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Sample records for natural dihydrochalcone induces

  1. Artificial sweetener neohesperidin dihydrochalcone showed antioxidative, anti-inflammatory and anti-apoptosis effects against paraquat-induced liver injury in mice.

    PubMed

    Shi, Qiong; Song, Xiufang; Fu, Juanli; Su, Chuanyang; Xia, Xiaomin; Song, Erqun; Song, Yang

    2015-12-01

    The present study evaluated the protective effect of artificial sweetener neohesperidin dihydrochalcone (NHDC) against paraquat (PQ)-induced acute liver injury in mice. A single dose of PQ (75mg/kg body weight, i.p.) induced acute liver toxicity with the evidences of increased liver damage biomarkers, aspartate transaminase (AST) and alanine transaminase (ALT) activities in serum. Consistently, PQ decreased the antioxidant capacity by reducing glutathione peroxidase (GP-X), glutathione-S-transferase (GST) and catalase (CAT) activities, glutathione (GSH) level and total antioxidant capacity (T-AOC), as well as increasing reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) levels. Histopathological examination revealed that PQ induced numerous changes in the liver tissues. Immunochemical staining assay indicated the upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. However, NHDC ameliorates PQ-induced hepatic toxicity in mice by reversing these parameters. Additionally, NHDC significantly inhibited PQ-induced nuclear factor-kappa B (NF-κB) expression and mitochondrial-driven apoptotic signaling. TUNEL assay confirmed that PQ-induced apoptosis was relieved by NHDC. In conclusion, these findings suggested that NHDC showed potent antioxidant, anti-inflammatory and anti-apoptotic effects against PQ-induced acute liver damage. PMID:26362205

  2. Orphan flavonoids and dihydrochalcones from Primula exudates.

    PubMed

    Bhutia, Tshering Doma; Valant-Vetschera, Karin M; Brecker, Lothar

    2013-08-01

    Two orphan flavonoids containing an oxepin structure in ring A and named as Primcortusin (1) and 3'-OH-Primcortusin (2) were isolated from leaf exudates of Primula cortusoides, while P. glutinosa exudates yielded two dihydrochalcone derivatives (3,4). These novel structures have not been detected in other species of Primula so far. Chemical structures were elucidated by 2D NMR and mas spectrometry. The nature of compounds 1 and 2 is discussed, and ideas about their possible origin and that of unsubstituted flavone and other irregular substituted Primula flavones are presented.

  3. Neohesperidin dihydrochalcone down-regulates MyD88-dependent and -independent signaling by inhibiting endotoxin-induced trafficking of TLR4 to lipid rafts.

    PubMed

    Xia, Xiaomin; Fu, Juanli; Song, Xiufang; Shi, Qiong; Su, Chuanyang; Song, Erqun; Song, Yang

    2015-12-01

    Fulminant hepatic failure (FHF) is a lethal clinical syndrome characterized by the activation of macrophages and the increased production of inflammatory mediators. The purpose of this study was to investigate the effects of neohesperidin dihydrochalcone (NHDC), a widely-used low caloric artificial sweetener against FHF. An FHF experimental model was established in mice by intraperitoneal injection of D-galactosamine (d-GalN) (400mg/kg)/lipopolysaccharides (LPS) (10 μg/kg). Mice were orally administered NHDC for 6 continuous days and at 1h before d-GalN/LPS administration. RAW264.7 macrophages were used as an in vitro model. Cells were pre-treated with NHDC for 1h before stimulation with LPS (10 μg/ml) for 6h. d-GalN/LPS markedly increased the serum transaminase activities and levels of oxidative and inflammatory markers, which were significantly attenuated by NHDC. Mechanistic analysis indicated that NHDC inhibited LPS-induced myeloid differentiation factor 88 (MyD88) and TIR-containing adapter molecule (TRIF)-dependent signaling. Transient transfection of TLR4 or MyD88 siRNA inhibited the downstream inflammatory signaling. This effect could also be achieved by the pretreatment with NHDC. The fluorescence microscopy and flow cytometry results suggested that NHDC potently inhibited the binding of LPS to TLR4 in RAW264.7 macrophages. In addition, the inhibitory effect of NHDC on LPS-induced translocation of TLR4 into lipid raft domains played an important role in the amelioration of production of downstream pro-inflammatory molecules. Furthermore, the activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) by NHDC inhibited TLR4 signaling. In conclusion, our results suggest that NHDC attenuates d-GalN/LPS-induced FHF by inhibiting the TLR4-mediated inflammatory pathway, demonstrating a new application of NHDC as a hepatoprotective agent. PMID:26453923

  4. Artocarpus altilis (Parkinson) Fosberg Extracts and Geranyl Dihydrochalcone Inhibit STAT3 Activity in Prostate Cancer DU145 Cells.

    PubMed

    Jeon, Yoon Jung; Jung, Seung-Nam; Chang, Hyeyoun; Yun, Jieun; Lee, Chang Woo; Lee, Joonku; Choi, Sangho; Nash, Oyekanmi; Han, Dong Cho; Kwon, Byoung-Mog

    2015-05-01

    Artocarpus altilis (Parkinson) Fosberg has traditionally been used in Indonesia for the treatment of liver cirrhosis, hypertension, and diabetes. In many other countries, it is used for the treatment of malaria, yellow fever, and dengue fever. It has been reported that A. altilis extracts have antiatherosclerotic and cytoprotective effects, but its molecular targets in tumor cells are not yet fully understood. The A. altilis extracts and the partially purified fraction have been shown to inhibit STAT3 activity and the phosphorylation of STAT3 in a dose-dependent manner. To identify the active components, a bioassay-guided isolation of the partially purified fraction resulted in the identification of a geranyl dihydrochalcone, CG901. Its chemical structure was established on the basis of spectroscopic evidence and comparison with published data. The partially purified fraction and the isolated a geranyl dihydrochalcone, CG901, down-regulated the expression of STAT3 target genes, induced apoptosis in DU145 prostate cancer cells via caspase-3 and PARP degradation, and inhibited tumor growth in human prostate tumor (DU145) xenograft initiation model. These results suggest that A. altilis could be a good natural source and that the isolated compound will be a potential lead molecule for developing novel therapeutics against STAT3-related diseases, including cancer and inflammation.

  5. Artocarpus altilis (Parkinson) Fosberg Extracts and Geranyl Dihydrochalcone Inhibit STAT3 Activity in Prostate Cancer DU145 Cells.

    PubMed

    Jeon, Yoon Jung; Jung, Seung-Nam; Chang, Hyeyoun; Yun, Jieun; Lee, Chang Woo; Lee, Joonku; Choi, Sangho; Nash, Oyekanmi; Han, Dong Cho; Kwon, Byoung-Mog

    2015-05-01

    Artocarpus altilis (Parkinson) Fosberg has traditionally been used in Indonesia for the treatment of liver cirrhosis, hypertension, and diabetes. In many other countries, it is used for the treatment of malaria, yellow fever, and dengue fever. It has been reported that A. altilis extracts have antiatherosclerotic and cytoprotective effects, but its molecular targets in tumor cells are not yet fully understood. The A. altilis extracts and the partially purified fraction have been shown to inhibit STAT3 activity and the phosphorylation of STAT3 in a dose-dependent manner. To identify the active components, a bioassay-guided isolation of the partially purified fraction resulted in the identification of a geranyl dihydrochalcone, CG901. Its chemical structure was established on the basis of spectroscopic evidence and comparison with published data. The partially purified fraction and the isolated a geranyl dihydrochalcone, CG901, down-regulated the expression of STAT3 target genes, induced apoptosis in DU145 prostate cancer cells via caspase-3 and PARP degradation, and inhibited tumor growth in human prostate tumor (DU145) xenograft initiation model. These results suggest that A. altilis could be a good natural source and that the isolated compound will be a potential lead molecule for developing novel therapeutics against STAT3-related diseases, including cancer and inflammation. PMID:25682949

  6. Biotransformation of phloretin by amylosucrase yields three novel dihydrochalcone glucosides.

    PubMed

    Overwin, Heike; Wray, Victor; Hofer, Bernd

    2015-10-10

    Glycosylation is one of the most important tailoring reactions for natural products. It typically exerts profound direct or indirect effects on their biological activity. The dihydrochalcone phloretin and its known sugar derivatives, particularly phlori(d)zin, have been shown to influence various cellular processes. We found that a non-Leloir glycosyltransferase, amylosucrase from Neisseria polysaccharea, is an excellent catalyst for the stereospecific glucosylation of phloretin at the 4' position. Three novel phloretin derivatives were obtained, the first ones in which the sugar-aglycone bond possesses the configuration. A first biological characterization in a cell viability assay showed that each sugar attachment reduced the compound toxicity approximately two-fold. PMID:26200830

  7. Dihydrochalcones and homoisoflavanes from the red resin of Dracaena cochinchinensis (Chinese dragon's blood).

    PubMed

    Su, Xiao-Qin; Song, Yue-Lin; Zhang, Jing; Huo, Hui-Xia; Huang, Zheng; Zheng, Jiao; Zhang, Qian; Zhao, Yun-Fang; Xiao, Wei; Li, Jun; Tu, Peng-Fei

    2014-12-01

    Two new dihydrochalcones, 4-hydroxy-2,4'-dimethoxydihydrochalcone (1) and 3,4'-dihydroxy-2,4,6-trimethoxydihydrochalcone (2), and a new homoisoflavane, 7,3'-dihydroxy-8,4'-dimethoxyhomoisoflavane (3), along with 12 known compounds (4-15), were isolated from the red resin of Dracaena cochinchinensis (Chinese dragon's blood). Their structures were assigned by a variety of spectroscopic techniques. Diversity of cleavage pathways were proposed for dihydrochalcones and homoisoflavanes based on the mass spectroscopic behaviors of those identified compounds using hybrid ion trap-time of flight mass spectrometry. All the compounds were evaluated for their inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophages, and compound 9 exhibited mild inhibition of NO production in this assay with IC₅₀ value of 50.3 μM. PMID:25218969

  8. Dihydrochalcones and homoisoflavanes from the red resin of Dracaena cochinchinensis (Chinese dragon's blood).

    PubMed

    Su, Xiao-Qin; Song, Yue-Lin; Zhang, Jing; Huo, Hui-Xia; Huang, Zheng; Zheng, Jiao; Zhang, Qian; Zhao, Yun-Fang; Xiao, Wei; Li, Jun; Tu, Peng-Fei

    2014-12-01

    Two new dihydrochalcones, 4-hydroxy-2,4'-dimethoxydihydrochalcone (1) and 3,4'-dihydroxy-2,4,6-trimethoxydihydrochalcone (2), and a new homoisoflavane, 7,3'-dihydroxy-8,4'-dimethoxyhomoisoflavane (3), along with 12 known compounds (4-15), were isolated from the red resin of Dracaena cochinchinensis (Chinese dragon's blood). Their structures were assigned by a variety of spectroscopic techniques. Diversity of cleavage pathways were proposed for dihydrochalcones and homoisoflavanes based on the mass spectroscopic behaviors of those identified compounds using hybrid ion trap-time of flight mass spectrometry. All the compounds were evaluated for their inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophages, and compound 9 exhibited mild inhibition of NO production in this assay with IC₅₀ value of 50.3 μM.

  9. Improved water solubility of neohesperidin dihydrochalcone in sweetener blends.

    PubMed

    Benavente-García, O; Castillo, J; Del Baño, M J; Lorente, J

    2001-01-01

    Significant technological advantages in terms of sweetness synergy and hence cost-saving can be obtained if neohesperidin dihydrochalcone (NHDC) is used in sweetener blends with other intense or bulk sweeteners. The combination of NHDC with sodium saccharin or sodium cyclamate is an excellent method to improve the water solubility at room temperature of NHDC. In the case of NHDC-sodium saccharin, two different methods for blend preparation, a simple mixture and a cosolubilized mixture, can be used, with similar results obtained for solubility and solution stability properties. To improve temporally the water solubility of NHDC in combination with sodium cyclamate, it is absolutely necessary to prepare cosolubilized blends.

  10. A new prenylated dihydrochalcone from the leaves of Artocarpus lowii.

    PubMed

    Jamil, Shajarahtunnur; Sirat, Hasnah Mohd; Jantan, Ibrahim; Aimi, Norio; Kitajima, Mariko

    2008-07-01

    A new prenylated dihydrochalcone, 2',4'-dihydroxy-4-methoxy-3'-prenyldihydrochalcone (1), along with two known compounds, 2',4',4-trihydroxy-3'-prenylchalcone (2) and 2',4-dihydroxy-3',4'-(2,2-dimethylchromene)chalcone (3) were isolated from the leaves of Artocarpus lowii. The structures of 1-3 were elucidated by spectroscopic methods and by comparison with data reported in the literature. Compounds 1-3 showed strong free radical scavenging activity towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) measured by electron spin resonance (ESR) spectrometry.

  11. Geranyl dihydrochalcones from Artocarpus altilis and their antiausteric activity.

    PubMed

    Nguyen, Mai Thanh Thi; Nguyen, Nhan Trung; Nguyen, Khang Duy Huu; Dau, Hien Thu Thi; Nguyen, Hai Xuan; Dang, Phu Hoang; Le, Tam Minh; Nguyen Phan, Trong Huu; Tran, Anh Hai; Nguyen, Bac Duy; Ueda, Jun-Ya; Awale, Suresh

    2014-02-01

    Human pancreatic cancer cell lines have remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions is a novel antiausterity strategy in anticancer drug discovery. In this study, the methanolic extract of the leaves of Artocarpus altilis showed 100 % preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions at a concentration of 50 µg/mL. Further investigation of this extract led to the isolation of eight new geranylated dihydrochalcones named sakenins A-H (1-8) together with four known compounds (9-12). Among them, sakenins F (6) and H (8) were identified as potent preferentially cytotoxic candidates with PC50 values of 8.0 µM and 11.1 µM, respectively.

  12. Oxidation of the dihydrochalcone aspalathin leads to dimerization.

    PubMed

    Krafczyk, Nicole; Heinrich, Theres; Porzel, Andrea; Glomb, Marcus A

    2009-08-12

    Aspalathin and nothofagin are typical ingredients of unfermented rooibos (Krafczyk, N.; Glomb, M. A. J. Agric. Food Chem. 2008, 56, 3368). During oxidation these dihydrochalcones were degraded to higher molecular weight browning products under aerated and nonenzymatic conditions. In the early stages of browning reactions aspalathin formed two dimers. These two compounds were unequivocally established as atropisomers stemming from oxidative A to B ring coupling. Multilayer countercurrent chromatography (MLCCC) and preparative high-performance liquid chromatography (HPLC) were applied to obtain pure substances. The purity and identity of isolated dimers were confirmed by different NMR experiments, HPLC-DAD-MS, and HR-MS. In parallel to the formation of chromophores during the fermentation of black tea, the formation of aspalathin dimers implies an important mechanistic channel for the generation of color during the processing of rooibos. PMID:19601579

  13. The binding site for neohesperidin dihydrochalcone at the human sweet taste receptor

    PubMed Central

    Winnig, Marcel; Bufe, Bernd; Kratochwil, Nicole A; Slack, Jay P; Meyerhof, Wolfgang

    2007-01-01

    Background Differences in sweet taste perception among species depend on structural variations of the sweet taste receptor. The commercially used isovanillyl sweetener neohesperidin dihydrochalcone activates the human but not the rat sweet receptor TAS1R2+TAS1R3. Analysis of interspecies combinations and chimeras of rat and human TAS1R2+TAS1R3 suggested that the heptahelical domain of human TAS1R3 is crucial for the activation of the sweet receptor by neohesperidin dihydrochalcone. Results By mutational analysis combined with functional studies and molecular modeling we identified a set of different amino acid residues within the heptahelical domain of human TAS1R3 that forms the neohesperidin dihydrochalcone binding pocket. Sixteen amino acid residues in the transmembrane domains 2 to 7 and one in the extracellular loop 2 of hTAS1R3 influenced the receptor's response to neohesperidin dihydrochalcone. Some of these seventeen residues are also part of the binding sites for the sweetener cyclamate or the sweet taste inhibitor lactisole. In line with this observation, lactisole inhibited activation of the sweet receptor by neohesperidin dihydrochalcone and cyclamate competitively, whereas receptor activation by aspartame, a sweetener known to bind to the N-terminal domain of TAS1R2, was allosterically inhibited. Seven of the amino acid positions crucial for activation of hTAS1R2+hTAS1R3 by neohesperidin dihydrochalcone are thought to play a role in the binding of allosteric modulators of other class C GPCRs, further supporting our model of the neohesperidin dihydrochalcone pharmacophore. Conclusion From our data we conclude that we identified the neohesperidin dihydrochalcone binding site at the human sweet taste receptor, which overlaps with those for the sweetener cyclamate and the sweet taste inhibitor lactisole. This readily delivers a molecular explanation of our finding that lactisole is a competitive inhibitor of the receptor activation by neohesperidin

  14. Taste responses to neohesperidin dihydrochalcone in rats and baboon monkeys.

    PubMed

    Naim, M; Rogatka, H; Yamamoto, T; Zehavi, U

    1982-06-01

    Preference-aversion behavior to solutions containing neohesperidin dihydrochalcone (NHDHC) was studied rats and baboon monkeys. Electrophysiological responses evoked by application of NHDHC solutions to taste receptors innervated by the chorda tympani and the glossopharyngeal nerves were also measured. As a group, rats were indifferent to solutions containing up to 1.2 x 10(-3) M NHDHC in short and long-term preference tests. A solution containing the very high concentration of 8.2 x 10(-3) M NHDHC was consumed less than water by all rats. The aversive behavior of rats to the 8.2 x 10(-3) M NHDHC solution appeared to be due to taste quality rather than olfaction. When percent preferences were calculated on an individual basis for the long-term preference tests, 59% of the rats were indifferent to solutions containing up to 1.2 x 10(-3) M NHDHC, 33% of the animals found this solution aversive and less than 8% showed preference. Behavioral responses to a solution of 3.4 x 10(-4) M aspartame also varied considerably among rats. The electrophysiological data were in line with the behavioral responses suggesting weak taste responses for NHDHC in rats. More pronounced responses observed in the glossopharyngeal nerve as compared to the chorda tympani. Baboon monkeys showed a strong preference for solutions containing 1.6 x 10(-5) M-1.6 x 10(-3) M NHDHC. A solution of 1.6 x 10(-2) M was consumed to a lesser extent than water. It is concluded that baboon monkeys present a better experimental model than rats for investigating the sweetness of NHDHC.

  15. Quantitation of flavanols, proanthocyanidins, isoflavones, flavanones, dihydrochalcones, stilbenes, and benzoic Acid derivatives after identification by LC-MS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A general method was developed for the systematic quantitation of catechins, proanthocyanidins, isoflavones, flavanones, dihydrochalcones, stilbenes, and hydroxybenzoic acid derivatives (mainly hydrolyzable tannins) using the UV relative mole response factors (MRRF) of the reference standard from ea...

  16. Preparative isolation, quantification and antioxidant activity of dihydrochalcones from Sweet Tea (Lithocarpus polystachyus Rehd.).

    PubMed

    Sun, Yinshi; Li, Wei; Liu, Zhengbo

    2015-10-01

    Dihydrochalcones are the main active components of Lithocarpus polystachyus Rehd. (Sweet Tea), they are directly related to the sweet tonic beverage and traditional herb. In this work, two runs of preparative high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane/ethyl acetate/ethanol/water (1:4:3:4, v/v) were employed to separate three dihydrochalcones (phloridzin, trilobatin and phloretin) from Sweet Tea. About 6.4mg of phloridzin, 48.4mg of trilobatin, and 4.7mg of phloretin with purities of 96.7%, 98.4% and 98.1% were obtained from 130mg of the crude Sweet Tea extract. Phloridzin, trilobatin, and phloretin had effective radical scavenging activities, with IC50 values of 866.80, 20.16 and 179.47μg/mL, respectively, in a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical method. The contents of phloridzin, trilobatin and phloretin in dried old leaves and tender leaves of tea were in the range of 10.1-18.0, 113.7-128.8, 3.6-4.3mg/g and 9.3-9.8, 82.9-103.1, 1.9-2.5mg/g, respectively. The results indicated that the HPLC had good precision, accuracy and repeatability for the determination of three dihydrochalcones in samples.

  17. Antibacterial Balsacones J-M, Hydroxycinnamoylated Dihydrochalcones from Populus balsamifera Buds.

    PubMed

    Simard, François; Gauthier, Charles; Chiasson, Éric; Lavoie, Serge; Mshvildadze, Vakhtang; Legault, Jean; Pichette, André

    2015-05-22

    A phytochemical investigation of buds from the hardwood tree Populus balsamifera led to the isolation of six new cinnamoylated dihydrochalcones as pairs of racemates and one as a racemic mixture along with the known compound iryantherin-D (2), the absolute configuration of which was determined for the first time. The structures of balsacones J (1), K (3), L (4), and M (5) were elucidated on the basis of spectroscopic data (1D and 2D NMR, IR, and MS). Chiral HPLC separations were carried out, and the absolute configuration of the isolated enantiomers unambiguously established via X-ray diffraction analyses and electron circular dichroism spectroscopic data. Each of the purified enantiomers exhibited potent in vitro antibacterial activity against Staphylococcus aureus with IC50 values ranging from 0.61 to 6 μM.

  18. Dipeptidyl peptidase-IV inhibitory activity of dimeric dihydrochalcone glycosides from flowers of Helichrysum arenarium.

    PubMed

    Morikawa, Toshio; Ninomiya, Kiyofumi; Akaki, Junji; Kakihara, Namiko; Kuramoto, Hiroyuki; Matsumoto, Yurie; Hayakawa, Takao; Muraoka, Osamu; Wang, Li-Bo; Wu, Li-Jun; Nakamura, Seikou; Yoshikawa, Masayuki; Matsuda, Hisashi

    2015-10-01

    A methanol extract of everlasting flowers of Helichrysum arenarium L. Moench (Asteraceae) was found to inhibit the increase in blood glucose elevation in sucrose-loaded mice at 500 mg/kg p.o. The methanol extract also inhibited the enzymatic activity against dipeptidyl peptidase-IV (DPP-IV, IC50 = 41.2 μg/ml), but did not show intestinal α-glucosidase inhibitory activities. From the extract, three new dimeric dihydrochalcone glycosides, arenariumosides V-VII (2-4), were isolated, and the stereostructures were elucidated based on their spectroscopic properties and chemical evidence. Of the constituents, several flavonoid constituents, including 2-4, were isolated, and these isolated constituents were investigated for their DPP-IV inhibitory effects. Among them, chalconaringenin 2'-O-β-D-glucopyranoside (16, IC50 = 23.1 μM) and aureusidin 6-O-β-D-glucopyranoside (35, 24.3 μM) showed relatively strong inhibitory activities.

  19. Natural Antioxidants Against Arsenic-Induced Genotoxicity.

    PubMed

    Kumar, Munesh; Lalit, Minakshi; Thakur, Rajesh

    2016-03-01

    Arsenic is present in water, soil, and air in organic as well as in inorganic forms. However, inorganic arsenic is more toxic than organic and can cause many diseases including cancers in humans. Its genotoxic effect is considered as one of its carcinogenic actions. Arsenic can cause DNA strand breaks, deletion mutations, micronuclei formation, DNA-protein cross-linking, sister chromatid exchange, and DNA repair inhibition. Evidences indicate that arsenic causes DNA damage by generation of reactive free radicals. Nutritional supplementation of antioxidants has been proven highly beneficial against arsenic genotoxicity in experimental animals. Recent studies suggest that antioxidants protect mainly by reducing excess free radicals via restoring the activities of cellular enzymatic as well as non-enzymatic antioxidants and decreasing the oxidation processes such as lipid peroxidation and protein oxidation. The purpose of this review is to summarize the recent literature on arsenic-induced genotoxicity and its mitigation by naturally derived antioxidants in various biological systems.

  20. Brane induced gravity: Ghosts and naturalness

    NASA Astrophysics Data System (ADS)

    Eglseer, Ludwig; Niedermann, Florian; Schneider, Robert

    2015-10-01

    Linear stability of brane induced gravity in two codimensions on a static pure tension background is investigated. The brane is regularized as a ring of finite circumference in extra space. By explicitly calculating the vacuum persistence amplitude of the corresponding quantum theory, we show that the parameter space is divided into two regions—one corresponding to a stable Minkowski vacuum on the brane and one being plagued by ghost instabilities. This analytical result affirms a recent nonlinear, but mainly numerical analysis. The main result is that the ghost is absent for a sufficiently large brane tension, in perfect agreement with a value expected from a natural effective field theory point of view. Unfortunately, the linearly stable parameter regime is either ruled out phenomenologically or becomes unstable for nontrivial cosmologies. We argue that supercritical brane backgrounds constitute the remaining window of opportunity. In the special case of a tensionless brane, we find that the ghost exists for all phenomenologically relevant values of the induced gravity scale. Regarding this case, there are contradicting results in the literature, and we are able to fully resolve this controversy by explicitly uncovering the errors made in the "no-ghost" analysis. Finally, a Hamiltonian analysis generalizes the ghost result to more than two codimensions.

  1. Identification and cloning of an NADPH-dependent hydroxycinnamoyl-CoA double bond reductase involved in dihydrochalcone formation in Malus×domestica Borkh.

    PubMed

    Ibdah, Mwafaq; Berim, Anna; Martens, Stefan; Valderrama, Andrea Lorena Herrera; Palmieri, Luisa; Lewinsohn, Efraim; Gang, David R

    2014-11-01

    The apple tree (Malus sp.) is an agriculturally and economically important source of food and beverages. Many of the health beneficial properties of apples are due to (poly)phenolic metabolites that they contain, including various dihydrochalcones. Although many of the genes and enzymes involved in polyphenol biosynthesis are known in many plant species, the specific reactions that lead to the biosynthesis of the dihydrochalcone precursor, p-dihydrocoumaroyl-CoA (3), are unknown. To identify genes involved in the synthesis of these metabolites, existing genome databases of the Rosaceae were screened for apple genes with significant sequence similarity to Arabidopsis alkenal double bond reductases. Herein described are the isolation and characterization of a Malus hydroxycinnamoyl-CoA double bond reductase, which catalyzed the NADPH-dependent reduction of p-coumaroyl-CoA and feruloyl-CoA to p-dihydrocoumaroyl-CoA and dihydroferuloyl-CoA, respectively. Its apparent Km values for p-coumaroyl-CoA, feruloyl-CoA and NADPH were 96.6, 92.9 and 101.3μM, respectively. The Malus double bond reductase preferred feruloyl-CoA to p-coumaroyl-CoA as a substrate by a factor of 2.1 when comparing catalytic efficiencies in vitro. Expression analysis of the hydroxycinnamoyl-CoA double bond reductase gene revealed that its transcript levels showed significant variation in tissues of different developmental stages, but was expressed when expected for involvement in dihydrochalcone formation. Thus, the hydroxycinnamoyl-CoA double bond reductase appears to be responsible for the reduction of the α,β-unsaturated double bond of p-coumaroyl-CoA, the first step of dihydrochalcone biosynthesis in apple tissues, and may be involved in the production of these compounds.

  2. A new dimeric dihydrochalcone and a new prenylated flavone from the bud covers of Artocarpus altilis: potent inhibitors of cathepsin K.

    PubMed

    Patil, Ashok D; Freyer, Alan J; Killmer, Lew; Offen, Priscilla; Taylor, Paul B; Votta, Bartholomew J; Johnson, Randall K

    2002-04-01

    A MeOH/CH(2)Cl(2) extract of the bud covers of Artocarpus altilis collected in Micronesia showed activity in a cathepsin K inhibition assay. In addition to the three known flavonoids isolated from the bud covers of this species, two new compounds have been identified whose structures were determined on the basis of spectral data. These compounds include a dimeric dihydrochalcone, cycloaltilisin 6 (2), and a new prenylated flavone, cycloaltilisin 7 (3). Novel compounds 2 and 3 have IC(50) values of 98 and 840 nM, respectively, in cathepsin inhibition.

  3. Natural and Induced Environment in Low Earth Orbit

    NASA Technical Reports Server (NTRS)

    Wilson, John W.; Badavi, Francis F.; Kim, Myung-Hee Y.; Clowdsley, Martha S.; Heinbockel, John H.; Cucinotta, Francis A.; Badhwar, Gautam D.; Atwell, William; Huston, Stuart L.

    2002-01-01

    The long-term exposure of astronauts on the developing International Space Station (ISS) requires an accurate knowledge of the internal exposure environment for human risk assessment and other onboard processes. The natural environment is moderated by the solar wind which varies over the solar cycle. The neutron environment within the Shuttle in low Earth orbit has two sources. A time dependent model for the ambient environment is used to evaluate the natural and induced environment. The induced neutron environment is evaluated using measurements on STS-31 and STS-36 near the 1990 solar maximum.

  4. Quantitation of Flavanols, Proanthocyanidins, Isoflavones, Flavanones, Dihydrochalcones, Stilbenes, Benzoic Acid Derivatives Using Ultraviolet Absorbance after Identification by Liquid Chromatography–Mass Spectrometry

    PubMed Central

    Lin, Long-Ze; Harnly, James M.

    2013-01-01

    A general method was developed for the systematic quantitation of flavanols, proanthocyanidins, isoflavones, flavanones, dihydrochalcones, stilbenes, and hydroxybenzoic acid derivatives (mainly hydrolyzable tannins) based on UV band II absorbance arising from the benzoyl structure. The compound structures and the wavelength maximum were well correlated and were divided into four groups: the flavanols and proanthocyanidins at 278 nm, hydrolyzable tannins at 274 nm, flavanones at 288 nm, and isoflavones at 260 nm. Within each group, molar relative response factors (MRRFs) were computed for each compound based on the absorbance ratio of the compound and the group reference standard. Response factors were computed for the compounds as purchased (MRRF), after drying (MRRFD), and as the best predicted value (MRRFP). Concentrations for each compound were computed based on calibration with the group reference standard and the MRRFP. The quantitation of catechins, proanthocyanidins, and gallic acid derivatives in white tea was used as an example. PMID:22577798

  5. Interferon induces natural killer cell blastogenesis in vivo

    NASA Technical Reports Server (NTRS)

    Biron, C. A.; Sonnenfeld, G.; Welsh, R. M.

    1984-01-01

    Interferon (IFN), types beta and gamma, and IFN inducers polyinosinic-polycytidylic acid and lymphocytic choriomeningitis virus, all stimulated the generation of blast-natural killer (NK) cells in mouse spleens, Blast-NK cells were characterized on the basis of size, 3H-thymidine uptake, and NK cell markers These data indicate that in addition to augmenting NK cell-mediated lysis, IFN may regulate NK cell proliferation in vivo.

  6. Dephasing-Induced Control of Interference Nature in Three-Level Electromagnetically Induced Tansparency Systems

    PubMed Central

    Sun, Yong; Yang, Yaping; Chen, Hong; Zhu, Shiyao

    2015-01-01

    The influence of the dephasing on interference is investigated theoretically and experimentally in three-level electromagnetically induced transparency systems. The nature of the interference, constructive, no interference or destructive, can be controlled by adjusting the dephasing rates. This new phenomenon is experimentally observed in meta-atoms. The physics behind the dephasing-induced control of interference nature is the competing between stimulated emission and spontaneous emission. The random phase fluctuation due to the dephasing will result in the correlation and anti-correlation between the two dressed states, which will enhance and reduce the stimulated emission, respectively. PMID:26567708

  7. Nature of radiation-induced defects in quartz.

    PubMed

    Wang, Bu; Yu, Yingtian; Pignatelli, Isabella; Sant, Gaurav; Bauchy, Mathieu

    2015-07-14

    Although quartz (α-form) is a mineral used in numerous applications wherein radiation exposure is an issue, the nature of the atomistic defects formed during radiation-induced damage has not been fully clarified. Especially, the extent of oxygen vacancy formation is still debated, which is an issue of primary importance as optical techniques based on charged oxygen vacancies have been utilized to assess the level of radiation damage in quartz. In this paper, molecular dynamics simulations are applied to study the effects of ballistic impacts on the atomic network of quartz. We show that the defects that are formed mainly consist of over-coordinated Si and O, as well as Si-O connectivity defects, e.g., small Si-O rings and edge-sharing Si tetrahedra. Oxygen vacancies, on the contrary, are found in relatively low abundance, suggesting that characterizations based on E' centers do not adequately capture radiation-induced structural damage in quartz. Finally, we evaluate the dependence on the incident energy, of the amount of each type of the point defects formed, and quantify unambiguously the threshold displacement energies for both O and Si atoms. These results provide a comprehensive basis to assess the nature and extent of radiation damage in quartz. PMID:26178116

  8. Nature of radiation-induced defects in quartz

    SciTech Connect

    Wang, Bu; Yu, Yingtian; Bauchy, Mathieu; Pignatelli, Isabella; Sant, Gaurav

    2015-07-14

    Although quartz (α-form) is a mineral used in numerous applications wherein radiation exposure is an issue, the nature of the atomistic defects formed during radiation-induced damage has not been fully clarified. Especially, the extent of oxygen vacancy formation is still debated, which is an issue of primary importance as optical techniques based on charged oxygen vacancies have been utilized to assess the level of radiation damage in quartz. In this paper, molecular dynamics simulations are applied to study the effects of ballistic impacts on the atomic network of quartz. We show that the defects that are formed mainly consist of over-coordinated Si and O, as well as Si–O connectivity defects, e.g., small Si–O rings and edge-sharing Si tetrahedra. Oxygen vacancies, on the contrary, are found in relatively low abundance, suggesting that characterizations based on E′ centers do not adequately capture radiation-induced structural damage in quartz. Finally, we evaluate the dependence on the incident energy, of the amount of each type of the point defects formed, and quantify unambiguously the threshold displacement energies for both O and Si atoms. These results provide a comprehensive basis to assess the nature and extent of radiation damage in quartz.

  9. Anti-influenza A virus activity of a new dihydrochalcone diglycoside isolated from the Egyptian seagrass Thalassodendron ciliatum (Forsk.) den Hartog.

    PubMed

    Mohammed, Magdy M D; Hamdy, Abdel-Hamid A; El-Fiky, Nabaweye M; Mettwally, Walaa S A; El-Beih, Ahmed A; Kobayashi, Nobuyuki

    2014-01-01

    One new dihydrochalcone diglycoside has been isolated from the EtOAc fraction of the Egyptian seagrass Thalassodendrin ciliatum (Forsk.) den Hartog, and was identified as 6'-O-rhamnosyl-(1‴ → 6″)-glucopyranosyl asebogenin for which a trivial name Thalassodendrone was established. Furthermore, five known phenolics were isolated and identified as asebotin, quercetin 3,7-diglucoside, protocatechuic acid, ferulic acid and p-hydroxybenzoic acid. The structures of all the isolated compounds were established based on 1D and 2D NMR spectroscopy and high-resolution-mass spectrometer. High-resolution electrospray ionization mass spectra (HR-ESI-MS) were obtained using a JEOL JMS-T100TD spectrometer (JEOL Ltd., Tokyo, Japan). The anti-influenza A virus activity of the isolated new compound and asebotin was evaluated, and the obtained results revealed that the inhibition dose concentration of asebotin was more than that of Thalassodendrone with IC50 = 2.00 and 1.96 μg/mL, respectively, and with cytotoxic concentration (CC50) of 3.36 and 3.14 μg/mL, respectively.

  10. The nature of mutations induced by replication–transcription collisions.

    PubMed

    Sankar, T Sabari; Wastuwidyaningtyas, Brigitta D; Dong, Yuexin; Lewis, Sarah A; Wang, Jue D

    2016-07-01

    The DNA replication and transcription machineries share a common DNA template and thus can collide with each other co-directionally or head-on. Replication–transcription collisions can cause replication fork arrest, premature transcription termination, DNA breaks, and recombination intermediates threatening genome integrity. Collisions may also trigger mutations, which are major contributors to genetic disease and evolution. However, the nature and mechanisms of collision-induced mutagenesis remain poorly understood. Here we reveal the genetic consequences of replication–transcription collisions in actively dividing bacteria to be two classes of mutations: duplications/deletions and base substitutions in promoters. Both signatures are highly deleterious but are distinct from the previously well-characterized base substitutions in the coding sequence. Duplications/deletions are probably caused by replication stalling events that are triggered by collisions; their distribution patterns are consistent with where the fork first encounters a transcription complex upon entering a transcription unit. Promoter substitutions result mostly from head-on collisions and frequently occur at a nucleotide that is conserved in promoters recognized by the major σ factor in bacteria. This substitution is generated via adenine deamination on the template strand in the promoter open complex, as a consequence of head-on replication perturbing transcription initiation. We conclude that replication–transcription collisions induce distinct mutation signatures by antagonizing replication and transcription, not only in coding sequences but also in gene regulatory elements.

  11. Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers

    PubMed Central

    Mariño, Guillermo; Pietrocola, Federico; Madeo, Frank; Kroemer, Guido

    2014-01-01

    Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We surmise that there are 3 possibilities to mimic these effects, namely (i) the depletion of cytosolic AcCoA by interfering with its biosynthesis, (ii) the inhibition of acetyltransferases, which are enzymes that transfer acetyl groups from AcCoA to other molecules, mostly leucine residues in cellular proteins, or (iii) the stimulation of deacetylases, which catalyze the removal of acetyl groups from leucine residues. There are several examples of rather nontoxic natural compounds that act as AcCoA depleting agents (e.g., hydroxycitrate), acetyltransferase inhibitors (e.g., anacardic acid, curcumin, epigallocatechin-3-gallate, garcinol, spermidine) or deacetylase activators (e.g., nicotinamide, resveratrol), and that are highly efficient inducers of autophagy in vitro and in vivo, in rodents. Another common characteristic of these agents is their capacity to reduce aging-associated diseases and to confer protective responses against ischemia-induced organ damage. Hence, we classify them as “caloric restriction mimetics” (CRM). Here, we speculate that CRM may mediate their broad health-improving effects by triggering the same molecular pathways that usually are elicited by long-term caloric restriction or short-term starvation and that imply the induction of autophagy as an obligatory event conferring organismal, organ- or cytoprotection. PMID:25484097

  12. Natural and induced reduction of hexavalent chromium in soil

    NASA Astrophysics Data System (ADS)

    Leita, Liviana; Margon, Alja; Sinicco, Tania; Mondini, Claudio; Valentini, Massimiliano; Cantone, Pierpaolo

    2013-04-01

    Even though naturally elevated levels of chromium can be found naturally in some soils, distressing amounts of the hexavalent form (CrVI) are largely restricted to sites contaminated by anthropogenic activities. In fact, the widespread use of chromium in various industries and the frequently associated inadequate disposal of its by-products and wastes have created serious environmental pollution problems in many parts of the world. CrVI is toxic to plants, animals and humans and exhibits also mutagenic effects. However, being a strong oxidant, CrVI can be readily reduced to the much less harmful trivalent form (CrIII) when suitable electron donors are present in the environment. CrIII is relatively insoluble, less available for biological uptake, and thus definitely less toxic for web-biota. Various electron donors in soil can be involved in CrVI reduction in soil. The efficiency of CrVI reducing abiotic agents such as ferrous iron and sulphur compounds is well documented. Furthermore, CrVI reduction is also known to be significantly enhanced by a wide variety of cell-produced monosaccharides, including glucose. In this study we evaluated the dynamics of hexavalent chromium (CrVI) reduction in contaminated soil amended or not with iron sulphate or/and glucose and assessed the effects of CrVI on native or glucose-induced soil microbial biomass size and activity. CrVI negatively affected both soil microbial activity and the size of the microbial biomass. During the incubation period, the concentration of CrVI in soil decreased over time whether iron sulphate or/and glucose was added or not, but with different reduction rates. Soil therefore displayed a natural attenuation capacity towards chromate reduction. Addition of iron sulphate or/and glucose, however, increased the reduction rate by both abiotic and biotic mechanisms. Our data suggest that glucose is likely to have exerted an indirect role in the increased rate of CrVI reduction by promoting growth of

  13. Mapping Microbial Response Metabolomes for Induced Natural Product Discovery.

    PubMed

    Derewacz, Dagmara K; Covington, Brett C; McLean, John A; Bachmann, Brian O

    2015-09-18

    Intergeneric microbial interactions may originate a significant fraction of secondary metabolic gene regulation in nature. Herein, we expose a genomically characterized Nocardiopsis strain, with untapped polyketide biosynthetic potential, to intergeneric interactions via coculture with low inoculum exposure to Escherichia, Bacillus, Tsukamurella, and Rhodococcus. The challenge-induced responses of extracted metabolites were characterized via multivariate statistical and self-organizing map (SOM) analyses, revealing the magnitude and selectivity engendered by the limiting case of low inoculum exposure. The collected inventory of cocultures revealed substantial metabolomic expansion in comparison to monocultures with nearly 14% of metabolomic features in cocultures undetectable in monoculture conditions and many features unique to coculture genera. One set of SOM-identified responding features was isolated, structurally characterized by multidimensional NMR, and revealed to comprise previously unreported polyketides containing an unusual pyrrolidinol substructure and moderate and selective cytotoxicity. Designated ciromicin A and B, they are detected across mixed cultures with intergeneric preferences under coculture conditions. The structural novelty of ciromicin A is highlighted by its ability to undergo a diastereoselective photochemical 12-π electron rearrangement to ciromicin B at visible wavelengths. This study shows how organizing trends in metabolomic responses under coculture conditions can be harnessed to characterize multipartite cultures and identify previously silent secondary metabolism. PMID:26039241

  14. Space Shuttle externally induced environment compared with Skylab's natural environment

    NASA Technical Reports Server (NTRS)

    Susko, Michael

    1990-01-01

    Electret measurements obtained of the particulate contamination environment within the Space Shuttle Orbiter's cargo bay are presently compared with ground measurements of the particulates emitted by the Shuttle's SRBs, as well as with the expected natural particulate environment as measured by Skylab. Chemical analysis is shown to reveal the difference between natural and anthropogenic space debris; the most probable primary source of the Space Shuttle's particulate environment is the SRB exhaust.

  15. Natural and Human-induced Disturbances and Their Impacts on Forest Carbon Budgets in North America

    NASA Astrophysics Data System (ADS)

    Pan, Y.; Birdsey, R.; Chen, J. M.; McCullough, K.; Zhang, F.

    2014-12-01

    Natural and human-induced disturbances have profound impacts on forest carbon dynamics, and may cause the greatest uncertainty in estimating forest carbon budgets. In North America, three countries show very different forest disturbance patterns: Canadian forests are dominated by natural disturbances such as wildfires and insect outbreaks; forests of Mexico are more affected by human-induced land disturbances such as land-use change; while US forests are equally affected by human-induced and natural disturbances. As human-induced disturbances are closely linked to socioeconomic factors, natural disturbances are usually viewed as a natural process in forests and have equilibrium impacts on forests over the long run. However, with climate change and related changes in natural disturbance regimes in terms of frequency, intensity and scale, there are now fundamental changes in the nature of the impact of natural disturbances on forest carbon dynamics and even greater uncertainty about forest carbon budgets and feedbacks to the atmosphere and climate. In this study, we synthesize disturbance information for North America based on existing remote-sensing products, ground-based observations and modeling studies, evaluating impacts of disturbances on forest carbon budgets that are relevant to disturbance types, scales, frequency and intensity. The work represents the initial step of a more ambitious project tackling this research challenge for North America that crosses a broad climate gradient and diverse socioeconomic entities. The goal is to ultimately improve the estimates of forest carbon budgets and their potential for climate mitigation under changing environments.

  16. Lichen Symbiosis: Nature's High Yielding Machines for Induced Hydrogen Production

    PubMed Central

    Papazi, Aikaterini; Kastanaki, Elizabeth; Pirintsos, Stergios; Kotzabasis, Kiriakos

    2015-01-01

    Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939) and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont’s and photobiont’s consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration) establishes the required anoxic conditions for the activation of the phycobiont’s hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein) to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state) constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications. PMID:25826211

  17. Lichen symbiosis: nature's high yielding machines for induced hydrogen production.

    PubMed

    Papazi, Aikaterini; Kastanaki, Elizabeth; Pirintsos, Stergios; Kotzabasis, Kiriakos

    2015-01-01

    Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939) and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont's and photobiont's consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration) establishes the required anoxic conditions for the activation of the phycobiont's hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein) to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state) constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications.

  18. Lichen symbiosis: nature's high yielding machines for induced hydrogen production.

    PubMed

    Papazi, Aikaterini; Kastanaki, Elizabeth; Pirintsos, Stergios; Kotzabasis, Kiriakos

    2015-01-01

    Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939) and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont's and photobiont's consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration) establishes the required anoxic conditions for the activation of the phycobiont's hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein) to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state) constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications. PMID:25826211

  19. Natural and Laboratory-Induced Compaction Bands in Aztec Sandstone

    NASA Astrophysics Data System (ADS)

    Haimson, B. C.; Lee, H.

    2002-12-01

    The Aztec sandstone used in this research is from the Valley of Fire State Park area, Nevada. This Jurassic aeolian sandstone is extremely weak (uniaxial compressive strength of 1-2 MPa); porosity averages 26%; grains are subrounded and have a bimodal size distribution (0.1 mm and 0.5 mm); its mineral composition (K. Sternlof, personal comm.) is 93% quartz, 5% k-spar, and 2% kaolinite, Fe carbonate and others; grain bonding is primarily through suturing. Sternlof et al. (EOS, November, 2001) observed substantial exposure of mainly compactive deformation bands in the Aztec sandstone. We studied an SEM image of a compaction band found in a hand sample of the Aztec sandstone. We also conducted a drilling test in a 130x130x180 mm prismatic specimen subjected to a preset far-field true triaxial stress condition (\\sigmah = 15 MPa, \\sigmav = 25 MPa, \\sigmaH = 40 MPa). Drilling of a 20 mm dia. vertical hole created a long fracture-like thin tabular breakout along the \\sigmah springline and perpendicular to \\sigmaH direction. SEM analysis of the zones ahead of the breakout tips revealed narrow bands of presumed debonded intact grains interspersed with grain fragments. We infer that the fragments were formed from multiple splitting or crushing of compacted grains in the band of high compressive stress concentration developed along the \\sigmah springline. SEM images away from the breakout tip surroundings showed no such fragments. SEM study of the natural compaction band showed a similar arrangement of mainly intact grains surrounded by grain fragments. Using the Optimas optical software package, we found the percentage of pore area within the band ahead of the breakout tips to average 17%; outside of this zone it was 23%. In the natural compaction band pore area occupied 8.5% of the band; in the host rock adjacent to the compaction band it averaged 19%. These readings strongly suggest porosity reduction due to compaction in both cases. The close resemblance between the

  20. Contributions of biosurfactants to natural or induced bioremediation.

    PubMed

    Lawniczak, Lukasz; Marecik, Roman; Chrzanowski, Lukasz

    2013-03-01

    The number of studies dedicated to evaluating the influence of biosurfactants on bioremediation efficiency is constantly growing. Although significant progress regarding the explanation of mechanisms behind biosurfactant-induced effects could be observed, there are still many factors which are not sufficiently elucidated. This corresponds to the fact that although positive influence of biosurfactants is often reported, there are also numerous cases where no or negative effect was observed. This review summarizes the recent finding in the field of biosurfactant-amended bioremediation, focusing mainly on a critical approach towards potential limitations and causes of failure while investigating the effects of biosurfactants on the efficiency of biodegradation and phytoextraction processes. It also provides a summary of successive steps, which should be taken into consideration when designing biosurfactant-related treatment processes.

  1. Induced and Natural Seismicity: Earthquake Hazards and Risks in Ohio:

    NASA Astrophysics Data System (ADS)

    Besana-Ostman, G. M.; Worstall, R.; Tomastik, T.; Simmers, R.

    2013-12-01

    To adapt with increasing need to regulate all operations related to both the Utica and Marcellus shale play within the state, ODNR had recently strengthen its regulatory capability through implementation of stricter permit requirements, additional human resources and improved infrastructure. These ODNR's efforts on seismic risk reduction related to induced seismicity led to stricter regulations and many infrastructure changes related particularly to Class II wells. Permit requirement changes and more seismic monitoring stations were implemented together with additional injection data reporting from selected Class II well operators. Considering the possible risks related to seismic events in a region with relatively low seismicity, correlation between limited seismic data and injection volume information were undertaken. Interestingly, initial results showed some indications of both plugging and fracturing episodes. The real-time data transmission from seismic stations and availability of injection volume data enabled ODNR to interact with operators and manage wells dynamically. Furthermore, initial geomorphic and structural analyses indicated possible active faults in the northern and western portion of the state oriented NE-SW. The newly-mapped structures imply possible relatively bigger earthquakes in the region and consequently higher seismic risks. With the above-mentioned recent changes, ODNR have made critical improvement of its principal regulatory role in the state for oil and gas operations but also an important contribution to the state's seismic risk reduction endeavors. Close collaboration with other government agencies and the public, and working together with the well operators enhanced ODNR's capability to build a safety culture and achieve further public and industry participation towards a safer environment. Keywords: Induced seismicity, injection wells, seismic risks

  2. Thermal annealing-induced electric dipole relaxation in natural alexandrite

    NASA Astrophysics Data System (ADS)

    Scalvi, Rosa M. Fernandes; Li, Maximo Siu; Scalvi, Luis V. A.

    2005-02-01

    Electrical properties of natural alexandrite (BeAl2O4:Cr3+) are investigated by the thermally stimulated depolarization current (TSDC) technique. Samples are submitted to consecutive annealing processes and TSDC is carried out after each annealing, yielding bands with different parameters. These bands are fitted by a continuous distribution of relaxation parameters: activation energy and pre-exponential factor of the Arrhenius equation. It has been observed that annealing influences the dipole relaxation behavior, since it promotes a modification of Fe3+ and Cr3+ impurity distributions on sites of distinct symmetry: Al1 and Al2. In order to have a reference for comparison, TSDC is also carried out on a synthetic alexandrite sample, where the only impurity present is Cr3+ ion.

  3. Natural heme oxygenase-1 inducers in hepatobiliary function

    PubMed Central

    Volti, Giovanni Li; Sacerdoti, David; Giacomo, Claudia Di; Barcellona, Maria Luisa; Scacco, Antonio; Murabito, Paolo; Biondi, Antonio; Basile, Francesco; Gazzolo, Diego; Abella, Raul; Frigiola, Alessandro; Galvano, Fabio

    2008-01-01

    Many physiological effects of natural antioxidants, their extracts or their major active components, have been reported in recent decades. Most of these compounds are characterized by a phenolic structure, similar to that of α-tocopherol, and present antioxidant properties that have been demonstrated both in vitro and in vivo. Polyphenols may increase the capacity of endogenous antioxidant defences and modulate the cellular redox state. Changes in the cellular redox state may have wide-ranging consequences for cellular growth and differentiation. The majority of in vitro and in vivo studies conducted so far have attributed the protective effect of bioactive polyphenols to their chemical reactivity toward free radicals and their capacity to prevent the oxidation of important intracellular components. However, in recent years a possible novel aspect in the mode of action of these compounds has been suggested; that is, the ultimate stimulation of the heme oxygenase-1 (HO-1) pathway is likely to account for the established and powerful antioxidant/anti-inflammatory properties of these polyphenols. The products of the HO-catalyzed reaction, particularly carbon monoxide (CO) and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression by means of natural compounds contributes to protection against liver damage in various experimental models. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against various stressors in several pathological conditions. PMID:18985801

  4. On natural metamorphosis inducers of the cnidarians Hydractinia echinata (Hydrozoa) and Aurelia aurita (Scyphozoa)

    NASA Astrophysics Data System (ADS)

    Kroiher, M.; Berking, S.

    1999-11-01

    Hydractinia echinata and Aurelia aurita produce motile larvae which undergo metamorphosis to sessile polyps when induced by external cues. The polyps are found at restricted sites, A. aurita predominantly on rocks close to the shore, H. echinata on shells inhabited by hermit crabs. It has been argued that the differential distribution of the polyps in their natural environment largely reflects the distribution of the natural metamorphosis-inducing cues. In the case of H. echinata, bacteria of the genus Alteromonas were argued to meet these conditions. We found that almost all substrates collected in the littoral to induce metamorphosis in H. echinata, and several bacterial strains isolated from the sea, including the common E. coli, induce metamorphosis efficiently. In A. aurita metamorphosis may be induced by the water-air interface, whereby metamorphosis precedes (final) settlement.

  5. Nature of Pressure-induced Insulating States in Simple Metals

    NASA Astrophysics Data System (ADS)

    Naumov, Ivan; Hemley, Russell

    As experimentally established, all the alkali metals and heavy alkaline earth metals (Ca, Sr and Ba) become progressively less conductive on compression, at least up to some critical limit over a broad pressure range. Of these metals, Li and Na clearly undergo pressure-induced metal-insulator transitions, which may also be called reverse Mott transitions. Here, using group theory arguments and first-principles calculations, we show that such transitions can be understood in terms of band representations introduced by Zak. The valence bands in the insulating states are described by simple and composite band representations constructed from localized Wannier functions centered on points unoccupied by atoms. The character of the Wannier functions is closely related to the degree of s-p(-d) hybridization and reflects multi-center chemical bonding in these insulating states. The conditions under which an insulating state is allowed for structures having an integer number of atoms per primitive unit cell as well as re-entrant (i.e., metal-insulator-metal) transition sequences are detailed, resulting in predictions of semimetallic phases with flat surface states. The general principles developed are tested and applied to the alkali and alkaline earth metals, including elements where high-pressure insulating phases have been identified or reported (e.g., Li, Na, and Ca). This research was supported by EFree, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under Award DESC0001057.

  6. Local nature of impurity induced spin-orbit torques

    NASA Astrophysics Data System (ADS)

    Nikolaev, Sergey; Kalitsov, Alan; Chshiev, Mairbec; Mryasov, Oleg

    Spin-orbit torques are of a great interest due to their potential applications for spin electronics. Generally, it originates from strong spin orbit coupling of heavy 4d/5d elements and its mechanism is usually attributed either to the Spin Hall effect or Rashba spin-orbit coupling. We have developed a quantum-mechanical approach based on the non-equilibrium Green's function formalism and tight binding Hamiltonian model to study spin-orbit torques and extended our theory for the case of extrinsic spin-orbit coupling induced by impurities. For the sake of simplicity, we consider a magnetic material on a two dimensional lattice with a single non-magnetic impurity. However, our model can be easily extended for three dimensional layered heterostructures. Based on our calculations, we present the detailed analysis of the origin of local spin-orbit torques and persistent charge currents around the impurity, that give rise to spin-orbit torques even in equilibrium and explain the existence of anisotropy.

  7. The stochastic nature of growth of laser-induced damage

    NASA Astrophysics Data System (ADS)

    Carr, C. W.; Cross, David A.; Liao, Zhi M.; Norton, Mary A.; Negres, Raluca A.

    2015-07-01

    Laser fluence and operational tempo of ICF systems operating in the UV are typically limited by the growth of laser- induced damage on their final optics (primarily silica optics). In the early 2000 time frame, studies of laser damage growth with relevant large area beams revealed that for some laser conditions damage sites located on the exit surface of a fused silica optic grew following an exponential growth rule: D(n) = D0 exp (n α(φ)), where D is final site diameter, D0 is the initial diameter of the site, φ is the laser fluence, α(φ) is the growth coefficient, and n is the number of exposures. In general α is a linear function of φ, with a threshold of φTH. In recent years, it has been found that that growth behavior is actually considerably more complex. For example, it was found that α is not a constant for a given fluence but follows a probability distribution with a mean equal to α(φ). This is complicated by observations that these distributions are actually functions of the pulse shape, damage site size, and initial morphology of damage initiation. In addition, there is not a fixed fluence threshold for damage sites growth, which is better described by a probability of growth which depends on site size, morphology and laser fluence. Here will review these findings and discuss implications for the operation of large laser systems.

  8. Natural and induced B-1 cell immunity to infections raises questions of nature versus nurture.

    PubMed

    Baumgarth, Nicole; Waffarn, Elizabeth E; Nguyen, Trang T T

    2015-12-01

    Mouse B-1 cells are not only major producers of steady-state natural antibodies but also rapid responders to infections and inflammation. These discrete functions may be the outcomes of distinct environmental or developmental triggers that drive B-1 cells toward IgM production or an effector cell fate. Alternatively, distinct B-1 cell subsets may exist, which differ in their functional plasticity. In this paper, we summarize existing data suggesting that B-1 cells form a heterogeneous group of cells with distinct developmental requirements and nonoverlapping functions. Most spleen B-1 cells differ in development from that of bone marrow and peritoneal cavity B-1 cells, in that they develop in the absence of natural IgM. Functional heterogeneity is revealed by findings that B-1 cells in the bone marrow and spleen, but not the peritoneal cavity, generate natural serum IgM, while the latter are rapid responders to inflammatory and infectious insults, resulting in their relocation to secondary lymphoid tissues. A clearer understanding of the developmental and functional differences within the B-1 cell pool may reveal how they might be harnessed for prophylaxis or therapy. PMID:26060895

  9. Natural and induced B-1 cell immunity to infections raises questions of nature versus nurture.

    PubMed

    Baumgarth, Nicole; Waffarn, Elizabeth E; Nguyen, Trang T T

    2015-12-01

    Mouse B-1 cells are not only major producers of steady-state natural antibodies but also rapid responders to infections and inflammation. These discrete functions may be the outcomes of distinct environmental or developmental triggers that drive B-1 cells toward IgM production or an effector cell fate. Alternatively, distinct B-1 cell subsets may exist, which differ in their functional plasticity. In this paper, we summarize existing data suggesting that B-1 cells form a heterogeneous group of cells with distinct developmental requirements and nonoverlapping functions. Most spleen B-1 cells differ in development from that of bone marrow and peritoneal cavity B-1 cells, in that they develop in the absence of natural IgM. Functional heterogeneity is revealed by findings that B-1 cells in the bone marrow and spleen, but not the peritoneal cavity, generate natural serum IgM, while the latter are rapid responders to inflammatory and infectious insults, resulting in their relocation to secondary lymphoid tissues. A clearer understanding of the developmental and functional differences within the B-1 cell pool may reveal how they might be harnessed for prophylaxis or therapy.

  10. Dusty plasma cavities: Probe-induced and natural.

    PubMed

    Harris, B J; Matthews, L S; Hyde, T W

    2015-06-01

    A comprehensive exploration of regional dust evacuation in complex plasma crystals is presented. Voids created in three-dimensional crystals on the International Space Station have provided a rich foundation for experiments, but cavities in dust crystals formed in ground-based experiments have not received as much attention. Inside a modified Gaseous Electronics Conference rf cell, a powered vertical probe was used to clear the central area of a dust crystal, producing a cavity with high cylindrical symmetry. Cavities generated by three mechanisms are examined. First, repulsion of micrometer-sized particles by a negatively charged probe is investigated. A model of this effect developed for a dc plasma is modified and applied to explain experimental data in rf plasma. Second, the formation of natural cavities is surveyed; a radial ion drag proposed to occur due to a curved sheath is considered in conjunction with thermophoresis and a flattened confinement potential above the center of the electrode. Finally, cavity formation upon increasing the probe potential above the plasma floating potential is justified by a combination of ion drag and sheath edge modification. The cavities produced by these methods appear similar, but each is shown to be facilitated by fundamentally different processes.

  11. Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana

    PubMed Central

    Barrera, Patricia; Sülsen, Valeria P.; Lozano, Esteban; Rivera, Mónica; Beer, María Florencia; Tonn, Carlos; Martino, Virginia S.; Sosa, Miguel A.

    2013-01-01

    Leishmaniasis is a worldwide parasitic disease, caused by monoflagellate parasites of the genus Leishmania. In the search for more effective agents against these parasites, the identification of molecular targets has been attempted to ensure the efficiency of drugs and to avoid collateral damages on the host's cells. In this work, we have investigated some of the mechanisms of action of a group of natural sesquiterpene lactones that are effective against Leishmania mexicana mexicana promastigotes. We first observed that the antiproliferative effect of mexicanin I (Mxc), dehydroleucodine (DhL), psilostachyin (Psi), and, at lesser extent, psilostachyin C (Psi C) is blocked by 1.5 mM reduced glutathione. The reducing agent was also able to reverse the early effect of the compounds, suggesting that lactones may react with intracellular sulfhydryl groups. Moreover, we have shown that all the sesquiterpene lactones, except Psi C, significantly decreased the endogenous concentration of glutathione within the parasite. Consistent with these findings, the active sesquiterpene lactones increased between 2.7 and 5.4 times the generation of ROS by parasites. These results indicate that the induction of oxidative stress is at least one of the mechanisms of action of DhL, Mxc, and Psi on parasites while Psi C would act by another mechanism. PMID:23861697

  12. Rainfall Induced Natural Disaster in Central America, a challenge for Regional Risk Management

    NASA Astrophysics Data System (ADS)

    Estuardo Guinea Barrientos, Héctor; Swain, Ashok

    2013-04-01

    Rainfall induced natural disasters rank first among all natural disasters in Central America. According to the records of the EM-DAT international database, 248 out of 486 disasters registered in Central America were disasters triggered by rainfall invents, in countries like Belize and Honduras, rainfall-induced natural disasters, mainly floods and landslides, account for more than 90% of the total number of casualties as well as the economic damage of all the disasters. Due to the natural conditions of the Central American Isthmus, precipitation events often struck more than one country at the time, for example Hurricane Mitch in 1998 affected the entire Central American region causing more than 18,000 casualties. In this context, the Central America countries have been working on joint programs and policies aiming transboundary cooperation and management of natural disasters, a clear example of this effort is CEPREDENAC which is the intergovernmental body with the mandate of promoting activities, projects and programs towards reduction of the risks to disasters in order to avoid loss of life and economic assets in the Central America, however, transnational management face several challenges that fall mostly in the political, economical and technical areas. In this paper we described and analyzed the rainfall induced natural disasters, their impacts and the inherent management challenges in the Central American context. Key words: Central America, Natural Disasters, Risk Management, International Cooperation

  13. Natural cell-mediated cytotoxicity against Candida albicans induced by cyclophosphamide: nature of the in vitro cytotoxic effector.

    PubMed Central

    Baccarini, M; Bistoni, F; Puccetti, P; Garaci, E

    1983-01-01

    We have recently reported the in vivo modulation of resistance to experimental Candida albicans infection by cyclophosphamide (150 mg/kg intraperitoneally) in mice and have shown that increased resistance to the microbial challenge occurs 12 to 21 days after treatment with the drug (Bistoni et al., Infect. Immun. 40: 46-55, 1983). The event is accompanied by the appearance of a highly candidacidal cell population in the spleen and the activation of a subpopulation of natural cytotoxic effectors reactive in vitro against YAC-1 tumor cells. We now provide evidence that these anti-YAC-1 cytotoxic effectors are clearly distinct from the cyclophosphamide-induced candidacidal effectors, which seem to belong to a macrophage-monocyte lineage. The enhanced cytotoxic activity induced by cyclophosphamide was not restricted to C. albicans but was also exerted against a panel of Candida strains. PMID:6352489

  14. Numbers and proportions of leukemias in young people and adults induced by radiation of natural origin

    PubMed Central

    Kendall, Gerald; Little, Mark; Wakeford, Richard

    2014-01-01

    Natural sources contribute a large fraction of the radiation exposure of the general public. Under the linear no-threshold hypothesis risk decreases in proportion to decreasing dose without a threshold. We use recent estimates of doses to the red bone marrow to calculate the number and proportion of cases of leukemia in England induced by natural radiation. We calculate that 5–6% of cases of leukemia, excluding chronic lymphocytic leukemia, up to age 80 years are induced by this background radiation. In young people up to the age of 25 years the attributable fraction is 12–18%, substantially lower than a previous estimate. PMID:21334745

  15. Bistability of the naturally induced lactose utilization system of Escherichia coli

    NASA Astrophysics Data System (ADS)

    Stajic, Jelena; Wall, Michael

    2006-03-01

    In the absence of the preferred sugar glucose, lactose utilization machinery in the bacterium E. coli is activated. The genetic circuit responsible for this response, lac operon, has been observed to exhibit bistability when induced by an artificial inducer, TMG. Here we investigate conditions under which bistability might be observed in response to lactose. The aim of our study is to establish whether the natural system exhibits bistability, as is often assumed despite the lack of experimental support.

  16. Collision-Induced Dissociation Mass Spectrometry: A Powerful Tool for Natural Product Structure Elucidation.

    PubMed

    Johnson, Andrew R; Carlson, Erin E

    2015-11-01

    Mass spectrometry is a powerful tool in natural product structure elucidation, but our ability to directly correlate fragmentation spectra to these structures lags far behind similar efforts in peptide sequencing and proteomics. Often, manual data interpretation is required and our knowledge of the expected fragmentation patterns for many scaffolds is limited, further complicating analysis. Here, we summarize advances in natural product structure elucidation based upon the application of collision induced dissociation fragmentation mechanisms.

  17. Dendritic Cells in the Periphery Control Antigen-Specific Natural and Induced Regulatory T Cells

    PubMed Central

    Yamazaki, Sayuri; Morita, Akimichi

    2013-01-01

    Dendritic cells (DCs) are specialized antigen-presenting cells that regulate both immunity and tolerance. DCs in the periphery play a key role in expanding naturally occurring Foxp3+ CD25+ CD4+ regulatory T cells (Natural T-regs) and inducing Foxp3 expression (Induced T-regs) in Foxp3− CD4+ T cells. DCs are phenotypically and functionally heterogeneous, and further classified into several subsets depending on distinct marker expression and their location. Recent findings indicate the presence of specialized DC subsets that act to expand Natural T-regs or induce Foxp3+ T-regs from Foxp3− CD4+ T cells. For example, two major subsets of DCs in lymphoid organs act differentially in inducing Foxp3+ T-regs from Foxp3− cells or expanding Natural T-regs with model-antigen delivery by anti-DC subset monoclonal antibodies in vivo. Furthermore, DCs expressing CD103 in the intestine induce Foxp3+ T-regs from Foxp3− CD4+ T cells with endogenous TGF-β and retinoic acid. In addition, antigen-presenting DCs have a capacity to generate Foxp3+ T-regs in the oral cavity where many antigens and commensals exist, similar to intestine and skin. In skin and skin-draining lymph nodes, at least six DC subsets have been identified, suggesting a complex DC-T-reg network. Here, we will review the specific activity of DCs in expanding Natural T-regs and inducing Foxp3+ T-regs from Foxp3− precursors, and further discuss the critical function of DCs in maintaining tolerance at various locations including skin and oral cavity. PMID:23801989

  18. Carbamate pesticide-induced apoptosis and necrosis in human natural killer cells.

    PubMed

    Li, Q; Kobayashi, M; Kawada, T

    2014-01-01

    We previously found that ziram, a carbamate fungicide, significantly induced apoptosis and necrosis in human NK-92MI, a natural killer cell line. To investigate whether other carbamate pesticides also induce apoptosis and necrosis in human natural killer cell, we conducted further experiments with NK-92CI, a human natural killer cell line using a more sensitive assay. NK-92CI cells were treated with ziram, thiram, maneb or carbaryl at 0.031-40 microM for 2-24 h in the present study. Apoptosis and necrosis were determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspases 3 and mitochondrial cytochrome-c release were determined by flow cytometry. We found that ziram and thiram also induced apoptosis and necrosis in a time- and dose-dependent manner; however, maneb and carbaryl induced apoptosis and necrosis only at higher doses in NK-92CI cells. The strength of the apoptosis-inducing effect differed among the pesticides, and the order was as follows: thiram > ziram greater than maneb greater than carbaryl. NK-92CI was more sensitive to ziram than NK-92MI. Moreover, ziram and thiram significantly increased the intracellular level of active caspase 3 in NK-92CI and caspase inhibitor significantly inhibited the apoptosis. Ziram and thiram significantly caused mitochondrial cytochrome-c release in NK-92CI. These findings indicate that carbamate pesticides can induce apoptosis in natural killer cells, and the apoptosis is mediated by both the caspase-cascade and mitochondrial cytochrome-c pathways.

  19. Meiotic chromosome pairing behaviour of natural tetraploids and induced autotetraploids of Actinidia chinensis.

    PubMed

    Wu, Jin-Hu; Datson, Paul M; Manako, Kelvina I; Murray, Brian G

    2014-03-01

    Non-preferential chromosome pairing was identified in tetraploid Actinidia chinensis and a higher mean multivalent frequency in pollen mother cells was found in colchine-induced tetraploids of A. chinensis compared with naturally occurring tetraploids. Diploid and tetraploid Actinidia chinensis are used for the development of kiwifruit cultivars. Diploid germplasm can be exploited in a tetraploid breeding programme via unreduced (2n) gametes and chemical-induced chromosome doubling of diploid cultivars and selections. Meiotic chromosome behaviour in diploid A. chinensis 'Hort16A' and colchicine-induced tetraploids from 'Hort16A' was analysed and compared with that in a diploid male and tetraploid males of A. chinensis raised from seeds sourced from the wild in China. Both naturally occurring and induced tetraploids formed multivalents, but colchicine-induced tetraploids showed a higher mean multivalent frequency in the pollen mother cells. Lagging chromosomes at anaphase I and II were observed at low frequencies in the colchicine-induced tetraploids. To investigate whether preferential or non-preferential chromosome pairing occurs in tetraploid A. chinensis, the inheritance of microsatellite alleles was analysed in the tetraploid progeny of crosses between A. chinensis (4x) and A. arguta (4x). The frequencies of inherited microsatellite allelic combinations in the hybrids suggested that non-preferential chromosome pairing had occurred in the tetraploid A. chinensis parent. PMID:24306317

  20. Discriminating induced seismicity from natural earthquakes using moment tensors and source spectra

    NASA Astrophysics Data System (ADS)

    Zhang, Hongliang; Eaton, David W.; Li, Ge; Liu, Yajing; Harrington, Rebecca M.

    2016-02-01

    Earthquake source mechanisms and spectra can provide important clues to aid in discriminating between natural and induced events. In this study, we calculate moment tensors and stress drop values for eight recent induced earthquakes in the Western Canadian Sedimentary Basin with magnitudes between 3.2 and 4.4, as well as a nearby magnitude 5.3 event that is interpreted as a natural earthquake. We calculate full moment tensor solutions by performing a waveform-fitting procedure based on a 1-D transversely isotropic velocity model. In addition to a dominant double-couple (DC) signature that is common to nearly all events, most induced events exhibit significant non-double-couple components. A parameter sensitivity analysis indicates that spurious non-DC components are negligible if the signal to noise ratio (SNR) exceeds 10 and if the 1-D model differs from the true velocity structure by less than 5%. Estimated focal depths of induced events are significantly shallower than the typical range of focal depths for intraplate earthquakes in the Canadian Shield. Stress drops of the eight induced events were estimated using a generalized spectral-fitting method and fall within the typical range of 2 to 90 MPa for tectonic earthquakes. Elastic moduli changes due to the brittle damage production at the source, presence of multiple intersecting fractures, dilatant jogs created at the overlapping areas of multiple fractures, or non-planar pre-existing faults may explain the non-DC components for induced events.

  1. Natural or Induced: Identifying Natural and Induced Swarms from Pre-production and Co-production Microseismic Catalogs at the Coso Geothermal Field

    USGS Publications Warehouse

    Schoenball, Martin; Kaven, Joern; Glen, Jonathan M. G.; Davatzes, Nicholas C.

    2015-01-01

    Increased levels of seismicity coinciding with injection of reservoir fluids have prompted interest in methods to distinguish induced from natural seismicity. Discrimination between induced and natural seismicity is especially difficult in areas that have high levels of natural seismicity, such as the geothermal fields at the Salton Sea and Coso, both in California. Both areas show swarm-like sequences that could be related to natural, deep fluid migration as part of the natural hydrothermal system. Therefore, swarms often have spatio-temporal patterns that resemble fluid-induced seismicity, and might possibly share other characteristics. The Coso Geothermal Field and its surroundings is one of the most seismically active areas in California with a large proportion of its activity occurring as seismic swarms. Here we analyze clustered seismicity in and surrounding the currently produced reservoir comparatively for pre-production and co-production periods. We perform a cluster analysis, based on the inter-event distance in a space-time-energy domain to identify notable earthquake sequences. For each event j, the closest previous event i is identified and their relationship categorized. If this nearest neighbor’s distance is below a threshold based on the local minimum of the bimodal distribution of nearest neighbor distances, then the event j is included in the cluster as a child to this parent event i. If it is above the threshold, event j begins a new cluster. This process identifies subsets of events whose nearest neighbor distances and relative timing qualify as a cluster as well as a characterizing the parent-child relationships among events in the cluster. We apply this method to three different catalogs: (1) a two-year microseismic survey of the Coso geothermal area that was acquired before exploration drilling in the area began; (2) the HYS_catalog_2013 that contains 52,000 double-difference relocated events and covers the years 1981 to 2013; and (3) a

  2. Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

    PubMed Central

    Mohd Sairazi, Nur Shafika; Sirajudeen, K. N. S.; Asari, Mohd Asnizam; Muzaimi, Mustapha; Mummedy, Swamy; Sulaiman, Siti Amrah

    2015-01-01

    Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration. PMID:26793262

  3. Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts.

    PubMed

    Mohd Sairazi, Nur Shafika; Sirajudeen, K N S; Asari, Mohd Asnizam; Muzaimi, Mustapha; Mummedy, Swamy; Sulaiman, Siti Amrah

    2015-01-01

    Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.

  4. Velocity scaling of cue-induced smooth pursuit acceleration obeys constraints of natural motion.

    PubMed

    Ladda, Jennifer; Eggert, Thomas; Glasauer, Stefan; Straube, Andreas

    2007-09-01

    Information about the future trajectory of a visual target is contained not only in the history of target motion but also in static visual cues, e.g., the street provides information about the car's future trajectory. For most natural moving targets, this information imposes strong constraints on the relation between velocity and acceleration which can be exploited by predictive smooth pursuit mechanisms. We questioned how cue-induced predictive changes in pursuit direction depend on target speed and how cue- and target-induced pursuit interact. Subjects pursued a target entering a +/-90 degrees curve and moving on either a homogeneous background or on a low contrast static band indicating the future trajectory. The cue induced a predictive change of pursuit direction, which occurred before curve onset of the target. The predictive velocity component orthogonal to the initial pursuit direction started later and became faster with increasing target velocity. The predictive eye acceleration increased quadratically with target velocity and was independent of the initial target direction. After curve onset, cue- and target-induced pursuit velocity components were not linearly superimposed. The quadratic increase of eye acceleration with target velocity is consistent with the natural velocity scaling implied by the two-thirds power law, which is a characteristic of biological controlled movements. Comparison with linear pursuit models reveals that the ratio between eye acceleration and actual or expected retinal slip cannot be considered a constant gain factor. To obey a natural velocity scaling, this acceleration gain must linearly increase with target or pursuit velocity. We suggest that gain control mechanisms, which affect target-induced changes of pursuit velocity, act similarly on predictive changes of pursuit induced by static visual cues.

  5. Cardioactive and vasoactive effects of natural wild honey against cardiac malperformance induced by hyperadrenergic activity.

    PubMed

    Rakha, Miran K; Nabil, Zohour I; Hussein, Aida A

    2008-03-01

    Induction of hyperadrenergic activity was experimentally achieved in urethane-anesthetized rats using epinephrine (adrenaline). Acute administration of epinephrine (100 microg/kg) for 2 hours induced several cardiac disorders and vasomotor dysfunction. Pretreatment with natural wild honey (5 g/kg) for 1 hour prior to the injection with epinephrine (100 mug/kg) protected the anesthetized normal rats from the incidence of epinephrine-induced cardiac disorders and vasomotor dysfunction. Moreover, posttreatment with natural wild honey (5 g/kg) following the injection with epinephrine (100 microg/kg) for 1 hour showed several ameliorative outcomes to the electrocardiographic parameters and vasomotor dysfunction of anesthetized stressed rats. Furthermore, natural wild honey preserved the positive inotropic effect of epinephrine in both cases. Also, the total antioxidant capacity (AOC) of natural wild honey was found to be very pronounced. Levels of both reduced glutathione and ascorbic acid (vitamin C) were considered relatively high in natural wild honey. Activity of superoxide dismutase (SOD) was also high, whereas catalase activity was relatively low, especially when compared to the value of SOD activity. It would appear from the results of the present study that natural wild honey may exert its cardioprotective and therapeutic effects against epinephrine-induced cardiac disorders and vasomotor dysfunction directly, via its very pronounced total AOC and its great wealth of both enzymatic and nonenzymatic antioxidants involved in cardiovascular defense mechanisms, besides its substantial quantities of mineral elements such as magnesium, sodium, and chlorine, and/or indirectly, via the enhancement of the endothelium-derived relaxing factor nitric oxide release through the influence of ascorbic acid (vitamin C).

  6. Natural sunlight NO(3)(-)/NO(2)(-)-induced photo-degradation of phenylurea herbicides in water.

    PubMed

    Shankar, M V; Nélieu, S; Kerhoas, L; Einhorn, J

    2008-04-01

    The nitrate-induced photodegradation of phenylureas in water was demonstrated to occur efficiently using natural sunlight irradiation. The kinetics of disappearance was found to be dependent on the inducer and substrate concentrations, the phenylurea structure and the origin and composition of the aqueous matrix including the presence of nitrite. The measured effects under sunlight were of the same order of those measured previously in the lab using our solar light simulated system. However, by-product distribution might differ substantially particularly considering the nitration pathway. PMID:18262593

  7. Connecting model species to nature: predator-induced long-term sensitization in Aplysia californica.

    PubMed

    Mason, Maria J; Watkins, Amanda J; Wakabayashi, Jordann; Buechler, Jennifer; Pepino, Christine; Brown, Michelle; Wright, William G

    2014-08-01

    Previous research on sensitization in Aplysia was based entirely on unnatural noxious stimuli, usually electric shock, until our laboratory found that a natural noxious stimulus, a single sublethal lobster attack, causes short-term sensitization. We here extend that finding by demonstrating that multiple lobster attacks induce long-term sensitization (≥24 h) as well as similar, although not identical, neuronal correlates as observed after electric shock. Together these findings establish long- and short-term sensitization caused by sublethal predator attack as a natural equivalent to sensitization caused by artificial stimuli. PMID:25028394

  8. Estrus behavior and fecal steroid profiles in the Asiatic lion (Panthera leo persica) during natural and gonadotropin-induced estrus.

    PubMed

    Umapathy, Govindhaswamy; Sontakke, Sadanand D; Srinivasu, K; Kiran, Thomas; Kholkute, S D; Shivaji, S

    2007-10-01

    In this paper the behavior of the Asiatic lion was studied during natural and gonadotropin-induced estrus in relation to fecal estradiol and progesterone concentration. The average length of estrus was 5.4 days and no significant difference was observed between natural and gonadotropin-induced estrus. Vocalization and rolling were the major estrus behavioral activities of Asiatic lions and the frequency of these activities were similar in both natural and gonadotropin-induced estrus and treatment with exogenous gonadotropin did not alter estrus behavioral activities. A significant positive correlation was observed between fecal estradiol and frequency of estrus behavior during natural and gonadotropin-induced estrus. Following gonadotropin treatment estrus could be induced in 69% of animals and these induced animals ovulated following hCG treatment. This study reports for the first time the successful use of the non-invasive fecal steroid assay for monitoring the induction of estrus and ovulation in the Asiatic lion.

