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Sample records for endogenous indole protects

  1. Myo-inositol esters of indole-3-acetic acid are endogenous components of Zea mays L. shoot tissue

    Science.gov (United States)

    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.

  2. Immunolocalization of endogenous indole-3-acetic acid and abscisic acid in the shoot internodes of Fargesia yunnanensis bamboo during development

    Science.gov (United States)

    Shuguang Wang; Yongpeng Ma; Chengbin Wan; Chungyun Hse; Todd F. Shupe; Yujun Wang; Changming. Wang

    2016-01-01

    The Bambusoideae subfamily includes the fastest-growing plants worldwide, as a consequence of fast internode elongation. However, few studies have evaluated the temporal and spatial distribution of endogenous hormones during internode elongation. In this paper, endogenous indole-3-acetic acid (IAA) and abscisic acid (ABA) were detected in different developmental...

  3. Role of endogenous thiols in protection

    Science.gov (United States)

    Vos, O.

    Aminothiols represent the most important group of radioprotective compounds. The most effective compounds administered at an optimal dose and time before irradiation are able to provide a protection in mice with a dose reduction factor (DRF) of about 2-2.5. The working mechanism can partly be explained as a scavenging process of radicals induced in water and partly as a chemical repair process of injured DNA. The endogenous aminothiol which has far-out the highest intracellular concentration is glutathione (GSH). The importance of intracellular GSH in determining cellular radiosensitivity has been shown by irradiating cells that had very low GSH levels. Such cells appear to have a high radiosensitivity, especially in hypoxic conditions. On the other hand, it has been demonstrated that induction of a high GSH level (100-200% above the normal level) provides only a small protection. In vitro experiments with DNA indicate that thiols with a high positive charge condense in the vicinity of DNA and are effective protectors, whereas thiols with a negative charge are kep away from it and are poor protectors. In comparison with the most effective exogenous aminothiols like cysteamine and WR1065, GSH is not an effective radioprotector. Putative explanations for this relatively poor protective ability of GSH are presented.

  4. Novel non-indolic melatonin receptor agonists differentially entrain endogenous melatonin rhythm and increase its amplitude

    NARCIS (Netherlands)

    Drijfhout, W.J; de Vries, J.B; Homan, E.J; Brons, H.F; Copinga, S; Gruppen, G; Beresford, I.J M; Hagan, R.M; Grol, Cor; Westerink, B.H.C.

    1999-01-01

    In this study we have examined the ability of melatonin and four synthetic melatonin receptor agonists to entrain endogenous melatonin secretion in rats, free running in constant darkness. The circadian melatonin profile was measured by trans-pineal microdialysis, which not only reveals the time of

  5. Endogenous indole-3-acetic acid and ethylene evolution in tilted Metasequoia glyptostroboides stems in relation to compression-wood formation.

    Science.gov (United States)

    Du, Sheng; Sugano, Mami; Tsushima, Miho; Nakamura, Teruko; Yamamoto, Fukuju

    2004-04-01

    Eight-year-old Metasequoia glyptostroboides seedlings were tilted at a 45 degrees angle to induce compression-wood formation on the lower side of the stems. After 2 weeks of treatment, half of the seedlings were sampled and the remaining half were tilted to the opposite orientation to exchange the upper and lower sides and were kept for 2 more weeks until sampled. Cambium-emitted ethylene was analyzed by gas chromatography with flame-ionization detection. Endogenous indole-3-acetic acid (IAA) was measured by gas chromatography-mass spectrometry. Tracheid production and compression-wood formation were determined by light microscopy. Anatomical studies showed that tracheid production was promoted and compression-wood tracheids always developed on the gravitationally lower side of tilted stems in both the original tilting and the subsequent reverse-tilting periods. These were accompanied by an increase in IAA content in and an accelerated ethylene-evolution rate from the cambial region of the same side.

  6. Endogenous erythropoietin protects neuroretinal function in ischemic retinopathy.

    Science.gov (United States)

    Mowat, Freya M; Gonzalez, Francisco; Luhmann, Ulrich F O; Lange, Clemens A; Duran, Yanai; Smith, Alexander J; Maxwell, Patrick H; Ali, Robin R; Bainbridge, James W B

    2012-04-01

    Because retinal ischemia is a common cause of vision loss, we sought to determine the effects of ischemia on neuroretinal function and survival in murine oxygen-induced retinopathy (OIR) and to define the role of endogenous erythropoietin (EPO) in this model. OIR is a reproducible model of ischemia-induced retinal neovascularization; it is used commonly to develop antiangiogenic strategies. We investigated the effects of ischemia in murine OIR on retinal function and neurodegeneration by electroretinography and detailed morphology. OIR was associated with significant neuroretinal dysfunction, with reduced photopic and scotopic ERG responses and reduced b-wave/a-wave ratios consistent with specific inner-retinal dysfunction. OIR resulted in significantly increased apoptosis and atrophy of the inner retina in areas of ischemia. EPO deficiency in heterozygous Epo-Tag transgenic mice was associated with more profound retinal dysfunction after OIR, indicated by a significantly greater suppression of ERG amplitudes, but had no measurable effect on the extent of retinal ischemia, preretinal neovascularization, or neuroretinal degeneration in OIR. Systemic administration of recombinant EPO protected EPO-deficient mice against this additional suppression, but EPO supplementation in wild-type animals with OIR did not rescue neuroretinal dysfunction or degeneration. Murine OIR offers a valuable model of ischemic neuroretinal dysfunction and degeneration in which to investigate adaptive tissue responses and evaluate novel therapeutic approaches. Endogenous EPO can protect neuroretinal function in ischemic retinopathy. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Iridium-catalyzed direct synthesis of tryptamine derivatives from indoles: exploiting n-protected β-amino alcohols as alkylating agents.

    Science.gov (United States)

    Bartolucci, Silvia; Mari, Michele; Bedini, Annalida; Piersanti, Giovanni; Spadoni, Gilberto

    2015-03-20

    The selective C3-alkylation of indoles with N-protected ethanolamines involving the "borrowing hydrogen" strategy is described. This method provides convenient and sustainable access to several tryptamine derivatives.

  8. [Protective effects of endogenous carbon monoxide against myocardial ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Zhou, Zhen; Ma, Shuang; Liu, Jie; Ji, Qiao-Rong; Cao, Cheng-Zhu; Li, Xiao-Na; Tang, Feng; Zhang, Wei

    2018-04-25

    The present study is aimed to explore the effects of endogenous carbon monoxide on the ischemia-reperfusion in rats. Wistar rats were intraperitoneally injected with protoporphyrin cobalt chloride (CoPP, an endogenous carbon monoxide agonist, 5 mg/kg), zinc protoporphyrin (ZnPP, an endogenous carbon monoxide inhibitor, 5 mg/kg) or saline. Twenty-four hours after injection, the myocardial ischemia-reperfusion model was made by Langendorff isolated cardiac perfusion system, and cardiac function parameters were collected. Myocardial cGMP content was measured by ELISA, and the endogenous carbon monoxide in plasma and myocardial enzymes in perfusate at 10 min after reperfusion were measured by colorimetry. The results showed that before ischemia the cardiac functions of CoPP, ZnPP and control groups were stable, and there were no significant differences. After reperfusion, cardiac functions had significant differences among the three groups (P endogenous carbon monoxide can maintain cardiac function, shorten the time of cardiac function recovery, and play a protective role in cardiac ischemia-reperfusion.

  9. Circadian changes in endogenous concentrations of indole-3-acetic acid, melatonin, serotonin, abscisic acid and jasmonic acid in Characeae (Chara australis Brown).

    Science.gov (United States)

    Beilby, Mary J; Turi, Christina E; Baker, Teesha C; Tymm, Fiona Jm; Murch, Susan J

    2015-01-01

    Giant-celled Characeae (Chara australis Brown), grown for 4 months on 12/12 hr day/night cycle and summer/autumn temperatures, exhibited distinct concentration maxima in auxin (indole-3-acetic acid; IAA), melatonin and serotonin about 4 hr after subjective daybreak. These concentration peaks persisted after 3 day pretreatment in continuous darkness: confirming a circadian rhythm, rather than a response to "light on." The plants pretreated for 3 d in continuous light exhibited several large IAA concentration maxima throughout the 24 hr. The melatonin and serotonin concentrations decreased and were less synchronized with IAA. Chara plants grown on 9/15 hr day/night cycle for 4 months and winter/spring temperatures contained much smaller concentrations of IAA, melatonin and serotonin. The IAA concentration maxima were observed in subjective dark phase. Serotonin concentration peaks were weakly correlated with those of IAA. Melatonin concentration was low and mostly independent of circadian cycle. The "dark" IAA concentration peaks persisted in plants treated for 3 d in the dark. The plants pretreated for 3 d in the light again developed more IAA concentration peaks. In this case the concentration maxima in melatonin and serotonin became more synchronous with those in IAA. The abscisic acid (ABA) and jasmonic acid (JA) concentrations were also measured in plants on winter regime. The ABA concentration did not exhibit circadian pattern, while JA concentration peaks were out of phase with those of IAA. The data are discussed in terms of crosstalk between metabolic pathways.

  10. Endogenous Quantification of Abscisic Acid and Indole-3-Acetic Acid in Somatic and Zigotic Embryos of Nothofagus alpina (Poepp. & Endl. Oerst Cuantificación Endógena de Ácido Abscísico y Ácido Indol-3 Acético en Embriones Somáticos y Cigóticos de Nothofagus alpina (Poepp. & Endl. Oerst

    Directory of Open Access Journals (Sweden)

    Pricila Cartes Riquelme

    2011-12-01

    Full Text Available Abscisic acid (ABA and indole-3-acetic acid (IAA participate in the propagation of plants by somatic embryogenesis, causing polar structural differentiation of the embryo. The goal of the assay was to compare endogenous levels of ABA and IAA between somatic embryos (SE and zygotic embryos (ZE of Nothofagus alpina (Poepp. & Endl. Oerst. In this study, a somatic embryo maturation assay involving the addition of varying concentrations of exogenous ABA was performed on cotyledonary-stage of N. alpina. Furthermore, the endogenous levels of ABA and IAA were quantified in the immature ZE, the mature ZE, and the embryonic axis of a mature embryo of N. alpina. The current study utilized high performance liquid chromatography (HPLC for quantification. The maturation treatments performed did not present significant differences in the endogenous ABA levels in SE. However, significant differences did exist in levels of ABA and IAA between SE submitted to the different maturation treatments and mature ZE of N. alpina. The application of exogenous ABA to the culture medium increased endogenous ABA levels, therefore, increasing the number of germinated somatic embryos. Thus, the plant conversion process was also successfully completed in somatic embryos of N. alpina.El ácido abscísico (ABA y el ácido indol 3 acético (IAA participan en el proceso de propagación de plantas mediante embriogénesis somática, ya que permiten la diferenciación de la estructura polar del embrión, órganos y regiones meristemáticas de éste. En este estudio se llevó a cabo un ensayo de maduración de embriones somáticos en estado cotiledonar con la adición de diferentes concentraciones de ABA exógeno, además se determinaron niveles endógenos entre ZE inmaduro, ZE maduro, y eje embrionario aislado desde el embrión maduro para luego comparar niveles endógenos de ABA e IAA en embriones somáticos (SE y cigóticos (ZE de raulí, Nothofagus alpina (Poepp. & Endl. Oerst. La

  11. Novel protective role of endogenous cardiac myocyte P2X4 receptors in heart failure.

    Science.gov (United States)

    Yang, Tiehong; Shen, Jian-bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberly; Grady, James; Jacobson, Kenneth A; Liang, Bruce T

    2014-05-01

    Heart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload. Mice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation-induced postinfarct or transverse aorta constriction-induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N(5)-(1-iminoethyl)ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout. This study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection. © 2014 American Heart Association, Inc.

  12. Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

    OpenAIRE

    Kachadroka, Supatra; Hall, Alicia M.; Niedzielko, Tracy L.; Chongthammakun, Sukumal; Floyd, Candace L.

    2010-01-01

    Several groups have recently shown that 17β-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17β-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17β-estradiol-mediated protection by evaluating a delayed administration over a clinically relevan...

  13. Tumor-reactive immune cells protect against metastatic tumor and induce immunoediting of indolent but not quiescent tumor cells.

    Science.gov (United States)

    Payne, Kyle K; Keim, Rebecca C; Graham, Laura; Idowu, Michael O; Wan, Wen; Wang, Xiang-Yang; Toor, Amir A; Bear, Harry D; Manjili, Masoud H

    2016-09-01

    Two major barriers to cancer immunotherapy include tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens. To overcome these barriers, we reprogrammed tumor-immune cell cross-talk by combined use of decitabine and adoptive immunotherapy, containing tumor-sensitized T cells and CD25(+) NKT cells. Decitabine functioned to induce the expression of highly immunogenic cancer testis antigens in the tumor, while also reducing the frequency of myeloid-derived suppressor cells and the presence of CD25(+) NKT cells rendered T cells, resistant to remaining myeloid-derived suppressor cells. This combinatorial therapy significantly prolonged survival of animals bearing metastatic tumor cells. Adoptive immunotherapy also induced tumor immunoediting, resulting in tumor escape and associated disease-related mortality. To identify a tumor target that is incapable of escape from the immune response, we used dormant tumor cells. We used Adriamycin chemotherapy or radiation therapy, which simultaneously induce tumor cell death and tumor dormancy. Resultant dormant cells became refractory to additional doses of Adriamycin or radiation therapy, but they remained sensitive to tumor-reactive immune cells. Importantly, we discovered that dormant tumor cells contained indolent cells that expressed low levels of Ki67 and quiescent cells that were Ki67 negative. Whereas the former were prone to tumor immunoediting and escape, the latter did not demonstrate immunoediting. Our results suggest that immunotherapy could be highly effective against quiescent dormant tumor cells. The challenge is to develop combinatorial therapies that could establish a quiescent type of tumor dormancy, which would be the best target for immunotherapy. © The Author(s).

  14. Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

    Science.gov (United States)

    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

    2015-10-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

  15. Collateral blood flow in different cerebrovascular hierarchy provides endogenous protection in cerebral ischemia.

    Science.gov (United States)

    Luo, Chuanming; Liang, Fengyin; Ren, Huixia; Yao, Xiaoli; Liu, Qiang; Li, Mingyue; Qin, Dajiang; Yuan, Ti-Fei; Pei, Zhong; Su, Huanxing

    2017-11-01

    Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia. © 2016 International Society of

  16. Protective effect of indole-3-pyruvate against ultraviolet b-induced damage to cultured HaCaT keratinocytes and the skin of hairless mice.

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    Reiji Aoki

    Full Text Available Previous investigations demonstrated that pyruvate protects human keratinocytes against cell damage stemming from exposure to ultraviolet B (UVB radiation. This study endeavoured to elucidate the protective capacity of aromatic pyruvates (e.g., phenylpyruvate (PPyr, 4-hydroxyphenylpyruvate (HPPyr, and indole-3-pyruvate (IPyr against UVB-induced injury to skin cells, both in vitro and in vivo. Cultured human HaCaT keratinocytes were irradiated with UVB light (60 mJ/cm2 and maintained with or without test compounds (1-25 mM.In addition, the dorsal skin of hairless mice (HR-1 was treated with test compounds (10 μmol and exposed to UVB light (1 J/cm2 twice [corrected]. The ability of the test compounds to ameliorate UVB-induced cytotoxicity and inflammation was then assessed. Aromatic pyruvates reduced cytotoxicity in UVB-irradiated HaCaT keratinocytes, and also diminished the expression of interleukin 1β (IL-1β and interleukin 6 (IL-6. IPyr was more efficacious than either PPyr or HPPyr. Furthermore, only IPyr inhibited cyclooxygenase-2 (Cox-2 expression at both the mRNA and the protein level in UVB-treated keratinocytes. Topical application of IPyr to the dorsal skin of hairless mice reduced the severity of UVB-induced skin lesions, the augmentation of dermal thickness, and transepithelial water loss. Overproduction of IL-1β and IL-6 in response to UVB radiation was also suppressed in vivo by the topical administration of IPyr. These data strongly suggest that IPyr might find utility as a UVB-blocking reagent in therapeutic strategies to lessen UVB-induced inflammatory skin damage.

  17. Ethanol extract of Portulaca oleracea L. protects against hypoxia-induced neuro damage through modulating endogenous erythropoietin expression.

    Science.gov (United States)

    Wanyin, Wang; Liwei, Dong; Lin, Jia; Hailiang, Xin; Changquan, Ling; Min, Li

    2012-04-01

    In addition to its role in erythropoiesis, erythropoietin is also appreciated for its neuroprotective effects, and it has been suggested for treatment of some ischemic-hypoxic neurovascular diseases. The protective effects of endogenous erythropoietin in the brain give rise to the hypothesis that modulating erythropoietin expression might be a better way for treatment of ischemia-hypoxia neurovascular diseases. We have found that ethanol extract of Portulaca oleracea L. (EEPO) could increase erythropoietin expression in hypoxic mouse brain in our previous study. The present study is to investigate whether EEPO exerts its neuroprotective effects against hypoxia injury through regulating endogenous erythropoietin expression. The results demonstrated that EEPO decreased the serum neuron specific enolase level in hypoxia mice and the activity of caspase-3 in neuron, increased the neuron viability and attenuated the pathological damages caused by the hypoxia condition. Importantly, we also found that EEPO stimulated the endogenous erythropoietin expression at both mRNA and protein levels. Using the conditioned medium containing soluble erythropoietin receptor, we found that the neuroprotective effects of EEPO were dependent, at least partly, on erythropoietin expression. Although EEPO did not affect transcription of hypoxia inducible factor-1α (HIF-1α), it did stabilize expression of HIF-1α. It is concluded that EEPO has neuroprotective effects against hypoxia injury, which is at least partly through stimulating endogenous erythropoietin expression by stabilizing HIF-1α. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Effect of endogenous androgens on 17beta-estradiol-mediated protection after spinal cord injury in male rats.

    Science.gov (United States)

    Kachadroka, Supatra; Hall, Alicia M; Niedzielko, Tracy L; Chongthammakun, Sukumal; Floyd, Candace L

    2010-03-01

    Several groups have recently shown that 17beta-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17beta-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17beta-estradiol-mediated protection by evaluating a delayed administration over a clinically relevant dose range and manipulating testicular-derived testosterone. Adult male Sprague Dawley rats were either gonadectomized or left gonad-intact prior to SCI. SCI was produced by a midthoracic crush injury. At 30 min post SCI, animals received a subcutaneous pellet of 0.0, 0.05, 0.5, or 5.0 mg of 17beta-estradiol, released over 21 days. Hindlimb locomotion was analyzed weekly in the open field. Spinal cords were collected and analyzed for cell death, expression of Bcl-family proteins, and white-matter sparing. Post-SCI administration of the 0.5- or 5.0-mg pellet improved hindlimb locomotion, reduced urinary bladder size, increased neuronal survival, reduced apoptosis, improved the Bax/Bcl-xL protein ratio, and increased white-matter sparing. In the absence of endogenous testicular-derived androgens, SCI induced greater apoptosis, yet 17beta-estradiol administration reduced apoptosis to the same extent in gonadectomized and gonad-intact male rats. These data suggest that delayed post-SCI administration of a clinically relevant dose of 17beta-estradiol is protective in male rats, and endogenous androgens do not alter estrogen-mediated protection. These data suggest that 17beta-estradiol is an effective therapeutic intervention for reducing secondary damage after SCI in males, which could be readily translated to clinical trials.

  19. Protection of honeybee Apis mellifera by its endogenous and exogenous lactic flora against bacterial infections

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    Irakli Janashia

    2016-09-01

    Three exogenous bacteriocin-producing LAB strains were tested against the same pathogens and against 25 endogenous bacterial isolates representing 11 different LAB species. The screening showed that all the tested exogenous bacteriocin-producing strains inhibited the tested P. larvae strains. The endogenous LAB strains exhibited varied sensitivity profiles when treated with bacteriocin-producing strains. This raises similar challenges to those observed in antibiotic applications leading to dysbacteriosis, even though the efficacy of these bacteriocins against P. larvae in an in vitro system is evident.

  20. MnTM-4-PyP modulates endogenous antioxidant responses and protects primary cortical neurons against oxidative stress.

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    Cheng, Kuo-Yuan; Guo, Fei; Lu, Jia-Qi; Cao, Yuan-Zhao; Wang, Tian-Chang; Yang, Qi; Xia, Qing

    2015-05-01

    Oxidative stress is a direct cause of injury in various neural diseases. Manganese porphyrins (MnPs), a large category of superoxide dismutase (SOD) mimics, shown universally to have effects in numerous neural disease models in vivo. Given their complex intracellular redox activities, detailed mechanisms underlying the biomedical efficacies are not fully elucidated. This study sought to investigate the regulation of endogenous antioxidant systems by a MnP (MnTM-4-PyP) and its role in the protection against neural oxidative stress. Primary cortical neurons were treated with MnTM-4-PyP prior to hydrogen peroxide-induced oxidative stress. MnTM-4-PyP increased cell viability, reduced intracellular level of reactive oxygen species, inhibited mitochondrial apoptotic pathway, and ameliorated endoplasmic reticulum function. The protein levels and activities of endogenous SODs were elevated, but not those of catalase. SOD2 transcription was promoted in a transcription factor-specific manner. Additionally, we found FOXO3A and Sirt3 levels also increased. These effects were not observed with MnTM-4-PyP alone. Induction of various levels of endogenous antioxidant responses by MnTM-4-PyP has indispensable functions in its protection for cortical neurons against hydrogen peroxide-induced oxidative stress. © 2014 John Wiley & Sons Ltd.

  1. Indole-3-thiouronium nitrate

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    Martin Lutz

    2008-01-01

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

  2. RIA for indol alkaloids

    International Nuclear Information System (INIS)

    Arens, H.

    1979-01-01

    The technique of RIAs for indol alkaloids (ajmaline, ergotamine, ergocristine, ergometrine, and lysergic acid) is described, and applications for this RIA and the RIA for raubasine and serpentine are mentioned. The indol alkaloide RIAs are shown to be suitable both for alkaloid distribution measurements in Catharantus and Rauwolfia plants and C. purpurea sclerotia as well as for the selection of high-efficiency strains and the optimisation of cultures of plant tissues and saprophytic fungi. (orig./MG) [de

  3. Endogenous glutathione protects human skin fibroblasts against the cytotoxic action of UVB, UVA and near-visible radiations

    International Nuclear Information System (INIS)

    Tyrell, R.M.; Pidoux, Mireille

    1986-01-01

    Both the UVB (290-320 nm) and UVA (320-380 nm) regions of sunlight damage human skin cells but, particularly at the longer wavelengths, information is scant concerning the mechanism(s) of damage induction and the roles of cellular defense mechanisms. Following extensive glutathione depletion of cultured human skin fibroblasts, the cells become strongly sensitized to the cytotoxic action of near-visible (405 nm), UVA (334 nm, 365 nm) and UVB (313 nm) but not UVC (254 nm) radiations. In the critical UVB region, the magnitude of the protection afforded by endogenous glutathione approaches that of the protection provided by excision repair. The results suggest that a significant fraction of even UVB damage can be mediated by free radical attack and that a major role of glutathione in human skin cells is to protect them from the cytotoxic action of sunlight. (author)

  4. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

    International Nuclear Information System (INIS)

    Ohno, Kazuki; Okuda, Kosaku; Uehara, Takashi

    2015-01-01

    Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H 2 S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H 2 S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H 2 S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H 2 S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H 2 S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H 2 S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions

  5. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Kazuki; Okuda, Kosaku; Uehara, Takashi, E-mail: uehara@pharm.okayama-u.ac.jp

    2015-01-02

    Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H{sub 2}S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H{sub 2}S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H{sub 2}S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and the oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H{sub 2}S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H{sub 2}S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H{sub 2}S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions.

  6. Endogenous protection derived from activin A/Smads transduction loop stimulated via ischemic injury in PC12 cells.

    Science.gov (United States)

    Mang, Jing; Mei, Chun-Li; Wang, Jiao-Qi; Li, Zong-Shu; Chu, Ting-Ting; He, Jin-Ting; Xu, Zhong-Xin

    2013-10-17

    Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab). We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.

  7. Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Zhong-Xin Xu

    2013-10-01

    Full Text Available Activin A (ActA, a member of transforming growth factor-beta (TGF-b super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab. We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.

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

    International Nuclear Information System (INIS)

    Komoszynski, M.; Bandurski, R.S.

    1986-01-01

    Indole-3-acetyl-myo-inositol galactoside labeled with 3 H in the indole and 14 C 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 [ 3 H]indole-3-acetyl-myo-inositol and [ 3 H]indole-3-acetic acid which were then transported to the shoot with little radioactivity going to the root. With certain assumptions concerning the equilibration of applied [ 3 H]indole-3-acetyl-myo-inositol-[U- 14 C]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-acetic acid to the shoot and thus is comparable to indole-3-acetyl-myo-inositol as a source of indoleacetic acid for the shoot. Quantitative estimates of the amount of galactose in the kernels suggest that [ 3 H]indole-3-acetyl-myo-inositol-[ 14 C] galactose is hydrolyzed after the compound leaves the endosperm but before it reaches the shoot. In addition, [ 3 H]indole-3-acetyl-myo-inositol-[ 14 C]galactose supplies appreciable amounts of 14 C to the shoot and both 14 C and 3 H to an uncharacterized insoluble fraction of the endosperm

  9. Disease protection and interleukin-10 induction by endogenous interferon-β in multiple sclerosis?

    DEFF Research Database (Denmark)

    Hesse, D.; Krakauer, M.; Lund, H

    2011-01-01

    with increased spontaneous MX1 expression also had increased expression of other genes induced by regular IFN-ß treatment of MS. MX1 expression correlated with FOXP3 and IL10 expression, and IL10 expression correlated negatively with disease activity on magnetic resonance imaging. Further, in vivo IL10...... expression was lower in NAb-positive patients than in untreated patients with MS and healthy controls. Finally, ex vivo treatment of mononuclear blood cells with IFN-ß induced the expression of IL10, and this was blocked by the addition of serum from NAb-positive patients with MS. CONCLUSION: Our findings...... suggest that endogenous IFN-ß may induce the expression of immunoregulatory IL10 in MS and that this might be associated with dampening of inflammatory disease activity....

  10. BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity

    DEFF Research Database (Denmark)

    Rasmussen, Rikke D.; Gajjar, Madhavsai K.; Tuckova, Lucie

    2016-01-01

    Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Hi...

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

    Science.gov (United States)

    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.

  12. Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol

    International Nuclear Information System (INIS)

    Banu, Sakhila K.; Stanley, Jone A.; Sivakumar, Kirthiram K.; Arosh, Joe A.; Burghardt, Robert C.

    2016-01-01

    Resveratrol (RVT), a polyphenolic component in grapes and red wine, has been known for its cytoprotective actions against several diseases. However, beneficial effects of RVT against early exposure to endocrine disrupting chemicals (EDCs) have not been understood. EDCs are linked to several ovarian diseases such as premature ovarian failure, polycystic ovary syndrome, early menopause and infertility in women. Hexavalent chromium (CrVI) is a heavy metal EDC, and widely used in > 50 industries. Environmental contamination with CrVI in the US is rapidly increasing, predisposing the human to several illnesses including cancers and still birth. Our lab has been involved in determining the molecular mechanism of CrVI-induced female infertility and intervention strategies to mitigate CrVI effects. Lactating mother rats were exposed to CrVI (50 ppm potassium dichromate) from postpartum days 1–21 through drinking water with or without RVT (10 mg/kg body wt., through oral gavage daily). During this time, F1 females received respective treatments through mother's milk. On postnatal day (PND) 25, blood and the ovary, kidney and liver were collected from the F1 females for analyses. CrVI increased atresia of follicles by increasing cytochrome C and cleaved caspase-3; decreasing antiapoptotic proteins; decreasing estradiol (E 2 ) biosynthesis and enhancing metabolic clearance of E 2 , increasing oxidative stress and decreasing endogenous antioxidants. RVT mitigated the effects of CrVI by upregulating cell survival proteins and AOXs; and restored E 2 levels by inhibiting hydroxylation, glucuronidation and sulphation of E 2 . This is the first study to report the protective effects of RVT against any toxicant in the ovary. - Highlights: • Resveratrol (RVT) protects the ovary against CrVI-toxicity. • RVT mitigated CrVI-induced apoptosis and follicle atresia. • RVT restored estradiol level against CrVI-toxicity. • RVT inhibited metabolic clearance of estradiol in the

  13. Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Banu, Sakhila K., E-mail: skbanu@cvm.tamu.edu; Stanley, Jone A.; Sivakumar, Kirthiram K.; Arosh, Joe A.; Burghardt, Robert C.

    2016-07-15

    Resveratrol (RVT), a polyphenolic component in grapes and red wine, has been known for its cytoprotective actions against several diseases. However, beneficial effects of RVT against early exposure to endocrine disrupting chemicals (EDCs) have not been understood. EDCs are linked to several ovarian diseases such as premature ovarian failure, polycystic ovary syndrome, early menopause and infertility in women. Hexavalent chromium (CrVI) is a heavy metal EDC, and widely used in > 50 industries. Environmental contamination with CrVI in the US is rapidly increasing, predisposing the human to several illnesses including cancers and still birth. Our lab has been involved in determining the molecular mechanism of CrVI-induced female infertility and intervention strategies to mitigate CrVI effects. Lactating mother rats were exposed to CrVI (50 ppm potassium dichromate) from postpartum days 1–21 through drinking water with or without RVT (10 mg/kg body wt., through oral gavage daily). During this time, F1 females received respective treatments through mother's milk. On postnatal day (PND) 25, blood and the ovary, kidney and liver were collected from the F1 females for analyses. CrVI increased atresia of follicles by increasing cytochrome C and cleaved caspase-3; decreasing antiapoptotic proteins; decreasing estradiol (E{sub 2}) biosynthesis and enhancing metabolic clearance of E{sub 2}, increasing oxidative stress and decreasing endogenous antioxidants. RVT mitigated the effects of CrVI by upregulating cell survival proteins and AOXs; and restored E{sub 2} levels by inhibiting hydroxylation, glucuronidation and sulphation of E{sub 2}. This is the first study to report the protective effects of RVT against any toxicant in the ovary. - Highlights: • Resveratrol (RVT) protects the ovary against CrVI-toxicity. • RVT mitigated CrVI-induced apoptosis and follicle atresia. • RVT restored estradiol level against CrVI-toxicity. • RVT inhibited metabolic clearance of

  14. 3-Substituted 2-phenyl-indoles

    DEFF Research Database (Denmark)

    Johansson, Karl Henrik; Jørgensen, T.B.; Gloriam, D.E.

    2013-01-01

    -indoles with a variety of substituents at the indole 3-position. Herein we describe the development of optimised and efficient synthetic routes to a series of new 2-phenyl-indole building blocks 3 to 9 and show that these can be used to generate a broad variety of 3-substituted 2-phenyl-indoles of interest to medicinal...

  15. Combined radiation-protective and radiation-sensitizing agents. III. Radiosensitization by misonidazole as a function of concentrations of endogenous glutathione or exogenous thiols

    International Nuclear Information System (INIS)

    Koch, C.J.; Stobbe, C.C.; Baer, K.A.

    1986-01-01

    Radiosensitization of V79 Chinese hamster fibroblasts by 0.5 mM misonidazole is a smooth function of endogenous glutathione (GSH) levels as modulated upwards by pre-incubation in medium containing cysteamine, or downwards by pre-incubation in medium containing buthionine sulfoximine. The enhancement ratio (radiation sensitivity in nitrogen/radiation sensitivity in nitrogen +/- sensitizer or thiol) varies from 1.3 at 12 mM to 2.25 at less than 0.1 mM endogenous GSH. The enhanced radiosensitivity of thiol-depleted hypoxic cells is reversed when exogenous thiols are added, and for equivalent ER, the exogenous thiol concentrations are much lower than the endogenous GSH concentrations. Measurement of intracellular drug concentrations amplified rather than diminished the above discrepancy, since intracellular concentrations of cysteamine were lower and glutathione much lower than the extracellular concentrations. Three possible explanations are addressed: an external membrane component of damage is involved, long-range protection to DNA target radicals is possible from outside the cell (e.g., donation of electrons), and (c) endogenous glutathione is not in a free or exchangeable state (e.g., bound)

  16. Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells

    OpenAIRE

    Mang, Jing; Mei, Chun-Li; Wang, Jiao-Qi; Li, Zong-Shu; Chu, Ting-Ting; He, Jin-Ting; Xu, Zhong-Xin

    2013-01-01

    Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate isch...

  17. Endogenous antipyretics.

    Science.gov (United States)

    Roth, Joachim

    2006-09-01

    The febrile increase of body temperature is regarded as a component of the complex host response to infection or inflammation that accompanies the activation of the immune system. Late phases of fever appear mediated by pro-inflammatory cytokines called endogenous pyrogens. The rise of body temperature is beneficial because it accelerates several components of the activated immune system. To prevent an excessive and dangerous rise of body temperature the febrile response is controlled, limited in strength and duration, and sometimes even prevented by the actions of endogenous antipyretic substances liberated systemically or within the brain during fever. In most cases the antipyretic effects are achieved by an inhibitory influence on the formation or action of endogenous pyrogens, or by effects on neuronal thermoregulatory circuits that are activated during fever. Endogenous antipyretic substances include steroid hormones, neuropeptides, cytokines and other molecules. It is the purpose of this review to consider the current state in the research on endogenous antipyretic systems.

  18. Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Mørch, Marlene Thorsen; Holm, Thomas Hellesøe

    2015-01-01

    show elevated levels of Type I IFNs in the central nervous system (CNS), suggesting a role for endogenous Type I IFN during inflammation. However, the therapeutic benefit of Type I IFN produced in the CNS remains to be established. The aim of this study was to examine whether experimentally induced CNS......-endogenous Type I IFN influences EAE. Using IFN-β reporter mice, we showed that direct administration of polyinosinic-polycytidylic acid (poly I:C), a potent inducer of IFN-β, into the cerebrospinal fluid induced increased leukocyte numbers and transient upregulation of IFN-β in CD45/CD11b-positive cells located...... in the meninges and choroid plexus, as well as enhanced IFN-β expression by parenchymal microglial cells. Intrathecal injection of poly I:C to mice showing first symptoms of EAE substantially increased the normal disease-associated expression of IFN-α, IFN-β, interferon regulatory factor-7 and IL-10 in CNS...

  19. Ethylene-enhanced catabolism of [14C]indole-3-acetic acid to indole-3-carboxylic acid in citrus leaf tissues

    International Nuclear Information System (INIS)

    Sagee, O.; Riov, J.; Goren, J.

    1990-01-01

    Exogenous [ 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 [ 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

  20. Changes in endogenous hormone contents of pear stock ( Pyrus ...

    African Journals Online (AJOL)

    In this study, changes in endogenous hormone contents of pear stock seeds during cold stratification were investigated. Abscisic acid (ABA) content decreased with increase in the periods of stratification of pear stock seeds. However, gibberellic acid (GA) and indole-3-acetic acid (IAA) contents of Pyrus betulaefolia and ...

  1. Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla

    OpenAIRE

    Wei, Xin; Jiang, Li-Ping; Guo, Ying; Khan, Afsar; Liu, Ya-Ping; Yu, Hao-Fei; Wang, Bei; Ding, Cai-Feng; Zhu, Pei-Feng; Chen, Ying-Ying; Zhao, Yun-Li; Chen, Yong-Bing; Wang, Yi-Fen; Luo, Xiao-Dong

    2017-01-01

    Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness, cerebrovascular diseases, and nervous disorders in China. Previously, the neuro-protective activities of the alkaloids from U. rhynchophylla were intensively reported. In current work, three new indole alkaloids (1–3), identified as geissoschizic acid (1), geissoschizic acid N 4-oxide (2), and 3β-sitsirikine N 4-oxide (3), as well as 26 known analogues were isolated from U. rhynchophylla. However, in the ne...

  2. Endogene CGRP

    OpenAIRE

    Höfer, Martina

    2010-01-01

    Hintergrund und Ziele Die vorliegende tierexperimentelle Arbeit beschäftigt sich mit der Frage, welche Rolle endogenes Calcitonin-gene related peptide (CGRP) in der Niere spielt. Hierbei untersuchten wir die renale CGRP Freisetzung aus renalen Afferenzen in vitro anhand von gesunden Tieren und einem pathologischen Modell der Glomerulonephritis. Man weiß bereits, dass sowohl sympathische als auch primär sensorische Neuronen die Entzündung und die Immunantwort in der Peripherie regulieren (68)....

  3. Protection against β-amyloid neurotoxicity by a non-toxic endogenous N-terminal β-amyloid fragment and its active hexapeptide core sequence.

    Science.gov (United States)

    Forest, Kelly H; Alfulaij, Naghum; Arora, Komal; Taketa, Ruth; Sherrin, Tessi; Todorovic, Cedomir; Lawrence, James L M; Yoshikawa, Gene T; Ng, Ho-Leung; Hruby, Victor J; Nichols, Robert A

    2018-01-01

    High levels (μM) of beta amyloid (Aβ) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits, and apoptotic cell death. The hydrophobic C-terminal domain of Aβ, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aβ at low levels (pM-nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N-terminal domain of Aβ. An N-terminal Aβ fragment (1-15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aβ-induced impairments of long-term potentiation. Here, we show the impact of this N-terminal Aβ fragment and a shorter hexapeptide core sequence in the Aβ fragment (Aβcore: 10-15) to protect or reverse Aβ-induced neuronal toxicity, fear memory deficits and apoptotic death. The neuroprotective effects of the N-terminal Aβ fragment and Aβcore on Aβ-induced changes in mitochondrial function, oxidative stress, and apoptotic neuronal death were demonstrated via mitochondrial membrane potential, live reactive oxygen species, DNA fragmentation and cell survival assays using a model neuroblastoma cell line (differentiated NG108-15) and mouse hippocampal neuron cultures. The protective action of the N-terminal Aβ fragment and Aβcore against spatial memory processing deficits in amyloid precursor protein/PSEN1 (5XFAD) mice was demonstrated in contextual fear conditioning. Stabilized derivatives of the N-terminal Aβcore were also shown to be fully protective against Aβ-triggered oxidative stress. Together, these findings indicate an endogenous neuroprotective role for the N-terminal Aβ fragment, while active stabilized N-terminal Aβcore derivatives offer the potential for therapeutic application. © 2017 International Society for Neurochemistry.

  4. Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

    Science.gov (United States)

    Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

    2005-04-01

    Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

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

    Directory of Open Access Journals (Sweden)

    Nils Marsch

    2016-02-01

    Full Text Available 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-ylpentenones 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.

  6. Overexpression of Endogenous Anti-Oxidants with Selenium Supplementation Protects Trophoblast Cells from Reactive Oxygen Species-Induced Apoptosis in a Bcl-2-Dependent Manner.

    Science.gov (United States)

    Khera, Alisha; Vanderlelie, Jessica J; Holland, Olivia; Perkins, Anthony V

    2017-06-01

    The human placenta provides life support for the developing foetus, and a healthy placenta is a prerequisite to a healthy start to life. Placental tissue is subject to oxidative stress which can lead to pathological conditions of pregnancy such as preeclampsia, preterm labour and intrauterine growth restriction. Up-regulation of endogenous anti-oxidants may alleviate placental oxidative stress and provide a therapy for these complications of pregnancy. In this study, selenium supplementation, as inorganic sodium selenite (NaSel) or organic selenomethionine (SeMet), was used to increase the protein production and cellular activity of the important redox active proteins glutathione peroxidase (GPx) and thioredoxin reductase (Thx-Red). Placental trophoblast cell lines, BeWo, JEG-3 and Swan-71, were cultured in various concentrations of NaSel or SeMet for 24 h and cell extracts prepared for western blots and enzyme assays. Rotenone and antimycin were used to stimulate mitochondrial reactive oxygen species (ROS) production and induce apoptosis. Trophoblast cells supplemented with 100 nM NaSel and 500 nM SeMet exhibited significantly enhanced expression and activity of both GPx and Thx-Red. Antimycin and rotenone were found to generate ROS when measured by 2',7'-dichlorofluorescein diacetate (DCFDA) assay, and selenium supplementation was shown to reduce ROS production in a dose-dependent manner. Rotenone, 100 μM treatment for 4 h, caused trophoblast cell apoptosis as evidenced by increased Annexin V binding and decreased expression of Bcl-2. In both assays of apoptosis, selenium supplementation was able to prevent apoptosis, preserve Bcl-2 expression and protect trophoblast cells from mitochondrial oxidative stress. This data suggests that selenoproteins such as GPx and Thx-Red have an important role in protecting trophoblast cells from mitochondrial oxidative stress and that selenium supplementation may be important in treating some placental pathologies.

  7. Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase-activating polypeptide against hydrogen peroxide-induced oxidative damages in cultured rat astrocytes.

    Science.gov (United States)

    Douiri, Salma; Bahdoudi, Seyma; Hamdi, Yosra; Cubì, Roger; Basille, Magali; Fournier, Alain; Vaudry, Hubert; Tonon, Marie-Christine; Amri, Mohamed; Vaudry, David; Masmoudi-Kouki, Olfa

    2016-06-01

    Astroglial cells possess an array of cellular defense mechanisms, including superoxide dismutase (SOD) and catalase antioxidant enzymes, to prevent damages caused by oxidative stress. Nevertheless, astroglial cell viability and functionality can be affected by significant oxidative stress. We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent glioprotective agent that prevents hydrogen peroxide (H2 O2 )-induced apoptosis in cultured astrocytes. The purpose of this study was to investigate the potential protective effect of PACAP against oxidative-generated alteration of astrocytic antioxidant systems. Incubation of cells with subnanomolar concentrations of PACAP inhibited H2 O2 -evoked reactive oxygen species accumulation, mitochondrial respiratory burst, and caspase-3 mRNA level increase. PACAP also stimulated SOD and catalase activities in a concentration-dependent manner, and counteracted the inhibitory effect of H2 O2 on the activity of these two antioxidant enzymes. The protective action of PACAP against H2 O2 -evoked inhibition of antioxidant systems in astrocytes was protein kinase A, PKC, and MAP-kinase dependent. In the presence of H2 O2 , the SOD blocker NaCN and the catalase inhibitor 3-aminotriazole, both suppressed the protective effects of PACAP on SOD and catalase activities, mitochondrial function, and cell survival. Taken together, these results indicate that the anti-apoptotic effect of PACAP on astroglial cells can account for the activation of endogenous antioxidant enzymes and reduction in respiration rate, thus preserving mitochondrial integrity and preventing caspase-3 expression provoked by oxidative stress. Considering its powerful anti-apoptotic and anti-oxidative properties, the PACAPergic signaling system should thus be considered for the development of new therapeutical approaches to cure various pathologies involving oxidative neurodegeneration. We propose the following cascade for the

  8. Electrochemical Behavior of Biologically Important Indole Derivatives

    Directory of Open Access Journals (Sweden)

    Cigdem Karaaslan

    2011-01-01

    Full Text Available Voltammetric techniques are most suitable to investigate the redox properties of a new drug. Use of electrochemistry is an important approach in drug discovery and research as well as quality control, drug stability, and determination of physiological activity. The indole nucleus is an essential element of a number of natural and synthetic products with significant biological activity. Indole derivatives are the well-known electroactive compounds that are readily oxidized at carbon-based electrodes, and thus analytical procedures, such as electrochemical detection and voltammetry, have been developed for the determination of biologically important indoles. This paper explains some of the relevant and recent achievements in the electrochemistry processes and parameters mainly related to biologically important indole derivatives in view of drug discovery and analysis.

  9. Serum glutathione transferase does not respond to indole-3-carbinol: A pilot study

    Directory of Open Access Journals (Sweden)

    Daniel R McGrath

    2010-05-01

    Full Text Available Daniel R McGrath1, Hamid Frydoonfar2, Joshua J Hunt3, Chris J Dunkley3, Allan D Spigelman41Ipswich Hospital, Ipswich, UK; 2Hunter Pathology Service, New South Wales; 3Royal Newcastle Centre, Newcastle; 4St Vincent’s Clinical School, Sydney, AustraliaBackground: Despite the well recognized protective effect of cruciferous vegetables against various cancers, including human colorectal cancers, little is known about how this effect is conferred. It is thought that some phytochemicals found only in these vegetables confer the protection. These compounds include the glucosinolates, of which indole-3-carbinol is one. They are known to induce carcinogen-metabolizing (phase II enzymes, including the glutathione S-transferase (GST family. Other effects in humans are not well documented. We wished to assess the effect of indole-3-carbinol on GST enzymes.Methods: We carried out a placebo-controlled human volunteer study. All patients were given 400 mg daily of indole-3-carbinol for three months, followed by placebo. Serum samples were tested for the GSTM1 genotype by polymerase chain reaction. Serum GST levels were assessed using enzyme-linked immunosorbent assay and Western Blot methodologies.Results: Forty-nine volunteers completed the study. GSTM1 genotypes were obtained for all but two volunteers. A slightly greater proportion of volunteers were GSTM1-positive, in keeping with the general population. GST was detected in all patients. Total GST level was not affected by indole-3-carbinol dosing compared with placebo. Although not statistically significant, the GSTM1 genotype affected the serum GST level response to indole-3-carbinol.Conclusion: Indole-3-carbinol does not alter total serum GST levels during prolonged dosing.Keywords: pilot study, colorectal cancer, glutathione transferase, human, indole-3-carbinol

  10. Analysis of several irdoid and indole precursors of terpenoid indole alkaloids with a single HPLC run

    DEFF Research Database (Denmark)

    Dagnino, Denise; Schripsema, Jan; Verpoorte, Robert

    1996-01-01

    An isocratic HPLC system is described which allows the separation of the iridoid and indole precursors of terpenoid indole alkaloids, which are present in a single crude extract. The system consists of a column of LiChrospher 60 RP select B 5 my, 250x4 mm (Merck) with an eluent of 1 % formic acid...

  11. Novel indole-based inhibitors of IMPDH: introduction of hydrogen bond acceptors at indole C-3.

    Science.gov (United States)

    Watterson, Scott H; Dhar, T G Murali; Ballentine, Shelley K; Shen, Zhongqi; Barrish, Joel C; Cheney, Daniel; Fleener, Catherine A; Rouleau, Katherine A; Townsend, Robert; Hollenbaugh, Diane L; Iwanowicz, Edwin J

    2003-04-07

    The development of a series of novel indole-based inhibitors of 5'-inosine monophosphate dehydrogenase (IMPDH) is described. Various hydrogen bond acceptors at C-3 of the indole were explored. The synthesis and the structure-activity relationships (SARs) derived from in vitro studies are outlined.

  12. A simple, effective, green method for regioselective 3-acylation of unprotected indoles

    DEFF Research Database (Denmark)

    Tran, Phuong Huong; Tran, Hai N.; Hansen, Poul Erik

    2015-01-01

    A fast and green method is developed for regioselective acylation of indoles in the 3-position without the need for protection of the NH position. The method is based on Friedel-Crafts acylation using acid anhydrides. The method has been optimized, and Y(OTf)3 in catalytic amounts is found...

  13. Uniconazole effect on endogenous hormones, proteins and proline contents of barley plants (Hordium vulgare under salinity stress (NaCl

    Directory of Open Access Journals (Sweden)

    MOHAMED A. BAKHETA

    2014-05-01

    Full Text Available Bakheta MA, Hussein MM. 2014. Uniconazole effect on endogenous hormones, proteins and proline contents of barley plants (Hordium vulgare under salinity stress (NaCl. Nusantara Bioscience 6: 39-44. Pot experiments were carried out during two growth seasons 2010 / 2011 under greenhouse conditions of the National Research Centre, Dokki, Cairo, Egypt to investigate the response of barley plants (Hordium vulgare L grown under salinity stress (2500 or 5000 ppm to spraying with solutions of uniconazole at 150 or 200 ppm. The obtained results showed that irrigation with saline solutions caused increases in the amounts of abscisic acid (ABA, crude protein, total soluble-protein and proline contents. The results showed that spraying barley plants grown under saline solutions with uniconazole increased endogenous hormone contents of ABA, cytokinins, crude protein, total soluble protein and proline but caused decreases in the amounts of endogenous indole acetic acid (IAA and gibberellic acid (GA3. High protection of abscisic acid in treating plants with uniconazole and under salt stress (interaction effect increases proline, proteins and soluble protein which has been proposed to act as compatible solutes that adjust the osmotic potential in the cytoplasm. Thus, these biochemical characters can be used as a metabolic marker in relation to salinity stress.

  14. Studies on the Protective Effects of Scutellarein against Neuronal Injury by Ischemia through the Analysis of Endogenous Amino Acids and Ca2+ Concentration Together with Ca2+-ATPase Activity

    Directory of Open Access Journals (Sweden)

    Hao Tang

    2015-01-01

    Full Text Available Scutellarin, which is extracted from the dried plant of Erigeron breviscapus, has been reported to protect the neural injury against excitotoxicity induced by ischemia. However, there are a few studies on the protective effects of scutellarein, which is the main metabolite of scutellarin in vivo. Thus, this study investigated the neuroprotective effects of scutellarein on cerebral ischemia/reperfusion in rats by bilateral common carotid artery occlusion (BCCAO model, through the analysis of endogenous amino acids using HILIC-MS/MS, and evaluation of Ca2+ concentration together with Ca2+-ATPase activity. The results showed that scutellarein having good protective effects on cerebral ischemia/reperfusion might by decreasing the excitatory amino acids, increasing the inhibitory amino acids, lowing intracellular Ca2+ level, and improving Ca2+-ATPase activity, which suggested that scutellarein might be a promising potent agent for the therapy of ischemic cerebrovascular disease.

  15. Endogenous Lunar Volatiles

    Science.gov (United States)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Anand, M.; Boyce, J. W.; Burney, D.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Klima, R. L.; Magna, T.; Ni, P.; Steenstra, E.; Tartèse, R.; Vander Kaaden, K. E.

    2018-04-01

    This abstract discusses numerous outstanding questions on the topic of endogenous lunar volatiles that will need to be addressed in the coming years. Although substantial insights into endogenous lunar volatiles have been gained, more work remains.

  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

    Directory of Open Access Journals (Sweden)

    Hansruedi Glatt

    2013-07-01

    Full Text Available 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. Synthesis and Bioactivity of Secondary Metabolites from Marine Sponges Containing Dibrominated Indolic Systems

    Directory of Open Access Journals (Sweden)

    Azzurra Stefanucci

    2012-05-01

    Full Text Available Marine sponges. (e.g., Hyrtios sp., Dragmacidin sp., Aglophenia pleuma, Aplidium cyaneum, Aplidium meridianum. produce bioactive secondary metabolites involved in their defence mechanisms. Recently it was demonstrated that several of those compounds show a large variety of biological activities against different human diseases with possible applications in medicinal chemistry and in pharmaceutical fields, especially related to the new drug development process. Researchers have focused their attention principally on secondary metabolites with anti-cancer and cytotoxic activities. A common target for these molecules is the cytoskeleton, which has a central role in cellular proliferation, motility, and profusion involved in the metastatic process associate with tumors. In particular, many substances containing brominated indolic rings such as 5,6-dibromotryptamine, 5,6-dibromo-N-methyltryptamine, 5,6-dibromo-N-methyltryptophan (dibromoabrine, 5,6-dibromo-N,N-dimethyltryptamine and 5,6-dibromo-L-hypaphorine isolated from different marine sources, have shown anti-cancer activity, as well as antibiotic and anti-inflammatory properties. Considering the structural correlation between endogenous monoamine serotonin with marine indolic alkaloids 5,6-dibromoabrine and 5,6-dibromotryptamine, a potential use of some dibrominated indolic metabolites in the treatment of depression-related pathologies has also been hypothesized. Due to the potential applications in the treatment of various diseases and the increasing demand of these compounds for biological assays and the difficult of their isolation from marine sources, we report in this review a series of recent syntheses of marine dibrominated indole-containing products.

