methodology to produce 2-quinolones from arylhydrazines, 2-nitroalkenes and acetophenone.

  11. Quantification of free plus conjugated indoleacetic acid in arabidopsis requires correction for the nonenzymatic conversion of indolic nitriles.

    PubMed Central

    Llić, N; Normanly, J; Cohen, J D

    1996-01-01

    The genetic advantages to the use of Arabidopsis thaliana mutants for the study of auxin metabolism previously have been partially offset by the complexity of indolic metabolism in this plant and by the lack of proper methods. To address some of these problems, we developed isotopic labeling methods to determine amounts and examine the metabolism of indolic compounds in Arabidopsis. Isolation and indentification of endogenous indole-3-acetonitrile (IAN; a possible precursor of the auxin indole-3-acetic acid [IAA]) was carried out under mild conditions, thus proving its natural occurrence. We describe here the synthesis of 13C1-labeled IAN and its utility in the gas chromatography-mass spectrometry quantification of endogenous IAN levels. We also quantified the nonenzymatic conversion of IAN to IAA under conditions used to hydrolyze IAA conjugates. 13C1-Labeled IAN was used to assess the contribution of IAN to measured IAA following hydrolysis of IAA conjugates. We studied the stability and breakdown of the indolic glucosinolate glucobrassicin, which is known to be present in Arabidopsis. This is potentially an important concern when using Arabidopsis for studies of indolic biochemistry, since the levels of indolic auxins and auxin precursors are well below the levels of the indolic glucosinolates. We found that under conditions of extraction and base hydrolysis, formation of IAA from glucobrassicin was negligible. PMID:8754680

  12. Visible-light-induced aerobic dearomative reaction of indole derivatives: access to heterocycle fused or spirocyclo indolones.

    PubMed

    Zhang, Muliang; Duan, Yingqian; Li, Weipeng; Cheng, Yixiang; Zhu, Chengjian

    2016-04-04

    Oxazolo[3,2-a]indolone and spiro[furan-2,2'-indolin]one are synthesized by the visible-light-induced aerobic dearomative reaction of indoles. The common indole tethered alcohol at the N1 or C2 position reacts in a cascade fashion, providing facile access to diverse indolone scaffolds.

  13. Ultrasound assisted, ruthenium-exchanged FAU-Y zeolite catalyzed alkylation of indoles with epoxides under solvent free conditions.

    PubMed

    Khorshidi, Alireza

    2012-05-01

    Ruthenium-exchanged FAU-Y zeolite (RuY) was used as a recyclable catalyst for regioselective ring-opening of epoxides with indoles under irradiation of sonic waves. It was found that a solvent free process, under the above mentioned conditions provides good yields of the desired 3-alkylated indole derivatives. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Reaction of carbon nucleophiles with alkylideneindazolium and alkylideneindolium ions generated from their 3-(1-arylsulfonylalkyl) indazole and indole precursors.

    PubMed

    Marsili, Laura; Palmieri, Alessandro; Petrini, Marino

    2010-02-07

    Lewis acid promoted elimination of p-toluenesulfinc acid from sulfonyl indazoles and sulfonyl indoles generates the corresponding iminium ion that reacts with allyltin reagents, silyl enol ethers, silyl ketene acetals and electron-rich aromatics leading to functionalized indazole and indole derivatives.

  15. Potassium iodide catalyzed simultaneous C3-formylation and N-aminomethylation of indoles with 4-substituted-N,N-dimethylanilines.

    PubMed

    Li, Lan-Tao; Li, Hong-Ying; Xing, Li-Juan; Wen, Li-Juan; Wang, Peng; Wang, Bin

    2012-12-28

    A one-pot dual functionalization of indoles has been developed. The simultaneous C3-formylation and N-aminomethylation of indoles can be achieved using readily available potassium iodide as a catalyst and tert-butyl peroxybenzoate as a co-oxidant.

  16. Control of Domestic Rats & Mice, Training Guide--Rodent Control Series.

    ERIC Educational Resources Information Center

    Bjornson, Bayard F.; And Others

    As one booklet in a series on rodent control, this training guide has been developed to assist administrators, rodent-control operators, and others responsible for rodent-control operations in the training of employees in this field. Topics covered include rodents and human welfare, description and habits of domestic rats and mice, rodent-borne…

  17. Mass Spectrometric Characteristics of Prenylated Indole Derivatives from Marine-Derived Penicillium sp. NH-SL

    PubMed Central

    Ding, Hui; Ding, Wanjing; Ma, Zhongjun

    2017-01-01

    Two prenylated indole alkaloids were isolated from the ethyl acetate extracts of a marine-derived fungus Penicillium sp. NH-SL and one of them exhibited potent cytotoxic activity against mouse hepa 1c1c7 cells. In order to detect other bioactive analogs, we used liquid chromatogram tandem mass spectrometry (LC-MS/MS) to analyze the mass spectrometric characteristics of the isolated compounds as well as the crude extracts. As a result, three other analogs were detected, and their structures were deduced according to the similar fragmentation patterns. This is the first systematic report on the mass spectrometric characteristics of prenylated indole derivatives. PMID:28327529

  18. Substrate-Controlled Transformation of Azobenzenes to Indazoles and Indoles via Rh(III)-Catalysis.

    PubMed

    Cai, Shangjun; Lin, Songyun; Yi, Xiangli; Xi, Chanjuan

    2017-01-06

    Rh(III)-catalyzed substrate-controlled transformation of azobenzenes to indazoles and 2-acyl (NH) indoles is achieved via C-H functionalization. Generally, good functional groups tolerance, satisfying yields, and excellent regio-selectivity are achieved in this reaction. Mechanistically, the reaction with acrylates undergoes β-hydride elimination, while the reaction with vinyl ketones or acrylamides undergoes nucleophilic addition. Copper acetate was supposed to play different roles in the β-hydride elimination to furnish indazoles and nucleophilic addition of C-Rh bond to deliver 2-acyl (NH) indoles.