  9. Phenolic profile of Asturian (Spain) natural cider.

    PubMed

    Rodríguez Madrera, Roberto; Picinelli Lobo, Anna; Suárez Valles, Belén

    2006-01-11

    The polyphenolic composition of natural ciders from the Asturian community (Spain), during 2 consecutive years, was analyzed by RP-HPLC and the photodiode-array detection system, without previous extraction (direct injection). A total of 16 phenolic compounds (catechol, tyrosol, protocatechuic acid, hydrocaffeic acid, chlorogenic acid, hydrocoumaric acid, ferulic acid, (-)-epicatechin, (+)-catechin, procyanidins B2 and B5, phloretin-2'-xyloglucoside, phloridzin, hyperin, avicularin, and quercitrin) were identified and quantified. A fourth quercetin derivative, one dihydrochalcone-related compound, two unknown procyanidins, three hydroxycinnamic derivatives, and two unknown compounds were also found. Among the low-molecular-mass polyphenols analyzed, hydrocaffeic acid was the most abundant compound, representing more than 80% of the total polyphenolic acids. Procyanidins were the most important family among the flavonoid compounds. Discriminant analysis was allowed to correctly classify more than 93% of the ciders, according to the harvest year; the most discriminant variables were an unknown procyanidin and quercitrin. PMID:16390187

  10. The antitumor natural compound falcarindiol promotes cancer cell death by inducing endoplasmic reticulum stress

    PubMed Central

    Jin, H R; Zhao, J; Zhang, Z; Liao, Y; Wang, C-Z; Huang, W-H; Li, S-P; He, T-C; Yuan, C-S; Du, W

    2012-01-01

    Falcarindiol (FAD) is a natural polyyne with various beneficial biological activities. We show here that FAD preferentially kills colon cancer cells but not normal colon epithelial cells. Furthermore, FAD inhibits tumor growth in a xenograft tumor model and exhibits strong synergistic killing of cancer cells with 5-fluorouracil, an approved cancer chemotherapeutic drug. We demonstrate that FAD-induced cell death is mediated by induction of endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). Decreasing the level of ER stress, either by overexpressing the ER chaperone protein glucose-regulated protein 78 (GRP78) or by knockout of components of the UPR pathway, reduces FAD-induced apoptosis. In contrast, increasing the level of ER stress by knocking down GRP78 potentiates FAD-induced apoptosis. Finally, FAD-induced ER stress and apoptosis is correlated with the accumulation of ubiquitinated proteins, suggesting that FAD functions at least in part by interfering with proteasome function, leading to the accumulation of unfolded protein and induction of ER stress. Consistent with this, inhibition of protein synthesis by cycloheximide significantly decreases the accumulation of ubiquitinated proteins and blocks FAD-induced ER stress and cell death. Taken together, our study shows that FAD is a potential new anticancer agent that exerts its activity through inducing ER stress and apoptosis. PMID:22914324

  11. Serum Albumin and Ca2+ Are Natural Competence Inducers in the Human Pathogen Acinetobacter baumannii.

    PubMed

    Traglia, German Matias; Quinn, Brettni; Schramm, Sareda T J; Soler-Bistue, Alfonso; Ramirez, Maria Soledad

    2016-08-01

    The increasing frequency of bacteria showing antimicrobial resistance (AMR) raises the menace of entering into a postantibiotic era. Horizontal gene transfer (HGT) is one of the prime reasons for AMR acquisition. Acinetobacter baumannii is a nosocomial pathogen with outstanding abilities to survive in the hospital environment and to acquire resistance determinants. Its capacity to incorporate exogenous DNA is a major source of AMR genes; however, few studies have addressed this subject. The transformation machinery as well as the factors that induce natural competence in A. baumannii are unknown. In this study, we demonstrate that naturally competent strain A118 increases its natural transformation frequency upon the addition of Ca(2+)or albumin. We show that comEA and pilQ are involved in this process since their expression levels are increased upon the addition of these compounds. An unspecific protein, like casein, does not reproduce this effect, showing that albumin's effect is specific. Our work describes the first specific inducers of natural competence in A. baumannii Overall, our results suggest that the main protein in blood enhances HGT in A. baumannii, contributing to the increase of AMR in this threatening human pathogen.

  12. Recent Advances in Remote Sensing of Natural Hazards-Induced Atmospheric and Ionospheric Perturbations

    NASA Astrophysics Data System (ADS)

    Yang, Y. M.; Komjathy, A.; Meng, X.; Verkhoglyadova, O. P.; Langley, R. B.; Mannucci, A. J.

    2015-12-01

    Traveling ionospheric disturbances (TIDs) induced by acoustic-gravity waves in the neutral atmosphere have significant impact on trans-ionospheric radio waves such as Global Navigation Satellite System (GNSS, including Global Position System (GPS)) measurements. Natural hazards and solid Earth events, such as earthquakes, tsunamis and volcanic eruptions are actual sources that may trigger acoustic and gravity waves resulting in traveling ionospheric disturbances (TIDs) in the upper atmosphere. Trans-ionospheric radio wave measurements sense the total electron content (TEC) along the signal propagation path. In this research, we introduce a novel GPS-based detection and estimation technique for remote sensing of atmospheric wave-induced TIDs including space weather phenomena induced by major natural hazard events, using TEC time series collected from worldwide ground-based dual-frequency GNSS (including GPS) receiver networks. We demonstrate the ability of using ground- and space-based dual-frequency GPS measurements to detect and monitor tsunami wave propagation from the 2011 Tohoku-Oki earthquake and tsunami. Major wave trains with different propagation speeds and wavelengths were identified through analysis of the GPS remote sensing observations. Dominant physical characteristics of atmospheric wave-induced TIDs are found to be associated with specific tsunami propagations and oceanic Rayleigh waves. In this research, we compared GPS-based observations, corresponding model simulations and tsunami wave propagation. Results are shown to lead to a better understanding of the tsunami-induced ionosphere responses. Based on current distribution of Plate Boundary Observatory GPS stations, the results indicate that tsunami-induced TIDs may be detected about 60 minutes prior to tsunamis arriving at the U.S. west coast. It is expected that this GNSS-based technology will become an integral part of future early-warning systems.

  13. The Nature of Emission from Optical Breakdown Induced by Pulses of fs and ns Duration

    SciTech Connect

    Carr, C W; Feit, M D; Rubenchik, A M; Demange, P; Kucheyev, S; Shirk, M D; Radousky, H B; Demos, S G

    2004-11-09

    Spectral emission from optical breakdown in the bulk of a transparent dielectric contains information about the nature of the breakdown medium. We have made time resolved measurements of the breakdown induced emission caused by nanosecond and femtosecond infrared laser pulses. We previously demonstrated that the emission due to ns pulses is blackbody in nature allowing determination of the fireball temperature and pressure during and after the damage event. The emission due to femtosecond pulse breakdown is not blackbody in nature; two different spectral distributions being noted. In one case, the peak spectral distribution occurs at the second harmonic of the incident radiation, in the other the distribution is broader and flatter and presumably due to continuum generation. The differences between ns and fs breakdown emission can be explained by the differing breakdown region geometries for the two pulse durations. The possibility to use spectral emission as a diagnostic of the emission region morphology will be discussed.

  14. Differentiating induced and natural seismicity using space-time-magnitude statistics applied to the Coso Geothermal field

    USGS Publications Warehouse

    Schoenball, Martin; Davatzes, Nicholas C.; Glen, Jonathan M. G.

    2015-01-01

    A remarkable characteristic of earthquakes is their clustering in time and space, displaying their self-similarity. It remains to be tested if natural and induced earthquakes share the same behavior. We study natural and induced earthquakes comparatively in the same tectonic setting at the Coso Geothermal Field. Covering the preproduction and coproduction periods from 1981 to 2013, we analyze interevent times, spatial dimension, and frequency-size distributions for natural and induced earthquakes. Individually, these distributions are statistically indistinguishable. Determining the distribution of nearest neighbor distances in a combined space-time-magnitude metric, lets us identify clear differences between both kinds of seismicity. Compared to natural earthquakes, induced earthquakes feature a larger population of background seismicity and nearest neighbors at large magnitude rescaled times and small magnitude rescaled distances. Local stress perturbations induced by field operations appear to be strong enough to drive local faults through several seismic cycles and reactivate them after time periods on the order of a year.

  15. Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

    PubMed

    Yu, Zu-Yin; Xiao, He; Wang, Li-Mei; Shen, Xing; Jing, Yu; Wang, Lin; Sun, Wen-Feng; Zhang, Yan-Feng; Cui, Yu; Shan, Ya-Jun; Zhou, Wen-Bing; Xing, Shuang; Xiong, Guo-Lin; Liu, Xiao-Lan; Dong, Bo; Feng, Jian-Nan; Wang, Li-Sheng; Luo, Qing-Liang; Zhao, Qin-Shi; Cong, Yu-Wen

    2016-05-01

    All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698-709. ©2016 AACR.

  16. Distinguishing induced seismicity from natural seismicity in Ohio: Demonstrating the utility of waveform template matching

    NASA Astrophysics Data System (ADS)

    Skoumal, Robert J.; Brudzinski, Michael R.; Currie, Brian S.

    2015-09-01

    This study investigated the utility of multistation waveform cross correlation to help discern induced seismicity. Template matching was applied to all Ohio earthquakes cataloged since the arrival of nearby EarthScope TA stations in late 2010. Earthquakes that were within 5 km of fluid injection activities in regions that lacked previously documented seismicity were found to be swarmy. Moreover, the larger number of events produced by template matching for these swarmy sequences made it easier to establish more detailed temporal and spatial relationships between the seismicity and fluid injection activities, which is typically required for an earthquake to be considered induced. Study results detected three previously documented induced sequences (Youngstown, Poland Township, and Harrison County) and provided evidence that suggests two additional cases of induced seismicity (Belmont/Guernsey County and Washington County). Evidence for these cases suggested that unusual swarm-like behaviors in regions that lack previously documented seismicity can be used to help distinguish induced seismicity, complementing the traditional identification of an anthropogenic source spatially and temporally correlated with the seismicity. In support of this finding, we identified 17 additional cataloged earthquakes in regions of previously documented seismicity and away from disposal wells or hydraulic fracturing that returned very few template matches. The lack of swarminess helps to indicate that these events are most likely naturally occurring.

  17. Analysis of the adverse reactions induced by natural product-derived drugs

    PubMed Central

    Zeng, Zhi-Ping; Jiang, Jian-Guo

    2010-01-01

    Compared with the therapeutic effects of established medicinal drugs, it is often considered that natural product-derived drugs are of a more benign nature in side-effects, which has made natural medicines become a popular form of therapy. Traditional Chinese medicine (TCM) is generally considered as being natural and harmless. TCM has been paid much more attention than before and widely used for the treatment nowadays. However, with the increasing cases of adverse drug reactions (ADRs), the ADRs induced by TCM are becoming more widely recognized. Some ADRs are sometimes even life-threatening. This article reviews literatures on ADRs induced by TCM which was published in the past 10 years. A total of 3122 cases including complete data are selected for the present analysis. From the data of the 3122 cases, statistics is carried out to the distribution of administration routes and time of the occurrence of ADRs, the prognosis of ADRs, sex and age factors, types and clinical symptoms of ADRs, and drugs involved in ADRs. In addition, occurrence and influencing factors of TCM-induced diseases are also analysed, which includes spices confusion, processing drugs improperly, toxic components, long-term medication, improper concerted application, interaction of TCM and Western medicine. It is concluded that the efficacy and toxicity of TCM, often using the compound prescription involving various plants and animals, resulted from a variety of chemical constituents, which lead to a comprehensive response in the human body. The ‘toxicity’ of TCM should be correctly recognized and reasonably utilized. PMID:20233209

  18. Nitrate-induced photolysis in natural waters: Controls on concentrations of hydroxyl radical photo-intermediates by natural scavenging agents

    SciTech Connect

    Brezonik, P.L.; Fulkerson-Brekken, J.

    1998-10-01

    The importance of the principal natural scavenging agents for hydroxyl radicals ({sup {sm_bullet}}OH) was evaluated, and a general framework was developed to predict the significance of nitrate-induced, {sup {sm_bullet}}OH-mediated degradation of aquatic contaminants. Rate constants for *OH scavenging by dissolved organic matter (DOM) from five surface water sources were in a narrow range which is similar to previously reported values and suggests that the importance of DOM as a {sup {sm_bullet}}OH sink can be estimated simply from the dissolved organic carbon (DOC) concentration of a water. Scavenging of {sup {sm_bullet}}*OH by carbonate and bicarbonate is generally less important, but these ions can be the major cause of *OH scavenging in low DOC, high alkalinity waters. Use of the framework is illustrated by predicting levels of {sup {sm_bullet}}OH and half-lives of the corn herbicide acetochlor in waters ranging from pristine to highly influenced by agricultural activities.

  19. Numerical and experimental investigation of natural flow-induced vibrations of flexible hydrofoils

    NASA Astrophysics Data System (ADS)

    Chae, Eun Jung; Akcabay, Deniz Tolga; Lelong, Alexandra; Astolfi, Jacques Andre; Young, Yin Lu

    2016-07-01

    The objective of this work is to present combined numerical and experimental studies of natural flow-induced vibrations of flexible hydrofoils. The focus is on identifying the dependence of the foil's vibration frequencies and damping characteristics on the inflow velocity, angle of attack, and solid-to-fluid added mass ratio. Experimental results are shown for a cantilevered polyacetate (POM) hydrofoil tested in the cavitation tunnel at the French Naval Academy Research Institute (IRENav). The foil is observed to primarily behave as a chordwise rigid body and undergoes spanwise bending and twisting deformations, and the flow is observed to be effectively two-dimensional (2D) because of the strong lift retention at the free tip caused by a small gap with a thickness less than the wall boundary layer. Hence, the viscous fluid-structure interaction (FSI) model is formulated by coupling a 2D unsteady Reynolds-averaged Navier-Stokes (URANS) model with a two degree-of-freedom (2-DOF) model representing the spanwise tip bending and twisting deformations. Good agreements were observed between viscous FSI predictions and experimental measurements of natural flow-induced vibrations in fully turbulent and attached flow conditions. The foil vibrations were found to be dominated by the natural frequencies in absence of large scale vortex shedding due to flow separation. The natural frequencies and fluid damping coefficients were found to vary with velocity, angle of attack, and solid-to-fluid added mass ratio. In addition, the numerical results showed that the in-water to in-air natural frequency ratios decreased rapidly, and the fluid damping coefficients increased rapidly, as the solid-to-fluid added mass ratio decreases. Uncoupled mode (UM) linear potential theory was found to significantly over-predict the fluid damping for cases of lightweight flexible hydrofoils, and this over-prediction increased with higher velocity and lower solid-to-fluid added mass ratio.

  20. Models of Drug-induced Liver Injury for Evaluation of Phytotherapeutics and Other Natural Products

    PubMed Central

    Jaeschke, Hartmut; Williams, C. David; McGill, Mitchell R.; Xie, Yuchao; Ramachandran, Anup

    2013-01-01

    Extracts from medicinal plants, many of which have been used for centuries, are increasingly tested in models of hepatotoxicity. One of the most popular models to evaluate the hepatoprotective potential of natural products is acetaminophen (APAP)-induced liver injury, although other hepatotoxicity models such as carbon tetrachloride, thioacetamide, ethanol and endotoxin are occasionally used. APAP overdose is a clinically relevant model of drug-induced liver injury. Critical mechanisms and signaling pathways, which trigger necrotic cell death and sterile inflammation, are discussed. Although there is increasing understanding of the pathophysiology of APAP-induced liver injury, the mechanism is complex and prone to misinterpretation, especially when unknown chemicals such as plant extracts are tested. This review discusses the fundamental aspects that need to be considered when using this model, such as selection of the animal species or in vitro system, timing and dose-responses of signaling events, metabolic activation and protein adduct formation, the role of lipid peroxidation and apoptotic versus necrotic cell death, and the impact of the ensuing sterile inflammatory response. The goal is to enable researchers to select the appropriate model and experimental conditions for testing of natural products that will yield clinically relevant results and allow valid interpretations of the pharmacological mechanisms. PMID:23353004

  1. Numerical modelling of production-induced seismicity in natural gas exploitation

    NASA Astrophysics Data System (ADS)

    Zbinden, Dominik; Rinaldi, Antonio Pio; Urpi, Luca; Wiemer, Stefan

    2016-04-01

    Observations at several sites show that the exploitation of natural gas can induce seismicity. Studies have indicated that the pressure drop in the gas reservoir caused by production may lead to compaction, affecting the stress field in the surrounding rock formations. This in turn can reactivate pre-existing faults, hence inducing earthquakes. Despite the moderate magnitude of these seismic events, they can often be felt at the surface due to their shallow hypocenters, posing the population at risk. A well-known example is Groningen in the Netherlands, where production-induced seismicity has caused damage to houses located near the gas field. Given the public significance, it is highly relevant to understand the geomechanical processes involved during natural gas production. This work investigates the geomechanical behaviour of pre-existing faults during gas production. We use a simple model with a permeable reservoir cut by a fault zone and surrounded by impermeable rock formations, preventing the gas from escaping toward shallow depths. The permeabilities are chosen to be stress-dependent allowing for hydro-mechanical coupling. Our aim is to study different parameters, such as production rate, fault permeability and other rock properties, and analyze their influence on the strength of the seismic event as well as the reactivation time of the fault measured from the onset of production.

  2. Inducing uniform single-crystal like orientation in natural rubber with constrained uniaxial stretch.

    PubMed

    Zhou, Weiming; Meng, Lingpu; Lu, Jie; Wang, Zhen; Zhang, Wenhua; Huang, Ningdong; Chen, Liang; Li, Liangbin

    2015-07-01

    The effect of flow on crystallization is commonly attributed to entropic reduction, which is caused by stretch and orientation of polymer chains but overlooks the role of flow on final-state free energy. With the aid of in situ synchrotron radiation wide-angle X-ray diffraction (WAXD) and a homemade constrained uniaxial tensile testing machine, polycrystals possessing single-crystal-like orientation rather than uniaxial orientation are found during the constrained stretch of natural rubber, whereas the c-axis and a-axis align in the stretch direction (SD) and constrained direction (CD), respectively. Molecular dynamics simulation shows that aligning the a-axis of crystal nuclei in CD leads to the lowest free energy increase and favors crystal nucleation. This indicates that the nomenclature of strain-induced crystallization may not fully account for the nature of flow-induced crystallization (FIC) as strain mainly emphasizes the entropic reduction of initial melt, whereas stress rather than strain plays the dominant role in crystal deformation. The current work not only contributes to a comprehensive understanding of the mechanism of flow-induced crystallization but also demonstrates the potential application of constrained uniaxial tensile stretch for the creation of functional materials containing polycrystals that possess single-crystal-like orientation.

  3. The collapse of the Maya: Effects of natural and human-induced drought

    SciTech Connect

    Oglesby, Robert J; Erickson III, David J

    2010-02-01

    The collapse of the Maya civilization during the ninth century A.D. is a major conundrum in the history of mankind. This civilization reached a spectacular peak but then almost completely collapsed in the space of a few decades. While numerous explanations have been put forth to explain this collapse, in recent years, drought has gained favor. This is because water resources were a key for the Maya, especially to ensure their survival during the lengthy dry season that occurs where they lived. Natural drought is a known, recurring feature of this region, as evidenced by observational data, reconstructions of past times, and global climate model output. Results from simulations with a regional climate model demonstrate that deforestation by the Maya also likely induced warmer, drier, drought-like conditions. It is therefore hypothesized that the drought conditions devastating the Maya resulted from a combination of natural variability and human activities. Neither the natural drought or the human-induced effects alone were sufficient to cause the collapse, but the combination created a situation the Maya could not recover from. These results may have sobering implications for the present and future state of climate and water resources in Mesoamerica as ongoing massive deforestation is again occurring.

  4. [Natural inducing factors of grape bud dormancy and their regulation on respiratory metabolism during dormancy induction].

    PubMed

    Wang, Hai-bo; Wang, Xiao-di; Shi, Xiang-bin; Wang, Bao-liang; Zheng, Xiao-cui; Liu, Feng-zhi

    2015-12-01

    High chilling requirement grape (Vitis vinifera-V. labrusca cv. Summer Black) was used to evaluate its dormancy under short sunlight day (SD), long sunlight day (LD) and natural condition (CK). The results indicated that grape bud dormancy could be induced by natural low temperature and short sunlight alone or together. Short sunlight was the main contributor to the dormancy of grape bud, followed by natural low temperature. SD had more effect on dormancy induction under the same temperature when compared with LD. The grape dormancy induction stopped when the total respiratory rate reached the highest level. During the dormancy induction period, the proportion of pentose phosphate pathway (PPP) operation activity or capacity to total respiratory rate increased from 16.0% to 20.1% or 22.3% to 26.0%, respectively; similarly, the proportion of operation activity or capacity of alternate pathway to total respiratory rate rapidly increased, i.e., from 19.4% to 27.3% or 38.2% to 46.8%. Both low temperature and short sunlight could induce change of respiratory pathway on electron transport chain level. PMID:27112009

  5. Resistivity and induced polarization monitoring of salt transport under natural hydraulic gradients

    SciTech Connect

    Slater, L.D.; Sandberg, S.K.

    2000-04-01

    The authors demonstrate the use of resistivity/induced polarization (IP) monitoring of salt transport under natural hydraulic loads. Electrical monitoring of saline tracer transport during forced injection has been demonstrated previously. Detection of tracer transport under natural hydraulic loading is difficult because neither the hydraulic load nor the tracer resistivity can be controlled. In one study, the authors identify the electrical response to salt transport in a dynamic beach environment. Resistivity/IP imagine resolved the structure of the saltwater-freshwater interface and evidence for tide-induced groundwater transport. Resistivity increases in the near surface and at depth, upbeach of the high-tide mark, accompanied by tidal transgression. They attribute this to desaturation and decreasing salinity in the near surface and to decreasing salinity at depth, despite tidal transgression. Monitoring of groundwater levels indicates a phase lag between the tide level and groundwater level, supporting the electrical data. IP was insensitive to groundwater salinity variation. In a second study, the authors identify the electrical response to recharge-induced salt transport from a road-sale storage facility. Conductivity and IP models for monitoring lines, located on the basis of an EM31 survey, resolved the subsurface salt distribution, IP modeling resolved the sediment-bedrock interface. Modeling of monthly conductivity differences revealed conductivity increases and decreases at the locations of salt contamination, which correlate with the recharge pattern. They attribute near-surface conductivity increases after heavy rainfall to increasing saturation and ion dissolution. Corresponding conductivity decreases at depth are attributed to flushing of the bedrock with freshwater. Essentially, the opposite response was observed during a quiet monitoring period following heavy recharge. Near-surface IP changes are consistent with this interpretation. Salt

  6. Inhibition of hematopoietic recovery from radiation-induced myelosuppression by natural killer cells

    SciTech Connect

    Pantel, K.; Boertman, J.; Nakeff, A. )

    1990-05-01

    We have examined the role of natural killer (NK) cells in situ in the recovery of marrow hematopoiesis in B6D2F1 mice receiving various doses of total-body irradiation (TBI) as a well-characterized model for treatment-induced myelosuppression. Applying an in situ cytotoxic approach for ablating NK 1.1 cells, we have demonstrated that NK 1.1 cells differentially inhibit the recovery of hematopoietic stem cells (CFU-S) and their progenitor cells committed to granulocyte-macrophage differentiation from a sublethal dose of TBI (9 Gy) while not affecting the recovery of progenitor cells committed to either erythroid or megakaryocyte differentiation from TBI. However, recoveries of CFU-S and progenitor cells were unaffected by the ablation of NK cells prior to a moderate dose of TBI (2 Gy). These findings provide in situ evidence that NK cells are potential inhibitors of hematopoietic recovery from treatment-induced myelosuppression.

  7. Protection against hepatitis E virus infection by naturally acquired and vaccine-induced immunity.

    PubMed

    Zhang, J; Zhang, X-F; Zhou, C; Wang, Z-Z; Huang, S-J; Yao, X; Liang, Z-L; Wu, T; Li, J-X; Yan, Q; Yang, C-L; Jiang, H-M; Huang, H-J; Xian, Y-L; Shih, J W-K; Ng, M-H; Li, Y-M; Wang, J-Z; Zhu, F-C; Xia, N-S

    2014-06-01

    Immunity acquired from infection or vaccination protects humans from symptomatic hepatitis E. However, whether the risk of hepatitis E virus (HEV) infection is reduced by the immunity remains unknown. To understand this issue, a cohort with 12 409 participants randomized to receive the hepatitis E vaccine Hecolin(®) or placebo were serologically followed up for 2 years after vaccination. About half (47%) of participants were initially seropositive. A total of 139 infection episodes, evidenced by four-fold or greater rise of anti-HEV level or positive seroconversion, occurred in participants who received three doses of treatment. Risk of infection was highest among the baseline seronegative placebo group participants (2.04%). Pre-existing immunity and vaccine-induced immunity lower the risk significantly, to 0.52% and 0.30%, respectively. In conclusion, both vaccine-induced and naturally acquired immunity can effectively protect against HEV infection. PMID:24118636

  8. Nature of unusual spontaneous and field-induced phase transitions in multiferroics RMn 2O 5

    NASA Astrophysics Data System (ADS)

    Pyatakov, A. P.; Kadomtseva, A. M.; Vorob'ev, G. P.; Popov, Yu. F.; Krotov, S. S.; Zvezdin, A. K.; Lukina, M. M.

    2009-04-01

    Complex magnetic, magnetoelectric and magnetoelastic studies of spontaneous and field-induced phase transitions in TmMn 2O 5 were carried out. In the vicinity of spontaneous phase transition temperatures (35 and 25 K) the magnetoelectric and magnetoelastic dependences demonstrated the jumps of polarization and magnetostriction induced by the field ˜150 kOe. These anomalies can be attributed to the influence of magnetic field on the conditions of incommensurate-commensurate phase transition at 35 K and the reverse one at 25 K. In b-axis dependences the magnetic field-induced spin-reorientation phase transition was also observed below 20 K. Finally the magnetoelectric anomaly associated with metamagnetic transition is observed below the temperature of rare-earth subsystem ordering at relatively small critical fields of 5 kOe. This variety of spontaneous and induced phase transitions in RMn 2O 5 stems from the interplay of three magnetic subsystems: Mn 3+, Mn 4+, R 3+. The comparison with YMn 2O 5 highlights the role of rare earth in low-temperature region (metamagnetic and spin-reorientation phase transitions), while the phase transition at higher temperatures between incommensurate and commensurate phases should be ascribed to the different temperature dependences of Mn 3+ and Mn 4+ ions. The strong correlation of magnetoelastic and magnetoelectric properties observed in the whole class of RMn 2O 5 highlights their multiferroic nature.

  9. Chiral Selective Chemistry Induced by Natural Selection of Spin-Polarized Electrons.

    PubMed

    Rosenberg, Richard A; Mishra, Debabrata; Naaman, Ron

    2015-06-15

    The search to understand the origin of homochirality in nature has been ongoing since the time of Pasteur. Previous work has shown that DNA can act as a spin filter for low-energy electrons and that spin-polarized secondary electrons produced by X-ray irradiation of a magnetic substrate can induce chiral selective chemistry. In the present work it is demonstrated that secondary electrons from a substrate that are transmitted through a chiral overlayer cause enantiomeric selective chemistry in an adsorbed adlayer. We determine the quantum yields (QYs) for dissociation of (R)- or (S)-epichlorohydrin adsorbed on a chiral self-assembled layer of DNA on gold and on bare gold (for control). The results show that there is a significant difference in the QYs between the two enantiomers when adsorbed on DNA, but none when they are adsorbed on bare Au. We propose that the effect results from natural spin filtering effects cause by the chiral monolayer.

  10. Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth

    PubMed Central

    Zhou, YingJun; Liu, Yiliang Ellie; Cao, JianGuo; Zeng, GuangYao; Shen, Cui; Li, YanLan; Zhou, MeiChen; Chen, Yiding; Pu, Weiping; Potters, Louis; Shi, Eric Y.

    2009-01-01

    Purpose Lignans such as secoisolariciresinol diglucoside (SDG) in flaxseed, are metabolizes to bioactive mammalian lignans of END and ENL. Because mammalian lignans have chemical structural similarity to the natural estrogen, they are thought to behave like selective estrogen receptor modulators (SERM) and therefore have anticancer effect against hormone-related cancers. We isolated a series of lignan compounds, named as Vitexins, from the seed of Chinese herb Vitex Negundo. Experimental Design We purified several Vitexin lignan compounds. Cytotoxic and antitumor effects were analyzed in cancer cells and in tumor xenograft models. In vivo metabolism of Vitexins was determined in rat. Results Contrasts to the classical lignans, Vitexins were not metabolized to END and ENL. A mixture of Vitexins EVn-50 and purified Vitexin compound VB1 have cytotoxic effect on breast, prostate, and ovarian cancer cells and induces apoptosis with cleavage in PARP protein, up-regulation of Bax, and down-regulation of Bcl-2. This induction of apoptosis seems to be mediated by activation of caspases because inhibition of caspases activity significantly reduced induced apoptosis. We demonstrated a broad antitumor activity of EVn-50 on seven tumor xenograft models including breast, prostate, liver, and cervical cancers. Consistent with in vitro data, EVn-50 treatment induced apoptosis, down-regulated of Bcl-2, and up-regulated Bax in tumor xenografts. Conclusion Vitexin is a class of nature lignan compounds, whose action and anticancer effect is mediated by the mechanisms different from the classical lignans. Vitexin induced antitumor effect and cytotoxic activity is exerted through proapoptotic process, which is mediated by a decreased Bcl-2/Bax ratio and activation of caspases. PMID:19671865

  11. Photo-induced toxicity of titanium dioxide nanoparticles to Daphnia magna under natural sunlight.

    PubMed

    Mansfield, C M; Alloy, M M; Hamilton, J; Verbeck, G F; Newton, K; Klaine, S J; Roberts, A P

    2015-02-01

    Titanium dioxide nanoparticles (TiO2 NP) are one of the most abundantly utilized nanoparticles in the world. Studies have demonstrated the ability of the anatase crystal of TiO2 NP to produce reactive oxygen species (ROS) in the presence of ultraviolet radiation (UVR), a co-exposure likely to occur in aquatic ecosystems. The goal of this study was to examine the photo-induced toxicity of anatase TiO2 NP under natural sunlight to Daphnia magna. D. magna were exposed to a range of UVR intensities and anatase TiO2 concentrations in an outdoor exposure system using the sun as the source of UVR. Different UVR intensities were achieved using UVR opaque and transparent plastics. AnataseTiO2-NP demonstrated the reciprocal relationship seen in other phototoxic compounds such as polycyclic aromatic hydrocarbons (PAHs) at higher UVR treatments. The calculated 8h LC50 of anatase TiO2 NP was 139 ppb under full intensity ambient natural sunlight, 778 ppb under 50% natural sunlight, and >500 ppm under 10% natural sunlight. Mortality was also compared between animals allowed to accumulate a body burden of anatase TiO2 for 1h and organisms whose first exposure to anatase TiO2 aqueous suspensions occurred under UVR. A significantly greater toxic effect was observed in aqueous, low body burden suspensions than that of TiO2 1h body burdens, which is dissimilar from the model presented in PAHs. Anatase TiO2 presents a unique photo-induced toxic model that is different than that of established phototoxic compounds.

  12. Inducing physiological stress recovery with sounds of nature in a virtual reality forest--results from a pilot study.

    PubMed

    Annerstedt, Matilda; Jönsson, Peter; Wallergård, Mattias; Johansson, Gerd; Karlson, Björn; Grahn, Patrik; Hansen, Ase Marie; Währborg, Peter

    2013-06-13

    Experimental research on stress recovery in natural environments is limited, as is study of the effect of sounds of nature. After inducing stress by means of a virtual stress test, we explored physiological recovery in two different virtual natural environments (with and without exposure to sounds of nature) and in one control condition. Cardiovascular data and saliva cortisol were collected. Repeated ANOVA measurements indicated parasympathetic activation in the group subjected to sounds of nature in a virtual natural environment, suggesting enhanced stress recovery may occur in such surroundings. The group that recovered in virtual nature without sound and the control group displayed no particular autonomic activation or deactivation. The results demonstrate a potential mechanistic link between nature, the sounds of nature, and stress recovery, and suggest the potential importance of virtual reality as a tool in this research field.

  13. Target-induced natural killer cell loss as a measure of NK cell responses.

    PubMed

    Warren, Hilary

    2013-01-01

    Natural killer (NK) cells are an important effector cell of innate immunity. Their interaction with susceptible target cells triggers NK cell cytotoxicity and the release of cytokines. Immunofluorescence flow cytometry-based assays are now the preferred methods for measuring NK cell responses. For these assays, assessment is made on NK cells (CD3(-)CD56(+) CD16(+)) within the viable lymphocyte gate, defined by the parameters of size (FSC) and granularity (SSC). Accordingly, NK cells that have not dissociated from target cells at the time of measurement, or that have undergone target cell-induced apoptosis, are excluded from the viable lymphocyte gate and therefore from analysis. This unit describes a protocol for assessing NK cell function in response to various target cells (natural killing, antibody-dependent cell cytotoxicity, and NK cell alloreactivity) based on the loss of NK cells from the lymphocyte gate. This target-induced NK loss (TINKL) should provide a sensitive measure of NK cell responses in a clinical laboratory setting.

  14. Assay Development for the Discovery of Semaphorin 3B Inducing Agents from Natural Product Sources

    PubMed Central

    Yong, Yeonjoong; Pan, Li; Ren, Yulin; Fatima, Nighat; Ahmed, Safia; Chang, Leng Chee; Zhang, Xiaoli; Kinghorn, A. Douglas; Swanson, Steven M.; Carcache de Blanco, Esperanza J.

    2014-01-01

    Semaphorins are a class of membrane-bound and secreted proteins. They have been found to regulate basic cell functions such as axonal growth cone guidance and recent studies have focused on their effect on tumor progression. Semaphorin 3B (Sema 3B) particularly is a secreted protein that has been known to modulate proliferation and apoptosis, processes that are critical for tumor progression and development. In spite of its importance, there is yet no high-throughput screening assay available to detect or quantify the expression of Sema 3B for natural product anticancer drug discovery purposes. Therefore, the development of a new high-throughput bioassay for the discovery of Sema 3B inducing agents from natural product sources is described herein. A wide variety of pure compounds and extracts from plants and microorganisms has been found suitable for screening using this Sema 3B assay to detect and quantify the effect of Sema 3B inducing agents and thereby identify new selective bioactive Sema 3B lead compounds for anticancer drug discovery and development. Also, this new bioassay procedure is based on a high-throughput platform using an enzyme-linked immunosorbent assay that involves the optimization of sensitivity and selectivity levels as well as accuracy, reproducibility, robustness, and cost effectiveness. PMID:25016954

  15. Comparison of naturally acquired and vaccine-induced antibodies to Haemophilus influenzae type b capsular polysaccharide.

    PubMed Central

    Jelonek, M T; Chang, S J; Chiu, C Y; Park, M K; Nahm, M H; Ward, J I

    1993-01-01

    The objective of this study was to assess qualitative differences in the types of Haemophilus influenzae type B (Hib) capsular polysaccharide (polyribosylribitol phosphate [PRP]) antibodies induced in children 15 to 27 months of age by (i) natural exposure, (ii) PRP vaccine, and by (iii) PRP-diphtheria toxoid conjugate vaccine, (iv) PRP-group B Neisseria meningitidis outer membrane vesicle conjugate vaccine, and (v) Haemophilus type B oligosaccharide conjugate vaccine (HbOC). The highest levels of total Hib-PRP antibody measured by radioimmunoassay and immunoglobulin G (IgG) measured by enzyme-linked immunosorbent assay were seen after HbOC immunization. IgG1 Hib-PRP antibodies predominated in all groups, and there were no differences between the groups in the proportion of IgG and IgA Hib-PRP antibodies. However, the proportions of IgM differed significantly by group. The highest proportions of IgM occurred in naturally acquired antibody and after PRP vaccine, and the lowest proportion occurred after HbOC vaccine. IgG light-chain V kappa type alpha PRP antibody was present in all groups, and the level correlated with the total IgG Hib-PRP antibody level. Therefore, HbOC induced the highest concentrations of V kappa II type alpha PRP antibody, and the naturally acquired antibody group had the lowest levels. IgG light-chain V kappa III antibody levels were also highest in the HbOC group, but there was no correlation between V kappa III antibody levels and total amount of IgG Hib-PRP antibody. These data demonstrate qualitative differences in the antibody repertoires induced by natural exposure, the Hib-PRP vaccine, and each of the different Hib conjugate vaccines. We doubt that there are major differences in the protection afforded by these different antibody repertoires, because these differences do not appear to correlate with differences in protective efficacy in older children. PMID:8225608

  16. Induced responses to competition and herbivory: natural selection on multi-trait phenotypic plasticity.

    PubMed

    Boege, Karina

    2010-09-01

    Herbivory and competition are two of the most common biotic stressors for plants. When occurring simultaneously, responses to one interaction can constrain the induction of responses to the other interaction due to resource limitation and other interactive effects. Thus, to maximize fitness when interacting with competitors and herbivores, plants are likely to express particular combinations of plastic responses. This study reports the interactive effects of herbivory and competition on responses induced in Tithonia tubaeformis plants and describes how natural selection acts on particular plastic responses and on their different combinations. Competition induced a stem elongation response, expressed through an increase in height and mean internode length, together with a decrease in basal diameter. Interestingly, realized resistance increased in both competition and herbivory treatments, suggesting a plastic response in both constitutive and induced resistance traits. Particular combinations of plastic responses defined three plant phenotypes: vigorous, elongated, and resistant plants. The ecological context in which plants grew modified the traits and the particular combinations of plastic responses that were favored by selection. Vigorous plants were favored by selection in all environments, except when they were damaged by herbivores in the absence of neighbors. The combination of responses defining an elongated plant phenotype was favored by selection in crowded conditions. Resistance was negatively selected in the absence of competition and herbivory but favored in the presence of both interactions. In addition, contextual analyses detected that population structure in heterogeneous environments can also influence the outcomes of selection. These findings suggest that natural selection can act on particular combinations of plastic responses, which may allow plants to adjust their phenotypes to those that promote greater fitness under particular ecological

  17. Natural and Induced Fracture Diagnostics from 4-D VSP Low Permeability Gas Reservoirs

    SciTech Connect

    Mark E. Willis; Daniel R. Burns; M. Nafi Toksoz

    2008-09-30

    Tight gas sand reservoirs generally contain thick gas-charged intervals that often have low porosity and very low permeability. Natural and induced fractures provide the only means of production. The objective of this work is to locate and characterize natural and induced fractures from analysis of scattered waves recorded on 4-D (time lapse) VSP data in order to optimize well placement and well spacing in these gas reservoirs. Using model data simulating the scattering of seismic energy from hydraulic fractures, we first show that it is possible to characterize the quality of fracturing based upon the amount of scattering. In addition, the picked arrival times of recorded microseismic events provide the velocity moveout for isolating the scattered energy on the 4-D VSP data. This concept is applied to a field dataset from the Jonah Field in Wyoming to characterize the quality of the induced hydraulic fractures. The time lapse (4D) VSP data from this field are imaged using a migration algorithm that utilizes shot travel time tables derived from the first breaks of the 3D VSPs and receiver travel time tables based on the microseismic arrival times and a regional velocity model. Four azimuthally varying shot tables are derived from picks of the first breaks of over 200 VSP records. We create images of the fracture planes through two of the hydraulically fractured wells in the field. The scattered energy shows correlation with the locations of the microseismic events. In addition, the azimuthal scattering is different from the azimuthal reflectivity of the reservoir, giving us more confidence that we have separated the scattered signal from simple formation reflectivity. Variation of the scattered energy along the image planes suggests variability in the quality of the fractures in three distinct zones.

  18. Standoff detection of natural bioaerosol by range-gated laser-induced fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Buteau, Sylvie; Simard, Jean-Robert; Roy, Gilles

    2005-11-01

    The biological threat has emerged as one of today's primary security challenges due to the increased accessibility to biological warfare technology and the limited efficiency of detection and protection measures against such menace. Defence Research and Development Canada (DRDC) has investigated various methods, including the improvement of atmospheric bioaerosol monitoring, to increase the readiness against such threat. By the end of the 90s, DRDC developed a standoff bioaerosol sensor based on intensified range-gated spectrometric detection of Laser Induced Fluorescence (LIF). This work has showed an important potential of detecting and discriminating in real-time several bioaerosols. The LIDAR system that monitors atmosphere cells from a standoff position induces specific spectrally wide fluorescence signals originating from inelastic interactions with complex molecules forming the building blocks of the bioaerosols. This LIF signal is spectrally collected by a combination of a dispersive element and a range-gated ICCD that records the spectral information within a range-selected atmospheric volume. To assess further the potential of discrimination of such technique, this innovative sensor was used to obtain spectral data of various natural bioaerosols. In order to evaluate the discrimination of biological agent simulants from naturally occurring background fluorescing materials, the obtained results were compared with the ones of bioaerosol simulants (Bacillius subtilis var globiggi (BG) and Erwinia herbicola (EH)) acquired in 2001. The robustness of the spectral data with time was also investigated. From our results, most of the studied natural materials showed a spectral shift of various degrees, and up to 10 nm, to the longer wavelength one year later.

  19. Characterization of Natural Attenuation in a uranium-contaminated site by means of Induced Polarization Imaging

    NASA Astrophysics Data System (ADS)

    Flores Orozco, Adrián; Bücker, Matthias; Williams, Kenneth

    2014-05-01

    Field experiments at the U.S. Department of Energy's (DOE) Integrated Field Research Challenge site (IFRC) in Rifle, Colorado (USA) have repeatedly demonstrated the ability of microorganisms to reductively immobilize uranium (U) in U tailings-contaminated groundwater accompanying organic carbon amendment. At the same time, geophysical monitoring during such amendment experiments has proven that Induced Polarization (IP) datasets can provide valuable information regarding geochemical changes induced by stimulated microbial activity, such as precipitation of metallic minerals (e.g. FeS) and accumulation of reactive, electroactive ions (Fe[II]). Based on these findings, we present a novel, modified application of the IP imaging method. Specifically, we utilized an IP characterization approach to delineate areas where fluvially deposited organic material, within aquifer sediments, naturally stimulates the activity of subsurface microflora, leading to both the natural immobilization of uranium and accumulation of reduced end-products (minerals and pore fluids) capable of generating anomalous IP signatures. These so-called 'naturally reduced zones' (NRZ's) are characterized by elevated rates of microbial activity relative to sediments having a lower concentration of organic matter. As noted and based on our previous experiments at the site, the accumulation of metallic minerals represents suitable targets for the exploration with IP tomographic methods. Here, we explore the application of the IP imaging method for the characterization of NRZ's at the scale of the floodplain. We present imaging results obtained through the inversion of 70 independent lines distributed along the floodplain (~600 m2). Imaging results are validated through comparisons with lithological data obtained from wells drilled at the site and laboratory analysis of sediment and groundwater samples. Our results show the applicability of the IP method for characterizing regions of the subsurface having

  20. Strain-induced crystallization and mechanical properties of functionalized graphene sheet-filled natural rubber

    SciTech Connect

    Ozbas, Bulent; Toki, Shigeyuki; Hsiao, Benjamin S.; Chu, Benjamin; Register, Richard A.; Aksay, Ilhan A.; Prud'homme, Robert K.; Adamson, Douglas H.

    2012-03-11

    The effects of functionalized graphene sheets (FGSs) on the mechanical properties and strain-induced crystallization of natural rubber (NR) are investigated. FGSs are predominantly single sheets of graphene with a lateral size of several hundreds of nanometers and a thickness of 1.5 nm. The effect of FGS and that of carbon black (CB) on the strain-induced crystallization of NR is compared by coupled tensile tests and X-ray diffraction experiments. Synchrotron X-ray scattering enables simultaneous measurements of stress and crystallization of NR in real time during sample stretching. The onset of crystallization occurs at significantly lower strains for FGS-filled NR samples compared with CB-filled NR, even at low loadings. Neat-NR exhibits strain-induced crystallization around a strain of 2.25, while incorporation of 1 and 4 wt % FGS shifts the crystallization to strains of 1.25 and 0.75, respectively. In contrast, loadings of 16 wt % CB do not significantly shift the critical strain for crystallization. Two-dimensional (2D) wide angle X-ray scattering patterns show minor polymer chain alignment during stretching, in accord with previous results for NR. Small angle X-ray scattering shows that FGS is aligned in the stretching direction, whereas CB does not show alignment or anisotropy. The mechanical properties of filled NR samples are investigated using cyclic tensile and dynamic mechanical measurements above and below the glass transition of NR.

  1. Tumor necrosis factor-{alpha} enhances IL-15-induced natural killer cell differentiation

    SciTech Connect

    Lee, Jiwon; Lee, Suk Hyung; Shin, Nara; Jeong, Mira; Kim, Mi Sun; Kim, Mi Jeong; Yoon, Suk Ran; Chung, Jin Woong; Kim, Tae-Don; Choi, Inpyo

    2009-09-04

    The differentiation of natural killer (NK) cells is regulated by various factors including soluble growth factors and transcription factors. Here, we have demonstrated that tumor necrosis factor-{alpha} (TNF-{alpha}) is a positive regulator of NK cell differentiation. TNF-{alpha} augmented the IL-15-induced expression of NK1.1 and CD122 in mature NK cells, and TNF-{alpha} alone also induced NK cell maturation as well as IL-15. TNF-{alpha} also increased IFN-{gamma} production in NK cells in the presence of IL-15. Meanwhile, mRNA expression of several transcription factors, including T-bet and GATA-3, was increased by the addition of TNF-{alpha} and IL-15. In addition, TNF-{alpha} increased nuclear factor-kappa B (NF-{kappa}B) activity in NK cells and inhibition of NF-{kappa}B impeded TNF-{alpha}-enhanced NK cell maturation. Overall, these data suggest that TNF-{alpha} significantly increased IL-15-driven NK cell differentiation by increasing the expression of transcription factors that play crucial roles in NK cell maturation and inducing the NF-{kappa}B activity.

  2. New-to-nature sophorose analog: a potent inducer for gene expression in Trichoderma reesei.

    PubMed

    Huang, Tom Tao; Wages, John M

    2016-04-01

    Controlled hydrolysis of lactonic sophorolipids from Starmerella bombicola yields a previously undescribed sophorose analog that potently induces cellulase in Trichoderma reesei Rut-C30. Acid treatment of natural sophorolipids results in a mixture of monoacetylated, deacetylated, and diacetylated sophorolipids in acidic and lactonic forms. Isolation of the active components of the mixture, followed by structure determination by MS and NMR, reveals a new chemical entity, in which the lactone ring has been opened at the C-1' rather than at the C-4″ position of the sophorose moiety. This sophorose ester is resistant to degradation by the host and is at least 28 times more powerful an inducer than sophorose in shake-flask culture. Even at low concentrations (0.05 mM), the chemically modified sophorolipid effectively induces cellulase. With further improvements, this highly enabling technology can potentially reduce the cost of enzymes produced in T. reesei and can facilitate the rapid deployment of enzyme plants to support the nascent cellulosic biofuels and biochemicals industries. PMID:26920480

  3. Physicochemical properties of natural actomyosin from threadfin bream (Nemipterus spp.) induced by high hydrostatic pressure.

    PubMed

    Zhou, Aimei; Lin, Liying; Liang, Yan; Benjakul, Soottawat; Shi, Xiaoling; Liu, Xin

    2014-08-01

    Changes of physicochemical properties in natural actomyosin (NAM) from threadfin bream (Nemipterus spp.) induced by high hydrostatic pressure (200, 400, 600MPa for 10, 30, 50min) were studied. The increase in turbidity of NAM was coincidental with the decrease in protein solubility with increasing pressure and time, suggesting the formation of protein aggregates. SDS-PAGE showed that polymerisation and degradation of myosin heavy chain were induced by high pressure. Ca(2+)-ATPase activity of NAM treated by high pressure was lost, suggesting the denaturation of myosin and the dissociation of actomyosin complex. Surface hydrophobicity of NAM increased when the pressure and pressurization time increased, indicating that the exposed hydrophobic residues increased upon application of high pressure. Decrease in total sulfhydryl content and increase in surface-reactive sulfhydryl content of NAM samples were observed with the extension of pressurizing time, indicating the formation of disulphide bonds through oxidation of SH groups or disulphide interchanges. The above changes of physicochemical properties suggested conformational changes of NAM from muscle of threadfin bream induced by high hydrostatic pressure.

  4. New-to-nature sophorose analog: a potent inducer for gene expression in Trichoderma reesei.

    PubMed

    Huang, Tom Tao; Wages, John M

    2016-04-01

    Controlled hydrolysis of lactonic sophorolipids from Starmerella bombicola yields a previously undescribed sophorose analog that potently induces cellulase in Trichoderma reesei Rut-C30. Acid treatment of natural sophorolipids results in a mixture of monoacetylated, deacetylated, and diacetylated sophorolipids in acidic and lactonic forms. Isolation of the active components of the mixture, followed by structure determination by MS and NMR, reveals a new chemical entity, in which the lactone ring has been opened at the C-1' rather than at the C-4″ position of the sophorose moiety. This sophorose ester is resistant to degradation by the host and is at least 28 times more powerful an inducer than sophorose in shake-flask culture. Even at low concentrations (0.05 mM), the chemically modified sophorolipid effectively induces cellulase. With further improvements, this highly enabling technology can potentially reduce the cost of enzymes produced in T. reesei and can facilitate the rapid deployment of enzyme plants to support the nascent cellulosic biofuels and biochemicals industries.

  5. Natural phenylpropanoids inhibit lipoprotein-induced endothelin-1 secretion by endothelial cells.

    PubMed

    Martin-Nizard, Françoise; Sahpaz, Sevser; Kandoussi, Abdelmejid; Carpentier, Marie; Fruchart, Jean-Charles; Duriez, Patrick; Bailleul, François

    2004-12-01

    There is increasing evidence that oxidized low-density lipoproteins (Ox-LDL) might be involved in the pathogenesis of atherosclerosis and it has been reported that polyphenols inhibit LDL peroxidation and atherosclerosis. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide isolated from endothelial cells and it induces smooth muscle cell proliferation. ET-1 secretion is increased in atheroma and induces deleterious effects such as vasospasm and atherosclerosis. The goal of this study was to test the effect of four natural phenolic compounds against copper-oxidized LDL (Cu-LDL)-induced ET-1 liberation by bovine aortic endothelial cells (BAEC). The tested compounds were phenylpropanoid glycosides previously isolated from the aerial parts of Marrubium vulgare L. (acteoside 1, forsythoside B 2, arenarioside 3 and ballotetroside 4). ET-1 secretion increased when cells were incubated with Cu-LDL but the compounds 1-4 inhibited this increase. These results were confirmed by quantitative-polymerase chain reaction (QPCR) analysis. Since ET-1 plays an important role in atherosclerosis development, our work suggests that the tested phenylpropanoids could have a beneficial effect in inhibiting atherosclerosis development. PMID:15563769

  6. Nature and occurrence of cooling-induced cracking in volcanic rocks

    NASA Astrophysics Data System (ADS)

    Browning, John; Meredith, Philip G.; Gudmundssom, Agust

    2015-04-01

    Several hypotheses have been proposed regarding the role of thermo-mechanical contraction in producing cracks and joints in volcanic rocks. Nevertheless, most studies of thermally-induced cracking to date have focused on the generation of cracks formed during heating. In this latter case, the cracks are formed under an overall compressional regime. By contrast, cooling cracks are formed under an overall tensile regime. Therefore, both the nature and mechanism of crack formation during cooling are hypothesised to be different from those for crack formation during heating. Furthermore, it remains unclear whether cooling simply reactivates pre-existing cracks, induces the growth of new cracks, or both. We present results from experiments based on a new method for testing ideas on cooling-induced cracking. Cored samples of volcanic rock (basaltic to dacitic in composition) were heated at varying rates to different maximum temperatures inside a tube furnace. In the highest temperature experiments samples of both rocks were raised to the liquidus temperature appropriate to their composition, forcing melt interaction and crack annealing. We present in-situ seismic velocity and acoustic emission data, which were recorded throughout each heating and cooling cycle. It is found consistently that the rate of acoustic emission is much higher during cooling than during heating. In addition, acoustic emission events produced on cooling tend to be significantly higher in energy than those produced during heating. We therefore suggest that cracks formed during cooling are significantly larger than those formed during heating. Thin-section and crack morphology analysis of our cyclically heated samples provide further evidence of contrasting fracture morphologies. These new data are important for assessing the contribution of cooling-induced damage within volcanic structures and layers such as sills and lava flows. Our observations may also help to constrain evolving ideas regarding

  7. The opioid/nonopioid nature of stress-induced analgesia and learned helplessness.

    PubMed

    Maier, S F; Sherman, J E; Lewis, J W; Terman, G W; Liebeskind, J C

    1983-01-01

    Exposure to a variety of stressors produces a subsequent analgesic reaction. This stress-induced analgesia (SIA) is sometimes opioid in nature (reversed by opiate antagonists and cross-tolerant with morphine) and sometimes nonopioid. Both 30 min of intermittent footshock and 60-80 five-sec tailshocks have been shown to produce opioid SIA, whereas 3 min of continuous footshock and 5-40 tailshocks produce nonopioid SIA. We report that both of the opioid SIA procedures produce a learned helplessness effect as assessed by shuttlebox escape acquisition and an analgesia that is reinstatable 24 hr. later. The nonopioid procedures produce neither a learned helplessness effect nor a reinstatable analgesia. It is argued that these data implicate the learning of uncontrollability in the activation of opioid systems.

  8. Moisture induced softening and swelling of natural cellulose fibres in composite applications

    NASA Astrophysics Data System (ADS)

    Gamstedt, E. K.

    2016-07-01

    Composites based on natural cellulose fibres are susceptible to moisture. The fibres as well as the composite will inevitably soften and swell as moisture is absorbed. The intention of the present paper is to shed some light on the mechanisms behind softening and swelling. Also references to modelling work are made, to predict the moisture-induced dimensional stability. Characterisation techniques and models of such kind can be useful in choosing suitable fibres for improved moisture resistance, and identifying the main controlling parameters which affect the engineering consequences of moisture absorption. Understanding of the mechanisms and the main contributions to swelling can rationalise materials development. The examples shown in this review attempt to show the benefits by experimental mechanics and modelling in development of moisture resistant cellulose composites.

  9. Nature of Defects Induced by Au Implantation in Hexagonal Silicon Carbide Single Crystals

    SciTech Connect

    Gentils, Aurelie; Barthe, Marie-France; Egger, Werner; Sperr, Peter

    2009-03-10

    Pulsed-slow-positron-beam-based positron lifetime spectroscopy was used to investigate the nature of vacancy defects induced by 20 MeV Au implantation in single crystals 6H-SiC. Preliminary analysis of the data shows that at lower fluence, below 10{sup 14} cm{sup -2}, a positron lifetime of 220 ps has been obtained: it could be associated with the divacancy V{sub Si}-V{sub C} in comparison with the literature. At higher fluence, above 10{sup 15} cm{sup -2}, a positron lifetime of 260-270 ps, increasing with the incident positron energy, has been observed after decomposition of the lifetime spectra. By comparison with lifetime calculations, open-volumes such as quadrivacancy (V{sub Si}-V{sub C}){sub 2} clusters could be associated with this value.

  10. Polypropylene/natural rubber thermoplastic vulcanizates by eco-friendly and sustainable electron induced reactive processing

    NASA Astrophysics Data System (ADS)

    Mondal, Manas; Gohs, Uwe; Wagenknecht, Udo; Heinrich, Gert

    2013-07-01

    TPVs are a special class of thermoplastic and elastomer blend where cross-linking of elastomeric phase takes place during melt mixing process known as dynamic vulcanization (DV). A 50/50 blend of natural rubber (NR) and polypropylene (PP) were dynamically vulcanized using Electron Induced Reactive Processing (EIReP) as a function of absorbed dose (150, 250, and 350 kGy) at fixed electron energy (1.5 MeV) and dose per rotation. Different methods like tensile test, DSC, melt rheology, and SEM have been employed to understand the structure-property relationship of the prepared samples. The results suggest that EIReP is a novel technique to offer handful of additional features without compromising the end user property.

  11. Quantum nature of the sign preference in ion-induced nucleation.

    PubMed

    Nadykto, Alexey B; Al Natsheh, Anas; Yu, Fangqun; Mikkelsen, K V; Ruuskanen, J

    2006-03-31

    Observed first in Wilson's pioneering experiments in the cloud chamber, the sign preference has remained a mystery for more than a century. We investigate the sign preference using a quantum approach and show that this puzzling phenomenon is essentially quantum in nature. It is shown that the effect of the chemical identity of the core ion is controlled by the electronic structure of the core ion through the influence on the intermolecular bonding energies during the initial steps of cluster formation. Our results demonstrate the superiority of the quantum approach and indicate fundamental problems of conventional ion-induced nucleation theories, in which the electronic structure of the core ion is either ignored or not treated rigorously. PMID:16605928

  12. Detection of cysteine protease in Taenia solium-induced brain granulomas in naturally infected pigs.

    PubMed

    Mkupasi, Ernatus Martin; Sikasunge, Chummy Sikalizyo; Ngowi, Helena Aminiel; Leifsson, Pall S; Johansen, Maria Vang

    2013-10-18

    In order to further characterize the immune response around the viable or degenerating Taenia solium cysts in the pig brain, the involvement of cysteine protease in the immune evasion was assessed. Brain tissues from 30 adult pigs naturally infected with T. solium cysticercosis were subjected to histopathology using hematoxylin and eosin stain, and immunohistochemistry using caspase-3 antibodies. Histopathological evaluation revealed lesions of stage I which was characterized by presence of viable parasite surrounded with minimal to moderate inflammatory cells and stage III characterized by the presence of a disintegrating parasite surrounded with high inflammatory cells. The results of immunohistochemistry indicated caspase-3 positive cells interspaced between inflammatory infiltrate mainly in stage I lesions, indicating the presence of cysteine protease. This result confirms the earlier hypothesis that cysteine protease may play a role in inducing immune evasion through apoptosis around viable T. solium cysts.

  13. Human-induced nitrogen-phosphorus imbalances alter natural and managed ecosystems across the globe.

    PubMed

    Peñuelas, Josep; Poulter, Benjamin; Sardans, Jordi; Ciais, Philippe; van der Velde, Marijn; Bopp, Laurent; Boucher, Olivier; Godderis, Yves; Hinsinger, Philippe; Llusia, Joan; Nardin, Elise; Vicca, Sara; Obersteiner, Michael; Janssens, Ivan A

    2013-01-01

    The availability of carbon from rising atmospheric carbon dioxide levels and of nitrogen from various human-induced inputs to ecosystems is continuously increasing; however, these increases are not paralleled by a similar increase in phosphorus inputs. The inexorable change in the stoichiometry of carbon and nitrogen relative to phosphorus has no equivalent in Earth's history. Here we report the profound and yet uncertain consequences of the human imprint on the phosphorus cycle and nitrogen:phosphorus stoichiometry for the structure, functioning and diversity of terrestrial and aquatic organisms and ecosystems. A mass balance approach is used to show that limited phosphorus and nitrogen availability are likely to jointly reduce future carbon storage by natural ecosystems during this century. Further, if phosphorus fertilizers cannot be made increasingly accessible, the crop yields projections of the Millennium Ecosystem Assessment imply an increase of the nutrient deficit in developing regions.

  14. Inducible nature of the enzymes involved in catabolism of caffeine and related methylxanthines.

    PubMed

    Dash, Swati Sucharita; Gummadi, Sathyanarayana N

    2008-08-01

    Previously isolated strain of Pseudomonas sp. has the capability of utilizing caffeine as the sole source of carbon and nitrogen and degrading caffeine at higher concentrations (>10 g l(-1)). In this study, an assay has been developed to study the enzymatic conversion of caffeine to subsequent methylxanthines by cell free extracts of Pseudomonas sp., the activity of which has been stabilized by use of stabilizers in the lysis buffer. Growth of the strain in various methylxanthines and later enzyme assay demonstrated that the enzyme(s) involved in degradation of caffeine and other methylxanthines were inducible in nature. The results also indicated that more than one enzyme are involved in degradation of caffeine to xanthine, which constitute the primary steps in bacterial caffeine catabolism.

  15. Antihepatotoxic nature of Ulva reticulata (Chlorophyceae) on acetaminophen-induced hepatoxicity in experimental rats.

    PubMed

    Balaji Raghavendra Rao, H; Sathivel, A; Devaki, T

    2004-01-01

    Ulva reticulata, a marine edible green alga, is a known source of proteins, vitamins, and sulfated polysaccharides. Though there are many reports in the literature regarding the composition and antiviral property of Ulva sp., studies of the antihepatotoxic property of green seaweeds in animal model are scarce. We have studied the antihepatotoxic nature of this marine green edible alga, U. reticulata, in a hot water extract (150 mg/kg of body weight for a period of 15 days) against acetaminophen- induced hepatotoxicity in experimental albino rats. The acetaminophen-induced rats showed significant elevation in levels of the serum marker enzymes aspartate transaminase and alanine transaminase and of lipid peroxides in liver tissue with decreased levels of antioxidant enzymes such as superoxide dismutase and catalase. The levels of reduced glutathione and vitamins (E and C) were also decreased in the liver tissue of acetaminophen-intoxicated rats. The oral pretreatment with a hot water extract of U. reticulata reduced the hepatotoxicity triggered by acetaminophen considerably by improving the antioxidant status in experimental animals with depleted levels of lipid peroxides. These results indicate that the oral pretreatment with a hot water extract of U. reticulata in rats is effective in reducing the hepatic oxidative stress via free radical scavenging properties, suggesting an antihepatotoxic activity. PMID:15671697

  16. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia.

    PubMed

    Romee, Rizwan; Rosario, Maximillian; Berrien-Elliott, Melissa M; Wagner, Julia A; Jewell, Brea A; Schappe, Timothy; Leong, Jeffrey W; Abdel-Latif, Sara; Schneider, Stephanie E; Willey, Sarah; Neal, Carly C; Yu, Liyang; Oh, Stephen T; Lee, Yi-Shan; Mulder, Arend; Claas, Frans; Cooper, Megan A; Fehniger, Todd A

    2016-09-21

    Natural killer (NK) cells are an emerging cellular immunotherapy for patients with acute myeloid leukemia (AML); however, the best approach to maximize NK cell antileukemia potential is unclear. Cytokine-induced memory-like NK cells differentiate after a brief preactivation with interleukin-12 (IL-12), IL-15, and IL-18 and exhibit enhanced responses to cytokine or activating receptor restimulation for weeks to months after preactivation. We hypothesized that memory-like NK cells exhibit enhanced antileukemia functionality. We demonstrated that human memory-like NK cells have enhanced interferon-γ production and cytotoxicity against leukemia cell lines or primary human AML blasts in vitro. Using mass cytometry, we found that memory-like NK cell functional responses were triggered against primary AML blasts, regardless of killer cell immunoglobulin-like receptor (KIR) to KIR-ligand interactions. In addition, multidimensional analyses identified distinct phenotypes of control and memory-like NK cells from the same individuals. Human memory-like NK cells xenografted into mice substantially reduced AML burden in vivo and improved overall survival. In the context of a first-in-human phase 1 clinical trial, adoptively transferred memory-like NK cells proliferated and expanded in AML patients and demonstrated robust responses against leukemia targets. Clinical responses were observed in five of nine evaluable patients, including four complete remissions. Thus, harnessing cytokine-induced memory-like NK cell responses represents a promising translational immunotherapy approach for patients with AML.

  17. Natural selection underlies apparent stress-induced mutagenesis in a bacteriophage infection model.

    PubMed

    Yosef, Ido; Edgar, Rotem; Levy, Asaf; Amitai, Gil; Sorek, Rotem; Munitz, Ariel; Qimron, Udi

    2016-01-01

    The emergence of mutations following growth-limiting conditions underlies bacterial drug resistance, viral escape from the immune system and fundamental evolution-driven events. Intriguingly, whether mutations are induced by growth limitation conditions or are randomly generated during growth and then selected by growth limitation conditions remains an open question(1). Here, we show that bacteriophage T7 undergoes apparent stress-induced mutagenesis when selected for improved recognition of its host's receptor. In our unique experimental set-up, the growth limitation condition is physically and temporally separated from mutagenesis: growth limitation occurs while phage DNA is outside the host, and spontaneous mutations occur during phage DNA replication inside the host. We show that the selected beneficial mutations are not pre-existing and that the initial slow phage growth is enabled by the phage particle's low-efficiency DNA injection into the host. Thus, the phage particle allows phage populations to initially extend their host range without mutagenesis by virtue of residual recognition of the host receptor. Mutations appear during non-selective intracellular replication, and the frequency of mutant phages increases by natural selection acting on free phages, which are not capable of mutagenesis. PMID:27572836

  18. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia.

    PubMed

    Romee, Rizwan; Rosario, Maximillian; Berrien-Elliott, Melissa M; Wagner, Julia A; Jewell, Brea A; Schappe, Timothy; Leong, Jeffrey W; Abdel-Latif, Sara; Schneider, Stephanie E; Willey, Sarah; Neal, Carly C; Yu, Liyang; Oh, Stephen T; Lee, Yi-Shan; Mulder, Arend; Claas, Frans; Cooper, Megan A; Fehniger, Todd A

    2016-09-21

    Natural killer (NK) cells are an emerging cellular immunotherapy for patients with acute myeloid leukemia (AML); however, the best approach to maximize NK cell antileukemia potential is unclear. Cytokine-induced memory-like NK cells differentiate after a brief preactivation with interleukin-12 (IL-12), IL-15, and IL-18 and exhibit enhanced responses to cytokine or activating receptor restimulation for weeks to months after preactivation. We hypothesized that memory-like NK cells exhibit enhanced antileukemia functionality. We demonstrated that human memory-like NK cells have enhanced interferon-γ production and cytotoxicity against leukemia cell lines or primary human AML blasts in vitro. Using mass cytometry, we found that memory-like NK cell functional responses were triggered against primary AML blasts, regardless of killer cell immunoglobulin-like receptor (KIR) to KIR-ligand interactions. In addition, multidimensional analyses identified distinct phenotypes of control and memory-like NK cells from the same individuals. Human memory-like NK cells xenografted into mice substantially reduced AML burden in vivo and improved overall survival. In the context of a first-in-human phase 1 clinical trial, adoptively transferred memory-like NK cells proliferated and expanded in AML patients and demonstrated robust responses against leukemia targets. Clinical responses were observed in five of nine evaluable patients, including four complete remissions. Thus, harnessing cytokine-induced memory-like NK cell responses represents a promising translational immunotherapy approach for patients with AML. PMID:27655849

  19. Porphyromonas gingivalis Lipopolysaccharide Induced Proliferation and Activation of Natural Killer Cells in Vivo.

    PubMed

    Wang, Yuhua; Zhang, Wei; Xu, Li; Jin, Jun-O

    2016-01-01

    Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) promoted different innate immune activation than that promoted by Escherichia coli (E. coli) LPS. In this study, we examined the effect of P. gingivalis LPS on the proliferation and activation of natural killer (NK) cells in vivo and compared that function with that of E. coli LPS. Administration of P. gingivalis LPS to C57BL/6 mice induced stronger proliferation of NK cells in the spleen and submandibular lymph nodes (sLNs) and increased the number of circulating NK cells in blood compared to those treated with E. coli LPS. However, P. gingivalis LPS did not induce interferon-gamma (IFN-γ) production and CD69 expression in the spleen and sLN NK cells in vivo, and this was attributed to the minimal activation of the spleen and sLN dendritic cells (DCs), including low levels of co-stimulatory molecule expression and pro-inflammatory cytokine production. Furthermore, P. gingivalis LPS-treated NK cells showed less cytotoxic activity against Yac-1 target cells than E. coli LPS-treated NK cells. Hence, these data demonstrated that P. gingivalis LPS promoted limited activation of spleen and sLN NK cells in vivo, and this may play a role in the chronic inflammatory state observed in periodontal disease. PMID:27548133

  20. Natural repressors of P-induced hybrid dysgenesis in Drosophila melanogaster: a model for repressor evolution.

    PubMed

    Corish, P; Black, D M; Featherston, D W; Merriam, J; Dover, G A

    1996-04-01

    Type I repressors control P element transposition and comprise full length elements and elements with small 3' deletions in the final exon. Using a sensitive assay for measuring the strength of repression of P element transposition in somatic and germline tissues, we have isolated and characterized a naturally occurring type I repressor element from a Q population of Drosophila melanogaster. We demonstrate that the almost complete repression of transposition in this population is a mixture of KP elements with intermediate levels of repression, and the strong contribution of a single 2.6 kb P element deletion derivative, which we call SR (Strong Repressor). A deletion in the final intron of SR allows for the constitutive production of a putative 75 kDa repressor protein in germline tissues in addition to the production of the 66 kDa repressor in the soma, which would result in a biparental mode of inheritance of repression. Based on the four observed classes of natural Q populations, we propose a model in which populations containing SR-like elements, capable of producing strong type I repressor constitutively, have a selective advantage over populations which rely either on maternally transmitted P cytotype or on KP-induced weak levels of repression. Such populations may subsequently spread and constitute an evolutionary stable strategy for the repression of hybrid dysgenesis in Drosophila melanogaster. PMID:8801184

  1. Natural repressors of P-induced hybrid dysgenesis in Drosophila melanogaster: a model for repressor evolution.

    PubMed

    Corish, P; Black, D M; Featherston, D W; Merriam, J; Dover, G A

    1996-04-01

    Type I repressors control P element transposition and comprise full length elements and elements with small 3' deletions in the final exon. Using a sensitive assay for measuring the strength of repression of P element transposition in somatic and germline tissues, we have isolated and characterized a naturally occurring type I repressor element from a Q population of Drosophila melanogaster. We demonstrate that the almost complete repression of transposition in this population is a mixture of KP elements with intermediate levels of repression, and the strong contribution of a single 2.6 kb P element deletion derivative, which we call SR (Strong Repressor). A deletion in the final intron of SR allows for the constitutive production of a putative 75 kDa repressor protein in germline tissues in addition to the production of the 66 kDa repressor in the soma, which would result in a biparental mode of inheritance of repression. Based on the four observed classes of natural Q populations, we propose a model in which populations containing SR-like elements, capable of producing strong type I repressor constitutively, have a selective advantage over populations which rely either on maternally transmitted P cytotype or on KP-induced weak levels of repression. Such populations may subsequently spread and constitute an evolutionary stable strategy for the repression of hybrid dysgenesis in Drosophila melanogaster.

  2. Infection with Wolbachia protects mosquitoes against Plasmodium-induced mortality in a natural system.

    PubMed

    Zélé, F; Nicot, A; Duron, O; Rivero, A

    2012-07-01

    In recent years, there has been a shift in the one host-one parasite paradigm with the realization that, in the field, most hosts are coinfected with multiple parasites. Coinfections are particularly relevant when the host is a vector of diseases, because multiple infections can have drastic consequences for parasite transmission at both the ecological and evolutionary timescales. Wolbachia pipientis is the most common parasitic microorganism in insects, and as such, it is of special interest for understanding the role of coinfections in the outcome of parasite infections. Here, we investigate whether Wolbachia can modulate the effect of Plasmodium on what is, arguably, the most important component of the vectorial capacity of mosquitoes: their longevity. For this purpose, and in contrast to recent studies that have focused on mosquito-Plasmodium and/or mosquito-Wolbachia combinations not found in nature, we work on a Wolbachia-mosquito-Plasmodium triad with a common evolutionary history. Our results show that Wolbachia protects mosquitoes from Plasmodium-induced mortality. The results are consistent across two different strains of Wolbachia and repeatable across two different experimental blocks. To our knowledge, this is the first time that such an effect has been shown for Plasmodium-infected mosquitoes and, in particular, in a natural Wolbachia-host combination. We discuss different mechanistic and evolutionary explanations for these results as well as their consequences for Plasmodium transmission. PMID:22533729

  3. Natural products and complementary therapies for chemotherapy-induced peripheral neuropathy: A systematic review.

    PubMed

    Brami, Cloé; Bao, Ting; Deng, Gary

    2016-02-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side-effect without any FDA-approved treatment option. Prior reviews focus mostly on pharmacological interventions, but nonpharmaceutical interventions have also been evaluated. A Web of Science and PubMed database search to identify relevant RCTs from January 2005 to May 2015 included the terms: CIPN, cancer; and supplements, vitamin E, goshajinkigan, kampo, acetyl-L-carnitine, carnitine, alpha-lipoic acid, omega-3, glutamine, or glutamate; or massage, acupuncture, mind-body practice, yoga, meditation, Tai-Chi, physical activity, or exercise. Of 1465 publications screened, 12 RCTs evaluated natural products and one evaluated electroacupuncture. Vitamin E may help prevent CIPN. L-Glutamine, goshajinkigan, and omega-3 are also promising. Acetyl-L-carnitine may worsen CIPN and alpha-lipoic acid activity is unknown. Electroacupuncture was not superior to placebo. No RCTs were published regarding other complementary therapies, although some studies mention positive incidental findings. Natural products and complementary therapies deserve further investigation, given the lack of effective CIPN interventions. PMID:26652982

  4. Buoyancy and Pressure Induced Flow of Hot Gases in Vertical Shafts with Natural and Forced Ventilation

    NASA Astrophysics Data System (ADS)

    Jaluria, Yogesh; Tamm, Gunnar Olavi

    2014-11-01

    An experimental investigation was conducted to study buoyancy and pressure induced flow of hot gases in vertical shafts to model smoke propagation in elevator and ventilation shafts of high rise building fires. Various configurations were tested with regard to natural and forced ventilation imposed at the upper and lower surfaces of the vertical shaft. The aspect ratio was taken at a typical value of 6. From a lower vent, the inlet conditions for smoke and hot gases were varied in terms of the Reynolds and Grashof numbers. The forced ventilation at the upper or lower boundary was of the same order as the bulk shaft flow. Measurements were taken within the shaft to allow a detailed study of the steady state flow and thermal fields established for various shaft configurations and inlet conditions, from which optimal means for smoke alleviation in high rise building fires may be developed. Results indicated a wall plume as the primary transport mechanism for smoke propagating from the inlet towards the exhaust region. Recirculation and entrainment dominated at high inlet Grashof number flows, while increased inlet Reynolds numbers allowed greater mixing in the shaft. The development and stability of these flow patterns and their effects on the smoke behavior were assessed for several shaft configurations with different inlet conditions. The comparisons indicated that the fastest smoke removal and lowest overall shaft temperatures occur for a configuration with natural ventilation at the top surface and forced ventilation up from the shaft bottom.

  5. Investigations of plasma induced effects on the surface properties of lignocellulosic natural coir fibres

    NASA Astrophysics Data System (ADS)

    Praveen, K. M.; Thomas, Sabu; Grohens, Yves; Mozetič, Miran; Junkar, Ita; Primc, Gregor; Gorjanc, Marija

    2016-04-01

    The development of lignocellulosic natural-fibre-reinforced polymers composites are constrained by two limitations: the upper temperature at which the fibre can be processed and the significant differences between the surface energy of the fibre and the polymer matrix. Since the fibres and matrices are chemically different, strong adhesion at their interface is needed for the effective transfer of stress and bond distribution throughout the interface. The present study investigated the plasma induced effects on the surface properties of natural coir fibres. Weakly ionized oxygen plasma was created in two different discharge chambers by an inductively coupled radiofrequency (RF) discharge. The water absorption studies showed an increase of water sorption from 39% to 100%. The morphological study using scanning electron microscopy (SEM) analysis also confirmed the surface changes which were observed after the plasma treatment. The topographic measurements and phase imaging done using atomic force microscopy (AFM) indicated difference in topographic features and etching of coir wall, which points to the removal of the first layer of coir fibre. X-ray photoelectron spectroscopy (XPS) analysis revealed that the oxygen content measured for samples treated at 50 Pa increased from initial 18% to about 32%.

  6. Hot colors: the nature and specificity of color-induced nasal thermal sensations.

    PubMed

    Michael, George A; Galich, Hélène; Relland, Solveig; Prud'hon, Sabine

    2010-03-01

    The nature of the recently discovered color-induced nasal thermal sensations was investigated in four Experiments. Subjects were required to fixate a bottle containing a red or green solution presented centrally (Exp1 and Exp4) or laterally (Exp2) and to sniff another bottle, always the same one, but which they were not allowed to see, containing 10 ml of a colorless, odorless and trigeminal-free solution. Each nostril was tested separately, and subjects were asked whether the sniffed solution induced warming or cooling sensations (plus an ambient sensation in Exp4) in the nasal cavity. The results of Experiments 1 and 2 confirmed the warming/left nostril-cooling/right nostril dissociation, suggesting the existence of different lateralized processes for thermal processing. However, Experiment 2 failed to demonstrate dominance of warming responses when subjects' eyes were directed to the left or cooling responses when they were directed to the right. Nor did gaze direction interact with the tested nostril. This suggests that the color-induced thermal sensations are specifically related to the nasal trigeminal system, rather than a general process related to general hemispheric activity. When the exposed bottles were colorless (Exp3), no lateralized patterns were observed, suggesting, in combination with the results of Experiments 1 and 2, that both color cues and nasal stimulations are necessary for lateralized patterns to arise. Rendering the temperature judgment even more difficult (Exp4), made the lateralized patterns shift towards the associated (i.e., ambient) responses. The results are discussed in a general framework which considers that, even in the absence of real thermal stimulus, preparing to process thermal stimuli in the nasal cavity may activate the underlying lateralized neural mechanisms, and that those mechanisms are reflected in the responses.

  7. Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain.

    PubMed

    Pavlovsky, A A; Boehning, D; Li, D; Zhang, Y; Fan, X; Green, T A

    2013-08-29

    Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30 min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction. PMID:23644055

  8. Psychological Stress, Cocaine and Natural Reward Each Induce Endoplasmic Reticulum Stress Genes in Rat Brain

    PubMed Central

    Pavlovsky, Ashly A.; Boehning, Darren; Li, Dingge; Zhang, Yafang; Fan, Xiuzhen; Green, Thomas A.

    2013-01-01

    Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors Activating Transcription Factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently it is unknown the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative PCR and RNA sequencing. Restraint stress and cocaine induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components XBP1 and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30 min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction. PMID:23644055

  9. Photosensitized rose Bengal-induced phototoxicity on human melanoma cell line under natural sunlight exposure.

    PubMed

    Srivastav, Ajeet K; Mujtaba, Syed Faiz; Dwivedi, Ashish; Amar, Saroj K; Goyal, Shruti; Verma, Ankit; Kushwaha, Hari N; Chaturvedi, Rajnish K; Ray, Ratan Singh

    2016-03-01

    Rose Bengal (RB) is an anionic water-soluble xanthene dye, which used for many years to assess eye cornea and conjunctiva damage. RB showed strong absorption maxima (λmax) under visible light followed by UV-B and UV-A. RB under sunlight exposure showed a time-dependent photodegradation. Our results show that photosensitized RB generates (1)O2 via Type-II photodynamic pathway and induced DNA damage under sunlight/UV-R exposure. 2'dGuO degradation, micronuclei formation, and single- and double-strand breakage were the outcome of photogenotoxicity caused by RB. Quenching studies with NaN3 advocate the involvement of (1)O2 in RB photogenotoxicity. RB induced linoleic acid photoperoxidation, which was parallel to (1)O2-mediated DNA damage. Oxidative stress in A375 cell line (human melanoma cell line) was detected through DCF-DA assay. Photosensitized RB decreased maximum cellular viability under sunlight followed by UV-B and UV-A exposures. Apoptosis was detected as a pattern of cell death through the increased of caspase-3 activity, decreased mitochondrial membrane potential, and PS translocation through inner to outer plasma membrane. Increased cytosolic levels of Bax also advocate the apoptotic cell death. We propose a p53-mediated apoptosis via increased expression of Bax gene and protein. Thus, the exact mechanism behind RB phototoxicity was the involvement of (1)O2, which induced oxidative stress-mediated DNA and membrane damage, finally apoptotic cell death under natural sunlight exposure. The study suggests that after the use of RB, sunlight exposure may avoid to prevent from its harmful effects.

