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Sample records for cobra naja naja

  1. Neutralization of cobra venom by cocktail antiserum against venom proteins of cobra (Naja naja naja).

    PubMed

    Venkatesan, C; Sarathi, M; Balasubramanaiyan, G; Vimal, S; Madan, N; Sundar Raj, N; Mohammed Yusuf Bilal, S; Nazeer Basha, A; Farook, M A; Sahul Hameed, A S; Sridevi, G

    2014-01-01

    Naja naja venom was characterized by its immunochemical properties and electrophoretic pattern which revealed eight protein bands (14 kDa, 24 kDa, 29 kDa, 45 kDa, 48 kDa, 65 kDa, 72 kDa and 99 kDa) by SDS-PAGE in reducing condition after staining with Coomassie Brilliant Blue. The results showed that Naja venom presented high lethal activity. Whole venom antiserum or individual venom protein antiserum (14 kDa, 29 kDa, 65 kDa, 72 kDa and 99 kDa) of venom could recognize N. naja venom by Western blotting and ELISA, and N. naja venom presented antibody titer when assayed by ELISA. The neutralization tests showed that the polyvalent antiserum neutralized lethal activities by both in vivo and in vitro studies using mice and Vero cells. The antiserum could neutralize the lethal activities in in-vivo and antivenom administered after injection of cobra venom through intraperitoneal route in mice. The cocktail antiserum also could neutralize the cytotoxic activities in Vero cell line by MTT and Neutral red assays. The results of the present study suggest that cocktail antiserum neutralizes the lethal activities in both in vitro and in vivo models using the antiserum against cobra venom and its individual venom proteins serum produced in rabbits. PMID:24176716

  2. [Envenoming by Malayan cobra (Naja naja sputatrix)--case report].

    PubMed

    Ciszowski, Krzysztof; Hartwich, Artur

    2004-01-01

    Malayan cobra (Naja naja sputatrix) is the venomous snake of the Elapidae family which involves at least three species of Asian spitting cobras, according to the new taxonomy. This snake occurs naturally in southeastern Asia and in Poland it is kept only in the private breedings. Its venom mainly contains neurotoxins which have paralyzing activities to the nervous system and cardiotoxins which act cytolytically. The present study shows a case of the forty-one-year-old man professionally engaging in venomous reptiles who was bitten in his left ring finger by the Malayan cobra. No general symptoms, especially neurotoxic, were observed in the patient after the snake bite, but there was a significant local tissue injury including necrosis. In the bite site the infection with Morganella morganii developed with consequent phlegmon within the hand and the forearm. Additionally, features of haemolysis and injury of muscles with elevated level of serum creatine phosphokinase (CPK) were present. The local injuries of tissues were treated surgically including the amputation of the bitten finger which has undergone the necrosis. No specific antivenom was used in the treatment. PMID:15521620

  3. Screening of plants containing Naja naja siamensis cobra venom inhibitory activity using modified ELISA technique.

    PubMed

    Daduang, Sakda; Sattayasai, Nison; Sattayasai, Jintana; Tophrom, Pattara; Thammathaworn, Achra; Chaveerach, Arunrat; Konkchaiyaphum, Monruedee

    2005-06-15

    Enzyme-linked immunosorbent assay (ELISA) has been modified for screening plants with antagonistic activity to Naja naja siamensis cobra venom. Aqueous extracts from plants were investigated for their inhibitory effects on the binding of anti-cobra venom antibody to antigen, cobra venom, fixed onto 96-well microtiter plates. Ingredients in extracts were allowed to react with immobilized venom before the subsequent addition of antivenom antibody. Venom components affected by exposure to the extracts, unable to interact with their specific antibody, were predicted to be unable to bind to their native destinations or natural receptors. Curcuma cf. zedoaria, an old Thai medicinal plant, showed clear inhibitory activity in the ELISA test. Neurotoxin and protein degradative enzymes, major components in venom, were identified as targets of this extract in Western immunoblotting analysis. Ingredients in the extract showed high affinity to the toxin in competition assay by immunoprecipitation. The extract attenuated toxin activity by extending contraction time of diaphragm muscle after envenomation and had a potency to protect cellular proteins from venom degradative enzymes. Curcuma parviflora, with less activity in ELISA, exhibited acceptable results in two experiments but negative results in two experiments, whereas Curcuma longa, having low activity in the ELISA test, never showed any favorable results. Screening of 36 samples could classify plants into an inhibition range of 0 to 86%. This modified ELISA is recommended as a preliminary screening method for inhibitors with a large number of samples. PMID:15907878

  4. Hematology and plasma biochemistry of wild-caught Indian cobra Naja naja (Linnaeus, 1758)

    PubMed Central

    2014-01-01

    Background Hematology and plasma biochemistry parameters are useful in the assessment and management of snake physiological status. Although reference ranges are readily available for many snake species, they are lacking for most venomous ophidians. We determined hematology and plasma biochemistry reference ranges for the wild-caught Indian cobra, Naja naja. Results Blood samples, taken from the ventral tail vein, were assessed for erythrocyte count, total leukocyte count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration, considering the sex of snakes. Results revealed the erythrocyte numbers (male, 390000 ± 12503.33/mm3 and female, 347500 ± 7505.55/mm3), shapes and the centrally located oval nuclei. Leukocytes were round, circular or disk-shaped, and the mean size was larger in male than female snakes. The maximum number of leukocytes was found to be 11700 ± 100/mm3 in male and 12100 ± 200/mm3 in female snakes, and mean values of differential leukocyte count differed statistically between male and female snakes. The total leukocyte levels were found to be higher in female snakes, but the levels of hemoglobin, hematocrit, and MCV values were higher in male snakes. However, the MCH and MCHC values remained higher in female snakes throughout the study period. Mean protein and cholesterol contents differed significantly between male (45.32 ± 1.76 and 3.76 ± 0.06 mg/mL) and female (12.47 ± 0.82 and 4.72 ± 0.2 mg/mL) snakes. Conclusions In conclusion, monitoring snake hematological and biochemical parameters can serve as a means to evaluate the physiological and health status of N. naja populations, which may be a useful indicator of their environmental status. PMID:24735569

  5. Black cobra (Naja naja karachiensis) lysates exhibit broad-spectrum antimicrobial activities

    PubMed Central

    Sagheer, Mehwish; Siddiqui, Ruqaiyyah; Iqbal, Junaid; Khan, Naveed Ahmed

    2014-01-01

    It is hypothesized that animals living in polluted environments possess antimicrobials to counter pathogenic microbes. The fact that snakes feed on germ-infested rodents suggests that they encounter pathogenic microbes and likely possess antimicrobials. The venom is used only to paralyze the rodent, but the ability of snakes to counter potential infections in the gut due to disease-ridden rodents requires robust action of the immune system against a broad range of pathogens. To test this hypothesis, crude lysates of different organs of Naja naja karachiensis (black cobra) were tested for antimicrobial properties. The antimicrobial activities of extracts were tested against selected bacterial pathogens (neuropathogenic Escherichia coli K1, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Streptococcus pneumonia), protist (Acanthamoeba castellanii), and filamentous fungus (Fusarium solani). The findings revealed that plasma and various organ extracts of N. n. karachiensis exhibited antimicrobial activity against E. coli K1, MRSA, P. aeruginosa, S. pneumoniae, A. castellanii, and F. solani in a concentration-dependent manner. The results of this study are promising for the development of new antimicrobials. PMID:24625321

  6. Culturable Aerobic and Facultative Anaerobic Intestinal Bacterial Flora of Black Cobra (Naja naja karachiensis) in Southern Pakistan

    PubMed Central

    Iqbal, Junaid; Sagheer, Mehwish; Tabassum, Nazneen; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2014-01-01

    Using morphological analysis and biochemical testing, here for the first time, we determined the culturable gut bacterial flora (aerobes and facultative anaerobes) in the venomous Black Cobra (Naja naja karachiensis) from South Asia. The findings revealed that these snakes inhabit potentially pathogenic bacteria including Serratia marcescens, Pseudomonas aeruginosa, Shewanella putrefaciens, Aeromonas hydrophila, Salmonella sp., Moraxella sp., Bacillus sp., Ochrobactrum anthropi, and Providencia rettgeri. These findings are of concern, as injury from snake bite can result in wound infections and tissue necrosis leading to sepsis/necrotizing fasciitis and/or expose consumers of snake meat/medicine in the community to infections. PMID:25002979

  7. Culturable Aerobic and Facultative Anaerobic Intestinal Bacterial Flora of Black Cobra (Naja naja karachiensis) in Southern Pakistan.

    PubMed

    Iqbal, Junaid; Sagheer, Mehwish; Tabassum, Nazneen; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2014-01-01

    Using morphological analysis and biochemical testing, here for the first time, we determined the culturable gut bacterial flora (aerobes and facultative anaerobes) in the venomous Black Cobra (Naja naja karachiensis) from South Asia. The findings revealed that these snakes inhabit potentially pathogenic bacteria including Serratia marcescens, Pseudomonas aeruginosa, Shewanella putrefaciens, Aeromonas hydrophila, Salmonella sp., Moraxella sp., Bacillus sp., Ochrobactrum anthropi, and Providencia rettgeri. These findings are of concern, as injury from snake bite can result in wound infections and tissue necrosis leading to sepsis/necrotizing fasciitis and/or expose consumers of snake meat/medicine in the community to infections. PMID:25002979

  8. Fibrinogenolytic toxin from Indian monocled cobra (Naja kaouthia) venom.

    PubMed

    Sekhar, C Chandra; Chakrabarty, Dibakar

    2011-06-01

    A fibrinogenolytic toxin of molecular weight 6.5 kDa has been purified from the venom of Indian monocled cobra (Naja kaouthia) by repeated cation exchange chromatography on CM-sephadex C-50. The purified toxin did not show any phospholipase activity but was mildly hemolytic on human erythrocytes. This toxin, called Lahirin, cleaved fibrinogen in a dose- and time-dependent manner. The digestion process apparently started with the A alpha chain, and gradually other lower-molecular-weight chains were also cleaved to low-molecular-weight peptides. The fibrinolytic activity was completely lost after treatment with ethylene di-amine tetra acetic acid (EDTA). However, exposure to 100 degree C for 1 min or pre-treatment with phenyl methyl sulfonyl fluoride (PMSF) did not affect the fibrinolytic activity. Cleavage of di-sulphide bonds by beta-mercaptoethanol or unfolding the protein with 4 M urea caused complete loss of activity of pure Lahirin. PMID:21654088

  9. Unfolding stabilities of two paralogous proteins from Naja naja naja (Indian cobra) as probed by molecular dynamics simulations.

    PubMed

    Gorai, Biswajit; Sivaraman, Thirunavukkarasu

    2013-09-01

    Structurally similar but functionally different two paralogous proteins, CTX1 (a cardiotoxin) and LNTX2 (an alpha-neurotoxin), from venom of Naja naja naja have been homology modeled and subjected to molecular dynamics (MD) simulations at four different temperatures (298 K, 310 K, 373 K & 473 K) under close quarters of physiological conditions. Each MD simulation was performed for 25 ns and trajectory structures stored at every 25 ps were used to probe various structural events occurring in the temperature-induced unfolding of the proteins. Notwithstanding their similar scaffolds, the two proteins are drastically differing in their unfolding stabilities from each other. The structural orders of flexibilities for the CTX1 and LNTX2 were found to be loop II > loop III > loop I > C-terminal and C-terminal > loop I > loop III > loop II, respectively. Based on the comprehensive analyses of the simulation data and studies on the various structural interactions of all cardiotoxins (CTXs) and alpha-neurotoxins (NTXs) for which three-dimensional structures determined by experimental techniques are available to date, we have herein proposed a hypothesis ('CN network') rationalizing the differential stabilities of the CTXs and NTXs belonging to a three-finger toxin superfamily of snake venoms. PMID:23791667

  10. Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization.

    PubMed

    Wong, Kin Ying; Tan, Choo Hock; Tan, Nget Hong

    2016-06-01

    Geographical variations of snake venoms can result in suboptimal effectiveness of Indian antivenoms that are currently used in most South Asian countries. This study investigated the toxicity and neutralization profile of the venom and toxins from Pakistani spectacled cobra, Naja naja, using VINS polyvalent antivenom (VPAV, India), Naja kaouthia monovalent antivenom (NKMAV, Thailand), and neuro bivalent antivenom (NBAV, Taiwan). Cation-exchange and reverse-phase high-performance liquid chromatography fractionations followed by toxin identification through liquid chromatography-mass spectrometry (MS)/MS indicated that the venom comprised mainly of postsynaptic neurotoxins (NTXs) (long neurotoxins [LNTXs], 28.3%; short neurotoxins [SNTXs], 8%), cytotoxins (CTXs) (31.2%), and acidic phospholipases A2 (12.3%). NKMAV is the most effective in neutralizing the lethal effect of the venom (potency = 1.1 mg venom/mL) and its LNTX (potency = 0.5 mg toxin/mL), consistent with the high content of LNTX in N. kaouthia venom. VPAV was effective in neutralizing the CTX (potency = 0.4 mg toxin/mL), in agreement with the higher CTX abundance in Indian cobra venom. All the three antivenoms were weak in neutralizing the SNTX (potency = 0.03-0.04 mg toxin/mL), including NBAV that was raised from the SNTX-rich Taiwanese cobra venom. In a challenge-rescue experiment, envenomed mice were prevented from death by a maximal dose of VPAV (intravenous 200 μL) but the recovery from paralysis was slow, indicating the need for higher or repeated doses of VPAV. Our results suggest that optimal neutralization for Pakistani N. naja venom may be achieved by improving the formulation of antivenom production to enhance antivenom immunoreactivity against long and SNTXs. PMID:27022154

  11. Antihaemorrhagic potentials of Fagonia cretica against Naja naja karachiensis (black Pakistan cobra) venom.

    PubMed

    Razi, Muhammad Tahir; Asad, Muhammad Hassham Hassan Bin; Khan, Taous; Chaudhary, Muhammad Zabta; Ansari, Muhammad Tayyab; Arshad, Muhammad Anwar; Saqib, Qazi Najam-us

    2011-12-01

    Plants have been extensively used as a remedy for the treatment of snake bites. The aim of this study was to determine the antivenom potentials of methanolic extract from the aerial parts (leaves and twigs) of Fagonia cretica L. on a haemorrhage induced by venom from Naja naja karachiensis. The haemorrhagic response of venom was dose dependent from 0.1 to 4.0 µg per 1.5 µL phosphate buffer saline (PBS) on vitelline veins of fertilised hens' eggs in their shells. The extract effectively eliminated and neutralised, in a dose-dependent manner, the haemorrhagic activity of snake venom. The minimum effective neutralising dose of F. cretica extract was found to be 15 µg per 1.5 µL PBS. The extract possesses potentials as haemorrhagic inhibitor against snake venom compared to the standard antiserum and various plants reported in the literature. This study also provides a scientific base for the use of F. cretica in traditional medicine for the treatment of snake bite. PMID:21656416

  12. Cross-Reactivity against Naja sumatrana (Black Spitting Cobra) Envenoming from the Haffkine Antivenom in a Mouse Model

    PubMed Central

    Lim, Francis; Earnest, Arul; Gopalakrishnakone, Ponnampalam

    2013-01-01

    Naja sumatrana is the dominant cobra species in Malaysia, Singapore, Borneo, and Sumatra, and it does not have specific antivenom. The Haffkine antivenom has been advocated instead. This study aims to determine the efficacy of this antivenom against Naja sumatrana envenoming using a mouse model. Methods. Male Swiss albino mice were used. Intravenous LD50 was first determined separately for Naja naja and Naja sumatrana venom. ED50 was determined by preincubating antivenom with each venom at 2.5 LD50 before administering the mixture into the tail vein. Validation was carried out using a challenge test. Each mouse received 111 µg of Naja sumatrana venom intramuscularly followed by intraperitoneal administration of dilute Haffkine antivenom. Survival was recorded 24 hours after envenoming. Results. The LD50 of Naja naja venom was 78.13 µg, standard error (SE) 13.3 µg. The ED50 of the Haffkine antivenom against Naja naja venom was 45.9 mg, SE 7.5 mg. The LD50 and ED50 of Naja sumatrana venom were 55.5 µg, SE 12.0 µg; and 73.9 mg, SE 12.0 mg, respectively. The intra-peritoneal ED50 against 111 µg intramuscular Naja sumatrana venom was 136.95 mg, SE 36.74 mg. Conclusion. The Haffkine polyvalent antivenom exhibited cross-neutralisation against Naja sumatrana venom when used at a higher dose. PMID:23997967

  13. Naja naja oxiana Cobra Venom Cytotoxins CTI and CTII Disrupt Mitochondrial Membrane Integrity: Implications for Basic Three-Fingered Cytotoxins

    PubMed Central

    Gasanov, Sardar E.; Shrivastava, Indira H.; Israilov, Firuz S.; Kim, Aleksandr A.; Rylova, Kamila A.; Zhang, Boris; Dagda, Ruben K.

    2015-01-01

    Cobra venom cytotoxins are basic three-fingered, amphipathic, non-enzymatic proteins that constitute a major fraction of cobra venom. While cytotoxins cause mitochondrial dysfunction in different cell types, the mechanisms by which cytotoxins bind to mitochondria remain unknown. We analyzed the abilities of CTI and CTII, S-type and P-type cytotoxins from Naja naja oxiana respectively, to associate with isolated mitochondrial fractions or with model membranes that simulate the mitochondrial lipid environment by using a myriad of biophysical techniques. Phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy data suggest that both cytotoxins bind to isolated mitochondrial fractions and promote the formation of aberrant non-bilayer structures. We then hypothesized that CTI and CTII bind to cardiolipin (CL) to disrupt mitochondrial membranes. Collectively, 31P-NMR, electron paramagnetic resonance (EPR), proton NMR (1H-NMR), deuterium NMR (2H-NMR) spectroscopy, differential scanning calorimetry, and erythrosine phosphorescence assays suggest that CTI and CTII bind to CL to generate non-bilayer structures and promote the permeabilization, dehydration and fusion of large unilamellar phosphatidylcholine (PC) liposomes enriched with CL. On the other hand, CTII but not CTI caused biophysical alterations of large unilamellar PC liposomes enriched with phosphatidylserine (PS). Mechanistically, single molecule docking simulations identified putative CL, PS and PC binding sites in CTI and CTII. While the predicted binding sites for PS and PC share a high number of interactive amino acid residues in CTI and CTII, the CL biding sites in CTII and CTI are more divergent as it contains additional interactive amino acid residues. Overall, our data suggest that cytotoxins physically associate with mitochondrial membranes by binding to CL to disrupt mitochondrial structural integrity. PMID:26091109

  14. Anti arthritic and anti inflammatory activity of a cytotoxic protein NN-32 from Indian spectacle cobra (Naja naja) venom in male albino rats.

    PubMed

    Gomes, Antony; Datta, Poulami; Das, Tanaya; Biswas, Ajoy Kumar; Gomes, Aparna

    2014-11-01

    The anti arthritic and anti inflammatory activity of NN-32, a cytotoxic protein from Indian spectacle cobra snake (Naja naja) venom has been studied in Freund's complete adjuvant (FCA) induced arthritis and carrageenan induced anti inflammatory model. NN-32 treatment showed significant decrease in physical and urinary parameters, serum enzymes, serum cytokines levels as compared to arthritic control group of rats. NN-32 treatment recovered carrageenan induced inflammation as compared to control group of rats. The findings showed that the cytotoxic protein NN-32 shares anti arthritic and anti inflammatory activity and thus NN-32 may target complex pathophysiological processes like cancer- arthritis-inflammation. PMID:25026566

  15. Post-ovipositional development of the monocled cobra, Naja kaouthia (Serpentes: Elapidae).

    PubMed

    Jackson, Kate

    2002-01-01

    External morphological development between oviposition and hatching of the monocled cobra, Naja kaouthia, is described. Ten developmental stages are diagnosed according to nine features. These include fusion of the body wall musculature along the ventral midline, appearance of the endolymphatic ducts, formation of the eyelid, and the appearance of scales on the head and body. Additional observations of the developing skull are made at four of these ten stages, based on cleared and stained heads. PMID:16351869

  16. Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation.

    PubMed

    Lewin, Matthew R; Samuel, Stephen P; Wexler, David S; Bickler, Philip; Vaiyapuri, Sakthivel; Mensh, Brett D

    2014-01-01

    Objective. Most snakebite deaths occur prior to hospital arrival; yet inexpensive, effective, and easy to administer out-of-hospital treatments do not exist. Acetylcholinesterase inhibitors can be therapeutic in neurotoxic envenomations when administered intravenously, but nasally delivered drugs could facilitate prehospital therapy for these patients. We tested the feasibility of this idea in experimentally envenomed mice. Methods. Mice received intraperitoneal injections of Naja naja venom 2.5 to 10 times the estimated LD50 and then received 5  μ L neostigmine (0.5 mg/mL) or 5  μ L normal saline by nasal administration. Animals were observed up to 12 hours and survivors were euthanized. Results. 100% of control mice died. Untreated mice injected with 2.5× LD50 Naja naja died at average 193 minutes after injection, while 10 of 15 (67%) of treated mice survived and were behaviorally normal by 6 hours (P < 0.02). In the 5× LD50 group, survival was prolonged from 45 minutes to 196 minutes (P = 0.01) and for 10× LD50 mice, survival increased from 30 to 175 minutes (P < 0.02). Conclusion. This pilot suggests that intranasal drugs can improve survival and is the first direct demonstration that such an approach is plausible, suggesting means by which treatment could be initiated before reaching the hospital. Further investigation of this approach to neurotoxic and other types of envenomation is warranted. PMID:24955095

  17. Early Treatment with Intranasal Neostigmine Reduces Mortality in a Mouse Model of Naja naja (Indian Cobra) Envenomation

    PubMed Central

    Lewin, Matthew R.; Samuel, Stephen P.; Wexler, David S.; Bickler, Philip; Vaiyapuri, Sakthivel; Mensh, Brett D.

    2014-01-01

    Objective. Most snakebite deaths occur prior to hospital arrival; yet inexpensive, effective, and easy to administer out-of-hospital treatments do not exist. Acetylcholinesterase inhibitors can be therapeutic in neurotoxic envenomations when administered intravenously, but nasally delivered drugs could facilitate prehospital therapy for these patients. We tested the feasibility of this idea in experimentally envenomed mice. Methods. Mice received intraperitoneal injections of Naja naja venom 2.5 to 10 times the estimated LD50 and then received 5 μL neostigmine (0.5 mg/mL) or 5 μL normal saline by nasal administration. Animals were observed up to 12 hours and survivors were euthanized. Results. 100% of control mice died. Untreated mice injected with 2.5× LD50 Naja naja died at average 193 minutes after injection, while 10 of 15 (67%) of treated mice survived and were behaviorally normal by 6 hours (P < 0.02). In the 5× LD50 group, survival was prolonged from 45 minutes to 196 minutes (P = 0.01) and for 10× LD50 mice, survival increased from 30 to 175 minutes (P < 0.02). Conclusion. This pilot suggests that intranasal drugs can improve survival and is the first direct demonstration that such an approach is plausible, suggesting means by which treatment could be initiated before reaching the hospital. Further investigation of this approach to neurotoxic and other types of envenomation is warranted. PMID:24955095

  18. The Antimicrobial Activity of an Acidic Phospholipase A₂ (NN-XIa-PLA₂) from the Venom of Naja naja naja (Indian Cobra).

    PubMed

    Sudarshan, S; Dhananjaya, B L

    2015-08-01

    Microbial resistance against antibiotics is considered as a potentially serious threat to public health. Therefore, there is much interest in developing new molecules with novel modes of action. In this study, when antimicrobial potential of an acidic protein-NN-XIa-PLA2 (Naja naja venom phospholipase A2 fraction-XIa) of N. naja venom was evaluated, it demonstrated potent bactericidal action against the human pathogenic strains. It inhibited more significantly, the gram-positive bacteria, when compared to gram-negative bacteria. The minimum inhibitory concentration (MIC) values ranged from 17 to 20 μg/ml. It was interesting to observe that the NN-XIa-PLA2 showed comparable antibacterial activity to the standard antibiotics used. It was found that there was a strong correlation between phospholipase A2 (PLA2) activities, hemolytic, and antimicrobial activity. Further, it is found that in the presence of p-bromophenacyl bromide (p-BPB), there is a significant decrease in enzymatic activity and associated antimicrobial activities, suggesting that a strong correlation exists between catalytic activity and antimicrobial effects, which thereby destabilize the membrane bilayer. However, other mechanisms cannot be completely ruled out. Thus, these studies encourage further in-depth study on molecular mechanisms of antibacterial properties and thereby help in development of this protein into a possible therapeutic lead molecule for treating bacterial infections. PMID:26109249

  19. Comparison of the primary structures, cytotoxicities, and affinities to phospholipids of five kinds of cytotoxins from the venom of Indian cobra, Naja naja.

    PubMed

    Suzuki-Matsubara, Mieko; Athauda, Senarath B P; Suzuki, Yoshiyuki; Matsubara, Kazumi; Moriyama, Akihiko

    2016-01-01

    The molecular mechanism underlying the hemolytic and cytolytic processes of cobra cytotoxins (CTXs) is not yet fully elucidated. To examine this, we analyzed the amino acid sequences, hemolytic and cytotoxic activities, and affinities to phospholipids of the five major CTXs purified from the venom of Indian cobra, Naja naja. CTX2, CTX7, and CTX8 belonged to S-type, and CTX9 and CTX10 to P-type. Comparisons of CTX7 with CTX8 and CTX9 with CTX10 revealed similar primary structures and hemolytic and cytolytic activities. CTX2, whose primary structure was rather different from the others, showed several times weaker hemolytic and cytolytic biological activities than the others. The comparison of CTX2 with CTX7 suggested the importance of Lys30 in loop II for the strong hemolytic and cytolytic activities of S-type CTXs. Cloning of 12 CTX cDNAs from the Naja naja venom cDNA library revealed that 18 out of 23 substitutions found in CTX cDNAs were nonsynonymous. This clearly indicated the accelerated evolution of CTX genes. Multiple sequence alignment of 51 kinds of CTX cDNAs and calculations of nonsynonymous and synonymous substitutions indicated that the codons coding the three loops' regions, which may interact with the hydrophobic tails of phospholipids, have undergone an accelerated evolution. In contrast, the codons coding for amino acid residues considered to participate in the recognition and binding of the hydrophilic head groups of phospholipids, eight Cys residues, and those likely stabilizing β core structure, were all conserved. PMID:26456928

  20. The Development of the Skull of the Egyptian Cobra Naja h. haje (Squamata: Serpentes: Elapidae)

    PubMed Central

    Khannoon, Eraqi R.; Evans, Susan E.