  19. Intermolecular dearomative C2-arylation of N-Ac indoles activated by FeCl3.

    PubMed

    Nandi, Raj Kumar; Ratsch, Friederike; Beaud, Rodolphe; Guillot, Régis; Kouklovsky, Cyrille; Vincent, Guillaume

    2016-04-18

    We report the FeCl3-mediated direct addition of electron-rich arenes to the C2-position of electrophilic N-Ac indoles under mild conditions (room temperature, air). No functional group is required on the arene nucleophile: one of its C-H bonds is added to the C2[double bond, length as m-dash]C3 double bond of the indole nucleus in a Friedel-Crafts-type reaction. This dearomatisation process delivered a broad range of C2-arylated indolines.

  20. Competition between solvent quenching and indole quenching of 9-fluorenone: a spectroscopic and computational study.

    PubMed

    Schneck, Crystal M; Poncheri, Adam J; Jennings, John T; Snyder, Deanna L; Worlinsky, Jill L; Basu, Swarna

    2010-02-01

    The interaction between 9-fluorenone, various indoles and solvents has been studied using steady-state fluorescence spectroscopy and quantum chemical calculations. It was determined that polar protic solvents such as methanol and ethanol significantly quenched the fluorescence of 9-fluorenone but various indoles reversed the solvent quenching. The effect of various solvents on the 9-fluorenone carbonyl vibration was investigated using infrared spectroscopy. Ab initio calculations using Gaussian03 were also carried out in order to determine the minimum energy conformations of these systems along with binding energies.

  1. Synthesis and pharmacological evaluation of indole-based sigma receptor ligands

    PubMed Central

    Mésangeau, Christophe; Amata, Emanuele; Alsharif, Walid; Seminerio, Michael J.; Robson, Matthew J.; Matsumoto, Rae R.; Poupaert, Jacques H.; McCurdy, Christopher R.

    2011-01-01

    A series of novel indole-based analogues were prepared and their affinities for sigma receptors were determined using in vitro radioligand binding assays. The results of this study identified several compounds with nanomolar sigma-2 affinity and significant selectivity over sigma-1 receptors. In particular, 2-(4-(3-(4-fluorophenyl)indol-1-yl)butyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (9f) was found to display high affinity at sigma-2 receptors with good selectivity (σ-1/σ-2 = 395). The pharmacological binding profile for this compound was established with other relevant nonsigma sites. PMID:21899931

  2. Benzannulation via the Reaction of Ynamides and Vinylketenes. Application to the Synthesis of Highly Substituted Indoles

    PubMed Central

    Lam, Tin Yiu; Wang, Yu-Pu

    2013-01-01

    A two-stage “tandem strategy” for the synthesis of indoles with a high level of substitution on the six-membered ring is described. Benzannulation based on the reaction of cyclobutenones with ynamides proceeds via a cascade of four pericyclic reactions to produce multiply substituted aniline derivatives in which the position ortho to the nitrogen can bear a wide range of functionalized substituents. In the second stage of the tandem strategy, highly substituted indoles are generated via acid-, base-, and palladium-catalyzed cyclization and annulation processes. PMID:23952525

  3. Mass Spectrometric Characteristics of Prenylated Indole Derivatives from Marine-Derived Penicillium sp. NH-SL.

    PubMed

    Ding, Hui; Ding, Wanjing; Ma, Zhongjun

    2017-03-22

    Two prenylated indole alkaloids were isolated from the ethyl acetate extracts of a marine-derived fungus Penicillium sp. NH-SL and one of them exhibited potent cytotoxic activity against mouse hepa 1c1c7 cells. In order to detect other bioactive analogs, we used liquid chromatogram tandem mass spectrometry (LC-MS/MS) to analyze the mass spectrometric characteristics of the isolated compounds as well as the crude extracts. As a result, three other analogs were detected, and their structures were deduced according to the similar fragmentation patterns. This is the first systematic report on the mass spectrometric characteristics of prenylated indole derivatives.

  4. Strategies for the synthesis of novel indole alkaloid-based screening libraries for drug discovery.

    PubMed

    Fokas, Demosthenes; Yu, Libing; Baldino, Carmen M

    2005-01-01

    A series of diverse indole-based chemotypes were synthesized from beta-tetrahydrocarboline (beta-THC) scaffolds prepared from commercially and readily available tryptamines and alpha-ketoesters. Diversity can be generated within these chemotypes through the following strategies: (a) appendage of substituents to the beta-THC scaffold, prepared in situ or as a template, through further elaboration and (b) skeletal modifications to the beta-THC scaffold via ring forming or ring breaking reactions. The strategies described here are amenable to high throughput solution-phase parallel synthesis, providing access to novel indole-based screening libraries for drug discovery.

  5. Bendamustine HCL for the treatment of relapsed indolent non-Hodgkin’s lymphoma

    PubMed Central

    Weide, Rudolf

    2008-01-01

    Bendamustine is an alkylating agent which also shows properties of a purine analog. Because of its unique mechanism of action it shows activity in relapsed indolent lymphomas which are resistant to alkylating agents, purine analogs, and rituximab. Bendamustine has a favorable toxicity profile causing no alopecia and only a moderate hematotoxicity and gastrointestinal toxicity. Combinations of bendamustine with mitoxantrone and rituximab and with rituximab alone have been shown to be highly active in relapsed/refractory indolent lymphomas and mantle cell lymphomas achieving long lasting complete remissions. Because of only moderate toxicity these combinations can be applied safely in elderly patients who can be treated in an outpatient setting. PMID:19209254

  6. Selective synthesis of indazoles and indoles via triazene-alkyne cyclization switched by different metals.

    PubMed

    Fang, Yan; Wang, Chengming; Su, Shengqin; Yu, Haizhu; Huang, Yong

    2014-02-21

    We described two orthogonal heterocycle syntheses, where an arene bearing both an alkyne and a triazene functionality underwent two distinct cyclization pathways mediated by different transition metals. Starting from the same substrates, a synthesis of 2H-indazole was accomplished by a Cu(II) salt promoted oxidative cyclization, while 2-substituted indoles could be accessed via a Ag(I) salt mediated N-N bond cleavage. This method represents the first synthesis of indoles from alkynyl triazenes. Computational analysis was performed for both reaction pathways, supporting a Lewis acid role for Cu and a π-acid catalysis for Ag.

