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Sample records for indole protects rodent

  1. Combining Zn Ion Catalysis with Homogeneous Gold Catalysis: An Efficient Annulation Approach to N-Protected Indoles.

    PubMed

    Wang, Yanzhao; Liu, Lianzhu; Zhang, Liming

    2013-02-01

    The Fischer indole synthesis is perhaps the most powerful method for indole preparation, but it often suffers from low regioselectivities with unsymmetric aliphatic ketone substrates and strong acidic conditions and is not suitable for α,β-unsaturated ketones. In this article, we disclose an efficient synthesis of N-protected indoles from N-arylhydroxamic acids/N-aryl-N-hydroxycarbamates and a variety of alkynes via a cooperative gold and zinc catalysis. The zinc catalysis is similar to the related zinc ion catalysis in metalloenzymes such as human carbonic anhydrase II and substantially enhances the O-nucleophilicity of N-acylated hydroxamines by forming the corresponding Zn chelates. The Zn chelates can attack gold-activated alkynes to form O-alkenyl-N-arylhydroxamates, which can undergo facile 3,3-sigmatropic rearrangements and subsequent cyclodehydrations to yield N-protected indole products. This new chemistry offers several important improvements over the Fischer indole synthesis: a) the reaction conditions are mildly acidic and can tolerate sensitive groups such as Boc; b) broader substrate scopes including substrates with pendant carbonyl groups (reactive in the Fischer chemistry) and alkyl chlorides (e.g., 3f); c) better regioselectivities for the formation of 2-substituted indoles under much milder conditions; d) 2-alkenylindoles can be prepared readily in good to excellent yields, but the Fischer chemistry could not; e) with internal alkynes both steric and electronic controls are available for achieving good regioselectivities, while the Fischer chemistry is in general problematic.

  2. Protection by dietary compounds against mutation in a transgenic rodent.

    PubMed

    de Boer, J G

    2001-11-01

    One of the most relevant biomarkers of genotoxicity and, potentially, carcinogenesis is the occurrence of mutations. Data indicate that carcinogens are highly specific with regard to their target tissue in inducing both tumors and mutations. This specificity may reflect the dependence on tissue-specific metabolic activation, the organ-specific environment or both. Ideally, therefore, mutation should be determined in a real animal rather than in a cell culture system. The lacI transgenic rodent model provides such a system. We have used this model to investigate tissue, species and sex specificity of mutation induced by selected dietary carcinogens and to examine how some compounds may alter the induction of mutation. We have studied mutation using several chemicals, including the dietary heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the environmentally important aromatic hydrocarbon benzo[a]pyrene and the food contaminant aflatoxin B1. We have shown that the mutagenic potency of these chemicals can be modulated by other dietary compounds, including green tea and conjugated linoleic acid, and the dioxin 2,3,7,8-tetrachlorodibenzo[b,e][1,4]dioxin (TCDD). These results demonstrate that the lacI transgenic rodent is a useful model for the study of chemoprevention in vivo.

  3. 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

  4. Mushroom lectin protects arsenic induced apoptosis in hepatocytes of rodents.

    PubMed

    Rana, Tanmoy; Bera, Asit Kumar; Das, Subhashree; Bhattacharya, Debasis; Pan, Diganta; Bandyopadhyay, Subhasish; De, Sumanta; Das, Subrata Kumar

    2011-04-01

    Acute and chronic arsenic exposure result in toxicity both in human and animal beings and cause many hepatic and renal manifestations. The present study stated that mushroom lectin prevents arsenic-induced apoptosis. Apoptosis was measured by morphological alterations, cell proliferation index (CPI), phagocytic activity (nitro blue tetrazolium index; NBT), nitric oxide (NO) production, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, DNA fragmentation and caspase-3 activity. Arsenic exposure at 5 μM in the form of sodium arsenite resulted in significant elevation of deformed cells, NO production, TUNEL stained nuclei of hepatocytes, DNA fragmentation and caspase-3 activity. But the CPI and NBT index were significantly declined in arsenic-treated hepatocytes. The beneficial effect of mushroom lectin at 10 μg/mL, 20 μg/mL and 50 μg/mL) showed increased CPI and phagocytic activity. Mushroom lectin at those concentrations reduced deformed cells, NO production, DNA fragmentation and caspase-3 activity of hepatocytes. But significant better protection was observed in 50 μg/mL mushroom lectin-treated hepatocytes. This finding may be of therapeutic benefit in people suffering from chronic arsenic exposure.

  5. Protective effect of androgens against inflammation induced cartilage degradation in male rodents.

    PubMed Central

    Da Silva, J A; Larbre, J P; Spector, T D; Perry, L A; Scott, D L; Willoughby, D A

    1993-01-01

    OBJECTIVES--Rheumatoid arthritis (RA) is a disease which predominantly affects women. Interestingly, low serum androgen levels and clinical improvement with androgen replacement have been reported in male patients. The aetiopathogenic role of sex hormones in arthritis and their potential long term effects on joint destruction and disability remains unclear, however. This study was designed to investigate the potential influence of sex hormones on inflammation induced cartilage degradation in male rodents. METHODS--An in vivo model of cotton wrapped cartilage implants was used to assess the effects of androgen, oestradiol, and progesterone on inflammation induced cartilage degradation, and in vitro techniques were used to investigate the direct actions on cartilage metabolism and cytokine production in male animals. RESULTS--Orchidectomy resulted in accelerated cartilage damage which was reversed by replacement of physiological levels of androgens. Granulomatous tissue from castrated male rodents produced higher amounts of interleukin 1. Sex hormones reduced spontaneous proteoglycan loss in vitro but did not interfere with the effects of interleukin 1 on cultured cartilage. CONCLUSIONS--Androgens appear to protect cartilage from inflammation induced breakdown in male animals. These results support a pathogenic role for hypoandrogenism in rheumatoid arthritis and suggest that long term androgen replacement may help prevent joint damage and disability. PMID:8484695

  6. Immunization with vesicular stomatitis virus vaccine expressing the Ebola glycoprotein provides sustained long-term protection in rodents.

    PubMed

    Wong, Gary; Audet, Jonathan; Fernando, Lisa; Fausther-Bovendo, Hugues; Alimonti, Judie B; Kobinger, Gary P; Qiu, Xiangguo

    2014-09-29

    Ebola virus (EBOV) infections cause lethal hemorrhagic fever in humans, resulting in up to 90% mortality. EBOV outbreaks are sporadic and unpredictable in nature; therefore, a vaccine that is able to provide durable immunity is needed to protect those who are at risk of exposure to the virus. This study assesses the long-term efficacy of the vesicular stomatitis virus (VSV)-based vaccine (VSVΔG/EBOVGP) in two rodent models of EBOV infection. Mice and guinea pigs were first immunized with 2×10(4) or 2×10(5) plaque forming units (PFU) of VSVΔG/EBOVGP, respectively. Challenge of mice with a lethal dose of mouse-adapted EBOV (MA-EBOV) at 6.5 and 9 months after vaccination provided complete protection, and 80% (12 of 15 survivors) protection at 12 months after vaccination. Challenge of guinea pigs with a lethal dose of guinea pig-adapted EBOV (GA-EBOV) at 7, 12 and 18 months after vaccination resulted in 83% (5 of 6 survivors) at 7 months after vaccination, and 100% survival at 12 and 18 months after vaccination. No weight loss or clinical signs were observed in the surviving animals. Antibody responses were analyzed using sera from individual rodents. Levels of EBOV glycoprotein-specific IgG antibody measured immediately before challenge appeared to correlate with protection. These studies confirm that vaccination with VSVΔG/EBOVGP is able to confer long-term protection against Ebola infection in mice and guinea pigs, and support follow-up studies in non-human primates. PMID:25173474

  7. 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.

  8. 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

  9. Protective Effects of Indole-3-Carbinol-Loaded Poly(lactic-co-glycolic acid) Nanoparticles Against Glutamate-Induced Neurotoxicity.

    PubMed

    Jeong, Ji Heun; Kim, Jwa-Jin; Bak, Dong Ho; Yu, Kwang Sik; Lee, Je Hun; Lee, Nam Seob; Jeong, Young Gil; Kim, Do Kyung; Kim, Dong-Kwan; Han, Seung-Yun

    2015-10-01

    Indole-3-carbinol (I3C) has anti-oxidant and anti-inflammatory properties. Nonetheless, the potential of I3C to treat neurodegenerative diseases remains unclear because of its poor ability to penetrate the blood-brain barrier (BBB). Because polymer-based drug delivery systems stabilized by surfactants have been intensively utilized as a strategy to cross the blood-brain barrier, we prepared I3C-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) that were stabilized by Tween 80 (T80) (I3C-PLGA-T80-NPs) and examined their neuroprotective potential in vitro. We prepared I3C-PLGA-T80-NPs with an oil-in-water (o/w) emulsion solvent evaporation technique and confirmed their successful synthesis with both transmission electron microscopy and Fourier transform-infrared spectroscopy. I3C-PLGA-T80-NPs were then used to treat PC12 neuronal cells injured by glutamate excitotoxicity (GE) and examined the resulting survival rates compared with PC12 cells treated with I3C only. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay revealed higher survival rates in I3C-PLGA-T80-NPs-treated cells after GE injury compared with those treated with I3C only. Furthermore, I3C-PLGA-T80-NPs decreased the levels of reactive oxygen species (ROS) and apoptosis-related enzymes (Caspase-3 and -8) in GE-damaged neuronal cells. Taken together, I3C-PLGA-T80-NPs might possess neuroprotective effects against GE through ROS scavenging and subsequent apoptosis blockage. PMID:26726441

  10. Lactobacillus casei strain Shirota protects against nonalcoholic steatohepatitis development in a rodent model.

    PubMed

    Okubo, Hirofumi; Sakoda, Hideyuki; Kushiyama, Akifumi; Fujishiro, Midori; Nakatsu, Yusuke; Fukushima, Toshiaki; Matsunaga, Yasuka; Kamata, Hideaki; Asahara, Takashi; Yoshida, Yasuto; Chonan, Osamu; Iwashita, Misaki; Nishimura, Fusanori; Asano, Tomoichiro

    2013-12-01

    Gut microbiota alterations are associated with various disorders. In this study, gut microbiota changes were investigated in a methionine-choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH) rodent model, and the effects of administering Lactobacillus casei strain Shirota (LcS) on the development of NASH were also investigated. Mice were divided into three groups, given the normal chow diet (NCD), MCD diet, or the MCD diet plus daily oral administration of LcS for 6 wk. Gut microbiota analyses for the three groups revealed that lactic acid bacteria such as Bifidobacterium and Lactobacillus in feces were markedly reduced by the MCD diet. Interestingly, oral administration of LcS to MCD diet-fed mice increased not only the L. casei subgroup but also other lactic acid bacteria. Subsequently, NASH development was evaluated based on hepatic histochemical findings, serum parameters, and various mRNA and/or protein expression levels. LcS intervention markedly suppressed MCD-diet-induced NASH development, with reduced serum lipopolysaccharide concentrations, suppression of inflammation and fibrosis in the liver, and reduced colon inflammation. Therefore, reduced populations of lactic acid bacteria in the colon may be involved in the pathogenesis of MCD diet-induced NASH, suggesting normalization of gut microbiota to be effective for treating NASH.

  11. Adjudin protects rodent cochlear hair cells against gentamicin ototoxicity via the SIRT3-ROS pathway.

    PubMed

    Quan, Yizhou; Xia, Li; Shao, Jiaxiang; Yin, Shankai; Cheng, C Yan; Xia, Weiliang; Gao, Wei-Qiang

    2015-01-01

    Hearing loss resulting from hair cell degeneration is a common disease that affects millions of people worldwide. Strategies to overcome the apparent irreversible hair cell loss in mammals become paramount for hearing protection. Here we reported that, by using a well-established gentamicin-induced hair cell loss model in vitro, adjudin, a multi-functional small molecule drug, protected cochlear hair cells from gentamicin damage. Immunohistochemistry, Western blotting and quantitative RT-PCR analyses revealed that adjudin exerted its otoprotective effects by up-regulating the level of Sirt3, a member of Sirtuin family protein located in mitochondria, which regulates reactive oxygen species (ROS) production in cochlear cells and inhibits the production of ROS and apoptotic cells induced by gentamicin. Sirt3 silencing experiments confirmed that Sirt3-ROS signaling axis mediated hair cell protection against gentamicin by adjudin, at least in part. Furthermore, adjudin's otoprotection effects were also observed in an in vivo gentamicin-injured animal model. Taken together, these findings identify adjudin as a novel otoprotective small molecule via elevating Sirt3 levels and Sirt3 may be of therapeutic value in hair cell protection from ototoxic insults.

  12. Adjudin protects rodent cochlear hair cells against gentamicin ototoxicity via the SIRT3-ROS pathway

    PubMed Central

    Quan, Yizhou; Xia, Li; Shao, Jiaxiang; Yin, Shankai; Cheng, C. Yan; Xia, Weiliang; Gao, Wei-Qiang

    2015-01-01

    Hearing loss resulting from hair cell degeneration is a common disease that affects millions of people worldwide. Strategies to overcome the apparent irreversible hair cell loss in mammals become paramount for hearing protection. Here we reported that, by using a well-established gentamicin-induced hair cell loss model in vitro, adjudin, a multi-functional small molecule drug, protected cochlear hair cells from gentamicin damage. Immunohistochemistry, Western blotting and quantitative RT-PCR analyses revealed that adjudin exerted its otoprotective effects by up-regulating the level of Sirt3, a member of Sirtuin family protein located in mitochondria, which regulates reactive oxygen species (ROS) production in cochlear cells and inhibits the production of ROS and apoptotic cells induced by gentamicin. Sirt3 silencing experiments confirmed that Sirt3-ROS signaling axis mediated hair cell protection against gentamicin by adjudin, at least in part. Furthermore, adjudin's otoprotection effects were also observed in an in vivo gentamicin-injured animal model. Taken together, these findings identify adjudin as a novel otoprotective small molecule via elevating Sirt3 levels and Sirt3 may be of therapeutic value in hair cell protection from ototoxic insults. PMID:25640330

  13. 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

  14. 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

    2016-01-01

    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.

  15. 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

  16. 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

  17. 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

    2016-03-01

    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.

  18. 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.

  19. 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)

  20. Protective Effect of SAHA against LPS-induced Liver Damage in Rodents

    PubMed Central

    Zhao, Yili; Zhou, Peter; Liu, Baoling; Bambakidis, Ted; Mazitschek, Ralph; Alam, Hasan B.; Li, Yongqing

    2014-01-01

    BACKGROUND Lipopolysaccharide (LPS) has a deleterious effect on several organs including the liver and eventually leads to endotoxic shock and death. LPS-induced hepatotoxicity is characterized by disturbed intracellular redox balance and excessive reactive oxygen species (ROS) accumulation, leading to liver injury. We have shown that treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACI), improves survival in a murine model of LPS-induced shock, but the protective effect of SAHA against liver damage remains unknown. The goal of this study was to investigate the mechanism underlying SAHA action in murine livers. METHOD Male C57BL/6J mice (6-8 weeks) weighing 20-25 g were randomly divided into three groups: (A) a sham group was given isotonic sodium chloride solution (10 μL/g body weight, intraperitoneal, i.p.) with DMSO (1 μl/g body weight, i.p.); (B) a LPS group was challenged with LPS (20 mg/kg, i.p.) dissolved in isotonic sodium chloride solution with DMSO; (C) a LPS plus SAHA group was treated with SAHA (50 mg/kg, i.p.) dissolved in DMSO immediately after injection of LPS (20 mg/kg, i.p.). Mice were anesthetized, and their livers were harvested 6 or 24 hours after injection to analyze whether SAHA affected production of reactive oxygen species (ROS) and activation of apoptotic proteins in the liver cells of challenged mice. RESULTS SAHA counteracted LPS-induced production of ROS (thiobarbituric acid reactive substances (TBARS) and nitrite) and reversed an LPS-induced decrease in antioxidant enzyme, glutathione (GSH). SAHA also attenuated LPS-induced hepatic apoptosis. Moreover, SAHA inhibited activation of the redox-sensitive kinase, apoptosis signal-regulating kinase-1 (ASK1), and the mitogen-activated protein kinases (MAPKs) p38 and Jun N-terminal kinase (JNK). CONCLUSION Our data indicates, for the first time, that SAHA is capable of alleviating LPS-induced hepatotoxicity and suggests that a blockade of the upstream

  1. Cu-mediated direct regioselective C-2 chlorination of indoles.

    PubMed

    Zhao, Jing; Cheng, Xiuzhi; Le, Jun; Yang, Wei; Xue, Fengtian; Zhang, Xuan; Jiang, Chao

    2015-09-14

    Cu-mediated C-2 chlorination of indoles was accomplished with copper(ii) chloride through the use of a directing pyrimidyl protection group. A highly regioselective manner can be achieved on a range of indole substrates with excellent functional group tolerance. PMID:26247622

  2. Biosynthesis of Fungal Indole Alkaloids

    PubMed Central

    Xu, Wei; Gavia, Diego J.; Tang, Yi

    2014-01-01

    This review provides a summary of recent research advances in elucidating the biosynthesis of fungal indole alkaloids. Different strategies used to incorporate and derivatize the indole/indoline moieties in various families of fungal indole alkaloids will be discussed, including tryptophan-containing nonribosomal peptides and polyketide-nonribosomal peptide hybrids; and alkaloids derived from other indole building blocks. This review also includes discussion regarding the downstream modifications that generate chemical and structural diversity among indole alkaloids. PMID:25180619

  3. Indole-3-ethanol Oxidase

    PubMed Central

    Percival, Frank W.; Purves, William K.; Vickery, Larry E.

    1973-01-01

    We report the further characterization of indole-3-ethanol oxidase from cucumber seedlings. The effects of various inhibitors suggest that the enzyme may be a flavoprotein with a metal ion and sulfhydryl groups required for full activity. Indole-3-acetaldehyde, a product of the reaction, inhibits the enzyme. This inhibition is overcome by O2 but not by indole-3-ethanol, indicating that the kinetic mechanism of the enzyme is a ping-pong Bi-Bi. The enzyme undergoes cooperative interactions with indoleethanol, yielding Hill coefficients as high as 2.96. Gibberellins are without effect on the enzyme, but it is inhibited by several acidic indoles possessing growth-promoting activity and by two synthetic auxins, 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid. Increasing concentrations of indoleacetic acid (IAA) brought about a slight reduction in the indoleethanol concentration producing halfmaximal velocity. Increasing levels of indoleethanol decreased the concentration of IAA required for half-maximal inhibition. At low concentrations of indoleethanol, low levels of IAA activated rather than inhibited. The effect of IAA was not overcome at higher levels of indoleethanol. These results may be interpreted as showing that IAA is a noncompetitive inhibitor which binds to that conformation of the enzyme which also binds indoleethanol. The significance of these interactions for the regulation of IAA biosynthesis is discussed. PMID:16658401

  4. Developmental regulation of group I metabotropic glutamate receptors in the premature brain and their protective role in a rodent model of periventricular leukomalacia.

    PubMed

    Jantzie, Lauren L; Talos, Delia M; Selip, Debra B; An, Li; Jackson, Michele C; Folkerth, Rebecca D; Deng, Wenbin; Jensen, Frances E

    2010-11-01

    Cerebral white matter injury in premature infants, known as periventricular leukomalacia (PVL), is common after hypoxia-ischemia (HI). While ionotropic glutamate receptors (iGluRs) can mediate immature white matter injury, we have previously shown that excitotoxic injury to premyelinating oligodendrocytes (preOLs) in vitro can be attenuated by group I metabotropic glutamate receptor (mGluR) agonists. Thus, we evaluated mGluR expression in developing white matter in rat and human brain, and tested the protective efficacy of a central nervous system (CNS)-penetrating mGluR agonist on injury to developing oligodendrocytes (OLs) in vivo. Group I mGluRs (mGluR1 and mGluR5) were strongly expressed on OLs in neonatal rodent cerebral white matter throughout normal development, with highest expression early in development on preOLs. Specifically at P6, mGluR1 and mGLuR5 were most highly expressed on GalC-positive OLs compared to neurons, axons, astrocytes and microglia. Systemic administration of (1S,3R) 1-aminocyclopentane-trans-1,3,-dicarboxylic acid (ACPD) significantly attenuated the loss of myelin basic protein in the white matter following HI in P6 rats. Assessment of postmortem human tissue showed both mGluR1 and mGluR5 localized on immature OLs in white matter throughout development, with mGluR5 highest in the preterm period. These data indicate group I mGluRs are highly expressed on OLs during the peak period of vulnerability to HI and modulation of mGluRs is protective in a rodent model of PVL. Group I mGluRs may represent important therapeutic targets for protection from HI-mediated white matter injury.

  5. Repetitive live sporozoites inoculation under arteether chemoprophylaxis confers protection against subsequent sporozoite challenge in rodent malaria model.

    PubMed

    Bhardwaj, Jyoti; Siddiqui, Arif Jamal; Goyal, Manish; Prakash, Kirtika; Soni, Awakash; Puri, Sunil K

    2016-06-01

    Inoculation with live sporozoites under prophylactic antimalarial cover (CPS-immunization) represents an alternate approach to develop sterile, reproducible, and long-term protection against malaria. Here, we have employed arteether (ART), a semi synthetic derivative of artemisinin to explore its potential as a chemoprophylaxis candidate in CPS approach and systematically compared the protective potential of arteether with mefloquine, azithromycin and primaquine. Blood stage patency and quantitative RT-PCR of liver stage parasite load were monitored as primary key end-points for protection against malaria challenge infection. For this purpose, sequential exposures of Plasmodium yoelii sporozoites under prophylactic treatment with arteether (ART), mefloquine (MFQ), azithromycin (AZ) or primaquine (PQ) was conducted in experimental Swiss mice. Our results show that during the first three sequential exposures (1st, 2nd and 3rd challenge) no marked difference in the blood stage patency was observed between control and CPS-ART group. However, delayed patency was recorded following 4th sporozoite challenge and mice enjoyed sterile protection after 5th sporozoite challenge. A similar response was observed in CPS-MFQ group, whereas earlier protection was recorded in CPS-AZ group i.e., after 4th sprozoite challenge. However, mice under PQ cover did not show any protection/delay in patency even after five sequential sporozoite inoculations, possibly due to inhibition of liver stage development. Furthermore, protection acquired by CPS-immunization is stage-specific as the protected mice remained susceptible to challenge with blood stage parasites. In short, the present study demonstrates that sporozoite administration under ART, MFQ or AZ treatment confers strong protection against subsequent sporozoite infection and the acquired response is dependent on the presence of liver stage parasites.

  6. 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

    2009-01-01

    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.

  7. 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

    2015-07-01

    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.

  8. Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models

    PubMed Central

    Shen, Xiujin; Jiang, Hong; Ying, Meike; Xie, Zhoutao; Li, Xiayu; Wang, Haibing; Zhao, Jie; Lin, Chuan; Wang, Yucheng; Feng, Shi; Shen, Jia; Weng, Chunhua; Lin, Weiqiang; Wang, Huiping; Zhou, Qin; Bi, Yan; Li, Meng; Wang, Lingyan; Zhu, Tongyu; Huang, Xiaoru; Lan, Hui-Yao; Zhou, Jing; Chen, Jianghua

    2016-01-01

    Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway. PMID:27580845

  9. Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models.

    PubMed

    Shen, Xiujin; Jiang, Hong; Ying, Meike; Xie, Zhoutao; Li, Xiayu; Wang, Haibing; Zhao, Jie; Lin, Chuan; Wang, Yucheng; Feng, Shi; Shen, Jia; Weng, Chunhua; Lin, Weiqiang; Wang, Huiping; Zhou, Qin; Bi, Yan; Li, Meng; Wang, Lingyan; Zhu, Tongyu; Huang, Xiaoru; Lan, Hui-Yao; Zhou, Jing; Chen, Jianghua

    2016-01-01

    Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway. PMID:27580845

  10. 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

  11. Astrocytic Toll-Like Receptor 3 Is Associated with Ischemic Preconditioning- Induced Protection against Brain Ischemia in Rodents

    PubMed Central

    Li, Yang; Xu, Xu-lin; Guo, Lian-jun; Lu, Qing; Wang, Jian

    2014-01-01

    Background Cerebral ischemic preconditioning (IPC) protects brain against ischemic injury. Activation of Toll-like receptor 3 (TLR3) signaling can induce neuroprotective mediators, but whether astrocytic TLR3 signaling is involved in IPC-induced ischemic tolerance is not known. Methods IPC was modeled in mice with three brief episodes of bilateral carotid occlusion. In vitro, IPC was modeled in astrocytes by 1-h oxygen-glucose deprivation (OGD). Injury and components of the TLR3 signaling pathway were measured after a subsequent protracted ischemic event. A neutralizing antibody against TLR3 was used to evaluate the role of TLR3 signaling in ischemic tolerance. Results IPC in vivo reduced brain damage from permanent middle cerebral artery occlusion in mice and increased expression of TLR3 in cortical astrocytes. IPC also reduced damage in isolated astrocytes after 12-h OGD. In astrocytes, IPC or 12-h OGD alone increased TLR3 expression, and 12-h OGD alone increased expression of phosphorylated NFκB (pNFκB). However, IPC or 12-h OGD alone did not alter the expression of Toll/interleukin receptor domain-containing adaptor-inducing IFNβ (TRIF) or phosphorylated interferon regulatory factor 3 (pIRF3). Exposure to IPC before OGD increased TRIF and pIRF3 expression but decreased pNFκB expression. Analysis of cytokines showed that 12-h OGD alone increased IFNβ and IL-6 secretion; 12-h OGD preceded by IPC further increased IFNβ secretion but decreased IL-6 secretion. Preconditioning with TLR3 ligand Poly I:C increased pIRF3 expression and protected astrocytes against ischemic injury; however, cells treated with a neutralizing antibody against TLR3 lacked the IPC- and Poly I:C-induced ischemic protection and augmentation of IFNβ. Conclusions The results suggest that IPC-induced ischemic tolerance is mediated by astrocytic TLR3 signaling. This reprogramming of TLR3 signaling by IPC in astrocytes may play an important role in suppression of the post

  12. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates

    PubMed Central

    Pierantoni, Angiolo; Esposito, Maria Luisa; Ammendola, Virginia; Napolitano, Federico; Grazioli, Fabiana; Abbate, Adele; del Sorbo, Mariarosaria; Siani, Loredana; D’Alise, Anna Morena; Taglioni, Alessandra; Perretta, Gemma; Siccardi, Antonio; Soprana, Elisa; Panigada, Maddalena; Thom, Michelle; Scarselli, Elisa; Folgori, Antonella; Colloca, Stefano; Taylor, Geraldine; Cortese, Riccardo; Nicosia, Alfredo; Capone, Stefania; Vitelli, Alessandra

    2015-01-01

    Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing. PMID:26015988

  13. Baculovirus-Vectored Multistage Plasmodium vivax Vaccine Induces Both Protective and Transmission-Blocking Immunities against Transgenic Rodent Malaria Parasites

    PubMed Central

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

    2014-01-01

    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. PMID:25092912

  14. 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.

  15. Enhanced protection against renal ischemia-reperfusion injury with combined melatonin and exendin-4 in a rodent model.

    PubMed

    Chang, Yi-Chih; Hsu, Shu-Yuan; Yang, Chih-Chao; Sung, Pei-Hsun; Chen, Yi-Ling; Huang, Tien-Hung; Kao, Gour-Shenq; Chen, Sheng-Yi; Chen, Kuan-Hung; Chiang, Hsin-Ju; Yip, Hon-Kan; Lee, Fan-Yen

    2016-08-01

    We tested the hypothesis that combined treatment with melatonin, an anti-oxidant, and exendin-4, an anti-inflammatory agent, was superior to either alone for protecting the kidney from ischemia-reperfusion (IR) injury. Male adult Sprague-Dawley rats (n=40) were equally divided into group 1 (sham-operated control), group 2 (IR only, IR=1h/72h), group 3 (IR-exendin-4, 10 µg/kg at 30 min, 24 h, 48 h after IR procedure), group 4 (IR-melatonin, i.p. 50 mg at 30 min, then 20 mg at 6 and 18 h after IR procedure), and group 5 (combined IR-exendin-4-melatonin). All animals were sacrificed by 72 h after IR/sham procedure. The results showed that the kidney injury score, plasma creatinine, and blood urea nitrogen (BUN) levels were highest in group 2 and lowest in group 1, significantly higher in groups 3 and 4 than those in group 5 and significantly higher in group 3 than those in group 4 (all p < 0.001). The protein expressions of inflammatory (toll-like receptor 4, inducible nitric oxide synthase, interleukin-1β), apoptotic (mitochondrial Bax, cleaved caspase-3 and poly(ADP-ribose) polymerase, p53), podocyte integrity (E-cadherin, P-cadherin), and cell survival (phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin) biomarkers, as well the podocyte dysfunction biomarkers (Wnt1/Wnt4/β-catenin) displayed a pattern identical to that of creatinine level among the five groups (all p < 0.001). Microscopic findings demonstrated that podocyte dysfunction (Wnt1/Wnt4/β-catenin expression) and inflammatory (CD14 and F4/80-positively stained cells) biomarkers exhibited an identical pattern, whereas that of antioxidant (HO-1(+), NQO-1(+) cells) biomarkers showed an opposite pattern compared to that of creatinine level among the five groups (all p < 0.001). Combined melatonin-exendin-4 therapy offered an additional benefit in protecting the kidney from acute IR injury.

  16. Enhanced protection against renal ischemia-reperfusion injury with combined melatonin and exendin-4 in a rodent model.

    PubMed

    Chang, Yi-Chih; Hsu, Shu-Yuan; Yang, Chih-Chao; Sung, Pei-Hsun; Chen, Yi-Ling; Huang, Tien-Hung; Kao, Gour-Shenq; Chen, Sheng-Yi; Chen, Kuan-Hung; Chiang, Hsin-Ju; Yip, Hon-Kan; Lee, Fan-Yen

    2016-08-01

    We tested the hypothesis that combined treatment with melatonin, an anti-oxidant, and exendin-4, an anti-inflammatory agent, was superior to either alone for protecting the kidney from ischemia-reperfusion (IR) injury. Male adult Sprague-Dawley rats (n=40) were equally divided into group 1 (sham-operated control), group 2 (IR only, IR=1h/72h), group 3 (IR-exendin-4, 10 µg/kg at 30 min, 24 h, 48 h after IR procedure), group 4 (IR-melatonin, i.p. 50 mg at 30 min, then 20 mg at 6 and 18 h after IR procedure), and group 5 (combined IR-exendin-4-melatonin). All animals were sacrificed by 72 h after IR/sham procedure. The results showed that the kidney injury score, plasma creatinine, and blood urea nitrogen (BUN) levels were highest in group 2 and lowest in group 1, significantly higher in groups 3 and 4 than those in group 5 and significantly higher in group 3 than those in group 4 (all p < 0.001). The protein expressions of inflammatory (toll-like receptor 4, inducible nitric oxide synthase, interleukin-1β), apoptotic (mitochondrial Bax, cleaved caspase-3 and poly(ADP-ribose) polymerase, p53), podocyte integrity (E-cadherin, P-cadherin), and cell survival (phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin) biomarkers, as well the podocyte dysfunction biomarkers (Wnt1/Wnt4/β-catenin) displayed a pattern identical to that of creatinine level among the five groups (all p < 0.001). Microscopic findings demonstrated that podocyte dysfunction (Wnt1/Wnt4/β-catenin expression) and inflammatory (CD14 and F4/80-positively stained cells) biomarkers exhibited an identical pattern, whereas that of antioxidant (HO-1(+), NQO-1(+) cells) biomarkers showed an opposite pattern compared to that of creatinine level among the five groups (all p < 0.001). Combined melatonin-exendin-4 therapy offered an additional benefit in protecting the kidney from acute IR injury. PMID:27037275

  17. Electrophilic Substitution Reactions of Indoles

    NASA Astrophysics Data System (ADS)

    Sundberg, Richard J.

    The topic of this chapter is electrophilic substitution of indole and its derivatives. The indole ring is highly reactive at its 3-position toward protonation, halogenation, alkylation and acylation. Electrophilic substitution can be combined with inter- or intramolecular addition at C-2. Intramolecular alkylation by iminium ions (Pictet-Spengler reaction) is particularly useful. Enantioselectivity can be achieved in many conjugate addition reactions. These reactions have been applied to synthesis of both natural products and drugs.

  18. Synthesis and comparison of antioxidant properties of indole-based melatonin analogue indole amino Acid derivatives.

    PubMed

    Suzen, Sibel; Cihaner, Seyhan Sezen; Coban, Tulay

    2012-01-01

    Increased levels of reactive oxygen species attributed to oxidative stress have been found to be responsible for the development of some vital diseases such as cardiovascular, neurodegenerative and autoimmune diseases. Recently, it was observed that melatonin is a highly important antioxidant, and melatonin analogues are under investigation to find out improved antioxidant activity. In this study, 14 melatonin -based analogue indole amino acid and N-protected amino acid derivatives were synthesized and elucidated spectrometrically. To investigate the antioxidant activity of the synthesized compounds and to compare with melatonin, butylhydroxytoluene and vitamin E, lipid peroxidation inhibition and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activities were tested. The results indicated that the synthesized new indole amino acid derivatives have similar activities to melatonin in 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity assay but more potent activities in lipid peroxidation inhibition assay.

  19. Protective effects of systemic treatment with methylprednisolone in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION).

    PubMed

    Huang, Tzu-Lun; Huang, Shun-Ping; Chang, Chung-Hsing; Lin, Kung-Hung; Chang, Shu-Wen; Tsai, Rong-Kung

    2015-02-01

    This study investigated the protective effects of the administration of steroids on optic nerves (ON) and retinal ganglion cells (RGCs) in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION). We induced rAION using rose bengal and argon laser irradiation in a photodynamic procedure on the optic discs of rats. The treated groups received methylprednisolone (MP) via peritoneal injection for 2 weeks. The control group received intraperitoneal injections of phosphate-buffered saline (PBS) post-rAION. At the 4th week post-infarct, MP treatments significantly rescued the RGCs (mm(2)) in the central retinas (1920 ± 210, p < 0.001) and mid-peripheral retinas (950 ± 240, respectively, p = 0.018) compared with those of the PBS-treated rats (central: 900 ± 210 and mid-peripheral: 440 ± 180). Functional assessment with flash visual-evoked potentials demonstrated that P1 latency (ms) was shortened in the MP group compared to the PBS group (108 ± 14 and 147 ± 9, respectively, p < 0.001). In addition, the P1 amplitude (uV) was enhanced in the MP group compared to the PBS group (55 ± 12 and 41 ± 13, respectively, p < 0.05). TUNEL assays showed a decrease in the number of apoptotic cells in the RGC layers of MP-treated retinas compared to the PBS-treated group (p < 0.05). ED1 positive cells (/HPF) were significantly decreased in the ONs of the MP group compared to the PBS group (p < 0.001). In conclusion, systemic administration of MP had neuroprotective effects on RGC survival and ON function in the rAION animal model. PMID:25543054

  20. 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

  1. 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

    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

  2. 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.

  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. Indole alkaloids from Antirhea lucida.

    PubMed

    Weniger, B; Rafik, W; Bastida, J; Quirion, J C; Anton, R

    1995-12-01

    A new indole alkaloid, N,N-methyl-3'-indolylmethyl-5-methoxytryptamine, as well as the known gramine, N,N-dimethyltryptamine and 6-methoxy-2-methyl-1,2,3,4-tetrahydro-beta-carboline were isolated from the roots of Antirhea lucida (Sw.) Hook (Rubiaceae). Their structures were established by spectroscopic methods.

  5. Endocrine diseases of rodents.

    PubMed

    Collins, Bobby R

    2008-01-01

    The frequency of documented endocrine diseases in rodents and other small mammals varies considerably among the species maintained as pets, biomedical research animals, or display animals in zoos. The clinical diagnosis of endocrine diseases almost never occurs in free-ranging animals in their native habitat. Feral animals that have clinical endocrine disease, such as neoplasia, adrenal cortical hyperplasia, or diabetes, would exhibit clinical signs of altered behavior that would result in their removal by predators. The diagnosis of endocrine disease thus takes place in the relatively protective environment of captivity. This observation should forewarn pet owners and clinicians caring for these animals that the environment contributes to the development of endocrine diseases in these animals.

  6. Biochemical Characterization of Indole Prenyltransferases

    PubMed Central

    Yu, Xia; Liu, Yan; Xie, Xiulan; Zheng, Xiao-Dong; Li, Shu-Ming

    2012-01-01

    The putative prenyltransferase gene ACLA_031240 belonging to the dimethylallyltryptophan synthase superfamily was identified in the genome sequence of Aspergillus clavatus and overexpressed in Escherichia coli. The soluble His-tagged protein EAW08391 was purified to near homogeneity and used for biochemical investigation with diverse aromatic substrates in the presence of different prenyl diphosphates. It has shown that in the presence of dimethylallyl diphosphate (DMAPP), the recombinant enzyme accepted very well simple indole derivatives with l-tryptophan as the best substrate. Product formation was also observed for tryptophan-containing cyclic dipeptides but with much lower conversion yields. In contrast, no product formation was detected in the reaction mixtures of l-tryptophan with geranyl or farnesyl diphosphate. Structure elucidation of the enzyme products by NMR and MS analyses proved unequivocally the highly regiospecific regular prenylation at C-5 of the indole nucleus of the simple indole derivatives. EAW08391 was therefore termed 5-dimethylallyltryptophan synthase, and it filled the last gap in the toolbox of indole prenyltransferases regarding their prenylation positions. Km values of 5-dimethylallyltryptophan synthase were determined for l-tryptophan and DMAPP at 34 and 76 μm, respectively. Average turnover number (kcat) at 1.1 s−1 was calculated from kinetic data of l-tryptophan and DMAPP. Catalytic efficiencies of 5-dimethylallyltryptophan synthase for l-tryptophan at 25,588 s−1·m−1 and for other 11 simple indole derivatives up to 1538 s−1·m−1 provided evidence for its potential usage as a catalyst for chemoenzymatic synthesis. PMID:22123822

  7. 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)

  8. 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.

  9. INDUCED SUSCEPTIBILITY OF THE BLOOD TO INDOL

    PubMed Central

    Rhoads, C. P.; Miller, D. K.

    1938-01-01

    1. Indol, orally administered, causes anemia when certain deficient diets are fed. 2. The same amount of indol causes no considerable hematologic disturbance when normal diets are fed. 3. The anemia can be cured by supplementing the diet with liver extract, or by substituting a normal diet for the deficient diet. 4. Neither the diet alone nor the administration of indol alone produces marked anemia under the experimental conditions observed. PMID:19870720

  10. Study on the synthesis of the cyclopenta[f]indole core of raputindole A

    PubMed Central

    Marsch, Nils; Kock, Mario

    2016-01-01

    Summary The raputindoles from the rutaceous tree Raputia simulans share a cyclopenta[f]indole partial structure the synthesis of which is subject of this investigation. An efficient route to a series of 1,5-di(indol-6-yl)pentenones was developed via Mo/Au-catalyzed Meyer–Schuster rearrangement of tertiary propargylic alcohol precursors. However, none of the enones underwent the desired Nazarov cyclization to a cyclopenta[f]indole. More suitable were 6-hydroxyallylated indolines which gave good yields of cyclopenta[f]indolines after treatment with SnCl4, as soon as sterically demanding β-cyclocitral adducts were reacted. Most successful were Pt(II) and Au(I)-catalyzed cyclizations of N-TIPS-protected indolin-6-yl-substituted propargylacetates which provided the hydrogenated tricyclic cyclopenta[f]indole core system in high yield. PMID:26977193

  11. Study on the synthesis of the cyclopenta[f]indole core of raputindole A.

    PubMed

    Marsch, Nils; Kock, Mario; Lindel, Thomas

    2016-01-01

    The raputindoles from the rutaceous tree Raputia simulans share a cyclopenta[f]indole partial structure the synthesis of which is subject of this investigation. An efficient route to a series of 1,5-di(indol-6-yl)pentenones was developed via Mo/Au-catalyzed Meyer-Schuster rearrangement of tertiary propargylic alcohol precursors. However, none of the enones underwent the desired Nazarov cyclization to a cyclopenta[f]indole. More suitable were 6-hydroxyallylated indolines which gave good yields of cyclopenta[f]indolines after treatment with SnCl4, as soon as sterically demanding β-cyclocitral adducts were reacted. Most successful were Pt(II) and Au(I)-catalyzed cyclizations of N-TIPS-protected indolin-6-yl-substituted propargylacetates which provided the hydrogenated tricyclic cyclopenta[f]indole core system in high yield. PMID:26977193

  12. 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.

  13. 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.

  14. 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

  15. Responses of Pisum sativum L. to exogenous indole acetic acid application under manganese toxicity.

    PubMed

    Gangwar, Savita; Singh, Vijay Pratap; Maurya, Jagat Narayan

    2011-06-01

    Responses of pea (Pisum sativum L.) seedlings to manganese (50, 100 and 250 μM) and indole acetic acid (10 and 100 μM) treatments were investigated. Single and combined exposure of pea to manganese and 100 μM indole acetic acid decreased root and shoot fresh mass, chlorophyll, carotenoids, protein and nitrogen while ammonium content increased compared to the control. Combined treatment of pea with 250 μM manganese and 100 μM indole acetic acid decreased root and shoot fresh mass by 54% and 51%, chlorophyll and carotenoids by 31% and 26%, root and shoot protein by 47% and 44%, and root and shoot nitrogen by 44% and 40%, respectively. Activities of glutamine synthetase and glutamate synthase were decreased by the exposure of manganese and 100 μM indole acetic acid while glutamate dehydrogenase activity increased. Combined application of 250 μM manganese and 100 μM indole acetic acid decreased root and shoot glutamine synthetase activity by 44% and 39%, and glutamate synthase activity by 39% and 37% while root and shoot glutamate dehydrogenase activity increased by 47% and 42%, respectively compared to the control. In contrast, application of 10 μM indole acetic acid together with manganese decreased the negative impacts of manganese, and promoted seedling growth compared to the manganese treatments alone. This study has shown that 10 μM indole acetic acid protected pea seedlings appreciably from manganese toxicity by regulating ammonium content and the activities of enzymes of ammonium assimilation, while 100 μM of indole acetic acid exhibited opposite response under manganese toxicity. PMID:21516457

  16. 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.