  18. Synthesis of New Functionalized Indoles Based on Ethyl Indol-2-carboxylate

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    Ahmed T. A. Boraei

    2016-03-01

    Full Text Available Successful alkylations of the nitrogen of ethyl indol-2-carboxylate were carried out using aq. KOH in acetone. The respective N-alkylated acids could be obtained without separating the N-alkylated esters by increasing the amount of KOH and water. The use of NaOMe in methanol led to transesterification instead of the alkylation, while the use of NaOEt led to low yields of the N-alkylated acids. Hydrazinolysis of the ester gave indol-2-carbohydrazide which then was allowed to react with different aromatic aldehydes and ketones in ethanol catalyzed by acetic acid. Indol-2-thiosemicarbazide was used in a heterocyclization reaction to form thiazoles. The new structures were confirmed using NMR, mass spectrometry and X-ray single crystal analysis.

  19. Endogenous Prospect Theory

    OpenAIRE

    Schmidt, Ulrich; Zank, Horst

    2010-01-01

    In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This paper provides an axiomatization of a new specification of cumulative prospect theory, termed endogenous prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

  20. Are endogenous feline leukemia viruses really endogenous?

    Science.gov (United States)

    Stewart, H; Jarrett, O; Hosie, M J; Willett, B J

    2011-10-15

    Full length endogenous feline leukemia virus (FeLV) proviruses exist within the genomes of many breeds of domestic cat raising the possibility that they may also exist in a transmissible exogenous form. Such viruses would share receptor usage with the recombinant FeLV-B subgroup, a viral subgroup that arises in vivo by recombination between exogenous subgroup A virus (FeLV-A) and endogenous FeLV. Accordingly, all isolates of FeLV-B made to date have contained a "helper" FeLV-A, consistent with their recombinatorial origin. In order to assess whether endogenous viruses are transmitted between cats, we examined primary isolates of FeLV for which the viral subgroup had been determined for the presence of a subgroup B virus that lacked an FeLV-A. Here we describe the identification of two primary field isolates of FeLV (2518 and 4314) that appeared to contain subgroup B virus only by classical interference assays, raising the possibility of between-host transmission of endogenous FeLV. Sequencing of the env gene and U3 region of the 3' long terminal repeat (LTR) confirmed that both viral genomes contained endogenous viral env genes. However the viral 3' LTRs appeared exogenous in origin with a putative 3' recombination breakpoint residing at the 3' end of the env gene. Further, the FeLV-2518 virions also co-packaged a truncated FeLV-A genome containing a defective env gene, termed FeLV-2518(A) whilst no helper subgroup A viral genome was detected in virions of FeLV-4314. The acquisition of an exogenous LTR by the endogenous FeLV in 4314 may have allowed a recombinant FeLV variant to outgrow an exogenous FeLV-A virus that was presumably present during first infection. Given time, a similar evolution may also occur within the 2518 isolate. The data suggest that endogenous FeLVs may be mobilised by acquisition of exogenous LTRs yielding novel viruses that type biologically as FeLV-B. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Endogenous Locus Reporter Assays.

    Science.gov (United States)

    Liu, Yaping; Hermes, Jeffrey; Li, Jing; Tudor, Matthew

    2018-01-01

    Reporter gene assays are widely used in high-throughput screening (HTS) to identify compounds that modulate gene expression. Traditionally a reporter gene assay is built by cloning an endogenous promoter sequence or synthetic response elements in the regulatory region of a reporter gene to monitor transcriptional activity of a specific biological process (exogenous reporter assay). In contrast, an endogenous locus reporter has a reporter gene inserted in the endogenous gene locus that allows the reporter gene to be expressed under the control of the same regulatory elements as the endogenous gene, thus more accurately reflecting the changes seen in the regulation of the actual gene. In this chapter, we introduce some of the considerations behind building a reporter gene assay for high-throughput compound screening and describe the methods we have utilized to establish 1536-well format endogenous locus reporter and exogenous reporter assays for the screening of compounds that modulate Myc pathway activity.

  2. Production of endogenous pyrogen.

    Science.gov (United States)

    Dinarello, C A

    1979-01-01

    The production and release of endogenous pyrogen by the host is the first step in the pathogenesis of fever. Endogenous pyrogen is a low-molecular-weight protein released from phagocytic leukocytes in response to several substances of diverse nature. Some of these agents stimulate production of endogenous pyrogen because they are toxic; others act as antigens and interact with either antibody or sensitized lymphocytes in order to induce its production. Some tumors of macrophage origin produce the molecule spontaneously. Whatever the mechanism involved, endogenous pyrogen is synthesized following transcription of new DNA and translation of mRNA into new protein. Once synthesis is completed, the molecule is released without significant intracellular storage. Recent evidence suggests that following release, molecular aggregates form which are biologically active. In its monomer form, endogenous pyrogen is a potent fever-producing substance and mediates fever by its action on the thermoregulatory center.

  3. α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology

    Directory of Open Access Journals (Sweden)

    Tetsade Piermartiri

    2015-11-01

    Full Text Available α-Linolenic acid (ALA is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB, brain-derived neurotrophic factor (BDNF, a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders.

  4. Photomonomerization of pyrimidine dimers by indoles and proteins

    Energy Technology Data Exchange (ETDEWEB)

    Chen, J.; Huang, C.W.; Hinman, L.; Gordon, M.P.; Deranleau, D.A.

    1976-01-01

    Model systems for the study of photoreactivation have been developed that utilize a variety of indole derivatives. These systems can split uracil cis-syn cyclobutadipyrimidine, either free or in RNA, when irradiated at wavelengths absorbed only by the indole moiety. The ability of indole compounds to split dimers is closely related to their electronic properties. Those of high electron-donor capacity such as indole, 3-methylindole, indole-3-acetic acid, 5-hydroxytryptophan and tryptophan are good photosensitizers, with efficacy in that order. Indoles with electron-withdrawing substituents such as indole-3-carboxylic acid, indole-3-aldehyde and oxindole are inactive in the monomerization reaction. These findings support the proposed mechanism that the photosensitized monomerization occurs as a result of electron transfer from the excited indole molecules to the pyrimidine bases. Proteins containing fully exposed tryptophan residues (chicken egg white lysozyme and bovine diisopropylphosphoryltrypsin) also cause the splitting of the /sup 14/C-labeled dimers under the same conditions. In the case of lysozyme the quantum yield of monomerization is similar to that of free tryptophan. Much of the monomerization ability of lysozyme was lost after the solvent-available tryptophan had been oxidized by treatment with N-bromosuccinimide. Bovine pancreatic ribonuclease A, a protein devoid of tryptophan, failed to exhibit photosensitized monomerization of uracil dimers. The biological implication of these reactions involving a protein with an exposed tryptophan residue is discussed. Although indoles are able to split the dimers in RNA, they fail to photoreactivate uv-damaged TMV-RNA. Indole-3-acetic acid, 3-methylindole and 5-hydroxytryptophan rapidly inactive viral RNA when irradiated at 313 nm, possibly because of side reactions.

  5. Indole alkaloids from leaves and twigs of Rauvolfia verticillata.

    Science.gov (United States)

    Zhang, Bing-Jie; Peng, Lei; Wu, Zhi-Kun; Bao, Mei-Fen; Liu, Ya-Ping; Cheng, Gui-Guang; Luo, Xiao-Dong; Cai, Xiang-Hai

    2013-01-01

    Seven new indole alkaloids, rauverines A-G (1-7), and 19 known indole alkaloids were isolated from the leaves and twigs of Rauvolfia verticillata. All compounds showed no cytotoxicity against five human cancer cell lines, human myeloid leukemia (HL-60), hepatocellular carcinoma (SMMC-7721), lung cancer (A-549), breast cancer (MCF-7), and colon cancer (SW480) cells.

  6. The electrochemical polymerization of indole with thiophene

    International Nuclear Information System (INIS)

    Sarac, S.

    2004-01-01

    Electropolymerization of indole (IN) in the presence of thiophene (Th) was followed by in situ spectrochemical studies. A correlation between absorbance (390 nm) and charge (at 600 mV) values indicated that oligomeric species were formed in solution, and similar results were found with in situ measurements. The copolymer was characterized by FT-IR, UV-Visible Spectroscopy, Cyclic Voltammetry and four-point probe conductymeter. The increase in conductivity by the incorporation of Th into polyindole was about 60 times for a feed ratio n I N/n T H=1:10 and 19 times for n I N/n T H=1:1. Similar effects were also observed during in situ spectroelectrochemical measurements of copolymer formation. It was also found that the cyclic voltametry peak potentials for the electrogrowth of copolymer films were closely correlated to the conductivities of the corresponding films (measured separately by four-point probe method), thereby allowing us to use the peak potential currents to predict the final copolymer film conductivities during the electrochemical growth process. The ex-situ spectroelectrocopolymerization of indole was also obtained in acetonitril medium.The Tg value of the polymer also increased with the incorporation of Th. The results strongly suggest that IN and Th copolymerize on the electrode surface as well as in solution

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

    Energy Technology Data Exchange (ETDEWEB)

    Kamath, A.; Vaidyanathan, C.S. (Indiana Institute of Science, Bangalore (India))

    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.

  8. Indole and 3-indolylacetonitrile inhibit spore maturation in Paenibacillus alvei

    Directory of Open Access Journals (Sweden)

    Cho Moo

    2011-05-01

    Full Text Available Abstract Background Bacteria use diverse signaling molecules to ensure the survival of the species in environmental niches. A variety of both Gram-positive and Gram-negative bacteria produce large quantities of indole that functions as an intercellular signal controlling diverse aspects of bacterial physiology. Results In this study, we sought a novel role of indole in a Gram-positive bacteria Paenibacillus alvei that can produce extracellular indole at a concentration of up to 300 μM in the stationary phase in Luria-Bertani medium. Unlike previous studies, our data show that the production of indole in P. alvei is strictly controlled by catabolite repression since the addition of glucose and glycerol completely turns off the indole production. The addition of exogenous indole markedly inhibits the heat resistance of P. alvei without affecting cell growth. Observation of cell morphology with electron microscopy shows that indole inhibits the development of spore coats and cortex in P. alvei. As a result of the immature spore formation of P. alvei, indole also decreases P. alvei survival when exposed to antibiotics, low pH, and ethanol. Additionally, indole derivatives also influence the heat resistance; for example, a plant auxin, 3-indolylacetonitrile dramatically (2900-fold decreased the heat resistance of P. alvei, while another auxin 3-indoleacetic acid had a less significant influence on the heat resistance of P. alvei. Conclusions Together, our results demonstrate that indole and plant auxin 3-indolylacetonitrile inhibit spore maturation of P. alvei and that 3-indolylacetonitrile presents an opportunity for the control of heat and antimicrobial resistant spores of Gram-positive bacteria.

  9. Endogenous Pyrogen Physiology.

    Science.gov (United States)

    Beisel, William R.

    1980-01-01

    Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)

  10. Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla.

    Science.gov (United States)

    Wei, Xin; Jiang, Li-Ping; Guo, Ying; Khan, Afsar; Liu, Ya-Ping; Yu, Hao-Fei; Wang, Bei; Ding, Cai-Feng; Zhu, Pei-Feng; Chen, Ying-Ying; Zhao, Yun-Li; Chen, Yong-Bing; Wang, Yi-Fen; Luo, Xiao-Dong

    2017-10-01

    Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness, cerebrovascular diseases, and nervous disorders in China. Previously, the neuro-protective activities of the alkaloids from U. rhynchophylla were intensively reported. In current work, three new indole alkaloids (1-3), identified as geissoschizic acid (1), geissoschizic acid N 4 -oxide (2), and 3β-sitsirikine N 4 -oxide (3), as well as 26 known analogues were isolated from U. rhynchophylla. However, in the neural stem cells (NSCs) proliferation assay for all isolated compounds, geissoschizic acid (1), geissoschizic acid N 4 -oxide (2), isocorynoxeine (6), isorhynchophylline (7), (4S)-akuammigine N-oxide (8), and (4S)-rhynchophylline N-oxide (10) showed unexpected inhibitory activities at 10 μM. Unlike previous neuro-protective reports, as a warning or caution, our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U. rhynchophylla, while the structure-activity relationships of the isolated compounds were discussed also.

  11. Hexacyclic monoterpenoid indole alkaloids from Rauvolfia verticillata.

    Science.gov (United States)

    Gao, Yuan; Yu, Ai-Lin; Li, Gen-Tao; Hai, Ping; Li, Yan; Liu, Ji-Kai; Wang, Fei

    2015-12-01

    Five new hexacyclic monoterpenoid indole alkaloids, rauvovertine A (1), 17-epi-rauvovertine A (2), rauvovertine B (3), 17-epi-rauvovertine B (4), and rauvovertine C (5) together with 17 known analogues were isolated from the stems of Rauvolfia verticillata. Compounds 1/2 and 3/4 were obtained as C-17 epimeric mixtures due to rapid hemiacetal tautomerism in solution. The structures of 1-5 were established by spectroscopic analysis and with the aid of molecular modeling. The new alkaloids were evaluated for their cytotoxicity in vitro against human tumor HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice

    Directory of Open Access Journals (Sweden)

    Do Hyeong Gwon

    2017-09-01

    Full Text Available Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI. Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs from ω6-Polyunsaturated fatty acids (ω6-PUFAs without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt were divided into four groups: wt sham (n = 10, fat-1 sham (n = 10, wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15, and fat-1 IRI (n = 15. Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR. Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

  13. High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

    Science.gov (United States)

    Gwon, Do Hyeong; Hwang, Tae Woong; Ro, Ju-Ye; Kang, Yoon-Joong; Jeong, Jin Young; Kim, Do-Kyung; Lim, Kyu; Kim, Dong Woon; Choi, Dae Eun; Kim, Jwa-Jin

    2017-09-30

    Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham ( n = 10), fat-1 sham ( n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI ( n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

  14. Electron attachment to indole and related molecules

    Energy Technology Data Exchange (ETDEWEB)

    Modelli, Alberto, E-mail: alberto.modelli@unibo.it [Dipartimento di Chimica “G. Ciamician”, Universitá di Bologna, via Selmi 2, 40126 Bologna (Italy); Centro Interdipartimentale di Ricerca in Scienze Ambientali (CIRSA), Universitá di Bologna, via S. Alberto 163, 48123 Ravenna (Italy); Jones, Derek, E-mail: d.jones@isof.cnr.it [ISOF, Istituto per la Sintesi Organica e la Fotoreattività, C.N.R., via Gobetti 101, 40129 Bologna (Italy); Pshenichnyuk, Stanislav A., E-mail: sapsh@anrb.ru [Institute of Molecule and Crystal Physics, Ufa Research Centre, Russian Academy of Sciences, Prospekt Oktyabrya 151, 450075 Ufa (Russian Federation)

    2013-11-14

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

  15. Oligomerization of Indole Derivatives with Incorporation of Thiols

    Directory of Open Access Journals (Sweden)

    Jarl E.S. Wikberg

    2008-08-01

    Full Text Available Abstract: Two molecules of indole derivative, e.g. indole-5-carboxylic acid, reacted with one molecule of thiol, e.g. 1,2-ethanedithiol, in the presence of trifluoroacetic acid to yield adducts such as 3-[2-(2-amino-5-carboxyphenyl-1-(2-mercaptoethylthioethyl]-1Hindole-5-carboxylic acid. Parallel formation of dimers, such as 2,3-dihydro-1H,1'H-2,3'-biindole-5,5'-dicarboxylic acid and trimers, such as 3,3'-[2-(2-amino-5-carboxyphenyl ethane-1,1-diyl]bis(1H-indole-5-carboxylic acid of the indole derivatives was also observed. Reaction of a mixture of indole and indole-5-carboxylic acid with 2-phenylethanethiol proceeded in a regioselective way, affording 3-[2-(2-aminophenyl-1-(phenethylthioethyl]-1H-indole-5-carboxylic acid. An additional product of this reaction was 3-[2-(2-aminophenyl-1-(phenethylthioethyl]-2,3-dihydro-1H,1'H-2,3'-biindole-5'-carboxylic acid, which upon standing in DMSO-d6 solution gave 3-[2-(2-aminophenyl-1-(phenethylthioethyl]-1H,1'H-2,3'-biindole-5'-carboxylic acid. Structures of all compounds were elucidated by NMR, and a mechanism for their formation was suggested.

  16. The Endogenous Exposome

    Science.gov (United States)

    Nakamura, Jun; Mutlu, Esra; Sharma, Vyom; Collins, Leonard; Bodnar, Wanda; Yu, Rui; Lai, Yongquan; Moeller, Benjamin; Lu, Kun; Swenberg, James

    2014-01-01

    The concept of the Exposome, is a compilation of diseases and one’s lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the Endogenous Exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions. PMID:24767943

  17. Role of endogenous substances in enhancing radioresistance background

    International Nuclear Information System (INIS)

    Goncharenko, E.N.; Gorskaya, T.G.; Graevskaya, E.Eh.; Kozlova, M.A.

    1979-01-01

    Presumable sources of endogenous were studied amines in radiosensitive tissues under the effect of radioprotective agents were studied. The data obtained support the idea that mast cells of rats, having large deposits of biogenous amines, might be one of the reserves contributing to mobilization of endogeneous protective resources of the organism treated with radioprotective agents

  18. Cytokines as endogenous pyrogens.

    Science.gov (United States)

    Dinarello, C A

    1999-03-01

    Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.

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

    Science.gov (United States)

    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.

  20. Rhenium and Manganese-Catalyzed Selective Alkenylation of Indoles

    KAUST Repository

    Wang, Chengming

    2018-04-06

    An efficient rhenium‐catalyzed regioselective C‐H bond alkenylation of indoles is reported. The protocol operates well for internal as well as terminal alkynes, affording products in good to excellent yields. Furthermore, a manganese catalyzed, acid free, regioselective C2‐alkenylation of indoles with internal alkynes is described. The directing groups can be easily removed after the reaction and the resulting products can be used as valuable building blocks for the synthesis of diverse heterocyclic compounds.

  1. Rhenium and Manganese-Catalyzed Selective Alkenylation of Indoles

    KAUST Repository

    Wang, Chengming; Rueping, Magnus

    2018-01-01

    An efficient rhenium‐catalyzed regioselective C‐H bond alkenylation of indoles is reported. The protocol operates well for internal as well as terminal alkynes, affording products in good to excellent yields. Furthermore, a manganese catalyzed, acid free, regioselective C2‐alkenylation of indoles with internal alkynes is described. The directing groups can be easily removed after the reaction and the resulting products can be used as valuable building blocks for the synthesis of diverse heterocyclic compounds.

  2. 2-(4-Methoxy-1H-indol-3-ylacetonitrile

    Directory of Open Access Journals (Sweden)

    Yong-Hong Lu

    2012-01-01

    Full Text Available In the title compound, C11H10N2O, the cyanide group is twisted away from the indole-ring plane [Ccy—Cme—Car—Car = 70.7 (2°; cy = cyanide, me = methylene, ar = aromatic], whereas the methoxy C atom is almost coplanar with the ring system [displacement = 0.014 (5 Å]. In the crystal, N—H...N hydrogen bonds link the molecules into C(7 chains propagating in [100].

  3. Evolution of endogenous analgesia

    NARCIS (Netherlands)

    Niesters, Marieke

    2014-01-01

    Endogenous pain modulation is a complex phenomenon involved in the perception of pain. It consists of top-down inhibitory and facilitatory pathways that originate at higher sites within the central nervous system and converge at dorsal horn neurons in the spinal cord, to modulate incoming afferent

  4. Unemployment and endogenous growth

    NARCIS (Netherlands)

    van Schaik, A.B.T.M.; de Groot, H.L.F.

    1995-01-01

    In this paper we develop a two-sector endogenous growth model with a dual labour market, based on efficiency wages. Growth is driven by intentional R&D performed in the high-tech and high-wage sector. It is examined how a change in rivalry among firms affects simultaneously growth and unemployment.

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

    Science.gov (United States)

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

    2017-02-01

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

  6. The electrochemical synthesis and corrosion behaviour of TiO2/poly(indole-co-aniline multilayer coating: Experimental and theoretical approach

    Directory of Open Access Journals (Sweden)

    Serap Toprak Döşlü

    2018-01-01

    Full Text Available The aim of this study was to protect stainless steel against corrosion via poly (indole-co-aniline with the help of titanium dioxide pre-coating. Different monomer ratios (1:1 and 1:9 were applied in order to determine the suitable chain composition to synthesize the copolymer in lithium perchlorate containing acetonitrile. The structures, morphologies, electrochemical properties and corrosion resistances of the mono and multi-layer coatings were investigated by Fourier-transform infrared spectra, scanning electron microscope, energy dispersive X-ray spectrometer, electrochemical impedance spectroscopy and anodic polarization. Furthermore the geometric structure and electronic properties of indole, aniline, and indole-co-aniline (dimmer molecules have been investigated by quantum calculations. The results indicated that corrosion protection of copolymers was increased via titanium dioxide pre-coating. The 1:1 copolymer coating showed better corrosion prevention than 1:9 coating. The correlation was determined between experimental and theoretical parameters.

  7. Hematopoietic stem cell transplantation for indolent lymphomas

    International Nuclear Information System (INIS)

    Izutsu, Koji

    2008-01-01

    Described are the review of the transplantation in the title (SCT), and the possible impact on its application and outcome of radio-immunotherapy (RIT) by new antibody drugs like ibritumomab tiuxetan (Ibr) and tositumomab (Tos), and of chemotherapy by purine analogs. Various regimens for the combination of auto-SCT, allo-SCT, chemotherapy and total body irradiation (TBI) have been used to treat the recurrent and progressive indolent lymphoma including follicular lymphoma (FL); however, their outcomes are still controversial. Introduction of new drugs like rituximab (Rit), Ibr and Tos has made it possible to extend the options of the regimen. For instance, in auto-SCT in FL, a high dose Rit therapy is used for in vivo purging to reduce tumor cell contamination of the graft instead of the exhausting, high-cost pretreatment for the in vitro purging with cyclophosphamide (CY)/TBI hitherto. In addition, RIT by Tos at the absorbed dose of 20-27 Gy in the critical organs with CY/VP16 combination is reportedly superior to CY/VP16/TBI. In allo-SCT where recurrence frequency is known low despite high mortality due to various complications, many regimens involving fludarabine/TBI have been also reported. Thus there has been neither clear standard for SCT in the lymphoma nor yet its prognosis after the therapy with new drugs described and the accumulation of their findings hereafter is important for future SCT application. (R.T.)

  8. Endogenous growth and the environment

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  9. Endogenous growth and environmental policy

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  10. Stable isotope labeling, in vivo, of D- and L-tryptophan pools in lemna gibba and the low incorporation of label into indole-3-acetic acid

    International Nuclear Information System (INIS)

    Baldi, B.G.; Maher, B.R.; Slovin, J.P.; Cohen, J.D.

    1991-01-01

    The authors present evidence that the role of tryptophan and other potential intermediates in the pathways that could lead to indole derivatives needs to be reexamined. Two lines of Lemna gibba were tested for uptake of [ 15 N-indole]-labeled tryptophan isomers and incorporation of that label into free indole-3-acetic acid (IAA). Both lines required levels of L-[ 15 N]tryptophan 2 to 3 orders of magnitude over endogenous levels in order to obtain measurable incorporation of label into IAA. Labeled L-tryptophan was extractable from plant tissue after feeding and showed no measurable isomerization into D-tryptophan. D-[ 15 N]trytophan supplied to Lemna at rates of approximately 400 times excess of endogenous D-tryptophan levels (to yield an isotopic enrichment equal to that which allowed detection of the incorporation of L-tryptophan into IAA), did not result in measurable incorporation of label into free IAA. These results demonstrate that L-tryptophan is a more direct precursor to IAA than the D isomer and suggest (a) that the availability of tryptophan in vivo is not a limiting factor in the biosynthesis of IAA, thus implying that other regulatory mechanisms are in operation and (b) that L-tryptophan also may not be a primary precursor to IAA in plants

  11. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  12. Exogenous vs. Endogenous Separation

    OpenAIRE

    Ramey, Garey

    2008-01-01

    This paper assesses how various approaches to modelling the separation margin a¤ect the ability of the Mortensen-Pissarides job matching model to explain key facts about the aggregate labor market. Allowing for realistic time variation in the separation rate, whether exogenous or endogenous, greatly in- creases the unemployment variability generated by the model. Speci…cations with exogenous separation rates, whether constant or time-varying, fail to pro- duce realistic volatility and prod...

  13. Indolent Systemic Mastocytosis – a Case Report

    Directory of Open Access Journals (Sweden)

    Vujanović Ljuba

    2017-09-01

    Full Text Available Indolent systemic mastocytosis is a benign form of systemic mastocytosis characterized by an abnormal proliferation of mast cells either in the bone marrow or in numerous tissues. Case Report: A 27-year-old female patient was admitted to our department due to urticaria which started a month ago. Before the skin changes appeared, our patient suffered from a toothache, so she took various painkillers (nimesulide, ibuprofen, acetylsalicylic acid, paracetamol. During skin examination, individual hyperpigmented macules on the trunk and lower limbs were observed as incidental findings. The patient reported having them for the last two years. Darier's sign was positive. Following the examination, she was admitted due to suspected urticaria pigmentosa. Laboratory Findings: erythrocyte sedimentation rate: 9 mm/h; complete blood count, urine, blood glucose, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, urea, creatinine, and uric acid were within normal ranges. Electrolytes: sodium, potassium, chlorine clearance, total calcium and calcium ionized, osteocalcin, and crosslaps were within normal ranges as well. Fibrinogen: 5.57 g/l; 5-Hydroxyindoleacetic acid: 49.8 umol/dU (10.4 - 31.2. Bone densitometry, chest x-ray and upper abdomen ultrasound findings were normal. The suspected clinical diagnosis of urticaria pigmentosa was confirmed by skin biopsy. Histopathological examination of the bone marrow showed moderately increased cellularity (60 - 70%. All three types of blood cells were slightly multiplied. Focal infiltrations were found in the perivascular area, consisting of elongated, oval cells with abundant eosinophilic granular cytoplasm. The nuclei were regular, oval shaped with finely granular chromatin and inconspicuous nucleoli. No nuclear atypia was found. These cells are highly CD117-positive. This finding strongly indicated bone marrow infiltration in systemic mastocytosis. The

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

    Science.gov (United States)

    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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Ashok eAiyar

    2014-06-01

    Full Text Available 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-dioxygenase, 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

  17. The Endogenous Feedback Network

    DEFF Research Database (Denmark)

    Augustenborg, Claudia Carrara

    2010-01-01

    proposals, it will first be considered the extents of their reciprocal compatibility, tentatively shaping an integrated, theoretical profile of consciousness. A new theory, the Endogenous Feedback Network (EFN) will consequently be introduced which, beside being able to accommodate the main tenets...... of the reviewed theories, appears able to compensate for the explanatory gaps they leave behind. The EFN proposes consciousness as the phenomenon emerging from a distinct network of neural paths broadcasting the neural changes associated to any mental process. It additionally argues for the need to include a 5th...

  18. Hume and Endogenous Money

    OpenAIRE

    Maria Pia Paganelli

    2006-01-01

    David Hume’s monetary theory has three standard yet inconsistent readings. As a forefather of the quantity theory of money, Hume sees money as neutral. As an inflationist, Hume sees an active positive role for monetary policy. As a monetarist, Hume sees an active positive role for monetary policy only in the short run. This paper reads Hume consistently instead by showing that for Hume money is endogenous and demand-driven. Hume would read the money equation in terms of reverse causation and ...

  19. New zwitterionic monoterpene indole alkaloids from Uncaria rhynchophylla.

    Science.gov (United States)

    Guo, Qiang; Yang, Hongshuai; Liu, Xinyu; Si, Xiali; Liang, Hong; Tu, Pengfei; Zhang, Qingying

    2018-01-31

    Four new zwitterionic monoterpene indole alkaloids, rhynchophyllioniums A-D (1-4), together with eight known alkaloids (5-12), were isolated from the hook-bearing stems of Uncaria rhynchophylla. Their structures were elucidated by extensive spectroscopic data analysis of MS, 1D and 2D NMR, and ECD, and the zwitterionic forms and absolute configurations of 1 and 2 were unambiguously confirmed by single crystal X-ray diffraction analysis. All the isolates, including the monoterpene indole alkaloids with free C-22 carboxyl group and those with C-22 carboxyl methyl ester, were proved to be naturally coexisting in the herb by LC-MS analysis. This is the first report of monoterpene indole alkaloids that exist in the form of zwitterion. Additionally, the cytotoxic activities of all isolates against A549, HepG2, and MCF-7 cell lines are reported. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Responses of membrane lipid peroxidation and endogenous hormones of soybean seedlings to UV-B radiation and rare earth

    International Nuclear Information System (INIS)

    Yan Shengrong; Yang Chunhe; Zhang Yuequn

    2009-01-01

    [Objective] The aim was to provide strategies for development of rare earth and control of environmental pollution. [Method] Responses of membrane lipid peroxidation and endogenous hormones of soybean seedlings to UV-B radiation and rare earth were studied through hydroponics in laboratory. [Result] The results showed that under irradiation of UV-B(T1-0.15 W/m2 and T2-0.45 W/m2), chlorophyll and indole-3-acetic acid(IAA) contents firstly decreased during the stress phase (1-5d) and then increased during the restoration phase (6-9d) while contents of malonadialdehyde(MDA) and abscisic acid(ABA) gradually increased during the imposition of UV-B radiation (1-5d) and subsequently decreased during recovery from UV-B stress (6-9d) . With adding of La (Ⅲ) with the concentration of 20mg•L-1, the decline/rise trend of chlorophyll, IAA, MDA and ABA contents was slowed down during the stress period while the rise/decline speed was accelerated during the recovery period. [Conclusion] It suggests that the regulation of La (Ⅲ) on membrane lipid peroxidation and endogenous hormones could increase chlorophyll and IAA contents, improve the metabolism of reactive oxygen species (ROS), inhibit membrane lipid peroxidation, decrease the accumulation amount of ABA and alleviate injury of UV-B radiation to soybean seedlings. Further, the protective potential of La (Ⅲ) was better under low UV-B radiation than under high one

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

    OpenAIRE

    Shimshoni, JA; Winkler, I; Golan, E; Nutt, D

    2016-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-...

  2. Combining Semi-Endogenous and Fully Endogenous Growth: a Generalization.

    OpenAIRE

    Cozzi, Guido

    2017-01-01

    This paper shows that combining the semi-endogenous and the fully endogenous growth mechanisms with a general CES aggregator, either growth process can prevail in the balanced growth path depending on their degree of complementarity/substitutability. Policy-induced long-run economic switches to the fully endogenous steady state as the R&D employment ratio surpasses a positive threshold are possible if the two growth engines are gross substitutes.

  3. Small molecule n-(alpha-peroxy) indole compounds and methods of use

    KAUST Repository

    Wang, Xinbo; Lai, Zhiping; Pan, Yupeng; Huang, Kuo-Wei; Wang, Zhigang

    2017-01-01

    The invention relates to novel N-(α-peroxy)indole compounds of Formula I and methods for use. (I) The N-(α-peroxy)indole compounds described herein are useful for treating or preventing parasitic infections, bacterial infections, and cancer in subjects. The methods include administering an N-(α-peroxy)indole compound as described herein to a subject. Also described herein are methods for synthesizing N-(α-peroxy )indole compounds.

  4. Small molecule n-(alpha-peroxy) indole compounds and methods of use

    KAUST Repository

    Wang, Xinbo

    2017-11-16

    The invention relates to novel N-(α-peroxy)indole compounds of Formula I and methods for use. (I) The N-(α-peroxy)indole compounds described herein are useful for treating or preventing parasitic infections, bacterial infections, and cancer in subjects. The methods include administering an N-(α-peroxy)indole compound as described herein to a subject. Also described herein are methods for synthesizing N-(α-peroxy )indole compounds.

  5. Synthesis of quinolino[2 ,3 :8,7]cyclooct[ b]indole

    Indian Academy of Sciences (India)

    Among the nitrogen heterocycles, indole is an impor- tant structural components in alkaloids and many phar- maceutical agents. Indole exhibits a high degree of biological activities including antifungal, antibacterial, antitumour, anti-HIV and DNA interactions. Substi- tuted indoles have been referred to as 'privileged struc-.

  6. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    OpenAIRE

    Rachma, Meutia Safrina

    2011-01-01

    There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

  7. Endogeneity Of Indonesian Money Supply

    OpenAIRE

    Rachma, Meutia Safrina

    2010-01-01

    There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

  8. Habits, aspirations and endogenous fertility

    OpenAIRE

    Luciano Fanti

    2012-01-01

    Motivated by the increasing literature on endogenous preferences as well as on endogenous fertility, this paper investigates the implications of the interaction of the endogenous determination of the number of children with habit and aspiration formation in an OLG model. In contrast with the previous literature, we show that greater aspirations may lead to higher savings, and more interestingly, always increase the neoclassical economic growth.

  9. Endogenous Monetary Policy Regime Change

    OpenAIRE

    Troy Davig; Eric M. Leeper

    2006-01-01

    This paper makes changes in monetary policy rules (or regimes) endogenous. Changes are triggered when certain endogenous variables cross specified thresholds. Rational expectations equilibria are examined in three models of threshold switching to illustrate that (i) expectations formation effects generated by the possibility of regime change can be quantitatively important; (ii) symmetric shocks can have asymmetric effects; (iii) endogenous switching is a natural way to formally model preempt...

  10. Endogenous property rights

    NARCIS (Netherlands)

    Dari-Mattiacci, G.; Guerriero, C.

    2014-01-01

    Albeit the relevance of property rights is well known, their determinants are still poorly understood. When property is fully protected, some buyers with valuation higher than that of original owners are inefficiently excluded from trade due to transaction costs. When protection of property is weak,

  11. Endogenous Lunar Volatiles

    Science.gov (United States)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Boyce, J. W.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Magna, T.; Ni, P.; Tartese, R.; hide

    2017-01-01

    The chapter will begin with an introduction that defines magmatic volatiles (e.g., H, F, Cl, S) versus geochemical volatiles (e.g., K, Rb, Zn). We will discuss our approach of understanding both types of volatiles in lunar samples and lay the ground work for how we will determine the overall volatile budget of the Moon. We will then discuss the importance of endogenous volatiles in shaping the "Newer Views of the Moon", specifically how endogenous volatiles feed forward into processes such as the origin of the Moon, magmatic differentiation, volcanism, and secondary processes during surface and crustal interactions. After the introduction, we will include a re-view/synthesis on the current state of 1) apatite compositions (volatile abundances and isotopic compositions); 2) nominally anhydrous mineral phases (moderately to highly volatile); 3) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar pyroclastic glass beads; 4) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar basalts; 5) volatile (moderately to highly volatile) abundances in and isotopic compositions of melt inclusions; and finally 6) experimental constraints on mineral-melt partitioning of moderately to highly volatile elements under lunar conditions. We anticipate that each section will summarize results since 2007 and focus on new results published since the 2015 Am Min review paper on lunar volatiles [9]. The next section will discuss how to use sample abundances of volatiles to understand the source region and potential caveats in estimating source abundances of volatiles. The following section will include our best estimates of volatile abundances and isotopic compositions (where permitted by available data) for each volatile element of interest in a number of important lunar reservoirs, including the crust, mantle, KREEP, and bulk Moon. The final section of the chapter will focus upon future work, outstanding questions

  12. Transformation of indole and quinoline by Desulfobacterium indolicum (DSM 3383)

    DEFF Research Database (Denmark)

    Licht, D.; Johansen, S.S.; Arvin, E.

    1996-01-01

    kinetics. The kinetic parameters for indole were an apparent maximum specific transformation rate (V-Amax) of 263 mu mol mg total protein(-1) day(-1) and an apparent half-saturation constant (K-Am) of 139 mu M. The V-Amax for quinoline was 170 mu mol mg total protein(-1) day(-1) and K-Am was 92 mu M...

  13. Prognostic Assessment in Patients with Indolent B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Luca Arcaini

    2012-01-01

    Full Text Available Follicular lymphoma (FL is an indolent lymphoma with long median survival. Many studies have been performed to build up prognostic scores potentially useful to identify patients with poorer outcome. In 2004, an international consortium coordinated by the International Follicular Lymphoma Prognostic Factor project was established and a new prognostic study was launched (FLIPI2 using progression-free survival (PFS as main endpoint and integrating all the modern parameters prospectively collected. Low-grade non-Hodgkin lymphomas were once considered as a heterogenous group of lymphomas characterized by an indolent clinical course. Each entity is characterized by unique clinicobiologic features. Some studies have been focused on prognostic factors in single lymphoma subtypes, with the development of specific-entity scores based on retrospective series, for instance splenic marginal zone lymphoma (SMZL. A widely accepted prognostic tool for clinical usage for indolent non-follicular B-cell lymphomas is largely awaited. In this paper we summarized the current evidence regarding prognostic assessment of indolent follicular and non-follicular lymphomas.

  14. Transcriptional profiling of three key genes of terpenoid indole ...

    African Journals Online (AJOL)

    SAM

    2014-03-19

    Mar 19, 2014 ... indole alkaloid pathway in Catharanthus roseus under different tissue culture .... R 5'-GCA GCA GAC ACT CAA AAT CTC CTC C-3'. 62. CYP72A1 ... generated using both the software programs, and Microsoft Excel. The ΔΔCT ...

  15. 1H-indol-3-yl-methyl

    African Journals Online (AJOL)

    Methods: 2-(1H-indol-3-yl)acetic acid (1) was reacted with absolute ethanol and catalytic amount of ... dehydration in the same pot with CBr4 and Ph3P. [6]. ... and used after distillation. ... distilled water or by solvent extraction depending.

  16. Indole alkaloids from Rauvolfia bahiensis A.DC. (Apocynaceae).

    Science.gov (United States)

    Kato, Lucilia; Marques Braga, Raquel; Koch, Ingrid; Sumiko Kinoshita, Luiza

    2002-06-01

    Four indole alkaloids, 12-methoxy-N(a)-methyl-vellosimine, demethoxypurpeline, 12-methoxyaffinisine, and 12-methoxy-vellosimine, in addition to picrinine, vinorine, raucaffrinoline, normacusine B, norseredamine, seredamine, 10-methoxynormacusine B, norpurpeline and purpeline, were isolated from the bark or leaf extracts of Rauvolfia bahiensis.

  17. Rauvotetraphyllines A-E, new indole alkaloids from Rauvolfia tetraphylla

    OpenAIRE

    Gao, Yuan; Zhou, Dong-Sheng; Kong, Ling-Mei; Hai, Ping; Li, Yan; Wang, Fei; Liu, Ji-Kai

    2012-01-01

    Five new indole alkaloids rauvotetraphyllines A–E (1–5), together with eight known analogues, were isolated from the aerial parts of Rauvolfia tetraphylla. The structures were established by means of spectroscopic methods. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s13659-012-0012-5 and is accessible for authorized users.

  18. Biooxidation of indole and characteristics of the responsible enzymes

    African Journals Online (AJOL)

    Indole, an electron-rich N-aromatic heterocyclic organic compound, functions as a popular component of fragrances, indicator of some diseases and signal molecule in plant, animal and microorganism, respectively. It also serves as the precursor, core building block and functional group of many important biochemical ...

  19. Characterization of indole acetic acid endophyte producers in ...

    African Journals Online (AJOL)

    This work contributes to the knowledge of the phytobacteria diversity in aquatic plants, particularly in Lemnaceae species; here the majority of the isolates have been characterized as higher indole acetic acid producers, recommended as candidates for their use as biofertilizers. Key words: Plant growth-promoting bacteria, ...

  20. 2-(7-Methyl-1H-indol-3-ylacetonitrile

    Directory of Open Access Journals (Sweden)

    Yu-Hua Ge

    2012-01-01

    Full Text Available In the title compound, C11H10N2, the carbonitrile group is twisted away from the indole plane [Ccy—Cme—Car—Car = 66.6 (2°; cy = cyanide, me = methylene and ar = aromatic]. In the crystal, N—H...N hydrogen bonds link the molecules into C(7 chains propagating in the [001] direction.

  1. Endogenous fertility and development traps with endogenous lifetime

    OpenAIRE

    Fanti, Luciano; Gori, Luca

    2010-01-01

    We extend the literature on endogenous lifetime and economic growth by Chakraborty (2004) and Bunzel and Qiao (2005) to endogenous fertility. We show that development traps due to underinvestments in health cannot appear when fertility is an economic decision variable and the costs of children are represented by a constant fraction of the parents' income used for their upbringing.

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

    Directory of Open Access Journals (Sweden)

    Mohammed Mujahid

    Full Text Available 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.

  3. Effects of gamma-irradiation on elongation and indole-3-acetic acid level of maize (Zea mays) coleoptiles

    International Nuclear Information System (INIS)

    Momiyama, M.; Koshiba, T.; Furukawa, K.; Kamiya, Y.; Sato, M.

    1999-01-01

    The effects of gamma-irradiation on elongation and the level of indole-3-acetic acid (IAA) of maize (Zea mays) coleoptiles were investigated. When 3-day-old seedlings of maize were exposed to gamma-radiation lower than 1 kGy, a temporal retardation of coleoptile elongation was induced. This retardation was at least partly ascribed to a temporal decrease in the amount of free IAA in coleoptile tips on the basis of the following facts: (1) the reactivity to IAA of the elongating coleoptile cells was not altered by irradiation; (2) endogenous IAA level in the tip of irradiated coleoptiles was at first unchanged, but then declined before returning to nearly the same level as that of the non-irradiated control; and (3) the amount of IAA that diffused from coleoptile tip sections showed a similar pattern to that of endogenous IAA. The rate of conversion between free and conjugated IAA was not significantly affected by irradiation. These results suggest that a temporal inhibition of maize coleoptile elongation induced by gamma-irradiation can be ascribed to the reduction of endogenous IAA level in the coleoptile tip, and this may originate from the modulation in the rate of IAA biosynthesis or catabolism. (author)

  4. Indole-3-butyric acid promotes adventitious rooting in Arabidopsis thaliana thin cell layers by conversion into indole-3-acetic acid and stimulation of anthranilate synthase activity.

    Science.gov (United States)

    Fattorini, L; Veloccia, A; Della Rovere, F; D'Angeli, S; Falasca, G; Altamura, M M

    2017-07-11

    Indole-3-acetic acid (IAA), and its precursor indole-3-butyric acid (IBA), control adventitious root (AR) formation in planta. Adventitious roots are also crucial for propagation via cuttings. However, IBA role(s) is/are still far to be elucidated. In Arabidopsis thaliana stem cuttings, 10 μM IBA is more AR-inductive than 10 μM IAA, and, in thin cell layers (TCLs), IBA induces ARs when combined with 0.1 μM kinetin (Kin). It is unknown whether arabidopsis TCLs produce ARs under IBA alone (10 μM) or IAA alone (10 μM), and whether they contain endogenous IAA/IBA at culture onset, possibly interfering with the exogenous IBA/IAA input. Moreover, it is unknown whether an IBA-to-IAA conversion is active in TCLs, and positively affects AR formation, possibly through the activity of the nitric oxide (NO) deriving from the conversion process. Revealed undetectable levels of both auxins at culture onset, showing that arabidopsis TCLs were optimal for investigating AR-formation under the total control of exogenous auxins. The AR-response of TCLs from various ecotypes, transgenic lines and knockout mutants was analyzed under different treatments. It was shown that ARs are better induced by IBA than IAA and IBA + Kin. IBA induced IAA-efflux (PIN1) and IAA-influx (AUX1/LAX3) genes, IAA-influx carriers activities, and expression of ANTHRANILATE SYNTHASE -alpha1 (ASA1), a gene involved in IAA-biosynthesis. ASA1 and ANTHRANILATE SYNTHASE -beta1 (ASB1), the other subunit of the same enzyme, positively affected AR-formation in the presence of exogenous IBA, because the AR-response in the TCLs of their mutant wei2wei7 was highly reduced. The AR-response of IBA-treated TCLs from ech2ibr10 mutant, blocked into IBA-to-IAA-conversion, was also strongly reduced. Nitric oxide, an IAA downstream signal and a by-product of IBA-to-IAA conversion, was early detected in IAA- and IBA-treated TCLs, but at higher levels in the latter explants. Altogether, results showed that IBA induced

  5. The effects of isatin (indole-2, 3-dione on pituitary adenylate cyclase-activating polypeptide-induced hyperthermia in rats

    Directory of Open Access Journals (Sweden)

    Tóth Gábor

    2002-02-01

    Full Text Available Abstract Background Previous studies have demonstrated that centrally administered natriuretic peptides and pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38 have hyperthermic properties. Isatin (indole-2, 3-dione is an endogenous indole that has previously been found to inhibit hyperthermic effects of natriuretic peptides. In this study the aim was to investigate the effects of isatin on thermoregulatory actions of PACAP-38, in rats. Results One μg intracerebroventricular (icv. injection of PACAP-38 had hyperthermic effect in male, Wistar rats, with an onset of the effect at 2 h and a decline by the 6th h after administration. Intraperitoneal (ip. injection of different doses of isatin (25-50 mg/kg significantly decreased the hyperthermic effect of 1 μg PACAP-38 (icv., whereas 12.5 mg/kg isatin (ip. had no inhibiting effect. Isatin alone did not modify the body temperature of the animals. Conclusion The mechanisms that participate in the mediation of the PACAP-38-induced hyperthermia may be modified by isatin. The capability of isatin to antagonize the hyperthermia induced by all members of the natriuretic peptide family and by PACAP-38 makes it unlikely to be acting directly on receptors for natriuretic peptides or on those for PACAP in these hyperthermic processes.

  6. Unveiling the biotransformation mechanism of indole in a Cupriavidus sp. strain.

    Science.gov (United States)

    Qu, Yuanyuan; Ma, Qiao; Liu, Ziyan; Wang, Weiwei; Tang, Hongzhi; Zhou, Jiti; Xu, Ping

    2017-12-01

    Indole, an important signaling molecule as well as a typical N-heterocyclic aromatic pollutant, is widespread in nature. However, the biotransformation mechanisms of indole are still poorly studied. Here, we sought to unlock the genetic determinants of indole biotransformation in strain Cupriavidus sp. SHE based on genomics, proteomics and functional studies. A total of 177 proteins were notably altered (118 up- and 59 downregulated) in cells grown in indole mineral salt medium when compared with that in sodium citrate medium. RT-qPCR and gene knockout assays demonstrated that an indole oxygenase gene cluster was responsible for the indole upstream metabolism. A functional indole oxygenase, termed IndA, was identified in the cluster, and its catalytic efficiency was higher than those of previously reported indole oxidation enzymes. Furthermore, the indole downstream metabolism was found to proceed via the atypical CoA-thioester pathway rather than conventional gentisate and salicylate pathways. This unusual pathway was catalyzed by a conserved 2-aminobenzoyl-CoA gene cluster, among which the 2-aminobenzoyl-CoA ligase initiated anthranilate transformation. This study unveils the genetic determinants of indole biotransformation and will provide new insights into our understanding of indole biodegradation in natural environments and its functional studies. © 2017 John Wiley & Sons Ltd.

  7. Biodegradation of indole at high concentration by persolvent fermentation with Pseudomonas sp. ST-200.

    Science.gov (United States)

    Doukyu, N; Aono, R

    1997-05-01

    Pseudomonas sp. strain ST-200 grew on indole as a sole carbon source. The minimal inhibitory concentration of indole was 0.3 mg/ml for ST-200. However, ST-200 grew in a persolvent fermentation system containing a large amount of indole (a medium containing 20% by vol. diphenylmethane and 4 mg/ml indole), because most of the indole was partitioned in the organic solvent layer. When the organism was grown in the medium containing indole at 1 mg/ml in the presence of diphenylmethane, more than 98% of the indole was consumed after 48h. Isatic acid (0.4 mg/ml) and isatin (0.03 mg/ml) were produced as the metabolites in the aqueous medium layer.

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

    Science.gov (United States)

    Chadha, Navriti; Silakari, Om

    2017-07-07

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

  9. Protective

    Directory of Open Access Journals (Sweden)

    Wessam M. Abdel-Wahab

    2013-10-01

    Full Text Available Many active ingredients extracted from herbal and medicinal plants are extensively studied for their beneficial effects. Antioxidant activity and free radical scavenging properties of thymoquinone (TQ have been reported. The present study evaluated the possible protective effects of TQ against the toxicity and oxidative stress of sodium fluoride (NaF in the liver of rats. Rats were divided into four groups, the first group served as the control group and was administered distilled water whereas the NaF group received NaF orally at a dose of 10 mg/kg for 4 weeks, TQ group was administered TQ orally at a dose of 10 mg/kg for 5 weeks, and the NaF-TQ group was first given TQ for 1 week and was secondly administered 10 mg/kg/day NaF in association with 10 mg/kg TQ for 4 weeks. Rats intoxicated with NaF showed a significant increase in lipid peroxidation whereas the level of reduced glutathione (GSH and the activity of superoxide dismutase (SOD, catalase (CAT, glutathione S-transferase (GST and glutathione peroxidase (GPx were reduced in hepatic tissues. The proper functioning of the liver was also disrupted as indicated by alterations in the measured liver function indices and biochemical parameters. TQ supplementation counteracted the NaF-induced hepatotoxicity probably due to its strong antioxidant activity. In conclusion, the results obtained clearly indicated the role of oxidative stress in the induction of NaF toxicity and suggested hepatoprotective effects of TQ against the toxicity of fluoride compounds.

  10. The TosMIC approach to 3-(oxazol-5-yl) indoles: application to the synthesis of indole-based IMPDH inhibitors.

    Science.gov (United States)

    Dhar, T G Murali; Shen, Zhongqi; Fleener, Catherine A; Rouleau, Katherine A; Barrish, Joel C; Hollenbaugh, Diane L; Iwanowicz, Edwin J

    2002-11-18

    A modified approach to the synthesis of 3-(oxazolyl-5-yl) indoles is reported. This method was applied to the synthesis of series of novel indole based inhibitors of inosine monophosphate dehydrogenase (IMPDH). The synthesis and the structure-activity relationships (SARs), derived from in vitro studies, for this new series of inhibitors is given.