  7. Synthesis of functionalized indole- and benzo-fused heterocyclic derivatives through anionic benzyne cyclization.

    PubMed

    Barluenga, José; Fañanás, Francisco J; Sanz, Roberto; Fernández, Yolanda

    2002-05-03

    The development of a new method for the regioselective synthesis of functionalized indoles and six-membered benzo-fused N-, O-, and S-heterocycles is reported. The key step involves the generation of a benzyne-tethered vinyl or aryllithium compound that undergoes a subsequent intramolecular anionic cyclization. Reaction of the organolithium intermediates with selected electrophiles allows the preparation of a wide variety of indole, tetrahydrocarbazole, dihydrofenantridine, dibenzopyran, and dibenzothiopyran derivatives. Finally, the application of this strategy to the appropriate starting materials allows the preparation of some tryptamine and serotonin analogues.

  8. Chemistry and biology of indoles and indazoles: a mini-review.

    PubMed

    Ali, Nasir Ali Shafakat; Dar, Bashir Ahmad; Pradhan, Vidya; Farooqui, Mazahar

    2013-10-01

    The present review article is related with the method of preparation, importance and medicinal application of indole and indazoles. The studies of heterocycles is an evergreen field in the branch of organic chemistry and always attract the attention of chemists working not only in the area of natural products but also in the synthetic chemistry. Moreover many useful drugs have emerged from the successful investigation carried out in this branch. The derivatives of indoles and indazoles exhibits antibacterial, anticancer, antionidants, anti-inflammatory, antidiabetic, antiviral, atniproliferative, antituberculosis, antispermetogenic activity, antipsychotic drugs etc.

  9. 4-[Bis(1H-indol-3-yl)meth-yl]benzonitrile.

    PubMed

    Deng, Xiang; Wu, Di; Huang, Xiaomei; Luo, Feihua

    2011-07-01

    In the title mol-ecule, C(24)H(17)N(3), the didhedral angles formed by the mean planes of the indole ring systems and the benzene ring are 86.44 (7) and 86.96 (7)°. The dihedral angle between the two indole ring systems is 72.08 (6)°. In the crystal, inter-molecular bifurcated (N-H)(2)⋯N hydrogen bonds link mol-ecules into sheets lying parallel to (010).

  10. Changes in tau phosphorylation in hibernating rodents.

    PubMed

    León-Espinosa, Gonzalo; García, Esther; García-Escudero, Vega; Hernández, Félix; Defelipe, Javier; Avila, Jesús

    2013-07-01

    Tau is a cytoskeletal protein present mainly in the neurons of vertebrates. By comparing the sequence of tau molecule among different vertebrates, it was found that the variability of the N-terminal sequence in tau protein is higher than that of the C-terminal region. The N-terminal region is involved mainly in the binding of tau to cellular membranes, whereas the C-terminal region of the tau molecule contains the microtubule-binding sites. We have compared the sequence of Syrian hamster tau with the sequences of other hibernating and nonhibernating rodents and investigated how differences in the N-terminal region of tau could affect the phosphorylation level and tau binding to cell membranes. We also describe a change, in tau phosphorylation, on a casein kinase 1 (ck1)-dependent site that is found only in hibernating rodents. This ck1 site seems to play an important role in the regulation of tau binding to membranes. Copyright © 2013 Wiley Periodicals, Inc.

  11. Rodent models of treatment-resistant depression

    PubMed Central

    Caldarone, Barbara J.; Zachariou, Venetia; King, Sarah L

    2015-01-01

    Major depression is a prevalent and debilitating disorder and a substantial proportion of patients fail to reach remission following standard antidepressant pharmacological treatment. Limited efficacy with currently available antidepressant drugs highlights the need to develop more effective medications for treatment resistant patients and emphasizes the importance of developing better preclinical models that focus on treatment resistant populations. This review discusses methods to adapt and refine rodent behavioral models that are predictive of antidepressant efficacy to identify populations that show reduced responsiveness or are resistant to traditional antidepressants. Methods include separating antidepressant responders from non-responders, administering treatments that render animals resistant to traditional pharmacological treatments, and identifying genetic models that show antidepressant resistance. This review also examines pharmacological and non-pharmacological treatments regimes that have been effective in refractory patients and how some of these approaches have been used to validate animal models of treatment-resistant depression. The goals in developing rodent models of treatment-resistant depression are to understand the neurobiological mechanisms involved in antidepressant resistance and to develop valid models to test novel therapies that would be effective in patients that do not respond to traditional monoaminergic antidepressants. PMID:25460020

  12. Syntheses of 2-substituted indoles and fused indoles by photostimulated reactions of o-iodoanilines with carbanions by the SRN1 mechanism.

    PubMed

    Barolo, Silvia M; Lukach, Andrés E; Rossi, Roberto A

    2003-04-04

    2-Substituted indoles (5a,b and 7) and fused indoles (9a-c, 11a,b, and 12) have been obtained by the S(RN)1 mechanism from photostimulated reactions of o-iodoaniline (1) and 1-halo-2-naphthalen-2-ylamines (3a,b) with enolate ions of acyclic (acetophenone (6), 2- (4a) and 4-acetylpyridine (4b)) and cyclic ketones (1- (8a) and 2-indanone (10a), 1- (8b) and 2-tetralone (10b) and 1-benzosuberone (8c)) in DMSO and liquid ammonia as solvents. The carbanions derived from 4a,b, 8a, and 10b are novel nucleophiles that form new C-C bonds by the S(RN)1 mechanism.

  13. Synthesis and antitumoral evaluation of indole alkaloid analogues containing an hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indole skeleton.