  17. Design and synthesis of spiro[indole-thiazolidine]spiro[indole-pyrans] as antimicrobial agents.

    PubMed

    Sakhuja, Rajeev; Panda, Siva S; Khanna, Leena; Khurana, Shilpi; Jain, Subhash C

    2011-09-15

    A series of novel spiro[indole-thiazolidine]spiro[indole-pyran] derivatives were synthesized from N-(bromoalkyl)indol-2,3-diones via monospiro-bisindole intermediates; the two indole nuclei being connected via N-(CH(2))(n)-N linker. Synthesized compounds were evaluated for their antimicrobial activities in vitro against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, and Staphylococcus epidermis), four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumonia) as well as four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, and Candida albicans) using Cup plate method. Bis spiro-indoles exhibited stronger antibacterial and antifungal efficiency than their corresponding mono spiro-indoles. Compound 10e, the most active derivative was shown to inhibit the growth of all bacterial strains and two fungal strains (A. niger and C. albicans). PMID:21782421

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

    PubMed

    Jiang, Bo; Yi, Mian-Shuai; Shi, Feng; Tu, Shu-Jiang; Pindi, Suresh; McDowell, Patrick; Li, Guigen

    2012-01-21

    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.

  19. 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

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

    PubMed

    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

  1. 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. PMID:20060418

  2. 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

  3. Mechanistic studies on the indole prenyltransferases.

    PubMed

    Tanner, Martin E

    2015-01-01

    Covering: up to 2014. Prenylated indole alkaloids comprise a large and structurally diverse family of natural products that often display potent biological activities. In recent years a large family of prenyltransferases that install prenyl groups onto the indole core have been discovered. While the vast majority of these enzymes are evolutionarily related and share a common protein fold, they are remarkably versatile in their ability to catalyze reverse and normal prenylations at all positions on the indole ring. This highlight article will focus on recent studies of the mechanisms utilized by indole prenyltransferases. While all of the prenylation reactions may follow a direct electrophilic aromatic substitution mechanism, studies of structure and reactivity suggest that in some cases prenylation may first occur at the nucleophilic C-3 position, and subsequent rearrangements then generate the final product.

  4. 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

  5. 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

  6. Common rodent procedures.

    PubMed

    Klaphake, Eric

    2006-05-01

    Rodents are commonly owned exotic animal pets that may be seen by veterinary practitioners. Although most owners presenting their animals do care about their pets, they may not be aware of the diagnostic possibilities and challenges that can be offered by rodents to the veterinarian. Understanding clinical anatomy, proper hand-ling technique, realistic management of emergency presentations,correct and feasible diagnostic sampling, anesthesia, and humane euthanasia procedures is important to enhancing the doctor-client-patient relationship, especially when financial constraints may be imposed by the owner. PMID:16759953

  7. Biosynthesis of indole-3-acetic acid via the indole-3-acetamide pathway in Streptomyces spp.

    PubMed

    Manulis, S; Shafrir, H; Epstein, E; Lichter, A; Barash, I

    1994-05-01

    Various Streptomyces spp. including S. violaceus, S. scabies, S. griseus, S. exfoliatus, S. coelicolor and S. lividans secrete indole-3-acetic acid (IAA) when fed with L-tryptophan (Trp). Production of IAA was detected in Streptomyces strains causing potato scab as well as in non-pathogenic strains. The pathways for IAA synthesis from Trp were investigated in S. violaceus and S. exfoliatus. Indole-3-acetamide (IAM), indole-3-lactic acid (ILA), indole-3-ethanol (IEt) and IAA were identified by HPLC and GC-MS. Streptomyces cells were capable of catabolizing IAM, ILA, IEt and indole-3-acetaldehyde (IAAId) into IAA. Incorporation of radioactivity into IAM, IAA and ILA but not IEt was detected when cells were fed with L-[3-14C]tryptophan. Results indicate the presence of the IAM pathway (Trp-->IAM-->IAA) and the possible presence of additional pathways for IAA biosynthesis in Streptomyces. PMID:8025670

  8. 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

  9. Catalytic functionalization of indoles in a new dimension.

    PubMed

    Bandini, Marco; Eichholzer, Astrid

    2009-01-01

    140 years ago Adolf von Baeyer proposed the structure of a heteroaromatic compound which revolutionized organic and medical chemistry: indole. After more than a century, indole itself and the complexity of naturally occurring indole derivatives continue to inspire and influence developments in synthetic chemistry. In particular, the ubiquitous presence of indole rings in pharmaceuticals, agrochemicals, and functional materials are testament to the ever increasing interest in the design of mild and efficient synthetic routes to functionalized indole derivatives. This Review emphasizes the achievements in the selective catalytic functionalization of indoles (C-C bond-forming processes) over the last four years.

  10. Rodent models of osteoporosis

    PubMed Central

    Sophocleous, Antonia; Idris, Aymen I

    2014-01-01

    The aim of this protocol is to provide a detailed description of male and female rodent models of osteoporosis. In addition to indications on the methods of performing the surgical procedures, the choice of reliable and safe anaesthetics is also described. Post-operative care, including analgesia administration for pain management, is also discussed. Ovariectomy in rodents is a procedure where ovaries are surgically excised. Hormonal changes resulting from ovary removal lead to an oestrogen-deprived state, which enhances bone remodelling, causes bone loss and increases bone fracture risk. Therefore, ovariectomy has been considered as the most common preclinical model for understanding the pathophysiology of menopause-associated events and for developing new treatment strategies for tackling post-menopausal osteoporosis. This protocol also provides a detailed description of orchidectomy, a model for androgen-deficient osteoporosis in rodents. Endocrine changes following testes removal lead to hypogonadism, which results in accelerated bone loss, increasing osteoporosis risk. Orchidectomised rodent models have been proposed to mimic male osteoporosis and therefore remain a valuable tool for understanding androgen deficiency in aged men. Although it would have been particularly difficult to assemble an internationally acceptable description of surgical procedures, here we have attempted to provide a comprehensive guide for best practice in performing ovariectomy and orchidectomy in laboratory rodents. Research scientists are reminded that they should follow their own institution's interpretation of such guidelines. Ultimately, however, all animal procedures must be overseen by the local Animal Welfare and Ethical Review Body and conducted under licences approved by a regulatory ethics committee. PMID:25852854

  11. 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

  12. Developmental expression of GPR3 in rodent cerebellar granule neurons is associated with cell survival and protects neurons from various apoptotic stimuli.

    PubMed

    Tanaka, Shigeru; Miyagi, Tatsuhiro; Dohi, Eisuke; Seki, Takahiro; Hide, Izumi; Sotomaru, Yusuke; Saeki, Yoshinaga; Antonio Chiocca, E; Matsumoto, Masayasu; Sakai, Norio

    2014-08-01

    MCAO, GPR3-knockout mice exhibited a significantly larger infarct area than did wild-type mice. Collectively, these in vitro and in vivo results suggest that the developmental expression of constitutively active Gs-coupled GPR3 activates the ERK and Akt signaling pathways at the basal level, thereby protecting neurons from apoptosis that is induced by various stimuli. PMID:24769160

  13. Normal coordinate analysis of the indole ring

    NASA Astrophysics Data System (ADS)

    Takeuchi, Hideo; Harada, Issei

    Normal coordinate calculations have been performed for indole and 11 deuterated indoles. The set of valence force constants obtained is able to reproduce i.r. and Raman frequencies with an average error of about 6 cm -1. Extension of the force field to skatole has also been made and the calculated frequency shifts on isotopic substitutions are compared with the experimental ones of tryptophan. The general agreement between the calculation and experiment suggests that the vibrational modes obtained here are of practical use in the interpretation of Raman spectra of proteins containing tryptophan residues.

  14. Complementary Flavonoid Prenylations by Fungal Indole Prenyltransferases.

    PubMed

    Zhou, Kang; Yu, Xia; Xie, Xiulan; Li, Shu-Ming

    2015-09-25

    Flavonoids are found mainly in plants and exhibit diverse biological and pharmacological activities, which can often be enhanced by prenylations. In plants, such reactions are catalyzed by membrane-bound prenyltransferases. In this study, the prenylation of nine flavonoids from different classes by a soluble fungal prenyltransferase (AnaPT) involved in the biosynthesis of the prenylated indole alkaloid acetylaszonalenin is demonstrated. The behavior of AnaPT toward flavonoids regarding substrate acceptance and prenylation positions clearly differs from that of the indole prenyltransferase 7-DMATS. The two enzymes are therefore complementary in flavonoid prenylations.

  15. 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.

  16. 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

    2013-01-01

    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.

  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 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

  18. An indolent case of severe acute respiratory syndrome.

    PubMed

    Lam, Man-Fai; Ooi, Gaik C; Lam, Bing; Ho, James C; Seto, Wing H; Ho, Pak L; Wong, Poon C; Liang, Raymond; Lam, Wah K; Tsang, Kenneth W

    2004-01-01

    Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003. Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. She presented initially with fever and a normal chest radiograph. Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly. Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated.

  19. The benzyne Fischer-indole reaction.

    PubMed

    McAusland, Donald; Seo, Sangwon; Pintori, Didier G; Finlayson, Jonathan; Greaney, Michael F

    2011-07-15

    A new approach to the Fischer-indole synthesis is reported that uses the reactive intermediate benzyne. The addition of N-tosyl hydrazones to arynes, generated through fluoride activation of 2-(trimethylsilyl)phenyl triflate precursors, leads to efficient N-arylation. Addition of a Lewis acid to the same reaction pot then affords N-tosylindole products via Fischer cyclization.

  20. Asymmetric Hydrogenation of Unprotected Indoles Catalyzed by η(6)-Arene/N-Me-sulfonyldiamine-Ru(II) Complexes.

    PubMed

    Touge, Taichiro; Arai, Takayoshi

    2016-09-01

    Protecting-group-free transformation is a challenging and important issue in atom-economical organic synthesis. The η(6)-arene/N-Me-sulfonyldiamine-Ru(II)-BF4 complex-catalyzed asymmetric hydrogenation of 2-substituted unprotected indoles in weakly acidic hexafluoroisopropanol gives optically active indoline compounds with up to >99% ee. Under mild reaction media, halogen atoms and synthetically important protecting groups (e.g., silyl ether, acetal, benzyl ether, and ester) on indoles are maintained, which is advantageous for the synthesis of further complex indoline molecules. PMID:27509089

  1. Collective Synthesis of 3-Acylindoles, Indole-3-carboxylic Esters, Indole-3-sulfinic Acids, and 3-(Methylsulfonyl)indoles from Free (N-H) Indoles via Common N-Indolyl Triethylborate.

    PubMed

    Zhang, Zhi-Wei; Xue, Hong; Li, Hailing; Kang, Huaiping; Feng, Juan; Lin, Aijun; Liu, Shouxin

    2016-08-01

    A general and direct C3 functionalization of free (N-H) indoles with readily available electrophiles such as acid chlorides, chloroformates, thionyl chloride, and methylsulfonyl chloride via a common N-indolyl triethylborate intermediate is reported. The reaction proceeds smoothly under mild conditions in up to 93% yield. Indoles with substituents at the C2, C4, C5, C6, and C7 positions are well tolerated. The easy accessibility of a variety of important 3-acylindoles, indole-3-carboxylic esters, indole-3-sulfinic acids, and 3-(methylsulfonyl)indoles demonstrates the high degree of compatibility and practicability of this method. PMID:27457258

  2. 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.

  3. Reflections on Rodent Implantation.

    PubMed

    Cha, Jeeyeon M; Dey, Sudhansu K

    2015-01-01

    Embryo implantation is a complex process involving endocrine, paracrine, autocrine, and juxtacrine modulators that span cell-cell and cell-matrix interactions. The quality of implantation is predictive for pregnancy success. Earlier observational studies formed the basis for genetic and molecular approaches that ensued with emerging technological advances. However, the precise sequence and details of the molecular interactions involved have yet to be defined. This review reflects briefly on aspects of our current understanding of rodent implantation as a tribute to Roger Short's lifelong contributions to the field of reproductive physiology. PMID:26450495

  4. Biodegradation of indole by a newly isolated Cupriavidus sp. SHE.

    PubMed

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

    2015-08-01

    Indole, a typical nitrogen heterocyclic aromatic pollutant, is extensively spread in industrial wastewater. Microbial degradation has been proven to be a feasible approach to remove indole, whereas the microbial resources are fairly limited. A bacterial strain designated as SHE was isolated and found to be an efficient indole degrader. It was identified as Cupriavidus sp. according to 16S rRNA gene analysis. Strain SHE could utilize indole as the sole carbon source and almost completely degrade 100mg/L of indole within 24hr. It still harbored relatively high indole degradation capacity within pH4-9 and temperature 25°C-35°C. Experiments also showed that some heavy metals such as Mn(2+), Pb(2+) and Co(2+) did not pose severe inhibition on indole degradation. Based on high performance liquid chromatography-mass spectrum analysis, isatin was identified as a minor intermediate during the process of indole biodegradation. A major yellow product with m/z 265.0605 (C15H8N2O3) was generated and accumulated, suggesting a novel indole conversion pathway existed. Genome analysis of strain SHE indicated that there existed a rich set of oxidoreductases, which might be the key reason for the efficient degradation of indole. The robust degradation ability of strain SHE makes it a promising candidate for the treatment of indole containing wastewater. PMID:26257355

  5. Biodegradation of indole by a newly isolated Cupriavidus sp. SHE.

    PubMed

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

    2015-08-01

    Indole, a typical nitrogen heterocyclic aromatic pollutant, is extensively spread in industrial wastewater. Microbial degradation has been proven to be a feasible approach to remove indole, whereas the microbial resources are fairly limited. A bacterial strain designated as SHE was isolated and found to be an efficient indole degrader. It was identified as Cupriavidus sp. according to 16S rRNA gene analysis. Strain SHE could utilize indole as the sole carbon source and almost completely degrade 100mg/L of indole within 24hr. It still harbored relatively high indole degradation capacity within pH4-9 and temperature 25°C-35°C. Experiments also showed that some heavy metals such as Mn(2+), Pb(2+) and Co(2+) did not pose severe inhibition on indole degradation. Based on high performance liquid chromatography-mass spectrum analysis, isatin was identified as a minor intermediate during the process of indole biodegradation. A major yellow product with m/z 265.0605 (C15H8N2O3) was generated and accumulated, suggesting a novel indole conversion pathway existed. Genome analysis of strain SHE indicated that there existed a rich set of oxidoreductases, which might be the key reason for the efficient degradation of indole. The robust degradation ability of strain SHE makes it a promising candidate for the treatment of indole containing wastewater.

  6. Environmental enrichment for laboratory rodents.

    PubMed

    Hutchinson, Eric; Avery, Anne; Vandewoude, Sue

    2005-01-01

    Modernization of housing and husbandry techniques for rodents has minimized confounding variables. The result has been vastly improved health maintenance and reproducibility of research findings, advances that have decreased the numbers of animals needed to attain statistically significant results. Even though not all aspects of rodent manipulation have been strictly defined, as housing and handling procedures have become increasingly standardized, many animal care personnel have recognized the lack of complexity of the rodents' environment. Concern for this aspect of animal well-being has led many research facilities to provide "environmental enrichment" for rodents. Additionally, regulatory agencies in the United States and Europe have also been increasingly concerned about this issue relative to laboratory animal husbandry. However, little is known about the influence such husbandry modifications may have on biological parameters. In this article, laws and guidelines relating to rodent enrichment are reviewed, the natural behaviors of select rodent species are discussed, and an overview of widely used types of enrichment in laboratory rodent management is provided. The literature evaluating effects of rodent enrichment is reviewed both in terms of neurological development and as an experimental variable, and results of a study evaluating the effect of enrichment on immune and physiological parameters are reported. Survey data on current enrichment practices in a large multi-institutional organization are presented, and practical aspects requiring consideration when devising a rodent enrichment program are discussed.

  7. 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.

  8. Antifungal activities of some indole derivatives.

    PubMed

    Xu, Hui; Wang, Qin; Yang, Wen-Bin

    2010-01-01

    Nine indole derivatives were evaluated in vitro against Fusarium graminearum, Alternaria alternata, Helminthosporium sorokinianum, Pyricularia oryzae, Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. cucumarinum, and Alternaria brassicae. Most of the compounds were found to possess antifungal activities. Especially compounds 2, 5, 8, and 9 exhibited broad-spectrum antifungal activities against the above-mentioned seven phytopathogenic fungi, and showed more potent activities than hymexazole, a commercial agricultural fungicide. PMID:20737910

  9. 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.

  10. 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

  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. PMID:26670055

  12. Emended descriptions of indole negative and indole positive isolates of Brachyspira (Serpulina) hyodysenteriae.

    PubMed

    Fellström, C; Karlsson, M; Pettersson, B; Zimmerman, U; Gunnarsson, A; Aspan, A

    1999-12-01

    Two type/reference strains of Brachyspira (B.) hyodysenteriae, 14 Belgian and German indole negative, and 14 Belgian, German and Swedish indole positive field isolates of strongly beta-haemolytic intestinal spirochaetes were compared by pulsed-field gel electrophoresis (PFGE) patterns, biochemical reaction patterns, 16S rDNA sequences and MIC determinations of six antibacterial substances. Three tests for indole production, including a spot indole test, were compared with congruent results. All field isolates were classified as B. hyodysenteriae due to a high genetic and phenotypic similarity with the type strains. The Belgian and German indole negative isolates had identical and unique PFGE patterns for the tested restriction enzymes MluI and SalI, as well as identical 16S rDNA sequences, and they could not be differentiated by any of the methods used. Seven unique PFGE patterns were achieved from the 14 indole positive field isolates. The patterns were identical and unique for epidemiologically related isolates. Type/reference strains and isolates without known relation to other tested isolates showed unique banding patterns. The MICs of tylosin, tiamulin, erythromycin, clindamycin, carbadox and virginiamycin were determined in broth for all isolates. In contrast to Belgian and German isolates, the majority of the Swedish field isolates were susceptible to tylosin, erythromycin and clindamycin. Probable pathways of infection for some of the Swedish isolates were determined. The PFGE patterns of epidemic clones of B. hyodysenteriae remained stable for a period of up to 8 years. In vivo development of resistance to macrolide and lincosamide antibiotics due to use of tylosin was clearly indicated for two epidemic clones. PMID:10596806

  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. 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.

  15. Palladium-Catalyzed Oxidative Sulfenylation of Indoles and Related Electron-Rich Heteroarenes with Aryl Boronic Acids and Elemental Sulfur.

    PubMed

    Li, Jianxiao; Li, Chunsheng; Yang, Shaorong; An, Yanni; Wu, Wanqing; Jiang, Huanfeng

    2016-09-01

    An efficient and convenient palladium-catalyzed C-H bond oxidative sulfenylation of indoles and related electron-rich heteroarenes with aryl boronic acids and elemental sulfur has been described. This procedure provides a useful and direct approach for the assembly of a wide range of structurally diverse 3-sulfenylheteroarenes with moderate to excellent yields from simple and readily available starting materials. Moreover, this synthetic protocol is suitable for N-protected and unprotected indoles. Notably, the construction of two C-S bonds in one step was also achieved in this transformation. PMID:27500941

  16. Aerobic palladium(II)-catalyzed dehydrogenation of cyclohexene-1-carbonyl indole amides: an indole-directed aromatization.

    PubMed

    Kandukuri, Sandeep R; Oestreich, Martin

    2012-10-01

    A palladium(II)-catalyzed oxidative dehydrogenation of cyclohexene-1-carbonyl indole amides yielding the corresponding benzoylindoles is reported. The new aromatization is also applied to functionalized indoles such as tryptamine and tryptophan. The tethered indole is likely acting as a directing group for allylic C-H bond activation, and there is evidence for a mechanism proceeding through 1,3-diene formation followed by aromatization. PMID:22950832

  17. 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.

  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.

  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. Galanthindole: a new indole alkaloid from Galanthus plicatus ssp. byzantinus.

    PubMed

    Unver, Nehir; Kaya, G Irem; Werner, Christa; Verpoorte, Robert; Gözler, Belkis

    2003-09-01

    A new indole alkaloid, galanthindole, was isolated from Galanthus plicatus ssp. byzantinus (Amaryllidaceae), a plant native to northwestern Turkey. Incorporating a non-fused indole ring, galanthindole may represent the prototype of a new subgroup of the Amaryllidaceae alkaloids. Two other bases, (+)-11-hydroxyvittatine and hordenine, are also reported from the same plant.

  1. Electrophilicity: the "dark-side" of indole chemistry.

    PubMed

    Bandini, Marco

    2013-08-28

    Indole is by far one of the most popular heterocyclic scaffolds in nature. The intriguing and challenging molecular architectures of polycyclic, naturally occurring indolyl compounds constitute a continuous stimulus for development in organic synthesis. The field had a formidable boom across the new millennium when catalysis started revolutionizing the chemistry of indole, providing always more convincing and sustainable solutions to the selective "decoration" of this pharmacophore. A common guideline of these approaches relies on the intrinsic overexpression of electron density of the indole core. Despite less diffusion, the "dark-side" of indole reactivity, electrophilicity, has been also elegantly documented with direct applications towards the realization of specific interatomic connections that would be difficult to obtain by means of conventional indole reactivity. The present Perspective article summarizes the major findings that brought the research area from the pioneering findings of the 60s to the state of the art.

  2. New pathway for the biodegradation of indole in Aspergillus niger

    SciTech Connect

    Kamath, A.; Vaidyanathan, C.S. )

    1990-01-01

    Indole and its derivatives form a class of toxic recalcitrant environmental pollutants. The growth of Aspergillus niger was inhibited by very low concentrations (0.005 to 0.02%) of indole, even when 125- to 500-fold excess glucose was present in the medium. When 0.02% indole was added, the fungus showed a lag phase for about 30 h and the uptake of glucose was inhibited. Indole was metabolized by a new pathway via indoxyl (3-hydroxyindole), N-formylanthranilic acid, anthranilic acid, 2,3-dihydroxybenzoic acid, and catechol, which was further degraded by an ortho cleavage. The enzymes N-formylanthranilate deformylase, anthranilate hydroxylase, 2,3-dihydroxybenzoate decarboxylase, and catechol dioxygenase were induced by indole as early as after 5 h of growth, and their activities were demonstrated in a cell-free system.

  3. Synthesis and characterization of novel indole derivatives reveal improved therapeutic agents for treatment of ischemia/reperfusion (I/R) injury.

    PubMed

    Bi, Wei; Bi, Yue; Xue, Ping; Zhang, Yanrong; Gao, Xiang; Wang, Zhibo; Li, Meng; Baudy-Floc'h, Michèle; Ngerebara, Nathaniel; Gibson, K Michael; Bi, Lanrong

    2010-09-23

    To develop more potent therapeutic agents with therapeutic efficacy for ischemia/reperfusion (I/R) injury, we linked an antiinflammatory moiety (1,3-dioxane derivative) to the key pharmacophoric moiety of melatonin. We hypothesized that the resulting new indole derivatives might induce a synergistic protection against oxidative damage associated with I/R injury. Our results indicate that one of these indole derivatives (7) manifests potent antiinflammatory antioxidant effects and exerts a protective effect against skeletal muscle injury and associated lung injury following limb I/R in rats. PMID:20731361

  4. 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

  5. Antitumor Activity of Bis-Indole Derivatives

    PubMed Central

    Andreani, Aldo; Burnelli, Silvia; Granaiola, Massimiliano; Leoni, Alberto; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Varoli, Lucilla; Landi, Laura; Prata, Cecilia; Berridge, Michael V.; Grasso, Carole; Fiebig, Heinz-Herbert; Kelter, Gerhard; Burger, Angelika M.; Kunkel, Mark W.

    2009-01-01

    This paper reports the synthesis of compounds formed by two indole systems separated by a heterocycle (pyridine or piperazine). As a primary screening, the new compounds were submitted to the National Cancer Institute for evaluation of antitumor activity in the human cell line screen. The pyridine derivatives were far more active than the piperazine derivatives. For the study of the mechanism of action, the most active compounds were subjected to COMPARE analysis and to further biological tests including proteasome inhibition and inhibition of plasma membrane electron transport. The compound bearing the 5-methoxy-2-indolinone moiety was subjected to the first in vivo experiment (hollow fiber assay) and was active. It was therefore selected for the second in vivo experiment (human tumor xenograft in mice). In conclusion we demonstrated that this approach was successful since some of the compounds described are much more active than the numerous, so far prepared and tested 3-indolylmethylene-2-indolinones. PMID:18598018

  6. 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

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

    PubMed

    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

  8. 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. PMID:21261883

  9. 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.

  10. 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.

  11. 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. PMID:25155666

  12. Metal-Catalyzed Cross-Coupling Reactions for Indoles

    NASA Astrophysics Data System (ADS)

    Li, Jie Jack; Gribble, Gordon W.

    Metal-catalyzed cross-coupling reactions for indoles are reviewed. Palladium-catalyzed cross-coupling reactions are the most widely explored and applied of all metal-catalyzed cross-coupling reactions. Applications of Kumada coupling, Negishi coupling, Suzuki coupling, Stille coupling, Sonogashira reaction, the Heck reaction, carbonylation, and C-N bond formation reactions in indoles are summarized. In addition, other transition metal-catalyzed cross-coupling reactions using copper, rhodium, iron, and nickel in indole synthesis are also discussed.

  13. Synthesis and anti-inflammatory activity of indole glucosinolates.

    PubMed

    Vo, Quan V; Trenerry, Craige; Rochfort, Simone; Wadeson, Jenny; Leyton, Carolina; Hughes, Andrew B

    2014-01-15

    The nitronate and nitrovinyl methods to synthesize indole glucosinolates (GLs) have been investigated. The results were applied to generally the most prevalent natural indole glucosinolates to synthesize 4-methoxyglucobrassicin (MGB) and neo-glucobrassicin (NGB) in moderate overall yield for the first time. The anti-inflammatory activity of the synthetic indole GLs was determined by inhibition of TNF-α secretion in LPS-stimulated THP-1 cells. The data showed that glucobrassicin (GB) exhibited higher activity than other synthetic indolyl GLs. PMID:24360830

  14. 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

  15. 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.

  16. 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....

  17. 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....

  18. 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....

  19. 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....

  20. 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....

  1. 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

  2. Indole and 7-benzyloxyindole attenuate the virulence of Staphylococcus aureus.

    PubMed

    Lee, Jin-Hyung; Cho, Hyun Seob; Kim, Younghoon; Kim, Jung-Ae; Banskota, Suhrid; Cho, Moo Hwan; Lee, Jintae

    2013-05-01

    Human pathogens can readily develop drug resistance due to the long-term use of antibiotics that mostly inhibit bacterial growth. Unlike antibiotics, antivirulence compounds diminish bacterial virulence without affecting cell viability and thus, may not lead to drug resistance. Staphylococcus aureus is a major agent of nosocomial infections and produces diverse virulence factors, such as the yellow carotenoid staphyloxanthin, which promotes resistance to reactive oxygen species (ROS) and the host immune system. To identify novel antivirulence compounds, bacterial signal indole present in animal gut and diverse indole derivatives were investigated with respect to reducing staphyloxanthin production and the hemolytic activity of S. aureus. Treatment with indole or its derivative 7-benzyloxyindole (7BOI) caused S. aureus to become colorless and inhibited its hemolytic ability without affecting bacterial growth. As a result, S. aureus was more easily killed by hydrogen peroxide (H₂O₂) and by human whole blood in the presence of indole or 7BOI. In addition, 7BOI attenuated S. aureus virulence in an in vivo model of nematode Caenorhabditis elegans, which is readily infected and killed by S. aureus. Transcriptional analyses showed that both indole and 7BOI repressed the expressions of several virulence genes such as α-hemolysin gene hla, enterotoxin seb, and the protease genes splA and sspA and modulated the expressions of the important regulatory genes agrA and sarA. These findings show that indole derivatives are potential candidates for use in antivirulence strategies against persistent S. aureus infection. PMID:23318836

  3. 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

  4. 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. PMID:23604981

  5. N-alkenyl indoles as useful intermediates for alkaloid synthesis.

    PubMed

    Li, Hao; Boonnak, Nawong; Padwa, Albert

    2011-11-18

    A mild cross-coupling reaction to access several N-alkenyl-substituted indoles has been developed. The coupling procedure involves treating a NH-indole with various alkenyl bromides using a combination of 10 mol % of copper(I) iodide and 20 mol % of ethylenediamine as the catalyst in dioxane at 110 °C in the presence of K(3)PO(4) as the base. When treated with acid, these unique enamines produce a dimeric product derived from a preferred protonation reaction at the enamine π-bond. A cationic cyclization reaction of the readily available 2-(2-(1H-indol-1-yl)allyl)cyclopentanol was utilized to construct tetracyclic indole derivatives with a quaternary stereocenter attached to the C(2)-position of the indole ring. An alternative strategy for selective functionalization at the C(2)-position of a N-alkenyl-substituted indole derivative that was also studied involves a radical cyclization of a xanthate derivative. The work described provides an attractive route to the tetracyclic core of some vinca alkaloids, including the tetrahydroisoquinocarbazole RS-2135. PMID:22007631

  6. 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. PMID:27101475

  7. Synthesis of Fused Polycyclic Indoles by Brønsted Acid-Catalyzed Intramolecular Alkylation of Indoles with Alcohols.

    PubMed

    Suárez, Anisley; Gohain, Mukut; Fernández-Rodríguez, Manuel A; Sanz, Roberto

    2015-10-16

    An efficient methodology for the synthesis of a series of new fused polyclyclic indoles has been developed by Brønsted acid-catalyzed intramolecular Friedel-Crafts reactions of properly designed indolyl alcohols. PMID:26418556

  8. Bioactive indole alkaloids isolated from Alstonia angustifolia

    PubMed Central

    Pan, Li; Terrazas, César; Muñoz Acuña, Ulyana; Ninh, Tran Ngoc; Chai, Heebyung; Carcache de Blanco, Esperanza J.; Soejarto, Djaja D.; Satoskar, Abhay R.

    2014-01-01

    Bioassay-guided fractionation was conducted on a CHCl3-soluble extract of the stem bark of Alstonia angustifolia (Apocynaceae) collected in Vietnam using the HT-29 human colon cancer cell line, and led to the isolation of a new sarpagine-type indole alkaloid (1), together with nine known alkaloids, including four macroline-derived alkaloids (2–5), a sarpagine-type alkaloid (6), and four macroline-pleiocarpamine bisindole alkaloids (7–10). The structure of the new compound (1) was determined on the basis of spectroscopic data interpretation. Compounds 1–10 were evaluated in vitro for their NF-κB (p65) inhibitory activity against the Hela cells in an ELISA assay. The new sarpagine alkaloid, N(4)-methyltalpinine (1), was found to show significant NF-κB inhibitory activity (ED50 = 1.2 µM). Furthermore, all the isolates (1–10) were evaluated in vitro for their antileishmanial activity, and compounds (1–4, 6 and 8–10) exhibited leishmaniacidal activity against promastigotes of Leishmania mexicana. PMID:25584095

  9. 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.

  10. Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Secreting Merozoite Surface Protein 1 (MSP1) Induces Protection against Rodent Malaria Parasite Infection Depending on MSP1-stimulated Interferon γ and Parasite-specific Antibodies

    PubMed Central

    Matsumoto, Sohkichi; Yukitake, Hideharu; Kanbara, Hiroji; Yamada, Takeshi

    1998-01-01

    The merozoite surface protein 1 (MSP1) has emerged as a leading malaria vaccine candidate at the erythrocytic stage. Recombinant bacillus Calmette-Guérin (rBCG), which expressed a COOH-terminal 15-kD fragment of MSP1 of Plasmodium yoelii (MSP1-15) as a fusion protein with a secretory protein of Mycobacterium kansasii, was constructed. Immunization of mice with this rBCG induced a higher degree of protection against blood-stage parasite infection than with recombinant MSP1-15 in the RIBI adjuvant (RIBI ImmunoChem Research, Inc., Hamilton, MT) or incomplete Freund's adjuvant systems. We studied the mechanism of protection induced by MSP1-15, and found that interferon (IFN)-γ had a major role in protection in all adjuvant systems we examined. Mice that produced low amounts of MSP1-15 stimulated IFN-γ and could not control parasite infection. The antibody against MSP1-15 did not play a major role in protection in this system. After parasite infection, immunoglobulin G2a antibodies, which had been produced by IFN-γ stimulation, were induced and subsequently played an important role in eradicating parasites. Thus, both cellular and humoral immune responses were essential for protection from malaria disease. These data revealed that BCG is a powerful adjuvant to induce such a protective immune response against malaria parasites. PMID:9730886

  11. 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

  12. Design, synthesis and biological evaluation of novel chiral oxazino-indoles as potential and selective neuroprotective agents against Aβ25-35-induced neuronal damage.

    PubMed

    Chen, Jing; Tao, Ling-Xue; Xiao, Wei; Ji, Sha-Sha; Wang, Jian-Rong; Li, Xu-Wen; Zhang, Hai-Yan; Guo, Yue-Wei

    2016-08-01

    A series of chiral oxazino-indoles have been synthesized via a key intermolecular oxa-Pictet-Spengler reaction. These compounds exhibited significant and selective neuroprotective effects against Aβ25-35-induced neuronal damage. This is the first report of evaluating the influence of chiral diversity of oxazino-indoles on their neuroprotective activities, with the structure-activity relationship been analyzed. The highly active compounds 3f, 3g, 4g, 4h, and 6b all performed over 90% cell protection, providing a new direction for the development of neuroprotective agents against Alzheimer's disease. PMID:27301369

  13. 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. PMID:27558084

  14. 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.

  15. 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

  16. Environmental factors affecting indole metabolism under anaerobic conditions.

    PubMed Central

    Madsen, E L; Francis, A J; Bollag, J M

    1988-01-01

    The influence of physiological and environmental factors on the accumulation of oxindole during anaerobic indole metabolism was investigated by high-performance liquid chromatography. Under methanogenic conditions, indole was temporarily converted to oxindole in stoichiometric amounts in media inoculated with three freshwater sediments and an organic soil. In media inoculated with methanogenic sewage sludge, the modest amounts of oxindole detected at 35 degrees C reached higher concentrations and persisted longer when the incubation temperature was decreased from 35 to 15 degrees C. Also, decreasing the concentration of sewage sludge used as an inoculum from 50 to 1% caused an increase in the accumulation of oxindole from 10 to 75% of the indole added. Under denitrifying conditions, regardless of the concentration or source of the inoculum, oxindole appeared in trace amounts but did not accumulate during indole metabolism. In addition, denitrifying consortia which previously metabolized indole degraded oxindole with no lag period. Our data suggest that oxindole accumulation under methanogenic, but not under denitrifying conditions is caused by differences between relative rates of oxindole production and destruction. PMID:3345080

  17. Evolution of aromatic prenyltransferases in the biosynthesis of indole derivatives.

    PubMed

    Li, Shu-Ming

    2009-01-01

    A series of putative indole prenyltransferase genes could be identified in the genome sequences of different fungal strains including Aspergillus fumigatus and Neosartorya fischeri. The gene products show significant sequence similarities to dimethylallyltryptophan synthases from different fungi. We have cloned and overexpressed seven of these genes, fgaPT1, fgaPT2, ftmPT1, ftmPT2, 7-dmats, cdpNPT and anaPT in Escherichia coli and Saccharomyces cerevisiae. The overproduced enzymes were characterised biochemically. Three additional indole prenyltransferases, DmaW-Cs, TdiB and MaPT were also identified and characterised in the last years. Sequence analysis and comparison with known aromatic prenyltransferases as well as biochemical investigation revealed that these enzymes belong to a group of aromatic prenyltransferases. The characterised prenyltransferases are soluble proteins, catalyse different prenyl transfer reactions on indole moieties of various substrates and do not require divalent metal ions for their prenyl transfer reactions. In addition, indole prenyltransferases carry tryptophan aminopeptidase activity, which strengths their relationship in the evolution. These properties differ clearly from membrane-bound aromatic prenyltransferases from different sources and soluble prenyltransferases from bacteria. All of the indole prenyltransferases accepted only dimethylallyl diphosphate as prenyl donor. On the other hand, they showed broad substrate specificity towards their aromatic substrates. Diverse simple tryptophan derivatives and tryptophan-containing cyclic dipeptides were accepted by these enzymes, providing a strategy for convenient production of biologically active substances, e.g. by chemoenzymatic synthesis.

  18. Development and Characterization of Monoclonal Antibodies Specific for 3-(1-naphthoyl) Indole Derivatives.

    PubMed

    Nakayama, Hiroshi; Kenjyou, Noriko; Ito, Yuji

    2016-02-01

    3-(1-naphthoyl) indole is one of the raw materials that synthesizes a synthetic cannabinoid such as 1-pentyl-3-(1-naphthoyl) indole (JWH-018) and 1-butyl-3-(1-naphthoyl) indole (JWH-073). It is important to detect the 3-(1-naphthoyl) indole derivatives rapidly, sensitively, and comprehensively. We developed two monoclonal antibodies (MAb) against 3-(1-naphthoyl) indole derivatives, named NT1 (IgG1) and NT2 (IgG1), which were possibly effective for detecting 3-(1-naphthoyl) indole derivatives. The cross-reactive ability of these MAbs was evaluated using a competitive enzyme-linked immunosorbent assay (ELISA). In the results, we found both of these antibodies recognize 3-(1-naphthoyl) indole and its derivatives. However neither of these antibodies recognize naphtoic acid, 4-methyl-naphtoic acid, and indole. Sixty to 100 nanomole per liter of 3-(1-naphthoyl) indole derivatives, such as 1-methyl-3-(1-naphthoyl) indole, 1-ethyl-3-(1-naphthoyl) indole, and 1-octyl-3-(1-naphthoyl) indole, can be detected using both of the obtained MAbs. Thus, the MAbs produced in this study could be a useful tool for the detection of 3-(1-naphthoyl) indole derivatives. PMID:26871514

  19. Development and Characterization of Monoclonal Antibodies Specific for 3-(1-naphthoyl) Indole Derivatives.

    PubMed

    Nakayama, Hiroshi; Kenjyou, Noriko; Ito, Yuji

    2016-02-01

    3-(1-naphthoyl) indole is one of the raw materials that synthesizes a synthetic cannabinoid such as 1-pentyl-3-(1-naphthoyl) indole (JWH-018) and 1-butyl-3-(1-naphthoyl) indole (JWH-073). It is important to detect the 3-(1-naphthoyl) indole derivatives rapidly, sensitively, and comprehensively. We developed two monoclonal antibodies (MAb) against 3-(1-naphthoyl) indole derivatives, named NT1 (IgG1) and NT2 (IgG1), which were possibly effective for detecting 3-(1-naphthoyl) indole derivatives. The cross-reactive ability of these MAbs was evaluated using a competitive enzyme-linked immunosorbent assay (ELISA). In the results, we found both of these antibodies recognize 3-(1-naphthoyl) indole and its derivatives. However neither of these antibodies recognize naphtoic acid, 4-methyl-naphtoic acid, and indole. Sixty to 100 nanomole per liter of 3-(1-naphthoyl) indole derivatives, such as 1-methyl-3-(1-naphthoyl) indole, 1-ethyl-3-(1-naphthoyl) indole, and 1-octyl-3-(1-naphthoyl) indole, can be detected using both of the obtained MAbs. Thus, the MAbs produced in this study could be a useful tool for the detection of 3-(1-naphthoyl) indole derivatives.

  20. 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.

  1. Clinical hematology of rodent species.

    PubMed

    Pilny, Anthony A

    2008-09-01

    Pet rodents, such as rats, guinea pigs, and chinchillas, differ from more traditional companion animal species in many aspects of their hematologic parameters. Animals within this order have much diversity in size, anatomy, methods of restraint, and blood collection technique. Appropriate sample collection is often the most challenging aspect of the diagnostic protocol, and inappropriate restraint may cause a stress response that interferes with blood test results. For many of these patients, sedation is required and can also affect results as well. In most cases, however, obtaining a standard database is necessary and very possible when providing medical care for this popular group of pets. PMID:18675732

  2. [Occurrence of indole alkaloids among secondary metabolites of soil Aspergillus].

    PubMed

    Vinokurova, N G; Khmel'nitskaia, I I; Baskunov, B P; Arinbasarov, M U

    2003-01-01

    The occurrence of indole alkaloids among secondary fungal metabolites was studied in species of the genus Aspergillus, isolated from soils that were sampled in various regions of Russia (a total of 102 isolates of the species A. niger, A. phoenicis, A. fumigatus, A. flavus, A. versicolor, A. ustus, A. clavatus, and A. ochraceus). Clavine alkaloids were represented by fumigaclavine, which was formed by A. fumigatus. alpha-Cyclopiazonic acid was formed by isolates of A. fumigatus, A. flavus, A. versicolor, A. phoenicis, and A. clavatus. The occurrence of indole-containing diketopiperazine alkaloids was documented for isolates of A. flavus, A. fumigatus, A. clavatus, and A. ochraceus. No indole-containing metabolites were found among the metabolites of A. ustus or A. niger. PMID:12722658

  3. 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

  4. Inhibition of the MAP3 kinase Tpl2 protects rodent and human β-cells from apoptosis and dysfunction induced by cytokines and enhances anti-inflammatory actions of exendin-4

    PubMed Central

    Varin, E M; Wojtusciszyn, A; Broca, C; Muller, D; Ravier, M A; Ceppo, F; Renard, E; Tanti, J-F; Dalle, S

    2016-01-01

    Proinflammatory cytokines exert cytotoxic effects on β-cells, and are involved in the pathogenesis of type I and type II diabetes and in the drastic loss of β-cells following islet transplantation. Cytokines induce apoptosis and alter the function of differentiated β-cells. Although the MAP3 kinase tumor progression locus 2 (Tpl2) is known to integrate signals from inflammatory stimuli in macrophages, fibroblasts and adipocytes, its role in β-cells is unknown. We demonstrate that Tpl2 is expressed in INS-1E β-cells, mouse and human islets, is activated and upregulated by cytokines and mediates ERK1/2, JNK and p38 activation. Tpl2 inhibition protects β-cells, mouse and human islets from cytokine-induced apoptosis and preserves glucose-induced insulin secretion in mouse and human islets exposed to cytokines. Moreover, Tpl2 inhibition does not affect survival or positive effects of glucose (i.e., ERK1/2 phosphorylation and basal insulin secretion). The protection against cytokine-induced β-cell apoptosis is strengthened when Tpl2 inhibition is combined with the glucagon-like peptide-1 (GLP-1) analog exendin-4 in INS-1E cells. Furthermore, when combined with exendin-4, Tpl2 inhibition prevents cytokine-induced death and dysfunction of human islets. This study proposes that Tpl2 inhibitors, used either alone or combined with a GLP-1 analog, represent potential novel and effective therapeutic strategies to protect diabetic β-cells. PMID:26794660

  5. 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.