  11. Terbium(III) ions as sensitizers of oxidation of indole and its derivatives in Fenton system

    Energy Technology Data Exchange (ETDEWEB)

    Kaczmarek, Małgorzata, E-mail: mkaczmar@amu.edu.pl; Staninski, Krzysztof

    2017-03-15

    Oxidation of indole and its derivatives in the Fenton system as a source of oxidising agents, in the presence of terbium(III) ions was studied by chemiluminescence methods to get the kinetic curves of emission decay and spectral distributions of chemiluminescence. Terbium(III) ions acted as a sensitizer of the mixtures Tb(III)-Fe(II)/Fe(III)-H{sub 2}O{sub 2}-indole or its derivative (tryptophan, tryptamine, indole-3-acetic acid and indole-3-acetyl aspartic acid). For the above indolic compounds, linear dependencies of integrated intensity of chemiluminescence on concentration of indolic compound in water and in water-acetonitrile solution were obtained. The limits of detection (LOD) and quantification (LOQ) of the indolic compounds studied were found to be by one or two orders of magnitude lower in the system with terbium(III) ions than without them. - Highlights: • Chemiluminescence emitted on oxidation of indolic compounds in Fenton system. • Tb (III) ions as sensitizers of indolic compounds oxidation in solutions. • Linear relations between CL intensity and indolic compound concentration.

  12. Degradation of N-heterocyclic indole by a novel endophytic fungus Phomopsis liquidambari.

    Science.gov (United States)

    Chen, Yan; Xie, Xing-Guang; Ren, Cheng-Gang; Dai, Chuan-Chao

    2013-02-01

    A broad-spectrum endophytic Phomopsis liquidambari, was used to degrade environmental pollutant indole. In the condition of using indole as sole carbon and nitrogen source, the optimum concentration of indole supplied was determined to be 100 mg L(-1), with 41.7% ratio of indole degradation within 120 h. Exogenous addition of plant litter significantly increased indole degradation to 99.1% within 60 h. Indole oxidation to oxindole and isatin were the key steps limiting indole degradation. Plant litter addition induced fungus to produce laccase and LiP to non-specific oxidize indole. The results of fungal metabolites pathway through HPLC-MS and NMR analysis showed that indole was firstly oxidized to oxindole and isatin, and deoxidated to indolenie-2-dione, then hydroxylated to 2-dioxindole, which pyridine ring were cleaved through C-N position and changed to 2-aminobenzoic acid. Such metabolic pathway was similar with bacterial degradation of indole-3-acetic acid in plant. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. 1-Propyl-1H-indole-2,3-dione

    Directory of Open Access Journals (Sweden)

    Fatima Zahrae Qachchachi

    2016-04-01

    Full Text Available In the title compound, C11H11NO2, the 1H-indole-2,3-dione unit is essentially planar, with an r.m.s. deviation of 0.0387 (13 Å. This plane makes a dihedral angle of 72.19 (17° with the plane of the propyl substituent. In the crystal, chains propagating along the b axis are formed through C—H...O hydrogen bonds.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    OpenAIRE

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

    2015-01-01

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

  16. Tetracyclic indole alkaloids with antinematode activity from Uncaria rhynchophylla.

    Science.gov (United States)

    Kong, Fandong; Ma, Qingyun; Huang, Shengzhuo; Yang, Shuang; Fu, Linran; Zhou, Liman; Dai, Haofu; Yu, Zhifang; Zhao, Youxing

    2017-06-01

    A new tetracyclic indole alkaloid, 17-O-methyl-3,4,5,6-tetradehydrogeissoschizine, together with seven known ones, were isolated from the aerial part of Uncaria rhynchophylla. Their structures were unambiguously elucidated by spectroscopic methods and comparing with the literature data. Among them, compounds 1, 3, 4 and 6-8 showed potent to moderate antinematode activities against Panagrellus redivevus at a concentration of 250 μg/mL.

  17. Endogenous 5-methylcytosine protects neighboring guanines from N7 and O6-methylation and O6-pyridyloxobutylation by the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

    Science.gov (United States)

    Ziegel, Rebecca; Shallop, Anthony; Upadhyaya, Pramod; Jones, Roger; Tretyakova, Natalia

    2004-01-20

    All CG dinucleotides along exons 5-8 of the p53 tumor suppressor gene contain endogenous 5-methylcytosine (MeC). These same sites (e.g., codons 157, 158, 245, 248, and 273) are mutational hot spots in smoking-induced lung cancer. Several groups used the UvrABC endonuclease incision assay to demonstrate that methylated CG dinucleotides of the p53 gene are the preferred binding sites for the diol epoxides of bay region polycyclic aromatic hydrocarbons (PAH). In contrast, effects of endogenous cytosine methylation on the distribution of DNA lesions induced by tobacco-specific nitrosamines, e.g., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), have not been elucidated. In the work presented here, a stable isotope labeling HPLC-ESI-MS/MS approach was employed to analyze the reactivity of the N7 and O6 positions of guanines within hemimethylated and fully methylated CG dinucleotides toward NNK-derived methylating and pyridyloxobutylating species. 15N3-labeled guanine bases were placed within synthetic DNA sequences representing endogenously methylated p53 codons 154, 157, and 248, followed by treatment with acetylated precursors to NNK diazohydroxides. HPLC-ESI-MS/MS analysis was used to determine the relative yields of N7- and O6-guanine adducts at the 15N3-labeled position. In all cases, the presence of MeC inhibited the formation of N7-methylguanine, O6-methylguanine, and O6-pyridyloxobutylguanine at a neighboring G, with the greatest decrease observed in fully methylated dinucleotides and at guanines preceded by MeC. Furthermore, the O6-Me-dG/N7-Me-G molar ratios were decreased in the presence of the 5'-neighboring MeC, suggesting that the observed decline in O6-alkylguanine adduct yields is, at least partially, a result of an altered reactivity pattern in methylated CG dinucleotides. These results indicate that, unlike N2-guanine adducts of PAH diol epoxides, NNK-induced N7- and O6-alkylguanine adducts are not preferentially formed at the endogenously

  18. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    Directory of Open Access Journals (Sweden)

    Meutia Safrina Rachma

    2011-09-01

    Full Text Available There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5-2010(6, the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not have control power on money supply. The bank is only able to maintain the stability and control the movement of broad money supply. Keywords: Endogenous variable, money supply, vector autoregressionJEL classification numbers: E51, E52, E58

  19. 59 eyes with endogenous endophthalmitis

    DEFF Research Database (Denmark)

    Bjerrum, Søren Solborg; la Cour, Morten

    2017-01-01

    BACKGROUND: To study the epidemiology of patients with endogenous endophthalmitis in Denmark. MATERIAL AND METHODS: Retrospective and prospective case series of 59 eyes in patients with endogenous endophthalmitis in Denmark between 2000 and 2016. RESULTS: The age of the patients ranged from 28 to......, the visual outcome and the mortality of the patients. The epidemiology of the disease is very different in Scandinavia compared to Asia. The visual prognosis remains grave and the majority of the eyes lose useful vision....

  20. Diversification of indoles via microwave-assisted ligand-free copper-catalyzed N-arylation

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jae Kwan; Lee, Jin Hee; Kim, Tae Sung; Yum, Eul Kgun [Dept. of Chemistry, Chu ngnam National University, Daejon (Korea, Republic of); Park, Jee Jung [Western Seoul Center Korea Basic Science Institute, Seoul (Korea, Republic of)

    2016-12-15

    A simple, efficient Cu{sub 2}O catalyst system under microwave irradiation was developed for N-arylation of various indoles without ligands and additives. Diverse N-heteroarylated indoles were prepared by coupling indoles with various heteroaryl halides within 1 h. The selective reactivity of bromoindole with aryl iodide provided N-aryl bromoindoles, which could be useful intermediates for palladium-catalyzed Heck and Suzuki coupling reactions.

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

    Science.gov (United States)

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

    2015-01-28

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

  2. Síndrome alucinógeno, indoles alucinógenos

    OpenAIRE

    Serés García, L.

    2016-01-01

    Hallucinogenic syndrome and hallucinogenic indoles This work summarizes the information about the hallucinogenic mushrooms: history, active components, toxicity, clinical studies, diagnosis, treatment and legal aspects.

  3. A turn-on indole-based sensor for hydrogen sulfate ion.

    Science.gov (United States)

    Wan, Chin-Feng; Yang, Shih-Tse; Lin, Hsiang-Yi; Chang, Ya-Ju; Wu, An-Tai

    2014-08-01

    A simple indole-based receptor 1 was prepared by a simple Schiff-base reaction of 1H-indole-3-carbaldehyde with ethane 1,2-diamine and its fluoroionophoric properties toward anions were investigated. Indole-based receptor 1 acts as a selective turn-on fluorescent sensor for HSO4(-) in methanol among a series of tested anions. Fluorescence spectroscopy, ultraviolet and nuclear magnetic resonance imaging support that the HSO4(-) indeed interacted with imine nitrogen and the proton of nitrogen in indole ring. Copyright © 2013 John Wiley & Sons, Ltd.

  4. Determinación espectrofluorimétrica de fitohormonas derivadas del indol y del naftaleno

    OpenAIRE

    Blanc García, María del Rosario

    2014-01-01

    Se realiza el estudio de las propiedades fluorescentes y la puesta a punto de metodología espectrofluorimétrica en disolución y en fase sólida para la determinación en aguas, suelos y formulaciones comerciales de las fitohormonas derivadas del indol: acido indol-3-acetico. acido indol-3-butirico, acido indol-3-propinoico y acido 5-hidroxiindol-3-acetico; y del naftaleno: acido 1-naftilacetico y 1-naftilacetamida. se lleva a cabo la determinación individual de cada una de las fitohormonas as...

  5. Simple syntheses of 3-substituted indoles and their application for high yield 14C-labelling

    International Nuclear Information System (INIS)

    Schallenberg, J.; Meyer, E.

    1983-01-01

    Methods are described which allow the synthesis of several plant indole alkaloids and their metabolites at different scales. Compounds synthesized include gramine (1) (3-dimethylaminomethylindole) which is directly derived from indole, while its biosynthetic precursors 3-aminomethylindole (3) and 3-methylaminomethylindole (2) as well as indole3-carboxylic acid (7) are synthesized via indole-3-aldehyde (6). Slight changes of the experimental conditions allow syntheses with high yields not only at the molar but also at the μmolar level. This is extremely useful when isotope labelled compounds of high specific radioactivity are required for studies of plant metabolism. (orig.)

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

    Science.gov (United States)

    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. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

  7. Further comparisons of endogenous pyrogens and leukocytic endogenous mediators.

    Science.gov (United States)

    Kampschmidt, R F; Upchurch, H F; Worthington, M L

    1983-07-01

    It was recently shown (Murphy et al., Infect. Immun. 34:177-183), that rabbit macrophages produce two biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a molecular weight of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16-h rabbit peritoneal exudates. These acute peritoneal exudates were produced by the intraperitoneal injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37 degrees C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats, or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma iron and zinc levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with isoelectric points between 4.5 and 5.0. These proteins are produced by macrophages in the lung, liver, or in chronic peritoneal exudates. In these experiments, the lower-isoelectric-point endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens were found to have leukocytic endogenous mediator activity in mice but to be completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma iron, increased blood neutrophils, but failed to elevate plasma fibrinogen.

  8. The endogenous hallucinogen and trace amine N,N-dimethyltryptamine (DMT displays potent protective effects against hypoxia via sigma-1 receptor activation in human primary iPSC-derived cortical neurons and microglia-like immune cells

    Directory of Open Access Journals (Sweden)

    Attila Szabo

    2016-09-01

    Full Text Available N,N-dimethyltryptamine (DMT is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R, an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, and in monocyte-derived macrophages and dendritic cells. Here we report that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2 through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1 suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

  9. The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells.

    Science.gov (United States)

    Szabo, Attila; Kovacs, Attila; Riba, Jordi; Djurovic, Srdjan; Rajnavolgyi, Eva; Frecska, Ede

    2016-01-01

    N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

  10. Mild one-pot Horner-Wadsworth-Emmons olefination and intramolecular N-arylation for the syntheses of indoles, all regio-isomeric azaindoles, and thienopyrroles.

    Science.gov (United States)

    Choi, Ji Hye; Lim, Hwan Jung

    2015-05-14

    The syntheses of various N-protected aromatic-ring fused pyrrole-2-carboxylate derivatives have been accomplished using mild one-pot Horner-Wadsworth-Emmons olefination and Cu-catalyzed intramolecular N-arylation reactions. The optimized mild one-pot reaction conditions of various 2-bromo arylcarboxaldehydes with commercially available N-protected phosphonoglycine trimethylesters gave the desired aromatic-ring fused pyrrole-2-carboxylates, such as substituted indole-, all regio-isomeric azaindole-, and thienopyrrole-2-carboxylates, in good to excellent yields. These conditions showed broad substrate compatibility, without the loss of the protecting group.

  11. Indole alkaloids and other constituents of Rauwolfia serpentina.

    Science.gov (United States)

    Itoh, Atsuko; Kumashiro, Tomoko; Yamaguchi, Machiko; Nagakura, Naotaka; Mizushina, Yoshiyuki; Nishi, Toyoyuki; Tanahashi, Takao

    2005-06-01

    From the dried roots of Rauwolfia serpentina were isolated five new indole alkaloids, N(b)-methylajmaline (1), N(b)-methylisoajmaline (2), 3-hydroxysarpagine (3), yohimbinic acid (4), isorauhimbinic acid (5), a new iridoid glucoside, 7-epiloganin (6), and a new sucrose derivative, 6'-O-(3,4,5-trimethoxybenzoyl)glomeratose A (7), together with 20 known compounds. The structures of the new compounds were determined by spectroscopic and chemical means. The inhibitory activities of the selected alkaloids on topoisomerase I and II and their cytotoxicity against the human promyelocytic leukemia (HL-60) cell lines were assessed.

  12. Five new indole alkaloids from the leaves of Rauvolfia yunnanensis.

    Science.gov (United States)

    Geng, Chang-An; Liu, Xi-Kui

    2013-09-01

    Five new indole alkaloids, rauvoloids A-E (1-5), together with two known ones, raucaffrinoline (6) and perakine (7) were isolated from the leaves of Rauvolfia yunnanensis. Their structures were elucidated by extensive spectroscopic methods. Structurally, rauvoloids A (1), B-C (2-3) and D (4) with unusual substitution patterns (no substitution, Cl and (1E)-3-oxo-butenyl, respectively) at C-20, are the first examples of perakine-type alkaloids with C18 and C22 skeletons. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Synthesis of 14C- and 2H-labeled 1,3 dihydro-3, 3-dimethyl-5-(1,4,5,6,- tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one (LY195115), an orally effective positive inotrope

    International Nuclear Information System (INIS)

    Robertson, D.W.; Krushinski, J.H.; Kau, D.

    1986-01-01

    The synthesis of 14 C- and 2 H-labeled 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol -2-one (LY195115), an extremely potent, orally-effective cardiotonic with inotropic and vasodilator activities is described. The 14 C-label was introduced in the antepenultimate step by reaction of a β-chloroketone precursor with Na 14 CN; acid-catalyzed hydrolysis and cyclization with hydrazine provided the tetrahydropyridazinone bearing the 14 C-label in the oxo-carbon. 1,3-Dihydro-3,3-di(methyl-d 3 ) -2H-indol-2-one was prepared by exhaustive methylation of 1-acetyl-1,3-dihydro-2H-indol-2-one with sodium hydride and iodomethane-d 3 , followed by removal of the nitrogen protecting group. This labeled material was converted in two steps to [ 2 H 6 ]-LY195115. (author)

  14. Nm23-M2/NDP kinase B induces endogenous c-myc and nm23-M1/NDP kinase A overexpression in BAF3 cells. Both NDP kinases protect the cells from oxidative stress-induced death

    International Nuclear Information System (INIS)

    Arnaud-Dabernat, Sandrine; Masse, Karine; Smani, Moneim; Peuchant, Evelyne; Landry, Marc; Bourbon, Pierre-Marie; Le Floch, Renaud; Daniel, Jean-Yves; Larou, Monique

    2004-01-01

    The nm23 gene family encodes nucleoside diphosphate kinases (NDPKs) which supply the cell with (d)NTPs. The human NDPKB, also known as the PuF protein, binds the c-myc promoter and transactivates the c-myc protooncogene. We have now studied the effects of mouse NDPKA and NDPKB overexpression on endogenous c-myc transactivation in the mouse BAF3 and the rat PC12 cell lines. c-myc transcripts were found to be up-regulated by NDPKB only in the BAF3 line. This suggests that c-myc transcriptional control via NDPKB depends on the presence of cell-specific co-factors. Unexpectedly, NDPKB also induced NDPKA expression. This new effect was found in both cell lines, suggesting that NDPKB-dependent nm23-M1 gene transactivation requires cis and/or trans elements different from those involved in c-myc transactivation. Moreover, the BAF3 cell proliferation capacities were found to be independent of NDPKA or B cell contents. Interestingly, cell death induced by c-myc overexpression or H 2 O 2 exposure was decreased in nm23-transfected compared to control BAF3 cells. These data collectively suggest that NDPKs might improve cell survival by a mechanism coupling DNA repair and transcriptional regulation of genes involved in DNA damage response

  15. 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.

    Science.gov (United States)

    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.

  16. Comparative photocatalytic study of two selected pesticide derivatives, indole-3-acetic acid and indole-3-butyric acid in aqueous suspensions of titanium dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Qamar, M. [Department of Chemistry, Aligarh Muslim University, Aligarh 202002 (India); Muneer, M. [Department of Chemistry, Aligarh Muslim University, Aligarh 202002 (India)]. E-mail: cht12mm@amu.ac.in

    2005-04-11

    Heterogeneous photocatalysed degradation of two selected pesticide derivatives such as indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) has been investigated in aqueous suspensions of titanium dioxide by monitoring the change in substrate concentration employing UV spectroscopic analysis technique and depletion in total organic carbon (TOC) content as a function of irradiation time. The degradation kinetics was studied under different conditions such as pH, types of TiO{sub 2,} substrate and catalyst concentration, and in the presence of electron acceptor such as hydrogen peroxide (H{sub 2}O{sub 2}) besides molecular oxygen. The degradation rates were found to be strongly influenced by all the above parameters. The photocatalyst Degussa P25 showed comparatively highest photocatalytics. The pesticide derivative, indole-3-acetic acid was found to degrade slightly faster than indole-3-butyric acid.

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

    Science.gov (United States)

    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.

  18. Monopoly Insurance and Endogenous Information

    DEFF Research Database (Denmark)

    Lagerlöf, Johan N. M.; Schottmüller, Christoph

    2018-01-01

    We study a monopoly insurance model with endogenous information acquisi- tion. Through a continuous effort choice, consumers can determine the precision of a privately observed signal that is informative about their accident risk. The equilibrium effort is, depending on parameter values, either...

  19. Endogeneously arising network allocation rules

    NARCIS (Netherlands)

    Slikker, M.

    2006-01-01

    In this paper we study endogenously arising network allocation rules. We focus on three allocation rules: the Myerson value, the position value and the component-wise egalitarian solution. For any of these three rules we provide a characterization based on component efficiency and some balanced

  20. Endogenizing Prospect Theory's Reference Point

    OpenAIRE

    Ulrich Schmidt; Horst Zank

    2010-01-01

    In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This note provides a foundation of prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

  1. Efficient One-Pot Synthesis of Indol-3-yl-Glycines via Uncatalyzed Friedel-Crafts Reaction in Water

    Directory of Open Access Journals (Sweden)

    Mehdi Ghandi

    2009-03-01

    Full Text Available The three component reaction of primary aliphatic amines, glyoxalic acid and indole or N-methylindole in water at ambient temperature affords indol-3-yl or N-methylindol-3-yl-glycine in almost quantitative yields.

  2. Efficient one-pot synthesis of indol-3-yl-glycines via uncatalyzed Friedel-Crafts reaction in water.

    Science.gov (United States)

    Ghandi, Mehdi; Taheri, Abuzar

    2009-03-05

    The three component reaction of primary aliphatic amines, glyoxalic acid and indole or N-methylindole in water at ambient temperature affords indol-3-yl or N-methylindol-3-yl-glycine in almost quantitative yields.

  3. Soluble Polymer-supported Synthesis of Indoles via Palladium-mediat -ed Heteroannulation of Terminal Alkynes with o-Iodoanilines

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A soluble polymer-supported synthesis of indoles via palladium-mediated hetero- annulation of terminal alkynes with o-iodoanilines has been described. The protocol provides a useful tool for constructing combinatorial indole libraries.

  4. Rh(III-Catalyzed, Highly Selectively Direct C–H Alkylation of Indoles with Diazo Compounds

    Directory of Open Access Journals (Sweden)

    Kang Wan

    2016-06-01

    Full Text Available Rh(III-catalyzed regioselective alkylation of indoles with diazo compounds as a highly efficient and atom-economic protocol for the synthesis of alkyl substituted indoles has been developed. The reaction could proceed under mild conditions and afford a series of desired products in good to excellent yields.

  5. 2-tert-Butyl-5,6,7,8,9,10-hexahydrocyclohepta[b]indole

    Directory of Open Access Journals (Sweden)

    Janina Wobbe

    2011-09-01

    Full Text Available 2-tert-Butyl-5,6,7,8,9,10-hexahydrocyclohepta[b]indole was synthesized by reaction of cycloheptanone and (4-tert-butylphenylhydrazine hydrochloride in the presence of sodium acetate and sulfuric acid in glacial acetic acid via Fischer indole synthesis.

  6. Human endogenous retroviruses in neurologic disease.

    Science.gov (United States)

    Christensen, Tove

    2016-01-01

    Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  7. Synthesis of 8-phenyl-10H-pyrido[1,2-α]indole salts from 2,3,3-trimethyl-3H-indole chlorides with cinnamaldehyde

    International Nuclear Information System (INIS)

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

    1987-01-01

    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-α]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)

  8. The pyruvate kinase of Stigmatella aurantiaca is an indole binding protein and essential for development.

    Science.gov (United States)

    Stamm, Irmela; Lottspeich, Friedrich; Plaga, Wulf

    2005-06-01

    Myxospore formation of the myxobacterium Stigmatella aurantiaca can be uncoupled from the cooperative development i.e. fruiting body formation, by low concentrations of indole. Two putative indole receptor proteins were isolated by their capacity to bind indole and identified as pyruvate kinase (PK) and aldehyde dehydrogenase. The PK activity of Stigmatella crude extracts was stimulated by indole. Cloning of the PK gene (pykA) and the construction of a pykA disruption mutant strikingly revealed that PK is essential for multicellular development: Fruiting body formation was abolished in the mutant strain and indole-induced spore formation was delayed. The developmental defects could be complemented by insertion of the pykA gene at the mtaB locus of the Stigmatella genome excluding any polar effects of the pykA disruption.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    V. L. Maruthanila

    2014-01-01

    Full Text Available 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.

  11. Design and synthesis of an indol derivative as antibacterial agent against Staphylococcus aureus.

    Science.gov (United States)

    Lenin, Hau-Heredia; Lauro, Figueroa-Valverde; Marcela, Rosas-Nexticapa; Socorro, Herrera-Meza; Maria, López-Ramos; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Josefa, Paat-Estrella; Regina, Cauich-Carrillo; Saidy, Euan-Hau

    2017-10-01

    Several indole derivatives with antibacterial activity have been prepared using different protocols; however, some require special reagents and conditions. The aim of this study involved the synthesis of some indole derivatives using estrone and OTBS-estrone as chemical tools. The synthesis of the indole derivatives involves reactions such as follows: (1) synthesis of two indol derivatives ( 4 or 5 ) by reaction of estrone or OTBS-estrone with phenylhydrazine in medium acid; (2) reaction of 4 or 5 with 6-cloro-1-hexyne in medium basic to form two hexynyl-indol ( 7 or 8 ); (3) preparation of indol-propargylic alcohol derivatives ( 10 or 11 ) by reaction of benzaldehyde with 7 or 8 in medium basic; (4) synthesis of indol-aldehydes ( 12 or 13 ) via oxidation of 10 or 11 with DMSO; (5) synthesis of indeno-indol-carbaldehyde ( 15 or 16 ) via alkynylation/cyclization of 12 or 13 with hexyne in presence of copper(II); (6) preparation indeno-indol-carbaldehyde complex ( 19 or 20 ) via alkynylation/cyclization of 12 or 13 with 1-(hex-5-yn-1-yl)-2-phenyl-1 H -imidazole. The antibacterial effect exerted by the indol-steroid derivatives against Streptococcus pneumoniae and Staphylococcus aureus bacteria was evaluated using dilution method and the minimum inhibitory concentration (MIC). The results showed that only the compound 19 inhibit the growth bacterial of S. aureus . In conclusion, these data indicate that antibacterial activity of 19 can be due mainly to functional groups involved in the chemical structure in comparison with the compounds studied.

  12. S-Alkylated/aralkylated 2-(1H-indol-3-yl-methyl)-1,3,4- oxadiazole-5 ...

    African Journals Online (AJOL)

    ylmethyl)-1,3,4- oxadiazole-5-thiol derivatives. Methods: 2-(1H-indol-3-yl)acetic acid (1) was reacted with absolute ethanol and catalytic amount of sulfuric acid to form ethyl 2-(1H-indol-3-yl)acetate (2) which was transformed to 2-(1H-indol-3- ...

  13. Endogenous opiates and behavior: 2014.

    Science.gov (United States)

    Bodnar, Richard J

    2016-01-01

    This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular

  14. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2017-01-01

    We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely and is i......We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely...... and is indistinguishable from that of a generalized version of the classical Vickrey bottleneck model, based on exogenous trip-timing preferences, but optimal policies differ: the Vickrey model will misstate the benefits of a capacity increase, it will underpredict the benefits of congestion pricing, and pricing may make...

  15. Exogenic and endogenic Europa minerals

    Science.gov (United States)

    Maynard-Casely, H. E.; Brand, H. E. A.; Wilson, S. A.

    2016-12-01

    The Galileo Near Infrared Mapping Spectrometer (NIMS) identified a significant `non-ice' component upon the surface of Jupiter's moon Europa. Current explanations invoke both endogenic and exogenic origins for this material. It has long been suggested that magnesium and sodium sulfate minerals could have leached from the rock below a putative ocean (endogenic) 1 and that sulfuric acid hydrate minerals could have been radiologically produced from ionised sulfur originally from Io's volcanoes (exogenic) 2. However, a more recent theory proposes that the `non-ice' component could be radiation damaged NaCl leached from Europa's speculative ocean 3. What if the minerals are actually from combination of both endogenic and exogenic sources? To investigate this possibility we have focused on discovering new minerals that might form in the combination of the latter two cases, that is a mixture of leached sulfates hydrates with radiologically produced sulfuric acid. To this end we have explored a number of solutions in the MgSO4-H2SO4-H2O and Na2SO4-H2SO4-H2O systems, between 80 and 280 K with synchrotron x-ray powder diffraction. We report a number of new materials formed in this these ternary systems. This suggests that it should be considered that the `non-ice' component of the Europa's surface could be a material derived from endogenic and exogenic components. 1 Kargel, J. S. Brine volcanism and the interior structures of asteroids and icy satellites. Icarus 94, 368-390 (1991). 2 Carlson, R. W., Anderson, M. S., Mehlman, R. & Johnson, R. E. Distribution of hydrate on Europa: Further evidence for sulfuric acid hydrate. Icarus 177, 461-471, doi:10.1016/j.icarus.2005.03.026 (2005). 3 Hand, K. P. & Carlson, R. W. Europa's surface color suggests an ocean rich with sodium chloride. Geophysical Research Letters, 2015GL063559, doi:10.1002/2015gl063559 (2015).

  16. Money, banks and endogenous volatility

    OpenAIRE

    Pere Gomis-Porqueras

    2000-01-01

    In this paper I consider a monetary growth model in which banks provide liquidity, and the government fixes a constant rate of money creation. There are two underlying assets in the economy, money and capital. Money is dominated in rate of return. In contrast to other papers with a larger set of government liabilities, I find a unique equilibrium when agents' risk aversion is moderate. However, indeterminacies and endogenous volatility can be observed when agents are relatively risk averse.

  17. REFERENCE MODELS OF ENDOGENOUS ECONOMIC GROWTH

    OpenAIRE

    GEAMĂNU MARINELA

    2012-01-01

    The new endogenous growth theories are a very important research area for shaping the most effective policies and long term sustainable development strategies. Endogenous growth theory has emerged as a reaction to the imperfections of neoclassical theory, by the fact that the economic growth is the endogenous product of an economical system.

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

    Science.gov (United States)

    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.

  19. INDOL-3-CARBINOL IN THE TREATMENT OF BENIGN BREAST DISORDERS

    Directory of Open Access Journals (Sweden)

    E. T. Zulkarnayeva

    2008-01-01

    Full Text Available 123 patients with various forms of fibrocystic mastopathy (n=114 and fibroadenoma of mammry gland (n=9 were enrolled into the study. Indol-3-carbinol (indinol, Close corporation «Mirax-Pharma» was administered in the dose of 300—400 mg per day for 3—6 months. Disappearance of complaints to pain was observed in 35% of patients after 3 months of therapy and in 63% — after 6 months of therapy. Objective signs of fibrocystic mastopathy completely regressed in 9% of patients after 3 months of therapy and in 16% — after 6 month of therapy. Overall considerable improvement of condition or complete cure was seen in 55% of patients after 3 month of treatment and in 92% — after 6 months of therapy. Thus, indinol is highly effective and safe agent for treatment of different types of mastopathy.

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

    Science.gov (United States)

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

    2017-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

  1. Wounding of Arabidopsis leaves induces indole-3-carbinol-dependent autophagy in roots of Arabidopsis thaliana.

    Science.gov (United States)

    Katz, Ella; Chamovitz, Daniel A

    2017-09-01

    In cruciferous plants insect attack or physical damage induce the synthesis of the glucosinolate breakdown product indole-3-carbinol, which plays a key role in the defense against attackers. Indole-3-carbinol also affects plant growth and development, acting as an auxin antagonist by binding to the TIR1 auxin receptor. Other potential functions of indole-3-carbinol and the underlying mechanisms in plant biology are unknown. Here we show that an indole-3-carbinol-dependent signal induces specific autophagy in root cells. Leaf treatment with exogenous indole-3-carbinol or leaf-wounding induced autophagy and inhibited auxin response in the root. This induction is lost in glucosinolate-defective mutants, indicating that the effect of indole-3-carbinol is transported in the plants. Thus, indole-3-carbinol is not only a defensive metabolite that repels insects, but is also involved in long-distance communication regulating growth and development in plants. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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.

  3. Indole, a Signaling Molecule Produced by the Gut Microbiota, Negatively Impacts Emotional Behaviors in Rats

    Directory of Open Access Journals (Sweden)

    Mathilde Jaglin

    2018-04-01

    Full Text Available Gut microbiota produces a wide and diverse array of metabolites that are an integral part of the host metabolome. The emergence of the gut microbiome-brain axis concept has prompted investigations on the role of gut microbiota dysbioses in the pathophysiology of brain diseases. Specifically, the search for microbe-related metabolomic signatures in human patients and animal models of psychiatric disorders has pointed out the importance of the microbial metabolism of aromatic amino acids. Here, we investigated the effect of indole on brain and behavior in rats. Indole is produced by gut microbiota from tryptophan, through the tryptophanase enzyme encoded by the tnaA gene. First, we mimicked an acute and high overproduction of indole by injecting this compound in the cecum of conventional rats. This treatment led to a dramatic decrease of motor activity. The neurodepressant oxidized derivatives of indole, oxindole and isatin, accumulated in the brain. In addition, increase in eye blinking frequency and in c-Fos protein expression in the dorsal vagal complex denoted a vagus nerve activation. Second, we mimicked a chronic and moderate overproduction of indole by colonizing germ-free rats with the indole-producing bacterial species Escherichia coli. We compared emotional behaviors of these rats with those of germ-free rats colonized with a genetically-engineered counterpart strain unable to produce indole. Rats overproducing indole displayed higher helplessness in the tail suspension test, and enhanced anxiety-like behavior in the novelty, elevated plus maze and open-field tests. Vagus nerve activation was suggested by an increase in eye blinking frequency. However, unlike the conventional rats dosed with a high amount of indole, the motor activity was not altered and neither oxindole nor isatin could be detected in the brain. Further studies are required for a comprehensive understanding of the mechanisms supporting indole effects on emotional

  4. 2-(2,3-Dihydro-1H-indol-3-yl)ethanol

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Sommer, Michael Bech; Heckmann, Dieter

    2004-01-01

    The first direct resolution of racemic 2-(2,3-dihydro-lH-indol-3-yl)ethanol-prepared by catalytic hydrogenation of 2-(lH-indol-3-yl)ethanol-has been accomplished by chiral simulated moving bed (SMB) chromatography. The single enantiomers were isolated as their dihydrogen phosphate salts. Single......-crystal X-ray analyses were successful, revealing that the (+)-enantiomer of 2-(2,3-dihydro-lH-indol-3-yl)ethanol has the (S) configuration. Chirality 16:126-130, 2004....

  5. Gold-catalyzed Bicyclization of Diaryl Alkynes: Synthesis of Polycyclic Fused Indole and Spirooxindole Derivatives.

    Science.gov (United States)

    Cai, Ju; Wu, Bing; Rong, Guangwei; Zhang, Cheng; Qiu, Lihua; Xu, Xinfang

    2018-04-13

    An unprecedented gold-catalyzed bicyclization reaction of diaryl alkynes has been developed for the synthesis of indoles in good to high yields. Mechanistically, this alkyne bifunctionalization transformation was terminated by a stepwise formal X-H insertion reaction to furnish the corresponding polycyclic-frameworks with structural diversity, and the key intermediate 3 H-indole was isolated and characterized for the first time. In addition, further transformation of these generated tetracyclic-indoles with PCC as the oxidant provided straightforward access to the spirooxindoles in high yields.

  6. Thermodynamic properties of alkyl 1H-indole carboxylate derivatives: A combined experimental and computational study

    International Nuclear Information System (INIS)

    Carvalho, Tânia M.T.; Amaral, Luísa M.P.F.; Morais, Victor M.F.; Ribeiro da Silva, Maria D.M.C.

    2016-01-01

    Highlights: • Combustion of methyl 1H-indole-3-carboxylate and ethyl 1H-indole-2-carboxylate by static bomb calorimetry. • The Knudsen mass-loss effusion technique was used to measure the vapour pressures of compounds at different temperatures. • Enthalpies of sublimation of methyl 1H-indole-3-carboxylate and ethyl 1H-indole-2-carboxylate. • Gas-phase enthalpies of formation of methyl 1H-indole-3-carboxylate and ethyl 1H-indole-2-carboxylate have been derived. • Gas-phase enthalpies of formation estimated from G3(MP2) calculations. - Abstract: The standard (p"o = 0.1 MPa) molar enthalpies of formation, in the crystalline phase, of methyl 1H-indole-3-carboxylate and ethyl 1H-indole-2-carboxylate, at T = 298.15 K, were derived from measurements of the standard massic energies of combustion using a static bomb combustion calorimeter. The Knudsen effusion technique was used to measure the vapour pressures as a function of the temperature, which allowed determining the standard molar enthalpies of sublimation of these compounds. The standard (p"o = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T = 298.15 K, were calculated by combining, for each compound, the standard molar enthalpy of formation, in the crystalline phase, and the standard molar enthalpy of sublimation, yielding −(207.6 ± 3.6) kJ·mol"−"1 and −(234.4 ± 2.4) kJ·mol"−"1, for methyl 1H-indole-3-carboxylate and ethyl 1H-indole-2-carboxylate, respectively. Quantum chemical studies were also conducted, in order to complement the experimental study. The gas-phase enthalpies of formation were estimated from high level ab initio molecular orbital calculations, at the G3(MP2) level, for the compounds studied experimentally, extending the study to the methyl 1H-indole-2-carboxylate and ethyl 1H-indole-3-carboxylate. The results obtained were compared with the experimental data and were also analysed in terms of structural enthalpic group contributions.

  7. Indole, a Signaling Molecule Produced by the Gut Microbiota, Negatively Impacts Emotional Behaviors in Rats

    Science.gov (United States)

    Jaglin, Mathilde; Rhimi, Moez; Philippe, Catherine; Pons, Nicolas; Bruneau, Aurélia; Goustard, Bénédicte; Daugé, Valérie; Maguin, Emmanuelle; Naudon, Laurent; Rabot, Sylvie

    2018-01-01

    Gut microbiota produces a wide and diverse array of metabolites that are an integral part of the host metabolome. The emergence of the gut microbiome-brain axis concept has prompted investigations on the role of gut microbiota dysbioses in the pathophysiology of brain diseases. Specifically, the search for microbe-related metabolomic signatures in human patients and animal models of psychiatric disorders has pointed out the importance of the microbial metabolism of aromatic amino acids. Here, we investigated the effect of indole on brain and behavior in rats. Indole is produced by gut microbiota from tryptophan, through the tryptophanase enzyme encoded by the tnaA gene. First, we mimicked an acute and high overproduction of indole by injecting this compound in the cecum of conventional rats. This treatment led to a dramatic decrease of motor activity. The neurodepressant oxidized derivatives of indole, oxindole and isatin, accumulated in the brain. In addition, increase in eye blinking frequency and in c-Fos protein expression in the dorsal vagal complex denoted a vagus nerve activation. Second, we mimicked a chronic and moderate overproduction of indole by colonizing germ-free rats with the indole-producing bacterial species Escherichia coli. We compared emotional behaviors of these rats with those of germ-free rats colonized with a genetically-engineered counterpart strain unable to produce indole. Rats overproducing indole displayed higher helplessness in the tail suspension test, and enhanced anxiety-like behavior in the novelty, elevated plus maze and open-field tests. Vagus nerve activation was suggested by an increase in eye blinking frequency. However, unlike the conventional rats dosed with a high amount of indole, the motor activity was not altered and neither oxindole nor isatin could be detected in the brain. Further studies are required for a comprehensive understanding of the mechanisms supporting indole effects on emotional behaviors. As our findings

  8. Excited state electric dipole moment of 5-hydroxy indole and 5-hydroxy indole 3-acetic acid through solvatochromic shifts

    International Nuclear Information System (INIS)

    Rani, G. Neeraja; Ayachit, Narasimha H.

    2010-01-01

    The determination of excited state electric dipole moment through solvatochromic shifts is one of the easiest approaches to understand the molecular structure in the excited state. These studies have gained importance due to their application in photo science, especially if they are of biological importance. In view of this the excited state electric dipole moments of two substituted indoles which are of biological importance are determined and reported here. The fluorescence shifts have been used and the results found seem to be more consistent in comparison with the one calculated through absorption shifts. The results presented are also discussed. A qualitative estimate of the orientation of the dipole moments in ground and excited state are also presented and discussed. The method proposed by Ayachit and Neeraja Rani is used in view of the several advantages it has.

  9. Inflation gifts and endogenous growth through learning-by-doing

    OpenAIRE

    Andrea Vaona

    2013-01-01

    We investigate the link between inflation, growth and unemployment nesting a model of fair wages into one of endogenous growth of learning by doing and assuming that firms protect wages' purchasing power against inflation in exchange of worker's effort. Unemployment decreases with higher inflation and real growth rates. These effects tends to vanish as inflation and growth increase. Depending on the assumptions on learning-by-doing mechanisms, the effect of inflation on growth can be either n...

  10. On the origins of endogenous thoughts.

    Science.gov (United States)

    Tillas, Alexandros

    2017-05-01

    Endogenous thoughts are thoughts that we activate in a top-down manner or in the absence of the appropriate stimuli. We use endogenous thoughts to plan or recall past events. In this sense, endogenous thinking is one of the hallmarks of our cognitive lives. In this paper, I investigate how it is that we come to possess endogenous control over our thoughts. Starting from the close relation between language and thinking, I look into speech production-a process motorically controlled by the inferior frontal gyrus (IFG). Interestingly, IFG is also closely related to silent talking, as well as volition. The connection between IFG and volition is important given that endogenous thoughts are or at least greatly resemble voluntary actions. Against this background, I argue that IFG is key to understanding the origins of conscious endogenous thoughts. Furthermore, I look into goal-directed thinking and show that IFG plays a key role also in unconscious endogenous thinking.

  11. Measurement of release of endogenous GABA and catabolites of [3H]GABA from synaptosomal preparations using ion-exchange chromatography

    International Nuclear Information System (INIS)

    Grove, J.; Gardner, C.R.; Richards, M.H.

    1982-01-01

    Picomole quantities of endogenous GABA in acidified superfusates of synaptosomal preparations have been measured using micro-bore ion-exchange chromatography and post-column formation of the fluorescent iso-indole derivative. Using this technique superfusates have been analyzed directly, without further manipulations, to investigate the release of endogenous GABA. Spontaneous release of GABA was 2-5 pmol/200 microliters superfusate increasing to 20 pmol/200 microliters with potassium stimulation. When gamma-vinyl GABA (RMI 71754), an inhibitor of GABA-T was injected into rats (750 mg/kg) and synaptosomes prepared the potassium-evoked release of GABA was increased 3-fold compared to controls. Chromatographic separations and measurement of release of endogenous and radiolabeled GABA allowed the real specific activity of released GABA to be calculated. Only when 500 microM amino-oxyacetic acid was added during isolation of synaptosomes was the specific activity of released GABA the same as the initial specific activity

  12. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2010-01-01

    and leisure, but agglomeration economies at home and at work lead to scheduling preferences forming endogenously. Using bottleneck congestion technology, we obtain an equilibrium queuing pattern consistent with a general version of the Vickrey bottleneck model. However, the policy implications are different....... Compared to the predictions of an analyst observing untolled equilibrium and taking scheduling preferences as exogenous, we find that both the optimal capacity and the marginal external cost of congestion have changed. The benefits of tolling are greater, and the optimal time varying toll is different....

  13. Endogenous money, circuits and financialization

    OpenAIRE

    Malcolm Sawyer

    2013-01-01

    This paper locates the endogenous money approach in a circuitist framework. It argues for the significance of the credit creation process for the evolution of the economy and the absence of any notion of ‘neutrality of money’. Clearing banks are distinguished from other financial institutions as the providers of initial finance in a circuit whereas other financial institutions operate in a final finance circuit. Financialization is here viewed in terms of the growth of financial assets an...

  14. An endogenous aryl hydrocarbon receptor ligand inhibits proliferation and migration of human ovarian cancer cells.

    Science.gov (United States)

    Wang, Kai; Li, Yan; Jiang, Yi-Zhou; Dai, Cai-Feng; Patankar, Manish S; Song, Jia-Sheng; Zheng, Jing

    2013-10-28

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor mediates many biological processes. Herein, we investigated if 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE, an endogenous AhR ligand) regulated proliferation and migration of human ovarian cancer cells via AhR. We found that AhR was widely present in many histotypes of ovarian cancer tissues. ITE suppressed OVCAR-3 cell proliferation and SKOV-3 cell migration in vitro, which were blocked by AhR knockdown. ITE also suppressed OVCAR-3 cell growth in mice. These data suggest that the ITE might potentially be used for therapeutic intervention for at least a subset of human ovarian cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. A combined experimental and theoretical study on vibrational and electronic properties of (5-methoxy-1H-indol-1-yl(5-methoxy-1H-indol-2-ylmethanone

    Directory of Open Access Journals (Sweden)

    Al-Wabli Reem I.

    2017-11-01

    Full Text Available (5-Methoxy-1H-indol-1-yl(5-methoxy-1H-indol-2-ylmethanone (MIMIM is a bis-indolic derivative that can be used as a precursor to a variety of melatonin receptor ligands. In this work, the energetic and spectroscopic profiles of MIMIM were studied by a combined DFT and experimental approach. The IR, Raman, UV-Vis, 1H NMR and 13C NMR spectra were calculated by PBEPBE and B3LYP methods, and compared with experimental ones. Results showed good agreement between theoretical and experimental values. Mulliken population and natural bond orbital analysis were also performed by time-dependent DFT approach to evaluate the electronic properties of the title molecule.

  16. Tulongicin, an Antibacterial Tri-Indole Alkaloid from a Deep-Water Topsentia sp. Sponge.

    Science.gov (United States)

    Liu, Hong-Bing; Lauro, Gianluigi; O'Connor, Robert D; Lohith, Katheryn; Kelly, Michelle; Colin, Patrick; Bifulco, Giuseppe; Bewley, Carole A

    2017-09-22

    Antibacterial-guided fractionation of an extract of a deep-water Topsentia sp. marine sponge led to the isolation of two new indole alkaloids, tulongicin A (1) and dihydrospongotine C (2), along with two known analogues, spongotine C (3) and dibromodeoxytopsentin (4). Their planar structures were determined by NMR spectroscopy. Their absolute configurations were determined through a combination of experimental and computational analyses. Tulongicin (1) is the first natural product to contain a di(6-Br-1H-indol-3-yl)methyl group linked to an imidazole core. The coexistence of tri-indole 1 and bis-indole alcohol 2 suggests a possible route to 1. All of the compounds showed strong antimicrobial activity against Staphylococcus aureus.

  17. Asymmetric Synthesis of Optically Active Spirocyclic Indoline Scaffolds through an Enantioselective Reduction of Indoles

    KAUST Repository

    Borrmann, Ruediger; Knop, Nils; Rueping, Magnus

    2016-01-01

    An enantioselective synthesis of spirocyclic indoline scaffolds was achieved by applying an asymmetric iridium-catalyzed hydrogenation of 3H-indoles. Low catalyst loadings and mild reaction conditions provide a broad range of differently substituted

  18. Radiotherapy of indolent orbital lymphomas. Two radiation concepts

    Energy Technology Data Exchange (ETDEWEB)

    Koenig, Laila; Stade, Robert; Rieber, Juliane; Debus, Juergen; Herfarth, Klaus [Universitaetsklinikum Heidelberg, Abteilung RadioOnkologie und Strahlentherapie, Heidelberg (Germany)

    2016-06-15

    The aim of this work was to retrospectively analyze efficacy, toxicity, and relapse rates of conventional (CRT) and low-dose radiotherapy (LDRT) in patients with indolent orbital lymphomas. From 1987-2014, 45 patients (median age 64 years) with 52 lesions of indolent orbital lymphomas were treated with CRT (median dose 36 Gy, range 26-46 Gy) and 7 patients (median age 75 years) with 8 lesions were treated with LDRT (2 fractions of 2.0 Gy). Median follow-up was 133 months (range 2-329 months) in the CRT group and 25 months (range 10-41 months) in the LDRT group. Overall response rates were 97.7 % (CRT) and 100 % (LDRT). The 2- and 5-year local progression-free survival (PFS) rates were 93.5 and 88.6 %, distant PFS 95.0 and 89.9 %, and overall survival 100 and 85.6 % after CRT. In the LDRT group, 2-year local PFS and overall survival remained 100 %, respectively, and distant PFS 68.6 %. Acute radiotherapy-related complications (grades 1-2) were detected in virtually all eyes treated with CRT. Cataracts developed in only patients who were irradiated with more than 34 Gy. LDRT was well tolerated with only mild acute and late complications. Primary radiotherapy of indolent orbital lymphomas is an effective treatment with high response rates and excellent local control in CRT and LDRT. In combination with close follow-up, LDRT may be an attractive alternative since re-irradiation even with conventional doses is still feasible. (orig.) [German] Ziel der Arbeit war die Analyse von Effektivitaet, Nebenwirkungen und Rezidivraten nach konventioneller (CRT) und Niedrigdosisbestrahlung (LDRT) indolenter Orbitalymphome. Retrospektiv evaluiert wurden 45 zwischen 1987 und 2014 behandelte Patienten (medianes Alter 64 Jahre) mit insgesamt 52 Laesionen indolenter Orbitalymphome, die mittels CRT (mediane Dosis 36 Gy, 26-46 Gy) therapiert wurden.; 7 Patienten mit insgesamt 8 Laesionen erhielten eine LDRT (2 x 2,0 Gy). Das mediane Follow-Up betrug 133 Monate (2-239 Monate) in der CRT

  19. Study on the extraction, purification and quantification of jasmonic acid, abscisic acid and indole-3-acetic acid in plants.

    Science.gov (United States)

    Zhang, Feng Juan; Jin, You Ju; Xu, Xing You; Lu, Rong Chun; Chen, Hua Jun

    2008-01-01

    Jasmonic acid (JA), abscisic acid (ABA) and indole-3-acetic acid (IAA) are important plant hormones. Plant hormones are difficult to analyse because they occur in small concentrations and other substances in the plant interfere with their detection. To develop a new, inexpensive procedure for the rapid extraction and purification of IAA, ABA and JA from various plant species. Samples were prepared by extraction of plant tissues with methanol and ethyl acetate. Then the extracts were further purified and enriched with C(18) cartridges. The final extracts were derivatised with diazomethane and then measured by GC-MS. The results of the new methodology were compared with those of the Creelman and Mullet procedure. Sequential elution of the assimilates from the C(18 )cartridges revealed that IAA and ABA eluted in 40% methanol, while JA subsequently eluted in 60% methanol. The new plant hormone extraction and purification procedure produced results that were comparable to those obtained with the Creelman and Mullet's procedure. This new procedure requires only 0.5 g leaf samples to quantify these compounds with high reliability and can simultaneously determine the concentrations of the three plant hormones. A simple, inexpensive method was developed for determining endogenous IAA, ABA and JA concentrations in plant tissue.

  20. Decarboxylation of indole-3-acetic acid and inhibition of growth in Avena sativa seedlings by plant-derived photosensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Brennan, T.M. [Dickinson Coll., Carlisle, PA (United States). Dept. of Biology

    1996-12-01

    A number of plant phototoxins, when supplemented with UVA (320-400 nm) radiation, are capable of sensitizing the decomposition of indole-3-acetic acid (IAA), as measured by release of {sup 14}CO{sub 2} from carboxyl-labeled IAA. Alpha-terthienyl ({alpha}T) and harmine caused significant rates of IAA decarboxylation at concentrations as low as 1 nM and were approximately 80% as effective as riboflavin and flavin mononucleotide. Partial inhibition by sodium azide indicates that the {alpha}T-induced decarboxylation of IAA is predominately, but not entirely, a type II reaction mediated by singlet oxygen. Based on changes in UV absorption spectra, it appears that the hormones gibberellic acid, abscisic acid and 6-benzylaminopurine (a cytokinin) are less susceptible to photosensitized decomposition than is IAA. Alpha-terthienyl plus UVA also inhibited elongation growth and reduced endogenous IAA levels in Avena sativa L. coleoptile sections and promoted senescence in intact Avena seedlings. These results confirm the alelopathic potential of plant photosensitizers such as {alpha}T and indicate that the phytohormone IAA may represent an additional target for the action of photosensitizers. (Author).