  10. Natural furocoumarins as inducers and inhibitors of cytochrome P450 1A1 in rat hepatocytes.

    PubMed

    Baumgart, Annette; Schmidt, Melanie; Schmitz, Hans-Joachim; Schrenk, Dieter

    2005-02-15

    Furocoumarins are natural plant constituents present in medicinal plants and in a variety of foods such as grapefruit juice. They are phototoxic and act as potent inhibitors of drug metabolism. We have investigated the interaction of four furocoumarins angelicin, bergamottin, isopimpinellin, and 8-methoxypsoralen with the expression and activity of aryl hydrocarbon receptor (AhR)-regulated CYP1A1 in rat hepatocytes in primary culture, both in the presence and absence of light. In intact hepatocytes pretreated with 2,3,7,8-tetrachlorodibenzo-p-dioxin and in microsomes isolated thereof, all furocoumarins tested acted as potent inhibitors of CYP1A1 activity bergamottin being the most potent inhibitor in microsomes with an IC(50) of 10 nM in the presence and 60 nM in the absence of light. 8-Methoxypsoralen and angelicin led to a significant induction of CYP1A1 mRNA in hepatocytes, while all furocoumarins except bergamottin increased xenobiotic-responsive element-driven reporter gene expression in transfected H4IIE rat hepatoma cells when light was excluded. Furthermore, all furocoumarins tested induced the expression of endogenous, immunoreactive CYP1A1 protein, primarily in the dark. In conclusion, our results demonstrate that individual furocoumarins present in food and medicinal plants can interfere with AhR-regulated CYP1A1 expression and activity in at least three major ways, i.e., (i) act as highly potent inhibitors of the catalytic activity of CYP1A1 both in the presence and absence of light, (ii) induce CYP1A1 gene expression in the absence of light via activation of the AhR, and (iii) induce CYP1A1 gene expression without activation of the AhR.

  11. Natural Disaster Induced Losses at Household Level: A Study on the Disaster Affected Migrants

    NASA Astrophysics Data System (ADS)

    Ishtiaque, A.; Nazem, N. I.; Jerin, T.

    2015-12-01

    Given its geographical location Bangladesh frequently confronts natural disasters. Disaster induced losses often obligate socio-economic dislocation from rural areas to large urban centers. After incurring what type/amount of losses people migrate is still unknown. In this paper we focus on migrants who migrated due to natural disasters. Thus, the objectives of this paper are, first, ascertaining the proportion of disaster migrants in Dhaka city; second, determining types of natural disasters which compel rural out-migration; third, assessing the resource and economic losses stem from these disasters at household level. Using the slum database (N = 4966), we select eight slums randomly with a purpose to include migrants from maximum districts available. In order to identify the proportion of disaster affected migrants a census is conducted in 407 households of those 8 slums and the result demonstrates that 18.43% of the migrants are disaster affected, which was only 5% in 1993. Out of all hydro-meteorological disasters, river bank erosion (RBE), followed by flood, drives most people out of their abode. However, unlike RBE migrants, migrants affected by flood usually return to their origin after certain period. In-depth interviews on the disaster migrants reveal that RBE claims total loss of homestead land & agricultural land while flood causes 20% and 23% loss respectively. Agricultural income decreases 96% because of RBE whereas flood victims encounter 98% decrease. People also incur 79% & 69% loss in livestock owing to RBE and flood severally. These disasters cause more than eighty percent reduction in total monthly income. Albeit RBE appears more vigorous but total economic loss is greater in flood- on average each household experiences a loss of BDT 350,555 due to flood and BDT 300,000 on account of RBE. Receiving no substantial support from community or government the affected people are compelled to migrate.

  12. Sulphoraphane, a naturally occurring isothiocyanate induces apoptosis in breast cancer cells by targeting heat shock proteins

    SciTech Connect

    Sarkar, Ruma; Mukherjee, Sutapa; Biswas, Jaydip; Roy, Madhumita

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer HSPs (27, 70 and 90) and HSF1 are overexpressed in MCF-7 and MDA-MB-231 cells. Black-Right-Pointing-Pointer Sulphoraphane, a natural isothiocyanate inhibited HSPs and HSF1 expressions. Black-Right-Pointing-Pointer Inhibition of HSPs and HSF1 lead to regulation of apoptotic proteins. Black-Right-Pointing-Pointer Alteration of apoptotic proteins activate of caspases particularly caspase 3 and 9 leading to induction of apoptosis. Black-Right-Pointing-Pointer Alteration of apoptotic proteins induce caspases leading to induction of apoptosis. -- Abstract: Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport and/or stabilization by acting as a molecular chaperone, leading to inhibition of apoptosis by both caspase dependent and/or independent pathways. HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion and metastasis. HSPs particularly 27, 70, 90 and the transcription factor heat shock factor1 (HSF1) play key roles in the etiology of breast cancer and can be considered as potential therapeutic target. The present study was designed to investigate the role of sulphoraphane, a natural isothiocyanate on HSPs (27, 70, 90) and HSF1 in two different breast cancer cell lines MCF-7 and MDA-MB-231 cells expressing wild type and mutated p53 respectively, vis-a-vis in normal breast epithelial cell line MCF-12F. It was furthermore investigated whether modulation of HSPs and HSF1 could induce apoptosis in these cells by altering the expressions of p53, p21 and some apoptotic proteins like Bcl-2, Bax, Bid, Bad, Apaf-1 and AIF. Sulphoraphane was found to down-regulate the expressions of HSP70, 90 and HSF1, though the effect on HSP27 was not pronounced. Consequences of HSP inhibition was upregulation of p21 irrespective of p53 status. Bax, Bad, Apaf-1, AIF were upregulated followed by down-regulation of Bcl-2 and this effect was prominent

  13. Human gammadelta T lymphocytes exert natural and IL-2-induced cytotoxicity to neuroblastoma cells.

    PubMed

    Schilbach, K E; Geiselhart, A; Wessels, J T; Niethammer, D; Handgretinger, R

    2000-01-01

    Human gammadelta T lymphocytes play an important role in nonadaptive reactions to infection and early tumor defense. This is the first report that freshly isolated, native gammadelta T cells of some healthy donors can kill human neuroblastoma cells to varying degrees. Their killing ability was increased and maintained during expansion and cultivation with interleukin-2 (IL-2; 400 IU/mL) for as long as 30 days (100% specific lysis at an effector-to-target cell (E:T) ratio of 20:1). gammadelta T lymphocytes without this spontaneous killing ability gained a specific cytolytic activity of 81% +/- 10.4% SD after stimulation with IL-2 for 24 hours. gammadelta cells were isolated from peripheral blood by positive enrichment (using a magnetic cell sorting system; purity, 95.2% +/- 3.2% SD, n = 21). High natural cytotoxic activity against human neuroblastoma cell lines (>50% specific lysis at an E:T ratio of 20:1) was exhibited by one of 11 donors, whereas two of 11 showed medium cytotoxicity (30% to 50% specific lysis). Eight of 11 donors showed very slight or no lytic activity against human neuroblastoma cells (<30% specific lysis). gammadelta T cells were also cytotoxic against Daudi (32.7% specific lysis at an E:T ratio of 20:1), Raji (10.3%), Colo 205 (23.1%), A 204 (54%), K 562 (100%), and SK-N-MC (100%) cells. Isolated gammadelta T cells were grown in Iscove modified Dulbecco medium with IL-2 (400 IU/mL). Increased cell proliferation (38.5% to 182%) was induced with phytohemagglutinin, IL-15, Clodronat, OKT3, or various combinations of these. Results of cold target inhibition assays suggest a natural killer-like activity of the gammadelta T-cell killing mechanism. Peptidase or papain render neuroblastoma cells unsusceptible to gammadelta T-cell killing, suggesting the involvement of antigen peptide(s) in the process of neuroblastoma cell killing. Treatment with acid phosphatase reduced specific lysis by 66.5% +/- 34.1% SD, which suggests a binding to phosphorylated

  14. Earthquake Seismic Risk Reduction in Ohio: ODNR's Efforts to Address Issues with Natural and Induced Seismicity

    NASA Astrophysics Data System (ADS)

    Besana-Ostman, G. M.

    2013-05-01

    With the increasing concerns regarding both natural and induced seismicity in Ohio, ODNR (Ohio Department of Natural Resources) initial efforts on seismic risk reduction paved way to various changes and improvement to tackle several major issues. For natural earthquakes, regional seismicity indicates a NE-SW structure in the northern portion of the area associated with a number of moderate historical earthquakes but no active trace identified. On the other hand, earthquakes of 1986 and 2011 are most probably incidents of induced seismicity that trigger more public uproar against disposal of regulated waste waters through injections. ODNR, in efforts to adapt with increasing need to regulate all operations related to both the Utica and Marcellus shale play within the state, had recently strengthen itself both through additional human resources and improved infrastructure. Tougher regulations and additional field tests were required that took effect immediately when a M4 earthquake was associated with the operations of an injection well. Public meetings were undertaken focused on educating many local inhabitants related to oil and gas operations, hydraulic fracturing, injection wells, and seismicity. Trainings for new and existing staff were regularly done especially for field inspection, data management and technology advancements. Considering the existing seismic stations that are few and distant related to sites of the injection wells, additional seismic stations were installed to gather baseline data and monitor for earthquakes within the injection area(s). Furthermore, to assess if the sites of the injection wells are safe from active structures, initial geomorphic and structural analyses indicated possible active faults in the northern portion of state oriented NE-SW. With the above-mentioned recent changes, ODNR had made a significant leap not only in the improvement of its principal regulatory role in the state for oil and gas operations but also in its

  15. Discrimination between induced and natural seismicity by means of nonlinear analysis

    NASA Astrophysics Data System (ADS)

    Turuntaev, S. B.; Melchaeva, O. Yu.; Vorohobina, S. V.

    2012-04-01

    The effect of human activity on the Earth's interior often causes activation of seismic processes, i.e., generates induced seismicity. Nowadays, the problem of distinguishing between the natural and induced seismicity have become important. The increasing interest to this problem is caused by the issues which seem to be far from related to seismicity, for examples, the reduction of greenhouse gas emissions into the atmosphere through the transition to the so-called green energy sources (such as hydrothermal power plants). Some geothermal power plants are located in the seismically active regions, which impedes referring the increase in seismic activity to the induced effects or natural variations. Efficient methods for analyzing the behavior of complex dynamical systems (to which the geophysical systems pertain) were developed in the field of nonlinear dynamics. In particular, these methods allow one to identify the changes in the state of the system, which are caused by external action. If a system exposed to some impact has changed its state, the processes in this system will contain a deterministic component defined by the external factor. The appearance of the deterministic component should decrease the fractal dimension of the attractor in the phase space of the system states (if such attractor is distinguished) and decrease the dimension of the embedding space (the number of the key parameters required for describing the behavior of the system). The Grassberger-Procaccia method is the widest-adopted approach for estimating the dimensions of the attractor and the embedding space. In the presented work, we use this method for analyzing the seismicity in several regions that suffered from technogeneous impacts. In some cases considered, the seismicity was not obviously induced. Four data sets were analyzed: (1) the seismicity in the region of the Romashkino oil field, Russia; (2) the seismic activity before and after the large-scale explosions on Burlykiya and

  16. Differentiating Induced and Natural Seismicity Using Space-Time-Magnitude Statistics Applied to the Coso Geothermal Field

    NASA Astrophysics Data System (ADS)

    Schoenball, M.; Davatzes, N. C.; Glen, J. M. G.

    2015-12-01

    A remarkable characteristic of earthquakes is their clustering in time and space, displaying their self-similarity. It remains to be tested if natural and induced earthquakes share the same behavior. The Coso Geothermal Field is one of the most seismically active areas in California and features an abundance of natural seismicity due to active tectonics and a large number of induced earthquakes resulting from geothermal power production since 1987. We study natural and induced earthquakes comparatively in the same tectonic setting at the Coso Geothermal Field. Covering the pre- and co-production periods from 1981 to 2013, we analyze inter-event times, spatial dimension, and frequency-size distributions for natural and induced earthquakes. Individually, these distributions are statistically indistinguishable. Determining the distribution of nearest-neighbor distances in a combined space-time-magnitude metric lets us identify the triggering relationship of an earthquake pair. Nearest-neighbor pairs naturally fall into two populations that are categorized as either clustered (triggered) or background (independent) events. At Coso, induced earthquakes feature a larger fraction of background seismicity compared to natural earthquakes. Furthermore, they contain a population of independent pairs at large magnitude-rescaled times and small magnitude-rescaled distances. This implies that unlike tectonic processes, stress changes induced by the field operations occur on much smaller time scales and appear to be large enough to drive small-scale faults through several seismic cycles during relatively short observation period. As a result, we record events close to previous hypocenters that occur up to a year after the preceding earthquake.

  17. Natural radioactivity contents in tobacco and radiation dose induced from smoking.

    PubMed

    Shousha, Hany A; Ahmad, Fawzia

    2012-06-01

    One of the causative factors for cancer-inducing mechanisms in humans is radioactive elements present in tobacco leaves used in the manufacture of cigarettes. Smoking of tobacco and its products increases the internal intake and radiation dose due to naturally occurring radionuclides that are considered to be one of the most significant causes of lung cancer. In this work, different commercial types of cigarettes, cigar and moassel were collected from market. Naturally occurring radionuclides (226)Ra and (214)Bi ((238)U series), (228)Ac and (228)Ra ((232)Th series), (40)K  and man-made (137)Cs were measured in tobacco using gamma-ray spectrometer. Results show that the average concentrations of (238)U, (232)Th and (40)K were 4.564, 3.940 and 1289.53 Bq kg(-1), respectively. This reflects their origin from the soil by root uptake and fertilisers used in the cultivation of tobacco plants. Concentration of (137)Cs was 0.348 Bq kg(-1) due to root uptake or deposition onto the leaf foliage. For smokers, the annual effective dose due to inhalation of (238)U varied from 49.35 to 139.40 μSv(-1) (average 104.27 μSv y(-1)), while of (232)Th from 23.86 to 111.06 μSv y(-1) (average 65.52 μSv y(-1)). The annual effective dose resulting from (137)Cs was varied from 10.96 to 24.01 nSv y(-1) (average 19.41 nSv y(-1)).

  18. Natural antioxidants protect against lead-induced damage during pregnancy and lactation in rat's pups.

    PubMed

    Massó-González, Elvira Luján; Antonio-García, María Teresa

    2009-11-01

    The aim of this study was to add further evidence to the biochemical changes produced in lead-exposed pups and to investigate the potential role of natural antioxidants against the lead-induced damage. Pregnant Wistar rats received treatments with drinking water, divided into four groups, as follows: (1) distilled water; (2) lead (300mg/L); (3) lead+Zn (20mg/L)+vitamins A (50,000U/L), C (2g/L), E (500mg/L) and B(6) (500mg/L); and (4) vitamins+Zn solution. We found a significant decrease in haemoglobin and haematocrit values as well and an increase in haemolysis among lead-exposed pups. Vitamins and zinc supplementation were effective in restoring delta-aminolevulinic acid dehydratase, inhibited by lead in erythrocytes, but did not reach control values. Lead exposure increased the production of thiobarbituric acid reactive substances (TBARS) and catalase activity in kidneys and liver that were reduced by the co-administration of vitamins and zinc. Our findings suggest that administration of antioxidants during gestation and lactation could prevent some of the negative effects of lead.

  19. Repair of naturally occurring mismatches can induce mutations in flanking DNA

    PubMed Central

    Chen, Jia; Miller, Brendan F; Furano, Anthony V

    2014-01-01

    ‘Normal’ genomic DNA contains hundreds of mismatches that are generated daily by the spontaneous deamination of C (U/G) and methyl-C (T/G). Thus, a mutagenic effect of their repair could constitute a serious genetic burden. We show here that while mismatches introduced into human cells on an SV40-based episome were invariably repaired, this process induced mutations in flanking DNA at a significantly higher rate than no mismatch controls. Most mutations involved the C of TpC, the substrate of some single strand-specific APOBEC cytidine deaminases, similar to the mutations that can typify the ‘mutator phenotype’ of numerous tumors. siRNA knockdowns and chromatin immunoprecipitation showed that TpC preferring APOBECs mediate the mutagenesis, and siRNA knockdowns showed that both the base excision and mismatch repair pathways are involved. That naturally occurring mispairs can be converted to mutators, represents an heretofore unsuspected source of genetic changes that could underlie disease, aging, and evolutionary change. DOI: http://dx.doi.org/10.7554/eLife.02001.001 PMID:24843013

  20. Repair of naturally occurring mismatches can induce mutations in flanking DNA.

    PubMed

    Chen, Jia; Miller, Brendan F; Furano, Anthony V

    2014-01-01

    'Normal' genomic DNA contains hundreds of mismatches that are generated daily by the spontaneous deamination of C (U/G) and methyl-C (T/G). Thus, a mutagenic effect of their repair could constitute a serious genetic burden. We show here that while mismatches introduced into human cells on an SV40-based episome were invariably repaired, this process induced mutations in flanking DNA at a significantly higher rate than no mismatch controls. Most mutations involved the C of TpC, the substrate of some single strand-specific APOBEC cytidine deaminases, similar to the mutations that can typify the 'mutator phenotype' of numerous tumors. siRNA knockdowns and chromatin immunoprecipitation showed that TpC preferring APOBECs mediate the mutagenesis, and siRNA knockdowns showed that both the base excision and mismatch repair pathways are involved. That naturally occurring mispairs can be converted to mutators, represents an heretofore unsuspected source of genetic changes that could underlie disease, aging, and evolutionary change.DOI: http://dx.doi.org/10.7554/eLife.02001.001. PMID:24843013

  1. Natural interspecific and intraspecific horizontal transfer of parthenogenesis-inducing Wolbachia in Trichogramma wasps.

    PubMed Central

    Huigens, M. E.; de Almeida, R. P.; Boons, P. A. H.; Luck, R. F.; Stouthamer, R.

    2004-01-01

    The intracellular bacterium Wolbachia is one of the most common symbionts in arthropods and, because of its manipulative effects on host reproduction, is assumed to be an important factor in several evolutionary processes. These bacteria are mainly vertically transmitted from mother to daughter through the egg cytoplasm, and horizontal transmission is generally assumed to be rare. Here, we show natural inter- and intraspecific horizontal transfer of parthenogenesis-inducing Wolbachia between parasitoid wasps of the genus Trichogramma. Horizontal transfer was observed when infected and uninfected larvae shared the same host egg. This is the first report, to our knowledge, on interspecific horizontal transfer of Wolbachia between closely related sympatric species. Some originally uninfected immature wasps acquired Wolbachia while inside the host egg, but not all of these newly infected females exhibited the parthenogenesis phenotype. In general, intraspecific horizontal transfer was more successful than interspecific transfer. Wolbachia underwent vertical transmission in the new species but the infection tended to be lost within several generations. Our results have important implications for understanding the evolution of Wolbachia-host associations. PMID:15129961

  2. Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR

    PubMed Central

    Pondugula, Satyanarayana R.; Flannery, Patrick C.; Abbott, Kodye L.; Coleman, Elaine S.; Mani, Sridhar; Samuel, Temesgen; Xie, Wen

    2015-01-01

    Activation of human pregnane X receptor (hPXR)-regulated expression of cytochrome P450 3A4 (CYP3A4) and multidrug resistance protein 1 (MDR1) plays an important role in mediating adverse drug interactions. Given the common use of natural products as part of adjunct human health behavior, there is a growing concern about natural products for their potential to induce undesired drug interactions through the activation of hPXR-regulated CYP3A4 and MDR1. Here, we studied whether 3,3′-diindolylmethane (DIM), a natural health supplement, could induce hPXR-mediated regulation of CYP3A4 and MDR1 in human hepatocytes and intestinal cells. DIM, at its physiologically relevant concentrations, not only induced hPXR transactivation of CYP3A4 promoter activity but also induced gene expression of CYP3A4 and MDR1. DIM decreased intracellular accumulation of MDR1 substrate rhodamine 123, suggesting that DIM induces the functional expression of MDR1. Pharmacologic inhibition or genetic knockdown of hPXR resulted in attenuation of DIM induced CYP3A4 and MDR1 gene expression, suggesting that DIM induces CYP3A4 and MDR1 in an hPXR-dependent manner. Together, these results support our conclusion that DIM induces hPXR-regulated CYP3A4 and MDR1 gene expression. The inductive effects of DIM on CYP3A4 and MDR1 expression caution the use of DIM in conjunction with other medications metabolized and transported via CYP3A4 and MDR1, respectively. PMID:25542144

  3. The Natural History of Acute Recovery of Blast-Induced Mild Traumatic Brain Injury: A Case Series During War.

    PubMed

    Larres, David T; Carr, Walter; Gonzales, Elizandro G; Hawley, Jason S

    2016-05-01

    Traumatic brain injury (TBI) secondary to blast exposure is a common injury in the Global War on Terrorism, but little is known about the acute effects, recovery, pathophysiology, and neuropathology of blast-induced mild TBI (mTBI) in humans in a battlefield environment. Moreover, there is ongoing debate whether blast-induced mTBI is a different injury with a unique pathophysiology compared with mTBI from blunt trauma. In the case series reported here from Craig Joint Theater Hospital at Bagram Airfield, Afghanistan, 15 military service members with acute concussion/mTBI associated with blast exposure were evaluated within the first 24 hours after concussion and on days 2, 3, 5, and 7 with a Graded Symptom Checklist and a balance assessment, the Balance Error Scoring System. These data suggest that the recovery in blast-induced mTBI follows the pattern of recovery in sports-related concussion reported in The National Collegiate Athletic Association Concussion Study. In this retrospective case series, we provide the first description of the natural history of acute recovery in blast-induced mTBI, and we suspect, given our experience treating military service members, that further observations of the natural history of recovery in blast-induced mTBI will continue to mirror the natural history of recovery in sports concussion.

  4. The Natural History of Acute Recovery of Blast-Induced Mild Traumatic Brain Injury: A Case Series During War.

    PubMed

    Larres, David T; Carr, Walter; Gonzales, Elizandro G; Hawley, Jason S

    2016-05-01

    Traumatic brain injury (TBI) secondary to blast exposure is a common injury in the Global War on Terrorism, but little is known about the acute effects, recovery, pathophysiology, and neuropathology of blast-induced mild TBI (mTBI) in humans in a battlefield environment. Moreover, there is ongoing debate whether blast-induced mTBI is a different injury with a unique pathophysiology compared with mTBI from blunt trauma. In the case series reported here from Craig Joint Theater Hospital at Bagram Airfield, Afghanistan, 15 military service members with acute concussion/mTBI associated with blast exposure were evaluated within the first 24 hours after concussion and on days 2, 3, 5, and 7 with a Graded Symptom Checklist and a balance assessment, the Balance Error Scoring System. These data suggest that the recovery in blast-induced mTBI follows the pattern of recovery in sports-related concussion reported in The National Collegiate Athletic Association Concussion Study. In this retrospective case series, we provide the first description of the natural history of acute recovery in blast-induced mTBI, and we suspect, given our experience treating military service members, that further observations of the natural history of recovery in blast-induced mTBI will continue to mirror the natural history of recovery in sports concussion. PMID:27168549

  5. Effects of natural and human-induced hypoxia on coastal benthos

    NASA Astrophysics Data System (ADS)

    Levin, L. A.; Ekau, W.; Gooday, A. J.; Jorissen, F.; Middelburg, J. J.; Naqvi, S. W. A.; Neira, C.; Rabalais, N. N.; Zhang, J.

    2009-10-01

    Coastal hypoxia (defined here as <1.42 ml L-1; 62.5 μM; 2 mg L-1, approx. 30% oxygen saturation) develops seasonally in many estuaries, fjords, and along open coasts as a result of natural upwelling or from anthropogenic eutrophication induced by riverine nutrient inputs. Permanent hypoxia occurs naturally in some isolated seas and marine basins as well as in open slope oxygen minimum zones. Responses of benthos to hypoxia depend on the duration, predictability, and intensity of oxygen depletion and on whether H2S is formed. Under suboxic conditions, large mats of filamentous sulfide oxidizing bacteria cover the seabed and consume sulfide. They are hypothesized to provide a detoxified microhabitat for eukaryotic benthic communities. Calcareous foraminiferans and nematodes are particularly tolerant of low oxygen concentrations and may attain high densities and dominance, often in association with microbial mats. When oxygen is sufficient to support metazoans, small, soft-bodied invertebrates (typically annelids), often with short generation times and elaborate branchial structures, predominate. Large taxa are more sensitive than small taxa to hypoxia. Crustaceans and echinoderms are typically more sensitive to hypoxia, with lower oxygen thresholds, than annelids, sipunculans, molluscs and cnidarians. Mobile fish and shellfish will migrate away from low-oxygen areas. Within a species, early life stages may be more subject to oxygen stress than older life stages. Hypoxia alters both the structure and function of benthic communities, but effects may differ with regional hypoxia history. Human-caused hypoxia is generally linked to eutrophication, and occurs adjacent to watersheds with large populations or agricultural activities. Many occurrences are seasonal, within estuaries, fjords or enclosed seas of the North Atlantic and the NW Pacific Oceans. Benthic faunal responses, elicited at oxygen levels below 2 ml L-1, typically involve avoidance or mortality of large

  6. TLR-induced cytokines promote effective proinflammatory natural Th17 cell responses.

    PubMed

    Massot, Bérangère; Michel, Marie-Laure; Diem, Séverine; Ohnmacht, Caspar; Latour, Sylvain; Dy, Michel; Eberl, Gérard; Leite-de-Moraes, Maria C

    2014-06-15

    Naive CD4 lymphocytes undergo a polarization process in the periphery to become induced Th17 (iTh17) cells. Using retinoic acid-related orphan receptor γt (RORγt)-gfp mice, we found that RORγt and the transcription factor promyelocytic leukemia zinc finger (PLZF) are valuable new markers to identify the recently described natural Th17 (nTh17) cell population. nTh17 cells are thymically committed to promptly produce large amounts of IL-17 and IL-22. In this study, we show that, in addition to responding to TCR cross-linking, nTh17 cells secrete IL-17 and IL-22 when stimulated with IL-23 plus IL-1β, either in recombinant form or in supernatants from TLR4-activated dendritic cells. This innate-like ability of RORγt(+) nTh17 cells to respond to TLR4-induced cytokines was not shared by iTh17 cells. The other distinct properties of RORγt(+) nTh17 cells are their high expression of PLZF and their absence from lamina propria; iTh17 cells are found therein. RORγt(+) nTh17 cells are present in the thymus of germ-free RORγt-gfp and IL-6(-/-) RORΓ: t-gfp mice, indicating that these cells do not require symbiotic microbiota or IL-6 for their generation. Finally, we found that PLZF(+)RORγt(+) nTh17 cells represent one of the primary IL-17-producing innate-like T cell populations in a TLR7 imiquimod model of psoriasis-like disorder, indicating their involvement in this kind of lesion. Collectively, our results reveal RORγt and PLZF as characteristic markers for identifying nTh17 cells and demonstrate one of their novel properties: the ability to respond promptly to TLR-dependent proinflammatory stimuli without TCR engagement, placing them as members of the innate-like T cell family.

  7. The natural organosulfur compound dipropyltetrasulfide prevents HOCl-induced systemic sclerosis in the mouse

    PubMed Central

    2013-01-01

    Introduction The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has antibiotic and anticancer properties, as a treatment for HOCl-induced systemic sclerosis in the mouse. Methods The prooxidative, antiproliferative, and cytotoxic effects of DPTTS were evaluated ex vivo on fibroblasts from normal and HOCl mice. In vivo, the antifibrotic and immunomodulating properties of DPTTS were evaluated in the skin and lungs of HOCl mice. Results H2O2 production was higher in fibroblasts derived from HOCl mice than in normal fibroblasts (P < 0.05). DPTTS did not increase H2O2 production in normal fibroblasts, but DPTTS dose-dependently increased H2O2 production in HOCl fibroblasts (P < 0.001 with 40 μM DPTTS). Because H2O2 reached a lethal threshold in cells from HOCl mice, the antiproliferative, cytotoxic, and proapoptotic effects of DPTTS were significantly higher in HOCl fibroblasts than for normal fibroblasts. In vivo, DPTTS decreased dermal thickness (P < 0.001), collagen content in skin (P < 0.01) and lungs (P < 0.05), αSMA (P < 0.01) and pSMAD2/3 (P < 0.01) expression in skin, formation of advanced oxidation protein products and anti-DNA topoisomerase-1 antibodies in serum (P < 0.05) versus untreated HOCl mice. Moreover, in HOCl mice, DPTTS reduced splenic B-cell counts (P < 0.01), the proliferative rates of B-splenocytes stimulated by lipopolysaccharide (P < 0.05), and T-splenocytes stimulated by anti-CD3/CD28 mAb (P < 0.001). Ex vivo, it also reduced the production of IL-4 and IL-13 by activated T cells (P < 0.05 in both cases). Conclusions The natural organosulfur compound DPTTS prevents skin and lung fibrosis in the mouse through the selective killing of diseased fibroblasts and its immunomodulating properties. DPTTS may be a potential treatment for systemic sclerosis. PMID:24286210

  8. A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells

    PubMed Central

    Adan Gökbulut, Aysun; Yaşar, Mustafa; Baran, Yusuf

    2015-01-01

    Objective: The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by Naturin Natural Products, İzmir, Turkey), on 232B4 chronic lymphocytic leukemia (CLL) cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells. Materials and Methods: The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry. Results: We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase. Conclusion: KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1. PMID:26316479

  9. Induction of the metabolic regulator Txnip in fasting-induced and natural torpor.

    PubMed

    Hand, Laura E; Saer, Ben R C; Hui, Simon T; Jinnah, Hyder A; Steinlechner, Stephan; Loudon, Andrew S I; Bechtold, David A

    2013-06-01

    Torpor is a physiological state characterized by controlled lowering of metabolic rate and core body temperature, allowing substantial energy savings during periods of reduced food availability or harsh environmental conditions. The hypothalamus coordinates energy homeostasis and thermoregulation and plays a key role in directing torpor. We recently showed that mice lacking the orphan G protein-coupled receptor Gpr50 readily enter torpor in response to fasting and have now used these mice to conduct a microarray analysis of hypothalamic gene expression changes related to the torpor state. This revealed a strong induction of thioredoxin-interacting protein (Txnip) in the hypothalamus of torpid mice, which was confirmed by quantitative RT-PCR and Western blot analyses. In situ hybridization identified the ependyma lining the third ventricle as the principal site of torpor-related expression of Txnip. To characterize further the relationship between Txnip and torpor, we profiled Txnip expression in mice during prolonged fasting, cold exposure, and 2-deoxyglucose-induced hypometabolism, as well as in naturally occurring torpor bouts in the Siberian hamster. Strikingly, pronounced up-regulation of Txnip expression was only observed in wild-type mice when driven into torpor and during torpor in the Siberian hamster. Increase of Txnip was not limited to the hypothalamus, with exaggerated expression in white adipose tissue, brown adipose tissue, and liver also demonstrated in torpid mice. Given the recent identification of Txnip as a molecular nutrient sensor important in the regulation of energy metabolism, our data suggest that elevated Txnip expression is critical to regulating energy expenditure and fuel use during the extreme hypometabolic state of torpor.

  10. Molecular Characterization of Two Natural Hotspots in the Drosophila buzzatii Genome Induced by Transposon Insertions

    PubMed Central

    Cáceres, Mario; Puig, Marta; Ruiz, Alfredo

    2001-01-01

    Transposable elements (TEs) have been implicated in the generation of genetic rearrangements, but their potential to mediate changes in the organization and architecture of host genomes could be even greater than previously thought. Here, we describe the naturally occurring structural and nucleotide variation around two TE insertions in the genome of Drosophila buzzatii. The studied regions correspond to the breakpoints of a widespread chromosomal inversion generated by ectopic recombination between oppositely oriented copies of a TE named Galileo. A detailed molecular analysis by Southern hybridization, PCR amplification, and DNA sequencing of 7.1 kb surrounding the inversion breakpoints in 39 D. buzzatii lines revealed an unprecedented degree of restructuring, consisting of 22 insertions of ten previously undescribed TEs, 13 deletions, 1 duplication, and 1 small inversion. All of these alterations occurred exclusively in inverted chromosomes and appear to have accumulated after the insertion of the Galileo elements, within or close to them. The nucleotide variation at the studied regions is six times lower in inverted than in noninverted chromosomes, suggesting that most of the observed changes originated in only 84,000 years. Galileo elements thus seemed to promote the transformation of these, otherwise normal, chromosomal regions in genetically unstable hotspots and highly efficient traps for transposon insertions. The particular features of two new Galileo copies found indicate that this TE belongs to the Foldback family. Together, our results strengthen the importance of TEs, and especially DNA transposons, as inducers of genome plasticity in evolution. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF368842–AF368859 and AF368861–AF368900. In addition, sequences submitted under accession nos. AF162796–AF162799 were used as a basis for this study.] PMID:11483576

  11. Studying human respiratory disease in animals--role of induced and naturally occurring models.

    PubMed

    Williams, Kurt; Roman, Jesse

    2016-01-01

    Respiratory disorders like asthma, emphysema, and pulmonary fibrosis affect millions of Americans and many more worldwide. Despite advancements in medical research that have led to improved understanding of the pathophysiology of these conditions and sometimes to new therapeutic interventions, these disorders are for the most part chronic and progressive; current interventions are not curative and do not halt disease progression. A major obstacle to further advancements relates to the absence of animal models that exactly resemble the human condition, which delays the elucidation of relevant mechanisms of action, the unveiling of biomarkers of disease progression, and identification of new targets for intervention in patients. There are currently many induced animal models of human respiratory disease available for study, and even though they mimic features of human disease, discoveries in these models have not always translated into safe and effective treatments in humans. A major obstacle relates to the genetic, anatomical, and functional variations amongst species, which represents the major challenge to overcome when searching for appropriate models of respiratory disease. Nevertheless, rodents, in particular mice, have become the most common species used for experimentation, due to their relatively low cost, size, and adequate understanding of murine genetics, among other advantages. Less well known is the fact that domestic animals also suffer from respiratory illnesses similar to those found in humans. Asthma, bronchitis, pneumonia, and pulmonary fibrosis are among the many disorders occurring naturally in dogs, cats, and horses, among other species. These models might better resemble the human condition and are emphasized here, but further investigations are needed to determine their relevance.

  12. Design And Ground Testing For The Expert PL4/PL5 'Natural And Roughness Induced Transition'

    NASA Astrophysics Data System (ADS)

    Masutti, Davie; Chazot, Olivier; Donelli, Raffaele; de Rosa, Donato

    2011-05-01

    Unpredicted boundary layer transition can impact dramatically the stability of the vehicle, its aerodynamic coefficients and reduce the efficiency of the thermal protection system. In this frame, ESA started the EXPERT (European eXPErimental Reentry Testbed) program to pro- vide and perform in-flight experiments in order to obtain aerothermodynamic data for the validation of numerical models and of ground-to-flight extrapolation methodologies. Considering the boundary layer transition investigation, the EXPERT vehicle is equipped with two specific payloads, PL4 and PL5, concerning respectively the study of the natural and roughness induced transition. The paper is a survey on the design process of these two in-flight experiments and it covers the major analyses and findings encountered during the development of the payloads. A large amount of transition criteria have been investigated and used to estimate either the dangerousness of the height of the distributed roughness, arising due to nose erosion, or the effectiveness of height of the isolated roughness element forcing the boundary layer transition. Supporting the PL4 design, linear stability computations and CFD analyses have been performed by CIRA on the EXPERT flight vehicle to determine the amplification factor of the boundary layer instabilities at different point of the re-entry trajectory. Ground test experiments regarding the PL5 are carried on in the Mach 6 VKI H3 Hypersonic Wind Tunnel with a Reynolds numbers ranging from 18E6/m to 26E6/m. Infrared measurements (Stanton number) and flow visualization are used on a 1/16 scaled model of the EXPERT vehicle and a flat plate to validate the Potter and Whitfield criterion as a suitable methodology for ground-to-flight extrapolation and the payload design.

  13. Activation of decidual invariant natural killer T cells promotes lipopolysaccharide-induced preterm birth.

    PubMed

    Li, Liping; Yang, Jing; Jiang, Yao; Tu, Jiaoqin; Schust, Danny J

    2015-04-01

    Invariant natural killer T (iNKT) cells are crucial for host defense against a variety of microbial pathogens, but the underlying mechanisms of iNKT cells activation by microbes are not fully explained. In this study, we investigated the molecular mechanisms of iNKT cell activation in lipopolysaccharide (LPS)-stimulated preterm birth using an adoptive transfer system and diverse neutralizing antibodies (Abs) and inhibitors. We found that adoptive transfer of decidual iNKT cells to LPS-stimulated iNKT cell deficient Jα18(-/-) mice that lack invariant Vα14Jα281T cell receptor (TCR) expression significantly decreased the time to delivery and increased the percentage of decidual iNKT cells. Neutralizing Abs against Toll-like receptor 4 (TLR-4), CD1d, interleukin (IL)-12 and IL-18, and inhibitors blocking the activation of nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) p38 and extracellular signal-regulated kinase (ERK) significantly reduced in vivo percentages of decidual iNKT cells, their intracellular interferon (IFN)-γ production and surface CD69 expression. In vitro, in the presence of the same Abs and inhibitors used as in vivo, decidual iNKT cells co-cultured with LPS-pulsed dendritic cells (DCs) showed significantly decreased extracellular and intracellular IFN-γ secretion and surface CD69 expression. Our data demonstrate that the activation of decidual iNKT cells plays an important role in inflammation-induced preterm birth. Activation of decidual iNKT cells also requires TLR4-mediated NF-κB, MAPK p38 and ERK pathways, the proinflammatory cytokines IL-12 and IL-18, and endogenous glycolipid antigens presented by CD1d.

  14. Structural and spectroscopic changes to natural nontronite induced by experimental impacts between 10 and 40 GPa

    NASA Astrophysics Data System (ADS)

    Friedlander, Lonia R.; Glotch, Timothy D.; Bish, David L.; Dyar, M. Darby; Sharp, Thomas G.; Sklute, Elizabeth C.; Michalski, Joseph R.

    2015-05-01

    Many phyllosilicate deposits remotely detected on Mars occur within bombarded terrains. Shock metamorphism from meteor impacts alters mineral structures, producing changed mineral spectra. Thus, impacts have likely affected the spectra of remotely sensed Martian phyllosilicates. We present spectral analysis results for a natural nontronite sample before and after laboratory-generated impacts over five peak pressures between 10 and 40 GPa. We conducted a suite of spectroscopic analyses to characterize the sample's impact-induced structural and spectral changes. Nontronite becomes increasingly disordered with increasing peak impact pressure. Every infrared spectroscopic technique used showed evidence of structural changes at shock pressures above ~25 GPa. Reflectance spectroscopy in the visible near-infrared region is primarily sensitive to the vibrations of metal-OH and interlayer H2O groups in the nontronite octahedral sheet. Midinfrared (MIR) spectroscopic techniques are sensitive to the vibrations of silicon and oxygen in the nontronite tetrahedral sheet. Because the tetrahedral and octahedral sheets of nontronite deform differently, impact-driven structural deformation may contribute to differences in phyllosilicate detection between remote sensing techniques sensitive to different parts of the nontronite structure. Observed spectroscopic changes also indicated that the sample's octahedral and tetrahedral sheets were structurally deformed but not completely dehydroxylated. This finding is an important distinction from previous studies of thermally altered phyllosilicates in which dehydroxylation follows dehydration in a stepwise progression preceding structural deformation. Impact alteration may thus complicate mineral-specific identifications based on the location of OH-group bands in remotely detected spectra. This is a key implication for Martian remote sensing arising from our results.

  15. Induced Pluripotent Stem Cell-Derived Natural Killer Cells for Treatment of Ovarian Cancer.

    PubMed

    Hermanson, David L; Bendzick, Laura; Pribyl, Lee; McCullar, Valarie; Vogel, Rachel Isaksson; Miller, Jeff S; Geller, Melissa A; Kaufman, Dan S

    2016-01-01

    Natural killer (NK) cells can provide effective immunotherapy for ovarian cancer. Here, we evaluated the ability of NK cells isolated from peripheral blood (PB) and NK cells derived from induced pluripotent stem cell (iPSC) to mediate killing of ovarian cancer cells in a mouse xenograft model. A mouse xenograft model was used to evaluate the intraperitoneal delivery of three different NK cell populations: iPSC-derived NK cells, PB-NK cells that had been activated and expanded in long-term culture, and overnight activated PB-NK cells that were isolated through CD3/CD19 depletion of PB B and T cells. Bioluminescent imaging was used to monitor tumor burden of luciferase expressing tumor lines. Tumors were allowed to establish prior to administering NK cells via intraperitoneal injection. These studies demonstrate a single dose of any of the three NK cell populations significantly reduced tumor burden. When mice were given three doses of either iPSC-NK cells or expanded PB-NK cells, the median survival improved from 73 days in mice untreated to 98 and 97 days for treated mice, respectively. From these studies, we conclude iPSC-derived NK cells mediate antiovarian cancer killing at least as well as PB-NK cells, making these cells a viable resource for immunotherapy for ovarian cancer. Due to their ability to be easily differentiated into NK cells and their long-term expansion potential, iPSCs can be used to produce large numbers of well-defined NK cells that can be banked and used to treat a large number of patients including treatment with multiple doses if necessary.

  16. Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies

    PubMed Central

    Pittari, Gianfranco; Filippini, Perla; Gentilcore, Giusy; Grivel, Jean-Charles; Rutella, Sergio

    2015-01-01

    Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies. PMID:26029215

  17. A quantitative analysis of microbially-induced calcite precipitation employing artificial and naturally-occurring sediments

    NASA Astrophysics Data System (ADS)

    Lokier, Stephen; Krieg Dosier, Ginger

    2013-04-01

    Microbially-induced calcite precipitation is a strong candidate for the production of sustainable construction materials. The process employs the microbe Sporosarcina pasteurii as an agent to microbially mediate the precipitation of calcium carbonate to bind unconsolidated sediment. As this process can be achieved under ambient temperature conditions and can utilise a wide variety of easily-available sediments, potentially including waste materials, it is envisioned that this procedure could significantly reduce carbon-dioxide emissions in the construction industry. This study describes and quantifies the precipitation of calcite cement in a range of naturally-occurring sediments compared with a control matrix. The study establishes the optimum treatment time for effective cement precipitation in order to produce a material that meets the standards required for construction whilst keeping economic and environmental outlays at a minimum. The 'control sediment' employed industrial-grade glass beads with a grain size range of 595-1180 microns (16-30 US mesh). Sporosarcina pasteurii were mixed in a solution of urea and calcium chloride and then inoculated into the control sediment. The microbes attach to the surface of the sediment grains and employ urea as a source of energy to produce ammonia and carbon dioxide. By so doing, they increase the pH of the solution allowing calcium carbonate to precipitate at the cell walls to act as nucleation points facilitating the precipitation of cements as a grain-coating and biocementing the unconsolidated sediment. The solution treatment was repeated at eight hour intervals with samples removed for detailed analysis after each every five consecutive treatments (i.e. 40 hours). The process was repeated to produce 20 samples with treatment times between 40 and 800 hours. Cemented samples were impregnated with blue epoxy and examined petrographically to monitor cement development. Modal analysis was undertaken on each cemented

  18. Laser-beam-induced current microscopy of electric fields in natural minerals caused by impurity zonation and structural defects

    NASA Astrophysics Data System (ADS)

    Laird, Jamie S.; Johnson, Brett C.; Ryan, Chris G.

    2012-08-01

    Regions of band-bending in semiconducting sulfide minerals are thought to drive both electrochemical reactions with passing fluids resulting in precious metal ore genesis in undersaturated solutions, and bacterial oxidation by ferro-oxidans. Better understanding the role of these regions and their surface texturing on likely seeding spots and growth/dissolution rates requires large scale imaging of regions sustaining these fields. In this paper, we describe a system and methodology based on a scanning laser microscope technique called laser-beam-induced current (LBIC) for imaging fields in natural sulfides. The technique is illustrated on a synthetic junction fabricated using Au and Pt Schottky barriers on natural cubic pyrite, followed by an initial scope on a natural chalcopyrite assemblage. Different modes of LBIC imaging are discussed in light of complexity within real mineral assemblages. The remote contact mode is found to be ideal for natural samples and reasons for this conclusion are detailed.

  19. Human natural immunoglobulin M antibodies induce apoptosis of human neuroblastoma cells by binding to a Mr 260,000 antigen.

    PubMed

    David, K; Ollert, M W; Vollmert, C; Heiligtag, S; Eickhoff, B; Erttmann, R; Bredehorst, R; Vogel, C W

    1999-08-01

    Sera of healthy humans contain natural cytotoxic IgM antibodies that specifically recognize a Mr 260,000 antigen (NB-p260) on the surface of human neuroblastoma (NB) cells. Here we demonstrate that anti-NB IgM antibodies prepared from different healthy individuals induce, in all human NB cell lines analyzed thus far, typical morphological and biochemical features of apoptosis including nuclear fragmentation, chromatin condensation, and DNA fragmentation. Both the binding of human anti-NB IgM to NB cells and the induction of apoptosis could be inhibited by preincubation of NB cells with murine IgG raised against purified NB-p260. Furthermore, preincubation of human anti-NB IgM with purified NB-p260 immobilized onto a solid support abolished its ability to induce apoptosis in NB cells. Natural human anti-NB IgM failed to bind to and induce apoptosis in control tumor cell lines that lack expression of NB-p260. The anti-NB IgM-induced apoptotic response was also observed in vivo in xenografted human NB tumors. After a single i.v. injection of anti-NB IgM into nude rats bearing solid NB xenografts, many areas of pyknotic cells with fragmented nuclei were observed that stained positive using the terminal dUTP nick end labeling method. In conclusion, the data demonstrate that natural anti-NB IgM antibodies in the sera of healthy individuals are potent mediators of apoptotic cell death of NB cells both in vitro and in vivo. The NB-p260 antigen was identified as the apoptosis-inducing receptor for anti-NB IgM. Whereas natural anti-NB IgM and NB-p260 may be useful tools for immunotherapy of NB, their biological significance remains to be determined.

  20. 2016 one-year seismic hazard forecast for the Central and Eastern United States from induced and natural earthquakes

    USGS Publications Warehouse

    Petersen, Mark D.; Mueller, Charles S.; Moschetti, Morgan P.; Hoover, Susan M.; Llenos, Andrea L.; Ellsworth, William L.; Michael, Andrew J.; Rubinstein, Justin L.; McGarr, Arthur F.; Rukstales, Kenneth S.

    2016-03-28

    The U.S. Geological Survey (USGS) has produced a 1-year seismic hazard forecast for 2016 for the Central and Eastern United States (CEUS) that includes contributions from both induced and natural earthquakes. The model assumes that earthquake rates calculated from several different time windows will remain relatively stationary and can be used to forecast earthquake hazard and damage intensity for the year 2016. This assessment is the first step in developing an operational earthquake forecast for the CEUS, and the analysis could be revised with updated seismicity and model parameters. Consensus input models consider alternative earthquake catalog durations, smoothing parameters, maximum magnitudes, and ground motion estimates, and represent uncertainties in earthquake occurrence and diversity of opinion in the science community. Ground shaking seismic hazard for 1-percent probability of exceedance in 1 year reaches 0.6 g (as a fraction of standard gravity [g]) in northern Oklahoma and southern Kansas, and about 0.2 g in the Raton Basin of Colorado and New Mexico, in central Arkansas, and in north-central Texas near Dallas. Near some areas of active induced earthquakes, hazard is higher than in the 2014 USGS National Seismic Hazard Model (NHSM) by more than a factor of 3; the 2014 NHSM did not consider induced earthquakes. In some areas, previously observed induced earthquakes have stopped, so the seismic hazard reverts back to the 2014 NSHM. Increased seismic activity, whether defined as induced or natural, produces high hazard. Conversion of ground shaking to seismic intensity indicates that some places in Oklahoma, Kansas, Colorado, New Mexico, Texas, and Arkansas may experience damage if the induced seismicity continues unabated. The chance of having Modified Mercalli Intensity (MMI) VI or greater (damaging earthquake shaking) is 5–12 percent per year in north-central Oklahoma and southern Kansas, similar to the chance of damage caused by natural earthquakes

  1. 2016 one-year seismic hazard forecast for the Central and Eastern United States from induced and natural earthquakes

    USGS Publications Warehouse

    Petersen, Mark D.; Mueller, Charles S.; Moschetti, Morgan P.; Hoover, Susan M.; Llenos, Andrea L.; Ellsworth, William L.; Michael, Andrew J.; Rubinstein, Justin L.; McGarr, Arthur F.; Rukstales, Kenneth S.

    2016-01-01

    The U.S. Geological Survey (USGS) has produced a 1-year seismic hazard forecast for 2016 for the Central and Eastern United States (CEUS) that includes contributions from both induced and natural earthquakes. The model assumes that earthquake rates calculated from several different time windows will remain relatively stationary and can be used to forecast earthquake hazard and damage intensity for the year 2016. This assessment is the first step in developing an operational earthquake forecast for the CEUS, and the analysis could be revised with updated seismicity and model parameters. Consensus input models consider alternative earthquake catalog durations, smoothing parameters, maximum magnitudes, and ground motion estimates, and represent uncertainties in earthquake occurrence and diversity of opinion in the science community. Ground shaking seismic hazard for 1-percent probability of exceedance in 1 year reaches 0.6 g (as a fraction of standard gravity [g]) in northern Oklahoma and southern Kansas, and about 0.2 g in the Raton Basin of Colorado and New Mexico, in central Arkansas, and in north-central Texas near Dallas. Near some areas of active induced earthquakes, hazard is higher than in the 2014 USGS National Seismic Hazard Model (NHSM) by more than a factor of 3; the 2014 NHSM did not consider induced earthquakes. In some areas, previously observed induced earthquakes have stopped, so the seismic hazard reverts back to the 2014 NSHM. Increased seismic activity, whether defined as induced or natural, produces high hazard. Conversion of ground shaking to seismic intensity indicates that some places in Oklahoma, Kansas, Colorado, New Mexico, Texas, and Arkansas may experience damage if the induced seismicity continues unabated. The chance of having Modified Mercalli Intensity (MMI) VI or greater (damaging earthquake shaking) is 5–12 percent per year in north-central Oklahoma and southern Kansas, similar to the chance of damage caused by natural earthquakes

  2. The Illusion of the Positive: The impact of natural and induced mood on older adults’ false recall

    PubMed Central

    Emery, Lisa; Hess, Thomas M.; Elliot, Tonya

    2012-01-01

    Recent research suggests that affective and motivational processes can influence age differences in memory. In the current study, we examine the impact of both natural and induced mood state on age differences in false recall. Older and younger adults performed a version of the Deese-Roediger-McDermott (DRM; Roediger & McDermott, 1995) false memory paradigm in either their natural mood state or after a positive or negative mood induction. Results indicated that, after accounting for age differences in basic cognitive function, age-related differences in positive mood during the testing session were related to increased false recall in older adults. Inducing older adults into a positive mood also exacerbated age differences in false memory. In contrast, veridical recall did not appear to be systematically influenced by mood. Together, these results suggest that positive mood states can impact older adults’ information processing and potentially increase underlying cognitive age differences. PMID:22292431

  3. Impacts of natural and human-induced disturbances on carbon dynamics in Northern Eurasia

    NASA Astrophysics Data System (ADS)

    Shvidenko, A.; Shchepashchenko, D.

    2012-12-01

    Disturbance regimes (DR) of vegetation ecosystems of Northern Eurasia (NE, limited to Russian territories) are represented by complicated and interacting sets of natural and human-induced disturbances (D). We present a unified classification of D and DR in major land cover classes of Northern Eurasia (forests, agriculture, wetlands, shrubs & grasses), their connections to succession regularities, and minimal informative set of indicators, which are able to describe both specifics of individual types of D and their impacts on annual carbon budget. The assessment of extent, severity and consequences of D was done based on an Integrated Land Information System for Russia, which accumulated all relevant spatially distributed information including multi-sensor and multi-temporal remote sensing concept, in situ measurements and ground data from diverse inventories and surveys. Major emissions caused by D are produced by consumption of plant products (agriculture and forestry), wild fire, and biotic D (basically insect outbreaks). For example, the annual flux due to human consumption of plant products is estimated at 170 Tg C yr-1. Wild fire in 1998-2010 enveloped 106.9 x 106 ha-1, on average 8.23 x 106 ha-1 yr-1, with variation from 4.2 to 17.3 x 106 ha-1 yr-1. Average direct carbon emissions due to wildfire were estimated to be at 121.0 Tg C yr-1, including 84.6% as C-CO2, 8.2% C-CO, C-CH4 - 1.1%, C-NMHC - 1.2%, organic carbon - 1.2% and black carbon - 0.1%, particulate matter 3.5%, of which PM2.5 - 1.2%. About 2/3 of burnt area and carbon emissions were on forest land. While the area of fire on wetlands was only 7.3%, this land class delivered 15.2% of the total fire emissions. Emissions caused by biotic D (accounted for forests only) is estimated at 50.8 Tg C yr-1. Overall, direct emissions due to D amounted at about 350 Tg C yr-1, or ~7% of annual Net Primary Production of terrestrial ecosystems of Russia. These data do not include long-term consequences of D, which

  4. The influence of age and genetics on natural resistance to experimentally induced feline infectious peritonitis.

    PubMed

    Pedersen, Niels C; Liu, Hongwei; Gandolfi, Barbara; Lyons, Leslie A

    2014-11-15

    Naturally occurring feline infectious peritonitis (FIP) is usually fatal, giving the impression that immunity to the FIP virus (FIPV) is extremely poor. This impression may be incorrect, because not all cats experimentally exposed to FIPV develop FIP. There is also a belief that the incidence of FIP may be affected by a number of host, virus, and environmental cofactors. However, the contribution of these cofactors to immunity and disease incidence has not been determined. The present study followed 111 random-bred specific pathogen free (SPF) cats that were obtained from a single research breeding colony and experimentally infected with FIPV. The cats were from several studies conducted over the past 5 years, and as a result, some of them had prior exposure to feline enteric coronavirus (FECV) or avirulent FIPVs. The cats were housed under optimized conditions of nutrition, husbandry, and quarantine to eliminate most of the cofactors implicated in FIPV infection outcome and were uniformly challenge exposed to the same field strain of serotype 1 FIPV. Forty of the 111 (36%) cats survived their initial challenge exposure to a Type I cat-passaged field strains of FIPV. Six of these 40 survivors succumbed to FIP to a second or third challenge exposure, suggesting that immunity was not always sustained. Exposure to non-FIP-inducing feline coronaviruses prior to challenge with virulent FIPV did not significantly affect FIP incidence but did accelerate the disease course in some cats. There were no significant differences in FIP incidence between males and females, but resistance increased significantly between 6 months and 1 or more years of age. Genetic testing was done on 107 of the 111 infected cats. Multidimensional scaling (MDS) segregated the 107 cats into three distinct families based primarily on a common sire(s), and resistant and susceptible cats were equally distributed within each family. Genome-wide association studies (GWAS) on 73 cats that died of FIP

  5. The influence of age and genetics on natural resistance to experimentally induced feline infectious peritonitis.

    PubMed

    Pedersen, Niels C; Liu, Hongwei; Gandolfi, Barbara; Lyons, Leslie A

    2014-11-15

    Naturally occurring feline infectious peritonitis (FIP) is usually fatal, giving the impression that immunity to the FIP virus (FIPV) is extremely poor. This impression may be incorrect, because not all cats experimentally exposed to FIPV develop FIP. There is also a belief that the incidence of FIP may be affected by a number of host, virus, and environmental cofactors. However, the contribution of these cofactors to immunity and disease incidence has not been determined. The present study followed 111 random-bred specific pathogen free (SPF) cats that were obtained from a single research breeding colony and experimentally infected with FIPV. The cats were from several studies conducted over the past 5 years, and as a result, some of them had prior exposure to feline enteric coronavirus (FECV) or avirulent FIPVs. The cats were housed under optimized conditions of nutrition, husbandry, and quarantine to eliminate most of the cofactors implicated in FIPV infection outcome and were uniformly challenge exposed to the same field strain of serotype 1 FIPV. Forty of the 111 (36%) cats survived their initial challenge exposure to a Type I cat-passaged field strains of FIPV. Six of these 40 survivors succumbed to FIP to a second or third challenge exposure, suggesting that immunity was not always sustained. Exposure to non-FIP-inducing feline coronaviruses prior to challenge with virulent FIPV did not significantly affect FIP incidence but did accelerate the disease course in some cats. There were no significant differences in FIP incidence between males and females, but resistance increased significantly between 6 months and 1 or more years of age. Genetic testing was done on 107 of the 111 infected cats. Multidimensional scaling (MDS) segregated the 107 cats into three distinct families based primarily on a common sire(s), and resistant and susceptible cats were equally distributed within each family. Genome-wide association studies (GWAS) on 73 cats that died of FIP

  6. SmI(2)-induced reductive cyclizations for the synthesis of cyclic ethers and applications in natural product synthesis.

    PubMed

    Nakata, Tadashi

    2010-06-01

    This tutorial review covers SmI(2)-induced reductive cyclizations of beta-alkoxyacrylate, beta-alkoxyvinyl sulfone, and beta-alkoxyvinyl sulfoxide, as methods for efficient construction of cyclic ethers. These cyclizations were developed as tools to aid in the total synthesis of marine polycyclic ethers, whose complex, synthetically challenging structures and potent bioactivities have attracted the attention of numerous synthetic organic chemists. Applications of the methods to total syntheses of various natural products containing cyclic ether are also described.

  7. Citrus aurantium increases seizure latency to PTZ induced seizures in zebrafish thru NMDA and mGluR's I and II

    PubMed Central

    Rosa-Falero, Coral; Torres-Rodríguez, Stephanie; Jordán, Claudia; Licier, Rígel; Santiago, Yolimar; Toledo, Zuleyma; Santiago, Marely; Serrano, Kiara; Sosa, Jeffrey; Ortiz, José G.

    2015-01-01

    Epilepsy is a serious neurological condition and pharmacotherapy is not effective for all patients and causes serious adverse effects and pharmacokinetic and pharmacodynamic interactions. Natural products and ethnobotanical resources can help develop new therapeutic options for conditions like epilepsy. In Puerto Rico, ethnobotanical resources highlight the anxiolytic properties of a tea like preparation made from the leaves of the Citrus aurantium tree or bitter orange. Studies performed with essential oils from the peel of the fruit have shown to increase seizure latency to pentylenetetrazole (PTZ) and maximal electroshock seizure in mice. We characterized the extract composition, and used a model of PTZ induces seizures in the zebrafish and a receptor-ligand binding assay to determine if this preparation has anticonvulsant properties and its mechanism of action. We determined that the aqueous extract made from the leaves of the C. aurantium tree contains hesperidin, neohesperidin, and neohesperidin dihydrochalcone. Using our zebrafish model, we determined that exposure to the C. aurantium 28 mg/mL extract in aquarium water increases seizure latency by 119% compared to controls. We ruled out a mechanism involving GABAA receptors using the selective antagonist gabazine. We used two approaches to study the role of glutamate in the mechanism of the C. aurantium extract. The ligand binding assay revealed C. aurantium extracts at concentrations of 0.42 to 5.6 mg/mL significantly reduced [3H]Glu binding indicating an interaction with glutamate receptors, in particular with NMDA receptors and mGluR II. This interaction was confirmed with our animal model using selective receptor antagonists and we identified an interaction with mGluR I, not observed in the ligand binding experiment. These study provide evidence of the anticonvulsant properties of the aqueous extract made from the leaves of the C. aurantium tree and a mechanism involving NMDA and mGluR's I and II. PMID

  8. Inhibitory action of conventional food-grade natural antioxidants and of natural antioxidants of new development on the thermal-induced oxidation of cholesterol.

    PubMed

    Valenzuela, Alfonso; Sanhueza, Julio; Alonso, Pilar; Corbari, Alicia; Nieto, Susana

    2004-03-01

    Cholesterol is a molecule with an unsaturated bond; therefore, like polyunsaturated fatty acids, it is prone to oxidation. Cholesterol oxidation products (COPs) are found in many common foods and have been shown to be atherogenic, cytotoxic, mutagenic and possibly carcinogenic. Therefore, efforts to prevent or to avoid COPs formation during manufacture and/or processing of foods are of high priority. The effect of natural antioxidants on COPs formation has not been extensively studied. We assayed the effect of some widely applied natural antioxidants, such as tocopherol homologs (alpha-T, gamma-T, and delta-T) and rosemary extract, and of some natural products of newly developed as antioxidants, such as the flavonoids quercetin, catechin, morin, and rutin, and also of an alkaloid-derived product, boldine, to inhibit cholesterol oxidation of soybean oil, added of cholesterol, induced in the Rancimat test conditions (150 degrees C and air bubbling). Formation of six different COPs at the induction period and at the 100 microS conductivity value was monitored by gas chromatography. Under the experimental conditions gamma-T, quercetin, and rosemary extract prove effective to inhibit both soybean oil oxidation and COP formation. alpha-T, catechin, and morin are less efficient to prevent COP formation. delta-T, rutin and boldine are devoid of protective action against COP formation. gamma-T, quercetin and rosemary extract may inhibit COP formation from the nucleus and from the lateral chain of the cholesterol molecule.

  9. Natural compound oblongifolin C inhibits autophagic flux, and induces apoptosis and mitochondrial dysfunction in human cholangiocarcinoma QBC939 cells

    PubMed Central

    Zhang, Aiqing; He, Wei; Shi, Huimin; Huang, Xiaodan; Ji, Guozhong

    2016-01-01

    The compounds, which are obtained from natural plants or microbes may offer potential as one of the strategies for the management of cholangiocarcinoma. Oblongifolin C (OC), a natural small molecule compound extracted and purified from Garcinia yunnanensis Hu, can activate the mitochondrial apoptotic pathway in human cervical cancer cells. However, the direct effects of OC on cholangiocarcinoma cells are not well defined. The effect of OC on cell apoptosis and its underlying mechanisms were investigated in cultured QBC939 cells by the methyl thiazol tetrazolium assay, mitochondrial membrane potential, ATP content and western blot analysis. The present study reported that the in vitro treatment of human cholangiocarcinoma QBC939 cells with different concentrations (5, 10, 20 and 40 μM) of OC decreased cell viability and induced apoptosis in a dose-dependent manner. The results of the present study also showed that OC-induced QBC939 cell apoptosis was mediated through the inhibition of autophagy and mitochondrial dysfunction (MtD). Additionally, inhibiting autophagy increased OC-induced apoptosis and MtD, whereas exposure to the autophagy inducer, rapmycin, attenuated these changes. Together, the results of the present study are the first, to the best of our knowledge, to identify OC as a chemotherapeutic agent against human cholangiocarcinoma QBC939 cells in vitro via the regulation of autophagy and MtD. PMID:27499017

  10. Identification Of Natural Dyes On Archaeological Textile Objects Using Laser Induced Fluorescent Technique

    NASA Astrophysics Data System (ADS)

    Abdel-Kareem, O.; Eltokhy, A.; Harith, M. A.

    2011-09-01

    This study aims to evaluate the use of Laser Fluorescent as a non-destructive technique for identification of natural dyes on archaeological textile objects. In this study wool textile samples were dyed with 10 natural dyes such as cochineal, cutch, henna, indigo, Lac, madder, safflower, saffron, sumac and turmeric. These dyes common present on archaeological textile objects to be used as standard dyed textile samples. These selected natural dyes will be used as known references that can be used a guide to identify unknown archaeological dyes. The dyed textile samples were investigated with laser radiation in different wavelengths to detect the best wavelengths for identification each dye. This study confirms that Laser Florescent is very useful and a rapid technique can be used as a non-destructive technique for identification of natural dyes on archaeological textile objects. The results obtained with this study can be a guide for all conservators in identification of natural organic dyes on archaeological textile objects.

  11. Identification Of Natural Dyes On Archaeological Textile Objects Using Laser Induced Fluorescent Technique

    SciTech Connect

    Abdel-Kareem, O.; Eltokhy, A.; Harith, M. A.

    2011-09-22

    This study aims to evaluate the use of Laser Fluorescent as a non-destructive technique for identification of natural dyes on archaeological textile objects. In this study wool textile samples were dyed with 10 natural dyes such as cochineal, cutch, henna, indigo, Lac, madder, safflower, saffron, sumac and turmeric. These dyes common present on archaeological textile objects to be used as standard dyed textile samples. These selected natural dyes will be used as known references that can be used a guide to identify unknown archaeological dyes. The dyed textile samples were investigated with laser radiation in different wavelengths to detect the best wavelengths for identification each dye. This study confirms that Laser Florescent is very useful and a rapid technique can be used as a non-destructive technique for identification of natural dyes on archaeological textile objects. The results obtained with this study can be a guide for all conservators in identification of natural organic dyes on archaeological textile objects.

  12. Ectoin: an effective natural substance to prevent UVA-induced premature photoaging.

    PubMed

    Buenger, J; Driller, H

    2004-01-01

    With the help of a new 'UVA stress model', it was shown that Ectoin protects the skin from the effects of UVA-induced cell damage in a number of different ways. Using cell cultures, high-performance thin-layer chromatography, gel electrophoresis mobility shift assays, reverse transcriptase polymerase chain reaction, ion exchange chromatography and UV spectroscopy, it was demonstrated that the UVA-induced second messenger release, transcription factor AP-2 activation, intercellular adhesion molecule-1 expression and mitochondrial DNA mutation could be prevented. The results obtained clearly demonstrate that Ectoin counteracts the effects of UVA-induced and accelerated skin aging at different cell levels.

  13. The intensive terahertz electroluminescence induced by Bloch oscillations in SiC natural superlattices.

    PubMed

    Sankin, Vladimir; Andrianov, Alexandr; Petrov, Alexey; Zakhar'in, Alexey; Lepneva, Ala; Shkrebiy, Pavel

    2012-10-09

    : We report on efficient terahertz (THz) emission from high-electric-field-biased SiC structures with a natural superlattice at liquid helium temperatures. The emission spectrum demonstrates a single line, the maximum of which shifts linearly with increases in bias field. We attribute this emission to steady-state Bloch oscillations of electrons in the SiC natural superlattice. The properties of the THz emission agree fairly with the parameters of the Bloch oscillator regime, which have been proven by high-field electron transport studies of SiC structures with natural superlattices.

  14. The intensive terahertz electroluminescence induced by Bloch oscillations in SiC natural superlattices

    PubMed Central

    2012-01-01

    We report on efficient terahertz (THz) emission from high-electric-field-biased SiC structures with a natural superlattice at liquid helium temperatures. The emission spectrum demonstrates a single line, the maximum of which shifts linearly with increases in bias field. We attribute this emission to steady-state Bloch oscillations of electrons in the SiC natural superlattice. The properties of the THz emission agree fairly with the parameters of the Bloch oscillator regime, which have been proven by high-field electron transport studies of SiC structures with natural superlattices. PMID:23043773

  15. Leishmanicidal and cytotoxic activities of extracts and naturally-occurring compounds from two Lauraceae species.

    PubMed

    Sánchez-Suárez, Jeysson; Coy-Barrera, Ericsson; Cuca, Luis Enrique; Delgado, Gabriela

    2011-02-01

    The in vitro leishmanicidal effects of ethanolic extracts and fifteen naturally-occurring compounds (five lignans, eight neolignans, a diterpene and a dihydrochalcone), obtained from Pleurothyrium cinereum and Ocotea macrophylla, were evaluated on promastigotes of Leishmania panamensis and L. braziliensis. In addition, in order to determine the selective action on Leishmania species as a safety principle, in vitro cytotoxicity on J774 cells was also evaluated for test compounds and extracts. One extract and seven compounds showed activity against Leishmania parasites at different levels. Dihydroflavokawin B (8) was found to be the most potent antileishmanial compound on both parasites, whilst (+)-otobaphenol (14), was found to be the most selective compound on L. panamensis. PMID:21425681

  16. Light-Induced Transformations of the C60 Derivative, Fullerenol: Interactions with Natural Organic Matter

    EPA Science Inventory

    Recent studies have indicated that fullerenes, an important class of nanomaterials, are photodegraded by solar radiation and can sensitize the photoproduction of reactive oxygen species such as singlet oxygen. Because natural organic matter (NOM) can retard photoreactions that a...

  17. Natural and induced polyploidy in Acacia dealbata Link. and Acacia mangium Willd.

    PubMed

    Blakesley, David; Allen, Annabel; Pellny, Till K; Roberts, Andy V

    2002-09-01

    Seeds were obtained from seven natural populations of Acacia dealbata, three natural populations of A. mangium and a seed orchard of A. mangium, representing the natural range of the two species. Polyploids were discovered in two of the seven populations of A. dealbata. The 2C DNA amount for diploid A. dealbata (2n = 2x = 26) was 1.74 pg, and for diploid A. mangium (2n = 2x = 26) was 1.30 pg. A naturally occurring tetraploid of A. dealbata (2n = 4x = 52) had a 2C DNA amount of 3.41 pg and a naturally occurring triploid genotype had a 2C DNA amount of 2.53 pg. The use of colchicine and oryzalin was investigated as a means of producing higher frequencies of tetraploids of both A. mangium and A. dealbata for incorporation into breeding programmes. Colchicine treatment gave tetraploid frequencies up to 29% for A. dealbata seedlings, and up to 18% for A. mangium seedlings. In contrast, no tetraploid A. mangium was detected following oryzalin treatment, and the low frequencies of tetraploids observed in A. dealbata could be attributed to their natural occurrence. PMID:12234151

  18. Natural and Induced Polyploidy in Acacia dealbata Link. and Acacia mangium Willd.

    PubMed Central

    BLAKESLEY, DAVID; ALLEN, ANNABEL; PELLNY, TILL K.; ROBERTS, ANDY V.

    2002-01-01

    Seeds were obtained from seven natural populations of Acacia dealbata, three natural populations of A. mangium and a seed orchard of A. mangium, representing the natural range of the two species. Polyploids were discovered in two of the seven populations of A. dealbata. The 2C DNA amount for diploid A. dealbata (2n = 2x = 26) was 1·74 pg, and for diploid A. mangium (2n = 2x = 26) was 1·30 pg. A naturally occurring tetraploid of A. dealbata (2n = 4x = 52) had a 2C DNA amount of 3·41 pg and a naturally occurring triploid genotype had a 2C DNA amount of 2·53 pg. The use of colchicine and oryzalin was investigated as a means of producing higher frequencies of tetraploids of both A. mangium and A. dealbata for incorporation into breeding programmes. Colchicine treatment gave tetraploid frequencies up to 29 % for A. dealbata seedlings, and up to 18 % for A. mangium seedlings. In contrast, no tetraploid A. mangium was detected following oryzalin treatment, and the low frequencies of tetraploids observed in A. dealbata could be attributed to their natural occurrence. PMID:12234151

  19. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death

    SciTech Connect

    Lyu, Qing; Tou, Fangfang; Su, Hong; Wu, Xiaoyong; Chen, Xinyi; Zheng, Zhi

    2015-06-19

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway.

  20. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death.

    PubMed

    Lyu, Qing; Tou, Fangfang; Su, Hong; Wu, Xiaoyong; Chen, Xinyi; Zheng, Zhi

    2015-06-19

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death.

  1. Gamma-ray induced degradation of diazinon and atrazine in natural groundwaters.

    PubMed

    Mohamed, K A; Basfar, A A; Al-Shahrani, A A

    2009-07-30

    Degradation of diazinon and atrazine pesticides present in natural groundwaters was investigated on a laboratory scale upon gamma-irradiation from a (60)Co source. The effects of pesticide type, initial concentration, characteristics of natural groundwater, potential radical scavengers and absorbed dose on efficiency of pesticide degradation were investigated using GC-MS. gamma-Irradiation experiments were carried out for three concentrations (i.e. 0.329, 1.643 and 3.286 microM/diazinon and 0.464, 2.318 and 4.636 microM/atrazine) with irradiation doses over the range 0.5-5.6 kGy for diazinon and 0.2-21 kGy for atrazine. gamma-Radiolysis showed that diazinon was much easier to degrade by ionizing radiation compared to atrazine in all natural groundwater samples. This was observed at the three initial concentrations over the range irradiation doses. The irradiation doses required for degradation of 50 and 90% diazinon (distilled water) and atrazine (humic aqueous solution) at the three concentrations were not sufficient to degrade the same concentrations in different natural groundwater samples. Moreover, the presence of naturally occurring inorganic scavengers in solutions of diazinon and atrazine decreased significantly the efficiency of radiolytic degradation of pesticides, especially at higher concentrations.

  2. [On the nature of the light-induced component of dark respiration of plants].

    PubMed

    Ivlev, A A; Dubinskiĭ, Iu A

    2011-01-01

    The data on the isotope composition of carbon of CO2 of the light-induced dark respiration component have been analyzed using the oscillation model of photosynthesis. It was concluded that this component originates during the transformation of sucrose accumulated by the plant in the oxygenase phase of photosynthetic oscillations in the light period into organic acids. The transformation occurs in the dark period. It this process, C-3 and C-4 atoms, which determine the "heavy" isotope composition of carbon of CO2 of the light-induced dark respiration component are split off from the hexose link of sucrose. PMID:21950073

  3. Transfer Appropriate Forgetting: The Cue-Dependent Nature of Retrieval-Induced Forgetting

    ERIC Educational Resources Information Center

    Perfect, Timothy J.; Stark, Louisa-Jayne; Tree, Jeremy J.; Moulin, Christopher J. A.; Ahmed, Lubna; Hutter, Russell

    2004-01-01

    Retrieval-induced forgetting is the failure to recall a previously studied word following repeated retrieval of a related item. It has been argued that this is due to retrieval competition between practiced and unpracticed items, which results in inhibition of the non-recalled item, detectable with an independent cue at final test. Three…

  4. Natural and artificial methods for inducing the luteal phase in the koala (Phascolarctos cinereus).

    PubMed

    Johnston, S D; McGowan, M R; O'Callaghan, P; Cox, R; Nicolson, V

    2000-09-01

    An experiment was conducted in which female koalas were mated for different durations of intromission and ejaculation to confirm that the luteal phase of the oestrous cycle in koalas is induced by the physical act of mating. Results showed that induction of a luteal phase in the koala usually required a complete duration of penile thrusting behaviour from the male. It is proposed that induction of a luteal phase in koalas may involve a copuloceptive reflex, triggered by the thrusting of the male's penis into the female's urogenital sinus. Although interrupted mating in koalas may be used to induce a luteal phase in preparation for an artificial insemination programme, this study showed that there is a 12.5% probability that pregnancy will result from semen prematurely emitted by the teaser male. A dose of 250 iu hCG was administered intramuscularly to eight oestrous females to determine whether it was possible to induce a luteal phase artificially. In contrast to control females, which received sterile saline injections, all females injected with hCG showed a significant increase in progestogen concentration above that of basal values, indicating that a luteal phase had been induced successfully. PMID:11006146

  5. Role of Induced Magnetic Field on Transient Natural Convection Flow in a Vertical Channel: The Riemann Sum Approximation Approach

    NASA Astrophysics Data System (ADS)

    Jha, B. K.; Sani, I.

    2015-02-01

    This paper investigates the role of induced magnetic field on a transient natural convection flow of an electrically conducting, incompressible and viscous fluid in a vertical channel formed by two infinite vertical parallel plates. The transient flow formation inside the channel is due to sudden asymmetric heating of channel walls. The time dependent momentum, energy and magnetic induction equations are solved semi-analytically using the Laplace transform technique along with the Riemann-sum approximation method. The solutions obtained are validated by comparisons with the closed form solutions obtained for the steady states which have been derived separately and also by the implicit finite difference method. Graphical results for the temperature, velocity, induced magnetic field, current density, and skin-friction based on the semi-analytical solutions are presented and discussed.

  6. New Insights into the Relationship Between Network Structure and Strain Induced Crystallization in Unvolcanized Natural Rubber by Synchrotron X-ray Diffraction

    SciTech Connect

    Toki, S.; Hsiao, B; Amnuaypornsri, S; Sakdapipanich, J

    2009-01-01

    The relationship between the network structure and strain-induced crystallization in un-vulcanized as well as vulcanized natural rubbers (NR) and synthetic poly-isoprene rubbers (IR) was investigated via synchrotron wide-angle X-ray diffraction (WAXD) technique. It was found that the presence of a naturally occurring network structure formed by natural components in un-vulcanized NR significantly facilitates strain-induced crystallization and enhances modulus and tensile strength. The stress-strain relation in vulcanized NR is due to the combined effect of chemical and naturally occurring networks. The weakness of naturally occurring network against stress and temperature suggests that vulcanized NR has additional relaxation mechanism due to naturally occurring network. The superior mechanical properties in NR compared with IR are mainly due to the existence of naturally occurring network structure.

  7. Methylprednisolone pulse therapy induced fall in natural killer cell activity in rheumatoid arthritis.

    PubMed

    Pedersen, B K; Beyer, J M; Rasmussen, A; Klarlund, K; Pedersen, B N; Helin, P

    1984-10-01

    Natural killer (NK) cell activity was studied in 8 patients with classic or definite rheumatoid arthritis (RA) by investigating the killing of K 562 cells by peripheral blood lymphocytes before, during, and after intravenous methylprednisolone pulse therapy (MPPT). MPPT produced a considerable fall in NK activity and after 3 months NK activity was less than half that before MPPT. PMID:6516854

  8. Connecting Model Species to Nature: Predator-Induced Long-Term Sensitization in "Aplysia Californica"

    ERIC Educational Resources Information Center

    Mason, Maria J.; Watkins, Amanda J.; Wakabayashi, Jordann; Buechler, Jennifer; Pepino, Christine; Brown, Michelle; Wright, William G.

    2014-01-01

    Previous research on sensitization in "Aplysia" was based entirely on unnatural noxious stimuli, usually electric shock, until our laboratory found that a natural noxious stimulus, a single sublethal lobster attack, causes short-term sensitization. We here extend that finding by demonstrating that multiple lobster attacks induce…

  9. An interpretation of induced electric currents in long pipelines caused by natural geomagnetic sources of the upper atmosphere

    USGS Publications Warehouse

    Campbell, W.H.

    1986-01-01

    Electric currents in long pipelines can contribute to corrosion effects that limit the pipe's lifetime. One cause of such electric currents is the geomagnetic field variations that have sources in the Earth's upper atmosphere. Knowledge of the general behavior of the sources allows a prediction of the occurrence times, favorable locations for the pipeline effects, and long-term projections of corrosion contributions. The source spectral characteristics, the Earth's conductivity profile, and a corrosion-frequency dependence limit the period range of the natural field changes that affect the pipe. The corrosion contribution by induced currents from geomagnetic sources should be evaluated for pipelines that are located at high and at equatorial latitudes. At midlatitude locations, the times of these natural current maxima should be avoided for the necessary accurate monitoring of the pipe-to-soil potential. ?? 1986 D. Reidel Publishing Company.

  10. Similarities in Gene Expression during the Postharvest-Induced Senescence of Spears and Natural Foliar Senescence of Asparagus.

    PubMed Central

    King, G. A.; Davies, K. M.; Stewart, R. J.; Borst, W. M.

    1995-01-01

    Changes in gene expression and tissue composition were investigated during foliar development and natural senescence of asparagus (Asparagus officinalis L.). Three phases in development and senescence of the foliage were characterized: early fern growth, mature fern, and senescence, when a marked loss of chlorophyll, sucrose, and protein occurred and major changes in translatable mRNAs were detected. Transcripts for three asparagus spear harvest-induced cDNA clones, pTIP9, pTIP11, and pTIP12 (G.A. King and K.M. Davies [1992] Plant Physiol 100: 1661-1669), accumulated during natural foliar senescence, suggesting that the underlying regulatory mechanisms may be similar in both developmental situations. We have used our knowledge of asparagus spear physiology, the probable proteins encoded by the cDNA clones, and our fern development data to propose that sugar depletion regulates the accumulation of at least pTIP12 transcripts in senescing asparagus tissue. PMID:12228457

  11. The possible effects of the natural and induced space environment on the optical and thermal properties of EOS surfaces

    NASA Technical Reports Server (NTRS)

    Maag, Carl R.; Heppner, Richard A.