    2015-01-01

    Background The study of craniofacial development is important in understanding the ontogenetic processes behind morphological diversity. A complete morphological description of the embryonic skull development of the Egyptian cobra, Naja h. haje, is lacking and there has been little comparative discussion of skull development either among elapid snakes or between them and other snakes. Methodology/Principal Findings We present a description of skull development through a full sequence of developmental stages of the Egyptian cobra, and compare it to other snakes. Associated soft tissues of the head are noted where relevant. The first visible ossification centres are in the supratemporal, prearticular and surangular, with slight ossification visible in parts of the maxilla, prefrontal, and dentary. Epiotic centres of ossification are present in the supraoccipital, and the body of the supraoccipital forms from the tectum posterior not the tectum synoticum. The venom glands are visible as distinct bodies as early at stage 5 and enlarge later to extend from the otic capsule to the maxilla level with the anterior margin of the eye. The gland becomes more prominent shortly before hatching, concomitant with the development of the fangs. The tongue shows incipient forking at stage 5, and becomes fully bifid at stage 6. Conclusions/Significance We present the first detailed staging series of cranial development for the Egyptian cobra, Naja h. haje. This is one of the first studies since the classical works of G. de Beer and W. Parker that provides a detailed description of cranial development in an advanced snake species. It allows us to correct errors and misinterpretations in previous accounts which were based on a small sample of specimens of uncertain age. Our results highlight potentially significant variation in supraoccipital formation among squamates and the need for further research in this area. PMID:25860015

  1. Improved method for the isolation, characterization and examination of neuromuscular and toxic properties of selected polypeptide fractions from the crude venom of the Taiwan cobra Naja naja atra.

    PubMed

    Ständker, L; Harvey, A L; Fürst, S; Mathes, I; Forssmann, W G; Escalona de Motta, G; Béress, L

    2012-09-15

    An improved chromatographic method was developed to isolate and purify polypeptides and proteins from the crude venom of the Taiwan cobra Naja naja atra. The procedure devised is simple, easy to reproduce, and enables large scale isolation of almost all polypeptides and proteins in this cobra venom. Six pure polypeptide fractions of the venom were isolated and characterized using gel filtration on Sephadex G50 (medium), ion exchange chromatography on SP-Sephadex C25, desalting on Sephadex G25 (fine) and preparative HPLC on a RPC 18 column. The neuromuscular activity of these fractions was tested on the chick biventer cervicis nerve-muscle preparation and their toxicity (LD(50)) was determined after i.v. administration in mice. Their antinociceptive activity was tested in the mouse abdominal test by i.v. application. Two of these polypeptide samples had major physiological effects: one acted as a cardiotoxin causing reversible myocardial contractures with no effect on muscle twitches elicited by nerve stimulation (NS); another was a neurotoxin that blocked muscle contractions in response to NS and exogenously added acetylcholine. The cardiotoxic fraction was identified as CTX I, a well-known cardiotoxin present in this venom, and the neurotoxin was identified as neurotoxin-α with an LD50 in mice of 0.075 mg/kg. PMID:22677803

  2. An analysis of venom ontogeny and prey-specific toxicity in the Monocled Cobra (Naja kaouthia).

    PubMed

    Modahl, Cassandra M; Mukherjee, Ashis K; Mackessy, Stephen P

    2016-09-01

    Venoms of snakes of the family Elapidae (cobras, kraits, mambas, and relatives) are predominantly composed of numerous phospholipases A2 (PLA2s) and three-finger toxins (3FTxs), some of which are lethal while others are not significantly toxic. Currently, the only identified prey-specific toxins are several nonconventional 3FTxs, and given the large diversity of 3FTxs within Monocled Cobra (Naja kaouthia) venom, it was hypothesized that several 3FTxs, previously found to be non-toxic or weakly toxic 3FTxs in murine models, could potentially be toxic towards non-murine prey. Additionally, it was hypothesized that ontogenetic dietary shifts will be correlated with observable changes in specific 3FTx isoform abundance. Adult and juvenile N. kaouthia venom composition was investigated using ion-exchange FPLC, 1D and 2D SDS-PAGE, mass spectrometry, and various enzymatic and LD50 assays. Alpha-cobratoxin (α-elapitoxin) was the only significantly toxic (LD50 < 1 μg/g) 3FTx found in N. kaouthia venom and was equally toxic toward both lizard and mouse models. The abundance and diversity of 3FTxs and most enzyme activities did not vary between adult and juvenile cobra venoms; however, total venom PLA2 activity and specific PLA2 isoforms did vary, with juveniles lacking several of the least acidic PLA2s, and these differences could have both biological (related to predation) and clinical (antivenom efficacy) implications. Nevertheless, the ubiquitous presence of α-cobratoxin in both adult and juvenile cobra venoms, with high toxicity toward both reptiles and mammals, represents a venom compositional strategy wherein a single potent toxin effectively immobilizes a variety of prey types encountered across life history stages. PMID:27163885

  3. Phospholipase A2-interacting weak neurotoxins from venom of monocled cobra Naja kaouthia display cell-specific cytotoxicity.

    PubMed

    Mukherjee, Ashis K

    2008-06-15

    The molecular weights of two phospholipase A(2) (PLA(2))-interacting polypeptides (kaouthiotoxins (KTXs)-KTX-A and KTX-B) purified from the venom of monocled cobra Naja kaouthia, were estimated by mass spectrometry as 7722 and 7627Da, respectively. Binary sequence alignment showed that both KTXs share substantial sequence homology with weak neurotoxins from cobra venom and they were devoid of any enzymatic activity. Their pI was determined at pH 8.1 showing basic nature of these proteins. KTXs displayed cell-specific cytotoxicity on mammalian and insect cells. PMID:18456298

  4. Characterization of monoclonal antibodies against Naja naja oxiana neurotoxin I.

    PubMed

    Stiles, B G; Sexton, F W; Guest, S B; Olson, M A; Hack, D C

    1994-10-01

    Seven monoclonal antibodies (mAbs) were developed against neurotoxin I (NT-1), a protein from central Asian cobra (Naja naja oxiana) venom which binds specifically to nicotinic acetylcholine receptor (AchR). All of the mAbs cross-reacted with another long-chain post-synaptic neurotoxin, Bungarus multicinctus alpha-bungarotoxin (alpha-BT), but not Naja naja kaouthia alpha-cobratoxin, in an enzyme-linked immunosorbent assay (e.l.i.s.a.). Short-chain post-synaptic neurotoxins like Naja naja atra cobrotoxin, Laticauda semifasciata erabutoxin b, or N. n. oxiana neurotoxin II did not cross-react with the NT-1 mAbs, but an antigen(s) found in Dendroaspis polylepis, Acanthophis antarcticus and Pseudechis australis venoms was immunoreactive. The e.l.i.s.a. readings for dithiothreitol-reduced NT-1 and NT-1 mAbs ranged from 13 to 27% of those for native toxin but reduced alpha-BT was not immunoreactive. Synthetic NT-1 peptides were used in epitope-mapping studies and two, non-contiguous regions (Cys15-Tyr23 and Lys25-Gly33 or Pro17-Lys25 and Asp29-Lys37) were recognized by the NT-1 mAbs. The NT-1 mAbs individually inhibited 31-71% of alpha-BT binding to AchR in vitro and afforded a slight protective effect in vivo with a toxin: antibody mole ratio of 1:1.5. This report is the first to describe mAbs which recognize and protect against a heterologous, long-chain, post-synaptic neurotoxin from snake venom. PMID:7945236

  5. Characterization of monoclonal antibodies against Naja naja oxiana neurotoxin I.

    PubMed Central

    Stiles, B G; Sexton, F W; Guest, S B; Olson, M A; Hack, D C

    1994-01-01

    Seven monoclonal antibodies (mAbs) were developed against neurotoxin I (NT-1), a protein from central Asian cobra (Naja naja oxiana) venom which binds specifically to nicotinic acetylcholine receptor (AchR). All of the mAbs cross-reacted with another long-chain post-synaptic neurotoxin, Bungarus multicinctus alpha-bungarotoxin (alpha-BT), but not Naja naja kaouthia alpha-cobratoxin, in an enzyme-linked immunosorbent assay (e.l.i.s.a.). Short-chain post-synaptic neurotoxins like Naja naja atra cobrotoxin, Laticauda semifasciata erabutoxin b, or N. n. oxiana neurotoxin II did not cross-react with the NT-1 mAbs, but an antigen(s) found in Dendroaspis polylepis, Acanthophis antarcticus and Pseudechis australis venoms was immunoreactive. The e.l.i.s.a. readings for dithiothreitol-reduced NT-1 and NT-1 mAbs ranged from 13 to 27% of those for native toxin but reduced alpha-BT was not immunoreactive. Synthetic NT-1 peptides were used in epitope-mapping studies and two, non-contiguous regions (Cys15-Tyr23 and Lys25-Gly33 or Pro17-Lys25 and Asp29-Lys37) were recognized by the NT-1 mAbs. The NT-1 mAbs individually inhibited 31-71% of alpha-BT binding to AchR in vitro and afforded a slight protective effect in vivo with a toxin: antibody mole ratio of 1:1.5. This report is the first to describe mAbs which recognize and protect against a heterologous, long-chain, post-synaptic neurotoxin from snake venom. PMID:7945236

  6. Purification and characterization of an anticoagulant phospholipase A(2) from Indian monocled cobra (Naja kaouthia) venom.

    PubMed

    Doley, Robin; Mukherjee, Ashis Kumar

    2003-01-01

    An anticoagulant, non-toxic phospholipase A(2) was isolated from the venom of Indian monocled cobra (Naja kaouthia) by a combination of ion-exchange chromatography on CM-Sephadex C-50 and gel filtration on Sephadex G-50. This purified protein named NK-PLA(2)-I, had a subunit molecular mass of 13.6 kDa and migrated as a dimer under non-reduced condition in SDS-PAGE. NK-PLA(2)-I was a highly thermostable protein requiring basic pH optima for its catalytic activity and showed preferential hydrolysis of phosphotidylcholine. This protein exhibited higher anticoagulant, indirect hemolysis, liver and heart tissue damaging activity but exerted less toxicity, direct hemolysis, edema and lung tissue damaging activity as compared to whole venom. Treatment of NK-PLA(2)-I with rho-BPB, TPCK, PMSF, antivenom and heating had almost equal effect on PLA(2), and other pharmacological properties except in vitro tissue damaging activity. Current investigation provides a fairly good indication that NK-PLA(2)-I induces various pharmacological effects by mechanisms, which are either dependent or independent of its catalytic activity. PMID:12467665

  7. Unique features of myogenesis in Egyptian cobra (Naja haje) (Squamata: Serpentes: Elapidae).

    PubMed

    Khannoon, Eraqi R; Rupik, Weronika; Lewandowski, Damian; Dubińska-Magiera, Magda; Swadźba, Elwira; Daczewska, Małgorzata

    2016-03-01

    During early stages of myotomal myogenesis, the myotome of Egyptian cobra (Naja haje) is composed of homogenous populations of mononucleated primary myotubes. At later developmental phase, primary myotubes are accompanied by closely adhering mononucleated cells. Based on localization and morphology, we assume that mononucleated cells share features with satellite cells involved in muscle growth. An indirect morphological evidence of the fusion of mononucleated cells with myotubes is the presence of numerous vesicles in the subsarcolemmal region of myotubes adjacent to mononucleated cell. As differentiation proceeded, secondary muscle fibres appeared with considerably smaller diameter as compared to primary muscle fibre. Studies on N. haje myotomal myogenesis revealed some unique features of muscle differentiation. TEM analysis showed in the N. haje myotomes two classes of muscle fibres. The first class was characterized by typical for fast muscle fibres regular distribution of myofibrils which fill the whole volume of muscle fibre sarcoplasm. White muscle fibres in studied species were a prominent group of muscles in the myotome. The second class showed tightly paced myofibrils surrounding the centrally located nucleus accompanied by numerous vesicles of different diameter. The sarcoplasm of these cells was characterized by numerous lipid droplets. Based on morphological features, we believe that muscle capable of lipid storage belong to slow muscle fibres and the presence of lipid droplets in the sarcoplasm of these muscles during myogenesis might be a crucial adaptive mechanisms for subsequent hibernation in adults. This phenomenon was, for the first time, described in studies on N. haje myogenesis. PMID:26025263

  8. [Fibrinogen/fibrin-specific enzymes from copperhead (Agkistrodon halys halys) and cobra (Naja oxiana eichwald) snake venoms].

    PubMed

    Yunusova, E S; Sadykov, E S; Sultanalieva, N M; Shkinev, A V

    2016-03-01

    Ability of fractions of cobra's (Naja oxiana Eichwald) and copperhead snake's (Agkistrodon halys halys) venoms to hydrolyze fibrinogen/fibrin was studied. In cobra's snake a component with molecular mass of nearly 60 kDa was found to hydrolyze a-chain of fibrinogen but failed to hydrolyze casein/azocasein and fibrin. A fibrinogen-specific metalloproteinase, the enzyme was inhibited by EDTA. Cobra's venom reduced the mass of donor's fresh blood clots. The copperhead snake's venom and the fractions obtained by gel-filtration (HW-50) and ion exchange chromatography (DEAE-650) were found to hydrolyze casein/azocasein, a- and b-chains of fibrinogen/fibrin and donor's blood clots. The results from the study of the venom and proteolytically active fractions are the evidence for a thrombolytic potential in a copperhead snake's venom. PMID:27420616

  9. The first representative of glycosylated three-fingered toxins. Cytotoxin from the Naja kaouthia cobra venom.

    PubMed

    Osipov, Alexey V; Astapova, Maria V; Tsetlin, Victor I; Utkin, Yuri N

    2004-05-01

    There are different glycosylated proteins in snake venoms, but no glycosylated representatives of a large family of three-fingered toxins have previously been detected. A new glycoprotein was isolated from the venom of the Thai cobra Naja kaouthia. MALDI MS of the glycoprotein contained an array of peaks in the range from approximately 8900 to approximately 9400 Da indicating its microheterogeneity. Carbohydrate analysis showed the presence of mannose, galactose, N-acetylglucosamine, fucose and neuraminic acid. The N-terminal sequence of the glycoprotein was identical to that of cytotoxin 3 (CX3) from N. kaouthia, and CD spectra of the glycoprotein and CX3 were almost the same. Cleavage of a glycan moiety by N-glycosidase F gave a protein of molecular mass practically coinciding with that of CX3. MALDI MS of the tryptic digest of reduced glycoprotein S-pyridylethylated at cysteine residues, contained peaks corresponding to all tryptic fragments of CX3, with the exception of fragment 24-30. The peak corresponding to this peptide appeared in the mass-spectrum of similarly treated deglycosylated glycoprotein. These data show that the potential N-glycosylation site at Asn29 in CX3 is utilized for glycan attachment and that the glycoprotein is glycosylated CX3. In vivo toxicity of the glycoprotein to the cricket Gryllus assimilis was twofold lower than that of CX3. The cytotoxic activity of the glycoprotein towards HL60 cells was about two orders of magnitude lower than that of CX3, but could be made equal to the CX3 cytotoxicity by deglycosylation. Thus for the first time we have isolated a glycosylated three-fingered snake venom toxin wherein glycosylation appears to modulate its biological activity. PMID:15128311

  10. The protective effects of Mucuna pruriens seed extract against histopathological changes induced by Malayan cobra (Naja sputatrix) venom in rats.

    PubMed

    Fung, S Y; Tan, N H; Liew, S H; Sim, S M; Aguiyi, J C

    2009-04-01

    Seed of Mucuna pruriens (Velvet beans) has been prescribed by traditional medicine practitioners in Nigeria as a prophylactic oral antisnake remedy. In the present studies, we investigated the protective effects of M. pruriens seed extract (MPE) against histopathological changes induced by intravenous injection of Naja sputatrix (Malayan cobra) venom in rats pretreated with the seed extract. Examination by light microscope revealed that the venom induced histopathological changes in heart and blood vessels in liver, but no effect on brain, lung, kidney and spleen. The induced changes were prevented by pretreatment of the rats with MPE. Our results suggest that MPE pretreatment protects rat heart and liver blood vessels against cobra venom-induced damages. PMID:19696731

  11. Antibacterial activity of an acidic phospholipase A2 (NN-XIb-PLA2) from the venom of Naja naja (Indian cobra).

    PubMed

    Sudarshan, S; Dhananjaya, B L

    2016-01-01

    The resistance of bacteria against the use of conventional antibiotics has become a serious threat to public health and considering the associated side effect with antibiotics; new strategies to find and develop new molecules with novel modes of action has received grate attention in recent years. In this study, when the antibacterial potential of an acidic protein-NN-XIb-PLA2 (Naja naja venom phospholipase A2 fraction-XIb) of Naja naja venom was evaluated, it showed significant bactericidal action against the human pathogenic strains tested. It inhibited more effectively the gram positive bacteria like Staphylococcus aureus and Bacillus subtilis, when compared to gram negative bacteria like Escherichia coli, Vibrio cholerae, Klebsiell pneumoniae and Salmonella paratyphi. It inhibited the bacterial growth, with a MIC values ranging from 17 to 20 µg/ml. It was interesting to observe that NN-XIb-PLA2 showed comparable antibacterial activity to the used standards antibiotics. It was found that their was a strong correlation between PLA2 activities, hemolytic and antibacterial activity. Furthermore, it is found that in the presence of p-bromophenacyl bromide (p-BPB), there is a significant decrease in enzymatic activity and associated antibacterial activities, suggesting that a strong association exists between catalytic activity and antimicrobial effects, which thereby destabilize the membrane bilayer. These studies encourage further in dept study on molecular mechanisms of bactericidal properties of NN-XIb-PLA2 and thereby help in development of this protein into a possible therapeutic lead molecule for treating bacterial infections. PMID:26885465

  12. Snake venomics of monocled cobra (Naja kaouthia) and investigation of human IgG response against venom toxins.

    PubMed

    Laustsen, Andreas H; Gutiérrez, José María; Lohse, Brian; Rasmussen, Arne R; Fernández, Julián; Milbo, Christina; Lomonte, Bruno

    2015-06-01

    The venom proteome of the monocled cobra, Naja kaouthia, from Thailand, was characterized by RP-HPLC, SDS-PAGE, and MALDI-TOF-TOF analyses, yielding 38 different proteins that were either identified or assigned to families. Estimation of relative protein abundances revealed that venom is dominated by three-finger toxins (77.5%; including 24.3% cytotoxins and 53.2% neurotoxins) and phospholipases A2 (13.5%). It also contains lower proportions of components belonging to nerve growth factor, ohanin/vespryn, cysteine-rich secretory protein, C-type lectin/lectin-like, nucleotidase, phosphodiesterase, metalloproteinase, l-amino acid oxidase, cobra venom factor, and cytidyltransferase protein families. Small amounts of three nucleosides were also evidenced: adenosine, guanosine, and inosine. The most relevant lethal components, categorized by means of a 'toxicity score', were α-neurotoxins, followed by cytotoxins/cardiotoxins. IgGs isolated from a person who had repeatedly self-immunized with a variety of snake venoms were immunoprofiled by ELISA against all venom fractions. Stronger responses against larger toxins, but lower against the most critical α-neurotoxins were obtained. As expected, no neutralization potential against N. kaouthia venom was therefore detected. Combined, our results display a high level of venom complexity, unveil the most relevant toxins to be neutralized, and provide prospects of discovering human IgGs with toxin neutralizing abilities through use of phage display screening. PMID:25771242

  13. Anti-platelet activity of a three-finger toxin (3FTx) from Indian monocled cobra (Naja kaouthia) venom.

    PubMed

    Chanda, Chandrasekhar; Sarkar, Angshuman; Sistla, Srinivas; Chakrabarty, Dibakar

    2013-11-22

    A low molecular weight anti-platelet peptide (6.9 kDa) has been purified from Naja kaouthia venom and was named KT-6.9. MALDI-TOF/TOF mass spectrometry analysis revealed the homology of KT-6.9 peptide sequence with many three finger toxin family members. KT-6.9 inhibited human platelet aggregation process in a dose dependent manner. It has inhibited ADP, thrombin and arachidonic acid induced platelet aggregation process in dose dependent manner, but did not inhibit collagen and ristocetin induced platelet aggregation. Strong inhibition (70%) of the ADP induced platelet aggregation by KT-6.9 suggests competition with ADP for its receptors on platelet surface. Anti-platelet activity of KT-6.9 was found to be 25 times stronger than that of anti-platelet drug clopidogrel. Binding of KT-6.9 to platelet surface was confirmed by surface plasma resonance analysis using BIAcore X100. Binding was also observed by a modified sandwich ELISA method using anti-KT-6.9 antibodies. KT-6.9 is probably the first 3 FTx from Indian monocled cobra venom reported as a platelet aggregation inhibitor. PMID:24183721

  14. The Phylogeographical Pattern and Conservation of the Chinese Cobra (Naja atra) across Its Range Based on Mitochondrial Control Region Sequences

    PubMed Central

    Lin, Long-Hui; Hua, Lei; Qu, Yan-Fu; Gao, Jian-Fang; Ji, Xiang

    2014-01-01

    The vulnerable Chinese cobra (Naja atra) ranges from southeastern China south of the Yangtze River to northern Vietnam and Laos. Large mountain ranges and water bodies may influence the pattern of genetic diversity of this species. We sequenced the mitochondrial DNA control region (1029 bp) using 285 individuals collected from 23 localities across the species' range and obtained 18 sequences unique to Taiwan from GenBank for phylogenetic and population analysis. Two distinct clades were identified, one including haplotypes from the two westernmost localities (Hekou and Miyi) and the other including haplotypes from all sampling sites except Miyi. A strong population structure was found (Φst = 0.76, P<0.0001) with high haplotype diversity (h = 1.00) and low nucleotide diversity (π = 0.0049). The Luoxiao and Nanling Mountains act as historical geographical barriers limiting gene exchange. In the haplotype network there were two “star” clusters. Haplotypes from populations east of the Luoxiao Mountains were represented within one cluster and haplotypes from populations west of the mountain range within the other, with haplotypes from populations south of the Nanling Mountains in between. Lineage sorting between mainland and island populations is incomplete. It remains unknown as to how much adaptive differentiation there is between population groups or within each group. We caution against long-distance transfers within any group, especially when environmental differences are apparent. PMID:25184236

  15. Structure of N-terminal sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser of Aβ-peptide with phospholipase A2 from venom of Andaman Cobra sub-species Naja naja sagittifera at 2.0 Å resolution.

    PubMed

    Mirza, Zeenat; Pillai, Vikram Gopalakrishna; Zhong, Wei-Zhu

    2014-01-01

    Alzheimer's disease (AD) is one of the most significant social and health burdens of the present century. Plaques formed by extracellular deposits of amyloid β (Aβ) are the prime player of AD's neuropathology. Studies have implicated the varied role of phospholipase A2 (PLA2) in brain where it contributes to neuronal growth and inflammatory response. Overall contour and chemical nature of the substrate-binding channel in the low molecular weight PLA2s are similar. This study involves the reductionist fragment-based approach to understand the structure adopted by N-terminal fragment of Alzheimer's Aβ peptide in its complex with PLA2. In the current communication, we report the structure determined by X-ray crystallography of N-terminal sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser (DAEFRHDS) of Aβ-peptide with a Group I PLA2 purified from venom of Andaman Cobra sub-species Naja naja sagittifera at 2.0 Å resolution (Protein Data Bank (PDB) Code: 3JQ5). This is probably the first attempt to structurally establish interaction between amyloid-β peptide fragment and hydrophobic substrate binding site of PLA2 involving H bond and van der Waals interactions. We speculate that higher affinity between Aβ and PLA2 has the therapeutic potential of decreasing the Aβ-Aβ interaction, thereby reducing the amyloid aggregation and plaque formation in AD. PMID:24619194

  16. Structure of N-Terminal Sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser of Aβ-Peptide with Phospholipase A2 from Venom of Andaman Cobra Sub-Species Naja naja sagittifera at 2.0 Å Resolution

    PubMed Central

    Mirza, Zeenat; Pillai, Vikram Gopalakrishna; Zhong, Wei-Zhu

    2014-01-01

    Alzheimer’s disease (AD) is one of the most significant social and health burdens of the present century. Plaques formed by extracellular deposits of amyloid β (Aβ) are the prime player of AD’s neuropathology. Studies have implicated the varied role of phospholipase A2 (PLA2) in brain where it contributes to neuronal growth and inflammatory response. Overall contour and chemical nature of the substrate-binding channel in the low molecular weight PLA2s are similar. This study involves the reductionist fragment-based approach to understand the structure adopted by N-terminal fragment of Alzheimer’s Aβ peptide in its complex with PLA2. In the current communication, we report the structure determined by X-ray crystallography of N-terminal sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser (DAEFRHDS) of Aβ-peptide with a Group I PLA2 purified from venom of Andaman Cobra sub-species Naja naja sagittifera at 2.0 Å resolution (Protein Data Bank (PDB) Code: 3JQ5). This is probably the first attempt to structurally establish interaction between amyloid-β peptide fragment and hydrophobic substrate binding site of PLA2 involving H bond and van der Waals interactions. We speculate that higher affinity between Aβ and PLA2 has the therapeutic potential of decreasing the Aβ–Aβ interaction, thereby reducing the amyloid aggregation and plaque formation in AD. PMID:24619194

  17. Geographical venom variations of the Southeast Asian monocled cobra (Naja kaouthia): venom-induced neuromuscular depression and antivenom neutralization.