  1. Human-Specific Endogenous Retroviruses

    Directory of Open Access Journals (Sweden)

    Anton Buzdin

    2007-01-01

    Full Text Available This review focuses on a small family of human-specific genomic repetitive elements, presented by 134 members that shaped ~330 kb of the human DNA. Although modest in terms of its copy number, this group appeared to modify the human genome activity by endogenizing ~50 functional copies of viral genes that may have important implications in the immune response, cancer progression, and antiretroviral host defense. A total of 134 potential promoters and enhancers have been added to the human DNA, about 50% of them in the close gene vicinity and 22% in gene introns. For 60 such human-specific promoters, their activity was confirmed by in vivo assays, with the transcriptional level varying ~1000-fold from hardly detectable to as high as ~3% of β-actin transcript level. New polyadenylation signals have been provided to four human RNAs, and a number of potential antisense regulators of known human genes appeared due to human-specific retroviral insertional activity. This information is given here in the context of other major genomic changes underlining differences between human and chimpanzee DNAs. Finally, a comprehensive database, is available for download, of human-specific and polymorphic endogenous retroviruses is presented, which encompasses the data on their genomic localization, primary structure, encoded viral genes, human gene neighborhood, transcriptional activity, and methylation status.

  2. Endogenous Opiates and Behavior: 2006

    Science.gov (United States)

    Bodnar, Richard J.

    2009-01-01

    This paper is the twenty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning thirty years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:17949854

  3. Endogenous opiates and behavior: 2012.

    Science.gov (United States)

    Bodnar, Richard J

    2013-12-01

    This paper is the thirty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2012 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  5. An NPF transporter exports a central monoterpene indole alkaloid intermediate from the vacuole

    DEFF Research Database (Denmark)

    Payne, Richard; Xu, Deyang; Foureau, Emilien

    2017-01-01

    Plants sequester intermediates of metabolic pathways into different cellular compartments, but the mechanisms by which these molecules are transported remain poorly understood. Monoterpene indole alkaloids, a class of specialized metabolites that includes the anticancer agent vincristine, antimal......Plants sequester intermediates of metabolic pathways into different cellular compartments, but the mechanisms by which these molecules are transported remain poorly understood. Monoterpene indole alkaloids, a class of specialized metabolites that includes the anticancer agent vincristine...

  6. Ruthenium(II)-catalyzed direct addition of indole/pyrrole C2-H bonds to alkynes.

    Science.gov (United States)

    Liang, Libo; Fu, Shaomin; Lin, Dongen; Zhang, Xiao-Qi; Deng, Yuanfu; Jiang, Huanfeng; Zeng, Wei

    2014-10-17

    A ruthenium-catalyzed C2-hydroindolation of alkynes has been achieved. This protocol provides a rapid and concise access to kinds of 2-alkenyl-substituted N-(2-pyridyl)indoles in which the pyridyl moiety can be easily removed to afford free (N-H) indoles under mild conditions. Various arenes and alkynes, including electron-deficient and electron-rich internal alkynes and terminal alkynes, allow for this transformation.

  7. Aleuria aurantia - indole metabolites of fruit bodies, mycelial culture and culture medium

    Directory of Open Access Journals (Sweden)

    Janina Węgiel

    2014-08-01

    Full Text Available The aim of present study was to investigate and compare indole metabolites of fruit bodies, mycelium cultivated in vitro and culture medium of the fungus Aleuria aurantia (Fr. Fuck. By use of a number of chromatographic and spectroscopic methods several indole metabolites have been detected and identified among other the 3-indolebutyric acid was produced and extracted to the culture medium. Furthermore 3-indoleatonitrile and tryptophane degradative products have been found both in fruit bodies and mycelium.

  8. A Scalable Method for Regioselective 3-Acylation of 2-Substituted Indoles under Basic Conditions

    DEFF Research Database (Denmark)

    Johansson, Karl Henrik; Urruticoechea, Andoni; Larsen, Inna

    2015-01-01

    Privileged structures such as 2-arylindoles are recurrent molecular scaffolds in bioactive molecules. We here present an operationally simple, high yielding and scalable method for regioselective 3-acylation of 2-substituted indoles under basic conditions using functionalized acid chlorides. The ....... The method shows good tolerance to both electron-withdrawing and donating substituents on the indole scaffold and gives ready access to a variety of functionalized 3-acylindole building blocks suited for further derivatization....

  9. Role of endogenous serotonin in the mechanism of action of radioprotective substances

    International Nuclear Information System (INIS)

    Konstantinova, M.M.; Nekrasova, I.V.; Gusareva, Eh.V.; Dontsova, G.V.

    1978-01-01

    A study is made of a correlation between radiomodifying activity of noradrenaline (NA), N-ethylmaleimide (NEM) and a combination of these agents and their effect on the content of endogenous serotonin in cells of Ehrlich's ascites tumor and E. coli B. There is no uniformity in the response of different cells and uniform direction of the changes in their radioresistance and endogenous serotonin content both under the effect of the substances (NA and NEM) given separately and under a combined effect of the protector and the agent, which removes the protective effect or prevents realization of the latter (NEM). This enables us to arrive at a conclusion that endogenous serotonin is not the only factor responsible for the radioprotective effect of the protective substances. At the same time, it is not excluded that endogenous serotonin is involved in the chain of reactions which are necessary for the radioprotective effect to come into play

  10. Electric Dipole Transition Moments and Solvent-Dependent Interactions of Fluorescent Boron-Nitrogen Substituted Indole Derivatives.

    Science.gov (United States)

    Saif, Mari; Widom, Julia R; Xu, Senmiao; Abbey, Eric R; Liu, Shih-Yuan; Marcus, Andrew H

    2015-06-25

    Fluorescent analogues of the indole side chain of tryptophan can be useful spectroscopic probes of protein-protein and protein-DNA interactions. Here we present linear dichroism and solvent-dependent spectroscopic studies of two fluorescent analogues of indole, in which the organic C═C unit is substituted with the isosteric inorganic B-N unit. We studied the so-called "external" BN indole, which has C2v symmetry, and the "fused" BN indole with Cs symmetry. We performed a combination of absorption and fluorescence spectroscopy, ultraviolet linear dichroism (UV-LD) in stretched poly(ethylene) (PE) films, and quantum chemical calculations on both BN indole compounds. Our measurements allowed us to characterize the degree of alignment for both molecules in stretched PE films. We thus determined the orientations and magnitudes of the two lowest energy electric dipole transition moments (EDTMs) for external BN indole, and the two lowest energy EDTMs for fused BN indole within the 30 000-45 000 cm(-1) spectral range. We compared our experimental results to those of quantum chemical calculations using standard density functional theory (DFT). Our theoretical predictions for the low-energy EDTMs are in good agreement with our experimental data. The absorption and fluorescence spectra of the external and the fused BN indoles are sensitive to solvent polarity. Our results indicate that the fused BN indole experiences much greater solvation interactions with polar solvents than does the external BN indole.

  11. Possible Interactions between the Biosynthetic Pathways of Indole Glucosinolate and Auxin

    Directory of Open Access Journals (Sweden)

    Siva K. Malka

    2017-12-01

    Full Text Available Glucosinolates (GLS are a group of plant secondary metabolites mainly found in Cruciferous plants, share a core structure consisting of a β-thioglucose moiety and a sulfonated oxime, but differ by a variable side chain derived from one of the several amino acids. These compounds are hydrolyzed upon cell damage by thioglucosidase (myrosinase, and the resulting degradation products are toxic to many pathogens and herbivores. Human beings use these compounds as flavor compounds, anti-carcinogens, and bio-pesticides. GLS metabolism is complexly linked to auxin homeostasis. Indole GLS contributes to auxin biosynthesis via metabolic intermediates indole-3-acetaldoxime (IAOx and indole-3-acetonitrile (IAN. IAOx is proposed to be a metabolic branch point for biosynthesis of indole GLS, IAA, and camalexin. Interruption of metabolic channeling of IAOx into indole GLS leads to high-auxin production in GLS mutants. IAN is also produced as a hydrolyzed product of indole GLS and metabolized to IAA by nitrilases. In this review, we will discuss current knowledge on involvement of GLS in auxin homeostasis.

  12. Endogenous money: the evolutionary versus revolutionary views

    OpenAIRE

    Louis-Philippe Rochon; Sergio Rossi

    2013-01-01

    The purpose of this paper is to shed light on the endogenous nature of money. Contrary to the established post-Keynesian, or evolutionary, view, this paper argues that money has always been endogenous, irrespective of the historical period. Instead of the evolutionary theory of money and banking that can be traced back to Chick (1986), this paper puts forward a revolutionary definition of endogenous money consistent with many aspects of post-Keynesian economics as well as with the monetary ci...

  13. Endogenous price flexibility and optimal monetary policy

    OpenAIRE

    Ozge Senay; Alan Sutherland

    2014-01-01

    Much of the literature on optimal monetary policy uses models in which the degree of nominal price flexibility is exogenous. There are, however, good reasons to suppose that the degree of price flexibility adjusts endogenously to changes in monetary conditions. This article extends the standard new Keynesian model to incorporate an endogenous degree of price flexibility. The model shows that endogenizing the degree of price flexibility tends to shift optimal monetary policy towards complete i...

  14. Metabolic regulation of the plant hormone indole-3-acetic acid

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis

    Science.gov (United States)

    Quintana, Francisco J.; Murugaiyan, Gopal; Farez, Mauricio F.; Mitsdoerffer, Meike; Tukpah, Ann-Marcia; Burns, Evan J.; Weiner, Howard L.

    2010-01-01

    The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) participates in the differentiation of FoxP3+ Treg, Tr1 cells, and IL-17–producing T cells (Th17). Most of our understanding on the role of AHR on the FoxP3+ Treg compartment results from studies using the toxic synthetic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin. Thus, the physiological relevance of AHR signaling on FoxP3+ Treg in vivo is unclear. We studied mice that carry a GFP reporter in the endogenous foxp3 locus and a mutated AHR protein with reduced affinity for its ligands, and found that AHR signaling participates in the differentiation of FoxP3+ Treg in vivo. Moreover, we found that treatment with the endogenous AHR ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) given parenterally or orally induces FoxP3+ Treg that suppress experimental autoimmune encephalomyelitis. ITE acts not only on T cells, but also directly on dendritic cells to induce tolerogenic dendritic cells that support FoxP3+ Treg differentiation in a retinoic acid-dependent manner. Thus, our work demonstrates that the endogenous AHR ligand ITE promotes the induction of active immunologic tolerance by direct effects on dendritic and T cells, and identifies nontoxic endogenous AHR ligands as potential unique compounds for the treatment of autoimmune disorders. PMID:21068375

  16. Endogenous, Imperfectly Competitive Business Cycles

    DEFF Research Database (Denmark)

    Whitta-Jacobsen, Hans Jørgen

    We investigate how imperfect competition affects the occurrence and the properties of endogenous, rational expectations business cycles in an overlapping generations model with constant returns to scale in production. The model has explicit product and labor markets all characterized...... by monopolistic competition. An implicit assumption of barriers to entry justifies that the number of firms is fixed even when positive profits occur. It turns out that both market power of firms on the product markets and market power of unions on the labor markets make the occurrence of cycles more likely....... In particular, imperfect competition on the product markets and the positive profits associated with it may have the effect that there is a cycle even if the labor supply curve is increasing in the real-wage rate. For competitive cycles is required not only a decreasing labor supply curve, but a wage elasticity...

  17. Endogenous and Exogenous Natural Adjuvants for Vaccine Development.

    Science.gov (United States)

    Bolhassani, Azam; Talebi, Somayeh; Anvar, Ali

    2017-01-01

    Objective & Background: Various adjuvants are usually co-injected with an antigen for stimulation of effective immune responses. Adjuvants are able to elicit innate immune responses at the injection site. Depending on the activated type of innate responses, adjuvants can modify the quality and quantity of adaptive immune responses. Their mechanisms of action in vaccine development include: a) enhancement of the total antibody titers; b) reduction of the antigen dose; c) induction of potent cell-mediated immunity; d) increase in the speed and duration of the protective response; e) stimulation of mucosal immunity; and f) cross-protection. Up to now, different exogenous adjuvants have been identified to boost immune responses including inorganic compounds, mineral oil, bacterial products, non-bacterial organics, detergents or Quil A, plant saponins, Freund's complete or incomplete adjuvants, and delivery systems. However, some immune responses can be generated in the absence of the exogenous adjuvants. Indeed, endogenous adjuvants released from the cells were known as the danger signals and immunogenic compounds. Several main endogenous adjuvants contain cytokines, chemokines, alarmins, dendritic cells (DCs), toll like receptor (TLR) ligands or agonists, and antibodies. In this review, the immune activities of the natural adjuvants especially endogenous adjuvants and their mechanisms of action are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Induction of Biofilm Formation in the Betaproteobacterium Burkholderia unamae CK43B Exposed to Exogenous Indole and Gallic Acid

    Science.gov (United States)

    Kim, Dongyeop; Sitepu, Irnayuli R.

    2013-01-01

    Burkholderia unamae CK43B, a member of the Betaproteobacteria that was isolated from the rhizosphere of a Shorea balangeran sapling in a tropical peat swamp forest, produces neither indole nor extracellular polymeric substances associated with biofilm formation. When cultured in a modified Winogradsky's medium supplemented with up to 1.7 mM indole, B. unamae CK43B maintains its planktonic state by cell swelling and effectively degrades exogenous indole. However, in medium supplemented with 1.7 mM exogenous indole and 1.0 mM gallic acid, B. unamae CK43B produced extracellular polymeric substances and formed a biofilm. The concentration indicated above of gallic acid alone had no effect on either the growth or the differentiation of B. unamae CK43B cells above a certain concentration threshold, whereas it inhibited indole degradation by B. unamae CK43B to 3-hydroxyindoxyl. In addition, coculture of B. unamae CK43B with indole-producing Escherichia coli in nutrient-rich Luria-Bertani medium supplemented with 1.0 mM gallic acid led to the formation of mixed cell aggregates. The viability and active growth of B. unamae CK43B cells in a coculture system with Escherichia coli were evidenced by fluorescence in situ hybridization. Our data thus suggest that indole facilitates intergenus communication between indole-producing gammaproteobacteria and some indole-degrading bacteria, particularly in gallic acid-rich environments. PMID:23747701

  19. Applying Endogenous Knowledge in the African Context ...

    African Journals Online (AJOL)

    The question presented in this article is how to improve the dispute resolution competence of practitioners in Africa. The response offered involves enhancing the endogenous knowledge of a dispute and how to resolve it. This requires not only an understanding of what endogenous knowledge is, but also an alignment of ...

  20. Endogenous Peer Effects: Fact or Fiction?

    Science.gov (United States)

    Yeung, Ryan; Nguyen-Hoang, Phuong

    2016-01-01

    The authors examine endogenous peer effects, which occur when a student's behavior or outcome is a function of the behavior or outcome of his or her peer group. Endogenous peer effects have important implications for educational policies such as busing, school choice and tracking. In this study, the authors quantitatively review the literature on…

  1. Human endogenous retroviruses and ADHD.

    Science.gov (United States)

    Balestrieri, Emanuela; Pitzianti, Mariabernarda; Matteucci, Claudia; D'Agati, Elisa; Sorrentino, Roberta; Baratta, Antonia; Caterina, Rosa; Zenobi, Rossella; Curatolo, Paolo; Garaci, Enrico; Sinibaldi-Vallebona, Paola; Pasini, Augusto

    2014-08-01

    Several lines of evidences suggest that human endogenous retroviruses (HERVs) are implicated in the development of many complex diseases with a multifactorial aetiology and a strong heritability, such as neurological and psychiatric diseases. Attention deficit hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that results from a complex interaction of environmental, biological and genetic factors. Our aim was to analyse the expression levels of three HERV families (HERV-H, K and W) in patients with ADHD. The expression of retroviral mRNAs from the three HERV families was evaluated in peripheral blood mononuclear cells (PBMCs) from 30 patients with ADHD and 30 healthy controls by quantitative RT-PCR. The expression levels of HERV-H are significantly higher in patients with ADHD compared to healthy controls, while there are no differences in the expression levels of HERV-K and W. Since the ADHD aetiology is due to a complex interaction of environmental, biological and genetic factors, HERVs may represent one link among these factors and clinical phenotype of ADHD. A future confirmation of HERV-H overexpression in a larger number of ADHD patients will make possible to identify it as a new parameter for this clinical condition, also contributing to deepen the study on the role of HERVs in the neurodevelopment diseases.

  2. Mechanisms and Therapeutic Implications of Cell Death Induction by Indole Compounds

    International Nuclear Information System (INIS)

    Ahmad, Aamir; Sakr, Wael A.; Rahman, KM Wahidur

    2011-01-01

    Indole compounds, obtained from cruciferous vegetables, are well-known for their anti-cancer properties. In particular, indole-3-carbinol (I3C) and its dimeric product, 3,3′-diindolylmethane (DIM), have been widely investigated for their effectiveness against a number of human cancers in vitro as well as in vivo. These compounds are effective inducers of apoptosis and the accumulating evidence documenting their ability to modulate multiple cellular signaling pathways is a testimony to their pleiotropic behavior. Here we attempt to update current understanding on the various mechanisms that are responsible for the apoptosis-inducing effects by these compounds. The significance of apoptosis-induction as a desirable attribute of anti-cancer agents such as indole compounds cannot be overstated. However, an equally intriguing property of these compounds is their ability to sensitize cancer cells to standard chemotherapeutic agents. Such chemosensitizing effects of indole compounds can potentially have major clinical implications because these non-toxic compounds can reduce the toxicity and drug-resistance associated with available chemotherapies. Combinational therapy is increasingly being realized to be better than single agent therapy and, through this review article, we aim to provide a rationale behind combination of natural compounds such as indoles with conventional therapeutics

  3. Effect of CPPU on Carbohydrate and Endogenous Hormone Levels in Young Macadamia Fruit.

    Directory of Open Access Journals (Sweden)

    Hui Zeng

    Full Text Available N-(2-Chloro-4-pyridyl-N'-phenylurea (CPPU is a highly active cytokinin-like plant growth regulator that promotes chlorophyll biosynthesis, cell division, and cell expansion. It also increases fruit set and accelerates fruit enlargement. However, there has been no report about the effect of CPPU on fruit development and its physiological mechanism in macadamia. In this study, we investigated the effect of CPPU treatment at early fruit development via foliar spray or raceme soaking at 20 mg·L-1 on fruit set and related physiology in macadamia. Changes in carbohydrate contents and endogenous hormones in leaves, bearing shoots and fruit were also examined. Results showed that CPPU significantly reduced young fruit drop and delayed the wave of fruit drop by 1-2 weeks. The treatment significantly decreased the contents of total soluble sugars and starch in the leaves, but increased them in the bearing shoots and total soluble sugars in the husk (pericarp and seeds. These findings suggested that CPPU promoted carbohydrate mobilization from the leaves to the fruit. In addition, CPPU increased the contents of indole-3-acetic acid (IAA, gibberellin acid (GA3, and zeatin riboside (ZR and decreased the abscisic acid (ABA in the husk. Therefore, CPPU treatment reduced the early fruit drop by increasing carbohydrate availability and by modifying the balance among endogenous hormones.

  4. Gravity effects on endogenous movements

    Science.gov (United States)

    Johnsson, Anders; Antonsen, Frank

    Gravity effects on endogenous movements A. Johnsson * and F. Antonsen *+ * Department of Physics, Norwegian University of Science and Technology,NO-7491, Trond-heim, Norway, E-mail: anders.johnsson@ntnu.no + Present address: Statoil Research Center Trondheim, NO-7005, Trondheim, Norway Circumnutations in stems/shoots exist in many plants and often consists of more or less regular helical movements around the plumb line under Earth conditions. Recent results on circumnu-tations of Arabidopsis in space (Johnsson et al. 2009) showed that minute amplitude oscilla-tions exist in weightlessness, but that centripetal acceleration (mimicking the gravity) amplified and/or created large amplitude oscillations. Fundamental mechanisms underlying these results will be discussed by modeling the plant tissue as a cylinder of cells coupled together. As a starting point we have modeled (Antonsen 1998) standing waves on a ring of biological cells, as first discussed in a classical paper (Turing 1952). If the coupled cells can change their water content, an `extension' wave could move around the ring. We have studied several, stacked rings of cells coupled into a cylinder that together represent a cylindrical plant tissue. Waves of extensions travelling around the cylinder could then represent the observable circumnutations. The coupling between cells can be due to cell-to-cell diffusion, or to transport via channels, and the coupling can be modeled to vary in both longitudinal and transversal direction of the cylinder. The results from ISS experiments indicate that this cylindrical model of coupled cells should be able to 1) show self-sustained oscillations without the impact of gravity (being en-dogenous) and 2) show how an environmental factor like gravity can amplify or generate the oscillatory movements. Gravity has been introduced in the model by a negative, time-delayed feed-back transport across the cylinder. This represents the physiological reactions to acceler

  5. The role of bendamustine in the treatment of indolent non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Aldoss, Ibrahim T; Blumel, Susan M; Bierman, Philip J

    2009-01-01

    There is no consensus on recommendations for the treatment of relapsed and refractory indolent non-Hodgkin lymphoma (NHL). Bendamustine hydrochloride (bendamustine) has recently been approved for treatment of these patients. Bendamustine is a uniquely structured alkylating agent that lacks cross-resistance with other alkylators. This agent has a high degree of activity against a variety of tumor cell lines. Clinically, bendamustine has demonstrated activity against indolent NHL, chronic lymphocytic lymphoma, multiple myeloma and mantle cell lymphoma. Moreover, studies have validated its activity in patients with indolent NHL who are resistant to purine analogs and rituximab. The cytotoxic activity of bendamustine has been shown to be synergistic with rituximab in hematological malignancies. The incidence of alopecia is significantly less than with other alkylating agents. Myelosuppression is the major toxicity associated with bendamustine

  6. Outcome determinants for transformed indolent lymphomas treated with or without autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Madsen, Charlotte; Pedersen, Martin Bjerregård; Vase, Maja Ølholm

    2015-01-01

    either simultaneously or after a period of overt indolent disease. We also analyzed, whether prior rituximab treatment during the indolent course of the disease affected outcome after transformation. PATIENTS AND METHODS: Eighty-five patients (≤68 years) with histologically confirmed TIL were included...... at diagnosis (Composite/discordant TIL) and (iii) patients transformed after prolonged prior indolent disease (sequential TIL). RESULTS: Fifty-four patients (64%) received ASCT consolidation and 31 (36%) did not. Within the 'all TIL' cohort, the 5-year OS and PFS for R-chemo + ASCT versus R-chemo alone, were...... 67% versus 48% (P = 0.11) and 60% versus 30% (P = 0.02), respectively. Furthermore, in 'Composite/discordant TIL' R-chemo + ASCT showed no impact on OS (76% versus 67%; P = 0.66) or PFS (71% versus 62%; P = 0.54). Conversely, R-chemo + ASCT improved the outcome of 'sequential TIL' (OS 62% versus 36...

  7. Methylome-wide Sequencing Detects DNA Hypermethylation Distinguishing Indolent from Aggressive Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Bhasin

    2015-12-01

    Full Text Available A critical need in understanding the biology of prostate cancer is characterizing the molecular differences between indolent and aggressive cases. Because DNA methylation can capture the regulatory state of tumors, we analyzed differential methylation patterns genome-wide among benign prostatic tissue and low-grade and high-grade prostate cancer and found extensive, focal hypermethylation regions unique to high-grade disease. These hypermethylation regions occurred not only in the promoters of genes but also in gene bodies and at intergenic regions that are enriched for DNA-protein binding sites. Integration with existing RNA-sequencing (RNA-seq and survival data revealed regions where DNA methylation correlates with reduced gene expression associated with poor outcome. Regions specific to aggressive disease are proximal to genes with distinct functions from regions shared by indolent and aggressive disease. Our compendium of methylation changes reveals crucial molecular distinctions between indolent and aggressive prostate cancer.

  8. Identification and biochemical characterization of an Arabidopsis indole-3-acetic acid glucosyltransferase.

    Science.gov (United States)

    Jackson, R G; Lim, E K; Li, Y; Kowalczyk, M; Sandberg, G; Hoggett, J; Ashford, D A; Bowles, D J

    2001-02-09

    Biochemical characterization of recombinant gene products following a phylogenetic analysis of the UDP-glucosyltransferase (UGT) multigene family of Arabidopsis has identified one enzyme (UGT84B1) with high activity toward the plant hormone indole-3-acetic acid (IAA) and three related enzymes (UGT84B2, UGT75B1, and UGT75B2) with trace activities. The identity of the IAA conjugate has been confirmed to be 1-O-indole acetyl glucose ester. A sequence annotated as a UDP-glucose:IAA glucosyltransferase (IAA-UGT) in the Arabidopsis genome and expressed sequence tag data bases given its similarity to the maize iaglu gene sequence showed no activity toward IAA. This study describes the first biochemical analysis of a recombinant IAA-UGT and provides the foundation for future genetic approaches to understand the role of 1-O-indole acetyl glucose ester in Arabidopsis.

  9. Indole Compounds Related to Auxins and Goitrogens of Woad (Isatis tinctoria L.).

    Science.gov (United States)

    Elliott, M C; Stowe, B B

    1971-03-01

    Five conspicuous indole derivatives are present in leaves and other tissues of woad (Isatis tinctoria L.). They were identified as tryptophan, isatan B, glucobrassicin, neoglucobrassicin, and glucobrassicin-1-sulfonate. The latter three indole glucosinolates are present at levels of at least 260, 69, and 200 milligrams per kilogram fresh weight and were isolated as crystalline salts. Comparison of physical and chemical properties, particularly NMR spectral analysis, confirms that the 1-methoxyglucobrassicin structure suggested for neoglucobrassicin is correct, whereas further evidence for the even more unusual sulfonation of the ring nitrogen in glucobrassicin-1-sulfonate was obtained. Glucobrassicin-1-sulfonate has an enzymic degradation pattern identical to that of glucobrassicin. As it too releases thiocyanate, it must be added to the list of known plant goitrogens. These studies and the techniques described establish woad as exceptionally suitable higher plant material for metabolic studies of indoles related to goitrogens and auxins.

  10. Indole Compounds Related to Auxins and Goitrogens of Woad (Isatis tinctoria L.) 1

    Science.gov (United States)

    Elliott, Malcolm C.; Stowe, Bruce B.

    1971-01-01

    Five conspicuous indole derivatives are present in leaves and other tissues of woad (Isatis tinctoria L.). They were identified as tryptophan, isatan B, glucobrassicin, neoglucobrassicin, and glucobrassicin-1-sulfonate. The latter three indole glucosinolates are present at levels of at least 260, 69, and 200 milligrams per kilogram fresh weight and were isolated as crystalline salts. Comparison of physical and chemical properties, particularly NMR spectral analysis, confirms that the 1-methoxyglucobrassicin structure suggested for neoglucobrassicin is correct, whereas further evidence for the even more unusual sulfonation of the ring nitrogen in glucobrassicin-1-sulfonate was obtained. Glucobrassicin-1-sulfonate has an enzymic degradation pattern identical to that of glucobrassicin. As it too releases thiocyanate, it must be added to the list of known plant goitrogens. These studies and the techniques described establish woad as exceptionally suitable higher plant material for metabolic studies of indoles related to goitrogens and auxins. PMID:16657624

  11. Controlled indole-3-acetaldoxime production through ethanol-induced expression of CYP79B2

    DEFF Research Database (Denmark)

    Mikkelsen, M.D.; Fuller, V.L.; Hansen, Bjarne Gram

    2009-01-01

    Indole-3-acetaldoxime (IAOx) is a key branching point between primary and secondary metabolism. IAOx serves as an intermediate in the biosynthesis of indole glucosinolates (I-GLSs), camalexin and the plant hormone indole-3-acetic acid (IAA). The cytochrome P450s CYP79B2 and CYP79B3 catalyze......OH)-inducible CYP79B2 construct into double (cyp79b2 cyp79b3) or triple (cyp79b2 cyp79b3 cyp83b1) mutant lines. We show EtOH-dependent induction of camalexin and identify a number of candidate IAA homeostasis- or defense-related genes by clustered microarray analysis. The transgenic mutant lines are thus promising...

  12. Bendamustine HCL for the treatment of relapsed indolent non-Hodgkin’s lymphoma

    Directory of Open Access Journals (Sweden)

    Rudolf Weide

    2008-09-01

    Full Text Available Rudolf WeidePraxisklinik für Hämatologie und Onkologie, Koblenz, GermanyAbstract: Bendamustine is an alkylating agent which also shows properties of a purine analog. Because of its unique mechanism of action it shows activity in relapsed indolent lymphomas which are resistant to alkylating agents, purine analogs, and rituximab. Bendamustine has a favorable toxicity profile causing no alopecia and only a moderate hematotoxicity and gastrointestinal toxicity. Combinations of bendamustine with mitoxantrone and rituximab and with rituximab alone have been shown to be highly active in relapsed/refractory indolent lymphomas and mantle cell lymphomas achieving long lasting complete remissions. Because of only moderate toxicity these combinations can be applied safely in elderly patients who can be treated in an outpatient setting.Keywords: bendamustine, relapsed-indolent, non-Hodgkin’s lymphoma

  13. Cutaneous and subcutaneous Ewing's sarcoma: an indolent disease

    International Nuclear Information System (INIS)

    Chow, Edward; Merchant, Thomas E.; Pappo, Alberto; Jenkins, Jesse J.; Shah, Amit B.; Kun, Larry E.

    2000-01-01

    has developed local recurrence or distant metastasis. Several of the patients developed treatment-related sequelae, including veno-occlusive disease of the lung and hemorrhagic cystitis (1), myelodysplastic syndrome (1), chemotherapy-induced ovarian failure (1), moist desquamation (1), and dermatofibroma within the radiotherapy volumes (1). Conclusions: Cutaneous and subcutaneous ES are associated with an indolent course and a favorable prognosis when treated with combined modality therapy. Elimination of radiation therapy following complete resection has been tested in the POG 9354 trial. The high rate of local control, low rate of metastatic disease, and excellent overall outcome may suggest a role for less intensive chemotherapy, as well as tailoring to diminish or avoid radiation therapy in completely resected cases, with a goal to minimize toxicity while maintaining a high cure rate

  14. Synthesis and evaluation of the plant growth regulator property of indolic compounds derived from safrole

    International Nuclear Information System (INIS)

    Marchi, Irineu; Rebelo, Ricardo Andrade; Rosa, Flavia A. Fernandes da; Maiochi, Riceli A.

    2007-01-01

    The present work describes the use of piperonal, a derivative of the secondary metabolite safrole, for the synthesis of new 5,6-methylenedioxy substituted indole carboxylic acids structurally related to the indol-3-yl-acetic acid (AIA, I). The route comprises six steps beginning with piperonal with an overall yield of 19%. Compound IX was tested towards its plant growth regulator properties in bioassays specific for auxine activity. The in vitro assays were performed in a germination chamber and were of two types: root growth in germinated seeds of Lactuca sativa, Cucumbis sativus and Raphanus sativus and peciole biotest using Phaseolus vulgaris. (author)

  15. A new natural auaternary indole slkaloid isolated from Tabernaemontana laeta Mart. (Apocynaceae

    Directory of Open Access Journals (Sweden)

    Medeiros Walter L. B.

    2001-01-01

    Full Text Available A new natural quaternary alkaloid, Nb-methylvoachalotine (1, was obtained from the root bark of Tabernaemontana laeta together with three dimeric indole alkaloids, conodurine (2, voacamine (3 and tabernamine (4, and the monomeric indole alkaloids 19S-heyneanine (5, coronaridine (6 and voacangine (7. The known triterpenes alpha-amyrin acetate, beta-amyrin acetate, lupeol acetate and taraxasterol acetate and the phytosterol beta-sitosterol and its 3-O-beta-D-glucoside were also identified. The structures of the compounds were elucidated based on spectroscopic studies.

  16. Extending the versatility of the Hemetsberger-Knittel indole synthesis through microwave and flow chemistry.

    Science.gov (United States)

    Ranasinghe, Nadeesha; Jones, Graham B

    2013-03-15

    Microwave, flow and combination methodologies have been applied to the synthesis of a number of substituted indoles. Based on the Hemetsberger-Knittel (HK) process, modifications allow formation of products rapidly and in high yield. Adapting the methodology allows formation of 2-unsubstituted indoles and derivatives, and a route to analogs of the antitumor agent PLX-4032 is demonstrated. The utility of the HK substrates is further demonstrated through bioconjugation and subsequent ring closure and via Huisgen type [3+2] cycloaddition chemistry, allowing formation of peptide adducts which can be subsequently labeled with fluorine tags. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Rauvomines A and B, Two Monoterpenoid Indole Alkaloids from Rauvolfia vomitoria.

    Science.gov (United States)

    Zeng, Jun; Zhang, Dong-Bo; Zhou, Pan-Pan; Zhang, Qi-Li; Zhao, Lei; Chen, Jian-Jun; Gao, Kun

    2017-08-04

    Two unusual normonoterpenoid indole alkaloids rauvomine A (1) and rauvomine B (2), together with two known compounds peraksine (3) and alstoyunine A (4), were isolated from the aerial parts of Rauvolfia vomitoria. The structures with absolute configurations of 1 and 2 were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound 2 is a novel C 18 normonoterpenoid indole alkaloid with a substituted cyclopropane ring that forms an unusual 6/5/6/6/3/5 hexcyclic rearranged ring system. The plausible biogenetic pathways of 1 and 2 were proposed. Compound 2 exhibited significant anti-inflammatory activity.

  18. Mass Spectrometric Characteristics of Prenylated Indole Derivatives from Marine-Derived Penicillium sp. NH-SL.

    Science.gov (United States)

    Ding, Hui; Ding, Wanjing; Ma, Zhongjun

    2017-03-22

    Two prenylated indole alkaloids were isolated from the ethyl acetate extracts of a marine-derived fungus Penicillium sp. NH-SL and one of them exhibited potent cytotoxic activity against mouse hepa 1c1c7 cells. In order to detect other bioactive analogs, we used liquid chromatogram tandem mass spectrometry (LC-MS/MS) to analyze the mass spectrometric characteristics of the isolated compounds as well as the crude extracts. As a result, three other analogs were detected, and their structures were deduced according to the similar fragmentation patterns. This is the first systematic report on the mass spectrometric characteristics of prenylated indole derivatives.

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

    Directory of Open Access Journals (Sweden)

    Paul P. Kelly

    2015-09-01

    Full Text Available 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.

  20. A review on indole alkaloids isolated from Uncaria rhynchophylla and their pharmacological studies.

    Science.gov (United States)

    Ndagijimana, Andre; Wang, Xiaoming; Pan, Guixiang; Zhang, Fan; Feng, Hong; Olaleye, Olajide

    2013-04-01

    Uncaria rhynchophylla (Miq.) Jacks, Rubiaceae, is one of the original plants of the important Chinese crude drug, Gou-teng, mainly used for the treatment of convulsion, hypertension, epilepsy, eclampsia, and cerebral diseases. The pharmacological activities of this plant are related to the presence of active compounds predominantly indole alkaloids. In this article, we have reviewed some reports about the pharmacological activities of the main indole alkaloids isolated from U. rhynchophylla. This review paper will contribute to the studies on the chemistry, safety and quality control of medicinal preparations containing Uncaria species. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. AMT (3-(2-aminopropyl)indole) and 5-IT (5-(2-aminopropyl)indole): an analytical challenge and implications for forensic analysis.

    Science.gov (United States)

    Elliott, Simon P; Brandt, Simon D; Freeman, Sally; Archer, Roland P

    2013-03-01

    5-(2-Aminopropyl)indole (5-IT) and 3-(2-aminopropyl)indole (α-methyltryptamine, AMT) are isomeric substances and their differentiation can be a challenge under routine analytical conditions, especially when reference material is unavailable. 5-IT represents a very recent addition to the battery of new psychoactive substances that are commercially available from online retailers. This report illustrates how subtle differences observed under mass spectral and UV conditions can help to facilitate the differentiation between the two isomers. Analyses included (1)  H and (13) C NMR, GC-EI/CI ion trap MS, applications of several U/HPLC-DAD and HPLC-MS methods. Investigations currently underway also highlight the confirmation that AMT was detected in a number of fatal intoxications. These findings also demonstrate that there is a potential risk of misidentification when dealing with both substances. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Contagion risk in endogenous financial networks

    International Nuclear Information System (INIS)

    Li, Shouwei; Sui, Xin

    2016-01-01

    Highlights: • We propose an endogenous financial network model. • Endogenous networks include interbank networks, inter-firm networks and bank-firm networks. • We investigate contagion risk in endogenous financial networks. - Abstract: In this paper, we investigate contagion risk in an endogenous financial network, which is characterized by credit relationships connecting downstream and upstream firms, interbank credit relationships and credit relationships connecting firms and banks. The findings suggest that: increasing the number of potential lenders randomly selected can lead to an increase in the number of bank bankruptcies, while the number of firm bankruptcies presents a trend of increase after the decrease; after the intensity of choice parameter rises beyond a threshold, the number of bankruptcies in three sectors (downstream firms, upstream firms and banks) shows a relatively large margin of increase, and keeps at a relatively high level; there exists different trends for bankruptcies in different sectors with the change of the parameter of credits’ interest rates.

  3. Endogenous Money, Output and Prices in India

    OpenAIRE

    Das, Rituparna

    2009-01-01

    This paper proposes to quantify the macroeconometric relationships among the variables broad money, lending by banks, price, and output in India using simultaneous equations system keeping in view the issue of endogeneity.

  4. Some observations about the endogenous money theory

    OpenAIRE

    Bertocco Giancarlo

    2006-01-01

    The endogenous money theory constitutes the core element of the post-keynesian monetary theory. The first formulation of this theory can be found in the works of Kaldor published in the 1970s. Taking these studies as a starting point, the post-keynesians elaborated two versions of the endogenous money theory which differ in their assumptions about the behaviour of the monetary authorities and the banking system, and hence offer different conclusions about the slope of the money supply curve. ...

  5. Invasive fungal infections in endogenous Cushing's syndrome

    Science.gov (United States)

    Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

    2010-01-01

    Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

  6. Endogenous Money Supply and Money Demand

    OpenAIRE

    Woon Gyu Choi; Seonghwan Oh

    2000-01-01

    This paper explores the behavior of money demand by explicitly accounting for the money supply endogeneity arising from endogenous monetary policy and financial innovations. Our theoretical analysis indicates that money supply factors matter in the money demand function when the money supply partially responds to money demand. Our empirical results with U.S. data provide strong evidence for the relevance of the policy stance to the demand for MI under a regime in which monetary policy is subs...

  7. Ciliary neurotrophic factor is an endogenous pyrogen.

    Science.gov (United States)

    Shapiro, L; Zhang, X X; Rupp, R G; Wolff, S M; Dinarello, C A

    1993-09-15

    Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) following intravenous injection; CNTF fever was blocked by pretreatment with indomethacin. The fever induced by CNTF was not due to contaminating endotoxins. Increasing doses of CNTF resulted in prolongation of the fever, suggesting the subsequent induction of additional endogenous pyrogenic activity. After passive transfer of plasma obtained during CNTF-induced fever, endogenous pyrogen activity was not present in the circulation; CNTF also did not induce the endogenous pyrogens interleukin 1, tumor necrosis factor, or interleukin 6 in vitro. Nevertheless, a second endogenous pyrogen may originate within the central nervous system following the systemic injection of CNTF. Of the four endogenous pyrogens described to date (interleukin 1, tumor necrosis factor, interferon, and interleukin 6), CNTF, like interleukin 6, utilizes the cell-surface gp 130 signal-transduction apparatus.

  8. Reappraisal of nodal Epstein-Barr Virus-negative cytotoxic T-cell lymphoma: identification of indolent CD5+ diseases.

    Science.gov (United States)

    Yamashita, Daisuke; Shimada, Kazuyuki; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Kohno, Kei; Satou, Akira; Sakakibara, Ayako; Nakamura, Shigeo; Asano, Naoko; Kato, Seiichi

    2018-05-29

    Nodal cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (CTL) has recently been recognized as a clinicopathologically distinct disease. To further characterize this disease, here we compared 58 patients with Epstein-Barr virus (EBV)-negative CTL to 48 patients with EBV-positive CTL. The two groups did not differ in histopathology, T-cell receptor (TCR) expression or rearrangement incidences, or survival curves. However, patients with EBV-negative CTL less frequently showed hepatic involvement (P = 0.007), B symptoms (P = 0.020), hemophagocytosis (P = 0.024), and detectable CD4 (P = 0.002) and CD5 (P = 0.009). Univariate and multivariate analyses identified three factors that independently predicted favorable survival, onset age diseases: CD5 + TCRαβ (n = 13), and CD5 + NK-cell type lacking TCR expression or clonal TCRγ rearrangement (n = 4). The survival curves for these two groups were significantly superior to others (n = 29, P diseases appear to be unique in their indolent clinical behavior, and should be managed differently from other diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Indole alkaloids and terpenoids from Tabernaemontana markgrafiana

    DEFF Research Database (Denmark)

    Nielsen, H.B.; Hazell, A.; Hazell, R.

    1994-01-01

    The bark of Tabernaemontana markgrafiana yielded five acetylated pentacyclic triterpenes and 24 monoterpene indole alkaloids. The major triterpene was baurenyl acetate, which constituted ca 6% of the crude petrol extract. An X-ray study of iso-ursenyl acetate was carried out for the first time...

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

    Science.gov (United States)

    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.

  11. Distribution of indole in tissues of dairy cattle, swine, and laying pullets

    International Nuclear Information System (INIS)

    Eisele, G.R.

    1986-01-01

    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 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

  12. Catalytic α-arylation of imines leading to N-unprotected indoles and azaindoles

    KAUST Repository

    Marelli, Enrico

    2016-03-30

    A Palladium-N-heterocyclic carbene-catalyzed methodology for the synthesis of substituted, N-unprotected indoles and azaindoles is reported. The protocol permits access to various, highly substituted members of these classes of compounds. Although two possible reactions pathways (deprotonative and Heck-like) can be proposed, control experiments, supported by computational studies, point towards a deprotonative mechanism being operative.

  13. Taichunamides: Prenylated Indole Alkaloids from Aspergillus taichungensis (IBT 19404)

    DEFF Research Database (Denmark)

    Kagiyama, Ippei; Kato, Hikaru; Nehira, Tatsuo

    2016-01-01

    Seven new prenylated indole alkaloids, taichunamides A–G, were isolated from the fungus Aspergillus taichungensis (IBT 19404). Taichunamides A and B contained an azetidine and 4‐pyridone units, respectively, and are likely biosynthesized from notoamide S via (+)‐6‐epi‐stephacidin A. Taichunamides...... these cores within the three species likely arise from an intramolecular hetero Diels–Alder reaction....

  14. Anti-Toxoplasma Activity of 2-(Naphthalene-2-γlthiol-1H Indole.

    Directory of Open Access Journals (Sweden)

    Qasem Asgari

    2015-06-01

    Full Text Available This study was undertaken to evaluate the viability, infectivity and immunity of Toxoplasma gondii tachyzoites exposed to 2-(naphthalene-2-ylthio-1H-indole.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.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.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.

  15. A facile synthesis of 1,2,3-triazolyl indole hybrids via SbCl3 ...

    Indian Academy of Sciences (India)

    Ponnuswamy A and Jagatheesan R 2011 Acta Cryst. E67 o2707. 27. Fun H K, Hemamalini M, Shanmugavelan P,. Ponnuswamy A and Jagatheesan R 2011 Acta Cryst. E67 o2776. 28. Sundberg R J 1996 The Chemistry of Indoles, New York: Academic Press 113. 29. (a) Saxton J E 1997 Nat. Prod. Rep. 14 559; (b) Toyota.

  16. Gene expression analysis predicts insect venom anaphylaxis in indolent systemic mastocytosis

    NARCIS (Netherlands)

    Niedoszytko, M.; Bruinenberg, M.; van Doormaal, J. J.; de Monchy, J. G. R.; Nedoszytko, B.; Koppelman, G. H.; Nawijn, M. C.; Wijmenga, C.; Jassem, E.; Oude Elberink, J. N. G.

    P>Background: Anaphylaxis to insect venom (Hymenoptera) is most severe in patients with mastocytosis and may even lead to death. However, not all patients with mastocytosis suffer from anaphylaxis. The aim of the study was to analyze differences in gene expression between patients with indolent

  17. Simple and efficient Knoevenagel synthesis of (E)-2-((1H-indol-3-yl ...

    Indian Academy of Sciences (India)

    Simple and efficient Knoevenagel synthesis of (E)-2-((1H-indol-3-yl) ... there has been a growing interest in Knoevenagel prod- ucts because many of them have ..... providing financial support and to the authorities of. Jawaharlal Nehru ...

  18. High resolution mass spectrometry studies of sulforaphane and indole-3-carbinol in broccoli.

    Science.gov (United States)

    Kokotou, Maroula G; Revelou, Panagiota-Kyriaki; Pappas, Christos; Constantinou-Kokotou, Violetta

    2017-12-15

    Broccoli is a rich source of bioactive compounds. Among them, sulforaphane and indole-3-carbinol have attracted a lot of attention, since their consumption is associated with reduced risk of cancer. In this work, the development of an efficient and direct method for the simultaneous determination of sulforaphane and indole-3-carbinol in broccoli using UPLC-HRMS/MS is described. The correlation coefficient, and limits of detection (LOD) and quantification (LOQ) were 0.993, 0.77mg/L and 2.35mg/L for sulforaphane and 0.997, 0.42mg/L, 1.29mg/L for indole-3-carbinol, respectively. The content of sulforaphane and indole-3-carbinol varied between 72±9-304±2mg and 77±1-117±3mg per 100g of fresh florets, respectively. Taking into consideration the differences in cultivar, geography, season and environmental factors, the results agreed with values published in the literature using other techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Inductive effect of methyl group in a series of methylated indoles: A ...

    Indian Academy of Sciences (India)

    Vol. 125, No. 4, July 2013, pp. 905–912. c Indian Academy of Sciences. Inductive effect of methyl group in a series of methylated indoles: A graph theoretical analysis in the light of density functional theory and correlation with experimental charge transfer transition energies. AMIT S TIWARYa,∗ and ASOK K MUKHERJEEb.

  20. Catalytic α-arylation of imines leading to N-unprotected indoles and azaindoles

    KAUST Repository

    Marelli, Enrico; Corpet, Martin; Minenkov, Yury; Neyyappadath, Rifahath; Bismuto, Alessandro; Buccolini, Giulia; Curcio, Massimiliano; Cavallo, Luigi; Nolan, Steven P.

    2016-01-01

    A Palladium-N-heterocyclic carbene-catalyzed methodology for the synthesis of substituted, N-unprotected indoles and azaindoles is reported. The protocol permits access to various, highly substituted members of these classes of compounds. Although two possible reactions pathways (deprotonative and Heck-like) can be proposed, control experiments, supported by computational studies, point towards a deprotonative mechanism being operative.

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

    Science.gov (United States)

    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.

  2. Simple synthesis of pyrrolo[3,2-e]indole-1-carbonitriles

    Directory of Open Access Journals (Sweden)

    Adam Trawczyński

    2013-05-01

    Full Text Available Alkylation of 5-nitroindol-4-ylacetonitriles with ethyl chloroacetate, α-halomethyl ketones, and chloroacetonitrile followed by a treatment of the products with chlorotrimethylsilane in the presence of DBU gives 1-cyanopyrrolo[3,2-e]indoles substituted in position 2 with electron-withdrawing groups.

  3. Moessbauer studies of iron(III)-(indole-3-alkanoic acids) systems in frozen aqueous solutions

    International Nuclear Information System (INIS)

    Kovacs, K.; Kuzmann, E.; Homonnay, Z.; Szilagyi, P.A.; Vertes, A.; Kamnev, A.A.; Sharma, V.K.

    2005-01-01

    Moessbauer investigations of iron(III) salts in aqueous solutions in the presence of indole-3-alkanoic acid ligands are described. The measurements showed two parallel reactions between the ligands and ferric ions: a complex formation and a redox process. The oxidation process takes place in the ligands, and a part of Fe 3+ is reduced to Fe 2+ . (author)

  4. Validation of a multi-analyte HPLC-DAD method for determination of uric acid, creatinine, homovanillic acid, niacinamide, hippuric acid, indole-3-acetic acid and 2-methylhippuric acid in human urine.

    Science.gov (United States)

    Remane, Daniela; Grunwald, Soeren; Hoeke, Henrike; Mueller, Andrea; Roeder, Stefan; von Bergen, Martin; Wissenbach, Dirk K

    2015-08-15

    During the last decades exposure sciences and epidemiological studies attracts more attention to unravel the mechanisms for the development of chronic diseases. According to this an existing HPLC-DAD method for determination of creatinine in urine samples was expended for seven analytes and validated. Creatinine, uric acid, homovanillic acid, niacinamide, hippuric acid, indole-3-acetic acid, and 2-methylhippuric acid were separated by gradient elution (formate buffer/methanol) using an Eclipse Plus C18 Rapid Resolution column (4.6mm×100mm). No interfering signals were detected in mobile phase. After injection of blank urine samples signals for the endogenous compounds but no interferences were detected. All analytes were linear in the selected calibration range and a non weighted calibration model was chosen. Bias, intra-day and inter-day precision for all analytes were below 20% for quality control (QC) low and below 10% for QC medium and high. The limits of quantification in mobile phase were in line with reported reference values but had to be adjusted in urine for homovanillic acid (45mg/L), niacinamide 58.5(mg/L), and indole-3-acetic acid (63mg/L). Comparison of creatinine data obtained by the existing method with those of the developed method showing differences from -120mg/L to +110mg/L with a mean of differences of 29.0mg/L for 50 authentic urine samples. Analyzing 50 authentic urine samples, uric acid, creatinine, hippuric acid, and 2-methylhippuric acid were detected in (nearly) all samples. However, homovanillic acid was detected in 40%, niacinamide in 4% and indole-3-acetic acid was never detected within the selected samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Indole compounds in some culinary-medicinal higher basidiomycetes from Poland.

    Science.gov (United States)

    Muszynska, Bozena; Sutkowska-Ziaja, Katarzyna; Ekiert, Halina

    2011-01-01

    Methanolic extracts of two species collected from natural habitats in Poland, Boletus edulis and Suillus luteus, and one species from a commercial source, Pleurotus ostreatus, were analyzed for the presence of non-hallucinogenic indole compounds. The contents of indole compounds in these species were both qualitatively and quantitatively diverse, ranging from 0.01 to 34.11 mg/100 g d.w. Two of 11 tested indole compounds, 5-hydroxytryptophan (0.18, 2.08, 1.63 mg/100 g d.w.) and serotonin (6.52, 10.14, 34.11 mg/100 g d.w.), were present in all three species under study. B. edulis and S. luteus were found to contain L-tryptophan (0.39 and 2.61 mg/100g d.w.) and melatonin (0.68 and 0.71 mg/100 g d.w.). Tryptamine was present in two species, i.e., B. edulis (1.17 mg/100 g d.w.) and in P. ostreatus (0.91 mg/100 g d.w.), in which slight amounts of indole acetonitrile (0.04 and 0.01 mg/100 g d.w., respectively) were also identified. Indoleacetic acid was a common metabolite for P. ostreatus and S. luteus and its contents amounted to 0.21 and 0.04 mg/100 g d.w., respectively. Indole compounds degradation products kynurenic acid (2.63 mg/100 g d.w.) and kynurenine sulfate were (19.57 mg/100 g d.w.) were observed only in S. luteus.