    1992-01-01

    Space missions, including that of EOS (Earth Observing System), will continue to be subjected to both the natural and induced space environment. The concerns associated with this fact will not go away. The NASA and DoD have recognized the need for long-life stability of materials and structures to the space environment. The major areas of interest include: thermal cycling, UV degradation, space radiation exposure, orbital debris, atomic oxygen erosion, and contamination control. Having flown a number of space environmental effects monitors, SAIC has developed both a data base to understand the magnitude of this problem and mitigation techniques to reduce the impact.

  12. Rapid changes in extracellular glutamate induced by natural arousing stimuli and intravenous cocaine in the nucleus accumbens shell and core.

    PubMed

    Wakabayashi, Ken T; Kiyatkin, Eugene A

    2012-07-01

    Glutamate (Glu) is a major excitatory neurotransmitter, playing a crucial role in the functioning of the nucleus accumbens (NAc), a critical area implicated in somatosensory integration and regulation of motivated behavior. In this study, high-speed amperometry with enzyme-based biosensors was used in freely moving rats to examine changes in extracellular Glu in the NAc shell and core induced by a tone, tail pinch (TP), social interaction with a male conspecific (SI), and intravenous (iv) cocaine (1 mg/kg). To establish the contribution of Glu to electrochemical signal changes, similar recordings were conducted with null (Glu(0)) sensors, which were exposed to the same chemical and physical environment but were insensitive to Glu. TP, SI, and cocaine, but not a tone, induced relatively large and prolonged current increases detected by both Glu and Glu(0) sensors. However, current differentials revealed very rapid, much smaller, and transient increases in extracellular Glu levels, more predominantly in the NAc shell than core. In contrast to monophasic responses with natural stimuli, cocaine induced a biphasic Glu increase in the shell, with a transient peak during the injection and a slower postinjection peak. Therefore, Glu is phasically released in the NAc after exposure to natural arousing stimuli and cocaine; this release is rapid, stimulus dependent, and structure specific, suggesting its role in triggering neural and behavioral activation induced by these stimuli. This study also demonstrates the need for multiple in vitro and in vivo controls to reveal relatively small, highly phasic, and transient fluctuations in Glu levels occurring under behaviorally relevant conditions. PMID:22496525

  13. US -endorphin-(1-27) is a naturally occurring antagonist to etorphine-induced analgesia

    SciTech Connect

    Nicolas, P.; Li, C.H.

    1985-05-01

    The potent opioid peptide US -endorphin is found in the brain and pituitary with two related fragments, US -endorphin-(1-27) and US -endorphin-(1-26). The fragments, retain substantial opioid-receptor binding activity but are virtually inactive analgesically. US -Endorphin-(1-27) inhibits US -endorphin-induced and etorphine-induced analgesia when coinjected intracerebroventricularly into mice. Antagonism by competition at the same site(s) is suggested from parallel shifts of the dose-response curves of etorphine or US -endorphin in the presence of US -endorphin-(1-27). Its potency is 4-5 times greater than that of the opiate antagonist naloxone. US -Endorphin-(1-26) does not antagonize the antinociceptive action of etorphine or US -endorphin in doses up to 500 pmol per animal.

  14. Natural Antioxidant Betanin Protects Rats from Paraquat-Induced Acute Lung Injury Interstitial Pneumonia

    PubMed Central

    Ma, Deshun; Zhang, Miao; Yang, Xuelian; Tan, Dehong

    2015-01-01

    The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-α levels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further. PMID:25861636

  15. Natural antioxidant betanin protects rats from paraquat-induced acute lung injury interstitial pneumonia.

    PubMed

    Han, Junyan; Ma, Deshun; Zhang, Miao; Yang, Xuelian; Tan, Dehong

    2015-01-01

    The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-α levels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further.

  16. A Transient Model of Induced Natural Circulation Thermal Cycling for Hydrogen Isotope Separation

    SciTech Connect

    SHADDAY, MARTIN

    2005-07-12

    The property of selective temperature dependence of adsorption and desorption of hydrogen isotopes by palladium is used for isotope separation. A proposal to use natural circulation of nitrogen to alternately heat and cool a packed bed of palladium coated beads is under active investigation, and a device consisting of two interlocking natural convection loops is being designed. A transient numerical model of the device has been developed to aid the design process. It is a one-dimensional finite-difference model, using the Boussinesq approximation. The thermal inertia of the pipe walls and other heat structures as well as the heater control logic is included in the model. Two system configurations were modeled and results are compared.

  17. Natural Cardiogenesis-Based Template Predicts Cardiogenic Potential of Induced Pluripotent Stem Cell Lines

    PubMed Central

    Martinez-Fernandez, Almudena; Li, Xing; Hartjes, Katherine A.; Terzic, Andre; Nelson, Timothy J.

    2014-01-01

    Background Cardiac development is a complex process resulting in an integrated, multi-lineage tissue with developmental corruption in early embryogenesis leading to congenital heart disease. Interrogation of individual genes has provided the backbone for cardiac developmental biology, yet a comprehensive transcriptome derived from natural cardiogenesis is required to gauge innate developmental milestones. Methods and Results Stage-specific cardiac structures were dissected from eight distinctive mouse embryonic time points to produce genome-wide expressome analysis across cardiogenesis. In reference to this native cardiogenic expression roadmap, divergent iPSC-derived cardiac expression profiles were mapped from pro-cardiogenic 3-factor (SOX2, OCT4, KLF4) and less-cardiogenic 4-factor (plus c-MYC) reprogrammed cells. Expression of cardiac-related genes from 3F-iPSC differentiated in vitro at days 5 and 11 recapitulated expression profiles of natural embryos at days E7.5–E8.5 and E14.5–E18.5, respectively. In contrast, 4F-iPSC demonstrated incomplete cardiogenic gene expression profiles beginning at day 5 of differentiation. Differential gene expression within the pluripotent state revealed 23 distinguishing candidate genes among pluripotent cell lines with divergent cardiogenic potentials. A confirmed panel of 12 genes, differentially expressed between high and low cardiogenic lines, was transformed into a predictive score sufficient to discriminate individual iPSC lines according to relative cardiogenic potential. Conclusions Transcriptome analysis attuned to natural embryonic cardiogenesis provides a robust platform to probe coordinated cardiac specification and maturation from bioengineered stem cell-based model systems. A panel of developmental-related genes allowed differential prognosis of cardiogenic competency, thus prioritizing cell lines according to natural blueprint to streamline functional applications. PMID:24036272

  18. Variation in oxygen isotope ratio of dissolved orthophosphate induced by uptake process in natural coral holobionts

    NASA Astrophysics Data System (ADS)

    Ferrera, Charissa M.; Miyajima, Toshihiro; Watanabe, Atsushi; Umezawa, Yu; Morimoto, Naoko; San Diego-McGlone, Maria Lourdes; Nadaoka, Kazuo

    2016-06-01

    A model incubation experiment using natural zooxanthellate corals was conducted to evaluate the influence of phosphate uptake by coral holobionts on oxygen isotope ratio of dissolved PO4 3- (δ18Op). Live coral samples of Acropora digitifera, Porites cylindrica, and Heliopora coerulea were collected from coral reefs around Ishigaki Island (Okinawa, Japan) and Bolinao (northern Luzon, Philippines) and incubated for 3-5 d after acclimatization under natural light conditions with elevated concentrations of PO4 3-. Phosphate uptake by corals behaved linearly with incubation time, with uptake rate depending on temperature. δ18Op usually increased with time toward the equilibrium value with respect to oxygen isotope exchange with ambient seawater, but sometimes became higher than equilibrium value at the end of incubation. The magnitude of the isotope effect associated with uptake depended on coral species; the greatest effect was in A. digitifera and the smallest in H. coerulea. However, it varied even within samples of a single coral species, which suggests multiple uptake processes with different isotope effects operating simultaneously with varying relative contributions in the coral holobionts used. In natural environments where concentrations of PO4 3- are much lower than those used during incubation, PO4 3- is presumably turned over much faster and the δ18Op easily altered by corals and other major primary producers. This should be taken into consideration when using δ18Op as an indicator of external PO4 3- sources in coastal ecosystems.

  19. Natural small-molecule enhancers of autophagy induce autophagic cell death in apoptosis-defective cells

    PubMed Central

    Law, Betty Yuen Kwan; Chan, Wai Kit; Xu, Su Wei; Wang, Jing Rong; Bai, Li Ping; Liu, Liang; Wong, Vincent Kam Wai

    2014-01-01

    Resistance of cancer cells to chemotherapy is a significant problem in oncology, and the development of sensitising agents or small-molecules with new mechanisms of action to kill these cells is needed. Autophagy is a cellular process responsible for the turnover of misfolded proteins or damaged organelles, and it also recycles nutrients to maintain energy levels for cell survival. In some apoptosis-resistant cancer cells, autophagy can also enhance the efficacy of anti-cancer drugs through autophagy-mediated mechanisms of cell death. Because the modulation of autophagic processes can be therapeutically useful to circumvent chemoresistance and enhance the effects of cancer treatment, the identification of novel autophagic enhancers for use in oncology is highly desirable. Many novel anti-cancer compounds have been isolated from natural products; therefore, we worked to discover natural, anti-cancer small-molecule enhancers of autophagy. Here, we have identified a group of natural alkaloid small-molecules that function as novel autophagic enhancers. These alkaloids, including liensinine, isoliensinine, dauricine and cepharanthine, stimulated AMPK-mTOR dependent induction of autophagy and autophagic cell death in a panel of apoptosis-resistant cells. Taken together, our work provides novel insights into the biological functions, mechanisms and potential therapeutic values of alkaloids for the induction of autophagy. PMID:24981420

  20. Study of plasma natural convection induced by electron beam in atmosphere [

    SciTech Connect

    Deng, Yongfeng Han, Xianwei; Tan, Yonghua

    2014-06-15

    Using high-energy electron beams to ionize air is an effective way to produce a large-size plasma in the atmosphere. In particular, with a steady-state high power generator, some unique phenomena can be achieved, including natural convection of the plasma. The characteristics of this convection are studied both experimentally and numerically. The results show that an asymmetrical temperature field develops with magnitudes that vary from 295 K to 389 K at a pressure of 100 Torr. Natural convection is greatly enhanced under 760 Torr. Nevertheless, plasma transport is negligible in this convection flow field and only the plasma core tends to move upward. Parameter analysis is performed to discern influencing factors on this phenomenon. The beam current, reflecting the Rayleigh number Ra effect, correlates with convection intensity, which indicates that energy deposition is the underlying key factor in determining such convections. Finally, natural convection is concluded to be an intrinsic property of the electron beam when focused into dense air, and can be achieved by carefully adjusting equipment operations parameters.

  1. Protection of Erwinia amylovora bacteriophage Y2 from UV-induced damage by natural compounds

    PubMed Central

    Born, Yannick; Bosshard, Lars; Duffy, Brion; Loessner, Martin J.; Fieseler, Lars

    2015-01-01

    Bacteriophages have regained much attention as biocontrol agents against bacterial pathogens. However, with respect to stability, phages are biomolecules and are therefore sensitive to a number of environmental influences. UV-irradiation can readily inactivate phage infectivity, which impedes their potential application in the plant phyllosphere. Therefore, phages for control of Erwinia amylovora, the causative agent of fire blight, need to be protected from UV-damage by adequate measures. We investigated the protective effect of different light-absorbing substances on phage particles exposed to UV-light. For this, natural extracts from carrot, red pepper, and beetroot, casein and soy peptone in solution, and purified substances such as astaxanthin, aromatic amino acids, and Tween 80 were prepared and tested as natural sunscreens for phage. All compounds were found to significantly increase half-life of UV-irradiated phage particles and they did not negatively affect phage viability or infectivity. Altogether, a range of readily available, natural substances are suitable as UV-protectants to prevent phage particles from UV-light damage. PMID:26904378

  2. Snag characteristics and dynamics following natural and artificially induced mortality in a managed loblolly pine forest

    SciTech Connect

    Zarnoch, Stanley J.; Vukovich, Mark A.; Kilgo, John C.; Blake, John I.

    2013-09-01

    A 14-year study of snag characteristics was established in 41- to 44-year old loblolly pine (Pinus taeda L.) stands in southeastern USA. During the initial 5.5 years, no stand manipulation or unusually high-mortality events occurred. Afterwards, three treatments were applied consisting of trees thinned and removed, trees felled and not removed, and artificial creation of snags produced by girdling and herbicide injection. The thinned treatments were designed to maintain the same live canopy density as the snag-created treatment, disregarding snags that remained standing.We monitored snag height, diameter, density, volume, and bark percentage; the number of cavities was monitored in natural snags only. During the first 5.5 years, recruitment and loss rates were stable, resulting in a stable snag population. Large snags (≥25 cm diameter) were common, but subcanopy small snags (10 to <25 cm diameter) dominated numerically. Large natural snags survived (90% quantile) significantly longer (6.0–9.4 years) than smaller snags (4.4–6.9 years). Large artificial snags persisted the longest (11.8 years). Cavities in natural snags developed within 3 years following tree death. The mean number of cavities per snag was five times greater in large versus small snags and large snags were more likely to have multiple cavities, emphasizing the importance of mature pine stands for cavity-dependent wildlife species.

  3. Natural variation in small molecule-induced TIR-NB-LRR signaling induces root growth arrest via EDS1- and PAD4-complexed R protein VICTR in Arabidopsis.

    PubMed

    Kim, Tae-Houn; Kunz, Hans-Henning; Bhattacharjee, Saikat; Hauser, Felix; Park, Jiyoung; Engineer, Cawas; Liu, Amy; Ha, Tracy; Parker, Jane E; Gassmann, Walter; Schroeder, Julian I

    2012-12-01

    In a chemical genetics screen we identified the small-molecule [5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione (DFPM) that triggers rapid inhibition of early abscisic acid signal transduction via PHYTOALEXIN DEFICIENT4 (PAD4)- and ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)-dependent immune signaling mechanisms. However, mechanisms upstream of EDS1 and PAD4 in DFPM-mediated signaling remain unknown. Here, we report that DFPM generates an Arabidopsis thaliana accession-specific root growth arrest in Columbia-0 (Col-0) plants. The genetic locus responsible for this natural variant, VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response), encodes a TIR-NB-LRR (for Toll-Interleukin1 Receptor-nucleotide binding-Leucine-rich repeat) protein. Analyses of T-DNA insertion victr alleles showed that VICTR is necessary for DFPM-induced root growth arrest and inhibition of abscisic acid-induced stomatal closing. Transgenic expression of the Col-0 VICTR allele in DFPM-insensitive Arabidopsis accessions recapitulated the DFPM-induced root growth arrest. EDS1 and PAD4, both central regulators of basal resistance and effector-triggered immunity, as well as HSP90 chaperones and their cochaperones RAR1 and SGT1B, are required for the DFPM-induced root growth arrest. Salicylic acid and jasmonic acid signaling pathway components are dispensable. We further demonstrate that VICTR associates with EDS1 and PAD4 in a nuclear protein complex. These findings show a previously unexplored association between a TIR-NB-LRR protein and PAD4 and identify functions of plant immune signaling components in the regulation of root meristematic zone-targeted growth arrest.

  4. Natural variation in small molecule-induced TIR-NB-LRR signaling induces root growth arrest via EDS1- and PAD4-complexed R protein VICTR in Arabidopsis.

    PubMed

    Kim, Tae-Houn; Kunz, Hans-Henning; Bhattacharjee, Saikat; Hauser, Felix; Park, Jiyoung; Engineer, Cawas; Liu, Amy; Ha, Tracy; Parker, Jane E; Gassmann, Walter; Schroeder, Julian I

    2012-12-01

    In a chemical genetics screen we identified the small-molecule [5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione (DFPM) that triggers rapid inhibition of early abscisic acid signal transduction via PHYTOALEXIN DEFICIENT4 (PAD4)- and ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)-dependent immune signaling mechanisms. However, mechanisms upstream of EDS1 and PAD4 in DFPM-mediated signaling remain unknown. Here, we report that DFPM generates an Arabidopsis thaliana accession-specific root growth arrest in Columbia-0 (Col-0) plants. The genetic locus responsible for this natural variant, VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response), encodes a TIR-NB-LRR (for Toll-Interleukin1 Receptor-nucleotide binding-Leucine-rich repeat) protein. Analyses of T-DNA insertion victr alleles showed that VICTR is necessary for DFPM-induced root growth arrest and inhibition of abscisic acid-induced stomatal closing. Transgenic expression of the Col-0 VICTR allele in DFPM-insensitive Arabidopsis accessions recapitulated the DFPM-induced root growth arrest. EDS1 and PAD4, both central regulators of basal resistance and effector-triggered immunity, as well as HSP90 chaperones and their cochaperones RAR1 and SGT1B, are required for the DFPM-induced root growth arrest. Salicylic acid and jasmonic acid signaling pathway components are dispensable. We further demonstrate that VICTR associates with EDS1 and PAD4 in a nuclear protein complex. These findings show a previously unexplored association between a TIR-NB-LRR protein and PAD4 and identify functions of plant immune signaling components in the regulation of root meristematic zone-targeted growth arrest. PMID:23275581

  5. A senescence-associated gene of Arabidopsis thaliana is distinctively regulated during natural and artificially induced leaf senescence.

    PubMed

    Oh, S A; Lee, S Y; Chung, I K; Lee, C H; Nam, H G

    1996-02-01

    We have characterized the structure and expression of a senescence-associated gene (sen1) of Arabidopsis thaliana. The protein-coding region of the gene consists of 5 exons encoding 182 amino acids. The encoded peptide shows noticeable similarity to the bacterial sulfide dehydrogenase and 81% identity to the peptide encoded by the radish din1 gene. The 5'-upstream region contains sequence motifs resembling the heat-shock- and ABA-responsive elements and the TCA motif conserved among stress-inducible genes. Examination of the expression patterns of the sen1 gene under various senescing conditions along with measurements of photochemical efficiency and of chlorophyll content revealed that the sen1 gene expression is associated with Arabidopsis leaf senescence. During the normal growth phase, the gene is strongly induced in leaves at 25 days after germination when inflorescence stems are 2-3 cm high, and then the mRNA level is maintained at a comparable level in naturally senescing leaves. In addition, dark-induced senescence of detached leaves or of leaves in planta resulted in a high-level induction of the gene. Expression of the sen1 gene was also strongly induced in leaves subjected to senescence by 0.1mM abscisic acid or 1 mM ethephon treatment. The induced expression of the gene by dark treatment was not significantly repressed by treatment with 0.1 mM cytokinin or 50 mM CaCl2 which delayed loss of chlorophyll but not that of photochemical efficiency.

  6. The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells.

    PubMed

    Ramos-Torres, Ágata; Bort, Alicia; Morell, Cecilia; Rodríguez-Henche, Nieves; Díaz-Laviada, Inés

    2016-01-12

    Capsaicin, the pungent ingredient of red hot chili peepers, has been shown to have anti-cancer activities in several cancer cells, including prostate cancer. Several molecular mechanisms have been proposed on its chemopreventive action, including ceramide accumulation, endoplasmic reticulum stress induction and NFκB inhibition. However, the precise mechanisms by which capsaicin exerts its anti-proliferative effect in prostate cancer cells remain questionable. Herein, we have tested the involvement of autophagy on the capsaicin mechanism of action on prostate cancer LNCaP and PC-3 cells.The results showed that capsaicin induced prostate cancer cell death in a time- and concentration-dependent manner, increased the levels of microtubule-associated protein light chain 3-II (LC3-II, a marker of autophagy) and the accumulation of the cargo protein p62 suggesting an autophagy blockage. Moreover, confocal microscopy revealed that capsaicin treatment increased lysosomes which co-localized with LC3 positive vesicles in a similar extent to that produced by the lysosomal protease inhibitors E64 and pepstatin pointing to an autophagolysosomes breakdown inhibition. Furthermore, we found that capsaicin triggered ROS generation in cells, while the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Co-treatment of cells with NAC and capsaicin abrogated the effects of capsaicin on autophagy and cell death. Normal prostate PNT2 and RWPE-1 cells were more resistant to capsaicin-induced cytotoxicity and did not accumulate p62 protein.Taken together, these results suggest that ROS-mediated capsaicin-induced autophagy blockage contributes to antiproliferation in prostate cancer cells, which provides new insights into the anticancer molecular mechanism of capsaicin. PMID:26625315

  7. The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells

    PubMed Central

    Ramos-Torres, Ágata; Bort, Alicia; Morell, Cecilia; Rodríguez-Henche, Nieves; Díaz-Laviada, Inés

    2016-01-01

    Capsaicin, the pungent ingredient of red hot chili peepers, has been shown to have anti-cancer activities in several cancer cells, including prostate cancer. Several molecular mechanisms have been proposed on its chemopreventive action, including ceramide accumulation, endoplasmic reticulum stress induction and NFκB inhibition. However, the precise mechanisms by which capsaicin exerts its anti-proliferative effect in prostate cancer cells remain questionable. Herein, we have tested the involvement of autophagy on the capsaicin mechanism of action on prostate cancer LNCaP and PC-3 cells. The results showed that capsaicin induced prostate cancer cell death in a time- and concentration-dependent manner, increased the levels of microtubule-associated protein light chain 3-II (LC3-II, a marker of autophagy) and the accumulation of the cargo protein p62 suggesting an autophagy blockage. Moreover, confocal microscopy revealed that capsaicin treatment increased lysosomes which co-localized with LC3 positive vesicles in a similar extent to that produced by the lysosomal protease inhibitors E64 and pepstatin pointing to an autophagolysosomes breakdown inhibition. Furthermore, we found that capsaicin triggered ROS generation in cells, while the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Co-treatment of cells with NAC and capsaicin abrogated the effects of capsaicin on autophagy and cell death. Normal prostate PNT2 and RWPE-1 cells were more resistant to capsaicin-induced cytotoxicity and did not accumulate p62 protein. Taken together, these results suggest that ROS-mediated capsaicin-induced autophagy blockage contributes to antiproliferation in prostate cancer cells, which provides new insights into the anticancer molecular mechanism of capsaicin. PMID:26625315

  8. The pepper's natural ingredient capsaicin induces autophagy blockage in prostate cancer cells.

    PubMed

    Ramos-Torres, Ágata; Bort, Alicia; Morell, Cecilia; Rodríguez-Henche, Nieves; Díaz-Laviada, Inés

    2016-01-12

    Capsaicin, the pungent ingredient of red hot chili peepers, has been shown to have anti-cancer activities in several cancer cells, including prostate cancer. Several molecular mechanisms have been proposed on its chemopreventive action, including ceramide accumulation, endoplasmic reticulum stress induction and NFκB inhibition. However, the precise mechanisms by which capsaicin exerts its anti-proliferative effect in prostate cancer cells remain questionable. Herein, we have tested the involvement of autophagy on the capsaicin mechanism of action on prostate cancer LNCaP and PC-3 cells.The results showed that capsaicin induced prostate cancer cell death in a time- and concentration-dependent manner, increased the levels of microtubule-associated protein light chain 3-II (LC3-II, a marker of autophagy) and the accumulation of the cargo protein p62 suggesting an autophagy blockage. Moreover, confocal microscopy revealed that capsaicin treatment increased lysosomes which co-localized with LC3 positive vesicles in a similar extent to that produced by the lysosomal protease inhibitors E64 and pepstatin pointing to an autophagolysosomes breakdown inhibition. Furthermore, we found that capsaicin triggered ROS generation in cells, while the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Co-treatment of cells with NAC and capsaicin abrogated the effects of capsaicin on autophagy and cell death. Normal prostate PNT2 and RWPE-1 cells were more resistant to capsaicin-induced cytotoxicity and did not accumulate p62 protein.Taken together, these results suggest that ROS-mediated capsaicin-induced autophagy blockage contributes to antiproliferation in prostate cancer cells, which provides new insights into the anticancer molecular mechanism of capsaicin.

  9. Natural micro-scale heterogeneity induced solute and nanoparticle retardation in fractured crystalline rock.

    PubMed

    Huber, F; Enzmann, F; Wenka, A; Bouby, M; Dentz, M; Schäfer, T

    2012-05-15

    We studied tracer (Tritiated Water (HTO); Tritium replaces one of the stable hydrogen atoms in the H(2)O molecule) and nanoparticle (quantum dots (QD)) transport by means of column migration experiments and comparison to 3D CFD modeling. Concerning the modeling approach, a natural single fracture was scanned using micro computed tomography (μCT) serving as direct input for the model generation. The 3D simulation does not incorporate any chemical processes besides the molecular diffusion coefficient solely reflecting the impact of fracture heterogeneity on mass (solute and nanoparticles) transport. Complex fluid velocity distributions (flow channeling and flowpath heterogeneity) evolve as direct function of fracture geometry. Both experimental and simulated solute and colloidal breakthrough curves show heavy tailing (non-Fickian transport behavior), respectively. Regarding the type of quantum dots and geochemical conditions prevailing (Grimsel ground water chemistry, QD and diorite surface charge, respectively and porosity of the Äspö diorite drill core) experimental breakthrough of the quantum dots always arrives faster than the solute tracer in line with the modeling results. Besides retardation processes like sorption, filtration, straining or matrix diffusion, the results show that natural 3D fracture heterogeneity represents an important additional retardation mechanism for solutes and colloidal phases. This is clearly verified by the numerical simulations, where the 3D real natural fracture geometry and the resulting complex flow velocity distribution is the only possible process causing solute/nanoparticle retardation. Differences between the experimental results and the simulations are discussed with respect to uncertainties in the μCT measurements and experimental and simulation boundary conditions, respectively. PMID:22484609

  10. Natural micro-scale heterogeneity induced solute and nanoparticle retardation in fractured crystalline rock.

    PubMed

    Huber, F; Enzmann, F; Wenka, A; Bouby, M; Dentz, M; Schäfer, T

    2012-05-15

    We studied tracer (Tritiated Water (HTO); Tritium replaces one of the stable hydrogen atoms in the H(2)O molecule) and nanoparticle (quantum dots (QD)) transport by means of column migration experiments and comparison to 3D CFD modeling. Concerning the modeling approach, a natural single fracture was scanned using micro computed tomography (μCT) serving as direct input for the model generation. The 3D simulation does not incorporate any chemical processes besides the molecular diffusion coefficient solely reflecting the impact of fracture heterogeneity on mass (solute and nanoparticles) transport. Complex fluid velocity distributions (flow channeling and flowpath heterogeneity) evolve as direct function of fracture geometry. Both experimental and simulated solute and colloidal breakthrough curves show heavy tailing (non-Fickian transport behavior), respectively. Regarding the type of quantum dots and geochemical conditions prevailing (Grimsel ground water chemistry, QD and diorite surface charge, respectively and porosity of the Äspö diorite drill core) experimental breakthrough of the quantum dots always arrives faster than the solute tracer in line with the modeling results. Besides retardation processes like sorption, filtration, straining or matrix diffusion, the results show that natural 3D fracture heterogeneity represents an important additional retardation mechanism for solutes and colloidal phases. This is clearly verified by the numerical simulations, where the 3D real natural fracture geometry and the resulting complex flow velocity distribution is the only possible process causing solute/nanoparticle retardation. Differences between the experimental results and the simulations are discussed with respect to uncertainties in the μCT measurements and experimental and simulation boundary conditions, respectively.

  11. Natural breeding with bulls experimentally infected with Neospora caninum failed to induce seroconversion in dams.

    PubMed

    Osoro, K; Ortega-Mora, L M; Martínez, A; Serrano-Martínez, E; Ferre, I

    2009-03-01

    Four bulls and 56 heifers seronegative to Neospora caninum were used to determine the feasibility of venereal transmission in bovine neosporosis under natural conditions. Bulls were experimentally infected with 10(8) live N. caninum tachyzoites. Two of them with the Nc-1 isolate and the other two with the Nc-Spain-7 isolate. After 13 months of initial infection, each bull was re-infected with the same isolate and dose. The experiments were carried out from March to September during 2006 and 2007 where groups of cyclic heifers were naturally mated by the experimentally infected bulls. In year 2006, two bulls infected with different N. caninum isolate serviced 12 heifers each. In year 2007, the same bulls serviced the same heifers a second time (now primiparous) and six new heifers were also added to each group. In addition, the other two bulls serviced 10 additional heifers each. Experimental animals were monitored for 30 weeks and serum samples were collected weekly and fortnightly in years 2006 and 2007, respectively to evaluate the presence of specific antibodies to N. caninum. Experimentally infected bulls showed a significant increase of specific IgG antibodies from 13 (Nc-SP-7) and 21 (Nc-1) days post-infection. Serum IgG antibody responses of individual animals were similar in kinetics but slightly different in magnitude. Serum samples from heifers were all negative. Pregnant rates were 100% in heifers and 91% in primiparous animals. Calves did not show precolostral specific antibodies to N. caninum. Venereal transmission of bovine neosporosis under natural grazing conditions is unlikely to occur.

  12. Delivering sustainable crop protection systems via the seed: exploiting natural constitutive and inducible defence pathways

    PubMed Central

    Pickett, John A.; Aradottír, Gudbjorg I.; Birkett, Michael A.; Bruce, Toby J. A.; Hooper, Antony M.; Midega, Charles A. O.; Jones, Huw D.; Matthes, Michaela C.; Napier, Johnathan A.; Pittchar, Jimmy O.; Smart, Lesley E.; Woodcock, Christine M.; Khan, Zeyaur R.

    2014-01-01

    To reduce the need for seasonal inputs, crop protection will have to be delivered via the seed and other planting material. Plant secondary metabolism can be harnessed for this purpose by new breeding technologies, genetic modification and companion cropping, the latter already on-farm in sub-Saharan Africa. Secondary metabolites offer the prospect of pest management as robust as that provided by current pesticides, for which many lead compounds were, or are currently deployed as, natural products. Evidence of success and promise is given for pest management in industrial and developing agriculture. Additionally, opportunities for solving wider problems of sustainable crop protection, and also production, are discussed. PMID:24535389

  13. Understanding the nature of heavy pentaquarks and searching for them in pion-induced reactions

    NASA Astrophysics Data System (ADS)

    Liu, Xiao-Hai; Oka, Makoto

    2016-10-01

    We investigate the reaction π- p →π- J / ψp via the open-charm hadron rescattering diagrams. Due to the presence of the triangle singularity (TS) in the rescattering amplitudes, the TS peaks can simulate the pentaquark-like resonances arising in the J / ψp invariant mass distributions, which may bring ambiguities on our understanding of the nature of the exotic states. Searching for the heavy pentaquark in different processes may help us to clarify the ambiguities, because of the highly process-dependent characteristic of the TS mechanism.

  14. A bifractal nature of reticular patterns induced by oxygen plasma on polymer films

    PubMed Central

    Bae, Junwan; Lee, I. J.

    2015-01-01

    Plasma etching was demonstrated to be a promising tool for generating self-organized nano-patterns on various commercial films. Unfortunately, dynamic scaling approach toward fundamental understanding of the formation and growth of the plasma-induced nano-structure has not always been straightforward. The temporal evolution of self-aligned nano-patterns may often evolve with an additional scale-invariance, which leads to breakdown of the well-established dynamic scaling law. The concept of a bifractal interface is successfully applied to reticular patterns induced by oxygen plasma on the surface of polymer films. The reticular pattern, composed of nano-size self-aligned protuberances and underlying structure, develops two types of anomalous dynamic scaling characterized by super-roughening and intrinsic anomalous scaling, respectively. The diffusion and aggregation of short-cleaved chains under the plasma environment are responsible for the regular distribution of the nano-size protuberances. Remarkably, it is uncovered that the dynamic roughening of the underlying structure is governed by a relaxation mechanism described by the Edwards-Wilkinson universality class with a conservative noise. The evidence for the basic phase, characterized by the negative roughness and growth exponents, has been elusive since its first theoretical consideration more than two decades ago. PMID:25997075

  15. Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways.

    PubMed

    Wang, Di; Zhang, Yongfeng; Lu, Jiahui; Wang, Yang; Wang, Junyue; Meng, Qingfan; Lee, Robert J; Wang, Di; Teng, Lesheng

    2016-01-01

    Cordycepin, a major compound separated from Cordyceps sinensis, is known as a potential novel candidate for cancer therapy. Breast cancer, the most typical cancer diagnosed among women, remains a global health problem. In this study, the anti-breast cancer property of cordycepin and its underlying mechanisms was investigated. The direct effects of cordycepin on breast cancer cells both in in vitro and in vivo experiments were evaluated. Cordycepin exerted cytotoxicity in MCF-7 and MDA-MB-231 cells confirmed by reduced cell viability, inhibition of cell proliferation, enhanced lactate dehydrogenase release and reactive oxygen species accumulation, induced mitochondrial dysfunction and nuclear apoptosis in human breast cancer cells. Cordycepin increased the activation of pro-apoptotic proteins, including caspase-8, caspase-9, caspase-3 and Bax, and suppressed the expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2). The inhibition on MCF-7-xenografted tumor growth in nude mice further confirmed cordycepin's anti-breast cancer effect. These aforementioned results reveal that cordycepin induces apoptosis in human breast cancer cells via caspase-dependent pathways. The data shed light on the possibility of cordycepin being a safe agent for breast cancer treatment. PMID:26996021

  16. Substantive nature of sleep in updating the temporal conditions necessary for inducing units of internal sensations.

    PubMed

    Vadakkan, Kunjumon I

    2016-01-01

    Unlike other organs that operate continuously, such as the heart and kidneys, many of the operations of the nervous system shut down during sleep. The evolutionarily conserved unconscious state of sleep that puts animals at risk from predators indicates that it is an indispensable integral part of systems operation. A reasonable expectation is that any hypothesis for the mechanism of the nervous system functions should be able to provide an explanation for sleep. In this regard, the semblance hypothesis is examined. Postsynaptic membranes are continuously being depolarized by the quantally-released neurotransmitter molecules arriving from their presynaptic terminals. In this context, an incidental lateral activation of the postsynaptic membrane is expected to induce a semblance (cellular hallucination of arrival of activity from its presynaptic terminal, which forms a unit for internal sensation) of the arrival of activity from its presynaptic terminal as a systems property. This restricts induction of semblance to a context of a very high ratio of the duration of the default state of neurotransmitter-induced postsynaptic depolarization to the total duration of incidental lateral activations of the postsynaptic membrane. This requirement spans within a time-bin of a few sleep-wake cycles. Since the duration of quantal release remains maximized, the above requirement can be achieved only by ceiling the total duration of incidental lateral activations of the postsynaptic membrane, which necessitates a state of sleep. PMID:27656266

  17. Fitness consequences of natural variation in flooding-induced shoot elongation in Rumex palustris.

    PubMed

    Chen, Xin; Visser, Eric J W; de Kroon, Hans; Pierik, Ronald; Voesenek, Laurentius A C J; Huber, Heidrun

    2011-04-01

    • Plants can respond to their environment by morphological plasticity. Generally, the potential benefits of adaptive plastic responses are beyond doubt under predictable environmental changes. However, the net benefits may be less straightforward when plants encounter temporal stresses, such as flooding in river flood plains. • Here, we tested whether the balance of costs and benefits associated with flooding-induced shoot elongation depends on the flooding regime, by subjecting Rumex palustris plants with different elongation capacity to submergence of different frequency and duration. • Our results showed that reaching the surface by shoot elongation is associated with fitness benefits, as under less frequent, but longer, flooding episodes plants emerging above the floodwater had greater biomass production than plants that were kept below the surface. As we predicted, slow-elongating plants had clear advantages over fast-elongating ones if submergence was frequent but of short duration, indicating that elongation also incurs costs. • Our data suggest that high costs select for weak plasticity under frequent environmental change. In contrast to our predictions, however, fast-elongating plants did not have an overall advantage over slow-elongating plants when floods lasted longer. This indicates that the delicate balance between benefits and costs of flooding-induced elongation depends on the specific characteristics of the flooding regime.

  18. Stuttering, induced fluency, and natural fluency: a hierarchical series of activation likelihood estimation meta-analyses.

    PubMed

    Budde, Kristin S; Barron, Daniel S; Fox, Peter T

    2014-12-01

    Developmental stuttering is a speech disorder most likely due to a heritable form of developmental dysmyelination impairing the function of the speech-motor system. Speech-induced brain-activation patterns in persons who stutter (PWS) are anomalous in various ways; the consistency of these aberrant patterns is a matter of ongoing debate. Here, we present a hierarchical series of coordinate-based meta-analyses addressing this issue. Two tiers of meta-analyses were performed on a 17-paper dataset (202 PWS; 167 fluent controls). Four large-scale (top-tier) meta-analyses were performed, two for each subject group (PWS and controls). These analyses robustly confirmed the regional effects previously postulated as "neural signatures of stuttering" (Brown, Ingham, Ingham, Laird, & Fox, 2005) and extended this designation to additional regions. Two smaller-scale (lower-tier) meta-analyses refined the interpretation of the large-scale analyses: (1) a between-group contrast targeting differences between PWS and controls (stuttering trait); and (2) a within-group contrast (PWS only) of stuttering with induced fluency (stuttering state).

  19. Stuttering, Induced Fluency, and Natural Fluency: A Hierarchical Series of Activation Likelihood Estimation Meta-Analyses

    PubMed Central

    Budde, Kristin S.; Barron, Daniel S.; Fox, Peter T.

    2015-01-01

    Developmental stuttering is a speech disorder most likely due to a heritable form of developmental dysmyelination impairing the function of the speech-motor system. Speech-induced brain-activation patterns in persons who stutter (PWS) are anomalous in various ways; the consistency of these aberrant patterns is a matter of ongoing debate. Here, we present a hierarchical series of coordinate-based meta-analyses addressing this issue. Two tiers of meta-analyses were performed on a 17-paper dataset (202 PWS; 167 fluent controls). Four large-scale (top-tier) meta-analyses were performed, two for each subject group (PWS and controls). These analyses robustly confirmed the regional effects previously postulated as “neural signatures of stuttering” (Brown 2005) and extended this designation to additional regions. Two smaller-scale (lower-tier) meta-analyses refined the interpretation of the large-scale analyses: 1) a between-group contrast targeting differences between PWS and controls (stuttering trait); and 2) a within-group contrast (PWS only) of stuttering with induced fluency (stuttering state). PMID:25463820

  20. Discriminating Mining Induced Seismicity from Natural Tectonic Earthquakes in the Wasatch Plateau Region of Central Utah

    NASA Astrophysics Data System (ADS)

    Stein, J. R.; Pankow, K. L.; Koper, K. D.; McCarter, M. K.

    2014-12-01

    On average, several hundred earthquakes are located each year within the Wasatch Plateau region of central Utah. This region includes the boundary between the relatively stable Colorado Plateau and the actively extending Basin and Range physiographic provinces. Earthquakes in this region tend to fall in the intermountain seismic belt (ISB), a continuous band of seismicity that extends from Montana to Arizona. While most of the earthquakes in the ISB are of tectonic origin, events in the Wasatch Plateau also include mining induced seismicity (MIS) from local underground coal mining operations. Using a catalog of 16,182 seismic events (-0.25 < M < 4.5) recorded from 1981 to 2011, we use double difference relocation and waveform cross correlation techniques to help discriminate between these two populations of events. Double difference relocation greatly improves the relative locations between the many events that occur in this area. From the relative relocations, spatial differences between event types are used to differentiate between shallow MIS and considerably deeper events associated with tectonic seismicity. Additionally, waveform cross-correlation is used to cluster events with similar waveforms—meaning that events in each cluster should have a similar source location and mechanism—in order to more finely group seismic events occurring in the Wasatch Plateau. The results of this study provide both an increased understanding of the influence mining induced seismicity has on the number of earthquakes detected within this region, as well as better constraints on the deeper tectonic structure.

  1. Preliminary investigation of topical nitroglycerin formulations containing natural wound healing agent in diabetes-induced foot ulcer.

    PubMed

    Hotkar, Mukesh S; Avachat, Amelia M; Bhosale, Sagar S; Oswal, Yogesh M

    2015-04-01

    Nitroglycerin (NTG) is an organic nitrate rapidly denitrated by enzymes to release free radical nitric oxide and shows improved wound healing and tissue protection from oxidative damage. The purpose of this study was to evaluate whether topical application of NTG in the form of gel/ointment along with a natural wound healing agent, aloe vera, would bring about wound healing by using diabetes-induced foot ulcer model and rat excision wound model. All these formulations were evaluated for pH, viscosity, drug content and ex vivo diffusion studies using rat skin. Based on ex vivo permeation studies, the formulation consisting of carbopol 974p as a gelling agent and aloe vera was found to be suitable. The in vivo study used streptozotocin-induced diabetic foot ulcer and rat excision wound models to analyse wound healing activity. The wound size in animals of all treated groups was significantly reduced compared with that of the diabetic control and marketed treated animals. This study showed that the gel formed with carbopol 974p (1%) and aloe vera promotes significant wound healing and closure in diabetic rats compared with the commercial product and provides a promising product to be used in diabetes-induced foot ulcer.

  2. Inositol hexaphosphate-induced enhancement of natural killer cell activity correlates with suppression of colon carcinogenesis in rats

    PubMed Central

    Zhang, Zheng; Song, Yang; Wang, Xiu-Li

    2005-01-01

    AIM: To investigate the anti-neoplastic effect of inositol hexaphosphate (InsP6 or phytic acid) on dimethylhydrazine (DMH)-induced colon tumor in rats and its effect on blood natural killer (NK) cell activity. METHODS: Healthy Wistar rats, 4 wk old, were divided into control group (fed with common food) and InsP6 group (fed with common food+2% sodium inositol hexaphosphate in the drinking water), 15 rats in each group. Both groups were injected with 1,2-dimethylhydrazine subcutaneously (20 mg/kg body weight) once a week for 20 wk. Rats were killed after 21 wk. The whole large intestine was isolated to determine the general condition of tumors and to test blood NK cell activity by lactate-dehydrogenase-release assay. RESULTS: Administration of InsP6 significantly increased blood NK cell activity in DMH-induced colorectal tumor in rats. InsP6 group had a smaller tumor size on average and a smaller number of tumors than the control group. Its mortality was also higher than that in control. However, the variables of body weight and tumor incidence were not significantly different between the two groups. CONCLUSION: InsP6 can increase blood NK cell activity in DMH-induced colon tumor in rats and inhibit tumor growth and metastasis in rats. PMID:16124063

  3. Human APOBEC3 Induced Mutation of Human Immunodeficiency Virus Type-1 Contributes to Adaptation and Evolution in Natural Infection

    PubMed Central

    Kim, Eun-Young; Lorenzo-Redondo, Ramon; Little, Susan J.; Chung, Yoon-Seok; Phalora, Prabhjeet K.; Maljkovic Berry, Irina; Archer, John; Penugonda, Sudhir; Fischer, Will; Richman, Douglas D.; Bhattacharya, Tanmoy; Malim, Michael H.; Wolinsky, Steven M.

    2014-01-01

    Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A) mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1) cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA)-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection. PMID:25080100

  4. Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function

    PubMed Central

    Voo, Kui S.; Bover, Laura; Harline, Megan L.; Vien, Long T.; Facchinetti, Valeria; Arima, Kazuhiko; Kwak, Larry W.; Liu, Yong J.

    2013-01-01

    Current cancer vaccines induce tumor-specific T cell responses without sustained tumor regression because immunosuppressive elements within the tumor induce exhaustion of effector T cells and infiltration of immune-suppressive regulatory T cells (Tregs). Therefore, much effort has been made to generate agonistic Abs targeting members of the TNFR superfamily, such as OX40, 4- 1BB, and GITR, expressed on effector T cells and Tregs, to reinvigorate T cell effector function and block Treg-suppressive function. In this article, we describe the development of a panel of anti-human OX40 agonistic mouse mAbs that could promote effector CD4+ and CD8+ T cell proliferation, inhibit the induction of CD4+ IL-10 -producing type 1 regulatory T cells, inhibit the expansion of ICOS+IL-10+ Tregs, inhibit TGF-b–induced FOXP3 expression on naive CD4+ T cells, and block natural Treg–suppressive function. We humanized two anti–human OX40 mAb clones, and they retained the potency of their parental clones. These Abs should provide broad opportunities for potential combination therapy to treat a wide realm of cancers and preventative vaccines against infectious diseases. PMID:24014877

  5. Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function.

    PubMed

    Voo, Kui S; Bover, Laura; Harline, Megan L; Vien, Long T; Facchinetti, Valeria; Arima, Kazuhiko; Kwak, Larry W; Liu, Yong J

    2013-10-01

    Current cancer vaccines induce tumor-specific T cell responses without sustained tumor regression because immunosuppressive elements within the tumor induce exhaustion of effector T cells and infiltration of immune-suppressive regulatory T cells (Tregs). Therefore, much effort has been made to generate agonistic Abs targeting members of the TNFR superfamily, such as OX40, 4-1BB, and GITR, expressed on effector T cells and Tregs, to reinvigorate T cell effector function and block Treg-suppressive function. In this article, we describe the development of a panel of anti-human OX40 agonistic mouse mAbs that could promote effector CD4(+) and CD8(+) T cell proliferation, inhibit the induction of CD4(+) IL-10 -producing type 1 regulatory T cells, inhibit the expansion of ICOS(+)IL-10(+) Tregs, inhibit TGF-β-induced FOXP3 expression on naive CD4(+) T cells, and block natural Treg-suppressive function. We humanized two anti-human OX40 mAb clones, and they retained the potency of their parental clones. These Abs should provide broad opportunities for potential combination therapy to treat a wide realm of cancers and preventative vaccines against infectious diseases. PMID:24014877

  6. Plasma Fibrinogen Is a Natural Deterrent to Amyloid β–Induced Platelet Activation and Neuronal Toxicity

    PubMed Central

    Sonkar, Vijay K; Kulkarni, Paresh P; Chaurasia, Susheel N; Dash, Ayusman; Jauhari, Abhishek; Parmar, Devendra; Yadav, Sanjay; Dash, Debabrata

    2016-01-01

    Alzheimer’s disease (AD) is a devastating neurodegenerative disorder, characterized by extensive loss of neurons and deposition of amyloid β (Aβ) in the form of extracellular plaques. Aβ is considered to have a critical role in synaptic loss and neuronal death underlying cognitive decline. Platelets contribute to 95% of circulating amyloid precursor protein that releases Aβ into circulation. We have recently demonstrated that the Aβ active fragment containing amino acid sequence 25–35 (Aβ25–35) is highly thrombogenic in nature and elicits strong aggregation of washed human platelets in a RhoA-dependent manner. In this study, we evaluated the influence of fibrinogen on Aβ-induced platelet activation. Intriguingly, Aβ failed to induce aggregation of platelets suspended in plasma but not in buffer. Fibrinogen brought about dose-dependent decline in aggregatory response of washed human platelets elicited by Aβ25–35, which could be reversed by increasing doses of Aβ. Fibrinogen also attenuated Aβ-induced platelet responses such as secretion, clot retraction, rise in cytosolic Ca+2 and reactive oxygen species. Fibrinogen prevented intracellular accumulation of full-length Aβ peptide (Aβ42) in platelets as well as neuronal cells. We conclude that fibrinogen serves as a physiological check against the adverse effects of Aβ by preventing its interaction with cells. PMID:27262026

  7. Cytotoxicity induced by exposure to natural and synthetic tremolite asbestos: an in vitro pilot study.

    PubMed

    Pugnaloni, Armanda; Giantomassi, Federica; Lucarini, Guendalina; Capella, Silvana; Bloise, Andrea; Di Primio, Roberto; Belluso, Elena

    2013-03-01

    Mineral fibers are potential carcinogens to humans. In order to help clarify the etiology of the pathological effects of asbestos, cellular reactions to natural and synthetic asbestos fibers were compared using a lung alveolar cancer cell line (A549 epithelial cells), considered the first target of inhaled micro-environmental contaminants. Natural asbestos tremolite (NAT) fibers were collected from rocks in NW Italy. Synthetic asbestos tremolite (SAT) was iron-free and therefore considered as standard tremolite. Both fibers, subjected to mineralogical characterization by X-ray powder diffractometry, electron microscopy and energy dispersive spectrometry, fell within the definition of respirable and potentially carcinogenic fibers. Several signs of functional and structural cell damage were found after treatment with both fibers, documented by viability, motility, and morphological perturbations. Phalloidin labeling showed irregular distribution of cytoskeletal F-actin, whereas immunohistochemical investigations showed abnormal expression of VEGF, Cdc42, β-catenin, assessed as risks indicators for cancer development. Both fibers caused significant loss of viability, even compared to UICC crocidolite, but, while SAT fibers exerted a more direct cytotoxic effect, survival of damaged cells expressing high VEGF levels was detected after NAT contact. This in vitro pilot study outlines potential health risks of NAT fibers in vivo related to their iron content, which could trigger signaling networks connected with cell proliferation and neoplastic transformation. PMID:22578742

  8. Impact-induced shock and the formation of natural quasicrystals in the early solar system.

    PubMed

    Hollister, Lincoln S; Bindi, Luca; Yao, Nan; Poirier, Gerald R; Andronicos, Christopher L; MacPherson, Glenn J; Lin, Chaney; Distler, Vadim V; Eddy, Michael P; Kostin, Alexander; Kryachko, Valery; Steinhardt, William M; Yudovskaya, Marina; Eiler, John M; Guan, Yunbin; Clarke, Jamil J; Steinhardt, Paul J

    2014-06-13

    The discovery of a natural quasicrystal, icosahedrite (Al63Cu24Fe13), accompanied by khatyrkite (CuAl2) and cupalite (CuAl) in the CV3 carbonaceous chondrite Khatyrka has posed a mystery as to what extraterrestrial processes led to the formation and preservation of these metal alloys. Here we present a range of evidence, including the discovery of high-pressure phases never observed before in a CV3 chondrite, indicating that an impact shock generated a heterogeneous distribution of pressures and temperatures in which some portions reached at least 5 GPa and 1,200 °C. The conditions were sufficient to melt Al-Cu-bearing minerals, which then rapidly solidified into icosahedrite and other Al-Cu metal phases. The meteorite also contains heretofore unobserved phases of iron-nickel and iron sulphide with substantial amounts of Al and Cu. The presence of these phases in Khatyrka provides further proof that the Al-Cu alloys are natural products of unusual processes that occurred in the early solar system.

  9. Impact-induced shock and the formation of natural quasicrystals in the early solar system.

    PubMed

    Hollister, Lincoln S; Bindi, Luca; Yao, Nan; Poirier, Gerald R; Andronicos, Christopher L; MacPherson, Glenn J; Lin, Chaney; Distler, Vadim V; Eddy, Michael P; Kostin, Alexander; Kryachko, Valery; Steinhardt, William M; Yudovskaya, Marina; Eiler, John M; Guan, Yunbin; Clarke, Jamil J; Steinhardt, Paul J

    2014-01-01

    The discovery of a natural quasicrystal, icosahedrite (Al63Cu24Fe13), accompanied by khatyrkite (CuAl2) and cupalite (CuAl) in the CV3 carbonaceous chondrite Khatyrka has posed a mystery as to what extraterrestrial processes led to the formation and preservation of these metal alloys. Here we present a range of evidence, including the discovery of high-pressure phases never observed before in a CV3 chondrite, indicating that an impact shock generated a heterogeneous distribution of pressures and temperatures in which some portions reached at least 5 GPa and 1,200 °C. The conditions were sufficient to melt Al-Cu-bearing minerals, which then rapidly solidified into icosahedrite and other Al-Cu metal phases. The meteorite also contains heretofore unobserved phases of iron-nickel and iron sulphide with substantial amounts of Al and Cu. The presence of these phases in Khatyrka provides further proof that the Al-Cu alloys are natural products of unusual processes that occurred in the early solar system. PMID:24925481

  10. Investigating natural organic carbon removal and structural alteration induced by pulsed ultrasound.

    PubMed

    Al-Juboori, Raed A; Yusaf, Talal; Aravinthan, Vasantha; Bowtell, Leslie

    2016-01-15

    The application of pulsed ultrasound for DOC removal from natural water samples has been thoroughly investigated in this work. Natural water samples were treated with ultrasound at power levels of 48 and 84 W with treatment times of 5 and 15 min. Chemical fractionation was conducted for both untreated and treated samples to clearly identify the change in DOC structure caused by ultrasonic treatments. Statistical analyses applying 2(3) factorial design were performed to study the behaviour of the response (i.e. DOC removal) under different operating conditions. Overall, ultrasonic treatments resulted in DOC removal of 7-15% depending on the applied operating conditions. The treated water had high microbial loading that interfered with DOC removal due primarily to the release of microbial products when exposed to ultrasound. Pulse ultrasound was found to be more effective than the continuous mode for DOC removal at the same effective power level. A regression model was developed and tested for DOC removal prediction. The model was adequate in predicting DOC removal with a maximum deviation from the experimental data of <11%. Pulsed ultrasound at low power levels and short treatment times was found to be the most energy efficient treatment for DOC removal. PMID:26473704

  11. B-1 Cell Heterogeneity and the Regulation of Natural and Antigen-Induced IgM Production.

    PubMed

    Baumgarth, Nicole

    2016-01-01

    A small subset of B cells, termed B-1 cells, with developmental origins, phenotypes, and functions that are distinct from those of conventional B cells exist in mice. It contributes the vast majority of spontaneously produced "natural" IgM. Natural IgM is constitutively produced, even in the absence of microbiota, and fulfills many distinct functions in tissue homeostasis and host defense. B-1 cells also respond with IgM production to innate signals and pathogen exposure, while maintaining steady-state levels natural IgM. Thus, within the B-1 cell pool, cells of distinct and heterogeneous functionality must exist to facilitate these different functions. This review considers three factors that may contribute to this heterogeneity: first, developmental differences regarding the origins of the precursors, second, tissue-specific signals that may differentially affect B-1 cells in the tissue compartments, and finally responsiveness to self-antigens as well as innate and antigen-specific signals. All three are likely to shape the repertoire and responsiveness of B-1 cells to homeostatic- and antigen-induced signals and thus contribute to the functional heterogeneity among these innate-like B cells. PMID:27667991

  12. Natural and human-induced sinkhole hazards in Saudi Arabia: distribution, investigation, causes and impacts

    NASA Astrophysics Data System (ADS)

    Youssef, Ahmed M.; Al-Harbi, Hasan M.; Gutiérrez, Francisco; Zabramwi, Yasser A.; Bulkhi, Ali B.; Zahrani, Saeed A.; Bahamil, Alaa M.; Zahrani, Ahmed J.; Otaibi, Zaam A.; El-Haddad, Bosy A.

    2016-05-01

    Approximately 60 % of the 2,150,000 km2 area of Saudi Arabia is underlain by soluble sediments (carbonate and evaporite rock formations, salt diapirs, sabkha deposits). Despite its hyper-arid climate, a wide variety of recent sinkholes have been reported in numerous areas, involving significant property losses. Human activities, most notably groundwater extraction, have induced unstable conditions on pre-existing cavities. This work provides an overview of the sinkhole hazard in Saudi Arabia, a scarcely explored topic. It identifies the main karst formations and the distribution of the most problematic sinkhole areas, illustrated through several case studies covering the wide spectrum of subsidence mechanisms. Some of the main investigation methods are presented through selected examples, including remote sensing, trenching and geophysics. Based on the available data, the main causal factors are identified and further actions that should be undertaken to better assess and manage the risk are discussed.

  13. Mouse and pig models for studies of natural and vaccine-induced immunity to Bordetella pertussis.

    PubMed

    Mills, Kingston H G; Gerdts, Volker

    2014-04-01

    The increasing incidence of whooping cough in many developed countries has been linked with waning immunity induced after immunization with acellular pertussis (aP) vaccines. The rational design of an improved aP vaccine requires a full understanding of the mechanism of protective immunity and preclinical studies in animal models. Infection of mice and pigs with Bordetella pertussis has many features of the infection seen in humans and has already provided valuable information on the roles of innate and adaptive immune responses in protection. Recent findings in these models have already indicated that it may be possible to develop an improved aP vaccine based on a formulation that includes a Toll-like receptor agonist as an adjuvant.

  14. A 107-year-old coral from Florida Bay: barometer of natural and man- induced catastrophes?

    USGS Publications Warehouse

    Hudson, J.H.; Powell, G.V.N.; Robblee, M.B.; Smith, T. J.

    1989-01-01

    The 107-yr growth history of a massive coral Solenastrea bournoni from Florida Bay was reconstructed with X-ray imagery from a single 4 in. diameter (10 cm) core that penetrated the exact epicenter of the 95.3 cm high colony. Growth increments totalled 952.9 mm, averaging 8.9 mm/yr over the life of the coral. Growth rate trends in the Florida Bay coral were compared to those in a Montastraea annularis of similar age from a nearby patch reef on the Atlantic Ocean side of the Florida Keys. It was concluded that growth rate, at least in these specimens, is a questionable indicator of past hurricanes and freezes. There does appear to be, however, a possible cause-and-effect relationship between major man-induced environmental perturbations and a prolonged reduction in growth rate in each coral's growth record. -from Authors

  15. Grass leaf silicification: Natural selection for an inducible defense against herbivores.

    PubMed

    McNaughton, S J; Tarrants, J L

    1983-02-01

    Plants from four populations of three species of African grasses were collected from grasslands in Tanzania's Serengeti National Park that differ in the grazing intensity that they experience. Plants were grown in the laboratory in a factorial experiment in which variables were plant origin, species identification of plants, defoliation intensity, and supply of soluble silicate in the nutrient medium. All plants accumulated silica in leaf blades in the absence of soluble silicate from the nutrient medium. Plants native to the more heavily grazed grassland accumulated more silica in their leaf blades than did plants from the less heavily grazed site. Blade silica content was higher when plants were defoliated, indicating that silicification is an inducible defense against herbivores. The quantitative heterogeneity of this qualitatively homogeneous plant defense system may have contributed to the evolution of high species diversity in the grazing fauna.

  16. Grass leaf silicification: Natural selection for an inducible defense against herbivores

    PubMed Central

    McNaughton, S. J.; Tarrants, J. L.

    1983-01-01

    Plants from four populations of three species of African grasses were collected from grasslands in Tanzania's Serengeti National Park that differ in the grazing intensity that they experience. Plants were grown in the laboratory in a factorial experiment in which variables were plant origin, species identification of plants, defoliation intensity, and supply of soluble silicate in the nutrient medium. All plants accumulated silica in leaf blades in the absence of soluble silicate from the nutrient medium. Plants native to the more heavily grazed grassland accumulated more silica in their leaf blades than did plants from the less heavily grazed site. Blade silica content was higher when plants were defoliated, indicating that silicification is an inducible defense against herbivores. The quantitative heterogeneity of this qualitatively homogeneous plant defense system may have contributed to the evolution of high species diversity in the grazing fauna. PMID:16578767

  17. Monitoring natural and anthropogenic induced variations in water availability across Africa

    NASA Astrophysics Data System (ADS)

    Ahmed, M.; Sultan, M.; Wahr, J. M.; Yan, E.

    2014-12-01

    Africa, the second-driest continent in the world after Australia, is one of the most vulnerable continents to climate change. Understanding the impacts of climatic and anthropogenic factors on Africa's hydrologic systems is vital for the assessment and utilization of Africa's water resources. In this study, we utilize the Gravity Recovery and Climate Experiment (GRACE) and land surface models (LSM; GLDAS and CLM4.5) in conjunction with other readily-available temporal climatic and remote sensing, geological and hydrological datasets for monitoring the spatial and temporal trends in Terrestrial Water Storage (TWS) over a time period of 10 years (01/2003-12/2012) over the African continent and to investigate the nature (e.g., climatic and/or human pressures-related) of, and the controlling factors causing, these variations. Spatial and temporal (i.e., time series analysis) correlations of the trends extracted from GRACE-derived (TWSGRACE) and LSM-derived (TWSLSM) TWS indicate the following: (1) Large (≥ 90 % by area) sectors of Africa are undergoing statistically significant TWSGRACE and TWSLSM variations due to natural and anthropogenic causes; (2) a general correspondence between TWSGRACE and TWSLSM over areas (e.g., Niger and Mozambique NE basins in eastern and western Africa) largely controlled by natural (i.e., increase/decrease in precipitation and/or temperature) causes; (3) discrepancies are observed over areas that witnessed extensive anthropogenic effects measured by TWSGRACE but unaccounted for by TWSLSM. Examples include: (a) strong (compared to that observed by TWSLSM) negative TWSGRACE trends were observed over areas that witnessed heavy groundwater extraction (e.g., Western, Desert, Egypt); (b) strong (compared to that observed by TWSLSM) positive TWSGRACE over Lake Volta reservoir; and (c) strong (compared to that observed by TWSLSM) negative trends over areas undergoing heavy deforestation (e.g., northern and NW Congo Basin); (4) additional

  18. The gene pat-2, which induces natural parthenocarpy, alters the gibberellin content in unpollinated tomato ovaries.

    PubMed

    Fos, M; Nuez, F; García-Martínez, J L

    2000-02-01

    We investigated the role of gibberellins (GAs) in the effect of pat-2, a recessive mutation that induces facultative parthenocarpic fruit development in tomato (Lycopersicon esculentum Mill.) using near-isogenic lines with two different genetic backgrounds. Unpollinated wild-type Madrigal (MA/wt) and Cuarenteno (CU/wt) ovaries degenerated, but GA(3) application induced parthenocarpic fruit growth. On the contrary, parthenocarpic growth of MA/pat-2 and CU/pat-2 fruits, which occurs in the absence of pollination and hormone application, was not affected by GA(3). Pollinated MA/wt and parthenocarpic MA/pat-2 ovary development was negated by paclobutrazol, and this inhibitory effect was counteracted by GA(3). The main GAs of the early-13-hydroxylation pathway (GA(1), GA(3), GA(8), GA(19), GA(20), GA(29), GA(44), GA(53), and, tentatively, GA(81)) and two GAs of the non-13-hydroxylation pathway (GA(9) and GA(34)) were identified in MA/wt ovaries by gas chromatography-selected ion monitoring. GAs were quantified in unpollinated ovaries at flower bud, pre-anthesis, and anthesis. In unpollinated MA/pat-2 and CU/pat-2 ovaries, the GA(20) content was much higher (up to 160 times higher) and the GA(19) content was lower than in the corresponding non-parthenocarpic ovaries. The application of an inhibitor of 2-oxoglutarate-dependent dioxygenases suggested that GA(20) is not active per se. The pat-2 mutation may increase GA 20-oxidase activity in unpollinated ovaries, leading to a higher synthesis of GA(20), the precursor of an active GA. PMID:10677440

  19. The gene pat-2, which induces natural parthenocarpy, alters the gibberellin content in unpollinated tomato ovaries.

    PubMed

    Fos, M; Nuez, F; García-Martínez, J L

    2000-02-01

    We investigated the role of gibberellins (GAs) in the effect of pat-2, a recessive mutation that induces facultative parthenocarpic fruit development in tomato (Lycopersicon esculentum Mill.) using near-isogenic lines with two different genetic backgrounds. Unpollinated wild-type Madrigal (MA/wt) and Cuarenteno (CU/wt) ovaries degenerated, but GA(3) application induced parthenocarpic fruit growth. On the contrary, parthenocarpic growth of MA/pat-2 and CU/pat-2 fruits, which occurs in the absence of pollination and hormone application, was not affected by GA(3). Pollinated MA/wt and parthenocarpic MA/pat-2 ovary development was negated by paclobutrazol, and this inhibitory effect was counteracted by GA(3). The main GAs of the early-13-hydroxylation pathway (GA(1), GA(3), GA(8), GA(19), GA(20), GA(29), GA(44), GA(53), and, tentatively, GA(81)) and two GAs of the non-13-hydroxylation pathway (GA(9) and GA(34)) were identified in MA/wt ovaries by gas chromatography-selected ion monitoring. GAs were quantified in unpollinated ovaries at flower bud, pre-anthesis, and anthesis. In unpollinated MA/pat-2 and CU/pat-2 ovaries, the GA(20) content was much higher (up to 160 times higher) and the GA(19) content was lower than in the corresponding non-parthenocarpic ovaries. The application of an inhibitor of 2-oxoglutarate-dependent dioxygenases suggested that GA(20) is not active per se. The pat-2 mutation may increase GA 20-oxidase activity in unpollinated ovaries, leading to a higher synthesis of GA(20), the precursor of an active GA.

  20. Cytosine Methylation Alteration in Natural Populations of Leymus chinensis Induced by Multiple Abiotic Stresses

    PubMed Central

    Yu, Yingjie; Yang, Xuejiao; Wang, Huaying; Shi, Fengxue; Liu, Ying; Liu, Jushan; Li, Linfeng; Wang, Deli; Liu, Bao

    2013-01-01

    Background Human activity has a profound effect on the global environment and caused frequent occurrence of climatic fluctuations. To survive, plants need to adapt to the changing environmental conditions through altering their morphological and physiological traits. One known mechanism for phenotypic innovation to be achieved is environment-induced rapid yet inheritable epigenetic changes. Therefore, the use of molecular techniques to address the epigenetic mechanisms underpinning stress adaptation in plants is an important and challenging topic in biological research. In this study, we investigated the impact of warming, nitrogen (N) addition, and warming+nitrogen (N) addition stresses on the cytosine methylation status of Leymus chinensis Tzvel. at the population level by using the amplified fragment length polymorphism (AFLP), methylation-sensitive amplified polymorphism (MSAP) and retrotransposon based sequence-specific amplification polymorphism (SSAP) techniques. Methodology/Principal Findings Our results showed that, although the percentages of cytosine methylation changes in SSAP are significantly higher than those in MSAP, all the treatment groups showed similar alteration patterns of hypermethylation and hypomethylation. It meant that the abiotic stresses have induced the alterations in cytosine methylation patterns, and the levels of cytosine methylation changes around the transposable element are higher than the other genomic regions. In addition, the identification and analysis of differentially methylated loci (DML) indicated that the abiotic stresses have also caused targeted methylation changes at specific loci and these DML might have contributed to the capability of plants in adaptation to the abiotic stresses. Conclusions/Significance Our results demonstrated that abiotic stresses related to global warming and nitrogen deposition readily evoke alterations of cytosine methylation, and which may provide a molecular basis for rapid adaptation by

  1. Molecular nature of ultraviolet B light-induced deletions in the murine epidermis.

    PubMed

    Horiguchi, M; Masumura, K I; Ikehata, H; Ono, T; Kanke, Y; Nohmi, T

    2001-05-15

    Depletion of the stratospheric ozone layer leads to an increase in ambient UV loads, which are expected to raise skin cancer incidences. Tumor development in the skin could be a multistep process in which various genetic alterations, such as point mutations and deletions, occur successively. Here, we demonstrate that UVB irradiation efficiently induces deletions in the epidermis using a novel transgenic mouse, gpt delta. In this mouse model, deletions in lambda DNA integrated in the chromosome are preferentially selected as Spi(-) (sensitive to P2 interference) phages, which can then be subjected to molecular analysis. The mice were exposed to UVB at single doses of 0.3, 0.5, 1.0, 1.5, and 2.0 kJ/m(2). After 4 weeks, lambda phage was rescued from the genomic DNA of the epidermis by in vitro packaging reactions. The mutant frequencies of Spi(-) with large deletions in the epidermis increased >15-fold at a UVB dose of 0.5 kJ/m(2) over the control. Molecular sizes of most of the large deletions were >1000 bp. More than one-half of the large deletions occurred between short direct-repeat sequences from 1 to 6 bp, and the remainder had flush ends. In the unirradiated mouse, almost all of the Spi(-) mutants were 1-bp frameshifts in runs of identical bases. These results suggest that UVB irradiation induces deletions in the murine epidermis, and most of the deletions are generated through end-joining of double strand breaks in DNA.

  2. Can Dark Matter Induce Cosmological Evolution of the Fundamental Constants of Nature?

    NASA Astrophysics Data System (ADS)

    Stadnik, Y. V.; Flambaum, V. V.

    2015-11-01

    We demonstrate that massive fields, such as dark matter, can directly produce a cosmological evolution of the fundamental constants of nature. We show that a scalar or pseudoscalar (axionlike) dark matter field ϕ , which forms a coherently oscillating classical field and interacts with standard model particles via quadratic couplings in ϕ , produces "slow" cosmological evolution and oscillating variations of the fundamental constants. We derive limits on the quadratic interactions of ϕ with the photon, electron, and light quarks from measurements of the primordial 4He abundance produced during big bang nucleosynthesis and recent atomic dysprosium spectroscopy measurements. These limits improve on existing constraints by up to 15 orders of magnitude. We also derive limits on the previously unconstrained linear and quadratic interactions of ϕ with the massive vector bosons from measurements of the primordial 4He abundance.

  3. Glutathione diminishes Dibutyltin- and tributyltin-induced loss of lytic function in human natural killer cells

    PubMed Central

    Powell, Jeralyn J.; Davis, McLisa V.; Whalen, Margaret M.

    2008-01-01

    This study investigated whether reduced glutathione (GSH) was able to alter the negative effects of tributyltin (TBT) or dibutyltin (DBT) on the lytic function of human natural killer (NK) cells. NK cells are an intital immune defense against the development of tumors or viral infections. TBT and DBT are widespread environmental contaminants, due to their various industrial applications. Both TBT and DBT have been shown to decrease the ability of NK cells to lyse tumor cells (lytic function). The results indicated that the presence of GSH during exposure of NK cells to TBT or DBT diminished the negative effect of the BT on the lytic function of NK cells. This suggests that interaction TBT and DBT with functionally relevant sulfhydryl groups in NK cells may be part of the mechanism by which they decrease NK lytic function. PMID:18821099

  4. Can Dark Matter Induce Cosmological Evolution of the Fundamental Constants of Nature?

    PubMed

    Stadnik, Y V; Flambaum, V V

    2015-11-13

    We demonstrate that massive fields, such as dark matter, can directly produce a cosmological evolution of the fundamental constants of nature. We show that a scalar or pseudoscalar (axionlike) dark matter field ϕ, which forms a coherently oscillating classical field and interacts with standard model particles via quadratic couplings in ϕ, produces "slow" cosmological evolution and oscillating variations of the fundamental constants. We derive limits on the quadratic interactions of ϕ with the photon, electron, and light quarks from measurements of the primordial (4)He abundance produced during big bang nucleosynthesis and recent atomic dysprosium spectroscopy measurements. These limits improve on existing constraints by up to 15 orders of magnitude. We also derive limits on the previously unconstrained linear and quadratic interactions of ϕ with the massive vector bosons from measurements of the primordial (4)He abundance.

  5. The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine.

    PubMed

    Chidley, Christopher; Trauger, Sunia A; Birsoy, Kıvanç; O'Shea, Erin K

    2016-01-01

    Phenotypic screens allow the identification of small molecules with promising anticancer activity, but the difficulty in characterizing the mechanism of action of these compounds in human cells often undermines their value as drug leads. Here, we used a loss-of-function genetic screen in human haploid KBM7 cells to discover the mechanism of action of the anticancer natural product ophiobolin A (OPA). We found that genetic inactivation of de novo synthesis of phosphatidylethanolamine (PE) mitigates OPA cytotoxicity by reducing cellular PE levels. OPA reacts with the ethanolamine head group of PE in human cells to form pyrrole-containing covalent cytotoxic adducts and these adducts lead to lipid bilayer destabilization. Our characterization of this unusual cytotoxicity mechanism, made possible by unbiased genetic screening in human cells, suggests that the selective antitumor activity displayed by OPA may be due to altered membrane PE levels in cancer cells. PMID:27403889

  6. Plasma-Induced Degradation of Polypropene Plastics in Natural Volatile Constituents of Ledum palustre Herb

    NASA Astrophysics Data System (ADS)

    Yu, Hong; Yu, Shenjing; Ren, Chunsheng; Xiu, Zhilong

    2012-02-01

    Polypropene (PP) plastics can be effectively degraded by natural volatile constituents from Ledum palustre catalyzed by atmospheric air dielectric barrier (DBD) plasma. The electron spin resonance (ESR) result indicates that the volatile constituents produce radicals in aerobic condition energized by power sources such as light, UV, plasma and so on. The degradation is a novel chemically oxidative way and it is initiated by a series of radical reactions. Lots of active and oxidative species, radicals, products and high energy electromagnetic field in plasma aggravate the degradation process. The results about PP maximum tensile strength (σbmax) confirm this conclusion. PP plastic heavily loses its extensibility, mechanical integrity and strength in a short time after suffering a synergetic treatment of the herb extract and air DBD plasma with no toxic residues left. The components of herb extract keep almost unchanged and may be reused. This study offers a new approach to manage and recycle typical plastics.

  7. Anticedants and natural prevention of environmental toxicants induced accelerated aging of skin.

    PubMed

    Tanuja Yadav; Mishra, Shivangi; Das, Shefali; Aggarwal, Shikha; Rani, Vibha

    2015-01-01

    Skin is frequently exposed to a variety of environmental and chemical agents that accelerate ageing. External stress such as UV radiations (UVR) and environmental pollutants majorly deteriorate the skin morphology, by activating certain intrinsic factors such as Reactive Oxygen Species (ROS) which trigger the activation of Matrix Metalloproteinases (MMPs) and inflammatory responses hence damaging the extracellular matrix (ECM) components. To counter this, an exogenous supply of anti-oxidants, is required since the endogenous anti-oxidant system cannot alone suffice the need. Bio-prospecting of natural resources for anti-oxidants has hence been intensified. Immense research is being carried out to identify potential plants with potent anti-oxidant activity against skin ageing. This review summarizes the major factors responsible for premature skin ageing and the plants being targeted to lessen the impact of those. PMID:25555260

  8. Can Dark Matter Induce Cosmological Evolution of the Fundamental Constants of Nature?

    PubMed

    Stadnik, Y V; Flambaum, V V

    2015-11-13

    We demonstrate that massive fields, such as dark matter, can directly produce a cosmological evolution of the fundamental constants of nature. We show that a scalar or pseudoscalar (axionlike) dark matter field ϕ, which forms a coherently oscillating classical field and interacts with standard model particles via quadratic couplings in ϕ, produces "slow" cosmological evolution and oscillating variations of the fundamental constants. We derive limits on the quadratic interactions of ϕ with the photon, electron, and light quarks from measurements of the primordial (4)He abundance produced during big bang nucleosynthesis and recent atomic dysprosium spectroscopy measurements. These limits improve on existing constraints by up to 15 orders of magnitude. We also derive limits on the previously unconstrained linear and quadratic interactions of ϕ with the massive vector bosons from measurements of the primordial (4)He abundance. PMID:26613429

  9. Anticedants and natural prevention of environmental toxicants induced accelerated aging of skin.

    PubMed

    Tanuja Yadav; Mishra, Shivangi; Das, Shefali; Aggarwal, Shikha; Rani, Vibha

    2015-01-01

    Skin is frequently exposed to a variety of environmental and chemical agents that accelerate ageing. External stress such as UV radiations (UVR) and environmental pollutants majorly deteriorate the skin morphology, by activating certain intrinsic factors such as Reactive Oxygen Species (ROS) which trigger the activation of Matrix Metalloproteinases (MMPs) and inflammatory responses hence damaging the extracellular matrix (ECM) components. To counter this, an exogenous supply of anti-oxidants, is required since the endogenous anti-oxidant system cannot alone suffice the need. Bio-prospecting of natural resources for anti-oxidants has hence been intensified. Immense research is being carried out to identify potential plants with potent anti-oxidant activity against skin ageing. This review summarizes the major factors responsible for premature skin ageing and the plants being targeted to lessen the impact of those.

  10. [Music therapy induced alternations in natural killer cell count and function].

    PubMed

    Hasegawa, Y; Kubota, N; Inagaki, T; Shinagawa, N

    2001-03-01

    The effects of music therapy on natural killer (NK) cell count and activity (NKCA) were studied in 19 persons. Alzheimer's disease, cerebrovessel disease and Parkinson's disease subjects were assigned to a music therapy. Blood samples were drawn at rest and after completion of music therapy. Music therapy did not change the number of circulating lymphocytes. The percentage of NK cells increased during music therapy, along with an increase in the NK cell activity. The proportion of T cells, CD4 and CD8 did not change significantly during music therapy. One hour after the music therapy session, plasma adrenaline increased but cortisol and noradrenalin did not change. The results indicate that music therapy can significantly increase NK cell count and activity. The change in NK cell and function were independent of neuro-degenerative diseases.

  11. Molecular nature of mutations induced by high-LET irradiation with argon and carbon ions in Arabidopsis thaliana.

    PubMed

    Hirano, Tomonari; Kazama, Yusuke; Ohbu, Sumie; Shirakawa, Yuki; Liu, Yang; Kambara, Tadashi; Fukunishi, Nobuhisa; Abe, Tomoko

    2012-07-01

    Linear energy transfer (LET) is an important parameter to be considered in heavy-ion mutagenesis. However, in plants, no quantitative data are available on the molecular nature of the mutations induced with high-LET radiation above 101-124keVμm(-1). In this study, we irradiated dry seeds of Arabidopsis thaliana with Ar and C ions with an LET of 290keVμm(-1). We analyzed the DNA alterations caused by the higher-LET radiation. Mutants were identified from the M(2) pools. In total, 14 and 13 mutated genes, including bin2, egy1, gl1, gl2, hy1, hy3-5, ttg1, and var2, were identified in the plants derived from Ar- and C-ions irradiation, respectively. In the mutants from both irradiations, deletion was the most frequent type of mutation; 13 of the 14 mutated genes from the Ar ion-irradiated plants and 11 of the 13 mutated genes from the C ion-irradiated plants harbored deletions. Analysis of junction regions generated by the 2 types of irradiation suggested that alternative non-homologous end-joining was the predominant pathway of repair of break points. Among the deletions, the proportion of large deletions (>100bp) was about 54% for Ar-ion irradiation and about 64% for C-ion irradiation. Both current results and previously reported data revealed that the proportions of the large deletions induced by 290-keVμm(-1) radiations were higher than those of the large deletions induced by lower-LET radiations (6% for 22.5-30.0keVμm(-1) and 27% for 101-124keVμm(-1)). Therefore, the 290keVμm(-1) heavy-ion beams can effectively induce large deletions and will prove useful as novel mutagens for plant breeding and analysis of gene functions, particularly tandemly arrayed genes.

  12. Staphylococcal Phenotypes Induced by Naturally Occurring and Synthetic Membrane-Interactive Polyphenolic β-Lactam Resistance Modifiers

    PubMed Central

    Palacios, Lucia; Rosado, Helena; Micol, Vicente; Rosato, Adriana E.; Bernal, Patricia; Arroyo, Raquel; Grounds, Helen; Anderson, James C.; Stabler, Richard A.; Taylor, Peter W.