    PubMed

    Tan, Kae Yi; Tan, Choo Hock; Sim, Si Mui; Fung, Shin Yee; Tan, Nget Hong

    2016-01-01

    The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t90, time to 90% twitch inhibition), followed by NK-V and NK-M. Acetylcholine and carbachol failed to reverse the blockade, indicating irreversible/pseudo-irreversible post-synaptic neuromuscular blockade. KCl restored the twitches variably (NK-M preparation being the least responsive), consistent with different degree of muscle damage. The findings support that NK-T venom has the most abundant curarimimetic alpha-neurotoxins, while NK-M venom contains more tissue-damaging cytotoxins. Pre-incubation of tissue with N. kaouthia monovalent antivenom (NKMAV) prevented venom-induced twitch depression, with the NK-T preparation needing the largest antivenom dose. NKMAV added after the onset of neuromuscular depression could only halt the inhibitory progression but failed to restore full contraction. The findings highlight the urgency of early antivenom administration to sequester as much circulating neurotoxins as possible, thereby hastening toxin elimination from the circulation. In envenomed mice, NKMAV administered upon the first neurological sign neutralized the neurotoxic effect, with the slowest full recovery noticed in the NK-T group. This is consistent with the high abundance of neurotoxins in the NK-T venom, implying that a larger amount or repeated dosing of NKMAV may be required in NK-T envenomation. PMID:26972756

  18. Pathogenesis of dermonecrosis induced by venom of the spitting cobra, Naja nigricollis: An experimental study in mice.

    PubMed

    Rivel, Mario; Solano, Daniela; Herrera, María; Vargas, Mariángela; Villalta, Mauren; Segura, Álvaro; Arias, Ana Silvia; León, Guillermo; Gutiérrez, José María

    2016-09-01

    The pathogenesis of dermonecrosis induced by the venom of the African spitting cobra Naja nigricollis was investigated in a mouse model. Intradermal injection of venom induced a macroscopic necrotic lesion. Histological examination revealed early edema of the dermis, followed by blistering, loss of skin appendages and reduction in cellularity. By 24 h, necrosis of the dermis was evident, sections of epidermis were lost, and a fibrinoid hyaline material filled the damaged areas. Abundant inflammatory infiltrate was present in the hypodermis and basal dermis, and there was an increment in the expression of matrix metalloproteinases (MMPs). Thrombi were observed in blood vessels. Abundant cells were present in the dermis by 7 days. By 14 and 28 days, re-epithelization had occurred, collagen was widespread in the dermis, and few skin appendages were present. The RP-HPLC fractions that reproduced the necrotic activity were composed of low molecular mass cytotoxins of the three-finger toxin family and, to a lesser extent, of phospholipases A2 (PLA2). Inhibition of PLA2 of venom by p-bromophenacyl bromide did not reduce the area of necrosis, but modified the appearance of necrotic regions. Depletion of neutrophils and inhibition of venom metalloproteinases and tissue MMPs did not affect dermonecrosis. IgG and F(ab')2 antivenoms were effective in the neutralization of dermonecrosis when incubated with venom prior to injection. However, when antivenoms were administered immediately after venom injection, dermonecrosis was reduced only to a partial extent, underscoring the difficulties in neutralizing this effect with antivenoms. PMID:27288896

  19. Anticoagulant mechanism and platelet deaggregation property of a non-cytotoxic, acidic phospholipase A2 purified from Indian cobra (Naja naja) venom: inhibition of anticoagulant activity by low molecular weight heparin.

    PubMed

    Dutta, Sumita; Gogoi, Debananda; Mukherjee, Ashis K

    2015-03-01

    In the present study, anticoagulant and platelet modulating activities of an acidic phospholipase A2 (NnPLA2-I) purified from Indian cobra Naja naja venom was investigated. The NnPLA2-I displayed a mass of 15.2 kDa and 14,186.0 Da when analyzed by SDS-PAGE and MALDI-TOF-MS, respectively. Peptide mass fingerprinting analysis of the NnPLA2-I showed its significant similarity with phospholipase A2 enzymes purified from cobra venom. BLAST analysis of one tryptic peptide sequence of NnPLA2-I demonstrated putative conserved domains of the PLA2-like superfamily. The Km and Vmax values of NnPLA2-I toward hydrolysis of its most preferred substrate-phosphotidylcholine (PC)-were determined to be 0.72 mM and 29.3 μmol min(-1) mg(-1), respectively. The anticoagulant activity of NnPLA2-I was found to be higher than the anticoagulant activity of heparin/AT-III or warfarin. The histidine modifying reagent, monovalent and polyvalent antivenom differentially inhibited the catalytic and anticoagulant activities of NnPLA2-I. Low molecular weight heparin did not inhibit the catalytic and platelet deaggregation activity of NnPLA2-I, albeit its anticoagulant activity was significantly reduced. The NnPLA2-I showed a non-enzymatic, mixed inhibition of thrombin with a Ki value of 9.3 nM. Heparin significantly decreased, with an IC50 value of 15.23 mIU, the thrombin inhibitory activity of NnPLA2-I. The NnPLA2-I uniquely increased the amidolytic activity of FXa without influencing its prothrombin activating property. NnPLA2-I showed dose-dependent deaggregation of platelet rich plasma (PRP) and inhibited the collagen and thrombin-induced aggregation of PRP. However, deaggregation of washed platelets by NnPLA2-I demonstrated in presence of PC or platelet poor plasma. Alkylation of histidine residue of NnPLA2-I resulted in 95% and 21% reduction of its platelet deaggregation and platelet binding properties, respectively. NnPLA2-I did not show cytotoxicity against human glioblastoma U87MG cells

  20. Antivenom activity of triterpenoid (C34H68O2) from Leucas aspera Linn. against Naja naja naja venom induced toxicity: antioxidant and histological study in mice.

    PubMed

    Venkatesan, C; Sarathi, M; Balasubramanian, G; Thomas, John; Balachander, V; Babu, V Sarath; Bilal, S Mohammed Yusuf; Majeed, S Abdul; Madan, N; Raj, N Sundar; Vimal, S; Nambi, K S N; Hameed, A S Sahul

    2014-04-01

    The isolated and identified triterpenoid, 1-hydroxytetratriacontane-4-one (C34H68O2), obtained from the methanolic leaf extract of Leucas aspera Linn. was explored for the first time for antisnake venom activity. The plant (L. aspera Linn.) extract significantly antagonized the spectacled cobra (Naja naja naja) venom induced lethal activity in a mouse model. It was compared with commercial antiserum obtained from King Institute of Preventive Medicine (Chennai, Tamil Nadu, India). N. naja naja venom induced a significant decrease in antioxidant superoxide dismutase, glutathione (GSH) peroxidase, catalase, reduced GSH and glutathione-S-transferase activities and increased lipid peroxidase (LPO) activity in different organs such as heart, liver, kidney and lungs. The histological changes following the antivenom treatment were also evaluated in all these organs. There were significant alterations in the histology. Triterpenoid from methanol extract of L. aspera Linn. at a dose level of 75 mg per mouse significantly attenuated (neutralized) the venom-induced antioxidant status and also the LPO activity in different organs. PMID:23857030

  1. The absence of antagonism between extracts of Clinacanthus nutans Burm. and Naja naja siamensis venom.

    PubMed

    Cherdchu, C; Poopyruchpong, N; Adchariyasucha, R; Ratanabanangkoon, K

    1977-06-01

    Clinacanthus nutans Burm, a herb reputed in Thailand and Malaysia to be "snakebite antidote" has been tested in vitro and in vivo for antivenin activity. The aqueous extract of C. nutans leaves has been found to have no effect on the inhibition of neuromuscular transmission produced by purified Naja naja siamensis neurotoxin in isolated rat phrenic-nerve diaphragm preparations. The extract of C. nutans, when given orally or intraperitoneally, are ineffective in prolonging the survival time of experimental mice receiving lethal doses of N.n. siamensis crude venom. Oral administrations of the herb extracts pretreated with alpha-amylase or beta-amylase also fail to protect the animal. It is concluded that the extract of C. nutans can not antagonize the action of cobra venom. PMID:199949

  2. Immunological cross-reactivity and neutralization of the principal toxins of Naja sumatrana and related cobra venoms by a Thai polyvalent antivenom (Neuro Polyvalent Snake Antivenom).

    PubMed

    Leong, Poh Kuan; Fung, Shin Yee; Tan, Choo Hock; Sim, Si Mui; Tan, Nget Hong

    2015-09-01

    The low potency of cobra antivenom has been an area of concern in immunotherapy for cobra envenomation. This study sought to investigate factors limiting the neutralizing potency of cobra antivenom, using a murine model. We examined the immunological reactivity and neutralizing potency of a Thai polyvalent antivenom against the principal toxins of Naja sumatrana (Equatorial spitting cobra) venom and two related Asiatic cobra venom α-neurotoxins. The antivenom possesses moderate neutralizing potency against phospholipases A2 (P, potency of 0.98mg/mL) and moderately weak neutralizing potency against long-chain α-neurotoxins (0.26-0.42mg/mL) but was only weakly effective in neutralizing the short-chain α-neurotoxins and cardiotoxins (0.05-0.08mg/mL). The poor neutralizing potency of the antivenom on the low molecular mass short-chain neurotoxins and cardiotoxins is presumably the main limiting factor of the efficacy of the cobra antivenom. Our results also showed that phospholipase A2, which exhibited the highest ELISA reactivity and avidity, was most effectively neutralized, whereas N. sumatrana short-chain neurotoxin, which exhibited the lowest ELISA reactivity and avidity, was least effectively neutralized by the antivenom. These observations suggest that low immunoreactivity (low ELISA reactivity and avidity) is one of the reasons for poor neutralization of the cobra venom low molecular mass toxins. Nevertheless, the overall results show that there is a lack of congruence between the immunological reactivity of the toxins toward antivenom and the effectiveness of toxin neutralization by the antivenom, indicating that there are other factors that also contribute to the weak neutralization capacity of the antivenom. Several suggestions have been put forward to overcome the low efficacy of the cobra antivenom. The use of a 'proper-mix' formulation of cobra venoms as immunogen, whereby the immunogen mixture used for hyperimmunization contains a mix of various types

  3. Protective effects of melatonin against oxidative damage induced by Egyptian cobra (Naja haje) crude venom in rats.

    PubMed

    Abdel Moneim, Ahmed E; Ortiz, Francisco; Leonardo-Mendonça, Roberto C; Vergano-Villodres, Roberto; Guerrero-Martínez, Jose Antonio; López, Luis C; Acuña-Castroviejo, Darío; Escames, Germaine

    2015-03-01

    Naja haje envenomation is one of the leading causes of death due to snakebite. Antiserum therapy sometimes fails to provide enough protection against venom toxicity. In this study, we investigated the protective effects of melatonin against N. haje venom in rats. The animals were injected with venom (0.25mg/kg) and/or melatonin (10mg/kg) and compared with vehicle-treated rats. There was oxidative/nitrosative damage and apoptosis in the liver, heart, and kidneys of venom-injected rats. Melatonin counteracted the increased lipoperoxidation and nitric oxide, prevented decreased glutathione peroxidase and reductase activity, reduced the glutathione disulfide/glutathione (GSSG/GSH) ratio, and maintained the GSH pool. Furthermore, melatonin administration was associated with a reduction of apoptosis, which was increased in venom-injected rats. Overall, these results suggest that melatonin mitigates oxidative/nitrosative stress in venom-induced cardio-hepato-renal injury in rats. Our results suggest that melatonin treatment may ameliorate some of the effects of N. haje envenomation. PMID:25542296

  4. The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits.

    PubMed

    Yap, Michelle Khai Khun; Tan, Nget Hong; Sim, Si Mui; Fung, Shin Yee; Tan, Choo Hock

    2015-10-01

    The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab')2 ] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab')2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab')2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence. PMID:25819552

  5. A comparative study of venomics of Naja naja from India and Sri Lanka, clinical manifestations and antivenomics of an Indian polyspecific antivenom.

    PubMed

    Sintiprungrat, Kitisak; Watcharatanyatip, Kamolwan; Senevirathne, W D S T; Chaisuriya, Papada; Chokchaichamnankit, Daranee; Srisomsap, Chantragan; Ratanabanangkoon, Kavi

    2016-01-30

    Naja naja (Indian cobra) from Sri Lanka and India is the WHO Category 1 medically important snakes in both countries. Some antivenom produced against Indian N. naja (NNi) were less effective against Sri Lankan N. naja (NNsl). Proteomes of NNi and NNsl venoms were studied by RP-HPLC, SDS-PAGE and LC/MS/MS. Six protein families were identified in both venoms with the most abundant were the 3 finger toxins (3FTs) where cytotoxins (CTX) subtype predominated, followed by phospholipase A2, cysteine-rich venom protein, snake venom metalloproteases, venom growth factors, and protease inhibitors. Qualitative and quantitative differences in the venomics profiles were observed. Some proteins were isolated from either NNi or NNsl venom. Postsynaptic neurotoxins (NTX) were identified for the first time in NNsl venom. Thus, there are geographic intra-specific variations of venom composition of the two N. naja. The relative abundance of CTX and NTX explained well the clinical manifestations of these venoms. Antivenomics study of an Indian antivenom (Vins) showed the antibodies effectively bound all venom toxins from both snakes but more avidly to the Indian venom proteins. The lower antibody affinity towards the 'heterologous' venom was the likely cause of poor efficacy of the Indian antivenom used to treat NNsl envenoming. PMID:26506536

  6. Purification, characterization and primary structure of a chymotrypsin inhibitor from Naja atra venom.

    PubMed

    Zhou, Xing-Ding; Jin, Yang; Lu, Qiu-Min; Li, Dong-Sheng; Zhu, Shao-Wen; Wang, Wan-Yu; Xiong, Yu-Liang

    2004-02-01

    A chymotrypsin inhibitor, designated NA-CI, was isolated from the venom of the Chinese cobra Naja atra by three-step chromatography. It inhibited bovine alpha-chymotrypsin with a Ki of 25 nM. The molecular mass of NA-CI was determined to be 6403.8 Da by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) analysis. The complete amino acid sequence was determined after digestion of S-carboxymethylated inhibitor with Staphylococcus aureus V8 protease and porcine trypsin. NA-CI was a single polypeptide chain composed of 57 amino acid residues. The main contact site with the protease (P1) has a Phe, showing the specificity of the inhibitor. NA-CI shared great similarity with the chymotrypsin inhibitor from Naja naja venom (identities=89.5%) and other snake venom protease inhibitors. PMID:14990218

  7. Purification, partial characterization, crystallization and preliminary X-ray diffraction of a novel cardiotoxin-like basic protein from Naja naja atra (South Anhui) venom

    SciTech Connect

    Rong, Hui; Li, Yan; Lou, Xiao-hua; Zhang, Xio; Gao, Yong-xiang; Teng, Mai-kun Niu, Li-wen

    2007-02-01

    A novel cardiotoxin-like basic protein from Naja naja atra was crystallized and diffraction data were collected to 2.35 Å resolution. A novel cardiotoxin-like basic protein was isolated from the venom of the Chinese cobra (Naja naja atra) from the south of Anhui in China. The protein inhibits the expression of vascular endothelial growth factor and basic fibroblast growth factor in human lung cancer cell line H1299 and induces the haemolysis of rabbit erythrocytes under low-lecithin conditions. After a two-step chromatographic purification, the resultant 7 kDa protein was crystallized by the hanging-drop vapour-diffusion method at room temperature. A complete data set was collected to 2.35 Å resolution using an in-house X-ray diffraction system. The crystal belongs to space group P4{sub 1}2{sub 1}2, with unit-cell parameters a = b = 43.2, c = 147.9 Å. There are two molecules in the crystallographic asymmetric unit.

  8. Differential hydrolysis of erythrocyte and mitochondrial membrane phospholipids by two phospholipase A2 isoenzymes (NK-PLA2-I and NK-PLA2-II) from the venom of the Indian monocled cobra Naja kaouthia.

    PubMed

    Doley, Robin; King, Glenn F; Mukherjee, Ashis K

    2004-05-01

    We previously demonstrated that venom from the Indian monocled cobra Naja kaouthia is a rich source of phospholipase A2 enzymes, and we purified and characterized a major PLA2 isoenzyme (NK-PLA2-I) from N. kaouthia venom. In the present study, we report the purification and biochemical characterization of a second PLA2 isoenzyme (NK-PLA2-II) from the same venom. A comparison of the membrane phospholipid hydrolysis patterns by these two PLA2s has revealed that they cause significantly more damage to mitochondrial membranes (NK-PLA2-I > NK-PLA2-II) as compared to erythrocyte membranes due to more efficient binding of the enzymes to mitochondrial membranes. Fatty acid release patterns by these PLA2s from the membrane phospholipid PC-pools indicate that NK-PLA2-I does not discriminate between saturated and unsaturated fatty acids whereas NK-PLA2-II shows a preference for unsaturated fatty acids during the initial phase of attack. The current investigation provides new insight into the molecular arrangement of NK-PLA2-sensitive domains in erythrocyte and mitochondrial membranes and highlights the contribution of polar, but uncharged, amino acids such as serine and cysteine in NK-PLA2 induced membrane damage. PMID:15081888

  9. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra

    PubMed Central

    Chen, Cao-Xin; Chen, Jie-Yu; Kou, Jian-Qun; Xu, Yin-Li; Wang, Shu-Zhi; Zhu, Qi; Yang, Lu; Qin, Zheng-Hong

    2015-01-01

    Cardiotoxin (CTX) from Naja naja atra venom (NNAV) reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis. PMID:25767552

  10. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra.

    PubMed

    Chen, Cao-Xin; Chen, Jie-Yu; Kou, Jian-Qun; Xu, Yin-Li; Wang, Shu-Zhi; Zhu, Qi; Yang, Lu; Qin, Zheng-Hong

    2015-01-01

    Cardiotoxin (CTX) from Naja naja atra venom (NNAV) reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis. PMID:25767552

  11. Two Acidic, Anticoagulant PLA2 Isoenzymes Purified from the Venom of Monocled Cobra Naja kaouthia Exhibit Different Potency to Inhibit Thrombin and Factor Xa via Phospholipids Independent, Non-Enzymatic Mechanism

    PubMed Central

    Mukherjee, Ashis K.; Kalita, Bhargab; Thakur, Rupamoni

    2014-01-01

    Background The monocled cobra (Naja kaouthia) is responsible for snakebite fatality in Indian subcontinent and in south-western China. Phospholipase A2 (PLA2; EC 3.1.1.4) is one of the toxic components of snake venom. The present study explores the mechanism and rationale(s) for the differences in anticoagulant potency of two acidic PLA2 isoenzymes, Nk-PLA2α (13463.91 Da) and Nk-PLA2β (13282.38 Da) purified from the venom of N. kaouthia. Principal Findings By LC-MS/MS analysis, these PLA2s showed highest similarity (23.5% sequence coverage) with PLA2 III isolated from monocled cobra venom. The catalytic activity of Nk-PLA2β exceeds that of Nk-PLA2α. Heparin differentially regulated the catalytic and anticoagulant activities of these Nk-PLA2 isoenzymes. The anticoagulant potency of Nk-PLA2α was comparable to commercial anticoagulants warfarin, and heparin/antithrombin-III albeit Nk-PLA2β demonstrated highest anticoagulant activity. The anticoagulant action of these PLA2s was partially contributed by a small but specific hydrolysis of plasma phospholipids. The strong anticoagulant effect of Nk-PLA2α and Nk-PLA2β was achieved via preferential, non-enzymatic inhibition of FXa (Ki = 43 nM) and thrombin (Ki = 8.3 nM), respectively. Kinetics study suggests that the Nk-PLA2 isoenzymes inhibit their “pharmacological target(s)” by uncompetitive mechanism without the requirement of phospholipids/Ca2+. The anticoagulant potency of Nk-PLA2β which is higher than that of Nk-PLA2α is corroborated by its superior catalytic activity, its higher capacity for binding to phosphatidylcholine, and its greater strength of thrombin inhibition. These PLA2 isoenzymes thus have evolved to affect haemostasis by different mechanisms. The Nk-PLA2β partially inhibited the thrombin-induced aggregation of mammalian platelets suggesting its therapeutic application in the prevention of unwanted clot formation. Conclusion/Significance In order to develop peptide-based superior

  12. Naja naja karachiensis Envenomation: Biochemical Parameters for Cardiac, Liver, and Renal Damage along with Their Neutralization by Medicinal Plants

    PubMed Central

    Asad, Muhammad Hassham Hassan Bin; Ubaid, Muhammad; Durr-e-Sabih; Sajjad, Ashif; Mehmood, Rubada; Mahmood, Qaisar; Ansari, Muhammad Muzzmil; Karim, Sabiha; Mehmood, Zahid; Hussain, Izhar

    2014-01-01

    Naja naja karachiensis envenomation was found to hit more drastically heart, liver, and kidneys. 400 μg/kg of venom-raised moderate serum levels of ALT (72 ± 4.70 U/L, 0.1 > P > 0.05), AST (157 ± 24.24 U/L, 0.1 > P > 0.05), urea (42 ± 3.08 mg/dL, 0.05 > P > 0.02), creatinine (1.74 ± 0.03 mg/dL, 0.01 > P > 0.001), CK-MB (21 ± 1.5 U/L, 0.05 > P > 0.02), and LDH (2064 ± 15.98 U/L, P < 0.001) were injected in experimental rabbits. However, lethality was enhanced with 800 μg/kg of venom in terms of significant release of ALT (86 ± 5.0 U/L, 0.05 > P > 0.02), AST (251 ± 18.2 U/L, 0.01 > P > 0.001), urea (57.6 ± 3.84 mg/dL, 0.02 > P > 0.01), creatinine (2.1 ± 0.10 mg/dL, 0.02 > P > 0.01), CK-MB (77 ± 11.22 U/L, 0.05 > P > 0.02), and LDH (2562 ± 25.14 U/L, P ≪ 0.001). Among twenty-eight tested medicinal plant extracts, only Stenolobium stans (L.) Seem was found the best antivenom (P > 0.5) compared to the efficacy of standard antidote (ALT = 52.5 ± 3.51 U/L, AST = 69.5 ± 18.55 U/L, urea = 31.5 ± 0.50 mg/dL, creatinine = 1.08 ± 0.02 mg/dL, CK-MB = 09 ± 0.85 U/L, and LDH = 763 ± 6.01 U/L). Other plant extracts were proved less beneficial and partly neutralized the toxicities posed by cobra venom. However, it is essential in future to isolate and characterize bioactive compound(s) from Stenolobium stans (L.) Seem extract to overcome the complications of snake bite. PMID:24877153

  13. Mucuna pruriens Linn. seed extract pretreatment protects against cardiorespiratory and neuromuscular depressant effects of Naja sputatrix (Javan spitting cobra) venom in rats.

    PubMed

    Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Marinello, Enrico; Guerranti, Roberto; Aguiyi, John Chinyere

    2011-04-01

    Mucuna pruriens has been used by native Nigerians as a prophylactic for snakebite. The protective effects of M. pruriens seed extract (MPE) were investigated against the pharmacological actions of N. sputatrix (Javan spitting cobra) venom in rats. The results showed that MPE-pretreatment protected against cardiorespiratory and, to a lesser extent, neuromuscular depressant effects of N. sputatrix venom. These may be explained at least in part by the neutralisation of the cobra venom toxins by anti-MPE antibodies elicited by the MPE pretreatment. PMID:21614888

  14. Elapid snake venom analyses show the specificity of the peptide composition at the level of genera Naja and Notechis.

    PubMed

    Munawar, Aisha; Trusch, Maria; Georgieva, Dessislava; Hildebrand, Diana; Kwiatkowski, Marcel; Behnken, Henning; Harder, Sönke; Arni, Raghuvir; Spencer, Patrick; Schlüter, Hartmut; Betzel, Christian

    2014-03-01

    Elapid snake venom is a highly valuable, but till now mainly unexplored, source of pharmacologically important peptides. We analyzed the peptide fractions with molecular masses up to 10 kDa of two elapid snake venoms-that of the African cobra, N. m. mossambica (genus Naja), and the Peninsula tiger snake, N. scutatus, from Kangaroo Island (genus Notechis). A combination of chromatographic methods was used to isolate the peptides, which were characterized by combining complimentary mass spectrometric techniques. Comparative analysis of the peptide compositions of two venoms showed specificity at the genus level. Three-finger (3-F) cytotoxins, bradykinin-potentiating peptides (BPPs) and a bradykinin inhibitor were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic trypsin inhibitor (BPTI)-type inhibitors and a natriuretic peptide were identified in the N. venom. The inhibiting activity of the peptides was confirmed in vitro with a selected array of proteases. Cytotoxin 1 (P01467) from the Naja venom might be involved in the disturbance of cellular processes by inhibiting the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and viperid snake venoms was observed, suggesting that these molecules play a key role in snake venoms and also indicating that these peptides were recruited into the snake venom prior to the evolutionary divergence of the snakes. PMID:24590383

  15. Elapid Snake Venom Analyses Show the Specificity of the Peptide Composition at the Level of Genera Naja and Notechis

    PubMed Central

    Munawar, Aisha; Trusch, Maria; Georgieva, Dessislava; Hildebrand, Diana; Kwiatkowski, Marcel; Behnken, Henning; Harder, Sönke; Arni, Raghuvir; Spencer, Patrick; Schlüter, Hartmut; Betzel, Christian

    2014-01-01

    Elapid snake venom is a highly valuable, but till now mainly unexplored, source of pharmacologically important peptides. We analyzed the peptide fractions with molecular masses up to 10 kDa of two elapid snake venoms—that of the African cobra, N. m. mossambica (genus Naja), and the Peninsula tiger snake, N. scutatus, from Kangaroo Island (genus Notechis). A combination of chromatographic methods was used to isolate the peptides, which were characterized by combining complimentary mass spectrometric techniques. Comparative analysis of the peptide compositions of two venoms showed specificity at the genus level. Three-finger (3-F) cytotoxins, bradykinin-potentiating peptides (BPPs) and a bradykinin inhibitor were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic trypsin inhibitor (BPTI)-type inhibitors and a natriuretic peptide were identified in the N. venom. The inhibiting activity of the peptides was confirmed in vitro with a selected array of proteases. Cytotoxin 1 (P01467) from the Naja venom might be involved in the disturbance of cellular processes by inhibiting the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and viperid snake venoms was observed, suggesting that these molecules play a key role in snake venoms and also indicating that these peptides were recruited into the snake venom prior to the evolutionary divergence of the snakes. PMID:24590383

  16. Effect of Annona senegalensis rootbark extracts on Naja nigricotlis nigricotlis venom in rats.

    PubMed

    Adzu, B; Abubakar, M S; Izebe, K S; Akumka, D D; Gamaniel, K S

    2005-01-15

    Annona senegalensis Pers (family: Annonaceae) is used traditionally in Nigeria to treat victims of snakebite. The potency of the methanol extract of the root bark of the plant was tested against cobra (Naja nigricotlis nigricotlis Wetch) venom in rats. The extract was also tested on brine shrimp (Artemia saline Leach). The activity of the extract against the venom induced mortality, occurrence of toxic signs, activity on liver enzymes as well as its ability to reverse experimentally induced increase in body temperature were evaluated. Results indicated that the extract caused reduction in the induced hyperthermia and directly detoxified the snake venom used by 16-33%. It, however, failed to restore the biochemical functions (sGOT and sGPT) of the liver. The extract exhibited an LC(50) of 232.7 microg/ml in the brine shrimp test. PMID:15619571

  17. Peripheral and spinal antihyperalgesic activity of najanalgesin isolated from Naja naja atra in a rat experimental model of neuropathic pain.