  6. An indole-deficient Escherichia coli strain improves screening of cytochromes P450 for biotechnological applications.

    Science.gov (United States)

    Brixius-Anderko, Simone; Hannemann, Frank; Ringle, Michael; Khatri, Yogan; Bernhardt, Rita

    2017-05-01

    Escherichia coli has developed into an attractive organism for heterologous cytochrome P450 production, but, in some cases, was restricted as a host in view of a screening of orphan cytochromes P450 or mutant libraries in the context of molecular evolution due to the formation of the cytochrome P450 inhibitor indole by the enzyme tryptophanase (TnaA). To overcome this effect, we disrupted the tnaA gene locus of E. coli C43(DE3) and evaluated the new strain for whole-cell substrate conversions with three indole-sensitive cytochromes P450, myxobacterial CYP264A1, and CYP109D1 as well as bovine steroidogenic CYP21A2. For purified CYP264A1 and CYP21A2, the half maximal inhibitory indole concentration was determined to be 140 and 500 μM, which is within the physiological concentration range occurring during cultivation of E. coli in complex medium. Biotransformations with C43(DE3)_∆tnaA achieved a 30% higher product formation in the case of CYP21A2 and an even fourfold increase with CYP264A1 compared with C43(DE3) cells. In whole-cell conversion based on CYP109D1, which converts indole to indigo, we could successfully avoid this reaction. Results in microplate format indicate that our newly designed strain is a suitable host for a fast and efficient screening of indole-influenced cytochromes P450 in complex medium. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  7. Dynamic Modeling of Indole Glucosinolate Hydrolysis and Its Impact on Auxin Signaling

    Directory of Open Access Journals (Sweden)

    Daniel Vik

    2018-04-01

    Full Text Available Plants release chemicals to deter attackers. Arabidopsis thaliana relies on multiple defense compounds, including indol-3-ylmethyl glucosinolate (I3G, which upon hydrolysis initiated by myrosinase enzymes releases a multitude of bioactive compounds, among others, indole-3-acetonitrile and indole-3-acetoisothiocyanate. The highly unstable isothiocyanate rapidly reacts with other molecules. One of the products, indole-3-carbinol, was reported to inhibit auxin signaling through binding to the TIR1 auxin receptor. On the contrary, the nitrile product of I3G hydrolysis can be converted by nitrilase enzymes to form the primary auxin molecule, indole-3-acetic acid, which activates TIR1. This suggests that auxin signaling is subject to both antagonistic and protagonistic effects of I3G hydrolysis upon attack. We hypothesize that I3G hydrolysis and auxin signaling form an incoherent feedforward loop and we build a mathematical model to examine the regulatory network dynamics. We use molecular docking to investigate the possible antagonistic properties of different I3G hydrolysis products by competitive binding to the TIR1 receptor. Our simulations reveal an uncoupling of auxin concentration and signaling, and we determine that enzyme activity and antagonist binding affinity are key parameters for this uncoupling. The molecular docking predicts that several I3G hydrolysis products strongly antagonize auxin signaling. By comparing a tissue disrupting attack – e.g., by chewing insects or necrotrophic pathogens that causes rapid release of I3G hydrolysis products – to sustained cell-autonomous I3G hydrolysis, e.g., upon infection by biotrophic pathogens, we find that each scenario gives rise to distinct auxin signaling dynamics. This suggests that plants have different defense versus growth strategies depending on the nature of the attack.

  8. An electrochemical sensor for indole in plasma based on MWCNTs-chitosan modified screen-printed carbon electrode.

    Science.gov (United States)

    Jin, Mingchao; Zhang, Xiaoqing; Zhen, Qianna; He, Yifan; Chen, Xiao; Lyu, Wenjing; Han, Runchuan; Ding, Min

    2017-12-15

    Indole is an essential metabolite in intestinal tract. The dysregulation of plasma indole concentration occurred in various diseases. In this study, the indole in plasma was determined directly using electrochemical sensor with multiwall carbon nanotubes-chitosan (MWCNTs-CS) modified screen-printed carbon electrode (SPCE). The electrochemical behavior of indole was elucidated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) on the MWCNTs-CS composites modified SPCE (MWCNTs-CS/SPCE). The results showed that the current responses of indole improved greatly due to the high catalytic activity and electron transfer reaction of nano-composites. Under the optimized conditions, the linear range of indole was from 5 to 100μgL -1 with the detection limit of 0.5μgL -1 (S/N = 3). This novel electrochemical sensor exhibited acceptable accuracies and precisions with the variations less than 7.3% and 9.0%, respectively. Furthermore, high performance liquid chromatography (HPLC) method was utilized to compare with the established electrochemical method for the determination of indole in plasma. The results showed a high correlation between the two methods. At last, the electrochemical sensor was successfully applied to detect the level of indole in plasma samples with satisfactory selectivity and sensitivity. The concentrations of plasma indole in healthy pregnant women and gestational diabetes mellitus (GDM) patients were 5.3 (4.1-7.0)μgL -1 and 7.2 (4.5-9.4)μgL -1 , respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Host-virus interactions of mammalian endogenous retroviruses

    OpenAIRE

    Farkašová, Helena

    2017-01-01

    Endogenous retroviruses (ERVs) originate by germline infection and subsequent mendelian inheritance of their exogenous counterparts. With notable exceptions, all mammalian ERVs are evolutionarily old and fixed in the population of its host species. Some groups of retroviruses were believed not to be able to form endogenous copies. We discovered an additional endogenous Lentivirus and a first endogenous Deltaretrovirus. Both of these groups were previously considered unable to form endogenous ...

  10. [The endogenous opioid system and drug addiction].

    Science.gov (United States)

    Maldonado, R

    2010-01-01

    Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits. Several neurotransmitters, including the endogenous opioid system are involved in these changes. The opioid system plays a pivotal role in different aspects of addiction. Thus, opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within the reward circuits. Opioid receptors and peptides are selectively involved in several components of the addictive processes induced by opioids, cannabinoids, psychostimulants, alcohol and nicotine. This review is focused on the contribution of each component of the endogenous opioid system in the addictive properties of the different drugs of abuse. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  11. Endogenous vs. exogenous regulations in the commons

    DEFF Research Database (Denmark)

    Abatayo, Anna Lou; Lynham, John

    2016-01-01

    It is widely believed that there is strong experimental evidence to support the idea that exogenously imposed regulations crowd out the intrinsic motivations of common pool resource (CPR) users to refrain from over-harvesting. We introduce a novel experimental design that attempts to disentangle...... potential confounds in previous experiments. A key feature of our experimental design is to have the exact same regulations chosen endogenously as those that are imposed exogenously. When we compare the same regulations chosen endogenously to those externally imposed, we observe no differences in extraction...... endogenous regulations with communication and exogenous regulations without communication. Our results suggest that externally imposed regulations do not crowd out intrinsic motivations in the lab and they confirm that communication facilitates cooperation to reduce extraction....

  12. The synthesis of [3H]-indole-3-carbinol, a natural anti-carcinogen from cruciferous vegetables

    International Nuclear Information System (INIS)

    Dashwood, R.H.; Uyetake, Lyle; Fong, A.T.; Hendricks, J.D.; Bailey, G.S.

    1989-01-01

    Indole-3-carbinol is a natural anti-carcinogen found as a glucosinolate in cruciferous vegetables such as cabbage, cauliflower and broccoli. A complete understanding of the mechanisms of anti-carcinogenesis by this dietary inhibitor requires improved insight into the disposition and metabolic fate of indole-3-carbinol in vivo. Such metabolic studies have been hampered by the lack of a commercial source of radiolabelled compound. This provided the main impetus for the work reported here, the synthesis of 5-[ 3 H]-indole-3-carbinol from 5-bromoindole. (author)

  13. Uso del 3-(2-isotiocianatoetil)-5-metoxi-1H-indol para el tratamiento de enfermedades neurodegenerativas

    OpenAIRE

    León Martínez, Rafael; Egea Maiquez, Javier; Buendía Abaitua, Izaskun; Parada, Esther; Navarro, Elisa

    2013-01-01

    La presente invención se refiere al uso del 3-(2- isotiocianatoetil)-5-metoxi-1H-indol o de una composición que comprende el 3-(2-isotiocianatoetil)- 5-metoxi-1H-indol para el tratamiento de enfermedades que cursan con declive de la capacidad cognitiva o motoras secundarias a degeneración neuronal. La presente invención también se refiere al uso del 3-(2-isotiocianatoetil)-5- metoxi-1H-indol para el tratamiento de otras enfermedades neurodegenerativas que c...

  14. Further brominated bis- and tris-indole alkaloids from the deep-water New Caledonian marine sponge Orina Sp.

    Science.gov (United States)

    Bifulco, G; Bruno, I; Riccio, R; Lavayre, J; Bourdy, G

    1995-08-01

    Two tris-indole alkaloids, (+/-) gelliusines A and B [1], have been isolated for the first time from a marine source, the New Caledonian sponge, Orina sp. (or Gellius sp.), along with five further indole constituents [2-6]. Compound 6 has been identified as 2,2-bis-(6'-bromo-3'-indolyl(-ethylamine, previously isolated from the tunicate Didemnum candidum, but the remaining four indoles [2-5] are novel compounds. These showed anti-serotonin activity and a strong affinity for somatostatin and neuropeptide Y receptors in receptor-binding assays.

  15. The synthesis of ( sup 3 H)-indole-3-carbinol, a natural anti-carcinogen from cruciferous vegetables

    Energy Technology Data Exchange (ETDEWEB)

    Dashwood, R H; Uyetake, Lyle; Fong, A T; Hendricks, J D; Bailey, G S [Oregon State Univ., Corvallis, OR (USA). Dept. of Food Science and Technology

    1989-08-01

    Indole-3-carbinol is a natural anti-carcinogen found as a glucosinolate in cruciferous vegetables such as cabbage, cauliflower and broccoli. A complete understanding of the mechanisms of anti-carcinogenesis by this dietary inhibitor requires improved insight into the disposition and metabolic fate of indole-3-carbinol in vivo. Such metabolic studies have been hampered by the lack of a commercial source of radiolabelled compound. This provided the main impetus for the work reported here, the synthesis of 5-({sup 3}H)-indole-3-carbinol from 5-bromoindole. (author).

  16. Feeding Releases Endogenous Opioids in Humans.

    Science.gov (United States)

    Tuulari, Jetro J; Tuominen, Lauri; de Boer, Femke E; Hirvonen, Jussi; Helin, Semi; Nuutila, Pirjo; Nummenmaa, Lauri

    2017-08-23

    The endogenous opioid system supports a multitude of functions related to appetitive behavior in humans and animals, and it has been proposed to govern hedonic aspects of feeding thus contributing to the development of obesity. Here we used positron emission tomography to investigate whether feeding results in hedonia-dependent endogenous opioid release in humans. Ten healthy males were recruited for the study. They were scanned with the μ-opioid-specific ligand [ 11 C]carfentanil three times, as follows: after a palatable meal, a nonpalatable meal, and after an overnight fast. Subjective mood, satiety, and circulating hormone levels were measured. Feeding induced significant endogenous opioid release throughout the brain. This response was more pronounced following a nonpalatable meal versus a palatable meal, and independent of the subjective hedonic responses to feeding. We conclude that feeding consistently triggers cerebral opioid release even in the absence of subjective pleasure associated with feeding, suggesting that metabolic and homeostatic rather than exclusively hedonic responses play a role in the feeding-triggered cerebral opioid release. SIGNIFICANCE STATEMENT The endogenous opioid system supports both hedonic and homeostatic functions. It has been proposed that overeating and concomitant opioid release could downregulate opioid receptors and promote the development of obesity. However, it remains unresolved whether feeding leads to endogenous opioid release in humans. We used in vivo positron emission tomography to test whether feeding triggers cerebral opioid release and whether this response is associated with pleasurable sensations. We scanned volunteers using the μ-opioid receptor-specific radioligand [ 11 C]carfentanil three times, as follows: after an overnight fast, after consuming a palatable meal, and after consuming a nonpalatable meal. Feeding led to significant endogenous opioid release, and this occurred also in the absence of feeding

  17. Endogenous network of firms and systemic risk

    Science.gov (United States)

    Ma, Qianting; He, Jianmin; Li, Shouwei

    2018-02-01

    We construct an endogenous network characterized by commercial credit relationships connecting the upstream and downstream firms. Simulation results indicate that the endogenous network model displays a scale-free property which exists in real-world firm systems. In terms of the network structure, with the expansion of the scale of network nodes, the systemic risk increases significantly, while the heterogeneities of network nodes have no effect on systemic risk. As for firm micro-behaviors, including the selection range of trading partners, actual output, labor requirement, price of intermediate products and employee salaries, increase of all these parameters will lead to higher systemic risk.

  18. Endogenous Generalized Weights under DEA Control

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    Non-parametric efficiency analysis, such as Data Envelopment Analysis (DEA) relies so far on endogenous local or exogenous general weights, based on revealed preferences or market prices. However, as DEA is gaining popularity in regulation and normative budgeting, the strategic interest...... of the evaluated industry calls for attention. We offer endogenous general prices based on a reformulation of DEA where the units collectively propose the set of weights that maximize their efficiency. Thus, the sector-wide efficiency is then a result of compromising the scores of more specialized smaller units...

  19. An endogenous model of the credit network

    Science.gov (United States)

    He, Jianmin; Sui, Xin; Li, Shouwei

    2016-01-01

    In this paper, an endogenous credit network model of firm-bank agents is constructed. The model describes the endogenous formation of firm-firm, firm-bank and bank-bank credit relationships. By means of simulations, the model is capable of showing some obvious similarities with empirical evidence found by other scholars: the upper-tail of firm size distribution can be well fitted with a power-law; the bank size distribution can be lognormally distributed with a power-law tail; the bank in-degrees of the interbank credit network as well as the firm-bank credit network fall into two-power-law distributions.

  20. Animal spirits, competitive markets, and endogenous growth

    Science.gov (United States)

    Miyazaki, Kenji

    2013-10-01

    This paper uses a simple model with an endogenous discount rate and linear technology to investigate whether a competitive equilibrium has a higher balanced growth path (BGP) than the social planning solution and whether the BGP is determinate or indeterminate. The implications are as follows. To start with, people with an instinct to compare themselves with others possess an endogenous discount rate. In turn, this instinct affects the economic growth rate in a competitive market economy. The competitive market economy also sometimes achieves higher economic growth than a social planning economy. However, the outcomes of market economy occasionally fluctuate because of the presence of the self-fulfilling prophecy or animal spirits.

  1. [Mechanisms of leukocyte formation of endogenous pyrogen].

    Science.gov (United States)

    Rybakina, E G; Sorokin, A V

    1982-06-01

    A study was made of the kinetics of endogenous pyrogen production by rabbit blood and exudate leukocytes and possible role played by the products of activated leukocytes in autoregulation of the process. It was established that accumulation of endogenous pyrogen in the cell precedes its release by stimulated cells. Then the processes of active pyrogen formation and release gel interdependent: pyrogen formed releases from the cell; the lowering of pyrogen concentration in the cell is accompanied by the decrease of its content in the medium. No stimulating effect of the products activated during leukocyte inflammation on pyrogen formation by blood leukocytes was discovered.

  2. Endogenous opioid systems: physiological role in the self-limitation of seizures.

    Science.gov (United States)

    Tortella, F C; Long, J B; Holaday, J W

    1985-04-15

    Immediately following a seizure, the severity of subsequent seizures is significantly reduced. The involvement of endogenous opioid systems as a physiological regulator of this postseizure inhibition was studied in rats using repeated maximal electroshock (MES) seizures. Both the opiate antagonist (-)-naloxone and morphine tolerance abolished the progressive seizure protection associated with repeated MES. We propose that endogenous opioids, activated by a prior seizure, provide a central homeostatic inhibitory mechanism which may be responsible for the initiation of a postictal refractory state in the epileptic.

  3. Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses

    Science.gov (United States)

    2012-01-01

    Background The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. Results MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. Conclusions We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells. PMID:22727223

  4. Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses.

    Science.gov (United States)

    Arjan-Odedra, Shetal; Swanson, Chad M; Sherer, Nathan M; Wolinsky, Steven M; Malim, Michael H

    2012-06-22

    The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells.

  5. Optimal income taxation with endogenous human capital

    NARCIS (Netherlands)

    Jacobs, B.

    2005-01-01

    This paper augments the theory of optimal linear income taxation by taking into account human capital accumulation as a dimension of labor supply. The distribution of earning potentials is endogenous because agents differ in the ability to learn. Taxation affects utilization rates of human capital

  6. Essays on Policy Evaluation with Endogenous Adoption

    Science.gov (United States)

    Gentile, Elisabetta

    2011-01-01

    Over the last decade, experimental and quasi-experimental methods have been favored by researchers in empirical economics, as they provide unbiased causal estimates. However, when implementing a program, it is often not possible to randomly assign subjects to treatment, leading to a possible endogeneity bias. This dissertation consists of two…

  7. Place branding, embeddedness and endogenous rural development

    NARCIS (Netherlands)

    Donner, Mechthild; Horlings, Lummina; Fort, Fatiha; Vellema, Sietze

    2017-01-01

    This article deals with place branding on the regional scale, in the rural context of food and tourism networks in Europe. Place branding is linked to the concepts of endogenous rural development, territory and embeddedness, by analysing how the valorisation of specific rural assets takes shape.

  8. Climate changes and farmers' endogenous adaptation strategies ...

    African Journals Online (AJOL)

    It has been claimed that climate changes impact studies often assume certain adaptations and little explicit examination of how, when, why, and under what conditions they occur. This research aims at analysing the endogenous strategies developed by farmers in agricultural land and crop management. With random ...

  9. Endogenous thrombin potential in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Aziz, Mubeena; Sidelmann, Johannes Jakobsen; Wissing, Marie Louise Muff

    2015-01-01

    OBJECTIVES: The objective of this study is to investigate plasma endogenous thrombin generation in four different phenotypes of polycystic ovary syndrome (PCOS) defined by Body Mass Index (BMI) and insulin resistance (IR). PCOS is diagnosed according to the Rotterdam criteria. DESIGN: Multicenter...

  10. Immigration, Endogenous Technology Adoption and Wages

    NARCIS (Netherlands)

    Ray Chaudhuri, A.; Pandey, Manish

    2015-01-01

    We document that immigration to U.S. states has increased the mass of workers at the lower range of the skill distribution. We use this change in skill distribution of workers to analyze the effect of immigration on wages. Our model allows firms to endogenously respond to the immigration-induced

  11. HERVd: the Human Endogenous Retrovirus Database: update

    Czech Academy of Sciences Publication Activity Database

    Pačes, Jan; Pavlíček, A.; Zíka, Radek; Jurka, J.; Pačes, Václav

    2004-01-01

    Roč. 32, č. 1 (2004), s. 50-50 ISSN 0305-1048 R&D Projects: GA MŠk LN00A079 Institutional research plan: CEZ:AV0Z5052915 Keywords : human * endogenous retrovirus * database Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.260, year: 2004

  12. Endogenous Quality Effects of Trade Policy

    NARCIS (Netherlands)

    J.L. Moraga-Gonzalez (José Luis); J.M.A. Viaene (Jean-Marie)

    1999-01-01

    textabstractWe study the optimal trade policy against a foreign oligopoly with endogenous quality. We show that, under the Most Favoured Nation (MFN) clause, a uniform tariff policy is always welfare improving over the free trade equilibrium. However, a nonuniform tariff policy is always desirable

  13. Optimized Formation of Benzyl Isothiocyanate by Endogenous ...

    African Journals Online (AJOL)

    Purpose: To use endogenous myrosinase in Carica papaya seed to convert benzyl glucosinolate (BG) to benzyl isothiocyanate (BITC) and then extract it for further studies. Methods: Process variables including seed powder particle size, sample-to-solvent ratio, pH of buffer solution, enzymolysis temperature, enzymolysis ...

  14. Structural classification of endogenous regulatory oligopeptides.

    Science.gov (United States)

    Zamyatnin, A A

    1991-07-01

    Based on the criteria of 50% identity in the amino acid sequence, a new method for grouping endogenous regulatory oligopeptides into structural families is presented. Data from the EROP-Moscow data bank on 579 oligopeptides fitting a preset spectrum of functional activities revealed 73 structural oligopeptide groups, 36 of which were called families.

  15. Endogenous retrovirus sequences expressed in male mammalian ...

    African Journals Online (AJOL)

    Objectives: To review the research findings on the expression of endogenous retroviruses and retroviral-related particles in male mammalian reproductive tissues, and to discuss their possible role in normal cellular events and association with disease conditions in male reproductive tissues. Data sources: Published ...

  16. The Limit of Public Policy : Endogenous Preferences

    NARCIS (Netherlands)

    Bar-Gill, O.; Fershtman, C.

    2000-01-01

    In designing public policy it is not enough to consider the possible reaction of individuals to the chosen policy.Public policy may also affect the formation of preferences and norms in a society.The endogenous evolution of preferences, in addition to introducing a conceptual difficulty in

  17. Endogeneity in Strategy-Performance Analysis

    DEFF Research Database (Denmark)

    Rocha, Vera; Van Praag, Mirjam; B. Folta, Timothy

    2018-01-01

    , such as employees, strategic partners, customers, or investors, whose choices and preferences also affect the final decision. We discuss how endogeneity can plague the measurement of the performance effects of these two-sided strategic decisions—which are more complex, but more realistic, than prior representations...

  18. Managing spillovers: an endogenous sunk cost approach

    Czech Academy of Sciences Publication Activity Database

    Senyuta, Olena; Žigić, Krešimir

    2016-01-01

    Roč. 35, June (2016), s. 45-64 ISSN 0167-6245 R&D Projects: GA ČR(CZ) GAP402/12/0961 Institutional support: PRVOUK-P23 Keywords : endogenous sunk costs * innovations * knowledge spillovers Subject RIV: AH - Economics Impact factor: 0.739, year: 2016

  19. Applying Endogenous Knowledge in the African Context ...

    African Journals Online (AJOL)

    This requires not only an understanding of what endogenous knowledge is, but also an alignment of personal values, innovative strategies and an attitude of activism. An integral part of an extensive skills set to implement specifi c dispute resolution strategies is the ability to facilitate the free sharing of information about all ...

  20. Endogenous retrovirus sequences expressed in male mammalian ...

    African Journals Online (AJOL)

    In humans, one ERV family, human endogenous retrovirus- K (HERV-K) is abundantly expressed, and is associated with germ cell tumours, while ERV3 env is expressed in normal human testis. Conclusion: The expression of ERVs in male reproductive tissues suggests a possible role in normal and disease conditions ...

  1. [Endogenous pyrogen formation by bone marrow cells].

    Science.gov (United States)

    Efremov, O M; Sorokin, A V; El'kina, O A

    1978-01-01

    The cells of the rabbit bone marrow produced endogenous pyrogen in response to stimulation with bacterial lipopolysaccharide. Incubation of the cells in medium No 199 containing a 15% homologous serum is optimal for the release of pyrogen. It is supposed that the cells of the bone marrow take part in the formation of endgenous pyrogen and in the mechanism of pyrexia in the organism.

  2. An efficient protocol for the synthesis of highly sensitive indole imines utilizing green chemistry: optimization of reaction conditions.

    Science.gov (United States)

    Nisar, Bushra; Rubab, Syeda Laila; Raza, Abdul Rauf; Tariq, Sobia; Sultan, Ayesha; Tahir, Muhammad Nawaz

    2018-04-11

    Novel and highly sensitive indole-based imines have been synthesized. Their synthesis has been compared employing a variety of protocols. Ultimately, a convenient, economical and high yielding set of conditions employing green chemistry have been designed for their synthesis.

  3. Loss of endogenous thymosin β4 accelerates glomerular disease.

    Science.gov (United States)

    Vasilopoulou, Elisavet; Kolatsi-Joannou, Maria; Lindenmeyer, Maja T; White, Kathryn E; Robson, Michael G; Cohen, Clemens D; Sebire, Neil J; Riley, Paul R; Winyard, Paul J; Long, David A

    2016-11-01

    Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin β 4 regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin β 4 improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin β 4 in the kidney is unknown. We demonstrate that thymosin β 4 is expressed prominently in podocytes of developing and adult mouse glomeruli. Global loss of thymosin β 4 did not affect healthy glomeruli, but accelerated the severity of immune-mediated nephrotoxic nephritis with worse renal function, periglomerular inflammation, and fibrosis. Lack of thymosin β 4 in nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin β 4 in the migration of these cells. Thymosin β 4 knockdown in cultured podocytes also increased migration in a wound-healing assay, accompanied by F-actin rearrangement and increased RhoA activity. We propose that endogenous thymosin β 4 is a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  4. Endogenous egg immune defenses in the yellow mealworm beetle (Tenebrio molitor).

    Science.gov (United States)

    Jacobs, Chris G C; Gallagher, Joe D; Evison, Sophie E F; Heckel, David G; Vilcinskas, Andreas; Vogel, Heiko

    2017-05-01

    In order to survive microbe encounters, insects rely on both physical barriers as well as local and systemic immune responses. Most research focusses on adult or larval defenses however, whereas insect eggs are also in need of protection. Lately, the defense of eggs against microbes has received an increasing amount of attention, be it through endogenous egg defenses, trans-generational immune priming (TGIP) or parental investment. Here we studied the endogenous immune response in eggs and adults of Tenebrio molitor. We show that many immune genes are induced in both adults and eggs. Furthermore, we show that eggs reach comparable levels of immune gene expression as adults. These findings show that the eggs of Tenebrio are capable of an impressive endogenous immune response, and indicate that such inducible egg defenses are likely common in insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    Science.gov (United States)

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

    Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid

  6. Improved Potency of Indole-Based NorA Efflux Pump Inhibitors: From Serendipity toward Rational Design and Development.

    Science.gov (United States)

    Buonerba, Federica; Lepri, Susan; Goracci, Laura; Schindler, Bryan D; Seo, Susan M; Kaatz, Glenn W; Cruciani, Gabriele

    2017-01-12

    The NorA efflux pump is a potential drug target for reversal of resistance to selected antibacterial agents, and recently we described indole-based inhibitor candidates. Herein we report a second class of inhibitors derived from them but with significant differences in shape and size. In particular, compounds 13 and 14 are very potent inhibitors in that they demonstrated the lowest IC 50 values (2 μM) ever observed among all indole-based compounds we have evaluated.

  7. Microwave Assisted Synthesis of Novel Imidazolopyridinyl Indoles as Potent Antioxidant and Antimicrobial Agents

    Directory of Open Access Journals (Sweden)

    Jaiprakash S. Biradar

    2014-01-01

    Full Text Available We describe herein the design, synthesis, and pharmacological evaluation of novel series of imidazolopyridinyl indole analogues as potent antioxidants and antimicrobials. These novel compounds (3a–i were synthesized by reacting 3,5-disubstituted-indole-2-carboxylic acid (1a–i with 2,3-diamino pyridine (2 in excellent yield. The novel products were confirmed by their IR, 1H NMR, 13C NMR, mass spectral, and analytical data. These compounds were screened for their antioxidant and antimicrobial activities. Among the compounds tested, 3a–d showed the highest total antioxidant capacity, scavenging, and antimicrobial activities. Compounds 3c-d and 3g-h have shown excellent ferric reducing activity.

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

    Directory of Open Access Journals (Sweden)

    Arnold Berstad

    2015-08-01

    Full Text Available 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.

  9. Strategies for the capillary electrophoretic separation of indole alkaloids in Psilocybe semilanceata.

    Science.gov (United States)

    Pedersen-Bjergaard, S; Rasmussen, K E; Sannes, E

    1998-01-01

    While the hallucinogenic mushrooms Psilocybe semilanceata have previously been analyzed for the indole alkaloids psilocybin and baeocystin by capillary zone electrophoresis (CZE) at pH 11.5, the present work focused on the development of an alternative and complementary capillary electrophoretic method for their identification. Owing to their structural similarity and zwitterionic nature, the compounds were difficult to resolve based on different interactions with cationic or anionic micelles. However, while the attempts with micellar electrokinetic chromatography (MEKC) were unsuccessful, rapid derivatization with propyl chloroformate and reanalysis by CZE at pH 11.5 was effective to support identification of the two indole alkaloids. Psilocin was difficult to analyze by CZE at pH 11.5 owing to comigration with the electroosmotic flow. For this compound, the pH of the running buffer was reduced to 7.2 to effectively enhance the electrophoretic mobility.

  10. Marine Natural Product Bis-indole Alkaloid Caulerpin: Chemistry and Biology.

    Science.gov (United States)

    Lunagariya, Jignesh; Bhadja, Poonam; Zhong, Shenghui; Vekariya, Rohit; Xu, Shihai

    2017-09-27

    Marine bis-indole alkaloids comprise a large and increasingly growing class of secondary metabolites, and continue to deliver a great variety of structural templates. The alkaloids derived from marine resources play a crucial role in medicinal chemistry and as chemical agents. In particular, bis-indole alkaloid caulerpin isolated from marine green algae Caulerpa and a red algae Chondria armata at various places around the world, and tested against several therapeutic areas such as anti-diabetic, antinociceptive, anti-inflammatory, anti-tumor, anti-larvicidal, anti-herpes, anti-tubercular, anti-microbial and immunostimulating activity as well as means of other chemical agents. Herein, we summarized discovery of caulerpin, and its potential medicinal and chemical applications in chronological order with various aspects. Additionally, synthesis of caulerpin, its functional analogues, and structural isomer have also been reviewed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. In the margin Valerius Massimus, «De indole» III 1

    Directory of Open Access Journals (Sweden)

    Barbara SCARDIGLI

    2013-03-01

    Full Text Available The article examines five episodes concerning four figures (Emilius Lepidus, Cato Uticensis, Cassius Longinus and Alcibiades, presented by Valerio Massimo (3,1 in relation to the topic of De Indole. Precocious qualities and singular attitudes can also be seen in many other young people in the Antique period and, in the end, only Alcibiades and Cato fit into the proposed topic.

  12. Asymmetric Synthesis of Optically Active Spirocyclic Indoline Scaffolds through an Enantioselective Reduction of Indoles

    KAUST Repository

    Borrmann, Ruediger

    2016-11-30

    An enantioselective synthesis of spirocyclic indoline scaffolds was achieved by applying an asymmetric iridium-catalyzed hydrogenation of 3H-indoles. Low catalyst loadings and mild reaction conditions provide a broad range of differently substituted products with excellent yields and enantioselectivities. The developed methodology allows an efficient synthesis of this important spirocyclic structural motif, which is present in numerous biologically active molecules and privileged structures in medicinal chemistry.

  13. 2-Benzyl-6-chloro-1-(4-methylphenyl-1H-indole-3-carbonitrile

    Directory of Open Access Journals (Sweden)

    Qiao Yan

    2011-12-01

    Full Text Available In the title compound, C23H17ClN2, the dihedral angle between the indole ring and the attached tolyl ring is 86.97 (8°. Weak C—H...N(nitrile hydrogen bonding, and C—H...π(aromatic and short Cl...π(aromatic [3.628 (1 Å] interactions consolidate the crystal packing.

  14. Divergent Reactivity of Rhodium(I) Carbenes Derived from Indole Annulations.

    Science.gov (United States)

    Li, Xiaoxun; Li, Hui; Song, Wangze; Tseng, Po-Sen; Liu, Lingyan; Guzei, Ilia A; Tang, Weiping

    2015-10-26

    Rhodium(I) carbenes were generated from propargylic alcohol derivatives as the result of a dehydrative indole annulation. Depending on the choice of the electron-withdrawing group on the aniline nitrogen nucleophile, either a cyclopropanation product or dimerization product was obtained chemoselectively. Intramolecular hydroamidation occurred for the same type of propargylic alcohol derivatives when other transition-metal catalysts were employed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Effect of indole-3-butyric acid (IBA) on in vitro root induction in ...

    African Journals Online (AJOL)

    Root induction pre-developed in vitro plantlets of orchid was carried out using indole-3-butyric acid (IBA) (0, 0.5, 1.0, 1.5, 2.0, 2.5 and 3 mM) on basal Murashige and Skoog (MS) medium. Among the concentrations of IBA, the number of roots per plantlet with 1 mM IBA was found to be the highest (2.25 roots per plantlet) ...

  16. Retrospective study on clinical management of indolent ulcers in Boxer dogs

    Directory of Open Access Journals (Sweden)

    Ana Paula Hvenegaard

    2011-10-01

    Full Text Available Indolent ulcers are superficial corneal ulcers secondary to several changes on the corneal surface. They are frequently observed in middle-aged Boxer dogs, cause pain of acute onset and requires appropriate treatment. Aiming to evaluate the efficacy of clinical managements on the rate of healing of indolent ulcers, a retrospective study was conducted (1997-2008. Results demonstrated that proteinase inhibitors were the most often prescribed medication, and its administration did not interfere on the healing rate, as well as observed in dogs that received 1% atropine, antibiotics and anti-inflammatory drugs. Healing was delayed in dogs administered orally with vitamin C, but the healing process was faster on those dogs that went through corneal debridement/cauterization. In conclusion, to know the various types of treatments seems to be fundamental for the rapid resolution of the disease. It is suggested that debridement/cauterization, administration of proteinase inhibitor eye drops, prophylactic topical antibiotics and oral vitamin C, should be considered as an effective clinical management for indolent ulcers in Boxer dogs.

  17. Disruption of endolysosomal trafficking pathways in glioma cells by methuosis-inducing indole-based chalcones.

    Science.gov (United States)

    Mbah, Nneka E; Overmeyer, Jean H; Maltese, William A

    2017-06-01

    Methuosis is a form of non-apoptotic cell death involving massive vacuolization of macropinosome-derived endocytic compartments, followed by a decline in metabolic activity and loss of membrane integrity. To explore the induction of methuosis as a potential therapeutic strategy for killing cancer cells, we have developed small molecules (indole-based chalcones) that trigger this form of cell death in glioblastoma and other cancer cell lines. Here, we report that in addition to causing fusion and expansion of macropinosome compartments, the lead compound, 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), disrupts vesicular trafficking at the lysosomal nexus, manifested by impaired degradation of EGF and LDL receptors, defective processing of procathepsins, and accumulation of autophagosomes. In contrast, secretion of the ectodomain derived from a prototypical type-I membrane glycoprotein, β-amyloid precursor protein, is increased rather than diminished. A closely related MOMIPP analog, which causes substantial vacuolization without reducing cell viability, also impedes cathepsin processing and autophagic flux, but has more modest effects on receptor degradation. A third analog, which causes neither vacuolization nor loss of viability, has no effect on endolysosomal trafficking. The results suggest that differential cytotoxicity of structurally similar indole-based chalcones is related, at least in part, to the severity of their effects on endolysosomal trafficking pathways.

  18. Distribution and Variation of Indole Glucosinolates in Woad (Isatis tinctoria L.).

    Science.gov (United States)

    Elliott, M C; Stowe, B B

    1971-10-01

    The exceptionally high levels in woad (Isatis tinctoria L.) of three indolic goitrogens, namely glucobrassicin, neoglucobrassicin, and glucobrassicin-1-sulfonate, permit the facile study of their distribution in the plant and their changes during its development. Woad seeds contain as much as 0.23% fresh weight of glucobrassicin but no other indole glucosinolate, while 1-week-old seedlings also contain substantial amounts of neoglucobrassicin and glucobrassicin-1-sulfonate in their shoots whether grown in the light or dark. The sulfonate is not found in roots, and light depresses neoglucobrassicin levels in shoots. Sterile root cultures synthesize glucobrassicin and neoglucobrassicin, and significant quantities of these were even found to be excreted by the roots of intact sterile seedlings in culture. This may explain the long known deleterious effect of woad and other cruciferous crops on subsequent plantings and the observation could be of ecological importance. Long term changes in levels of all three substances in the plant are similar and are compatible with earlier suggestions that the compounds could be auxin precursors at the time of flower stem elongation. Since sterile seedlings readily incorporate (35)SO(4) (2-) into indole glucosinolates and relative specific radioactivities suggest that glucobrassicin is the precursor of the other two compounds, pathways of goitrogen biosynthesis should be relatively easily determined in this material.

  19. Distribution and Variation of Indole Glucosinolates in Woad (Isatis tinctoria L.) 1

    Science.gov (United States)

    Elliott, Malcolm C.; Stowe, Bruce B.

    1971-01-01

    The exceptionally high levels in woad (Isatis tinctoria L.) of three indolic goitrogens, namely glucobrassicin, neoglucobrassicin, and glucobrassicin-1-sulfonate, permit the facile study of their distribution in the plant and their changes during its development. Woad seeds contain as much as 0.23% fresh weight of glucobrassicin but no other indole glucosinolate, while 1-week-old seedlings also contain substantial amounts of neoglucobrassicin and glucobrassicin-1-sulfonate in their shoots whether grown in the light or dark. The sulfonate is not found in roots, and light depresses neoglucobrassicin levels in shoots. Sterile root cultures synthesize glucobrassicin and neoglucobrassicin, and significant quantities of these were even found to be excreted by the roots of intact sterile seedlings in culture. This may explain the long known deleterious effect of woad and other cruciferous crops on subsequent plantings and the observation could be of ecological importance. Long term changes in levels of all three substances in the plant are similar and are compatible with earlier suggestions that the compounds could be auxin precursors at the time of flower stem elongation. Since sterile seedlings readily incorporate 35SO42− into indole glucosinolates and relative specific radioactivities suggest that glucobrassicin is the precursor of the other two compounds, pathways of goitrogen biosynthesis should be relatively easily determined in this material. PMID:16657825

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

    Science.gov (United States)

    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 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.

  1. A photoelectron imaging and quantum chemistry study of the deprotonated indole anion.

    Science.gov (United States)

    Parkes, Michael A; Crellin, Jonathan; Henley, Alice; Fielding, Helen H

    2018-05-29

    Indole is an important molecular motif in many biological molecules and exists in its deprotonated anionic form in the cyan fluorescent protein, an analogue of green fluorescent protein. However, the electronic structure of the deprotonated indole anion has been relatively unexplored. Here, we use a combination of anion photoelectron velocity-map imaging measurements and quantum chemistry calculations to probe the electronic structure of the deprotonated indole anion. We report vertical detachment energies (VDEs) of 2.45 ± 0.05 eV and 3.20 ± 0.05 eV, respectively. The value for D0 is in agreement with recent high-resolution measurements whereas the value for D1 is a new measurement. We find that the first electronically excited singlet state of the anion, S1(ππ*), lies above the VDE and has shape resonance character with respect to the D0 detachment continuum and Feshbach resonance character with respect to the D1 continuum.

  2. The role of human endogenous retroviruses in brain development and function.

    Science.gov (United States)

    Mortelmans, Kristien; Wang-Johanning, Feng; Johanning, Gary L

    2016-01-01

    Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  3. Bendamustine mitoxantrone and rituximab (BMR): a new effective regimen for refractory or relapsed indolent lymphomas.

    Science.gov (United States)

    Weide, Rudolf; Heymanns, Jochen; Gores, Annette; Köppler, Hubert

    2002-02-01

    Bendamustine (B) and mitoxantrone (M) have been shown to be potent cytotoxic drugs for the treatment of relapsed or refractory indolent lymphomas. The anti-CD20 monoclonal antibody rituximab (R) has produced an overall response rate (ORR) of 50% as a single agent in relapsed or refractory indolent lymphomas. We posed the question whether a combination of the above agents (BMR) could improve these results. This study was an open label, single center pilot study for patients with relapsed or refractory, CD20-positive (indolent) lymphoma or chronic lymphocytic leukaemia. The therapy consisted of bendamustine (80 mg/m2, day 1-3), mitoxantrone (10 mg/m2, day 1), rituximab (375 mg/m2, week 2-5). BM was repeated on day 36 or when the haematological parameters had recovered. The maximum therapy consisted of one BMR-cycle, followed by five BM courses. Treatment was stopped when the disease responded with PR/CR. During March 1999 and December 2000, 20 patients received the BMR-regimen (four secondary high grade lymphoma, 12 indolent lymphoma, four B-CLL). The median age of the patients was 67 years (range 36-82) and their performance status ranged from 0 to 3. Median number of previous treatment regimens was two (1-6). Of the lymphoma patients, 14 had stage IV disease, 1 stage III and 1 stage II. B-CLL patients were all Rai stage IV (Binet C). Overall response rate was 95% (19/20) with seven patients achieving a CR (35%) and 12 patients achieving a PR (60%). Median time to progression is 7 months (1-21) with a median observation time of 7 months (1-21). Response is still durable in 15/20 patients (75%) (1+ to 21+ months after therapy). Symptomatic, reversible grade three or four haematotoxicity occurred in 4/20 patients (20%). Non-symptomatic grade three or four haematotoxicity was seen in 9/20 patients (45%). No major non-haematological toxicity was observed. In conclusion, BMR is a well tolerated, very effective outpatient regimen of treatment for relapsed and refractory

  4. Endogenous Magnetic Reconnection in Solar Coronal Loops

    Science.gov (United States)

    Asgari-Targhi, M.; Coppi, B.; Basu, B.; Fletcher, A.; Golub, L.

    2017-12-01

    We propose that a magneto-thermal reconnection process occurring in coronal loops be the source of the heating of the Solar Corona [1]. In the adopted model, magnetic reconnection is associated with electron temperature gradients, anisotropic electron temperature fluctuations and plasma current density gradients [2]. The input parameters for our theoretical model are derived from the most recent observations of the Solar Corona. In addition, the relevant (endogenous) collective modes can produce high energy particle populations. An endogenous reconnection process is defined as being driven by factors internal to the region where reconnection takes place. *Sponsored in part by the U.S. D.O.E. and the Kavli Foundation* [1] Beafume, P., Coppi, B. and Golub, L., (1992) Ap. J. 393, 396. [2] Coppi, B. and Basu, B. (2017) MIT-LNS Report HEP 17/01.

  5. Endogenous opioids encode relative taste preference.

    Science.gov (United States)

    Taha, Sharif A; Norsted, Ebba; Lee, Lillian S; Lang, Penelope D; Lee, Brian S; Woolley, Joshua D; Fields, Howard L

    2006-08-01

    Endogenous opioid signaling contributes to the neural control of food intake. Opioid signaling is thought to regulate palatability, the reward value of a food item as determined by orosensory cues such as taste and texture. The reward value of a food reflects not only these sensory properties but also the relative value of competing food choices. In the present experiment, we used a consummatory contrast paradigm to manipulate the relative value of a sucrose solution for two groups of rats. Systemic injection of the nonspecific opioid antagonist naltrexone suppressed sucrose intake; for both groups, however, this suppression was selective, occurring only for the relatively more valuable sucrose solution. Our results indicate that endogenous opioid signaling contributes to the encoding of relative reward value.

  6. Endogenous Natural Complement Inhibitor Regulates Cardiac Development

    DEFF Research Database (Denmark)

    Mortensen, Simon A; Skov, Louise L; Kjaer-Sorensen, Kasper

    2017-01-01

    mechanisms during fetal development and adult homeostasis. In this article, we describe the function of an endogenous complement inhibitor, mannan-binding lectin (MBL)-associated protein (MAp)44, in regulating the composition of a serine protease-pattern recognition receptor complex, MBL-associated serine...... of MAp44 caused impaired cardiogenesis, lowered heart rate, and decreased cardiac output. These defects were associated with aberrant neural crest cell behavior. We found that MAp44 competed with MASP-3 for pattern recognition molecule interaction, and knockdown of endogenous MAp44 expression could...... be rescued by overexpression of wild-type MAp44. Our observations provide evidence that immune molecules are centrally involved in the orchestration of cardiac tissue development....

  7. Endogeneity of Money Supply: Evidence From Turkey

    Directory of Open Access Journals (Sweden)

    Oguzhan Cepni

    2017-02-01

    Full Text Available There is a long discussion among academics and central bankers about the theories of money supply. According to the exogenous view, central banks have the full control over money supply via policy actions including the adjustments of interest rates and reserve ratios, both of which alter commercial banks’ lending decisions. However, the theory of endogenous money supply emphasizes the role of demand for bank loans in money creation. More specifically, banks create money by meeting the demand of economic agents. In this study, we investigate which of the money supply theories holds in Turkish economy for the period 2006-2015 by employing cointegration and causality tests. Our findings show that the causality runs from bank loans to money supply both in the short and long terms, which supports the endogenous view in a sense that central bank and the banks fully meet the total demand for money in Turkish economy.

  8. Independent effects of endogenous and exogenous attention in touch.

    Science.gov (United States)

    Jones, Alexander; Forster, Bettina

    2013-12-01

    Endogenous and exogenous attention in touch have typically been investigated separately. Here we use a double-cueing paradigm manipulating both types of orienting in each trial. Bilateral endogenous cues induced long-lasting facilitation of endogenous attention up to 2 s. However, the exogenous cue only elicited an effect at short intervals. Our results favour a supramodal account of attention and this study provides new insight into how endogenous and exogenous attention operates in the tactile modality.

  9. Endogenous pyrogen-like substance produced by reptiles.

    Science.gov (United States)

    Bernheim, H A; Kluger, M J

    1977-06-01

    1. Injection of lizards (Dipsosaurus dorsalis) with rabbit endogenous pyrogen led to a fever. Injections with denatured endogenous pyrogen did not affect body temperature. 2. Injection of lizards with lizard endogenous pyrogen led to a fever of short duration, while injection of denatured lizard endogenous pyrogen produced no change in body temperature. 3. These data support the hypothesis that the febrile mechanism observed in the higher vertebrates has its origins in some primitive vertebrate.

  10. A General Theory of Endogenous Market Structures

    OpenAIRE

    Federico Etro; Paolo Bertoletti

    2014-01-01

    We provide a unified approach to imperfect (monopolistic, Bertrand and Cournot) competition equilibria with demand functions derived from symmetric preferences over a large but finite number of goods. The equilibrium markups depend on the Morishima Elasticity of Substitution/Complementarity between goods, and can be derived directly from the utility functions and ranked unambiguously. We characterize the endogenous market structures, their dependence on market size, income and firms’ producti...

  11. Pensions with Heterogenous Individuals and Endogenous Fertility

    OpenAIRE

    Cremer, Helmuth; Gahvari, Firouz; Pestieau, Pierre

    2004-01-01

    This paper studies the design of pension schemes in a society where fertility is endogenous and parents differ in their ability to raise children. In a world with perfect information, a pay-as-you-go social security system is characterized by equal pensions for all but different contributions which may or may not increase with the number of children. Additionally, fertility must be subsidized at the margin to correct for the externality that accompanies fertility. In a world of asymmetric inf...

  12. Endogenous Growth, Monetary Shocks and Nominal Rigidities

    OpenAIRE

    Annicchiarico, Barbara; Pelloni, Alessandra; Lorenza, Rossi

    2010-01-01

    We introduce endogenous growth in an otherwise standard NK model with staggered prices and wages. Some results follow: (i) monetary volatility negatively affects long-run growth; (ii) the relation between nominal volatility and growth depends on the persistence of the nominal shocks and on the Taylor rule considered; (iii) a Taylor rule with smoothing increases the negative effect of nominal volatility on mean growth.

  13. Social Security, Intergenerational Transfers, and Endogenous Growth

    OpenAIRE

    Junsen Zhang; Junxi Zhang

    1998-01-01

    In this paper, the effects of social security in a simple model of endogenous growth with alternative motives of having children are analyzed. It shows how the effects of social security depend on the size of the social security tax, the motive to have children, and the pattern of intergenerational transfers. The pattern of intergenerational transfers itself, however, is shown to change with the social security tax rate. When the social security tax is not too high, social security increases ...

  14. The endogeneity of money and the eurosystem

    OpenAIRE

    Steiger, Otto

    2004-01-01

    The endogenous theory of money, developed by Basil Moore, argues that the supply of central bank money in modern economies is not under the control of the central bank. According to this view, a central bank typically supplies cash reserves automatically on demand at its minimum lending rate, resulting in a clearly horizontal money supply function. While the paper agrees with Moore that the supply of central bank money cannot be determined exogenously by the central bank, it wonders whether t...

  15. Endogeneity of Money Supply: Evidence From Turkey

    OpenAIRE

    Oguzhan Cepni; Ibrahim Ethem Guney

    2017-01-01

    There is a long discussion among academics and central bankers about the theories of money supply. According to the exogenous view, central banks have the full control over money supply via policy actions including the adjustments of interest rates and reserve ratios, both of which alter commercial banks’ lending decisions. However, the theory of endogenous money supply emphasizes the role of demand for bank loans in money creation. More specifically, banks create money by meeting the demand ...

  16. Ciliary neurotrophic factor is an endogenous pyrogen.

    OpenAIRE

    Shapiro, L; Zhang, X X; Rupp, R G; Wolff, S M; Dinarello, C A

    1993-01-01

    Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) foll...

  17. Endogenous Retroviruses in the Genomics Era.

    Science.gov (United States)

    Johnson, Welkin E

    2015-11-01

    Endogenous retroviruses comprise millions of discrete genetic loci distributed within the genomes of extant vertebrates. These sequences, which are clearly related to exogenous retroviruses, represent retroviral infections of the deep past, and their abundance suggests that retroviruses were a near-constant presence throughout the evolutionary history of modern vertebrates. Endogenous retroviruses contribute in myriad ways to the evolution of host genomes, as mutagens and as sources of genetic novelty (both coding and regulatory) to be acted upon by the twin engines of random genetic drift and natural selection. Importantly, the richness and complexity of endogenous retrovirus data can be used to understand how viruses spread and adapt on evolutionary timescales by combining population genetics and evolutionary theory with a detailed understanding of retrovirus biology (gleaned from the study of extant retroviruses). In addition to revealing the impact of viruses on organismal evolution, such studies can help us better understand, by looking back in time, how life-history traits, as well as ecological and geological events, influence the movement of viruses within and between populations.

  18. Endogenous cueing attenuates object substitution masking.

    Science.gov (United States)

    Germeys, Filip; Pomianowska, I; De Graef, P; Zaenen, P; Verfaillie, K

    2010-07-01

    Object substitution masking (OSM) is a form of visual masking in which a briefly presented target surrounded by four small dots is masked by the continuing presence of the four dots after target offset. A major parameter in the prediction of OSM is the time required for attention to be directed to the target following its onset. Object substitution theory (Di Lollo et al. in J Exp Psychol Gen 129:481-507, 2000) predicts that the sooner attention can be focused at the target's location, the less masking will ensue. However, recently Luiga and Bachmann (Psychol Res 71:634-640, 2007) presented evidence that precueing of attention to the target location prior to target-plus-mask onset by means of a central (endogenous) arrow cue does not reduce OSM. When attention was cued exogenously, OSM was attenuated. Based on these results, Luiga and Bachmann argued that object substitution theory should be adapted by differentiating the ways of directing attention to the target location. The goal of the present study was to further examine the dissociation between the effects of endogenous and exogenous precueing on OSM. Contrary to Luiga and Bachmann, our results show that prior shifts of attention to the target location initiated by both exogenous and endogenous cues reduce OSM as predicted by object substitution theory and its computational model CMOS.