    2014-01-01

    Galloyl catechins, in particular (-)-epicatechin gallate (ECg), have the capacity to abrogate β-lactam resistance in methicillin-resistant strains of Staphylococcus aureus (MRSA); they also prevent biofilm formation, reduce the secretion of a large proportion of the exoproteome and induce profound changes to cell morphology. Current evidence suggests that these reversible phenotypic traits result from their intercalation into the bacterial cytoplasmic membrane. We have endeavoured to potentiate the capacity of ECg to modify the MRSA phenotype by stepwise removal of hydroxyl groups from the B-ring pharmacophore and the A:C fused ring system of the naturally occurring molecule. ECg binds rapidly to the membrane, inducing up-regulation of genes responsible for protection against cell wall stress and maintenance of membrane integrity and function. Studies with artificial membranes modelled on the lipid composition of the staphylococcal bilayer indicated that ECg adopts a position deep within the lipid palisade, eliciting major alterations in the thermotropic behaviour of the bilayer. The non-galloylated homolog (-)-epicatechin enhanced ECg-mediated effects by facilitating entry of ECg molecules into the membrane. ECg analogs with unnatural B-ring hydroxylation patterns induced higher levels of gene expression and more profound changes to MRSA membrane fluidity than ECg but adopted a more superficial location within the bilayer. ECg possessed a high affinity for the positively charged staphylococcal membrane and induced changes to the biophysical properties of the bilayer that are likely to account for its capacity to disperse the cell wall biosynthetic machinery responsible for β-lactam resistance. The ability to enhance these properties by chemical modification of ECg raises the possibility that more potent analogs could be developed for clinical evaluation. PMID:24699700

  13. Levo-tetrahydropalmatine, a natural, mixed dopamine receptor antagonist, inhibits methamphetamine self-administration and methamphetamine-induced reinstatement.

    PubMed

    Gong, Xiaokang; Yue, Kai; Ma, Baomiao; Xing, Junqiao; Gan, Yongping; Wang, Daisong; Jin, Guozhang; Li, Chaoying

    2016-05-01

    Despite the high prevalence of methamphetamine (METH) use, no FDA-approved pharmacological treatment is currently available for individuals with a METH addiction. Levo-tetrahydropalmatine (l-THP) is an alkaloid substance derived from corydalis and stephania that has been used in traditional Asian medicine for its analgesic, sedative and hypnotic properties. Previous pharmacological studies of l-THP indicated that it not only binds to D1 and D2 receptors but also has a low affinity for D3 receptors and may function as an antagonist. The unique pharmacological profile of l-THP suggests that it may have potential therapeutic effects on drug addiction; however, the effects of l-THP in individuals with METH addictions are largely unknown. In this study, we investigated the effects of l-THP on METH self-administration and METH-induced reinstatement. In our experiments, l-THP (1.25, 2.50 and 5.00 mg/kg, i.p.) decreased METH self-administration under the fixed-ratio 1 schedule. l-THP (2.50 and 5.00 mg/kg, i.p) also prevented the METH-induced reinstatement of METH-seeking behaviors. Interestingly, l-THP (1.25 and 2.50mg/kg, i.p) did not affect locomotor activity following METH injection (1mg/kg) suggesting that the observed effects of l-THP (2.50mg/kg) on METH-induced reinstatement were not due to motor impairments. Thus, l-THP (a natural, mixed dopamine (DA) receptor antagonist) attenuates METH self-administration and METH-induced reinstatement. PMID:26806555

  14. Tracking Down the Causes of Recent Induced and Natural Intraplate Earthquakes with 3D Seismological Analyses in Northwest Germany

    NASA Astrophysics Data System (ADS)

    Uta, P.; Brandes, C.; Boennemann, C.; Plenefisch, T.; Winsemann, J.

    2015-12-01

    Northwest Germany is a typical low strain intraplate region with a low seismic activity. Nevertheless, 58 well documented earthquakes with magnitudes of 0.5 - 4.3 affected the area in the last 40 years. Most of the epicenters were located in the vicinity of active natural gas fields and some inside. Accordingly, the earthquakes were interpreted as a consequence of hydrocarbon recovery (e.g. Dahm et al. 2007, Bischoff et al. 2013) and classified as induced events in the bulletins of the Federal Institute for Geosciences and Natural Resources (BGR). The two major ones have magnitudes of 4.3 and 4.0. They are the strongest earthquakes ever recorded in Northern Germany. Consequently, these events raise the question whether the ongoing extraction itself can cause them or if other natural tectonic processes like glacial isostatic adjustment may considerably contribute to their initiation. Recent studies of Brandes et al. (2012) imply that lithospheric stress changes due to post glacial isostatic adjustment might be also a potential natural cause for earthquakes in Central Europe. In order to better analyse the earthquakes and to test this latter hypothesis we performed a relocalization of the events with the NonLinLoc (Lomax et al. 2000) program package and two differently scaled 3D P-wave velocity models. Depending on the station coverage for a distinct event, either a fine gridded local model (88 x 73 x 15 km, WEG-model, made available by the industry) or a coarse regional model (1600 x 1600 x 45 km, data from CRUST1.0, Laske et al. 2013) and for some cases a combination of both models was used for the relocalization. The results confirm the trend of the older routine analysis: The majority of the events are located at the margins of the natural gas fields, some of them are now located closer to them. Focal depths mostly vary between 3.5 km and 10 km. However, for some of the events, especially for the older events with relatively bad station coverage, the error bars

  15. Were the 2011 Prague, Oklahoma Earthquakes Natural, Induced, or Something in Between?

    NASA Astrophysics Data System (ADS)

    McGarr, A.

    2013-12-01

    Two hypotheses have been proposed for the origin of the Prague, Oklahoma earthquake sequence, which is under debate. I offer a third explanation, whereby this sequence was triggered by approximately 12 million cubic m of wastewater injected into the epicentral zone, from five high-volume injection wells. This sequence included three earthquakes of M5 or greater: a M5 foreshock, the M5.7 main shock, and a M5 aftershock (Keranen et al., Geology, 2013). The main shock, which caused substantial damage, is of exceptional importance in the central and eastern United States because it is the second largest earthquake that has been recorded in this vast region. Because of its importance in assessing seismic hazard, especially in central Oklahoma, there is an urgent need to understand its origin. The first hypothesis argues that the Prague earthquakes are of natural origin (Keller and Holland, OGS website, 2013). As shown by Ellsworth et al. (abstract, SSA Meeting, 2012,), the seismicity in central Oklahoma has increased dramatically starting in 2009. This increase is inconsistent with natural processes that are likely to occur in this geologically stable area. Instead, it seems more likely that the increase in seismicity is related to the increase of fluid injection activities related to expanding oil and gas operations. Even so, the Prague earthquakes themselves could be a natural sequence. The second hypothesis argues that the M5 foreshock was triggered by pore pressure increase due to wastewater injected from two wells near the northeast end of the epicentral zone. This M5 event, in turn, increased the Coulomb stress on a pre-existing fault triggering the M5.7 mainshock and its numerous aftershocks (Keranen, et al., 2013). This hypothesis focuses on two nearly co-located disposal wells, Stasta 1 and 2, that together injected nearly 100,000 cubic m of wastewater into the basal aquifer during the years leading up to the Prague earthquakes. There are, however, five much

  16. Effects of natural and human-induced hypoxia on coastal benthos

    NASA Astrophysics Data System (ADS)

    Levin, L. A.; Ekau, W.; Gooday, A. J.; Jorissen, F.; Middelburg, J. J.; Naqvi, W.; Neira, C.; Rabalais, N. N.; Zhang, J.

    2009-04-01

    Coastal hypoxia (<1.42 ml L-1; 62.5 μM; 2 mg L-1, approx. 30% oxygen saturation) occurs seasonally in many estuaries, fjords, and along open coasts subject to upwelling or excessive riverine nutrient input, and permanently in some isolated seas and marine basins. Underlying causes of hypoxia include enhanced nutrient input from natural causes (upwelling) or anthropogenic origin (eutrophication) and reduction of mixing by limited circulation or enhanced stratification; combined these lead to higher surface water production, microbial respiration and eventual oxygen depletion. Advective inputs of low-oxygen waters may initiate or expand hypoxic conditions. Responses of estuarine, enclosed sea, and open shelf benthos to hypoxia depend on the duration, predictability, and intensity of oxygen depletion and on whether H2S is formed. Under suboxic conditions, large mats of filamentous sulfide oxidizing bacteria cover the seabed and consume sulfide, thereby providing a detoxified microhabitat for eukaryotic benthic communities. Calcareous foraminiferans and nematodes are particularly tolerant of low oxygen concentrations and may attain high densities and dominance, often in association with microbial mats. When oxygen is sufficient to support metazoans, small, soft-bodied invertebrates (typically annelids), often with short generation times and elaborate branchial structures, predominate. Large taxa are more sensitive than small taxa to hypoxia. Crustaceans and echinoderms are typically more sensitive to hypoxia, with lower oxygen thresholds, than annelids, sipunculans, molluscs and cnidarians. Mobile fish and shellfish will migrate away from low-oxygen areas. Within a species, early life stages may be more subject to oxygen stress than older life stages. Hypoxia alters both the structure and function of benthic communities, but effects may differ with regional hypoxia history. Human-caused hypoxia is generally linked to eutrophication, and occurs adjacent to watersheds

  17. In situ stress heterogeneity induced by weak natural fractures and faults with high slip-tendency

    NASA Astrophysics Data System (ADS)

    Chang, Chandong

    2014-05-01

    In situ stress measurements typically conducted using several geotechnical methods (hydraulic fracturing and overcoring) often show quite scattered and inconsistent stress magnitudes. Would they be artifacts from test errors or genuine stress signals in the crust? I report two field examples of stress measurements, in which lateral stresses represented by maximum (SHmax) and minimum (Shmin) horizontal principal stresses scatter quite widely, to investigate the cause of the observed stress heterogeneity. Hydraulic fracturing stress measurements were conducted in vertical boreholes at two different locations in South Korea. The boreholes are 300 and 400 m deep, respectively, both penetrating granites. Several isolated intervals of intact rocks over depths in the boreholes were vertically fractured by injecting water. Magnitudes of Shmin were determined from shut-in pressures. Magnitudes of SHmax were estimated based on the Hubbert-Willis (1957) equation using reliably determined hydraulic fracturing tensile strengths. The stress states in both locations are in reverse faulting stress regimes, in which vertical stress (Sv) is the least principal stress. The magnitudes of SHmax are generally within or close to stress range limited by frictional coefficients of 0.6-1.0 of nearby faults. However, SHmax do not increase consistently with depth, but rather scatter quite significantly. Over only a few tens of meter depth interval, the SHmax magnitudes jump up and down by an order of ~10 MPa, often resulting in lower SHmax values at deeper depths. Near the depths of relatively low stress, natural fractures and faults with wide apertures (for instance, wider than ~10 mm, observed from borehole image logs) are abundant, and near those of relatively high stress, those wide discontinuities are scarce. Such wide discontinuities are inferred to be filled with weak gouges or rock fragments, and thus tend to have relatively low frictional coefficients. In particular, the wide

  18. Naturally occurring and experimentally induced castor bean (Ricinus communis) poisoning in ducks

    USGS Publications Warehouse

    Jensen, W.I.; Allen, J.P.

    1981-01-01

    Castor bean (Ricinus communis) poisoning accounted for the death of several thousand ducks in the Texas panhandle in the fall and winter months of 1969-1971. Signs of intoxication resembled those of botulism, except for mucoid, blood-tinged excreta. The most common lesions were severe fatty change in the liver, widely distributed internal petechial hemorrhages or ecchymoses, and catarrhal enteritis. Nearly intact castor beans were found in the stomach of one duck during field necropsy. Fragments of seed coat resembling castor bean were found in the stomachs of 10 of 14 ducks examined in the laboratory. Clinical signs and postmortem lesions observed in wild ducks were induced experimentally in mallards (Anas platyrhynchos) by force-feeding intact castor beans. Toxicity titrations were erratic, but the LD50 appeared to be between three and four seeds. The mouse toxicity test, used to detect Clostridium botulinum toxin in the blood serum of intoxicated ducks, was negative in every case. Hemagglutination and precipitin tests generally failed to detect castor bean in extracts of excreta or intestinal contents of experimentally intoxicated ducks.

  19. Human monoclonal antibodies against West Nile virus induced by natural infection neutralize at a postattachment step.

    PubMed

    Vogt, Matthew R; Moesker, Bastiaan; Goudsmit, Jaap; Jongeneelen, Mandy; Austin, S Kyle; Oliphant, Theodore; Nelson, Steevenson; Pierson, Theodore C; Wilschut, Jan; Throsby, Mark; Diamond, Michael S

    2009-07-01

    West Nile virus (WNV) is a neurotropic flavivirus that is now a primary cause of epidemic encephalitis in North America. Studies of mice have demonstrated that the humoral immune response against WNV limits primary infection and protects against a secondary challenge. The most-potent neutralizing mouse monoclonal antibodies (MAbs) recognize an epitope on the lateral ridge of domain III (DIII-lr) of the envelope (E) protein. However, studies with serum from human patients show that antibodies against the DIII-lr epitope comprise, at best, a minor component of the human anti-WNV antibody response. Herein, we characterize in detail two WNV-specific human MAbs, CR4348 and CR4354, that were isolated from B-cell populations of convalescent patients. These MAbs strongly neutralize WNV infection of cultured cells, protect mice against lethal infection in vivo, and yet poorly recognize recombinant forms of the E protein. Instead, CR4348 and CR4354 bind determinants on intact WNV virions and subviral particles in a pH-sensitive manner, and neutralization is altered by mutations at the dimer interface in domain II and the hinge between domains I and II, respectively. CR4348 and CR4354 human MAbs neutralize infection at a postattachment step in the viral life cycle, likely by inhibiting acid-induced fusion within the endosome.

  20. Theoretical modeling of yields for proton-induced reactions on natural and enriched molybdenum targets.

    PubMed

    Celler, A; Hou, X; Bénard, F; Ruth, T

    2011-09-01

    Recent acute shortage of medical radioisotopes prompted investigations into alternative methods of production and the use of a cyclotron and ¹⁰⁰Mo(p,2n)(99m)Tc reaction has been considered. In this context, the production yields of (99m)Tc and various other radioactive and stable isotopes which will be created in the process have to be investigated, as these may affect the diagnostic outcome and radiation dosimetry in human studies. Reaction conditions (beam and target characteristics, and irradiation and cooling times) need to be optimized in order to maximize the amount of (99m)Tc and minimize impurities. Although ultimately careful experimental verification of these conditions must be performed, theoretical calculations can provide the initial guidance allowing for extensive investigations at little cost. We report the results of theoretically determined reaction yields for (99m)Tc and other radioactive isotopes created when natural and enriched molybdenum targets are irradiated by protons. The cross-section calculations were performed using a computer program EMPIRE for the proton energy range 6-30 MeV. A computer graphical user interface for automatic calculation of production yields taking into account various reaction channels leading to the same final product has been created. The proposed approach allows us to theoretically estimate the amount of (99m)Tc and its ratio relative to (99g)Tc and other radioisotopes which must be considered reaction contaminants, potentially contributing to additional patient dose in diagnostic studies.

  1. Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation.

    PubMed Central

    Dinges, D F; Douglas, S D; Zaugg, L; Campbell, D E; McMann, J M; Whitehouse, W G; Orne, E C; Kapoor, S C; Icaza, E; Orne, M T

    1994-01-01

    The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep. PMID:7910171

  2. Natural selection canalizes expression variation of environmentally induced plasticity-enabling genes.

    PubMed

    Shaw, Joseph R; Hampton, Thomas H; King, Benjamin L; Whitehead, Andrew; Galvez, Fernando; Gross, Robert H; Keith, Nathan; Notch, Emily; Jung, Dawoon; Glaholt, Stephen P; Chen, Celia Y; Colbourne, John K; Stanton, Bruce A

    2014-11-01

    Many organisms survive fluctuating and extreme environmental conditions by manifesting multiple distinct phenotypes during adulthood by means of developmental processes that enable phenotypic plasticity. We report on the discovery of putative plasticity-enabling genes that are involved in transforming the gill of the euryhaline teleost fish, Fundulus heteroclitus, from its freshwater to its seawater gill-type, a process that alters both morphology and function. Gene expression that normally enables osmotic plasticity is inhibited by arsenic. Gene sets defined by antagonistic interactions between arsenic and salinity show reduced transcriptional variation among individual fish, suggesting unusually accurate and precise regulatory control of these genes, consistent with the hypothesis that they participate in a canalized developmental response. We observe that natural selection acts to preserve canalized gene expression in populations of killifish that are most tolerant to abrupt salinity change and that these populations show the least variability in their transcription of genes enabling plasticity of the gill. We found that genes participating in this highly canalized and conserved plasticity-enabling response had significantly fewer and less complex associations with transcriptional regulators than genes that respond only to arsenic or salinity. Collectively these findings, which are drawn from the relationships between environmental challenge, plasticity, and canalization among populations, suggest that the selective processes that facilitate phenotypic plasticity do so by targeting the regulatory networks that gives rise to the response. These findings also provide a generalized, conceptual framework of how genes might interact with the environment and evolve toward the development of plastic traits. PMID:25158801

  3. Mannheimia haemolytica A1-induced fibrinosuppurative meningoencephalitis in a naturally-infected Holstein-Friesian calf.

    PubMed

    Aschenbroich, S; Nemeth, N; Rech, R; Briggs, R; Sanchez, S; Brown, C

    2013-01-01

    Mannheimia haemolytica is an opportunistic bacterium that is widely recognized among the bovine respiratory disease complex as the predominant pathogen causing broncho- and pleuropneumonia in cattle. Among the characterized M. haemolytica serotypes, A1 is the major cause of severe pulmonary lesions in cattle. This report describes post-mortem findings in a Holstein-Friesian calf with fibrinosuppurative meningoencephalitis and fibrinonecrotizing, haemorrhagic broncho- and pleuropneumonia, from which M. haemolytica and bovine viral diarrhoea virus (BVDV) were isolated. Microscopical evaluation showed expansion of the brainstem and cerebellar leptomeninges by neutrophils and fibrin, associated with gram-negative coccobacilli. Occasional blood vessels within the midbrain and cerebellum contained fibrin thrombi. Bacterial culture of cerebellum and lung yielded M. haemolytica with unusually high haemolytic activity. The isolates were confirmed as serotype A1 by rapid plate agglutination. Lung tissue was positive for BVDV by polymerase chain reaction. The broncho- and pleuropneumonia in this calf were consistent with typical mannheimiosis due to serotype A1; however, extrapulmonary infections due to M. haemolytica, as seen in this case, are rarely reported. To our knowledge, this is the first documentation of a natural BVDV and M. haemolytica co-infection associated with fibrinosuppurative meningoencephalitis in a calf.

  4. Low Dose Focused Ultrasound Induces Enhanced Tumor Accumulation of Natural Killer Cells

    PubMed Central

    Sta Maria, Naomi S.; Barnes, Samuel R.; Weist, Michael R.; Colcher, David; Raubitschek, Andrew A.; Jacobs, Russell E.

    2015-01-01

    Natural killer (NK) cells play a vital antitumor role as part of the innate immune system. Efficacy of adoptive transfer of NK cells depends on their ability to recognize and target tumors. We investigated whether low dose focused ultrasound with microbubbles (ldbFUS) could facilitate the targeting and accumulation of NK cells in a mouse xenograft of human colorectal adenocarcinoma (carcinoembryonic antigen (CEA)-expressing LS-174T implanted in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice) in the presence of an anti-CEA immunocytokine (ICK), hT84.66/M5A-IL-2 (M5A-IL-2). Human NK cells were labeled with an FDA-approved ultra-small superparamagnetic iron oxide particle, ferumoxytol. Simultaneous with the intravenous injection of microbubbles, focused ultrasound was applied to the tumor. In vivo longitudinal magnetic resonance imaging (MRI) identified enhanced accumulation of NK cells in the ensonified tumor, which was validated by endpoint histology. Significant accumulation of NK cells was observed up to 24 hrs at the tumor site when ensonified with 0.50 MPa peak acoustic pressure ldbFUS, whereas tumors treated with at 0.25 MPa showed no detectable NK cell accumulation. These clinically translatable results show that ldbFUS of the tumor mass can potentiate tumor homing of NK cells that can be evaluated non-invasively using MRI. PMID:26556731

  5. Natural selection canalizes expression variation of environmentally induced plasticity-enabling genes.

    PubMed

    Shaw, Joseph R; Hampton, Thomas H; King, Benjamin L; Whitehead, Andrew; Galvez, Fernando; Gross, Robert H; Keith, Nathan; Notch, Emily; Jung, Dawoon; Glaholt, Stephen P; Chen, Celia Y; Colbourne, John K; Stanton, Bruce A

    2014-11-01

    Many organisms survive fluctuating and extreme environmental conditions by manifesting multiple distinct phenotypes during adulthood by means of developmental processes that enable phenotypic plasticity. We report on the discovery of putative plasticity-enabling genes that are involved in transforming the gill of the euryhaline teleost fish, Fundulus heteroclitus, from its freshwater to its seawater gill-type, a process that alters both morphology and function. Gene expression that normally enables osmotic plasticity is inhibited by arsenic. Gene sets defined by antagonistic interactions between arsenic and salinity show reduced transcriptional variation among individual fish, suggesting unusually accurate and precise regulatory control of these genes, consistent with the hypothesis that they participate in a canalized developmental response. We observe that natural selection acts to preserve canalized gene expression in populations of killifish that are most tolerant to abrupt salinity change and that these populations show the least variability in their transcription of genes enabling plasticity of the gill. We found that genes participating in this highly canalized and conserved plasticity-enabling response had significantly fewer and less complex associations with transcriptional regulators than genes that respond only to arsenic or salinity. Collectively these findings, which are drawn from the relationships between environmental challenge, plasticity, and canalization among populations, suggest that the selective processes that facilitate phenotypic plasticity do so by targeting the regulatory networks that gives rise to the response. These findings also provide a generalized, conceptual framework of how genes might interact with the environment and evolve toward the development of plastic traits.

  6. Radial segregation induced by natural convection and melt/solid interface shape in vertical Bridgman growth

    NASA Technical Reports Server (NTRS)

    Chang, C. J.; Brown, R. A.

    1983-01-01

    The roles of natural convection in the melt and the shape of the melt/solid interface on radial dopant segregation are analyzed for a prototype of vertical Bridgman crystal growth system by finite element methods that solve simultaneously for the velocity field in the melt, the shape of the solidification isotherm, and the temperature distribution in both phases. Results are presented for crystal and melt with thermophysical properties similar to those of gallium-doped germanium in Bridgman configurations with melt below (thermally destabilizing) and above (stabilizing) the crystal. Steady axisymmetric flow are classified according to Rayleigh number as either being nearly the growth velocity, having a weak cellular structure or having large amplitude cellular convention. The flows in the two Bridgman configurations are driven by different temperature gradients and are in opposite directions. Finite element calculations for the transport of a dilute dopant by these flow fields reveal radial segregation levels as large as sixty percent of the mean concentration. Segregation is found most severe at an intermediate value of Rayleigh number above which the dopant distribution along the interface levels as the intensity of the flow increases.

  7. Bone remodelling in the natural acetabulum is influenced by muscle force-induced bone stress.

    PubMed

    Fernandez, Justin; Sartori, Massimo; Lloyd, David; Munro, Jacob; Shim, Vickie

    2014-01-01

    A modelling framework using the international Physiome Project is presented for evaluating the role of muscles on acetabular stress patterns in the natural hip. The novel developments include the following: (i) an efficient method for model generation with validation; (ii) the inclusion of electromyography-estimated muscle forces from gait; and (iii) the role that muscles play in the hip stress pattern. The 3D finite element hip model includes anatomically based muscle area attachments, material properties derived from Hounsfield units and validation against an Instron compression test. The primary outcome from this study is that hip loading applied as anatomically accurate muscle forces redistributes the stress pattern and reduces peak stress throughout the pelvis and within the acetabulum compared with applying the same net hip force without muscles through the femur. Muscle forces also increased stress where large muscles have small insertion sites. This has implications for the hip where bone stress and strain are key excitation variables used to initiate bone remodelling based on the strain-based bone remodelling theory. Inclusion of muscle forces reduces the predicted sites and degree of remodelling. The secondary outcome is that the key muscles that influenced remodelling in the acetabulum were the rectus femoris, adductor magnus and iliacus.

  8. The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine

    PubMed Central

    Chidley, Christopher; Trauger, Sunia A; Birsoy, Kıvanç; O'Shea, Erin K

    2016-01-01

    Phenotypic screens allow the identification of small molecules with promising anticancer activity, but the difficulty in characterizing the mechanism of action of these compounds in human cells often undermines their value as drug leads. Here, we used a loss-of-function genetic screen in human haploid KBM7 cells to discover the mechanism of action of the anticancer natural product ophiobolin A (OPA). We found that genetic inactivation of de novo synthesis of phosphatidylethanolamine (PE) mitigates OPA cytotoxicity by reducing cellular PE levels. OPA reacts with the ethanolamine head group of PE in human cells to form pyrrole-containing covalent cytotoxic adducts and these adducts lead to lipid bilayer destabilization. Our characterization of this unusual cytotoxicity mechanism, made possible by unbiased genetic screening in human cells, suggests that the selective antitumor activity displayed by OPA may be due to altered membrane PE levels in cancer cells. DOI: http://dx.doi.org/10.7554/eLife.14601.001 PMID:27403889

  9. Photochemically-induced fluorescence dosage of non-fluorescent pyrethroid (Etofenprox) in natural water using a cationic micellar medium.

    PubMed

    Adamou, Rabani; Coly, Atanasse; Abdoulaye, Alassane; Soumaila, Maimouna; Moussa, Idrissa; Ikhiri, Khalid; Tine, Alphonse

    2011-07-01

    An analytical method based on the use of UV-irradiation to produce fluorescent derivatives from Etofenprox a non-fluorescent pyrethroid insecticide is described. The impact of cetyltrimethylammonium chloride (CTAC) micellar medium on the Etofenprox photochemically-induced fluorescence (PIF) is reported. Parameters influencing the sensitivity and repeatability of the PIF method have been optimized. The alkaline medium (NaOH 6 × 10(-2) M) + CTAC surfactant molecules (3.84 mg/ml) in acetonitrile is found to be very suitable for this pyrethroid insecticide analysis in environment matrices. Linear dynamic range is established over more than two orders of magnitude. The limit of detection is lower than 5 ng/ml. The method seems to be suitable for environmental matrices quality control. Application to the analysis of spiked natural waters gave recoveries rate ranged from 94 to 104% and 107 to 115% respectively for river and pound water. PMID:21222143

  10. Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute infection in naive adult woodchucks.

    PubMed

    Freitas, Natalia; Lukash, Tetyana; Dudek, Megan; Litwin, Sam; Menne, Stephan; Gudima, Severin O

    2015-07-01

    Woodchuck hepatitis virus (WHV) is often used as surrogate to study mechanism of HBV infection. Currently, most infections are conducted using strains WHV7 or WHV8 that have very high sequence identity. This study focused on natural strain WHVNY that is more genetically distant from WHV7. Three naive adult woodchucks inoculated with WHVNY developed productive acute infection with long lasting viremia. However, only one of two woodchucks infected with WHV7 at the same multiplicity demonstrated productive liver infection. Quantification of intracellular WHV RNA and DNA replication intermediates; percentages of core antigen-positive hepatocytes; and serum relaxed circular DNA showed that strains WHVNY and WHV7 displayed comparable replication levels and capacities to induce acute infection in naive adult woodchucks. Strain WHVNY was therefore validated as valuable reagent to analyze the mechanism of hepadnavirus infection, especially in co- and super-infection settings, which required discrimination between two related virus genomes replicating in the same liver. PMID:25979221

  11. Evaluation of alkali concentration in conditions relevant to oxygen/natural gas glass furnaces by laser-induced breakdown spectroscopy.

    SciTech Connect

    Walsh, Peter M.; Molina, Alejandro; Shaddix, Christopher R.; Blevins, Linda Gail; Sickafoose, Shane M.

    2005-01-01

    A number of industrial combustion systems are adopting oxygen-enhanced firing to improve heat transfer characteristics and reduce emissions. The exhaust gas from these systems is dominated by H2O and CO2 and therefore has substantially different gas properties from traditional combustion exhaust. In the past, laser-induced breakdown spectroscopy (LIBS) has been successfully used for the evaluation of alkali aerosol concentrations in air-based combustion systems. This paper presents results of LIBS measurements of alkali concentrations in a laboratory calibration setup and in an oxygen/natural gas container glass furnace. It shows how both gas conditions (composition and temperature) and the molecular form of the alkali species affect the LIBS signals. The paper proposes strategies for mitigating these effects in future applications of LIBS in oxygen-enhanced combustion systems.

  12. Cross section measurements of deuteron induced nuclear reactions on natural titanium up to 34 MeV.

    PubMed

    Duchemin, C; Guertin, A; Haddad, F; Michel, N; Métivier, V

    2015-09-01

    Experimental cross sections for deuteron induced nuclear reactions on natural titanium were measured, using the stacked-foil technique and gamma spectrometry, up to 34 MeV with beams provided by the ARRONAX cyclotron. The experimental cross section values were monitored using the (nat)Ti(d,x)(48)V reaction, recommended by the IAEA. The excitation functions for (nat)Ti(d,x)(44m,46,47,48)Sc are presented and compared with the existing ones and with the TALYS 1.6 code calculations using default models. Our experimental values are in good agreement with data found in the literature. TALYS 1.6 is not able to give a good estimation of the production cross sections investigated in this work. These production cross sections of scandium isotopes fit with the new Coordinated Research Project (CRP) launched by the International Atomic Energy Agency (IAEA) to expand the database of monitor reactions. PMID:26103622

  13. A marching-walking hybrid induces step length adaptation and transfers to natural walking

    PubMed Central

    Long, Andrew W.; Finley, James M.

    2015-01-01

    Walking is highly adaptable to new demands and environments. We have previously studied adaptation of locomotor patterns via a split-belt treadmill, where subjects learn to walk with one foot moving faster than the other. Subjects learn to adapt their walking pattern by changing the location (spatial) and time (temporal) of foot placement. Here we asked whether we can induce adaptation of a specific walking pattern when one limb does not “walk” but instead marches in place (i.e., marching-walking hybrid). The marching leg's movement is limited during the stance phase, and thus certain sensory signals important for walking may be reduced. We hypothesized that this would produce a spatial-temporal strategy different from that of normal split-belt adaptation. Healthy subjects performed two experiments to determine whether they could adapt their spatial-temporal pattern of step lengths during the marching-walking hybrid and whether the learning transfers to over ground walking. Results showed that the hybrid group did adapt their step lengths, but the time course of adaptation and deadaption was slower than that for the split-belt group. We also observed that the hybrid group utilized a mostly spatial strategy whereas the split-belt group utilized both spatial and temporal strategies. Surprisingly, we found no significant difference between the hybrid and split-belt groups in over ground transfer. Moreover, the hybrid group retained more of the learned pattern when they returned to the treadmill. These findings suggest that physical rehabilitation with this marching-walking paradigm on conventional treadmills may produce changes in symmetry comparable to what is observed during split-belt training. PMID:25867742

  14. Passive seismic monitoring of natural and induced earthquakes: case studies, future directions and socio-economic relevance

    USGS Publications Warehouse

    Bohnhoff, Marco; Dresen, Georg; Ellsworth, William L.; Ito, Hisao; Cloetingh, Sierd; Negendank, Jörg

    2010-01-01

    An important discovery in crustal mechanics has been that the Earth’s crust is commonly stressed close to failure, even in tectonically quiet areas. As a result, small natural or man-made perturbations to the local stress field may trigger earthquakes. To understand these processes, Passive Seismic Monitoring (PSM) with seismometer arrays is a widely used technique that has been successfully applied to study seismicity at different magnitude levels ranging from acoustic emissions generated in the laboratory under controlled conditions, to seismicity induced by hydraulic stimulations in geological reservoirs, and up to great earthquakes occurring along plate boundaries. In all these environments the appropriate deployment of seismic sensors, i.e., directly on the rock sample, at the earth’s surface or in boreholes close to the seismic sources allows for the detection and location of brittle failure processes at sufficiently low magnitude-detection threshold and with adequate spatial resolution for further analysis. One principal aim is to develop an improved understanding of the physical processes occurring at the seismic source and their relationship to the host geologic environment. In this paper we review selected case studies and future directions of PSM efforts across a wide range of scales and environments. These include induced failure within small rock samples, hydrocarbon reservoirs, and natural seismicity at convergent and transform plate boundaries. Each example represents a milestone with regard to bridging the gap between laboratory-scale experiments under controlled boundary conditions and large-scale field studies. The common motivation for all studies is to refine the understanding of how earthquakes nucleate, how they proceed and how they interact in space and time. This is of special relevance at the larger end of the magnitude scale, i.e., for large devastating earthquakes due to their severe socio-economic impact.

  15. Historical changes in channel network extent and channel planform in an intensively managed landscape: Natural versus human-induced effects

    NASA Astrophysics Data System (ADS)

    Rhoads, Bruce L.; Lewis, Quinn W.; Andresen, William

    2016-01-01

    Humans have become major geomorphological agents, effecting substantial change in the characteristics of Earth's physical landscapes. The agricultural Midwest of the United States is a region marked by pronounced human influence at the landscape scale. Humans undoubtedly have strongly influenced critical zone processes, including fluvial processes, in intensively managed agricultural landscapes, yet the exact nature of human alteration of these processes is unknown. This study documents historical changes in the extent of the stream channel network and in channel planform within the upper Sangamon River basin - an intensively managed agricultural watershed in Illinois. Results indicate that the modern channel network is nearly three times more extensive than the channel network in the 1820s. Most change in drainage density has occurred in headwater portions of the basin where numerous drainage ditches have been added to the network to drain flat uplands. No detectable change in channel position is evident between 1940 and 2012 along about 60% of the total length of the Sangamon River and its major tributaries. Nearly 30% of the total length exhibits change related to meander dynamics (cutoffs and lateral migration), whereas about 8% has changed as a result of channelization. Channelized sections typically remain straight for decades following human modification, supporting the notion that humans produce long-lasting catastrophic change in channel planform in this region. The findings confirm that humans are effective agents of morphological change in fluvial systems in this intensively managed watershed. Documenting human-induced versus natural changes in fluvial systems is important for evaluating how other critical zone processes in intensively managed landscapes have been affected by these changes. Human-induced changes in channel extent and planform most likely have altered this landscape from one dominated by biogeochemical transformations and storage of water

  16. Comparison of oestrous intensity between natural oestrus and oestrus induced with ovsynch based treatments in Japanese black cows.

    PubMed

    Meng Chao, Lu; Sato, S; Yoshida, K; Kawano, Y; Kojima, T; Kubota, C

    2010-02-01

    The aim of this study was to examine the possible differences of oestrous intensity between natural oestrus and induced oestrus using the walking activity measuring device. Walking activity was used as an evaluation index of oestrous intensity. A total of 27 Japanese Black cows, more than 40 days after calving and clinically normal, were randomly assigned to three groups. Walking activity was recorded using a commercially available computerized pedometer system. The treatment groups consisted of an Ovsynch (n = 8) and a controlled internal drugs releasing device (CIDR) + Ovsynch (n = 9) group. The control group (n = 10) received no treatment. Walking activity was examined in all groups. Timed artificial insemination (timed AI) was performed at 16 hours after the onset of oestrus in the control group and at 24 h after second administration of GnRH in the treatment groups. Duration of oestrus had a tendency to be shorter in both the Ovsynch and the CIDR + Ovsynch groups when compared with the control group. The time required from the onset of oestrus to the time showing the highest number of steps of walking (the time to peak) showed a tendency to be shorter in CIDR + Ovsynch group. The number of steps of walking at peak and overall walking activities were significantly lower in both treatment groups than in the control group. Both activity and super-activity periods of time in the treatment groups were shorter than the control group. No difference was observed in the conception rate between the control (50.0%; 10/20), Ovsynch (50.0%; 4/8) and CIDR + Ovsynch groups (66.7%; 6/9). This study demonstrates that the oestrous intensity of cows in oestrus was different between natural oestrus and induced oestrus and also between the methods of the synchronization, but no difference was observed in the conception rate among the three groups.

  17. Natural and human-induced hypoxia and consequences for coastal areas: synthesis and future development

    NASA Astrophysics Data System (ADS)

    Zhang, J.; Gilbert, D.; Gooday, A.; Levin, L.; Naqvi, W.; Middelburg, J.; Scranton, M.; Ekau, W.; Pena, A.; Dewitte, B.; Oguz, T.; Monteiro, P. M. S.; Urban, E.; Rabalais, N.; Ittekkot, V.; Kemp, W. M.; Ulloa, O.; Elmgren, R.; Escobar-Briones, E.; van der Plas, A.

    2009-11-01

    Hypoxia has become a world-wide phenomenon in the global coastal ocean and causes deterioration of structure and function of ecosystems. Based on the collective contributions of members of SCOR Working Group #128, the present study provides an overview of the major aspects of coastal hypoxia in different biogeochemical provinces, including estuaries, upwelling areas, fjords and semi-enclosed basins, with various external forcings, ecosystem responses, feedbacks and potential impact on the sustainability of the fishery and economics. The obvious external forcings include fresh water runoff and other factors contributing to stratification, organic matter and nutrient loadings, as well as exchange between coastal and open ocean water masses; their different interactions set up mechanisms that drive the system towards hypoxia. However, whether the coastal environment becomes hypoxic or not, under the combination of external forcings, depends also on the nature of the ecosystem, e.g. physical and geographic settings. It is understood that coastal hypoxia has a profound impact on the sustainability of ecosystems, which can be seen, for example, by the change in the food-web structure and system function; other influences can be compression and loss of habitat, as well as change in life cycle and reproduction. In most cases, the ecosystem responds to the low dissolved oxygen in a non-linear way and has pronounced feedbacks to other compartments of the Earth System, hence affecting human society. Our knowledge and previous experiences illustrate that there is a need to develop new observational tools and models to support integrated research of biogeochemical dynamics and ecosystem behaviour that will improve confidence in remediation management strategies for coastal hypoxia.

  18. Thyroid iodine content and serum thyroglobulin: cues to the natural history of destruction-induced thyroiditis

    SciTech Connect

    Smallridge, R.C.; De Keyser, F.M.; Van Herle, A.J.; Butkus, N.E.; Wartofsky, L.

    1986-06-01

    Twenty-eight patients with destructive thyroiditis were followed to study the natural history of healing of thyroid gland injury. All had sequential measurements of thyroidal iodine (/sup 127/I) content by fluorescent scanning (normal mean, 10.1 mg), 17 had serial serum thyroglobulin (Tg) measurements (normal, less than 21 ng/ml), and 13 had perchlorate discharge studies during the recovery phase. Seventeen patients had painful subacute thyroiditis (SAT), 9 had painless thyroiditis with thyrotoxicosis (PTT), and 2 had postpartum thyroiditis with thyrotoxicosis (PPT). Thyroidal iodine content decreased from a mean of 9.8 to a nadir of 3.8 mg in patients with SAT and from 8.5 to a nadir of 3.5 mg in patients with PTT. Mean serum Tg concentrations were highest (approximately 165 ng/ml) in both groups 1-3 months after the onset of symptoms. Abnormalities in both /sup 127/I content and Tg levels persisted for 2 or more yr in some individuals. No patient had detectable Tg antibodies by hemagglutination, but low titers were detected intermittently by sensitive RIA in 5 PTT patients. Microsomal antibodies were positive in only 1 of 16 SAT patients, but in 4 of 7 PTT patients and in both PPT patients. Three patients had positive perchlorate discharge tests (2 of 8 with SAT, 0 of 4 with PTT, and 1 of 1 with PPT). Permanent hypothyroidism occurred in 3 patients (2 with PTT; 1 with SAT and positive antibodies), but did not correlate with perchlorate results. HLA typing and serum immunoglobulin measurements were not useful for predicting the clinical course. These data indicate that several years may be necessary for complete resolution of destructive thyroiditis; many patients have evidence of thyroid injury persisting long after serum thyroid hormone and TSH levels become normal.

  19. Transfer of cryopreserved - thawed embryos in hCG induced natural or clomiphene citrate cycles yields similar live birth rates in normo-ovulatory women

    PubMed Central

    Fatemi, Human M.; Blockeel, Christophe; Stoop, Dominic; Albuarki, H.; Verheyen, Greta; Devroey, Paul

    2010-01-01

    Introduction The purpose of this retrospective analysis is to compare the efficiency of hCG-induced natural and Clomiphene citrate (CC) cycles in normovulatory patients undergoing frozen embryo transfer (FET). Materials and methods It was retrospectively conducted in the Dutchspeaking Free University of Brussels and covered the period from April 2003 to August 2006. In particular, 428 day-three FET cycles belonging to the two comparative groups were recruited. Of these FET cycles, 261 were hCG-induced natural and 167 clomiphene citrate-induced cycles. Results No statistically significant difference was observed in live birth rate between CC and natural group (22.2% versus 22.6%), respectively (P = 0.708). Except for the number of embryos transferred (1.72 ± 0.46 for CC group versus 1.63 ± 0.48 for natural group, P = 0.045), no other parameters seem to influence the outcome. Discussion To our knowledge, this is the first attempt to investigate which of the above mentioned regimens is optimal for normo-ovulatory women in FET cycles. A similar delivery outcome was observed for hCG–induced natural and CC-induced cycles used for endometrial preparation in FET. PMID:20703796

  20. R-(-)-{beta}-O-methylsynephrine, a natural product, inhibits VEGF-induced angiogenesis in vitro and in vivo

    SciTech Connect

    Kim, Nam Hee; Pham, Ngoc Bich; Quinn, Ronald J.; Kwon, Ho Jeong

    2010-08-13

    Research highlights: {yields} R-(-)-{beta}-O-methylsynephrine (OMe-Syn) is a natural compound isolated from a plant of the Rutaceae family. {yields} OMe-Syn possesses lead-like physicochemical properties, conferring good solubility. {yields} OMe-Syn effectively inhibited VEGF-induced angiogenesis in vitro and in vivo. {yields} OMe-Syn could be a novel basis for a small molecule targeting angiogenesis. -- Abstract: R-(-)-{beta}-O-methylsynephrine (OMe-Syn) is an active compound isolated from a plant of the Rutaceae family. We conducted cell proliferation assays on various cell lines and found that OMe-Syn more strongly inhibited the growth of human umbilical vein endothelial cells (HUVECs) than that of other normal and cancer cell lines tested. In angiogenesis assays, it inhibited vascular endothelial growth factor (VEGF)-induced invasion and tube formation of HUVECs with no toxicity. The anti-angiogenic activity of OMe-Syn was also validated in vivo using the chorioallantonic membrane (CAM) assay in growing chick embryos. Expression of the growth factors VEGF, hepatocyte growth factor, and basic fibroblast growth factor was suppressed by OMe-Syn in a dose-dependent manner. Taken together, our results indicate that this compound could be a novel basis for a small molecule targeting angiogenesis.

  1. Prior morphine experience induces long-term increases in social interest and in appetitive behavior for natural reward.

    PubMed

    Nocjar, Christine; Panksepp, Jaak

    2007-08-01

    Brain opioids regulate social emotional responsivity. One neuro-evolutionary theory of addiction suggests that exogenous opiates may induce addiction via opioid-controlled emotional changes; with the drug eventually fulfilling the need for social comfort that is normally provided by endogenous opioids. This view predicts that past opiate experience may enduringly alter social responsivity. Although the acute social effects of opiates are well known, little evidence is available concerning the enduring effects of past opiate experience on social motivation aside from copulatory behaviors. This study evaluated the long-term effects of 10 daily morphine (10mg/kg/day) or saline injections on social and non-social motivated behaviors. Following 3 days or 2 weeks drug abstinence, social interest, food-seeking, and sexual pursuit were assessed. After 2-weeks opiate withdrawal, sexual pursuit and food-seeking behaviors were significantly increased. After a shorter 3-day withdrawal, these effects were not seen. Importantly, social interest was consistently magnified, even after short-term 3-day opiate withdrawal, and it was magnified more than sexual or food pursuit. These findings indicate that the incentive for social and non-social natural rewards were increased following withdrawal from intermittent opiate treatment, but that different morphine-induced neuroadaptations may regulate their expression.

  2. Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis

    PubMed Central

    Kumagai, Kenichi; Horikawa, Tatsuya; Shigematsu, Hiroaki; Matsubara, Ryota; Kitaura, Kazutaka; Eguchi, Takanori; Kobayashi, Hiroshi; Nakasone, Yasunari; Sato, Koichiro; Yamada, Hiroyuki; Suzuki, Satsuki; Hamada, Yoshiki; Suzuki, Ryuji

    2016-01-01

    Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK) T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion–induced allergic contact dermatitis. PMID:26771600

  3. A natural small molecule, catechol, induces c-Myc degradation by directly targeting ERK2 in lung cancer

    PubMed Central

    Lim, Do Young; Shin, Seung Ho; Lee, Mee-Hyun; Malakhova, Margarita; Kurinov, Igor; Wu, Qiong; Xu, Jinglong; Jiang, Yanan; Dong, Ziming; Liu, Kangdong; Lee, Kun Yeong; Bae, Ki Beom; Choi, Bu Young; Deng, Yibin; Bode, Ann; Dong, Zigang

    2016-01-01

    Various carcinogens induce EGFR/RAS/MAPK signaling, which is critical in the development of lung cancer. In particular, constitutive activation of extracellular signal-regulated kinase 2 (ERK2) is observed in many lung cancer patients, and therefore developing compounds capable of targeting ERK2 in lung carcinogenesis could be beneficial. We examined the therapeutic effect of catechol in lung cancer treatment. Catechol suppressed anchorage-independent growth of murine KP2 and human H460 lung cancer cell lines in a dose-dependent manner. Catechol inhibited ERK2 kinase activity in vitro, and its direct binding to the ERK2 active site was confirmed by X-ray crystallography. Phosphorylation of c-Myc, a substrate of ERK2, was decreased in catechol-treated lung cancer cells and resulted in reduced protein stability and subsequent down-regulation of total c-Myc. Treatment with catechol induced G1 phase arrest in lung cancer cells and decreased protein expression related to G1-S progression. In addition, we showed that catechol inhibited the growth of both allograft and xenograft lung cancer tumors in vivo. In summary, catechol exerted inhibitory effects on the ERK2/c-Myc signaling axis to reduce lung cancer tumor growth in vitro and in vivo, including a preclinical patient-derived xenograft (PDX) model. These findings suggest that catechol, a natural small molecule, possesses potential as a novel therapeutic agent against lung carcinogenesis in future clinical approaches. PMID:27167001

  4. Natural organic matter-induced alleviation of the phytotoxicity to rice (Oryza sativa L.) caused by copper oxide nanoparticles.

    PubMed

    Peng, Cheng; Zhang, Hai; Fang, Huaxiang; Xu, Chen; Huang, Haomin; Wang, Yi; Sun, Lijuan; Yuan, Xiaofeng; Chen, Yingxu; Shi, Jiyan

    2015-09-01

    Natural organic matter (NOM) can interact with engineered nanoparticles (NPs) in the environment and modify their behavior and toxicity to organisms. In the present study, the phytotoxicity of copper oxide (CuO) NPs to rice seedlings in the presence of humic acid as a model NOM was investigated. The results showed that CuO NPs induced the inhibition of root elongation, aberrations in root morphology and ultrastructure, and losses of cell viability and membrane integrity. The adverse effects partly resulted from the generation of reactive oxygen species caused by CuO NPs, which led to lipid peroxidation, mitochondrial dysfunction, and programmed cell death in rice seedlings. However, all the phytotoxicity was alleviated with the addition of humic acid because humic acid coatings on nanoparticle surfaces enhanced electrostatic and steric repulsion between the CuO NPs and the plant cell wall/membrane, reducing contact between NPs and plant and CuO NP-induced oxidative damage to plant cells. The present study's results shed light on the mechanism underlying NP phytotoxicity and highlight the influence of NOM on the bioavailability and toxicity of NPs.

  5. Possible Immune Regulation of Natural Killer T Cells in a Murine Model of Metal Ion-Induced Allergic Contact Dermatitis.

    PubMed

    Kumagai, Kenichi; Horikawa, Tatsuya; Shigematsu, Hiroaki; Matsubara, Ryota; Kitaura, Kazutaka; Eguchi, Takanori; Kobayashi, Hiroshi; Nakasone, Yasunari; Sato, Koichiro; Yamada, Hiroyuki; Suzuki, Satsuki; Hamada, Yoshiki; Suzuki, Ryuji

    2016-01-12

    Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK) T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion-induced allergic contact dermatitis.

  6. Chloroplastic oxidative burst induced by tenuazonic acid, a natural photosynthesis inhibitor, triggers cell necrosis in Eupatorium adenophorum Spreng.

    PubMed

    Chen, Shiguo; Yin, Chunyan; Qiang, Sheng; Zhou, Fenyan; Dai, Xinbin

    2010-03-01

    Tenuazonic acid (TeA), a nonhost-specific phytotoxin produced by Alternaria alternata, was determined to be a novel natural photosynthesis inhibitor owning several action sites in chloroplasts. To further elucidate the mode of its action, studies were conducted to assess the production and involvement of reactive oxygen species (ROS) in the toxic activity of TeA. A series of experiments indicated that TeA treatment can induce chloroplast-derived ROS generation including not only (1)O(2) but also superoxide radical, H(2)O(2) and hydroxyl radicals in Eupatorium adenophorum mesophyll cells, resulting from electron leakage and charge recombination in PSII as well as thylakoid overenergization due to inhibition of the PSII electron transport beyond Q(A) and the reduction of end acceptors on the PSI acceptor side and chloroplast ATPase activity. The initial production of TeA-induced ROS was restricted to chloroplasts and accompanied with a certain degree of chloroplast damage. Subsequently, abundant ROS were quickly dispersed throughout whole cell and cellular compartments, causing a series of irreversible cellular harm such as chlorophyll breakdown, lipid peroxidation, plasma membrane rupture, chromatin condensation, DNA cleavage, and organelle disintegration, and finally resulting in rapid cell destruction and leaf necrosis. These results show that TeA causing cell necrosis of host-plants is a result of direct oxidative damage from chloroplast-mediated ROS eruption.

  7. Articulated coralline algae of the genus Amphiroa are highly effective natural inducers of settlement in the tropical abalone Haliotis asinina.

    PubMed

    Williams, Elizabeth A; Craigie, Alina; Yeates, Alice; Degnan, Sandie M

    2008-08-01

    The initiation of metamorphosis in marine invertebrates is strongly linked to the environment. Planktonic larvae typically are induced to settle and metamorphose by external cues such as coralline algae (Corallinaceae, Rhodophyta). Although coralline algae are globally abundant, invertebrate larvae of many taxa settle in response to a very limited suite of species. This specificity impacts population structure, as only locations with the appropriate coralline species can attract new recruits. Abalone (Gastropoda, Haliotidae) are among those taxa in which closely related species are known to respond to different coralline algae. Here we identify highly inductive natural cues of the tropical abalone Haliotis asinina. In contrast to reports for other abalone, the greatest proportion of H. asinina larvae are induced to settle and metamorphose (92.8% to 100% metamorphosis by 48 h postinduction) by articulated corallines of the genus Amphiroa. Comparison with field distribution data for different corallines suggests larvae are likely to be settling on the seaward side of the reef crest. We then compare the response of six different H. asinina larval families to five different coralline species to demonstrate that induction by the best inductive cue (Amphiroa spp.) effectively extinguishes substantial intraspecific variation in the timing of settlement.

  8. Natural and human-induced variability in the composition of fish assemblages in the Northwestern Cuban shelf.

    PubMed

    González-Sansón, Gaspar; Aguilar, Consuelo; Hernández, Ivet; Cabrera, Yureidy; Suarez-Montes, Noelis; Bretos, Fernando; Guggenheim, David

    2009-09-01

    The main goal of the study was to obtain field data to build a baseline of fish assemblage composition that can be used comparatively for future analyses of the impact of human actions in the region. A basic network of 68 sampling stations was defined for the entire region (4,050 km2). Fish assemblage species and size composition was estimated using visual census methods at three different spatial scales: a) entire region, b) inside the main reef area and c) along a human impact coastal gradient. Multivariate numerical analyses revealed habitat type as the main factor inducing spatial variability of fish community composition, while the level of human impact appears to play the main role in fish assemblage composition changes along the coast. A trend of decreasing fish size toward the east supports the theory of more severe human impact due to overfishing and higher urban pollution in that direction. This is the first detailed study along the northwest coast of Cuba that focuses on fish community structure and the natural and human-induced variations at different spatial scales for the entire NW shelf. This research also provides input for a more comprehensive understanding of coastal marine fish communities' status in the Gulf of Mexico basin.

  9. B-1 Cell Heterogeneity and the Regulation of Natural and Antigen-Induced IgM Production

    PubMed Central

    Baumgarth, Nicole

    2016-01-01

    A small subset of B cells, termed B-1 cells, with developmental origins, phenotypes, and functions that are distinct from those of conventional B cells exist in mice. It contributes the vast majority of spontaneously produced “natural” IgM. Natural IgM is constitutively produced, even in the absence of microbiota, and fulfills many distinct functions in tissue homeostasis and host defense. B-1 cells also respond with IgM production to innate signals and pathogen exposure, while maintaining steady-state levels natural IgM. Thus, within the B-1 cell pool, cells of distinct and heterogeneous functionality must exist to facilitate these different functions. This review considers three factors that may contribute to this heterogeneity: first, developmental differences regarding the origins of the precursors, second, tissue-specific signals that may differentially affect B-1 cells in the tissue compartments, and finally responsiveness to self-antigens as well as innate and antigen-specific signals. All three are likely to shape the repertoire and responsiveness of B-1 cells to homeostatic- and antigen-induced signals and thus contribute to the functional heterogeneity among these innate-like B cells. PMID:27667991

  10. B-1 Cell Heterogeneity and the Regulation of Natural and Antigen-Induced IgM Production

    PubMed Central

    Baumgarth, Nicole

    2016-01-01

    A small subset of B cells, termed B-1 cells, with developmental origins, phenotypes, and functions that are distinct from those of conventional B cells exist in mice. It contributes the vast majority of spontaneously produced “natural” IgM. Natural IgM is constitutively produced, even in the absence of microbiota, and fulfills many distinct functions in tissue homeostasis and host defense. B-1 cells also respond with IgM production to innate signals and pathogen exposure, while maintaining steady-state levels natural IgM. Thus, within the B-1 cell pool, cells of distinct and heterogeneous functionality must exist to facilitate these different functions. This review considers three factors that may contribute to this heterogeneity: first, developmental differences regarding the origins of the precursors, second, tissue-specific signals that may differentially affect B-1 cells in the tissue compartments, and finally responsiveness to self-antigens as well as innate and antigen-specific signals. All three are likely to shape the repertoire and responsiveness of B-1 cells to homeostatic- and antigen-induced signals and thus contribute to the functional heterogeneity among these innate-like B cells.

  11. Usefulness of cyclodextrin media for the determination of alpha-cypermethrin by photochemically induced fluorescence: analytical applications to natural waters.

    PubMed

    Mbaye, Moussa; Gaye Seye, Mame Diabou; Coly, Atanasse; Tine, Alphonse; Aaron, Jean-Jacques

    2009-06-01

    The photochemically induced fluorescence (PIF) spectral properties of alpha-cypermethrin in organic solvents (hexane, dichloromethane, acetonitrile, ethanol) and in cyclodextrin aqueous solutions (beta-CD and 2-hydroxypropyl-beta-CD, 2-HP-beta-CD) were investigated. The photolysis kinetics of alpha-cypermethrin were evaluated in the various media. The PIF signal was found to be significantly enhanced in the CD media relative to the organic solvents. The stoichiometry and the formation constants of the alpha-cypermethrin inclusion complexes formed with the CDs were determined. The analytical performances of the PIF method were improved in the presence of HP-beta-CD relative to the other media, and a CD-enhanced PIF analytical method was developed. The limits of detection and limits of quantification ranged, respectively, between 6 and 98 ng/mL and between 24 and 343 ng/mL, depending on the medium. Application to the analysis of tap water and Senegal natural water samples collected close to agricultural areas and spiked with alpha-cypermethrin yielded satisfactory recoveries going from about 77% to 98%. An interference study of foreign species, including pesticides and inorganic ions likely to be present in natural waters, was also carried out.

  12. Natural isoprenoids inhibit LPS-induced-production of cytokines and nitric oxide in aminobisphosphonate-treated monocytes.

    PubMed

    Marcuzzi, Annalisa; Tommasini, Alberto; Crovella, Sergio; Pontillo, Alessandra

    2010-06-01

    The inhibition of mevalonate pathway through genetic defects (mevalonate kinase deficiency, MKD) or pharmacologic drugs (aminobisphosphonates) causes a shortage of intermediate compounds and, in particular, of geranylgeranyl-pyrophosphate (GGPP) associated to the activation of caspase-1 and IL-1beta release. Geraniol (GOH), farnesol (FOH), geranylgeraniol (GGOH) and menthol (MOH), due to their isoprenoid structure, are supposed to enter the mevalonate pathway and to by-pass the biochemical block, reconstituting the pathway. Considering the already known side effects of aminobisphosphonates, and the lack of a specific treatment for MKD, we evaluated the impact of these natural isoprenoids compounds in a RAW cell lines chemically treated with the aminobisphosphonate alendronate, and in monocytes isolated from 2 patients affected by MKD. GOH, FOH, GGOH and MOH were all capable to diminish inflammatory marker levels induced by LPS. These natural isoprenoids could be proposed as novel therapeutic approach for the still orphan drug MKD, but also considered for the evaluation of possible inflammatory side effects of aminobisphosphonates.

  13. Navigating natural variation in herbivory-induced secondary metabolism in coyote tobacco populations using MS/MS structural analysis.

    PubMed

    Li, Dapeng; Baldwin, Ian T; Gaquerel, Emmanuel

    2015-07-28

    Natural variation can be extremely useful in unraveling the determinants of phenotypic trait evolution but has rarely been analyzed with unbiased metabolic profiling to understand how its effects are organized at the level of biochemical pathways. Native populations of Nicotiana attenuata, a wild tobacco species, have been shown to be highly genetically diverse for traits important for their interactions with insects. To resolve the chemodiversity existing in these populations, we developed a metabolomics and computational pipeline to annotate leaf metabolic responses to Manduca sexta herbivory. We selected seeds from 43 accessions of different populations from the southwestern United States--including the well-characterized Utah 30th generation inbred accession--and grew 183 plants in the glasshouse for standardized herbivory elicitation. Metabolic profiles were generated from elicited leaves of each plant using a high-throughput ultra HPLC (UHPLC)-quadrupole TOFMS (qTOFMS) method, processed to systematically infer covariation patterns among biochemically related metabolites, as well as unknown ones, and finally assembled to map natural variation. Navigating this map revealed metabolic branch-specific variations that surprisingly only partly overlapped with jasmonate accumulation polymorphisms and deviated from canonical jasmonate signaling. Fragmentation analysis via indiscriminant tandem mass spectrometry (idMS/MS) was conducted with 10 accessions that spanned a large proportion of the variance found in the complete accession dataset, and compound spectra were computationally assembled into spectral similarity networks. The biological information captured by this networking approach facilitates the mining of the mass spectral data of unknowns with high natural variation, as demonstrated by the annotation of a strongly herbivory-inducible phenolic derivative, and can guide pathway analysis. PMID:26170304

  14. Navigating natural variation in herbivory-induced secondary metabolism in coyote tobacco populations using MS/MS structural analysis.

    PubMed

    Li, Dapeng; Baldwin, Ian T; Gaquerel, Emmanuel

    2015-07-28

    Natural variation can be extremely useful in unraveling the determinants of phenotypic trait evolution but has rarely been analyzed with unbiased metabolic profiling to understand how its effects are organized at the level of biochemical pathways. Native populations of Nicotiana attenuata, a wild tobacco species, have been shown to be highly genetically diverse for traits important for their interactions with insects. To resolve the chemodiversity existing in these populations, we developed a metabolomics and computational pipeline to annotate leaf metabolic responses to Manduca sexta herbivory. We selected seeds from 43 accessions of different populations from the southwestern United States--including the well-characterized Utah 30th generation inbred accession--and grew 183 plants in the glasshouse for standardized herbivory elicitation. Metabolic profiles were generated from elicited leaves of each plant using a high-throughput ultra HPLC (UHPLC)-quadrupole TOFMS (qTOFMS) method, processed to systematically infer covariation patterns among biochemically related metabolites, as well as unknown ones, and finally assembled to map natural variation. Navigating this map revealed metabolic branch-specific variations that surprisingly only partly overlapped with jasmonate accumulation polymorphisms and deviated from canonical jasmonate signaling. Fragmentation analysis via indiscriminant tandem mass spectrometry (idMS/MS) was conducted with 10 accessions that spanned a large proportion of the variance found in the complete accession dataset, and compound spectra were computationally assembled into spectral similarity networks. The biological information captured by this networking approach facilitates the mining of the mass spectral data of unknowns with high natural variation, as demonstrated by the annotation of a strongly herbivory-inducible phenolic derivative, and can guide pathway analysis.

  15. Comparative Study of Ultrasonication-Induced and Naturally Self-Assembled Silk Fibroin-Wool Keratin Hydrogel Biomaterials

    PubMed Central

    Vu, Trang; Xue, Ye; Vuong, Trinh; Erbe, Matthew; Bennet, Christopher; Palazzo, Ben; Popielski, Lucas; Rodriguez, Nelson; Hu, Xiao

    2016-01-01

    This study reports the formation of biocompatible hydrogels using protein polymers from natural silk cocoon fibroins and sheep wool keratins. Silk fibroin protein contains β-sheet secondary structures, allowing for the formation of physical cross-linkers in the hydrogels. Comparative studies were performed on two groups of samples. In the first group, ultrasonication was used to induce a quick gelation of a protein aqueous solution, enhancing the ability of Bombyx mori silk fibroin chains to quickly entrap the wool keratin protein molecules homogenously. In the second group, silk/keratin mixtures were left at room temperature for days, resulting in naturally-assembled gelled solutions. It was found that silk/wool blended solutions can form hydrogels at different mixing ratios, with perfectly interconnected gel structure when the wool content was less than 30 weight percent (wt %) for the first group (ultrasonication), and 10 wt % for the second group (natural gel). Differential scanning calorimetry (DSC) and temperature modulated DSC (TMDSC) were used to confirm that the fibroin/keratin hydrogel system was well-blended without phase separation. Fourier transform infrared spectroscopy (FTIR) was used to investigate the secondary structures of blended protein gels. It was found that intermolecular β-sheet contents significantly increase as the system contains more silk for both groups of samples, resulting in stable crystalline cross-linkers in the blended hydrogel structures. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to analyze the samples’ characteristic morphology on both micro- and nanoscales, which showed that ultrasonic waves can significantly enhance the cross-linker formation and avoid phase separation between silk and keratin molecules in the blended systems. With the ability to form cross-linkages non-chemically, these silk/wool hydrogels may be economically useful for various biomedical applications, thanks to the

  16. Comparative Study of Ultrasonication-Induced and Naturally Self-Assembled Silk Fibroin-Wool Keratin Hydrogel Biomaterials.

    PubMed

    Vu, Trang; Xue, Ye; Vuong, Trinh; Erbe, Matthew; Bennet, Christopher; Palazzo, Ben; Popielski, Lucas; Rodriguez, Nelson; Hu, Xiao

    2016-01-01

    This study reports the formation of biocompatible hydrogels using protein polymers from natural silk cocoon fibroins and sheep wool keratins. Silk fibroin protein contains β-sheet secondary structures, allowing for the formation of physical cross-linkers in the hydrogels. Comparative studies were performed on two groups of samples. In the first group, ultrasonication was used to induce a quick gelation of a protein aqueous solution, enhancing the ability of Bombyx mori silk fibroin chains to quickly entrap the wool keratin protein molecules homogenously. In the second group, silk/keratin mixtures were left at room temperature for days, resulting in naturally-assembled gelled solutions. It was found that silk/wool blended solutions can form hydrogels at different mixing ratios, with perfectly interconnected gel structure when the wool content was less than 30 weight percent (wt %) for the first group (ultrasonication), and 10 wt % for the second group (natural gel). Differential scanning calorimetry (DSC) and temperature modulated DSC (TMDSC) were used to confirm that the fibroin/keratin hydrogel system was well-blended without phase separation. Fourier transform infrared spectroscopy (FTIR) was used to investigate the secondary structures of blended protein gels. It was found that intermolecular β-sheet contents significantly increase as the system contains more silk for both groups of samples, resulting in stable crystalline cross-linkers in the blended hydrogel structures. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to analyze the samples' characteristic morphology on both micro- and nanoscales, which showed that ultrasonic waves can significantly enhance the cross-linker formation and avoid phase separation between silk and keratin molecules in the blended systems. With the ability to form cross-linkages non-chemically, these silk/wool hydrogels may be economically useful for various biomedical applications, thanks to the

  17. Natural and human-induced driving factors in the evolution of tidal channels: case studies in the Venice Lagoon (Italy).

    NASA Astrophysics Data System (ADS)

    Rizzetto, Federica

    2013-04-01

    Coastal wetlands are largely affected by a complex variety of both natural and anthropogenic factors, which induce evident, often irreversible, geomorphological transformations. In particular, this research focuses on the main processes that influence the evolution of tidal channels in salt marshes and shows the results derived from the analysis of some case studies in the Venice Lagoon (northwestern Adriatic Sea, Italy). Here tidal network has been recognized as significantly sensitive to sea-level rise and tide oscillations (Rizzetto and Tosi, 2011; Rizzetto and Tosi, 2012), but it is also vulnerable to human impact. The sites were selected in areas characterized by low anthropogenic pressure to prevent strong human interferences from completely masking the effects of natural forces. The interpretation of a large number of high-resolution aerial photographs, taken since the mid 1930s, allowed identifying in detail tidal channel evolution, both in the long- and in the short-term. The observation of historical and recent topographic maps completed the study and provided other important data to define the modifications occurred in the past two centuries. The channel planform changes were determined through the morphometric analysis of the tidal network, carried out using a Geographic Information System software. These modifications were interpreted in the light of sea-level oscillations (i.e. relative sea-level rise and strength/frequency of high tides, which are increasing owing to climate changes), variations of sediment supply, and human activities occurred in the past century. The joint analysis of all the data allowed distinguishing the changes induced by both relative sea-level rise and high tides on planform pattern and evolution of tidal channels, and identifying the effects of human interferences, which magnified the impact of natural factors (e.g. groundwater exploitation responsible for high subsidence rates between 1950 and 1970 and, consequently, for an

  18. A man-induced landslide in Lower Austria: natural conditions versus man-made causes

    NASA Astrophysics Data System (ADS)

    Kittel, Roland; Ottner, Franz; Damm, Bodo; Terhorst, Birgit

    2010-05-01

    In many cases, composition and characteristics of hillslope sediments are of particular importance related to landslide research in low mountain areas. The interaction of geologic, geomorphologic, and hydrologic factors determines the susceptibility for mass movements, which is affected by human impact as well. The present study aims to investigate factors that control mass movements and natural and anthropogenic impacts. On March 8th 2009, a landslide of 30.000 to 50.000 m³ occurred that destroyed a large part of a sports ground in the village of Hintersdorf, municipality of St. Andrä-Wördern (Lower Austria). As a result of extensive water supply ground liquefaction was initiated and the slide mass moved in form of a mud flow about 200 m down slope. As a consequence a small forest area and a fishpond were destroyed and an adjacent road was damaged. Closely to the event, first studies started and showed that the Hintersdorf landslide was triggered by extensive water saturation combined with hydrostatic pressure inside the slide mass. Heavy and long-lasting rainfalls and the start of snowmelt caused strong seepage and soil water saturation. Furthermore, insufficient ground drainage and overflow of a small retention pond intensified the unfavourable impact on soil-mechanical stability. Further studies included archive data analyse, field survey, as well as laboratory analyse and showed that high landslide susceptibility at the Hintersdorf landslide site was caused by a bundle of factors that control the process: The sports ground was built nearby the head of a trough valley that collects interflow and surface run-off from the surrounding slopes. The Flysch bedrock is covered extensively by clayey slope deposits. Furthermore, in the area of the valley head a waste deposit was operated up to the 1980's that resulted in a thick waste filling there. The Hintersdorf sports ground was constructed in 1984 on top of the waste body. Preliminary results show that hillslope

  19. Elaborating the Role of Natural Products-Induced Autophagy in Cancer Treatment: Achievements and Artifacts in the State of the Art

    PubMed Central

    2015-01-01

    Autophagy is a homeostatic process that is highly conserved across different types of mammalian cells. Autophagy is able to relieve tumor cell from nutrient and oxidative stress during the rapid expansion of cancer. Excessive and sustained autophagy may lead to cell death and tumor shrinkage. It was shown in literature that many anticancer natural compounds and extracts could initiate autophagy in tumor cells. As summarized in this review, the tumor suppressive action of natural products-induced autophagy may lead to cell senescence, provoke apoptosis-independent cell death, and complement apoptotic cell death by robust or target-specific mechanisms. In some cases, natural products-induced autophagy could protect tumor cells from apoptotic death. Technical variations in detecting autophagy affect data quality, and study focus should be made on elaborating the role of autophagy in deciding cell fate. In vivo study monitoring of autophagy in cancer treatment is expected to be the future direction. The clinical-relevant action of autophagy-inducing natural products should be highlighted in future study. As natural products are an important resource in discovery of lead compound of anticancer drug, study on the role of autophagy in tumor suppressive effect of natural products continues to be necessary and emerging. PMID:25821829

  20. Soil and geomorphological parameters to characterize natural environmental and human induced changes within the Guadarrama Range (Central Spain)

    NASA Astrophysics Data System (ADS)

    Schmid, Thomas; Inclán-Cuartas, Rosa M.; Santolaria-Canales, Edmundo; Saa, Antonio; Rodríguez-Rastrero, Manuel; Tanarro-Garcia, Luis M.; Luque, Esperanza; Pelayo, Marta; Ubeda, Jose; Tarquis, Ana; Diaz-Puente, Javier; De Marcos, Javier; Rodriguez-Alonso, Javier; Hernandez, Carlos; Palacios, David; Gallardo-Díaz, Juan; Fidel González-Rouco, J.

    2016-04-01

    Mediterranean mountain ecosystems are often complex and remarkably diverse and are seen as important sources of biological diversity. They play a key role in the water and sediment cycle for lowland regions as well as preventing and mitigating natural hazards especially those related to drought such as fire risk. However, these ecosystems are fragile and vulnerable to changes due to their particular and extreme climatic and biogeographic conditions. Some of the main pressures on mountain biodiversity are caused by changes in land use practices, infrastructure and urban development, unsustainable tourism, overexploitation of natural resources, fragmentation of habitats, particularly when located close to large population centers, as well as by pressures related toclimate change. The objective of this work is to select soil and geomorphological parameters in order to characterize natural environmental and human induced changes within the newly created National Park of the Sierra de Guadarrama in Central Spain, where the presence of the Madrid metropolitan area is the main factor of impact. This is carried out within the framework of the Guadarrama Monitoring Network (GuMNet) of the Campus de ExcelenciaInternacionalMoncloa, where long-term monitoring of the atmosphere, soil and bedrock are priority. This network has a total of ten stations located to the NW of Madrid and in this case, three stations have been selected to represent different ecosystems that include: 1) an alluvial plain in a lowland pasture area (La Herreria at 920 m a.s.l.), 2) mid mountain pine-forested and pasture area (Raso del Pino at 1801 m a.s.l.) and 3) high mountain grassland and rock area (Dos Hermanas at 2225 m a.s.l.). At each station a site geomorphological description, soil profile description and sampling was carried out. In the high mountain area information was obtained for monitoring frost heave activity and downslope soil movement. Basic soil laboratory analyses have been carried out

  1. In-vivo quantification of natural incipient caries lesions using the quantitative light-induced fluoroscence method: a reproducibility study

    NASA Astrophysics Data System (ADS)

    Tranaeus, Sofia; Shi, Xie-Qi; Trollsas, Karin; Lindgren, Lars-Erik; Angmar-Mansson, Birgit

    2000-03-01

    A new method for detection and quantification of natural incipient caries lesions, the Quantitative Light-induced Fluorescence method (QLF), has recently been developed. The aim of this study was to test the repeatability and reproducibility of the analytical part of the method. In vivo captured images (CCD-video camera, Panasonic WV-KS 152, with an argon ion laser as light source) of 15 different incipient caries lesions on smooth surfaces were analyzed by three analysts. The images were analyzed three times in a randomized order, twice for the first reconstructed area (P1A1 and P1A2), and then once for a second one (P2A1). Three parameters were measured, lesion area (mm2), average change in fluorescence (%), and maximum change in fluorescence (%) in the lesion. Repeated measures ANOVA were used to calculate the intra-, and inter-examiner reliability. Intra-examiner reliability for all three analysts showed an intra-class correlation coefficient, R, between 0.93 and 0.99 (for the analyses with the first patch, P1A1 and P1A2, as well as between the first and the second patch, P1A1 and P2A1). Inter-examiner reliability showed an inter-class correlation coefficient, R, between 0.95 and 0.99 (for analyses P1A1, P1A2 and P2A1). It was concluded that the Quantitative Light- induced fluorescence method showed excellent repeatability and reproducibility concerning the analytical part of the method.

  2. Final technical report for Phenomic Analysis of Natural and Induced Variation in Brachypodium Distachyon DE-SC0001526

    SciTech Connect

    Vogel, John P.

    2014-12-17

    The goal of this project was to apply high-throughput, non-destructive phenotyping (phenomics) to collections of natural variants and induced mutants of the model grass Brachypodium distachyon and characterize a small subset of that material in detail. B. distachyon is well suited to this phenomic approach because its small size and rapid generation time allow researchers to grow many plants under carefully controlled conditions. In addition, the simple diploid genetics, high quality genome sequence and existence of numerous experimental tools available for B. distachyon allow us to rapidly identify genes affecting specific phenotypes. Our phenomic analysis revealed great diversity in biofuel-relevant traits like growth rate, biomass and photosynthetic rate. This clearly demonstrated the feasibility of applying a phenomic approach to the model grass B. distachyon. We also demonstrated the utility of B. distachyon for studying mature root system, something that is virtually impossible to do with biomass crops. We showed tremendous natural variation in root architecture that can potentially be used to design crops with superior nutrient and water harvesting capability. Finally, we demonstrated the speed with which we can link specific genes to specific phenotypes by studying two mutants in detail. Importantly, in both cases, the specific biological lessons learned were grass-specific and could not have been learned from a dicot model system. Furthermore, one of the genes affects cell wall integrity and thus may be a useful target in the context of biomass crop improvement. Ultimately, all this information can be used to accelerate the creation of improved biomass crops.

  3. Hypothalamic Agouti-Related Peptide mRNA is Elevated During Natural and Stress-Induced Anorexia.

    PubMed

    Dunn, I C; Wilson, P W; D'Eath, R B; Boswell, T

    2015-09-01

    As part of their natural lives, animals can undergo periods of voluntarily reduced food intake and body weight (i.e. animal anorexias) that are beneficial for survival or breeding, such as during territorial behaviour, hibernation, migration and incubation of eggs. For incubation, a change in the defended level of body weight or 'sliding set point' appears to be involved, although the neural mechanisms reponsible for this are unknown. We investigated how neuropeptide gene expression in the arcuate nucleus of the domestic chicken responded to a 60-70% voluntary reduction in food intake measured both after incubation and after an environmental stressor involving transfer to unfamiliar housing. We hypothesised that gene expression would not change in these circumstances because the reduced food intake and body weight represented a defended level in birds with free access to food. Unexpectedly, we observed increased gene expression of the orexigenic peptide agouti-related peptide (AgRP) in both incubating and transferred animals compared to controls. Also pro-opiomelanocortin (POMC) mRNA was higher in incubating hens and significantly increased 6 days after exposure to the stressor. Conversely expression of neuropeptide Y and cocaine- and amphetamine-regulated transcript gene was unchanged in both experimental situations. We conclude that AgRP expression remains sensitive to the level of energy stores during natural anorexias, which is of adaptive advantage, although its normal orexigenic effects are over-ridden by inhibitory signals. In the case of stress-induced anorexia, increased POMC may contribute to this inhibitory role, whereas, for incubation, reduced feeding may also be associated with increased expression in the hypothalamus of the anorexigenic peptide vasoactive intestinal peptide.

  4. Occupational asthma and immunologic responses induced by inhaled carmine among employees at a factory making natural dyes.

    PubMed

    Quirce, S; Cuevas, M; Olaguibel, J M; Tabar, A I

    1994-01-01

    Carmine is a natural red dye widely used as a food coloring agent and for cosmetic manufacture. It is extracted from the dried females of the insect Dactylopius coccus var. Costa (cochineal). Although it has been reported that inhalation of carmine may give rise to occupational asthma and extrinsic allergic alveolitis, there is little evidence of its immunogenic capacity. We studied nine current employees at a factory making natural dyes and one former employee who had left this plant after occupational asthma developed. A current employee had work-related symptoms of rhinitis and asthma that were confirmed by bronchial provocation tests, and another worker had rhinitis. Immunologic sensitization to carmine and cochineal was evaluated by means of skin testing and determination of serum-specific IgE and IgG subclass antibodies by RAST and ELISA, respectively. The specificity of the RAST assay was investigated by RAST inhibition with different fractions of carmine. The three workers with respiratory symptoms had positive skin prick test reactions to both carmine and cochineal. An immediate response to the bronchial provocation test with carmine and cochineal was observed in the current employee with asthma. Specific IgE antibodies against carmine and cochineal were found only in this worker. RAST inhibition studies indicated that the main allergen had a molecular weight between 10 and 30 kd. Specific IgG antibodies against carmine and cochineal, mainly the subclasses IgG1, IgG3, and IgG4, were found in the 10 subjects surveyed. These findings suggest that carmine may induce immunologic responses, most likely IgE mediated in workers with symptoms of occupational asthma. PMID:8308181

  5. Theoretical dosimetry estimations for radioisotopes produced by proton-induced reactions on natural and enriched molybdenum targets

    NASA Astrophysics Data System (ADS)

    Hou, X.; Celler, A.; Grimes, J.; Bénard, F.; Ruth, T.

    2012-03-01

    This study presents a summary of the dosimetry calculations performed for three technetium agents most commonly used in nuclear medicine diagnostic studies, namely sestamibi™, phosphonates and pertechnetate, labeled with cyclotron-produced technetium. Calculated patient doses were compared to those that would be delivered by the same radiotracers labeled with technetium obtained from a generator produced in a reactor. The main difference is that technetium from a generator is pure, i.e. contains only 99mTc and its decay product 99gTc, while in a cyclotron a large number of other stable and radioactive isotopes are created. In our calculations only technetium radioisotopes (ground and isomeric states) were considered as they will be included in the radiotracer labeling process and will contribute to the patient dose. Other elements should be removed by chemical purification. These dose estimates are based on our theoretical calculations of the proton-induced reaction cross sections and radioisotope production yields. Thick targets of enriched (three different compositions) and natural molybdenum, and three initial beam energies (16, 19 and 24 MeV) were considered for irradiation times of 3, 6 and 12 h with a beam current of 200 µA. The doses were calculated for injection times corresponding to 0, 2, 8, 12 and 24 h after the end of beam.

  6. Natural organic matter (NOM) induces oxidative stress in freshwater amphipods Gammarus lacustris Sars and Gammarus tigrinus (Sexton).

    PubMed

    Timofeyev, Maxim A; Shatilina, Zhanna M; Kolesnichenko, Aleksey V; Bedulina, Darya S; Kolesnichenko, Viktoria V; Pflugmacher, Stephan; Steinberg, Christian E W

    2006-08-01

    Humic substances comprise the majority of natural organic matter (NOM) on Earth, including dissolved organic matter in freshwater systems. Recent studies show that these substances directly interact with aquatic organisms as chemical stressors. The aim of the present study was to investigate the mode of action of dissolved NOM on the freshwater amphipods Gammarus lacustris Sars and Gammarus tigrinus (Sexton), and in particular, to determine if NOM induces or promotes internal oxidative stress. NOM was isolated by reverse osmosis from a brown-water lake in Brandenburg State, Germany. Oxidative stress markers, such as lipid peroxidation, cell internal hydrogen peroxide concentration, as well as peroxidase, catalase and glutathione S-transferase activities, were quantified. Exposure of both amphipod species to NOM caused a significant increase in lipid peroxidation, hydrogen peroxide concentration, catalase, peroxidase and glutathione S-transferase activities. Both species showed a two-stage antioxidant response: the first stage allowed the organisms to effectively eliminate ROS and to protect cells from damage, whereas the second stage leads to H2O2 accumulation in combination with destruction of lipid structures in the cells and, finally, functional damage or even death of the organism. PMID:16542708

  7. Synthetic tactile perception induced by transcranial alternating-current stimulation can substitute for natural sensory stimulus in behaving rabbits

    PubMed Central

    Márquez-Ruiz, Javier; Ammann, Claudia; Leal-Campanario, Rocío; Ruffini, Giulio; Gruart, Agnès; Delgado-García, José M.