  6. 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...

  7. Brønsted Acid-Catalyzed Cascade Reactions Involving 1,2-Indole Migration.

    PubMed

    Álvarez, Estela; Nieto Faza, Olalla; Silva López, Carlos; Fernández-Rodríguez, Manuel A; Sanz, Roberto

    2015-09-01

    A cascade reaction of indoles with propargylic diols involving an unprecedented metal-free 1,2-indole migration onto an alkyne was carried out. DFT calculations support a mechanism consisting of a concerted nucleophilic attack of the indole nucleus with loss of water, followed by the 1,2-migration and subsequent Nazarov cyclization. This Brønsted acid-catalyzed protocol affords indole-functionalized benzofulvene derivatives in high yields. PMID:26211757

  8. 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

  9. Regulation of Indole Signalling during the Transition of E. coli from Exponential to Stationary Phase.

    PubMed

    Gaimster, Hannah; Summers, David

    2015-01-01

    During the transition from exponential to stationary phase E. coli produces a substantial quantity of the small, aromatic signalling molecule indole. In LB medium the supernatant indole concentration reaches a maximum of 0.5-1 mM. At this concentration indole has been implicated in many processes inducing acid resistance and the modulation of virulence. It has recently been shown that cell-associated indole transiently reaches a very high concentration (approx. 60 mM) during stationary phase entry, presumably because indole is being produced more rapidly than it can leave the cell. It is proposed that this indole pulse inhibits growth and cell division, causing the culture to enter stationary phase before nutrients are completely exhausted, with benefits for survival in long-term stationary phase. This study asks how E. coli cells rapidly upregulate indole production during stationary phase entry and why the indole pulse has a duration of only 10-15 min. We find that at the start of the pulse tryptophanase synthesis is triggered by glucose depletion and that this is correlates with the up-regulation of indole synthesis. The magnitude and duration of the resulting indole pulse are dependent upon the availability of exogenous tryptophan. Indole production stops when all the available tryptophan is depleted and the cell-associated indole equilibrates with the supernatant.

  10. Regulation of Indole Signalling during the Transition of E. coli from Exponential to Stationary Phase

    PubMed Central

    Gaimster, Hannah; Summers, David

    2015-01-01

    During the transition from exponential to stationary phase E. coli produces a substantial quantity of the small, aromatic signalling molecule indole. In LB medium the supernatant indole concentration reaches a maximum of 0.5–1 mM. At this concentration indole has been implicated in many processes inducing acid resistance and the modulation of virulence. It has recently been shown that cell-associated indole transiently reaches a very high concentration (approx. 60 mM) during stationary phase entry, presumably because indole is being produced more rapidly than it can leave the cell. It is proposed that this indole pulse inhibits growth and cell division, causing the culture to enter stationary phase before nutrients are completely exhausted, with benefits for survival in long-term stationary phase. This study asks how E. coli cells rapidly upregulate indole production during stationary phase entry and why the indole pulse has a duration of only 10–15 min. We find that at the start of the pulse tryptophanase synthesis is triggered by glucose depletion and that this is correlates with the up-regulation of indole synthesis. The magnitude and duration of the resulting indole pulse are dependent upon the availability of exogenous tryptophan. Indole production stops when all the available tryptophan is depleted and the cell-associated indole equilibrates with the supernatant. PMID:26332864

  11. Direct regioselective oxidative cross-coupling of indoles with methyl ketones: a novel route to C3-dicarbonylation of indoles.

    PubMed

    Gao, Qinghe; Zhang, Jingjing; Wu, Xia; Liu, Shan; Wu, Anxin

    2015-01-01

    The first C3-dicarbonylation of indoles was realized through direct oxidative cross-coupling of indoles with methyl ketones in the presence of molecular iodine and pyrrolidine. This reaction constructed a highly efficient indolyl diketones scaffold, which might be regarded as a useful biological and pharmacological tool in the exploration of therapeutic A2BAR modulators. The use of inexpensive molecular iodine and pyrrolidine and a broad substrate scope make this protocol very practical. Preliminary mechanistic studies indicate that two paths are involved in this process.

  12. Rodents as agents of ecological change

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rodents have the potential to exert a wide array of ecological pressures in any given ecosystem. The negative impacts to plant communities in general, especially cultivated crops, are typically cited as examples of rodent grazing pressure. Considerable research has been conducted on the negative imp...

  13. Rodent Control: Seal Up! Trap Up! Clean Up!

    MedlinePlus

    ... successfully trapping rodents in and around the home. Seal Up! Seal up holes inside and outside the home to ... infested areas. Before cleaning, trap the rodents and seal up any entryways to ensure that no rodents ...

  14. KO(t)Bu-Mediated Coupling of Indoles and [60]Fullerene: Transition-Metal-Free and General Synthesis of 1,2-(3-Indole)(hydro)[60]fullerenes.

    PubMed

    Li, Fei; Haj Elhussin, Imad Elddin; Li, Shengli; Zhou, Hongping; Wu, Jieying; Tian, Yupeng

    2015-11-01

    Direct coupling of indoles with C60 has been achieved for the first time. Transition-metal-free KO(t)Bu-mediated reaction of indoles to [60]fullerene has been developed as a practical and efficient method for the synthesis of various 1,2-(3-indole)(hydro)[60]fullerenes that are otherwise difficult to direct synthesize in an efficient and selective manner. This methodology tolerates sensitive functionalities such as chloro, ester, and nitro on indole and builds molecular complexity rapidly, with most reactions reaching completion in <1 h. A plausible reaction mechanism is proposed to explain the high regioselectivity at the 3-position of the indoles and the formation of 1,2-(3-indole)(hydro)[60]fullerenes.

  15. 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.

  16. Photolysis of Indole-Containing Mycotoxins to Fluorescent Products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Gas-phase electronic spectrum of the indole radical cation

    NASA Astrophysics Data System (ADS)

    Chalyavi, N.; Catani, K. J.; Sanelli, J. A.; Dryza, V.; Bieske, E. J.

    2015-08-01

    The visible and near-UV electronic spectrum of the indole radical cation is measured in the gas phase by photodissociation of indole+-Ar and indole+-He complexes in a tandem mass spectrometer. A series of resolved vibronic transitions extending from 610 to 460 nm are assigned to the D2 ← D0 band system, while weak transitions between 390 and 360 nm are assigned to the D3 ← D0 system, and a stronger, broad, unresolved absorption between 350 and 300 nm is attributed to the D4 ← D0 system. Time-dependent density functional theory calculations are used to assign vibronic structure of the D2 ← D0 band system, and show that the main active vibrational modes correspond to in-plane ring deformations. The strongest D2 ← D0 vibronic transitions of indole+-He do not correspond with any catalogued diffuse interstellar bands, even considering band displacements of up to 50 cm-1possibly caused by the attached He atom.

  18. 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

    2016-08-01

    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. PMID:27403650

  19. Copper-catalyzed intermolecular asymmetric propargylic dearomatization of indoles.

    PubMed

    Shao, Wen; Li, He; Liu, Chuan; Liu, Chen-Jiang; You, Shu-Li

    2015-06-22

    The first copper-catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee. PMID:25968474

  20. 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

    2016-08-01

    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.

  1. 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.

  2. Exposure to rodents and rodent-borne viruses among persons with elevated occupational risk.

    PubMed

    Fritz, Curtis L; Fulhorst, Charles F; Enge, Barryett; Winthrop, Kevin L; Glaser, Carol A; Vugia, Duc J

    2002-10-01

    Persons who have frequent contact with rodents as part of their occupation may be at increased risk of exposure to rodent-borne viruses such as Sin Nombre virus (SNV), the agent of hantavirus pulmonary syndrome, and Whitewater Arroyo virus (WWA), a New World arenavirus. Eighty-one persons with possible occupational exposure to rodents completed questionnaires and provided specimens for serologic testing. Seventy-two participants reported handling rodents as part of their job. The mean total number of rodents handled during participants' careers was approximately 2200. IgG antibody to lymphocytic choriomeningitis virus was detected in serum from one (1.2%) participant. IgG antibody to SNV, WWA, and Amapari viruses was not detected in any of the serum specimens. Despite considerable exposure to rodents, participants did not have significant serological evidence of exposure to rodent-borne viruses. PMID:12391776

  3. 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. PMID:27604726

  4. Indole molecules as inhibitors of tubulin polymerization: potential new anticancer agents, an update (2013-2015).

    PubMed

    Patil, Renukadevi; Patil, Siddappa A; Beaman, Kenneth D; Patil, Shivaputra A

    2016-07-01

    Discovery of new indole-based tubulin polymerization inhibitors will continue to dominate the synthetic efforts of many medicinal chemists working in the field. The indole ring system is an essential part of several tubulin inhibitors identified in the recent years. The present review article will update the synthesis, anticancer and tubulin inhibition activities of several important new indole classes such as 2-phenylindoles (28, 29 & 30), oxindoles (35 & 38), indole-3-acrylamides (44), indolines (46), aroylindoles (49), carbozoles (75, 76 & 82), azacarbolines (87) and annulated indoles (100-105). PMID:27476704

  5. Explaining level inversion of the La and Lb States of indole and indole derivatives in polar solvents.

    PubMed

    Brisker-Klaiman, Daria; Dreuw, Andreas

    2015-06-01

    Quantum chemical methods are used to study the solvent effects on the spectra of indole and a series of methyl-substituted indoles. We focus on the low-lying L(a) and L(b) states and study their interplay. We find that the solvent mainly affects emission from the L(a) state, by stabilizing its energy in its excited-state geometry. The stabilization of the L(a) state increases with increasing solvent polarity, which accounts for the large fluorescence shift observed in indoles and leads to an inversion in the nature of the lowest emitting state, from L(b) in vacuum to L(a) in water. To the best of our knowledge, this is the first theoretical evidence for level inversion done for a series of indoles. The underlying mechanism of level inversion is analyzed in detail. The usual interpretation of level inversion in terms of their static dipole moment is criticized and an improved predictive measurement is suggested.

  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. PMID:27570307

  8. 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. PMID:27263428

  9. 3-Methylindole (skatole) and indole production by mixed populations of pig fecal bacteria.

    PubMed Central

    Jensen, M T; Cox, R P; Jensen, B B

    1995-01-01

    Pig fecal slurries converted added L-tryptophan either to indole without detectable intermediates or to 3-methylindole (skatole) via indole-3-acetate. The initial rate of production of 3-methylindole was greatest at pH 6.5 and less at pH 5.0 and 8.0; the initial rates of indole production were similar at pH 6.5 and 8.0. More than 80% of the tryptophan added was converted to 3-methylindole at pH 5.0; at pH 8.0 85% was converted to indole. Both pathways had similar Km values for tryptophan and similar maximum rates. Indole-3-carbinol and indole-3-acetonitrile completely inhibited the production of 3-methylindole from indole-3-acetate but had no effect on the reactions involving L-tryptophan. PMID:7487051

  10. A Rapid and Specific Method for the Detection of Indole in Complex Biological Samples

    PubMed Central

    Chappell, Cynthia; Gonzales, Christopher; Okhuysen, Pablo

    2015-01-01

    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. PMID:26386049

  11. 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

  12. 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

  13. Rodent-borne diseases in Thailand: targeting rodent carriers and risky habitats

    PubMed Central

    Herbreteau, Vincent; Bordes, Frédéric; Jittapalapong, Sathaporn; Supputamongkol, Yupin; Morand, Serge

    2012-01-01

    Background Comparative analysis, which aims at investigating ecological and evolutionary patterns among species, may help at targeting reservoirs of zoonotic diseases particularly in countries presenting high biodiversity. Here, we developed a simple method to target rodent reservoirs using published studies screening microparasite infections. Methods We compiled surveys of microparasites investigated in rodents trapped in Thailand. The data comprise a total of 17,358 rodents from 18 species that have been investigated for a total of 10 microparasites (viruses, bacteria and protozoans). We used residual variation of microparasite richness controlled for both rodent sample size and pathogens’ screening effort to identify major rodent reservoirs and potential risky habitats. Results Microparasite species richness was positively related to rodent sample size and pathogens’ screening effort. The investigation of the residual variations of microparasite species richness showed that several rodent species harboured more pathogens than expected by the regression model. Similarly, higher pathogen richness than expected was observed in rodents living in non-flooded lands, forests and paddy fields. Conclusion Our results suggest to target some rodent species that are not commonly investigated for pathogen screening or surveillance such as R. adamanensis or B. savilei, and that non-flooded lands and forests should be more taken into caution, whereas much surveys focused on paddy rice fields and households. PMID:22957129

  14. 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.

  15. 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.

  16. 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. PMID:24405288

  17. 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.

  18. 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.

  19. 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. PMID:23971813

  20. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract

    PubMed Central

    Perry, Anamarija M.; Warnke, Roger A.; Hu, Qinglong; Gaulard, Philippe; Copie-Bergman, Christiane; Alkan, Serhan; Wang, Huan-You; Cheng, Jason X.; Bacon, Chris M.; Delabie, Jan; Ranheim, Erik; Kucuk, Can; Hu, XiaoZhou; Weisenburger, Dennis D.

    2013-01-01

    Primary gastrointestinal (GI) T-cell lymphoma is an infrequent and aggressive disease. However, rare indolent clonal T-cell proliferations in the GI tract have been described. We report 10 cases of GI involvement by an indolent T-cell lymphoproliferative disease, including 6 men and 4 women with a median age of 48 years (range, 15-77 years). Presenting symptoms included abdominal pain, diarrhea, vomiting, food intolerance, and dyspepsia. The lesions involved oral cavity, esophagus, stomach, small intestine, and colon. The infiltrates were dense, but nondestructive, and composed of small, mature-appearing lymphoid cells. Eight cases were CD4−/CD8+, 1 was CD4+/CD8−, and another was CD4−/CD8−. T-cell receptor-γ chain gene rearrangement identified a clonal population in all 10 cases. There was no evidence of STAT3 SH2 domain mutation or activation. Six patients received chemotherapy because of an initial diagnosis of peripheral T-cell lymphoma, with little or no response, whereas the other 4 were followed without therapy. After a median follow-up of 38 months (range, 9-175 months), 9 patients were alive with persistent disease and 1 was free of disease. We propose the name “indolent T-LPD of the GI tract” for these lesions that can easily be mistaken for intestinal peripheral T-cell lymphoma, and lead to aggressive therapy. PMID:24009234

  1. 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

  2. The Fecal Viral Flora of Wild Rodents

    PubMed Central

    Phan, Tung G.; Kapusinszky, Beatrix; Wang, Chunlin; Rose, Robert K.; Lipton, Howard L.; Delwart, Eric L.

    2011-01-01

    The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat) collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in mammals. PMID:21909269

  3. 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.

  4. 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. PMID:26567952

  5. 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.

  6. Anthranilate Deteriorates the Structure of Pseudomonas aeruginosa Biofilms and Antagonizes the Biofilm-Enhancing Indole Effect

    PubMed Central

    Kim, Soo-Kyoung; Park, Ha-Young

    2015-01-01

    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. PMID:25616795

  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. 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. PMID:27005963

  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 MAM rodent model of schizophrenia.

    PubMed

    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 hyperlocomotion, which can be utilized to verify the MAM phenotype.

  11. 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

  12. Asymmetric Total Synthesis of the Indole Diterpene Alkaloid Paspaline.

    PubMed

    Sharpe, Robert J; Johnson, Jeffrey S

    2015-10-01

    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.

  13. 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.

  14. Indole-based allosteric inhibitors of HIV-1 integrase.

    PubMed

    Patel, Pratiq A; Kvaratskhelia, Nina; Mansour, Yara; Antwi, Janet; Feng, Lei; Koneru, Pratibha; Kobe, Mathew J; Jena, Nivedita; Shi, Guqin; Mohamed, Mosaad S; Li, Chenglong; Kessl, Jacques J; Fuchs, James R

    2016-10-01

    Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket. The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC50=4.5μM) and, as predicted based on the geometry of the five- versus six-membered ring, retained activity against the A128T IN mutant that confers resistance to many quinoline-based ALLINIs. PMID:27568085

  15. 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

  16. Extraction and analysis of indole derivatives from fungal biomass.

    PubMed

    Gartz, J

    1994-01-01

    The occurrence and extraction of indole derivatives in six species from four genera of higher fungi were investigated. By using pure methanol for extraction of the mushrooms analysis revealed the highest concentrations of psilocybin and baeocystin. The psilocin content of the species was higher by using aqueous solutions of alcohols than with methanol alone but was an artificial phenomenon caused by enzymatic destruction of psilocybin. The extraction with dilute acetic acid yielded better results than with the water containing alcohols. The simple one-step procedure with methanol for the quantitative extraction is still the safest method to obtain the genuine alkaloids from fungal biomass.

  17. Antifouling indole alkaloids from two marine derived fungi.

    PubMed

    He, Fei; Han, Zhuang; Peng, Jiang; Qian, Pei-Yuan; Qi, Shu-Hua

    2013-03-01

    In order to find non-toxic antifouling natural products from marine microorganisms, the chemical constituents of two marine derived fungi Penicillium sp. and Aspergillus sydowii have been investigated under bio-guided fractionation. A new indolyl diketopiperazine compound, penilloid A (1), together with 15 known ones were isolated from these two strains. The structure of 1 was elucidated on the basis of NMR and mass spectra. Some alkaloids showed significant antifouling and antibacterial activities. The results indicate that indole alkaloids could be a potential antifouling agent resource.

  18. A new prenylated indole diketopiperazine alkaloid from Eurotium cristatum.

    PubMed

    Zou, Xianwei; Li, Ying; Zhang, Xiaona; Li, Qian; Liu, Xuan; Huang, Yun; Tang, Tao; Zheng, Saijing; Wang, Weimiao; Tang, Jintian

    2014-11-03

    A new prenylated indole diketopiperazine alkaloid, cristatumin F (1), and four known metabolites, echinulin (2), dehydroechinulin (3), neoechinulin A (4) and variecolorin O (5), were isolated from the crude extract of the fungus Eurotium cristatum. The structure of 1 was elucidated primarily by NMR and MS methods. The absolute configuration of 1 was assigned using Marfey's method applied to its acid hydrolyzate. Cristatumin F (1) showed modest radical scavenging activity against DPPH radicals, and exhibited marginal attenuation of 3T3L1 pre-adipocytes.

  19. Chronic infection of rodents by Machupo virus.

    PubMed

    Johnson, K M; Mackenzie, R B; Webb, P A; Kuns, M L

    1965-12-17

    Machupo virus, the etiologic agent of human hemorrhagic fever in Bolivia, induced chronic asymptomatic infection in laboratory hamsters and colonized individuals of the peridomestic, wild, South American rodent, Calomys callosus. Viruria was detected for more than 500 and 150 days, respectively, in the two species. Chronic viremia was shown only for Calomys. Virus-neutralizing substances were present in parenterally infected adult animals, but not in animals born to, and in contact with, an infected female. Chronic infection in wild rodents may be an important mechanism in the natural history of Machupo and related virus infections.

  20. 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.

  1. 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

  2. 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. PMID:24982671

  3. Construction of Pyrrolo[1,2-a]indoles via Cobalt(III)-Catalyzed Enaminylation of 1-(Pyrimidin-2-yl)-1H-indoles with Ketenimines and Subsequent Base-Promoted Cyclization.

    PubMed

    Zhou, Xiaorong; Fan, Zili; Zhang, Zhiyin; Lu, Ping; Wang, Yanguang

    2016-09-16

    A cobalt(III)-catalyzed cross-coupling reaction of 1-(pyrimidin-2-yl)-1H-indoles with ketenimines is reported. The reaction provided 2-enaminylated indole derivatives in moderate to excellent yields with a broad substrate scope. The prepared 2-enaminylated indoles could be conveniently converted into pyrrolo[1,2-a]indoles, which are an important class of compounds in medicinal chemistry. PMID:27599189

  4. Pharmacokinetics of DS-96, an alkylpolyamine lipopolysaccharide sequestrant, in rodents.

    PubMed

    Shrestha, Anurupa; Li, Rongti; Sil, Diptesh; Pardeshi, Neha N; Schwarting, Nancy; Schorno, Karl S; Rajewski, Roger A; Datta, Apurba; David, Sunil A

    2008-12-01

    The pharmacokinetics of DS-96, an N-alkylhomospermine analog designed to sequester bacterial lipopolysaccharides, has been determined in rodent species. The elimination half-life in mice and rats are about 400 and 500 min, respectively, with other PK parameters being quite similar in the two rodent species. Interestingly, the mouse intravenous plasma concentration time curves exhibit an apparent absorption phase. While the rat intravenous data did not exhibit a pronounced apparent absorption phase immediately following injection, plasma levels did increase between 10 and 30 min following an expected drop from time 0 to 5 min. The data are consistent with first-pass uptake, possibly by the lung, with back diffusion as a function of time. The observed C(max) values of 1.36 microg/mL in the mouse intraperitoneal model suggest that a plasma concentration of 0.5-1 microg/mL corresponds to complete protection for a 200 ng/animal dose of intraperitoneally administered LPS in the D-galactosamine-primed model of endotoxin-induced lethality.

  5. Indole prenyltransferases from fungi: a new enzyme group with high potential for the production of prenylated indole derivatives.

    PubMed

    Steffan, N; Grundmann, A; Yin, W-B; Kremer, A; Li, S-M

    2009-01-01

    Prenylated indole derivatives are hybrid natural products containing both aromatic and isoprenoid moieties and are widely spread in plants, fungi and bacteria. Some of these complex natural products, e.g. the ergot alkaloids ergotamine and fumigaclavine C as well as the diketopiperazine derivative fumitremorgin C and its biosynthetic precursors tryprostatin A and B, show a wide range of biological and pharmacological activities. Prenyl transfer reactions catalysed by prenyltransferases represent key steps in the biosynthesis of these compounds and often result in formation of products which possess biological activities distinct from their non-prenylated precursors. Recently, a series of putative indole prenyltransferase genes could be identified in the genome sequences of different fungal strains including Aspergillus fumigatus. The gene products show significant sequence similarities to dimethylallyltryptophan synthases from fungi. We have cloned and overexpressed six of these genes, fgaPT1, fgaPT2, ftmPT1, ftmPT2, 7-dmats and cdpNPT from A. fumigatus in E. coli and S. cerevisiae. The overproduced enzymes were characterised biochemically. Three additional prenyltransferases, DmaW-Cs, TdiB and MaPT were identified and characterised in a Clavicipitalean fungus, Aspergillus nidulans and Malbranchea aurantiaca, respectively. Sequence analysis and alignments with known aromatic prenyltransferases as well as phylogenetic analysis revealed that these enzymes belong to a new group of "aromatic prenyltransferases". They differ clearly from membrane-bound aromatic prenyltransferases from different sources and soluble prenyltransferases from bacteria. The characterised enzymes are soluble proteins, catalyse different prenyl transfer reactions on indole moieties of various substrates and do not require divalent metal ions for their enzymatic reactions. All of the enzymes accepted only dimethylallyl diphosphate as prenyl donor. On the other hand, they showed broad substrate

  6. Indole prenyltransferases from fungi: a new enzyme group with high potential for the production of prenylated indole derivatives.

    PubMed

    Steffan, N; Grundmann, A; Yin, W-B; Kremer, A; Li, S-M

    2009-01-01

    Prenylated indole derivatives are hybrid natural products containing both aromatic and isoprenoid moieties and are widely spread in plants, fungi and bacteria. Some of these complex natural products, e.g. the ergot alkaloids ergotamine and fumigaclavine C as well as the diketopiperazine derivative fumitremorgin C and its biosynthetic precursors tryprostatin A and B, show a wide range of biological and pharmacological activities. Prenyl transfer reactions catalysed by prenyltransferases represent key steps in the biosynthesis of these compounds and often result in formation of products which possess biological activities distinct from their non-prenylated precursors. Recently, a series of putative indole prenyltransferase genes could be identified in the genome sequences of different fungal strains including Aspergillus fumigatus. The gene products show significant sequence similarities to dimethylallyltryptophan synthases from fungi. We have cloned and overexpressed six of these genes, fgaPT1, fgaPT2, ftmPT1, ftmPT2, 7-dmats and cdpNPT from A. fumigatus in E. coli and S. cerevisiae. The overproduced enzymes were characterised biochemically. Three additional prenyltransferases, DmaW-Cs, TdiB and MaPT were identified and characterised in a Clavicipitalean fungus, Aspergillus nidulans and Malbranchea aurantiaca, respectively. Sequence analysis and alignments with known aromatic prenyltransferases as well as phylogenetic analysis revealed that these enzymes belong to a new group of "aromatic prenyltransferases". They differ clearly from membrane-bound aromatic prenyltransferases from different sources and soluble prenyltransferases from bacteria. The characterised enzymes are soluble proteins, catalyse different prenyl transfer reactions on indole moieties of various substrates and do not require divalent metal ions for their enzymatic reactions. All of the enzymes accepted only dimethylallyl diphosphate as prenyl donor. On the other hand, they showed broad substrate

  7. 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.

  8. Formation of Cyclohepta[b]indole Scaffolds via Heck Cyclization: A Strategy for Structural Analogues of Ervatamine Group of Indole Alkaloid.

    PubMed

    Goswami, Progyashree; Borah, Arun Jyoti; Phukan, Prodeep

    2015-01-01

    Ervatamine, silicine, methuenine, etc., are naturally occurring alkaloids that exhibit antimicrobial, anticancer, and anti-HIV activities. Indole fused with a seven-membered carbocyclic ring is a commonly observed structural feature among this series of bioactive compounds. This work describes a strategic approach for the synthesis of cyclohepta[b]indole structural scaffolds. The synthetic strategy consists of a solvent-free Baylis-Hillman reaction of 2-bromobenzaldehydes, followed by iodine-catalyzed C-alkylation of indole with the Baylis-Hillman adducts. Finally, intramolecular Heck coupling reaction using Pd(OAc)2 as catalyst in the presence of benzyltrimethylammonium bromide under microwave condition produced the desired cyclohepta[b]indole derivatives.

  9. (E)-2-Methyl-3-(2-methyl-2-nitrovinyl)-1H-indole and (E)-3-(2-methyl-2-nitrovinyl)-2-phenyl-1H-indole.

    PubMed

    Sonar, Vijayakumar N; Parkin, Sean; Crooks, Peter A

    2005-08-01

    In the title compounds, C12H12N2O2, (I), and C17H14N2O2, (II), respectively, the indole rings are planar and the vinyl groups lie out of the indole planes, making dihedral angles of 33.48 (5) and 41.31 (8) degrees , respectively. In (II), the dihedral angle between the phenyl and indole ring planes is 32.06 (6) degrees . In both molecules, the double bond connecting the methylnitrovinyl group and the indole nucleus adopts an E configuration. Notwithstanding the differences in space group [C2/c for (I) and P2(1)2(1)2(1) for (II)], the mode of packing of compounds (I) and (II) is determined by similar intermolecular N-H...O hydrogen-bonding interactions, forming chains that run parallel to [101] in (I) and [001] in (II).

  10. Gold-catalyzed synthesis of tetrahydrocarbazole derivatives through an intermolecular cycloaddition of vinyl indoles and N-allenamides.

    PubMed

    Pirovano, Valentina; Decataldo, Laura; Rossi, Elisabetta; Vicente, Rubén

    2013-05-01

    A gold-catalyzed formal [4+2] cycloaddition of vinyl indoles and N-allenamides leading to tetrahydrocarbazoles is described. Moreover, new multicomponent reactions of vinyl indoles with two allene molecules are reported.

  11. N-Amination of pyrrole and indole heterocycles with monochloramine (NH2Cl).

    PubMed

    Hynes, John; Doubleday, Wendel W; Dyckman, Alaric J; Godfrey, Jollie D; Grosso, John A; Kiau, Susanne; Leftheris, Katerina

    2004-02-20

    A survey of several electrophilic ammonia reagents for the N-amination of indole- and pyrrole-containing heterocycles revealed that monochloramine (NH(2)Cl) is an excellent reagent for this transformation. Pyrroles and indoles containing a variety of substitution were aminated on nitrogen with isolated yields ranging from 45% to 97%. PMID:14961694

  12. 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. PMID:25040570

  13. Synthesis and preliminary evaluation of 3-thiocyanato-1H-indoles as potential anticancer agents.

    PubMed

    Fortes, Margiani P; da Silva, Paulo B N; da Silva, Teresinha G; Kaufman, Teodoro S; Militão, Gardenia C G; Silveira, Claudio C

    2016-08-01

    A novel series of twenty 3-thiocyanato-1H-indoles, carrying diversification at positions N-1, C-2 and C-5 of the heterocyclic core, were synthesized; their antiproliferative activity against four human cancer cell lines (HL60, HEP-2, NCI-H292 and MCF-7) was evaluated, employing doxorubicin as positive control. Indole, N-methylindole and 2-(4-chlorophenyl)-N-methylindole demonstrated to be essentially inactive, whereas several of their congener 3-thiocyanato-1H-indoles displayed good to excellent levels of potency (IC50 ≤ 6 μM), while being non-hemolytic. N-Phenyl-3-thiocyanato-1H-indole and 1-methyl-2-(4-chlorophenyl)-3-thiocyanato-1H-indole showed good to high potency against all the cell lines. On the other side, the N-(4-chlorophenyl)-, 2-(4-chlorophenyl)- and 2-phenyl- 3-thiocyanato-1H-indole derivatives were slightly less active against the test cell lines. Overall, these results suggest that the indole-3-thiocyanate motif can be suitably decorated to afford highly cytotoxic compounds and that the substituted indole can be employed as a useful scaffold toward more potent compounds.

  14. Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway.

    PubMed

    Alverez, Celeste; Bulfer, Stacie L; Chakrasali, Ramappa; Chimenti, Michael S; Deshaies, Raymond J; Green, Neal; Kelly, Mark; LaPorte, Matthew G; Lewis, Taber S; Liang, Mary; Moore, William J; Neitz, R Jeffrey; Peshkov, Vsevolod A; Walters, Michael A; Zhang, Feng; Arkin, Michelle R; Wipf, Peter; Huryn, Donna M

    2016-02-11

    A high-throughput screen to discover inhibitors of p97 ATPase activity identified an indole amide that bound to an allosteric site of the protein. Medicinal chemistry optimization led to improvements in potency and solubility. Indole amide 3 represents a novel uncompetitive inhibitor with excellent physical and pharmaceutical properties that can be used as a starting point for drug discovery efforts. PMID:26985295

  15. Comparison of three reagents for detecting indole production by anaerobic bacteria in microtest systems.

    PubMed Central

    Lombard, G L; Dowell, V R

    1983-01-01

    Three reagents for detecting indole, Kovac, Ehrlich, and p-dimethylaminocinnamaldehyde (DMCA), were evaluated with commercial microtest systems for characterizing and identifying anaerobic bacteria. The DMCA reagent, the most sensitive of the three reagents, gave a positive reaction with 445 of 449 strains of various indole-producing anaerobic bacteria. There was 99.6% agreement between the results obtained with the DMCA in the microtest systems and results using the conventional tube test to detect indole by using xylene extraction and Ehrlich reagent. Ehrlich reagent detected indole in 163 of 176 (92.6%) indole-positive strains when the inoculum was overlaid with mineral oil before incubation. Kovac reagent was the least sensitive of the reagents tested. When the inoculum was overlaid with mineral oil, Kovac reagent detected only 80 of 108 (74.0%) of indole-positive strains. In addition to being the most sensitive reagent for detection indole, DMCA also allowed detection of indole derivatives (skatole, 3-indolepropionic acid, and 3-indolebutyric acid) produced by some clostridia. PMID:6630445

  16. Metal free sulfenylation and bis-sulfenylation of indoles: persulfate mediated synthesis.

    PubMed

    Prasad, Ch Durga; Kumar, Shailesh; Sattar, Moh; Adhikary, Amit; Kumar, Sangit

    2013-12-14

    A method which avoids metal and halogen for the synthesis of 3-arylthioindoles from indoles and diaryl disulfides using ammonium persulfate in methanol has been presented. Moreover, double C-H sulfenylation of indoles at 2 and 3-positions has also been achieved using iodine and ammonium persulfate. PMID:24166084

  17. 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). PMID:26959867

  18. Two new cytotoxic indole alkaloids from a deep-sea sediment derived metagenomic clone.

    PubMed

    Yan, Xia; Tang, Xi-Xiang; Chen, Lin; Yi, Zhi-Wei; Fang, Mei-Juan; Wu, Zhen; Qiu, Ying-Kun

    2014-04-01

    Two new indole alkaloids, metagenetriindole A (1) and metagenebiindole A (2), were identified from deep-sea sediment metagenomic clone derived Escherichia coli fermentation broth. The structures of new compounds were elucidated by spectroscopic methods. The two new indole alkaloids demonstrated moderately cytotoxic activity against CNE2, Bel7402 and HT1080 cancer cell lines in vitro.

  19. Synthesis of 8-phenyl-10H-pyrido(1,2-. cap alpha. )indole salts from 2,3,3-trimethyl-3H-indole chlorides with cinnamaldehyde

    SciTech Connect

    Shachkus, A.A.; Degutis, Yu.A.

    1987-10-01

    Reaction of 2,3,3-trimethyl-3H-indole chloride with cinnamic and 4-dimethylaminocinnamic aldehydes led to salts of 8-phenyl and 8-(4-dimethylaminophenyl)-10,10-dimethyl-10H-pyrido(1,2-..cap alpha..)indole. PMR spectra were recorded on a Tesla BS-487C (80 MHz) instrument (internal standard HMDS) and IR spectra on a UR-20 spectrometer (KBr pellets).

  20. 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. PMID:27193305

  1. 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…

  2. 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

  3. 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. PMID:26701202

  4. 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.

  5. 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...

  6. 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....

  7. 7 CFR 58.247 - 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. 58.247 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, 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...

  9. 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...

  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, 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...

  12. 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...

  13. 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...

  14. 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....

  15. 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....

  16. 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...

  17. 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....

  18. 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...

  19. 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.

  20. [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. PMID:25771679

  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. Aplysinopsins--marine indole alkaloids: chemistry, bioactivity and ecological significance.

    PubMed

    Bialonska, Dobroslawa; Zjawiony, Jordan K

    2009-01-01

    Aplysinopsins are tryptophan-derived marine natural products isolated from numerous genera of sponges and scleractinian corals, as well as from one sea anemone and one nudibranch. Aplysinopsins are widely distributed in the Pacific, Indonesia, Caribbean, and Mediterranean regions. Up to date, around 30 analogues occurring in Nature have been reported. Natural aplysinopsins differ in the bromination pattern of the indole ring, variation in the structure of the C ring, including the number and position of N-methylation, the presence and configuration of the C-8-C-1' double bond, and the oxidation state of the 2-aminoimidazoline fragment. Aplysinopsins can also occur in the form of dimers. This review summarizes 30 years' research on aplysinopsins. The origin, isolation sources, chemistry, bioactivity, and ecological functions of aplysinopsins are comprehensively reviewed. PMID:19597579

  3. 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.

  4. 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). PMID:27320301

  5. Aplysinopsins - Marine Indole Alkaloids: Chemistry, Bioactivity and Ecological Significance

    PubMed Central

    Bialonska, Dobroslawa; Zjawiony, Jordan K.

    2009-01-01

    Aplysinopsins are tryptophan-derived marine natural products isolated from numerous genera of sponges and scleractinian corals, as well as from one sea anemone and one nudibranch. Aplysinopsins are widely distributed in the Pacific, Indonesia, Caribbean, and Mediterranean regions. Up to date, around 30 analogues occurring in Nature have been reported. Natural aplysinopsins differ in the bromination pattern of the indole ring, variation in the structure of the C ring, including the number and position of N-methylation, the presence and configuration of the C-8-C-1′ double bond, and the oxidation state of the 2-aminoimidazoline fragment. Aplysinopsins can also occur in the form of dimers. This review summarizes 30 years’ research on aplysinopsins. The origin, isolation sources, chemistry, bioactivity, and ecological functions of aplysinopsins are comprehensively reviewed. PMID:19597579

  6. 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).

  7. Biogenetically inspired synthesis and skeletal diversification of indole alkaloids.

    PubMed

    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.

  8. 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.

  9. 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.

  10. Nonradiative decay mechanisms of complexed indole derivatives studied by time-resolved fluorescence

    NASA Astrophysics Data System (ADS)

    Schauerte, Joseph A.; Gafni, Ari

    1990-05-01

    Ground and excited state characteristics of substituted indole derivatives reveal a sensitivity of indoles' electronic properties to the nature and location of substitutions on the indole ring. These substitutions affect both the nature of the excited electronic state and the susceptibility of this state to non-radiative decay processes. A number of mechanisms that deactivate the excited state have been identified including intersystem crossing, electron photoejection into polar solvents, and >N-H dissociation in polar solvents (see Glasser & Lami,1986) . While the >N-H group has been implicated in non-radiative decay processes in polar solvents, covalent substitutions elsewhere on the indole molecule may modulate the importance of this site in non-radiative decay mechanisms or alternatively these substitutions may introduce new deactivation mechanisms. Additionally, complexes formed between indole derivatives and β-cyclodextrin cavities show different sensitivity to excited state deactivation mechanisms dependent upon the location and nature of the covalent substitution. We have investigated the excited states of some indole derivatives substituted at position 5, para to the >N-H group on the benzyl ring, to determine the effect of such covalent substitutions on the fluorescence emission characteristics of the indole ring as well as on its susceptibility to alternate excited state decay mechanisms.

  11. Evidences of Hfq associates with tryptophanase and affects extracellular indole levels.

    PubMed

    Zhang, Yinghua; Hong, Guofan

    2009-08-01

    In this study, we observed a novel property of Escherichia coli Hfq protein: it possibly influenced extracellular indole levels. The extracellular indole concentrations were increased in Hfq mutant cells and decreased in Hfq overexpression cells in a cell density-dependent manner. The decreased extracellular indole levels in Hfq overexpression cells caused the postponement of entering into stationary phase. Indole was produced by tryptophanase, the gene product of tnaA, which catalyzed tryptophan into indole, ammonia and pyruvate. Further studies showed that at cell density of 0.8 but not at 0.4, tryptophanase activities of total cell extracts were affected by Hfq mutation or overexpression. Protein pull-down assay and co-immunoprecipitation experiments revealed that Hfq associated with tryptophanase under relatively higher extracellular indole levels, suggesting this was a feedback control of indole production. The association of Hfq and tryptophanase might be indirect because purified Hfq could not affect the values of Km and Vmax of purified tryptophanase.

  12. 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.

  13. Inhibition of monoamine oxidase by indole-5,6-dicarbonitrile derivatives.

    PubMed

    Chirkova, Zhanna V; Kabanova, Mariya V; Filimonov, Sergey I; Abramov, Igor G; Petzer, Anél; Petzer, Jacobus P; Firgang, Sergey I; Suponitsky, Kyrill Yu

    2015-03-15

    Recent studies have found that phthalonitrile derivatives are remarkably potent inhibitors of human monoamine oxidase (MAO) A and B. In an attempt to further determine the structure-activity relationships (SARs) for MAO inhibition by this class of compounds and to discover novel potent MAO inhibitors, the present study investigated the MAO inhibition properties of a series consisting of indole-5,6-dicarbonitrile derivatives. The results document that 3-chloro-1H-indole-5,6-dicarbonitrile derivatives exhibited potent inhibition of the MAOs. For example, 3-chloro-2-(4-methylphenyl)-1H-indole-5,6-dicarbonitrile inhibited MAO-A and MAO-B with IC50 values of 0.014μM and 0.017μM, respectively. It was further shown that this compound acts as a reversible and competitive inhibitor of both MAO isoforms. An analysis of the SARs for MAO inhibition by 3-chloro-1H-indole-5,6-dicarbonitriles showed that methylation of the indole nitrogen eliminates MAO-B inhibition activity, and replacement of the 2-phenyl ring with the thienyl results in a 9-fold reduction of MAO-B inhibition activity. A series of 3-bromo-1-hydroxy-1H-indole-5,6-dicarbonitriles are, in turn, comparatively weaker MAO inhibitors. It may be concluded that indole-5,6-dicarbonitrile derivatives are suitable leads for the design MAO inhibitors for the treatment of disorders such as Parkinson's disease and depression.

  14. 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

  15. Indole synthesis by conjugate addition of anilines to activated acetylenes and an unusual ligand-free copper(II)-mediated intramolecular cross-coupling.

    PubMed

    Gao, Detian; Back, Thomas G

    2012-11-12

    A versatile new synthesis of indoles was achieved by the conjugate addition of N-formyl-2-haloanilines to acetylenic sulfones, ketones, and esters followed by a copper-catalyzed intramolecular C-arylation. The conjugate addition step was conducted under exceptionally mild conditions at room temperature in basic, aqueous DMF. Surprisingly, the C-arylation was performed most effectively by employing copper(II) acetate as the catalyst in the absence of external ligands, without the need for protection from air or water. An unusual feature of this process, for the case of acetylenic ketones, is the ability of the initial conjugate-addition product to serve as a ligand for the catalyst, which enables it to participate in the catalysis of its further transformation to the final indole product. Mechanistic studies, including EPR experiments, indicated that copper(II) is reduced to the active copper(I) species by the formate ion that is produced by the base-catalyzed hydrolysis of DMF. This process also served to recycle any copper(II) that was produced by the adventitious oxidation of copper(I), thereby preventing deactivation of the catalyst. Several examples of reactions involving acetylenic sulfones attached to a modified Merrifield resin demonstrated the feasibility of solid-phase synthesis of indoles by using this protocol, and tricyclic products were obtained in one pot by employing acetylenic sulfones that contain chloroalkyl substituents. PMID:23019064

  16. 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. PMID:24189618

  17. Rodent reservoirs of future zoonotic diseases.

    PubMed

    Han, Barbara A; Schmidt, John Paul; Bowden, Sarah E; Drake, John M

    2015-06-01

    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.