    PubMed

    Liang, Ying-Xia; Jiang, Wei-Jian; Han, Li-Ping; Zhao, Shu-Jin

    2009-09-01

    Snake venoms are a rich source of various compounds that have applications in medicine and biochemistry. Recently, it has been demonstrated that najanalgesin isolated from the venom of Naja naja atra exerts analgesic effects on acute pain in mice. The objective of this study was to evaluate the antinociceptive effect of najanalgesin in a rat model of neuropathic pain, induced by L5 spinal nerve ligation and transaction. We observed that intraperitoneal (i.p.) administration of najanalgesin produced significant increase in hind paw withdrawal latency (HWL) in response to both mechanical and thermal stimulation. Moreover, a single dose of najanalgesin was able to induce antinociceptive activity that lasted for 1 week. Intrathecal injection of najanalgesin increased the HWL in response to mechanical stimuli. The antinociceptive effect of najanalgesin administered intrathecally was partly inhibited by intrathecal injection of naloxone or atropine. These results demonstrate that najanalgesin has antinociceptive effects on the central and peripheral system in the rat neuropathic pain model. The opioid receptor and muscatinic receptor are involved in najanalgesin-induced antinociception in the spinal cord. This research supports the possibility of using najanalgesin as a novel pharmacotherapeutic agent for neuropathic pain. PMID:19442704

  18. Antinociceptive and Anti-Inflammatory Effects of Orally Administrated Denatured Naja Naja Atra Venom on Murine Rheumatoid Arthritis Models

    PubMed Central

    Zhu, Kou-Zhu; Liu, Yan-Li; Gu, Jin-Hua; Qin, Zheng-Hong

    2013-01-01

    To investigate the antinociceptive and anti-inflammatory activities of the denatured Naja Naja atra venom (NNAV) in rheumatoid arthritis-associated models, the denatured NNAV (heat treated; 30, 90, 270 μg/kg), the native NNAV (untreated with heat; 90 μg/kg), and Tripterygium wilfordii polyglycoside (TWP, 15 mg/kg) were administrated orally either prophylactically or therapeutically. We measured time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg-white-induced inflammation, and granuloma weight in formalin-soaked filter paper-induced granuloma. For adjuvant-induced arthritis (AIA) rats, paw edema, mechanical withdrawal threshold, serum levels of TNF-α and IL-10, and histopathological changes of the affected paw were assessed. We found that the denatured NNAV (90, 270 μg/kg) significantly reduced time of licking paw, paw volume, and granuloma weight in above inflammatory models and also attenuated paw edema, mechanical hyperalgesia, and histopathology changes in AIA rats. Additionally, the increase in serum TNF-α and the decrease in serum IL-10 in AIA rats were reversed by the denatured NNAV. Although the native NNAV and TWP rendered the similar pharmacological actions on the above four models with less potency than that of the denatured NNAV, these findings demonstrate that oral administration of the denatured NNAV produces antinociceptive and anti-inflammatory activities on rheumatoid arthritis. PMID:23634171

  19. The role of the N-terminal leucine residue in snake venom cardiotoxin II (Naja naja atra).

    PubMed

    Wu, C Y; Chen, W C; Ho, C L; Chen, S T; Wang, K T

    1997-04-28

    The N-terminal leucine residue of snake venom cardiotoxin II (CTX II) (Naja naja atra) was systematically replaced with D-leucine (CTXII-L1-D-L), glycine (CTXII-L1G) or deleted [CTXII-(2-60)] to study the role of leucine residue in CTX II molecule. CTX II, CTXL1-D-L, CTXL1G and CTX(2-60) were produced by chemical synthesis method and purified by high performance liquid chromatography. Owing to folding problem in CTXII-(2-60), only CTX II, CTXII-L1-D-L and CTXII-L1G were produced in a pure form and characterized by amino acid analysis, mass spectrometry and peptide mapping. In the structural aspect, changing the Leu-1 by D-Leu or Gly causes a drastic alteration in the whole CTX II structure as detected by circular dichroism, 1-anilino-naphthalene-8-sulfonate (ANS) fluorescence assay. In the functional aspect, both CTXII-L1-D-L and CTXII-L1G are still retained substantial biological activity of CTX II. Therefore, the results indicate that both the chirality and the side-chain of the N-terminal leucine residue of CTX II are important elements in maintaining the whole CTX II structure. In addition, this study is the first report in elucidating the reason why the first N-terminal residue of most CTXs (90.3%) is leucine residue. PMID:9168920

  20. 5'-NUCLEOTIDASES OF NAJA NAJA KARACHIENSIS SNAKE VENOM: THEIR DETERMINATION, TOXICITIES AND REMEDIAL APPROACH BY NATURAL INHIBITORS (MEDICINAL PLANTS).

    PubMed

    Bin Asd, Muhammad Hassham Hassan; Iqbal, Muhammad; Akram, Muhammad Rouf; Khawaja, Naeem Raza; Muneer, Saiqa; Shabbir, Muhammad Zubair; Khan, Muhammad Saqib; Murtaza, Ghulam; Hussain, Izhar

    2016-01-01

    Present study was carried out regarding enzymatic assay for 5'-nucleotidase enzymes present in snake venom Naja naja karachiensis and to evaluate twenty eight medicinal plants as their antidotes. Elevated enzymatic activities i.e., 119, 183, 262 and 335 U/mL were observed in 10, 20, 30 and 40 µg of crude venom, respectively, in dose dependent manner. Among various plant extracts only two (Bauhinia vaiiegate L. and Citms linion (L.) Burm. f.) were found 94% effective at 160 µg to neutralize 112 U/mL activities (p 0.5) while reference standard was proved 93.2% useful at 80 pg to halt 111 U/mL activities. Cedrus deodara G. Don, Enicostemna hyssopifolium (Willd.) Verdoom, Terminalia arjuma Wight & Am. and Zingiber officinalis Rosc. (at 160 µg) were found ≥90% effective (0.5 ≥ p ≥ 0.1) while Citrulus colocynthis, Fogonia cretica L., Rhazya stticta Dcne and Stenolobiun stans (L.) D. Don (at 320 µg) were proved 90% effective (0.05 ≥ p ≥ 0.02). The remaining plant extracts were observed abortive (p ≥ 0.001) in neutralization of 5'-nucleotidases enzymatic actions. This study emphasizes further characterization of active plant extracts to further explore the antivenom influences of these herbal remedies against deleterious effects produced by 5'-nucleotidase enzymes after snake bite envenomation. PMID:27476285

  1. Venom ophthalmia from Naja mossambica in KwaZulu Natal, South Africa: a reminder to all that for ocular chemical injury, dilution is the solution.

    PubMed

    Hoffman, Jeremy

    2015-10-01

    Venom ophthalmia caused by venoms of spitting elapids such as the Mozambique Spitting Cobra (Naja mossambica) is seen in regions where people live in close proximity to elapids, such as in the KwaZulu Natal region of South Africa. We report such a case in a 43-year-old woman who presented to Mosvold Hospital, a district hospital in South Africa. Clinical features and best practice management of venom ophthalmia will be discussed. PMID:25614535

  2. Antivenom potential of ethanolic extract of Cordia macleodii bark against Naja venom

    PubMed Central

    Soni, Pranay; Bodakhe, Surendra H.

    2014-01-01

    Objective To evaluate the antivenom potential of ethanolic extract of bark of Cordia macleodii against Naja venom induced pharmacological effects such as lethality, hemorrhagic lesion, necrotizing lesion, edema, cardiotoxicity and neurotoxicity. Methods Wistar strain rats were challenged with Naja venom and treated with the ethanolic extract of Cordia macleodii bark. The effectiveness of the extract to neutralize the lethalities of Naja venom was investigated as recommended by WHO. Results At the dose of 400 and 800 mg/kg ethanolic extract of Cordia macleodii bark significantly inhibited the Naja venom induced lethality, hemorrhagic lesion, necrotizing lesion and edema in rats. Ethanolic extract of Cordia macleodii bark was effective in neutralizing the coagulant and defibrinogenating activity of Naja venom. The cardiotoxic effects in isolated frog heart and neurotoxic activity studies on frog rectus abdominus muscle were also antagonized by ethanolic extract of Cordia macleodii bark. Conclusions It is concluded that the protective effect of extract of Cordia macleodii against Naja venom poisoning may be mediated by the cardiotonic, proteolysin neutralization, anti-inflammatory, antiserotonic and antihistaminic activity. It is possible that the protective effect may also be due to precipitation of active venom constituents. PMID:25183127

  3. Inhibition of Naja kaouthia venom activities by plant polyphenols.

    PubMed

    Pithayanukul, Pimolpan; Ruenraroengsak, Pakatip; Bavovada, Rapepol; Pakmanee, Narumol; Suttisri, Rutt; Saen-oon, Suwipa

    2005-03-21

    Plant polyphenols from the aqueous extracts of Pentace burmanica, Pithecellobium dulce, Areca catechu and Quercus infectoria were tested for their inhibitory activities against Naja kaouthia (NK) venom by in vitro neutralization method. The first three extracts could completely inhibit the lethality of the venom at 4 LD50 concentration and the venom necrotizing activity at the minimum necrotizing dose while also inhibited up to 90% of the acetylcholinesterase activity of NK venom at much lower tannin concentrations than that of Quercus infectoria. The ED50 of plant tannins in inhibiting NK venom activities varied according to condensed tannins and their content in the extracts. Molecular docking of the complexes between alpha-cobratoxin and either hydrolysable or condensed tannins at their lowest energetic conformations were proposed. The anti-venom activities of these plant polyphenols by selectively blocking the nicotinic acetylcholine receptor and non-selectively by precipitation of the venom proteins were suggested. PMID:15740891

  4. Modulated mechanism of phosphatidylserine on the catalytic activity of Naja naja atra phospholipase A2 and Notechis scutatus scutatus notexin.

    PubMed

    Chiou, Yi-Ling; Lin, Shinne-Ren; Hu, Wan-Ping; Chang, Long-Sen

    2014-12-15

    Phosphatidylserine (PS) externalization is a hallmark for apoptotic death of cells. Previous studies showed that Naja naja atra phospholipase A2 (NnaPLA2) and Notechis scutatus scutatus notexin induced apoptosis of human cancer cells. However, NnaPLA2 and notexin did not markedly disrupt the integrity of cellular membrane as evidenced by membrane permeability of propidium iodide. These findings reflected that the ability of NnaPLA2 and notexin to hydrolyze membrane phospholipids may be affected by PS externalization. To address that question, this study investigated the membrane-interacted mode and catalytic activity of NnaPLA2 and notexin toward outer leaflet (phosphatidylcholine/sphingomyelin/cholesterol, PC/SM/Chol) and inner leaflet (phosphatidylserine/phosphatidylethanolamine/cholesterol, PS/PE/Chol) of plasma membrane-mimicking vesicles. PS incorporation promoted enzymatic activity of NnaPLA2 and notexin on PC and PC/SM vesicles, but suppressed NnaPLA2 and notexin activity on PC/SM/Chol and PE/Chol vesicles. PS incorporation increased the membrane fluidity of PC vesicles but reduced membrane fluidity of PC/SM, PC/SM/Chol and PE/Chol vesicles. PS increased the phospholipid order of all the tested vesicles. Moreover, PS incorporation did not greatly alter the binding affinity of notexin and NnaPLA2 with phospholipid vesicles. Acrylamide quenching studies and trinitrophenylation of Lys residues revealed that membrane-bound mode of notexin and NnaPLA2 varied with the targeted membrane compositions. The fine structure of catalytic site in NnaPLA2 and notexin in all the tested vesicles showed different changes. Collectively, the present data suggest that membrane-inserted PS modulates PLA2 interfacial activity via its effects on membrane structure and membrane-bound mode of NnaPLA2 and notexin, and membrane compositions determine the effect of PS on PLA2 activity. PMID:25449100

  5. Biodistribution and kinetic studies of technetium-99m labeled Naja naja karachiensis venom via gamma scintigraphic and SPECT images.

    PubMed

    Bin-Asad, Muhammad Hassham-Hassan; e-Sabih, Durr; Ahmad, Israr; Choudhry, Bashir Ahmad; Murtaza, Ghulam; Hussain, Izhar

    2015-07-01

    Naja naja karachiensis have been responsible for plentiful deaths in Pakistan. To investigate bio distribution and blood kinetics, venom was labeled with the radiotracer (technetium-99m) by following the method of direct labeling technique. Its maximum labeling percentage was 97.7% (pH 6, 100 µg stannous chloride dihydrate) which was higher than some other reported venom. Radio labeled venom was stable for more than 4 hours both in vivo (96%) and in vitro (serum 94.1%, saline 94.3%) experimentations. Intravenous doses of venom (250 µg, 0.5 mCi) were found to be evenly distributed (having R/L ratio=1.0) in all parts of sacrificed rabbits. Kidneys (53.75% activity/g) and urinary bladder (23.70% activity/g) were found with the copious quantity of injected dose of venom. Rest of all other organs was found with subsequent remaining dose of venom. Among them, lungs (14.2% activity/g), liver (4.32% activity/g), bones (1.38% activity/g), heart (0.8% activity/g), blood (0.56% activity/g), skin (0.45% activity/g), intestines (0.35% activity/g), skeleton muscles (0.3% activity/g), brain (0.14% activity/g) and stomach (0.05% activity/g) are included. After 24 hours of injection, poisoned blood of rabbits was almost cleared from venom. Gamma scintigraphic images (up to 2 hours) along with bio distribution suggest that kidneys are main organs of excretion in rabbits. Elimination started immediately after administration of venom however, possible sites for metabolism of venom are liver and lungs. More accumulation of venom in heart compared to brain suggests its higher affinity (thus possible higher toxicity) to cardiac muscles as compared to brain tissues. PMID:26142502

  6. Local antivenom treatment for ophthalmic injuries caused by a Naja atra.

    PubMed

    Fung, Hin Tat; Lam, Ka Keung; Wong, Oi Fung; Lam, Tommy Shing Kit

    2010-06-01

    We report a case of local antivenom therapy for ocular exposure to the venom of Naja atra. An 83-year-old woman sustained conjunctival and corneal injuries by the venom of a spitting N. atra. Local instillation of N. naja antivenom quickly relieved the pain as measured by visual analog scale, and she recovered uneventfully. Good recovery ensuing topical antivenom administration for ocular exposure to the venom of spitting N. atra and Naja nigricollis has been described in literature, but the pain response was not thoroughly documented. The mechanism of antivenom for pain relief remains to be established. In light of the associated positive outcome observed in human, the role of ocular antivenom therapy merits further study. PMID:20499225

  7. Ophidascaris wangi sp. n. and O. najae (Gedoelst, 1916) (Ascaridida: Ascaridoidea) from snakes in China.

    PubMed

    Li, Liang; Guo, Yan-Ning; Li, Jian; Zhang, Lu-Ping

    2014-12-01

    Ophidascaris wangi sp. n. collected from the king rat snake Elaphe carinata (Günther) (Serpentes: Colubridae) in China is described using both light and scanning electron microscopy. The new species differs from its congeners in the presence of narrow lateral alae originating a short distance posterior to the base of the ventrolateral lips, its relatively long oesophagus (3.57-4.54 mm long, representing 6.6-7.6% of body length), its short spicules (1.89-2.14 mm long, representing 3.9-4.3% of body length), the number and arrangement of caudal papillae (49-57 pairs in total, arranged as follows: 43-51 pairs precloacal, 2 pairs joined paracloacal and 4 pairs postcloacal), the presence of a particular papilliform medioventral, postcloacal ornamentation and the morphology of the eggs and tip of the female tail. In addition, Ophidascaris najae (Gedoelst, 1916), collected from the king cobra Ophiophagus hannah Cantor (Serpentes: Elapidae) in China, is also redescribed. The morphology of the cervical papillae, labial denticles and phasmids of the female is described for the first time. PMID:25651700

  8. Purification and cloning of cysteine-rich proteins from Trimeresurus jerdonii and Naja atra venoms.

    PubMed

    Jin, Yang; Lu, Qiumin; Zhou, Xingding; Zhu, Shaowen; Li, Rui; Wang, Wanyu; Xiong, Yuliang

    2003-10-01

    Three 26 kDa proteins, named as TJ-CRVP, NA-CRVP1 and NA-CRVP2, were isolated from the venoms of Trimeresurus jerdonii and Naja atra, respectively. The N-terminal sequences of TJ-CRVP and NA-CRVPs were determined. These components were devoid of the enzymatic activities tested, such as phospholipase A(2), arginine esterase, proteolysis, L-amino acid oxidase, 5'nucleotidase, acetylcholinesterase. Furthermore, these three components did not have the following biological activities: coagulant and anticoagulant activities, lethal activity, myotoxicity, hemorrhagic activity, platelet aggregation and platelet aggregation-inhibiting activities. These proteins are named as cysteine-rich venom protein (CRVP) because their sequences showed high level of similarity with mammalian cysteine-rich secretory protein (CRISP) family. Recently, some CRISP-like proteins were also isolated from several different snake venoms, including Agkistrodon blomhoffi, Trimeresurus flavoviridis, Lanticauda semifascita and king cobra. We presumed that CRVP might be a common component in snake venoms. Of particular interest, phylogenetic analysis and sequence alignment showed that NA-CRVP1 and ophanin, both from elapid snakes, share higher similarity with CRVPs from Viperidae snakes. PMID:14529736

  9. PID15, a novel 6 kDa secreted peptide, mediates Naja naja venom phospholipase A2 induced apoptosis in isolated human peripheral lymphocytes

    PubMed Central

    2014-01-01

    Background Snake venoms are a complex mixture of active principles mainly peptides and proteins also including amino acids, nucleotides, free lipids, carbohydrates and metallic elements bound to proteins that interfere in several biological systems. In this study, we aimed to understand the mode of action of the apoptosis inducing ability of Naja naja venom phospholipase A2 (NV-PLA2) using isolated human peripheral lymphocytes. Results Human peripheral lymphocytes when incubated with Naja naja venom phospholipase A2 (NV-PLA2) induced up to 68% DNA fragmentation. The dialysed conditioned media obtained by incubating lymphocytes with NV-PLA2 at 15th min induced 44% DNA fragmentation, referred to as cmlp-active. Cmlp-active showed 20.5% increased protein concentration than the corresponding control condition media cmlp-c-15. Test for creatine kinase activity in cmlp-active proved negative and negligible amount of lactate dehydrogenase did not show significant DNA fragmentation. Fractionation of cmlp-active on Sephadex G-25 showed two peaks, major peak induced 38% DNA fragmentation, which was further rechromatographed on Sephadex G-25. The single peak obtained was named PID15 (Phospholipase A 2 Induced DNA fragmentation factor secreted at 15 th min). Q-Tof MS/MS analysis of PID-15 showed it is a 6 kDa peptide. PID15 sequence analysis gave 40 amino acids in the following order, msilpcknvs iwvikdtaas dkevvlgsdr aikflylatg. The homology search for the sequence revealed it to be an Apoptosis Inducing Factor (AIF). Conclusion Results indicate that the secretion of PID15 is dependent on concentration of NV-PLA2 treatment, incubation time and also on temperature and the probable membrane origin of PID15 and not of cytosolic origin with apoptosis inducing ability. PMID:25030355

  10. Acetylcholine receptors in the ciliary ganglion and in the iris muscle of the chick: specific binding and effect on the synaptic transmission of the neurotoxin from Naja naja siamensis.

    PubMed Central

    Conti-Tronconi, B.; Gotti, C.; Paggi, P.; Rossi, A.

    1979-01-01

    1 A specific binding of Naja naja siamensis neurotoxin was found both in the iris and in the ciliary ganglion of the chick. 2 Naja-toxin (125 nM) caused a complete block of the iris muscle contraction induced by carbamylcholine. 3 Naja-toxin had a different effect on the two neuronal populations present in the ganglion: it blocked the synaptically evoked response of the ciliary cells, while the response of the choroid ones was only slightly reduced. The effects were the same in a wide range of concentrations (125 to 2500 nM). 4 The results obtained in the iris show the existence of an acetylcholine receptor population similar to the nicotinic receptor of the skeletal muscle. 5 In the ciliary ganglion the results confirm the existence of different acetylcholine receptors on the two cell types. PMID:222384

  11. Study on camel IgG purification: a new approach to prepare Naja Naja Oxiana antivenom as passive immunization for therapy.

    PubMed

    Khamehchian, Sedigheh; Zolfagharian, Hossein; Dounighi, Naser Mohammadpour; Tebianian, Majid; Madani, Rasool

    2014-01-01

    A combined process of ammonium sulfate precipitation (salting out) and ion-exchange chromatography on DEAE-Sepharose CL-6B was used to prepare camel antivenom (IgG) against Naja Naja Oxiana for therapy. In the ammonium sulfate precipitation, the best condition for fractionation of IgG from the other proteins in camel serum was 55% precipitate. The camel IgG presented as 2 bands with molecular masses of 250 and 100 kDa, the latter corresponding to heavy chain IgG, on 10% gel electrophoresis. A trace amount of non-IgG proteins was not isolated and remained in this precipitate. Therefore in order to effectively separate albumin and the other nonspecific proteins from the IgG, the 25% precipitate of ammonium sulfate precipitation of serum was subjected to DEAE-Sepharose CL-6B column chromatography. A peak of antibody (IgG) could be obtained by elution with sodium phosphate buffer. In this stage, 2 bands of molecular masses of 150 and 75 kDa were observed on 7% gel electrophoresis. A comparative study was performed between camel IgG and conventional horse F(ab) 2 antivenoms in term of potency (serum neutralization test and ELISA). Our results showed that the potency of camel antivenom was 4-fold higher than that of horse. It is suggested the combined ammonium sulfate precipitation and ion-exchange chromatography process effectively removed residual proteins in the final camel IgG preparation and can be a suitable method for large-scale refinement of therapeutic camel antivenoms. PMID:24642472

  12. Interactions of PLA2-s from Vipera lebetina, Vipera berus berus and Naja naja oxiana Venom with Platelets, Bacterial and Cancer Cells

    PubMed Central

    Samel, Mari; Vija, Heiki; Kurvet, Imbi; Künnis-Beres, Kai; Trummal, Katrin; Subbi, Juhan; Kahru, Anne; Siigur, Jüri

    2013-01-01

    Secretory phospholipasesA2 (sPLA2s) form a large family of structurally related enzymes widespread in nature. Herein, we studied the inhibitory effects of sPLA2s from Vipera lebetina (VLPLA2), Vipera berus berus (VBBPLA2), and Naja naja oxiana (NNOPLA2) venoms on (i) human platelets, (ii) four different bacterial strains (gram-negative Escherichia coli and Vibrio fischeri; gram-positive Staphylococcus aureus and Bacillus subtilis) and (iii) five types of cancer cells (PC-3, LNCaP, MCF-7, K-562 and B16-F10) in vitro. sPLA2s inhibited collagen-induced platelet aggregation: VBBPLA2 IC50 = 0.054, VLPLA2 IC50 = 0.072, NNOPLA2 IC50 = 0.814 μM. p-Bromophenacylbromide-inhibited sPLA2 had no inhibitory action on platelets. 36.17 μM VBBPLA2 completely inhibited the growth of gram-positive Bacillus subtilis whereas no growth inhibition was observed towards gram-negative Escherichia coli. The inhibitory action of sPLA2s (~0.7 μM and ~7 μM) towards cancer cells depended on both venom and cell type. VBBPLA2 (7.2 μM) inhibited significantly the viability of K-562 cells and the cell death appeared apoptotic. The sPLA2s exhibited no inhibitory effect towards LNCaP cells and some effect (8%–20%) towards other cells. Thus, already sub-μM concentrations of sPLA2s inhibited collagen-induced platelet aggregation and from the current suite of studied svPLA2s and test cells, VBBPLA2 was the most growth inhibitory towards Bacillus subtilis and K-562 cells. PMID:23348053

  13. Biochemical and biological characterization of Naja kaouthia venom from North-East India and its neutralization by polyvalent antivenom.