  19. Endogenous growth theory and regional development policy

    Directory of Open Access Journals (Sweden)

    Cvetanović Slobodan

    2015-01-01

    Full Text Available The numerous versions of endogenous explanations of economic growth emphasize the importance of technological change driving forces, as well as the existence of appropriate institutional arrangements. Endogenous growth theory contributes to a better understanding of various experiences with long-term growth of countries and regions. It changes the key assumptions of the Neoclassical growth theory and participates in the modern regional development physiology explanation. Based on these conclusions, the paper: a explicates the most important theoretical postulates of the theory, b explains the most important factors of economic growth in the regions in light of the Endogenous growth theory messages and c emphasizes the key determinants of regional competitiveness which in our view is conceptually between the phenomena of micro- and macro-competitiveness and represents their necessary and unique connection. First of all, micro-competitiveness is transformed into a regional competitiveness; then regional competitiveness is transformed into a macro-competitiveness. In turn, macro - influences the microeconomic competitiveness, and the circle is closed. After that, the process starts over again.

  20. Fanconi anemia proteins and endogenous stresses

    Energy Technology Data Exchange (ETDEWEB)

    Pang Qishen [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States); Andreassen, Paul R., E-mail: Paul.Andreassen@cchmc.org [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States)

    2009-07-31

    Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

  1. Fanconi anemia proteins and endogenous stresses

    International Nuclear Information System (INIS)

    Pang Qishen; Andreassen, Paul R.

    2009-01-01

    Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

  2. Induced pluripotency with endogenous and inducible genes

    International Nuclear Information System (INIS)

    Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

    2008-01-01

    The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER TAM ) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols

  3. Endogenous lung regeneration: potential and limitations.

    Science.gov (United States)

    Rock, Jason; Königshoff, Melanie

    2012-12-15

    The exploration of the endogenous regenerative potential of the diseased adult human lung represents an innovative and exciting task. In this pulmonary perspective, we discuss three major components essential for endogenous lung repair and regeneration: epithelial progenitor populations, developmental signaling pathways that regulate their reparative and regenerative potential, and the surrounding extracellular matrix in the human diseased lung. Over the past years, several distinct epithelial progenitor populations have been discovered within the lung, all of which most likely respond to different injuries by varying degrees. It has become evident that several progenitor populations are mutually involved in maintenance and repair, which is highly regulated by developmental pathways, such as Wnt or Notch signaling. Third, endogenous progenitor cells and developmental signaling pathways act in close spatiotemporal synergy with the extracellular matrix. These three components define and refine the highly dynamic microenvironment of the lung, which is altered in a disease-specific fashion in several chronic lung diseases. The search for the right mixture to induce efficient and controlled repair and regeneration of the diseased lung is ongoing and will open completely novel avenues for the treatment of patients with chronic lung disease.

  4. Endogenous viral elements in animal genomes.

    Directory of Open Access Journals (Sweden)

    Aris Katzourakis

    2010-11-01

    Full Text Available Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized.

  5. Endogenous leukotriene formation during anaphylactic shock

    International Nuclear Information System (INIS)

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-01-01

    Leukotriene (LT)C 4 is a biologically active substance, presumed to play major roles as a mediator of allergic and anaphylactic reactions. It is formed e.g. by basophilic and eosinophilic leukocytes, monocytes, macrophages, and mast cells. In cells having IgE receptors, bridging of these by divalent anti-IgE-receptor antibodies or by interaction between receptor-bound IgE and anti-IgE will induce LTC 4 formation. Leukotriene formation has also been demonstrated in other in vitro models of immediate hypersensivity. The biological actions of LTC 4 , comprise induction of airway obstruction, constriction of coronary arteries, hypotension, and plasma extravasation. Leukotriene formation in vivo may mediate anaphylactic shock symptoms and cause the death of an animal. In order to prove the presumed mediator role of this substance in anaphylactic reactions, it is necessary to demonstrate its endogenous formation during shock. Studies on the metabolism of LTC 4 have revealed rapid catabolism by various transformations of the peptide substituent. Recently, three metabolites were demonstrated to be excreted as end-products in man (LTE 4 ,) and the rat (N-acetyl LTE 4 and N-acetyl 11-trans LTE 4 ). By monitoring biliary N-acetyl LTE 4 levels, endogenous leukotriene formation in the rat was demonstrated in vivo after tissue trauma and endotoxin shock. We now wish to report evidence for endogenous leukotriene C 4 production during anaphylactic shock in guinea pigs. 37 refs. (author)

  6. Exercise induced asthma and endogenous opioids.

    Science.gov (United States)

    Gaillard, R C; Bachman, M; Rochat, T; Egger, D; de Haller, R; Junod, A F

    1986-01-01

    Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma. PMID:2944240

  7. The search for an endogenous activator.

    Science.gov (United States)

    Gekowski, K. M.; Atkins, E.

    1985-01-01

    Certain febrile diseases are unaccompanied by infection or apparent hypersensitivity. In myocardial infarction or pulmonary embolism, for example, fever has been attributed to inflammation and/or tissue necrosis. Exogenous (microbial) pyrogens stimulate both human and animal monocytes/macrophages to produce endogenous pyrogen (EP) in vitro. To determine if plasma and cellular endogeneous mediators (EMs) of inflammation induced EP production, human mononuclear cells (M/L) were incubated for 18 hours with varying amounts of EM and the supernates assayed for EP in rabbits. Neutrophils (PMNs), which do not generate EP and yet are a feature of acute inflammation, were tested. Neither viable, phorbol myristic acetate-stimulated PMNs nor sonicated PMNs, red blood cells, or M/L stimulated human monocytes to produce EP. Human C3b and C5a, which mediate phagocytosis and chemotaxis, respectively, were also inactive. Despite its chemoattractant properties, the synthetic peptide FMLP failed to induce EP release. Since Poly I:Poly C (PIC: a synthetic, double-stranded RNA) is a potent pyrogen in rabbits, we investigated PIC, as well as a native, single-stranded RNA (from E. coli) and DNA (from calf thymus). None was active in vitro, and only PIC caused fever when given to rabbits intravenously. In summary, we have been unable to find an endogenous activator of EP from human monocytes to explain fevers associated with inflammation alone. PMID:3875936

  8. Preparation of Benzo[c]carbazol-6-amines via Manganese-Catalyzed Enaminylation of 1-(Pyrimidin-2-yl)-1H-indoles with Ketenimines and Subsequent Oxidative Cyclization.

    Science.gov (United States)

    Zhou, Xiaorong; Li, Zhenmin; Zhang, Zhiyin; Lu, Ping; Wang, Yanguang

    2018-03-02

    Manganese-catalyzed C 2 -H enaminylation 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. A migration of the directing group pyrimidinyl occurred during this process. The synthesized 2-enaminyl indoles could be conveniently converted into 5-aryl-7H-benzo[c]carbazol-6-amines.

  9. Development of a solid-phase extraction method with simple MEKC-UV analysis for simultaneous detection of indole metabolites in human urine after administration of indole dietary supplement.

    Science.gov (United States)

    Phonchai, Apichai; Wilairat, Prapin; Chantiwas, Rattikan

    2017-11-01

    This work presents the development of a solid phase extraction method with simple MEKC-UV analysis for the simultaneous determination of indole-3-carbinol (I3C) and its metabolites (3, 3'-diindolylmethane (DIM), indole-3-carboxaldehyde (I3CAL), indole-3-acetonitrile (I3A)) in human urine after oral administration of an indole dietary supplement. Solid phase extraction (SPE) method was applied for the first time for simultaneous analysis of these indole metabolites. The MEKC separation method was developed in a previous work. Three commercial SPE cartridges, each with different sorbent materials, were investigated: Sep-Pak ® C18, Oasis ® HLB and Oasis ® WCX. The Sep-Pak ® C18 material provided the highest extraction recovery of 88-113% (n = 9), for the four target indole metabolites (I3C, DIM, I3CAL and I3A). The optimal washing and elution solutions were 40% methanol/water (v/v) and 100% methanol, respectively, and optimal elution volume was 2.0mL. The specificity of the proposed SPE method was evaluated with negative control urine samples (n = 10) from healthy volunteers who had not taken the dietary supplement or vegetables known to contain indole compounds. Linear calibration curves were in the range of 0.2-25μgmL -1 (r 2 > 0.998) using diphenylamine (DPA) as the internal standard. Intra-day and inter-day precisions were 3.5-12.3%RSD and 2.7-14.1%RSD, respectively. Limits of detection and quantification were 0.05-0.10μgmL -1 and 0.10-0.50μgmL -1 , respectively. The four target indole compounds were separated within only 5min by MEKC-UV analysis. Urine from 5 subjects who had taken a dietary supplement containing I3C and DIM were found to contain only the DIM metabolite at concentrations ranging from 0.10 to 0.35µgmL -1 . Accuracy of the proposed method based on the percentage recovery of spiked urine samples were 70-108%, 82-116%, 82-132% and 80-100% for I3C, I3CAL, I3A and DIM, respectively. The Sep-Pak ® C18 cartridge was highly effective in

  10. A 9-vinyladenine-based molecularly imprinted polymeric membrane for the efficient recognition of plant hormone 1H-indole-3-acetic acid

    International Nuclear Information System (INIS)

    Chen Changbao; Chen Yanjun; Zhou Jie; Wu Chunhui

    2006-01-01

    9-Vinyladenine was synthesized as a novel functional monomer for molecular imprinting techniques and its structure was established with elemental analysis and 1 H NMR spectroscopy. The binding mechanism between this functional monomer 9-vinyladenine and the plant hormone 1 H-indole-3-acetic acid in acetonitrile was studied with UV-vis spectrophotometry. Based on this study, using 1 H-indole-3-acetic acid as a template molecule, a specific 9-vinyladenine-based molecularly imprinted polymeric membrane was prepared. Then, the resultant polymeric membrane morphologies were visualized with scanning electron microscopy, and the membrane permselectivity for 1 H-indole-3-acetic acid, 1 H-indole-3-butyric acid and kinetin was tested with separate experiments and competitive diffusion experiments. These results showed that the imprinted polymeric membrane prepared with 9-vinyladenine exhibited higher transport selectivity for the template molecule 1 H-indole-3-acetic acid than 1 H-indole-3-butyric acid or kinetin. The membrane prepared with 9-vinyladenine also took on higher permselectivity for 1 H-indole-3-acetic acid in comparison with the imprinted membrane made with methacrylic acid. It is predicted that the 9-vinyladenine-based molecularly imprinted membrane may be applicable to the assay of 1 H-indole-3-acetic acid or for the preparation of a molecularly imprinted polymer sensor for the analysis of 1 H-indole-3-acetic acid in plant samples

  11. The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue.

    Science.gov (United States)

    Marusich, Julie A; Antonazzo, Kateland R; Blough, Bruce E; Brandt, Simon D; Kavanagh, Pierce V; Partilla, John S; Baumann, Michael H

    2016-02-01

    In recent years, use of psychoactive synthetic stimulants has grown rapidly. 5-(2-Aminopropyl)indole (5-IT) is a synthetic drug associated with a number of fatalities, that appears to be one of the newest 3,4-methylenedioxymethamphetamine (MDMA) replacements. Here, the monoamine-releasing properties of 5-IT, its structural isomer 6-(2-aminopropyl)indole (6-IT), and MDMA were compared using in vitro release assays at transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) in rat brain synaptosomes. In vivo pharmacology was assessed by locomotor activity and a functional observational battery (FOB) in mice. 5-IT and 6-IT were potent substrates at DAT, NET, and SERT. In contrast with the non-selective releasing properties of MDMA, 5-IT displayed greater potency for release at DAT over SERT, while 6-IT displayed greater potency for release at SERT over DAT. 5-IT produced locomotor stimulation and typical stimulant effects in the FOB similar to those produced by MDMA. Conversely, 6-IT increased behaviors associated with 5-HT toxicity. 5-IT likely has high abuse potential, which may be somewhat diminished by its slow onset of in vivo effects, whereas 6-IT may have low abuse liability, but enhanced risk for adverse effects. Results indicate that subtle differences in the chemical structure of transporter ligands can have profound effects on biological activity. The potent monoamine-releasing actions of 5-IT, coupled with its known inhibition of MAO A, could underlie its dangerous effects when administered alone, and in combination with other monoaminergic drugs or medications. Consequently, 5-IT and related compounds may pose substantial risk for abuse and serious adverse effects in human users. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Transport of Indole-3-Butyric Acid and Indole-3-Acetic Acid in Arabidopsis Hypocotyls Using Stable Isotope Labeling1[C][W][OA

    Science.gov (United States)

    Liu, Xing; Barkawi, Lana; Gardner, Gary; Cohen, Jerry D.

    2012-01-01

    The polar transport of the natural auxins indole-3-butyric acid (IBA) and indole-3-acetic acid (IAA) has been described in Arabidopsis (Arabidopsis thaliana) hypocotyls using radioactive tracers. Because radioactive assays alone cannot distinguish IBA from its metabolites, the detected transport from applied [3H]IBA may have resulted from the transport of IBA metabolites, including IAA. To test this hypothesis, we used a mass spectrometry-based method to quantify the transport of IBA in Arabidopsis hypocotyls by following the movement of [13C1]IBA and the [13C1]IAA derived from [13C1]IBA. We also assayed [13C6]IAA transport in a parallel control experiment. We found that the amount of transported [13C1]IBA was dramatically lower than [13C6]IAA, and the IBA transport was not reduced by the auxin transport inhibitor N-1-naphthylphthalamic acid. Significant amounts of the applied [13C1]IBA were converted to [13C1]IAA during transport, but [13C1]IBA transport was independent of IBA-to-IAA conversion. We also found that most of the [13C1]IBA was converted to ester-linked [13C1]IBA at the apical end of hypocotyls, and ester-linked [13C1]IBA was also found in the basal end at a level higher than free [13C1]IBA. In contrast, most of the [13C6]IAA was converted to amide-linked [13C6]IAA at the apical end of hypocotyls, but very little conjugated [13C6]IAA was found in the basal end. Our results demonstrate that the polar transport of IBA is much lower than IAA in Arabidopsis hypocotyls, and the transport mechanism is distinct from IAA transport. These experiments also establish a method for quantifying the movement of small molecules in plants using stable isotope labeling. PMID:22323783

  13. Endogenous hormone concentrations correlate with fructan metabolism throughout the phenological cycle in Chrysolaena obovata.

    Science.gov (United States)

    Rigui, Athos Poli; Gaspar, Marília; Oliveira, Vanessa F; Purgatto, Eduardo; Carvalho, Maria Angela Machado de

    2015-06-01

    Chrysolaena obovata, an Asteraceae of the Brazilian Cerrado, presents seasonal growth, marked by senescence of aerial organs in winter and subsequent regrowth at the end of this season. The underground reserve organs, the rhizophores, accumulate inulin-type fructans, which are known to confer tolerance to drought and low temperature. Fructans and fructan-metabolizing enzymes show a characteristic spatial and temporal distribution in the rhizophores during the developmental cycle. Previous studies have shown correlations between abscisic acid (ABA) or indole acetic acid (IAA), fructans, dormancy and tolerance to drought and cold, but the signalling mechanism for the beginning of dormancy and sprouting in this species is still unknown. Adult plants were sampled from the field across phenological phases including dormancy, sprouting and vegetative growth. Endogenous concentrations of ABA and IAA were determined by GC-MS-SIM (gas chromatography-mass spectrometry-selected ion monitoring), and measurements were made of fructan content and composition, and enzyme activities. The relative expression of corresponding genes during dormancy and sprouting were also determined. Plants showed a high fructan 1-exohydrolase (EC 3.2.1.153) activity and expression during sprouting in proximal segments of the rhizophores, indicating mobilization of fructan reserves, when ABA concentrations were relatively low and precipitation and temperature were at their minimum values. Concomitantly, higher IAA concentrations were consistent with the role of this regulator in promoting cell elongation and plant growth. With high rates of precipitation and high temperatures in summer, the fructan-synthesizing enzyme sucrose:sucrose 1-fructosyltransferase (EC 2.4.1.99) showed higher activity and expression in distal segments of the rhizophores, which decreased over the course of the vegetative stage when ABA concentrations were higher, possibly signalling the entry into dormancy. The results show

  14. Effects of soil drought stress on plant regeneration efficiency and endogenous hormone levels of immature embryos in wheat (Triticum aestivum L.)

    International Nuclear Information System (INIS)

    Bie, X.; Wang, K.; Liu, C.; Du, L.

    2017-01-01

    In this study, the water supply in soil for wheat mother donor plants was controlled, leading to drought stress conditions, and the relative soil water content (RSWC) was measured in different soil depths. The immature embryos of common wheat (Triticum aestivum L.) 13 days post anthesis (DPA) were used to test regeneration capacity. The accumulation of the plant growth regulators (PGRs) including abscisic acid (ABA), indole-3-acetic acid (IAA), and hydrogen peroxide (H2O2) in the wheat embryos grown under the two conditions was measured. The results indicated that RSWC difference between the drought treatment and the irrigated control was more than 13% at the various soil depths, with the maximum difference was observed at 40 cm depth. Tissue culture evaluation showed that the plant regeneration efficiency of the immature embryos grown under drought stress treatment was significantly higher than that of the tissues grown under the control condition. Assay for PGR found that the drought stress caused obviously increased concentration of endogenous ABA and H2O2, and slightly decreased level of IAA in the target tissues. Therefore, it seems that the concentration of endogenous ABA, IAA, and H2O2 in immature wheat embryos is very important in regeneration capacity. Drought stress can improve the regeneration capacity by changing the levels of ABA, IAA, and H2O2. Our results would be helpful to efficient development of genetically modified wheat plants through improvement of regeneration via manipulating the endogenous PGRs. (author)

  15. Relationship between endogenous hormonal content and somatic organogenesis in callus of peach (Prunus persica L. Batsch) cultivars and Prunus persica×Prunus dulcis rootstocks.

    Science.gov (United States)

    Pérez-Jiménez, Margarita; Cantero-Navarro, Elena; Pérez-Alfocea, Francisco; Le-Disquet, Isabel; Guivarc'h, Anne; Cos-Terrer, José

    2014-05-01

    The relationship between endogenous hormones content and the induction of somatic peach plant was studied. To induce multiple shoots from callus derived from the base of stem explants of the scion cultivars 'UFO-3', 'Flariba' and 'Alice Bigi', and the peach×almond rootstocks 'Garnem' and 'GF677', propagated plants were cultured on Murashige and Skoog salts augmented with 0.1mgL(-1) of indolebutyric acid, 1mgL(-1) of 6-benzylaminopurine and 3% sucrose. The highest regeneration rate was obtained with the peach×almond rootstocks. Endogenous levels of abscisic acid (ABA), indole-3-acetic acid (IAA), zeatin (Z), zeatin riboside (ZR), ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC), salicylic acid (SA), and jasmonic acid (JA) were analyzed in the organogenic callus. Lower levels of several hormones, namely Z, ZR, ABA, and ACC were found in the peach×almond rootstock compared to peach cultivars, while IAA and SA presented inconclusive returns. These results suggest that the difference in somatic organogenesis capacity observed in peach and peach×almond hybrids is markedly affected by the endogenous hormonal content of the studied genotypes. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. [3H]Indole-3-acetyl-myo-inositol hydrolysis by extracts of Zea mays L. vegetative tissue

    Science.gov (United States)

    Hall, P. J.; Bandurski, R. S.

    1986-01-01

    [3H]Indole-3-acetyl-myo-inositol was hydrolyzed by buffered extracts of acetone powders prepared from 4 day shoots of dark grown Zea mays L. seedlings. The hydrolytic activity was proportional to the amount of extract added and was linear for up to 6 hours at 37 degrees C. Boiled or alcohol denatured extracts were inactive. Analysis of reaction mixtures by high performance liquid chromatography demonstrated that not all isomers of indole-3-acetyl-myo-inositol were hydrolyzed at the same rate. Buffered extracts of acetone powders were prepared from coleoptiles and mesocotyls. The rates of hydrolysis observed with coleoptile extracts were greater than those observed with mesocotyl extracts. Active extracts also catalyzed the hydrolysis of esterase substrates such as alpha-naphthyl acetate and the methyl esters of indoleacetic acid and naphthyleneacetic acid. Attempts to purify the indole-3-acetyl-myo-inositol hydrolyzing activity by chromatographic procedures resulted in only slight purification with large losses of activity. Chromatography over hydroxylapatite allowed separation of two enzymically active fractions, one of which catalyzed the hydrolysis of both indole-3-acetyl-myo-inositol and esterase substrates. With the other enzymic hydrolysis of esterase substrates was readily demonstrated, but no hydrolysis of indole-3-acetyl-myo-inositol was ever detected.

  17. [3H]Indole-3-acetyl-myo-inositol hydrolysis by extracts of Zea mays L. vegetative tissue

    International Nuclear Information System (INIS)

    Hall, P.J.; Bandurski, R.S.

    1986-01-01

    [ 3 H]Indole-3-acetyl-myo-inositol was hydrolyzed by buffered extracts of acetone powders prepared from 4 day shoots of dark grown Zea mays L. seedlings. The hydrolytic activity was proportional to the amount of extract added and was linear for up to 6 hours at 37 0 C. Boiled or alcohol denatured extracts were inactive. Analysis of reaction mixtures by high performance liquid chromatography demonstrated that not all isomers of indole-3-acetyl-myo-inositol were hydrolyzed at the same rate. Buffered extracts of acetone powders were prepared from coleoptiles and mesocotyls. The rates of hydrolysis observed with coleoptile extracts were greater than those observed with mesocotyl extracts. Active extracts also catalyzed the hydrolysis of esterase substrates such as α-naphthyl acetate and the methyl esters of indoleacetic acid and naphthyleneacetic acid. Attempts to purify the indole-3-acetyl-myo-inositol hydrolyzing activity by chromatographic procedures resulted in only slight purification with large losses of activity. Chromatography over hydroxylapatite allowed separation of two enzymically active fractions, one of which catalyzed the hydrolysis of both indole-3-acetyl-myo-inositol and esterase substrates. With the other fraction enzymic hydrolysis of esterase substrates was readily demonstrated, but no hydrolysis of indole-3-acetyl-myo-inositol was ever detected

  18. Electrochemical and quantum chemical studies of some indole derivatives as corrosion inhibitors for C38 steel in molar hydrochloric acid

    International Nuclear Information System (INIS)

    Lebrini, M.; Robert, F.; Vezin, H.; Roos, C.

    2010-01-01

    A comparative study of 9H-pyrido[3,4-b]indole (norharmane) and 1-methyl-9H-pyrido[3,4-b]indole (harmane) as inhibitors for C38 steel corrosion in 1 M HCl solution at 25 o C was carried out. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques were applied to study the metal corrosion behavior in the absence and presence of different concentrations of these inhibitors. The OCP as a function of time were also established. Cathodic and anodic polarization curves show that norharmane and harmane are a mixed-type inhibitors. Adsorption of indole derivatives on the C38 steel surface, in 1 M HCl solution, follows the Langmuir adsorption isotherm model. The ΔG ads o values were calculated and discussed. The potential of zero charge (PZC) of the C38 steel in inhibited solution was studied by the EIS method, and a mechanism for the adsorption process was proposed. Raman spectroscopy confirmed that indole molecules strongly adsorbed onto the steel surface. The electronic properties of indole derivates, obtained using the AM1 semi-empirical quantum chemical approach, were correlated with their experimental efficiencies using the linear resistance model (LR).

  19. [Auxin synthesis by the higher fungus Lentinus edodes (Berk.) Sing in the presence of low concentrations of indole compounds].

    Science.gov (United States)

    Tsivileva, O M; Loshchinina, E A; Makarov, O E; Nikitina, V E

    2012-01-01

    The auxin formation in a submerged culture of the xylotrophic basidiomycete Lentinus edodes (Berk.) Sing (Lentinula edodes (Berk.) Pegler) (shiitake) is studied. Biologically active substances of an indole nature are identified, "the effect of small doses" of which lies in not only the stimulation of growth of the mycelium (indole-3-acetic acid, 2 x 10(-7)-2 x 10(-4) g/l), but also in the induction of tryptophan-independent paths of auxin biosynthesis. The above-mentioned path is realized in the presence of exogenous indole (1 x 10(-3)-1 x 10(-4) g/l), as well as while inducing the biosynthesis of indole-3-acetic acid by its microadditives (1 x 10(-5)-1 x 10(-8) g/l), and is accompanied by the formation of anthranilic acid (up to 1.5 mg/l). Induction of the generative development stage ofshiitake by indole derivatives is revealed. It was found that among the studied compounds only indoleacetamide at a concentration of an order of x 10(-4) g/l in the culture fluid of L. edodes had a pronounced stimulatory effect on the formation of shiitake's brown mycelial film.

  20. Novel fused oxazepino-indoles (FOIs) attenuate liver carcinogenesis via IL-6/JAK2/STAT3 signaling blockade as evidenced through data-based mathematical modeling.

    Science.gov (United States)

    Singh, Ashok K; Bhadauria, Archana Singh; Kumar, Umesh; Raj, Vinit; Maurya, Vimal; Kumar, Dinesh; Maity, Biswanath; Prakash, Anand; De, Arnab; Samanta, Amalesh; Saha, Sudipta

    2018-05-15

    To potentiate the well-documented tumor protecting ability of paullones, literatures demand for rational modifications in paullone ring structure and exploration of a precise mechanism underlying their antitumor effects. Thus, recently we synthesized novel paullone-like scaffold, 5H-benzo [2, 3][1,4]oxazepino[5,6-b]indoles, where compounds 13a and 14a attenuated the growth of liver cancer specific Hep-G2 cells in vitro and formed stable binding complex with IL-6. Henceforth, we hypothesized that this action is probably due to the blockade of IL-6 mediated JAK2/STAT3 signaling cascade. A preclinical study was conducted using NDEA-induced HCC rat model by oral administration of FOIs at 10 mg/kg dose for 15 days. The molecular insights were confirmed through ELISA, qRT-PCR, western blot analyses. The study was further confirmed by data-based mathematical modeling using the quantitative data obtained from western blot analysis. 1 H NMR based metabolomics study was also performed to unveil metabolite discriminations among various studied groups. We identified that the HCC condition was produced due to the IL-6 induced activation of JAK2 and STAT3 which, in turn, was due to enhanced phosphorylation of JAK2 and STAT3. The treatment with FOIs led to the significant blockade of the IL-6 mediated JAK2/STAT3 signaling pathway. Besides, FOIs showed their potential ability in restoring perturbed metabolites linked to HCC. In particular, the anticancer efficacy of compound 13a was comparable or somewhat better than marketed chemotherapeutics, 5-flurouracil. These findings altogether opened up possibilities of developing fused oxazepino-indoles (FOIs) as new candidate molecule for plausible alternative of paullones to treat liver cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Identification of (2-aminopropyl)indole positional isomers in forensic samples.

    Science.gov (United States)

    Scott, Kenneth R; Power, John D; McDermott, Seán D; O'Brien, John E; Talbot, Brian N; Barry, Michael G; Kavanagh, Pierce V

    2014-01-01

    In 2012, 5-(2-aminopropyl)indole (5-API, 5-IT) was reported by Norwegian authorities to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) via the Early Warning System (EWS). The 3- isomer, 3-(2-aminopropyl)indole (3-API, AMT, alpha-methyltryptamine), has been available on the recreational drugs market for a somewhat longer time, having first been reported to the EMCDDA by Finnish authorities in 2001. Both isomers are available from online vendors of 'legal highs'. Recently, three forensic drug cases (two tablets and one powder) were presented for routine analysis and the active constituent was tentatively identified as an API isomer. The six positional isomers (2-, 3-, 4-, 5-, 6- and 7-(2-aminopropyl)indoles) were synthesized and analyses by a combination gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS) showed that these could be readily discriminated thus facilitating the identification of 3-API in the tablets and 5-API in the powder. With exception of 5- and 6-APIs, which co-eluted, it was found possible to separate the isomers by GC without derivatization. LC separation also proved to be a feasible method for the discrimination of the isomers. Although the 2- and 7- isomers were not fully resolved by LC, it was found possible to distinguish them using their product ion spectra as the 2- isomer produced the m/z 132 fragment ion formed by loss of vinylamine, whereas the 7- isomer formed m/z 158 through loss of methylamine. In the synthesis 2-API, a novel tricyclic by-product was formed in an annulation reaction where the reaction solvent, tetrahydrofuran, was incorporated into the molecule. Copyright © 2013 John Wiley & Sons, Ltd.

  2. New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity

    Directory of Open Access Journals (Sweden)

    Mehran Fadaeinasab

    2015-11-01

    Full Text Available Background/Aims: Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1 and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2, along with five known, macusine B (3, vinorine (4, undulifoline (5, isoresrpiline (6 and rescinnamine (7 were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE and butyrylcholinesterase (BChE. Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Conclusion: Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations.

  3. New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity.

    Science.gov (United States)

    Fadaeinasab, Mehran; Basiri, Alireza; Kia, Yalda; Karimian, Hamed; Ali, Hapipah Mohd; Murugaiyah, Vikneswaran

    2015-01-01

    Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1) and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2), along with five known, macusine B (3), vinorine (4), undulifoline (5), isoresrpiline (6) and rescinnamine (7) were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations. © 2015 S. Karger AG, Basel.

  4. Effect of diazotrophic bacteria as phosphate solubilizing and indolic compound producers on maize plants

    Directory of Open Access Journals (Sweden)

    Mónica Del Pilar López Ortega

    2013-07-01

    Full Text Available Phosphorus is limiting for growth of maize plants, and because of that use of fertilizers like Rock Phosphate has been proposed. However, direct use of Rock Phosphate is not recommended because of its low availability, so it is necessary to improve it. In this study, a group of diazotrophic bacteria were evaluated as phosphate-solubilizing bacteria, for their production of indolic compounds and for their effects on growth of maize plants. Strains of the genera Azosporillum, Azotobacter, Rhizobium and Klebsiella, were quantitatively evaluated for solubilization of Ca3(PO42 and rock phosphate as a single source of phosphorous in SRS culture media. Additionally, the phosphatase enzyme activity was quantified at pH 5.0, 7.0 and 8.0 using p-nitrophenyl phosphate, and production of indolic compound was determined by colorimetric quantification. The effect of inoculation of bacteria on maize was determined in a completely randomized greenhouse experiment where root and shoot dry weights and phosphorus content were assessed. Results showed that strain C50 produced 107.2 mg .L-1 of available-P after 12 days of fermentation, and AC10 strain had the highest phosphatase activity at pH 8 with 12.7 mg of p-nitrophenol mL .h-1. All strains synthetized indolic compounds, and strain AV5 strain produced the most at 63.03 µg .mL-1. These diazotrophic bacteria increased plant biomass up to 39 % and accumulation of phosphorus by 10%. Hence, use of diazotrphic phosphate-solubilizing bacteria may represent an alternative technology for fertilization systems in maize plants.

  5. Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: Maternal diets rich in indole-3-carbinol versus sulforaphane

    Energy Technology Data Exchange (ETDEWEB)

    Shorey, Lyndsey E.; Madeen, Erin P. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); Atwell, Lauren L.; Ho, Emily [Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, 97331 (United States); Löhr, Christiane V. [Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); College of Veterinary Medicine, Oregon State University, Corvallis, OR, 97331 (United States); Pereira, Clifford B. [Department of Statistics, Oregon State University, Corvallis, OR, 97331 (United States); Dashwood, Roderick H. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States); Williams, David E., E-mail: david.williams@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331 (United States)

    2013-07-01

    Cruciferous vegetable components have been documented to exhibit anticancer properties. Targets of action span multiple mechanisms deregulated during cancer progression, ranging from altered carcinogen metabolism to the restoration of epigenetic machinery. Furthermore, the developing fetus is highly susceptible to changes in nutritional status and to environmental toxicants. Thus, we have exploited a mouse model of transplacental carcinogenesis to assess the impact of maternal dietary supplementation on cancer risk in offspring. In this study, transplacental and lactational exposure to a maternal dose of 15 mg/Kg B.W. of dibenzo[def,p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000 ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity and tumorigenesis when incorporated into the maternal diet at 10% wt/wt. Purified SFN, incorporated in the maternal diet at 400 ppm, also decreased the latency of DBC-dependent morbidity. Interestingly, I3C abrogated the effect of SFN when the two purified compounds were administered in equimolar combination (500 ppm I3C and 600 ppm SFN). SFN metabolites measured in the plasma of neonates positively correlated with exposure levels via the maternal diet but not with offspring mortality. These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period. - Highlights: • Dietary supplementation may modulate cancer risk in a mouse model of lymphoma. • Cruciferous vegetables may not contain sufficient I3C

  6. Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: Maternal diets rich in indole-3-carbinol versus sulforaphane

    International Nuclear Information System (INIS)

    Shorey, Lyndsey E.; Madeen, Erin P.; Atwell, Lauren L.; Ho, Emily; Löhr, Christiane V.; Pereira, Clifford B.; Dashwood, Roderick H.; Williams, David E.

    2013-01-01

    Cruciferous vegetable components have been documented to exhibit anticancer properties. Targets of action span multiple mechanisms deregulated during cancer progression, ranging from altered carcinogen metabolism to the restoration of epigenetic machinery. Furthermore, the developing fetus is highly susceptible to changes in nutritional status and to environmental toxicants. Thus, we have exploited a mouse model of transplacental carcinogenesis to assess the impact of maternal dietary supplementation on cancer risk in offspring. In this study, transplacental and lactational exposure to a maternal dose of 15 mg/Kg B.W. of dibenzo[def,p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000 ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity and tumorigenesis when incorporated into the maternal diet at 10% wt/wt. Purified SFN, incorporated in the maternal diet at 400 ppm, also decreased the latency of DBC-dependent morbidity. Interestingly, I3C abrogated the effect of SFN when the two purified compounds were administered in equimolar combination (500 ppm I3C and 600 ppm SFN). SFN metabolites measured in the plasma of neonates positively correlated with exposure levels via the maternal diet but not with offspring mortality. These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period. - Highlights: • Dietary supplementation may modulate cancer risk in a mouse model of lymphoma. • Cruciferous vegetables may not contain sufficient I3C

  7. Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats.

    Science.gov (United States)

    El-Shinnawy, Nashwa A; Abd-Elmageid, Samira A; Alshailabi, Eda M A

    2014-05-01

    The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.

  8. Undifferentiated pleomorphic sarcoma: indolent, tail-like recurrence of a high-grade tumor

    Energy Technology Data Exchange (ETDEWEB)

    Alpert, Justin S. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Boland, Patrick [Memorial Sloan Kettering Cancer Center, Division of Orthopaedic Surgery, Department of Surgery, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States); Hameed, Meera [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Panicek, David M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States)

    2018-01-15

    Recurrence of a soft tissue sarcoma typically manifests as a round or oval mass at imaging, and recurrent high-grade soft tissue sarcomas generally enlarge relatively rapidly. We present a case of high-grade undifferentiated pleomorphic sarcoma in the calf of a 48-year-old male that recurred as a thin, curvilinear ''tail'' of enhancing tissue at magnetic resonance imaging (MRI), with extremely indolent growth over a 7-year period. The unusual imaging finding of a slowly enlarging ''tail'' should not be dismissed as postoperative changes, even for a high-grade soft tissue sarcoma. (orig.)

  9. Structure determination of two new indole-diterpenoids from Penicillium sp. CM-7 by NMR spectroscopy.

    Science.gov (United States)

    Zhang, Yu-Hong; Huang, Sheng-Dong; Pan, Hua-Qi; Bian, Xi-Qing; Wang, Zai-Ying; Han, Ai-Hong; Bai, Jiao

    2014-06-01

    Two new indole-diterpenoids 4b-deoxy-1'-O-acetylpaxilline (1) and 4b-deoxypenijanthine A (2) were isolated from the fermentation broth and the mycelia of the soil fungus Penicillium sp. CM-7, along with three known structurally related compounds, 1'-O-acetylpaxilline (3), paspaline (4) and 3-deoxo-4b-deoxypaxilline (5). The structures of compounds 1 and 2 were elucidated by extensive spectroscopic methods, especially 2D NMR, and their absolute configurations were suggested on the basis of the circular dichroism spectral analysis and the NOESY data. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Methyl transfer in glucosinolate biosynthesis mediated by indole glucosinolate O-Methyltransferase 5

    DEFF Research Database (Denmark)

    Pfalz, Marina; Mukhaimar, Maisara; Perreau, François

    2016-01-01

    in position 1 (1-IG modification) or 4 (4-IG modification). Products of the 4-IG modification pathway mediate plant-enemy interactions and are particularly important for Arabidopsis innate immunity. While CYP81Fs encoding cytochrome P450 monooxygenases and IGMTs encoding indole glucosinolate O...... with moderate similarity to previously characterized IGMTs, encodes the methyltransferase that is responsible for the conversion of 1OHI3M to 1MOI3M. Disruption of IGMT5 function increases resistance against the root-knot nematode Meloidogyne javanica and suggests a potential role for the 1-IG modification...

  11. Fischer Indole Synthesis in the Gas Phase, the Solution Phase, and at the Electrospray Droplet Interface.

    Science.gov (United States)

    Bain, Ryan M; Ayrton, Stephen T; Cooks, R Graham

    2017-07-01

    Previous reports have shown that reactions occurring in the microdroplets formed during electrospray ionization can, under the right conditions, exhibit significantly greater rates than the corresponding bulk solution-phase reactions. The observed acceleration under electrospray ionization could result from a solution-phase, a gas-phase, or an interfacial reaction. This study shows that a gas-phase ion/molecule (or ion/ion) reaction is not responsible for the observed rate enhancement in the particular case of the Fischer indole synthesis. The results show that the accelerated reaction proceeds in the microdroplets, and evidence is provided that an interfacial process is involved. Graphical Abstract GRAPHICAL ABSTRACT TEXT HERE] -->.

  12. Metabolic pathways of quinoline, indole and their methylated analogs by Desulfobacterium indolicum (DSM 3383)

    DEFF Research Database (Denmark)

    Johansen, S.S.; Licht, D.; Arvin, E.

    1997-01-01

    The transformation of quinoline, isoquinoline and 3-, 4-, 6- and 8-methylquinoline by Desulfobacterium indolicum was compared with that of the N-containing analogues indole and 1-, 2-, 3- and 7-methylindole. The metabolites were identified using high-performance liquid chromatography with UV dete...... inhibited. An incomplete transformation of some methylated compounds was observed, e.g. for 3- and 6-methylquinoline and 3- and 7-methylindole, with residual concentrations of 0.5-4 mg/l in relation to initial concentrations of 10-15 mg/l....

  13. 1-[(1-Methyl-1H-imidazol-5-ylmethyl]-1H-indole-5-carbonitrile

    Directory of Open Access Journals (Sweden)

    Josephus Jacobus de Jager

    2012-12-01

    Full Text Available In the title compound, C14H12N4, the dihedral angle between the indole ring system (r.m.s. deviation = 0.010 Å and the imidazole ring is 77.70 (6°. In the crystal, molecules are linked by C—H...N hydrogen bonds. One set of hydrogen bonds forms an undulating chain running parallel to the b-axis direction, while the other undulating chain is parallel to the c-axis direction. In combination, (100 sheets result.

  14. Environmental policy, pollution, unemployment and endogenous growth

    DEFF Research Database (Denmark)

    Pedersen, Lars Haagen; Nielsen, Søren Bo; Sørensen, Peter Birch

    1995-01-01

    The paper develops a model of endogenous economic growth with pollution externalities and a labor market distorted by union monopoly power and by taxes and transfers. We study the optimal second-best pollution tax and abatement policy and find that a shift toward greener preferences will tend...... to reduce unemployment, although it will hamper growth. We also find that greater labor-market distortions call for higher pollution tax rates. Finally, we show that a switch from quantity control of pollution combined with grandfathering of pollution rights to regulation via emission charges has...

  15. Optimal pollution taxes and endogenous technological progress

    International Nuclear Information System (INIS)

    Parry, I.W.H.

    1995-01-01

    The optimal pollution tax becomes complicated when allowance is made for endogenous innovation, under a patent system. However, if anything, it is below marginal environmental damages, to counteract monopoly pricing by the patent holder, the common pool effect associated with research and a possible excess of patent holder revenue over the social benefits from innovation when environmental damages are convex. In cases where patents are weak at securing appropriability, for example when rivals can easily imitate around patented technologies, awarding research prizes or contracts is probably more efficient than raising the pollution tax. 24 refs., 4 figs

  16. Diverging patterns with endogenous labor migration.

    Science.gov (United States)

    Reichlin, P; Rustichini, A

    1998-05-05

    "The standard neoclassical model cannot explain persistent migration flows and lack of cross-country convergence when capital and labor are mobile. Here we present a model where both phenomena may take place.... Our model is based on the Arrow-Romer approach to endogenous growth theory. We single out the importance of a (however weak) scale effect from the size of the workforce.... The main conclusion of this simple model is that lack of convergence, or even divergence, among countries is possible, even with perfect capital mobility and labor mobility." excerpt

  17. Endogenous population growth may imply chaos.

    Science.gov (United States)

    Prskawetz, A; Feichtinger, G

    1995-01-01

    The authors consider a discrete-time neoclassical growth model with an endogenous rate of population growth. The resulting one-dimensional map for the capital intensity has a tilted z-shape. Using the theory of nonlinear dynamical systems, they obtain numerical results on the qualitative behavior of time paths for changing parameter values. Besides stable and periodic solutions, erratic time paths may result. In particular, myopic and far-sighted economies--assumed to be characterized by low and high savings rate respectively--are characterized by stable per capita capital stocks, while solutions with chaotic windows exist between these two extremes.

  18. Psychological rehabilitation of patients with endogenous disease

    Directory of Open Access Journals (Sweden)

    Tamara Kryvonis

    2013-07-01

    Full Text Available The rationale for early psychotherapeutic intervention in combination with psychopharmatherapy in patients with endogenous disorders is provided. The mechanisms of psychological defenses to deal with traumatic experience, used by personalities functioning on a psychotic level, are also described here. Characteristic behavior patterns of extended family members in terms of emotional codependence are provided. Individual pathopsychology is considered as a symptom of abnormal functioning of the family. Emphasis is placed on the importance of inclusion of family members in psychotherapeutic interaction in order to correct interpersonal relations.

  19. Endogenous Turnover of Cyanogenic Glycosides in Plants

    DEFF Research Database (Denmark)

    Picmanova, Martina

    , there is strong evidence that CNglcs serve a no less significant purpose as a transport and storage form of reduced nitrogen which may be remobilized and recycled to balance the needs of primary metabolism during certain developmental events. Reduced nitrogen from CNglcs may be recovered either via HCN refixation...... revealed the formation of glycosides of amides, carboxylic acids and "anitriles", including their di- and triglycosides, evidently derived from CNglcs. Based on results common to the three phylogenetically unrelated plant species, a recycling endogenous turnover pathway for CNglcs was suggested in which...

  20. Maintenance, endogeneous, respiration, lysis, decay and predation

    DEFF Research Database (Denmark)

    loosdrecht, Marc C. M. Van; Henze, Mogens

    1999-01-01

    mechanism is microbiologically correct. The lysis/decay model mechanism is a strongly simplified representation of reality. This paper tries to review the processes grouped under endogenous respiration in activated sludge models. Mechanisms and processes such as maintenance, lysis, internal and external...... decay, predation and death-regeneration are discussed. From recent microbial research it has become evident that cells do not die by themselves. Bacteria are however subject to predation by protozoa. Bacteria store reserve polymers that in absence of external substrate are used for growth...

  1. [Formation of endogenous pyrogen by mononuclear phagocytes].

    Science.gov (United States)

    Agasarov, L G

    1980-03-01

    Incubation of alveolar macrophages of rabbits and peritoneal macrophages of the abdominal cavity washing of albino mice does not lead to endogenous pyrogen release. Peritoneal macrophages obtained after peritoneal administration to mice of thioglycollate, glycogen or heterologous blood cells do not discharge pyrogen either during incubation without additional stimulation. Macrophages isolated after intraperitoneal administration of heterologous blood cells do not exhibit pyrogenic activity possibly because of a long period of time elapsed after phagocytosis of foreign agents. The triggering of pyrogen formation by macrophages can be effected by means of in vitro phagocytosis of corpuscular particles: staphylococci or heterologous blood cells.

  2. A Role of Endogenous Progesterone in Stroke Cerebroprotection Revealed by the Neural-Specific Deletion of Its Intracellular Receptors.

    Science.gov (United States)

    Zhu, Xiaoyan; Fréchou, Magalie; Liere, Philippe; Zhang, Shaodong; Pianos, Antoine; Fernandez, Neïké; Denier, Christian; Mattern, Claudia; Schumacher, Michael; Guennoun, Rachida

    2017-11-08

    Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult. Here, we used steroid profiling by gas chromatography-tandem mass spectrometry (GC-MS/MS) for exploring adaptive and sex-specific changes in brain levels of progesterone and its metabolites after MCAO. We show that, in the male mouse brain, progesterone is mainly metabolized via 5α-reduction leading to 5α-dihydroprogesterone (5α-DHP), also a progesterone receptor (PR) agonist ligand in neural cells, then to 3α,5α-tetrahydroprogesterone (3α,5α-THP). In the female mouse brain, levels of 5α-DHP and 3α,5α-THP are lower and levels of 20α-DHP are higher than in males. After MCAO, levels of progesterone and 5α-DHP are upregulated rapidly to pregnancy-like levels in the male but not in the female brain. To assess whether endogenous progesterone and 5α-DHP contribute to the resistance of neural cells to ischemic damage, we inactivated PR selectively in the CNS. Deletion of PR in the brain reduced its resistance to MCAO, resulting in increased infarct volumes and neurological deficits in both sexes. Importantly, endogenous PR ligands continue to protect the brain of aging mice. These results uncover the unexpected importance of endogenous progesterone and its metabolites in cerebroprotection. They also reveal that the female reproductive hormone progesterone is an endogenous cerebroprotective neurosteroid in both sexes. SIGNIFICANCE STATEMENT The brain responds to injury with protective signaling and has a remarkable capacity to protect itself. We show here that, in response to ischemic stroke, levels of progesterone and its neuroactive metabolite 5α-dihydroprogesterone are upregulated rapidly in the male mouse brain but not in the

  3. Effects of Organic Solvents on Indigo Formation by Pseudomonas sp. strain ST-200 Grown with High Levels of Indole.

    Science.gov (United States)

    Doukyu, N; Arai, T; Aono, R

    1998-01-01

    The indole tolerance level of Pseudomonas sp. strain ST-200 was 0.25 mg/ml. The level was raised to 4 mg/ml when diphenylmethane was added to the medium to 20% by volume. ST-200 grown in this two-phase culture system containing indole (1 mg/ml) and diphenylmethane (0.2 ml/ml) produced a water-soluble yellow pigment, isatic acid, and two water-insoluble and diphenylmethane-soluble pigments, blue indigo and purple indirubin. The amounts of the water-insoluble pigments corresponded to 0.5% (indigo) and 0.2% (indirubin) of the indole added to the medium. Of the conditions tried, indigo and indirubin were formed only when ST-200 was grown in the two-phase system overlaid with organic solvents with appropriate polarity.

  4. Crystal structure of rac-3-[2,3-bis(phenylsulfanyl-3H-indol-3-yl]propanoic acid

    Directory of Open Access Journals (Sweden)

    Wayland E. Noland

    2015-11-01

    Full Text Available The title compound, C23H19NO2S2, was obtained as an unexpected regioisomer from an attempted synthesis of an intermediate for a substituent-effect study on ergot alkaloids. This is the first report of a 1H-indole monothioating at the 2- and 3-positions to give a 3H-indole. In the crystal, the acid H atom is twisted roughly 180° from the typical carboxy conformation and forms centrosymmetric O—H...N hydrogen-bonded dimers with the indole N atom of an inversion-related molecule. Together with a weak C—H...O hydrogen bond involving the carbonyl O atom, chains are formed along [100].

  5. Indole-3-acetic acid biosynthesis in Fusarium delphinoides strain GPK, a causal agent of Wilt in Chickpea.

    Science.gov (United States)

    Kulkarni, Guruprasad B; Sanjeevkumar, S; Kirankumar, B; Santoshkumar, M; Karegoudar, T B

    2013-02-01

    Fusarium delphinoides (Ascomycota; Nectriaceae) is an indole-3-acetic acid (IAA) producing plant pathogen and a causal agent of wilt in chickpea. The IAA biosynthetic pathway in F. delphinoides strain GPK (FDG) was examined by analyzing metabolic intermediates and by feeding experiments. Gas chromatograph (GC) analysis of FDG culture filtrates showed the presence of metabolic intermediates of indole-3-pyruvic acid (IPyA), indole-3-acetamide (IAM), and tryptamine (TRA) pathways. The different IAA biosynthetic pathways were further confirmed by identifying the presence of different enzymes of these pathways. Substrate specificity study of aromatic amino acid aminotransferase revealed that the enzyme is highly specific for tryptophan (Trp) and α-ketoglutarate (α-kg) as amino group donor and acceptor, respectively. Furthermore, the concentration-dependent effect of exogenous IAA on fungal growth was established. Low concentration of exogenous IAA increases the fungal growth and at high concentration it decreases the growth of FDG.

  6. Synthesis and Structural Characterization of 1-[2-(5-Nitro-1H-indol-2-ylphenyl]methylpyridinium Chloride

    Directory of Open Access Journals (Sweden)

    John B. Bremner

    2011-09-01

    Full Text Available In the course of studies on hybrid antibacterials incorporating 2-aryl-5-nitro-1H-indole moieties as potential bacterial NorA efflux pump inhibitors, the compound 1-[2-(5-nitro-1H-indol-2-ylphenyl]methylpyridinium chloride (2 was synthesized and structurally characterized. This pyridinium chloride salt crystallized in the monoclinic space group P21/c with the following unit cell dimensions: a 10.274(3 Å, b 13.101(4 Å, c 13.439(4 Å, b 107.702(7°, V 1723.2(9 Å3, Z (f.u. = 4; R1 = 0.048, and wR2 = 0.13. Of interest in the single crystal X-ray structure is the (intramolecular disposition of the pyridinium plane over the indole heterocyclic residue [interplanar dihedral angle 17.91(4°].