    2016-01-01

    The use of brain-derived signals for controlling external devices has long attracted the attention from neuroscientists and engineers during last decades. Although much effort has been dedicated to establishing effective brain-to-computer communication, computer-to-brain communication feedback for “closing the loop” is now becoming a major research theme. While intracortical microstimulation of the sensory cortex has already been successfully used for this purpose, its future application in humans partly relies on the use of non-invasive brain stimulation technologies. In the present study, we explore the potential use of transcranial alternating-current stimulation (tACS) for synthetic tactile perception in alert behaving animals. More specifically, we determined the effects of tACS on sensory local field potentials (LFPs) and motor output and tested its capability for inducing tactile perception using classical eyeblink conditioning in the behaving animal. We demonstrated that tACS of the primary somatosensory cortex vibrissa area could indeed substitute natural stimuli during training in the associative learning paradigm. PMID:26790614

  8. Theoretical dosimetry estimations for radioisotopes produced by proton-induced reactions on natural and enriched molybdenum targets.

    PubMed

    Hou, X; Celler, A; Grimes, J; Bénard, F; Ruth, T

    2012-03-21

    This study presents a summary of the dosimetry calculations performed for three technetium agents most commonly used in nuclear medicine diagnostic studies, namely sestamibi™, phosphonates and pertechnetate, labeled with cyclotron-produced technetium. Calculated patient doses were compared to those that would be delivered by the same radiotracers labeled with technetium obtained from a generator produced in a reactor. The main difference is that technetium from a generator is pure, i.e. contains only (99m)Tc and its decay product (99g)Tc, while in a cyclotron a large number of other stable and radioactive isotopes are created. In our calculations only technetium radioisotopes (ground and isomeric states) were considered as they will be included in the radiotracer labeling process and will contribute to the patient dose. Other elements should be removed by chemical purification. These dose estimates are based on our theoretical calculations of the proton-induced reaction cross sections and radioisotope production yields. Thick targets of enriched (three different compositions) and natural molybdenum, and three initial beam energies (16, 19 and 24 MeV) were considered for irradiation times of 3, 6 and 12 h with a beam current of 200 µA. The doses were calculated for injection times corresponding to 0, 2, 8, 12 and 24 h after the end of beam.

  9. Evidence of native radiation-induced paramagnetic defects in natural illites from unconformity-type uranium deposits

    NASA Astrophysics Data System (ADS)

    Morichon, E.; Allard, T.; Beaufort, D.; Patrier, P.

    2008-07-01

    This study presents the first unequivocal identification of natural radiation-induced defects in illites. Middle Proterozoic illites related to unconformity-type uranium deposits of Canada and Australia were studied using electron paramagnetic resonance (EPR) spectroscopy at X- and Q-band frequencies. The saturation behaviour of EPR spectra as a function of power demonstrates that native defects of illites are different from those known in other clays as kaolinite, dickite or smectite. Q-band spectra indicate the presence of several at least two native defects. The EPR signal is dominated by an axially distorted spectrum with apparent principal components as follows: g ∥ = 2.032 and g ⊥ = 1.993. The corresponding defect is named as Ai center. The study of oriented specimen confirms the strong anisotropy, and shows that the main defect has its g ∥ component perpendicular to the (ab) plane of illite. These defects in illite correspond to electron holes located on oxygen atoms of the structure and likely associated to Si, according to the lack of hyperfine structure. The Ai center in illite has similar EPR parameters to the A center in kaolinite and dickite. The isochronal annealing data suggest that illite can be used as a dosimeter in the geosphere. However, the determination of half-life and activation energy of the Ai center requires additional work.

  10. Collision-Induced Dissociation Fragmentation Inside Disulfide C-Terminal Loops of Natural Non-Tryptic Peptides

    NASA Astrophysics Data System (ADS)

    Samgina, Tatiana Y.; Vorontsov, Egor A.; Gorshkov, Vladimir A.; Artemenko, Konstantin A.; Zubarev, Roman A.; Ytterberg, Jimmy A.; Lebedev, Albert T.

    2013-07-01

    Collision-induced dissociation (CID) spectra of long non-tryptic peptides are usually quite complicated and rather difficult to interpret. Disulfide bond formed by two cysteine residues at C-terminus of frog skin peptides precludes one to determine sequence inside the forming loop. Thereby, chemical modification of S-S bonds is often used in "bottom up" sequencing approach. However, low-energy CID spectra of natural non-tryptic peptides with C-terminal disulfide cycle demonstrate an unusual fragmentation route, which may be used to elucidate the "hidden" C-terminal sequence. Low charge state protonated molecules experience peptide bond cleavage at the N-terminus of C-terminal cysteine. The forming isomeric acyclic ions serve as precursors for a series of b-type ions revealing sequence inside former disulfide cycle. The reaction is preferable for peptides with basic lysine residues inside the cycle. It may also be activated by acidic protons of Asp and Glu residues neighboring the loop. The observed cleavages may be quite competitive, revealing the sequence inside disulfide cycle, although S-S bond rupture does not occur in this case.

  11. New excitation functions for proton induced reactions on natural titanium, nickel and copper up to 70 MeV

    NASA Astrophysics Data System (ADS)

    Garrido, E.; Duchemin, C.; Guertin, A.; Haddad, F.; Michel, N.; Métivier, V.

    2016-09-01

    New excitation functions for proton induced nuclear reactions on natural titanium, nickel and copper were measured, using the stacked-foil technique and gamma spectrometry, up to 70 MeV. The experimental cross sections were measured using the Ti-nat(p,x) V-48, Ni-nat(p,x) Ni-57 and Cu-nat(p,x) Zn-62,Co-56 monitor reactions recommended by the International Atomic Energy Agency (IAEA), depending on the investigated energy range. Data have been extracted for the Ti-nat(p,x) Sc-43,44m,46,47,48, V-48, K-42,43, Ni-nat(p,x) Ni-56,57, Co-55,56,57,58, Mn-52,54, Cu-nat(p,x) Cu-61,64, Ni-57, Co-56,57,58,60, Zn-62,65, Mn-54 reactions. Our results are discussed and compared to the existing ones as well as with the TALYS code version 1.6 calculations using default models. Our experimental data are in overall good agreement with the literature. TALYS is able to reproduce, in most cases, the experimental trend. Our new experimental results allow to expand our knowledge on these excitation functions, to confirm the existing trends and to give additional values on a large energy range. This work is in line with the new Coordinated Research Project (CRP) launched by the IAEA to expand the database of monitor reactions.

  12. Synthetic tactile perception induced by transcranial alternating-current stimulation can substitute for natural sensory stimulus in behaving rabbits.

    PubMed

    Márquez-Ruiz, Javier; Ammann, Claudia; Leal-Campanario, Rocío; Ruffini, Giulio; Gruart, Agnès; Delgado-García, José M

    2016-01-01

    The use of brain-derived signals for controlling external devices has long attracted the attention from neuroscientists and engineers during last decades. Although much effort has been dedicated to establishing effective brain-to-computer communication, computer-to-brain communication feedback for "closing the loop" is now becoming a major research theme. While intracortical microstimulation of the sensory cortex has already been successfully used for this purpose, its future application in humans partly relies on the use of non-invasive brain stimulation technologies. In the present study, we explore the potential use of transcranial alternating-current stimulation (tACS) for synthetic tactile perception in alert behaving animals. More specifically, we determined the effects of tACS on sensory local field potentials (LFPs) and motor output and tested its capability for inducing tactile perception using classical eyeblink conditioning in the behaving animal. We demonstrated that tACS of the primary somatosensory cortex vibrissa area could indeed substitute natural stimuli during training in the associative learning paradigm. PMID:26790614

  13. Beta-carotene-induced enhancement of natural killer cell activity in elderly men: an investigation of the role of cytokines.

    PubMed

    Santos, M S; Gaziano, J M; Leka, L S; Beharka, A A; Hennekens, C H; Meydani, S N

    1998-07-01

    We showed previously that natural killer (NK) cell activity is significantly greater in elderly men supplemented with beta-carotene than in those taking placebo. In an attempt to determine the mechanism of beta-carotene's effect, we analyzed the production of NK cell-enhancing cytokines (interferon alpha, interferon gamma, and interleukin 12). Boston-area participants in the Physicians' Health Study (men aged 65-88 y; mean age, 73 y) who had been supplemented with beta-carotene (50 mg on alternate days) for an average of 12 y were enrolled in a randomized, placebo-controlled, double-blind study. Elderly subjects taking beta-carotene supplements had significantly greater plasma beta-carotene concentrations than those taking placebo. Beta-carotene-supplemented elderly men had significantly greater NK cell activity than did elderly men receiving placebo. Percentages of NK cells (CD16+CD56+) were not significantly different between the beta-carotene and placebo groups. Production of interleukin 12, interferon alpha, or concanavalin A-stimulated interferon gamma by cultured peripheral blood mononuclear cells was not significantly different between beta-carotene-supplemented elderly and those taking placebo. Our results indicate that beta-carotene-induced enhancement of NK cell activity is not mediated by changes in percentages of CD16+CD56+ NK cells nor through up-regulation of interleukin 12 or interferon alpha.

  14. Purpurogallin, a Natural Phenol, Attenuates High-Mobility Group Box 1 in Subarachnoid Hemorrhage Induced Vasospasm in a Rat Model

    PubMed Central

    Chang, Chih-Zen; Wu, Shu-Chuan; Kwan, Aij-Lie

    2014-01-01

    High-mobility group box 1 (HMGB1) was shown to be an important extracellular mediator involved in vascular inflammation of animals following subarachnoid hemorrhage (SAH). This study is of interest to examine the efficacy of purpurogallin, a natural phenol, on the alternation of cytokines and HMGB1 in a SAH model. A rodent double hemorrhage SAH model was employed. Basilar arteries (BAs) were harvested to examine HMGB1 mRNA and protein expression (Western blot). CSF samples were to examine IL-1β, IL-6, IL-8, and TNF-α (rt-PCR). Deformed endothelial wall, tortuous elastic lamina, and necrotic smooth muscle were observed in the vessels of SAH groups but were absent in the purpurogallin group. IL-1β, IL-6, and TNF-α in the SAH only and SAH plus vehicle groups were significantly elevated (P < 0.01). Purpurgallin dose-dependently reduced HMGB1 protein expression. Likewise, high dose purpurogallin reduced TNF-α and HMGB1 mRNA levels. In conclusion, purpurogallin exerts its neuroinflammation effect through the dual effect of inhibiting IL-6 and TNF-α mRNA expression and reducing HMGB1 protein and mRNA expression. This study supports purpurogallin could attenuate both proinflammatory cytokines and late-onset inflammasome in SAH induced vasospasm. PMID:25485154

  15. Investigating untypical seismicity distribution in Upper Silesia hard coal mine - insight into natural, human-induced and coseismic stress changes.

    NASA Astrophysics Data System (ADS)

    Kozłowska, Maria; Orlecka-Sikora, Beata; Rudziński, Łukasz; Cielesta, Szymon; Mutke, Grzegorz

    2016-04-01

    The Upper Silesia Coal Basin (USCB) in southern Poland is the place of intense seismicity accompanying coal mining. The exploitation of three longwall panels in one of USCB coal mines held between 2005 and 2010 was accompanied by seismicity characterized by very unusual time-space distribution. The earthquakes did not follow the depth of mining but exhibited changing depths from great below to close to mined seam. What is more, most of the strongest seismic events with ML>2.2 recorded during exploitation of these longwall panels occurred when exploitation had approached the axis of Bytom syncline, local tectonic structure intersecting several mines in Upper Silesia. Strong event's hypocenters were thus at close epicentral distance to both Bytom syncline axis and active mining front but at the great depth below mined seam. Such rather unusual seismicity pattern provided the unique opportunity to study the possible coupling of natural, human-induced and coseismic stresses in longwall coal mining environment. In present study we focused on distribution of seismicity of one of the longwall panels and in particular on the strongest event which occurred during its exploitation, ML3.7 event. The full moment tensor solution of the event showed that it occurred as almost vertical reverse faulting on a northeast-striking plane consistent with approximate strike of Bytom syncline. To evaluate inducing factor of ongoing and past exploitation we performed geomechanical modelling of its influence on strain and stress in the rock mass at the target depth of ML3.7 event. The estimated mining stress changes exhibited changing vertical stress regime which might have promoted failure on preexisting, almost vertical planes of weakness. Also, the amplitude of vertical displacement along the profile at the earthquake's depth was of similar order as the estimated slip on the fault. The earthquakes' rate variation in time showed no increase in activity right after the occurrence of ML3

  16. Natural vs human-induced changes at the Tauranga Harbour area (New Zealand): a time -series acoustic seabed classification comparison

    NASA Astrophysics Data System (ADS)

    Capperucci, Ruggero Maria; Bartholomä, Alexander; Renken, Sabrina; De Lange, Willem

    2013-04-01

    The Tauranga Harbour Bay (New Zealand) is a mesotidal estuary system, enclosed by the Matakana barrier island. It hosts the leading export port in New Zealand and the second largest import port by value. Coastal changes are well documented over the last decades, mainly at the southern entrance of the area, between Matakana Island and Mt. Maunganui. It is an extremely dynamic environment, where natural processes are strongly influenced by human activities. In particular, the understanding of the recent evolution of the system is crucial for policymakers. In fact, the cumulative impact due to the maintenance of the port (mainly dredging activities, shipping, facilities construction, but also increasing tourism) and its already approved expansion clashes with the claim of the local Maori communities, which recently leaded to a court action. A hydroacoustic multiple-device survey (Side-scan Sonar SSS, Multibeam Echo-sounder MBES and Single Beam Echo-sounder) coupled with sediment sampling was carried out in March 2011 over an area of 0.8 km2, southern Matakana Island, along the Western Channel. The area is not directly impacted by dredging activities, resulting in an optimal testing site for assessing indirect effects of human disturbance on coastal dynamics. The main goals were: 1. To test the response of different acoustic systems in such a highly dynamic environment; 2. To study the influence of dredging activities on sediment dynamics and habitat changes, by means of comparing the current data with existing ones, in order to distinguish between natural and human induced changes Results demonstrate a good agreement between acoustic classifications from different systems. They seem to be mainly driven by the sediment distribution, with a distinctive fingerprint given by shells and shell fragments. Nevertheless, the presence of relevant topographic features (i.e. large bedform fields) influences swath-looking systems (SSS and MBES). SSS and MBES classifications tend

  17. Accidental Predissociation: A Special Case of Photo-Induced Isotope Fractionation Effect and Possible Occurrence in Nature

    NASA Astrophysics Data System (ADS)

    Chakraborty, S.; Thiemens, M. H.

    2009-12-01

    Photo-Induced Isotope Fractionation Effects (PHIFE) are known to produce isotopic frac-tionation in some photo-dissociating molecules (1-2). The PHIFE formalism is based on the Born-Oppenheimer approximation and the Reflection Principle. The isotopic fractionation arises principally from the spectral shift induced by the small difference in zero point energy between isotopologues and the contraction of the wave function due to isotopic substitution, consequently, the associated isotopic fractionations depends on the reduced mass of the isotopically substi-tuted species. The PHIFE formalism is only applicable to the molecules which undergo direct photo-dissociation that possess continuous absorption spectra. Simple molecules (N2, O2, CO) however do not follow a direct dissociation pathway and dissociate through an indirect process termed predissociation, which occurs when the molecule is excited to a quasi-bound state energetically above the dissociation continuum. The PHIFE formalism is not applicable when the absorption spectra are discrete. The assumption that the lightest isotopologues are preferentially predissociated is only valid for restricted predissociation cases. There is a special case of predissociation known as ‘accidental predissociation’ (3), which takes place through an intermediate bound state in two steps (i) leakage to an intermediate bound state (coupled through spin orbit interaction) and, (ii) predissociation to a third quasi-bound state from the intermediate state. Line broadening at an accidental predissociation is a function of the magnitude of coupling matrix elements and the linewidths are strongly influenced by isotopic substitution (4). An anomalous isotopic effect in accidental predissociation was spectroscopically observed in CO (5), N2 (4) and BeH (6). We measured the isotopic fractionation for the first time in two accidental predissociating states of CO through VUV photodissociation using the 9.0.2 beamline at ALS (7-8). In

  18. Grazing-induced effects on soil properties modify plant competitive interactions in semi-natural mountain grasslands.

    PubMed

    Medina-Roldán, Eduardo; Paz-Ferreiro, Jorge; Bardgett, Richard D

    2012-09-01

    Plant-soil feedbacks are widely recognized as playing a significant role in structuring plant communities through their effects on plant-plant interactions. However, the question of whether plant-soil feedbacks can be indirectly driven by other ecological agents, such as large herbivores, which are known to strongly modify plant community structure and soil properties, remains poorly explored. We tested in a glasshouse experiment how changes in soil properties resulting from long-term sheep grazing affect competitive interactions (intra- and inter-specific) of two graminoid species: Nardus stricta, which is typically abundant under high sheep grazing pressure in British mountain grasslands; and Eriophorum vaginatum, whose abundance is typically diminished under grazing. Both species were grown in monocultures and mixtures at different densities in soils taken from adjacent grazed and ungrazed mountain grassland in the Yorkshire Dales, northern England. Nardus stricta performed better (shoot and root biomass) when grown in grazing-conditioned soil, independent of whether or not it grew under inter-specific competition. Eriophorum vaginatum also grew better when planted in soil from the grazed site, but this occurred only when it did not experience inter-specific competition with N. stricta. This indicates that plant-soil feedback for E. vaginatum is dependent on the presence of an inter-specific competitor. A yield density model showed that indirect effects of grazing increased the intensity of intra-specific competition in both species in comparison with ungrazed-conditioned soil. However, indirect effects of grazing on the intensity of inter-specific competition were species-specific favouring N. stricta. We explain these asymmetric grazing-induced effects on competition on the basis of traits of the superior competitor and grazing effects on soil nutrients. Finally, we discuss the relevance of our findings for plant community dynamics in grazed, semi-natural

  19. Differential dependence on nuclear factor-κB-inducing kinase among natural killer T-cell subsets in their development

    PubMed Central

    Noma, Haruka; Eshima, Koji; Satoh, Masashi; Iwabuchi, Kazuya

    2015-01-01

    Natural killer T cells (NKT cells) are comprised of several subsets. However, the possible differences in their developmental mechanisms have not been fully investigated. To evaluate the dependence of some NKT subpopulations on nuclear factor-κB-inducing kinase (NIK) for their generation, we analysed the differentiation of NKT cells, dividing them into subsets in various tissues of alymphoplasia (aly/aly), a mutant mouse strain that lacks functional NIK. The results indicated that the efficient differentiation of both invariant NKT (iNKT) and non-iNKT cells relied on NIK expression in non-haematopoietic cells; however, the dependence of non-iNKT cells was lower than that of iNKT cells. Especially, the differentiation of CD8+ non-iNKT cells was markedly resistant to the aly mutation. The proportion of two other NKT cell subsets, NK1.1+ γδ T cells and NK1.1− iNKT cells, was also significantly reduced in aly/aly mice, and this defect in their development was reversed in wild-type host mice given aly/aly bone marrow cells. In exerting effector functions, NIK in NKT-αβ cells appeared dispensable, as NIK-deficient NKT-αβ cells could secrete interleukin-4 or interferon-γ and exhibit cytolytic activity at a level comparable to that of aly/+ NKT-αβ cells. Collectively, these results imply that the NIK in thymic stroma may be critically involved in the differentiation of most NKT cell subsets (although the level of NIK dependence may vary among the subsets), and also that NIK in NKT-αβ cells may be dispensable for their effector function. PMID:25988531

  20. Effect of imaging geometry on evaluating natural white-spot lesions using quantitative light-induced fluorescence.

    PubMed

    Ando, Masatoshi; Eckert, George J; Stookey, George K; Zero, Domenick T

    2004-01-01

    The objective of this study was to determine the effect of imaging geometry on evaluating natural white-spot lesions with quantitative light-induced fluorescence (QLF). A total of 34 specimens were prepared from extracted human premolars and permanent molars with white spots on the interproximal surface. The specimens were each adjusted to a final thickness of 3.0 mm. Images were acquired with the QLF system perpendicular to the white spots and at 5 degrees intervals up to 30 degrees above and below the perpendicular. The specimens were rotated around the buccolingual axis of the tooth (pitch angle) and around the long axis of the tooth (roll angle). The averages of fluorescence loss (DeltaF, %) and lesion size (mm2) were determined with QLF. Another variable, DeltaQ, which was defined as the fluorescence loss integrated over the lesion size (% x mm2), was also calculated. DeltaF was smaller when lesions were viewed from the cervical direction (angles less than 90 degrees ), and became bigger when viewed from the coronal direction. Roll angle did not significantly affect DeltaF. Apparent lesion size diminished with deviations from 90 degrees in both directions for pitch and roll angles. DeltaQ was affected by pitch and roll angles with the largest value at 90 degrees and values decreasing in both directions from 90 degrees. In general, there were significant differences for angles larger than 20 degrees from the perpendicular for all three QLF variables. This study suggests that angle is an important factor to control when performing QLF studies; however, small changes (deviations within 20 degrees ) have a minimal effect on QLF variables. PMID:14684976

  1. Activation of natural killer T cells in NZB/W mice induces Th1-type immune responses exacerbating lupus.

    PubMed

    Zeng, Defu; Liu, Yinping; Sidobre, Stephane; Kronenberg, Mitchell; Strober, Samuel

    2003-10-01

    In vivo treatment of mice with the natural killer T (NKT) cell ligand, alpha-galactosylceramide (alphaGalCer), ameliorates autoimmune diabetes and experimental autoimmune encephalomyelitis (EAE) by shifting pathogenic Th1-type immune responses to nonpathogenic Th2-type responses. In the current study, in vivo activation of NKT cells in adult NZB/W mice by multiple injections of alphaGalCer induced an abnormal Th1-type immune response as compared with the Th2-type response observed in nonautoimmune C57BL/6 mice. This resulted in decreased serum levels of IgE, increased levels of IgG2a and IgG2a anti-double-stranded DNA (anti-dsDNA) Ab's, and exacerbated lupus. Conversely, treatment of NZB/W mice with blocking anti-CD1d mAb augmented Th2-type responses, increased serum levels of IgE, decreased levels of IgG2a and IgG2a anti-dsDNA Ab's, and ameliorated lupus. While total CD4+ T cells markedly augmented in vitro IgM anti-dsDNA Ab secretion by splenic B cells, the non-CD1d-reactive (CD1d-alphaGalCer tetramer-negative) CD4+ T cells (accounting for 95% of all CD4+ T cells) failed to augment Ab secretion. The CD1d-reactive tetramer-positive CD4+ T cells augmented anti-dsDNA Ab secretion about tenfold. In conclusion, activation of NKT cells augments Th1-type immune responses and autoantibody secretion that contribute to lupus development in adult NZB/W mice, and anti-CD1d mAb might be useful for treating lupus.

  2. Enhanced enzyme production with the pelleted form of D. squalens in laboratory bioreactors using added natural lignin inducer.

    PubMed

    Babič, Janja; Pavko, Aleksander

    2012-03-01

    White-rot fungi are extensively used in various submerged biotechnology processes to produce ligninolytic enzymes. Transfer of the process from the laboratory to the industrial level requires optimization of the cultivation conditions on the laboratory scale. An interesting area of optimization is pellet growth since this morphological form solves problems such as the decreased oxygen concentration, limited heat, and nutrient transport, which usually occur in dispersed mycelium cultures. Many submerged fermentations with basidiomycetes in pellet form were done with Phanerochaete, Trametes, and Bjerkandera species, among others. In our study, another promising basidiomycete, D. squalens, was used for ligninolytic enzyme production. With the addition of wood particles (sawdust) as a natural inducer and optimization of mixing and aeration conditions in laboratory stirred tank (STR) and bubble column (BCR) reactors on pellet growth and morphology, the secretion of laccase and the manganese-dependent peroxidase into the medium was substantially enhanced. The maximum mean pellet radius was achieved after 10 days in the BCR (5.1 mm) where pellets were fluffy and 5 days in the STR (3.5 mm) where they were round and smooth. The maximum Lac activity (1,882 U l(-1)) was obtained after 12 days in the STR, while maximum MnP activity (449.8 U l(-1)) occurred after 18 days in the BCR. The pellet size and morphology depended on the agitation and aeration conditions and consequently influenced a particular enzyme synthesis. The enzyme activities were high and comparable with the activities found for other investigations in reactors with basidiomycetes in the form of pellets. PMID:21922328

  3. A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection.

    PubMed

    Melgaço, Juliana Gil; Morgado, Lucas Nóbrega; Santiago, Marta Almeida; Oliveira, Jaqueline Mendes de; Lewis-Ximenez, Lia Laura; Hasselmann, Bárbara; Cruz, Oswaldo Gonçalves; Pinto, Marcelo Alves; Vitral, Claudia Lamarca

    2015-07-31

    Based on current studies on the effects of single dose vaccines on antibody production, Latin American countries have adopted a single dose vaccine program. However, no data are available on the activation of cellular response to a single dose of hepatitis A. Our study investigated the functional reactivity of the memory cell phenotype after hepatitis A virus (HAV) stimulation through administration of the first or second dose of HAV vaccine and compared the response to that of a baseline group to an initial natural infection. Proliferation assays showed that the first vaccine dose induced HAV-specific cellular response; this response was similar to that induced by a second dose or an initial natural infection. Thus, from the first dose to the second dose, increase in the frequencies of classical memory B cells, TCD8 cells, and central memory TCD4 and TCD8 cells were observed. Regarding cytokine production, increased IL-6, IL-10, TNF, and IFNγ levels were observed after vaccination. Our findings suggest that a single dose of HAV vaccine promotes HAV-specific memory cell response similar to that induced by a natural infection. The HAV-specific T cell immunity induced by primary vaccination persisted independently of the protective plasma antibody level. In addition, our results suggest that a single dose immunization system could serve as an alternative strategy for the prevention of hepatitis A in developing countries.

  4. 2-Methoxy-6-acetyl-7-methyljuglone (MAM), a natural naphthoquinone, induces NO-dependent apoptosis and necroptosis by H2O2-dependent JNK activation in cancer cells.

    PubMed

    Sun, Wen; Bao, Jiaolin; Lin, Wei; Gao, Hongwei; Zhao, Wenwen; Zhang, Qingwen; Leung, Chung-Hang; Ma, Dik-Lung; Lu, Jinjian; Chen, Xiuping

    2016-03-01

    Redox signaling plays a fundamental role in maintaining cell physiological activities. A deregulation of this balance through oxidative stress or nitrosative stress has been implicated in cancer. Here, we reported that 2-methoxy-6-acetyl-7-methyl juglone (MAM), a natural naphthoquinone isolated from Polygonum cuspidatum Sieb. et Zucc, caused hydrogen peroxide (H2O2) dependent activation of JNK and induced the expression of inducible nitric oxide synthase (iNOS), thereby leading to nitric oxide (NO) generation in multiple cancer cells. Nitrosative stress induced necroptosis in A549 lung cancer cells, but resulted in caspase-dependent intrinsic apoptosis in B16-F10 melanoma and MCF7 breast cancer cells. In addition, a decrease in GSH/GSSG levels accompanied with increased ROS production was observed. Reversal of ROS generation and cell death in GSH pretreated cells indicated the involvement of GSH depletion in MAM mediated cytotoxicity. In summary, a natural product MAM induced NO-dependent multiple forms of cell death in cancer cells mediated by H2O2-dependent JNK activation in cancer cells. GSH depletion might play an initial role in MAM-induced cytotoxicity. PMID:26802903

  5. Mangiferin, a Natural Xanthone, Protects Murine Liver in Pb(II) Induced Hepatic Damage and Cell Death via MAP Kinase, NF-κB and Mitochondria Dependent Pathways

    PubMed Central

    Pal, Pabitra Bikash; Sinha, Krishnendu; Sil, Parames C.

    2013-01-01

    One of the most well-known naturally occurring environmental heavy metals, lead (Pb) has been reported to cause liver injury and cellular apoptosis by disturbing the prooxidant-antioxidant balance via oxidative stress. Several studies, on the other hand, reported that mangiferin, a naturally occurring xanthone, has been used for a broad range of therapeutic purposes. In the present study, we, therefore, investigated the molecular mechanisms of the protective action of mangiferin against lead-induced hepatic pathophysiology. Lead [Pb(II)] in the form of Pb(NO3)2 (at a dose of 5 mg/kg body weight, 6 days, orally) induced oxidative stress, hepatic dysfunction and cell death in murine liver. Post treatment of mangiferin at a dose of 100 mg/kg body weight (6 days, orally), on the other hand, diminished the formation of reactive oxygen species (ROS) and reduced the levels of serum marker enzymes [alanine aminotranferase (ALT) and alkaline phosphatase (ALP)]. Mangiferin also reduced Pb(II) induced alterations in antioxidant machineries, restored the mitochondrial membrane potential as well as mutual regulation of Bcl-2/Bax. Furthermore, mangiferin inhibited Pb(II)-induced activation of mitogen-activated protein kinases (MAPKs) (phospho-ERK 1/2, phosphor-JNK phospho- p38), nuclear translocation of NF-κB and apoptotic cell death as was evidenced by DNA fragmentation, FACS analysis and histological assessment. In vitro studies using hepatocytes as the working model also showed the protective effect of mangiferin in Pb(II) induced cytotoxicity. All these beneficial effects of mangiferin contributes to the considerable reduction of apoptotic hepatic cell death induced by Pb(II). Overall results demonstrate that mangiferin exhibit both antioxidative and antiapoptotic properties and protects the organ in Pb(II) induced hepatic dysfunction. PMID:23451106

  6. Airborne simultaneous spectroscopic detection of laser-induced water Raman backscatter and fluorescence from chlorophyll a and other naturally occurring pigments

    NASA Technical Reports Server (NTRS)

    Hoge, F. E.; Swift, R. N.

    1981-01-01

    The airborne laser-induced spectral emission bands obtained simultaneously from water Raman backscatter and the fluorescence of chlorophyll and other naturally occurring waterborne pigments are reported here for the first time. The importance of this type data lies not only in its single-shot multispectral character but also in the application of the Raman line for correction or calibration of the spatial variation of the laser penetration depth without the need for in situ water attenuation measurements. The entire laser-induced fluorescence and Raman scatter emissions resulting from each separate 532-nm 10-nsec laser pulse are collected and spectrally dispersed in a diffraction grating spectrometer having forty photomultiplier tube detectors. Results from field experiments conducted in the North Sea and the Chesapeake Bay/Potomac River are presented. Difficulties involving the multispectral resolution of the induced emissions are addressed, and feasible solutions are suggested together with new instrument configurations and future research directions.

  7. Expectations induced by natural-like temporal fluctuations are independent of attention decrement: evidence from behavior and early visual evoked potentials.

    PubMed

    Derosiere, Gerard; Farrugia, Nicolas; Perrey, Stéphane; Ward, Tomas; Torre, Kjerstin

    2015-01-01

    Temporal expectations and attention decrement affect human behavior in opposing ways: the former positively, the latter negatively yet both exhibit similar neural signatures - i.e., reduction in the early event-related potential components' amplitude - despite different underlying mechanisms. Furthermore, there is a significant and growing debate in the literature regarding the putative role of attention in the encoding of expectations in perception. The question then arises as to what are the behavioral and neural consequences, if any, of attention decrement on temporal expectations and related enhancement of sensory information processing. Here, we investigated behavioral performance and visual N1a, N1p and P1 components during a sustained attention reaction time task inducing attention decrement under two conditions. In one condition, the inter-stimulus intervals (ISIs) were randomly distributed to impede expectation effects while for the other, the ISI exhibited natural-like long-term correlations supposed to induce temporal expectations. Behavioral results show that natural-like fluctuations in ISI indeed induced faster RT due to temporal expectations. These temporal expectations were beneficial even under attention decrement circumstances. Further, temporal expectations were associated with reduced N1a amplitude while attention decrement was associated with reduced N1p amplitude. Our findings provide evidence that the effects of temporal expectations and attention decrement induced in a single task can be independent at the behavioral level, and are supported at separate information processing stages at the neural level in vision. PMID:25224996

  8. Analysis of natural and artificial ultramarine blue pigments using laser induced breakdown and pulsed Raman spectroscopy, statistical analysis and light microscopy.

    PubMed

    Osticioli, I; Mendes, N F C; Nevin, A; Gil, Francisco P S C; Becucci, M; Castellucci, E

    2009-08-01

    Pulsed laser induced breakdown spectroscopy (LIBS) and Raman spectroscopy were performed using a novel laboratory setup employing the same Nd:YAG laser emission at 532 nm for the analysis of five commercially available pigments collectively known as "ultramarine blue", a sodium silicate material of either mineral origin or an artificially produced glass. LIBS and Raman spectroscopy have provided information regarding the elemental and molecular composition of the samples; additionally, an analytical protocol for the differentiation between natural (lapis lazuli) and artificial ultramarine blue pigments is proposed. In particular LIBS analysis has allowed the discrimination between pigments on the basis of peaks ascribed to calcium. The presence of calcite in the natural blue pigments has been confirmed following Raman spectroscopy in specific areas of the samples, and micro-Raman and optical microscopy have further corroborated the presence of calcite inclusions in the samples of natural origin. Finally multivariate analysis of Laser induced breakdown spectra using principal component analysis (PCA) further enhanced the differentiation between natural and artificial ultramarine blue pigments. PMID:19129003

  9. Analysis of natural and artificial ultramarine blue pigments using laser induced breakdown and pulsed Raman spectroscopy, statistical analysis and light microscopy

    NASA Astrophysics Data System (ADS)

    Osticioli, I.; Mendes, N. F. C.; Nevin, A.; Gil, Francisco P. S. C.; Becucci, M.; Castellucci, E.

    2009-08-01

    Pulsed laser induced breakdown spectroscopy (LIBS) and Raman spectroscopy were performed using a novel laboratory setup employing the same Nd:YAG laser emission at 532 nm for the analysis of five commercially available pigments collectively known as "ultramarine blue", a sodium silicate material of either mineral origin or an artificially produced glass. LIBS and Raman spectroscopy have provided information regarding the elemental and molecular composition of the samples; additionally, an analytical protocol for the differentiation between natural (lapis lazuli) and artificial ultramarine blue pigments is proposed. In particular LIBS analysis has allowed the discrimination between pigments on the basis of peaks ascribed to calcium. The presence of calcite in the natural blue pigments has been confirmed following Raman spectroscopy in specific areas of the samples, and micro-Raman and optical microscopy have further corroborated the presence of calcite inclusions in the samples of natural origin. Finally multivariate analysis of Laser induced breakdown spectra using principal component analysis (PCA) further enhanced the differentiation between natural and artificial ultramarine blue pigments.

  10. Analysis of natural and artificial ultramarine blue pigments using laser induced breakdown and pulsed Raman spectroscopy, statistical analysis and light microscopy.

    PubMed

    Osticioli, I; Mendes, N F C; Nevin, A; Gil, Francisco P S C; Becucci, M; Castellucci, E

    2009-08-01

    Pulsed laser induced breakdown spectroscopy (LIBS) and Raman spectroscopy were performed using a novel laboratory setup employing the same Nd:YAG laser emission at 532 nm for the analysis of five commercially available pigments collectively known as "ultramarine blue", a sodium silicate material of either mineral origin or an artificially produced glass. LIBS and Raman spectroscopy have provided information regarding the elemental and molecular composition of the samples; additionally, an analytical protocol for the differentiation between natural (lapis lazuli) and artificial ultramarine blue pigments is proposed. In particular LIBS analysis has allowed the discrimination between pigments on the basis of peaks ascribed to calcium. The presence of calcite in the natural blue pigments has been confirmed following Raman spectroscopy in specific areas of the samples, and micro-Raman and optical microscopy have further corroborated the presence of calcite inclusions in the samples of natural origin. Finally multivariate analysis of Laser induced breakdown spectra using principal component analysis (PCA) further enhanced the differentiation between natural and artificial ultramarine blue pigments.

  11. Laboratory animal models to study foot-and-mouth disease: a review with emphasis on natural and vaccine-induced immunity

    PubMed Central

    Habiela, Mohammed; Seago, Julian; Perez-Martin, Eva; Waters, Ryan; Windsor, Miriam; Salguero, Francisco J.; Wood, James; Charleston, Bryan

    2014-01-01

    Laboratory animal models have provided valuable insight into foot-and-mouth disease virus (FMDV) pathogenesis in epidemiologically important target species. While not perfect, these models have delivered an accelerated time frame to characterize the immune responses in natural hosts and a platform to evaluate therapeutics and vaccine candidates at a reduced cost. Further expansion of these models in mice has allowed access to genetic mutations not available for target species, providing a powerful and versatile experimental system to interrogate the immune response to FMDV and to target more expensive studies in natural hosts. The purpose of this review is to describe commonly used FMDV infection models in laboratory animals and to cite examples of when these models have failed or successfully provided insight relevant for target species, with an emphasis on natural and vaccine-induced immunity. PMID:25000962

  12. Laboratory animal models to study foot-and-mouth disease: a review with emphasis on natural and vaccine-induced immunity.

    PubMed

    Habiela, Mohammed; Seago, Julian; Perez-Martin, Eva; Waters, Ryan; Windsor, Miriam; Salguero, Francisco J; Wood, James; Charleston, Bryan; Juleff, Nicholas

    2014-11-01

    Laboratory animal models have provided valuable insight into foot-and-mouth disease virus (FMDV) pathogenesis in epidemiologically important target species. While not perfect, these models have delivered an accelerated time frame to characterize the immune responses in natural hosts and a platform to evaluate therapeutics and vaccine candidates at a reduced cost. Further expansion of these models in mice has allowed access to genetic mutations not available for target species, providing a powerful and versatile experimental system to interrogate the immune response to FMDV and to target more expensive studies in natural hosts. The purpose of this review is to describe commonly used FMDV infection models in laboratory animals and to cite examples of when these models have failed or successfully provided insight relevant for target species, with an emphasis on natural and vaccine-induced immunity. PMID:25000962

  13. Monosodium glutamate-induced arcuate nucleus damage affects both natural torpor and 2DG-induced torpor-like hypothermia in Siberian hamsters.

    PubMed

    Pelz, Kimberly M; Routman, David; Driscoll, Joseph R; Kriegsfeld, Lance J; Dark, John

    2008-01-01

    Siberian hamsters (Phodopus sungorus) have the ability to express daily torpor and decrease their body temperature to approximately 15 degrees C, providing a significant savings in energy expenditure. Daily torpor in hamsters is cued by winterlike photoperiods and occurs coincident with the annual nadirs in body fat reserves and chronic leptin concentrations. To better understand the neural mechanisms underlying torpor, Siberian hamster pups were postnatally treated with saline or MSG to ablate arcuate nucleus neurons that likely possess leptin receptors. Body temperature was studied telemetrically in cold-acclimated (10 degrees C) male and female hamsters moved to a winterlike photoperiod (10:14-h light-dark cycle) (experiments 1 and 2) or that remained in a summerlike photoperiod (14:10-h light-dark cycle) (experiment 3). In experiment 1, even though other photoperiodic responses persisted, MSG-induced arcuate nucleus ablations prevented the photoperiod-dependent torpor observed in saline-treated Siberian hamsters. MSG-treated hamsters tended to possess greater fat reserves. To determine whether reductions in body fat would increase frequency of photoperiod-induced torpor after MSG treatment, hamsters underwent 2 wk of food restriction (70% of ad libitum) in experiment 2. Although food restriction did increase the frequency of torpor in both MSG- and saline-treated hamsters, it failed to normalize the proportion of MSG-treated hamsters undergoing photoperiod-dependent torpor. In experiment 3, postnatal MSG treatments reduced the proportion of hamsters entering 2DG-induced torpor-like hypothermia by approximately 50% compared with saline-treated hamsters (38 vs. 72%). In those MSG-treated hamsters that did become hypothermic, their minimum temperature during hypothermia was significantly greater than comparable saline-treated hamsters. We conclude that 1) arcuate nucleus mechanisms mediate photoperiod-induced torpor, 2) food-restriction-induced torpor may also be

  14. PRELIMINARY OBSERVATIONS OF ATRAZINE-INDUCED EFFECTS UPON GONADAL DIFFERENTIATION IN RIVULUS MARMORATUS, A NATURALLY HERMAPHRODITIC FISH

    EPA Science Inventory

    The commonly used agricultural herbicide atrazine has been recognized as an endocrine disrupting chemical. In amphibians and reptiles, atrazine has been reported to alter sexual differentiation and induce secondary sexual characteristics that have been attributed to enhanced arom...

  15. Protective Capacity of Resveratrol, a Natural Polyphenolic Compound, against Deoxynivalenol-Induced Intestinal Barrier Dysfunction and Bacterial Translocation.

    PubMed

    Ling, Ka-Ho; Wan, Murphy Lam Yim; El-Nezami, Hani; Wang, Mingfu

    2016-05-16

    Contamination of food/feedstuffs by mycotoxins is a serious problem worldwide, causing severe economic losses and serious health problems in animals/humans. Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Grapes and red wine are rich in polyphenols, such as resveratrol (RES), which has striking antioxidant and anti-inflammatory activities. RES is a food-derived component; therefore, it may be simultaneously present with DON in the gastrointestinal tract. The aim of this study was to explore in vitro protective effects of RES against DON-induced intestinal damage. The results showed that RES could protect DON-induced bacteria translocation because of enhanced of intestinal barrier function by restoring the DON-induced decrease in transepithelial electrical resistance and increase in paracellular permeability. Further mechanistic studies demonstrated that RES protects against DON-induced barrier dysfunction by promoting the assembly of claudin-4 in the tight junction complex. This is probably mediated through modulation of IL-6 and IL-8 secretion via mitogen-activated protein kinase-dependent pathways. Our results imply that RES can protect against DON-induced intestinal damage and that RES may be used as a novel dietary intervention strategy to reduce DON toxicity in animals/humans. PMID:27058607

  16. Protective Capacity of Resveratrol, a Natural Polyphenolic Compound, against Deoxynivalenol-Induced Intestinal Barrier Dysfunction and Bacterial Translocation.

    PubMed

    Ling, Ka-Ho; Wan, Murphy Lam Yim; El-Nezami, Hani; Wang, Mingfu

    2016-05-16

    Contamination of food/feedstuffs by mycotoxins is a serious problem worldwide, causing severe economic losses and serious health problems in animals/humans. Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Grapes and red wine are rich in polyphenols, such as resveratrol (RES), which has striking antioxidant and anti-inflammatory activities. RES is a food-derived component; therefore, it may be simultaneously present with DON in the gastrointestinal tract. The aim of this study was to explore in vitro protective effects of RES against DON-induced intestinal damage. The results showed that RES could protect DON-induced bacteria translocation because of enhanced of intestinal barrier function by restoring the DON-induced decrease in transepithelial electrical resistance and increase in paracellular permeability. Further mechanistic studies demonstrated that RES protects against DON-induced barrier dysfunction by promoting the assembly of claudin-4 in the tight junction complex. This is probably mediated through modulation of IL-6 and IL-8 secretion via mitogen-activated protein kinase-dependent pathways. Our results imply that RES can protect against DON-induced intestinal damage and that RES may be used as a novel dietary intervention strategy to reduce DON toxicity in animals/humans.

  17. Maslinic Acid, a Natural Triterpene, Induces a Death Receptor-Mediated Apoptotic Mechanism in Caco-2 p53-Deficient Colon Adenocarcinoma Cells

    PubMed Central

    Reyes-Zurita, Fernando J.; Rufino-Palomares, Eva E.; García-Salguero, Leticia; Peragón, Juan; Medina, Pedro P.; Parra, Andrés; Cascante, Marta; Lupiáñez, José A.

    2016-01-01

    Maslinic acid (MA) is a natural triterpene present in high concentrations in the waxy skin of olives. We have previously reported that MA induces apoptotic cell death via the mitochondrial apoptotic pathway in HT29 colon cancer cells. Here, we show that MA induces apoptosis in Caco-2 colon cancer cells via the extrinsic apoptotic pathway in a dose-dependent manner. MA triggered a series of effects associated with apoptosis, including the cleavage of caspases -8 and -3, and increased the levels of t-Bid within a few hours of its addition to the culture medium. MA had no effect on the expression of the Bax protein, release of cytochrome-c or on the mitochondrial membrane potential. This suggests that MA triggered the extrinsic apoptotic pathway in this cell type, as opposed to the intrinsic pathway found in the HT29 colon-cancer cell line. Our results suggest that the apoptotic mechanism induced in Caco-2 may be different from that found in HT29 colon-cancer cells, and that in Caco-2 cells MA seems to work independently of p53. Natural antitumoral agents capable of activating both the extrinsic and intrinsic apoptotic pathways could be of great use in treating colon-cancer of whatever origin. PMID:26751572

  18. An analogue peptide from the Cancer/Testis antigen PASD1 induces CD8+ T cell responses against naturally processed peptide

    PubMed Central

    Hardwick, Nicola; Buchan, Sarah; Ingram, Wendy; Khan, Ghazala; Vittes, Gisella; Rice, Jason; Pulford, Karen; Mufti, Ghulam; Stevenson, Freda; Guinn, Barbara-ann

    2013-01-01

    We have previously identified the novel Cancer/Testis antigen PASD1 by immunoscreening a testis library with pooled acute myeloid leukemia (AML) patient sera. To develop a cytotoxic T lymphocyte (CTL)-inducing vaccine, we have now investigated the carboxy-terminal region, known to contain serological determinants, for MHC class I (HLA-A⋆0201)-binding peptides. Algorithm-selected natural peptides failed to show detectable HLA-A⋆0201 binding in T2 assays. However, anchor-modified analogue peptides showed enhanced binding, with decreased off-rates. Analogue peptide-loaded antigen-presenting cells (APCs) induced IFN-γ production by T cells from normal donors and patients. In addition, peptide-specific T cells could be expanded from cancer patients by stimulation with the PASD1 analogue peptide Pa14. For clinical application, a DNA fusion gene vaccine encoding Pa14 was designed and tested in “humanized” mice. Splenocytes from vaccinated mice showed in vitro cytotoxicity against tumour cells, either exogenously loaded with the corresponding wild-type peptide (Pw8) or expressing endogenously processed PASD1 protein. We show for the first time that a DNA vaccine encoding an altered PASD1 epitope can induce CTLs to target the natural peptide expressed by human tumour cells. PMID:23882161

  19. Enhanced Cognitive Effects of Demethoxycurcumin, a Natural Derivative of Curcumin on Scopolamine-Induced Memory Impairment in Mice.

    PubMed

    Lim, Dong Wook; Son, Hyun Jung; Um, Min Young; Kim, In-Ho; Han, Daeseok; Cho, Suengmok; Lee, Chang-Ho

    2016-08-05

    In the present study, we examined the ameliorating effects of demethoxycurcumin (DMC) on memory impairment induced by scopolamine using passive avoidance and Morris water maze tests in mice. Moreover, to determine the neurobiological effects underlying the ameliorating effects of the DMC, choline acetyltransferase (ChAT) immunoreactivity was evaluated in mice exposed to scopolamine. Our results demonstrated that chronic oral administration (28 days) of DMC (10 mg/kg) improved scopolamine-induced learning impairment in the passive avoidance task and memory impairment in the Morris water maze. Moreover, Choline acetyltransferase (ChAT) activity in the DMC-treated group was significantly increased to 33.03% compared with the control group. Our present finding suggests that DMC ameliorates memory impairments induced by scopolamine treatment through reversing the reduction of hippocampal ChAT expression in mice.

  20. Enhanced Cognitive Effects of Demethoxycurcumin, a Natural Derivative of Curcumin on Scopolamine-Induced Memory Impairment in Mice.

    PubMed

    Lim, Dong Wook; Son, Hyun Jung; Um, Min Young; Kim, In-Ho; Han, Daeseok; Cho, Suengmok; Lee, Chang-Ho

    2016-01-01

    In the present study, we examined the ameliorating effects of demethoxycurcumin (DMC) on memory impairment induced by scopolamine using passive avoidance and Morris water maze tests in mice. Moreover, to determine the neurobiological effects underlying the ameliorating effects of the DMC, choline acetyltransferase (ChAT) immunoreactivity was evaluated in mice exposed to scopolamine. Our results demonstrated that chronic oral administration (28 days) of DMC (10 mg/kg) improved scopolamine-induced learning impairment in the passive avoidance task and memory impairment in the Morris water maze. Moreover, Choline acetyltransferase (ChAT) activity in the DMC-treated group was significantly increased to 33.03% compared with the control group. Our present finding suggests that DMC ameliorates memory impairments induced by scopolamine treatment through reversing the reduction of hippocampal ChAT expression in mice. PMID:27527139

  1. Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural model of lentivirus-induced renal disease changes.

    PubMed

    Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

    2012-09-01

    Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy. PMID:23170163

  2. Renal Alterations in Feline Immunodeficiency Virus (FIV)-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

    PubMed Central

    Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

    2012-01-01

    Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy. PMID:23170163

  3. Skin cancer induced by natural UV-radiation as an occupational disease—requirements for its notification and recognition.

    PubMed

    Diepgen, Thomas L; Brandenburg, Stephan; Aberer, Werner; Bauer, Andrea; Drexler, Hans; Fartasch, Manigé; John, Swen Malte; Krohn, Steffen; Palfner, Stefanie; Römer, Wolfgang; Schuhmacher-Stock, Uta; Elsner, Peter

    2014-12-01

    In Germany over 2.5 million employees have an increased risk of skin cancer due to their occupational exposure to natural UV-irradiation. The medical consultation board "Occupational diseases" of the Ministry of Labor and Social affairs has investigated the association between occupational UV-irradiation and skin cancer risk and recommends to add the following new occupational disease into the appendix1 of the German ordinance on occupational diseases: "Squamous cell carcinoma and multiple actinic keratosis due to natural UV-irradiation". In this article we report in the view of the German Society of Occupational and Environmental Dermatology (ABD) and the German Statutory accident insurance (DGUV), whose criteria have to be fulfilled for the notification and recognition of an occupational skin cancer due to natural UV-irradiation.

  4. L-stepholidine, a natural dopamine receptor D1 agonist and D2 antagonist, inhibits heroin-induced reinstatement.

    PubMed

    Ma, Baomiao; Yue, Kai; Chen, Lin; Tian, Xiang; Ru, Qin; Gan, Yongping; Wang, Daisong; Jin, Guozhang; Li, Chaoying

    2014-01-24

    L-Stepholidine (l-SPD), an alkaloid extract of the Chinese herb Stephania intermedia, is the first compound known to exhibit mixed dopamine D1 receptor agonist/D2 antagonist properties and is a potential medication for the treatment of opiate addiction. The aim of the present study was to investigate the effects of pretreatment with L-SPD on heroin-seeking behavior induced by heroin priming. Male Sprague-Dawley rats were trained to self-administer heroin (0.05mg/kg per infusion) under a fixed ratio 1 schedule for 12 consecutive days and nose-poke responding was extinguished for 12 days, after which reinstatement of drug seeking was induced by heroin priming. Pretreatment with L-SPD (2.5, 5.0 and 10.0mg/kg, i.p.) inhibited the heroin-induced reinstatement of heroin-seeking behavior. Importantly, L-SPD did not affect locomotion, indicating that the observed effects of L-SPD on reinstatement are not the result of motor impairments. The present data suggested that l-SPD inhibits heroin-induced reinstatement and its potential for the treatment of heroin relapse.

  5. Prenylated Dihydrochalcones from Artocarpus altilis as Antiausterity Agents.

    PubMed

    Nguyen, Mai Thanh Thi; Nguyen, Nhan Trung; Awale, Suresh

    2015-01-01

    Human pancreatic cancer cell lines have remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. A novel antiausterity strategy in anticancer drug discovery led to the discovery of agents that preferentially inhibit the survival of cancer cells under low nutrient conditions. Artocarpus altilis (Family: Moraceae) is commonly referred to as breadfruit, traditionally for the treatment of many diseases. Many prenylated flavonoid and prenylated chalocones together with their cancer cell cytotoxicity were reported from this plant. This chapter briefly summarizes the constituents, biosynthesis, cytotoxicity, and antiausterity activity on PANC-1 human pancreatic cancer cell line of A. altilis.

  6. Prenylated Dihydrochalcones from Artocarpus altilis as Antiausterity Agents.

    PubMed

    Nguyen, Mai Thanh Thi; Nguyen, Nhan Trung; Awale, Suresh

    2015-01-01

    Human pancreatic cancer cell lines have remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. A novel antiausterity strategy in anticancer drug discovery led to the discovery of agents that preferentially inhibit the survival of cancer cells under low nutrient conditions. Artocarpus altilis (Family: Moraceae) is commonly referred to as breadfruit, traditionally for the treatment of many diseases. Many prenylated flavonoid and prenylated chalocones together with their cancer cell cytotoxicity were reported from this plant. This chapter briefly summarizes the constituents, biosynthesis, cytotoxicity, and antiausterity activity on PANC-1 human pancreatic cancer cell line of A. altilis. PMID:26298457

  7. Effects of human-induced alteration of groundwater flow on concentrations of naturally-occurring trace elements at water-supply wells

    USGS Publications Warehouse

    Ayotte, J.D.; Szabo, Z.; Focazio, M.J.; Eberts, S.M.

    2011-01-01

    The effects of human-induced alteration of groundwater flow patterns on concentrations of naturally-occurring trace elements were examined in five hydrologically distinct aquifer systems in the USA. Although naturally occurring, these trace elements can exceed concentrations that are considered harmful to human health. The results show that pumping-induced hydraulic gradient changes and artificial connection of aquifers by well screens can mix chemically distinct groundwater. Chemical reactions between these mixed groundwaters and solid aquifer materials can result in the mobilization of trace elements such as U, As and Ra, with subsequent transport to water-supply wells. For example, in the High Plains aquifer near York, Nebraska, mixing of shallow, oxygenated, lower-pH water from an unconfined aquifer with deeper, confined, anoxic, higher-pH water is facilitated by wells screened across both aquifers. The resulting higher-O2, lower-pH mixed groundwater facilitated the mobilization of U from solid aquifer materials, and dissolved U concentrations were observed to increase significantly in nearby supply wells. Similar instances of trace element mobilization due to human-induced mixing of groundwaters were documented in: (1) the Floridan aquifer system near Tampa, Florida (As and U), (2) Paleozoic sedimentary aquifers in eastern Wisconsin (As), (3) the basin-fill aquifer underlying the California Central Valley near Modesto (U), and (4) Coastal Plain aquifers of New Jersey (Ra). Adverse water-quality impacts attributed to human activities are commonly assumed to be related solely to the release of the various anthropogenic contaminants to the environment. The results show that human activities including various land uses, well drilling, and pumping rates and volumes can adversely impact the quality of water in supply wells, when associated with naturally-occurring trace elements in aquifer materials. This occurs by causing subtle but significant changes in

  8. Early Murine Cytomegalovirus (MCMV) Infection Induces Liver Natural Killer (NK) Cell Inflammation and Protection Through Macrophage Inflammatory Protein 1α (MIP-1α)–dependent Pathways

    PubMed Central

    Salazar-Mather, Thais P.; Orange, Jordan S.; Biron, Christine A.

    1998-01-01

    Natural killer (NK) cells mediate defense against early murine cytomegalovirus (MCMV) infections in liver. The chemokine, macrophage inflammatory protein 1α (MIP-1α), can promote inflammatory responses. Our studies evaluated contributions of NK cells to early MCMV-induced liver inflammation and MIP-1α requirements for inflammation and delivery of antiviral defenses. NK cells were shown to be responsible for focal inflammation, and to be induced to migrate at high levels, in MCMV-infected livers. MIP-1α gene expression was elevated at coinciding times, and mice deficient in MIP-1α function were dramatically inhibited in both inflammatory and protective liver responses. The results precisely define MIP-1α–dependent steps required to achieve NK cell inflammation during, and mechanisms promoting defense against, viral infections in tissues. PMID:9419206

  9. Reactive oxygen species induced by therapeutic CD20 antibodies inhibit natural killer cell-mediated antibody-dependent cellular cytotoxicity against primary CLL cells.

    PubMed

    Werlenius, Olle; Aurelius, Johan; Hallner, Alexander; Akhiani, Ali A; Simpanen, Maria; Martner, Anna; Andersson, Per-Ola; Hellstrand, Kristoffer; Thorén, Fredrik B

    2016-05-31

    The antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells is assumed to contribute to the clinical efficacy of monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL) and other hematopoietic malignancies of B cell origin. We sought to determine whether reactive oxygen species (ROS)-producing monocytes regulate the ADCC of NK cells against primary CLL cells using anti-CD20 as the linking antibody. The monoclonal CD20 antibodies rituximab and ofatumumab were found to trigger substantial release of ROS from monocytes. Antibody-exposed monocytes induced NK cell apoptosis and restricted NK cell-mediated ADCC against autologous CLL cells. The presence of inhibitors of ROS formation and scavengers of ROS preserved NK cell viability and restored NK cell-mediated ADCC against primary CLL cells. We propose that limiting the antibody-induced induction of immunosuppressive ROS may improve the anti-leukemic efficacy of anti-CD20 therapy in CLL. PMID:27097113

  10. Natural disaster vulnerability and human-induced pressure assessment in small islands developing states: A case study in the Union of the Comoros

    NASA Astrophysics Data System (ADS)

    Burak, S.; Meddeb, R.

    2012-04-01

    The Comoros Islands are part of the Small Island Developing States (SIDS) located in the Indian Ocean. SIDS are islands and low-lying coastal nations that face common barriers to sustainable development, including limited resources, poor economic resilience, and vulnerability to sea level rise and natural disasters. The Comoros Archipelago is made up of four islands but the present study was conducted on three islands, namely Mwali (Mohéli), Ngazidja (Grande Comore) and Dzwani (Anjouan) that are aligned in the Mozambique Channel and spread over a surface area of 1862 km2. These islands are exposed to natural disaster coupled with human-induced pressure on natural resources. The major natural disaster vulnerability has been identified by the National AdaptationProgramme of Action (NAPA, 2006) as climate change, whose likely adverse impacts on the Comoros Islands are: i) changes in rainfall patterns; ii) increases in temperature; iii) salinization of coastal aquifers as a result of salt water intrusion due to sea level rise; and iv) increased frequency of severe weather conditions (such as tropical cyclones, droughts, heavy rainfall and flooding). In addition, existing practices related to natural resources management (primarily land, forest and water management) are very poor and this failure is increasingly threatening water and food security, resulting in a decline of economic growth and standards of living within the Comoros. Human-induced pressure combined with climate change impact is the inherent vulnerabilities of these islands. The government of the Union of the Comoros is aware of the alarming nature of climate change impact and has put in place several projects aiming at implementing adaptation measures in order to help increase the resilience of the vulnerable population in the face of this threat. These projects involve strengthening institutions, policy and regulations so as to improve the management of natural resources, among other measures. The

  11. Analysis of the effect of a sunscreen agent on the suppression of natural killer cell activity induced in human subjects by radiation from solarium lamps

    SciTech Connect

    Hersey, P.; MacDonald, M.; Burns, C.; Schibeci, S.; Matthews, H.; Wilkinson, F.J.

    1987-03-01

    Previous studies in rodents have shown that ultraviolet radiation (UVR) may have direct effects on the immune system in the skin and at higher doses may induce systemic suppression of immune responses. We have previously shown that UVR from sun or solarium beds may induce systemic effects in human subjects. The purpose of the present study was to examine whether these systemic effects in human subjects could be prevented by use of commercially available sunscreen agents. Groups of 12 normal subjects were exposed to radiation from solarium lamps after application of a sunscreen agent or the base used in its preparation. Twelve half-hourly exposures induced a depression of natural killer (NK) cell activity against a melanoma and the K562 target cell which was not prevented by use of the sunscreen agent. Changes in functional activity were accompanied by a reduction in NK cell numbers assessed by Leu-11 monoclonal antibodies against the labile Fc receptor. Application of the sunscreen agent also did not protect against effects of solarium exposure on recall antigen skin tests and immunoglobulin production in vitro in pokeweed mitogen-stimulated cultures of B and T cells. These results suggest that further evaluation of the wave-length spectrum of UVR and the effectiveness of sunscreen agents in prevention of UVR-induced effects on the immune system is needed.

  12. Fetal Hemoglobin Inducers from the Natural World: A Novel Approach for Identification of Drugs for the Treatment of β-Thalassemia and Sickle-Cell Anemia

    PubMed Central

    Bianchi, Nicoletta; Zuccato, Cristina; Lampronti, Ilaria; Borgatti, Monica; Gambari, Roberto

    2009-01-01

    The objective of this review is to present examples of lead compounds identified from biological material (fungi, plant extracts and agro-industry material) and of possible interest in the field of a pharmacological approach to the therapy of β-thalassemia using molecules able to stimulate production of fetal hemoglobin (HbF) in adults. Concerning the employment of HbF inducers as potential drugs for pharmacological treatment of β-thalassemia, the following conclusions can be reached: (i) this therapeutic approach is reasonable, on the basis of the clinical parameters exhibited by hereditary persistence of fetal hemoglobin patients, (ii) clinical trials (even if still limited) employing HbF inducers were effective in ameliorating the symptoms of β-thalassemia patients, (iii) good correlation of in vivo and in vitro results of HbF synthesis and γ-globin mRNA accumulation indicates that in vitro testing might be predictive of in vivo responses and (iv) combined use of different inducers might be useful to maximize HbF, both in vitro and in vivo. In this review, we present three examples of HbF inducers from the natural world: (i) angelicin and linear psoralens, contained in plant extracts from Angelica arcangelica and Aegle marmelos, (ii) resveratrol, a polyphenol found in grapes and several plant extracts and (iii) rapamycin, isolated from Streptomyces hygroscopicus. PMID:18955291

  13. Stress-Induced In Vivo Recruitment of Human Cytotoxic Natural Killer Cells Favors Subsets with Distinct Receptor Profiles and Associates with Increased Epinephrine Levels

    PubMed Central

    Bigler, Marc B.; Egli, Simon B.; Hysek, Cédric M.; Hoenger, Gideon; Schmied, Laurent; Baldin, Fabian S.; Marquardsen, Florian A.; Recher, Mike; Liechti, Matthias E.; Hess, Christoph; Berger, Christoph T.

    2015-01-01

    Background Acute stress drives a ‘high-alert’ response in the immune system. Psychoactive drugs induce distinct stress hormone profiles, offering a sought-after opportunity to dissect the in vivo immunological effects of acute stress in humans. Methods 3,4-methylenedioxymethamphetamine (MDMA), methylphenidate (MPH), or both, were administered to healthy volunteers in a randomized, double-blind, placebo-controlled crossover-study. Lymphocyte subset frequencies, natural killer (NK) cell immune-phenotypes, and changes in effector function were assessed, and linked to stress hormone levels and expression of CD62L, CX3CR1, CD18, and stress hormone receptors on NK cells. Results MDMA/MPH > MDMA > MPH robustly induced an epinephrine-dominant stress response. Immunologically, rapid redistribution of peripheral blood lymphocyte-subsets towards phenotypically mature NK cells occurred. NK cytotoxicity was unaltered, but they expressed slightly reduced levels of the activating receptor NKG2D. Preferential circulation of mature NK cells was associated with high epinephrine receptor expression among this subset, as well as expression of integrin ligands previously linked to epinephrine-induced endothelial detachment. Conclusion The acute epinephrine-induced stress response was characterized by rapid accumulation of mature and functional NK cells in the peripheral circulation. This is in line with studies using other acute stressors and supports the role of the acute stress response in rapidly mobilizing the innate immune system to counteract incoming threats. PMID:26700184

  14. Natural montmorillonite induced photooxidation of As(III) in aqueous suspensions: roles and sources of hydroxyl and hydroperoxyl/superoxide radicals.

    PubMed

    Wang, Yajie; Xu, Jing; Li, Jinjun; Wu, Feng

    2013-09-15

    Photooxidation of arsenite(As(III)) in a suspension of natural montmorillonite under the irradiation of metal halide lamp (λ ≥ 313 nm)has been investigated. The results showed that the natural montmorillonite induced the photooxidation of As(III) by generating hydroxyl radicals (HO·) and hydroperoxyl/superoxide radicals (HO₂·/O₂⁻·). HO· which was responsible for the As(III) photooxidation. Approximately 38% of HO· was generated by the photolysis of ferric ions, and the formation of the remaining 62% was strongly dependent on the HO₂·/O₂⁻·. The presence of free ironions (Fe(2+) and Fe(3+)), made significant contributions to the photogeneration of these reactive oxygen species (ROS). The photooxidation of As(III) in natural montmorillonite suspensions was greatly influenced by the pH values. The photooxidation of As(III) by natural montmorillonite followed the Langmuir-Hinshelwood equation. In addition, the photooxidation of As(III) could be enhanced by the addition of humic acid. This work demonstrates that photooxidation may be an important environmental process for the oxidation of As(III) and may be a way to remove As(III) from acidic surface water containing iron-bearing clay minerals. PMID:23770489

  15. Application of flow injection analysis--photo-induced fluorescence (FIA-PIF) for the determination of α-cypermethrin pesticide residues in natural waters.

    PubMed

    Mbaye, M; Gaye Seye, M D; Aaron, J J; Coly, A; Tine, A

    2011-04-01

    Flow injection analysis combined with photo-induced fluorescence (FIA-PIF) has been applied for the determination of α-cypermethrin pesticide residues in Senegalese natural waters, using organic solutions and cyclodextrin (β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin) aqueous media. The α-cypermethrin insecticide has a very weak natural fluorescence, but it is converted into strongly fluorescent photoproduct(s) by UV irradiation. Cyclodextrins were found to enhance the PIF signal. FIA parameters, including mobile phase flow rate, injected volume, and reactor length, were optimized. Analytical performances of the FIA-PIF method for the determination of α-cypermethrin were satisfactory, with concentration linear dynamic ranges over one to two orders of magnitude and with rather low limits of detection and limits of quantification, in the ng mL(-1) range, and relative standard deviations comprised between 1.2% and 3.8%. Application of FIA-PIF for the analysis of fortified natural water samples collected from Senegal yielded good recovery values (84-112%). Because of its high sampling rate, the FIA-PIF method constitutes a rapid analytical tool, useful for quantification of α-cypermethrin residues in natural waters.

  16. Radiation-Induced Defects in Kaolinite as Tracers of Past Occurrence of Radionuclides in a Natural Analogue of High Level Nuclear Waste Repository

    NASA Astrophysics Data System (ADS)

    Allard, T.; Fourdrin, C.; Calas, G.

    2007-05-01

    Understanding the processes controlling migrations of radioelements at the Earth's surface is an important issue for the long-term safety assessment of high level nuclear waste repositories (HLNWR). Evidence of past occurrence and transfer of radionuclides can be found using radiation-induced defects in minerals. Clay minerals are particularly relevant because of their widespread occurrence at the Earth's surface and their finely divided nature which provides high contact area with radioactive fluids. Owing to its sensitivity to radiations, kaolinite can be used as natural, in situ dosimeter. Kaolinite is known to contain radiation-induced defects which are detected by Electron Paramagnetic Resonance. They are differentiated by their nature, their production kinetics and their thermal stability. One of these defects is stable at the scale of geological periods and provides a record of past radionuclide occurrence. Based on artificial irradiations, a methodology has been subsequently proposed to determine paleodose cumulated by kaolinite since its formation. The paleodose can be used to derive equivalent radioelement concentrations, provided that the age of kaolinite formation can be constrained. This allows quantitative reconstruction of past transfers of radioelements in natural systems. An example is given for the Nopal I U-deposit (Chihuahua, Mexico), hosted in hydrothermally altered volcanic tufs and considered as analogue of the Yucca Mountain site. The paleodoses experienced by kaolinites were determined from the concentration of defects and dosimetry parameters of experimental irradiations. Using few geochemical assumption, a equivalent U-content responsible for defects in kaolinite was calculated from the paleodose, a dose rate balance and model ages of kaolinites constrained by tectonic phases. In a former study, the ages were assumptions derived from regional tectonic events. In thepresent study, ages of mineralization events are measured from U

  17. COMPARISON OF LUNG ATTENUATION AND HETEROGENEITY BETWEEN CATS WITH EXPERIMENTALLY INDUCED ALLERGIC ASTHMA, NATURALLY OCCURRING ASTHMA AND NORMAL CATS.

    PubMed

    Masseau, Isabelle; Banuelos, Alina; Dodam, John; Cohn, Leah A; Reinero, Carol

    2015-01-01

    Airway remodeling is a prominent feature of feline allergic asthma but requires biopsy for characterization. Computed tomography (CT) has appeal as a minimally invasive diagnostic test. The purpose of this prospective case-control study was to compare indices of airway remodeling between cats with experimentally induced, spontaneous asthma and healthy unaffected cats using CT. We hypothesized that experimental and spontaneous feline asthma would have similar CT airway remodeling characteristics and that these would be significantly different in healthy cats. Experimentally induced asthmatic research cats (n = 5), spontaneously asthmatic pet cats (n = 6), and healthy research cats (n = 5) were scanned unrestrained using a 64-detector row CT scanner. Inspiratory breath-hold CT scans were also performed in experimentally induced asthmatic and healthy cats. Mean ± extent variation of lung attenuation for each cat was determined using an airway inspector software program and CT images were scored for lung heterogeneity by a board-certified veterinary radiologist who was unaware of cat group status. Groups were compared using one-way ANOVA (unrestrained scans) and the Student's t-test (anesthetized scans) with significance defined as P < 0.10. Experimentally asthmatic and spontaneously asthmatic cats had significantly (P = 0.028 and P = 0.073, respectively) increased lung attenuation compared to healthy cats. Heterogeneity scores were higher in experimentally induced asthmatic cat than in healthy cats. Objective quantification of lung heterogeneity and lung volume did not differ among the three groups (P = 0.311, P = 0.181, respectively). Findings supported our hypothesis. Inspiratory breath-hold anesthetized CT scans facilitated discrimination between asthmatic and healthy cats in comparison to unrestrained CT scans.

  18. Lutein, a Natural Carotenoid, Induces α-1,3-Glucan Accumulation on the Cell Wall Surface of Fungal Plant Pathogens.

    PubMed

    Otaka, Junnosuke; Seo, Shigemi; Nishimura, Marie

    2016-01-01

    α-1,3-Glucan, a component of the fungal cell wall, is a refractory polysaccharide for most plants. Previously, we showed that various fungal plant pathogens masked their cell wall surfaces with α-1,3-glucan to evade plant immunity. This surface accumulation of α-1,3-glucan was infection specific, suggesting that plant factors might induce its production in fungi. Through immunofluorescence observations of fungal cell walls, we found that carrot (Daucus carota) extract induced the accumulation of α-1,3-glucan on germlings in Colletotrichum fioriniae, a polyphagous fungal pathogen that causes anthracnose disease in various dicot plants. Bioassay-guided fractionation of carrot leaf extract successfully identified two active substances that caused α-1,3-glucan accumulation in this fungus: lutein, a carotenoid widely distributed in plants, and stigmasterol, a plant-specific membrane component. Lutein, which had a greater effect on C. fioriniae, also induced α-1,3-glucan accumulation in other Colletotrichum species and in the phylogenetically distant rice pathogen Cochliobolus miyabeanus, but not in the rice pathogen Magnaporthe oryzae belonging to the same phylogenetic subclass as Colletotrichum. Our results suggested that fungal plant pathogens reorganize their cell wall components in response to specific plant-derived compounds, which these pathogens may encounter during infection. PMID:27483218

  19. Lutein, a Natural Carotenoid, Induces α-1,3-Glucan Accumulation on the Cell Wall Surface of Fungal Plant Pathogens.

    PubMed

    Otaka, Junnosuke; Seo, Shigemi; Nishimura, Marie

    2016-07-28

    α-1,3-Glucan, a component of the fungal cell wall, is a refractory polysaccharide for most plants. Previously, we showed that various fungal plant pathogens masked their cell wall surfaces with α-1,3-glucan to evade plant immunity. This surface accumulation of α-1,3-glucan was infection specific, suggesting that plant factors might induce its production in fungi. Through immunofluorescence observations of fungal cell walls, we found that carrot (Daucus carota) extract induced the accumulation of α-1,3-glucan on germlings in Colletotrichum fioriniae, a polyphagous fungal pathogen that causes anthracnose disease in various dicot plants. Bioassay-guided fractionation of carrot leaf extract successfully identified two active substances that caused α-1,3-glucan accumulation in this fungus: lutein, a carotenoid widely distributed in plants, and stigmasterol, a plant-specific membrane component. Lutein, which had a greater effect on C. fioriniae, also induced α-1,3-glucan accumulation in other Colletotrichum species and in the phylogenetically distant rice pathogen Cochliobolus miyabeanus, but not in the rice pathogen Magnaporthe oryzae belonging to the same phylogenetic subclass as Colletotrichum. Our results suggested that fungal plant pathogens reorganize their cell wall components in response to specific plant-derived compounds, which these pathogens may encounter during infection.

  20. Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

    SciTech Connect

    Ribeiro, Ruy M

    2008-01-01

    Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell prolifeation are key factors in AIDS pathogenesis.

  1. Adenovirus Specific Pre-Immunity Induced by Natural Route of Infection Does Not Impair Transduction by Adenoviral Vaccine Vectors in Mice

    PubMed Central

    de Andrade Pereira, Bruna; E. Maduro Bouillet, Leoneide; Dorigo, Natalia A.; Fraefel, Cornel; Bruna-Romero, Oscar

    2015-01-01

    Recombinant human adenovirus serotype 5 (HAd5V) vectors are gold standards of T-cell immunogenicity as they efficiently induce also humoral responses to exogenous antigens, in particular when used in prime-boost protocols. Some investigators have shown that pre-existing immunity to adenoviruses interferes with transduction by adenoviral vectors, but the actual extent of this interference is not known since it has been mostly studied in mice using unnatural routes of infection and virus doses. Here we studied the effects of HAd5V-specific immune responses induced by intranasal infection on the transduction efficiency of recombinant adenovirus vectors. Of interest, when HAd5V immunity was induced in mice by the natural respiratory route, the pre-existing immunity against HAd5V did not significantly interfere with the B and T-cell immune responses against the transgene products induced after a prime/boost inoculation protocol with a recombinant HAd5V-vector, as measured by ELISA and in vivo cytotoxic T-cell assays, respectively. We also correlated the levels of HAd5V-specific neutralizing antibodies (Ad5NAbs) induced in mice with the levels of Ad5NAb titers found in humans. The data indicate that approximately 60% of the human serum samples tested displayed Ad5NAb levels that could be overcome with a prime-boost vaccination protocol. These results suggest that recombinant HAd5V vectors are potentially useful for prime-boost vaccination strategies, at least when pre-existing immunity against HAd5V is at low or medium levels. PMID:26679149

  2. Anthropogenic changes to seawater buffer capacity combined with natural reef metabolism induce extreme future coral reef CO2 conditions.

    PubMed

    Shaw, Emily C; McNeil, Ben I; Tilbrook, Bronte; Matear, Richard; Bates, Michael L

    2013-05-01

    Ocean acidification, via an anthropogenic increase in seawater carbon dioxide (CO2 ), is potentially a major threat to coral reefs and other marine ecosystems. However, our understanding of how natural short-term diurnal CO2 variability in coral reefs influences longer term anthropogenic ocean acidification remains unclear. Here, we combine observed natural carbonate chemistry variability with future carbonate chemistry predictions for a coral reef flat in the Great Barrier Reef based on the RCP8.5 CO2 emissions scenario. Rather than observing a linear increase in reef flat partial pressure of CO2 (pCO2 ) in concert with rising atmospheric concentrations, the inclusion of in situ diurnal variability results in a highly nonlinear threefold amplification of the pCO2 signal by the end of the century. This significant nonlinear amplification of diurnal pCO2 variability occurs as a result of combining natural diurnal biological CO2 metabolism with long-term decreases in seawater buffer capacity, which occurs via increasing anthropogenic CO2 absorption by the ocean. Under the same benthic community composition, the amplification in the variability in pCO2 is likely to lead to exposure to mean maximum daily pCO2 levels of ca. 2100 μatm, with corrosive conditions with respect to aragonite by end-century at our study site. Minimum pCO2 levels will become lower relative to the mean offshore value (ca. threefold increase in the difference between offshore and minimum reef flat pCO2 ) by end-century, leading to a further increase in the pCO2 range that organisms are exposed to. The biological consequences of short-term exposure to these extreme CO2 conditions, coupled with elevated long-term mean CO2 conditions are currently unknown and future laboratory experiments will need to incorporate natural variability to test this. The amplification of pCO2 that we describe here is not unique to our study location, but will occur in all shallow coastal environments where high

  3. Human cytomegalovirus-induced NKG2C(hi) CD57(hi) natural killer cells are effectors dependent on humoral antiviral immunity.

    PubMed

    Wu, Zeguang; Sinzger, Christian; Frascaroli, Giada; Reichel, Johanna; Bayer, Carina; Wang, Li; Schirmbeck, Reinhold; Mertens, Thomas

    2013-07-01

    Recent studies indicate that expansion of NKG2C-positive natural killer (NK) cells is associated with human cytomegalovirus (HCMV); however, their activity in response to HCMV-infected cells remains unclear. We show that NKG2C(hi) CD57(hi) NK cells gated on CD3(neg) CD56(dim) cells can be phenotypically identified as HCMV-induced NK cells that can be activated by HCMV-infected cells. Using HCMV-infected autologous macrophages as targets, we were able to show that these NKG2C(hi) CD57(hi) NK cells are highly responsive to HCMV-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. We further demonstrate that NKG2C(hi) CD57(hi) NK cells are intrinsically responsive to signaling through CD16 cross-linking. Our findings show that the activity of pathogen-induced innate immune cells can be enhanced by adaptive humoral immunity. Understanding the activity of NKG2C(hi) CD57(hi) NK cells against HCMV-infected cells will be of relevance for the further development of adoptive immunotherapy.

  4. The help of Advanced Satellite Interferometry in assessing the effect of human-induced surface deformation in naturally subsiding areas. Methodological approach and applications

    NASA Astrophysics Data System (ADS)

    Tamburini, Andrea; Giannico, Chiara; Del Conte, Sara; Teatini, Pietro

    2014-05-01

    Underground water extraction, natural gas storage either in depleted hydrocarbon reservoirs or in aquifers, and excavations for civil works (e.g. underground passageways, car parks, etc.) in flat areas are responsible for surface deformation that can damage pre-existing structures and modify drainage pathways. Deformation patterns associated to different underground show in many cases typical patterns. Their recognition can help in disentangling different processes when occurring in areas already affected by natural subsidence, such as coastal areas and inner sedimentary plains. Moreover, assessing the extent of human-induced deformation can help in identifying causes, modelling phenomena, predicting their evolution and adopting proper remedial measures. Advanced Satellite Interferometry provides a synoptic view of surface displacements over large areas and long time-spans and has become a standard in several Italian regions where underground fluid injection and withdrawal is going on. The integration of interferometric measurements with ground (leveling, GPS) and underground (borehole extensometers, piezometers, micro-seismic) monitoring networks can provide an exhaustive framework of the effect induced at surface level by underground human activities at local and regional scale. Documented case studies demonstrating the effectiveness of the above approach will be presented.