    PubMed

    Das, Diganta; Urs, Nanjaraj; Hiremath, Vilas; Vishwanath, Bannikuppe Sannanaik; Doley, Robin

    2013-01-01

    This study describes biochemical and biological properties of Naja kaouthia (Indian monocled cobra) venom of North-East India. The LD50 of the crude venom was found to be 0.148mg/kg and neurotoxicitic symptoms like paralysis of lower limbs and heavy difficulty in breathing at sub-lethal dose in mice was observed. The venom exhibited PLA2, indirect hemolytic and myotoxic activities but showed weak proteolytic and low direct hemolytic activities. It did not exhibit any hemorrhage when injected intradermally to mice. Anticoagulant activity was prominent when recalcification, prothrombin and activated partial thrombinplastin time were tested on platelet poor plasma. Rotem analysis of whole citrated blood in presence of venom showed delay in coagulation time and clot formation time. Fibrinogen of whole citrated blood was depleted by venom when analyzed in Sonoclot. Crude venom at 10µg and after 16hr of incubation was found to degrade α chain of fibrinogen. Neutralization study showed that Indian polyvalent antivenom could neutralize some of the biochemical and biological activities as well as its fibrinogenolytic activity. PMID:24349704

  14. Biochemical and biological characterization of Naja kaouthia venom from North-East India and its neutralization by polyvalent antivenom

    PubMed Central

    Das, Diganta; Urs, Nanjaraj; Hiremath, Vilas; Vishwanath, Bannikuppe Sannanaik; Doley, Robin

    2013-01-01

    This study describes biochemical and biological properties of Naja kaouthia (Indian monocled cobra) venom of North-East India. The LD50 of the crude venom was found to be 0.148mg/kg and neurotoxicitic symptoms like paralysis of lower limbs and heavy difficulty in breathing at sub-lethal dose in mice was observed. The venom exhibited PLA2, indirect hemolytic and myotoxic activities but showed weak proteolytic and low direct hemolytic activities. It did not exhibit any hemorrhage when injected intradermally to mice. Anticoagulant activity was prominent when recalcification, prothrombin and activated partial thrombinplastin time were tested on platelet poor plasma. Rotem analysis of whole citrated blood in presence of venom showed delay in coagulation time and clot formation time. Fibrinogen of whole citrated blood was depleted by venom when analyzed in Sonoclot. Crude venom at 10µg and after 16hr of incubation was found to degrade α chain of fibrinogen. Neutralization study showed that Indian polyvalent antivenom could neutralize some of the biochemical and biological activities as well as its fibrinogenolytic activity. PMID:24349704

  15. Venom gland transcriptomes of two elapid snakes (Bungarus multicinctus and Naja atra) and evolution of toxin genes

    PubMed Central

    2011-01-01

    Background Kraits (genus Bungarus) and cobras (genus Naja) are two representative toxic genera of elapids in the old world. Although they are closely related genera and both of their venoms are very toxic, the compositions of their venoms are very different. To unveil their detailed venoms and their evolutionary patterns, we constructed venom gland cDNA libraries and genomic bacterial artificial chromosome (BAC) libraries for Bungarus multicinctus and Naja atra, respectively. We sequenced about 1500 cDNA clones for each of the venom cDNA libraries and screened BAC libraries of the two snakes by blot analysis using four kinds of toxin probes; i.e., three-finger toxin (3FTx), phospholipase A2 (PLA2), kunitz-type protease inhibitor (Kunitz), and natriuretic peptide (NP). Results In total, 1092 valid expressed sequences tags (ESTs) for B. multicinctus and 1166 ESTs for N. atra were generated. About 70% of these ESTs can be annotated as snake toxin transcripts. 3FTx (64.5%) and β bungarotoxin (25.1%) comprise the main toxin classes in B. multicinctus, while 3FTx (95.8%) is the dominant toxin in N. atra. We also observed several less abundant venom families in B. multicinctus and N. atra, such as PLA2, C-type lectins, and Kunitz. Peculiarly a cluster of NP precursors with tandem NPs was detected in B. multicinctus. A total of 71 positive toxin BAC clones in B. multicinctus and N. atra were identified using four kinds of toxin probes (3FTx, PLA2, Kunitz, and NP), among which 39 3FTx-postive BACs were sequenced to reveal gene structures of 3FTx toxin genes. Conclusions Based on the toxin ESTs and 3FTx gene sequences, the major components of B. multicinctus venom transcriptome are neurotoxins, including long chain alpha neurotoxins (α-ntx) and the recently originated β bungarotoxin, whereas the N. atra venom transcriptome mainly contains 3FTxs with cytotoxicity and neurotoxicity (short chain α-ntx). The data also revealed that tandem duplications contributed the most to

  16. Cytotoxic potency of cardiotoxin from Naja sputatrix: development of a new cytolytic assay.

    PubMed Central

    Ma, Donghui; Armugam, Arunmozhiarasi; Jeyaseelan, Kandiah

    2002-01-01

    The possible involvement of specific regions/loops of cardiotoxin from Naja sputatrix venom in mediating its cytolytic activity is evaluated using a new cytolytic assay. In this assay, the amount of chloramphenicol acetyltransferase (CAT) that is released upon lysis of the cellular membranes by the cytotoxin has been measured as an index of cytolysis. This newly developed CAT system is more sensitive than the traditional haemolysis method utilizing red blood cells or the lactate dehydrogenase assay for cytolysis. Series of chimaeric toxin molecules have been constructed by swapping the loops between highly hydrophilic neurotoxin and highly hydrophobic cardiotoxin molecules from Naja sputatrix, which are known to exhibit structural similarity (three-finger conformation) but to have different functional properties. Comparison of the cytolytic activities of the recombinant chimaeric toxins demonstrated the possible involvement of all three loops of cardiotoxin in its cytolytic potency. However, the first two loops of the protein appear to make the major contribution to its lytic activity. cDNAs encoding cardiotoxin and the chimaeric toxins, when expressed in transfected cultured Chinese hamster ovary cells, resulted in cell lysis, indicating that these cDNAs can be developed as useful cytolytic agents. PMID:12027804

  17. Neutralization of the Principal Toxins from the Venoms of Thai Naja kaouthia and Malaysian Hydrophis schistosus: Insights into Toxin-Specific Neutralization by Two Different Antivenoms.

    PubMed

    Tan, Kae Yi; Tan, Choo Hock; Fung, Shin Yee; Tan, Nget Hong

    2016-04-01

    Antivenom neutralization against cobra venoms is generally low in potency, presumably due to poor toxin-specific immunoreactivity. This study aimed to investigate the effectiveness of two elapid antivenoms to neutralize the principal toxins purified from the venoms of the Thai monocled cobra (Naja kaouthia, Nk-T) and the Malaysian beaked sea snake (Hydrophis schistosus, Hs-M). In mice, N. kaouthia Monovalent Antivenom (NKMAV) neutralization against Nk-T long neurotoxin (LNTX) and cytotoxin was moderate (potency of 2.89-6.44 mg toxin/g antivenom protein) but poor against the short neurotoxin (SNTX) (1.33 mg/g). Its cross-neutralization against Hs-M LNTX of Hs-M is compatible (0.18 mg/g) but much weaker against Hs-M SNTX (0.22 mg/g). Using CSL (Seqirus Limited) Sea Snake Antivenom (SSAV), we observed consistently weak neutralization of antivenom against SNTX of both species, suggesting that this is the limiting factor on the potency of antivenom neutralization against venoms containing SNTX. Nevertheless, SSAV outperformed NKMAV in neutralizing SNTXs of both species (0.61-2.49 mg/g). The superior efficacy of SSAV against SNTX is probably partly attributable to the high abundance of SNTX in sea snake venom used as immunogen in SSAV production. The findings indicate that improving the potency of cobra antivenom may be possible with a proper immunogen formulation that seeks to overcome the limitation on SNTX immunoreactivity. PMID:27023606

  18. Neutralization of the Principal Toxins from the Venoms of Thai Naja kaouthia and Malaysian Hydrophis schistosus: Insights into Toxin-Specific Neutralization by Two Different Antivenoms

    PubMed Central

    Tan, Kae Yi; Tan, Choo Hock; Fung, Shin Yee; Tan, Nget Hong

    2016-01-01

    Antivenom neutralization against cobra venoms is generally low in potency, presumably due to poor toxin-specific immunoreactivity. This study aimed to investigate the effectiveness of two elapid antivenoms to neutralize the principal toxins purified from the venoms of the Thai monocled cobra (Naja kaouthia, Nk-T) and the Malaysian beaked sea snake (Hydrophis schistosus, Hs-M). In mice, N. kaouthia Monovalent Antivenom (NKMAV) neutralization against Nk-T long neurotoxin (LNTX) and cytotoxin was moderate (potency of 2.89–6.44 mg toxin/g antivenom protein) but poor against the short neurotoxin (SNTX) (1.33 mg/g). Its cross-neutralization against Hs-M LNTX of Hs-M is compatible (0.18 mg/g) but much weaker against Hs-M SNTX (0.22 mg/g). Using CSL (Seqirus Limited) Sea Snake Antivenom (SSAV), we observed consistently weak neutralization of antivenom against SNTX of both species, suggesting that this is the limiting factor on the potency of antivenom neutralization against venoms containing SNTX. Nevertheless, SSAV outperformed NKMAV in neutralizing SNTXs of both species (0.61–2.49 mg/g). The superior efficacy of SSAV against SNTX is probably partly attributable to the high abundance of SNTX in sea snake venom used as immunogen in SSAV production. The findings indicate that improving the potency of cobra antivenom may be possible with a proper immunogen formulation that seeks to overcome the limitation on SNTX immunoreactivity. PMID:27023606

  19. Humanized-Single Domain Antibodies (VH/VHH) that Bound Specifically to Naja kaouthia Phospholipase A2 and Neutralized the Enzymatic Activity

    PubMed Central

    Chavanayarn, Charnwit; Thanongsaksrikul, Jeeraphong; Thueng-in, Kanyarat; Bangphoomi, Kunan; Sookrung, Nitat; Chaicumpa, Wanpen

    2012-01-01

    Naja kaouthia (monocled cobra) venom contains many isoforms of secreted phospholipase A2 (sPLA2). The PLA2 exerts several pharmacologic and toxic effects in the snake bitten subject, dependent or independent on the enzymatic activity. N. kaouthia venom appeared in two protein profiles, P3 and P5, after fractionating the venom by ion exchange column chromatography. In this study, phage clones displaying humanized-camel single domain antibodies (VH/VHH) that bound specifically to the P3 and P5 were selected from a humanized-camel VH/VHH phage display library. Two phagemid transfected E. coli clones (P3-1 and P3-3) produced humanized-VHH, while another clone (P3-7) produced humanized-VH. At the optimal venom:antibody ratio, the VH/VHH purified from the E. coli homogenates neutralized PLA2 enzyme activity comparable to the horse immune serum against the N. kaouthia holo-venom. Homology modeling and molecular docking revealed that the VH/VHH covered the areas around the PLA2 catalytic groove and inserted their Complementarity Determining Regions (CDRs) into the enzymatic cleft. It is envisaged that the VH/VHH would ameliorate/abrogate the principal toxicity of the venom PLA2 (membrane phospholipid catabolism leading to cellular and subcellular membrane damage which consequently causes hemolysis, hemorrhage, and dermo-/myo-necrosis), if they were used for passive immunotherapy of the cobra bitten victim. The speculation needs further investigations. PMID:22852068

  20. Bacteriology of Naja atra Snakebite Wound and Its Implications for Antibiotic Therapy.

    PubMed

    Mao, Yan-Chiao; Liu, Po-Yu; Hung, Dong-Zong; Lai, Wei-Cheng; Huang, Shih-Ting; Hung, Yao-Min; Yang, Chen-Chang

    2016-05-01

    A total of 112 cases of Naja atra envenomation were examined at two referring hospitals: Taichung Veterans General Hospital in central Taiwan and Taipei Veterans General Hospital (VGH-TP) in northern Taiwan. Overall, 77% (86/112) of cases developed clinically suspected wound infections and 54% (61/112) required surgery secondary to tissue necrosis, finger or toe gangrene, and/or necrotizing fasciitis. Morganella morganii was the most abundant gram-negative bacterial strain isolated from bite wounds, followed by Proteus spp., Aeromonas hydrophila, Pseudomonas aeruginosa, and Providencia spp. in descending order; Enterococcus spp. were the most common gram-positive bacteria and Bacteroides spp. were the only anaerobic bacteria. A few episodes of bacteremia were caused by Bacteroides and Shewanella spp. There were no significant variations in the distribution of bacterial species between these two hospitals except for a higher incidence of M. morganii, Enterococcus spp., and polymicrobial infection observed at VGH-TP, which may have been related to variations in the fecal flora of prey and oral flora of individual snakes in different geographic areas in Taiwan. According to the susceptibility test involving various pathogens, first-line drug options for the management of N. atra snakebite wound infections may include monotherapy with ureidopenicillin or combination therapy with aminopenicillin and a third-generation cephalosporin or fluoroquinolone. A prospective evaluation of empiric antibiotic therapy for the management of N. atra snakebite should be considered. PMID:26976881

  1. MOLECULAR MODEL OF CYTOTOXIN-1 FROM NAJA MOSSAMBICA MOSSAMBICA VENOM IN COMPLEX WITH CHYMOTRYPSIN.

    PubMed

    Munawar, Aisha; Akrem, Ahmed; Hussain, Ashiq; Spencer, Patrick; Betzel, Christian

    2015-01-01

    Snake venom is a myriad of biologically active proteins and peptides. Three finger toxins are highly conserved in their molecular structure, but interestingly possess diverse biological functions. During the course of evolution the introduction of subtle mutations in loop regions and slight variations in the three dimensional structure, has resulted in their functional versatility. Cytotoxin-1 (UniProt ID: P01467), isolated from Naja mossambica mossambica, showed the potential to inhibit chymotrypsin and the chymotryptic activity of the 20S proteasome. In the present work we describe a molecular model of cytotoxin-1 in complex with chymotrypsin, prepared by the online server ClusPro. Analysis of the molecular model shows that Cytotoxin-1 (P01467) binds to chymotrypsin through its loop I located near the N-terminus. The concave side of loop I of the toxin fits well in the substrate binding pocket of the protease. We propose Phe10 as the dedicated P1 site of the ligand. Being a potent inhibitor of the 20S proteasome, cytotoxin-1 (P01467) can serve as a potential antitumor agent. Already snake venom cytotoxins have been investigated for their ability as an anticancer agent. The molecular model of cytotoxin-1 in complex with chymotrypsin provides important information towards understanding the complex formation. PMID:27167912

  2. Design of specific peptide inhibitors for group I phospholipase A2: structure of a complex formed between phospholipase A2 from Naja naja sagittifera (group I) and a designed peptide inhibitor Val-Ala-Phe-Arg-Ser (VAFRS) at 1.9 A resolution reveals unique features.

    PubMed

    Singh, Rajendra Kumar; Vikram, P; Makker, Jyoti; Jabeen, Talat; Sharma, Sujata; Dey, Sharmistha; Kaur, Punit; Srinivasan, A; Singh, Tej P

    2003-10-14

    Phospholipase A(2) (PLA(2)) (E. C. 3.1.1.4) is a common enzyme in the two-way cascade mechanism leading to the production of proinflammatory compounds known as eicosanoids. The binding of phospholipase A(2) to the membrane surface and hydrolysis of phospholipids are thought to involve the formation of a hydrophobic channel into which a single substrate molecule diffuses before its cleavage. To regulate the production of proinflammatory compounds, a specific peptide inhibitor Val-Ala-Phe-Arg-Ser (VAFRS) for the group I PLA(2) enzymes has been designed and synthesized. PLA(2) was isolated from Indian cobra (Naja naja sagittifera) venom and purified to homogeneity. The binding studies indicated the K(i) value of 1.02 +/- 0.10 x 10(-8) M. The purified PLA(2) samples and the designed inhibitor VAFRS were cocrystallized. The crystal structure of the complex was determined and refined to 1.9 A resolution. The peptide binds to PLA(2) at the active site and fills the hydrophobic channel completely. However, its placement with respect to the channel is in the opposite direction as compared to those observed in group II PLA(2)'s. Furthermore, the predominant intermolecular interactions involve strong electrostatic interactions between the side chains of peptide Arg and Asp 49 of PLA(2) together with a number of van der Waals interactions with other residues. A good number of observed interactions between the peptide and the protein indicate the significance of a structure-based drug design approach. The novel factor in the present sequence of the peptide is related to the introduction of a positively charged residue at the C-terminal part of the peptide. PMID:14529280

  3. Central loop of non-conventional toxin WTX from Naja kaouthia is important for interaction with nicotinic acetylcholine receptors.

    PubMed

    Lyukmanova, Ekaterina N; Shulepko, Mikhail A; Shenkarev, Zakhar O; Kasheverov, Igor E; Chugunov, Anton O; Kulbatskii, Dmitrii S; Myshkin, Mikhail Yu; Utkin, Yuri N; Efremov, Roman G; Tsetlin, Victor I; Arseniev, Alexander S; Kirpichnikov, Mikhail P; Dolgikh, Dmitry A

    2016-09-01

    'Three-finger' toxin WTX from Naja kaouthia interacts with nicotinic and muscarinic acetylcholine receptors (nAChRs and mAChRs). Mutagenesis and competition experiments with (125)I-α-bungarotoxin revealed that Arg31 and Arg32 residues from the WTX loop II are important for binding to Torpedo californica and human α7 nAChRs. Computer modeling suggested that loop II occupies the orthosteric binding site at α7 nAChR. The similar toxin interface was previously described as a major determinant of allosteric interactions with mAChRs. PMID:27343701

  4. Spectroscopic investigations on the binding of persimmon tannin to phospholipase A 2 from Chinese cobra ( Naja naja atra)

    NASA Astrophysics Data System (ADS)

    Yang, Jie; Zhong, Li; Zou, Bo; Tian, Yan; Xu, Shu-fen; Yao, Ping; Li, Chun-mei

    2012-01-01

    To understand the anti-venom mechanism of persimmon tannin, the interaction between persimmon tannin (PT) and phospholipase A 2 (PLA 2) under physiological conditions was investigated by fluorescence quenching technique in combination with Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra techniques. The results revealed that gradual fluorescence quenching was observed by titration of PLA 2 (2.0 μM) with increasing concentrations of PT (from 0 to 2.025 μM), and the type of quenching was found to be a static quenching process. Stern-Volmer plots were not linear but had an intersection at CPT ≈ 1.0 μM, indicating that PT binded to more than one class of sites on PLA 2. The binding sites calculated on basis of Scatchard plots were about 2, supporting this result. The enthalpy change (Δ H) and entropy change (Δ S) of the binding sites were -17.44 kJ/mol and 59.90 kJ/mol·, separately, suggesting that hydrophobic interaction played a main role in the binding. In addition, synchronous fluorescence, FT-IR and CD spectra showed that dramatic conformational changes in PLA 2 were induced by its interaction with PT.

  5. Phytomedical investigation of Najas minor All. in the view of the chemical constituents.

    PubMed

    Topuzovic, Marina D; Radojevic, Ivana D; Dekic, Milan S; Radulovic, Niko S; Vasic, Sava M; Comic, Ljiljana R; Licina, Braho Z

    2015-01-01

    Plants are an abundant natural source of effective antibiotic compounds. Phytomedical investigations of certain plants haven't still been conducted. One of them is Najas minor (N. minor), an aquatic plant with confirmed allelopathy. Research conducted in this study showed the influence of water and ethyl acetate extracts of N. minor on microorganisms, in the view of chemical profiling of volatile constituents and the concentrations of total phenols, flavonoids and tannins. Antimicrobial activity was defined by determining minimum inhibitory and minimum microbicidal concentrations using microdilution method. Influence on bacterial biofilm formation was performed by tissue culture plate method. The total phenolics, flavonoids and condensed tannins were determined by Folin-Ciocalteu, aluminum chloride and butanol-HCl colorimetric methods. Chemical profiling of volatile constituents was investigated by GC and GC-MS. Water extract didn't have antimicrobial activity below 5000 µg/mL. Ethyl acetate extract has shown strong antimicrobial activity on G+ bacteria - Staphylococcus aureus PMFKGB12 and Bacillus subtilis (MIC < 78.13 µg/mL). The best antibiofilm activity was obtained on Escherichia coli ATCC25922 (BIC50 at 719 µg/mL). Water extract had higher yield. Ethyl acetate extract had a significantly greater amount of total phenolics, flavonoids and tannins. As major constituent hexahydrofarnesyl acetone was identified. The ethyl acetate extract effected only G+ bacteria, but the biofilm formation of G-bacteria was suppressed. There was a connection between those in vivo and in vitro effects against pathogenic bacterial biofilm formation. All of this points to a so far unexplored potential of N. minor. PMID:26535038

  6. Antisnake Venom Activity of Hibiscus aethiopicus L. against Echis ocellatus and Naja n. nigricollis.

    PubMed

    Hasson, S S; Al-Jabri, A A; Sallam, T A; Al-Balushi, M S; Mothana, R A A

    2010-01-01

    The objective of the study is to investigate whether the Hibiscus aethiopicus L. plant has neutralization activity against venoms of two clinically important snakes. The H. aethiopicus was dried and extracted with water. Different assays were performed to evaluate the plant's acute toxicity and its anti-snake venom activities. The results showed that H. aethiopicus extract alone had no effect on the viability of C(2)C(12) muscle cells, but significantly (P < .05) protected muscle cells against the toxic effects of E. ocellatus venom at 55, 150, and 300 mug/mL. The maximum protective effect of the extract was exhibited at 75 mug/mL. The extract significantly (P < .001) inhibited the cytotoxic effects of E. ocellatus venom at 300 mug/mL. All rabbits (n = 10) and guinea pigs (n = 10) were alive after the two weeks of given the lethal dosage 16 g/Kg of the H. aethiopicus extract herbal solution. No abnormal behaviour was observed of both groups of animals. All guinea pigs (n = 3) treated with venoms alone (5 mg/kg) died. However, all guinea pigs (n = 21) treated with venom (5 mg/kg) and the extract (400 to 1000 mg/kg) survived. Guinea pigs (n = 3) treated with Naja n. nigricollis venom alone (2.5 mg/kg) and guinea pigs (n = 21) venom with the extract (400 to 1000 mg/kg) died. The H. aethiopicus completely (100%) blocked the haemorrhagic activity of E. ocellatus in the egg embryo at 3.3 mg/mL of extract. These findings suggest that H. aethiopicus may contain an endogenous inhibitor of venom-induced haemorrhage. PMID:20628507

  7. Humanized-single domain antibodies (VH/VHH) that bound specifically to Naja kaouthia phospholipase A2 and neutralized the enzymatic activity.

    PubMed

    Chavanayarn, Charnwit; Thanongsaksrikul, Jeeraphong; Thueng-In, Kanyarat; Bangphoomi, Kunan; Sookrung, Nitat; Chaicumpa, Wanpen

    2012-07-01

    Naja kaouthia (monocled cobra) venom contains many isoforms of secreted phospholipase A2 (sPLA(2)). The PLA(2) exerts several pharmacologic and toxic effects in the snake bitten subject, dependent or independent on the enzymatic activity. N. kaouthia venom appeared in two protein profiles, P3 and P5, after fractionating the venom by ion exchange column chromatography. In this study, phage clones displaying humanized-camel single domain antibodies (VH/V(H)H) that bound specifically to the P3 and P5 were selected from a humanized-camel VH/V(H)H phage display library. Two phagemid transfected E. coli clones (P3-1 and P3-3) produced humanized-V(H)H, while another clone (P3-7) produced humanized-VH. At the optimal venom:antibody ratio, the VH/V(H)H purified from the E. coli homogenates neutralized PLA(2) enzyme activity comparable to the horse immune serum against the N. kaouthia holo-venom. Homology modeling and molecular docking revealed that the VH/V(H)H covered the areas around the PLA(2) catalytic groove and inserted their Complementarity Determining Regions (CDRs) into the enzymatic cleft. It is envisaged that the VH/V(H)H would ameliorate/abrogate the principal toxicity of the venom PLA(2) (membrane phospholipid catabolism leading to cellular and subcellular membrane damage which consequently causes hemolysis, hemorrhage, and dermo-/myo-necrosis), if they were used for passive immunotherapy of the cobra bitten victim. The speculation needs further investigations. PMID:22852068

  8. Biological activities of Peristrophe bivalvis extracts: promising potential for anti-snake venoms against Naja kaouthia and Trimeresurus albolabris venoms.

    PubMed

    Phaopongthai, Jatuporn; Noiphrom, Jureeporn; Phaopongthai, Supat; Pakmanee, Narumol; Sichaem, Jirapast

    2016-01-01

    This study evaluates the in vitro anti-snake venom potential of Peristrophe bivalvis (PB) extracts against Naja kaouthia (NK) and Trimeresurus albolabris (TA) venoms, including inhibition of cytotoxic effects and enzymatic activities, and the binding-precipitation of extracts and venom proteins analysis. In addition, the antioxidant, cytotoxic and in vivo acute oral toxic activities of PB extracts are also reported. The in vitro cytotoxic and enzymatic analysis reveals that the ethanol extracts of stems and leaves of PB showed good anti-snake venom activity against NK and TA venoms. In addition, the antioxidant result indicated that only the ethanol extract of leaves exhibited weak DPPH radical-scavenging activity. The ethanol whole-plant extract of PB also showed no cytotoxicity against four cell lines. Moreover, the in vivo acute oral toxicity result of the ethanol whole-plant extract showed that all treated rats did not exhibit abnormal toxic signs or deaths. PMID:25942501

  9. Purification, N-terminal sequencing, crystallization and preliminary structural determination of atratoxin-b, a short-chain alpha-neurotoxin from Naja atra venom.

    PubMed

    Lou, Xiaohua; Tu, Xiongying; Pan, Guoqiang; Xu, Chaoyin; Fan, Rong; Lu, Wanhua; Deng, Wenhan; Rao, Pingfan; Teng, Maikun; Niu, Liwen

    2003-06-01

    Atratoxin-b, a short-chain alpha-neurotoxin purified from Naja atra (mainland Chinese cobra) venom using a three-step chromatography procedure, has an apparent molecular mass of 6950 Da with an alkaline pI value (>9.5) and consists of one single polypeptide chain as estimated by MALDI-TOF mass spectrometry and SDS-PAGE. The protein is toxic to mice, with an in vitro LD(50) of about 0.18 mg kg(-1). Its N-terminal amino-acid sequence, LECHNQQSSQTPTIT, displays a very high homology to those of other alpha-neurotoxins. The overall three-dimensional structure of atratoxin-b is very similar to that of the homologous erabutoxin-a, as shown by the crystallographic molecular replacement and preliminary refinement results, with an R factor and R(free) of 27 and 29%, respectively. The microcrystal slowly grew to dimensions of approximate 0.1 x 0.1 x 0.15 mm over eight months using hanging-drop vapour-diffusion method. It gave a set of diffraction data to 1.56 A resolution using X-rays of wavelength 1.1516 A generated by the X-ray Diffraction and Scattering Station of beamline U7B at the National Synchrotron Radiation Laboratory (Hefei, China); this is the first example of the use of this beamline in protein crystallography. The crystals belong to the tetragonal space group P4(1)2(1)2, with unit-cell parameters a = 49.28, c = 44.80 A, corresponding to one molecule per asymmetric unit and a volume-to-mass ratio of 1.96 A(3) Da(-1). PMID:12777767

  10. Arsenic accumulation and tolerance in rootless macrophyte Najas indica are mediated through antioxidants, amino acids and phytochelatins.