  7. Probing Endogenous Collagen by Laser Induced Autofluorescence in Burn Wound Biopsies- A Pilot Study.

    Science.gov (United States)

    Prabhu, Vijendra; Acharya, Anusha; Rao, Bola Sadashiva Satish; Rathnakar, Bharath; Kumar, Pramod; Guddattu, Vasudeva; Mahato, Krishna Kishore

    2018-04-19

    The focus of the current study was to interrogate the predictive potential of laser-induced autofluorescence (LIAF) by objectively assessing collagen synthesis in burn wound granulation tissues ex vivo. Prior grafting, granulation tissues (20 samples) following burn injury were collected from 17 subjects of age range 18- 60 years with patient/donor consent and the corresponding autofluorescence spectra were recorded at 325 nm He-Cd laser (≈ 2 mW) excitations. The resulting endogenous collagen intensity from the above tissue samples was computed by normalizing the NADH levels. In addition, the hydroxyproline content was also estimated biochemically from the same granulation tissues. A comparative assessment of both LIAF and biochemical estimations for endogenous collagen by hydroxyproline resulted in strong positive correlation among them. The above relevant observations suggest that LIAF is equally informative as that of biochemical estimations, in evaluating endogenous collagen content in wound granulation tissues. Thus, it can be concluded that LIAF has the predictive potential, as a non-invasive objective tool to measure the endogenous collagen levels in wound biopsy tissues and provide complementary data conducive for making clinical decisions. This article is protected by copyright. All rights reserved.

  8. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior.

    Science.gov (United States)

    Hindle, Samantha J; Munji, Roeben N; Dolghih, Elena; Gaskins, Garrett; Orng, Souvinh; Ishimoto, Hiroshi; Soung, Allison; DeSalvo, Michael; Kitamoto, Toshihiro; Keiser, Michael J; Jacobson, Matthew P; Daneman, Richard; Bainton, Roland J

    2017-10-31

    Central nervous system (CNS) chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB). Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice). Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior

    Directory of Open Access Journals (Sweden)

    Samantha J. Hindle

    2017-10-01

    Full Text Available Summary: Central nervous system (CNS chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB. Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice. Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. : Hindle et al. shed light on the curious finding that some drugs cause behavioral side-effects despite negligible access into the brain. These authors propose a unifying hypothesis that links blood-brain barrier drug transporter function and brain access of circulating steroids to common CNS adverse drug responses. Keywords: drug side effect mechanisms, central nervous system, blood brain barrier, behavior, toxicology, drug transporters, endobiotics, steroid hormones

  10. The clinical significance of gastrointestinal decontamination in the occurrence of endogenous infections.

    Science.gov (United States)

    Ozawa, A; Nagao, T; Sawamura, S; Ikigai, H

    1984-12-01

    No significant difference was seen in the incidence of infections between subjects receiving complete, selective and no decontamination aimed at the intestinal microflora in studies evaluating the preventative potential against endogenous infections in the compromised host maintained under protective isolation. This finding is reported together with a report of Serratia marcescens septicemia in a patient with leukemia who was given antibiotics systemically and kept under protective isolation. The establishment of opportunistic infections in relation to these results is discussed in terms of the biological phenomena of the interaction between the intestinal flora and the host, and between the species comprising the intestinal flora.

  11. Endogenous fibrinolysis facilitates clot retraction in vivo.

    Science.gov (United States)

    Samson, Andre L; Alwis, Imala; Maclean, Jessica A A; Priyananda, Pramith; Hawkett, Brian; Schoenwaelder, Simone M; Jackson, Shaun P

    2017-12-07

    Clot retraction refers to the process whereby activated platelets transduce contractile forces onto the fibrin network of a thrombus, which over time increases clot density and decreases clot size. This process is considered important for promoting clot stability and maintaining blood vessel patency. Insights into the mechanisms regulating clot retraction at sites of vascular injury have been hampered by a paucity of in vivo experimental models. By pairing localized vascular injury with thrombin microinjection in the mesenteric circulation of mice, we have demonstrated that the fibrin network of thrombi progressively compacts over a 2-hour period. This was a genuine retraction process, as treating thrombi with blebbistatin to inhibit myosin IIa-mediated platelet contractility prevented shrinkage of the fibrin network. Real-time confocal analysis of fibrinolysis after recombinant tissue-type plasminogen activator (tPA) administration revealed that incomplete proteolysis of fibrin polymers markedly facilitated clot retraction. Similarly, inhibiting endogenous fibrinolysis with tranexamic acid reduced retraction of fibrin polymers in vivo. In vitro clot retraction experiments indicated that subthreshold doses of tPA facilitated clot retraction through a plasmin-dependent mechanism. These effects correlated with changes in the elastic modulus of fibrin clots. These findings define the endogenous fibrinolytic system as an important regulator of clot retraction, and show that promoting clot retraction is a novel and complementary means by which fibrinolytic enzymes can reduce thrombus size. © 2017 by The American Society of Hematology.

  12. Endogenous antispermatogenic agents: prospects for male contraception.

    Science.gov (United States)

    Ewing, L L; Robaire, B

    1978-01-01

    A review of endogenous antispermatogenic agents as prospects for male contraception is reported. It is demonstrated that endogenous compounds exert regulatory influences at 4 major levels in the male: 1) between germ cells; 2) between Sertoli and germ cells; 3) between Leydig cells and seminiferous tubules; and 4) between the central nervous system and the testis. Efforts to interrupt spermatogenesis have failed to find application as male contraceptives for various reasons: 1) some investigators ignored the vulnerable control points by utilizing nonspecific agents; 2) others attacked a vulnerable control point but used synthetic drugs that had deleterious side effects; and 3) still others attacked a vulnerable control point with a relatively innocuous drug but used an impractical mode of drug administration. The potential for devising innovative techniques for administering relatively innocuous drugs at dosages sufficient to produce sterility without causing deleterious side effects is demonstrated. The most promising solution for the development of an antispermatogenic male contraceptive is the interference with the adenohypophyseal-gonadal axis via the subcutaneous sustained release of steroid formulations containing either androgen-danazol, androgen-progestin, or androgen-estrogen formulations. Another promising agent would be luteinizing releasing hormone agonist-androgen formulation.

  13. Insertional Polymorphisms of Endogenous Feline Leukemia Viruses

    Science.gov (United States)

    Roca, Alfred L.; Nash, William G.; Menninger, Joan C.; Murphy, William J.; O'Brien, Stephen J.

    2005-01-01

    The number, chromosomal distribution, and insertional polymorphisms of endogenous feline leukemia viruses (enFeLVs) were determined in four domestic cats (Burmese, Egyptian Mau, Persian, and nonbreed) using fluorescent in situ hybridization and radiation hybrid mapping. Twenty-nine distinct enFeLV loci were detected across 12 of the 18 autosomes. Each cat carried enFeLV at only 9 to 16 of the loci, and many loci were heterozygous for presence of the provirus. Thus, an average of 19 autosomal copies of enFeLV were present per cat diploid genome. Only five of the autosomal enFeLV sites were present in all four cats, and at only one autosomal locus, B4q15, was enFeLV present in both homologues of all four cats. A single enFeLV occurred in the X chromosome of the Burmese cat, while three to five enFeLV proviruses occurred in each Y chromosome. The X chromosome and nine autosomal enFeLV loci were telomeric, suggesting that ectopic recombination between nonhomologous subtelomeres may contribute to enFeLV distribution. Since endogenous FeLVs may affect the infectiousness or pathogenicity of exogenous FeLVs, genomic variation in enFeLVs represents a candidate for genetic influences on FeLV leukemogenesis in cats. PMID:15767400

  14. Endogenous Technology Adoption and Medical Costs.

    Science.gov (United States)

    Lamiraud, Karine; Lhuillery, Stephane

    2016-09-01

    Despite the claim that technology has been one of the most important drivers of healthcare spending growth over the past decades, technology variables are rarely introduced explicitly in cost equations. Furthermore, technology is often considered exogenous. Using 1996-2007 panel data on Swiss geographical areas, we assessed the impact of technology availability on per capita healthcare spending covered by basic health insurance whilst controlling for the endogeneity of health technology availability variables. Our results suggest that medical research, patent intensity and the density of employees working in the medical device industry are influential factors for the adoption of technology and can be used as instruments for technology availability variables in the cost equation. These results are similar to previous findings: CT and PET scanner adoption is associated with increased healthcare spending, whilst increased availability of percutaneous transluminal coronary angioplasty facilities is associated with reductions in per capita spending. However, our results suggest that the magnitude of these relationships is much greater in absolute value than that suggested by previous studies that did not control for the possible endogeneity of the availability of technologies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Cloning and characterization of indole synthase (INS) and a putative tryptophan synthase α-subunit (TSA) genes from Polygonum tinctorium.

    Science.gov (United States)

    Jin, Zhehao; Kim, Jin-Hee; Park, Sang Un; Kim, Soo-Un

    2016-12-01

    Two cDNAs for indole-3-glycerol phosphate lyase homolog were cloned from Polygonum tinctorium. One encoded cytosolic indole synthase possibly in indigoid synthesis, whereas the other encoded a putative tryptophan synthase α-subunit. Indigo is an old natural blue dye produced by plants such as Polygonum tinctorium. Key step in plant indigoid biosynthesis is production of indole by indole-3-glycerol phosphate lyase (IGL). Two tryptophan synthase α-subunit (TSA) homologs, PtIGL-short and -long, were isolated by RACE PCR from P. tinctorium. The genome of the plant contained two genes coding for IGL. The short and the long forms, respectively, encoded 273 and 316 amino acid residue-long proteins. The short form complemented E. coli ΔtnaA ΔtrpA mutant on tryptophan-depleted agar plate signifying production of free indole, and thus was named indole synthase gene (PtINS). The long form, either intact or without the transit peptide sequence, did not complement the mutant and was tentatively named PtTSA. PtTSA was delivered into chloroplast as predicted by 42-residue-long targeting sequence, whereas PtINS was localized in cytosol. Genomic structure analysis suggested that a TSA duplicate acquired splicing sites during the course of evolution toward PtINS so that the targeting sequence-containing pre-mRNA segment was deleted as an intron. PtINS had about two to fivefolds higher transcript level than that of PtTSA, and treatment of 2,1,3-benzothiadiazole caused the relative transcript level of PtINS over PtTSA was significantly enhanced in the plant. The results indicate participation of PtINS in indigoid production.

  16. Profiling of tryptophan-related plasma indoles in patients with carcinoid tumors by automated, on-line, solid-phase extraction and HPLC with fluorescence detection

    NARCIS (Netherlands)

    Kema, IP; Meijer, WG; Meiborg, G; Ooms, B; Willemse, PHB; de Vries, EGE

    2001-01-01

    Background: Profiling of the plasma indoles tryptophan, 5-hydroxytryptophan (5-HTP), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) is useful in the diagnosis and follow-up of patients with carcinoid tumors. We describe an automated method for the profiling of these indoles in protein-containing

  17. Facile Iodine-Catalyzed Michael Addition of Indoles to α,α′-Bis(arylmethylene)cyclopentanones: An Efficient Synthesis of E-2-(3-Indolylphenylmethyl)-5-phenylmethylenecyclopentanones

    Science.gov (United States)

    Pal, Rammohan; Das Gupta, Arpita; Mallik, Asok K.

    2012-01-01

    Iodine-catalyzed reaction of indoles with α,α′-bis(arylmethylene)cyclopentanones afforded one diastereomer of the corresponding Michael adducts, namely, E-2-(3-indolylphenylmethyl)-5-phenylmethylenecyclopentanones, in a good yield. The products form a new group of indole derivatives. PMID:24052849

  18. One-Pot Synthesis of N-(α-Peroxy)Indole/Carbazole via Chemoselective Three-Component Condensation Reaction in Open Atmosphere

    KAUST Repository

    Wang, Xinbo; Pan, Yupeng; Huang, Kuo-Wei; Lai, Zhiping

    2015-01-01

    A facile one-pot synthesis of N-(α-peroxy)indole and N-(α-peroxy)carbazole has been developed using metal-free, organo-acid-catalyzed three-component condensation reactions of indole/carbazole, aldehyde, and peroxide. Based on the reaction

  19. Facile synthetic approach for 5-aryl-9-hydroxypyrano [3,2-f] indole-2(8H-one

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    2016-11-01

    Full Text Available An appropriate method for the synthesis of 5-aryl-9-hydroxypyrano[3,2-f]indole-2(8H-one was described. The targeted compounds were obtained starting from vanillin via nine steps. Interestingly, in the final cyclization step, the intermediate 4-(2-halogeno phenyl-7-methoxy-1H-indole-6-yl propiolate could convert directly into the final product in one step reaction using PtCl4 or Pd(PPh34/trifluoroacetic acid as catalysts. The possible catalytic mechanism for PtCl4 and Pd(PPh34/trifluoroacetic acid was discussed.

  20. Oxidation of indole-3-acetic acid to oxindole-3-acetic acid by an enzyme preparation from Zea mays

    Science.gov (United States)

    Reinecke, D. M.; Bandurski, R. S.

    1988-01-01

    Indole-3-acetic acid is oxidized to oxindole-3-acetic acid by Zea mays tissue extracts. Shoot, root, and endosperm tissues have enzyme activities of 1 to 10 picomoles per hour per milligram protein. The enzyme is heat labile, is soluble, and requires oxygen for activity. Cofactors of mixed function oxygenase, peroxidase, and intermolecular dioxygenase are not stimulatory to enzymic activity. A heat-stable, detergent-extractable component from corn enhances enzyme activity 6- to 10-fold. This is the first demonstration of the in vitro enzymic oxidation of indole-3-acetic acid to oxindole-3-acetic acid in higher plants.

  1. Dragmacidin G, a Bioactive Bis-Indole Alkaloid from a Deep-Water Sponge of the Genus Spongosorites.

    Science.gov (United States)

    Wright, Amy E; Killday, K Brian; Chakrabarti, Debopam; Guzmán, Esther A; Harmody, Dedra; McCarthy, Peter J; Pitts, Tara; Pomponi, Shirley A; Reed, John K; Roberts, Bracken F; Rodrigues Felix, Carolina; Rohde, Kyle H

    2017-01-11

    A deep-water sponge of the genus Spongosorites has yielded a bis-indole alkaloid which we have named dragmacidin G. Dragmacidin G was first reported by us in the patent literature and has recently been reported by Hitora et al. from a sponge of the genus Lipastrotheya . Dragmacidin G is the first in this series of compounds to have a pyrazine ring linking the two indole rings. It also has a rare N -(2-mercaptoethyl)-guanidine side chain. Dragmacidin G shows a broad spectrum of biological activity including inhibition of methicillin-resistant Staphylococcus aureus , Mycobacterium tuberculosis , Plasmodium falciparum, and a panel of pancreatic cancer cell lines.

  2. Dragmacidin G, a Bioactive Bis-Indole Alkaloid from a Deep-Water Sponge of the Genus Spongosorites

    Directory of Open Access Journals (Sweden)

    Amy E. Wright

    2017-01-01

    Full Text Available A deep-water sponge of the genus Spongosorites has yielded a bis-indole alkaloid which we have named dragmacidin G. Dragmacidin G was first reported by us in the patent literature and has recently been reported by Hitora et al. from a sponge of the genus Lipastrotheya. Dragmacidin G is the first in this series of compounds to have a pyrazine ring linking the two indole rings. It also has a rare N-(2-mercaptoethyl-guanidine side chain. Dragmacidin G shows a broad spectrum of biological activity including inhibition of methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, Plasmodium falciparum, and a panel of pancreatic cancer cell lines.

  3. Iridium- and ruthenium-catalysed synthesis of 2,3-disubstituted indoles from anilines and vicinal diols

    DEFF Research Database (Denmark)

    Tursky, Matyas; Lorentz-Petersen, Linda Luise Reeh; Olsen, L. B.

    2010-01-01

    A straightforward and atom-economical method is described for the synthesis of 2,3-disubstituted indoles. Anilines and 1,2-diols are condensed under neat conditions with catalytic amounts of either [Cp*IrCl2](2)/MsOH or RuCl3 center dot xH(2)O/phosphine (phosphine = PPh3 or xantphos). The reactio...... the alpha-hydroxyimine which rearranges to the corresponding alpha-aminoketone. Acid-or metal-catalysed electrophilic ring-closure with the release of water then furnishes the indole product....

  4. A cluster of deaths involving 5-(2-aminopropyl)indole (5-IT).

    Science.gov (United States)

    Kronstrand, Robert; Roman, Markus; Dahlgren, Maria; Thelander, Gunilla; Wikström, Maria; Druid, Henrik

    2013-10-01

    During 2012, the designer drug 5-(2-aminopropyl)indole emerged in Sweden, and became available at different web sites under the name 5-IT or 5-API. This compound is an indole derivative and a positional isomer of alpha-methyltryptamine. In this paper, we report the pathology and toxicology from 15 deaths involving 5-IT. Routine postmortem toxicology was performed in femoral blood, using a targeted screening for pharmaceuticals and drugs of abuse with liquid chromatography time-of-flight technology, and positive results were quantified using chromatographic techniques. For 5-IT, a new method was developed using ultra-high-performance liquid chromatography and tandem mass spectrometry. In 11 cases, intoxication was the cause of death. Two cases were signed out as causa ignota, and they were considered to be natural deaths. All determinations of 5-IT were performed in femoral blood and the concentrations ranged from 0.7 to 18.6 µg/g. Two cases had 5-IT as the only drug identified, while the others presented with other psychotropic drugs or medications in the blood as well. Shortly after this series of deaths, 5-IT was scheduled as a hazardous substance according to the regulation Certain Goods Dangerous to Health on 18 September 2012 prohibiting the handling and selling of the drug. Since then, no positive cases have been found.

  5. Facile synthesis of indole-pyrimidine hybrids and evaluation of their anticancer and antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Nikhila Gokhale

    2017-11-01

    Full Text Available The paper describes the facile synthesis of new N-cyclopropyl-1-methyl-1H-indole-2-carboxamide derivatives bearing substituted 2-amino pyrimidine moiety at position-3 of the indole ring. All the intermediate and title compounds were characterized adeptly by 1H NMR, 13C NMR, ESI–MS and elemental analyses. These compounds were evaluated for their in vitro anticancer activity against HeLa, HepG2 and MCF-7 cells. Three among 22 molecules, showed more than 70% growth inhibition against all three tested cancer cells. The nature of the substituent group on the pyrimidine ring (R2 affected significantly the anti-proliferative activity of the molecules. The anti-microbial evaluation of the title molecules revealed the significance of fluoro/chloro groups (R2 in enhancing their inhibition activity. Eight molecules which contain fluoro/chloro groups showed potent anti-microbial activity. In addition, the active molecules displayed negligible toxicity to benign Vero cells.

  6. Inhibitory effect of indole analogs against Paenibacillus larvae, the causal agent of American foulbrood disease.

    Science.gov (United States)

    Alvarado, Israel; Margotta, Joseph W; Aoki, Mai M; Flores, Fernando; Agudelo, Fresia; Michel, Guillermo; Elekonich, Michelle M; Abel-Santos, Ernesto

    2017-09-01

    Paenibacillus larvae, a Gram-positive bacterium, causes American foulbrood (AFB) in honey bee larvae (Apis mellifera Linnaeus [Hymenoptera: Apidae]). P. larvae spores exit dormancy in the gut of bee larvae, the germinated cells proliferate, and ultimately bacteremia kills the host. Hence, spore germination is a required step for establishing AFB disease. We previously found that P. larvae spores germinate in response to l-tyrosine plus uric acid in vitro. Additionally, we determined that indole and phenol blocked spore germination. In this work, we evaluated the antagonistic effect of 35 indole and phenol analogs and identified strong inhibitors of P. larvae spore germination in vitro. We further tested the most promising candidate, 5-chloroindole, and found that it significantly reduced bacterial proliferation. Finally, feeding artificial worker jelly containing anti-germination compounds to AFB-exposed larvae significantly decreased AFB infection in laboratory-reared honey bee larvae. Together, these results suggest that inhibitors of P. larvae spore germination could provide another method to control AFB. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

  7. Rituximab and new regimens for indolent lymphoma: a brief update from 2012 ASCO Annual Meeting

    Directory of Open Access Journals (Sweden)

    Zhao Jiangning

    2012-08-01

    Full Text Available Abstract Indolent lymphoma (IL, the second most common lymphoma, remains incurable with chemotherapy alone. While R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone remains the standard frontline regimen for diffuse Large B –cell lymphoma, the optimal chemotherapy regimen for frontline therapy of advanced IL remains uncertain. FCR (fludarabine, cyclophosphamide, rituximab has been shown to be better than fludarabine alone and fludarabine plus cyclophosphamide for IL. In FOLL05 trial, R-CHOP was compared with R-CVP (cyclophosphamide, vincristine, prednisone and R-FM (fludarabine, mitoxantrone. The study showed that R-CHOP appears to have the best risk-benefit ratio for IL. The StiL NHL1 trial showed that BR (bendamustine, rituximab has longer progression free survival and is better tolerated than R-CHOP. Long-term complications with secondary malignancies between the two regimens appear to be comparable. In this review, new combination regimens reported at 2012 ASCO annual meeting were evaluated for frontline and salvage therapy of indolent lymphoma.

  8. Unravelling Protein-Protein Interaction Networks Linked to Aliphatic and Indole Glucosinolate Biosynthetic Pathways in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Sebastian J. Nintemann

    2017-11-01

    Full Text Available Within the cell, biosynthetic pathways are embedded in protein-protein interaction networks. In Arabidopsis, the biosynthetic pathways of aliphatic and indole glucosinolate defense compounds are well-characterized. However, little is known about the spatial orchestration of these enzymes and their interplay with the cellular environment. To address these aspects, we applied two complementary, untargeted approaches—split-ubiquitin yeast 2-hybrid and co-immunoprecipitation screens—to identify proteins interacting with CYP83A1 and CYP83B1, two homologous enzymes specific for aliphatic and indole glucosinolate biosynthesis, respectively. Our analyses reveal distinct functional networks with substantial interconnection among the identified interactors for both pathway-specific markers, and add to our knowledge about how biochemical pathways are connected to cellular processes. Specifically, a group of protein interactors involved in cell death and the hypersensitive response provides a potential link between the glucosinolate defense compounds and defense against biotrophic pathogens, mediated by protein-protein interactions.

  9. Whole body magnetic resonance in indolent lymphomas under watchful waiting. The time is now

    Energy Technology Data Exchange (ETDEWEB)

    Galia, Massimo; Albano, Domenico; Midiri, Massimo; Lagalla, Roberto [University of Palermo, Department of Radiology, Di.Bi.Med., Palermo (Italy); Tarella, Corrado [European Institute of Oncology, Hemato-Oncology Division, Milan (Italy); Patti, Caterina; Mule, Antonino [Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Department of Hematology I, Palermo (Italy); Sconfienza, Luca Maria [IRCCS Istituto Ortopedico Galeazzi, Unit of Diagnostic and Interventional Radiology, Milano (Italy); Universita degli Studi di Milano, Department of Biomedical Sciences for Health, Milano (Italy); Alongi, Pierpaolo [Fondazione Istituto G. Giglio, Contrada Pietrapollastra-Pisciotto, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy)

    2018-03-15

    The indolent non-Hodgkin lymphomas (i-NHLs) are characterised by 'indolent' clinical behaviour with slow growth and prolonged natural history. The watchful waiting (WW) strategy is a frequently employed treatment option in these patients. This implies a strict monitoring by imaging examinations, including 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) and CT. A major concern is radiation exposure due to regularly monitoring by conventional imaging procedures. Several studies have demonstrated the reliability of whole-body magnetic resonance imaging (WB-MRI) for lymphoma staging. WB-MRI could be useful for active surveillance in i-NHLs providing the suspect of disease progression that can be then confirmed by additional diagnostic procedures, including 18F-FDG-PET/CT. The directive 2013/59 by the European Union claims that if a radiation-free imaging technique allows obtaining the same diagnostic results, it should be invariably used. In this setting, WB-MRI may be considered a reasonable option in i-NHLs under WW, replacing imaging modalities that cause exposure to ionising radiations. This will help to reduce the cancer risk in i-NHL patients for whom chemo-/radiotherapy remain the usual treatment options following the usually long WW phase. The scientific community should raise the awareness of the risk of ionising radiations in i-NHLs and the emphasise the need for establishing the proper place of WB-MRI in lymphoma imaging. (orig.)

  10. Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression

    International Nuclear Information System (INIS)

    Busbee, Philip B.; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2014-01-01

    Staphylococcal enterotoxin B (SEB) is a potent exotoxin produced by the Staphylococcus aureus. This toxin is classified as a superantigen because of its ability to directly bind with MHC-II class molecules followed by activation of a large proportion of T cells bearing specific Vβ-T cell receptors. Commonly associated with classic food poisoning, SEB has also been shown to induce toxic shock syndrome, and is also considered to be a potential biological warfare agent because it is easily aerosolized. In the present study, we assessed the ability of indole-3-carbinol (I3C) and one of its byproducts, 3,3′-diindolylmethane (DIM), found in cruciferous vegetables, to counteract the effects of SEB-induced activation of T cells in mice. Both I3C and DIM were found to decrease the activation, proliferation, and cytokine production by SEB-activated Vβ8 + T cells in vitro and in vivo. Interestingly, inhibitors of histone deacetylase class I (HDAC-I), but not class II (HDAC-II), showed significant decrease in SEB-induced T cell activation and cytokine production, thereby suggesting that epigenetic modulation plays a critical role in the regulation of SEB-induced inflammation. In addition, I3C and DIM caused a decrease in HDAC-I but not HDAC-II in SEB-activated T cells, thereby suggesting that I3C and DIM may inhibit SEB-mediated T cell activation by acting as HDAC-I inhibitors. These studies not only suggest for the first time that plant-derived indoles are potent suppressors of SEB-induced T cell activation and cytokine storm but also that they may mediate these effects by acting as HDAC inhibitors. - Highlights: • I3C and DIM reduce SEB-induced T cell activation and inflammatory cytokines. • Inhibiting class I HDACs reduces T cell activation and inflammatory cytokines. • Inhibiting class II HDACs increases T cell activation and inflammatory cytokines. • I3C and DIM selectively reduce mRNA expression of class I HDACs. • Novel use and mechanism to counteract SEB

  11. Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression

    Energy Technology Data Exchange (ETDEWEB)

    Busbee, Philip B.; Nagarkatti, Mitzi; Nagarkatti, Prakash S., E-mail: prakash@mailbox.sc.edu

    2014-01-01

    Staphylococcal enterotoxin B (SEB) is a potent exotoxin produced by the Staphylococcus aureus. This toxin is classified as a superantigen because of its ability to directly bind with MHC-II class molecules followed by activation of a large proportion of T cells bearing specific Vβ-T cell receptors. Commonly associated with classic food poisoning, SEB has also been shown to induce toxic shock syndrome, and is also considered to be a potential biological warfare agent because it is easily aerosolized. In the present study, we assessed the ability of indole-3-carbinol (I3C) and one of its byproducts, 3,3′-diindolylmethane (DIM), found in cruciferous vegetables, to counteract the effects of SEB-induced activation of T cells in mice. Both I3C and DIM were found to decrease the activation, proliferation, and cytokine production by SEB-activated Vβ8{sup +} T cells in vitro and in vivo. Interestingly, inhibitors of histone deacetylase class I (HDAC-I), but not class II (HDAC-II), showed significant decrease in SEB-induced T cell activation and cytokine production, thereby suggesting that epigenetic modulation plays a critical role in the regulation of SEB-induced inflammation. In addition, I3C and DIM caused a decrease in HDAC-I but not HDAC-II in SEB-activated T cells, thereby suggesting that I3C and DIM may inhibit SEB-mediated T cell activation by acting as HDAC-I inhibitors. These studies not only suggest for the first time that plant-derived indoles are potent suppressors of SEB-induced T cell activation and cytokine storm but also that they may mediate these effects by acting as HDAC inhibitors. - Highlights: • I3C and DIM reduce SEB-induced T cell activation and inflammatory cytokines. • Inhibiting class I HDACs reduces T cell activation and inflammatory cytokines. • Inhibiting class II HDACs increases T cell activation and inflammatory cytokines. • I3C and DIM selectively reduce mRNA expression of class I HDACs. • Novel use and mechanism to counteract

  12. Indole-3-Acetic Acid Is Produced by Emiliania huxleyi Coccolith-Bearing Cells and Triggers a Physiological Response in Bald Cells.

    Science.gov (United States)

    Labeeuw, Leen; Khey, Joleen; Bramucci, Anna R; Atwal, Harjot; de la Mata, A Paulina; Harynuk, James; Case, Rebecca J

    2016-01-01

    Indole-3-acetic acid (IAA) is an auxin produced by terrestrial plants which influences development through a variety of cellular mechanisms, such as altering cell orientation, organ development, fertility, and cell elongation. IAA is also produced by bacterial pathogens and symbionts of plants and algae, allowing them to manipulate growth and development of their host. They do so by either producing excess exogenous IAA or hijacking the IAA biosynthesis pathway of their host. The endogenous production of IAA by algae remains contentious. Using Emiliania huxleyi, a globally abundant marine haptophyte, we investigated the presence and potential role of IAA in algae. Homologs of genes involved in several tryptophan-dependent IAA biosynthesis pathways were identified in E. huxleyi. This suggests that this haptophyte can synthesize IAA using various precursors derived from tryptophan. Addition of L-tryptophan to E. huxleyi stimulated IAA production, which could be detected using Salkowski's reagent and GC × GC-TOFMS in the C cell type (coccolith bearing), but not in the N cell type (bald). Various concentrations of IAA were exogenously added to these two cell types to identify a physiological response in E. huxleyi. The N cell type, which did not produce IAA, was more sensitive to it, showing an increased variation in cell size, membrane permeability, and a corresponding increase in the photosynthetic potential quantum yield of Photosystem II (PSII). A roseobacter (bacteria commonly associated with E. huxleyi) Ruegeria sp. R11, previously shown to produce IAA, was co-cultured with E. huxleyi C and N cells. IAA could not be detected from these co-cultures, and even when stimulated by addition of L-tryptophan, they produced less IAA than axenic C type culture similarly induced. This suggests that IAA plays a novel role signaling between different E. huxleyi cell types, rather than between a bacteria and its algal host.

  13. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    Science.gov (United States)

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

    Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR.

  14. International Environmental Agreements with Endogenous or Exogenous Risk

    OpenAIRE

    Fuhai Hong; Larry Karp

    2014-01-01

    We examine the effect of endogenous and exogenous risk on the equilibrium (expected) membership of an International Environmental Agreement when countries are risk averse. Endogenous risk arises when countries use mixed rather than pure strategies at the participation game, and exogenous risk arises from the inherent uncertainty about the costs and benefits of increased abate- ment. Under endogenous risk, an increase in risk aversion increases expected participation. Under exogenous risk and ...

  15. Horizontalists, verticalists, and structuralists: The theory of endogenous money reassessed

    OpenAIRE

    Palley, Thomas I.

    2013-01-01

    This paper uses the occasion of the twenty-fifth anniversary of Basil Moore’s book, Horizontalists and Verticalists, to reassess the theory of endogenous money. The paper distinguishes between horizontalists, verticalists, and structuralists. It argues Moore’s horizontalist representation of endogenous money was an over-simplification that discarded important enduring insights from monetary theory. The structuralist approach to endogenous money retains the basic insight that the money supply ...

  16. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...

  17. Sucessfull management of bilateral presumed Candida endogenous endophtalmitis following pancreatitis

    Directory of Open Access Journals (Sweden)

    Ricardo Evangelista Marrocos de Aragão

    2016-06-01

    Full Text Available ABSTRACT Endogenous endophthalmitis is a rare, and frequently devastating, ophthalmic disease. It occurs mostly in immunocompromised patients, or those with diabetes mellitus, cancer or intravenous drugs users. Candida infection is the most common cause of endogenous endophthalmitis. Ocular candidiasis develops within days to weeks of fungemia. The association of treatment for pancreatitis with endophthalmitis is unusual. Treatment with broad-spectrum antibiotics and total parenteral nutrition may explain endogenous endophthalmitis. We report the case of a patient with pancreatitis treated with broad-spectrum antibiotics and total parenteral nutrition who developed bilateral presumed Candida endogenous endophthalmitis that was successfully treated with vitrectomy and intravitreal amphotericin B.

  18. Changing Endogenous Development: the Territorial Capital

    Directory of Open Access Journals (Sweden)

    Balázs István Tóth

    2011-12-01

    Full Text Available The aim of this research is to analyze territorial capital as a new paradigm to make best use of endogenous assets. The study is dealing with the preconditions, meaning and possible theoretical taxonomies of territorial capital. In this study I emphasize that the cumulative effects of regional potentials are more important than economies of scale and location factors. I present different approaches and interpretations of territorial capital, then make an attempt to create an own model. I try to find answers for questions, such as why territorial capital shows a new perspective of urban and regional development; how cognitive elements of territorial capital provide increasing return; how territorial capital influences competitiveness and what kind of relation it has with cohesion.

  19. Public Procurement of Innovation as Endogenous

    DEFF Research Database (Denmark)

    Rolfstam, Max

    Public procurement used as an innovation policy instrument has attracted attention the last decade. It has been argued that public procurement can be used to stimulate innovation from the demand-side. This paper problematizes ‘demand’ understood as a problem defined by a public procurer given...... to potential suppliers to solve. By drawing on a cross-case analysis of two similar projects the paper attempts to explicate an understanding of the role of public procurement of innovation not primarily as a ‘demand-side innovation instrument’, as such thinking might run the risk of ignoring important...... underlying mechanisms critical for success. Instead the paper views public procurement of innovation as an instrument of endogenous- exogenous knowledge conversion....

  20. Endogenous Markups, Firm Productivity and International Trade:

    DEFF Research Database (Denmark)

    Bellone, Flora; Musso, Patrick; Nesta, Lionel

    ) markups are positively related to firm productivity; 3) markups are negatively related to import penetration; 4) markups are positively related to firm export intensity and markups are higher on the export market than on the domestic ones in the presence of trade barriers and/or if competitors...... on the export market are less efficient than competitors on the domestic market. We estimate micro-level price cost margins (PCMs) using firm-level data extending the techniques developed by Hall (1986, 1988) and extended by Domowitz et al. (1988) and Roeger (1995) for the French manufacturing industry from......In this paper, we test key micro-level theoretical predictions ofMelitz and Ottaviano (MO) (2008), a model of international trade with heterogenous firms and endogenous mark-ups. At the firm-level, the MO model predicts that: 1) firm markups are negatively related to domestic market size; 2...

  1. Involvement of Endogenous Retroviruses in Prion Diseases

    Directory of Open Access Journals (Sweden)

    Yong-Sun Kim

    2013-08-01

    Full Text Available For millions of years, vertebrates have been continuously exposed to infection by retroviruses. Ancient retroviral infection of germline cells resulted in the formation and accumulation of inherited retrovirus sequences in host genomes. These inherited retroviruses are referred to as endogenous retroviruses (ERVs, and recent estimates have revealed that a significant portion of animal genomes is made up of ERVs. Although various host factors have suppressed ERV activation, both positive and negative functions have been reported for some ERVs in normal and abnormal physiological conditions, such as in disease states. Similar to other complex diseases, ERV activation has been observed in prion diseases, and this review will discuss the potential involvement of ERVs in prion diseases.

  2. Exogenous and endogenous landforms in the Mediterranean

    Science.gov (United States)

    Acar, Julia

    2017-04-01

    11th graders have already learned about endogenous forces and now we are having a closer look at the exogenous forces which act on the Earth's surface. The Po River-system, for example, is responsible for the formation of the alpine region. Students are asked to find out how this works with the help of the rock-cycle scheme, several suitable maps and information on weathering and the texture of rocks, erosion, etc. We will form groups that will look at different types of rock formations (including an example in the Mediterranean region each). Depending on the number of lessons available we will add the exogenous effect of flowing water and ice (glacial over forming) to the topic. At the end every group will present their findings explaining the scientific context by using topographic examples.

  3. Unfunded pensions and endogenous labor supply

    DEFF Research Database (Denmark)

    Andersen, Torben M.; Bhattacharya, Joydeep

    A classic result in dynamic public economics, dating back to Aaron (1966) and Samuelson (1975), states that there is no welfare rationale for PAYG pensions in a dynamically-efficient neoclassical economy with exogenous labor supply. This paper argues that this result, under the fairly-mild restri......A classic result in dynamic public economics, dating back to Aaron (1966) and Samuelson (1975), states that there is no welfare rationale for PAYG pensions in a dynamically-efficient neoclassical economy with exogenous labor supply. This paper argues that this result, under the fairly......-mild restriction that the old be no less risk-averse than the young, extends to a neoclassical economy with endogenous labor supply....

  4. Transfer of endogenous pyrogens across artificial membranes?

    Science.gov (United States)

    Lonnemann, G; Linnenweber, S; Burg, M; Koch, K M

    1998-05-01

    Synthetic high-flux dialyzer membranes used in continuous veno-venous hemofiltration are permeable to middle molecular size endogenous pyrogens, the pro-inflammatory cytokines IL-1 beta and TNF-alpha. The quantities removed by sieving are, however, negligible in vitro as well as in vivo. Adsorption of cytokines to the membrane polymer is the major mechanism of pyrogen removal. Adsorption seems to be semispecific for pro-inflammatory cytokines because levels of anti-inflammatory mediators were not changed or even increased during CVVH. Thus, CVVH may change cytokine profiles in septic patients supporting the predominance of anti-inflammatory over pro-inflammatory activity in plasma. It remains to be demonstrated whether modifications of extracorporeal blood purification systems (high-volume CVVH, plasma separation + adsorption) are able to amplify the change in cytokine profiles and whether this change influences outcome of septic patients.

  5. Endogenous Methanol Regulates Mammalian Gene Activity

    Science.gov (United States)

    Komarova, Tatiana V.; Petrunia, Igor V.; Shindyapina, Anastasia V.; Silachev, Denis N.; Sheshukova, Ekaterina V.; Kiryanov, Gleb I.; Dorokhov, Yuri L.

    2014-01-01

    We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH) converts methanol into toxic formaldehyde. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP) and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signalling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis. PMID:24587296

  6. Dynamic option pricing with endogenous stochastic arbitrage

    Science.gov (United States)

    Contreras, Mauricio; Montalva, Rodrigo; Pellicer, Rely; Villena, Marcelo

    2010-09-01

    Only few efforts have been made in order to relax one of the key assumptions of the Black-Scholes model: the no-arbitrage assumption. This is despite the fact that arbitrage processes usually exist in the real world, even though they tend to be short-lived. The purpose of this paper is to develop an option pricing model with endogenous stochastic arbitrage, capable of modelling in a general fashion any future and underlying asset that deviate itself from its market equilibrium. Thus, this investigation calibrates empirically the arbitrage on the futures on the S&P 500 index using transaction data from September 1997 to June 2009, from here a specific type of arbitrage called “arbitrage bubble”, based on a t-step function, is identified and hence used in our model. The theoretical results obtained for Binary and European call options, for this kind of arbitrage, show that an investment strategy that takes advantage of the identified arbitrage possibility can be defined, whenever it is possible to anticipate in relative terms the amplitude and timespan of the process. Finally, the new trajectory of the stock price is analytically estimated for a specific case of arbitrage and some numerical illustrations are developed. We find that the consequences of a finite and small endogenous arbitrage not only change the trajectory of the asset price during the period when it started, but also after the arbitrage bubble has already gone. In this context, our model will allow us to calibrate the B-S model to that new trajectory even when the arbitrage already started.

  7. How Active Are Porcine Endogenous Retroviruses (PERVs?

    Directory of Open Access Journals (Sweden)

    Joachim Denner

    2016-08-01

    Full Text Available Porcine endogenous retroviruses (PERVs represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs, which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated nuclease (CRISPR/Cas technology.

  8. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-05-01

    Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

  9. Endogenous methanol regulates mammalian gene activity.

    Directory of Open Access Journals (Sweden)

    Tatiana V Komarova

    Full Text Available We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH converts methanol into toxic formaldehyde. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signalling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis.

  10. Mycobacterium tuberculosis has diminished capacity to counteract redox stress induced by elevated levels of endogenous superoxide.

    Science.gov (United States)

    Tyagi, Priyanka; Dharmaraja, Allimuthu T; Bhaskar, Ashima; Chakrapani, Harinath; Singh, Amit

    2015-07-01

    Mycobacterium tuberculosis (Mtb) has evolved protective and detoxification mechanisms to maintain cytoplasmic redox balance in response to exogenous oxidative stress encountered inside host phagocytes. In contrast, little is known about the dynamic response of this pathogen to endogenous oxidative stress generated within Mtb. Using a noninvasive and specific biosensor of cytoplasmic redox state of Mtb, we for first time discovered a surprisingly high sensitivity of this pathogen to perturbation in redox homeostasis induced by elevated endogenous reactive oxygen species (ROS). We synthesized a series of hydroquinone-based small molecule ROS generators and found that ATD-3169 permeated mycobacteria to reliably enhance endogenous ROS including superoxide radicals. When Mtb strains including multidrug-resistant (MDR) and extensively drug-resistant (XDR) patient isolates were exposed to this compound, a dose-dependent, long-lasting, and irreversible oxidative shift in intramycobacterial redox potential was detected. Dynamic redox potential measurements revealed that Mtb had diminished capacity to restore cytoplasmic redox balance in comparison with Mycobacterium smegmatis (Msm), a fast growing nonpathogenic mycobacterial species. Accordingly, Mtb strains were extremely susceptible to inhibition by ATD-3169 but not Msm, suggesting a functional linkage between dynamic redox changes and survival. Microarray analysis showed major realignment of pathways involved in redox homeostasis, central metabolism, DNA repair, and cell wall lipid biosynthesis in response to ATD-3169, all consistent with enhanced endogenous ROS contributing to lethality induced by this compound. This work provides empirical evidence that the cytoplasmic redox poise of Mtb is uniquely sensitive to manipulation in steady-state endogenous ROS levels, thus revealing the importance of targeting intramycobacterial redox metabolism for controlling TB infection. Copyright © 2015 The Authors. Published by

  11. Effect of adeturone on the concentration of endogenous sulfhydryl groups in mouse spleen and liver

    International Nuclear Information System (INIS)

    Pantev, T.; Bychvarova, K.

    1981-01-01

    Levels of endogenous sulfhydryl groups (total, protein, and non-protein) in mouse liver and spleen were studied for response to the radioprotective drug Adeturone (AET adenosine triphosphate) as recorded at various time intervals (5 - 90 min) following administration of a 300 mg/kg b.w. dose. Spleen sulfhydryl concentration levels tended to elevation, with the peak effect noted at 45 min post-treatment. In the liver, augmentation was observed only for non-protein sylfhydryl groups, at 10 and 15 min post-treatment (time intervals when Adeturone affords maximum protection against radiation); at the 60 min, however, there was a statistically reliable drop. The findings indicate that Adeturone treatment produces response patterns of opposite directions in liver and spleen endogenous thiols. (A.B.)

  12. THE PROCESSES OF ENDOGENIZING IN THE ENDOGENOUS GROWTH: THE CASE OF TURKEY

    Directory of Open Access Journals (Sweden)

    OSMAN DEMİR

    2013-06-01

    Full Text Available The aim of this study is to state how the main inputs of endogenous growth, i.e. knowledge, human capital and technological progress are made endogenous by education, R&D, university-industry cooperation, learning by doing and diffusion within the production process. Competitiveness of firms and countries would increase as educated people enter into workforce; as R&D produces new technologies which are used in the production process; as theoretical knowledge meets with practice by university-industry cooperation; and as workers have more experience by learning by doing. In empirical analysis for Turkey is made by using data of 1970-2001 term it was found that a positive relationship among labour and capital factors and GNP and a negative relationship among education expenditures and foreign trade volume and capital stock.

  13. Palliation by Low-Dose Local Radiation Therapy for Indolent Non-Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Elisa K. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Fung, Sharon [Department of Clinical Study Coordination and Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Gospodarowicz, Mary; Hodgson, David; Wells, Woodrow; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Pintile, Melania [Department of Clinical Study Coordination and Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Southlake Regional Health Centre, Newmarket, Ontario (Canada); Tsang, Richard W., E-mail: richard.tsang@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)

    2011-12-01

    Purpose: The purpose of this study was to assess the efficacy of a 2 Multiplication-Sign 2 Gy (total dose, 4 Gy) palliative radiation therapy (RT) regimen for treating patients with indolent non-Hodgkin lymphoma (NHL) in terms of response rate, response duration, and symptom relief. Methods and Materials: A retrospective chart review was conducted. Between 2003 and 2007, 54 patients with NHL were treated to 85 anatomical sites with a 2 Multiplication-Sign 2 Gy palliative regimen. Local response was assessed by clinical and/or radiographic data. Symptoms before and after treatment for each site treated were obtained from clinical notes in patient medical records. Median follow-up time was 1.3 years. Results: For the 54 patients, the median age at time of treatment was 71.1 years old, and 57% of them were male. Of the 85 disease sites treated, 56% of sites had indolent histology, 28% of sites were diagnosed with chronic lymphocytic leukemia (CLL), 13% of sites had aggressive histology, and 2% of sites were shown to have other histology. Overall response rate (ORR) was 81% (49% complete response [CR], 32% partial response [PR]). The 2-year rate for freedom from local progression was 50% (95% CI, 37%-61%). The ORR for follicular lymphoma, Mucosa associated lymphoid tissue (MALT), and marginal zone lymphoma (MZL) histology was 88%, compared with a 59% rate for CLL histology (p = 0.005). While the ORR was similar for tumors of different sizes, the CR rate for patients with tumors <5 cm tended to be higher than those with tumors >10 cm (CR rate of 57% vs. 27%, respectively; p = 0.06). For the 48 sites with clearly documented symptoms at pretreatment, 92% of sites improved after low-dose RT. Conclusions: Short-course low-dose palliative radiotherapy (2 Multiplication-Sign 2 Gy) is an effective treatment that results in high response rates for indolent non-Hodgkin lymphoma. This treatment regimen provides effective symptomatic relief for tumor bulk of all sizes.

  14. Catabolism of indole-3-acetic acid and 4- and 5-chloroindole-3-acetic acid in Bradyrhizobium japonicum

    DEFF Research Database (Denmark)

    Jensen, J B; Egsgaard, H; Van Onckelen, H

    1995-01-01

    Some strains of Bradyrhizobium japonicum have the ability to catabolize indole-3-acetic acid. Indoleacetic acid (IAA), 4-chloro-IAA (4-Cl-IAA), and 5-Cl-IAA were metabolized to different extents by strains 61A24 and 110. Metabolites were isolated and analyzed by high-performance liquid chromatogr...

  15. N,N',N"-Tris[(5-methoxy-1H-indol-3-ylethyl]benzene-1,3,5-tricarboxamide

    Directory of Open Access Journals (Sweden)

    Ute Schmidt

    2015-03-01

    Full Text Available The title indole-based compound that enforces tripodal topology and is potential applicable for the use as artificial receptor, was prepared by a simple reaction of 1,3,5-benzenetricarbonyl trichloride with 5-methoxytryptamine. The compound was characterized by elemental analysis, 1H-NMR, 13C-NMR and mass spectrometry.

  16. Primary cutaneous peripheral T-cell lymphoma, unspecified with an indolent clinical course: a distinct peripheral T-cell lymphoma?

    LENUS (Irish Health Repository)

    Ryan, A J A

    2012-02-01

    Primary cutaneous peripheral T-cell lymphomas (PTL), unspecified, are rare lymphomas, with a poor prognosis. They grow and disseminate rapidly, leading to widespread disease. We report a case of PTL, unspecified occurring on the nose. Despite its aggressive histology, this tumour behaved indolently. It is remarkably similar, clinically and histologically, to four recently described cases that occurred on the ear.

  17. S-Alkylated/aralkylated 2-(1H-indol-3-yl-methyl)-1,3,4- oxadiazole-5 ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antibacterial, enzyme-inhibitory and hemolytic activities of Salkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol derivatives. Methods: Antibacterial activities of the compounds were evaluated using broth dilution method in 96 well plates. Enzyme inhibitory activities assays were ...

  18. Visible light-photocatalysed carbazole synthesis via a formal (4+2) cycloaddition of indole-derived bromides and alkynes.

    Science.gov (United States)

    Yuan, Zhi-Guang; Wang, Qiang; Zheng, Ang; Zhang, Kai; Lu, Liang-Qiu; Tang, Zilong; Xiao, Wen-Jing

    2016-04-14

    We successfully developed an unprecedented route to carbazole synthesis through a visible light-photocatalysed formal (4+2) cycloaddition of indole-derived bromides and alkynes. This novel protocol features extremely mild conditions, a broad substrate scope and high reaction efficiency.

  19. 3-oxo-rhazinilam: a new indole alkaloid from Rauvolfia serpentina x Rhazya stricta hybrid plant cell cultures.

    Science.gov (United States)

    Gerasimenko, I; Sheludko, Y; Stöckigt, J

    2001-01-01

    A new monoterpenoid indole alkaloid, 3-oxo-rhazinilam (1), was isolated from intergeneric somatic hybrid cell cultures of Rauvolfia serpentina and Rhazya stricta, and the structure was determined by detailed 1D and 2D NMR analysis. It was also proved that 3-oxo-rhazinilam (1) is a natural constituent of the hybrid cells.

  20. Cu(I)-Catalyzed Enantioselective Friedel-Crafts Alkylation of Indoles with 2-Aryl-N-sulfonylaziridines as Alkylating Agents.

    Science.gov (United States)

    Ge, Chen; Liu, Ren-Rong; Gao, Jian-Rong; Jia, Yi-Xia

    2016-07-01

    A highly enantioselective Friedel-Crafts alkylation of indoles with N-sulfonylaziridines as alkylating agents has been developed by utilizing the complex of Cu(CH3CN)4BF4/(S)-Segphos as a catalyst. A range of optically active tryptamine derivatives are obtained in good to excellent yields and enantioselectivities (up to >99% ee) via a kinetic resolution process.

  1. Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

    Directory of Open Access Journals (Sweden)

    Qiang Wei

    2013-08-01

    Full Text Available A chiral phosphoric acid-catalyzed selenofunctionalization of tryptamine derivatives provides access to 3a-(phenylselenyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole derivatives in high yields and with synthetically useful levels of enantioselectivity (up to 89% ee.

  2. Hamacanthins A and B, new antifungal bis indole alkaloids from the deep-water marine sponge, Hamacantha sp.

    Science.gov (United States)

    Gunasekera, S P; McCarthy, P J; Kelly-Borges, M

    1994-10-01

    Hamacanthin A [1] and hamacanthin B [2] are two bioactive dihydropyrazinonediylbis(indole) alkaloids isolated from a new species of deep-water marine sponge, Hamacantha sp. The hamacanthins are growth inhibitors of Candida albicans and Cryptococcus neoformans. Isolation and structure elucidation of 1 and 2 by nmr spectroscopy are described.

  3. In silico identification of BIM-1 (2-methyl-1H-indol-3-yl) as a potential ...

    African Journals Online (AJOL)

    In silico identification of BIM-1 (2-methyl-1H-indol-3-yl) as a potential therapeutic agent against elevated protein kinase C beta associated diseases. U Saeed, N Nawaz, Y Waheed, N Chaudry, HT Bhatti, S Urooj, H Waheed, M Ashraf, UHK Naizi ...

  4. An endogenous Taylor condition in an endogenous growth monetary policy model

    OpenAIRE

    Le, Mai Vo; Gillman, Max; Minford, Patrick

    2007-01-01

    The paper derives a Taylor condition as part of the agent's equilibrium behavior in an endogenous growth monetary economy. It shows the assumptions necessary to make it almost identical to the original Taylor rule, and that it can interchangably take a money supply growth rate form. From the money supply form, simple policy experiments are conducted. A full central bank policy model is derived that includes the Taylor condition along with equations comparable to the standard aggregate-demand/...