  5. Synchrotron X-ray Scattering; Sensile Strength and Strain-Induced Crystallization in Carbon Black Filled Natural Rubber

    SciTech Connect

    Toki,S.; Minouchi, N.; Sics, I.; Hsiao, B.; Kohjiya, S.

    2008-01-01

    The tensile strength of rubber depends on a combination of contributions, in particular on the finite extensibility of chain segments between network points and on strain-induced crystallization. In order to achieve high tensile strength at high strain at break, we optimized the composition and processing parameters to gain high molecular flexibility by the cure conditions, to acquire high flexibility of sulfur bridges by the accelerator, and to increase the modulus level without losing rubber molecule flexibility by carbon black. As a result, our formula performed a tensile strength of 42.5 MPa at 25 C under ISO-37, as officially measured by the Society of Rubber Industry, Japan, in 2004.

  6. Photodegradation of dimethyl sulfide (DMS) in natural waters: laboratory assessment of the nitrate-photolysis-induced DMS oxidation.

    PubMed

    Bouillon, René-Christian; Miller, William L

    2005-12-15

    The interaction of sunlight and dissolved chromophoric matter produces reactive chemical species that are significant in the removal of dimethyl sulfide (DMS) in the surface ocean. Using artificial solar radiation, we examined the role of several inorganic components of seawater on the kinetics of NO3- -photolysis-induced DMS removal in aqueous solution. This study strongly suggests that NO3- photolysis products react significantly with DMS in aqueous solution possibly via an electrophilic attack on the electron-rich sulfur atom. This supports previous field observations that indicate that NO3- photolysis has a substantial control on DMS photochemistry in nutrient-rich waters. A key finding of this research is that the oxidation rate of DMS induced by NO3- photolysis is dramatically enhanced in the presence of bromide ion. Moreover, our results suggest that bicarbonate/carbonate ions are involved in free radical production/scavenging processes important for DMS photochemistry. These reactions are pH dependent. We propose that DMS removal by some selective free radicals derived from bromide and bicarbonate/carbonate ion oxidation is a potentially important and previously unrecognized pathway for DMS photodegradation in marine waters. PMID:16475324

  7. Neurosupportive Role of Vanillin, a Natural Phenolic Compound, on Rotenone Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells

    PubMed Central

    Dhanalakshmi, Chinnasamy; Manivasagam, Thamilarasan; Nataraj, Jagatheesan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed

    2015-01-01

    Vanillin, a phenolic compound, has been reported to offer neuroprotection against experimental Huntington's disease and global ischemia by virtue of its antioxidant, anti-inflammatory, and antiapoptotic properties. The present study aims to elucidate the underlying neuroprotective mechanism of vanillin in rotenone induced neurotoxicity. Cell viability was assessed by exposing SH-SY5Y cells to various concentrations of rotenone (5–200 nM) for 24 h. The therapeutic effectiveness of vanillin against rotenone was measured by pretreatment of vanillin at various concentrations (5–200 nM) and then incubation with rotenone (100 nM). Using effective dose of vanillin (100 nM), mitochondrial membrane potential, levels of reactive oxygen species (ROS), and expression patterns of apoptotic markers were assessed. Toxicity of rotenone was accompanied by the loss of mitochondrial membrane potential, increased ROS generation, release of cyt-c, and enhanced expressions of proapoptotic and downregulation of antiapoptotic indices via the upregulation of p38 and JNK-MAPK pathway proteins. Our results indicated that the pretreatment of vanillin attenuated rotenone induced mitochondrial dysfunction, oxidative stress, and apoptosis. Thus, vanillin may serve as a potent therapeutic agent in the future by virtue of its multiple pharmacological properties in the treatment of neurodegenerative diseases including PD. PMID:26664453

  8. Moringa oleifera hydroethanolic extracts effectively alleviate acetaminophen-induced hepatotoxicity in experimental rats through their antioxidant nature.

    PubMed

    Fakurazi, Sharida; Sharifudin, Syazana Akmal; Arulselvan, Palanisamy

    2012-01-01

    The aim of the study was to investigate the in vitro antioxidant properties Moringa oleifera Lam. (MO) extracts and its curative role in acetaminophen (APAP)-induced toxic liver injury in rats caused by oxidative damage. The total phenolic content and antioxidant properties of hydroethanolic extracts of different MO edible parts were investigated by employing an established in vitro biological assay. In the antihepatotoxic study, either flowers or leaves extract (200 mg/kg or 400 mg/kg, i.p) were administered an hour after APAP administration, respectively. N-Acetylcysteine was used as the positive control against APAP-induced hepatotoxicity. The levels of liver markers such as alanine aminotransferase (ALT) and the levels of oxidative damage markers including malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) protein adduct, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were analysed and compared between experimental groups. Among MO edible parts the flower extracts contain the highest total phenolic content and antioxidant capacity, followed by leaves extract. The oxidative marker MDA, as well as 4-HNE protein adduct levels were elevated and GSH, SOD and CAT were significantly decreased in groups treated with hepatotoxin. The biochemical liver tissue oxidative markers measured in the rats treated with MO flowers and leaves hydroethanolic extracts showed a significant (p < 0.05) reduction in the severity of the liver damage. The results of this study strongly indicate the therapeutic properties of MO hydroethanolic extracts against acute liver injury and thereby scientifically support its traditional use. PMID:22781444

  9. Ochnaflavone, naturally occurring biflavonoid, inhibits phospholipase A2 dependent phosphatidylethanolamine degradation in a CCl4-induced rat liver microsome.

    PubMed

    Moon, Tae Chul; Hwang, Hwa Shin; Quan, Zhejiu; Son, Kun Ho; Kim, Cheorl-Ho; Kim, Hyun Pyo; Kang, Sam Sik; Son, Jong Keun; Chang, Hyeun Wook

    2006-12-01

    This study investigated the protective effects of a group IIA secretory phospholipase A2 (sPLA2-IIA) inhibitor, ochnaflavone, on the progression of carbon tetrachloride (CCl4)-induced acute liver injury in rat liver microsomes in vitro. When rat liver was incubated at 37 degrees C in the presence of CCl4, the level of phosphatidylethanolamine (PE) degradation increased markedly compared with the control. The rat 14 kDa platelet PLA2 antibody, R377, suppressed the degradation of PE. Pretreating the microsome with ochnaflavone (2-16 microM) reduced the level of PE degradation in a dose dependent manner. In addition, p-bromophenacy bromide (p-BPB), which is a PLA2 inhibitor, also inhibited PE degradation. However, the inhibitory activity was weaker than that of ochnaflavone. Further investigation showed that ochnaflavone not only inhibited the purified rat platelet sPLA2 activity in a dose dependent manner with an IC50 value of 3.45 microM, when arachidonyl PE was used as a substrate, but also inhibited lipid peroxidation in a dose dependent manner with an IC50 value of 7.16 microM. This result suggests that ochnaflavone prevents the progression of CCl4-induced PE hydrolysis by inhibiting the endogenous sPLA2 activity.

  10. Neurosupportive Role of Vanillin, a Natural Phenolic Compound, on Rotenone Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells.

    PubMed

    Dhanalakshmi, Chinnasamy; Manivasagam, Thamilarasan; Nataraj, Jagatheesan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed

    2015-01-01

    Vanillin, a phenolic compound, has been reported to offer neuroprotection against experimental Huntington's disease and global ischemia by virtue of its antioxidant, anti-inflammatory, and antiapoptotic properties. The present study aims to elucidate the underlying neuroprotective mechanism of vanillin in rotenone induced neurotoxicity. Cell viability was assessed by exposing SH-SY5Y cells to various concentrations of rotenone (5-200 nM) for 24 h. The therapeutic effectiveness of vanillin against rotenone was measured by pretreatment of vanillin at various concentrations (5-200 nM) and then incubation with rotenone (100 nM). Using effective dose of vanillin (100 nM), mitochondrial membrane potential, levels of reactive oxygen species (ROS), and expression patterns of apoptotic markers were assessed. Toxicity of rotenone was accompanied by the loss of mitochondrial membrane potential, increased ROS generation, release of cyt-c, and enhanced expressions of proapoptotic and downregulation of antiapoptotic indices via the upregulation of p38 and JNK-MAPK pathway proteins. Our results indicated that the pretreatment of vanillin attenuated rotenone induced mitochondrial dysfunction, oxidative stress, and apoptosis. Thus, vanillin may serve as a potent therapeutic agent in the future by virtue of its multiple pharmacological properties in the treatment of neurodegenerative diseases including PD.

  11. Moringa oleifera hydroethanolic extracts effectively alleviate acetaminophen-induced hepatotoxicity in experimental rats through their antioxidant nature.

    PubMed

    Fakurazi, Sharida; Sharifudin, Syazana Akmal; Arulselvan, Palanisamy

    2012-07-10

    The aim of the study was to investigate the in vitro antioxidant properties Moringa oleifera Lam. (MO) extracts and its curative role in acetaminophen (APAP)-induced toxic liver injury in rats caused by oxidative damage. The total phenolic content and antioxidant properties of hydroethanolic extracts of different MO edible parts were investigated by employing an established in vitro biological assay. In the antihepatotoxic study, either flowers or leaves extract (200 mg/kg or 400 mg/kg, i.p) were administered an hour after APAP administration, respectively. N-Acetylcysteine was used as the positive control against APAP-induced hepatotoxicity. The levels of liver markers such as alanine aminotransferase (ALT) and the levels of oxidative damage markers including malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) protein adduct, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were analysed and compared between experimental groups. Among MO edible parts the flower extracts contain the highest total phenolic content and antioxidant capacity, followed by leaves extract. The oxidative marker MDA, as well as 4-HNE protein adduct levels were elevated and GSH, SOD and CAT were significantly decreased in groups treated with hepatotoxin. The biochemical liver tissue oxidative markers measured in the rats treated with MO flowers and leaves hydroethanolic extracts showed a significant (p < 0.05) reduction in the severity of the liver damage. The results of this study strongly indicate the therapeutic properties of MO hydroethanolic extracts against acute liver injury and thereby scientifically support its traditional use.

  12. The Protective Effects of Insulin and Natural Honey against Hippocampal Cell Death in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Jafari Anarkooli, Iraj; Barzegar Ganji, Hossein; Pourheidar, Maryam

    2014-01-01

    We investigated the effects of insulin and honey as antioxidants to prevent the hippocampal cell death in streptozotocin-induced diabetic rats. We selected sixty Wister rats (5 groups of 12 animals each), including the control group (C), and four diabetic groups (control (D) and 3 groups treated with insulin (I), honey (H), and insulin plus honey (I + H)). Diabetes was induced by streptozotocin injection (IP, 60 mg/kg). Six weeks after the induction of diabetes, the group I received insulin (3-4 U/kg/day, SC), group H received honey (5 mg/kg/day, IP), and group I + H received a combination of the above at the same dose. Groups C and D received normal saline. Two weeks after treatment, rats were sacrificed and the hippocampus was extracted. Neuronal cell death in the hippocampal region was examined using trypan blue assay, “H & E” staining, and TUNEL assay. Cell viability assessment showed significantly lower number of living cells in group D than in group C. Besides, the mean number of living cells was significantly higher in group I, H, and I + H compared to group D. Therefore, it can be concluded that the treatment of the diabetic rats with insulin, honey, and a combination of insulin and honey can prevent neuronal cell death in different hippocampal areas of the studied samples. PMID:24745031

  13. Ultrasound characteristics of experimentally induced luteinized unruptured follicles (LUF) and naturally occurring hemorrhagic anovulatory follicles (HAF) in the mare.

    PubMed

    Cuervo-Arango, J; Newcombe, J R

    2012-02-01

    The development of hemorrhagic anovulatory follicles (HAF) involves luteinization and hemorrhage of the follicle. This is observed on ultrasound as an increase in the echogenicity of the granulosa layer and formation of echoic particles in the antrum. The inhibition of prostaglandin synthesis with flunixin meglumine (FM) during the periovulatory period induces ovulatory failure with development of luteinized unruptured follicles (LUF). These two types of anovulatory follicles appear to share similar ultrasound features but they have not been compared critically. The following endpoints: follicle diameter, follicular contents score, interval from hCG administration to beginning of follicular hemorrhage, interval from hemorrhage to organization of follicular contents, and cycle length were studied and compared in mares with HAF (n = 11) and LUF (n = 13). The objective of this study was to elucidate whether these two unruptured follicles have a consistent clinical pattern of development and therefore can be considered as part of the same anovulatory syndrome. None of the endpoints analyzed differed significantly between HAF and LUF. However, there was a greater individual variation in HAF as compared with LUF in regards to interval from hCG to hemorrhage, follicular diameter at the administration of hCG, and beginning of hemorrhage. In conclusion, HAF share a similar cascade of ultrasound characteristics with the experimentally induced LUF. This finding may provide new insights in elucidating the pathogenesis of HAF.

  14. The protective effects of insulin and natural honey against hippocampal cell death in streptozotocin-induced diabetic rats.

    PubMed

    Jafari Anarkooli, Iraj; Barzegar Ganji, Hossein; Pourheidar, Maryam

    2014-01-01

    We investigated the effects of insulin and honey as antioxidants to prevent the hippocampal cell death in streptozotocin-induced diabetic rats. We selected sixty Wister rats (5 groups of 12 animals each), including the control group (C), and four diabetic groups (control (D) and 3 groups treated with insulin (I), honey (H), and insulin plus honey (I + H)). Diabetes was induced by streptozotocin injection (IP, 60 mg/kg). Six weeks after the induction of diabetes, the group I received insulin (3-4 U/kg/day, SC), group H received honey (5 mg/kg/day, IP), and group I + H received a combination of the above at the same dose. Groups C and D received normal saline. Two weeks after treatment, rats were sacrificed and the hippocampus was extracted. Neuronal cell death in the hippocampal region was examined using trypan blue assay, "H & E" staining, and TUNEL assay. Cell viability assessment showed significantly lower number of living cells in group D than in group C. Besides, the mean number of living cells was significantly higher in group I, H, and I + H compared to group D. Therefore, it can be concluded that the treatment of the diabetic rats with insulin, honey, and a combination of insulin and honey can prevent neuronal cell death in different hippocampal areas of the studied samples. PMID:24745031

  15. Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy

    PubMed Central

    Dai, Xiaoyun; Zhang, Jingwen; Arfuso, Frank; Chinnathambi, Arunachalam; Zayed, ME; Alharbi, Sulaiman Ali; Kumar, Alan Prem

    2015-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to selectively induce apoptotic cell death in various tumor cells by engaging its death-inducing receptors (TRAIL-R1 and TRAIL-R2). This property has led to the development of a number of TRAIL–receptor agonists such as the soluble recombinant TRAIL and agonistic antibodies, which have shown promising anticancer activity in preclinical studies. However, besides activating caspase-dependent apoptosis in several cancer cells, TRAIL may also activate nonapoptotic signal transduction pathways such as nuclear factor-kappa B, mitogen-activated protein kinases, AKT, and signal transducers and activators of transcription 3, which may contribute to TRAIL resistance that is being now frequently encountered in various cancers. TRAIL resistance can be overcome by the application of efficient TRAIL-sensitizing pharmacological agents. Natural compounds have shown a great potential in sensitizing cells to TRAIL treatment through suppression of distinct survival pathways. In this review, we have summarized both apoptotic and nonapoptotic pathways activated by TRAIL, as well as recent advances in developing TRAIL–receptor agonists for cancer therapy. We also briefly discuss combination therapies that have shown great potential in overcoming TRAIL resistance in various tumors. PMID:25854879

  16. The ascidian natural product eusynstyelamide B is a novel topoisomerase II poison that induces DNA damage and growth arrest in prostate and breast cancer cells.

    PubMed

    Liberio, Michelle S; Sadowski, Martin C; Davis, Rohan A; Rockstroh, Anja; Vasireddy, Raj; Lehman, Melanie L; Nelson, Colleen C

    2015-12-22

    As part of an anti-cancer natural product drug discovery program, we recently identified eusynstyelamide B (EB), which displayed cytotoxicity against MDA-MB-231 breast cancer cells (IC50 = 5 μM) and induced apoptosis. Here, we investigated the mechanism of action of EB in cancer cell lines of the prostate (LNCaP) and breast (MDA-MB-231). EB inhibited cell growth (IC50 = 5 μM) and induced a G2 cell cycle arrest, as shown by a significant increase in the G2/M cell population in the absence of elevated levels of the mitotic marker phospho-histone H3. In contrast to MDA-MB-231 cells, EB did not induce cell death in LNCaP cells when treated for up to 10 days. Transcript profiling and Ingenuity Pathway Analysis suggested that EB activated DNA damage pathways in LNCaP cells. Consistent with this, CHK2 phosphorylation was increased, p21CIP1/WAF1 was up-regulated and CDC2 expression strongly reduced by EB. Importantly, EB caused DNA double-strand breaks, yet did not directly interact with DNA. Analysis of topoisomerase II-mediated decatenation discovered that EB is a novel topoisomerase II poison.

  17. Reconstructing a 180 yr record of natural and anthropogenic induced low-oxygen conditions from Louisiana continental shelf sediments

    USGS Publications Warehouse

    Osterman, L.E.; Poore, R.Z.; Swarzenski, P.W.; Turner, R.E.

    2005-01-01

    Hypoxia on the Louisiana continental shelf is tied to nutrient Loading and freshwater stratification from the Mississippi River. Variations in the relative abundance of low-oxygen-tolerant benthic foraminifers in four sediment cores from the Louisiana shelf provide a proxy record of low-oxygen events. Core chronologies are obtained using 210Pb dating techniques. The foraminiferal data are consistent with previous studies indicating that the intensity of hypoxic events (oxygen <2 mg /L) has increased over the past 50 yr owing to the higher nutrient loading associated with the use of commercial fertilizer, and also reveal several low-oxygen events between A.D. 1817 and 1910, prior to the widespread use of fertilizer. The pre-1910 low-oxygen events are associated with high Mississippi River discharge rates, indicating that these low-oxygen episodes are related to natural variations in river drainage that enhance transport of nutrients and freshwater to the continental shelf. Our data show that the low-oxygen events of the past few decades were more extreme than any that occurred in the previous ???180 yr, and support the interpretation that the increased use of fertilizer has amplified an otherwise naturally occurring process. ?? 2005 Geological Society of America.

  18. Pulchrin A, a New Natural Coumarin Derivative of Enicosanthellum pulchrum, Induces Apoptosis in Ovarian Cancer Cells via Intrinsic Pathway

    PubMed Central

    Nordin, Noraziah; Fadaeinasab, Mehran; Mohan, Syam; Mohd Hashim, Najihah; Othman, Rozana; Karimian, Hamed; Iman, Venus; Ramli, Noorlela; Mohd Ali, Hapipah; Abdul Majid, Nazia

    2016-01-01

    Drug resistance presents a challenge in chemotherapy and has attracted research interest worldwide and particular attention has been given to natural compounds to overcome this difficulty. Pulchrin A, a new compound isolated from natural products has demonstrated novel potential for development as a drug. The identification of pulchrin A was conducted using several spectroscopic techniques such as nuclear magnetic resonance, liquid chromatography mass spectrometer, infrared and ultraviolet spectrometry. The cytotoxicity effects on CAOV-3 cells indicates that pulchrin A is more active than cisplatin, which has an IC50 of 22.3 μM. Significant changes in cell morphology were present, such as cell membrane blebbing and formation of apoptotic bodies. The involvement of phosphatidylserine (PS) in apoptosis was confirmed by Annexin V-FITC after a 24 h treatment. Apoptosis was activated through the intrinsic pathway by activation of procaspases 3 and 9 as well as cleaved caspases 3 and 9 and ended at the executioner pathway, with the occurrence of DNA laddering. Apoptosis was further confirmed via gene and protein expression levels, in which Bcl-2 protein was down-regulated and Bax protein was up-regulated. Furthermore, the CAOV-3 cell cycle was disrupted at the G0/G1 phase, leading to apoptosis. Molecular modeling of Bcl-2 proteins demonstrated a high- binding affinity, which inhibited the function of Bcl-2 proteins and led to cell death. Results of the current study can shed light on the development of new therapeutic agents, particularly, human ovarian cancer treatments. PMID:27136097

  19. Herbivore-induced plant vaccination. Part I. The orchestration of plant defenses in nature and their fitness consequences in the wild tobacco Nicotiana attenuata.

    PubMed

    Kessler, André; Baldwin, Ian T

    2004-05-01

    A plant's responses to attack from particular pathogens and herbivores may result in resistance to subsequent attack from the same species, but may also affect different species. Such a cross-resistance, called immunization or vaccination, can benefit the plant, if the fitness consequences of attack from the initial attacker are less than those from subsequent attackers. Here, we report an example of naturally occurring vaccination of the native tobacco plant, Nicotiana attenuata, against Manduca hornworms by prior attack from the mirid bug, Tupiocoris notatus (Dicyphus minimus), which results from the elicitation of two categories of induced plant responses. First, attack from both herbivore species causes the plants in nature to release predator-attracting volatile organic compounds (VOCs), and the attracted generalist predator, Geocoris pallens, preferentially attacks the less mobile hornworm larvae. Second, attack from both mirids and hornworms increases the accumulation of secondary metabolites and proteinase inhibitors (PIs) in the leaf tissue, which is correlated with the slow growth of Manduca larvae. Mirid damage does not significantly reduce the fitness of the plant in nature, whereas attack from the hornworm reduces lifetime seed production. Consequently, plants that are attacked by mirids realize a significant fitness advantage in environments with both herbivores. The combination of growth-slowing direct defenses and predator-attracting indirect defenses results in greater hornworm mortality on mirid-attacked plants and provides the mechanism of the vaccination phenomenon.

  20. Development of particle induced gamma-ray emission methods for nondestructive determination of isotopic composition of boron and its total concentration in natural and enriched samples.

    PubMed

    Chhillar, Sumit; Acharya, Raghunath; Sodaye, Suparna; Pujari, Pradeep K

    2014-11-18

    We report simple particle induced gamma-ray emission (PIGE) methods using a 4 MeV proton beam for simultaneous and nondestructive determination of the isotopic composition of boron ((10)B/(11)B atom ratio) and total boron concentrations in various solid samples with natural isotopic composition and enriched with (10)B. It involves measurement of prompt gamma-rays at 429, 718, and 2125 keV from (10)B(p,αγ)(7)Be, (10)B(p, p'γ)(10)B, and (11)B(p, p'γ)(11)B reactions, respectively. The isotopic composition of boron in natural and enriched samples was determined by comparing peak area ratios corresponding to (10)B and (11)B of samples to natural boric acid standard. An in situ current normalized PIGE method, using F or Al, was standardized for total B concentration determination. The methods were validated by analyzing stoichiometric boron compounds and applied to samples such as boron carbide, boric acid, carborane, and borosilicate glass. Isotopic compositions of boron in the range of 0.247-2.0 corresponding to (10)B in the range of 19.8-67.0 atom % and total B concentrations in the range of 5-78 wt % were determined. It has been demonstrated that PIGE offers a simple and alternate method for total boron as well as isotopic composition determination in boron based solid samples, including neutron absorbers that are important in nuclear technology.

  1. Pulverization of quartz single crystal and natural quartzite induced by possible super-shear rupture during stick -slips

    NASA Astrophysics Data System (ADS)

    Nishikawa, O.; Muto, J.; Otsuki, K.

    2011-12-01

    Intensely pulverized rocks have been reported from large scale strike slip faults such as San Andreas Fault (e.g., Dor et al., 2006). These rocks are characterized by apparent lack of shear deformation, suggesting shattering and comminuation of grains possibly resulting from a rapid decrease in normal stress and perhaps transient fault opening during passage of the dynamic rupture front. Doan and Gary (2009) experimentally reported that the pulverization of granite requires high strain rates and could be explained by a super shear rupture. So far, there has been almost few experimental study on damage formation of wall rocks of fault in association with rupture propagation during a stick-slip using crustal materials. In order to clarify how rupture propagates and damages wall rocks during a stick-slip , we have performed experiments on a stick-slip with a single crystal of synthetic quartz and natural quartzite. We used a gas apparatus, and performed the experiments at confining pressures of 120-180 MPa and axial strain rate of 10-3/s. Single crystal s of dry synthetic quartz and natural quartzite were cored with a diameter of 20 mm and cut to a length of about 40 mm. Then the cores were cut 50° to the long axis of the core, and the precut surfaces were mirror polished. Axial stresses and shear strains along the fault surfaces were measured by strain gauges, and the data were sampled at 5 MHz . Our experimental results on single crystal of quartz yielded two different frictional behaviors and final states of samples: 1) simple fracturing state associated with multiple small stick-slips at the confining pressure (Pc) less than 160 MPa, where samples were split into fragments but no intense pulverization, 2) intense pulverization state associated with large stick-slips at Pc of 180 MPa, where samples were intensely pulverized into numerous small fragments. The size of the fragments extends down to submicron in the vicinity of the slip plane. In pulverized samples

  2. Nature and specificity of the immune response to collagen in type II collagen-induced arthritis in mice.

    PubMed Central

    Stuart, J M; Townes, A S; Kang, A H

    1982-01-01

    To determine the role of collagen-immunity in the development of collagen-induced arthritis, DBA/1 mice were immunized with type II collagen and observed for the development of polyarthritis. 96% of the mice immunized with native type II collagen developed inflammatory arthritis between 4 and 5 wk after primary immunization. Immunization with denatured type II collagen in exactly the same manner was not effective in inducing arthritis. Cell-mediated immunity in arthritic mice was assessed by measuring [3H]thymidine incorporation by mononuclear cells cultured in the presence of collagen. The maximal proliferative response to collagen occurred at 2 wk after immunization. Equally good incorporation of label occurred when cells were cultured with native or denatured type II collagen or type I collagen. The cellular response of nonarthritic mice immunized with denatured collagen was indistinguishable from that seen in arthritic mice. Humoral immunity was assessed by an ELISA assay for antibodies to collagen. The immunoglobulin M (IgM) response peaked at 2 wk and the IgG response at 5 wk after immunization. Antisera from arthritic mice immunized with native type II collagen were relatively specific for conformational determinants on the native type II molecule although some reactivity with denatured collagen was noted. Antisera from nonarthritic mice immunized with denatured collagen primarily recognized covalent structural determinants. It was concluded that native type II collagen was essential for the induction of arthritis and that an antibody response specific for native type II collagen may be important for the development of arthritis. Images PMID:6174550

  3. Elucidation of Complex Nature of PEG Induced Drought-Stress Response in Rice Root Using Comparative Proteomics Approach

    PubMed Central

    Agrawal, Lalit; Gupta, Swati; Mishra, Shashank K.; Pandey, Garima; Kumar, Susheel; Chauhan, Puneet S.; Chakrabarty, Debasis; Nautiyal, Chandra S.

    2016-01-01

    Along with many adaptive strategies, dynamic changes in protein abundance seem to be the common strategy to cope up with abiotic stresses which can be best explored through proteomics. Understanding of drought response is the key to decipher regulatory mechanism of better adaptation. Rice (Oryza sativa L.) proteome represents a phenomenal source of proteins that govern traits of agronomic importance, such as drought tolerance. In this study, a comparison of root cytoplasmic proteome was done for a drought tolerant rice (Heena) cultivar in PEG induced drought conditions. A total of 510 protein spots were observed by PDQuest analysis and 125 differentially regulated spots were subjected for MALDI-TOF MS-MS analysis out of which 102 protein spots identified which further led to identification of 78 proteins with a significant score. These 78 differentially expressed proteins appeared to be involved in different biological pathways. The largest percentage of identified proteins was involved in bioenergy and metabolism (29%) and mainly consists of malate dehydrogenase, succinyl-CoA, putative acetyl-CoA synthetase, and pyruvate dehydrogenase etc. This was followed by proteins related to cell defense and rescue (22%) such as monodehydroascorbate reductase and stress-induced protein sti1, then by protein biogenesis and storage class (21%) e.g. putative thiamine biosynthesis protein, putative beta-alanine synthase, and cysteine synthase. Further, cell signaling (9%) proteins like actin and prolyl endopeptidase, and proteins with miscellaneous function (19%) like Sgt1 and some hypothetical proteins were also represented a large contribution toward drought regulatory mechanism in rice. We propose that protein biogenesis, cell defense, and superior homeostasis may render better drought-adaptation. These findings might expedite the functional determination of the drought-responsive proteins and their prioritization as potential molecular targets for perfect adaptation. PMID

  4. Corosolic acid analogue, a natural triterpenoid saponin, induces apoptosis on human hepatocarcinoma cells through mitochondrial pathway in vitro.

    PubMed

    Qu, Liping; Zhang, Huiqing; Yang, Yanlong; Yang, Geliang; Xin, Hailiang; Ling, Changquan

    2016-08-01

    Context 2a,-3a,-24-Trihydroxyurs-12-en-28-oic acid (TEO, a corosolic acid analogue) is a triterpenoid saponin isolated from Actinidia valvata Dunn (Actinidiaceae), a well-known traditional Chinese medicine. Objective This study investigated the anti-proliferation and inducing apoptosis effects of TEO in three human hepatocellular carcinoma (HCC) cell lines. Materials and methods Cytotoxic activity of TEO was determined by the MTT assay at various concentrations from 2.5 to 40 μg/mL in BEL-7402, BEL-7404 and SMMC-7721 cell lines. Cell morphology was assessed by acridine orange/ethidium bromide and 4'-6-diamidino-2-phenylindole dihydrochloride staining and fluorescence microscopy. Cell-cycle distribution and DNA damage were determined by flow cytometry and comet assay. Mitochondrial dysfunction was assessed by JC-1 staining and transmission electron microscopy. Apoptosis changes were explored by Western blot, TNF-α and caspase-3, -8, -9 assays. Results TEO exhibited inhibition effects on BEL-7402, BEL-7404 and SMMC-7721 cells treated for 24 h, the IC50 values were 34.6, 30.8 and 30.5 μg/mL, respectively. TEO (40 μg/mL)-treated three cell lines increased by more than 21% in the G1 phase and presented the morphological change and DNA damage. TEO also declined the mitochondrial membrane potential and altered mitochondrial ultra-structure. Furthermore, caspase-3, caspase-8, caspase-9 and TNF-α were also activated. Mechanism investigation showed that TEO could decrease anti-apoptotic Bcl-2 protein expression, increase proapoptotic Bax and Bid proteins expressions and increase Bax/Bcl-2 ratio. Conclusion Our results demonstrate for the first time that TEO inhibited growth of HCC cell lines and induced G1 phase arrest. Moreover, proapoptotic effects of TEO were mediated through the activation of TNF-α, caspases and mitochondrial pathway. PMID:26810384

  5. The Gene pat-2, Which Induces Natural Parthenocarpy, Alters the Gibberellin Content in Unpollinated Tomato Ovaries1

    PubMed Central

    Fos, Mariano; Nuez, Fernando; García-Martínez, José L.

    2000-01-01

    We investigated the role of gibberellins (GAs) in the effect of pat-2, a recessive mutation that induces facultative parthenocarpic fruit development in tomato (Lycopersicon esculentum Mill.) using near-isogenic lines with two different genetic backgrounds. Unpollinated wild-type Madrigal (MA/wt) and Cuarenteno (CU/wt) ovaries degenerated, but GA3 application induced parthenocarpic fruit growth. On the contrary, parthenocarpic growth of MA/pat-2 and CU/pat-2 fruits, which occurs in the absence of pollination and hormone application, was not affected by GA3. Pollinated MA/wt and parthenocarpic MA/pat-2 ovary development was negated by paclobutrazol, and this inhibitory effect was counteracted by GA3. The main GAs of the early-13-hydroxylation pathway (GA1, GA3, GA8, GA19, GA20, GA29, GA44, GA53, and, tentatively, GA81) and two GAs of the non-13-hydroxylation pathway (GA9 and GA34) were identified in MA/wt ovaries by gas chromatography-selected ion monitoring. GAs were quantified in unpollinated ovaries at flower bud, pre-anthesis, and anthesis. In unpollinated MA/pat-2 and CU/pat-2 ovaries, the GA20 content was much higher (up to 160 times higher) and the GA19 content was lower than in the corresponding non-parthenocarpic ovaries. The application of an inhibitor of 2-oxoglutarate-dependent dioxygenases suggested that GA20 is not active per se. The pat-2 mutation may increase GA 20-oxidase activity in unpollinated ovaries, leading to a higher synthesis of GA20, the precursor of an active GA. PMID:10677440

  6. Quality assurance of temporal variability of natural decay chain and neutron induced background for low-level NORM analysis

    DOE PAGESBeta

    Yoho, Michael; Porterfield, Donivan R.; Landsberger, Sheldon

    2015-09-22

    In this study, twenty-one high purity germanium (HPGe) background spectra were collected over 2 years at Los Alamos National Laboratory. A quality assurance methodology was developed to monitor spectral background levels from thermal and fast neutron flux levels and naturally occurring radioactive material decay series radionuclides. 238U decay products above 222Rn demonstrated minimal temporal variability beyond that expected from counting statistics. 238U and 232Th progeny below Rn gas displayed at most twice the expected variability. Further, an analysis of the 139 keV 74Ge(n, γ) and 691 keV 72Ge(n, n') spectral features demonstrated temporal stability for both thermal and fast neutronmore » fluxes.« less

  7. Quality assurance of temporal variability of natural decay chain and neutron induced background for low-level NORM analysis

    SciTech Connect

    Yoho, Michael; Porterfield, Donivan R.; Landsberger, Sheldon

    2015-09-22

    In this study, twenty-one high purity germanium (HPGe) background spectra were collected over 2 years at Los Alamos National Laboratory. A quality assurance methodology was developed to monitor spectral background levels from thermal and fast neutron flux levels and naturally occurring radioactive material decay series radionuclides. 238U decay products above 222Rn demonstrated minimal temporal variability beyond that expected from counting statistics. 238U and 232Th progeny below Rn gas displayed at most twice the expected variability. Further, an analysis of the 139 keV 74Ge(n, γ) and 691 keV 72Ge(n, n') spectral features demonstrated temporal stability for both thermal and fast neutron fluxes.

  8. Conformational control of cofactors in nature - the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles.

    PubMed

    Senge, Mathias O; MacGowan, Stuart A; O'Brien, Jessica M

    2015-12-14

    Tetrapyrrole-containing proteins are one of the most fundamental classes of enzymes in nature and it remains an open question to give a chemical rationale for the multitude of biological reactions that can be catalyzed by these pigment-protein complexes. There are many fundamental processes where the same (i.e., chemically identical) porphyrin cofactor is involved in chemically quite distinct reactions. For example, heme is the active cofactor for oxygen transport and storage (hemoglobin, myoglobin) and for the incorporation of molecular oxygen in organic substrates (cytochrome P450). It is involved in the terminal oxidation (cytochrome c oxidase) and the metabolism of H2O2 (catalases and peroxidases) and catalyzes various electron transfer reactions in cytochromes. Likewise, in photosynthesis the same chlorophyll cofactor may function as a reaction center pigment (charge separation) or as an accessory pigment (exciton transfer) in light harvesting complexes (e.g., chlorophyll a). Whilst differences in the apoprotein sequences alone cannot explain the often drastic differences in physicochemical properties encountered for the same cofactor in diverse protein complexes, a critical factor for all biological functions must be the close structural interplay between bound cofactors and the respective apoprotein in addition to factors such as hydrogen bonding or electronic effects. Here, we explore how nature can use the same chemical molecule as a cofactor for chemically distinct reactions using the concept of conformational flexibility of tetrapyrroles. The multifaceted roles of tetrapyrroles are discussed in the context of the current knowledge on distorted porphyrins. Contemporary analytical methods now allow a more quantitative look at cofactors in protein complexes and the development of the field is illustrated by case studies on hemeproteins and photosynthetic complexes. Specific tetrapyrrole conformations are now used to prepare bioengineered designer proteins

  9. Systems biology approach to developing S(2)RM-based "systems therapeutics" and naturally induced pluripotent stem cells.

    PubMed

    Maguire, Greg; Friedman, Peter

    2015-05-26

    The degree to, and the mechanisms through, which stem cells are able to build, maintain, and heal the body have only recently begun to be understood. Much of the stem cell's power resides in the release of a multitude of molecules, called stem cell released molecules (SRM). A fundamentally new type of therapeutic, namely "systems therapeutic", can be realized by reverse engineering the mechanisms of the SRM processes. Recent data demonstrates that the composition of the SRM is different for each type of stem cell, as well as for different states of each cell type. Although systems biology has been successfully used to analyze multiple pathways, the approach is often used to develop a small molecule interacting at only one pathway in the system. A new model is emerging in biology where systems biology is used to develop a new technology acting at multiple pathways called "systems therapeutics". A natural set of healing pathways in the human that uses SRM is instructive and of practical use in developing systems therapeutics. Endogenous SRM processes in the human body use a combination of SRM from two or more stem cell types, designated as S(2)RM, doing so under various state dependent conditions for each cell type. Here we describe our approach in using state-dependent SRM from two or more stem cell types, S(2)RM technology, to develop a new class of therapeutics called "systems therapeutics." Given the ubiquitous and powerful nature of innate S(2)RM-based healing in the human body, this "systems therapeutic" approach using S(2)RM technology will be important for the development of anti-cancer therapeutics, antimicrobials, wound care products and procedures, and a number of other therapeutics for many indications.

  10. Conformational control of cofactors in nature - the influence of protein-induced macrocycle distortion on the biological function of tetrapyrroles.

    PubMed

    Senge, Mathias O; MacGowan, Stuart A; O'Brien, Jessica M

    2015-12-14

    Tetrapyrrole-containing proteins are one of the most fundamental classes of enzymes in nature and it remains an open question to give a chemical rationale for the multitude of biological reactions that can be catalyzed by these pigment-protein complexes. There are many fundamental processes where the same (i.e., chemically identical) porphyrin cofactor is involved in chemically quite distinct reactions. For example, heme is the active cofactor for oxygen transport and storage (hemoglobin, myoglobin) and for the incorporation of molecular oxygen in organic substrates (cytochrome P450). It is involved in the terminal oxidation (cytochrome c oxidase) and the metabolism of H2O2 (catalases and peroxidases) and catalyzes various electron transfer reactions in cytochromes. Likewise, in photosynthesis the same chlorophyll cofactor may function as a reaction center pigment (charge separation) or as an accessory pigment (exciton transfer) in light harvesting complexes (e.g., chlorophyll a). Whilst differences in the apoprotein sequences alone cannot explain the often drastic differences in physicochemical properties encountered for the same cofactor in diverse protein complexes, a critical factor for all biological functions must be the close structural interplay between bound cofactors and the respective apoprotein in addition to factors such as hydrogen bonding or electronic effects. Here, we explore how nature can use the same chemical molecule as a cofactor for chemically distinct reactions using the concept of conformational flexibility of tetrapyrroles. The multifaceted roles of tetrapyrroles are discussed in the context of the current knowledge on distorted porphyrins. Contemporary analytical methods now allow a more quantitative look at cofactors in protein complexes and the development of the field is illustrated by case studies on hemeproteins and photosynthetic complexes. Specific tetrapyrrole conformations are now used to prepare bioengineered designer proteins

  11. Class I-induced resistance to natural killing: identification of nonpermissive residues in HLA-A2.

    PubMed Central

    Storkus, W J; Salter, R D; Alexander, J; Ward, F E; Ruiz, R E; Cresswell, P; Dawson, J R

    1991-01-01

    Structural characteristics of major histocompatibility complex class I antigens associated with natural killer (NK)-resistance phenomena were examined. Previous research has shown that transfection of class I genomic DNA clones into class I-deficient, NK-sensitive target cell lines results in transfectants exhibiting class I+, NK-resistant phenotypes. In contrast to the HLA-A3, -B7, -B27, and -Bw58 class I molecules, the HLA-A2 class I molecules were shown not to protect target cells from NK activity. Here we show that this nonprotective phenotype maps to the alpha 1 domain of the HLA-A2 molecule by examining the NK-protective capacity of the natural interdomain recombinant HLA-Aw69 molecule. HLA-Aw69, which consists of an alpha 1 domain exhibiting homology with HLA-Aw68, and alpha 2/alpha 3/transmembrane-cytoplasmic domains, exhibiting homologies with HLA-A2, mimics HLA-Aw68 and provides HLA-A,B null target cell (C1R) transfectants with increased resistance to NK. Further, the inability of transfected HLA-A2 to confer protection against NK activity can be completely attributed to the expression of a "nonpermissive" residue at position 74 in the alpha 1 domain. Site-directed mutation of the His-74 residue in HLA-A2 to the Asp-74 (HLA-A3, -Aw68, -Aw69, -B7) residue generates a mutant that provides C1R cell line transfectants an NK-resistant phenotype. As His-74 blocks access to a side pocket in the HLA-A2 antigen-binding cleft, these results support the critical involvement of residues within the peptide-binding groove of class I molecules in determining the NK susceptibility phenotype of class I+ target cells. PMID:2068075

  12. The fate of biogenic iron during a phytoplankton bloom induced by natural fertilisation: Impact of copepod grazing

    NASA Astrophysics Data System (ADS)

    Sarthou, Géraldine; Vincent, Dorothée; Christaki, Urania; Obernosterer, Ingrid; Timmermans, Klaas R.; Brussaard, Corina P. D.

    2008-03-01

    The impact of copepod grazing on Fe regeneration was investigated in a naturally iron-fertilised area during Kerguelen Ocean and Plateau compared Study (KEOPS, Jan.-Feb. 2005). 55Fe-labelled natural plankton assemblages (<200 μm) were offered as food to copepod predators sampled in the field ( Calanus propinquus, Rhincalanus gigas, Metridia lucens and Oithona frigida). Diatoms ( Eucampia antarctica, Corethron inerme and Navicula spp.) constituted the bulk of the protists whereas microzooplankton (i.e. ciliates and dinoflagellates) were in very low abundance. Copepod grazing on phytoplankton ranged from 0.3 to 2.6 μgC ind -1 d -1 and reflected low utilisation of the food stocks (1-10% of total Chlorophyll a d -1) and low daily rations (0.2-3.3% body C d -1). Copepod grazing resulted in a 1.7-2.3-fold increase in Fe regeneration. Less than 1% of the regenerated Fe was complexed with hydrophobic organic ligands, as determined by extraction onto hydrophobic C18 columns. This suggests that Fe was regenerated as inorganic species and/or bound to freely soluble organic ligands. The biogenic Fe budget established from our study and literature based data indicates that most of the primary production is recycled through the detrital pool, which represents the largest Fe pool (49% of total Fe). Our iron budget further indicates that mesozooplankton and diatoms represent the dominant Fe biomasses above the Kerguelen plateau. The rate of Fe regeneration accounts for half of the Fe demand, strengthening the need for new Fe sources to sustain the massive phytoplankton bloom above the Kerguelen plateau.

  13. Systems biology approach to developing S2RM-based “systems therapeutics” and naturally induced pluripotent stem cells

    PubMed Central

    Maguire, Greg; Friedman, Peter

    2015-01-01

    The degree to, and the mechanisms through, which stem cells are able to build, maintain, and heal the body have only recently begun to be understood. Much of the stem cell’s power resides in the release of a multitude of molecules, called stem cell released molecules (SRM). A fundamentally new type of therapeutic, namely “systems therapeutic”, can be realized by reverse engineering the mechanisms of the SRM processes. Recent data demonstrates that the composition of the SRM is different for each type of stem cell, as well as for different states of each cell type. Although systems biology has been successfully used to analyze multiple pathways, the approach is often used to develop a small molecule interacting at only one pathway in the system. A new model is emerging in biology where systems biology is used to develop a new technology acting at multiple pathways called “systems therapeutics”. A natural set of healing pathways in the human that uses SRM is instructive and of practical use in developing systems therapeutics. Endogenous SRM processes in the human body use a combination of SRM from two or more stem cell types, designated as S2RM, doing so under various state dependent conditions for each cell type. Here we describe our approach in using state-dependent SRM from two or more stem cell types, S2RM technology, to develop a new class of therapeutics called “systems therapeutics.” Given the ubiquitous and powerful nature of innate S2RM-based healing in the human body, this “systems therapeutic” approach using S2RM technology will be important for the development of anti-cancer therapeutics, antimicrobials, wound care products and procedures, and a number of other therapeutics for many indications. PMID:26029345

  14. Effects of natural raw meal (NRM) on high-fat diet and dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6J mice

    PubMed Central

    Shin, Sung-Ho; Song, Jia-Le; Park, Myoung-Gyu; Park, Mi-Hyun; Hwang, Sung-Joo

    2015-01-01

    BACKGROUND/OBJECTIVES Colitis is a serious health problem, and chronic obesity is associated with the progression of colitis. The aim of this study was to determine the effects of natural raw meal (NRM) on high-fat diet (HFD, 45%) and dextran sulfate sodium (DSS, 2% w/v)-induced colitis in C57BL/6J mice. MATERIALS/METHODS Body weight, colon length, and colon weight-to-length ratio, were measured directly. Serum levels of obesity-related biomarkers, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), insulin, leptin, and adiponectin were determined using commercial kits. Serum levels of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were detected using a commercial ELISA kit. Histological study was performed using a hematoxylin and eosin (H&E) staining assay. Colonic mRNA expressions of TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were determined by RT-PCR assay. RESULTS Body weight and obesity-related biomarkers (TG, TC, LDL, HDL, insulin, leptin, and adiponectin) were regulated and obesity was prevented in NRM treated mice. NRM significantly suppressed colon shortening and reduced colon weight-to-length ratio in HFD+DSS induced colitis in C57BL/6J mice (P < 0.05). Histological observations suggested that NRM reduced edema, mucosal damage, and the loss of crypts induced by HFD and DSS. In addition, NRM decreased the serum levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6 and inhibited the mRNA expressions of these cytokines, and iNOS and COX-2 in colon mucosa (P < 0.05). CONCLUSION The results suggest that NRM has an anti-inflammatory effect against HFD and DSS-induced colitis in mice, and that these effects are due to the amelioration of HFD and/or DSS-induced inflammatory reactions. PMID:26634051

  15. Yogurt Containing the Probacteria Lactobacillus acidophilus Combined with Natural Antioxidants Mitigates Doxorubicin-Induced Cardiomyopathy in Rats.

    PubMed

    Abu-Elsaad, Nashwa M; Abd Elhameed, Ahmed G; El-Karef, Amr; Ibrahim, Tarek M

    2015-09-01

    Probiotics and antioxidants have a definite improving effect in cardiovascular diseases. This study aims at mitigating doxorubicin toxicity on cardiac function through consuming a functional food. Five groups of adult male Sprague-Dawley rats were used along 22 weeks. Group I received 30 g/kg/day food enriched with yogurt, green tea extract, and carrots (80, 0.84, and 100 g/kg diet, respectively) from the first week, group II received carvedilol 30 mg/kg/day orally from week 17, group III received both carvedilol and tested food, and groups IV and V were +ve and -ve control groups, respectively. In week 17, cardiomyopathy was induced by i.p. injection of 2.5 mg/kg doxorubicin every 48 h for 2 weeks. Histopathological and electrophysiological examinations and biochemical analysis were done. Lipid peroxidation, antioxidant effect, heart failure compensatory mediators, and proinflammatory cytokines were assessed. Tested food normalized time between the start of Q wave and the end of T wave on electrocardiogram (QT interval) and heart rate compared to the doxorubicin group (P<.05). It also improved hypertrophy indicated by a significant (P<.05) decrease in heart/body weight ratio, angiotensin-II (Ang-II), and atrial natriuretic peptide (ANP) serum levels. Histopathological examination of cardiac sections from the tested food group revealed less marked vacuolization and low perivascular fibrosis percentage (0.7803 ± 0.04). A significant (P<.001) decrease in serum creatine kinase-membrane bound, lactate dehydrogenase, triglycerides, cholesterol, low-density lipoprotein cholesterol, and tissue malondialdehyde (MDA) levels was observed in addition to an increase in serum Na(+)/K(+) ATP1A1 and cardiac reduced glutathione (GSH) levels. Tested food also lowered the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) serum levels significantly (P<.01). Probiotic food containing Lactobacillus acidophilus, green tea, and carrots can improve

  16. Temperature-induced water stress in high-latitude forests in response to natural and anthropogenic warming.

    PubMed

    Trahan, Matthew W; Schubert, Brian A

    2016-02-01

    The Arctic is particularly sensitive to climate change, but the independent effects of increasing atmospheric CO2 concentration (pCO2 ) and temperature on high-latitude forests are poorly understood. Here, we present a new, annually resolved record of stable carbon isotope (δ(13) C) data determined from Larix cajanderi tree cores collected from far northeastern Siberia in order to investigate the physiological response of these trees to regional warming. The tree-ring record, which extends from 1912 through 1961 (50 years), targets early twentieth-century warming (ETCW), a natural warming event in the 1920s to 1940s that was limited to Northern hemisphere high latitudes. Our data show that net carbon isotope fractionation (Δ(13) C), decreased by 1.7‰ across the ETCW, which is consistent with increased water stress in response to climate warming and dryer soils. To investigate whether this signal is present across the northern boreal forest, we compiled published carbon isotope data from 14 high-latitude sites within Europe, Asia, and North America. The resulting dataset covered the entire twentieth century and spanned both natural ETCW and anthropogenic Late Twentieth-Century Warming (~0.7 °C per decade). After correcting for a ~1‰ increase in Δ(13) C in response to twentieth century pCO2 rise, a significant negative relationship (r = -0.53, P < 0.0001) between the average, annual Δ(13) C values and regional annual temperature anomalies is observed, suggesting a strong control of temperature on the Δ(13) C value of trees growing at high latitudes. We calculate a 17% increase in intrinsic water-use efficiency within these forests across the twentieth century, of which approximately half is attributed to a decrease in stomatal conductance in order to conserve water in response to drying conditions, with the other half being attributed to increasing pCO2 . We conclude that annual tree-ring records from northern high-latitude forests record the effects of

  17. Temperature-induced water stress in high-latitude forests in response to natural and anthropogenic warming.

    PubMed

    Trahan, Matthew W; Schubert, Brian A

    2016-02-01

    The Arctic is particularly sensitive to climate change, but the independent effects of increasing atmospheric CO2 concentration (pCO2 ) and temperature on high-latitude forests are poorly understood. Here, we present a new, annually resolved record of stable carbon isotope (δ(13) C) data determined from Larix cajanderi tree cores collected from far northeastern Siberia in order to investigate the physiological response of these trees to regional warming. The tree-ring record, which extends from 1912 through 1961 (50 years), targets early twentieth-century warming (ETCW), a natural warming event in the 1920s to 1940s that was limited to Northern hemisphere high latitudes. Our data show that net carbon isotope fractionation (Δ(13) C), decreased by 1.7‰ across the ETCW, which is consistent with increased water stress in response to climate warming and dryer soils. To investigate whether this signal is present across the northern boreal forest, we compiled published carbon isotope data from 14 high-latitude sites within Europe, Asia, and North America. The resulting dataset covered the entire twentieth century and spanned both natural ETCW and anthropogenic Late Twentieth-Century Warming (~0.7 °C per decade). After correcting for a ~1‰ increase in Δ(13) C in response to twentieth century pCO2 rise, a significant negative relationship (r = -0.53, P < 0.0001) between the average, annual Δ(13) C values and regional annual temperature anomalies is observed, suggesting a strong control of temperature on the Δ(13) C value of trees growing at high latitudes. We calculate a 17% increase in intrinsic water-use efficiency within these forests across the twentieth century, of which approximately half is attributed to a decrease in stomatal conductance in order to conserve water in response to drying conditions, with the other half being attributed to increasing pCO2 . We conclude that annual tree-ring records from northern high-latitude forests record the effects of

  18. Cavity electromagnetically induced transparency of driven-three-level atoms: A transparent window narrowing below a natural width

    NASA Astrophysics Data System (ADS)

    Bentley, Cleo L.; Liu, Jiaren; Liao, Yan

    2000-02-01

    Steady-state dynamics of a Λ atom in a ring cavity driven by two coherent fields are studied for arbitrary detunings, arbitrary incoherent pumping, and coherent driving intensities. Effects of both cavity and effective atom number on electromagnetically induced transparency (EIT) are pointed out. New physical pictures for cavity EIT are given in terms of collective cooperative coefficients and dispersion experienced by the probe. In the regime of smaller collective cooperative coefficients, an absorption-gain profile is reduced to that of a general EIT estimated by the imaginary part of a corresponding dipole moment, and its transparency window is directly proportional to power broadening, if the total Rabi frequency is large enough. But in the region of larger collective cooperative coefficients which means a dense atomic medium, longer optical path, or high-Q cavity, EIT is determined not only by the imaginary part but also by the real part of the corresponding dipole moment, which results in the possibility of observing an EIT central peak with a subnatural width, while there may be nearly no power broadening.

  19. Proliferation inhibition, cell cycle arrest and apoptosis induced in HL-60 cells by a natural diterpene ester from Daphne mucronata

    PubMed Central

    Nouri, K.; Yazdanparast, R.

    2011-01-01

    Background and the purpose of the study Gnidilatimonoein (Gn), a new diterpene ester from Daphne mucronata, possesses strong anti-metastasis and anti-tumor activities. In this study, its apoptosis and differentiation capabilities were evaluated by using the leukemia HL-60 cell line. Material and methods Cell prolifaration inhibition was estimated by MTT assay. The occurrence of apoptosis was evaluated by EtBr/AO double staining technique, cell cycle analyses and detection of apoptotic cells by Annexin V-FITC and propodium iodide (PI). Differentiation of the cells was determined by NBT reduction assay and the expression of specific cell surface markers such as CD14 and CD11b, were analyzed by flow cytometry. Results The drug decreased the growth of the cells dose- and time-dependently and the IC50 was found to be 1.3 µM. Our data suggested that Gn induced both monocytic differentiation and apoptosis among HL-60 cells. In addition, cell cycle analyses showed an increase in G1 phase population by 24 hrs, which was gradually replaced by Sub-G1 cell population (apoptotic cells) by 72 hrs. Conclusion Based on these data, the Gn-treated HL-60 cells displayed differentiation-dependent apoptosis. Thus, Gn might be a good candidate for differentiation therapy of leukemia, pending full biological evaluation of the compound among the wide array of leukemia cells. PMID:22615651

  20. A candidate gene conversion event associated with natural and induced hypermutation of a human V[sub H]5 gene

    SciTech Connect

    Fairhurst, G.R.; Valles-Ayoub, Y.; Neshat, M.; Braun, J. )

    1994-03-15

    Follicular lymphomas undergo somatic hypermutation which results in substantial intraclonal heterogeneity and may contribute to tumor growth. To directly assay the mechanism of somatic hypermutation, the authors established a PCR-based assay to characterize rearranged V[sub H]5 genes of UV-irradiated germinal center (GC) B cells. This approach is based on the rationale that single-stranded intermediates of UV-induced DNA repair would mimic the physiological substrate for hypermutation. The authors predicted that UV-irradiated GC, but not mantle zone (MZ), B cells would introduce mutations selectively at rearranged, but not unrearranged V genes. This prediction was validated by two independent experiments in which tonsil cells were fractionated into GC or MZ B cells, UV-irradiated or left untreated, and cultured to allow time for DNA repair. Unrearranged and rearranged V[sub H][sub 5] genes were selectively PCR-amplified and analyzed by restriction digest or SSCP. In both experiments, a unique and predominant mutation was identified soley in rearranged V[sub H]5 genes of UV-irradiated GC B cells. Data suggest that these mutations are templated in the genome. One mutation was PCR-amplified from HeLa DNA and is widely distributed, whereas the other appears at low frequency in the population and has been isolated from two familial CLL and a T cell lymphoma. Identification of putative V[sub H]5 pseudogenes, now in progress, would strongly implicate gene conversion in diversification of the immunoglobulin repertoire.

  1. Threshold Dependence of Deep- and Near-subwavelength Ripples Formation on Natural MoS2 Induced by Femtosecond Laser.

    PubMed

    Pan, Yusong; Yang, Ming; Li, Yumei; Wang, Zhenhua; Zhang, Chunling; Zhao, Ying; Yao, Jianghong; Wu, Qiang; Xu, Jingjun

    2016-01-01

    Deep sub-wavelength ripples (DSRs) and near sub-wavelength ripples (NSRs) with uniform periods of ~160 nm and ~660 nm generated at the MoS2-vacuum interface is reported for the first time by the processing of femtosecond laser (800 nm, 120 fs, 1 kHz) in this paper. The DSRs and NSRs formation fluence thresholds are experimentally determined as 160 mJ/cm(2) and 192 mJ/cm(2), respectively. In addition, the ripple period is insensitive to the pulse number. Moreover, Raman analyses show that the MoS2 lattice in the irradiated area does not exhibit oxidation at room environment and the crystalline representation is well preserved in NSRs region. We attribute our result to the joint interactions of the spallation and sublimation of layered MoS2 together with the laser induced surface plasmon polaritons and propose an explanation to the threshold dependence of the ripple period. Our study provides some insights for ultrafast laser-matter interactions and indicates a simple effective method for future nano-fabrication of MoS2. PMID:26795074

  2. Naturally induced secondary radiation in interplanetary space: Preliminary analyses for gamma radiation and radioisotope production from thermal neutron activation

    NASA Technical Reports Server (NTRS)

    Plaza-Rosado, Heriberto

    1991-01-01

    Thermal neutron activation analyses were carried out for various space systems components to determine gamma radiation dose rates and food radiation contamination levels. The space systems components selected were those for which previous radiation studies existed. These include manned space vehicle radiation shielding, liquid hydrogen propellant tanks for a Mars mission, and a food supply used as space vehicle radiation shielding. The computational method used is based on the fast neutron distribution generated by the BRYNTRN and HZETRN transport codes for Galactic Cosmic Rays (GCR) at solar minimum conditions and intense solar flares in space systems components. The gamma dose rates for soft tissue are calculated for water and aluminum space vehicle slab shields considering volumetric source self-attenuation and exponential buildup factors. In the case of the lunar habitat with regolith shielding, a completely exposed spherical habitat was assumed for mathematical convenience and conservative calculations. Activation analysis of the food supply used as radiation shielding is presented for four selected nutrients: potassium, calcium, sodium, and phosphorus. Radioactive isotopes that could represent a health hazard if ingested are identified and their concentrations are identified. For nutrients soluble in water, it was found that all induced radioactivity was below the accepted maximum permissible concentrations.

  3. Induced neurocysticercosis in rhesus monkeys (Macaca mulatta) produces clinical signs and lesions similar to natural disease in man.

    PubMed

    Chowdhury, N; Saleque, A; Sood, N K; Singla, L D

    2014-01-01

    Neurocysticercosis is a serious endemic zoonosis resulting in increased cases of seizure and epilepsy in humans. The genesis of clinical manifestations of the disease through experimental animal models is poorly exploited. The monkeys may prove useful for the purpose due to their behavior and cognitive responses mimicking man. In this study, neurocysticercosis was induced in two rhesus monkeys each with 12,000 and 6,000 eggs, whereas three monkeys were given placebo. The monkeys given higher dose developed hyperexcitability, epileptic seizures, muscular tremors, digital cramps at 10 DPI, and finally paralysis of limbs, followed by death on 67 DPI, whereas the monkeys given lower dose showed delayed and milder clinical signs. On necropsy, all the infected monkeys showed numerous cysticerci in the brain. Histopathologically, heavily infected monkeys revealed liquefactive necrosis and formation of irregular cystic cavities lined by atrophied parenchymal septa with remnants of neuropil of the cerebrum. In contrast, the monkeys infected with lower dose showed formation of typical foreign body granulomas characterized by central liquefaction surrounded by chronic inflammatory response. It was concluded that the inflammatory and immune response exerted by the host against cysticerci, in turn, led to histopathological lesions and the resultant clinical signs thereof.

  4. Sea buckthorn (Hippophae rhamnoides L.) oil protects against chronic stress-induced inhibitory function of natural killer cells in rats.

    PubMed

    Diandong, Hou; Feng, Gu; Zaifu, Liang; Helland, Timothy; Weixin, Fu; Liping, Cai

    2016-03-01

    Chronic stress can suppress natural killer (NK) cell activity; this may also be related to the effect of stress on the neuroendocrine-immune network. Sea buckthorn (SBT) (Hippophae rhamnoides L.) is a thorny nitrogen fixing deciduous shrub, native to both Europe and Asia. It has been used as a medicinal plant in Tibetan and Mongolian traditional medicines. SBT has multifarious medical properties, including anti-fatigue as well as immunoregulatory effects. This study reports the effects of SBT oil with regard to the cytotoxicity and quantity of NK cells in the blood of a chronic-stress rat model, in addition to its mechanisms on the neuroendocrine-immune network. These results show that SBT oil, given by gavage to rats with chronic stress, could increase the following: body weight, NK cell quantities, and cytotoxicity, as well as the expression of perforin and granzyme B. The results also show that SBT oil in rats with chronic stress could suppress cortisol, ACTH, IL-1β and TNF-α levels, in addition to increasing 5-HT and IFN-γ serum levels. This leads to suggest that SBT oil, in rats with chronic stress, can increase NK cell cytotoxicity by upregulating the expression of perforin and granzyme B, thus causing associated effects of SBT oil on the neuroendocrine-immune network. PMID:26684638

  5. Compensatory Growth Induced in Zebrafish Larvae after Pre-Exposure to a Microcystis aeruginosa Natural Bloom Extract Containing Microcystins

    PubMed Central

    Ghazali, Issam El; Saqrane, Sanaa; Carvalho, Antonio Paulo; Ouahid, Youness; Oudra, Brahim; Del Campo, Francisca Fernandez; Vasconcelos, Vitor

    2009-01-01

    Early life stage tests with zebrafish (Danio rerio) were used to detect toxic effects of compounds from a Microcystis aeruginosa natural bloom extract on their embryolarval development. We carried out the exposure of developing stages of fish to complex cyanobacterial blooms containing hepatotoxic molecules - microcystins. Fish embryo tests performed with the bloom extract containing 3 mg·L−1 Eq microcystin-LR showed that after 24 h of exposure all fish embryos died. The same tests performed with other diluted extracts (containing 0.3, 0.1 and 0.03 mg·L−1 Eq microcystin-LR) were shown to have an influence on zebrafish development and a large number of embryos showed malformation signs (edema, bent and curving tail). After hatching the larvae were transferred to a medium without toxins to follow the larval development under the new conditions. The specific growth of the pre-exposed larvae was significantly more important than that of the control larvae. This may represent a compensatory growth used to reduce the difference in size with the control fish noted after hatching. PMID:19333438

  6. Role of Stearic Acid in the Strain-Induced Crystallization of Crosslinked Natural Rubber and Synthetic Cis-1,4-Polyisoprene

    SciTech Connect

    Kohjiya,S.; Tosaka, M.; Furutani, M.; Ikeda, Y.; Toki, S.; Hsiao, B.

    2007-01-01

    Strain-induced crystallization of crosslinked natural rubber (NR) and its synthetic analogue, cis-1,4-polyisoprene (IR), both mixed with various amounts of stearic acid (SA), were investigated by time-resolved X-ray diffraction using a powerful synchrotron radiation source and simultaneous mechanical (tensile) measurement. No acceleration or retardation was observed on NR in spite of the increase of SA amount. Even the SA-free IR crystallized upon stretching, and the overall crystallization behavior of IR shifted to the larger strain ratio with increasing SA content. No difference due to the SA was detected in the deformation of crystal lattice by stress for both NR and IR. These results suggested that the extended network chains are effective for the initiation of crystallization upon stretching, while the role of SA is trivial. These behaviors are much different from their crystallization at low temperature by standing, where SA acts as a nucleating agent.

  7. Excitation function for deuteron induced nuclear reactions on natural ytterbium for production of high specific activity 177g Lu in no-carrier-added form for metabolic radiotherapy.

    PubMed

    Manenti, Simone; Groppi, Flavia; Gandini, Andrea; Gini, Luigi; Abbas, Kamel; Holzwarth, Uwe; Simonelli, Federica; Bonardi, Mauro

    2011-01-01

    Deuteron-induced nuclear reactions for generation of no-carrier-added Lu radionuclides were investigated using the stacked-foil activation technique on natural Yb targets at energies up to E(d)=18.18 MeV. Excitation functions of the reactions (nat)Yb(d,xn)(169,170,171,172,173,174g,174m,176m,177g)Lu and (nat)Yb(d,pxn)(169,175,177)Yb have been measured, among them three ((169)Lu, (174m)Lu and (176m)Lu) are reported for the first time. The upper limit of the contamination from the long-lived metastable level (177m)Lu was evaluated too. Thick-target yields for all investigated radionuclides are calculated.

  8. Natural Variation in Small Molecule–Induced TIR-NB-LRR Signaling Induces Root Growth Arrest via EDS1- and PAD4-Complexed R Protein VICTR in Arabidopsis[C][W

    PubMed Central

    Kim, Tae-Houn; Kunz, Hans-Henning; Bhattacharjee, Saikat; Hauser, Felix; Park, Jiyoung; Engineer, Cawas; Liu, Amy; Ha, Tracy; Parker, Jane E.; Gassmann, Walter; Schroeder, Julian I.

    2012-01-01

    In a chemical genetics screen we identified the small-molecule [5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione (DFPM) that triggers rapid inhibition of early abscisic acid signal transduction via PHYTOALEXIN DEFICIENT4 (PAD4)- and ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)-dependent immune signaling mechanisms. However, mechanisms upstream of EDS1 and PAD4 in DFPM-mediated signaling remain unknown. Here, we report that DFPM generates an Arabidopsis thaliana accession-specific root growth arrest in Columbia-0 (Col-0) plants. The genetic locus responsible for this natural variant, VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response), encodes a TIR-NB-LRR (for Toll-Interleukin1 Receptor–nucleotide binding–Leucine-rich repeat) protein. Analyses of T-DNA insertion victr alleles showed that VICTR is necessary for DFPM-induced root growth arrest and inhibition of abscisic acid–induced stomatal closing. Transgenic expression of the Col-0 VICTR allele in DFPM-insensitive Arabidopsis accessions recapitulated the DFPM-induced root growth arrest. EDS1 and PAD4, both central regulators of basal resistance and effector-triggered immunity, as well as HSP90 chaperones and their cochaperones RAR1 and SGT1B, are required for the DFPM-induced root growth arrest. Salicylic acid and jasmonic acid signaling pathway components are dispensable. We further demonstrate that VICTR associates with EDS1 and PAD4 in a nuclear protein complex. These findings show a previously unexplored association between a TIR-NB-LRR protein and PAD4 and identify functions of plant immune signaling components in the regulation of root meristematic zone-targeted growth arrest. PMID:23275581

  9. Retrovirus-induced murine acquired immunodeficiency syndrome: natural history of infection and differing susceptibility of inbred mouse strains.

    PubMed

    Hartley, J W; Fredrickson, T N; Yetter, R A; Makino, M; Morse, H C

    1989-03-01

    C57BL mice (Fv-1b) develop a severe immunodeficiency disease following inoculation as adults with LP-BM5 murine leukemia virus (MuLV), a derivative of Duplan-Laterjet virus which contains B-tropic ecotropic and mink cell focus-inducing MuLVs and a putative defective genome which may be the proximal cause of disease. The stages of development of this disease were defined for C57BL mice on the basis of lymphadenopathy and splenomegaly; histopathological changes consistent with B-cell activation; and alterations in expression of cell surface antigens affected by proliferation of T cells, B cells, and macrophages. By using this disease profile as a standard, the response of adult mice of various inbred strains and selected F1 hybrids was compared. We show that although the strains which are highly sensitive are of the Fv-1b genotype (i.e., permissive for B-tropic MuLVs), certain Fv-1b strains, e.g., BALB/c and A/J, are resistant to murine acquired immunodeficiency syndrome, whereas certain Fv-1n strains (permissive for N-tropic MuLVs but restrictive for B-tropic MuLVs), notably P/N, BDP, and AKR, show moderate sensitivity and (C57BL/6 x CBA/N)F1 mice (Fv-1n/b and thus dually restrictive) are of relatively high susceptibility. The results of virus recovery tests suggest that apparently anomalous sensitivity, based on predicted Fv-1 restriction, may reflect MuLV induction and/or mutation to provide a helper virus for which the host is permissive.

  10. Retrovirus-induced murine acquired immunodeficiency syndrome: natural history of infection and differing susceptibility of inbred mouse strains.

    PubMed Central

    Hartley, J W; Fredrickson, T N; Yetter, R A; Makino, M; Morse, H C

    1989-01-01

    C57BL mice (Fv-1b) develop a severe immunodeficiency disease following inoculation as adults with LP-BM5 murine leukemia virus (MuLV), a derivative of Duplan-Laterjet virus which contains B-tropic ecotropic and mink cell focus-inducing MuLVs and a putative defective genome which may be the proximal cause of disease. The stages of development of this disease were defined for C57BL mice on the basis of lymphadenopathy and splenomegaly; histopathological changes consistent with B-cell activation; and alterations in expression of cell surface antigens affected by proliferation of T cells, B cells, and macrophages. By using this disease profile as a standard, the response of adult mice of various inbred strains and selected F1 hybrids was compared. We show that although the strains which are highly sensitive are of the Fv-1b genotype (i.e., permissive for B-tropic MuLVs), certain Fv-1b strains, e.g., BALB/c and A/J, are resistant to murine acquired immunodeficiency syndrome, whereas certain Fv-1n strains (permissive for N-tropic MuLVs but restrictive for B-tropic MuLVs), notably P/N, BDP, and AKR, show moderate sensitivity and (C57BL/6 x CBA/N)F1 mice (Fv-1n/b and thus dually restrictive) are of relatively high susceptibility. The results of virus recovery tests suggest that apparently anomalous sensitivity, based on predicted Fv-1 restriction, may reflect MuLV induction and/or mutation to provide a helper virus for which the host is permissive. Images PMID:2536830

  11. Natural inhibitors of indoleamine 3,5-dioxygenase induced by interferon-gamma in human neural stem cells.

    PubMed

    Chen, S; Corteling, R; Stevanato, L; Sinden, J

    2012-12-01

    Indoleamine dioxygenase (IDO) is a heme- containing enzyme that catalyzes the oxidation of tryptophan to N-formylkynurenine, kynurenine and the downstream quinolinic acid. Though IDO is physiologically important in maintaining tissue integrity, aberrant IDO expression represses T cell function and promotes regulatory T cells (Treg) in cancer. It additionally exacerbates Alzheimer, depression, Huntington and Parkinson diseases via quinolinic acid. Inhibition of IDO has thus been recently proposed as a strategy for treating cancer and neuronal disorders. In the present study, we have developed a cell-based assay to evaluate the suppressive effect of anti-inflammatory phytochemicals on the enzyme. When stimulated by INF-γ, profound high expressions of IDO-1 mRNA as well as the protein were detected in human neural stem cells (hNSC) and verified by real-time retro-transcribed PCR and western blot analysis, respectively. The protein activity was measured by kynurenine concentration and the assay was validated by dose-responsive inhibition of IDO-1 antagonists including 1-methyltryptaphan, indomethacin and acetylsalicylic acid. Among the tested compounds, apigenin, baicalein, chrysin, and wogonin exhibit a potent repressive activity with IC(50s) comparable to that of indomethacin. The inhibition was further found to be independent of gene expression and protein translation because of the unaltered levels of mRNA and protein expression. Although curcumin displayed a potent inhibitory activity to the enzyme, it appeared to be cytotoxic to hNSCs. Morphological examination of hNSC revealed that baicalein and wogonin at the inhibitory concentrations induced neurite outgrowth. In conclusion, our data shows that certain phytochemicals with 2-phenyl-1-benzopyran-4-one backbone (flavones) attenuate significantly the IDO-1 protein activity without harming hNSCs. The inhibitory activity might have partially contributed to the anti-cancer and neuro-protective property of the

  12. Stress-induced hypermutation as a physical property of life, a force of natural selection and its role in four thought experiments

    NASA Astrophysics Data System (ADS)

    Hilbert, Lennart

    2013-04-01

    The independence of genetic mutation rate from selection is central to neo-Darwinian evolutionary theory. However, it has been continuously challenged for more than 30 years by experimental evidence of genetic mutation rate transiently increasing in response to stress (stress-induced hypermutation, SIH). The prominent concept of evolved evolvability (EE) explains that natural selection for strategies more competitive at evolutionary adaptation itself gives rise to mechanisms dynamically adjusting mutation rates to environmental stress. Here, we theoretically investigate the alternative (not mutually exclusive) hypothesis that SIH is an inherent physical property of all genetically reproducing life. We define stress as any condition lowering the capability of utilizing metabolic resources for genome storage and replication. This thermodynamical analysis indicates stress-induced increases in the genetic mutation rate in genome storage and in genome replication as inherent physical properties of genetically reproducing life. Further integrating SIH into an overall organismic thermodynamic budget identifies SIH as a force of natural selection, alongside death rate, replication rate and constitutive mutation rate differences. We execute four thought experiments with a non-recombinant lesion mutant strain to predict experimental observations due to SIH in response to different stresses and stress combinations. We find (1) acceleration of adaptation over models without SIH, (2) possibility of adaptation at high stresses which are not explicable by mutation in genome replication alone and (3) different adaptive potential under high growth-inhibiting versus high lethal stresses. The predictions are directly comparable to culture experiments (colony size time courses, antibacterial resistance assay and occurrence of lesion-reversion mutant colonies) and genome sequence analysis. Considering suggestions of drug-mediated disruption of SIH and attempts to target mutation

  13. Natural Antisense Transcript for Hyaluronan Synthase 2 (HAS2-AS1) Induces Transcription of HAS2 via Protein O-GlcNAcylation*

    PubMed Central

    Vigetti, Davide; Deleonibus, Sara; Moretto, Paola; Bowen, Timothy; Fischer, Jens W.; Grandoch, Maria; Oberhuber, Alexander; Love, Dona C.; Hanover, John A.; Cinquetti, Raffaella; Karousou, Eugenia; Viola, Manuela; D'Angelo, Maria Luisa; Hascall, Vincent C.; De Luca, Giancarlo; Passi, Alberto

    2014-01-01

    Changes in the microenvironment organization within vascular walls are critical events in the pathogenesis of vascular pathologies, including atherosclerosis and restenosis. Hyaluronan (HA) accumulation into artery walls supports vessel thickening and is involved in many cardiocirculatory diseases. Excessive cytosolic glucose can enter the hexosamine biosynthetic pathway, increase UDP-N-acetylglucosamine (UDP-GlcNAc) availability, and lead to modification of cytosolic proteins via O-linked attachment of the monosaccharide β-N-GlcNAc (O-GlcNAcylation) from UDP-GlcNAc by the enzyme O-GlcNAc transferase. As many cytoplasmic and nuclear proteins can be glycosylated by O-GlcNAc, we studied whether the expression of the HA synthases that synthesize HA could be controlled by O-GlcNAcylation in human aortic smooth muscle cells. Among the three HAS isoenzymes, only HAS2 mRNA increased after O-GlcNAcylation induced by glucosamine treatments or by inhibiting O-GlcNAc transferase with PUGNAC (O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate). We found that the natural antisense transcript of HAS2 (HAS2-AS1) was absolutely necessary to induce the transcription of the HAS2 gene. Moreover, we found that O-GlcNAcylation modulated HAS2-AS1 promoter activation by recruiting the NF-κB subunit p65, but not the HAS2 promoter, whereas HAS2-AS1 natural antisense transcript, working in cis, regulated HAS2 transcription by altering the chromatin structure around the HAS2 proximal promoter via O-GlcNAcylation and acetylation. These results indicate that HAS2 transcription can be finely regulated not only by recruiting transcription factors to the promoter as previously described but also by modulating chromatin accessibility by epigenetic modifications. PMID:25183006

  14. Natural dipeptidyl peptidase-IV inhibitor mangiferin mitigates diabetes- and metabolic syndrome-induced changes in experimental rats

    PubMed Central

    Suman, Rajesh Kumar; Mohanty, Ipseeta Ray; Maheshwari, Ujwala; Borde, Manjusha K; Deshmukh, YA

    2016-01-01

    Background Mangiferin (MNG) is known to possess antidiabetic and antioxidant activity. However, there is no experimental evidence presently available in the literature with regard to its ameliorating effects on diabetes mellitus coexisting with metabolic syndrome. Objective The present study was designed to evaluate the protective effects of MNG on various components of metabolic syndrome with diabetes as an essential component. Material and methods Adult Wistar rats were fed high-fat diets for 10 weeks and challenged with streptozotocin (40 mg/kg) at week three (high-fat diabetic control group). After the confirmation of metabolic syndrome in the setting of diabetes, MNG 40 mg/kg was orally fed to these rats from the fourth to tenth week. Results The treatment with MNG showed beneficial effects on various components of metabolic syndrome, such as reduced dyslipidemia (decreased triglyceride, total cholesterol, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol) and diabetes mellitus (reduced blood glucose and glycosylated hemoglobin). In addition, an increase in serum insulin, C-peptide, and homeostasis model assessment-β and a reduction in homeostasis model assessment of insulin resistance-IR were observed in MNG-treated group compared with high-fat diabetic control group. MNG was also found to be cardioprotective (reduction in creatine phosphokinase-MB levels, atherogenic index, high-sensitivity C-reactive protein). Reduction in serum dipeptidyl peptidase–IV levels in the MNG-treated group correlated with improvement in insulin resistance and enhanced β-cell function. Conclusion The present study has demonstrated antidiabetic, hypolipidemic, and cardioprotective effects of MNG in the setting of diabetes with metabolic syndrome. Thus, MNG has the potential to be developed as a natural alternative to synthetic dipeptidyl peptidase-IV inhibitors beneficial in this comorbid condition. PMID:27621658

  15. Natural dipeptidyl peptidase-IV inhibitor mangiferin mitigates diabetes- and metabolic syndrome-induced changes in experimental rats

    PubMed Central

    Suman, Rajesh Kumar; Mohanty, Ipseeta Ray; Maheshwari, Ujwala; Borde, Manjusha K; Deshmukh, YA

    2016-01-01

    Background Mangiferin (MNG) is known to possess antidiabetic and antioxidant activity. However, there is no experimental evidence presently available in the literature with regard to its ameliorating effects on diabetes mellitus coexisting with metabolic syndrome. Objective The present study was designed to evaluate the protective effects of MNG on various components of metabolic syndrome with diabetes as an essential component. Material and methods Adult Wistar rats were fed high-fat diets for 10 weeks and challenged with streptozotocin (40 mg/kg) at week three (high-fat diabetic control group). After the confirmation of metabolic syndrome in the setting of diabetes, MNG 40 mg/kg was orally fed to these rats from the fourth to tenth week. Results The treatment with MNG showed beneficial effects on various components of metabolic syndrome, such as reduced dyslipidemia (decreased triglyceride, total cholesterol, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol) and diabetes mellitus (reduced blood glucose and glycosylated hemoglobin). In addition, an increase in serum insulin, C-peptide, and homeostasis model assessment-β and a reduction in homeostasis model assessment of insulin resistance-IR were observed in MNG-treated group compared with high-fat diabetic control group. MNG was also found to be cardioprotective (reduction in creatine phosphokinase-MB levels, atherogenic index, high-sensitivity C-reactive protein). Reduction in serum dipeptidyl peptidase–IV levels in the MNG-treated group correlated with improvement in insulin resistance and enhanced β-cell function. Conclusion The present study has demonstrated antidiabetic, hypolipidemic, and cardioprotective effects of MNG in the setting of diabetes with metabolic syndrome. Thus, MNG has the potential to be developed as a natural alternative to synthetic dipeptidyl peptidase-IV inhibitors beneficial in this comorbid condition.

  16. A Nucleotide-Analogue-Induced Gain of Function Corrects the Error-Prone Nature of Human DNA Polymerase iota

    SciTech Connect

    Ketkar, Amit; Zafar, Maroof K.; Banerjee, Surajit; Marquez, Victor E.; Egli, Martin; Eoff, Robert L.