  18. 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

  19. 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. PMID:27249068

  20. Models of Oxygen Induced Retinopathy in Rodents.

    PubMed

    Gammons, Melissa V; Bates, David O

    2016-01-01

    Much of the knowledge we have gained into the development of pathological ocular angiogenesis has come from the development of in vivo models that enable functional assessment of key components of signaling pathways in disease progression. Indeed, rodent models have facilitated identification of several therapeutics that target pathological angiogenesis. Two of the most widely used rodent models of oxygen induced retinopathy (OIR), Smith's mouse model and Penn's rat model reproducibly induce neovascularization reminiscent of the disease retinopathy of prematurity (ROP). In this chapter we discuss development of ROP in humans and compare features with that of the rat and mouse models, focusing both on the benefits and caveats of using such models. Furthermore, we discuss in detail the methodology of both procedures and discuss the importance of various features of the model. PMID:27172964

  1. Volumes of cochlear nucleus regions in rodents.

    PubMed

    Godfrey, Donald A; Lee, Augustine C; Hamilton, Walter D; Benjamin, Louis C; Vishwanath, Shilpa; Simo, Hermann; Godfrey, Lynn M; Mustapha, Abdurrahman I A A; Heffner, Rickye S

    2016-09-01

    The cochlear nucleus receives all the coded information about sound from the cochlea and is the source of auditory information for the rest of the central auditory system. As such, it is a critical auditory nucleus. The sizes of the cochlear nucleus as a whole and its three major subdivisions - anteroventral cochlear nucleus (AVCN), posteroventral cochlear nucleus (PVCN), and dorsal cochlear nucleus (DCN) - have been measured in a large number of mammals, but measurements of its subregions at a more detailed level for a variety of species have not previously been made. Size measurements are reported here for the summed granular regions, DCN layers, AVCN, PVCN, and interstitial nucleus in 15 different rodent species, as well as a lagomorph, carnivore, and small primate. This further refinement of measurements is important because the granular regions and superficial layers of the DCN appear to have some different functions than the other cochlear nucleus regions. Except for DCN layers in the mountain beaver, all regions were clearly identifiable in all the animals studied. Relative regional size differences among most of the rodents, and even the 3 non-rodents, were not large and did not show a consistent relation to their wide range of lifestyles and hearing parameters. However, the mountain beaver, and to a lesser extent the pocket gopher, two rodents that live in tunnel systems, had relative sizes of summed granular regions and DCN molecular layer distinctly larger than those of the other mammals. Among all the mammals studied, there was a high correlation between the size per body weight of summed granular regions and that of the DCN molecular layer, consistent with other evidence for a close relationship between granule cells and superficial DCN neurons. PMID:27435005

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Nutrient salts promote light-induced degradation of indole-3-acetic Acid in tissue culture media.

    PubMed

    Dunlap, J R; Robacker, K M

    1988-10-01

    The disappearance of indole-3-acetic acid (IAA) from cell-free liquid culture medium was followed in response to nutrient salts found in Murashige-Skoog salt base, light, and pH range of 4 to 7. The loss of IAA was accelerated by light or Murashige-Skoog salts. However, the combination of both light and Murashige-Skoog salts acted synergistically to catalyze the destruction of over 80% of the original IAA within 7 days of continuous incubation. Under these same conditions, the loss of IAA was decreased to approximately 50% by adjusting the initial pH of the medium to 7. Iron was identified as the single major contributor to light-catalyzed destruction of IAA. Removal of nitrates, which represented 87% of the molar salt composition, also reduced the light-catalyzed loss of IAA. Treatments that protected IAA from degradation, such as darkness or removal of iron from the medium, suppressed the growth of muskmelon (Cucumis melo. Naud., var. reticulatus) callus tissue cultured for 30 days. Treatments in the light that rapidly degraded IAA resulted in maximum growth. Consequently, the brief exposure to IAA prior to degradation was apparently sufficient to initiate physiological changes required for growth. Possible approaches to the preservation of IAA during incubation are discussed. PMID:16666312

  7. 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.

  8. The laser desorption/laser ionization mass spectra of some indole derivatives and alkaloids

    NASA Astrophysics Data System (ADS)

    Rogers, Kevin; Milnes, John; Gormally, John

    1992-06-01

    The laser desorption and laser ionization mass spectra of some indole derivatives and alkaloids are described with particular reference to their modes of fragmentation. Mass spectra of yohimbine, reserpine, quinine and quinidine are presented. Full experimental details are given.

  9. Synthesis of indoles and tryptophan derivatives via photoinduced nitrene C-H insertion.

    PubMed

    Junk, Lukas; Kazmaier, Uli

    2016-03-14

    Functionalized indoles and tryptophans can be obtained from stannylated alkenes and o-iodoanilines via Stille coupling. Subsequent azidation and photochemical nitrene generation results in the formation of the heterocyclic ring systems via C-H insertion. PMID:26869211

  10. Rh(III)-Catalyzed C-H Amidation of Indoles with Isocyanates.

    PubMed

    Jeong, Taejoo; Han, Sangil; Mishra, Neeraj Kumar; Sharma, Satyasheel; Lee, Seok-Yong; Oh, Joa Sub; Kwak, Jong Hwan; Jung, Young Hoon; Kim, In Su

    2015-07-17

    The rhodium(III)-catalyzed direct amidation of indoles and pyrroles with aryl and alkyl isocyanates is described. These transformations provide a facile and efficient construction of C2-amidated N-heterocyclic scaffolds.

  11. Lewis Acid-Catalyzed Indole Synthesis via Intramolecular Nucleophilic Attack of Phenyldiazoacetates to Iminium Ions

    PubMed Central

    Zhou, Lei; Doyle, Michael P.

    2009-01-01

    Lewis acids catalyze the cyclization of methyl phenyldiazoacetates with an ortho-imino group, prepared from o-aminophenylacetic acid, to give 2,3-substituted indoles in quantitative yields. PMID:19904905

  12. 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.

  13. 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

  14. Asymmetric synthesis of cyclic indole aminals via 1,3-stereoinduction.

    PubMed

    Li, Hongmei; Chen, Cheng-yi; Nguyen, Hoa; Cohen, Ryan; Maligres, Peter E; Yasuda, Nobuyoshi; Mangion, Ian; Zavialov, Ilia; Reibarkh, Mikhail; Chung, John Y L

    2014-09-19

    A general and efficient asymmetric synthesis of cyclic indoline aminals was developed with a high level of 1,3-stereoinduction through a dynamic crystallization-driven condensation. Dehydrogenation of the indoline aminals with potassium permanganate produced the corresponding cyclic indole aminals in high yields and excellent enantioselectivities. This general methodology was successfully applied to the synthesis of a wide variety of chiral cyclic indoline aminals and indole aminals with aromatic and aliphatic functional groups. PMID:25162915

  15. Copper-Catalyzed Oxidative C-H Amination of Tetrahydrofuran with Indole/Carbazole Derivatives.

    PubMed

    Yang, Qingjing; Choy, Pui Ying; Fu, Wai Chung; Fan, Baomin; Kwong, Fuk Yee

    2015-11-01

    A simple α-C-H amination of cyclic ether with indole/carbazole derivatives has been accomplished by employing copper(II) chloride/bipy as the catalyst system. In the presence of the di-tert-butyl peroxide oxidant, cyclic ethers such as tetrahydrofuran, 1,4-dioxane, and tetrahydropyran successfully undergo C-H/N-H cross dehydrogenative coupling (CDC) with various carbazole or indole derivatives in good-to-excellent yields. PMID:26485515

  16. 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.

  17. Rodents and Risk in the Mekong Delta of Vietnam: Seroprevalence of Selected Zoonotic Viruses in Rodents and Humans

    PubMed Central

    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

    2015-01-01

    Abstract 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. PMID:25629782

  18. 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

  19. L-Tryptophan catabolism by Rubrivivax benzoatilyticus JA2 occurs through indole 3-pyruvic acid pathway.

    PubMed

    Kumavath, Ranjith N; Ramana, Ch V; Sasikala, Ch

    2010-09-01

    Rubrivivax benzoatilyticus JA2 utilizes L: -tryptophan as the sole source of nitrogen for growth, and it has a doubling time of approximately 11 h (compared to 8 h with ammonium chloride). With cell free extracts in the presence of 2-oxoglutarate, indole-3-pyruvic acid, indole-3-acetaldehyde, indole-3-acetic acid, isatin, benzaldehyde, gallic acid and pyrogallol were identified using high performance liquid chromatography (HPLC) and liquid chromatography-mass spectroscopy (LC-MS) analysis. The conversion of L: -tryptophan into indole 3-pyruvic acid and glutamate by an enzyme aminotransferase was confirmed and the catabolism of indole-3-pyruvic acid via side chain oxidation followed by ring oxidation, gallic acid and pyrogallol were confirmed as metabolites. In addition, the proposed pathway sequential conversion of indole-3-pyruvic acid to the end product of pyrogallol was identified, including an enzymatic step that would convert isatin to benzaldehyde by an enzyme yet to be identified. At this stage of the study, the enzyme tryptophan aminotransferase in R. benzoatilyticus JA2 was demonstrated.

  20. 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.

  1. Bacterial Metabolite Indole Modulates Incretin Secretion from Intestinal Enteroendocrine L Cells

    PubMed Central

    Chimerel, Catalin; Emery, Edward; Summers, David K.; Keyser, Ulrich; Gribble, Fiona M.; Reimann, Frank

    2014-01-01

    Summary It has long been speculated that metabolites, produced by gut microbiota, influence host metabolism in health and diseases. Here, we reveal that indole, a metabolite produced from the dissimilation of tryptophan, is able to modulate the secretion of glucagon-like peptide-1 (GLP-1) from immortalized and primary mouse colonic L cells. Indole increased GLP-1 release during short exposures, but it reduced secretion over longer periods. These effects were attributed to the ability of indole to affect two key molecular mechanisms in L cells. On the one hand, indole inhibited voltage-gated K+ channels, increased the temporal width of action potentials fired by L cells, and led to enhanced Ca2+ entry, thereby acutely stimulating GLP-1 secretion. On the other hand, indole slowed ATP production by blocking NADH dehydrogenase, thus leading to a prolonged reduction of GLP-1 secretion. Our results identify indole as a signaling molecule by which gut microbiota communicate with L cells and influence host metabolism. PMID:25456122

  2. Toxin YafQ increases persister cell formation by reducing indole signalling.

    PubMed

    Hu, Ying; Kwan, Brian W; Osbourne, Devon O; Benedik, Michael J; Wood, Thomas K

    2015-04-01

    Persister cells survive antibiotic and other environmental stresses by slowing metabolism. Since toxins of toxin/antitoxin (TA) systems have been postulated to be responsible for persister cell formation, we investigated the influence of toxin YafQ of the YafQ/DinJ Escherichia coli TA system on persister cell formation. Under stress, YafQ alters metabolism by cleaving transcripts with in-frame 5'-AAA-G/A-3' sites. Production of YafQ increased persister cell formation with multiple antibiotics, and by investigating changes in protein expression, we found that YafQ reduced tryptophanase levels (TnaA mRNA has 16 putative YafQ cleavage sites). Consistently, TnaA mRNA levels were also reduced by YafQ. Tryptophanase is activated in the stationary phase by the stationary-phase sigma factor RpoS, which was also reduced dramatically upon production of YafQ. Tryptophanase converts tryptophan into indole, and as expected, indole levels were reduced by the production of YafQ. Corroborating the effect of YafQ on persistence, addition of indole reduced persistence. Furthermore, persistence increased upon deleting tnaA, and persistence decreased upon adding tryptophan to the medium to increase indole levels. Also, YafQ production had a much smaller effect on persistence in a strain unable to produce indole. Therefore, YafQ increases persistence by reducing indole, and TA systems are related to cell signalling.

  3. 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.

  4. Detection of Lyme Disease and Q Fever Agents in Wild Rodents in Central Italy

    PubMed Central

    Di Domenico, Marco; Dall'Acqua, Francesca; Sozio, Giulia; Cammà, Cesare

    2015-01-01

    Abstract The maintenance of tick-borne disease agents in the environment strictly depends on the relationship between tick vectors and their hosts, which act as reservoirs for these pathogens. A pilot study aimed to investigate wild rodents as reservoirs for zoonotic tick-borne pathogens (Borrelia burgdorferi sensu lato (s.l.), Coxiella burnetii, Francisella tularensis, and Anaplasma phagocytophilum) was carried out in an area of Gran Sasso e Monti della Laga National Park (Abruzzi Region, central Italy), a wide protected area where, despite sporadic reports of infection in humans and animals, eco-epidemiological data on these diseases are still not available. Rodents were trapped and released at the capture site after the collection of feeding ticks and blood samples. In all, 172 ticks were collected; the most frequent species was Ixodes acuminatus (53%). Out of 88 tick pools, 11 resulted positive for C. burnetii and 13 for B. burgdorferi s.l.; the Borrelia afzelii genospecies was identified in one Ixodes ricinus tick collected from one Apodemus sp. rodent. Out of 143 blood samples, seven Apodemus spp. and five Myodes glareolus were positive for B. burgdorferi s.l. and two Apodemus spp. were positive for C. burnetii. All samples (ticks and blood) were negative for F. tularensis and A. phagocytophilum. This is the first report of B. burgdorferi s.l. in the environment for Abruzzi Region. Data on the presence of B. burgdorferi s.l. are similar to that observed in other Mediterranean countries. The present work is also the first report of C. burnetii in wild rodents in Italy. C. burnetii infection has been largely investigated in Italy in ruminant farms by serology and molecular methods, but information on ecology and on the wild cycle are still lacking. Further studies including genotyping should be performed and species-specific differences between wild rodent reservoirs of Q fever and Lyme disease agents should be investigated. PMID:26134933

  5. 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).

  6. Clinical aspects of rodent dental anatomy.

    PubMed

    Crossley, D A

    1995-12-01

    The order Rodentia is vast, encompassing a large number of species with significant anatomical variations developed during natural adaptation to differing habitats. Many veterinarians have little knowledge of the anatomy of species other than the commoner domestic large herbivores and small carnivores. Clinicians require a basic knowledge of the relevant anatomy of species they are likely to be asked to treat. This article provides sufficient working knowledge of the oral and dental anatomy of those rodents commonly kept as pets to enable veterinarians to interpret clinical and radiographic findings when investigating suspected dental disease.

  7. 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.

  8. Tryptophan aminopeptidase activity of several indole prenyltransferases from Aspergillus fumigatus.

    PubMed

    Kremer, Anika; Li, Shu-Ming

    2008-07-21

    Recently, five indole prenyltransferases from Aspergillus fumigatus have been proven biochemically to be responsible for prenylations of diverse substrates. In this study, we show peptidase activities of 7-DMATS, FgaPT1, CdpNPT, and FtmPT1, with preference for linear peptides containing a tryptophanyl moiety at the N terminus. Testing of 31 peptides revealed that these enzymes shared similar substrate specificity and accepted H-L-Trp-L-Ala-OH and H-L-Trp-Gly-OH as best substrates for aminopeptidase activity. By using H-L-Trp-Gly-OH as substrate, Km values at 350, 380, 300, and 420 microM and enzymatic rate constants kcat/Km at 0.51, 0.24, 0.53, and 0.14 mM(-1)s(-1) were determined for 7-DMATS, FgaPT1, CdpNPT, and FtmPT1, respectively. In contrast to prenyltransferase activities, the aminopeptidase activities were strongly or completely inhibited by EDTA. Mn2+ increased the aminopeptidase activities of FtmPT1 and CdpNPT up to 4- and 6-fold, respectively. To the best of our knowledge, this is the first report on the catalytic promiscuity of prenyltransferases.

  9. Monoterpene indole alkaloids from the twigs of Kopsia arborea.

    PubMed

    Cheenpracha, Sarot; Raksat, Achara; Ritthiwigrom, Thunwadee; Laphookhieo, Surat

    2014-10-01

    The phytochemistry of Kopsia arborea Blume has received considerable attention, which has resulted in the isolation of a number of new unusual indole alkaloids with intriguing structures. In this study, a new eburnane-type alkaloid, phutdonginin (1), together with eight known alkaloids: 19-OH-(-)- eburnamonine (2), melodinine E (3), kopsinine (4), kopsilongine (5), kopsamine (6), (-)-methylenedioxy-1 1,12-kopsinaline (7), decarbomethoxykopsiline (8), and vincadifformine (9), were isolated from the twigs of K. arborea. Their structures were characterized extensively by 1D and 2D NMR spectroscopy and HR-ESI-MS. All compounds were submitted to TLC screening for acetylcholinesterase inhibitory activities. Only kopsamine and decarbomethoxykopsiline showed AChE inhibition with MIR values of 12.5 and 6.25 μg, respectively, compared with galanthamine (positive control, 0.004 μg). In addition, compounds 1 and 2 inhibited moderate antibacterial activity against E. coli TISTR 780 with the MIC value of 32 .g/mL. PMID:25522533

  10. 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…

  11. [Litomosoides, parasites of rodents; taxonomic consequences].

    PubMed

    Bain, O; Petit, G; Diagne, M

    1989-01-01

    A redescription of the type specimens of the three following species is given: L carinii (Travassos, 1919) from Sciurus sp. in Brazil. L, sigmodontis Chandler, 1931 from Sigmodon hispidus and L. scotti Forrester et Kinsella. 1977 from Oryzomys palustris in North America. A description of two brazilian species is also given: L. galizai n. sp. from (Ecomys trinitatus tapajinus and L. kohnae n. sp. from Nectomys squamipes. The conclusions are: The type species of the genus Litomosoides: L. sigmodontis, and L.carinii are two distinct species. As a result, the filaria which is widely used in drug trials has to be reinstated sigmodontis and not curinii. With the exception of the two parasite species of Geomyid rodents, which show affinities with the genus Litomosa, the species of Litomosoides may be devided into two groups, principally based on the morphology of the spicules: the sigmodontis group, with 13 species; the carinii group, with 8 species. Each group includes parasites of Chiuroptera, Marsupials and Rodents. The two new species (L. galizai and L. kohnae) belong to the group sigmodontis; they are characterised by the shape of the buccal capsule, the size of the spicules, the structure of the female body-wall and the microeilaria.

  12. Context learning in the rodent hippocampus.

    PubMed

    Fuhs, Mark C; Touretzky, David S

    2007-12-01

    We present a Bayesian statistical theory of context learning in the rodent hippocampus. While context is often defined in an experimental setting in relation to specific background cues or task demands, we advance a single, more general notion of context that suffices for a variety of learning phenomena. Specifically, a context is defined as a statistically stationary distribution of experiences, and context learning is defined as the problem of how to form contexts out of groups of experiences that cluster together in time. The challenge of context learning is solving the model selection problem: How many contexts make up the rodent's world? Solving this problem requires balancing two opposing goals: minimize the variability of the distribution of experiences within a context and minimize the likelihood of transitioning between contexts. The theory provides an understanding of why hippocampal place cell remapping sometimes develops gradually over many days of experience and why even consistent landmark differences may need to be relearned after other environmental changes. The theory provides an explanation for progressive performance improvements in serial reversal learning, based on a clear dissociation between the incremental process of context learning and the relatively abrupt context selection process. The impact of partial reinforcement on reversal learning is also addressed. Finally, the theory explains why alternating sequence learning does not consistently result in unique context-dependent sequence representations in hippocampus.

  13. 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

  14. Rodent Models of Amyotrophic Lateral Sclerosis.

    PubMed

    Philips, Thomas; Rothstein, Jeffrey D

    2015-06-01

    Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease affecting upper and lower motor neurons in the central nervous system. Patients with ALS develop extensive muscle wasting and atrophy leading to paralysis and death 3 to 5 years after disease onset. The condition may be familial (fALS 10%) or sporadic ALS (sALS, 90%). The large majority of fALS cases are due to genetic mutations in the Superoxide dismutase 1 gene (SOD1, 15% of fALS) and repeat nucleotide expansions in the gene encoding C9ORF72 (∼ 40% to 50% of fALS and ∼ 10% of sALS). Studies suggest that ALS is mediated through aberrant protein homeostasis (i.e., ER stress and autophagy) and/or changes in RNA processing (as in all non-SOD1-mediated ALS). In all of these cases, animal models suggest that the disorder is mediated non-cell autonomously, i.e., not only motor neurons are involved, but glial cells including microglia, astrocytes, and oligodendrocytes, and other neuronal subpopulations are also implicated in the pathogenesis. Provided in this unit is a review of ALS rodent models, including discussion of their relative advantages and disadvantages. Emphasis is placed on correlating the model phenotype with the human condition and the utility of the model for defining the disease process. Information is also presented on RNA processing studies in ALS research, with particular emphasis on the newest ALS rodent models.

  15. One-pot approach to 1,2-disubstituted indoles via Cu(II)-catalyzed coupling/cyclization under aerobic conditions and its application for the synthesis of polycyclic indoles.

    PubMed

    Gao, Jilong; Shao, Yingying; Zhu, Jiaoyan; Zhu, Jiaqi; Mao, Hui; Wang, Xiaoxia; Lv, Xin

    2014-10-01

    A straightforward assembly of 1,2-disubstituted indoles has been developed through a Cu(II)-catalyzed domino coupling/cyclization process. Under aerobic conditions, a wide range of 1,2-disubstituted indole derivatives were efficiently and facilely synthesized from 2-alkynylanilines and boronic acids. 2-(2-Bromoaryl)-1-aryl-1H-indoles, which were selectively generated in one pot under the Cu catalysis, afforded the indolo[1,2-f]phenanthridines via Pd-catalyzed intramolecular direct C(sp(2))-H arylation. The one-pot tandem approaches to the polycyclic indole derivatives were also successfully achieved. PMID:25211172

  16. Anticonvulsant and Neurotoxicity of Some Novel 1-([1,3,4]thiadiazino[6,5- b]indol-3-yl Semicarbazides.

    PubMed

    Deshmukh, Ravitas; Thakur, Alok S; Jha, Arvind K; Kumar, Sudhir P

    2015-01-01

    In the present study a series of new N(4)-(4-substituted benzylidene)-N(1)-([1,3,4]thiadiazino [6,5-b]indol-3-yl)semicarbazide (1-6), N(4)-([1,3,4]thiadiazino[6,5-b]indol-3-yl)-N(1)-(1-(4-substituted phenyl)ethylidene)semicarbazide (7-10), N(4)-([1,3,4]thiadiazino[6,5-b]indol-3-yl)-N(1)-((4-substituted phenyl)(phenyl)methylene) semicarbazide. (11-14) have been synthesized from isatin and thiosemicarbazide through multiple steps to meet structural necessities for the anticonvulsant activity. All the newly prepared compounds were characterized by spectral techniques like FT-IR, (1)H and (13)C NMR, EI-MS and elemental analysis. All the newly synthesized compounds were investigated for the anticonvulsant activity against maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) models and their neurotoxicity were also evaluated by rotarod test. The results obtained showed that 64% of the compounds showed protection in the MES test and 36% of the compounds showed protection in ScPTZ test. Some of the compounds also showed good activity after oral administration. Among the synthesized compounds, compound 14 was shown to be the most active compound showing activity at 100 and 300 mg/kg in MES and ScPTZ test with prolonged duration of action. In the present study, semicarbazones of hydroxy containing carbonyl compounds were depicted to be the potent molecule with low neurotoxicity and prolong duration of action on oral administration. The result of the present study may be used for the future development of novel anticonvulsants with broad spectrum of anticonvulsant activity. PMID:26100150

  17. Stereoselective synthesis of thiazino[4,3-a]indoles using the thia-Pictet-Spengler reaction of indoles bearing N-tethered thiols and vinylogous thiocarbonates.

    PubMed

    Gharpure, Santosh J; Nanda, Santosh K

    2016-06-28

    An inter- as well as intra-molecular thia-Pictet-Spengler cyclization of N-tethered thiols and vinylogous thiocarbonates is described for the stereoselective synthesis of N-fused thiazinoindole derivatives. The strategy is extended to one-pot, sequential Friedel-Crafts alkylation - Pictet-Spengler cyclization and the synthesis of thiazino-oxepino-indole. PMID:27011230

  18. Metal-free (Boc)2O-mediated C4-selective direct indolation of pyridines using TEMPO.

    PubMed

    Qin, Wen-Bing; Zhu, Jia-Yi; Kong, Yu-Bo; Bao, Yun-Hong; Chen, Zheng-Wang; Liu, Liang-Xian

    2014-06-28

    Direct metal-free C-4-selective indolation of pyridines is achieved for the first time using TEMPO and (Boc)2O. A variety of substituents on both indoles and pyridines are tolerated to give 3-(pyridin-4-yl)-1H-indole derivatives in moderate to excellent yields. This finding provides a novel approach for developing metal-free C-H functionalization of pyridines.

  19. 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.

  20. 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

  1. Some effects of indole on the interaction of amino acids with tryptophanase.

    PubMed

    Kazarinoff, M N; Snell, E E

    1980-07-10

    Although indole is a potent inhibitor (KI = 0.01 mM) of pyruvate formation from substrates of tryptophanase (EC 4.1.99.1, from Escherichia coli), we could not detect binding of indole to free tryptophanase (KD greater than 1.0 mM). However, indole, skatole, and toluene increased the affinity of tryptophanase for certain inhibitory amino acids. Binding of amino acids with small side chains (e.g. Ala, Gly) was increased, but there was little or no effect on the binding of amino acids with bulky side chains (e.g. norvaline, ethionine). These effects were quantitated by using changes in the absorption spectra of the enzyme . amino acid complexes. Indole decreases the absorbance obtainable at 500 nm for amino acids with small hydrophobic side chains (L-Ala, Gly), increases this absorbance for amino acids with small polar side chains (beta-cyano-L-alanine), and does not change the spectra of tryptophanase complexes with amino acids with bulky side chains, i.e. amino acids whose binding affinities are unaffected by indole. These spectral differences are interpreted in terms of an effect of bound indole (or side chain binding) on the partitioning of the bound amino acid between catalytic forms of the enzyme. The data indicate that substrate-induced conformational changes occur at the enzyme active site that generate a high affinity indole-binding site during catalytic turnover of tryptophanase and are important in the catalytic functioning of the enzyme. These changes also explain reproducible differences in KI values observed previously for amino acids in different assay systems used for steady state kinetic inhibition studies. The optimal conditions for the growth of E. coli for tryptophanase production are outlined, together with a procedure for purification of holotryptophanase.

  2. Chemical defenses of crucifers: elicitation and metabolism of phytoalexins and indole-3-acetonitrile in brown mustard and turnip.

    PubMed

    Pedras, M Soledade C; Nycholat, Corwin M; Montaut, Sabine; Xu, Yiming; Khan, Abdul Q

    2002-03-01

    The metabolism of the cruciferous phytoalexins brassinin and cyclobrassinin, and the related compounds indole-3-carboxaldehyde, glucobrassicin, and indole-3-acetaldoxime was investigated in various plant tissues of Brassica juncea and B. rapa. Metabolic studies with brassinin showed that stems of B. juncea metabolized radiolabeled brassinin to indole-3-acetic acid, via indole-3-carboxaldehyde, a detoxification pathway similar to that followed by the "blackleg" fungus (Phoma lingam/Leptosphaeria maculans). In addition, it was established that tetradeuterated brassinin was incorporated into the phytoalexin brassilexin in B. juncea and B. rapa. On the other hand, the tetradeuterated indole glucosinolate glucobrassicin was not incorporated into brassinin, although the chemical structures of brassinins and indole glucosinolates suggest an interconnected biogenesis. Importantly, tetradeuterated indole-3-acetaldoxime was an efficient precursor of phytoalexins brassinin, brassilexin, and spirobrassinin. Elicitation experiments in tissues of Brassica juncea and B. rapa showed that indole-3-acetonitrile was an inducible metabolite produced in leaves and stems of B. juncea but not in B. rapa. Indole-3-acetonitrile displayed antifungal activity similar to that of brassilexin, was metabolized by the blackleg fungus at slower rates than brassinin, cyclobrassinin, or brassilexin, and appeared to be involved in defense responses of B. juncea.

  3. 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.

  4. Vitamin K Contents of Rodent Diets: A Review

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  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. 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…

  7. Recent isolations of Lassa virus from Nigerian rodents

    PubMed Central

    Wulff, Herta; Fabiyi, A.; Monath, T. P.

    1975-01-01

    Rodents were trapped in the Benue-Plateau and North-Eastern States of Nigeria where Lassa fever had been reported in previous years. Eight Lassa virus strains were isolated from tissues and blood of rodents identified in the field as being of 3 different species: Mastomys natalensis, Rattus rattus, and Mus minutoides. All the infected rodents were collected in village habitats. These isolations indicate the presence of Lassa virus in wild rodents in Nigeria during periods when no human infections were evident. Prior studies in Sierra Leone have indicated that a single rodent species, M. natalensis, may be the important reservoir host of Lassa virus. Since the present study indicates that other rodent species may be involved as well, the ecology of Lassa virus may be more complicated than was heretofore supposed. In view of the importance of determining the geographic and species range of rodent hosts of Lassa virus, and because of the problems inherent in rodent identification under austere field conditions, it is urgent that further studies be conducted in the same areas of Nigeria to confirm these findings. PMID:1085216

  8. 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

  9. Prospects of chemosterilant and genetic control of rodents

    PubMed Central

    Marsh, Rex E.; Howard, Walter E.

    1973-01-01

    This paper discusses some requirements of an ideal rodent chemosterilant, analyses the advantages of chemosterilants over other control methods, and compares the potential values of chemosterilants that affect females, males, and both sexes. Examples are given of specific situations where chemosterilants will be valuable in rodent control, together with suggested methods of applying them. The theory and practicability of using genetics in rodent control are also discussed. Neither the chemosterilant nor the genetic method is expected to become a panacea, but their eventual application will be a significant advance in rodent-control technology. Since both approaches are based on sound biological principles and are relatively safe, they should be helpful in regulating rodent populations in the future. PMID:4583051

  10. Efficient isotopic tryptophan labeling of membrane proteins by an indole controlled process conduct.

    PubMed

    Berger, Christian; Berndt, Sandra; Pichert, Annelie; Theisgen, Stephan; Huster, Daniel

    2013-06-01

    A protocol for the efficient isotopic labeling of large G protein-coupled receptors with tryptophan in Escherichia coli as expression host was developed that sufficiently suppressed the naturally occurring L-tryptophan indole lyase, which cleaves tryptophan into indole, pyruvate, and ammonia resulting in scrambling of the isotopic label in the protein. Indole produced by the tryptophanase is naturally used as messenger for cell-cell communication. Detailed analysis of different process conducts led to the optimal expression strategy, which mimicked cell-cell communication by the addition of indole during expression. Discrete concentrations of indole and (15) N2 -L-tryptophan at dedicated time points in the fermentation drastically increased the isotopic labeling efficiency. Isotope scrambling was only observed in glutamine, asparagine, and arginine side chains but not in the backbone. This strategy allows producing specifically tryptophan labeled membrane proteins at high concentrations avoiding the disadvantages of the often low yields of auxotrophic E. coli strains. In the fermentation process carried out according to this protocol, we produced ∼15 mg of tryptophan labeled neuropeptide Y receptor type 2 per liter medium.

  11. 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

    2015-07-01

    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. PMID:26029791

  12. 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

    2015-07-01

    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.

  13. 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

    2013-04-01

    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.

  14. 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.

  15. Intraoperative cerebral blood flow imaging of rodents

    NASA Astrophysics Data System (ADS)

    Li, Hangdao; Li, Yao; Yuan, Lu; Wu, Caihong; Lu, Hongyang; Tong, Shanbao

    2014-09-01

    Intraoperative monitoring of cerebral blood flow (CBF) is of interest to neuroscience researchers, which offers the assessment of hemodynamic responses throughout the process of neurosurgery and provides an early biomarker for surgical guidance. However, intraoperative CBF imaging has been challenging due to animal's motion and position change during the surgery. In this paper, we presented a design of an operation bench integrated with laser speckle contrast imager which enables monitoring of the CBF intraoperatively. With a specially designed stereotaxic frame and imager, we were able to monitor the CBF changes in both hemispheres during the rodent surgery. The rotatable design of the operation plate and implementation of online image registration allow the technician to move the animal without disturbing the CBF imaging during surgery. The performance of the system was tested by middle cerebral artery occlusion model of rats.

  16. Oxytocin-dependent consolation behavior in rodents.

    PubMed

    Burkett, J P; Andari, E; Johnson, Z V; Curry, D C; de Waal, F B M; Young, L J

    2016-01-22

    Consolation behavior toward distressed others is common in humans and great apes, yet our ability to explore the biological mechanisms underlying this behavior is limited by its apparent absence in laboratory animals. Here, we provide empirical evidence that a rodent species, the highly social and monogamous prairie vole (Microtus ochrogaster), greatly increases partner-directed grooming toward familiar conspecifics (but not strangers) that have experienced an unobserved stressor, providing social buffering. Prairie voles also match the fear response, anxiety-related behaviors, and corticosterone increase of the stressed cagemate, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused into this region abolishes the partner-directed response, showing conserved neural mechanisms between prairie vole and human.

  17. Oxytocin-dependent consolation behavior in rodents

    PubMed Central

    Burkett, J. P.; Andari, E.; Johnson, Z. V.; Curry, D. C.; de Waal, F. B. M.; Young, L. J.

    2016-01-01

    Consolation behavior toward distressed others is common in humans and great apes, yet our ability to explore the biological mechanisms underlying this behavior is limited by its apparent absence in laboratory animals. Here, we provide empirical evidence that a rodent species, the highly social and monogamous prairie vole (Microtus ochrogaster), greatly increases partner-directed grooming toward familiar conspecifics (but not strangers) that have experienced an unobserved stressor, providing social buffering. Prairie voles also match the fear response, anxiety-related behaviors, and corticosterone increase of the stressed cagemate, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused into this region abolishes the partner-directed response, showing conserved neural mechanisms between prairie vole and human. PMID:26798013

  18. Oxytocin-dependent consolation behavior in rodents.

    PubMed

    Burkett, J P; Andari, E; Johnson, Z V; Curry, D C; de Waal, F B M; Young, L J

    2016-01-22

    Consolation behavior toward distressed others is common in humans and great apes, yet our ability to explore the biological mechanisms underlying this behavior is limited by its apparent absence in laboratory animals. Here, we provide empirical evidence that a rodent species, the highly social and monogamous prairie vole (Microtus ochrogaster), greatly increases partner-directed grooming toward familiar conspecifics (but not strangers) that have experienced an unobserved stressor, providing social buffering. Prairie voles also match the fear response, anxiety-related behaviors, and corticosterone increase of the stressed cagemate, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused into this region abolishes the partner-directed response, showing conserved neural mechanisms between prairie vole and human. PMID:26798013

  19. Hindlimb unloading: rodent analog for microgravity.

    PubMed

    Globus, Ruth K; Morey-Holton, Emily

    2016-05-15

    The rodent hindlimb unloading (HU) model was developed in the 1980s to make it possible to study mechanisms, responses, and treatments for the adverse consequences of spaceflight. Decades before development of the HU model, weightlessness was predicted to yield deficits in the principal tissues responsible for structure and movement on Earth, primarily muscle and bone. Indeed, results from early spaceflight and HU experiments confirmed the expected sensitivity of the musculoskeletal system to gravity loading. Results from human and animal spaceflight and HU experiments show that nearly all organ systems and tissues studied display some measurable changes, albeit sometimes minor and of uncertain relevance to astronaut health. The focus of this review is to examine key HU results for various organ systems including those related to stress; the immune, cardiovascular, and nervous systems; vision changes; and wound healing. Analysis of the validity of the HU model is important given its potential value for both hypothesis testing and countermeasure development. PMID:26869711

  20. Scatter-hoarding rodents prefer slightly astringent food.

    PubMed

    Wang, Bo; Chen, Jin

    2011-01-01

    The mutualistic interaction between scatter-hoarding rodents and their seed plants is highly complex yet poorly understood. Plants may benefit from the seed dispersal behavior of rodents, as long as seed consumption is minimized. In parallel, rodents may maximize foraging efficiency and cache high-quality resources for future consumption. Defensive compounds, such as tannins, are thought to be a major mechanism for plant control over rodent behavior. However, previous studies, using naturally occurring seeds, have not provided conclusive evidence supporting this hypothesis. Here, we test the importance of tannin concentrations on the scatter-hoarding behavior of rodents by using an artificial seed system. We combined feeding trials and field observations to examine the overall impact of seed tannin concentrations on rodent behavior and health. We found that rodents favored seeds with an intermediate amount of tannin (~5%) in the field. Meanwhile, in rodents that were fed a diet with different tannin content, only diets with high tannin content (25%, 15%, and 10%) caused a significant negative influence on rodent survival and health. Significant differences were not found among treatments with tannin levels of 0-5%. In contrast to many existing studies, our results clearly demonstrate that scatter-hoarding rodents prefer slightly 'astringent' food. In the co-evolutionary arms race between plants and animals, our results suggest that while tannins may play a significant role in reducing general predation levels by the faunal community, they have no precise control over the behavior of their mutualistic partner. Instead, the two partners appear to have reached an evolutionary point where both parties receive adequate benefits, with the year-to-year outcome being dependent on a wide range of factors beyond the control of either partner.

  1. [Ecological interactions among Yersinia in their common reservoir, the rodent].

    PubMed

    Alonso, J M

    1999-12-01

    Plague, due to Yersinia pestis, is still active in various foci in the Americas, in Africa and Asia, whereas it has been absent from Europe since the end of the 18th century, after having killed the two-thirds of the continent's inhabitants within four centuries. Various hypothesis have been proposed to attempt to explain the spontaneous "eradication" of plague from Europe, including the improvement of hygiene and habitat, changes in the rat population and cross-immunity induced by other infections, such as salmonellosis, leprosy and other yersiniosis. The only Yersinia currently isolated in Europe are the species genetically related to Y. pestis, Y. pseudotuberculosis and Y. enterocolitica, which are less virulent and mostly enteropathogenic. Y. pestis and Y. pseudotuberculosis have a DNA relatedness of 90%, whereas it is of only 60% with Y. enterocolitica. Y. pseudotuberculosis has been used as efficient vaccine against plague. Present world epidemiological data show that Y. enterocolitica is progressively replacing Y. pseudotuberculosis. Experimental infection by Y. enterocolitica, inducing a transitory and spontaneously cured infection in the immunocompetent host, only inducing opportunistic infections in the immunodeficient host, promotes efficient immunity against plague. Thus, it seems likely that the emergence of some variants of Yersinia, less virulent than Y. pestis, but able to induce a long-lasting protective immunity against plague, have contributed to its eradication by a silent enzootic infection among the wild reservoirs of rodents.

  2. Automatic cortical thickness analysis on rodent brain

    NASA Astrophysics Data System (ADS)

    Lee, Joohwi; Ehlers, Cindy; Crews, Fulton; Niethammer, Marc; Budin, Francois; Paniagua, Beatriz; Sulik, Kathy; Johns, Josephine; Styner, Martin; Oguz, Ipek

    2011-03-01

    Localized difference in the cortex is one of the most useful morphometric traits in human and animal brain studies. There are many tools and methods already developed to automatically measure and analyze cortical thickness for the human brain. However, these tools cannot be directly applied to rodent brains due to the different scales; even adult rodent brains are 50 to 100 times smaller than humans. This paper describes an algorithm for automatically measuring the cortical thickness of mouse and rat brains. The algorithm consists of three steps: segmentation, thickness measurement, and statistical analysis among experimental groups. The segmentation step provides the neocortex separation from other brain structures and thus is a preprocessing step for the thickness measurement. In the thickness measurement step, the thickness is computed by solving a Laplacian PDE and a transport equation. The Laplacian PDE first creates streamlines as an analogy of cortical columns; the transport equation computes the length of the streamlines. The result is stored as a thickness map over the neocortex surface. For the statistical analysis, it is important to sample thickness at corresponding points. This is achieved by the particle correspondence algorithm which minimizes entropy between dynamically moving sample points called particles. Since the computational cost of the correspondence algorithm may limit the number of corresponding points, we use thin-plate spline based interpolation to increase the number of corresponding sample points. As a driving application, we measured the thickness difference to assess the effects of adolescent intermittent ethanol exposure that persist into adulthood and performed t-test between the control and exposed rat groups. We found significantly differing regions in both hemispheres.

  3. A Curated Database of Rodent Uterotrophic Bioactivity

    PubMed Central

    Kleinstreuer, Nicole C.; Ceger, Patricia C.; Allen, David G.; Strickland, Judy; Chang, Xiaoqing; Hamm, Jonathan T.; Casey, Warren M.