    PubMed

    Ventosa-Andrés, Pilar; González-Vera, Juan A; Valdivielso, Angel M; Teresa García-López, M; Herranz, Rosario

    2008-10-15

    The scope of acid-mediated cyclative additions of electrophiles to tryptophan-derived alpha-amino nitriles for the synthesis of 10b-substituted-1,2,4,5,10b,10c-hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indoles analogues of indole alkaloids has been studied. The results demonstrate the high potential of the methodology for the synthesis of 10b-bromo-derivatives, by bromination with NBS, 10b-allyl-derivatives, by bromo-allyl exchange, and 10b-prenyl-derivatives, by reaction with prenyl bromide in the presence of Mg(NO(3))(2).6H(2)0. Some of the new pyrroloimidazoindole derivatives displayed moderate microM cytotoxicities in human cancer cell lines and at 10 microg/mL inhibited more than 50% EGFR or HIF-1alpha.

  14. AMT (3-(2-aminopropyl)indole) and 5-IT (5-(2-aminopropyl)indole): an analytical challenge and implications for forensic analysis.

    PubMed

    Elliott, Simon P; Brandt, Simon D; Freeman, Sally; Archer, Roland P

    2013-03-01

    5-(2-Aminopropyl)indole (5-IT) and 3-(2-aminopropyl)indole (α-methyltryptamine, AMT) are isomeric substances and their differentiation can be a challenge under routine analytical conditions, especially when reference material is unavailable. 5-IT represents a very recent addition to the battery of new psychoactive substances that are commercially available from online retailers. This report illustrates how subtle differences observed under mass spectral and UV conditions can help to facilitate the differentiation between the two isomers. Analyses included (1)  H and (13) C NMR, GC-EI/CI ion trap MS, applications of several U/HPLC-DAD and HPLC-MS methods. Investigations currently underway also highlight the confirmation that AMT was detected in a number of fatal intoxications. These findings also demonstrate that there is a potential risk of misidentification when dealing with both substances.

  15. 5-Meth-oxy-3-[(5-meth-oxy-1H-indol-3-yl)(phen-yl)meth-yl]-1H-indole.

    PubMed

    Narayanan, P; Sethusankar, K; Ramachandiran, K; Perumal, P T

    2011-12-01

    In the title compound, C(25)H(22)N(2)O(2), the indole rings are individually almost planar [with maximum deviations of 0.0116 (19) and 0.0113 (18) Å] and are almost orthogonal to each other, making a dihedral angle of 84.49 (6)°. The benzene ring is inclined at 72.83 (9) and 80.85 (9)° with respect to the indole rings. In the crystal, mol-ecules are linked by N-H⋯O inter-actions into chains running parallel to the c axis. The crystal structure is further stabilized by C-H⋯π inter-actions.

  16. Myo-inositol esters of indole-3-acetic acid are endogenous components of Zea mays L. shoot tissue

    NASA Technical Reports Server (NTRS)

    Chisnell, J. R.

    1984-01-01

    Indole-3-acetyl-myo-inositol esters have been demonstrated to be endogenous components of etiolated Zea mays shoots tissue. This was accomplished by comparison of the putative compounds with authentic, synthetic esters. The properties compared were liquid and gas-liquid chromatographic retention times and the 70-ev mass spectral fragmentation pattern of the pentaacetyl derivative. The amount of indole-3-acetyl-myo-inositol esters in the shoots was determined to be 74 nanomoles per kilogram fresh weight as measured by isotope dilution, accounting for 19% of the ester indole-3-acetic acid of the shoot. This work is the first characterization of an ester conjugate of indole-3-acetate acid from vegetative shoot tissue using multiple chromatographic properties and mass spectral identification. The kernel and the seedling shoot both contain indole-3-acetyl-myo-inositol esters, and these esters comprise approximately the same percentage of the total ester content of the kernel and of the shoot.

  17. Myo-inositol esters of indole-3-acetic acid are endogenous components of Zea mays L. shoot tissue

    NASA Technical Reports Server (NTRS)

    Chisnell, J. R.

    1984-01-01

    Indole-3-acetyl-myo-inositol esters have been demonstrated to be endogenous components of etiolated Zea mays shoots tissue. This was accomplished by comparison of the putative compounds with authentic, synthetic esters. The properties compared were liquid and gas-liquid chromatographic retention times and the 70-ev mass spectral fragmentation pattern of the pentaacetyl derivative. The amount of indole-3-acetyl-myo-inositol esters in the shoots was determined to be 74 nanomoles per kilogram fresh weight as measured by isotope dilution, accounting for 19% of the ester indole-3-acetic acid of the shoot. This work is the first characterization of an ester conjugate of indole-3-acetate acid from vegetative shoot tissue using multiple chromatographic properties and mass spectral identification. The kernel and the seedling shoot both contain indole-3-acetyl-myo-inositol esters, and these esters comprise approximately the same percentage of the total ester content of the kernel and of the shoot.

  18. The utility of Plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment.

    PubMed

    Goodman, Anna L; Forbes, Emily K; Williams, Andrew R; Douglas, Alexander D; de Cassan, Simone C; Bauza, Karolis; Biswas, Sumi; Dicks, Matthew D J; Llewellyn, David; Moore, Anne C; Janse, Chris J; Franke-Fayard, Blandine M; Gilbert, Sarah C; Hill, Adrian V S; Pleass, Richard J; Draper, Simon J

    2013-01-01

    Rodent malaria species Plasmodium yoelii and P. chabaudi have been widely used to validate vaccine approaches targeting blood-stage merozoite antigens. However, increasing data suggest the P. berghei rodent malaria may be able to circumvent vaccine-induced anti-merozoite responses. Here we confirm a failure to protect against P. berghei, despite successful antibody induction against leading merozoite antigens using protein-in-adjuvant or viral vectored vaccine delivery. No subunit vaccine approach showed efficacy in mice following immunization and challenge with the wild-type P. berghei strains ANKA or NK65, or against a chimeric parasite line encoding a merozoite antigen from P. falciparum. Protection was not improved in knockout mice lacking the inhibitory Fc receptor CD32b, nor against a Δsmac P. berghei parasite line with a non-sequestering phenotype. An improved understanding of the mechanisms responsible for protection, or failure of protection, against P. berghei merozoites could guide the development of an efficacious vaccine against P. falciparum.