    PubMed

    Tripathi, Rudra Deo; Singh, Ragini; Tripathi, Preeti; Dwivedi, Sanjay; Chauhan, Reshu; Adhikari, Bijan; Trivedi, Prabodh Kumar

    2014-12-01

    Arsenic (As) accumulation and tolerance response of a submerged rootless macrophyte Najas indica were evaluated during arsenate (As(V); 10-250 μM) and arsenite (As(III); 1-50 μM) exposure. Higher As accumulation at As(III) exposure and more tolerance upon As(V) exposure resulted in more toxicity during As(III) stress than As(V), which was evident through measurement of growth parameters and oxidative stress related parameters viz., lipid peroxidation (MDA content), electrical conductivity (EC) and hydrogen peroxide (H2O2) levels. Antioxidant enzymes and various amino acids were more prominent during moderate exposure of As(V), suggesting their possible role in As tolerance and detoxification. Various non-enzymatic antioxidant metabolites viz., ascorbic acid (ASC), glutathione (GSH), non-protein thiols (NPTs) and phytochelatins (PCs) biosynthesis involving phytochelatin synthase (PCS) activity increased more significantly during As(III) stress. However, PCs content seems inadequate in response to As accumulation leading to lower PC-SH:As molar ratio and higher As phytotoxicity during As(III) stress. N. indica may prove useful plant species for phytoremediation purpose in moderately As contaminated water bodies due to high As accumulation and tolerance potential. PMID:25456221

  11. The Plastid Genome of Najas flexilis: Adaptation to Submersed Environments Is Accompanied by the Complete Loss of the NDH Complex in an Aquatic Angiosperm

    PubMed Central

    Peredo, Elena L.; King, Ursula M.; Les, Donald H.

    2013-01-01

    The re-colonization of aquatic habitats by angiosperms has presented a difficult challenge to plants whose long evolutionary history primarily reflects adaptations to terrestrial conditions. Many aquatics must complete vital stages of their life cycle on the water surface by means of floating or emergent leaves and flowers. Only a few species, mainly within the order Alismatales, are able to complete all aspects of their life cycle including pollination, entirely underwater. Water-pollinated Alismatales include seagrasses and water nymphs (Najas), the latter being the only freshwater genus in the family Hydrocharitaceae with subsurface water-pollination. We have determined the complete nucleotide sequence of the plastid genome of Najas flexilis. The plastid genome of N. flexilis is a circular AT-rich DNA molecule of 156 kb, which displays a quadripartite structure with two inverted repeats (IR) separating the large single copy (LSC) from the small single copy (SSC) regions. In N. flexilis, as in other Alismatales, the rps19 and trnH genes are localized in the LSC region instead of within the IR regions as in other monocots. However, the N. flexilis plastid genome presents some anomalous modifications. The size of the SSC region is only one third of that reported for closely related species. The number of genes in the plastid is considerably less. Both features are due to loss of the eleven ndh genes in the Najas flexilis plastid. In angiosperms, the absence of ndh genes has been related mainly to the loss of photosynthetic function in parasitic plants. The ndh genes encode the NAD(P)H dehydrogenase complex, believed essential in terrestrial environments, where it increases photosynthetic efficiency in variable light intensities. The modified structure of the N. flexilis plastid genome suggests that adaptation to submersed environments, where light is scarce, has involved the loss of the NDH complex in at least some photosynthetic angiosperms. PMID:23861923

  12. The plastid genome of Najas flexilis: adaptation to submersed environments is accompanied by the complete loss of the NDH complex in an aquatic angiosperm.

    PubMed

    Peredo, Elena L; King, Ursula M; Les, Donald H

    2013-01-01

    The re-colonization of aquatic habitats by angiosperms has presented a difficult challenge to plants whose long evolutionary history primarily reflects adaptations to terrestrial conditions. Many aquatics must complete vital stages of their life cycle on the water surface by means of floating or emergent leaves and flowers. Only a few species, mainly within the order Alismatales, are able to complete all aspects of their life cycle including pollination, entirely underwater. Water-pollinated Alismatales include seagrasses and water nymphs (Najas), the latter being the only freshwater genus in the family Hydrocharitaceae with subsurface water-pollination. We have determined the complete nucleotide sequence of the plastid genome of Najas flexilis. The plastid genome of N. flexilis is a circular AT-rich DNA molecule of 156 kb, which displays a quadripartite structure with two inverted repeats (IR) separating the large single copy (LSC) from the small single copy (SSC) regions. In N. flexilis, as in other Alismatales, the rps19 and trnH genes are localized in the LSC region instead of within the IR regions as in other monocots. However, the N. flexilis plastid genome presents some anomalous modifications. The size of the SSC region is only one third of that reported for closely related species. The number of genes in the plastid is considerably less. Both features are due to loss of the eleven ndh genes in the Najas flexilis plastid. In angiosperms, the absence of ndh genes has been related mainly to the loss of photosynthetic function in parasitic plants. The ndh genes encode the NAD(P)H dehydrogenase complex, believed essential in terrestrial environments, where it increases photosynthetic efficiency in variable light intensities. The modified structure of the N. flexilis plastid genome suggests that adaptation to submersed environments, where light is scarce, has involved the loss of the NDH complex in at least some photosynthetic angiosperms. PMID:23861923

  13. Correlation between the phospholipids domains of the target cell membrane and the extent of Naja kaouthia PLA(2)-induced membrane damage: evidence of distinct catalytic and cytotoxic sites in PLA(2) molecules.

    PubMed

    Mukherjee, Ashis K

    2007-02-01

    Two phospholipase A(2) (PLA(2)) enzymes (NK-PLA(2)-A and NK-PLA(2)-B) were purified from the venom of the monocled cobra Naja kaouthia. The molecular weights of NK-PLA(2)-A and NK-PLA(2)-B, as estimated by mass spectrometry, were 13,619 and 13,303 Da respectively. Both phospholipases were highly thermostable, had maximum catalytic activity at basic pH, and showed preferential hydrolysis of phosphatidylcholine. Intravenous injection of either PLA(2) up to a dose of 10 mg/kg body weight was non-toxic to mice and did not show neurotoxic symptoms. The N. kaouthia PLA(2)s displayed anticoagulant and cytotoxic activity, but poor hemolytic activity. Both the PLA(2)s were more toxic to Sf9 and Tn cells compared to VERO cells. NK-PLA(2) exhibited selective lysis of wild-type baculovirus-infected Sf9 cells compared to normal cells. Amino acid modification studies and heating experiments suggest that separate sites in the NK-PLA(2) molecules are responsible for their catalytic, anticoagulant and cytotoxic activities. PMID:17127009

  14. Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage

    PubMed Central

    2005-01-01

    Cytotoxins from cobra venom are known to manifest cytotoxicity in various cell types. It is widely accepted that the plasma membrane is a target of cytotoxins, but the mechanism of their action remains obscure. Using the confocal spectral imaging technique, we show for the first time that cytotoxins from cobra venom penetrate readily into living cancer cells and accumulate markedly in lysosomes. Cytotoxins CT1 and CT2 from Naja oxiana, CT3 from Naja kaouthia and CT1 from Naja haje are demonstrated to possess this property with respect to human lung adenocarcinoma A549 and promyelocytic leukaemia HL60 cells. Immobilized plasma membrane binding accompanies the internalization of CT3 from Naja kaouthia in the HL60 cells, but it is very weak for other cytotoxins. Detectable membrane binding is not a property of any of the cytotoxins tested in A549 cells. The kinetics and concentration-dependence of cytotoxin accumulation in lysosomes correlate well with their cytotoxic effects. On the basis of the results obtained, we propose that lysosomes are a primary target of the lytic action of cytotoxins. Plasma membrane permeabilization seems to be a downstream event relative to lysosome rupture. Direct damage to the plasma membrane may be a complementary mechanism, but its relative contribution to the cytotoxic action depends on the cytotoxin structure and cell type. PMID:15847607

  15. Molecular cloning and characterization of a complement-depleting factor from king cobra, Ophiophagus hannah.

    PubMed

    Zeng, Lin; Sun, Qian-Yun; Jin, Yang; Zhang, Yong; Lee, Wen-Hui; Zhang, Yun

    2012-09-01

    Cobra venom factor (CVF) is an anti-complement factor existing in cobra venom. CVF proteins have been purified from the venoms of Naja haje, Naja siamensis, Naja atra, Naja kaouthia, Naja naja, Naja melanoleuca and Austrelaps superbus, but only three full-length cDNA sequences of CVF are available. In the present work, a cobra venom factor termed OVF was purified from the crude venom of Ophiophagus hannah by successive gel filtration, ion-exchange and heparin affinity chromatography steps. The purified OVF was homogenous on the SDS-PAGE gel with an apparent molecular weight of 140 kDa under non-reducing conditions. Under reducing conditions, OVF was divided into three bands with apparent molecular weight of 72 kDa (α chain), 45 kDa (β chain) and 32 kDa (γ chain), respectively. OVF consumed complement components with anti-complement activity of 154 units per mg. By using Reverse transcription-PCR and 5'-RACE assay, the open reading frame of OVF was obtained. MALDI-TOF and protein sequencing assays confirmed the cloned cDNA coding for OVF protein. The cDNA sequence of OVF is conservative when aligned with that of other CVFs. Phylogenetic analysis revealed OVF is closer to CVF from N. kaouthia than to AVF-1 and AVF-2 from A. superbus. Our results demonstrated that OVF has its unique features as following: 1) The N-terminal amino acid sequence of OVF γ chain is different from that of other known CVFs, suggesting that the OVF γ chain might be further processed; 2) Unlike N. kaouthia CVF and A. superbus AVF-1, which have potential N-linked glycosylation sites located in both α and β chain, OVF only has N-linked glycosylation site in its α chain as revealed by Schiff's reagent staining and protein sequence analysis; 3) In addition to the 27 well conserved cysteine residues in all known CVFs, OVF have an additional cysteine residue in its γ chain. Understanding the importance of above mentioned specific characteristics might provide useful information on structure

  16. Structural Insight into Specificity of Interactions between Nonconventional Three-finger Weak Toxin from Naja kaouthia (WTX) and Muscarinic Acetylcholine Receptors.

    PubMed

    Lyukmanova, Ekaterina N; Shenkarev, Zakhar O; Shulepko, Mikhail A; Paramonov, Alexander S; Chugunov, Anton O; Janickova, Helena; Dolejsi, Eva; Dolezal, Vladimir; Utkin, Yuri N; Tsetlin, Victor I; Arseniev, Alexander S; Efremov, Roman G; Dolgikh, Dmitry A; Kirpichnikov, Mikhail P

    2015-09-25

    Weak toxin from Naja kaouthia (WTX) belongs to the group of nonconventional "three-finger" snake neurotoxins. It irreversibly inhibits nicotinic acetylcholine receptors and allosterically interacts with muscarinic acetylcholine receptors (mAChRs). Using site-directed mutagenesis, NMR spectroscopy, and computer modeling, we investigated the recombinant mutant WTX analogue (rWTX) which, compared with the native toxin, has an additional N-terminal methionine residue. In comparison with the wild-type toxin, rWTX demonstrated an altered pharmacological profile, decreased binding of orthosteric antagonist N-methylscopolamine to human M1- and M2-mAChRs, and increased antagonist binding to M3-mAChR. Positively charged arginine residues located in the flexible loop II were found to be crucial for rWTX interactions with all types of mAChR. Computer modeling suggested that the rWTX loop II protrudes to the M1-mAChR allosteric ligand-binding site blocking the entrance to the orthosteric site. In contrast, toxin interacts with M3-mAChR by loop II without penetration into the allosteric site. Data obtained provide new structural insight into the target-specific allosteric regulation of mAChRs by "three-finger" snake neurotoxins. PMID:26242733

  17. Spitting cobras adjust their venom distribution to target distance.

    PubMed

    Berthé, Ruben Andres; de Pury, Stéphanie; Bleckmann, Horst; Westhoff, Guido

    2009-08-01

    If threatened by a human, spitting cobras defend themselves by ejecting their venom toward the face of the antagonist. Circulating head movements of the cobra ensure that the venom is distributed over the face. To assure an optimal distribution of the venom, the amplitudes of head movements should decrease with increasing target distance. To find out whether cobras (Naja pallida and N. nigricollis) adjust their spitting behavior according to target distance we induced spitting from different distances and analyzed their spitting patterns. Our results show that the spray pattern of spitting cobras is not fixed. Instead the snake matches its venom distribution to the size of the target independent of target distance. PMID:19462171

  18. Effects of two types of cobra venom factor on porcine complement activation and pulmonary artery pressure.

    PubMed Central

    Cheung, A K; Parker, C J; Wilcox, L

    1989-01-01

    Autologous porcine plasma that has been incubated with cuprophan haemodialysis membranes causes pulmonary hypertension and peripheral leucopenia following reinfusion into swine. These effects appear to be mediated by biologically active fragments of C3 and C5 that are generated as a consequence of ex vivo activation of complement. Putatively, C5a induces the leucopenia; however, the specific contributions of products of C3 and C5 activation to the pulmonary vasoconstriction have not been elucidated. In the present study, the effects of in vivo infusion of two different types of cobra venom factor (CVF) on peripheral leucocyte count and pulmonary artery pressure in the swine are reported. The CVF from Naja n. naja (CVF(TN)) was shown to activate both porcine C3 and C5, whereas the CVF from Naja h. haje (CVF(NH)) activated only C3. Both types of CVF produced pulmonary hypertension. Significant peripheral leucopenia, however, was observed only with CVF(TN). These results suggest that activation products of C3 contribute to the pulmonary hypertension but not to the peripheral leucopenia observed during haemodialysis using dialysis membranes that activate complement. PMID:12412765

  19. Development of an ELISA to assess the potency of horse therapeutic antivenom against Thai cobra venom.

    PubMed

    Rungsiwongse, J; Ratanabanangkoon, K

    1991-01-24

    An ELISA for the quantitation of antibodies against Naja naja siamensis venom proteins has been developed for use as a possible replacement for the in vivo neutralization assay of antivenom potency. Comparison was made with three preparations of venom proteins as antigens of ELISA: these were the crude venom, a toxin fraction and the purified principle postsynaptic neurotoxin of the Thai cobra. Eight batches of horse monovalent therapeutic anti-cobra antivenom, one of which served as positive reference, were assayed by the ELISAs and also by the in vivo neutralization assay using mice. When crude venom, the toxin fraction and the pure neurotoxin were used as antigens in the ELISAs, the correlation coefficients between the ELISA antibody titers and in vivo neutralization of the antivenoms were 0.82 (P less than 0.005), 0.94 (P less than 0.001) and 0.95 (P less than 0.001), respectively. Thus, the ELISA which measures only the antibody against the principle toxin of the snake venom should be most suitable for use as an in vitro assay of antivenom potency. The ELISA should also be useful for potency assessment and standardization of antivenoms against other elapid snake venoms whose lethal components are small, poorly immunogenic peptides. PMID:1995711

  20. Ophiophagus hannah venom: proteome, components bound by Naja kaouthia antivenin and neutralization by N. kaouthia neurotoxin-specific human ScFv.

    PubMed

    Danpaiboon, Witchuda; Reamtong, Onrapak; Sookrung, Nitat; Seesuay, Watee; Sakolvaree, Yuwaporn; Thanongsaksrikul, Jeeraphong; Dong-din-on, Fonthip; Srimanote, Potjanee; Thueng-in, Kanyarat; Chaicumpa, Wanpen

    2014-05-01

    Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah) is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5'-nucleotidase). N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv) cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins. PMID:24828754

  1. Ophiophagus hannah Venom: Proteome, Components Bound by Naja kaouthia Antivenin and Neutralization by N. kaouthia Neurotoxin-Specific Human ScFv

    PubMed Central

    Danpaiboon, Witchuda; Reamtong, Onrapak; Sookrung, Nitat; Seesuay, Watee; Sakolvaree, Yuwaporn; Thanongsaksrikul, Jeeraphong; Dong-din-on, Fonthip; Srimanote, Potjanee; Thueng-in, Kanyarat; Chaicumpa, Wanpen

    2014-01-01

    Venomous snakebites are an important health problem in tropical and subtropical countries. King cobra (Ophiophagus hannah) is the largest venomous snake found in South and Southeast Asia. In this study, the O. hannah venom proteome and the venom components cross-reactive to N. kaouthia monospecific antivenin were studied. O. hannah venom consisted of 14 different protein families, including three finger toxins, phospholipases, cysteine-rich secretory proteins, cobra venom factor, muscarinic toxin, L-amino acid oxidase, hypothetical proteins, low cysteine protein, phosphodiesterase, proteases, vespryn toxin, Kunitz, growth factor activators and others (coagulation factor, endonuclease, 5’-nucleotidase). N. kaouthia antivenin recognized several functionally different O. hannah venom proteins and mediated paratherapeutic efficacy by rescuing the O. hannah envenomed mice from lethality. An engineered human ScFv specific to N. kaouthia long neurotoxin (NkLN-HuScFv) cross-neutralized the O. hannah venom and extricated the O. hannah envenomed mice from death in a dose escalation manner. Homology modeling and molecular docking revealed that NkLN-HuScFv interacted with residues in loops 2 and 3 of the neurotoxins of both snake species, which are important for neuronal acetylcholine receptor binding. The data of this study are useful for snakebite treatment when and where the polyspecific antivenin is not available. Because the supply of horse-derived antivenin is limited and the preparation may cause some adverse effects in recipients, a cocktail of recombinant human ScFvs for various toxic venom components shared by different venomous snakes, exemplified by the in vitro produced NkLN-HuScFv in this study, should contribute to a possible future route for an improved alternative to the antivenins. PMID:24828754

  2. Nano gold conjugation, anti-arthritic potential and toxicity studies of snake Naja kaouthia (Lesson, 1831) venom protein toxin NKCT1 in male albino rats and mice.

    PubMed

    Saha, Partha Pratim; Bhowmik, Tanmoy; Dasgupta, Anjan Kumar; Gomes, Antony

    2014-08-01

    Nanoscience and Nanotechnology have found their way in the fields of pharmacology and medicine. The conjugation of drug to nanoparticles combines the properties of both. In this study, gold nanoparticle (GNP) was conjugated with NKCT1, a cytotoxic protein toxin from Indian cobra venom for evaluation of anti-arthritic activity and toxicity in experimental animal models. GNP conjugated NKCT1 (GNP-NKCT1) synthesized by NaBH4 reduction method was stable at room temperature (25 +/- 2 degrees C), pH 7.2. Hydrodynamic size of GNP-NKCT1 was 68-122 nm. Arthritis was developed by Freund's complete adjuvant induction in male albino rats and treatment was done with NKCT1/GNP-NKCT1/standard drug. The paw/ankle swelling, urinary markers, serum markers and cytokines were changed significantly in arthritic control rats which were restored after GNP-NKCT1 treatment. Acute toxicity study revealed that GNP conjugation increased the minimum lethal dose value of NKCT1 and partially reduced the NKCT1 induced increase of the serum biochemical tissue injury markers. Histopathological study showed partial restoration of toxic effect in kidney tissue after GNP conjugation. Normal lymphocyte count in culture was in the order of GNP-NKCT1 > NKCT1 > Indomethacine treatment. The present study confirmed that GNP conjugation increased the antiarthritic activity and decreased toxicity profile of NKCT1. PMID:25141538

  3. Immunoreactivity and two-dimensional gel-electrophoresis characterization of Egyptian cobra venom proteome.

    PubMed

    Almehdar, Hussein Abduelrahman; Adel-Sadek, Mahmoud Abass; Redwan, Elrashdy Moustafa

    2015-01-01

    The first and second (two) dimensional gel electrophoresis has a broad protein resolution power. It was used to separate and identify cobra venom proteome. The importance of characterizing venom proteins contents from the Egyptian elapidae, specifically neurotoxins, is based on the need to produce effective anti-venom. About 30-55distinct protein spots were identified on silver stained two-dimensional gels. Around two-thirds of the venom proteins displayed low a molecular weight and a migration into hydrophobic side. The venoms from Naja haja and Naja nigricollus showed 45-55 spots, while Walternnesia aegyptia had less (31-37) spots. The commercial prepared polyclonal antivenom had a strong signal for anionic and cationic venom protein spots with molecular weight 20-115 kDa. However, it showed weak or non immunoreactivity toward anionic low molecular weight spots (2.5-15 kDa). These results suggest the need to change the immunization schedule to include low molecular weight toxin-proteomes as separate dose or sequester injection. PMID:25553707

  4. In Vitro and In Vivo Evaluation of Polyherbal Formulation against Russell's Viper and Cobra Venom and Screening of Bioactive Components by Docking Studies

    PubMed Central

    Sakthivel, G.; Dey, Amitabha; Nongalleima, Kh.; Chavali, Murthy; Rimal Isaac, R. S.; Singh, N. Surjit; Deb, Lokesh

    2013-01-01

    The present study emphasizes to reveal the antivenom activity of Aristolochia bracteolata Lam., Tylophora indica (Burm.f.) Merrill, and Leucas aspera S. which were evaluated against venoms of Daboia russelli russelli (Russell's viper) and Naja naja (Indian cobra). The aqueous extracts of leaves and roots of the above-mentioned plants and their polyherbal (1 : 1 : 1) formulation at a dose of 200 mg/kg showed protection against envenomed mice with LD50 doses of 0.44 mg/kg and 0.28 mg/kg against Russell's viper and cobra venom, respectively. In in vitro antioxidant activities sample extracts showed free radical scavenging effects in dose dependent manner. Computational drug design and docking studies were carried out to predict the neutralizing principles of type I phospholipase A2 (PLA2) from Indian common krait venom. This confirmed that aristolochic acid and leucasin can neutralize type I PLA2 enzyme. Results suggest that these plants could serve as a source of natural antioxidants and common antidote for snake bite. However, further studies are needed to identify the lead molecule responsible for antidote activity. PMID:23533518

  5. Role of cardiotoxin and phospholipase A in the blockade of nerve conduction and depolarization of skeletal muscle induced by cobra venom

    PubMed Central

    Chang, C. C.; Chuang, Sing-Tai; Lee, C. Y.; Wei, J. W.

    1972-01-01

    1. The effects of phospholipase A (PhA), cardiotoxin (CTX) and neurotoxin (cobrotoxin) isolated from Formosan cobra (Naja naja atra) venom on conduction of the rat phrenic nerve and membrane potential of the rat diaphragm were studied. 2. Phospholipase A, lysolecithin and cobrotoxin were without effect on the axonal conduction. Cardiotoxin was the only active agent in cobra venom, but it was less potent than the crude venom. 3. The blocking action of cardiotoxin was markedly accelerated by the simultaneous administration of phospholipase A. However, the minimum effective concentration of cardiotoxin (100 μg/ml), was not decreased by phospholipase A. Pretreatment of the nerve with phospholipase A, followed by washout, did not alter the activity of cardiotoxin. 4. Cardiotoxin (3 μg/ml) completely depolarized the membrane of superficial muscle fibres within 60 min, being 3 times more potent than the crude venom. Phospholipase A, on the other hand, needed a dose 30 times higher and a prolonged period of incubation to induce depolarization of similar extent. Cobrotoxin was without effect on membrane potentials. 5. CaCl2 (10 mM) effectively antagonized the nerve blocking as well as the depolarizing effect of the crude venom, cardiotoxin or cardiotoxin plus phospholipase A. By contrast, the slow depolarizing effect of phospholipase A was enhanced by high concentrations of calcium. 6. Cardiotoxic fractions of Indian cobra venom affected both nerve conduction and diaphragm membrane potential in exactly the same way as cardiotoxin. Toxin A of the same venom was without effect. 7. It is concluded that the active agent in cobra venoms either on axonal conduction or on muscle membrane is cardiotoxin. The synergistic effect of phospholipase A on cardiotoxin appears to be due to acceleration rather than potentiation of its action. The mechanism of action of cardiotoxin and its synergism by phospholipase A are discussed. PMID:5041453

  6. Mapping tRNA structure in solution using double-strand-specific ribonuclease V1 from cobra venom.

    PubMed Central

    Lockard, R E; Kumar, A

    1981-01-01

    A method for mapping all base-paired stems in both elongation and initiator tRNAs is described using double-stranded-specific ribonuclease V1 from the venom of the cobra Naja naja oxiana. 32p-end-labeled RNA is first partially digested with double-strand-specific V1 nuclease under near physiological conditions, and the resultant fragments are than electrophoretically fractionated by size in adjacent lanes of a polyacrylamide gel run in 90% formamide. After autoradiography, the base-paired nucleotides are definitively located by comparing V1 generated bands with fragments of known length produced by both Neurospora endonuclease and base-specific ribonucleases. Using the substrates yeast tRNAPhe an E, coli tRNAfMet of known three-dimensional structure, we find V1 nuclease to cleave entirely within every base-paired stem. Our studies also reveal that nuclease V1 will digest paired nucleotides not hydrogen-bonded by standard Watson-Crick base-pairing. In yeast tRNAPhe cleavage of both wobble base-pairs and nucleotides involved in tertiary base-base hydrogen bonding is demonstrated. Images PMID:7031604

  7. The Crystal Structure of Cobra Venom Factor, a Cofactor for C3- and C5-Convertase CVFBb

    SciTech Connect

    Krishnan, Vengadesan; Ponnuraj, Karthe; Xu, Yuanyuan; Macon, Kevin; Volanakis, John E.; Narayana, Sthanam V.L.

    2009-05-26

    Cobra venom factor (CVF) is a functional analog of human complement component C3b, the active fragment of C3. Similar to C3b, in human and mammalian serum, CVF binds factor B, which is then cleaved by factor D, giving rise to the CVFBb complex that targets the same scissile bond in C3 as the authentic complement convertases C4bC2a and C3bBb. Unlike the latter, CVFBb is a stable complex and an efficient C5 convertase. We solved the crystal structure of CVF, isolated from Naja naja kouthia venom, at 2.6 {angstrom} resolution. The CVF crystal structure, an intermediate between C3b and C3c, lacks the TED domain and has the CUB domain in an identical position to that seen in C3b. The similarly positioned CUB and slightly displaced C345c domains of CVF could play a vital role in the formation of C3 convertases by providing important primary binding sites for factor B.