    2012-10-25

    Y-family DNA polymerases participate in replication stress and DNA damage tolerance mechanisms. The properties that allow these enzymes to copy past bulky adducts or distorted template DNA can result in a greater propensity for them to make mistakes. Of the four human Y-family members, human DNA polymerase iota (hpol{iota}) is the most error-prone. In the current study, we elucidate the molecular basis for improving the fidelity of hpol{iota} through use of the fixed-conformation nucleotide North-methanocarba-2{prime}-deoxyadenosine triphosphate (N-MC-dATP). Three crystal structures were solved of hpol{iota} in complex with DNA containing a template 2{prime}-deoxythymidine (dT) paired with an incoming dNTP or modified nucleotide triphosphate. The ternary complex of hpol{iota} inserting N-MC-dATP opposite dT reveals that the adenine ring is stabilized in the anti orientation about the pseudo-glycosyl torsion angle, which mimics precisely the mutagenic arrangement of dGTP:dT normally preferred by hpol{iota}. The stabilized anti conformation occurs without notable contacts from the protein but likely results from constraints imposed by the bicyclo[3.1.0]hexane scaffold of the modified nucleotide. Unmodified dATP and South-MC-dATP each adopt syn glycosyl orientations to form Hoogsteen base pairs with dT. The Hoogsteen orientation exhibits weaker base-stacking interactions and is less catalytically favorable than anti N-MC-dATP. Thus, N-MC-dATP corrects the error-prone nature of hpol{iota} by preventing the Hoogsteen base-pairing mode normally observed for hpol{iota}-catalyzed insertion of dATP opposite dT. These results provide a previously unrecognized means of altering the efficiency and the fidelity of a human translesion DNA polymerase.

  17. Cloning and characterization of IL-22 binding protein, a natural antagonist of IL-10-related T cell-derived inducible factor/IL-22.

    PubMed

    Dumoutier, L; Lejeune, D; Colau, D; Renauld, J C

    2001-06-15

    The class II cytokine receptor family includes the receptors for IFN-alphabeta, IFN-gamma, IL-10, and IL-10-related T cell-derived inducible factor/IL-22. By screening genomic DNA databases, we identified a gene encoding a protein of 231 aa, showing 33 and 34% amino acid identity with the extracellular domains of the IL-22 receptor and of the IL-20R/cytokine receptor family 2-8, respectively, but lacking the transmembrane and cytoplasmic domains. A lower but significant sequence identity was found with other members of this family such as the IL-10R (29%), cytokine receptor family 2-4/IL-10Rbeta (30%), tissue factor (26%), and the four IFN receptor chains (23-25%). This gene is located on chromosome 6q24, at 35 kb from the IFNGR1 gene, and is expressed in various tissues with maximal expression in breast, lungs, and colon. The recombinant protein was found to bind IL-10-related T cell-derived inducible factor/IL-22, and to inhibit the activity of this cytokine on hepatocytes and intestinal epithelial cells. We propose to name this natural cytokine antagonist IL-22BP for IL-22 binding protein.

  18. Conditioned tolerance to drug-induced (poly I:C) natural killer cell activation: effects of drug-dosage and context-specificity parameters.

    PubMed

    Dyck, D G; Driedger, S M; Nemeth, R; Osachuk, T A; Greenberg, A H

    1987-09-01

    Three experiments were conducted to evaluate the role of drug-dosage and stimulus-specificity parameters on the tolerance of drug-induced (poly I:C) natural killer (NK) cell activity. In the first experiment a protocol which provided mice with four weekly 20 micrograms/mouse ip injections of the immunostimulatory synthetic polynucleotide (poly I:C) following exposure to either a simple odor cue or a complex cue resulted in tolerance of NK cell activity. The identical protocol with a higher drug dose (50 micrograms/mouse) did not produce tolerance. In a second experiment, the stimulus specificity of tolerance was assessed by giving two groups of mice repeated signaled drug injections. For one of these groups the final poly I:C injection of the series was signaled, while for the other group it was not. Although both groups were tolerant relative to controls not previously exposed to the drug, indirect evidence of conditioning was obtained. Specifically, it was found that tolerance among mice receiving the signal on the test was such that they were not different from undrugged controls, while uncued mice had significantly higher levels of NK cell activity. The third experiment evaluated the role of stimulus specificity within an extinction paradigm. It was found that tolerance was reversed in mice provided with repeated nonreinforced reexposure to drug-signaling cues, while mice exposed to novel cues remained tolerant. These results further support the hypothesis that associative factors contribute to the tolerance of a drug-induced immune response.

  19. Dam-induced and natural channel changes in the Saskatchewan River below the E.B. Campbell Dam, Canada

    NASA Astrophysics Data System (ADS)

    Smith, Norman D.; Morozova, Galina S.; Pérez-Arlucea, Marta; Gibling, Martin R.

    2016-09-01

    portions of the avulsion belt, including the Mossy delta, but little bedload is returned to the parent channel. Dam-induced sediment starvation is speeding the rate at which a single dominant channel is evolving between the avulsion site and rejoined parent, a process that will likely shift the patterns of flood inundation in the future.

  20. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection.

    PubMed

    Ye, Lin; Wang, Jiaming; Beyer, Ashley I; Teque, Fernando; Cradick, Thomas J; Qi, Zhongxia; Chang, Judy C; Bao, Gang; Muench, Marcus O; Yu, Jingwei; Levy, Jay A; Kan, Yuet Wai

    2014-07-01

    Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp deletions (CCR5Δ32) are resistant to HIV-1 infection. In this study, we generated induced pluripotent stem cells (iPSCs) homozygous for the naturally occurring CCR5Δ32 mutation through genome editing of wild-type iPSCs using a combination of transcription activator-like effector nucleases (TALENs) or RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 together with the piggyBac technology. Remarkably, TALENs or CRISPR-Cas9-mediated double-strand DNA breaks resulted in up to 100% targeting of the colonies on one allele of which biallelic targeting occurred at an average of 14% with TALENs and 33% with CRISPR. Excision of the piggyBac using transposase seamlessly reproduced exactly the naturally occurring CCR5Δ32 mutation without detectable exogenous sequences. We differentiated these modified iPSCs into monocytes/macrophages and demonstrated their resistance to HIV-1 challenge. We propose that this strategy may provide an approach toward a functional cure of HIV-1 infection.

  1. Strain-Specific Variation in Murine Natural Killer Gene Complex Contributes to Differences in Immunosurveillance for Urethane-Induced Lung Cancer

    PubMed Central

    Kreisel, Daniel; Gelman, Andrew E.; Higashikubo, Ryuji; Lin, Xue; Vikis, Haris G.; White, J. Michael; Toth, Kelsey A.; Deshpande, Charuhas; Carreno, Beatriz M.; You, Ming; Taffner, Samantha M.; Yokoyama, Wayne M.; Bui, Jack D.; Schreiber, Robert D.; Krupnick, Alexander S.

    2012-01-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and results from a complex interaction between carcinogen exposure and inherent susceptibility. Despite its prevalence genetic factors that predispose to the development of lung cancer remain elusive. Inbred mouse models offer a unique and clinically relevant tool to study genetic factors that contribute to lung carcinogenesis due to the development of tumors that resemble human adenocarcinoma and broad strain-specific variation in cancer incidence after carcinogen administration. Here we set out to investigate whether strain-specific variability in tumor immunosurveillance contributes to differences in lung cancer. Using bone marrow transplantation we determined that hematopoietic cells from lung cancer-resistant mice could significantly impede the development of cancer in a susceptible strain. Furthermore, we show that this is not due to differences in tumor-promoting inflammatory changes or variability in immunosurveillance by the adaptive immune system, but results from strain-specific differences in natural killer cell (NK) cytotoxicity. Using a newly discovered congenic strain of mice we demonstrate a previously unrecognized role for strain-specific polymorphisms in the natural killer gene complex (NKC) in immunosurveillance for carcinogen-induced lung cancer. Since polymorphisms in the NKC are highly prevalent in man, our data may explain why certain individuals without obvious risk factors develop lung cancer while others remain resistant to the disease despite heavy environmental carcinogen exposure. PMID:22751136

  2. Role of protein kinase C in the TBT-induced inhibition of lytic function and MAPK activation in human natural killer cells

    PubMed Central

    Abraha, Abraham B.; Rana, Krupa; Whalen, Margaret M.

    2010-01-01

    Human natural killer (NK) cells are lymphocytes that destroy tumor and virally infected cells. Previous studies have shown that exposures of NK cells to tributyltin (TBT) greatly diminish their ability to destroy tumor cells (lytic function) while activating mitogen-activated protein kinases (MAPK) (p44/42, p38, and JNK) in the NK cells. The signaling pathway that regulates NK lytic function appears to include activation of protein kinase C (PKC) as well as MAPK activity. The TBT-induced activation of MAPKs would trigger a portion of the NK lytic signaling pathway, which would then leave the NK cell unable to trigger this pathway in response to a subsequent encounter with a target cell. In the present study we evaluated the involvement of PKC in the inhibition of NK lysis of tumor cells and activation of MAPKs caused by TBT exposures. TBT caused a 2–3 fold activation of PKC at concentrations ranging from 50–300 nM (16–98 ng/mL), indicating that activation of PKC occurs in response to TBT exposures. This would then leave the NK cell unable to respond to targets. Treatment with the PKC inhibitor, bisindolylmaleimide I, caused an 85% decrease in the ability of NK cells to lyse tumor cells validating the involvement of PKC in the lytic signaling pathway. The role of PKC in the activation of MAPKs by TBT was also investigated using bisindolylmaleimide I. The results indicated that in NK cells where PKC activation was blocked there was no activation of the MAPK, p44/42 in response to TBT. However, TBT-induced activation of the MAPKs, p38 and JNK did not require PKC activation. These results indicate the pivotal role of PKC in the TBT-induced loss of NK lytic function including the activation of p44/42 by TBT in NK cells. PMID:20390410

  3. Fractalkine (CX3CL1)- and interleukin-2-enriched neuroblastoma microenvironment induces eradication of metastases mediated by T cells and natural killer cells.

    PubMed

    Zeng, Yan; Huebener, Nicole; Fest, Stefan; Weixler, Silke; Schroeder, Ulrike; Gaedicke, Gerhard; Xiang, Rong; Schramm, Alexander; Eggert, Angelika; Reisfeld, Ralph A; Lode, Holger N

    2007-03-01

    Fractalkine (FKN) is a unique CX3C chemokine (CX3CL1) known to induce both adhesion and migration of leukocytes mediated by a membrane-bound and a soluble form, respectively. Its function is mediated through CX3C receptor (CX3CR), which is expressed by T(H)1 immune cells including T cells and natural killer (NK) cells. FKN was shown to be expressed in >90% of 68 neuroblastoma samples as determined by cDNA microarray analysis. Here, we characterized the effect of FKN in the neuroblastoma microenvironment using a syngeneic model genetically engineered to secrete FKN. We show FKN-mediated migration, adhesion, and IFN-gamma secretion of immune effector cells, but limited antineuroblastoma activity, in vitro and in vivo. Therefore, we tested the hypothesis that a combined increase of FKN and interleukin-2 (IL-2) in the neuroblastoma microenvironment induces an effective antitumor immune response. For this purpose, IL-2 was targeted to ganglioside GD2, which is highly expressed on neuroblastoma tissue, using an anti-GD2 antibody IL-2 immunocytokine (ch14.18-IL-2). Only mice bearing FKN- and IL-2-enriched neuroblastoma tumors exhibited a reduction in primary tumor growth and a complete eradication of experimental liver metastases. The depletion of T cells and NK cells in vivo abrogated the effect, and these effector cells showed the highest cytolytic activity in vitro. Finally, only the FKN- and IL-2-enriched neuroblastoma microenvironment resulted in T-cell activation and the release of proinflammatory cytokines. In summary, we showed for the first time the immunologic mechanisms by which targeted IL-2 treatment of neuroblastoma with an FKN-rich microenvironment induces an effective antitumor response.

  4. A novel synthetic derivative of the natural product berbamine inhibits cell viability and induces apoptosis of human osteosarcoma cells, associated with activation of JNK/AP-1 signaling.

    PubMed

    Yang, Fan; Nam, Sangkil; Zhao, Robin; Tian, Yan; Liu, Lucy; Horne, David A; Jove, Richard

    2013-11-01

    Osteosarcoma is the most common primary bone tumor in children and adolescents. There is a critical need to find more potent drugs for patients with metastatic or recurrent disease. Berbamine (BBM) is a natural compound derived from the Berberis amurensis plants. BBM and its derivatives have been shown to have antitumor effects in several cancers. Here, we report that a novel synthetic berbamine derivative, BBMD3, inhibits cell viability and induces apoptosis of G292, KHOS, and MG-63 human osteosarcoma cells. Induction of apoptosis in these tumor cells depends on activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP). Since pan-caspase inhibitor (Z-VAD-FMK) and caspase-9 inhibitor (Z-LEHD-FMK) could block the cleavage of PARP, the apoptosis induced by BBMD3 is through intrinsic signaling pathway. BBMD3 increased phosphorylation of c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK), resulting in increase of phosphorylated c-Jun and total c-Fos, the major components of transcriptional factor AP-1. JNK inhibitor could partially suppress antitumor effect of BBMD3 on osteosarcoma cells. BBMD3 increased the production of reactive oxygen species (ROS) and ROS scavenger, N-acetylcysteine (NAC), could block the phosphorylation of JNK and c-Jun induced by BBMD3. BBMD3 increased the expression of the pro-apototic gene Bad, associated with apoptosis induction. Finally, BBMD3 also decreased the expression of cyclin D1 and D2, the positive cell cycle regulators, which is correlated with growth inhibition in osteosarcoma cells. Collectively, these findings indicate that BBMD3 is a potentially promising drug for the treatment of human osteosarcoma.

  5. Detection of natural and stress-induced variability in reflectance spectra of apple trees using hyperspectral analysis

    NASA Astrophysics Data System (ADS)

    Delalieux, Stephanie; Keulemans, Wannes; van Aardt, Jan; Schrevens, Eddie; Coppin, Pol

    2005-10-01

    Early detection of biotic and abiotic stresses and subsequent steering of agricultural systems using hyperspectral sensors potentially could contribute to the pro-active treatment of production-limiting factors. Venturia inaequalis (apple scab) is an important biotic factor that can reduce yield in apple orchards. Previous hyperspectral research focused on (i) determining if Venturia inaequalis leaf infections could be differentiated from healthy leaves and (ii) investigating at which developmental stage Venturia inaequalis infection could be detected. Logistical regression and partial least squares discriminant analysis were used to select the hyperspectral bands that best define differences among treatments. It was clear that hyperspectral data provide the contiguous, high spectral resolution data that are needed to detect subtle changes in reflectance values between healthy and stressed vegetation. The research was extended to include tree-based modeling as an alternative classification method. Results suggested that good predictability could be achieved when classifying infected plants based on this supervised classification technique. It was concluded that the spectral domain around 1600 nm was best suited to discriminate between infected and non-infected leaves immediately after infection, while the visible spectral region became more important at a well-developed infection stage. Research was focused on young leaves, because of the decreased incidence of infection in older leaves, the so-called 'ontogenic resistance'. Additional research was performed to gain a better understanding of the processes occurring during the first days after leaf unfolding and to evaluate the natural spectral variability among leaves. An undisturbed 20-day growth profile was examined to assess variations in the reflectance spectra due to physiological changes at the different growth stages of the leaves. Results suggested that an accurate distinction could be made between

  6. Sunlight induced chlorophyll fluorescence in the near-infrared spectral region in natural waters: Interpretation of the narrow reflectance peak around 761 nm

    NASA Astrophysics Data System (ADS)

    Lu, Yingcheng; Li, Linhai; Hu, Chuanmin; Li, Lin; Zhang, Minwei; Sun, Shaojie; Lv, Chunguang

    2016-07-01

    Sunlight induced chlorophyll a fluorescence (SICF) can be used as a probe to estimate chlorophyll a concentrations (Chl) and infer phytoplankton physiology. SICF at ˜685 nm has been widely applied to studies of natural waters. SICF around 740 nm has been demonstrated to cause a narrow reflectance peak at ˜761 nm in the reflectance spectra of terrestrial vegetation. This narrow peak has also been observed in the reflectance spectra of natural waters, but its mechanism and applications have not yet been investigated and it has often been treated as measurement artifacts. In this study, we aimed to interpret this reflectance peak at ˜761 nm and discuss its potential applications for remote monitoring of natural waters. A derivative analysis of the spectral reflectance suggests that the 761 nm peak is due to SICF. It was also found that the fluorescence line height (FLH) at 761 nm significantly and linearly correlates with Chl. FLH(761 nm) showed a tighter relationship with Chl than the relationship between FLH(˜685 nm) and Chl mainly due to weaker perturbations by nonalgal materials around 761 nm. While it is not conclusive, a combination of FLH(761 nm) and FLH(˜685 nm) might have some potentials to discriminate cyanobacteria from other phytoplankton due to their different fluorescence responses at the two wavelengths. It was further found that reflectance spectra with a 5 nm spectral resolution are adequate to capture the spectral SICF feature at ˜761 nm. These preliminary results suggest that FLH(761 nm) need to be explored more for future applications in optically complex coastal and inland waters.

  7. Hepatotoxicity and endothelial dysfunction induced by high choline diet and the protective effects of phloretin in mice.

    PubMed

    Ren, Daoyuan; Liu, Yafei; Zhao, Yan; Yang, Xingbin

    2016-08-01

    The involvement of choline and its metabolite trimethylamine-N-oxide (TMAO) in endothelial dysfunction and atherosclerosis has been repeatedly confirmed. Phloretin, a dihydrochalcone flavonoid usually present in apples, possesses a variety of biological activities including vascular nutrition. This study was designed to investigate whether phloretin could alleviate or prevent high choline-induced vascular endothelial dysfunction and liver injury in mice. Mice were provided with 3% high choline water and given phloretin orally daily for 10 weeks. The high choline-treated mice showed the significant dyslipidemia and hyperglycemia with the impaired liver and vascular endothelium (p < 0.01). Administration of phloretin at 200 and 400 mg/kg bw significantly reduced the choline-induced elevation of serum TC, TG, LDL-C, AST, ALT, ET-1 and TXA2 (p < 0.01), and markedly antagonized the choline-induced decrease of serum PGI2, HDL-C and NO levels. Furthermore, phloretin elevated hepatic SOD and GSH-Px activities and decreased hepatic MDA levels of the mice exposed to high choline water. Moreover, histopathological test with the H&E and Oil Red O staining of liver sections confirmed the high choline diet-caused liver steatosis and the hepatoprotective effect of phloretin. These findings suggest that high choline causes oxidative damage, and phloretin alleviate vascular endothelial dysfunction and liver injury. PMID:27316781

  8. Aspalathin and Nothofagin from Rooibos (Aspalathus linearis) inhibits high glucose-induced inflammation in vitro and in vivo.

    PubMed

    Ku, Sae-Kwang; Kwak, Soyoung; Kim, Yaesol; Bae, Jong-Sup

    2015-02-01

    Vascular inflammation plays a key role in the initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Aspalathin (Asp) and nothofagin (Not) are two major active dihydrochalcones found in green rooibos, which have been reported for their antioxidant activity. In this study, we assessed whether Asp or Not can suppress vascular inflammation induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. We monitored the effects of Asp or Not on HG-induced vascular hyperpermeability, expression of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS), and activation of nuclear factor (NF)-κB in vitro and in vivo. Our data indicate that HG markedly increased vascular permeability, monocyte adhesion, expression of CAMs, formation of ROS, and activation of NF-κB. Remarkably, treatment of Asp or Not inhibited HG-mediated vascular hyperpermeability, adhesion of monocytes toward HUVECs, and expression of CAMs. In addition, Asp or Not suppressed the formation of ROS and the activation of NF-κB. Since vascular inflammation induced by HG is critical in the development of diabetic complications, our results suggest that Asp or Not may have significant benefits in the treatment of diabetic complications.

  9. Protective effects of a new phloretin derivative against UVB-induced damage in skin cell model and human volunteers.

    PubMed

    Shin, Seoungwoo; Kum, Hyunwoo; Ryu, Dehun; Kim, Minkyung; Jung, Eunsun; Park, Deokhoon

    2014-01-01

    The phenolic compound phloretin is a prominent member of the chemical class of dihydrochalcones. Phloretin is specifically found in apple and apple juice and known for its biological properties. We were particularly interested in its potential dermo-cosmetic applications. However, practical limitations of phloretin do exist due to its poor water-solubility. Phloretin was sulfonated with sulfuric acid (98%, wt) and mixed with saturated salt water to produce phloretin 3',3-disulfonate in order to increase its water-solubility. Here we reported the photoprotective effect of phloretin 3',3-disulfonate (PS), a new semi-synthetic derivative of phloretin. Results showed that PS attenuated cyclobutane pyrimidine dimer (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by ultraviolet B (UVB). The photoprotective effect of PS is tightly correlated to the enhancement of nucleotide excision repair (NER) gene expression. Furthemore, PS had inhibitory effects on UVB-induced release of the inflammatory mediators, such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of PS on human skin. Overall, the results demonstrated significant benefits of PS on the protection of keratinocytes against UVB-induced injuries and suggested its potential use in skin photoprotection. PMID:25334063

  10. Changes in host-mycorrhiza relationships revealed by stable isotopes after naturally-induced thinning of the stand: case study on Tuber aestivum.

    NASA Astrophysics Data System (ADS)

    Gavrichkova, Olga; Lauteri, Marco; Ciolfi, Marco; Chiocchini, Francesca; Paris, Pierluigi; Pisanelli, Andrea; Portarena, Silvia; Brugnoli, Enrico

    2016-04-01

    Terrestrial plants overcome nutrients and water limitations by forming mutualistic associations with mycorrhizal fungi. Fungi, in return, take advantage from the carbohydrates supplied by the host. Some mycorrhizal fruit bodies, like that of Tuber spp., have a peculiar gastronomic value with many efforts being undertaken to predict and enhance their productivity. However, many issues of truffle-producing mycorrhizal ecology are still poorly understood, in particular optimal conditions favoring fruit formation, potential host plants and host-mycorrhiza relationships. In this study, we tested the applicability of stable isotope measurements under natural abundance to identify the plants which likely host the mycorrhiza of Tuber aestivum and to characterize host-mycorrhizal nutrient, water and carbohydrate exchange under plant natural growing conditions and with the change of the forest cover after naturally occurred thinning. For these purposes, sampling of the fruit bodies of T. aestivum was performed during the growing season 2011 in a mixed broadleaved-coniferous forest in central Italy (initially the site was a manmade pine plantation). Nine truffle-producing parcels were identified with five being composed of the original Pinus pinaster -dominated vegetation and four in which pine was replaced by broadleaf species after both wind-induced thinning and natural dieback of pine trees. Seasonal variation of δ13C, δ15N and δ18O were analyzed in the fungal material, in the surrounding soil and in the plant material of the potential host species (xylem water in the trunk, branches and leaves, recently assimilated carbohydrates in phloem and leaves). The results showed a possibility of the identification of the mycorrhizal host species applying isotope analyses, with mycorrhiza receiving most part of the carbohydrates from the pine in pine-dominated parcels. Interestingly, in thinned parcels, the truffle bodies maintained isotope composition similar to bodies gathered

  11. Activation of p44/42 MAPK Plays a Role in the TBT-induced Loss of Human Natural Killer (NK) Cell Function

    PubMed Central

    Dudimah, Fred D.; Griffey, Denisha; Wang, Xiaofei; Whalen, Margaret M.

    2009-01-01

    Natural Killer (NK) cells destroy (lyse) tumor cells, virally infected cells and antibody-coated cells. Previous studies indicated that exposure to the environmental contaminant tributyltin (TBT) decreases the lytic function of NK cells and activates mitogen activated protein kinases (MAPK), including p44/42 (Aluoch and Whalen, 2005). If activation of p44/42 is required for TBT-induced decreases of lytic function, then activation of p44/42 to similar extents by pharmacological agents such as Phorbol 12-myristate 13-acetate (PMA) should mimic to some extent changes induced in NK cells with TBT exposures. NK cells were exposed to PMA concentrations between 0.25 and 10 nM for 10 min, 1 h, and 6 h before determining the lytic function (51Cr release assay) and phosphorylation state of MAPKs (Western blot). A 1 h exposure of NK cells to 5 nM PMA resulted in a loss of lytic function of 47%. Western blot analysis showed that a 1 h exposure to 5 nM PMA caused a 6 fold increase in phospho-p44/42 levels. Previous studies showed a 5 fold increase in phospho-p44/42 in response to a 1 h exposure to 300 nM TBT. Exposure to 300 nM TBT caused about a 40% decrease in lytic function. This study supports the hypothesis that p44/42 activation (as seen with TBT exposures) can cause a loss of NK-cell lytic function. PMID:20213532

  12. Qualitative analysis of mouse specific-locus mutations: information on genetic organization, gene expression, and the chromosomal nature of induced lesions

    SciTech Connect

    Russell, L.B.

    1982-01-01

    Analysis of mouse specific-locus (SL) mutations at three loci has identified over 33 distinct complementation groups - most of which are probably overlapping deficiencies - and 13 to 14 new functional units. The complementation maps that have been generated for the d-se and c regions include numerous vital functions; however, some of the genes in these regions are non-vital. At such loci, hypomorphic mutants must represent intragenic alterations, and some viable nulls could conceivably be intragenic lesions also. Analysis of SL mutations has provided information on genetic expression. Homozygous deficiencies can be completely viable or can kill at any one of a range of developmental stages. Heterozygonus deficiencies of up to 6 cM or more in genetic length have been recovered and propagated. The time of death of homozygous and the degree of inviability of heterozygous deficiencies are related more to specific content of the missing segment than to its length. Combinations of deficiencies with x-autosome translocations that inactivate the homologous region in a mosaic fashion have shown that organismic lethals are not necessarily cell lethal. The spectrum of mutations induced depends on the nature of the mutagen and the type of germ cell exposed. Radiation of spermatogonia produces intragenic as well as null mutations. Spontaneous mutations have an admixture of types not present in populations of mutations induced in germ cells, and this raises doubts concerning the accuracy of doubling-dose calculations in genetic risk estimation. The analysis of SL mutations has yielded genetic tools for the construction of detailed gene-dosage series, cis-trans comparisons, the mapping of known genes and identification of new genes, genetic rescue of various types, and the identification and isolation of DNA sequences. (ERB)

  13. Protective Vaccination against Papillomavirus-Induced Skin Tumors under Immunocompetent and Immunosuppressive Conditions: A Preclinical Study Using a Natural Outbred Animal Model

    PubMed Central

    Vinzón, Sabrina E.; Braspenning-Wesch, Ilona; Müller, Martin; Geissler, Edward K.; Nindl, Ingo; Gröne, Hermann-Josef

    2014-01-01

    Certain cutaneous human papillomaviruses (HPVs), which are ubiquitous and acquired early during childhood, can cause a variety of skin tumors and are likely involved in the development of non-melanoma skin cancer, especially in immunosuppressed patients. Hence, the burden of these clinical manifestations demands for a prophylactic approach. To evaluate whether protective efficacy of a vaccine is potentially translatable to patients, we used the rodent Mastomys coucha that is naturally infected with Mastomys natalensis papillomavirus (MnPV). This skin type papillomavirus induces not only benign skin tumours, such as papillomas and keratoacanthomas, but also squamous cell carcinomas, thereby allowing a straightforward read-out for successful vaccination in a small immunocompetent laboratory animal. Here, we examined the efficacy of a virus-like particle (VLP)-based vaccine on either previously or newly established infections. VLPs raise a strong and long-lasting neutralizing antibody response that confers protection even under systemic long-term cyclosporine A treatment. Remarkably, the vaccine completely prevents the appearance of benign as well as malignant skin tumors. Protection involves the maintenance of a low viral load in the skin by an antibody-dependent prevention of virus spread. Our results provide first evidence that VLPs elicit an effective immune response in the skin under immunocompetent and immunosuppressed conditions in an outbred animal model, irrespective of the infection status at the time of vaccination. These findings provide the basis for the clinical development of potent vaccination strategies against cutaneous HPV infections and HPV-induced tumors, especially in patients awaiting organ transplantation. PMID:24586150

  14. Juglanthraquinone C, a novel natural compound derived from Juglans mandshurica Maxim, induces S phase arrest and apoptosis in HepG2 cells.

    PubMed

    Yao, Yao; Zhang, Yu-Wei; Sun, Lu-Guo; Liu, Biao; Bao, Yong-Li; Lin, Hua; Zhang, Yu; Zheng, Li-Hua; Sun, Ying; Yu, Chun-Lei; Wu, Yin; Wang, Guan-Nan; Li, Yu-Xin

    2012-08-01

    Juglanthraquinone C (1,5-dihydroxy-9,10-anthraquinone-3-carboxylic acid, JC), a naturally occurring anthraquinone isolated from the stem bark of Juglans mandshurica, shows strong cytotoxicity in various human cancer cells in vitro. Here, we first performed a structure-activity relationship study of six anthraquinone compounds (JC, rhein, emodin, aloe-emodin, physcion and chrysophanol) to exploit the relationship between their structural features and activity. The results showed that JC exhibited the strongest cytotoxicity of all compounds evaluated. Next, we used JC to treat several human cancer cell lines and found that JC showed an inhibitory effect on cell viability in dose-dependent (2.5-10 μg/ml JC) and time-dependent (24-48 h) manners. Importantly, the inhibitory effect of JC on HepG2 (human hepatocellular carcinoma) cells was more significant as shown by an IC(50) value of 9 ± 1.4 μg/ml, and 36 ± 1.2 μg/ml in L02 (human normal liver) cells. Further study suggested that JC-induced inhibition HepG2 cell proliferation was associated with S phase arrest, decreased protein expression of proliferation marker Ki67, cyclin A and cyclin-dependent kinase (CDK) 2, and increased expression of cyclin E and CDK inhibitory protein Cip1/p21. In addition, JC significantly triggered apoptosis in HepG2 cells, which was characterized by increased chromatin condensation and DNA fragmentation, activation of caspase-9 and -3, and induction of a higher Bax/Bcl2 ratio. Collectively, our study demonstrated that JC can efficiently inhibit proliferation and induce apoptosis in HepG2 cells.

  15. CXCL10-induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo.

    PubMed

    Wennerberg, Erik; Kremer, Veronika; Childs, Richard; Lundqvist, Andreas

    2015-02-01

    Adoptive infusion of natural killer (NK) cells is being increasingly explored as a therapy in patients with cancer, although clinical responses are thus far limited to patients with hematological malignancies. Inadequate homing of infused NK cells to the tumor site represents a key factor that may explain the poor anti-tumor effect of NK cell therapy against solid tumors. One of the major players in the regulation of lymphocyte chemotaxis is the chemokine receptor chemokine (C-X-C motif) receptor 3 (CXCR3) which is expressed on activated NK cells and induces NK cell migration toward gradients of the chemokine (C-X-C motif) ligand (CXCL9, 10 and 11). Here, we show that ex vivo expansion of human NK cells results in a tenfold increased expression of the CXCR3 receptor compared with resting NK cells (p = 0.04). Consequently, these NK cells displayed an improved migratory capacity toward solid tumors, which was dependent on tumor-derived CXCL10. In xenograft models, adoptively transferred NK cells showed increased migration toward CXCL10-transfected melanoma tumors compared with CXCL10-negative wild-type tumors, resulting in significantly reduced tumor burden and increased survival (median survival 41 vs. 32 days, p = 0.03). Furthermore, administration of interferon-gamma locally in the tumor stimulated the production of CXCL10 in subcutaneous melanoma tumors resulting in increased infiltration of adoptively transferred CXCR3-positive expanded NK cells. Our findings demonstrate the importance of CXCL10-induced chemoattraction in the anti-tumor response of adoptively transferred expanded NK cells against solid melanoma tumors.

  16. Space Environment (Natural and Induced)

    NASA Technical Reports Server (NTRS)

    Kim, Myung-Hee Y.; George, Kerry A.; Cucinotta, Francis A.

    2007-01-01

    Considerable effort and improvement have been made in the study of ionizing radiation exposure occurring in various regions of space. Satellites and spacecrafts equipped with innovative instruments are continually refining particle data and providing more accurate information on the ionizing radiation environment. The major problem in accurate spectral definition of ionizing radiation appears to be the detailed energy spectra, especially at high energies, which is important parameter for accurate radiation risk assessment. Magnitude of risks posed by exposure to radiation in future space missions is subject to the accuracies of predictive forecast of event size of SPE, GCR environment, geomagnetic fields, and atmospheric radiation environment. Although heavy ion fragmentations and interactions are adequately resolved through laboratory study and model development, improvements in fragmentation cross sections for the light nuclei produced from HZE nuclei and their laboratory validation are still required to achieve the principal goal of planetary GCR simulation at a critical exposure site. More accurate prediction procedure for ionizing radiation environment can be made with a better understanding of the solar and space physics, fulfillment of required measurements for nuclear/atomic processes, and their validation and verification with spaceflights and heavy ion accelerators experiments. It is certainly true that the continued advancements in solar and space physics combining with physical measurements will strengthen the confidence of future manned exploration of solar system. Advancements in radiobiology will surely give the meaningful radiation hazard assessments for short and long term effects, by which appropriate and effective mitigation measures can be placed to ensure that humans safely live and work in the space, anywhere, anytime.

  17. Pollen Morphology and Boron Concentration in Floral Tissues as Factors Triggering Natural and GA-Induced Parthenocarpic Fruit Development in Grapevine.

    PubMed

    Alva, Orlando; Roa-Roco, Rosa Nair; Pérez-Díaz, Ricardo; Yáñez, Mónica; Tapia, Jaime; Moreno, Yerko; Ruiz-Lara, Simón; González, Enrique

    2015-01-01

    Parthenocarpic fruit development (PFD) reduces fruit yield and quality in grapevine. Parthenocarpic seedless berries arise from fruit set without effective fertilization due to defective pollen germination. PFD has been associated to micronutrient deficiency but the relation of this phenomenon with pollen polymorphism has not been reported before. In this work, six grapevine cultivars with different tendency for PFD and grown under micronutrient-sufficient conditions were analyzed to determine pollen structure and germination capability as well as PFD rates. Wide variation in non-germinative abnormal pollen was detected either among cultivars as well as for the same cultivar in different growing seasons. A straight correlation with PFD rates was found (R2 = 0.9896), suggesting that natural parthenocarpy is related to defective pollen development. Such relation was not observed when PFD was analyzed in grapevine plants exposed to exogenous gibberellin (GA) or abscissic acid (ABA) applications at pre-anthesis. Increase (GA treatment) or reduction (ABA treatment) in PFD rates without significative changes in abnormal pollen was determined. Although these plants were maintained at sufficient boron (B) condition, a down-regulation of the floral genes VvBOR3 and VvBOR4 together with a reduction of floral B content in GA-treated plants was established. These results suggest that impairment in B mobility to reproductive tissues and restriction of pollen tube growth could be involved in the GA-induced parthenocarpy.

  18. A Natural Bacterial-Derived Product, the Metalloprotease Arazyme, Inhibits Metastatic Murine Melanoma by Inducing MMP-8 Cross-Reactive Antibodies

    PubMed Central

    Pereira, Felipe V.; Ferreira-Guimarães, Carla A.; Paschoalin, Thaysa; Scutti, Jorge A. B.; Melo, Filipe M.; Silva, Luis S.; Melo, Amanda C. L.; Silva, Priscila; Tiago, Manoela; Matsuo, Alisson L.; Juliano, Luiz; Juliano, Maria A.; Carmona, Adriana K.; Travassos, Luiz R.; Rodrigues, Elaine G.

    2014-01-01

    The increased incidence, high rates of mortality and few effective means of treatment of malignant melanoma, stimulate the search for new anti-tumor agents and therapeutic targets to control this deadly metastatic disease. In the present work the antitumor effect of arazyme, a natural bacterial-derived metalloprotease secreted by Serratia proteomaculans, was investigated. Arazyme significantly reduced the number of pulmonary metastatic nodules after intravenous inoculation of B16F10 melanoma cells in syngeneic mice. In vitro, the enzyme showed a dose-dependent cytostatic effect in human and murine tumor cells, and this effect was associated to the proteolytic activity of arazyme, reducing the CD44 expression at the cell surface, and also reducing in vitro adhesion and in vitro/in vivo invasion of these cells. Arazyme treatment or immunization induced the production of protease-specific IgG that cross-reacted with melanoma MMP-8. In vitro, this antibody was cytotoxic to tumor cells, an effect increased by complement. In vivo, arazyme-specific IgG inhibited melanoma lung metastasis. We suggest that the antitumor activity of arazyme in a preclinical model may be due to a direct cytostatic activity of the protease in combination with the elicited anti-protease antibody, which cross-reacts with MMP-8 produced by tumor cells. Our results show that the bacterial metalloprotease arazyme is a promising novel antitumor chemotherapeutic agent. PMID:24788523

  19. On the mechanism of apatite-induced precipitation on 45S5 glass pellets coated with a natural-derived polymer

    NASA Astrophysics Data System (ADS)

    Araújo, Marco; Miola, Marta; Bertone, Elisa; Baldi, Giovanni; Perez, Javier; Verné, Enrica

    2015-10-01

    In this work, the bioactive glass 45S5 (also known by its commercial name Bioglass®) was successfully dip-coated by a natural derived biopolymer, increasing its apatite-forming ability. The biopolymer was shown to accelerate the first stages of bioactivity, inducing a fast transition to step 4 (formation of amorphous Casbnd P layer) in the apatite-forming ability mechanism. The faster precipitation of Ca/P crystals in the coated samples resulted in the formation of an intermediate amorphous octacalcium phosphate, which later transforms into an apatite layer with high thickness. The effect of the thickness of the coating was also studied on samples coated with polymer suspensions of different concentrations (0.15% and 1.5%, w/v), revealing that the kinetics of formation of the final hydroxycarbonate apatite layer increases with the thickness of the coating. The mechanism by which this apatite-forming ability is accelerated was also investigated, revealing that certain functional groups present in the structure of the polymer allow it to act as an organic matrix and preferential nucleation site for the growth of the hydroxycarbonate apatite layer.

  20. Pollen Morphology and Boron Concentration in Floral Tissues as Factors Triggering Natural and GA-Induced Parthenocarpic Fruit Development in Grapevine

    PubMed Central

    Pérez-Díaz, Ricardo; Yáñez, Mónica; Tapia, Jaime; Moreno, Yerko

    2015-01-01

    Parthenocarpic fruit development (PFD) reduces fruit yield and quality in grapevine. Parthenocarpic seedless berries arise from fruit set without effective fertilization due to defective pollen germination. PFD has been associated to micronutrient deficiency but the relation of this phenomenon with pollen polymorphism has not been reported before. In this work, six grapevine cultivars with different tendency for PFD and grown under micronutrient-sufficient conditions were analyzed to determine pollen structure and germination capability as well as PFD rates. Wide variation in non-germinative abnormal pollen was detected either among cultivars as well as for the same cultivar in different growing seasons. A straight correlation with PFD rates was found (R2 = 0.9896), suggesting that natural parthenocarpy is related to defective pollen development. Such relation was not observed when PFD was analyzed in grapevine plants exposed to exogenous gibberellin (GA) or abscissic acid (ABA) applications at pre-anthesis. Increase (GA treatment) or reduction (ABA treatment) in PFD rates without significative changes in abnormal pollen was determined. Although these plants were maintained at sufficient boron (B) condition, a down-regulation of the floral genes VvBOR3 and VvBOR4 together with a reduction of floral B content in GA-treated plants was established. These results suggest that impairment in B mobility to reproductive tissues and restriction of pollen tube growth could be involved in the GA-induced parthenocarpy. PMID:26440413

  1. Pollen Morphology and Boron Concentration in Floral Tissues as Factors Triggering Natural and GA-Induced Parthenocarpic Fruit Development in Grapevine.

    PubMed

    Alva, Orlando; Roa-Roco, Rosa Nair; Pérez-Díaz, Ricardo; Yáñez, Mónica; Tapia, Jaime; Moreno, Yerko; Ruiz-Lara, Simón; González, Enrique

    2015-01-01

    Parthenocarpic fruit development (PFD) reduces fruit yield and quality in grapevine. Parthenocarpic seedless berries arise from fruit set without effective fertilization due to defective pollen germination. PFD has been associated to micronutrient deficiency but the relation of this phenomenon with pollen polymorphism has not been reported before. In this work, six grapevine cultivars with different tendency for PFD and grown under micronutrient-sufficient conditions were analyzed to determine pollen structure and germination capability as well as PFD rates. Wide variation in non-germinative abnormal pollen was detected either among cultivars as well as for the same cultivar in different growing seasons. A straight correlation with PFD rates was found (R2 = 0.9896), suggesting that natural parthenocarpy is related to defective pollen development. Such relation was not observed when PFD was analyzed in grapevine plants exposed to exogenous gibberellin (GA) or abscissic acid (ABA) applications at pre-anthesis. Increase (GA treatment) or reduction (ABA treatment) in PFD rates without significative changes in abnormal pollen was determined. Although these plants were maintained at sufficient boron (B) condition, a down-regulation of the floral genes VvBOR3 and VvBOR4 together with a reduction of floral B content in GA-treated plants was established. These results suggest that impairment in B mobility to reproductive tissues and restriction of pollen tube growth could be involved in the GA-induced parthenocarpy. PMID:26440413

  2. A naturally occurring α(s1)-casein-derived peptide in bovine milk inhibits apoptosis of granulosa cells induced by serum-free conditions.

    PubMed

    Shimizu, T; Ganzorig, K; Miyamoto, A; Ishii, T; Urashima, T; Fukuda, K

    2014-03-01

    Several naturally occurring peptides in bovine milk were characterized by tandem mass spectrometry and Edman degradation. Chromatograms of peptide fractions (passed through an ultra-filtration membrane, nominal molecular weight limit 3000) prepared from colostrum (collected immediately after parturition) and transitional milk (collected 5 days postpartum) showed that they were almost identical. In total, six peptides, α(s1)-CN (f16-23) (RPKHPIKH), α(s1)-CN (f16-24) (RPKHPIKHQ), α(s1)-CN (f17-25) (PKHPIKHQG), α(s1)-CN (f46-52) (VFGKEKV), α(s1)-CN (f94-105) (HIQKEDVPSER), and β-CN (f121-128) (HKEMPFPK), were identified. One of the major peptides, the N-terminal fragment of αs1 -casein, varied structurally during early lactation: α(s1)-CN (f17-25) (PKHPIKHQG) and α(s1)-CN (f16-23) (RPKHPIKH)/α(s1)-CN (f16-24) (RPKHPIKHQ) were found in colostrum and transitional milk, respectively. A chemically synthesized peptide, α(s1)-CN (f16-23) (RPKHPIKH), inhibited apoptosis of bovine granulosa cells induced by serum-free conditions in a dose-dependent manner, in consequence of caspase-3 and caspase-9 suppressions. The physiological function of the peptide remains unclear, but it may have potential use as pharmaceutical agent and as an anti-apoptotic agent in cell culture medium. PMID:24399684

  3. Electron beam induced water-soluble silk fibroin nanoparticles as a natural antioxidant and reducing agent for a green synthesis of gold nanocolloid

    NASA Astrophysics Data System (ADS)

    Wongkrongsak, Soraya; Tangthong, Theeranan; Pasanphan, Wanvimol

    2016-01-01

    The research proposes a novel water-soluble silk fibroin nanoparticles (WSSF-NPs) created by electron beam irradiation. In this report, we demonstrate the effects of electron beam irradiation doses ranging from 1 to 30 kGy on the molecular weight (MW), nanostructure formation, antioxidant activity and reducing power of the WSSF-NPs. Electron beam-induced degradation of SF causing MW reduction from 250 to 37 kDa. Chemical characteristic functions of SF still remained after exposing to electron beam. The WSSF-NPs with the MW of 37 kDa exhibited spherical morphology with a nanoscaled size of 40 nm. Antioxidant activities and reducing powers were investigated using 2,2-diphenyl-1-picrylhryl free radical (DPPH•) scavenging activity and ferric reducing antioxidant power (FRAP) assays, respectively. The WSSF-NPs showed greater antioxidant activity and reducing power than non-irradiated SF. By increasing their antioxidant and reducing power efficiencies, WSSF-NPs potentially created gold nanocolloid. WSSF-NPs produced by electron beam irradiation would be a great merit for the uses as a natural antioxidant additive and a green reducing agent in biomedical, cosmetic and food applications.

  4. Bone marrow mesenchymal stem cells suppressing activation of allogeneic cytokine-induced killer/natural killer cells either by direct or indirect interaction.

    PubMed

    Li, Yang; Qu, Yu H; Wu, Yan F; Liu, Ling; Lin, Xiang H; Huang, Ke; Wei, Jing

    2015-04-01

    Bone marrow mesenchymal stem cells (MSC) were recently found to be associated with some special immunological characteristics, the immunoregulatory effect of MSC was dose-dependent. Low amount of MSC was associated with mild immunosuppression or even immune activation, while the high amount of that was associated with significant immunosuppressive effect. In this study, by using a transwell system, we explored the effect of MSC on the cell cycle, apoptosis rate and the expression of CD69, an activation marker, on the allogeneic cord blood derived cytokine-induced killer(CIK)/natural killer(NK) cells. The results showed that either by transwell or mixed cell-cell co-culture, the MSC can effect CIK/NK cells on the cell cycle, such as arrested in the G0/G1 phase, diminished the ratio of cells in S, G2/M phase, and increased the apoptosis of them. MSC can also depress the expression of CD69 on these killer cells, as well as increased the ratio of CD4(+) CD25(+) CD127(low) T regulatory (Treg) cells in the CIK/NK cell culture system. We draw conclusions that either by transwell or mixed co-culture, the MSC can suppress activation of allogeneic CB-CIK/NK cells in a dose-dependent manner.

  5. Parental exposure to natural mixtures of persistent organic pollutants (POP) induced changes in transcription of apoptosis-related genes in offspring zebrafish embryos.

    PubMed

    Lyche, Jan L; Grześ, Irena M; Karlsson, Camilla; Nourizadeh-Lillabadi, Rasoul; Aleström, Peter; Ropstad, Erik

    2016-01-01

    Apoptosis is an integral element of development that may also be initiated by environmental contaminants. The aim of the present study was to assess potential changes in the regulation of apoptotic genes in zebrafish embryos following parental exposure to two natural mixtures of persistent organic pollutants (POP). The mixture from Lake Mjøsa contained exceptionally high concentrations of polybrominated diphenyl ethers (PBDE), as well as relatively high levels of polychlorinated biphenyls (PCB) and dichlorodiphenyltrichloroethane (DDT). The mixture from Lake Losna contained background concentrations of POP. Genes involved in the apoptotic machinery were screened for their expression profile at four time points during embryonic development. Thirteen and 15 genes involved in apoptosis were found to be significantly upregulated in the high-exposure and background exposure groups, respectively, compared with controls. Modulation of apoptotic genes was restricted only to the first time point, which corresponds with the blastula stage. Although there were substantial differences in POP concentrations between mixtures, genes underlying the apoptosis process showed almost similar responses to the two mixtures. In both exposure groups the main executors of apoptosis p53, casp 2, casp 6, cassp 8, and BAX displayed upregulation compared to controls, suggesting that these POP induce apoptosis via a p53-dependent mechanism. Upregulation of genes that play a critical role in apoptosis suggests that disturbance of normal apoptotic signaling during gametogenesis and embryogenesis may be one of the central mechanisms involved in adverse reproductive effects produced by POP in zebrafish. PMID:27484141

  6. Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

    NASA Technical Reports Server (NTRS)

    Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

    2012-01-01

    Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

  7. Low-dose ionizing radiation induces direct activation of natural killer cells and provides a novel approach for adoptive cellular immunotherapy.

    PubMed

    Yang, Guozi; Kong, Qingyu; Wang, Guanjun; Jin, Haofan; Zhou, Lei; Yu, Dehai; Niu, Chao; Han, Wei; Li, Wei; Cui, Jiuwei

    2014-12-01

    Recent evidence indicates that limited availability and cytotoxicity have restricted the development of natural killer (NK) cells in adoptive cellular immunotherapy (ACI). While it has been reported that low-dose ionizing radiation (LDIR) could enhance the immune response in animal studies, the influence of LDIR at the cellular level has been less well defined. In this study, the authors aim to investigate the direct effects of LDIR on NK cells and the potential mechanism, and explore the application of activation and expansion of NK cells by LDIR in ACI. The authors found that expansion and cytotoxicity of NK cells were markedly augmented by LDIR. The levels of IFN-γ and TNF-α in the supernatants of cultured NK cells were significantly increased after LDIR. Additionally, the effect of the P38 inhibitor (SB203580) significantly decreased the expanded NK cell cytotoxicity, cytokine levels, and expression levels of FasL and perforin. These findings indicate that LDIR induces a direct expansion and activation of NK cells through possibly the P38-MAPK pathway, which provides a potential mechanism for stimulation of NK cells by LDIR and a novel but simplified approach for ACI.

  8. The natural toxin juglone causes degradation of p53 and induces rapid H2AX phosphorylation and cell death in human fibroblasts

    SciTech Connect

    Paulsen, Michelle T.; Ljungman, Mats . E-mail: ljungman@umich.edu

    2005-11-15

    Juglone (5-hydroxy-1,4-naphtoquinone) is a natural toxin produced by walnut trees. In this study we show that juglone differentially reduces viability of human cells in culture. Normal fibroblast were found to be especially sensitive to juglone and lost viability primarily through a rapid apoptotic and necrotic response. This response may have been triggered by DNA damage since juglone induced a rapid and strong phosphorylation of H2AX in all phases of the cell cycle. Furthermore, juglone inhibits mRNA synthesis in human fibroblasts in a dose-dependent manner. Surprisingly, juglone caused a drastic reduction of the basal level of p53 in human fibroblasts and this loss could not be fully rescued by proteasome and calpain I inhibitors. However, when cells were pretreated with UV light or ionizing radiation, juglone was not able to reduce the cellular levels of activated p53. Our results show that juglone has multiple effects on cells such as the induction of DNA damage, inhibition of transcription, reduction of p53 protein levels and the induction of cell death.

  9. The ANXA1 released from intestinal epithelial cells alleviate DSS-induced colitis by improving NKG2A expression of Natural Killer cells.

    PubMed

    Zou, Z; Zuo, D; Yang, J; Fan, H

    2016-09-01

    Inflammatory bowel disease (IBD) arises when intestinal immune homeostasis is broken, the maintenance of such homeostasis is principally controlled by cross talk between commensal bacteria, mucosal immune cells and intestinal epithelial cells (IECs). IECs can prevent the contact between luminal bacteria with immune cells through the formation of a physical barrier and the expression of antimicrobial peptides to maintain intestinal immune homeostasis. During Colitis the IECs can express increased ANXA1, which is important for regeneration of intestinal mucosa and function as a potent anti-inflammatory protein. Natural Killer (NK) cells can also suppress the progression of colitis. It is uncertain about the effect of the cross-talk between injured IECs and recruited NK cells during colitis. In this study, the expression of ANXA1 in IECS from DSS treated mice was increased, and more NK cells were recruited to intestinal mucosa. In addition, the expression of NKG2A was upregulated when co-cultured with NK cells. The results further proved that overexpression of NKG2A in NK cells was important for inhibiting the recruitment and activity of neutrophils to alleviate DSS-induced colitis. Here, we provide a new anti-inflammation mechanism about ANXA1 secreted from injured IECs, where ANXA1 can stimulate the expression of NKG2A in NK cells that affect the recruitment and activity of neutrophils necessary for pathology of colitis.

  10. SIV-induced Translocation of Bacterial Products in the Liver Mobilizes Myeloid Dendritic and Natural Killer Cells Associated With Liver Damage.

    PubMed

    Evans, Tristan I; Li, Haiying; Schafer, Jamie L; Klatt, Nichole R; Hao, Xing-Pei; Traslavina, Ryan P; Estes, Jacob D; Brenchley, Jason M; Reeves, R Keith

    2016-02-01

    Disruption of the mucosal epithelium during lentivirus infections permits translocation of microbial products into circulation, causing immune activation and driving disease. Although the liver directly filters blood from the intestine and is the first line of defense against gut-derived antigens, the effects of microbial products on the liver are unclear. In livers of normal macaques, minute levels of bacterial products were detectable, but increased 20-fold in simian immunodeficiency virus (SIV)-infected animals. Increased microbial products in the liver induced production of the chemoattractant CXCL16 by myeloid dendritic cells (mDCs), causing subsequent recruitment of hypercytotoxic natural killer (NK) cells expressing the CXCL16 receptor, CXCR6. Microbial accumulation, mDC activation, and cytotoxic NK cell frequencies were significantly correlated with markers of liver damage, and SIV-infected animals consistently had evidence of hepatitis and fibrosis. Collectively, these data indicate that SIV-associated accumulation of microbial products in the liver initiates a cascade of innate immune activation, resulting in liver damage.

  11. Successful cross-protective efficacy induced by heat-adapted live attenuated nephropathogenic infectious bronchitis virus derived from a natural recombinant strain.

    PubMed

    Lim, Tae-Hyun; Youn, Ha-Na; Yuk, Seong-Su; Kwon, Jung-Hoon; Hong, Woo-Tack; Gwon, Gyeong-Bin; Lee, Jung-Ah; Lee, Joong-Bok; Lee, Sang-Won; Song, Chang-Seon

    2015-12-16

    A natural recombinant nephropathogenic K40/09 strain of infectious bronchitis virus (IBV) was heat-adapted for possible future use as live attenuated vaccine. The K40/09 strain was selected during successive serial passages in specific-pathogen free (SPF) embryonated eggs at sub-optimal higher temperature (56°C). Unlike the parental strain, the attenuated strain, designated K40/09 HP50, was found to be safe in 1-day-old SPF chicks, which showed neither mortality nor signs of morbidity, and rarely induced ciliostasis or histological changes in the trachea and kidney after intraocular and fine-spray administration. K40/09 HP50 provided almost complete protection against two distinct subgroups of a nephropathogenic strain (KM91-like and QX-like subgroup) and elicited the production of high titers of neutralizing antibody (neutralization index of 3.6). We conclude that the K40/09 HP50 vaccine virus is rapidly attenuated by heat adaptation and exhibits the desired level of attenuation, immunogenicity, and protective efficacy required for a live attenuated vaccine. These results indicate that the K40/09 vaccine could be helpful for the reduction of economic losses caused by recently emergent nephropathogenic IBV infection in many countries.

  12. The ANXA1 released from intestinal epithelial cells alleviate DSS-induced colitis by improving NKG2A expression of Natural Killer cells.

    PubMed

    Zou, Z; Zuo, D; Yang, J; Fan, H

    2016-09-01

    Inflammatory bowel disease (IBD) arises when intestinal immune homeostasis is broken, the maintenance of such homeostasis is principally controlled by cross talk between commensal bacteria, mucosal immune cells and intestinal epithelial cells (IECs). IECs can prevent the contact between luminal bacteria with immune cells through the formation of a physical barrier and the expression of antimicrobial peptides to maintain intestinal immune homeostasis. During Colitis the IECs can express increased ANXA1, which is important for regeneration of intestinal mucosa and function as a potent anti-inflammatory protein. Natural Killer (NK) cells can also suppress the progression of colitis. It is uncertain about the effect of the cross-talk between injured IECs and recruited NK cells during colitis. In this study, the expression of ANXA1 in IECS from DSS treated mice was increased, and more NK cells were recruited to intestinal mucosa. In addition, the expression of NKG2A was upregulated when co-cultured with NK cells. The results further proved that overexpression of NKG2A in NK cells was important for inhibiting the recruitment and activity of neutrophils to alleviate DSS-induced colitis. Here, we provide a new anti-inflammation mechanism about ANXA1 secreted from injured IECs, where ANXA1 can stimulate the expression of NKG2A in NK cells that affect the recruitment and activity of neutrophils necessary for pathology of colitis. PMID:27435504

  13. Control of the Inflammatory Response Mechanisms Mediated by Natural and Induced Regulatory T-Cells in HCV-, HTLV-1-, and EBV-Associated Cancers

    PubMed Central

    Moralès, Olivier; Delhem, Nadira

    2014-01-01

    Virus infections are involved in chronic inflammation and, in some cases, cancer development. Although a viral infection activates the immune system's response that eradicates the pathogen mainly through inflammatory mechanisms, it is now recognized that this inflammatory condition is also favorable to the development of tumors. Indeed, it is well described that viruses, such as hepatitis C virus (HCV), Epstein Barr virus (EBV), human papillomavirus (HPV) or human T-cell lymphotropic virus type-1 (HTLV-1), are important risk factors for tumor malignancies. The inflammatory response is a fundamental immune mechanism which involves several molecular and cellular components consisting of cytokines and chemokines that are released by various proinflammatory cells. In parallel to this process, some endogenous recruited components release anti-inflammatory mediators to restore homeostasis. The development of tools and strategies using viruses to hijack the immune response is mostly linked to the presence of regulatory T-cells (Treg) that can inhibit inflammation and antiviral responses of other effector cells. In this review, we will focus on current understanding of the role of natural and induced Treg in the control and the resolution of inflammatory response in HCV-, HTLV-1-, and EBV-associated cancers. PMID:25525301

  14. Real-time vision, tactile cues, and visual form agnosia: removing haptic feedback from a "natural" grasping task induces pantomime-like grasps.

    PubMed

    Whitwell, Robert L; Ganel, Tzvi; Byrne, Caitlin M; Goodale, Melvyn A

    2015-01-01

    past. Compared to natural grasps, removing tactile feedback increased RT, slowed the velocity of the reach, reduced in-flight grip aperture, increased the slopes relating grip aperture to target width, and reduced the final grip aperture (FGA). All of these effects were also observed in the real time-pantomime grasping task. These effects seem to be independent of those that arise from using the mirror in general as we also compared grasps directed towards virtual targets to those directed at real ones viewed directly through a pane of glass. These comparisons showed that the grasps directed at virtual targets increased grip aperture, slowed the velocity of the reach, and reduced the slopes relating grip aperture to the widths of the target. Thus, using the mirror has real consequences on grasp kinematics, reflecting the importance of task-relevant sources of online visual information for the programming and updating of natural prehensile movements. Taken together, these results provide compelling support for the view that removing terminal tactile feedback, even when the grasps are target-directed, induces a switch from real-time visual control towards one that depends more on visual perception and cognitive supervision. Providing terminal tactile feedback and real-time visual information can evidently keep the dorsal visuomotor system operating normally for prehensile acts.

  15. Pathways of Leymus chinensis Individual Aboveground Biomass Decline in Natural Semiarid Grassland Induced by Overgrazing: A Study at the Plant Functional Trait Scale

    PubMed Central

    Wang, Zhen; Wu, Xinhong; Li, Xinle; Hu, Jing; Shi, Hongxiao; Guo, Fenghui; Zhang, Yong; Hou, Xiangyang

    2015-01-01

    Natural grassland productivity, which is based on an individual plant’s aboveground biomass (AB) and its interaction with herbivores, can obviously affect terrestrial ecosystem services and the grassland’s agricultural production. As plant traits have been linked to both AB and ecosystem success, they may provide a useful approach to understand the changes in individual plants and grassland productivity in response to grazing on a generic level. Unfortunately, the current lack of studies on how plant traits affect AB affected by herbivores leaves a major gap in our understanding of the mechanism of grassland productivity decline. This study, therefore, aims to analyze the paths of overgrazing-induced decline in the individual AB of Leymus chinensis (the dominant species of meadow-steppe grassland in northern China) on a plant functional trait scale. Using a paired-sampling approach, we compared the differences in the functional traits of L. chinensis in long-term grazing-excluded and experimental grazing grassland plots over a continuous period of approximately 20 years (located in meadow steppe lands in Hailar, Inner Mongolia, China). We found a highly significant decline in the individual height and biomass (leaf, stem, and the whole plant) of L. chinensis as a result of overgrazing. Biomass allocation and leaf mass per unit area were significantly affected by the variation in individual size. Grazing clearly enhanced the sensitivity of the leaf-to-stem biomass ratio in response to variation in individual size. Moreover, using a method of standardized major axis estimation, we found that the biomass in the leaves, stems, and the plant as a whole had highly significant allometric scaling with various functional traits. Also, the slopes of the allometric equations of these relationships were significantly altered by grazing. Therefore, a clear implication of this is that grazing promotes an asymmetrical response of different plant functional traits to variation

  16. Pathways of Leymus chinensis Individual Aboveground Biomass Decline in Natural Semiarid Grassland Induced by Overgrazing: A Study at the Plant Functional Trait Scale.

    PubMed

    Li, Xiliang; Liu, Zhiying; Wang, Zhen; Wu, Xinhong; Li, Xinle; Hu, Jing; Shi, Hongxiao; Guo, Fenghui; Zhang, Yong; Hou, Xiangyang

    2015-01-01

    Natural grassland productivity, which is based on an individual plant's aboveground biomass (AB) and its interaction with herbivores, can obviously affect terrestrial ecosystem services and the grassland's agricultural production. As plant traits have been linked to both AB and ecosystem success, they may provide a useful approach to understand the changes in individual plants and grassland productivity in response to grazing on a generic level. Unfortunately, the current lack of studies on how plant traits affect AB affected by herbivores leaves a major gap in our understanding of the mechanism of grassland productivity decline. This study, therefore, aims to analyze the paths of overgrazing-induced decline in the individual AB of Leymus chinensis (the dominant species of meadow-steppe grassland in northern China) on a plant functional trait scale. Using a paired-sampling approach, we compared the differences in the functional traits of L. chinensis in long-term grazing-excluded and experimental grazing grassland plots over a continuous period of approximately 20 years (located in meadow steppe lands in Hailar, Inner Mongolia, China). We found a highly significant decline in the individual height and biomass (leaf, stem, and the whole plant) of L. chinensis as a result of overgrazing. Biomass allocation and leaf mass per unit area were significantly affected by the variation in individual size. Grazing clearly enhanced the sensitivity of the leaf-to-stem biomass ratio in response to variation in individual size. Moreover, using a method of standardized major axis estimation, we found that the biomass in the leaves, stems, and the plant as a whole had highly significant allometric scaling with various functional traits. Also, the slopes of the allometric equations of these relationships were significantly altered by grazing. Therefore, a clear implication of this is that grazing promotes an asymmetrical response of different plant functional traits to variation in

  17. Ellagic acid, a natural polyphenol protects rat peripheral blood lymphocytes against nicotine-induced cellular and DNA damage in vitro: with the comparison of N-acetylcysteine.

    PubMed

    Sudheer, Adluri Ram; Muthukumaran, Shanmugavelu; Devipriya, Nagarajan; Menon, Venugopal Padmanabhan

    2007-01-25

    The present work is aimed at evaluating the protective effect of ellagic acid (EA), a natural polyphenolic compound that is widely distributed in fruits and nuts against nicotine-induced toxicity in rat peripheral blood lymphocytes. The effect of EA against nicotine toxicity was compared with N-acetylcysteine (NAC), a well-known antioxidant. Lymphocytes were exposed to nicotine at the doses of 0.125, 0.25, 0.5, 1, 2, 3 and 4 mM for 1h in culture media. Thiobarbituric acid reactive substances (TBARS), a lipid peroxidative marker and reduced glutathione (GSH), as indicative of endogenous antioxidant status were analyzed to fix the optimum dose. The lowest concentration eliciting significant damage was 1 mM nicotine and maximum damage was observed with 3 mM concentration, as evidenced by increased levels of TBARS and decreased levels of GSH. Hence, the test concentration was fixed at 3 mM nicotine. To establish most effective protective support we used five different concentrations of EA (10, 50, 100, 150 and 300 microM) against 3 mM nicotine. A dose-dependent inhibitory effect was observed with all doses of EA. Maximum protection was observed at the dose of 100 microM EA. So, 100 microM dose was used for further studies. We have tested five different concentrations of NAC-0.25, 0.5, 1, 2 and 4 mM to elucidate the optimum protective dose against nicotine toxicity. One millimolar NAC showed a significant protection against nicotine toxicity. Protective effect of EA against nicotine toxicity was elucidated by analyzing the lipid peroxidative index, viz., TBARS, hydroperoxides (HP) and endogenous antioxidant status, viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), Vitamins A, E and C. DNA damage and repair were assessed by using alkaline single-cell microgel electrophoresis (Comet assay) and micronucleus assay. There was a significant increase in the levels of lipid peroxidative index, severity in DNA damage and

  18. Gluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis: a randomized study

    PubMed Central

    Elkan, Ann-Charlotte; Sjöberg, Beatrice; Kolsrud, Björn; Ringertz, Bo; Hafström, Ingiäld; Frostegård, Johan

    2008-01-01

    Introduction The purpose of this study was to investigate the effects of vegan diet in patients with rheumatoid arthritis (RA) on blood lipids oxidized low-density lipoprotein (oxLDL) and natural atheroprotective antibodies against phosphorylcholine (anti-PCs). Methods Sixty-six patients with active RA were randomly assigned to either a vegan diet free of gluten (38 patients) or a well-balanced non-vegan diet (28 patients) for 1 year. Thirty patients in the vegan group completed more than 3 months on the diet regimen. Blood lipids were analyzed by routine methods, and oxLDL and anti-PCs were analyzed by enzyme-linked immunosorbent assay. Data and serum samples were obtained at baseline and after 3 and 12 months. Results Mean ages were 50.0 years for the vegan group and 50.8 years for controls. Gluten-free vegan diet induced lower body mass index (BMI) and low-density lipoprotein (LDL) and higher anti-PC IgM than control diet (p < 0.005). In the vegan group, BMI, LDL, and cholesterol decreased after both 3 and 12 months (p < 0.01) and oxLDL after 3 months (p = 0.021) and trendwise after 12 months (p = 0.090). Triglycerides and high-density lipoprotein did not change. IgA anti-PC levels increased after 3 months (p = 0.027) and IgM anti-PC levels increased trendwise after 12 months (p = 0.057). There was no difference in IgG anti-PC levels. In the control diet group, IgM anti-PC levels decreased both after 3 and 12 months (p < 0.01). When separating vegan patients into clinical responders and non-responders at 12 months, the effects on oxLDL and anti-PC IgA were seen only in responders (p < 0.05). Conclusion A gluten-free vegan diet in RA induces changes that are potentially atheroprotective and anti-inflammatory, including decreased LDL and oxLDL levels and raised anti-PC IgM and IgA levels. PMID:18348715

  19. Infection with foot-and-mouth disease virus (FMDV) induces a natural killer (NK) cell response in cattle that is lacking following vaccination.

    PubMed

    Patch, Jared R; Dar, Pervaiz A; Waters, Ryan; Toka, Felix N; Barrera, Jose; Schutta, Christopher; Kondabattula, Ganesh; Golde, William T

    2014-09-01

    Natural killer (NK) cells play a role in innate antiviral immunity by directly lysing virus-infected cells and producing antiviral cytokines such as interferon gamma (IFN-γ). We developed a system for characterizing the bovine NK response to foot-and-mouth disease virus (FMDV), which causes a disease of cloven-hoofed animals and remains a threat to livestock industries throughout the world. IL-2 stimulation of PBMC resulted in poor killing of human K562 cells, which are often used as NK target cells, while lysis of the bovine BL3.1 cell line was readily detected. Depletion of NKp46-expressing cells revealed that 80% of the killing induced by IL-2 could be attributed to NKp46(+) cells. In order to characterize the response of NK cells against FMDV in vivo, we infected groups of cattle with three different strains of the virus (A24 Cruzeiro, O1 Manisa, O Hong Kong) and evaluated the cytolytic ability of NK cells through the course of infection. We consistently observed a transient increase in cytolysis, although there was variation in magnitude and kinetics. This increase in cytolysis remained when CD3(+) cells were removed from the preparation of lymphocytes, indicating that cytolysis was independent of MHC-T cell receptor interaction or γδ T cell activation. In contrast, animals monitored following vaccination against FMDV did not exhibit any increase in NK killing. These data suggest that NK cells play a role in the host immune response of cattle against FMDV, and contrast with the suppression of NK activity previously observed in swine infected with FMDV.

  20. Natural history of pancreatitis-induced splenic vein thrombosis: a systematic review and meta-analysis of its incidence and rate of gastrointestinal bleeding

    PubMed Central

    Butler, James R; Eckert, George J; Zyromski, Nicholas J; Leonardi, Michael J; Lillemoe, Keith D; Howard, Thomas J

    2011-01-01

    Background Pancreatitis-induced splenic vein thrombosis (PISVT) is an acquired anatomic abnormality that impacts decision making in pancreatic surgery. Despite this influence, its incidence and the rate of associated gastrointestinal (GI) bleeding are imprecisely known. Methods The MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials and Cochrane Database of Systematic Reviews databases were searched from their inception to June 2010 for abstracts documenting PISVT in acute (AP) or chronic pancreatitis (CP). Two reviewers independently graded abstracts for inclusion in this review. Heterogeneity in combining data was assumed prior to pooling. Random-effects meta-analyses were performed to estimate percentages and 95% confidence intervals. Results After review of 241 abstracts, 47 studies and 52 case reports were graded as relevant. These represent a cohort of 805 patients with PISVT reported in the literature. A meta-analysis of studies meeting inclusion criteria shows mean incidences of PISVT of 14.1% in all patients, 22.6% in patients with AP and 12.4% in patients with CP. The incidence of associated splenomegaly was only 51.9% in these patients. Varices were identified in 53.0% of patients and were gastric in 77.3% of cases. The overall rate of GI bleeding was 12.3%. Conclusions Although reported incidences of PISVT vary widely across studies, an overall incidence of 14.1% is reported. Splenomegaly is an unreliable sign of PISVT. Although the true natural history of PISVT remains unknown, the collective reported rate of associated GI bleeding is 12.3%. PMID:22081918

  1. EM23, A Natural Sesquiterpene Lactone from Elephantopus mollis, Induces Apoptosis in Human Myeloid Leukemia Cells through Thioredoxin- and Reactive Oxygen Species-Mediated Signaling Pathways

    PubMed Central

    Li, Hongyu; Li, Manmei; Wang, Guocai; Shao, Fangyuan; Chen, Wenbo; Xia, Chao; Wang, Sheng; Li, Yaolan; Zhou, Guangxiong; Liu, Zhong

    2016-01-01

    Elephantopus mollis (EM) is a traditional herbal medicine with multiple pharmacological activities. However, the efficacy of EM in treating human leukemia is currently unknown. In the current study, we report that EM23, a natural sesquiterpene lactone isolated from EM, inhibits the proliferation of human chronic myeloid leukemia (CML) K562 cells and acute myeloid leukemia (AML) HL-60 cells by inducing apoptosis. Translocation of membrane-associated phospholipid phosphatidylserines, changes in cell morphology, activation of caspases, and cleavage of PARP were concomitant with this inhibition. The involvement of the mitochondrial pathway in EM23-mediated apoptosis was suggested by observed disruptions in mitochondrial membrane potential. Mechanistic studies indicated that EM23 caused a marked increase in the level of reactive oxygen species (ROS). Pretreatment with N-acetyl-L-cysteine, a ROS scavenger, almost fully reversed EM23-mediated apoptosis. In EM23-treated cells, the expression levels of thioredoxin (Trx) and thioredoxinreductase (TrxR), two components of the Trx system involved in maintaining cellular redox homeostasis, were significantly down-regulated. Concomitantly, Trx regulated the activation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream regulatory targets, the p38, JNK, and ERK MAPKs. EM23-mediated activation of ASK1/MAPKs was significantly inhibited in the presence of NAC. Furthermore, tumor necrosis factor alpha (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) was suppressed by EM23, as suggested by the observed blockage of p65 nuclear translocation, phosphorylation, and reversion of IκBα degradation following EM23 treatment. Taken together, these results provide important insights into the anticancer activities of the EM component EM23 against human CML K562 cells and AML HL-60 cells. PMID:27064563

  2. Human Induced Pluripotent Stem Cells Are Targets for Allogeneic and Autologous Natural Killer (NK) Cells and Killing Is Partly Mediated by the Activating NK Receptor DNAM-1

    PubMed Central

    Monecke, Sebastian; Cyganek, Lukas; Elsner, Leslie; Hübscher, Daniela; Walter, Lutz; Streckfuss-Bömeke, Katrin; Guan, Kaomei; Dressel, Ralf

    2015-01-01

    Human induced pluripotent stem cells (hiPSCs) could be used to generate autologous cells for therapeutic purposes, which are expected to be tolerated by the recipient. However, iPSC-derived grafts are at risk of giving rise to teratomas in the host, if residuals of tumorigenic cells are not rejected by the recipient. We have analyzed the susceptibility of hiPSC lines to allogeneic and autologous natural killer (NK) cells. IL-2-activated, in contrast to resting NK cells killed hiPSC lines efficiently (P=1.69x10-39). Notably, the specific lysis of the individual hiPSC lines by IL-2-activated NK cells was significantly different (P=1.72x10-6) and ranged between 46 % and 64 % in 51Cr-release assays when compared to K562 cells. The hiPSC lines were killed by both allogeneic and autologous NK cells although autologous NK cells were less efficient (P=8.63x10-6). Killing was partly dependent on the activating NK receptor DNAM-1 (P=8.22x10-7). The DNAM-1 ligands CD112 and CD155 as well as the NKG2D ligands MICA and MICB were expressed on the hiPSC lines. Low amounts of human leukocyte antigen (HLA) class I proteins, which serve as ligands for inhibitory and activating NK receptors were also detected. Thus, the susceptibility to NK cell killing appears to constitute a common feature of hiPSCs. Therefore, NK cells might reduce the risk of teratoma formation even after autologous transplantations of pluripotent stem cell-derived grafts that contain traces of pluripotent cells. PMID:25950680

  3. Incremental effect of natural tick challenge on the infection and treatment method-induced immunity against T. parva in cattle under agro-pastoral systems in Northern Tanzania.

    PubMed

    Kazungu, Yvette E M; Mwega, Elisa; Neselle, Moses Ole; Sallu, Raphael; Kimera, Sharadhuli I; Gwakisa, Paul

    2015-07-01

    This study was conducted to assess the incremental effect of natural tick challenge on the infection and treatment method-induced immunity against T. parva under agro-pastoral systems in Simanjiro district, Northern Tanzania. T. parva specific antibody percent positivity and prevalence of T. parva parasites were studied in relation to duration post vaccination and proximity to Tarangire National park. A total of 381 cattle were included in this study, of which 127 were unvaccinated and 254 had been vaccinated at different time points between 2008 and 2014. Antibody percent positivity (PP) determined by the PIM-based T. parva ELISA and the prevalence of T. parva parasites detected by a nested PCR based on the p104 gene were used to compare vaccinated and unvaccinated cattle. Results showed that seroprevalence was significantly higher in vaccinated than unvaccinated cattle (OR 10.89, p = 0.0341). Only 1.6% (6/381) of all cattle were seronegative and 5/6 of these were unvaccinated. Prevalence of T. parva parasites was significantly higher in vaccinated (50.39%) than unvaccinated (19.69%) cattle (OR 2.03, p = 0.0144). While there was a positive association between PP and duration post vaccination but the latter was inversely associated with T. parva parasite prevalence. This study also showed that cattle which were closer to the park had higher antibody PP and T. parva prevalence. It is concluded that duration post vaccination as well as proximity from the wildlife in Tarangire National park together may exert an incremental effect on the outcome of ECF vaccination by influencing stronger antibody immunity of cattle and ability to withhold high T. parva infection pressure under constant field tick challenge. Further, the high seroprevalence in vaccinated and unvaccinated cattle suggests a likely state of endemic stability to T. parva in the study area. PMID:26005108

  4. EM23, A Natural Sesquiterpene Lactone from Elephantopus mollis, Induces Apoptosis in Human Myeloid Leukemia Cells through Thioredoxin- and Reactive Oxygen Species-Mediated Signaling Pathways.

    PubMed

    Li, Hongyu; Li, Manmei; Wang, Guocai; Shao, Fangyuan; Chen, Wenbo; Xia, Chao; Wang, Sheng; Li, Yaolan; Zhou, Guangxiong; Liu, Zhong

    2016-01-01

    Elephantopus mollis (EM) is a traditional herbal medicine with multiple pharmacological activities. However, the efficacy of EM in treating human leukemia is currently unknown. In the current study, we report that EM23, a natural sesquiterpene lactone isolated from EM, inhibits the proliferation of human chronic myeloid leukemia (CML) K562 cells and acute myeloid leukemia (AML) HL-60 cells by inducing apoptosis. Translocation of membrane-associated phospholipid phosphatidylserines, changes in cell morphology, activation of caspases, and cleavage of PARP were concomitant with this inhibition. The involvement of the mitochondrial pathway in EM23-mediated apoptosis was suggested by observed disruptions in mitochondrial membrane potential. Mechanistic studies indicated that EM23 caused a marked increase in the level of reactive oxygen species (ROS). Pretreatment with N-acetyl-L-cysteine, a ROS scavenger, almost fully reversed EM23-mediated apoptosis. In EM23-treated cells, the expression levels of thioredoxin (Trx) and thioredoxinreductase (TrxR), two components of the Trx system involved in maintaining cellular redox homeostasis, were significantly down-regulated. Concomitantly, Trx regulated the activation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream regulatory targets, the p38, JNK, and ERK MAPKs. EM23-mediated activation of ASK1/MAPKs was significantly inhibited in the presence of NAC. Furthermore, tumor necrosis factor alpha (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) was suppressed by EM23, as suggested by the observed blockage of p65 nuclear translocation, phosphorylation, and reversion of IκBα degradation following EM23 treatment. Taken together, these results provide important insights into the anticancer activities of the EM component EM23 against human CML K562 cells and AML HL-60 cells. PMID:27064563

  5. Signatures of Fluid-Pressure Triggering, Natural and Induced: Comparing Migrating Earthquake Swarms in Long Valley Caldera, California and Azle, Texas

    NASA Astrophysics Data System (ADS)

    Shelly, D. R.; Ellsworth, W. L.; Montgomery-Brown, E. K.; Hill, D. P.; Prejean, S. G.; Mangan, M.

    2014-12-01

    permeability and accelerated fluid pressure diffusion via the newly ruptured fault patch. By integrating observations from natural and induced earthquake swarms, we aim to understand factors controlling the combined physics of faulting and fluid pressure diffusion in the crust.

  6. Role of interferon gamma and tumor necrosis factor-related apoptosis-inducing ligand receptor 1 single nucleotide polymorphism in natural clearance and treatment response of HCV infection.

    PubMed

    Azam, Sikandar; Manzoor, Sobia; Imran, Muhammad; Ashraf, Javed; Ashraf, Sarah; Resham, Saleha; Ghani, Eijaz

    2015-05-01

    Hepatitis C virus (HCV) pathogenesis and treatment outcomes are multifactorial phenomena involving both viral and host factors. This study was designed to determine the role of tumor necrosis factor-related apoptosis-inducing ligand receptor 1(TRAIL-R1) and interferon gamma (IFN-γ) genetic mutations in susceptibility and response to interferon-based therapy of hepatitis C virus (HCV) infection. The detection of TRAIL-R1 rs4242392 and IFN-γ rs2069707 single nucleotide polymorphisms was completed in 118 chronic HCV patients and 96 healthy controls by allele-specific polymerase chain reaction and restriction fragment length polymorphisms polymerase chain reaction. Patients were further categorized into sustained virological responder (SVR) and nonresponder (NR) groups on the basis of their response to interferon-based therapy for HCV infection. Real-time PCR was used for HCV quantification. HCV genotyping was performed by Ohno's method. The results demonstrated that the distribution of the TRAIL-R1 rs4242392TT genotype was significantly higher in the SVR group (78%) compared to the NR group (36%). It showed that chronic HCV patients possessing the TRAIL-R1 rs4242392TT genotype are better responders to interferon-based therapy (p<0.05). The prevalence of the TRAIL-R1 rs424239