    2015-01-01

    Background: Novel in vitro methods are being developed to identify chemicals that may interfere with estrogen receptor (ER) signaling, but the results are difficult to put into biological context because of reliance on reference chemicals established using results from other in vitro assays and because of the lack of high-quality in vivo reference data. The Organisation for Economic Co-operation and Development (OECD)-validated rodent uterotrophic bioassay is considered the “gold standard” for identifying potential ER agonists. Objectives: We performed a comprehensive literature review to identify and evaluate data from uterotrophic studies and to analyze study variability. Methods: We reviewed 670 articles with results from 2,615 uterotrophic bioassays using 235 unique chemicals. Study descriptors, such as species/strain, route of administration, dosing regimen, lowest effect level, and test outcome, were captured in a database of uterotrophic results. Studies were assessed for adherence to six criteria that were based on uterotrophic regulatory test guidelines. Studies meeting all six criteria (458 bioassays on 118 unique chemicals) were considered guideline-like (GL) and were subsequently analyzed. Results: The immature rat model was used for 76% of the GL studies. Active outcomes were more prevalent across rat models (74% active) than across mouse models (36% active). Of the 70 chemicals with at least two GL studies, 18 (26%) had discordant outcomes and were classified as both active and inactive. Many discordant results were attributable to differences in study design (e.g., injection vs. oral dosing). Conclusions: This uterotrophic database provides a valuable resource for understanding in vivo outcome variability and for evaluating the performance of in vitro assays that measure estrogenic activity. Citation: Kleinstreuer NC, Ceger PC, Allen DG, Strickland J, Chang X, Hamm JT, Casey WM. 2016. A curated database of rodent uterotrophic bioactivity. Environ

  4. Brain acetylcholinesterase activity recovery following acute methyl parathion intoxication in two feral rodent species: comparison to laboratory rodents

    SciTech Connect

    Roberts, D.K.; Silvey, N.J.; Bailey, E.M. Jr.

    1988-07-01

    Widespread use of organophosphorus insecticides (OPs) has produced both acute and chronic intoxication among nontarget organisms. Most such studies have included fish and birds as opposed to mammals. However, numerous OP toxicity studies have been conducted on laboratory rodents creating a temptation to apply this data to feral rodents. Chronic OP exposure has been reported to produce cholinergic adaptation which in turn lowers mortality rates following a subsequent acute anticholinesterase exposure. The relevance that these laboratory rodent studies have on feral rodents is subject to debate. Field studies involving OP exposure among nontarget feral mammals have produced contradictory results. Increased mortality as a result of repeated OP application has been reported. This observation may be of considerable importance to nontarget feral rodent populations due to the repetitive nature of OP application protocols. The ability of feral rodents to recover brain AChE activity (BAA) between OP application intervals undoubtedly promotes their survival. This study investigated and compared BAA recovery following acute oral methyl parathion intoxication among 2 feral rodent species and among 2 common laboratory rodent species.

  5. Domestic Rodent Control Training Manual: A Training Aid for the Rodent Control Category for Certification of Pesticide Applicators.

    ERIC Educational Resources Information Center

    Childress, William R., Jr.; And Others

    This training manual, designed for training applicants who wish to obtain certification in pesticide application relative to rodent control, covers the following topics: economic factors, public health factors, biological characteristics of domestic rodents, rat and mouse signs, trapping, repellents, poisons, baits, poisoned water, dumps, sewers,…

  6. Weak inter-actions in the crystal structures of two indole derivatives.

    PubMed

    Kerr, Jamie R; Trembleau, Laurent; Storey, John M D; Wardell, James L; Harrison, William T A

    2016-07-01

    We describe the syntheses and crystal structures of two indole derivatives, namely a second monoclinic polymorph of ethyl 5-chloro-1H-indole-2-carboxyl-ate C11H10ClNO2, (I), and ethyl 5-chloro-3-iodo-1H-indole-2-carboxyl-ate, 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 inter-actions, including π-π stacking, C-I⋯π, C-Cl-π inter-actions and I⋯Cl halogen bonds. PMID:27555941

  7. 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

  8. The inter-kingdom volatile signal indole promotes root development by interfering with auxin signalling.

    PubMed

    Bailly, Aurélien; Groenhagen, Ulrike; Schulz, Stefan; Geisler, Markus; Eberl, Leo; Weisskopf, Laure

    2014-12-01

    Recently, emission of volatile organic compounds (VOCs) has emerged as a mode of communication between bacteria and plants. Although some bacterial VOCs that promote plant growth have been identified, their underlying mechanism of action is unknown. Here we demonstrate that indole, which was identified using a screen for Arabidopsis growth promotion by VOCs from soil-borne bacteria, is a potent plant-growth modulator. Its prominent role in increasing the plant secondary root network is mediated by interfering with the auxin-signalling machinery. Using auxin reporter lines and classic auxin physiological and transport assays we show that the indole signal invades the plant body, reaches zones of auxin activity and acts in a polar auxin transport-dependent bimodal mechanism to trigger differential cellular auxin responses. Our results suggest that indole, beyond its importance as a bacterial signal molecule, can serve as a remote messenger to manipulate plant growth and development. PMID:25227998

  9. 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. PMID:18980369

  10. 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.

  11. A compound containing substituted indole ligand from a hyperaccumulator Sedum alfredii Hance under Zn exposure.

    PubMed

    Xing, Yan; Peng, Hongyun; Gao, Lingling; Luo, Ancheng; Yang, Xiaoe

    2013-01-01

    Sedum alfredii Hance is a fast-growing and high-biomass zinc (Zn) hyperaccumulator native to China. A compound containing substituted indole ligand was isolated from this Zn hyperaccumulator plants by sonication/ethanol extraction, macroporous resin column as well as preparative HPLC (P-HPLC). Hydroponic experiment showed that the concentrations of both Zn and the compound containing substituted indole ligand were remarkably increased in stems and leaves of both hyperaccumulator and non-hyperaccumulator as Zn rising from 0.5 to 50 micromol L(-1), with much more in the stems of hyperaccumulator than non-hyperaccumulator. At 50 micromol L(-1) Zn, hyperaccumulator grew normally but its non-hyperaccumulator suffered from strongly Zn-induced toxicity. This suggested that there was a positive correlation between the compound containing substituted indole ligand and Zn concentration in shoots of hyperaccumulator S. alfredii.

  12. The inter-kingdom volatile signal indole promotes root development by interfering with auxin signalling.

    PubMed

    Bailly, Aurélien; Groenhagen, Ulrike; Schulz, Stefan; Geisler, Markus; Eberl, Leo; Weisskopf, Laure

    2014-12-01

    Recently, emission of volatile organic compounds (VOCs) has emerged as a mode of communication between bacteria and plants. Although some bacterial VOCs that promote plant growth have been identified, their underlying mechanism of action is unknown. Here we demonstrate that indole, which was identified using a screen for Arabidopsis growth promotion by VOCs from soil-borne bacteria, is a potent plant-growth modulator. Its prominent role in increasing the plant secondary root network is mediated by interfering with the auxin-signalling machinery. Using auxin reporter lines and classic auxin physiological and transport assays we show that the indole signal invades the plant body, reaches zones of auxin activity and acts in a polar auxin transport-dependent bimodal mechanism to trigger differential cellular auxin responses. Our results suggest that indole, beyond its importance as a bacterial signal molecule, can serve as a remote messenger to manipulate plant growth and development.

  13. 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.

  14. Properties of the indole ring in metal complexes. A comparison with the phenol ring.

    PubMed

    Shimazaki, Yuichi; Yajima, Tatsuo; Yamauchi, Osamu

    2015-07-01

    Tryptophan (Trp), an essential amino acid, has an indole ring with a high electron density and is frequently seen at the proximal position of the metal site in metalloproteins. For example, the indole ring of Trp has been reported to interact weakly with Cu(I) in a Cu chaperone CusF. Another aromatic amino acid, tyrosine (Tyr), has a phenol ring, which is an important metal binding site in various metalloproteins. Although the structures of the aromatic rings are different, they both have a weakly acidic moiety and perform some similar roles in biological systems, such as radical formation and electron transfer. In this review, we focus on these and other properties of the indole and phenol rings in metal-containing systems.

  15. 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

  16. Applications of dimethylallyltryptophan synthases and other indole prenyltransferases for structural modification of natural products.

    PubMed

    Li, Shu-Ming

    2009-09-01

    A series of putative indole prenyltransferase genes could be identified in the genome sequences of different fungal strains including Aspergillus fumigatus and Neosartorya fischeri. The gene products show significant sequence similarities to dimethylallyltryptophan synthases from various fungi. These genes belong to different gene clusters and are involved in the biosynthesis of secondary metabolites. Ten of them were cloned and overexpressed in Escherichia coli and Saccharomyces cerevisiae and proven to be soluble proteins. They catalyse different prenyl transfer reactions onto indole moieties of various substrates and do not require divalent metal ions for their prenyl transfer reactions. These enzymes showed broad substrate specificities towards their aromatic substrates. Diverse simple tryptophan derivatives and tryptophan-containing cyclic dipeptides were accepted by several prenyltransferases as substrates and converted to prenylated derivatives. This feature of substrate flexibility was successfully used for regiospecific and stereospecific synthesis of different indole derivatives.

  17. Indolent non-Hodgkin lymphoma primarily involving the hard palate: outcome following radiotherapy.

    PubMed

    Milgrom, Sarah A; Yahalom, Joachim

    2013-06-01

    The aim of this study was to report the clinical and pathological characteristics, treatment strategies and outcome in patients with indolent non-Hodgkin lymphoma (NHL) primarily involving the hard palate. Nine consecutive patients with indolent NHL of the hard palate were identified. The palate was a site of initial disease for six patients (four stage IAE and two stage IIIAE) and of relapse for three. There were four cases of grade 1-2 follicular lymphoma (FL), two of mantle cell lymphoma (MCL) and three of marginal zone lymphoma (MZL). All nine patients received involved site radiation therapy (RT) alone. There was no grade ≥ 3 toxicity. At a median follow-up of 55 months, 5-year freedom from local progression was 100%, disease-free survival was 38% and overall survival was 80%. In conclusion, involved site RT is well tolerated and provides excellent local control in the management of indolent lymphoma of the hard palate. PMID:23083063

  18. Synthesis, structural investigations, and anti-cancer activity of new methyl indole-3-carboxylate derivatives

    NASA Astrophysics Data System (ADS)

    Niemyjska, Maria; Maciejewska, Dorota; Wolska, Irena; Truszkowski, Paweł

    2012-10-01

    Two new methyl indole-3-carboxylate derivatives: methyl 1-(3'-indolylmethane)-indole-3-carboxylate (1), and methyl 1-(1'-benzenosulfonyl-3'-indolylmethane)-indole-3-carboxylate (2) were synthesized. They are interesting as the analogs of 3,3'-diindolylmethane, which is intensively tested as a potent antitumor agent. Their solid-state structure was characterized using 13C CP/MAS NMR or X-ray diffraction measurements. Molecular modeling was used as a help in the structure elucidation. The solid-state NMR spectroscopy showed only one stable conformer of 1, but the X-ray diffraction results indicate that compound 2 crystallizes in the triclinic space group P-1 with two molecules, A and B, in the asymmetric unit. Both compounds inhibited the growth of melanoma, renal and breast cancers cell lines.

  19. Endocarp thickness affects seed removal speed by small rodents in a warm-temperate broad-leafed deciduous forest, China

    NASA Astrophysics Data System (ADS)

    Zhang, Hongmao; Zhang, Zhibin

    2008-11-01

    Seed traits are important factors affecting seed predation by rodents and thereby the success of recruitment. Seeds of many tree species have hard hulls. These are thought to confer mechanical protection, but the effect of endocarp thickness on seed predation by rodents has not been well investigated. Wild apricot ( Prunus armeniaca), wild peach ( Amygdalus davidiana), cultivated walnut ( Juglans regia), wild walnut ( Juglans mandshurica Maxim) and Liaodong oak ( Quercus liaotungensis) are very common tree species in northwestern Beijing city, China. Their seeds vary greatly in size, endocarp thickness, caloric value and tannin content. This paper aims to study the effects of seed traits on seed removal speed of these five tree species by small rodents in a temperate deciduous forest, with emphasis on the effect of endocarp thickness. The results indicated that speed of removal of seeds released at stations in the field decreased significantly with increasing endocarp thickness. We found no significant correlations between seed removal speed and other seed traits such as seed size, caloric value and tannin content. In seed selection experiments in small cages, Père David's rock squirrel ( Sciurotamias davidianus), a large-bodied, strong-jawed rodent, selected all of the five seed species, and the selection order among the five seed species was determined by endocarp thickness and the ratio of endocarp mass/seed mass. In contrast, the Korean field mouse ( Apodemus peninsulae) and Chinese white-bellied rat ( Niviventer confucianus), with relatively small bodies and weak jaws, preferred to select small seeds like acorns of Q. liaotungensis and seeds of P. armeniaca, indicating that rodent body size is also an important factor affecting food selection based on seed size. These results suggest endocarp thickness significantly reduces seed removal speed by rodents and then negatively affects dispersal fitness of seeds before seed removal of tree species in the study

  20. The role of rodents in the seed fate of a thorny shrub in an ancient wood pasture

    NASA Astrophysics Data System (ADS)

    Scheper, Jeroen; Smit, Christian

    2011-03-01

    Thorny shrubs play a crucial role for the diversity and dynamics in wood pastures: they protect non-defended plants from large herbivores and thus facilitate tree establishment in the landscape through associational resistance. How thorny shrubs themselves establish in wood pastures - the main bottleneck for a dynamic shifting of grassland - shrub - woodland mosaics - is an essential unanswered question. We studied post-primary dispersal seed fate - i.e. removal, predation, secondary dispersal and survival of seeds after primary dispersal - of the thorny shrub blackthorn ( Prunus spinosa) in an ancient wood pasture in the Netherlands. Blackthorn seeds are primarily dispersed by frugivorous birds and may secondarily be dispersed by scatter-hoarding rodents. We performed two cafeteria-style experiments with blackthorn seeds placed on dishes in the dominant vegetation types. In the first we monitored seed removal in grassland, swards or blackthorn shrubs and determined rodent species abundance by live-trapping. In the second we followed tagged blackthorn seeds under shrubs and in swards to determine seed removal, predation, survival and secondary dispersal patterns. Tagged seeds were retrieved using a metal detector and by visual means. We recorded dispersal direction and distance, vegetation type, seed handling (burial, consumption) and rodent species responsible via bite marks. Seed removal and number of live-trapped rodents differed between vegetation types, with higher removal and rodent captures under shrubs than in swards and grassland. All retrieved seeds were depredated, predominantly by the wood mouse ( Apodemus sylvaticus). Disproportionally high seed numbers were retrieved in the vegetation type where originally placed (shrubs or swards). Our study suggests that rodents play an important role for blackthorn in wood pastures, predominantly as seed predators rather than secondary seed dispersers. Predation is particularly high under blackthorn shrubs

  1. 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

  2. Bovine and rodent tamm-horsfall protein (THP) genes: cloning, structural analysis, and promoter identification.

    PubMed

    Yu, H; Papa, F; Sukhatme, V P

    1994-01-01

    We have isolated bovine and rodent cDNA and genomic clones encoding the kidney-specific Tamm-Horsfall protein (THP). In both species the gene contains 11 exons, the first of which is noncoding. Exon/intron junctions were analyzed and all were shown to follow the AG/GT rule. A kidney-specific DNase I hypersensitive site was mapped onto a rodent genomic fragment for which the sequence is highly conserved in three species (rat, cow, and human) over a stretch of 350 base pairs. Primer extension and RNase protection analysis identified a transcription start site at the 3' end of this conserved region. A TATA box is located at 32 nucleotides upstream of the start site in the bovine gene and 34 nucleotides upstream in the rodent gene. An inverted CCAAT motif occurs at 65 and 66 nucleotides upstream of the start site in the bovine and rodent genes, respectively. Other highly conserved regions were noted in this 350 bp region and these are likely to be binding sites for transcription factors. A functional assay based on an in vitro transcription system confirmed that the conserved region is an RNA Pol II promoter. The in vitro system accurately initiated transcription from the in vivo start site and was highly sensitive to inhibition by alpha-amanitin at a concentration of 2.5 micrograms/ml. These studies set the stage for the further definition of cis-acting sequences and trans-factors regulating expression of the THP gene, a model for kidney-specific gene expression.

  3. RpoS and Indole Signaling Control the Virulence of Vibrio anguillarum towards Gnotobiotic Sea Bass (Dicentrarchus labrax) Larvae

    PubMed Central

    Li, Xuan; Yang, Qian; Dierckens, Kristof; Milton, Debra L.; Defoirdt, Tom

    2014-01-01

    Quorum sensing, bacterial cell-to-cell communication with small signal molecules, controls the virulence of many pathogens. In contrast to other vibrios, neither the VanI/VanR acylhomoserine lactone quorum sensing system, nor the three-channel quorum sensing system affects virulence of the economically important aquatic pathogen Vibrio anguillarum. Indole is another molecule that recently gained attention as a putative signal molecule. The data presented in this study indicate that indole signaling and the alternative sigma factor RpoS have a significant impact on the virulence of V. anguillarum. Deletion of rpoS resulted in increased expression of the indole biosynthesis gene tnaA and in increased production of indole. Both rpoS deletion and the addition of exogenous indole (50–100 µM) resulted in decreased biofilm formation, exopolysaccharide production (a phenotype that is required for pathogenicity) and expression of the exopolysaccharide synthesis gene wbfD. Further, indole inhibitors increased the virulence of the rpoS deletion mutant, suggesting that indole acts downstream of RpoS. Finally, in addition to the phenotypes found to be affected by indole, the rpoS deletion mutant also showed increased motility and decreased sensitivity to oxidative stress. PMID:25360804

  4. Genome Sequence of an Efficient Indole-Degrading Bacterium, Cupriavidus sp. Strain IDO, with Potential Polyhydroxyalkanoate Production Applications

    PubMed Central

    Ma, Qiao; Zhang, Zhaojing; Li, Pengpeng

    2015-01-01

    Cupriavidus sp. strain IDO has been shown to efficiently transform indole, and the genus of Cupriavidus has been described as a promising cell factory for polyhydroxyalkanoate synthesis from low-cost wastes. Here, we report the draft genome sequence of strain IDO, which may provide useful genetic information on indole metabolism and polyhydroxyalkanoate production. PMID:25767238

  5. 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

  6. 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

  7. THE INCREASED SUSCEPTIBILITY TO HEMOLYSIS BY INDOL IN DOGS FED DEFICIENT DIETS

    PubMed Central

    Rhoads, C. P.; Barker, W. Halsey; Miller, D. K.

    1938-01-01

    1. Indol is more hemolytic in the presence of a deficiency complex than when a normal diet is fed. 2. The hemolytic effect can be abolished by supplementing the deficient diet with liver extract curative of pernicious anemia in man. 3. The hemolysis affects all hemoglobin-containing cells, including reticulocytes. 4. The repair of the anemia resulting from the administration of indol in the presence of a deficiency represents the cessation of a hemolytic process. 5. An abnormally low rate of production of erythrocytes may well be a factor in the production of the anemia. PMID:19870721

  8. Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

    PubMed Central

    Herter, Susanne; Kranz, David C; Turner, Nicholas J

    2015-01-01

    Summary Cytochrome P450 monooxygenases are useful biocatalysts for C–H activation, and there is a need to expand the range of these enzymes beyond what is naturally available. A panel of 93 variants of active self-sufficient P450cam[Tyr96Phe]-RhFRed fusion enzymes with a broad diversity in active site amino acids was developed by screening a large mutant library of 16,500 clones using a simple, highly sensitive colony-based colorimetric screen against indole. These mutants showed distinct fingerprints of activity not only when screened in oxidations of substituted indoles but also for unrelated oxidations such as benzylic hydroxylations. PMID:26664590

  9. Highly Regio- and Enantioselective Formal [3 + 2]-Annulation of Indoles with Electrophilic Enol Carbene Intermediates.

    PubMed

    Jing, Changcheng; Cheng, Qing-Qing; Deng, Yongming; Arman, Hadi; Doyle, Michael P

    2016-09-16

    Chiral cyclopentane-fused indolines are synthesized with high regio- and enantiocontrol by formal [3 + 2]-annulation reactions of indoles and electrophilic enol carbenes. High enantioselectivity and exclusive regiocontrol occurred with enoldiazoacetamides using a less sterically encumbered prolinate-ligated dirhodium(II) catalyst in reactions with N-substituted indoles without substituents at the 2- or 3-positions via a selective vinylogous addition process. In this transformation, donor-acceptor cyclopropenes generated from enoldiazoacetamides serve as the carbene precursors to form metal carbene intermediates. PMID:27589203

  10. Design, synthesis, and biological activity of oxime ether strobilurin derivatives containing indole moiety as novel fungicide.

    PubMed

    Xie, Ya-Qiang; Huang, Zi-Long; Yan, Hui-Dong; Li, Jun; Ye, Li-Yi; Che, Li-Ming; Tu, Song

    2015-06-01

    Twenty-one novel oxime ether strobilurins containing indole moiety, which employed an indole group to stabilize the E-styryl group in Enoxastrobin, were designed and synthesized. The biological assay indicated that most compounds exhibited potent fungicidal activities. The structure-activity relationship study demonstrated that the synthesized methyl 3-methoxypropenoate oxime ethers 7b-e exhibited remarkably high activities among all the synthesized oxime ether compounds 7. Moreover, the fungicidal activities of methyl α-(methoxyimino)benzeneacetate oxime ethers compounds 7f-i and N-methoxy-carbamic acid methyl esters compounds 7j-m showed significant differences compared to the corresponding products of ammonolysis. PMID:25346294

  11. Synthesis of 1H-indole-2,3-dione-3-thiosemicarbazone ribonucleosides as antibacterial agents.

    PubMed

    Kassab, Shaymaa E; Hegazy, Gehan H; Eid, Nahed M; Amin, Kamelia M; El-Gendy, Adel A

    2010-01-01

    A new isatin ribonucleoside (3) was synthesized in a good yield by trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalyzed coupling reaction between the silylated nitrogenated base of 1H-Indole-2,3-dione (1) and 1,2,3,5-tetra-O-acetyl-beta-D-ribfuranose (2). Thiosemicarbazides 4a-e were utilized by the prepared ribonucleoside (3) to give new series of 1H-indole-2,3-dione-3-thiosemicarbazone ribonucleosides 5a-e. All compounds tested as antibacterial agents showed slight inhibitory activity against the selected bacterial strains.

  12. Synthesis of functionalized indole- and benzo-fused heterocyclic derivatives through anionic benzyne cyclization.

    PubMed

    Barluenga, José; Fañanás, Francisco J; Sanz, Roberto; Fernández, Yolanda

    2002-05-01

    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.

  13. Antioxidant, cytotoxic activities, and structure-activity relationship of gallic acid-based indole derivatives.

    PubMed

    Khaledi, Hamid; Alhadi, Abeer A; Yehye, Wagee A; Ali, Hapipah Mohd; Abdulla, Mahmood A; Hassandarvish, Pouya

    2011-11-01

    A new series of gallic hydrazones containing an indole moiety was synthesized through the reaction of gallic hydrazide and different indole carboxaldehydes. Their antioxidant activities were determined on DPPH radical scavenging and inhibition of lipid peroxidation. The in-vitro cytotoxic activities of the compounds were evaluated against HCT-116 (human colon cancer cell line) and MCF-7 (estrogen-dependent human breast cancer cell line) by the MTT method. An attempt to correlate the biological results with their structural characteristics has been done. A limited positive structure activity relationship was found between cytotoxic and antioxidant activities.

  14. 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. PMID:27005518

  15. Structural Diversity and Biological Activities of Indole Diketopiperazine Alkaloids from Fungi.

    PubMed

    Ma, Yang-Min; Liang, Xi-Ai; Kong, Yang; Jia, Bin

    2016-09-01

    Indole diketopiperazine alkaloids are secondary metabolites of microorganisms that are widely distributed in filamentous fungi, especially in the genera Aspergillus and Penicillium of the phylum Ascomycota or sac fungi. These alkaloids represent a group of natural products characterized by diversity in both chemical structures and biological activities. This review aims to summarize 166 indole diketopiperazine alkaloids from fungi published from 1944 to mid-2015. The emphasis is on diverse chemical structures within these alkaloids and their relevant biological activities. The aim is to assess which of these compounds merit further study for purposes of drug development. PMID:27538469

  16. Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions.

    PubMed

    Kelly, Paul P; Eichler, Anja; Herter, Susanne; Kranz, David C; Turner, Nicholas J; Flitsch, Sabine L

    2015-01-01

    Cytochrome P450 monooxygenases are useful biocatalysts for C-H activation, and there is a need to expand the range of these enzymes beyond what is naturally available. A panel of 93 variants of active self-sufficient P450cam[Tyr96Phe]-RhFRed fusion enzymes with a broad diversity in active site amino acids was developed by screening a large mutant library of 16,500 clones using a simple, highly sensitive colony-based colorimetric screen against indole. These mutants showed distinct fingerprints of activity not only when screened in oxidations of substituted indoles but also for unrelated oxidations such as benzylic hydroxylations.

  17. [A new indole derivative from endophyte Myrothecium roridum IFB-E091 in Artemisia annua].

    PubMed

    Shen, Li; Li, Ling-yu; Zhang, Xiao-jun; Li, Ming; Song, Yong-chun

    2015-10-01

    Three compounds were isolated from solid culture of endophyte Myrothecium roridum IFB-E091 in Artemisia annua. Their structures were determined as (S)-(-)-N-[2-(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (1), N-(4-hydroxyphenethyl)acetamide (2) and asperfumoid (3), in which compound 1 was a new indole derivative. In cytotoxicity assay, the compound 1 had no obvious inhibition activity in human hepatoma cell line SMMC-7721 and human cervical carcinoma cell line HeLa. PMID:26837178

  18. Indole alkaloids from Vinca major and V. minor growing in Turkey.

    PubMed

    Bahadori, Fatemeh; Topçu, Gülaçti; Boğa, Mehmet; Türkekul, Ayla; Kolak, Ufuk; Kartal, Murat

    2012-06-01

    A new indole alkaloid, 11-hydroxypolyneuridine, was isolated from Vinca major subsp. major L. and the known indole alkaloids vallesiachotamine and isovallesiachotamine from Vinca minor L. This is the first report on the alkaloids of both Vinca species growing in Turkey; vallesiachotamine and isovallesiachotamine were isolated from a Vinca species for the first time. V. minor may be considered as a new source for these two alkaloids due to their occurrence in high amount in the aerial parts of the plant. The alkaloid extracts of the two Vinca species were found to have high lipid peroxidation inhibitory and DPPH radical scavenging activities. Anticholinesterase activity of the extracts was also very strong.

  19. Substituted indoles as HIV-1 non-nucleoside reverse transcriptase inhibitors: a patent evaluation (WO2015044928).

    PubMed

    Li, Xiao; Gao, Ping; Zhan, Peng; Liu, Xinyong

    2016-05-01

    The invention described in this patent (WO2015044928) is related to compounds based on the substituted indole scaffold, their synthetic process and application to inhibit HIV-1 replication as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Some of the newly claimed compounds presented improved potency against wild-type (WT) HIV-1 strain in comparison to previously disclosed indole-based NNRTIs and were also shown to be effective against common resistant HIV-1 strains. In light of their novel structural characteristics, simple synthetic route and improved anti-HIV activity, these compounds deserve further study as promising NNRTIs.

  20. Indole – the scent of a healthy ‘inner soil’

    PubMed Central

    Berstad, Arnold; Raa, Jan; Valeur, Jørgen

    2015-01-01

    Tryptophan is an essential amino acid with an indole nucleus. Humans cannot produce this amino acid themselves, but must obtain it through their diet. Much attention is currently paid to the wide physiological and clinical implications of the tryptophan-derived substances, serotonin and kynurenines, generated by human enzymes following the intestinal absorption of tryptophan. However, even before being absorbed, several microbial metabolites of tryptophan are formed, mainly from ‘malabsorbed’ (incompletely digested) proteins within the colon. The normal smell of human faeces is largely due to indole, one of the major metabolites. Recent studies indicate that this foul-smelling substance is also of utmost importance for our health. PMID:26282698

  1. Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions.

    PubMed

    Kelly, Paul P; Eichler, Anja; Herter, Susanne; Kranz, David C; Turner, Nicholas J; Flitsch, Sabine L

    2015-01-01

    Cytochrome P450 monooxygenases are useful biocatalysts for C-H activation, and there is a need to expand the range of these enzymes beyond what is naturally available. A panel of 93 variants of active self-sufficient P450cam[Tyr96Phe]-RhFRed fusion enzymes with a broad diversity in active site amino acids was developed by screening a large mutant library of 16,500 clones using a simple, highly sensitive colony-based colorimetric screen against indole. These mutants showed distinct fingerprints of activity not only when screened in oxidations of substituted indoles but also for unrelated oxidations such as benzylic hydroxylations. PMID:26664590

  2. The effects of UV-B stress on the production of terpenoid indole alkaloids in Catharanthus roseus hairy roots.

    PubMed

    Binder, Bernard Y K; Peebles, Christie A M; Shanks, Jacqueline V; San, Ka-Yiu

    2009-01-01

    In nature, plants generate protective secondary metabolites in response to environmental stresses. Such metabolites include terpenoid indole alkaloids (TIAs), which absorb UV-B light and serve putatively to protect the plant from harmful radiation. Catharanthus roseus plants, multiple shoot cultures, and cell suspension cultures exposed to UV-B light show significant increases in the production of TIAs, including precursors to vinblastine and vincristine, which have proven effective in the treatment of leukemia and lymphoma. Here, the effect of UV-B light on C. roseus hairy roots was examined. Analysis of alkaloid concentrations up to 168 h after UV-B exposure shows significant increases in the concentrations of lochnericine and significant decreases in the concentration of hörhammericine over time (ANOVA, P < 0.05). Our results also indicate that increasing UV-B exposure time up to 20 min caused significant increases in lochnericine, serpentine, and ajmalicine and a decrease in hörhammericine (t-test, p < 0.05). PMID:19479674

  3. Data quality in predictive toxicology: reproducibility of rodent carcinogenicity experiments.

    PubMed Central

    Gottmann, E; Kramer, S; Pfahringer, B; Helma, C

    2001-01-01

    We compared 121 replicate rodent carcinogenicity assays from the two parts (National Cancer Institute/National Toxicology Program and literature) of the Carcinogenic Potency Database (CPDB) to estimate the reliability of these experiments. We estimated a concordance of 57% between the overall rodent carcinogenicity classifications from both sources. This value did not improve substantially when additional biologic information (species, sex, strain, target organs) was considered. These results indicate that rodent carcinogenicity assays are much less reproducible than previously expected, an effect that should be considered in the development of structure-activity relationship models and the risk assessment process. PMID:11401763

  4. 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.

  5. Widespread vestibular activation of the rodent cortex.

    PubMed

    Rancz, Ede A; Moya, Javier; Drawitsch, Florian; Brichta, Alan M; Canals, Santiago; Margrie, Troy W

    2015-04-15

    Much of our understanding of the neuronal mechanisms of spatial navigation is derived from chronic recordings in rodents in which head-direction, place, and grid cells have all been described. However, despite the proposed importance of self-reference information to these internal representations of space, their congruence with vestibular signaling remains unclear. Here we have undertaken brain-wide functional mapping using both fMRI and electrophysiological methods to directly determine the spatial extent, strength, and time course of vestibular signaling across the rat forebrain. We find distributed activity throughout thalamic, limbic, and particularly primary sensory cortical areas in addition to known head-direction pathways. We also observe activation of frontal regions, including infralimbic and cingulate cortices, indicating integration of vestibular information throughout functionally diverse cortical regions. These whole-brain activity maps therefore suggest a widespread contribution of vestibular signaling to a self-centered framework for multimodal sensorimotor integration in support of movement planning, execution, spatial navigation, and autonomic responses to gravito-inertial changes. PMID:25878265

  6. Navigating actions through the rodent parietal cortex

    PubMed Central

    Whitlock, Jonathan R.

    2014-01-01

    The posterior parietal cortex (PPC) participates in a manifold of cognitive functions, including visual attention, working memory, spatial processing, and movement planning. Given the vast interconnectivity of PPC with sensory and motor areas, it is not surprising that neuronal recordings show that PPC often encodes mixtures of spatial information as well as the movements required to reach a goal. Recent work sought to discern the relative strength of spatial vs. motor signaling in PPC by recording single unit activity in PPC of freely behaving rats during selective changes in either the spatial layout of the local environment or in the pattern of locomotor behaviors executed during navigational tasks. The results revealed unequivocally a predominant sensitivity of PPC neurons to locomotor action structure, with subsets of cells even encoding upcoming movements more than 1 s in advance. In light of these and other recent findings in the field, I propose that one of the key contributions of PPC to navigation is the synthesis of goal-directed behavioral sequences, and that the rodent PPC may serve as an apt system to investigate cellular mechanisms for spatial motor planning as traditionally studied in humans and monkeys. PMID:24860475

  7. Hindlimb unloading rodent model: technical aspects

    NASA Technical Reports Server (NTRS)

    Morey-Holton, Emily R.; Globus, Ruth K.

    2002-01-01

    Since its inception at the National Aeronautics and Space Administration (NASA) Ames Research Center in the mid-1970s, many laboratories around the world have used the rat hindlimb unloading model to simulate weightlessness and to study various aspects of musculoskeletal loading. In this model, the hindlimbs of rodents are elevated to produce a 30 degrees head-down tilt, which results in a cephalad fluid shift and avoids weightbearing by the hindquarters. Although several reviews have described scientific results obtained with this model, this is the first review to focus on the technical aspects of hindlimb unloading. This review includes a history of the technique, a brief comparison with spaceflight data, technical details, extension of the model to mice, and other important technical considerations (e.g., housing, room temperature, unloading angle, the potential need for multiple control groups, age, body weight, the use of the forelimb tissues as internal controls, and when to remove animals from experiments). This paper is intended as a reference for researchers, reviewers of manuscripts, and institutional animal care and use committees. Over 800 references, related to the hindlimb unloading model, can be accessed via the electronic version of this article.

  8. Assessing spatial learning and memory in rodents.

    PubMed

    Vorhees, Charles V; Williams, Michael T

    2014-01-01

    Maneuvering safely through the environment is central to survival of almost all species. The ability to do this depends on learning and remembering locations. This capacity is encoded in the brain by two systems: one using cues outside the organism (distal cues), allocentric navigation, and one using self-movement, internal cues and nearby proximal cues, egocentric navigation. Allocentric navigation involves the hippocampus, entorhinal cortex, and surrounding structures; in humans this system encodes allocentric, semantic, and episodic memory. This form of memory is assessed in laboratory animals in many ways, but the dominant form of assessment is the Morris water maze (MWM). Egocentric navigation involves the dorsal striatum and connected structures; in humans this system encodes routes and integrated paths and, when overlearned, becomes procedural memory. In this article, several allocentric assessment methods for rodents are reviewed and compared with the MWM. MWM advantages (little training required, no food deprivation, ease of testing, rapid and reliable learning, insensitivity to differences in body weight and appetite, absence of nonperformers, control methods for proximal cue learning, and performance effects) and disadvantages (concern about stress, perhaps not as sensitive for working memory) are discussed. Evidence-based design improvements and testing methods are reviewed for both rats and mice. Experimental factors that apply generally to spatial navigation and to MWM specifically are considered. It is concluded that, on balance, the MWM has more advantages than disadvantages and compares favorably with other allocentric navigation tasks.

  9. Object recognition memory and the rodent hippocampus.

    PubMed

    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 task. Rats received 12 5-min exposures to two identical objects and then received either bilateral lesions of the hippocampus or sham surgery 1 d, 4 wk, or 8 wk after the final exposure. On a retention test 2 wk after surgery, the 1-d and 4-wk hippocampal lesion groups exhibited impaired object recognition memory. In contrast, the 8-wk hippocampal lesion group performed similarly to controls, and both groups exhibited a preference for the novel object. These same rats were then given four postoperative tests using unique object pairs and a 3-h delay between the exposure phase and the test phase. Hippocampal lesions produced moderate and reliable memory impairment. The results suggest that the hippocampus is important for object recognition memory.

  10. Assessing Spatial Learning and Memory in Rodents

    PubMed Central

    Vorhees, Charles V.; Williams, Michael T.

    2014-01-01

    Maneuvering safely through the environment is central to survival of almost all species. The ability to do this depends on learning and remembering locations. This capacity is encoded in the brain by two systems: one using cues outside the organism (distal cues), allocentric navigation, and one using self-movement, internal cues and nearby proximal cues, egocentric navigation. Allocentric navigation involves the hippocampus, entorhinal cortex, and surrounding structures; in humans this system encodes allocentric, semantic, and episodic memory. This form of memory is assessed in laboratory animals in many ways, but the dominant form of assessment is the Morris water maze (MWM). Egocentric navigation involves the dorsal striatum and connected structures; in humans this system encodes routes and integrated paths and, when overlearned, becomes procedural memory. In this article, several allocentric assessment methods for rodents are reviewed and compared with the MWM. MWM advantages (little training required, no food deprivation, ease of testing, rapid and reliable learning, insensitivity to differences in body weight and appetite, absence of nonperformers, control methods for proximal cue learning, and performance effects) and disadvantages (concern about stress, perhaps not as sensitive for working memory) are discussed. Evidence-based design improvements and testing methods are reviewed for both rats and mice. Experimental factors that apply generally to spatial navigation and to MWM specifically are considered. It is concluded that, on balance, the MWM has more advantages than disadvantages and compares favorably with other allocentric navigation tasks. PMID:25225309

  11. Cellular scaling rules for rodent brains.

    PubMed

    Herculano-Houzel, Suzana; Mota, Bruno; Lent, Roberto

    2006-08-01

    How do cell number and size determine brain size? Here, we show that, in the order Rodentia, increased size of the cerebral cortex, cerebellum, and remaining areas across six species is achieved through greater numbers of neurons of larger size, and much greater numbers of nonneuronal cells of roughly invariant size, such that the ratio between total neuronal and nonneuronal mass remains constant across species. Although relative cerebellar size remains stable among rodents, the number of cerebellar neurons increases with brain size more rapidly than in the cortex, such that the cerebellar fraction of total brain neurons increases with brain size. In contrast, although the relative cortical size increases with total brain size, the cortical fraction of total brain neurons remains constant. We propose that the faster increase in average neuronal size in the cerebral cortex than in the cerebellum as these structures gain neurons and the rapidly increasing glial numbers that generate glial mass to match total neuronal mass at a fixed glia/neuron total mass ratio are fundamental cellular constraints that lead to the relative expansion of cerebral cortical volume across species.

  12. Mother–Pup Interactions: Rodents and Humans

    PubMed Central

    Lucion, Aldo B.; Bortolini, Maria Cátira

    2014-01-01

    In order to survive after birth, mammalian infants need a caretaker, usually the mother. Several behavioral strategies have evolved to guarantee the transition from a period of intense caregiving to offspring independence. Here, we examine a selection of literature on the genetic, epigenetic, physiological, and behavioral factors relating to development and mother–infant interactions. We intend to show the utility of comparisons between rodent and human models for deepening knowledge regarding this key relationship. Particular attention is paid to the following factors: the distinct developmental stages of the mother–pup relationship as relating to behavior; examples of key genetic components of mammalian mother–infant interactions, specifically those coding for the hormones oxytocin and vasopressin; and the possible functions of gene imprinting in mediating interactions between genetics and environment in the mother–infant relationship. As early mother–infant attachment seems to establish the basic parameters for later social interactions, ongoing investigations in this area are essential. We propose the importance of interdisciplinary collaboration in order to better understand the network of genes, gene regulation, neuropeptide action, physiological processes, and feedback loops essential to understand the complex behaviors of mother–infant interaction. PMID:24616713

  13. Mother-pup interactions: rodents and humans.

    PubMed

    Lucion, Aldo B; Bortolini, Maria Cátira

    2014-01-01

    In order to survive after birth, mammalian infants need a caretaker, usually the mother. Several behavioral strategies have evolved to guarantee the transition from a period of intense caregiving to offspring independence. Here, we examine a selection of literature on the genetic, epigenetic, physiological, and behavioral factors relating to development and mother-infant interactions. We intend to show the utility of comparisons between rodent and human models for deepening knowledge regarding this key relationship. Particular attention is paid to the following factors: the distinct developmental stages of the mother-pup relationship as relating to behavior; examples of key genetic components of mammalian mother-infant interactions, specifically those coding for the hormones oxytocin and vasopressin; and the possible functions of gene imprinting in mediating interactions between genetics and environment in the mother-infant relationship. As early mother-infant attachment seems to establish the basic parameters for later social interactions, ongoing investigations in this area are essential. We propose the importance of interdisciplinary collaboration in order to better understand the network of genes, gene regulation, neuropeptide action, physiological processes, and feedback loops essential to understand the complex behaviors of mother-infant interaction. PMID:24616713

  14. First Isolates of Leptospira spp., from Rodents Captured in Angola

    PubMed Central

    Fortes-Gabriel, Elsa; Carreira, Teresa; Vieira, Maria Luísa

    2016-01-01

    Rodents play an important role in the transmission of pathogenic Leptospira spp. However, in Angola, neither the natural reservoirs of these spirochetes nor leptospirosis diagnosis has been considered. Regarding this gap, we captured rodents in Luanda and Huambo provinces to identify circulating Leptospira spp. Rodent kidney tissue was cultured and DNA amplified and sequenced. Culture isolates were evaluated for pathogenic status and typing with rabbit antisera; polymerase chain reaction (PCR) and sequencing were also performed. A total of 37 rodents were captured: Rattus rattus (15, 40.5%), Rattus norvegicus (9, 24.3%), and Mus musculus (13, 35.2%). Leptospiral DNA was amplified in eight (21.6%) kidney samples. From the cultures, we obtained four (10.8%) Leptospira isolates belonging to the Icterohaemorrhagiae and Ballum serogroups of Leptospira interrogans and Leptospira borgpetersenii genospecies, respectively. This study provides information about circulating leptospires spread by rats and mice in Angola. PMID:26928840

  15. First Isolates of Leptospira spp., from Rodents Captured in Angola.

    PubMed

    Fortes-Gabriel, Elsa; Carreira, Teresa; Vieira, Maria Luísa

    2016-05-01

    Rodents play an important role in the transmission of pathogenic Leptospira spp. However, in Angola, neither the natural reservoirs of these spirochetes nor leptospirosis diagnosis has been considered. Regarding this gap, we captured rodents in Luanda and Huambo provinces to identify circulating Leptospira spp. Rodent kidney tissue was cultured and DNA amplified and sequenced. Culture isolates were evaluated for pathogenic status and typing with rabbit antisera; polymerase chain reaction (PCR) and sequencing were also performed. A total of 37 rodents were captured: Rattus rattus (15, 40.5%), Rattus norvegicus (9, 24.3%), and Mus musculus (13, 35.2%). Leptospiral DNA was amplified in eight (21.6%) kidney samples. From the cultures, we obtained four (10.8%) Leptospira isolates belonging to the Icterohaemorrhagiae and Ballum serogroups of Leptospira interrogans and Leptospira borgpetersenii genospecies, respectively. This study provides information about circulating leptospires spread by rats and mice in Angola.