  19. Hunting, Food Preparation, and Consumption of Rodents in Lao PDR

    PubMed Central

    Suwannarong, Kanokwan; Chapman, Robert S.; Lantican, Cecile; Michaelides, Tula; Zimicki, Susan

    2015-01-01

    A cross-sectional study was conducted in 29 villages of Khamkeuth District in Bolikhamxay Province in the Lao PDR during March to May 2013. The study aimed to determine the characteristics associated with rodent consumption and related behaviors among different ethnic groups, ages, and genders. Five-hundred-eighty-four (584) males and females from 18-50 years of age participated in this study. Half of them were Hmong (292, 50%) while 152 respondents were Lao-Tai (26%) or other ethnic groups (140, 24%). Most of the respondents (79.5%) had farming as their main occupation. Prevalences of the studied outcomes were high: 39.9 for hunting or capturing rodents in the previous year, 77.7% for preparing rodents as food, and 86.3% for rodent consumption. Multivariable logistic regression analysis showed that likelihood of these types of rodent contact was more consistently associated with behavioral factors (gathering things from the forest and elsewhere, cultivation-related activities, and taking measures to prevent rodent-borne disease) than with socio-demographic, environmental, or cultural factors. The strongest associations were observed for gathering things; these associations were consistently positive and statistically significant. Although this study did not directly assess rodent-borne zoonosis risk, we believe that study findings raise concern that such risk may be substantial in the study area and other similar areas. Further epidemiological studies on the association between rodent-borne disease infection and rodent hunting, preparation for food, and consumption are recommended. Moreover, further studies are needed on the association between these potential exposure factors (i.e., rodent hunting, preparation for food, and consumption) and rodent-borne infections, especially among ethnic groups like the Hmong in Lao PDR and those in neighboring countries with similar socio-demographic, environmental, behavioral and cultural contexts. PMID:26196134

  20. Hunting, Food Preparation, and Consumption of Rodents in Lao PDR.

    PubMed

    Suwannarong, Kanokwan; Chapman, Robert S; Lantican, Cecile; Michaelides, Tula; Zimicki, Susan

    2015-01-01

    A cross-sectional study was conducted in 29 villages of Khamkeuth District in Bolikhamxay Province in the Lao PDR during March to May 2013. The study aimed to determine the characteristics associated with rodent consumption and related behaviors among different ethnic groups, ages, and genders. Five-hundred-eighty-four (584) males and females from 18-50 years of age participated in this study. Half of them were Hmong (292, 50%) while 152 respondents were Lao-Tai (26%) or other ethnic groups (140, 24%). Most of the respondents (79.5%) had farming as their main occupation. Prevalences of the studied outcomes were high: 39.9 for hunting or capturing rodents in the previous year, 77.7% for preparing rodents as food, and 86.3% for rodent consumption. Multivariable logistic regression analysis showed that likelihood of these types of rodent contact was more consistently associated with behavioral factors (gathering things from the forest and elsewhere, cultivation-related activities, and taking measures to prevent rodent-borne disease) than with socio-demographic, environmental, or cultural factors. The strongest associations were observed for gathering things; these associations were consistently positive and statistically significant. Although this study did not directly assess rodent-borne zoonosis risk, we believe that study findings raise concern that such risk may be substantial in the study area and other similar areas. Further epidemiological studies on the association between rodent-borne disease infection and rodent hunting, preparation for food, and consumption are recommended. Moreover, further studies are needed on the association between these potential exposure factors (i.e., rodent hunting, preparation for food, and consumption) and rodent-borne infections, especially among ethnic groups like the Hmong in Lao PDR and those in neighboring countries with similar socio-demographic, environmental, behavioral and cultural contexts.

  1. Characterization of a Nitrilase and a Nitrile Hydratase from Pseudomonas sp. Strain UW4 That Converts Indole-3-Acetonitrile to Indole-3-Acetic Acid

    PubMed Central

    Rose, David R.; Glick, Bernard R.

    2014-01-01

    Indole-3-acetic acid (IAA) is a fundamental phytohormone with the ability to control many aspects of plant growth and development. Pseudomonas sp. strain UW4 is a rhizospheric plant growth-promoting bacterium that produces and secretes IAA. While several putative IAA biosynthetic genes have been reported in this bacterium, the pathways leading to the production of IAA in strain UW4 are unclear. Here, the presence of the indole-3-acetamide (IAM) and indole-3-acetaldoxime/indole-3-acetonitrile (IAOx/IAN) pathways of IAA biosynthesis is described, and the specific role of two of the enzymes (nitrilase and nitrile hydratase) that mediate these pathways is assessed. The genes encoding these two enzymes were expressed in Escherichia coli, and the enzymes were isolated and characterized. Substrate-feeding assays indicate that the nitrilase produces both IAM and IAA from the IAN substrate, while the nitrile hydratase only produces IAM. The two nitrile-hydrolyzing enzymes have very different temperature and pH optimums. Nitrilase prefers a temperature of 50°C and a pH of 6, while nitrile hydratase prefers 4°C and a pH of 7.5. Based on multiple sequence alignments and motif analyses, physicochemical properties and enzyme assays, it is concluded that the UW4 nitrilase has an aromatic substrate specificity. The nitrile hydratase is identified as an iron-type metalloenzyme that does not require the help of a P47K activator protein to be active. These data are interpreted in terms of a preliminary model for the biosynthesis of IAA in this bacterium. PMID:24837382

  2. Visual Landmarks Facilitate Rodent Spatial Navigation in Virtual Reality Environments

    ERIC Educational Resources Information Center

    Youngstrom, Isaac A.; Strowbridge, Ben W.