  5. Copper is an endogenous modulator of neural circuit spontaneous activity.

    Science.gov (United States)

    Dodani, Sheel C; Firl, Alana; Chan, Jefferson; Nam, Christine I; Aron, Allegra T; Onak, Carl S; Ramos-Torres, Karla M; Paek, Jaeho; Webster, Corey M; Feller, Marla B; Chang, Christopher J

    2014-11-18

    For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu(+) sensor for one- and two-photon imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling.

  6. Human endogenous retroviruses and cancer prevention: evidence and prospects

    Directory of Open Access Journals (Sweden)

    Cegolon Luca

    2013-01-01

    Full Text Available Abstract Background Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity, hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Discussion Human endogenous retroviruses (HERVs are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well

  7. Human endogenous retroviruses and cancer prevention: evidence and prospects.

    Science.gov (United States)

    Cegolon, Luca; Salata, Cristiano; Weiderpass, Elisabete; Vineis, Paolo; Palù, Giorgio; Mastrangelo, Giuseppe

    2013-01-03

    Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues.Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system.HERV-K expression has been detected in different types of tumors.Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family.The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression.The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other tumors like sarcoma, lymphoma, bladder and

  8. Human endogenous retroviruses and cancer prevention: evidence and prospects

    International Nuclear Information System (INIS)

    Cegolon, Luca; Salata, Cristiano; Weiderpass, Elisabete; Vineis, Paolo; Palù, Giorgio; Mastrangelo, Giuseppe

    2013-01-01

    Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of cancers in addition to infections. Human endogenous retroviruses (HERVs) are a significant component of a wider family of retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human DNA and are ubiquitous in somatic and germinal tissues. Physiologic and pathologic processes are influenced by some biologically active HERV families. HERV antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system. HERV-K expression has been detected in different types of tumors. Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family. The abnormal expression of HERV-K seemingly triggers pathological processes leading to melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in melanoma maintenance and progression. The HERV-K-MEL antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other tumors like sarcoma, lymphoma, bladder

  9. Irradiation induced changes in endogenous regional distribution of catecholamines in rat brain and possible control through combined radioprotective treatments

    International Nuclear Information System (INIS)

    Hassan, S.H.M.; Elsayed, M.E.; Roushdy, H.M.; Maklaad, Y.A.

    1994-01-01

    The present study has been conducted aiming to evaluate the protective role of imidazole serotonin or their combination, on the radiation induced changes in the endogenous catecholamine contents in various areas of rat's brain : cortex, striatum, cerebellum, pons and medulla and thalamus and hypothalamus. Whole body gamma-irradiation (6 Gy) resulted in significant progressive decreases of catecholamine (epinephrine, norepinephrine and dopamine) contents, as investigated one and seven days post exposure. Administration of imidazole or serotonin showed to control radiation induced changes in catecholamine contents. Higher protection with lower potential risk of toxicity could be achieved by administration of lower doses of combined agents. The data suggest that, the endogenous concentration of catecholamines in the brain may play an important role in diagnosing the radiation hazard and evaluating the protective capacity of pharmacologic radioprotective. 2 figs

  10. Epigenetic interplay between mouse endogenous retroviruses and host genes.

    Science.gov (United States)

    Rebollo, Rita; Miceli-Royer, Katharine; Zhang, Ying; Farivar, Sharareh; Gagnier, Liane; Mager, Dixie L

    2012-10-03

    Transposable elements are often the targets of repressive epigenetic modifications such as DNA methylation that, in theory, have the potential to spread toward nearby genes and induce epigenetic silencing. To better understand the role of DNA methylation in the relationship between transposable elements and genes, we assessed the methylation state of mouse endogenous retroviruses (ERVs) located near genes. We found that ERVs of the ETn/MusD family show decreased DNA methylation when near transcription start sites in tissues where the nearby gene is expressed. ERVs belonging to the IAP family, however, are generally heavily methylated, regardless of the genomic environment and the tissue studied. Furthermore, we found full-length ETn and IAP copies that display differential DNA methylation between their two long terminal repeats (LTRs), suggesting that the environment surrounding gene promoters can prevent methylation of the nearby LTR. Spreading from methylated ERV copies to nearby genes was rarely observed, with the regions between the ERVs and genes apparently acting as a boundary, enriched in H3K4me3 and CTCF, which possibly protects the unmethylated gene promoter. Furthermore, the flanking regions of unmethylated ERV copies harbor H3K4me3, consistent with spreading of euchromatin from the host gene toward ERV insertions. We have shown that spreading of DNA methylation from ERV copies toward active gene promoters is rare. We provide evidence that genes can be protected from ERV-induced heterochromatin spreading by either blocking the invasion of repressive marks or by spreading euchromatin toward the ERV copy.

  11. Do Endogenous and Exogenous Action Control Compete for Perception?

    Science.gov (United States)

    Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

    2012-01-01

    Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the…

  12. Explaining Cigarette Smoking: An Endogenous-Exogenous Analysis.

    Science.gov (United States)

    McKillip, Jack

    Kruglanski's endogenous-exogenous partition, when applied to reasons given by smokers for smoking cigarettes, distinguishes two types of actions: (1) endogenous reasons implying that the behavior of consuming the cigarette is the goal of the action and the actor is positive toward the behavior, and (2) exogenous reasons implying that the behavior…

  13. Optimized endogenous post-stratification in forest inventories

    Science.gov (United States)

    Paul L. Patterson

    2012-01-01

    An example of endogenous post-stratification is the use of remote sensing data with a sample of ground data to build a logistic regression model to predict the probability that a plot is forested and using the predicted probabilities to form categories for post-stratification. An optimized endogenous post-stratified estimator of the proportion of forest has been...

  14. The Endogenous-Exogenous Partition in Attribution Theory

    Science.gov (United States)

    Kruglanski, Arie W.

    1975-01-01

    Within lay explanation of actions, several significant inferences are assumed to follow from the partition between endogenous and exogenous attributions. An endogenous action is judged to constitute an end in itself; an exogenous action is judged to serve as a means to some further end. (Editor/RK)

  15. Interaction between endogenous and exogenous orienting in crossmodal attention.

    Science.gov (United States)

    Chen, Xiaoxi; Chen, Qi; Gao, Dingguo; Yue, Zhenzhu

    2012-08-01

    Using a cue-target paradigm, we investigated the interaction between endogenous and exogenous orienting in cross-modal attention. A peripheral (exogenous) cue was presented after a central (endogenous) cue with a variable time interval. The endogenous and exogenous cues were presented in one sensory modality (auditory in Experiment 1 and visual in Experiment 2) whereas the target was presented in another modality. Both experiments showed a significant endogenous cuing effect (longer reaction times in the invalid condition than in the valid condition). However, exogenous cuing produced a facilitatory effect in both experiments in response to the target when endogenous cuing was valid, but it elicited a facilitatory effect in Experiment 1 and an inhibitory effect in Experiment 2 when endogenous cuing was invalid. These findings indicate that endogenous and exogenous cuing can co-operate in orienting attention to the crossmodal target. Moreover, the interaction between endogenous and exogenous orienting of attention is modulated by the modality between the cue and the target. © 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.

  16. Endogene opioider og deres terapeutiske anvendelse i smertebehandling

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, A T

    1990-01-01

    Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further investi...

  17. On the Endogeneity of the Mean-Variance Efficient Frontier.

    Science.gov (United States)

    Somerville, R. A.; O'Connell, Paul G. J.

    2002-01-01

    Explains that the endogeneity of the efficient frontier in the mean-variance model of portfolio selection is commonly obscured in portfolio selection literature and in widely used textbooks. Demonstrates endogeneity and discusses the impact of parameter changes on the mean-variance efficient frontier and on the beta coefficients of individual…

  18. Distance-dependent energy transfer between indole and anthracene moieties in Langmuir Blodgett films

    Science.gov (United States)

    Saha, D. C.; Bhattacharjee, D.; Misra, T. N.

    1998-09-01

    1,2-Diphenyl indole (DPI) and 9,10-diphenyl anthracene (DPA) are non-amphiphilic molecules but form excellent LB films when mixed with stearic acid (SA). Spectroscopic investigations of these films indicate formation of aggregates of DPI and DPA in the mixed LB films. DPA has been used as the quencher of the fluorescence of the DPI donor. Distance-dependent energy transfer between donor and acceptor monolayers in the LB film, where they can be precisely separated by inert spacers of stearic acid layers of varied thickness, is shown to satisfy Khun's quadratic equation. This suggests that the donor excitations are delocalized. The large critical transfer distance estimated from the experimental results has been attributed to the formation of aggregates of the molecules in a LB monolayer.

  19. Oxidative stress and production of bioactive monoterpene indole alkaloids: biotechnological implications.

    Science.gov (United States)

    Matsuura, Hélio Nitta; Rau, Mariana Ritter; Fett-Neto, Arthur Germano

    2014-02-01

    Monoterpene indole alkaloids (MIAs) encompass plant natural products with important pharmacological relevance. They include the anti-tumoral MIAs found in Catharanthus roseus and Camptotheca acuminata. The often low yields of bioactive alkaloids in plants has prompted research to identify the factors regulating MIA production. Oxidative stress is a general response associated with biotic and abiotic stresses leading to several secondary responses, including elicitation of MIA production. These changes in secondary metabolism may take place directly or via second messengers, such as Ca(2+) and reactive oxygen species (ROS). H2O2 is the main ROS that participates in MIA biosynthesis. This review analyzes the links between oxidative stress, elicitation of bioactive MIA production and their potential roles in antioxidant defense, as well as exploring the implications to developing biotechnological strategies relevant for alkaloid supply.

  20. Effect of ionizing radiation and indole butyric acid on rooting of olive cuttings

    International Nuclear Information System (INIS)

    Al-Bachir, Mahfouz

    1993-12-01

    This study was performed to investigate the effects of indole butyric acid (IBA) (2000 and 4000 ppm), low doses of gamma irradiation (2,4, and 6 Gy), combined treatment of IBA followed by irradiation, and irradiation followed by IBA on olive cuttings (Variety Khodairi). Rooting percentage, callus formation, vegetative growth root number, and the length of the roots were measured after 100 days of planting. The results indicated that IBA treatments in both concentrations increased the callus formation, rooting, vegetative growth, and the number and length of the roots. Low doses of gamma irradiation had no effects on rooting percentage in comparison with the hormonal treatments. Callus formation, rooting, vegetative growth, and length of the root of cuttings produced in 1990 were better than those produced in 1991, and cuttings produced in January were better than those produced in March and October. (author). 16 refs., 15 tabs

  1. MR-based trabecular bone microstructure is not altered in subjects with indolent systemic mastocytosis.

    Science.gov (United States)

    Baum, Thomas; Karampinos, Dimitrios C; Brockow, Knut; Seifert-Klauss, Vanadin; Jungmann, Pia M; Biedermann, Tilo; Rummeny, Ernst J; Bauer, Jan S; Müller, Dirk

    2015-01-01

    Subjects with indolent systemic mastocytosis (ISM) have an increased risk for osteoporosis. It has been demonstrated that trabecular bone microstructure analysis improves the prediction of bone strength beyond dual-energy X-ray absorptiometry-based bone mineral density. The purpose of this study was to obtain Magnetic Resonance (MR)-based trabecular bone microstructure parameters as advanced imaging biomarkers in subjects with ISM (n=18) and compare them with those of normal controls (n=18). Trabecular bone microstructure parameters were not significantly (P>.05) different between subjects with ISM and controls. These findings revealed important pathophysiological information about ISM-associated osteoporosis and may limit the use of trabecular bone microstructure analysis in this clinical setting. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Modification of indole by electron-rich atoms and their application in novel electron donor materials

    Science.gov (United States)

    Zhang, Maolin; Qin, Guangjiong; Liu, Jialei; Zhen, Zhen; Fedorchuk, A. A.; Lakshminarayana, G.; Albassam, A. A.; El-Naggar, A. M.; Ozga, Katarzyna; Kityk, I. V.

    2017-08-01

    Novel nonlinear optical (NLO) chromophore based on 6-(pyrrolidin-1-yl)-1H-indole as the electron donor group was designed and synthesized. The molecular structure of this chromophore was characterized by 1H NMR spectra, 13C NMR spectra, and MS spectra. The delocalized energy level was estimated by UV-Vis. spectra. The thermal property was studied by thermogravimetric analysis (TGA). The poled films containing chromophores ZML-1 with a loading density of 10 wt% in amorphous polycarbonate (APC) afford an average electro-optic (EO) coefficient (r33) of 19 pm/V at 1310 nm. Compared to the reported aniline-based chromophore (r33 = 12 pm/V) analogues, chromophore ZML-1 exhibits enhanced electro-optical activity.

  3. Indole alkaloids from the Marquesan plant Rauvolfia nukuhivensis and their effects on ion channels.

    Science.gov (United States)

    Martin, Nicolas J; Ferreiro, Sara F; Barbault, Florent; Nicolas, Mael; Lecellier, Gaël; Paetz, Christian; Gaysinski, Marc; Alonso, Eva; Thomas, Olivier P; Botana, Luis M; Raharivelomanana, Phila

    2015-01-01

    In addition to the already reported nukuhivensiums 1 and 2, 11 indole alkaloids were isolated from the bark of the plant Rauvolfia nukuhivensis, growing in the Marquesas archipelago. The known sandwicine (3), isosandwicine (4), spegatrine (8), lochneram (9), flavopereirine (13) have been found in this plant together with the norsandwicine (5), isonorsandwicine (6), Nb-methylisosandwicine (7), 10-methoxypanarine (10), nortueiaoine (11), tueiaoine (12). The structure elucidation was performed on the basis of a deep exploration of the NMR and HRESIMS data as well as comparison with literature data for similar compounds. Norsandwicine, 10-methoxypanarine, tueiaoine, and more importantly nukuhivensiums, were shown to significantly induce a reduction of IKr amplitude (HERG current). Molecular modelling through docking was performed in order to illustrate this result. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Bioactive Indole Derivatives from the South Pacific Marine Sponges Rhopaloeides odorabile and Hyrtios sp.

    Directory of Open Access Journals (Sweden)

    Marie-Lise Bourguet-Kondracki

    2011-05-01

    Full Text Available Indole derivatives including bromoindoles have been isolated from the South Pacific marine sponges Rhopaloeides odorabile and Hyrtios sp. Their structures were established through analysis of mass spectra and 1D and 2D NMR spectroscopic data. Their potential inhibitory phospholipase A2 (PLA2, antioxidant and cytotoxic activities were evaluated. The new derivative 5,6-dibromo-l-hypaphorine (9 isolated from Hyrtios sp. revealed a weak bee venom PLA2 inhibition (IC50 0.2 mM and a significant antioxidant activity with an Oxygen Radical Absorbance Capacity (ORAC value of 0.22. The sesquiterpene aureol (4, also isolated from Hyrtios sp., showed the most potent antioxidant activity with an ORAC value of 0.29.

  5. A novel approach to isoindolo[2,1-a]indol-6-ones.

    Science.gov (United States)

    Duncanson, Philip; Cheong, Yuen-Ki; Motevalli, Majid; Griffiths, D Vaughan

    2012-06-07

    A convenient route to isoindolo[2,1-a]indol-6-ones has been developed starting from the appropriate 2-(N-phthaloyl)benzoic acids. Formation of the acid chlorides with thionyl chloride followed by heating with triethyl phosphite in a suitable solvent resulted in a multistep reaction giving tetracyclic β-ketophosphonates that on reduction with sodium borohydride gave the required indolones in good overall yields. Analogous β-ketophosphonates were also prepared starting with N,N-(1,8-naphthaloyl)-2-aminobenzoic acid and 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzoic acids although of these only the naphthaloyl product could be reduced with sodium borohydride without cleaving the amide bond in the ring system.

  6. Spectrophotometric study of the protonation processes of some indole derivatives in sulfuric acid

    Directory of Open Access Journals (Sweden)

    GORAN M. STOJKOVIC

    1999-12-01

    Full Text Available The protonation of 3-methylindole, D-tryptophan, 3-formylindole, 3-acetylindole and indolyl-2-carboxylic acid in sulfuric acid media was studied by UV spectro-scopy. The measurement of the absorbance at four selected wavelengths enabled the calculation of the corresponding molar absorptivities. The results were used to calculate the pKa value of the protonated form of the indole derivatives by the Hammett Method. The Hammett postulate (the slope of the plot log [c(BH+/c(B] vs. H should be equal to 1 was tested. The dissociation constants and solvent parameter m* were also obtained by applying the Excess Acidity Method. The position of the additional protons in the protonated compounds is discussed.

  7. Indole diterpenoids from the endophytic fungus Drechmeria sp. as natural antimicrobial agents.

    Science.gov (United States)

    Zhao, Jian-Chao; Wang, Ya-Li; Zhang, Tian-Yuan; Chen, Zhong-Jian; Yang, Tian-Mei; Wu, Ying-Ying; Sun, Cheng-Peng; Ma, Xiao-Chi; Zhang, Yi-Xuan

    2018-04-01

    A fungal strain, Drechmeria sp., was isolated from the root of Panax notoginseng. Totally, seven new indole diterpenoids, drechmerins A-G (1-7), were isolated from the fermentation broth of Drechmeria sp. together with four known analogues (8-11). Their structures were determined on the basis of 1D and 2D NMR and electronic circular dichroism (ECD) spectroscopic analyses as well as theoretical calculations. All the isolated compounds were evaluated for their antimicrobial activities against Candida albicans, Staphylococcus aureus, Bacillus cereus, B. subtillis, Pseudomonas aeruginosa, and Klebsiella pneumonia, respectively. Drechmerin B (2) displayed antimicrobial activity against C. albicans with an MIC value of 12.5 μg/mL. Molecular docking was used to investigate interactions of peptide deformylase with compounds 1-3, 5-7, 9, and 10. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. On the mechanism for the formation of indole alkalois in Penicillium concavo-rugulosum

    International Nuclear Information System (INIS)

    Ohmomo, Sadahiro; Miyazaki, Kenji; Ohashi, Tsutomu; Abe, Matazo

    1977-01-01

    Experiments on the biosynthesis and microbiological conversion of indole alkaloids in Penicillium concavo-rugulosum were carried out with the growing and resting mycelia, respectively, of a selected strain of the same mold. The former experiments were performed by the use of DL-tryptophan-3- 14 C or DL-mevalonic acid-2- 14 C-lactone as a precursor, while the latter experiments by the use of rugulovasine A- 3 H, dihydrorugulovasine A- 3 H, 4-[γ,γ-dimethylallyl]-tryptophan- 3 H, chanoclavine-[I]- 3 H or the other tritiated ergoline alkaloids. The results of these experiments suggested that in the Penicillium mold employed there exist the following biosynthetic route: tryptophan+mevalonic acid → 4-[γ,γ-dimethylallyl]-tryptophan → rugulovasine A → dihydrorugulovasine A → dihydrorugulovasine A-lactam. (auth.)

  9. Study on the IAA (Indole acetic acid) Productivity of Soil Yeast Strain Isolats

    International Nuclear Information System (INIS)

    Nwe Nwe Soe Hlaing; Swe Zin Yu; San San Yu

    2011-12-01

    Twelve isolated soil yeast were tested in IAA production in peptone yeast glucose broth (PYG). All strains were screened for the Indole Acetic Acid (IAA) producing activity in PYG broth supplemented with or without L-Tryptophan (L-TRP) as precusor. IAA production was assayed calorimetrically using Salkowski's reagent. The concentration of IAA produced by yeast strains was measured by spectrophotometric method at 530nm. Y6 strain was the highest IAA producer (79ppm) at 9 days incubation period without tryptophan. Y3, Y10 and Y12 strains that were incubated without L-TRP also had the higher ability in the production of IAA than other yeast isolates. The selected yeasts having high IAA production activity were characterized by morphological study and biochemical tests including sugar assimilation and fermentation tests.

  10. Spectroscopic study of jet-cooled indole-3-carbinol by thermal evaporation

    International Nuclear Information System (INIS)

    Moon, Cheol Joo; Kim, Eun Bin; Min, Ahreum; Ahn, Ahreum; Seong, Yeon Guk; Choi, Myong Yong

    2016-01-01

    Cruciferous vegetables such as cabbage, kale, broccoli, and cauliflower have relatively high levels of indole-3-carbinol (I3C), which can be used as a possible cancer preventative agent particularly for breast, cervical, colorectal, and other hormone-related cancers. Thus, this naturally occurring substance, I3C, is now being used in dietary supplements. In conclusion, we have succeeded in obtaining the R2PI spectrum of a thermally unstable sample, I3C, by using a thermal buffer (herein, uracil) for the first time. Use of thermal evaporation method for thermally unstable biomolecules using thermal buffers will allow us to explore more gas phase spectroscopic studies for their intrinsic physiological properties in the near future

  11. New 3H-Indole Synthesis by Fischer’s Method. Part I.

    Directory of Open Access Journals (Sweden)

    Sami Sajjadifar

    2010-04-01

    Full Text Available Methyl indolenines (4a-c and(5a-c were prepared in high yield by a Fischer indole synthesis reaction of o,m-tolylhydrazine hydrochlorides (1a-b with isopropyl methyl ketone (2 and 2-methylcyclohexanone (3 in acetic acid at room temperature. o,p- Nitrophenylhydrazines (1c-d were reacted with 2-methylcyclohexanone (3 in acetic acid at reflux to give nitroindolenines (5d-e, while the attempted reactions of o,p-nitrohydrazines with isopropyl methyl ketone (2 in acetic acid were not successful. Compounds(1c-d were reacted with isopropyl methyl ketone (2 in acetic acid/HCl to give 2,3,3-trimethyl-5-nitro-indolenine (4e and 2,3,3-trimethyl-7-nitroindolenine (4d.

  12. Spectroscopic study of jet-cooled indole-3-carbinol by thermal evaporation

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Cheol Joo; Kim, Eun Bin; Min, Ahreum; Ahn, Ahreum; Seong, Yeon Guk; Choi, Myong Yong [Gyeongsang National University, Jinju (Korea, Republic of)

    2016-10-15

    Cruciferous vegetables such as cabbage, kale, broccoli, and cauliflower have relatively high levels of indole-3-carbinol (I3C), which can be used as a possible cancer preventative agent particularly for breast, cervical, colorectal, and other hormone-related cancers. Thus, this naturally occurring substance, I3C, is now being used in dietary supplements. In conclusion, we have succeeded in obtaining the R2PI spectrum of a thermally unstable sample, I3C, by using a thermal buffer (herein, uracil) for the first time. Use of thermal evaporation method for thermally unstable biomolecules using thermal buffers will allow us to explore more gas phase spectroscopic studies for their intrinsic physiological properties in the near future.

  13. Ultrastructure of sheep primordial follicles cultured in the presence of indol acetic acid, EGF, and FSH

    DEFF Research Database (Denmark)

    Andrade, Evelyn Rabelo; Hyttel, Poul; Landim-Alvarenga, Fernanda Da Cruz

    2011-01-01

    The aim of this study was to investigate the ultrastructural characteristics of primordial follicles after culturing of sheep ovarian cortical slices in the presence of indol acetic acid (IAA), Epidermal Growth Factor (EGF), and FSH. To evaluate ultrastructure of primordial follicles cultured...... in MEM (control) or in MEM containing IAA, EGF, and FSH, fragments of cultured tissue were processes for transmission electron microscopy. Except in the control, primordial follicles cultured in supplemented media for 6¿d were ultrastructurally normal. They had oocyte with intact nucleus...... and the cytoplasm contained heterogeneous-sized lipid droplets and numerous round or elongated mitochondria with intact parallel cristae were observed. Rough endoplasmic reticulum (RER) was rarely found. The granulosa cells cytoplasm contained a great number of mitochondria and abundant RER. In conclusion...

  14. Ultrastructure of Sheep Primordial Follicles Cultured in the Presence of Indol Acetic Acid, EGF, and FSH

    Directory of Open Access Journals (Sweden)

    Evelyn Rabelo Andrade

    2011-01-01

    Full Text Available The aim of this study was to investigate the ultrastructural characteristics of primordial follicles after culturing of sheep ovarian cortical slices in the presence of indol acetic acid (IAA, Epidermal Growth Factor (EGF, and FSH. To evaluate ultrastructure of primordial follicles cultured in MEM (control or in MEM containing IAA, EGF, and FSH, fragments of cultured tissue were processes for transmission electron microscopy. Except in the control, primordial follicles cultured in supplemented media for 6 d were ultrastructurally normal. They had oocyte with intact nucleus and the cytoplasm contained heterogeneous-sized lipid droplets and numerous round or elongated mitochondria with intact parallel cristae were observed. Rough endoplasmic reticulum (RER was rarely found. The granulosa cells cytoplasm contained a great number of mitochondria and abundant RER. In conclusion, the presence of IAA, EGF, and FSH helped to maintain ultrastructural integrity of sheep primordial follicles cultured in vitro.

  15. Antitumor activity of sequence-specific alkylating agents: pyrolle-imidazole CBI conjugates with indole linker.

    Science.gov (United States)

    Shinohara, Ken-ichi; Bando, Toshikazu; Sasaki, Shunta; Sakakibara, Yogo; Minoshima, Masafumi; Sugiyama, Hiroshi

    2006-03-01

    DNA-targeting agents, including cisplatin, bleomycin and mitomycin C, are used routinely in cancer treatments. However, these drugs are extremely toxic, attacking normal cells and causing severe side effects. One important question to consider in designing anticancer agents is whether the introduction of sequence selectivity to DNA-targeting agents can improve their efficacy as anticancer agents. In the present study, the growth inhibition activities of an indole-seco 1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) (1) and five conjugates with hairpin pyrrole-imidazole polyamides (2-6), which have different sequence specificities for DNA alkylation, were compared using 10 different cell lines. The average values of -log GI50 (50% growth inhibition concentration) for compounds 1-6 against the 10 cell lines were 8.33, 8.56, 8.29, 8.04, 8.23 and 8.83, showing that all of these compounds strongly inhibit cell growth. Interestingly, each alkylating agent caused significantly different growth inhibition patterns with each cell line. In particular, the correlation coefficients between the -log GI50 of compound 1 and its conjugates 2-6 showed extremely low values (Ralkylation lead to marked differences in biological activity. Comparison of the correlation coefficients between compounds 6 and 7, with the same sequence specificity as 6, and MS-247, with sequence specificity different from 6, when used against a panel of 37 human cancer cell lines further confirmed the above hypothesis.

  16. 1-(1H-indol-3-yl)ethanamine derivatives as potent Staphylococcus aureus NorA efflux pump inhibitors.

    Science.gov (United States)

    Hequet, Arnaud; Burchak, Olga N; Jeanty, Matthieu; Guinchard, Xavier; Le Pihive, Emmanuelle; Maigre, Laure; Bouhours, Pascale; Schneider, Dominique; Maurin, Max; Paris, Jean-Marc; Denis, Jean-Noël; Jolivalt, Claude

    2014-07-01

    The synthesis of 37 1-(1H-indol-3-yl)ethanamine derivatives, including 12 new compounds, was achieved through a series of simple and efficient chemical modifications. These indole derivatives displayed modest or no intrinsic anti-staphylococcal activity. By contrast, several of the compounds restored, in a concentration-dependent manner, the antibacterial activity of ciprofloxacin against Staphylococcus aureus strains that were resistant to fluoroquinolones due to overexpression of the NorA efflux pump. Structure-activity relationships studies revealed that the indolic aldonitrones halogenated at position 5 of the indole core were the most efficient inhibitors of the S. aureus NorA efflux pump. Among the compounds, (Z)-N-benzylidene-2-(tert-butoxycarbonylamino)-1-(5-iodo-1H-indol-3-yl)ethanamine oxide led to a fourfold decrease of the ciprofloxacin minimum inhibitory concentration against the SA-1199B strain when used at a concentration of 0.5 mg L(-1) . To the best of our knowledge, this activity is the highest reported to date for an indolic NorA inhibitor. In addition, a new antibacterial compound, tert-butyl (2-(3-hydroxyureido)-2-(1H-indol-3-yl)ethyl)carbamate, which is not toxic for human cells, was also found. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Primary thyroid disorders in endogenous Cushing's syndrome.

    Science.gov (United States)

    Niepomniszcze, Hugo; Pitoia, Fabian; Katz, Silvia B; Chervin, Raul; Bruno, Oscar D

    2002-09-01

    To study the prevalence of primary thyroid disorders in patients who underwent endogenous hypercortisolism. Retrospective evaluation of 59 patients with Cushing's syndrome (CS) who had, at least, a record of thyroid palpation by expert endocrinologists and basal measurements of TSH by second generation assays. When available, tri-iodothyronine and thyroxine serum levels, TRH-TSH tests and anti-thyroid antibodies were also analyzed. There were two age- and gender-matched control groups. The 'goiter control group' comprised 118 healthy subjects who underwent thyroid palpation. The 'antibody control group' was composed of 40 individuals who attended the blood bank of our hospital. Antibodies against thyroperoxidase and measurements of TSH were analyzed in their blood samples. Available files of 83 CS patients admitted to our endocrine unit from 1985 to 1998 were examined. Fifty-nine patients (52 women and 7 men) with a mean age of 36.2 years (range 14-61 years) met the above requirements. Diagnosis of hypercortisolism had been established by a standard 1-mg overnight dexamethasone suppression test and urinary free cortisol (UFC). Etiological diagnosis involved dynamic testing, measurements of ACTH levels and imaging techniques. After treatment, all but one of the patients were cured or controlled of their hypercortisolism. This was established by the finding of subnormal serum cortisol concentrations and/or subnormal 24-h UFC levels. Primary thyroid disorders were defined by the presence of one or more of the following diagnostic criteria: (i) goiter, (ii) positive anti-thyroid antibodies and/or (iii) primary thyroid function abnormalities. Eighteen (30.5%) patients had goiter (diffuse in 78% and nodular in 22%), 14 (23.7%) had primary subclinical hypothyroidism and 5 (8.4%) had hyperthyroidism. In 41 patients evaluated for antithyroid antibodies, it was found that 23 (56.1%) had positive titers. In a group of patients in which thyroid autoantibodies were measured

  18. Monocular channels have a functional role in endogenous orienting.

    Science.gov (United States)

    Saban, William; Sekely, Liora; Klein, Raymond M; Gabay, Shai

    2018-03-01

    The literature has long emphasized the role of higher cortical structures in endogenous orienting. Based on evolutionary explanation and previous data, we explored the possibility that lower monocular channels may also have a functional role in endogenous orienting of attention. Sensitive behavioral manipulation was used to probe the contribution of monocularly segregated regions in a simple cue - target detection task. A central spatially informative cue, and its ensuing target, were presented to the same or different eyes at varying cue-target intervals. Results indicated that the onset of endogenous orienting was apparent earlier when the cue and target were presented to the same eye. The data provides converging evidence for the notion that endogenous facilitation is modulated by monocular portions of the visual stream. This, in turn, suggests that higher cortical mechanisms are not exclusively responsible for endogenous orienting, and that a dynamic interaction between higher and lower neural levels, might be involved. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Endogenous retroviruses mobilized during friend murine leukemia virus infection.

    Science.gov (United States)

    Boi, Stefano; Rosenke, Kyle; Hansen, Ethan; Hendrick, Duncan; Malik, Frank; Evans, Leonard H

    2016-12-01

    We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses. Published by Elsevier Inc.

  20. Occurrence of indole compounds in some vegetables : toxicological implications of nitrosation with emphasis on mutagenicity

    NARCIS (Netherlands)

    Tiedink, H.G.M.

    1991-01-01

    From the introduction to the chemistry, occurrence and formation of N-nitroso compounds (NOC) (Chapter 1), it can be concluded that human exposure to these potent carcinogenic compounds is mainly through the endogenous nitrosation of dietary precursors. Vegetables are the major source of

  1. Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes.

    Science.gov (United States)

    Gilbert, C; Meik, J M; Dashevsky, D; Card, D C; Castoe, T A; Schaack, S

    2014-09-22

    We report the discovery of endogenous viral elements (EVEs) from Hepadnaviridae, Bornaviridae and Circoviridae in the speckled rattlesnake, Crotalus mitchellii, the first viperid snake for which a draft whole genome sequence assembly is available. Analysis of the draft assembly reveals genome fragments from the three virus families were inserted into the genome of this snake over the past 50 Myr. Cross-species PCR screening of orthologous loci and computational scanning of the python and king cobra genomes reveals that circoviruses integrated most recently (within the last approx. 10 Myr), whereas bornaviruses and hepadnaviruses integrated at least approximately 13 and approximately 50 Ma, respectively. This is, to our knowledge, the first report of circo-, borna- and hepadnaviruses in snakes and the first characterization of non-retroviral EVEs in non-avian reptiles. Our study provides a window into the historical dynamics of viruses in these host lineages and shows that their evolution involved multiple host-switches between mammals and reptiles. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  2. Endogenous T-Cell Therapy: Clinical Experience.

    Science.gov (United States)

    Yee, Cassian; Lizee, Greg; Schueneman, Aaron J

    2015-01-01

    Adoptive cellular therapy represents a robust means of augmenting the tumor-reactive effector population in patients with cancer by adoptive transfer of ex vivo expanded T cells. Three approaches have been developed to achieve this goal: the use of tumor-infiltrating lymphocytes or tumor-infiltrating lymphocytess extracted from patient biopsy material; the redirected engineering of lymphocytes using vectors expressing a chimeric antigen receptor and T-cell receptor; and third, the isolation and expansion of often low-frequency endogenous T cells (ETCs) reactive to tumor antigens from the peripheral blood of patients. This last form of adoptive transfer of T cells, known as ETC therapy, requires specialized methods to isolate and expand from peripheral blood the very low-frequency tumor-reactive T cells, methods that have been developed over the last 2 decades, to the point where such an approach may be broadly applicable not only for the treatment of melanoma but also for that of other solid tumor malignancies. One compelling feature of ETC is the ability to rapidly deploy clinical trials following identification of a tumor-associated target epitope, a feature that may be exploited to develop personalized antigen-specific T-cell therapy for patients with almost any solid tumor. With a well-validated antigen discovery pipeline in place, clinical studies combining ETC with agents that modulate the immune microenvironment can be developed that will transform ETC into a feasible treatment modality.

  3. Endogenous System Microbes as Treatment Process ...

    Science.gov (United States)

    Monitoring the efficacy of treatment strategies to remove pathogens in decentralized systems remains a challenge. Evaluating log reduction targets by measuring pathogen levels is hampered by their sporadic and low occurrence rates. Fecal indicator bacteria are used in centralized systems to indicate the presence of fecal pathogens, but are ineffective decentralized treatment process indicators as they generally occur at levels too low to assess log reduction targets. System challenge testing by spiking with high loads of fecal indicator organisms, like MS2 coliphage, has limitations, especially for large systems. Microbes that are endogenous to the decentralized system, occur in high abundances and mimic removal rates of bacterial, viral and/or parasitic protozoan pathogens during treatment could serve as alternative treatment process indicators to verify log reduction targets. To identify abundant microbes in wastewater, the bacterial and viral communities were examined using deep sequencing. Building infrastructure-associated bacteria, like Zoogloea, were observed as dominant members of the bacterial community in graywater. In blackwater, bacteriophage of the order Caudovirales constituted the majority of contiguous sequences from the viral community. This study identifies candidate treatment process indicators in decentralized systems that could be used to verify log removal during treatment. The association of the presence of treatment process indic

  4. Endogenous retroviral promoter exaptation in human cancer

    Directory of Open Access Journals (Sweden)

    Artem Babaian

    2016-12-01

    Full Text Available Abstract Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.

  5. Endogenous Retroviruses: With Us and Against Us

    Science.gov (United States)

    Meyer, Thomas J.; Rosenkrantz, Jimi L.; Carbone, Lucia; Chavez, Shawn L.

    2017-04-01

    Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe the roles ERVs may play in somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.

  6. Enterococcus faecalis Endogenous Endophthalmitis from Valvular Endocarditis

    Directory of Open Access Journals (Sweden)

    Sidnei Barge

    2013-01-01

    Full Text Available We report a case of a 74-year-old female, with a mitral heart valve, who presented with pain and blurred vision in the right eye for 2 days. Her visual acuity was light perception (LP in the right eye and 20/40 in the left eye. Slit lamp examination showed corneal edema and hypopyon, and a view of the right fundus was impossible. Echography showed vitreous condensation. One day after presentation, the patient developed acute lung edema requiring hospitalization, so she was not submitted to vitreous tap and intravitreal treatment. The cardiac and systemic evaluations revealed a mitral endocarditis secondary to Enterococcus faecalis. The patient improved systemically with treatment with gentamicin, vancomycin, and linezolid. Her visual acuity remained as no LP, and her intraocular pressure (IOP has been controlled with brimonidine bid despite developing a total cataract with 360° posterior synechia. A cardiac source for endogenous endophthalmitis should be considered in the presence of a prosthetic cardiac valve. The treatment and followup must be made in cooperation with a cardiologist specialist, but the ophthalmologist can play a key role in the diagnosis.

  7. Identification of a 23 kDa protein from maize photoaffinity-labelled with 5-azido-[7-3H]indol-3-ylacetic acid.

    OpenAIRE

    Feldwisch, J; Zettl, R; Campos, N; Palme, K

    1995-01-01

    A 23 kDa protein (p23) was identified in microsomal extracts from maize coleoptiles by photoaffinity labelling with 5-azido-[7-3H]indol-3-ylacetic acid ([3H]N3IAA). Labelling of p23 was blocked by unlabelled IAA, N3IAA, indol-3-ylbutyric acid and indol-3-yl-lactate. In addition, labelling was efficiently decreased by tryptophan, as well as by the scavenger p-aminobenzoic acid. Labelling was, however, not affected by synthetic auxins such as 1-naphthylacetic acid or 2,4-dichlorophenoxyacetic a...

  8. Effects of source and sink manipulation on distribution of 14C-assimilate and endogenous hormone contents of high-yield cotton in Xinjiang

    International Nuclear Information System (INIS)

    Luo Honghai; Zhao Ruihai; Li Junhua; Zhang Yali; Zhang Wangfeng

    2011-01-01

    Effects of leaf-cutting and bud-thinning treatment on partitioning of 14 C-assimilate and endogenous hormone contents of source leaf (respective axial leaf and sympodian leaf) during flowering and boll-setting stage in high-yield cotton were studied by using Gossipium hirsutum L. cv. Xinluzao 132 as plant material. Results showed that bud-thinning reduced the peak value of indole-3-acetic acid (IAA) delayed the accumulation of isopenteny ladenime and its riboside (iP + iPA), and decreased the contents of abscisic acid (ABA) zeatin and its riboside (Z + ZR) of source leaf. Thus, the export and partitioning of percentage of 14 C-assimilate in boll was significantly decreased at full bolling and boll opening stages. As a result, both of boll weight and yield in bud-thinning were significantly lower than control. Leaf-cutting significantly improved the content of cytokinins (CTKs) and the distributive percentage of 14 C-assimilates in boll. Furthermore, when leaves were cut 1/4 at anthesis, no differences were found in number of bolls per plant, boll weight and yield compared with control. These results suggested that regulating source-sink relation with key practices of cultivation would be of great importance to super-high and stable yield of cotton, as it would affect the changes of endogenous hormone levels and regulate the distribution of 14 C-assimilate between source and sink. (authors)

  9. Endogenous versus exogenous shocks in systems with memory

    Science.gov (United States)

    Sornette, D.; Helmstetter, A.

    2003-02-01

    Systems with long-range persistence and memory are shown to exhibit different precursory as well as recovery patterns in response to shocks of exogenous versus endogenous origins. By endogenous, we envision either fluctuations resulting from an underlying chaotic dynamics or from a stochastic forcing origin which may be external or be an effective coarse-grained description of the microscopic fluctuations. In this scenario, endogenous shocks result from a kind of constructive interference of accumulated fluctuations whose impacts survive longer than the large shocks themselves. As a consequence, the recovery after an endogenous shock is in general slower at early times and can be at long times either slower or faster than after an exogenous perturbation. This offers the tantalizing possibility of distinguishing between an endogenous versus exogenous cause of a given shock, even when there is no “smoking gun”. This could help in investigating the exogenous versus self-organized origins in problems such as the causes of major biological extinctions, of change of weather regimes and of the climate, in tracing the source of social upheaval and wars, and so on. Sornette et al., Volatility fingerprints of large stocks: endogenous versus exogenous, cond-mat/0204626 has already shown how this concept can be applied concretely to differentiate the effects on financial markets of the 11 September 2001 attack or of the coup against Gorbachev on 19 August 1991 (exogenous) from financial crashes such as October 1987 (endogenous).

  10. Vulnerability to glutamate toxicity of dopaminergic neurons is dependent on endogenous dopamine and MAPK activation.

    Science.gov (United States)

    Izumi, Yasuhiko; Yamamoto, Noriyuki; Matsuo, Takaaki; Wakita, Seiko; Takeuchi, Hiroki; Kume, Toshiaki; Katsuki, Hiroshi; Sawada, Hideyuki; Akaike, Akinori

    2009-07-01

    Dopaminergic neurons are more vulnerable than other types of neurons in cases of Parkinson disease and ischemic brain disease. An increasing amount of evidence suggests that endogenous dopamine plays a role in the vulnerability of dopaminergic neurons. Although glutamate toxicity contributes to the pathogenesis of these disorders, the sensitivity of dopaminergic neurons to glutamate toxicity has not been clarified. In this study, we demonstrated that dopaminergic neurons were preferentially affected by glutamate toxicity in rat mesencephalic cultures. Glutamate toxicity in dopaminergic neurons was blocked by inhibiting extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase, and p38 MAPK. Furthermore, depletion of dopamine by alpha-methyl-dl-p-tyrosine methyl ester (alpha-MT), an inhibitor of tyrosine hydroxylase (TH), protected dopaminergic neurons from the neurotoxicity. Exposure to glutamate facilitated phosphoryration of TH at Ser31 by ERK, which contributes to the increased TH activity. Inhibition of ERK had no additive effect on the protection offered by alpha-MT, whereas alpha-MT and c-jun N-terminal kinase or p38 MAPK inhibitors had additive effects and yielded full protection. These data suggest that endogenous dopamine is responsible for the vulnerability to glutamate toxicity of dopaminergic neurons and one of the mechanisms may be an enhancement of dopamine synthesis mediated by ERK.

  11. Dual Roles of Endogenous Platelet-activating Factor Acetylhydrolase in a Murine Model of Necrotizing Enterocolitis

    Science.gov (United States)

    Lu, Jing; Pierce, Marissa; Franklin, Andrew; Jilling, Tamas; Stafforini, Diana M.; Caplan, Michael

    2010-01-01

    Human preterm infants with necrotizing enterocolitis (NEC) have increased circulating and luminal levels of platelet-activating factor (PAF) and decreased serum PAF-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF. Formula supplemented with recombinant PAF-AH decreases NEC in a neonatal rat model. We hypothesized that endogenous PAF-AH contributes to neonatal intestinal homeostasis, and therefore developed PAF-AH−/− mice using standard approaches to study the role of this enzyme in the neonatal NEC model. Following exposure to a well-established NEC model, intestinal tissues were evaluated for histology, pro-inflammatory cytokine mRNA synthesis, and death using standard techniques. We found that mortality rates were significantly lower in PAF-AH−/− pups compared to wild-type controls before 24 hours of life but surviving PAF-AH−/− animals were more susceptible to NEC development compared to wild-type controls. Increased NEC incidence was associated with prominent inflammation characterized by elevated intestinal mRNA expression of sPLA2, iNOS and CXCL1. In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and since preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. PMID:20531249

  12. Mild Staphylococcus aureus Skin Infection Improves the Course of Subsequent Endogenous S. aureus Bacteremia in Mice.

    Directory of Open Access Journals (Sweden)

    Sanne van den Berg

    Full Text Available Staphylococcus aureus carriers with S. aureus bacteremia may have a reduced mortality risk compared to non-carriers. A role for the immune system is suggested. Here, we study in mice the effect of mild S. aureus skin infection prior to endogenous or exogenous S. aureus bacteremia, and evaluate protection in relation to anti-staphylococcal antibody levels. Skin infections once or twice by a clinical S. aureus isolate (isolate P or S. aureus strain 8325-4 were induced in mice free of S. aureus and anti-staphylococcal antibodies. Five weeks later, immunoglobulin G (IgG levels in blood against 25 S. aureus antigens were determined, and LD50 or LD100 bacteremia caused by S. aureus isolate P was induced. S. aureus skin infections led to elevated levels of anti-staphylococcal IgG in blood. One skin infection improved the course of subsequent severe endogenous bacteremia only. A second skin infection further improved animal survival rate, which was associated with increased pre-bacteremia IgG levels against Efb, IsaA, LukD, LukE, Nuc, PrsA and WTA. In conclusion, S. aureus isolate P skin infection in mice reduces the severity of subsequent endogenous S. aureus bacteremia only. Although cellular immune effects cannot be rules out, anti-staphylococcal IgG against specified antigens may contribute to this effect.

  13. Endogenous synthesis of corticosteroids in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Shimpei Higo

    Full Text Available BACKGROUND: Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC synthase, cytochrome P450(c21. METHODOLOGY/PRINCIPAL FINDINGS: The expression of P450(c21 was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG was demonstrated by metabolism analysis of (3H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21, P450(2D4, P450(11β1 and 3β-hydroxysteroid dehydrogenase (3β-HSD were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM doses of CORT for 1 h. CONCLUSIONS/SIGNIFICANCE: These results imply the complete pathway of corticosteroid synthesis of 'pregnenolone →PROG→DOC→CORT' in the hippocampal neurons. Both P450(c21 and P450(2D4 can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.

  14. Manager's effort and endogenous economic discrimination

    Directory of Open Access Journals (Sweden)

    Jaime Orrillo

    2004-09-01

    Full Text Available Assume a labor supply consisting of two types of workers, 1 and 2. Both workers are equally productive and exhibit supply functions with the same elasticity. We consider a firm (entrepreneur or shareholders that is competitive in the output market and monopsonistic in input markets. The firm uses the services of a manager who has a high human capital and whose wage is given by the market. It is supposed that the manager does not like to work with one type of worker, say type 1. If we allow the manager's effort to be an additional input without any extra (in addition to his salary cost for the firm, then the firm's pricing decision will be different for both workers. That is, there will be a wage differential and therefore endogenous economic discrimination2 in the labor markets.Vamos assumir que a oferta de trabalho consiste de dois tipos de trabalhadores, 1 e 2. Ambos os trabalhadores são igualmente produtivos e exibem funções de oferta com a mesma elasticidade. Consideramos uma firma (empresário ou acionistas, a qual é competitiva no mercado de produtos e monopsonista nos mercados de insumos. A firma usa os serviços de um gerente quem tem um alto capital humano e cujo salário é dado pelo mercado. Suponhamos que o gerente não gosta de trabalhar com um tipo de trabalhador, digamos o tipo 1. Se permitirmos que o esforço do gerente seja um insumo adicional sem nenhum custo extra (além de seu salário, a decisão de salários será diferente para ambos os trabalhadores. Isto é, haverá um diferencial de salários e, em conseqüência, uma discriminação econômica1 endógena nos mercados de trabalho.

  15. Demonstration of endogenous imipramine like material in rat brain

    International Nuclear Information System (INIS)

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-01-01

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits [ 3 H] imipramine specific binding and mimics the inhibitory effect of imipramine on [ 3 H] serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits [ 3 H] imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum

  16. Amplification and chromosomal dispersion of human endogenous retroviral sequences

    International Nuclear Information System (INIS)

    Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O'Brien, S.J.

    1986-01-01

    Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked

  17. Strategies for the photo-control of endogenous protein activity.

    Science.gov (United States)

    Brechun, Katherine E; Arndt, Katja M; Woolley, G Andrew

    2017-08-01

    Photo-controlled or 'optogenetic' effectors interfacing with endogenous protein machinery allow the roles of endogenous proteins to be probed. There are two main approaches being used to develop optogenetic effectors: (i) caging strategies using photo-controlled conformational changes, and (ii) protein relocalization strategies using photo-controlled protein-protein interactions. Numerous specific examples of these approaches have been reported and efforts to develop general methods for photo-control of endogenous proteins are a current focus. The development of improved screening and selection methods for photo-switchable proteins would advance the field. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Profiling the indole alkaloids in yohimbe bark with ultra-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Sun, Jianghao; Baker, Andrew; Chen, Pei

    2011-09-30

    An ultra-performance liquid chromatography/ion mobility quadrupole time-of-flight mass spectrometry (UPLC/IM-QTOF-MS) method was developed for profiling the indole alkaloids in yohimbe bark. Many indole alkaloids with the yohimbine or ajmalicine core structure, plus methylated, oxidized and reduced species, were characterized. Common fragments and mass differences are described. It was shown that the use of IMS could provide another molecular descriptor, i.e. molecular shape by rotationally averaged collision cross-section; this is of great value for identification of constituents when reference materials are usually not available. Using the combination of high resolution (~40000) accurate mass measurement with time-aligned parallel (TAP) fragmentation, MS(E) (where E represents collision energy), ion mobility mass spectrometry (IMS) and UPLC chromatography, a total 55 indole alkaloids were characterized and a few new indole alkaloids are reported for the first time. Published in 2011 by John Wiley & Sons, Ltd.

  19. Application of electrochemical frequency modulation for monitoring corrosion and corrosion inhibition of iron by some indole derivatives in molar hydrochloric acid

    International Nuclear Information System (INIS)

    Khaled, K.F.

    2008-01-01

    The corrosion inhibition effect of four indole derivatives, namely indole (IND), benzotriazole (BTA), benzothiazole (BSA) and benzoimidazole (BIA), have been used as possible corrosion inhibitors for pure iron in 1 M HCl. In this study, electrochemical frequency modulation, EFM was used as an effective method for corrosion rate determination in corrosion inhibition studies. By using EFM measurements, corrosion current density was determined without prior knowledge of Tafel slopes. Corrosion rates obtained using EFM, were compared to that obtained from other chemical and electrochemical techniques. The results obtained from EFM, EIS, Tafel and weight loss measurements were in good agreement. Tafel polarization measurements show that indole derivatives are cathodic-type inhibitors. Molecular simulation studies were applied to optimize the adsorption structures of indole derivatives. The inhibitor/iron/solvent interfaces were simulated and the adsorption energies of these inhibitors were calculated. Quantum chemical calculations have been performed and several quantum chemical indices were calculated and correlated with the corresponding inhibition efficiencies

  20. Design and synthesis of marine natural product-based 1H-indole-2,3-dione scaffold as a new antifouling/antibacterial agent against fouling bacteria.

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Rodrigues, C.; Mascarenhas, S.; DeSouza, L.

    Planococcus donghaensis, Erythrobacter litoralis, Alivibrio salmonicida, Vibrio furnisii. Overall, the modified analogues showed stronger activity than the parent marine natural product (isatin) and hence 1H-indole-2,3-dione scaffold has immense potential...