  16. Bone morphology of the hind limbs in two caviomorph rodents.

    PubMed

    de Araújo, F A P; Sesoko, N F; Rahal, S C; Teixeira, C R; Müller, T R; Machado, M R F

    2013-04-01

    In order to evaluate the hind limbs of caviomorph rodents a descriptive analysis of the Cuniculus paca (Linnaeus, 1766) and Hydrochoerus hydrochaeris (Linnaeus, 1766) was performed using anatomical specimens, radiography, computed tomography (CT) and full-coloured prototype models to generate bone anatomy data. The appendicular skeleton of the two largest rodents of Neotropical America was compared with the previously reported anatomical features of Rattus norvegicus (Berkenhout, 1769) and domestic Cavia porcellus (Linnaeus, 1758). The structures were analyzed macroscopically and particular findings of each species reported. Features including the presence of articular fibular projection and lunulae were observed in the stifle joint of all rodents. Imaging aided in anatomical description and, specifically in the identification of bone structures in Cuniculus paca and Hydrochoerus hydrochaeris. The imaging findings were correlated with the anatomical structures observed. The data may be used in future studies comparing these animals to other rodents and mammalian species.

  17. [Myobiiae parasites of rodents, Insectivora and Chiroptera (Acarina: Prostigmata)].

    PubMed

    Fain, A

    1976-02-01

    The author studies a collection of myobiid mites parasitic on rodents, insectivores and bats. This material contains 15 species, amongst them 7 species and 2 subspecies are new and are described for the first time.

  18. A NEW METHOD TO QUANTIFY CORE TEMPERATURE INSTABILITY IN RODENTS.

    EPA Science Inventory

    Methods to quantify instability of autonomic systems such as temperature regulation should be important in toxicant and drug safety studies. Stability of core temperature (Tc) in laboratory rodents is susceptible to a variety of stimuli. Calculating the temperature differential o...

  19. Zoonotic helminthes of commensal rodents in Talkha Center, Dakahlia Governorate.

    PubMed

    El Kady, Gamal A; Gheneam, Yousr Mosleh; Bahgat, Iman M

    2008-12-01

    Commensal rodents were trapped alive from different areas near garbage, canal edges, farm animals and the likes in Talkha Center over one year. A total of 135 rodents were collected, their species and index were Rattus norvegicus (0.11), R. r. frugivorous (0.13), R. r. alexandrinus (0.16) and Mus musculus (0.5). The zoonotic helminthes were trematodes (10 species), cestodes (4 species), and nematodes (10 species). The results were discussed on light of other works. PMID:19209769

  20. 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

  1. Catalytic C6 functionalization of 2,3-disubstituted indoles by scandium triflate.

    PubMed

    Liu, Hua; Zheng, Chao; You, Shu-Li

    2014-02-01

    We report herein an unprecedented direct catalytic C6 functionalization reaction of 2,3-disubstituted indoles with various N-Ts aziridines catalyzed by Sc(OTf)3 under mild conditions. Mechanistic studies revealed that a kinetically favored but reversible formal [3 + 2] annulation occurs initially. The direct C6 functionalization, although having a relatively higher energetic barrier, delivers the thermodynamically favorable products.

  2. Abiotic elicitation of indole phytoalexins and resistance to Leptosphaeria maculans within Brassiceae.

    PubMed

    Rouxel, T; Kollmann, A; Boulidard, L; Mithen, R

    1991-05-01

    Forty three accessions of Brassica species and one each of Sinapis and Raphanus were assessed for (i) resistance to Leptosphaeria maculans according to a coty-ledon-inoculation test and (ii) indole phytoalexin accumulation following abiotic elicitation with CuCl2. Five indole phytoalexins were determined in the lines following elicitation. Brassilexin, cyclobrassinin and cyclobrassinin sulphoxide were found within at least some lines of all species, whereas brassinin was only detected in B. oleracea and B. napus and methoxybrassinin within these two species and B. rapa and B. carinata. None of the five indole phytoalexins could be found in Raphanus sativus or Sinapis alba. The accumulation of large amounts of specific phytoalexins could be correlated with the presence of the different Brassica genomes. Lines possessing the B genome (B. nigra, B. juncea and B. carinata) which accumulated high amounts of brassilexin, displayed a hypersensitive resistance to infection whereas the majority of lines of B. oleracea, B. napus and B. rapa which did not accumulate large amounts of brassilexin, were susceptible. However, a B. nigra and a B. rapa line which only accumulated low amounts of brassilexin were highly resistant to the pathogen. Neither the accumulation of the other phytoalexins nor the total accumulation of indole phytoalexins could be related to resistance to L. maculans.

  3. Palladium-catalyzed synthesis of indoles via ammonia cross-coupling-alkyne cyclization.

    PubMed

    Alsabeh, Pamela G; Lundgren, Rylan J; Longobardi, Lauren E; Stradiotto, Mark

    2011-06-28

    The synthesis of indoles via the metal-catalyzed cross-coupling of ammonia is reported for the first time; the developed protocol also allows for the unprecedented use of methylamine or hydrazine as coupling partners. These Pd/Josiphos-catalyzed reactions proceed under relatively mild conditions for a range of 2-alkynylbromoarenes.

  4. Indole-3-acetic acid in Fusarium graminearum: Identification of biosynthetic pathways and characterization of physiological effects.

    PubMed

    Luo, Kun; Rocheleau, Hélène; Qi, Peng-Fei; Zheng, You-Liang; Zhao, Hui-Yan; Ouellet, Thérèse

    2016-09-01

    Fusarium graminearum is a devastating pathogenic fungus causing fusarium head blight (FHB) of wheat. This fungus can produce indole-3-acetic acid (IAA) and a very large amount of IAA accumulates in wheat head tissues during the first few days of infection by F. graminearum. Using liquid culture conditions, we have determined that F. graminearum can use tryptamine (TAM) and indole-3-acetonitrile (IAN) as biosynthetic intermediates to produce IAA. It is the first time that F. graminearum is shown to use the l-tryptophan-dependent TAM and IAN pathways rather than the indole-3-acetamide or indole-3-pyruvic acid pathways to produce IAA. Our experiments also showed that exogenous IAA was metabolized by F. graminearum. Exogenous IAA, TAM, and IAN inhibited mycelial growth; IAA and IAN also affected the hyphae branching pattern and delayed macroconidium germination. IAA and TAM had a small positive effect on the production of the mycotoxin 15-ADON while IAN inhibited its production. Our results showed that IAA and biosynthetic intermediates had a significant effect on F. graminearum physiology and suggested a new area of exploration for fungicidal compounds. PMID:27567719

  5. A visible-light-promoted aerobic metal-free C-3 thiocyanation of indoles.

    PubMed

    Fan, Weigang; Yang, Qi; Xu, Fengshan; Li, Pixu

    2014-11-01

    A simple and efficient visible-light-promoted method for the C-3 thiocyanation of indoles has been developed. The transformation uses Rose Bengal as the photocatalyst and air as the terminal oxidant. The reaction is mild, high-yielding, and environmentally benign.

  6. 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

  7. Spiro Fused Diterpene-Indole Alkaloids from a Creek-Bottom-Derived Aspergillus terreus

    PubMed Central

    Cai, Shengxin; Du, Lin; Gerea, Alexandra L.; King, Jarrod B.; You, Jianlan

    2013-01-01

    Four metabolites, teraspiridoles A–D (2–5), formed from the merger of diterpene and modified indole scaffold were obtained from an Aspergillus terreus isolate. The structures and absolute configurations of these natural products were established using NMR, mass spectrometry, Marfey’s method, VCD, and ECD data. Teraspiridole B (3) exhibited weak inhibition of planaria regeneration/survival. PMID:23924243

  8. Some new indole-coumarin hybrids; Synthesis, anticancer and Bcl-2 docking studies.

    PubMed

    Kamath, Pooja R; Sunil, Dhanya; Ajees, A Abdul; Pai, K S R; Das, Shubhankar

    2015-12-01

    Hybrid molecules have attracted attention for their improved biological activity, selectivity and lesser side effects profile, distinct from their individual components. In the quest for novel anticancer drug entities, three series of indole-coumarin hybrids - 3-(1-benzyl-1H-indol-2-yl)-2H-chromen-2-ones, 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carbaldehydes and 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carboxylic acids were synthesized. All the synthesized compounds were characterized by spectral techniques like IR, (1)H NMR, (13)C NMR, mass spectrometry and elemental analysis. In silico docking studies of synthesized molecules with apoptosis related gene Bcl-2 that is recognized to play an important role in tumerogenesis were carried out. Dose-dependent cytotoxic effect of the compounds in human breast adenocarcinoma (MCF-7) and normal cell lines were assessed using MTT assay and compared with that of the standard marketed drug, Vincristine. Compound 4c had a highly lipophilic bromine substituent capable of forming halogen bond and was identified as a potent molecule both in docking as well as cytotoxicity studies. Flow cytometric cell cycle analysis of 4c exhibited apoptotic mode of cell death due to cell cycle arrest in G2/M phase. Structure activity relationship of these hybrid molecules was also studied to determine the effect of steric and electronic properties of the substituents on cell viability.

  9. 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

  10. Synthesis of 2-vinylic indoles and derivatives via a Pd-catalyzed tandem coupling reaction.

    PubMed

    Fayol, Aude; Fang, Yuan-Qing; Lautens, Mark

    2006-09-14

    A novel one-step synthesis of valuable 2-vinylic indoles and their tricycle derivatives is described. This reaction, which utilizes a gem-dibromovinyl unit as a readily available starting material, occurs via an efficient Pd-catalyzed tandem Buchwald-Hartwig/Heck reaction. PMID:16956187

  11. Gold(I)-Catalyzed Dearomative Rautenstrauch Rearrangement: Enantioselective Access to Cyclopenta[b]indoles

    PubMed Central

    Zi, Weiwei; Wu, Hongmiao; Toste, F. Dean

    2016-01-01

    A highly enantioselective dearomative Rautenstrauch rearrangement catalyzed by cationic (S)-DTBM-Segphosgold(I) is reported. This reaction provides a straightforward method to prepare enantioenriched cyclopenta[b]indoles. These studies show vast difference in enantioselectivity in the reactions of propargyl acetates and propargyl acetals in the chiral ligand-controlled Rautenstrauch reaction. PMID:25710515

  12. [Spatial structure and mechanism of tyrosine phenol-lyase and tryptophan indole-lyase].

    PubMed

    Demidkina, T V; Anston, A A; Faleev, N G; Phillips, R S; Zakomyrdina, L N

    2009-01-01

    The bacterial tyrosine phenol-lyase (EC 4.1.99.2) and tryptoptophan indole-lyase (EC 4.1.99.1) belong to pyridoxal-5'-phosphate dependent beta-eliminating lyases, catalysing the reversible decomposition of L-tyrosine and L-tryptophan to pyruvate, ammonia, and phenol or indole correspondingly. Data on the three dimentional structures of the holoenzymes of tyrosine phenol-lyase and tryptophan indole-lyase and several enzyme-inhibitor complexes, modeling distinct reaction stages of the beta-elimination of L-tyrosine are described in the paper and structural bases of monovalent cations influence of activity of the enzymes are discussed. The spectral and catalytic properties of the mutant enzymes were studied. The data thus obtained have allowed us to elucidate the catalytic functions of a number of amino acid residues and conclude that the acid-base properties of the catalytic groups of the enzymes under the optimal for the catalysis conditions in hydrophobic active sites of tyrosine phenol-lyase and tryptoptophan indol-lyase are different from those in water solutions. Study of the mechanisms of labilization of Calpha-proton of the bound amino acids and activation of the leaving groups of the substrates during the catalytic process has demonstrated that in certain cases concerted reaction pathways are realized instead of stepwise ones. PMID:19425498

  13. 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. PMID:24158312

  14. Efficient direct 2,2,2-trifluoroethylation of indoles via C-H functionalization.

    PubMed

    Tolnai, Gergely L; Székely, Anna; Makó, Zita; Gáti, Tamás; Daru, János; Bihari, Tamás; Stirling, András; Novák, Zoltán

    2015-03-14

    A novel highly C3 selective metal free trifluoroethylation of indoles using 2,2,2-trifuoroethyl(mesityl)-iodonium triflate was developed. The methodology enables the introduction of a trifluoroethyl group in a fast and efficient reaction under mild conditions with high functional group tolerance. Beyond the synthetic developments, quantum chemical calculations provide a deeper understanding of the transformation. PMID:25682991

  15. A sulfenylation reaction: direct synthesis of 3-arylsulfinylindoles from arylsulfinic acids and indoles in water.

    PubMed

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

    2015-02-20

    A novel and efficient electrophilic sulfenylation of indoles with arylsulfinic acids is realized. The reaction utilizes readily available starting materials in water under catalyst- and additive-free conditions, providing an alternative and attractive approach to 3-arylsulfinylindoles with high yields. Preliminary mechanistic investigation suggested that the reaction is through an electrophilic substitution process.

  16. Synthesis and SAR of potent LXR agonists containing an indole pharmacophore

    SciTech Connect

    Washburn, David G.; Hoang, Tram H.; Campobasso, Nino; Smallwood, Angela; Parks, Derek J.; Webb, Christine L.; Frank, Kelly A.; Nord, Melanie; Duraiswami, Chaya; Evans, Christopher; Jaye, Michael; Thompson, Scott K.

    2009-03-27

    A novel series of 1H-indol-1-yl tertiary amine LXR agonists has been designed. Compounds from this series were potent agonists with good rat pharmacokinetic parameters. In addition, the crystal structure of an LXR agonist bound to LXR{alpha} will be disclosed.

  17. Clinical study of anesthetization by dezocine combined with propofol for indolent colonoscopy

    PubMed Central

    Xu, Bin-Bin; Zhao, Xiao-Liang; Xu, Gui-Ping

    2016-01-01

    AIM: To assess the use of dezocine combined with propofol for the anesthetization of patients undergoing indolent colonoscopy. METHODS: A cross-sectional survey of patients undergoing indolent colonoscopy in the Xinjiang People’s Hospital was conducted from April 1 to April 30, 2015. The survey collected patient general information and anesthesia data, including overall medical experience and pain management. Thirty minutes after colonoscopy surgery, samples of venous blood were collected and the biochemical indicators of gastrointestinal function were analyzed. RESULTS: There were 98 female and 62 male respondents. Indolent colonoscopy was found to be more suitable for mid to older-aged patients. The necessary conditions for the diagnosis of digestive diseases were required in 65 of the 73 inpatients. Adverse reactions to the intraoperative process included two cases of body movement and two cases of respiratory depression. Gastrin and vasoactive intestinal peptide levels were slightly increased. However, somatostatin and endothelin levels were slightly decreased. CONCLUSION: This study revealed that dezocine combined with propofol can be successfully used for the anesthetization of indolent colonoscopy patients without pain and should be widely used. PMID:27350739

  18. Pd-catalyzed cascade allylic alkylation and dearomatization reactions of indoles with vinyloxirane.

    PubMed

    Gao, Run-Duo; Xu, Qing-Long; Dai, Li-Xin; You, Shu-Li

    2016-09-14

    We have developed Pd-catalyzed intermolecular Friedel-Crafts-type allylic alkylation and allylic dearomatization reactions of substituted indoles bearing a nucleophilic group with vinyloxirane, providing an efficient method to synthesize structurally diverse tetrahydrocarboline and spiroindolenine derivatives under mild conditions. PMID:27511802

  19. Bendamustine: Safety and Efficacy in the Management of Indolent Non-Hodgkins Lymphoma

    PubMed Central

    Tageja, Nishant

    2011-01-01

    Bendamustine (Treanda, Ribomustin) was recently approved by the US Food and Drug Administration (FDA) for treatment of patients with rituximab refractory indolent lymphoma and is expected to turn into a frontline therapy option for indolent lymphoma. This compound with amphoteric properties was designed in the former Germany Democratic Republic in 1960s and re-discovered in 1990s with multiple successive well-designed studies. Bendamustine possesses a unique mechanism of action with potential antimetabolite properties, and only partial cross-resistance with other alkylators. Used in combination with rituximab in vitro, bendamustine shows synergistic effects against various leukemia and lymphoma cell lines. In clinical studies, bendamustine plus rituximab is highly effective in patients with relapsed-refractory indolent lymphoma, inducing remissions in 90% or more and a median progression-free survival of 23–24 months. The optimal dosing and schedule of bendamustine administration is largely undecided and varies among studies. Results of ongoing trials and dose-finding studies will help to further help ascertain the optimal place of bendamustine in the management of indolent NHL. PMID:21695099

  20. Construction of carbocyclic ring of indoles using ruthenium-catalyzed ring-closing olefin metathesis.

    PubMed

    Yoshida, Kazuhiro; Hayashi, Kazushi; Yanagisawa, Akira

    2011-09-16

    The selective synthesis of substituted indoles was achieved by the ring-closing olefin metathesis (RCM)/elimination sequence or the RCM/tautomerization sequence of functionalized pyrrole precursors. The RCM/elimination sequence was also applied to double ring closure to yield a substituted carbazole.

  1. Copper-catalyzed enantioselective C-H functionalization of indoles with an axially chiral bipyridine ligand.

    PubMed

    Gao, Xiang; Wu, Bo; Yan, Zhong; Zhou, Yong-Gui

    2016-09-21

    Using copper complexes with an axially chiral bipyridine ligand C4-ACBP as the catalyst, an enantioselective functionalization of indoles with diazo compounds was developed with up to 95% ee. This protocol paves the way for further applications of these ligands. PMID:27529404

  2. Chemical oxidation of a malodorous compound, indole, using iron entrapped in calcium alginate beads.

    PubMed

    Ben Hammouda, Samia; Adhoum, Nafaâ; Monser, Lotfi

    2016-01-15

    Iron-alginate beads (Fe-ABs) were successfully prepared by the ion-gelation method, and applied as heterogeneous Fenton catalysts for the removal of a malodorous compound 'indole'. Similarly, copper-enriched alginate beads (Cu-ABs) were synthesized and tested as like-Fenton catalyst, however, their application proved not to be effective for this purpose. Fe-ABs catalysts were characterized by FTIR, SEM, EDS and AAS spectroscopy. Results pointed out that the parameters affecting Fenton catalysis must be carefully chosen to avoid excessive iron release. Under optimal conditions, complete indole removal and considerably high reduction of TOC, without significant leaching was achieved. Indole decay followed a pseudo-first-order kinetics. The absolute rate constant for indole hydroxylation was 3.59×10(9) M(-1) s(-1), as determined by the competition kinetics method. Four reaction intermediates (Isatin, Dioxindole, Oxindole and Anthralinic acid) were identified by ULC/MS/MS analysis. Short-chain aliphatic carboxylic acids like formic, acetic, oxalic, maleic, oxamic and pyruvic acids were identified by ion exclusion chromatography and as end-products. Based on the identified by-products, a plausible mineralization pathway was proposed. Moreover, the catalyst was recovered quantitatively by simple filtration and reused for several times without significant loss of activity. PMID:26384996

  3. Galantamine derivatives with indole moiety: Docking, design, synthesis and acetylcholinesterase inhibitory activity.

    PubMed

    Atanasova, Mariyana; Stavrakov, Georgi; Philipova, Irena; Zheleva, Dimitrina; Yordanov, Nikola; Doytchinova, Irini

    2015-09-01

    The inhibitors of acetylcholinesterase are the main therapy against Alzheimer's disease. Among them, galantamine is the best tolerated and the most prescribed drug. In the present study, 41 galantamine derivatives with known acetylcholinesterase inhibitory activities expressed as IC50 were selected from the literature and docked into a recombinant human acetylcholinesterase by GOLD. A linear relationship between GoldScores and pIC50 values was found and used to design and predict novel galantamine derivatives with indole moiety in the side chain. The four best predicted compounds were synthesized and tested for inhibitory activity. All of them were between 11 and 95 times more active than galantamine. The novel galantamine derivatives with indole moiety have dual site binding to the enzyme--the galantamine moiety binds to the catalytic anionic site and the indole moiety binds to peripheral anionic site. Additionally, the indole moiety of one of the novel inhibitors binds in a region, close to the peripheral anionic site of the enzyme, where the Ω-loop of amyloid beta peptide adheres to acetylcholinesterase. This compound emerges as a promising lead compound for multi-target anti-Alzheimer therapy not only because of the strong inhibitory activity, but also because it is able to block the amyloid beta deposition on acetylcholinesterase. PMID:26260334

  4. 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.

  5. 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

  6. New monoclonal antibodies specific for 1-(5-fluoropentyl)-3-(2-iodobenzoyl)indole.

    PubMed

    Nakayama, Hiroshi; Kenjyou, Noriko

    2015-02-01

    1-(5-fluoropentyl)-3-(2-iodobenzoyl)indole (AM694) is one of the synthetic cannabinoids and an illegal drug in Japan. It is important to generate a monoclonal antibody (MAb) against AM694 for use in the rapid and sensitive detection of the drug. Two monoclonal antibodies, named HN0124 (IgG1) and NK0504 (IgG1), were obtained, which were possibly effective for detecting AM694 and its derivatives. The cross-reactive ability of these MAbs was evaluated using a competitive enzyme-linked immunosorbent assay. In the results, both of these antibodies recognize 1-(5-fluoropentyl)-3-(2-iodobenzoyl)indole, 1-(5-fluoropentyl)-3-(3-iodobenzoyl)indole, 1-(5-fluoropentyl)-3-(4-iodobenzoyl)indole. Forty nmol/L AM694 can be detected using HN0124 MAb. Thus, MAbs produced in this study could be considered a useful tool for the detection of AM694. PMID:25723285

  7. Direct C-H alkylation and indole formation of anilines with diazo compounds under rhodium catalysis.

    PubMed

    Mishra, Neeraj Kumar; Choi, Miji; Jo, Hyeim; Oh, Yongguk; Sharma, Satyasheel; Han, Sang Hoon; Jeong, Taejoo; Han, Sangil; Lee, Seok-Yong; Kim, In Su

    2015-12-18

    The rhodium(III)-catalyzed direct functionalization of aniline C-H bonds with α-diazo compounds is described. These transformations provide a facile construction of ortho-alkylated anilines with diazo malonates or highly substituted indoles with diazo acetoacetates.

  8. Transmission ecology of rodent-borne diseases: New frontiers.

    PubMed

    Bordes, Frédéric; Blasdell, Kim; Morand, Serge

    2015-09-01

    Rodents are recognized reservoir hosts for many human zoonotic pathogens. The current trends resulting from anthropocene defaunation suggest that in the future they, along with other small mammals, are likely to become the dominant mammals in almost all human-modified environments. Recent intricate studies on bat-borne emerging diseases have highlighted that many gaps exist in our understanding of the zoonotic transmission of rodent-borne pathogens. This has emphasized the need for scientists interested in rodent-borne diseases to integrate rodent ecology into their analysis of rodent-borne pathogen transmission in order to identify in more detail the mechanisms of spillover and chains of transmission. Further studies are required to better understand the true impact of rodent abundance and the importance of pathogen sharing and circulation in multi-host- multi-pathogen communities. We also need to explore in more depth the roles of generalist and abundant species as the potential links between pathogen-sharing, co-infections and disease transmission. PMID:26176684

  9. Serologic Survey of Orthopoxvirus Infection Among Rodents in Hungary

    PubMed Central

    Oldal, Miklós; Sironen, Tarja; Henttonen, Heikki; Vapalahti, Olli; Madai, Mónika; Horváth, Győző; Dallos, Bianka; Kutas, Anna; Földes, Fanni; Kemenesi, Gábor; Németh, Viktória; Bányai, Krisztián

    2015-01-01

    Abstract As a result of discontinuing vaccination against smallpox after the late 1970s, different orthopoxviruses (OPVs), such as cowpox virus (CPXV), have become a re-emerging healthcare threat among zoonotic pathogens. In Hungary, data on OPV prevalence among its rodent host species have been absent. Here, rodents belonging to four species, i.e., striped field mouse (Apodemus agrarius), yellow-necked mouse (A. flavicollis), wood mouse (A. sylvaticus) and bank vole (Myodes glareolus), were live trapped at 13 sampling plots on a 149-ha area in the Mecsek Mountains, Hungary, from March to September in 2011 and 2012. Rodent sera were collected and screened for OPV-reactive antibodies with an immunfluorescence assay (IFA). Among the 1587 tested rodents, 286 (18.0%) harbored OPV-specific antibodies. Seroprevalence was the highest for the bank vole (71.4%) and the striped field mouse (66.7%). Due to a masting event in the autumn of 2011 across Central Europe, the abundance of bank voles increased drastically in the 2012 season, raising the overall OPV seroprevalence. We provide the first data on OPV occurrence and seroprevalence in rodents in Hungary. The circulation of OPV in rodents in densely populated areas warrants further studies to elucidate the zoonotic potential of OPV in humans. PMID:25988441

  10. Spironolactone and colitis: Increased mortality in rodents and in humans

    PubMed Central

    Johnson, Laura A.; Govani, Shail M.; Joyce, Joel C.; Waljee, Akbar K.; Gillespie, Brenda W.; Higgins, Peter D. R.

    2011-01-01

    Background and Methods Crohn’s disease causes intestinal inflammation leading to intestinal fibrosis. Spironolactone is an anti-fibrotic medication commonly used in heart failure to reduce mortality. We examined whether spironolactone is anti-fibrotic in the context of intestinal inflammation. In vitro, spironolactone repressed fibrogenesis in TGFβ-stimulated human colonic myofibroblasts. However, spironolactone therapy significantly increased mortality in two rodent models of inflammation-induced intestinal fibrosis, suggesting spironolactone could be harmful during intestinal inflammation. Since IBD patients rarely receive spironolactone therapy, we examined whether spironolactone use was associated with mortality in a common cause of inflammatory colitis, Clostridium difficile infection (CDI). Results Spironolactone use during CDI infection was associated with increased mortality in a retrospective cohort of 4008 inpatients (15.9% vs. 9.1%, n=390 deaths, p<0.0001). In patients without liver disease, the adjusted OR for inpatient mortality associated with 80 mg spironolactone was 1.99 (95% CI: 1.51 – 2.63) In contrast to the main effect of spironolactone mortality, multivariable modeling revealed a protective interaction between liver disease and spironolactone dose. The adjusted odds ratio for mortality after CDI was 1.96 (95% CI: 1.50 – 2.55) for patients without liver disease on spironolactone vs. 1.28 (95% CI: 0.82 – 2.00) for patients with liver disease on spironolactone, when compared to a reference group without liver disease or spironolactone use. Conclusions We propose that discontinuation of spironolactone in patients without liver disease during CDI could reduce hospital mortality by 2-fold, potentially reducing mortality from CDI by 35,000 patients annually across Europe and the US. PMID:22081497

  11. Cannabinoids in Disguise: Δ9-Tetrahydrocannabinol-Like Effects of Tetramethylcyclopropyl Ketone Indoles

    PubMed Central

    Wiley, Jenny L.; Marusich, Julie A.; Lefever, Timothy W.; Grabenauer, Megan; Moore, Katherine N.; Thomas, Brian F.

    2013-01-01

    Synthetic indole-derived cannabinoids have become commonly used recreational drugs and continue to be abused despite their adverse consequences. As compounds that were identified early in the epidemic (e.g., naphthoylindoles) have become legally banned, new compounds have appeared on the drug market. Two tetramethylcyclopropyl ketone indoles, UR-144 [(1-pentyl-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone] and XLR-11 [(1-(5-fluoropentyl)-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone], recently have been identified in confiscated products. These compounds are structurally related to a series of CB2-selective compounds explored by Abbott Labs. The purpose of the present study was to evaluate the extent to which UR-144 and XLR-11 shared cannabinoid effects with Δ9-tetrahydrocannabinol (Δ9-THC). Indices of in vitro and in vivo activity at cannabinoid receptors were assessed. Similar to other psychoactive cannabinoid agonists, XLR-11 and UR-144 showed low nanomolar (< 30) affinity for CB1 and CB2 receptors, activated these receptors as full agonists, and produced dose-dependent effects that were blocked by rimonabant in mice, including antinociception, hypothermia, catalepsy and suppression of locomotor activity. The potency of both compounds was several-fold greater than Δ9-THC. XLR-11 and UR-144 also substituted for Δ9-THC in a Δ9-THC discrimination procedure in mice, effects that were attenuated by rimonabant. Analysis of urine from mice treated with the compounds revealed that both were extensively metabolized, with predominant urinary excretion as glucuronide conjugates. Together, these results demonstrate that UR-144 and XLR-11 share a pharmacological profile of in vitro and in vivo effects with Δ9-THC and other abused indole-derived cannabinoids and would be predicted to produce Δ9-THC-like subjective effects in humans. PMID:23916483

  12. Asymmetric Distribution of Glucose and Indole-3-Acetyl-myo-Inositol in Geostimulated Zea mays Seedlings 1

    PubMed Central

    Momonoki, Yoshie S.

    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. PMID:11537873

  13. Myo-Inositol Esters of Indole-3-acetic Acid as Seed Auxin Precursors of Zea mays L. 1

    PubMed Central

    Nowacki, Janusz; Bandurski, Robert S.

    1980-01-01

    Indole-3-acetyl-myo-inositol esters constitute 30% of the low molecular weight derivatives of indole-3-acetic acid (IAA) in seeds of Zea mays. [14C]Indole-3-acetyl-myo-inositol was applied to a cut in the endosperm of the seed and found to be transported from endosperm to shoot at 400 times the rate of transport of free IAA. The rate of transport of indole-3-acetyl-myo-inositol from endosperm to shoot was 6.3 picomoles per shoot per hour and thus adequate to serve as the seed auxin precursor for the free IAA diffusing downward from the shoot tip. Indole-3-acetyl-myo-inositol is the first seed auxin precursor to be identified. Application of either [14C]IAA or 14C-indole-3-acetyl-myo-inositol ester to the endosperm results in both free and esterified [14C]IAA in the seedling shoot. Esterification of free IAA and hydrolysis of indole-3-acetyl-myo-inositol occurred in the shoot and not the endosperm yielding ratios of ester to free IAA which approximate the ratios of ester to free IAA normally found in corn shoot tissue. This proves, for the first time, that esterified IAA and free IAA are interconvertible in the growing shoot. Since free IAA may be limiting for plant growth, knowledge that the free hormone is in “equilibrium” with its conjugates suggests new methods for the control of plant growth. PMID:16661205

  14. Indole inhibition of N-acylated homoserine lactone-mediated quorum signalling is widespread in Gram-negative bacteria.

    PubMed

    Hidalgo-Romano, Benjamin; Gollihar, Jimmy; Brown, Stacie A; Whiteley, Marvin; Valenzuela, Ernesto; Kaplan, Heidi B; Wood, Thomas K; McLean, Robert J C

    2014-11-01

    The LuxI/R quorum-sensing system and its associated N-acylated homoserine lactone (AHL) signal is widespread among Gram-negative bacteria. Although inhibition by indole of AHL quorum signalling in Pseudomonas aeruginosa and Acinetobacter oleivorans has been reported previously, it has not been documented among other species. Here, we show that co-culture with wild-type Escherichia coli, but not with E. coli tnaA mutants that lack tryptophanase and as a result do not produce indole, inhibits AHL-regulated pigmentation in Chromobacterium violaceum (violacein), Pseudomonas chlororaphis (phenazine) and Serratia marcescens (prodigiosin). Loss of pigmentation also occurred during pure culture growth of Chro. violaceum, P. chlororaphis and S. marcescens in the presence of physiologically relevant indole concentrations (0.5-1.0 mM). Inhibition of violacein production by indole was counteracted by the addition of the Chro. violaceum cognate autoinducer, N-decanoyl homoserine lactone (C10-HSL), in a dose-dependent manner. The addition of exogenous indole or co-culture with E. coli also affected Chro. violaceum transcription of vioA (violacein pigment production) and chiA (chitinase production), but had no effect on pykF (pyruvate kinase), which is not quorum regulated. Chro. violaceum AHL-regulated elastase and chitinase activity were inhibited by indole, as was motility. Growth of Chro. violaceum was not affected by indole or C10-HSL supplementation. Using a nematode-feeding virulence assay, we observed that survival of Caenorhabditis elegans exposed to Chro. violaceum, P. chlororaphis and S. marcescens was enhanced during indole supplementation. Overall, these studies suggest that indole represents a general inhibitor of AHL-based quorum signalling in Gram-negative bacteria. PMID:25165125

  15. Indole inhibition of N-acylated homoserine lactone-mediated quorum signalling is widespread in Gram-negative bacteria.

    PubMed

    Hidalgo-Romano, Benjamin; Gollihar, Jimmy; Brown, Stacie A; Whiteley, Marvin; Valenzuela, Ernesto; Kaplan, Heidi B; Wood, Thomas K; McLean, Robert J C

    2014-11-01

    The LuxI/R quorum-sensing system and its associated N-acylated homoserine lactone (AHL) signal is widespread among Gram-negative bacteria. Although inhibition by indole of AHL quorum signalling in Pseudomonas aeruginosa and Acinetobacter oleivorans has been reported previously, it has not been documented among other species. Here, we show that co-culture with wild-type Escherichia coli, but not with E. coli tnaA mutants that lack tryptophanase and as a result do not produce indole, inhibits AHL-regulated pigmentation in Chromobacterium violaceum (violacein), Pseudomonas chlororaphis (phenazine) and Serratia marcescens (prodigiosin). Loss of pigmentation also occurred during pure culture growth of Chro. violaceum, P. chlororaphis and S. marcescens in the presence of physiologically relevant indole concentrations (0.5-1.0 mM). Inhibition of violacein production by indole was counteracted by the addition of the Chro. violaceum cognate autoinducer, N-decanoyl homoserine lactone (C10-HSL), in a dose-dependent manner. The addition of exogenous indole or co-culture with E. coli also affected Chro. violaceum transcription of vioA (violacein pigment production) and chiA (chitinase production), but had no effect on pykF (pyruvate kinase), which is not quorum regulated. Chro. violaceum AHL-regulated elastase and chitinase activity were inhibited by indole, as was motility. Growth of Chro. violaceum was not affected by indole or C10-HSL supplementation. Using a nematode-feeding virulence assay, we observed that survival of Caenorhabditis elegans exposed to Chro. violaceum, P. chlororaphis and S. marcescens was enhanced during indole supplementation. Overall, these studies suggest that indole represents a general inhibitor of AHL-based quorum signalling in Gram-negative bacteria.

  16. Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

    PubMed Central

    Knepper, Kerstin; Vanderheiden, Sylvia

    2012-01-01

    Summary The synthesis of diverse substituted indole structures on solid supports is described. The immobilization of nitrobenzoic acid onto Merrifield resin and the subsequent treatment with alkenyl Grignard reagents delivered indole carboxylates bound to solid supports. In contrast to results in the liquid phase, ortho,ortho-unsubstituted nitroarenes also delivered indole moieties in good yields. Subsequent palladium-catalyzed reactions (Suzuki, Heck, Sonogashira, Stille) delivered, after cleavage, the desired molecules in moderate to good yields over four steps. The scope and limitations are presented. PMID:23019447

  17. Rhodium-Catalyzed Cyclization of 2-Ethynylanilines in the Presence of Isocyanates: Approach toward Indole-3-carboxamides.

    PubMed

    Mizukami, Akiho; Ise, Yumi; Kimachi, Tetsutaro; Inamoto, Kiyofumi

    2016-02-19

    Catalytic synthesis of indole-3-carboxamides from 2-ethynylanilines and isocyanates was achieved in the presence of a rhodium catalyst through a tandem-type, cyclization-addition sequence. This tandem-type process can be performed under mild reaction conditions, affording 2,3-disubstituted indoles in a one-pot manner generally in good to excellent yields. The broad substrate scope and good functional group compatibility make the method highly efficient and widely applicable, providing a facile and entirely novel route toward variously substituted indole-3-carboxamides.

  18. Quality of Life is Similar between Long-term Survivors of Indolent and Aggressive Non-Hodgkin Lymphoma.

    PubMed

    Beaven, Anne W; Samsa, Greg; Zimmerman, Sheryl; Smith, Sophia K

    2016-07-01

    Differences in quality of life (QOL) of long-term survivors of aggressive or indolent subtypes of non-Hodgkin lymphoma (NHL) have not been frequently evaluated. We assessed these differences by analyzing results of a large QOL survey of long-term NHL survivors. We hypothesized that the incurable nature of indolent NHL would relate to worse QOL in long-term survivors while the potentially cured long-term survivors of aggressive lymphoma would have better QOL. We found that QOL was similar between the two groups. Results suggest that patients with indolent NHL are coping well with their disease, yet experience some overall feelings of life threat. PMID:27379565

  19. Hypergravity Effects on Rodent Pregnancy and Parturition

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Baer, L. A.; Mills, N. A.; Wade, C. E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    No mammal has yet undergone birth, or parturition, in the microgravity of space. Previous studies (Ronco & Alberts, 2000) have shown that mid-pregnant rat dams exposed to spaceflight (0-g) and landed 48-72 hrs before term successfully delivered robust, healthy offspring Microgravity-exposed dams exhibited twice the expected numbers of labor contractions whereas length of pregnancy, duration of labor, fetal wastage, number of neonates born and litter gender ratios were identical to controls. In the present study, we report the results of rodent pregnancy and parturition at the opposite end of the gravity spectrum, in hypergravity. Dams exposed to either: 1.0-g, 1.5-g, 1.75-g or 2.0-g from Gestational day (G) 11 and throughout the births of their litters had comparable pregnancy and labor durations, fetal wastage, numbers of neonates born and litter Tender ratios. During parturition, hypergravity-exposed dams exhibited significantly fewer labor contractions as compared to 1.0-g controls. Dams that underwent birth in hypergravity had significantly fewer offspring surviving the immediate postpartum period (P1: 1.0-g, 11.92 +/- 2.84; 1.5-g, 10.88 +/- 2.17; 1.75-g, 9.22 +/-1.99; 2.0-g, 8.83 +/- 3.31). Within 24 hrs postpartum, neonatal survival was further diminished in hypergravity [P2: 100% (1.0-g); 96% (1.5-g); 96% (1.75-g); 73% (2.0-g)] and continued to decline (P10: 100%(1.0-g.); 90%(1.5-g); 87%(1.75-g), 40%(2.0-g)]. Neonatal losses stabilized by P5 for the 1.5-g andl.75-g conditions but continued until P9 for the 2.0-g condition. Together, these findings show that postnatal, but not prenatal, survival is compromised following birth in hypergravity, Maternal and neonatal factors that contribute to peri-parturitional vulnerability to altered gravity environments will be discussed.

  20. (Z)-3-(1H-Indol-3-yl)-2-(3-thienyl)acrylonitrile and (Z)-3-[1-(4-tert-butylbenzyl)-1H-indol-3-yl]-2-(3-thienyl)acrylonitrile.

    PubMed

    Sonar, Vijayakumar N; Parkin, Sean; Crooks, Peter A

    2005-02-01

    (Z)-3-(1H-Indol-3-yl)-2-(3-thienyl)acrylonitrile, C15H10N2S, (I), and (Z)-3-[1-(4-tert-butylbenzyl)-1H-indol-3-yl]-2-(3-thienyl)acrylonitrile, C26H24N2S, (II), were prepared by base-catalyzed reactions of the corresponding indole-3-carboxaldehyde with thiophene-3-acetonitrile. 1H/13C NMR spectral data and X-ray crystal structures of compounds (I) and (II) are presented. The olefinic bond connecting the indole and thiophene moieties has Z geometry in both cases, and the molecules crystallize in space groups P2(1)/c and C2/c for (I) and (II), respectively. Slight thienyl ring-flip disorder (ca 5.6%) was observed and modeled for (I).

  1. Minimal role for the circumsporozoite protein in the induction of sterile immunity by vaccination with live rodent malaria sporozoites.

    PubMed

    Mauduit, Marjorie; Tewari, Rita; Depinay, Nadya; Kayibanda, Michèle; Lallemand, Eliette; Chavatte, Jean-Marc; Snounou, Georges; Rénia, Laurent; Grüner, Anne Charlotte

    2010-05-01

    Immunization with live Plasmodium sporozoites under chloroquine prophylaxis (Spz plus CQ) induces sterile immunity against sporozoite challenge in rodents and, more importantly, in humans. Full protection is obtained with substantially fewer parasites than with the classic immunization with radiation-attenuated sporozoites. The sterile protection observed comprised a massive reduction in the hepatic parasite load and an additional effect at the blood stage level. Differences in the immune responses induced by the two protocols occur but are as yet little characterized. We have previously demonstrated that in mice immunized with irradiated sporozoites, immune responses against the circumsporozoite protein (CSP), the major component of the sporozoite's surface and the leading malaria vaccine candidate, were not essential for sterile protection. Here, we have employed transgenic Plasmodium berghei parasites in which the endogenous CSP was replaced by that of Plasmodium yoelii, another rodent malaria species, to assess the role of CSP in the sterile protection induced by the Spz-plus-CQ protocol. The data demonstrated that this role was minor because sterile immunity was obtained irrespective of the origin of CSP expressed by the parasites in this model of protection. The immunity was obtained through a single transient exposure of the host to the immunizing parasites (preerythrocytic and erythrocytic), a dose much smaller than that required for immunization with radiation-attenuated sporozoites.