    2012-01-01

    Because many different sensory modalities contribute to spatial learning in rodents, it has been difficult to determine whether spatial navigation can be guided solely by visual cues. Rodents moving within physical environments with visual cues engage a variety of nonvisual sensory systems that cannot be easily inhibited without lesioning brain…

  3. Lurking in the Shadows: Emerging Rodent Infectious Diseases

    PubMed Central

    Besselsen, David G.; Franklin, Craig L.; Livingston, Robert S.; Riley, Lela K.

    2013-01-01

    Rodent parvoviruses, Helicobacter spp., murine norovirus, and several other previously unknown infectious agents have “emerged” in laboratory rodents relatively recently. These agents have been discovered serendipitously or through active investigation of atypical serology results, cell culture contamination, unexpected histopathology, or previously unrecognized clinical disease syndromes. The potential research impact of these agents is not fully known. Infected rodents have demonstrated immunomodulation, tumor suppression, clinical disease (particularly in immunodeficient rodents), and histopathology. Perturbations of organismal and cellular physiology also likely occur. These agents posed unique challenges to laboratory animal resource programs once discovered; it was necessary to develop specific diagnostic assays and an understanding of their epidemiology and transmission routes before attempting eradication, and then evaluate eradication methods for efficacy. Even then management approaches varied significantly, from apathy to total exclusion, and such inconsistency has hindered the sharing and transfer of rodents among institutions, particularly for genetically modified rodent models that may not be readily available. As additional infectious agents are discovered in laboratory rodents in coming years, much of what researchers have learned from experiences with the recently identified pathogens will be applicable. This article provides an overview of the discovery, detection, and research impact of infectious agents recently identified in laboratory rodents. We also discuss emerging syndromes for which there is a suspected infectious etiology, and the unique challenges of managing newly emerging infectious agents. PMID:18506061

  4. Visual Landmarks Facilitate Rodent Spatial Navigation in Virtual Reality Environments

    ERIC Educational Resources Information Center

    Youngstrom, Isaac A.; Strowbridge, Ben W.

    2012-01-01

    Because many different sensory modalities contribute to spatial learning in rodents, it has been difficult to determine whether spatial navigation can be guided solely by visual cues. Rodents moving within physical environments with visual cues engage a variety of nonvisual sensory systems that cannot be easily inhibited without lesioning brain…

  5. PREDICTIVE SIMULATION MODELING FOR ANTIANDROGEN IMPACTS ON RODENT PROSTATE

    EPA Science Inventory

    Predictive simulation modeling for antiandrogen impacts on rodent prostate
    HA Barton1, RW Setzer1, LK Potter1,2
    1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Park, NC and 2Curriculum in Toxicology, UNC, Chapel Hill, NC

    Changes in rodent prostate weight and functi...

  6. Vitamin K Contents of Rodent Diets: A Review

    USDA-ARS?s Scientific Manuscript database

    Adequate nutrient intake is critical in the maintenance of normal physiological activity of rodents in biomedical studies. Vitamin K is an essential nutrient in rodent diets and functions as a cofactor for the y-carboxylation of certain proteins involved in blood coagulation and bone metabolism. Dif...

  7. PREDICTIVE SIMULATION MODELING FOR ANTIANDROGEN IMPACTS ON RODENT PROSTATE

    EPA Science Inventory

    Predictive simulation modeling for antiandrogen impacts on rodent prostate
    HA Barton1, RW Setzer1, LK Potter1,2
    1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Park, NC and 2Curriculum in Toxicology, UNC, Chapel Hill, NC

    Changes in rodent prostate weight and functi...

  8. Perturbation of Indole-3-Butyric Acid Homeostasis by the UDP-Glucosyltransferase UGT74E2 Modulates Arabidopsis Architecture and Water Stress Tolerance[W

    PubMed Central

    Tognetti, Vanesa B.; Van Aken, Olivier; Morreel, Kris; Vandenbroucke, Korneel; van de Cotte, Brigitte; De Clercq, Inge; Chiwocha, Sheila; Fenske, Ricarda; Prinsen, Els; Boerjan, Wout; Genty, Bernard; Stubbs, Keith A.; Inzé, Dirk; Van Breusegem, Frank

    2010-01-01

    Reactive oxygen species and redox signaling undergo synergistic and antagonistic interactions with phytohormones to regulate protective responses of plants against biotic and abiotic stresses. However, molecular insight into the nature of this crosstalk remains scarce. We demonstrate that the hydrogen peroxide–responsive UDP-glucosyltransferase UGT74E2 of Arabidopsis thaliana is involved in the modulation of plant architecture and water stress response through its activity toward the auxin indole-3-butyric acid (IBA). Biochemical characterization of recombinant UGT74E2 demonstrated that it strongly favors IBA as a substrate. Assessment of indole-3-acetic acid (IAA), IBA, and their conjugates in transgenic plants ectopically expressing UGT74E2 indicated that the catalytic specificity was maintained in planta. In these transgenic plants, not only were IBA-Glc concentrations increased, but also free IBA levels were elevated and the conjugated IAA pattern was modified. This perturbed IBA and IAA homeostasis was associated with architectural changes, including increased shoot branching and altered rosette shape, and resulted in significantly improved survival during drought and salt stress treatments. Hence, our results reveal that IBA and IBA-Glc are important regulators of morphological and physiological stress adaptation mechanisms and provide molecular evidence for the interplay between hydrogen peroxide and auxin homeostasis through the action of an IBA UGT. PMID:20798329

  9. Bartonella Infection in Rodents and Their Flea Ectoparasites: An Overview

    PubMed Central

    Gutiérrez, Ricardo; Krasnov, Boris; Morick, Danny; Gottlieb, Yuval; Khokhlova, Irina S.