  8. Cobrotoxin from Naja naja atra Venom Ameliorates Adriamycin Nephropathy in Rats

    PubMed Central

    Wang, Shu-Zhi; Xu, Yin-li; Zhu, Qi; Kou, Jian-qun; Qin, Zheng-Hong

    2015-01-01

    Chronic kidney disease (CKD) becomes a global health problem with high morbidity and mortality. Adriamycin- (ADR-) induced rodent chronic nephropathy is a classic experimental model of human minimal lesion nephrotic syndrome. The present study investigated the effect of cobrotoxin (CTX) on ADR-induced nephropathy. Rats were given 6 mg/kg ADR once through the tail vein to replicate ADR nephropathy model. CTX was administered to rats daily by placing a fast dissolving CTX membrane strip under the tongue starting from 5 days prior to ADR administration until the end of experiment. The results showed that CTX ameliorated the symptoms of ADR nephropathy syndrome with reduced body weight loss, proteinuria, hypoalbuminemia, dyslipidemia, serum electrolyte imbalance, oxidative stress, renal function abnormities, and kidney pathological lesions. Anti-inflammatory cytokine IL-10 expression was elevated after CTX administration in ADR nephropathy model. CTX inhibited the phosphorylation of IκB-α and NF-κB p65 nuclear translocation. Meanwhile, CTX upregulated the protein level of podocyte-specific nephrin and downregulated the level of fibrosis-related TGF-β. These findings suggest that CTX may be a potential drug for chronic kidney diseases. PMID:26640497

  9. Thrombolytic protein from cobra venom with anti-adhesive properties.

    PubMed

    Chanda, Chandrasekhar; Sarkar, Angshuman; Chakrabarty, Dibakar

    2016-01-15

    A metalloproteinase anticoagulant toxin of molecular weight 66 kDa has been purified from the venom of Indian monocled cobra (Naja kaouthia). This toxin named as NKV 66 cleaved fibrinogen in a dose and time dependent manner. The digestion process was specific to Aα chain and cleaved fibrinogen to peptide fragments. NKV 66 completely liquefied the fibrin clots developed in vitro in 18 h. Plasma recalcification time and thrombin time were significantly prolonged following treatment of plasma with NKV 66. NKV 66 significantly inhibited ADP and collagen induced platelet aggregation in a dose dependent manner. It showed disintegrin like activity on A549 cells cultured in vitro. About 40% inhibition of adherence of A549 cells to matrix was observed following NKV 66 treatment also NKV 66 treated A549 cells were drastically inhibited from passing through the matrix in cell invasion assays in vitro, suggesting anti-adhesive properties of NKV 66. PMID:26558696

  10. Genetic Structure and Demographic History Should Inform Conservation: Chinese Cobras Currently Treated as Homogenous Show Population Divergence

    PubMed Central

    Lin, Long-Hui; Qu, Yan-Fu; Li, Hong; Zhou, Kai-Ya; Ji, Xiang

    2012-01-01

    An understanding of population structure and genetic diversity is crucial for wildlife conservation and for determining the integrity of wildlife populations. The vulnerable Chinese cobra (Naja atra) has a distribution from the mouth of the Yangtze River down to northern Vietnam and Laos, within which several large mountain ranges and water bodies may influence population structure. We combined 12 microsatellite loci and 1117 bp of the mitochondrial cytochrome b gene to explore genetic structure and demographic history in this species, using 269 individuals from various localities in Mainland China and Vietnam. High levels of genetic variation were identified for both mtDNA and microsatellites. mtDNA data revealed two main (Vietnam + southern China + southwestern China; eastern + southeastern China) and one minor (comprising only two individuals from the westernmost site) clades. Microsatellite data divided the eastern + southeastern China clade further into two genetic clusters, which include individuals from the eastern and southeastern regions, respectively. The Luoxiao and Nanling Mountains may be important barriers affecting the diversification of lineages. In the haplotype network of cytchrome b, many haplotypes were represented within a “star” cluster and this and other tests suggest recent expansion. However, microsatellite analyses did not yield strong evidence for a recent bottleneck for any population or genetic cluster. The three main clusters identified here should be considered as independent management units for conservation purposes. The release of Chinese cobras into the wild should cease unless their origin can be determined, and this will avoid problems arising from unnatural homogenization. PMID:22558439

  11. 3D Flow in the Venom Channel of a Spitting Cobra: Do the Ridges in the Fangs Act as Fluid Guide Vanes?

    PubMed Central

    Triep, Michael; Hess, David; Chaves, Humberto; Brücker, Christoph; Balmert, Alexander; Westhoff, Guido; Bleckmann, Horst

    2013-01-01

    The spitting cobra Naja pallida can eject its venom towards an offender from a distance of up to two meters. The aim of this study was to understand the mechanisms responsible for the relatively large distance covered by the venom jet although the venom channel is only of micro-scale. Therefore, we analysed factors that influence secondary flow and pressure drop in the venom channel, which include the physical-chemical properties of venom liquid and the morphology of the venom channel. The cobra venom showed shear-reducing properties and the venom channel had paired ridges that span from the last third of the channel to its distal end, terminating laterally and in close proximity to the discharge orifice. To analyze the functional significance of these ridges we generated a numerical and an experimental model of the venom channel. Computational fluid dynamics (CFD) and Particle-Image Velocimetry (PIV) revealed that the paired interior ridges shape the flow structure upstream of the sharp 90° bend at the distal end. The occurrence of secondary flow structures resembling Dean-type vortical structures in the venom channel can be observed, which induce additional pressure loss. Comparing a venom channel featuring ridges with an identical channel featuring no ridges, one can observe a reduction of pressure loss of about 30%. Therefore it is concluded that the function of the ridges is similar to guide vanes used by engineers to reduce pressure loss in curved flow channels. PMID:23671569

  12. Hemostatic interference of Indian king cobra (Ophiophagus hannah) Venom. Comparison with three other snake venoms of the subcontinent.

    PubMed

    Gowtham, Yashonandana J; Kumar, M S; Girish, K S; Kemparaju, K

    2012-06-01

    Unlike Naja naja, Bungarus caeruleus, Echis carinatus, and Daboia/Vipera russellii venoms, Ophiophagus hannah venom is medically ignored in the Indian subcontinent. Being the biggest poisonous snake, O. hannah has been presumed to inject several lethal doses of venom in a single bite. Lack of therapeutic antivenom to O. hannah bite in India makes any attempt to save the victim a difficult exercise. This study was initiated to compare O. hannah venom with the above said venoms for possible interference in hemostasis. Ophiophagus hannah venom was found to actively interfere in hemostatic stages such as fibrin clot formation, platelet activation/aggregation, and fibrin clot dissolution. It decreased partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin clotting time (TCT). These activities are similar to that shown by E. carinatus and D. russellii venoms, and thus O. hannah venom was found to exert procoagulant activity through the common pathway of blood coagulation, while N. naja venom increased aPTT and TCT but not PT, and hence it was found to exert anticoagulant activity through the intrinsic pathway. Venoms of O. hannah, E. carinatus, and D. russellii lack plasminogen activation property as they do not hydrolyze azocasein, while they all show plasmin-like activity by degrading the fibrin clot. Although N. naja venom did not degrade azocasein, unlike other venoms, it showed feeble plasmin-like activity on fibrin clot. Venom of E. carinatus induced clotting of human platelet rich plasma (PRP), while the other three venoms interfered in agonist-induced platelet aggregation in PRP. Venom of O. hannah least inhibited the ADP induced platelet aggregation as compared to D. russellii and N. naja venoms. All these three venoms showed complete inhibition of epinephrine-induced aggregation at varied doses. However, O. hannah venom was unique in inhibiting thrombin induced aggregation. PMID:22817464

  13. COBRA Main Engine Project

    NASA Technical Reports Server (NTRS)

    Snoddy, Jim; Sides, Steve; Lyles, Garry M. (Technical Monitor)

    2002-01-01

    The COBRA (CO-Optimized Booster for Reusable Applications) project include the following: 1. COBRA main engine project team. 2. COBRA and RLX cycles selected. 3. COBRA proto-type engine approach enables mission success. 4. COBRA provides quick, low cost demo of cycle and technologies. 5. COBRA cycle I risk reduction supports. 6. Achieving engine safety. 6. RLX cycle I risk reduction supports. 7. Flight qualification. 9. Life extension engine testing.

  14. 'Cobra Hoods'

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This animation flips back and forth between left and right eye images of the odd rock formation dubbed 'Cobra Hoods' (center top). The images were taken by the panoramic camera on the Mars Exploration Rover Spirit. Rover scientists say this resistant rock is unlike anything they've seen on Mars so far. Spirit will investigate the rock in coming sols. These pictures was captured on sol 156 (June 11, 2004).

  15. Purification and Characterization of Nk-3FTx: A Three Finger Toxin from the Venom of North East Indian Monocled Cobra.

    PubMed

    Das, Diganta; Sharma, Maitreyee; Kumar Das, Hemanga; Pratim Sahu, Partha; Doley, Robin

    2016-02-01

    Snake venom three finger toxins (3FTxs) are a non-enzymatic family of venom proteins abundantly found in elapids. We have purified a 7579.5 ± 0.591 Da 3FTx named as Nk-3FTx from the venom of Naja kaouthia of North East India origin. The primary structure was determined by a combination of N-terminal sequencing and electrospray ionization liquid chromatography-mass spectrometry/mass spectrometry. Biochemical and biological characterization reveal that it is nontoxic to human cell lines and exhibit mild anticoagulant activity when tested on citrated human plasma. Nk-3FTx was found to affect the compound action potential (CAP) and nerve conduction velocity of isolated toad sciatic nerve. This is the first report of a non-conventional 3FTx from Naja kaouthia venom that reduces CAP for its neurotoxic effect. Further studies can be carried out to understand the mechanism of action and to explore its potential therapeutic application. PMID:26293154

  16. Antibacterial properties of KwaZulu natal snake venoms.

    PubMed

    Blaylock, R S

    2000-11-01

    The objective was to ascertain whether local snake venoms have antibacterial properties. The venoms of the common night adder (Causus rhombeatus), gaboon adder (Bitis gabonica), puff adder (Bitis arietans), black mamba (Dendroaspis polylepis), eastern green mamba (Dendroaspis augusticeps), forest cobra (Naja melanoleuca), snouted cobra (Naja annulifera) and Mozambique spitting cobra (Naja mossambica) were collected and, by gel diffusion, tested against the bacteria Staphylococcus aureus, Escherichia coli, Pseudomonas aeriginosa, Bacteriodes fragilis, Bacteroides intermedius, Clostridium sordellii and Clostridium perfringens. All snake venoms showed antibacterial activity, with the adders showing most activity against the aerobes while the cobras showed lesser, but equal activity against the aerobes and anaerobes. Black mamba venom only showed activity against C. perfringens. In conclusion, local snake venoms have antibacterial properties which are dependent on the venom and bacterial type; and in the Naja spp., for anaerobic bacteria, diminish in winter. There is liable to be more than one toxin component responsible. PMID:10775753

  17. The COBRA experiment

    NASA Astrophysics Data System (ADS)

    Wilson, J. R.

    2008-07-01

    The COBRA experiment aims to use a large array of CdZnTe semiconductor detectors to search for neutrinoless double beta decay. The COBRA collaboration are currently operating a small proto-type array of crystals in a low-background environment. This paper presents the current status of the experiment, results from current and previous proto-types and future prospects for COBRA.

  18. Collaborative Beamfocusing Radio (COBRA)

    NASA Astrophysics Data System (ADS)

    Rode, Jeremy P.; Hsu, Mark J.; Smith, David; Husain, Anis

    2013-05-01

    A Ziva team has recently demonstrated a novel technique called Collaborative Beamfocusing Radios (COBRA) which enables an ad-hoc collection of distributed commercial off-the-shelf software defined radios to coherently align and beamform to a remote radio. COBRA promises to operate even in high multipath and non-line-of-sight environments as well as mobile applications without resorting to computationally expensive closed loop techniques that are currently unable to operate with significant movement. COBRA exploits two key technologies to achieve coherent beamforming. The first is Time Reversal (TR) which compensates for multipath and automatically discovers the optimal spatio-temporal matched filter to enable peak signal gains (up to 20 dB) and diffraction-limited focusing at the intended receiver in NLOS and severe multipath environments. The second is time-aligned buffering which enables TR to synchronize distributed transmitters into a collaborative array. This time alignment algorithm avoids causality violations through the use of reciprocal buffering. Preserving spatio-temporal reciprocity through the TR capture and retransmission process achieves coherent alignment across multiple radios at ~GHz carriers using only standard quartz-oscillators. COBRA has been demonstrated in the lab, aligning two off-the-shelf software defined radios over-the-air to an accuracy of better than 2 degrees of carrier alignment at 450 MHz. The COBRA algorithms are lightweight, with computation in 5 ms on a smartphone class microprocessor. COBRA also has low start-up latency, achieving high accuracy from a cold-start in 30 ms. The COBRA technique opens up a large number of new capabilities in communications, and electronic warfare including selective spatial jamming, geolocation and anti-geolocation.

  19. The modified Cobra Seal

    SciTech Connect

    Ystesund, K.J.; Drayer, D.D.

    1990-01-01

    The Cobra Seal was developed in response to the International Atomic Energy Agency's request for an in situ verifiable seal. The Type E metal cap seal, still widely used by the IAEA, must be removed and returned to Agency headquarters for verification. The Cobra Seal allows an inspector to verify seal identity and integrity on site, without removing the seal. The seal consists of a loop of multi-strand fiber optic cable, which can be routed around or through the object to be sealed, and a seal body that secures the ends of the fiber optic cable. A cutting blade in the seal body randomly cuts a portion of the optical fibers in the cable. After the seal assembly is completed, a reference image is recorded of the unique pattern of light spots produced when the seal face is illuminated. Subsequent photographs of the seal pattern are compared to the original to establish the seal identity and integrity. This paper reviews the improvements and the technology of the cobra seal system. 3 refs., 5 figs.

  20. Taiwan cobra cardiotoxin III suppresses EGF/EGFR-mediated epithelial-to-mesenchymal transition and invasion of human breast cancer MDA-MB-231 cells.

    PubMed

    Tsai, Pei-Chien; Fu, Yaw-Syan; Chang, Long-Sen; Lin, Shinne-Ren

    2016-03-01

    Breast cancer is a highly malignant carcinoma and most deaths of breast cancer are caused by metastasis. The epithelial-to-mesenchymal transition (EMT) has emerged as a pivotal event in the development of the invasive and metastatic potentials of cancer progression. Epidermal growth factor (EGF) and its receptor, EGFR, play roles in cancer metastasis. CTX III, a basic polypeptide isolated from Naja naja atra venom, has been shown to exhibit anticancer activity; however, the effect of CTX III on the EMT of cancer cells remains elusive. CTX III treatment resulted in morphological changes from elongated and spindle shape to rounded and epithelial-like shape, induced upregulation of E-cadherin and concurrent downregulation of N-cadherin and Vimentin protein levels, corresponding to observed decreases in cell migration and invasion. CTX III treatment also decreased the expression of Snail and Twist in EGF-induced MDA-MB-231 cells. Concurrently, CTX III efficiently inhibited the EGFR phosphorylation and downstream activation of phosphatidylinositol 3-kinase (PI3K)/Akt and ERK1/2. The EGFR specific inhibitor AG1478 significantly suppressed ERK1/2 and Akt phosphorylation, cell migration and invasion, as well as the expressional changes associated with EMT markers in EGF-induced MDA-MB-231 cells. CTX III inhibitory effect on EGF-evoked invasion of MDA-MB-231 cells is mediated through suppressing EGF/EGFR activation and EMT process. PMID:26774845

  1. Cobra Probes Containing Replaceable Thermocouples

    NASA Technical Reports Server (NTRS)

    Jones, John; Redding, Adam

    2007-01-01

    A modification of the basic design of cobra probes provides for relatively easy replacement of broken thermocouples. Cobra probes are standard tube-type pressure probes that may also contain thermocouples and that are routinely used in wind tunnels and aeronautical hardware. They are so named because in side views, they resemble a cobra poised to attack. Heretofore, there has been no easy way to replace a broken thermocouple in a cobra probe: instead, it has been necessary to break the probe apart and then rebuild it, typically at a cost between $2,000 and $4,000 (2004 prices). The modified design makes it possible to replace the thermocouple, in minimal time and at relatively low cost, by inserting new thermocouple wire in a tube.

  2. Status and perspectives of COBRA

    NASA Astrophysics Data System (ADS)

    Fritts, M.; Zuber, K.

    2013-04-01

    The COBRA experiment is a search for neutrinoless double-beta decay using CdZnTe semiconductor detectors. Currently COBRA is collecting data from 32 coplanar grid (CPG) detectors installed in the Gran Sasso National Laboratory. This serves as a prototype for a proposed design of over 100 kg target mass in order to achieve the sensitivity necessary to probe new parameter space for 0νββ. Pixelated detector allowing tracking and thus particle identification are also explored as a unique option in double beta searches.

  3. Venomous snakebite in Thailand. I: Medically important snakes.

    PubMed

    Chanhome, L; Cox, M J; Wilde, H; Jintakoon, P; Chaiyabutr, N; Sitprija, V

    1998-05-01

    Thailand has an abundance of venomous snakes. Among the neurotoxic family Elapidae, there are three species of the genus Naja (cobras), three of the genus Bungarus (kraits), and the king cobra of the genus Ophiophagus. Other Elapidae snakes in Thailand include sea snakes and Asian coral snakes of the genus Calliophis. They have potent venoms but rarely bite humans. Tissue and hemotoxic snakes are represented by family Viperidae, subfamilies Viperinae and Crotalinae. They remain an occupational hazard for farmers and rubber tappers, causing serious morbidity but only rare deaths, since competent treatment is now widely available throughout Thailand. Purified equine antivenin is manufactured locally for the monocled and Siamese spitting cobras (Naja kaouthia and N. siamensis), king cobra (Ophiophagus hannah), banded krait (Bungarus fasciatus), most green pit vipers (Trimeresurus sp.), Malayan pit viper (Calloselasma rhodostoma), and the Siamese Russell's viper (Daboia russelli siamensis). PMID:9597848

  4. Acute acalculous cholecystitis: a rare complication of snake bite.

    PubMed

    Senthilkumaran, Subramanian; Menezes, Ritesh G; Pant, Sadip; Thirumalaikolundusubramanian, Ponniah

    2013-09-01

    Snake bite is an environmental and occupational hazard in many tropical and subtropical countries. It demands a high level of knowledge and skill in managing the envenomation syndrome. Herein, we describe a rare case of acute acalculous cholecystitis (AAC) that developed in a 36-year-old man after an Indian cobra (Naja naja) bite in the absence of any other predisposing factors for AAC. The probable mechanisms for the occurrence of AAC have been highlighted. Recognizing the possibility of such a complication after envenomation will definitely aid in early diagnosis and, subsequently, a better outcome. PMID:23473791

  5. Indian common krait envenomation presenting as coma and hypertension: A case report and literature review.

    PubMed

    Law, Arjun Datt; Agrawal, Anshu Kumar; Bhalla, Ashish

    2014-04-01

    Neuroparalytic snake bite is a common emergency situation encountered in India. Common krait (Bungarus caeruleus) and cobra (Naja naja) are important snakes causing neuroparalysis in North India. Despite severe neuroparalysis, patients who receive antivenin and ventilator support in time recover completely. Autonomic disturbances resulting in resting tachycardia, labile hypertension and sweating have been described in common krait envenomation. We present a case of common krait (B. caeruleus) envenomation presenting in the locked-in state and severe hypertension that remained in such a state for over 96 h before a gradual and sustained recovery. PMID:24812460

  6. Indian common krait envenomation presenting as coma and hypertension: A case report and literature review

    PubMed Central

    Law, Arjun Datt; Agrawal, Anshu Kumar; Bhalla, Ashish

    2014-01-01

    Neuroparalytic snake bite is a common emergency situation encountered in India. Common krait (Bungarus caeruleus) and cobra (Naja naja) are important snakes causing neuroparalysis in North India. Despite severe neuroparalysis, patients who receive antivenin and ventilator support in time recover completely. Autonomic disturbances resulting in resting tachycardia, labile hypertension and sweating have been described in common krait envenomation. We present a case of common krait (B. caeruleus) envenomation presenting in the locked-in state and severe hypertension that remained in such a state for over 96 h before a gradual and sustained recovery. PMID:24812460

  7. Status of the COBRA experiment

    NASA Astrophysics Data System (ADS)

    Zuber, Kai

    2009-11-01

    The current status of the COBRA experiment is described. Results on the 4-fold forbidden beta decay of 113Cd and a variety of double beta decay limits of Cd, Zn and Te isotopes are presented based on 18 kg×days of exposure with an array of sixteen CdZnTe semiconductor detectors. A short description on the activities with pixelated detectors for tracking is given.

  8. Status of the COBRA experiment

    SciTech Connect

    Zuber, Kai

    2009-11-09

    The current status of the COBRA experiment is described. Results on the 4-fold forbidden beta decay of {sup 113}Cd and a variety of double beta decay limits of Cd, Zn and Te isotopes are presented based on 18 kgxdays of exposure with an array of sixteen CdZnTe semiconductor detectors. A short description on the activities with pixelated detectors for tracking is given.

  9. 'Cobra Hoods' Coming At You

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This 3-D image taken by the left and right eyes of the panoramic camera on the Mars Exploration Rover Spirit shows the odd rock formation dubbed 'Cobra Hoods' (center). Rover scientists say this resistant rock is unlike anything they've seen on Mars so far. Spirit will investigate the rock in coming sols. The stereo pictures making up this image were captured on sol 156 (June 11, 2004).

  10. COBRA meteor radar antenna designs

    NASA Astrophysics Data System (ADS)

    Zainuddin, Mohamad

    A meteor radar system is one of the effective remote sensing techniques in measuring atmospheric parameters such as wind velocities, temperature, pressure and density which are essential in understanding the atmospheric dynamics in the Mesosphere Lower Thermosphere (MLT) region. Previous studies of very high frequency (VHF) meteors radar systems suggest that the minimum error for the estimation of the horizontal wind velocity from a radar interferometry algorithm should occur when the main beams of the transmit and receive antennas are pointing to between 30° to 50° elevation angles. Therefore, an ideal antenna design for VHF meteor radar systems would produce a pencil beam radiation pattern at a 45° elevation angle. However, both the transmit and receive antenna of the COBRA meteor radar system have major beams are pointing to between 60° to 65° degree elevation angles above a perfect ground plane. Besides transmitting maximum power at low elevation angles, the current antennas of the COBRA meteor radar are highly dependent on the ground plane to radiate maximum gains to between 60° to 65° degree elevation angles. Typically, the earth ground is considered as a common ground plane for many VHF antenna with acceptable performance. However, the earth ground could not effectively reflect most of the power at all time. Because the antennas are dependent on ground to radiate power at certain direction, an artificial ground plane or ground screen has to be built for the COBRA antenna system at the South Pole station, which is located on top of more than 2000 meter thick of ice sheet. This dissertation focuses on the analysis of the performance of the individual current antenna design with four different conditions namely in free space, above an infinite ground, lossy ground and finite ground. In the analysis of finite ground, the effects of varying wire spacing and the size of finite ground to the radiation pattern of a cross folded dipole antenna are investigated

  11. DNA Aptamers against Taiwan Banded Krait α-Bungarotoxin Recognize Taiwan Cobra Cardiotoxins

    PubMed Central

    Chen, Ying-Jung; Tsai, Chia-Yu; Hu, Wan-Ping; Chang, Long-Sen

    2016-01-01

    Bungarus multicinctus α-bungarotoxin (α-Bgt) and Naja atra cardiotoxins (CTXs) share a common structural scaffold, and their tertiary structures adopt three-fingered loop motifs. Four DNA aptamers against α-Bgt have been reported previously. Given that the binding of aptamers with targeted proteins depends on structural complementarity, in this study, we investigated whether DNA aptamers against α-Bgt could also recognize CTXs. It was found that N. atra cardiotoxin 3 (CTX3) reduced the electrophoretic mobility of aptamers against α-Bgt. Analysis of the changes in the fluorescence intensity of carboxyfluorescein-labeled aptamers upon binding toxin molecules revealed that CTX3 and α-Bgt could bind the tested aptamers. Moreover, the aptamers inhibited the membrane-damaging activity and cytotoxicity of CTX3. In addition to CTX3, other N. atra CTX isotoxins also bound to the aptamer against α-Bgt. Taken together, our data indicate that aptamers against α-Bgt show cross-reactivity with CTXs. The findings that aptamers against α-Bgt also suppress the biological activities of CTX3 highlight the potential utility of aptamers in regard to the broad inhibition of snake venom three-fingered proteins. PMID:26959062

  12. Isolation and cloning of a metalloproteinase from king cobra snake venom.

    PubMed

    Guo, Xiao-Xi; Zeng, Lin; Lee, Wen-Hui; Zhang, Yun; Jin, Yang

    2007-06-01

    A 50 kDa fibrinogenolytic protease, ohagin, from the venom of Ophiophagus hannah was isolated by a combination of gel filtration, ion-exchange and heparin affinity chromatography. Ohagin specifically degraded the alpha-chain of human fibrinogen and the proteolytic activity was completely abolished by EDTA, but not by PMSF, suggesting it is a metalloproteinase. It dose-dependently inhibited platelet aggregation induced by ADP, TMVA and stejnulxin. The full sequence of ohagin was deduced by cDNA cloning and confirmed by protein sequencing and peptide mass fingerprinting. The full-length cDNA sequence of ohagin encodes an open reading frame of 611 amino acids that includes signal peptide, proprotein and mature protein comprising metalloproteinase, disintegrin-like and cysteine-rich domains, suggesting it belongs to P-III class metalloproteinase. In addition, P-III class metalloproteinases from the venom glands of Naja atra, Bungarus multicinctus and Bungarus fasciatus were also cloned in this study. Sequence analysis and phylogenetic analysis indicated that metalloproteinases from elapid snake venoms form a new subgroup of P-III SVMPs. PMID:17337026

  13. Molecular characterization of L-amino acid oxidase from king cobra venom.

    PubMed

    Jin, Yang; Lee, Wen-Hui; Zeng, Lin; Zhang, Yun

    2007-09-15

    An L-amino acid oxidase from Ophiophagus hannah snake venom (Oh-LAAO) was purified by successive gel filtration, ion-exchange and heparin chromatography. Oh-LAAO did not induce platelet aggregation; however, it had potent inhibitory activity on platelet aggregation induced by ADP and U46619, but showed no effect on platelet aggregation induced by thrombin, mucetin, ristocetin and stejnulxin. By RT-PCR and 5'-RACE methods, the complete Oh-LAAO cDNA was cloned from the venom gland total RNA preparations. The cDNA sequence contains an open-reading frame (ORF) of 1476-bp, which encodes a protein of 491 amino acids comprising a signal peptide of 25 amino acids and 466-residue mature protein. The predicted protein sequence of Oh-LAAO was confirmed by N-terminal and trypsin-digested internal peptides sequencing together with peptide mass fingerprinting. cDNAs encoding for ORF of LAAOs from Bungarus fasciatus and B. multicinctus were cloned and reported in this study. In addition, partial cDNA encoding for Naja atra LAAO was also reported. Oh-LAAO shared approximately 50% protein sequence identity with other known snake venom LAAOs. Phylogenetic analysis indicated that Oh-LAAO is evolutionary distant to other snake venom LAAOs. PMID:17543361

  14. DNA Aptamers against Taiwan Banded Krait α-Bungarotoxin Recognize Taiwan Cobra Cardiotoxins.

    PubMed

    Chen, Ying-Jung; Tsai, Chia-Yu; Hu, Wan-Ping; Chang, Long-Sen

    2016-03-01

    Bungarus multicinctus α-bungarotoxin (α-Bgt) and Naja atra cardiotoxins (CTXs) share a common structural scaffold, and their tertiary structures adopt three-fingered loop motifs. Four DNA aptamers against α-Bgt have been reported previously. Given that the binding of aptamers with targeted proteins depends on structural complementarity, in this study, we investigated whether DNA aptamers against α-Bgt could also recognize CTXs. It was found that N. atra cardiotoxin 3 (CTX3) reduced the electrophoretic mobility of aptamers against α-Bgt. Analysis of the changes in the fluorescence intensity of carboxyfluorescein-labeled aptamers upon binding toxin molecules revealed that CTX3 and α-Bgt could bind the tested aptamers. Moreover, the aptamers inhibited the membrane-damaging activity and cytotoxicity of CTX3. In addition to CTX3, other N. atra CTX isotoxins also bound to the aptamer against α-Bgt. Taken together, our data indicate that aptamers against α-Bgt show cross-reactivity with CTXs. The findings that aptamers against α-Bgt also suppress the biological activities of CTX3 highlight the potential utility of aptamers in regard to the broad inhibition of snake venom three-fingered proteins. PMID:26959062

  15. Field testing of the Cobra Seal System

    SciTech Connect

    Yellin, E.; Vodrazka, P. ); Ystesund, K.; Drayer, D. )

    1990-01-01

    The Cobra Seal System consists of a passive fiber optic seal and verification equipment which have been modified to take advantage of current technology. The seal permits on-site verification without requiring replacement of the seal. The modifications to the original Cobra Seal System extended the maximum fiber optic cable length from 1 meter to 10 meters. This improvement allowed the Cobra Seal to be considered for application on dry irradiated fuel storage canisters at two Canadian facilities. These canisters are located in an exterior environment exposed to extreme weather conditions. This paper describe the application of the Cobra Seal to these canisters, a housing for the protection of the Cobra Seal body from the environment, and some preliminary results of the IAEA field tests. 4 refs.