  2. Global parasite and Rattus rodent invasions: The consequences for rodent-borne diseases.

    PubMed

    Morand, Serge; Bordes, Frédéric; Chen, Hsuan-Wien; Claude, Julien; Cosson, Jean-François; Galan, Maxime; Czirják, Gábor Á; Greenwood, Alex D; Latinne, Alice; Michaux, Johan; Ribas, Alexis

    2015-09-01

    We summarize the current knowledge on parasitism-related invasion processes of the globally invasive Rattus lineages, originating from Asia, and how these invasions have impacted the local epidemiology of rodent-borne diseases. Parasites play an important role in the invasion processes and successes of their hosts through multiple biological mechanisms such as "parasite release," "immunocompetence advantage," "biotic resistance" and "novel weapon." Parasites may also greatly increase the impact of invasions by spillover of parasites and other pathogens, introduced with invasive hosts, into new hosts, potentially leading to novel emerging diseases. Another potential impact is the ability of the invader to amplify local parasites by spillback. In both cases, local fauna and humans may be exposed to new health risks, which may decrease biodiversity and potentially cause increases in human morbidity and mortality. Here we review the current knowledge on these processes and propose some research priorities.

  3. Toxoplasmosis in rodents: ecological survey and first evidences in Thailand.

    PubMed

    Jittapalapong, Sathaporn; Sarataphan, Nachai; Maruyama, Soichi; Hugot, Jean-Pierre; Morand, Serge; Herbreteau, Vincent

    2011-03-01

    Domestic and wild rodents known as the most abundant and diversified order of mammals have a key role in the ecological food chain and also in the transmission of parasites and pathogens to other animals. While foraging on the ground, they can get infected by Toxoplasma gondii, a protozoan parasite, which is the causative agent of toxoplasmosis. Therefore, they serve as intermediate hosts of T. gondii and can transmit it to their predators. To assess their role in the maintenance of T. gondii lifecycle in Thailand, we sampled rodents in a range of biotopes representative of the high biodiversity and conducted a serological survey with latex agglutination test to detect anti-T. gondii antibodies. Overall, 21 of 461 (4.6%) rodents had diagnostically significant antibody titers (cutoff, 1:64). Every species with at least 37 individuals captured tested positive, confirming the wide range of potential mammalian hosts of toxoplasmosis. None of the ecological traits (sex, maturity, morphology, season, or habitat) was found significant to predict the susceptibility to T. gondii both univariately and in a multivariate analysis. However, high prevalences were reported in either forested or anthropized areas. This survey constitutes the first confirmed serological investigation of T. gondii in rodents in Thailand. The rarity of both domestic and wild felids in Thailand emphasizes the importance of rodents in maintaining T. gondii, and questions the involvement of other carnivores in the life cycle. PMID:20645868

  4. Thieving rodents as substitute dispersers of megafaunal seeds

    PubMed Central

    Jansen, Patrick A.; Hirsch, Ben T.; Emsens, Willem-Jan; Zamora-Gutierrez, Veronica; Wikelski, Martin; Kays, Roland

    2012-01-01

    The Neotropics have many plant species that seem to be adapted for seed dispersal by megafauna that went extinct in the late Pleistocene. Given the crucial importance of seed dispersal for plant persistence, it remains a mystery how these plants have survived more than 10,000 y without their mutualist dispersers. Here we present support for the hypothesis that secondary seed dispersal by scatter-hoarding rodents has facilitated the persistence of these large-seeded species. We used miniature radio transmitters to track the dispersal of reputedly megafaunal seeds by Central American agoutis, which scatter-hoard seeds in shallow caches in the soil throughout the forest. We found that seeds were initially cached at mostly short distances and then quickly dug up again. However, rather than eating the recovered seeds, agoutis continued to move and recache the seeds, up to 36 times. Agoutis dispersed an estimated 35% of seeds for >100 m. An estimated 14% of the cached seeds survived to the next year, when a new fruit crop became available to the rodents. Serial video-monitoring of cached seeds revealed that the stepwise dispersal was caused by agoutis repeatedly stealing and recaching each other’s buried seeds. Although previous studies suggest that rodents are poor dispersers, we demonstrate that communities of rodents can in fact provide highly effective long-distance seed dispersal. Our findings suggest that thieving scatter-hoarding rodents could substitute for extinct megafaunal seed dispersers of tropical large-seeded trees. PMID:22802644

  5. Distribution and characteristics of rodent picornaviruses in China

    PubMed Central

    Du, Jiang; Lu, Liang; Liu, Feng; Su, Haoxiang; Dong, Jie; Sun, Lilian; Zhu, Yafang; Ren, Xianwen; Yang, Fan; Guo, Fei; Liu, Qiyong; Wu, Zhiqiang; Jin, Qi

    2016-01-01

    Rodents are important reservoir hosts of many important zoonotic viruses. The family Picornaviridae contains clinically important pathogens that infect humans and animals, and increasing numbers of rodent picornaviruses have recently been associated with zoonoses. We collected 574 pharyngeal and anal swab specimens from 287 rodents of 10 different species from eight representative regions of China from October 2013 to July 2015. Seven representative sequences identified from six rodent species were amplified as full genomes and classified into four lineages. Three lineage 1 viruses belonged to a novel genus of picornaviruses and was more closely related to Hepatovirus than to others genera of picornaviruses based on aa homology. Lineage 2, lineage 3, and lineage 4 viruses belonged to the genera Rosavirus, Hunnivirus, and Enterovirus, respectively, representing new species. According to both phylogenetic and identity analyses, Lineage 2 viruses had a close relationship with rosavirus 2 which was recovered from the feces of a child in Gambia and Lineage 3 viruses had a close relationship with domestic animal Hunnivirus. Lineage 4 viruses provide the first evidence of these enteroviruses and their evolution in rodent hosts in China. PMID:27682620

  6. Fibroblasts From Long-Lived Rodent Species Exclude Cadmium

    PubMed Central

    Dostál, Lubomír; Kohler, William M.; Penner-Hahn, James E.; Miller, Richard A.

    2015-01-01

    Resistance to the lethal effects of cellular stressors, including the toxic heavy metal cadmium (Cd), is characteristic of fibroblast cell lines derived from long-lived bird and rodent species, as well as cell lines from several varieties of long-lived mutant mice. To explore the mechanism of resistance to Cd, we used inductively coupled plasma mass spectroscopy to measure the rate of Cd uptake into primary fibroblasts of 15 rodent species. These data indicate that fibroblasts from long-lived rodent species have slower rates of Cd uptake from the extracellular medium than those from short-lived species. In addition, fibroblasts from short-lived species export more zinc after exposure to extracellular Cd than cells from long-lived species. Lastly, fibroblasts from long-lived rodent species have lower baseline concentrations of two redox-active metals, iron and copper. Our results suggest that evolution of longevity among rodents required adjustment of cellular properties to alter metal homeostasis and to reduce the toxic effects of heavy metals that accumulate over the course of a longer life span. PMID:24522391

  7. A novel water delivery system for administering volatile chemicals while minimizing chemical waste in rodent toxicity studies.

    PubMed

    McDonald, A; Killough, P; Puckett, E; Best, D S; Simmons, J E; Pressman, J G; Narotsky, M G

    2010-01-01

    Rodent toxicity studies typically use water bottles to administer test chemicals via drinking water. However, water bottles provide inconsistent exposure of volatile chemicals due to varying headspace, and lead to excessive waste of test material. To refine drinking water toxicity studies in rodents by enhancing sample quality and consistency, and minimizing waste, we designed and implemented a novel water delivery system that keeps the water chilled, headspace free and protected from light. Materials used were resistant to chemical interaction. In this gravity-fed system, a 6-L Teflon water bag, stored in a polystyrene cooler on the cage rack, was connected to a stainless steel manifold delivering water to five cages via specialized drinking valves. Due to the absence of headspace in the water bag, this system allows consistent exposure of volatile chemicals. In addition, small diameter tubing throughout the system reduces the amount of test material residing in the system and minimizes chemical waste. PMID:19858168

  8. Structure-based design and biological evaluation of novel 2-(indol-2-yl) thiazole derivatives as xanthine oxidase inhibitors.

    PubMed

    Song, Jeong Uk; Jang, Jae Wan; Kim, Tae Hun; Park, Heuisul; Park, Wan Su; Jung, Sang-Hun; Kim, Geun Tae

    2016-02-01

    Inhibition of xanthine oxidase (XO) has obviously been a central concept for controlling hyperuricemia, which causes serious and painful inflammatory arthritis disease such as gout. We discovered a series of novel 2-(indol-2-yl)thiazole derivatives as XO inhibitors at the level of nanomolar activity. Structure-guided design using molecular modeling program (Accelrys Software program) provided an excellent basis for optimization of 2-(indol-2-yl)thiazole compounds. Structure-activity relationship indicated that hydrophobic alkoxy group (isopropoxy, cyclopentoxy) at 5-position and hydrogen binding acceptor (NO2, CN) at 7-position of indole ring appear as critical functional groups. Among the compounds, 2-(7-nitro-5-isopropoxy-indol-2-yl)-4-methylthiazole-5-carboxylic acid (9m) exhibits the most potent XO inhibitory activity (IC50 value: 5.1 nM) and the excellent uric acid lowering activity in potassium oxonate induced hyperuricemic rat model.

  9. General and selective C-3 alkylation of indoles with primary alcohols by a reusable Pt nanocluster catalyst.

    PubMed

    Siddiki, S M A Hakim; Kon, Kenichi; Shimizu, Ken-Ichi

    2013-10-18

    The platinum rule: Heterogeneous, additive-free C-3 selective alkylation of indoles by aliphatic and aromatic alcohols proceeded under transfer hydrogenation conditions with the reusable Pt/θ-Al2 O3 catalyst (see scheme; TON=turnover number).

  10. Intramolecular addition of diarylmethanols to imines promoted by KOt-Bu/DMF: a new synthetic approach to indole derivatives.

    PubMed

    Chen, Jia-Hua; Chen, Zi-Cong; Zhao, Hong; Zhang, Ting; Wang, Wei-Juan; Zou, Yong; Zhang, Xue-Jing; Yan, Ming

    2016-04-26

    KOt-Bu/DMF promoted intramolecular addition of diarylmethanols to imines was developed. A series of 2,3-disubstituted indoles was obtained in good yields. A reaction mechanism of radical cyclization and subsequent dehydration is proposed. PMID:27055383

  11. Oxidation of indole-3-acetic acid and oxindole-3-acetic acid to 2,3-dihydro-7-hydroxy-2-oxo-1H indole-3-acetic acid-7'-O-beta-D-glucopyranoside in Zea mays seedlings

    NASA Technical Reports Server (NTRS)

    Nonhebel, H. M.; Bandurski, R. S.

    1984-01-01

    Radiolabeled oxindole-3-acetic acid was metabolized by roots, shoots, and caryopses of dark grown Zea mays seedlings to 2,3-dihydro-7-hydroxy-2-oxo-1H indole-3-acetic acid-7'-O-beta-D-glycopyranoside with the simpler name of 7-hydroxyoxindole-3-acetic acid-glucoside. This compound was also formed from labeled indole-3-acetic acid supplied to intact seedlings and root segments. The glucoside of 7-hydroxyoxindole-3-acetic acid was also isolated as an endogenous compound in the caryopses and shoots of 4-day-old seedlings. It accumulates to a level of 4.8 nanomoles per plant in the kernel, more than 10 times the amount of oxindole-3-acetic acid. In the shoot it is present at levels comparable to that of oxindole-3-acetic acid and indole-3-acetic acid (62 picomoles per shoot). We conclude that 7-hydroxyoxindole-3-acetic acid-glucoside is a natural metabolite of indole-3-acetic acid in Z. mays seedlings. From the data presented in this paper and in previous work, we propose the following route as the principal catabolic pathway for indole-3-acetic acid in Zea seedlings: Indole-3-acetic acid --> Oxindole-3-acetic acid --> 7-Hydroxyoxindole-3-acetic acid --> 7-Hydroxyoxindole-3-acetic acid-glucoside.

  12. Female gender attenuates cytokine and chemokine expression and leukocyte recruitment in experimental rodent abdominal aortic aneurysms.

    PubMed

    Sinha, Indranil; Cho, Brenda S; Roelofs, Karen J; Stanley, James C; Henke, Peter K; Upchurch, Gilbert R

    2006-11-01

    Female gender appears to be protective in the development of abdominal aortic aneurysms (AAAs). This study sought to identify gender differences in cytokine and chemokine expression in an experimental rodent AAA model. Male and female rodent aortas were perfused with either saline (control) or elastase to induce AAA formation. Aortic diameter was determined and aortic tissue was harvested on postperfusion days 4 and 7. Cytokine and chemokine gene expression was examined using focused gene arrays. Immunohistochemistry was used to quantify aortic leukocyte infiltration. Data were analyzed by Student's t-tests and ANOVA. Elastase-perfused female rodents developed significantly smaller aneurysms compared to males by day 7 (93 +/- 10% vs. 201 +/- 25%, P = 0.003). Elastase-perfused female aortas exhibited a fivefold decrease in expression of the BMP family and ligands of the TNF superfamily compared to males. In addition, the expression of members of the TGF beta and VEGF families were three to fourfold lower in female elastase-perfused aortas compared to males. Multiple members of the interleukin, CC chemokine receptor, and CC ligand families were detectable in only the male elastase-perfused aortas. Female elastase-perfused aortas demonstrated a corollary twofold lower neutrophil count (females: 17.5 +/- 1.1 PMN/HPF; males: 41 +/- 5.2 neutrophils/HPF, P = 0.01) and a 1.5-fold lower macrophage count (females: 12 +/- 1.1 macrophages/HPF; males: 17.5 +/- 1.1 macrophages/HPF, P = 0.003) compared to male elastase-perfused aortas. This study documents decreased expression of multiple cytokines and chemokines and diminished leukocyte trafficking in female rat aortas compared to male aortas following elastase perfusion. These genes may contribute to the gender disparity seen in AAA formation. PMID:17182958

  13. Wildfires alter rodent community structure across four vegetation types in southern California, USA

    USGS Publications Warehouse

    Brehme, Cheryl S.; Clark, Denise R.; Rochester, Carlton J.; Fisher, Robert N.

    2011-01-01

    We surveyed burned and unburned plots across four habitat reserves in San Diego County, California, USA, in 2005 and 2006, to assess the effects of the 2003 wildfires on the community structure and relative abundance of rodent species. The reserves each contained multiple vegetation types (coastal sage scrub, chaparral, woodland, and grassland) and spanned from 250 m to 1078 m in elevation. Multivariate analyses revealed a more simplified rodent community structure in all burned habitats in comparison to unburned habitats. Reduction in shrub and tree cover was highly predictive of changes in post-fire rodent community structure in the burned coastal sage scrub and chaparral habitats. Reduction in cover was not predictive for the less substantially burned woodlands and grasslands, for which we hypothesized that interspecific competition played a greater role in post-fire community structure. Across vegetation types, generalists and open habitat specialists typically increased in relative abundance, whereas closed habitat specialists decreased. We documented significant increases in relative abundance of the deer mouse (Peromyscus maniculatus Wagner) and Dulzura kangaroo rat (Dipodomys simulans Merriam). In contrast, we found significant decreases in relative abundance for the California mouse (Peromyscus californicus Gambel), San Diego pocket mouse (Chaetodipus fallax Merriam), desert woodrat (Neotoma lepida Thomas), and brush mouse (Peromyscus boylii Baird). Currently, our research program involves assessment of whether habitat conservation plans (HCPs) in southern California provide long-term protection to HCP covered species, as well as preserve ecosystem function. The scenario of increased wildfires needs to be incorporated into this assessment. We discuss our results in relation to management and conservation planning under a future scenario of larger and more frequent wildfires in southern California.

  14. Indole production by the tryptophanase TnaA in Escherichia coli is determined by the amount of exogenous tryptophan.

    PubMed

    Li, Gang; Young, Kevin D

    2013-02-01

    The signalling molecule indole occurs in significant amounts in the mammalian intestinal tract and regulates diverse microbial processes, including bacterial motility, biofilm formation, antibiotic resistance and host cell invasion. In Escherichia coli, the enzyme tryptophanase (TnaA) produces indole from tryptophan, but it is not clear what determines how much indole E. coli can produce and excrete, making it difficult to interpret experiments that investigate the biological effects of indole at high concentrations. Here, we report that the final yield of indole depends directly, and perhaps solely, on the amount of exogenous tryptophan. When supplied with a range of tryptophan concentrations, E. coli converted this amino acid into an equal amount of indole, up to almost 5 mM, an amount well within the range of the highest concentrations so far examined for their physiological effects. Indole production relied heavily on the tryptophan-specific transporter TnaB, even though the alternative transporters AroP and Mtr could import sufficient tryptophan to induce tnaA expression. This TnaB requirement proceeded via tryptophan transport and was not caused by activation of TnaA itself. Bacterial growth was unaffected by the presence of TnaA in the absence of exogenous tryptophan, suggesting that the enzyme does not hydrolyse significant quantities of the internal anabolic amino acid pool. The results imply that E. coli synthesizes TnaA and TnaB mainly, or solely, for the purpose of converting exogenous tryptophan into indole, under conditions and for signalling purposes that remain to be fully elucidated.

  15. Arborisidine and Arbornamine, Two Monoterpenoid Indole Alkaloids with New Polycyclic Carbon-Nitrogen Skeletons Derived from a Common Pericine Precursor.

    PubMed

    Wong, Suet-Pick; Chong, Kam-Weng; Lim, Kuan-Hon; Lim, Siew-Huah; Low, Yun-Yee; Kam, Toh-Seok

    2016-04-01

    Two new monoterpene indole alkaloids, characterized by previously unencountered natural product skeletons, viz., arborisidine (1), incorporating indolizidine and cyclohexanone moieties fused to an indole unit, and arbornamine (2), incorporating an unprecedented 6/5/6/5/6 "arbornane" skeleton (distinct from the eburnan or tacaman skeleton), were isolated from a Malayan Kopsia arborea. The structures of the alkaloids were determined based on analysis of the NMR and MS data. Possible biogenetic pathways to these alkaloids from a common pericine precursor (3) are presented.

  16. Enantioselective palladium-catalyzed C-H functionalization of indoles using an axially chiral 2,2'-bipyridine ligand.

    PubMed

    Gao, Xiang; Wu, Bo; Huang, Wen-Xue; Chen, Mu-Wang; Zhou, Yong-Gui

    2015-10-01

    A palladium-catalyzed enantioselective CH functionalization of indoles was achieved with an axially chiral 2,2'-bipyridine ligand, thus providing the desired indol-3-acetate derivatives with up to 98 % ee. Moreover, the reaction protocol was also effective for asymmetric OH insertion reaction of phenols using α-aryl-α-diazoacetates. This represents the first successful application of bipyridine ligands with axial chirality in palladium-catalyzed carbene migratory insertion reactions.

  17. Rodents for comparative aging studies: from mice to beavers

    PubMed Central

    Bozzella, Michael J.; Seluanov, Andrei

    2008-01-01

    After humans, mice are the best-studied mammalian species in terms of their biology and genetics. Gerontological research has used mice and rats extensively to generate short- and long-lived mutants, study caloric restriction and more. Mice and rats are valuable model organisms thanks to their small size, short lifespans and fast reproduction. However, when the goal is to further extend the already long human lifespan, studying fast aging species may not provide all the answers. Remarkably, in addition to the fast-aging species, the order Rodentia contains multiple long-lived species with lifespans exceeding 20 years (naked mole-rat, beavers, porcupines, and some squirrels). This diversity opens great opportunities for comparative aging studies. Here we discuss the evolution of lifespan in rodents, review the biology of slow-aging rodents, and show an example of how the use of a comparative approach revealed that telomerase activity coevolved with body mass in rodents. PMID:19424861

  18. Rodents for comparative aging studies: from mice to beavers.

    PubMed

    Gorbunova, Vera; Bozzella, Michael J; Seluanov, Andrei

    2008-09-01

    After humans, mice are the best-studied mammalian species in terms of their biology and genetics. Gerontological research has used mice and rats extensively to generate short- and long-lived mutants, study caloric restriction and more. Mice and rats are valuable model organisms thanks to their small size, short lifespans and fast reproduction. However, when the goal is to further extend the already long human lifespan, studying fast aging species may not provide all the answers. Remarkably, in addition to the fast-aging species, the order Rodentia contains multiple long-lived species with lifespans exceeding 20 years (naked mole-rat, beavers, porcupines, and some squirrels). This diversity opens great opportunities for comparative aging studies. Here we discuss the evolution of lifespan in rodents, review the biology of slow-aging rodents, and show an example of how the use of a comparative approach revealed that telomerase activity coevolved with body mass in rodents. PMID:19424861

  19. Hantavirus infections in humans and commensal rodents in Singapore.

    PubMed

    Wong, T W; Chan, Y C; Joo, Y G; Lee, H W; Lee, P W; Yanagihara, R

    1989-01-01

    To determine the extent of hantavirus infection in Singapore, serological studies using the indirect immunofluorescent antibody (IFA) test were conducted on commensal rodents and on human patients in 4 diagnostic groups. Virus isolation using a Vero E6 cell line was performed on hantaviral antigen-positive rodent lung tissue. Of 142 rodents and 3 insectivores studied, 37 (26%) were seropositive for IFA. Rattus norvegicus was the predominant species captured, with the highest species-specific seropositive rate of 32% (36 of 113). A hantavirus strain, R36, was isolated from one R. norvegicus. Seropositive rates for human patients were: 8% respectively for dengue haemorrhagic fever suspects and for non-A non-B hepatitis patients, 3% for leptospirosis suspects and 2% for acute nephritis patients. 2 patients had marked liver dysfunction but mild renal involvement. This hepatitis-like manifestation appears to be a clinical variant of hantavirus infection.

  20. Can shrub cover increase predation risk for a desert rodent?

    USGS Publications Warehouse

    Schooley, R.L.; Sharpe, Peter B.

    1996-01-01

    Previous research indicates that predation risk may influence activity patterns, habitat partitioning, and community structure of nocturnal desert rodents. Shrub microhabitat is typically considered safer than open microhabitat for these small mammals. We investigated predation risk for Townsend's ground squirrels (Spermophilus townsendii), which are diurnal desert rodents that detect predators visually and use burrows for refuge. Our results suggested that shrub cover may increase risk for these squirrels by decreasing their ability to escape from predators. Our field experiment indicated that running speeds of juvenile squirrels were lower in shrub (Ceratoides lanata) habitat than in open areas. Shrub cover was also associated with shorter predator-detection distances (mammalian and avian) and fewer refuges (burrow entrances per hectare) than in open areas in one year but not in another. Our study demonstrated that the visual and locomotive obstruction of vegetative cover may increase predation risk for diurnal desert rodents and that elements of habitat-dependent risk may be temporally dynamic.

  1. Indole-based alkaloids from deep-sea bacterium Shewanella piezotolerans with antitumor activities.

    PubMed

    Wang, Yao; Tang, Xixiang; Shao, Zhongzhe; Ren, Jinwei; Liu, Dong; Proksch, Peter; Lin, Wenhan

    2014-05-01

    Chromatographic separation of a crude extract obtained from a fermentation broth of a chemically unknown bacterium Shewanella piezotolerans WP3 collected in deep-sea yielded three new indole alkaloids namely shewanellines A (1a), B (1b) and C (2), together with 12 known indole alkaloids. The structures were unambiguously elucidated on the basis of 1D and 2D NMR ((1)H, (13)C, COSY, HMBC, HSQC and NOESY) in association with MS and CD data. Compounds 1-4, 7, 9 and 11-14 were selected for the evaluation of their cytotoxic activities against human tumor cell lines HL-60 and BEL-7402, whereas compounds 2, 4 and 9 exhibited significant inhibition toward HL-60.

  2. Uptake and metabolism of indole compounds by the goldfish pineal organ

    SciTech Connect

    McNulty, J.A.

    1986-02-01

    Indole metabolism was studied in the pineal organ of the goldfish by radioautography and high-performance liquid chromatography. The rate of uptake of tritiated serotonin was rapid in vitro with dense labeling over the photoreceptor cells. Tritiated tryptophan was taken up at a slower rate and the label was distributed evenly over the epithelium. Continual light caused a reduction in the concentration of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) compared to groups exposed to constant darkness both in vivo and in explants, suggesting that these effects are not derived from photoreceptors outside the pineal organ. These data are consistent with the hypothesis that indole metabolism is functionally linked to phototransduction events in the pineal organ of lower vertebrates.

  3. Auxin Biosynthesis: Are the Indole-3-Acetic Acid and Phenylacetic Acid Biosynthesis Pathways Mirror Images?

    PubMed

    Cook, Sam D; Nichols, David S; Smith, Jason; Chourey, Prem S; McAdam, Erin L; Quittenden, Laura; Ross, John J

    2016-06-01

    The biosynthesis of the main auxin in plants (indole-3-acetic acid [IAA]) has been elucidated recently and is thought to involve the sequential conversion of Trp to indole-3-pyruvic acid to IAA However, the pathway leading to a less well studied auxin, phenylacetic acid (PAA), remains unclear. Here, we present evidence from metabolism experiments that PAA is synthesized from the amino acid Phe, via phenylpyruvate. In pea (Pisum sativum), the reverse reaction, phenylpyruvate to Phe, is also demonstrated. However, despite similarities between the pathways leading to IAA and PAA, evidence from mutants in pea and maize (Zea mays) indicate that IAA biosynthetic enzymes are not the main enzymes for PAA biosynthesis. Instead, we identified a putative aromatic aminotransferase (PsArAT) from pea that may function in the PAA synthesis pathway. PMID:27208245

  4. Exploring the 3-piperidin-4-yl-1H-indole scaffold as a novel antimalarial chemotype.

    PubMed

    Santos, Sofia A; Lukens, Amanda K; Coelho, Lis; Nogueira, Fátima; Wirth, Dyann F; Mazitschek, Ralph; Moreira, Rui; Paulo, Alexandra

    2015-09-18

    A series of 3-piperidin-4-yl-1H-indoles with building block diversity was synthesized based on a hit derived from an HTS whole-cell screen against Plasmodium falciparum. Thirty-eight compounds were obtained following a three-step synthetic approach and evaluated for anti-parasitic activity. The SAR shows that 3-piperidin-4-yl-1H-indole is intolerant to most N-piperidinyl modifications. Nevertheless, we were able to identify a new compound (10d) with lead-like properties (MW = 305; cLogP = 2.42), showing antimalarial activity against drug-resistant and sensitive strains (EC50 values ∼ 3 μM), selectivity for malaria parasite and no cross-resistance with chloroquine, thus representing a potential new chemotype for further optimization towards novel and affordable antimalarial drugs.

  5. Surface-enhanced Raman spectroscopy study of indolic molecules adsorbed on gold colloids

    NASA Astrophysics Data System (ADS)

    Tu, Qiang; Eisen, Jonathan; Chang, Chang

    2010-03-01

    Serotonin is both a ubiquitous neurotransmitter in the central nervous system and an important immunomodulator involved in various immune responses. The ability to unambiguously detect serotonin is therefore imperative in biomedical research. However, detection of serotonin and related indoles using immunohistochemistry has been largely limited by their small molecular size and the resultant uncertainty in antibody specificity. Here we show that surface-enhanced Raman spectroscopy (SERS) can be used to detect and distinguish serotonin from its various closely related precursors and metabolites. Compared with traditional antibody-based methods, SERS is highly specific and capable of real-time detection. We also quantify the relative concentration of serotonin against a background of other indoles using SERS. We expect this optical detection method to directly benefit a variety of immune and nervous systems studies involving serotonin.

  6. Inhibitors of HIV-1 attachment. Part 2: An initial survey of indole substitution patterns.

    PubMed

    Meanwell, Nicholas A; Wallace, Owen B; Fang, Haiquan; Wang, Henry; Deshpande, Milind; Wang, Tao; Yin, Zhiwei; Zhang, Zhongxing; Pearce, Bradley C; James, Jennifer; Yeung, Kap-Sun; Qiu, Zhilei; Kim Wright, J J; Yang, Zheng; Zadjura, Lisa; Tweedie, Donald L; Yeola, Suresh; Zhao, Fang; Ranadive, Sunanda; Robinson, Brett A; Gong, Yi-Fei; Wang, Hwei-Gene Heidi; Spicer, Timothy P; Blair, Wade S; Shi, Pei-Yong; Colonno, Richard J; Lin, Pin-Fang

    2009-04-01

    The effects of introducing simple halogen, alkyl, and alkoxy substituents to the 4, 5, 6 and 7 positions of 1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione, an inhibitor of the interaction between HIV gp120 and host cell CD4 receptors, on activity in an HIV entry assay was examined. Small substituents at C-4 generally resulted in increased potency whilst substitution at C-7 was readily tolerated and uniformly produced more potent HIV entry inhibitors. Substituents deployed at C-6 and, particularly, C-5 generally produced a modest to marked weakening of potency compared to the prototype. Small alkyl substituents at N-1 exerted minimal effect on activity whilst increasing the size of the alkyl moiety led to progressively reduced inhibitory properties. These studies establish a basic understanding of the indole element of the HIV attachment inhibitor pharmacophore.

  7. Dearomative Indole (3 + 2) Reactions with Azaoxyallyl Cations--New Method for the Synthesis of Pyrroloindolines.

    PubMed

    DiPoto, Maria C; Hughes, Russell P; Wu, Jimmy

    2015-12-01

    Herein, we report the first examples of the synthesis of pyrroloindolines by means of (3 + 2) dearomative annulation reactions between 3-substituted indoles and highly reactive azaoxyallyl cations. Computational studies using density functional theory (DFT) (B3LYP-D3/6-311G**++) support a stepwise reaction pathway in which initial C-C bond formation takes place at C3 of indole, followed by ring closure to give the observed products. Insights gleaned from these calculations indicate that the solvent, either TFE or HFIP, can stabilize the transition state through H-bonding interactions with oxygen of the azaoxyallyl cation and other relevant intermediates, thereby increasing the rates of these reactions. PMID:26562355

  8. Melokhanines A-J, Bioactive Monoterpenoid Indole Alkaloids with Diverse Skeletons from Melodinus khasianus.

    PubMed

    Cheng, Gui-Guang; Li, Dan; Hou, Bo; Li, Xiao-Nian; Liu, Lu; Chen, Ying-Ying; Lunga, Paul-Keilah; Khan, Afsar; Liu, Ya-Ping; Zuo, Zhi-Li; Luo, Xiao-Dong

    2016-09-23

    The new melokhanines A-J (1-10) and 22 known (11-32) alkaloids were isolated from the twigs and leaves of Melodinus khasianus. The new compounds and their absolute configurations were elucidated by extensive analysis of spectroscopic, X-ray diffraction, and computational data. Melokhanine A (1), composed of a hydroxyindolinone linked to an octahydrofuro[2,3-b]pyridine moiety, is an unprecedented monoterpenoid indole alkaloid. Melokhanines B-H (2-8) possess a new 6/5/5/6/6 pentacyclic indole alkaloid skeleton. Alkaloids 1-16, 25-27, 31, and 32 showed the best antibacterial activity against Pseudomonas aeruginosa (MIC range 2-22 μM). Among the seven dermatophytes tested, compound 1 showed significant inhibitory activity against Microsporum canis, M. ferrugineum, and Trichophyton ajelloi (MIC range 38-150 μM), i.e., half the efficacy of the positive control, griseofulvin. PMID:27584856

  9. Dearomative Indole (3 + 2) Reactions with Azaoxyallyl Cations--New Method for the Synthesis of Pyrroloindolines.

    PubMed

    DiPoto, Maria C; Hughes, Russell P; Wu, Jimmy

    2015-12-01

    Herein, we report the first examples of the synthesis of pyrroloindolines by means of (3 + 2) dearomative annulation reactions between 3-substituted indoles and highly reactive azaoxyallyl cations. Computational studies using density functional theory (DFT) (B3LYP-D3/6-311G**++) support a stepwise reaction pathway in which initial C-C bond formation takes place at C3 of indole, followed by ring closure to give the observed products. Insights gleaned from these calculations indicate that the solvent, either TFE or HFIP, can stabilize the transition state through H-bonding interactions with oxygen of the azaoxyallyl cation and other relevant intermediates, thereby increasing the rates of these reactions.

  10. Cytotoxic Indole Alkaloids against Human Leukemia Cell Lines from the Toxic Plant Peganum harmala

    PubMed Central

    Wang, Chunhua; Zhang, Zhenxue; Wang, Yihai; He, Xiangjiu

    2015-01-01

    Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The cytotoxicity against human leukemia cells was assayed for the alkaloids and some of them showed potent activity. Harmalacidine (compound 8, HMC) exhibited the highest cytotoxicity against U-937 cells with IC50 value of 3.1 ± 0.2 μmol/L. The cytotoxic mechanism of HMC was targeting the mitochondrial and protein tyrosine kinase signaling pathways (PTKs-Ras/Raf/ERK). The results strongly demonstrated that the alkaloids from Peganum harmala could be a promising candidate for the therapy of leukemia. PMID:26540074

  11. Novel indole based dual responsive 'turn-on' chemosensor for fluoride ion detection

    NASA Astrophysics Data System (ADS)

    Jeyanthi, Dharmaraj; Iniya, Murugan; Krishnaveni, Karuppiah; Chellappa, Duraisamy

    2015-02-01

    An efficient new dual channel chemosensor 2,3-bis((E)-(1H-indole-3-yl)methyleneamino)maleonitrile (DN) which exhibits selective sensing of F- ions in DMSO, was synthesized by a facile one step condensation reaction of indole-3-carboxaldehyde with diaminomaleonitrile. The probe DN was characterized by elemental analysis, 1H, 13C-NMR, ESI-MS and IR spectral techniques. Upon addition of F-, DN induces remarkable changes in both absorption and fluorescence spectra on the basis of charge transfer mechanism. The receptor DN serves for highly selective, sensitive detection of F- without the interference of other relevant anions. The Job's plot analysis indicates the binding stoichiometry to be 1:1 (host/guest).

  12. One-Pot Aminoethylation of Indoles/Pyrroles with Alkynes and Sulfonyl Azides.

    PubMed

    Rajasekar, Shanmugam; Yadagiri, Dongari; Anbarasan, Pazhamalai

    2015-11-16

    A general and efficient one-pot aminoethylation of substituted indoles/pyrroles was accomplished for the synthesis of various tryptamine derivatives employing a combination of alkynes and sulfonyl azides as readily accessible aminoethylating agents. The reaction features a successful integration of copper-catalyzed alkyne and azide cycloaddition to N-sulfonyl-1,2,3-triazole, rhodium-catalyzed selective insertion of α-iminocarbenes onto the C3-H bond of indoles, and reduction of the resultant enamides to tryptamine derivatives employing either NaCNBH3 or palladium catalyst, in one-pot. The reaction also showed excellent functional-group tolerance and allowed the synthesis of various substituted tryptamines in good to excellent yield. This transformation constitutes a one-pot formal regioselective functionalization of terminal alkynes. Utility of the synthesized tryptamine was further demonstrated in the synthesis of dihydro-β-carboline and tryptoline. PMID:26443500

  13. One-Pot Aminoethylation of Indoles/Pyrroles with Alkynes and Sulfonyl Azides.

    PubMed

    Rajasekar, Shanmugam; Yadagiri, Dongari; Anbarasan, Pazhamalai

    2015-11-16

    A general and efficient one-pot aminoethylation of substituted indoles/pyrroles was accomplished for the synthesis of various tryptamine derivatives employing a combination of alkynes and sulfonyl azides as readily accessible aminoethylating agents. The reaction features a successful integration of copper-catalyzed alkyne and azide cycloaddition to N-sulfonyl-1,2,3-triazole, rhodium-catalyzed selective insertion of α-iminocarbenes onto the C3-H bond of indoles, and reduction of the resultant enamides to tryptamine derivatives employing either NaCNBH3 or palladium catalyst, in one-pot. The reaction also showed excellent functional-group tolerance and allowed the synthesis of various substituted tryptamines in good to excellent yield. This transformation constitutes a one-pot formal regioselective functionalization of terminal alkynes. Utility of the synthesized tryptamine was further demonstrated in the synthesis of dihydro-β-carboline and tryptoline.

  14. Multiple infections of rodents with zoonotic pathogens in Austria.

    PubMed

    Schmidt, Sabrina; Essbauer, Sandra S; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald; Ulrich, Rainer G

    2014-07-01

    Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host-pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans.

  15. Synanthropic rodents as possible reservoirs of shigatoxigenic Escherichia coli strains

    PubMed Central

    Blanco Crivelli, Ximena; Rumi, María V.; Carfagnini, Julio C.; Degregorio, Osvaldo; Bentancor, Adriana B.

    2012-01-01

    Shigatoxigenic Escherichia coli (STEC) strains are worldwide zoonotic pathogen responsible for different cases of human disease including hemolytic uremic syndrome (HUS). Transmission of STEC to humans occurs through the consumption of food and water contaminated by faeces of carriers and by person-to-person contact. The objective of this study was two-fold: (1) to investigate whether synanthropic rodents are possible reservoirs of STEC in the urban area and (2) whether a particular genus out of synanthropic rodent is the principal carrier of STEC. One hundred and forty-five rodents were captured in Buenos Aires City. Screening for stx1/stx2 and rfbO157 was done by PCR from the confluence zone. STEC isolates were further characterized with biochemical tests by standard methods. Additional virulence factors (eae, ehxA, and saa) were also determined by PCR. Forty-one of the rodents were necropsied and sample of kidney and small and large intestine were taken for histopathological diagnosis. The samples sections were stained with hematoxylin-eosin, and observed by light microscopy to evaluate the systemic involvement of these species in natural infections. STEC was isolated from seven out of 27 suspect animals at screening. The following genotypes were found in the STEC strains: stx1/stx2/ehxA (1), stx2 (4), stx2/ehxA (1), stx2/ehxA/eae (1). Neither gross nor microscopic lesions compatible with those produced by Shiga toxin were observed in the studied organs of necropsied rodents. The bivariate analysis including the 145 rodent's data showed that the isolation of STEC is associated positively to Rattus genus. This synanthropic species may play a role in the transmissibility of the agent thus being a risk to the susceptible population. Their control should be included specifically in actions to dismiss the contamination of food and water by STEC in the urban area, as additional strategies for epidemiological control. PMID:23125967

  16. Multiple Infections of Rodents with Zoonotic Pathogens in Austria

    PubMed Central

    Schmidt, Sabrina; Essbauer, Sandra S.; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H.; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald

    2014-01-01

    Abstract Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host–pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans. PMID

  17. Initiation/promotion versus complete carcinogenicity in the rodent liver

    PubMed Central

    Ashby, John; Elliott, B. M.; Lefevre, P. A.; Styles, Jerry; Longstaff, E.

    1983-01-01

    4-N-Pyrrolidinylazobenzene (4N) is a close structural analog of the rodent liver carcinogen 4-dimethylaminoazobenzene (DAB). This structural similarity led us to evaluate it for genotoxic activity in vitro. We observed activity for 4N and DAB in the BHK cell transformation assay and subsequently in the Salmonella mutation assay of Ames. By a curious chance, Scribner, Miller and Miller, probably prompted by the same structural similarity, had synthesized 4N in the 1960s and found it to be noncarcinogenic to the rodent liver using a bioassay test protocol that detected DAB as carcinogenic. These findings were only described following the publication of our observations made in vitro. The conflict that apparently exists between these data can be interpreted in two separate ways. (a) Scribner et al. have suggested that 4N may be a carcinogenic initiator as opposed to a complete carcinogen like DAB. They also suggested that promotion of 4N-treated rodents with phenobarbitone might lead to the production of liver tumors. (b) We have evaluated the simpler concept that the activities observed for 4N in vitro define a carcinogenic potential that is not realized in vivo due to its rapid detoxification, at least in rodents. The first of these explanations implies that pure carcinogenic initiators may form a separate class of genotoxic agents from complete carcinogens, and perhaps of greater interest, that 4N might provide a valuable model compound for the study of carcinogenic promotion in the rodent liver. The second explanation regards potential carcinogenicity as a single property that can be defined in vitro and which may or may not be expressed in vivo depending on the enzymic environments encountered by the test chemical. It is clearly important to evaluate these different propositions in order to aid progress in the study of carcinogenic promotion, especially in the rodent liver. The presentation will describe our recent studies in vitro and in vivo in this connection

  18. Multiple infections of rodents with zoonotic pathogens in Austria.

    PubMed

    Schmidt, Sabrina; Essbauer, Sandra S; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald; Ulrich, Rainer G

    2014-07-01

    Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host-pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans. PMID:24915446

  19. Initiation/promotion versus complete carcinogenicity in the rodent liver.

    PubMed

    Ashby, J; Elliott, B M; Lefevre, P A; Styles, J; Longstaff, E

    1983-04-01

    4-N-Pyrrolidinylazobenzene (4N) is a close structural analog of the rodent liver carcinogen 4-dimethylaminoazobenzene (DAB). This structural similarity led us to evaluate it for genotoxic activity in vitro. We observed activity for 4N and DAB in the BHK cell transformation assay and subsequently in the Salmonella mutation assay of Ames. By a curious chance, Scribner, Miller and Miller, probably prompted by the same structural similarity, had synthesized 4N in the 1960s and found it to be noncarcinogenic to the rodent liver using a bioassay test protocol that detected DAB as carcinogenic. These findings were only described following the publication of our observations made in vitro. The conflict that apparently exists between these data can be interpreted in two separate ways. (a) Scribner et al. have suggested that 4N may be a carcinogenic initiator as opposed to a complete carcinogen like DAB. They also suggested that promotion of 4N-treated rodents with phenobarbitone might lead to the production of liver tumors. (b) We have evaluated the simpler concept that the activities observed for 4N in vitro define a carcinogenic potential that is not realized in vivo due to its rapid detoxification, at least in rodents. The first of these explanations implies that pure carcinogenic initiators may form a separate class of genotoxic agents from complete carcinogens, and perhaps of greater interest, that 4N might provide a valuable model compound for the study of carcinogenic promotion in the rodent liver. The second explanation regards potential carcinogenicity as a single property that can be defined in vitro and which may or may not be expressed in vivo depending on the enzymic environments encountered by the test chemical. It is clearly important to evaluate these different propositions in order to aid progress in the study of carcinogenic promotion, especially in the rodent liver. The presentation will describe our recent studies in vitro and in vivo in this connection.