    2015-01-01

    Abstract Epidemiological studies worldwide have reported a high prevalence and a great diversity of Bartonella species, both in rodents and their flea parasites. The interaction among Bartonella, wild rodents, and fleas reflects a high degree of adaptation among these organisms. Vertical and horizontal efficient Bartonella transmission pathways within flea communities and from fleas to rodents have been documented in competence studies, suggesting that fleas are key players in the transmission of Bartonella to rodents. Exploration of the ecological traits of rodents and their fleas may shed light on the mechanisms used by bartonellae to become established in these organisms. The present review explores the interrelations within the Bartonella–rodent–flea system. The role of the latter two components is emphasized. PMID:25629778

  10. Discovery of indole alkaloids with cannabinoid CB1 receptor antagonistic activity.

    PubMed

    Kitajima, Mariko; Iwai, Masumi; Kikura-Hanajiri, Ruri; Goda, Yukihiro; Iida, Mitsuru; Yabushita, Hisatoshi; Takayama, Hiromitsu

    2011-04-01

    Three indole alkaloids, voacamine (1), 3,6-oxidovoacangine (2), and a new alkaloid, 5-hydroxy-3,6-oxidovoacangine (3), isolated from Voacanga africana were found to exhibit potent cannabinoid CB1 receptor antagonistic activity. This is the first example of CB1 antagonists derived from natural alkaloids. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Au(III)/TPPMS-catalyzed benzylation of indoles with benzylic alcohols in water.

    PubMed

    Hikawa, Hidemasa; Suzuki, Hideharu; Azumaya, Isao

    2013-12-06

    A novel and efficient method for the Au(III)/TPPMS-catalyzed direct substitution reaction of benzhydryl and benzylic alcohols with indoles in water is developed. Au(III)/TPPMS is an effective catalyst for the benzylation of the strong π nucleophile 1-methylindole, while common Brønsted or Lewis acids are ineffective.

  12. Distribution of indole in tissues of dairy cattle, swine, and laying pullets

    SciTech Connect

    Eisele, G.R.

    1986-08-01

    Indole is a colorless crystalline solid which has been isolated from coal tar fractionation. High concentrations of indole (which is a major ruminal fermentation product of L-tryptophan) in blood of cattle causes hemolysis, hemoglobinuria, and renal necrosis. An end product of anaerobic metabolism of the colonic flora, indole has also been examined as a marker in patients with unresected large bowel cancer or polyps. With the increased release of numerous chemical substances into the biosphere, careful assessment of the health effects of chronic exposure to pollutants must be made. Much of the body burden of animals will come from ingested feed and water, with the primary route of human exposure being the consumption of the contaminated meat, milk, and eggs. The purpose of this study was to obtain baseline data on the uptake and distribution of /sup 14/C-indole in dairy cattle, swine, and laying pullets and the retention of this chemical in consumable products such as milk, meat, and eggs.

  13. Comparative Indole-3-Acetic Acid Levels in the Slender Pea and Other Pea Phenotypes 1

    PubMed Central

    Law, David M.; Davies, Peter J.

    1990-01-01

    Free indole-3-acetic acid levels were measured by gas chromatography-mass spectrometry in three ultra-tall `slender' Pisum sativum L. lines differing in gibberellin content. Measurements were made for apices and stem elongation zones of light-grown plants and values were compared with wild-type, dwarf, and nana phenotypes in which internode length is genetically regulated, purportedly via the gibberellin level. Indole-3-acetic acid levels of growing stems paralleled growth rates in all lines, and were high in all three slender genotypes. Growth was inhibited by p-chlorophenoxyisobutyric acid, demonstrating the requirement of auxin activity for stem elongation, and also by the ethylene precursor 1-aminocyclopropane-1-carboxylic acid. It is concluded that the slender phenotype may arise from constant activation of a gibberellin receptor or transduction chain event leading directly or indirectly to elevated levels of indole-3-acetic acid, and that increased indole-3-acetic acid levels are a significant factor in the promotion of stem elongation. PMID:16667653

  14. Highly diastereoselective samarium diiodide induced cyclizations of new 3-substituted indole derivatives.

    PubMed

    Beemelmanns, Christine; Reissig, Hans-Ulrich

    2009-11-07

    Herein, we describe the synthesis of new functionalized tricyclic and tetracyclic indole derivatives via samarium diiodide induced ketyl cyclizations. The intermediate samarium organyls were either protonated using different proton sources or alkylated with various electrophiles in a highly diastereoselective manner. The obtained products were subjected to further transformations leading to synthetically interesting building blocks.

  15. π-Extended thiadiazoles fused with thienopyrrole or indole moieties: synthesis, structures, and properties.

    PubMed

    Kato, Shin-ichiro; Furuya, Takayuki; Kobayashi, Atsushi; Nitani, Masashi; Ie, Yutaka; Aso, Yoshio; Yoshihara, Toshitada; Tobita, Seiji; Nakamura, Yosuke

    2012-09-07

    We report the syntheses, structures, photophysical properties, and redox characteristics of donor-acceptor-fused π-systems, namely π-extended thiadiazoles 1-5 fused with thienopyrrole or indole moieties. They were synthesized by the Stille coupling reactions followed by the PPh(3)-mediated reductive cyclizations as key steps. X-Ray crystallographic studies showed that isomeric 1b and 2b form significantly different packing from each other, and 1a and 4a afford supramolecular networks via multiple hydrogen bonding with water molecules. Thienopyrrole-fused compounds 1b and 2b displayed bathochromically shifted intramolecular charge-transfer (CT) bands and low oxidation potentials as compared to indole-fused analog 3b and showed moderate to good fluorescence quantum yields (Φ(f)) up to 0.73. In 3b-5b, the introduction of electron-donating substituents in the indole moieties substantially shifts the intramolecular CT absorption maxima bathochromically and leads to the elevation of the HOMO levels. The Φ(f) values of 3-5 (0.04-0.50) were found to be significantly dependent on the substituents in the indole moieties. The OFET properties with 1b and 2b as an active layer were also disclosed.

  16. Model Catalytic Studies of Novel Liquid Organic Hydrogen Carriers: Indole, Indoline and Octahydroindole on Pt(111).

    PubMed

    Schwarz, Matthias; Bachmann, Philipp; Silva, Thais Nascimento; Mohr, Susanne; Scheuermeyer, Marlene; Späth, Florian; Bauer, Udo; Düll, Fabian; Steinhauer, Johann; Hohner, Chantal; Döpper, Tibor; Noei, Heshmat; Stierle, Andreas; Papp, Christian; Steinrück, H-P; Wasserscheid, Peter; Görling, Andreas; Libuda, Jörg

    2017-08-16

    Indole derivatives were recently proposed as potential liquid organic hydrogen carriers (LOHC) for storage of renewable energies. In this work, we have investigated the adsorption, dehydrogenation and degradation mechanisms in the indole/indoline/octahydroindole system on Pt(111). We have combined infrared reflection absorption spectroscopy (IRAS), X-ray photoelectron spectroscopy (XPS) and DFT calculations. Indole multilayers show a crystallization transition at 200 K, in which the molecules adopt a strongly tilted orientation, before the multilayer desorbs at 220 K. For indoline, a less pronounced restructuring transition occurs at 150 K and multilayer desorption is observed at 200 K. Octahydroindole multilayers desorb already at 185 K, without any indication for restructuring. Adsorbed monolayers of all three compounds are stable up to room temperature and undergo deprotonation at the NH bond above 300 K. For indoline, the reaction is followed by partial dehydrogenation at the 5-membered ring, leading to the formation of a flat-lying di-σ-indolide in the temperature range from 330-390 K. Noteworthy, the same surface intermediate is formed from indole. In contrast, the reaction of octahydroindole with Pt(111) leads to the formation of a different intermediate, which originates from partial dehydrogenation of the 6-membered ring. Above 390 K, all three compounds again form the same strongly dehydrogenated and partially decomposed surface species. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Binary stress induces an increase in indole alkaloid biosynthesis in Catharanthus roseus

    PubMed Central

    Zhu, Wei; Yang, Bingxian; Komatsu, Setsuko; Lu, Xiaoping; Li, Ximin; Tian, Jingkui

    2015-01-01

    Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abundance of proteins related to tricarboxylic acid cycle and cell wall was largely increased; while, that of proteins related to tetrapyrrole synthesis and photosynthesis was decreased. Of note, 10-hydroxygeraniol oxidoreductase, which is involved in the biosynthesis of indole alkaloid was two-fold more abundant in treated group compared to the control. In addition, mRNA expression levels of genes involved in the indole alkaloid biosynthetic pathway indicated an up-regulation in their transcription in C. roseus under UV-B irradiation. These results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus. In addition, the induction of alkaloid biosynthesis appears to be responsive to binary stress. PMID:26284098

  18. Anti-Toxoplasma Activity of 2-(Naphthalene-2-γlthiol)-1H Indole

    PubMed Central

    ASGARI, Qasem; KESHAVARZ, Hossein; REZAEIAN, Mostafa; SADEGHPOUR, Hossein; MIRI, Ramin; MOTAZEDIAN, Mohammad Hossein

    2015-01-01

    Background: This study was undertaken to evaluate the viability, infectivity and immunity of Toxoplasma gondii tachyzoites exposed to 2-(naphthalene-2-ylthio)-1H-indole. Methods: Tachyzoites of RH strain were incubated in various concentrations of 2-(naphthalene-2-ylthio)-1H-indole (25–800 μM) for 1.5 hours. Then, they were stained by PI and analyzed by Fluorescence-activated cell sorting (FACS). To evaluate the infectivity, the tachyzoites exposed to the different concentrations of the compound were inoculated to 10 BALB/c mice groups. For Control, parasites exposed to DMSO (0.2% v/v) were also intraperitoneally inoculated into two groups of mice. The immunity of the exposed tachyzoites was evaluated by inoculation of the naïve parasite to the survived mice. Results: The LD50 of 2-(naphthalene-2-ylthio)-1H-indole was 57 μmol. The longevity of mice was dose dependent. Five mice out of group 400μmol and 3 out of group 800μmol showed immunization to the parasite. Conclusion: Our findings demonstrated the toxoplasmocidal activity of the compound. The presence of a well-organized transporter mechanism for indole compounds within the parasite in conjunction with several effective mechanisms of these compounds on Toxoplasma viability would open a window for production of new drugs and vaccines. PMID:26246814

  19. Indole Alkaloids from Plants as Potential Leads for Antidepressant Drugs: A Mini Review

    PubMed Central

    Hamid, Hazrulrizawati A.; Ramli, Aizi N. M.; Yusoff, Mashitah M.

    2017-01-01

    Depression is the most common illness observed in the elderly, adults, and children. Antidepressants prescribed are usually synthetic drugs and these can sometimes cause a wide range of unpleasant side effects. Current research is focussed on natural products from plants as they are a rich source of potent new drug leads. Besides Hypericum perforatum (St. John’s wort), the plants studied include Passiflora incarnata L. (passion flower), Mitragyna speciosa (kratom), Piper methysticum G. Forst (kava) and Valeriana officinalis L. Harman, harmol, harmine, harmalol and harmaline are indole alkaloids isolated from P. incarnata, while mitragynine is isolated from M. speciosa. The structure of isolated compounds from P. methysticum G. Forst and V. officinalis L. contains an indole moiety. The indole moiety is related to the neurotransmitter serotonin which is widely implicated for brain function and cognition as the endogenous receptor agonist. An imbalance in serotonin levels may influence mood in a way that leads to depression. The moiety is present in a number of antidepressants already on the market. Hence, the objective of this review is to discuss bioactive compounds containing the indole moiety from plants that can serve as potent antidepressants. PMID:28293192

  20. Enantioselective Friedel-Crafts alkylation for synthesis of 2-substituted indole derivatives.

    PubMed

    Zhang, Yulong; Liu, Xiaohua; Zhao, Xiaohu; Zhang, Jianlin; Zhou, Lin; Lin, Lili; Feng, Xiaoming

    2013-12-14

    An efficient catalytic asymmetric intermolecular C2 Friedel-Crafts alkylation reaction between N-methyl skatole and β,γ-unsaturated α-ketoesters has been realized by a chiral N,N'-dioxide-Ni(II) complex. The corresponding indole derivatives were obtained in good yield (up to 96%) with excellent enantioselectivities (up to 99% ee) under mild reaction conditions.