  20. Fluorescent complexes of DNA with DAPI 4′,6-diamidine-2-phenyl indole.2HCl or DCI 4′,6-dicarboxyamide-2-phenyl indole

    PubMed Central

    Kapuściński, Jan; Skoczylas, Bogna

    1978-01-01

    4′,6-Dioarboxyamide-2-phenyl indole (DCI), a non-ionic structural analogue of 4′,6-diamidine-2-phenyl indole·2HCl (DAPI), was synthesized in order to verify the hypothesis of intercalation of both dyes into the DNA double helix. The influence of pH, viscosity, and different concentrations of SDS (sodium dodecylsulphate) or NaCl on the optical and fluorescent properties and the changes in thermal transition of both dye complexes with DNA confirm the affinity of the dyes to the double helix as well as their stabilizing influence on the secondary DNA structure. The results of binding studies, carried out by fluorescent methods have shown that the dyes are strongly bound to DNA, though the number of binding sites is small. According to the experimental data, the fluorescent properties of DAPI and DCI complexes with DNA are connected with the intercalating binding mechanism of these dyes. On the other hand, the eventual ionic or hydrogen bonds of dyes outside the DNA helix do not change noticeably their fluorescent properties. PMID:31603

  1. Computational study of the interaction of indole-like molecules with water and hydrogen sulfide.

    PubMed

    Cabaleiro-Lago, Enrique M; Rodríguez-Otero, Jesús; Peña-Gallego, Ángeles

    2011-10-01

    The characteristics of the interaction between water and hydrogen sulfide with indole and a series of analogs obtained by substituting the NH group of indole by different heteroatoms have been studied by means of ab initio calculations. In all cases, minima were found corresponding to structures where water and hydrogen sulfide interact by means of X-H···π contacts. The interaction energies for all these π complexes are quite similar, spanning from -13.5 to -18.8 kJ/mol, and exhibiting the stability sequence NH > CH(2) ≈ PH > Se ≈ S > O, for both water and hydrogen sulfide. Though interaction energies are similar, hydrogen sulfide complexes are slightly favored over their water counterparts when interacting with the π cloud. σ-Type complexes were also considered for the systems studied, but only in the case of water complexes this kind of complexes is relevant. Only for complexes formed by water and indole, a significantly more stable σ-type complex was found with an interaction energy amounting to -23.6 kJ/mol. Oxygen and phosphorous derivatives also form σ-type complexes of similar stability as that observed for π ones. Despite the similar interaction energies exhibited by complexes with water and hydrogen sulfide, the nature of the interaction is very different. For π complexes with water the main contributions to the interaction energy are electrostatic and dispersive contributing with similar amounts, though slightly more from electrostatics. On the contrary, in hydrogen sulfide complexes dispersion is by far the main stabilizing contribution. For the σ-type complexes, the interaction is clearly dominated by the electrostatic contribution, especially in the indole-water complex.

  2. Determination of Endogenous Indole-3-Acetic Acid in Plagiochila arctica (Hepaticae) 1

    PubMed Central

    Law, David M.; Basile, Dominick V.; Basile, Margaret R.

    1985-01-01

    Endogenous indole-3-acetic acid (IAA) was found in axenically cultured gametophytes of the leafy liverwort, Plagiochila arctica Bryhn and Kaal., by high-performance liquid chromatography with electrochemical detection. Identification of the methylated auxin was confirmed by gas chromatography-mass spectrometry. Addition of 57 micromolar IAA to cultures increased relative production of ethylene. This is the first definitive (gas chromatography-mass spectrometry) demonstration of the natural occurrence of IAA in a bryophyte. PMID:16664164

  3. Monoterpene indole alkaloids from the stem bark of Mitragyna diversifolia and their acetylcholine esterase inhibitory effects.

    PubMed

    Cao, Xing-Fen; Wang, Jun-Song; Wang, Xiao-Bing; Luo, Jun; Wang, Hong-Ying; Kong, Ling-Yi

    2013-12-01

    Five monoterpene indole alkaloids, mitradiversifoline, with a unique rearranged skeleton, specionoxeine-N(4)-oxide, 7-hydroxyisopaynantheine, 3-dehydropaynantheine, and 3-isopaynantheine-N(4)-oxide, and 10 known ones, were isolated from Mitragyna diversifolia. All the isolates were evaluated for their inhibition of acetylcholinesterase activities, and four showed moderate activities, with IC50 values of 4.1, 5.2, 10.2, and 10.3 μM, respectively. PMID:24169379

  4. Solvent free selective dehydrogenation of indolic and carbazolic molecules with an iridium pincer catalyst.

    PubMed

    Brayton, Daniel F; Jensen, Craig M

    2014-06-01

    A previously known iridium POCOP pincer catalyst was found to selectively dehydrogenate the heterocyclic portion of several indolic and carbazolic molecules. These molecules were found to have an "activity window" (172-178 °C) upon which only the heterocyclic ring underwent dehydrogenation. All reactions were run solvent free, yields for selected substrates were excellent, and the products were isolated by either distillation or alumina plug filtration. PMID:24763968

  5. An antiplasmodial new (bis)indole alkaloid from the hard coral Tubastraea sp.

    PubMed

    Meyer, Michèle; Delberghe, Florence; Liron, Frédéric; Guillaume, Mireille; Valentin, Alexis; Guyot, Michèle

    2009-01-01

    Tubastarea sp., a stony coral (Dendrophylliidae) from the Great Hanish in the Archipelago of the Hanish Islands, Yemen, contains, in addition to the known aplysinopsin (1) and 6-bromo-3'-deimino-3'-oxoaplysinopsin (2), the new bis(indole) alkaloid (3). The structures of compounds (1-3) were elucidated by interpretation of spectral data. Compound 3 inhibits the growth of Plasmodium falciparum (chloroquine-resistant strain) with an IC(50) 1.2 microg mL(-1). PMID:19173125

  6. A Copper-Catalyzed Decarboxylative Amination/Hydroamination Sequence: Switchable Synthesis of Functionalized Indoles.

    PubMed

    Li, Tian-Ren; Cheng, Bei-Yi; Wang, Ya-Ni; Zhang, Mao-Mao; Lu, Liang-Qiu; Xiao, Wen-Jing

    2016-09-26

    A copper-catalyzed decarboxylative amination/hydroamination sequence of propargylic carbamates with various nucleophiles is described for the first time. It features an earth-abundant metal catalyst, mild reaction conditions, and high efficiency. Further treatments of the resultant key intermediates using an acid or a base in one pot enable the controllable and divergent synthesis of two types of functionalized indoles. Moreover, experiments to demonstrate the synthetic potential of this methodology are performed. PMID:27593696

  7. A general catalytic reaction sequence to access alkaloid-inspired indole polycycles.

    PubMed

    Danda, Adithi; Kumar, Kamal; Waldmann, Herbert

    2015-05-01

    A catalytic two-step reaction sequence was developed to access a range of complex heterocyclic frameworks based on biorelevant indole/oxindole scaffolds. The reaction sequence includes catalytic Pictet-Spengler cyclization followed by Au(I) catalyzed intramolecular hydroamination of acetylenes. A related cascade polycyclization of a designed β-carboline embodying a 1,5-enyne group yields the analogues of the alkaloid harmicine. PMID:25846800

  8. Stereoselective α-indolylation of enals via an organocatalytic formal cross-coupling with indoles.

    PubMed

    Hu, Yang; Ju, Lei; Lu, Lin; Ma, Hongmei; Yu, Xinhong

    2015-09-01

    We report a novel organocatalytic one-pot cascade bromination-Michael-type Friedel-Crafts alkylation dearomatization-nucleophilic rearrangement aromatization cascade process for the direct α-indolylation of unfunctionalized enals from readily available indoles with good yields and high E selectivity. The simplicity and practicality of its high efficiency for formation of a new C(sp(2))-C(sp(2)) bond constitute the most attractive advantage of this reaction. PMID:26199114

  9. 1-(1H-Indol-3-ylcarbonyl)-N-(4-methoxybenzyl)formamide.

    PubMed

    Sonar, Vijayakumar N; Parkin, Sean; Crooks, Peter A

    2006-03-01

    In the title compound, C18H16N2O3, the indole ring is planar and the two adjacent carbonyl groups are mutually trans oriented with a torsion angle of 144.8 (3) degrees. The single C-C bond linking the two carbonyl functionalities is 1.539 (4) A. Molecules are linked into a two-dimensional network by intermolecular N-H...O hydrogen bonds.

  10. The Synthesis and Pharmacological Evaluation of Adamantane-Derived Indoles: Cannabimimetic Drugs of Abuse

    PubMed Central

    2013-01-01

    Two novel adamantane derivatives, adamantan-1-yl(1-pentyl-1H-indol-3-yl)methanone (AB-001) and N-(adamtan-1-yl)-1-pentyl-1H-indole-3-carboxamide (SDB-001), were recently identified as cannabimimetic indoles of abuse. Conflicting anecdotal reports of the psychoactivity of AB-001 in humans, and a complete dearth of information about the bioactivity of SDB-001, prompted the preparation of AB-001, SDB-001, and several analogues intended to explore preliminary structure–activity relationships within this class. This study sought to elucidate which structural features of AB-001, SDB-001, and their analogues govern the cannabimimetic potency of these chemotypes in vitro and in vivo. All compounds showed similar full agonist profiles at CB1 (EC50 = 16–43 nM) and CB2 (EC50 = 29–216 nM) receptors in vitro using a FLIPR membrane potential assay, with the exception of SDB-002, which demonstrated partial agonist activity at CB2 receptors. The activity of AB-001, AB-002, and SDB-001 in rats was compared to that of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabimimetic indole JWH-018 using biotelemetry. SDB-001 dose-dependently induced hypothermia and reduced heart rate (maximal dose 10 mg/kg) with potency comparable to that of Δ9-tetrahydrocannabinol (Δ9-THC, maximal dose 10 mg/kg), and lower than that of JWH-018 (maximal dose 3 mg/kg). Additionally, the changes in body temperature and heart rate affected by SDB-001 are of longer duration than those of Δ9-THC or JWH-018, suggesting a different pharmacokinetic profile. In contrast, AB-001, and its homologue, AB-002, did not produce significant hypothermic and bradycardic effects, even at relatively higher doses (up to 30 mg/kg), indicating greatly reduced potency compared to Δ9-THC, JWH-018, and SDB-001. PMID:23551277

  11. One-pot gold-catalyzed synthesis of 3-silylethynyl indoles from unprotected o-alkynylanilines

    PubMed Central

    Brand, Jonathan P; Chevalley, Clara

    2011-01-01

    Summary The Au(III)-catalyzed cyclization of 2-alkynylanilines was combined in a one-pot procedure with the Au(I)-catalyzed C3-selective direct alkynylation of indoles using the benziodoxolone reagent TIPS-EBX to give a mild, easy and straightforward entry to 2-substituted-3-alkynylindoles. The reaction can be applied to unprotected anilines, was tolerant to functional groups and easy to carry out (RT, and requires neither an inert atmosphere nor special solvents). PMID:21647264

  12. Excitation-inhibition discoordination in rodent models of mental disorders

    PubMed Central

    Fenton, André A.

    2015-01-01

    Animal models of mental illness provide a foundation for evaluating hypotheses for the mechanistic causes of mental illness. Neurophysiological investigations of neural network activity in rodent models of mental dysfunction are reviewed from the conceptual framework of the discoordination hypothesis, which asserts that failures of neural coordination cause cognitive deficits in the judicious processing and use of information. Abnormal dynamic coordination of excitatory and inhibitory neural discharge in pharmacological and genetic rodent models support the discoordination hypothesis. These observations suggest excitation-inhibition discoordination and aberrant neural circuit dynamics as causes of cognitive impairment as well as therapeutic targets for cognition-promoting treatments. PMID:25895430

  13. Discovery of Novel Alphacoronaviruses in European Rodents and Shrews

    PubMed Central

    Tsoleridis, Theocharis; Onianwa, Okechukwu; Horncastle, Emma; Dayman, Emma; Zhu, Miaoran; Danjittrong, Taechasit; Wachtl, Marta; Behnke, Jerzy M.; Chapman, Sarah; Strong, Victoria; Dobbs, Phillipa; Ball, Jonathan K.; Tarlinton, Rachael E.; McClure, C. Patrick

    2016-01-01

    Eight hundred and thirteen European rodents and shrews encompassing seven different species were screened for alphacoronaviruses using PCR detection. Novel alphacoronaviruses were detected in the species Rattus norvegicus, Microtus agrestis, Sorex araneus and Myodes glareolus. These, together with the recently described Lucheng virus found in China, form a distinct rodent/shrew-specific clade within the coronavirus phylogeny. Across a highly conserved region of the viral polymerase gene, the new members of this clade were up to 22% dissimilar at the nucleotide level to the previously described Lucheng virus. As such they might represent distinct species of alphacoronaviruses. These data greatly extend our knowledge of wildlife reservoirs of alphacoronaviruses. PMID:27102167

  14. Experimental infection of Rio Mamore hantavirus in Sigmodontinae rodents

    PubMed Central

    de Souza, William Marciel; Machado, Alex Martins; Figueiredo, Luiz Tadeu Moraes

    2016-01-01

    This study shows an experimental spillover infection ofSigmodontinae rodents with Rio Mamore hantavirus (RIOMV).Necromys lasiurus and Akodon sp were infected with 103 RNA copies of RIOMV by intraperitoneal administration. The viral genome was detected in heart, lung, and kidney tissues 18 days after infection (ai), and viral excretion in urine and faeces began at four and six ai, respectively. These results reveal that urine and faeces of infected rodents contain the virus for at least 18 days. It is possible that inhaled aerosols of these excreta could transmit hantavirus to humans and other animals. PMID:27223653

  15. Stress, social behavior, and resilience: Insights from rodents

    PubMed Central

    Beery, Annaliese K.; Kaufer, Daniela

    2014-01-01

    The neurobiology of stress and the neurobiology of social behavior are deeply intertwined. The social environment interacts with stress on almost every front: social interactions can be potent stressors; they can buffer the response to an external stressor; and social behavior often changes in response to stressful life experience. This review explores mechanistic and behavioral links between stress, anxiety, resilience, and social behavior in rodents, with particular attention to different social contexts. We consider variation between several different rodent species and make connections to research on humans and non-human primates. PMID:25562050

  16. Experimental infection of Rio Mamore hantavirus in Sigmodontinae rodents.

    PubMed

    Souza, William Marciel de; Machado, Alex Martins; Figueiredo, Luiz Tadeu Moraes

    2016-05-24

    This study shows an experimental spillover infection of Sigmodontinae rodents with Rio Mamore hantavirus (RIOMV). Necromys lasiurus and Akodon sp were infected with 103 RNA copies of RIOMV by intraperitoneal administration. The viral genome was detected in heart, lung, and kidney tissues 18 days after infection (ai), and viral excretion in urine and faeces began at four and six ai, respectively. These results reveal that urine and faeces of infected rodents contain the virus for at least 18 days. It is possible that inhaled aerosols of these excreta could transmit hantavirus to humans and other animals. PMID:27223653

  17. Radioprotective Effects of Amifostine on Acute and Chronic Esophageal Injury in Rodents

    SciTech Connect

    Vujaskovic, Zeljko; Thrasher, Bradley A.; Jackson, Isabel L.; Brizel, Marla B.; Brizel, David M.

    2007-10-01

    Purpose: This study was performed to evaluate the protective benefit of amifostine against esophageal injury from fractionated radiation in a rodent model. Methods: Fractionated or sham esophageal irradiation was administered to Fisher-344 rats for 5 consecutive daily fractions of 9 Gy using 150 kV X-rays. Animals received an intraperitoneal injection of amifostine or placebo 30 min before each fraction. Histopathologic analyses for mucosal thickness, submucosal collagen deposition, activation of macrophages, oxidative stress and expression/activation of integrin{alpha}v{beta}6 and transforming growth factor (TGF)-{beta} were performed 5 days and 10 weeks after irradiation. Results: Pre-RT mean mucosal thickness was 35 {mu}m in both the placebo and the amifostine groups. Five days post-RT, mean mucosal thicknesses were 30 {mu}m in the placebo group versus 37 {mu}m in the amifostine group (p = 0.024). At 10 weeks post-RT, the group receiving amifostine experienced a significant decrease in tunica muscularis damage (p = 0.002), submucosal collagen deposition (p = 0.027), and macrophage accumulation (p = 0.026) when compared with the placebo group. The levels of immunoreactivity for oxidative stress, TGF-{beta}, and integrin{alpha}v{beta}6 were significantly decreased 10 weeks post-RT in the group receiving amifostine treatment compared with placebo group. Conclusions: This study demonstrates that amifostine given before each radiation fraction protects against acute and chronic esophageal injury in a rodent model. Protection of the mucosal epithelium integrity by amifostine prevents integrin{alpha}v{beta}6 expression which reduces TGF-{beta} activation and subsequent development of chronic esophageal injury in this model. Further investigation is necessary to determine the clinical relevance of these findings.

  18. Design, synthesis and antiproliferative activity of a novel class of indole-2-carboxylate derivatives.

    PubMed

    Ji, Xing-yue; Xue, Si-tu; Zhan, Yue-chen; Shen, Jia-jia; Wu, Lin-tao; Jin, Jie; Wang, Zhen; Li, Zhuo-rong

    2014-08-18

    Based on the chemical structure of Pyrroloquinoline quinone (PQQ), a novel class of indole-2-carboxylate derivatives was designed, synthesized and assayed for antiproliferative activity in cancer cells in vitro. The biological results showed that some derivatives exhibited significant antiproliferative activity against HepG2, A549 and MCF7 cells. Notably, the novel compounds, methyl 6-amino-4-cyclohexylmethoxy-1H-indole-2-carboxylate (6e) and methyl 4-isopropoxy-6-methoxy-1H-indole-2-carboxylate (9l) exhibited more potent antiproliferative activity than the reference drugs PQQ and etoposide in vitro, with IC50 values ranging from 3.78 ± 0.58 to 24.08 ± 1.76 μM. Further biological assay showed that both compounds 6e and 9l increased ROS generation dose-dependently, and induced PARP cleavage in A549 cells. Consequently, 6e and 9l appeared as promising anticancer lead compounds for further optimization.

  19. Indolic uremic solutes enhance procoagulant activity of red blood cells through phosphatidylserine exposure and microparticle release.

    PubMed

    Gao, Chunyan; Ji, Shuting; Dong, Weijun; Qi, Yushan; Song, Wen; Cui, Debin; Shi, Jialan

    2015-11-01

    Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs), the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS) and indole-3-acetic acid (IAA) on procoagulant activity (PCA) of erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS and IAA (mean and maximal concentrations reported in uremic patients). Phosphatidylserine (PS) exposure of RBCs and their microparticles (MPs) release were labeled with Alexa Fluor 488-lactadherin and detected by flow cytometer. Cytosolic Ca(2+) ([Ca(2+)]) with Fluo 3/AM was analyzed by flow cytometer. PCA was assessed by clotting time and purified coagulation complex assays. We found that PS exposure, MPs generation, and consequent PCA of RBCs at mean concentrations of IS and IAA enhanced and peaked in maximal uremic concentrations. Moreover, 128 nM lactadherin, a PS inhibitor, inhibited over 90% PCA of RBCs and RMPs. Eryptosis or damage, by indolic uremic solutes was due to, at least partially, the increase of cytosolic [Ca(2+)]. Our results suggest that RBC eryptosis in uremic solutes IS and IAA plays an important role in thrombus formation through releasing RMPs and exposing PS. Lactadherin acts as an efficient anticoagulant in this process. PMID:26516916

  20. Effects of indole amides on lettuce and onion germination and growth.

    PubMed

    Borgati, Thiago F; Boaventura, Maria Amelia D

    2011-01-01

    Auxins, such as indole-3-acetic acid (IAA), are important in plant germination and growth, while physiological polyamines, such as putrescine, are involved in cell proliferation and differentiation, and their concentrations increase during germination. In this work, novel indole amides were synthesized in good yields by monoacylation of morpholine and unprotected symmetrical diamines with indole-3-carboxylic acid, a putative metabolite of IAA, possessing no auxin-like activity. These amides were tested for their effects on seed germination and growth of the radicles and shoots of Lactuca sativa (lettuce) and Allium cepa (onion) seedlings, at 100.0, 1.0, and 0.01 microM concentrations. Germination was generally stimulated, with the exception of amide 3, derived from morpholine, at 100 microM. On radicle and shoot growth, the effect of these compounds was predominantly inhibitory. Compound 3 was the best inhibitor of growth of lettuce and onion, at the highest concentration. Amides, such as propanil, among others, are described as having herbicidal activity.

  1. Different N-H⋯π inter-actions in two indole derivatives.

    PubMed

    Kerr, Jamie R; Trembleau, Laurent; Storey, John M D; Wardell, James L; Harrison, William T A

    2016-05-01

    We describe the syntheses and crystal structures of two indole derivatives, namely 6-isopropyl-3-(2-nitro-1-phenyl-eth-yl)-1H-indole, C19H20N2O2, (I), and 2-(4-meth-oxy-phen-yl)-3-(2-nitro-1-phenyl-eth-yl)-1H-indole, C23H20N2O3, (II); the latter crystallizes with two mol-ecules (A and B) with similar conformations (r.m.s. overlay fit = 0.139 Å) in the asymmetric unit. Despite the presence of O atoms as potential acceptors for classical hydrogen bonds, the dominant inter-molecular inter-action in each crystal is an N-H⋯π bond, which generates chains in (I) and A+A and B+B inversion dimers in (II). A different aromatic ring acts as the acceptor in each case. The packing is consolidated by C-H⋯π inter-actions in each case but aromatic π-π stacking inter-actions are absent. PMID:27308022

  2. Enhancement of broccoli indole glucosinolates by methyl jasmonate treatment and effects on prostate carcinogenesis.

    PubMed

    Liu, Ann G; Juvik, John A; Jeffery, Elizabeth H; Berman-Booty, Lisa D; Clinton, Steven K; Erdman, John W

    2014-11-01

    Broccoli is rich in bioactive components, such as sulforaphane and indole-3-carbinol, which may impact cancer risk. The glucosinolate profile of broccoli can be manipulated through treatment with the plant stress hormone methyl jasmonate (MeJA). Our objective was to produce broccoli with enhanced levels of indole glucosinolates and determine its impact on prostate carcinogenesis. Brassica oleracea var. Green Magic was treated with a 250 μM MeJA solution 4 days prior to harvest. MeJA-treated broccoli had significantly increased levels of glucobrassicin, neoglucobrassicin, and gluconasturtiin (P < .05). Male transgenic adenocarcinoma of mouse prostate (TRAMP) mice (n = 99) were randomized into three diet groups at 5-7 weeks of age: AIN-93G control, 10% standard broccoli powder, or 10% MeJA broccoli powder. Diets were fed throughout the study until termination at 20 weeks of age. Hepatic CYP1A was induced with MeJA broccoli powder feeding, indicating biological activity of the indole glucosinolates. Following ∼ 15 weeks on diets, neither of the broccoli treatments significantly altered genitourinary tract weight, pathologic score, or metastasis incidence, indicating that broccoli powder at 10% of the diet was ineffective at reducing prostate carcinogenesis in the TRAMP model. Whereas broccoli powder feeding had no effect in this model of prostate cancer, our work demonstrates the feasibility of employing plant stress hormones exogenously to stimulate changes in phytochemical profiles, an approach that may be useful for optimizing bioactive component patterns in foods for chronic-disease-prevention studies.

  3. Different N—H⋯π inter­actions in 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 6-isopropyl-3-(2-nitro-1-phenyl­eth­yl)-1H-indole, C19H20N2O2, (I), and 2-(4-meth­oxy­phen­yl)-3-(2-nitro-1-phenyl­eth­yl)-1H-indole, C23H20N2O3, (II); the latter crystallizes with two mol­ecules (A and B) with similar conformations (r.m.s. overlay fit = 0.139 Å) in the asymmetric unit. Despite the presence of O atoms as potential acceptors for classical hydrogen bonds, the dominant inter­molecular inter­action in each crystal is an N—H⋯π bond, which generates chains in (I) and A+A and B+B inversion dimers in (II). A different aromatic ring acts as the acceptor in each case. The packing is consolidated by C—H⋯π inter­actions in each case but aromatic π–π stacking inter­actions are absent. PMID:27308022

  4. Production of the Phytohormone Indole-3-Acetic Acid by Estuarine Species of the Genus Vibrio▿

    PubMed Central

    Gutierrez, Casandra K.; Matsui, George Y.; Lincoln, David E.; Lovell, Charles R.

    2009-01-01

    Strains of Vibrio spp. isolated from roots of the estuarine grasses Spartina alterniflora and Juncus roemerianus produce the phytohormone indole-3-acetic acid (IAA). The colorimetric Salkowski assay was used for initial screening of IAA production. Gas chromatography-mass spectroscopy (GC-MS) was then employed to confirm and quantify IAA production. The accuracy of IAA quantification by the Salkowski assay was examined by comparison to GC-MS assay values. Indole-3-acetamide, an intermediate in IAA biosynthesis by the indole-3-acetamide pathway, was also identified by GC-MS. Multilocus sequence typing of concatenated 16S rRNA, recA, and rpoA genes was used for phylogenetic analysis of environmental isolates within the genus Vibrio. Eight Vibrio type strains and five additional species-level clades containing a total of 16 environmental isolates and representing five presumptive new species were identified as IAA-producing Vibrio species. Six additional environmental isolates similar to four of the Vibrio type strains were also IAA producers. To our knowledge, this is the first report of IAA production by species of the genus Vibrio or by bacteria isolated from an estuarine environment. PMID:19218411

  5. Regioselective cope rearrangement and prenyl transfers on indole scaffold mimicking fungal and bacterial dimethylallyltryptophan synthases.

    PubMed

    Thandavamurthy, Karthikeyan; Sharma, Deepti; Porwal, Suheel K; Ray, Dale; Viswanathan, Rajesh

    2014-11-01

    Aromatic prenyltransferases are an actively mined enzymatic class whose biosynthetic repertoire is growing. Indole prenyltransferases catalyze the formation of a diverse set of prenylated tryptophan and diketopiperazines, leading to the formation of fungal toxins with prolific biological activities. At a fundamental level, the mechanism of C4-prenylation of l-tryptophan recently has surfaced to engage a debate between a "direct" electrophilic alkylation mechanism (for wt DMATS and FgaPT2) versus an indole C3-C4 "Cope" rearrangement followed by rearomatization (for mutant FgaPT2). Herein we provide the first series of regioselectively tunable conditions for a Cope rearrangement between C3 and C4 positions. Biomimetic conditions are reported that effect a [3,3]-sigmatropic shift whose two-step process is interrogated for intramolecularity and rate-limiting general base-promoted mechanism. Solvent polarity serves a crucial role in changing the regioselectivity, resulting in sole [1,3]-shifts under decalin. An intermolecular variant is also reported that effectively prenylates the C3 position of l-tryptophan, resulting in products that mimic the structures accessed by bacterial indole prenyltransferases. We report an elaborate investigation that includes screening various substituents and measuring steric and electronic effects and stereoselectivity with synthetically useful transformations.

  6. Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma

    PubMed Central

    Merli, Michele; Carli, Giuseppe; Arcaini, Luca; Visco, Carlo

    2016-01-01

    The association of hepatitis C virus (HCV) and B-cell non-Hodgkin lymphomas (NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment (AT) with interferon (IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study (100 patients) the overall response rate (ORR) after first-line IFN-based AT was 77% (44% complete responses) and responses were sustainable (median duration of response 33 mo). These results were confirmed by a recent meta-analysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response (SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines’ recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents (DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression. PMID:27784957

  7. Profiling two indole-2-carboxamides for allosteric modulation of the CB1 receptor.

    PubMed

    Ahn, Kwang H; Mahmoud, Mariam M; Samala, Sushma; Lu, Dai; Kendall, Debra A

    2013-03-01

    Allosteric modulation of G-protein coupled receptors (GPCRs) represents a novel approach for fine-tuning GPCR functions. The cannabinoid CB1 receptor, a GPCR associated with the CNS, has been implicated in the treatment of drug addiction, pain, and appetite disorders. We report here the synthesis and pharmacological characterization of two indole-2-carboxamides:5-chloro-3-ethyl-1-methyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide (ICAM-a) and 5-chloro-3-pentyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide (ICAM-b). Although both ICAM-a and ICAM-b enhanced CP55, 940 binding, ICAM-b exhibited the strongest positive cooperativity thus far demonstrated for enhancing agonist binding to the CB1 receptor. Although it displayed negative modulatory effects on G-protein coupling to CB1, ICAM-b induced β-arrestin-mediated downstream activation of extracellular signal-regulated kinase (ERK) signaling. These results indicate that this compound represents a novel class of CB1 ligands that produce biased signaling via CB1.

  8. Prevalence and diversity of Bartonella in rodents of northern Thailand: a comparison with Bartonella in rodents from southern China.

    PubMed

    Castle, Kevin T; Kosoy, Michael; Lerdthusnee, Kriangkrai; Phelan, Lori; Bai, Ying; Gage, Kenneth L; Leepitakrat, Warisa; Monkanna, Taweesak; Khlaimanee, Nittaya; Chandranoi, Kirkvich; Jones, James W; Coleman, Russell E

    2004-04-01

    We report results of the first study to investigate the distribution and diversity of Bartonella in rodents from Thailand. Whole blood from 195 rodents, representing six species, was tested for the presence of Bartonella species using standard culture techniques. Isolates were obtained from 17 (8.7%) of the samples, and 14 of those isolates represented distinct strains, based upon partial sequencing of the citrate synthase (gltA) gene. Phylogenetic analysis of the isolates and other Bartonella species indicated that five unique isolates from Bandicota indica form a cluster that may represent a new Bartonella species. Two additional isolates from B. indica clustered together, and were nearly identical to an isolate from Apodemus draco collected in southern China. Importantly, a number of the isolates from Thailand rodents are closely related to B. grahamii and B. elizabethae, species which have been associated with human illness.

  9. Examining lethality risk for rodent studies of primary blast lung injury.

    PubMed

    Hubbard, William Brad; Hall, Christina; Siva Sai Suijith Sajja, Venkata; Lavik, Erink; VandeVord, Pamela

    2014-01-01

    While protective measures have been taken to mitigate injury to the thorax during a blast exposure, primary blast lung injury (PBLI) is still evident in mounted/in vehicle cases during military conflicts. Moreover, civilians, who are unprotected from blast exposure, can be severely harmed by terrorist attacks that use improvised explosive devices (IEDs). Since the lungs are the most susceptible organ due to their air-filled nature, PBLI is one of the most serious injuries seen in civilian blast cases. Determining lethality threshold for rodent studies is crucial to guide experimental designs centered on therapies for survival after PBLI or mechanistic understanding of the injury itself. Using an Advanced Blast Simulator, unprotected rats were exposed to a whole body blast to induce PBLI. The one-hour survival rate was assessed to determine operating conditions for a 50% lethality rate. Macroscopic and histological analysis of lung was conducted using hematoxylin and eosin staining. Results demonstrated lethality risk trends based on static blast overpressure (BOP) for rodent models, which may help standardized animal studies and contribute to scaling to the human level. The need for a standardized method of producing PBLI is pressing and establishing standard curves, such as a lethality risk curve for lung blasts, is crucial for this condensing of BOP methods. PMID:25405409

  10. IDENTIFICATION OF ENVIRONMENTAL CHEMICALS ASSOCIATED WITH THE DEVELOPMENT OF TOXICANT ASSOCIATED FATTY LIVER DISEASE IN RODENTS

    PubMed Central

    Al-Eryani, Laila; Wahlang, Banrida; Falkner, K.C.; Guardiola, J. J.; Clair, H.B.; Prough, R.A.; Cave, M.

    2014-01-01

    Background Toxicant associated fatty liver disease (TAFLD) is a recently identified form of non-alcoholic fatty liver disease (NAFLD) associated with exposure to industrial chemicals and environmental pollutants. Numerous studies have been conducted to test the association between industrial chemicals/ environmental pollutants and fatty liver disease both in vivo and in vitro. Objectives The objective of the paper is to report a list of chemicals associated with TAFLD. Methods Two federal databases of rodent toxicology studies– ToxRefDB (Environmental Protection Agency) and Chemical Effects in Biological Systems (CEBS, National Toxicology Program) were searched for liver endpoints. Combined, these two databases archive nearly 2000 rodent studies. TASH descriptors including fatty change, fatty necrosis, Oil red O positive staining, steatosis and lipid deposition were queried. Results Using these search terms, 123 chemicals associated with fatty liver were identified. Pesticides and solvents were the most frequently identified chemicals, while PCBs/dioxins were the most potent. About 44% of identified compounds were pesticides or their intermediates, and nearly 10% of pesticide registration studies in ToxRefDB were associated with fatty liver. Fungicides and herbicides were more frequently associated with fatty liver than insecticides. Conclusions More research on pesticides, solvents, metals and PCBs/dioxins in NAFLD/TAFLD is warranted due to their association with liver damage. PMID:25326588

  11. Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: Comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin

    SciTech Connect

    Bjeldanes, L.F.; Jinyoung Kim; Grose, K.R.; Bartholomew, J.C. ); Bradfield, C.A. )

    1991-11-01

    Indole-3-carbinol (I3C) is a secondary plant metabolite produced in vegetables of the Brassica genus, including cabbage, cauliflower, and brussels sprouts. I3C is both an anti-initiator and a promoter of carcinogenesis. Consumption of I3C by humans and rodents can lead to marked increases in activities of cytochrome P-450-dependent monooxygenases and in a variety of phase II drug-metabolizing enzymes. The authors have reported previously that the enzyme-inducing activity of I3C is mediated through a mechanism requiring exposure of the compound to the low-pH environment of the stomach. They report here the aromatic hydrocarbon responsiveness-receptor K{sub d} values (22 nM-90 nM), determined with C57BL/6J mouse liver cytosol and the in vitro- and in vivo-molar yields of the major acid condensation products of I3C. They also show that indolo (3,2-b)carbazole (ICZ) is produced form I3C in yields on the order of 0.01% in vitro and, after oral intubation, in vivo. ICZ has a K{sub d} of 190 pM for aromatic hydrocarbon responsiveness-receptor binding and an EC{sub 50} of 269 nM for induction of cytochrome P4501A1, as measured by ethoxyresorufin O-deethylase activity in murine hepatoma Hepa 1c1c7 cells. The binding affinity of ICZ is only a factor of 3.7 {times} 10{sup {minus}2} lower than that of the highly toxic environmental contaminant and cancer promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin. ICZ and related condensation products appear responsible for the enzyme-inducing effects of dietary I3C.

  12. Response of brown treesnakes to reduction of their rodent prey

    USGS Publications Warehouse

    Gragg, J.E.; Rodda, G.H.; Savidge, J.A.; White, Gary C.; Dean-Bradley, K.; Ellingson, A.R.

    2007-01-01

    Trapping brown treesnakes (Boiga irregularis; BTS) with live-mouse (Mus domesticus) lures is the principal control technique for this invasive species on Guam. Lure-based trapping is also used on other islands as a precaution against undetected arrivals and in response to verified BTS sightings. However, the effectiveness of lure-based trapping on other islands is questionable, as it has yielded no BTS despite other evidence of their presence. Some evidence suggests that high rodent numbers may interfere with BTS control. To test the relationship between rodent abundance and snake trappability, we conducted a controlled, replicated field experiment incorporating a rodenticide treatment during a BTS mark-recapture study. Using open population modeling in Program MARK, we estimated BTS apparent survival and recapture probabilities. Rodent reduction increased BTS recapture probabilities by 52-65% in 2002 and 22-36% in 2003, and it decreased apparent survival by <1% both years. This appears to be the first published instance of manipulating wild prey to influence snake behavior. Rodent reduction may enhance detection and control of BTS with traps on Guam and other islands. It may also amplify the effectiveness of oral toxicants against BTS.

  13. What does the oxygen isotope composition of rodent teeth record?

    NASA Astrophysics Data System (ADS)

    Royer, Aurélien; Lécuyer, Christophe; Montuire, Sophie; Amiot, Romain; Legendre, Serge; Cuenca-Bescós, Gloria; Jeannet, Marcel; Martineau, François

    2013-01-01

    Oxygen isotope compositions of tooth phosphate (δ18Op) were measured in 107 samples defined on the basis of teeth obtained from 375 specimens of extant rodents. These rodents were sampled from pellets collected in Europe from 38°N (Portugal) to 65°N (Finland) with most samples coming from sites located in France and Spain. Large oxygen isotopic variability in δ18Op is observed both at the intra- and inter-species scale within pellets from a given location. This isotopic variability is partly explained by heterochrony in tooth formation related to the short time of mineralization for all rodent species as well as the duration of mineralization that is species-dependent. Consequently, tooth phosphate of rodents records a short seasonal interval in the oxygen isotope compositions of meteoric waters (δ18Omw). In addition, inter-species isotopic variability observed in the same pellets suggests behavioural differences implying distinct isotopic compositions for species living in the same location. At the scale of Europe, a robust linear oxygen isotope fractionation equation was determined for Muroidea between the midrange δ18Op values and δ18Omw values: δ18Op=1.21(±0.20)δ18Omw+24.76(±2.70) with R2=0.79 (n=9; p<0.0001).

  14. 40 CFR 798.5460 - Rodent heritable translocation assays.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5460 Rodent... experienced in performing translocation testing shall include a substance known to produce translocations in..., and all female progeny should be discarded. (2) Testing for translocation heterozygosity. When...

  15. 40 CFR 798.5460 - Rodent heritable translocation assays.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5460 Rodent... experienced in performing translocation testing shall include a substance known to produce translocations in..., and all female progeny should be discarded. (2) Testing for translocation heterozygosity. When...

  16. 40 CFR 798.5460 - Rodent heritable translocation assays.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5460 Rodent... experienced in performing translocation testing shall include a substance known to produce translocations in..., and all female progeny should be discarded. (2) Testing for translocation heterozygosity. When...

  17. Phylogeography and evolutionary history of rodent-borne hantaviruses.

    PubMed

    Souza, W M; Bello, G; Amarilla, A A; Alfonso, H L; Aquino, V H; Figueiredo, L T M

    2014-01-01

    Hantavirus (Family Bunyaviridae) are mostly associated to rodents and transmitted to man by inhalation of aerosolized infected excreta of these animals. The human infection by hantaviruses can lead to severe diseases such as hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe, and pulmonary syndrome (HPS) in the Americas. To determine the origin, spreading and evolutionary dynamics of rodent-borne hantaviruses, 190 sequences of nucleoprotein (N) of hantaviruses identified in 30 countries, from 1985 to 2010, were retrieved from the GenBank and analyzed using the BEAST program. Our evolutionary analysis indicates that current genetic diversity of N gene of rodent-borne hantaviruses probably was originated around 2000 years ago. Hantavirus harbored by Murinae and Arvicolinae subfamilies, probably, were originated in Asia 500-700 years ago and later spread toward Siberia, Europe, Africa and North America. Hantavirus carried by Neotominae subfamily, probably, emerged 500-600 years ago in Central America and spread toward North America. Finally, hantaviruses associated to Sigmodontinae occurred in Brazil 400 years ago and were, probably, originated from Neotominae-associated virus from northern South America. These data offer subsidies to understand the time-scale and worldwide dissemination dynamics of rodent-borne hantaviruses.

  18. Andes hantavirus variant in rodents, southern Amazon Basin, Peru.

    PubMed

    Razuri, Hugo; Tokarz, Rafal; Ghersi, Bruno M; Salmon-Mulanovich, Gabriela; Guezala, M Claudia; Albujar, Christian; Mendoza, A Patricia; Tinoco, Yeny O; Cruz, Christopher; Silva, Maria; Vasquez, Alicia; Pacheco, Víctor; Ströher, Ute; Guerrero, Lisa Wiggleton; Cannon, Deborah; Nichol, Stuart T; Hirschberg, David L; Lipkin, W Ian; Bausch, Daniel G; Montgomery, Joel M

    2014-02-01

    We investigated hantaviruses in rodents in the southern Amazon Basin of Peru and identified an Andes virus variant from Neacomys spinosus mice. This finding extends the known range of this virus in South America and the range of recognized hantaviruses in Peru. Further studies of the epizoology of hantaviruses in this region are warranted.

  19. PERFLUOROOCTANE SULFONATE (PFOS) DISRUPTS THE THYROID STATUS IN LABORATORY RODENTS

    EPA Science Inventory

    PERFLUOROOCTANE SULFONATE (PFOS) DISRUPTS THE THYROID STATUS IN LABORATORY RODENTS. C. Lau, J.R. Thibodeaux, R.G. Hanson, B.E. Gray and J.M. Rogers. Reprod. Tox. Div. NHEERL, US EPA, Research Triangle Park, NC.

    PFOS is an environmental contaminant ubiquitously found in h...

  20. Evaluation of two oral baiting systems for wild rodents.

    PubMed

    Creekmore, T E; Fletcher, W O; Stallknecht, D E

    1998-04-01

    Tetracycline hydrochloride (TC)-treated peanut butter or rodent chow baits were distributed during March 1990, on separate 0.53 ha sites in Oglethorpe County, Georgia (USA). Rodents were trapped on a control site prior to bait distribution and on two baited sites 6 days post-distribution. Cleaned skulls from euthanized mammals were grossly examined for TC fluorescence using an ultraviolet (UV) light. Mandibles were sectioned and examined for TC fluorescence using an ultraviolet light microscope. All 21 cotton rats (Sigmodon hispidus), four eastern harvest mice (Rithrodontomys humulis), and two golden mice (Ochrotomys nuttalli) captured on the control site were negative for TC fluorescence. On the peanut butter bait site, mandible sections from 29 of 32 (91%) cotton rats, three of three (100%) eastern harvest mice, two of three (66%) golden mice, zero of five (0%) white-footed mice (Peromyscus leucopus), one of three (33%) short-tailed shrews (Blarina brevicauda), and zero of two (0%) least shrews (Cryptotis parva) were positive for TC. Results from the rodent chow bait site indicated that 18 of 25 (72%) cotton rats, zero of three (0%) eastern harvest mice, two of seven (29%) golden mice, zero of four (0%) white-footed mice, and zero of four (0%) least shrews were positive for TC fluorescence in mandible sections. These results suggest that a large portion of a free-ranging small rodent population can be administered biological markers or vaccines using baits. PMID:9577787