  16. Cobra communications switch integration program

    NASA Technical Reports Server (NTRS)

    Shively, Robert J.; Haworth, Loran A.; Szoboszlay, Zoltan; Murray, F. Gerald

    1989-01-01

    The paper describes a design modification to reduce the visual and manual workload associated with the radio selection and communications tasks in the U.S. Army AH-1 Cobra helicopter. The modification involves the integration of the radio selection and microphone actuating tasks into a single operation controlled by the transmit-intercom switch. Ground-based and flight tests were conducted to evaluate the modified configuration during twelve flight tasks. The results show that the proposed configuration performs twice as fast as the original configuration.

  17. Double Beta Decay Measurement with COBRA

    NASA Astrophysics Data System (ADS)

    Wilson, Jeanne R.

    2011-12-01

    The COBRA experiment aims to use a large array of CdZnTe semiconductor detectors to search for neutrinoless double beta decay. Extensive simulation studies and data collected with a small proto-type experiment have been used to address the major design specifications for a large scale experiment sensitive to 116Cd half-lives in excess of 1026 years. The current and future prospects of the COBRA experiment are presented.

  18. Prototype COBRA near-real-time processor

    NASA Astrophysics Data System (ADS)

    Earp, Samuel L.; Marshall, J. W.; Anthony, E. R.

    1996-05-01

    The U.S. Marine Corps COBRA countermine surveillance program has developed, as a risk- reduction alternative, a near real-time processor for the output of the COBRA multispectral camera. This processor has been tested using approximately 13.5 hours of video data from the COBRA DT-0 developmental test, representing approximately 243,000 frames of multispectral data. The results have been very encouraging--the system is robust and the minefield detection performance has met the goals of the COBRA program. The MITRE COBRA prototype processor is built from commercial-off-the-shelf VME bus technology. Video capture is provided by a Transtech TDM 435 capture/display VME card. Control is performed on a GMSV64 Super Sparc card that resides in two VME slots. The compute engine consists of two Pentek 4270 Quad TMS320C40 digital signal processing boards. There are two additional 6U VME boards to provide fast SCSI IO. The system is capable of capturing, digitizing and processing the COBRA data stream at between one-eighth and one-half real-time, depending on processing options. The nominal compute power of the system is 2.2 GOPS, 450 MFLOPS. The system is easily upgradeable due to the open architecture--one proposed upgrade will be to increase the number of available TMS320C40 processors to sixteen, providing real-time performance without compromising the current investment in software and hardware. The software for the system is primarily written in C, with hand-optimized assembler code for portions of the compute kernel. The algorithm that is implemented is based on the MITRE minefield detection algorithm detailed at AeroSense '95. The system development required a registration algorithm--this was the only algorithm development that was performed, the rest of the algorithms coming from previous MITRE effort on the COBRA program. Lessons learned from the development and upgrade/test plans will be presented.

  19. 78 FR 13662 - Cobra Pipeline Ltd.; Notice of Petition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Cobra Pipeline Ltd.; Notice of Petition Take notice that on February 4, 2013, Cobra Pipeline Ltd. (Cobra) filed in Docket No. PR13-32-000 to correct a Tariff Record filed on...

  20. 26 CFR 54.4980B-1 - COBRA in general.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 17 2013-04-01 2013-04-01 false COBRA in general. 54.4980B-1 Section 54.4980B-1... TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-1 COBRA in general. The COBRA continuation coverage... requirements were added to section 162 by the Consolidated Omnibus Budget Reconciliation Act of 1985...

  1. 26 CFR 54.4980B-1 - COBRA in general.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 17 2011-04-01 2011-04-01 false COBRA in general. 54.4980B-1 Section 54.4980B-1... TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-1 COBRA in general. The COBRA continuation coverage... requirements were added to section 162 by the Consolidated Omnibus Budget Reconciliation Act of 1985...

  2. 26 CFR 54.4980B-1 - COBRA in general.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 17 2014-04-01 2014-04-01 false COBRA in general. 54.4980B-1 Section 54.4980B-1... TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-1 COBRA in general. The COBRA continuation coverage... requirements were added to section 162 by the Consolidated Omnibus Budget Reconciliation Act of 1985...

  3. The COBRA Neutrinoless Double Beta Experiment.

    NASA Astrophysics Data System (ADS)

    Li, Qiang

    2008-04-01

    The COBRA is a proposed experiment to detect neutrinoless double beta decays of the isotope 116Cd. The COBRA design is based on CZT room temperature solid state detectors. A prototype of the experiment made of 64 1cm^3 detectors is running in the Gran Sasso underground laboratory. In this talk, I will discuss the design of the COBRA prototype experiment and possible designs of a large-scale experiment made of 410 kg of CZT detectors. We are currently evaluating the option to use CZT detector units with 200 micron spatial resolution. Such detectors would make it possible to track the electrons from double beta decays and to distinguish them from certain types of background events.

  4. Cobra sealing system; From field evaluation to practical safeguards application

    SciTech Connect

    Vodrazka, P.; Cermak, L. )

    1991-01-01

    After a successful conclusion of the Cobra seal IAEA field trials, the Cobra Seal System was installed in two Canadian facilities. The seals permit on-site verification without needing to replace them in extreme weather conditions, thus allowing a substantial time reduction for inspectors as well as minimizing intrusiveness of these activities. The paper describes experiences with practical installations of almost sixty Cobra seals including the selection of environmental conduits and housing. Examples of the results of the first several inspections utilizing a new version of the Cobra seal verifier are also included. Possible future outdoor applications of Cobra seals are described and some suggested improvements are outlined.

  5. The COBRA Double Beta Decay Experiment

    NASA Astrophysics Data System (ADS)

    Dawson, J. V.

    2007-03-01

    The progress of the COBRA neutrinoless double beta decay experiment is discussed. Potential backgrounds are described. Estimates on the contamination levels of 214Bi in the detectors have been made using previously acquired low background data. New crystals with a different passivation material show an improved background count rate of approximately one order of magnitude.

  6. The COBRA Double Beta Decay Search Experiment

    NASA Astrophysics Data System (ADS)

    Stewart, D. Y.

    2006-11-01

    The COBRA experiment aims to use a large quantity of CdZnTe semiconductor detectors to search for neutrinoless double beta decay. The current status of the experiment is discussed, and new limits on several double beta modes are presented. Future plans for a large scale experiment are also described.

  7. The COBRA double beta decay experiment

    NASA Astrophysics Data System (ADS)

    Oldorf, C.; Cobra Collaboration

    2012-08-01

    The COBRA experiment is searching for double beta decay using CdZnTe semiconductor detectors. The main focus is on the isotope 116Cd. In addition to pure energy measurements, pixelisation allows also for tracking capabilities. This kind of semiconductor tracker is unique in the field. The current status of the experiment is shown including the latest half-life limits.

  8. The COBRA double-beta decay experiment

    NASA Astrophysics Data System (ADS)

    Stewart, D. Y.; COBRA Collaboration

    2007-09-01

    The COBRA experiment aims to use a large quantity of Cadmium-Zinc-Telluride (CdZnTe) semiconductor detectors to search for neutrinoless double-beta decay (0 υββ). The current status of the experiment is discussed, and new limits on several double-beta modes are presented. Future plans for a large-scale experiment are also described.

  9. Instant Print-Braille Compatibility with COBRA.

    ERIC Educational Resources Information Center

    Durre, Ingeborg K.; Durre, Imke

    1999-01-01

    Describes an eight-dot computer Braille notation, COBRA, with integrated mathematical and scientific notation that achieves immediate print-Braille compatibility through one-to-one representation of letters and other characters. Text can be entered from the Braille or the Qwerty Keyboard and can be viewed simultaneously on the Braille display and…

  10. The COBRA Double Beta Decay Experiment

    SciTech Connect

    Dawson, J. V.

    2007-03-28

    The progress of the COBRA neutrinoless double beta decay experiment is discussed. Potential backgrounds are described. Estimates on the contamination levels of 214Bi in the detectors have been made using previously acquired low background data. New crystals with a different passivation material show an improved background count rate of approximately one order of magnitude.

  11. The COBRA Double Beta Decay Search Experiment

    SciTech Connect

    Stewart, D. Y.

    2006-11-17

    The COBRA experiment aims to use a large quantity of CdZnTe semiconductor detectors to search for neutrinoless double beta decay. The current status of the experiment is discussed, and new limits on several double beta modes are presented. Future plans for a large scale experiment are also described.

  12. Cobra Fiber-Optic Positioner Upgrade

    NASA Technical Reports Server (NTRS)

    Fisher, Charles D.; Braun, David F.; Kaluzny, Joel V.

    2013-01-01

    A prime focus spectrometer (PFS), along with corrective optics, will mount in place of the secondary mirror of the Subaru telescope on Mauna Kea, Hawaii. This will allow simultaneous observations of cosmologic targets. It will enable large-scale galactic archeology and dark energy surveys to help unlock the secrets of the universe. To perform these cosmologic surveys, an array of 2,400 optical fibers needs to be independently positioned within the 498-mm-diameter focal plane of the PFS instrument to collect light from galaxies and stars for spectrographic analyses. To allow for independent re-positioning of the fibers, a very small positioner (7.7 mm in diameter) is required. One hundred percent coverage of the focal plane is also required, so these small actuators need to cover a patrol region of 9.5 mm in diameter. To optimize the amount of light that can be collected, the fibers need to be placed within 5 micrometers of their intended target (either a star or galaxy). The Cobra Fiber Positioner was designed to meet the size and accuracy requirements stated above. Cobra is a two-degrees-of-freedom mechanism that can position an optical fiber in the focal plane of the PFS instrument to a precision of 5 micrometers. It is a theta-phi style positioner containing two rotary piezo tube motors with one offset from the other, which enables the optic fibers to be placed anywhere in a small circular patrol region. The patrol region of the actuator is such that the array of 2,400 positioners allows for full coverage of the instrument focal plane by overlapping the patrol areas. A second-generation Cobra positioner was designed based on lessons learned from the original prototype built in 2009. Improvements were made to the precision of the ceramic motor parts, and hard stops were redesigned to minimize friction and prevent jamming. These changes resulted in reducing the number of move iterations required to position the optical fiber within 5 micrometers of its target. At

  13. Non-covalent interaction of phospholipase A2 (PLA2) and kaouthiotoxin (KTX) from venom of Naja kaouthia exhibits marked synergism to potentiate their cytotoxicity on target cells

    PubMed Central

    Mukherjee, Ashis K

    2010-01-01

    Present study shows that non-covalent interaction of kaouthiotoxin (KTX) with their respective pohospholipase A2 (PLA2) from the venom of N. kaouthia displayed marked synergism to exert cytotoxicity without altering the biochemical properties of PLA2. For example, although NK-PLA2 or KTX alone did not induce appreciable hemolysis of washed human erythrocytes; however, the hemolytic potency of NK-PLA2: KTX complex was significantly higher. Identically, selective lysis of virus infected Sf9 and normal Tn insect cells was further enhanced by the cognate NK-PLA2: KTX complex as compared to individual components of the complex. Gas-chromatographic analysis of fatty acids released from intact erythrocytes by cytotoxic action of individual NK-PLA2 and NK-PLA2: KTX complex demonstrated that ratio between saturated fatty acids (SFA) and unsaturated FA (UFA) was increasing with time of hydrolysis of RBC either in the case of NK-PLA2 or NK-PLA2-KTX complex suggesting NK-PLA2-KTX complex apparently displayed the more preference for glycerophospholipids with SFAs on the sn-2 position. Therefore, it may be suggested that KTX first destabilize the target cell membrane followed by higher enzymatic activity of PLA2 on dislocated and disorganized phospholipid bilayers resulting in a significantly higher (p < 0.05) membrane damage by NK-PLA2-KTX complex compared to individual components of the complex. PMID:21544180

  14. Social'naja sreda ucascihsja i ih sansy na uspevaemost' (The Social Background of Students and Their Prospect of Success at School).

    ERIC Educational Resources Information Center

    Ushinsky (K.D) State Scientific Library of the Academy of Pedagogical Sciences, Moscow (USSR).

    This document is an English-language abstract (approximately 1,500 words) of the Soviet response to an IBE questionnaire. It states that various agencies of the Soviet State maintain a continuing concern about school dropouts. A number of measures have been adopted to encourage students to finish school, such as improving educational methods,…

  15. Recent progress of the COBRA experiment

    NASA Astrophysics Data System (ADS)

    Oldorf, Christian

    2012-07-01

    The COBRA experiment uses CdZnTe semiconductor detectors to search for neutrinoless double beta decays. The main focus is on the isotope 116Cd, with a decay energy of 2813.5 keV well above the highest naturally occurring gamma lines. Also 130Te and 106Cd, a double β+ emitter, are under investigation. An overview of the recent improvements of the COBRA low-background set-up at the LNGS underground laboratory is given, including first results obtained with new FADC readout electronics which allows background reduction by pulse-shape analysis. Furthermore studies on detector characterization, the use of liquid scintillator for background suppression and Monte-Carlo simulations of the shielding are presented. Also pixelated detectors and their capabilities of background reduction are discussed.

  16. Axial X Pinch Backlighting on COBRA

    NASA Astrophysics Data System (ADS)

    Blesener, Isaac; Greenly, John; Pikuz, Sergey; Shelkovenko, Tatiania; Hammer, David; Kusse, Bruce

    2008-11-01

    X pinch backlighting is a useful imaging technique whereby two or more wires are crossed at a single point and driven with a high current (300-500 kA). At the crossing point, a micron-scale sub-nanosecond x-ray source is produced that acts as a point source and can be used for point-projection imaging. Axial x pinch backlighting is a new technique that allows an end-on image of Z pinches. New load geometry was developed at Cornell University to allow all standard diagnostics to be used on the same shot as the axial x pinch backlighting diagnostic. High density plasma features have been observed that correlate well with XUV self-emission images previously recorded on COBRA and simulation results from GORGON. Data and images will be presented illustrating the latest results from COBRA. Future applications include the possibility of shockwave imaging in the center of thing foil cylinders.

  17. 26 CFR 54.4980B-5 - COBRA continuation coverage.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 17 2012-04-01 2012-04-01 false COBRA continuation coverage. 54.4980B-5 Section 54.4980B-5 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-5 COBRA continuation coverage. The following questions-and-answers address...

  18. 76 FR 51963 - Cobra Pipeline Ltd.; Notice of Baseline Filings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Cobra Pipeline Ltd.; Notice of Baseline Filings Take notice that on August 12, 2011, Cobra Pipeline Ltd. submitted a revised baseline filing of their Statement of...

  19. Seamless Handovers in Cobra Teardrop Satellite Arrays

    NASA Astrophysics Data System (ADS)

    Draim, John E.; Cefola, Paul J.; Ernandes, Kenneth J.

    2007-06-01

    Satellite systems provide the most efficient and possibly the only means of achieving two-way global communications with mobile systems (ships, aircraft, and vehicular traffic). To date, such systems have used only circular orbits, either GEO or LEO. Medium altitude elliptical constellations, on the other hand, can provide an efficient and affordable alternative to these architectures. Users also benefit from their very high average and minimum elevation angles, resulting in minimum signal attenuation. Cobra Teardrop is unique in that it employs time synchronized 8-h left- and right-leaning elliptical orbits giving mid-latitude observers the illusion of viewing a single satellite continuously orbiting almost directly overhead! In reality, observers see six different satellites per day, for 4 h each (while in their active duty cycles). By design, Teardrop satellites are physically in very close proximity at the handover points. This favorable geometry can be utilized to achieve a seamless handover from one satellite to the other (not requiring any electronic buffering). Handover is accomplished at the precise instant that the total path lengths from the transmitting station through both satellites to the receiving station are exactly equal. In these improved Cobra Teardrop arrays, an order of magnitude increase in global communications capacity (equivalent GEO slots) can be realized over earlier Basic Cobra systems. For decades into the future, these new orbital systems could satisfy a widely expanding range of commercial, government, and military high data rate communication requirements. These would include, but not be limited to, satellite cellular, air traffic control, meteorological, and combat net radio systems. With these arrays, a much larger number of system operators could be supported, without mutual electronic interference, than would ever be possible with circular orbits.

  20. Nested X Pinches on the COBRA Generator

    NASA Astrophysics Data System (ADS)

    Shelkovenko, T. A.; Pikuz, S. A.; McBride, R. D.; Knapp, P. F.; Wilhelm, H.; Hammer, D. A.; Sinars, D. B.

    2009-01-01

    Recent results of X pinch studies on the COBRA generator at Cornell University (peak current up to 1.2 MA and rise time of 100 ns) are presented. Using an initial configuration of wires before their twisting, similar to nested cylindrical wire arrays enables the assembly of a symmetric configuration at the X pinch crossing region. It also enables an investigation of multilayered X pinches. X pinches with different configurations, including with different materials in the inner and outer wire layers, were tested.

  1. Status of the double beta experiment COBRA

    NASA Astrophysics Data System (ADS)

    Zuber, K.

    2006-07-01

    The COBRA experiment is going to use a large number of CdZnTe semiconductor detectors to perform a search for various double beta decay modes. The current status of the experiment is presented, as well as first results. A half-life measurement of the fourfold forbidden non-unique beta-decay of 113Cd has been performed. Improved half-life limits for the ground state transitions of 64Zn for 0νβ+/EC and 0νEC/EC have been obtained. A short outlook on future activities is given.

  2. Nested X Pinches on the COBRA Generator

    SciTech Connect

    Shelkovenko, T. A.; Pikuz, S. A.; McBride, R. D.; Knapp, P. F.; Wilhelm, H.; Hammer, D. A.; Sinars, D. B.

    2009-01-21

    Recent results of X pinch studies on the COBRA generator at Cornell University (peak current up to 1.2 MA and rise time of 100 ns) are presented. Using an initial configuration of wires before their twisting, similar to nested cylindrical wire arrays enables the assembly of a symmetric configuration at the X pinch crossing region. It also enables an investigation of multilayered X pinches. X pinches with different configurations, including with different materials in the inner and outer wire layers, were tested.

  3. 77 FR 71190 - Cobra Pipeline Ltd.; Notice of Petition for Rate Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-29

    ... Energy Regulatory Commission Cobra Pipeline Ltd.; Notice of Petition for Rate Approval Take notice that on November 19, 2012, Cobra Pipeline Ltd. (Cobra) filed a Rate Election pursuant to 284.123(b)(1) of the Commissions regulations and to revise its Statement of Operating Conditions. Cobra proposes...

  4. COBRA/RELAP5; A merged version of the COBRA-TF and RELAP5/MOD3 codes

    SciTech Connect

    Lee, S.Y.; Jeong, J.J.; Kim, S.H. ); Chang, S.H.

    1992-08-01

    This paper reports that the best-estimate thermal-hydraulic codes RELAP5/MOD3 and COBRA-TF were adopted to the Apollo DN 10000 workstation and subsequently merged. This was done to combine the excellent features of the two codes and thus product a code with much enhanced capability. The resulting code was named COBRA/RELAP5. This code has features in common with COBRA/TRAC or TRAC-PF1; three-dimensional reactor vessel and one-dimensional loop modeling capability. The merging of the two codes is focused on the hydrodynamic model and numerical solution schemes. In COBRA/RELAP5, the system pressure matrices of the two codes are merged and solved simultaneously. The merged COBRA/RELAP5 calculations are done in process-level parallel mode on the Apollo DN10000 computer with two central processing units.

  5. Species identification from dried snake venom.

    PubMed

    Singh, Chandra S; Gaur, Ajay; Sreenivas, Ara; Singh, Lalji

    2012-05-01

    Illegal trade in snake parts has increased enormously. In spite of strict protection under wildlife act, a large number of snakes are being killed ruthlessly in India for venom and skin. Here, an interesting case involving confiscation of crystallized dried snake venom and subsequent DNA-based species identification is reported. The analysis using the universal primers for cytochrome b region of the mitochondrial DNA revealed that the venom was extracted from an Indian cobra (Naja naja). On the basis of this report, the forwarding authority booked a case in the court of law against the accused for illegal hunting of an endangered venomous snake and smuggling of snake venom. This approach thus has immense potential for rapid identification of snake species facing endangerment because of illegal trade. This is also the first report of DNA isolation from dried snake venom for species identification. PMID:22268640

  6. Diagnostics on the COBRA pulsed power generator

    NASA Astrophysics Data System (ADS)

    Shelkovenko, T. A.; Chalenski, D. A.; Chandler, K. M.; Douglass, J. D.; Greenly, J. B.; Hammer, D. A.; Kusse, B. R.; McBride, R. D.; Pikuz, S. A.

    2006-10-01

    The COBRA pulsed power generator has a variable current pulse wave form and amplitude (95-180ns rise time, up to 1MA peak current). It was designed to study wire array Z pinches and X pinches, including plasma formation, pinch implosion dynamics, and pinch plasma parameters as a function of current rise time. These loads have been studied using an extensive set of diagnostics with spatial and/or temporal resolution. The set of electrical diagnostics on the COBRA generator includes Rogowski coils to monitor the total load current and the current through individual return current posts, and there is also an inductive voltage monitor. A set of extreme ultraviolet and x-ray detectors is used to study the load radiation. Wire array and X pinch plasma formation and dynamics are studied using two-frame, point projection X-pinch x-ray imaging as well as with multiframe laser probing. Flat potassium acid phtalate crystal (KAP), convex, extreme luminosity imaging conical spectrograph, and focusing spectrograph with spatial resolution with mica crystal, pinhole cameras, and a camera with a slit and a step filter set (slip step-wedge camera) can be used in each pulse to monitor the x-ray emission from the X pinch(es) and arrays in several spectral bands.

  7. Diagnostics on the COBRA pulsed power generator

    SciTech Connect

    Shelkovenko, T. A.; Chalenski, D. A.; Chandler, K. M.; Douglass, J. D.; Greenly, J. B.; Hammer, D. A.; Kusse, B. R.; McBride, R. D.; Pikuz, S. A.

    2006-10-15

    The COBRA pulsed power generator has a variable current pulse wave form and amplitude (95-180 ns rise time, up to 1 MA peak current). It was designed to study wire array Z pinches and X pinches, including plasma formation, pinch implosion dynamics, and pinch plasma parameters as a function of current rise time. These loads have been studied using an extensive set of diagnostics with spatial and/or temporal resolution. The set of electrical diagnostics on the COBRA generator includes Rogowski coils to monitor the total load current and the current through individual return current posts, and there is also an inductive voltage monitor. A set of extreme ultraviolet and x-ray detectors is used to study the load radiation. Wire array and X pinch plasma formation and dynamics are studied using two-frame, point projection X-pinch x-ray imaging as well as with multiframe laser probing. Flat potassium acid phtalate crystal (KAP), convex, extreme luminosity imaging conical spectrograph, and focusing spectrograph with spatial resolution with mica crystal, pinhole cameras, and a camera with a slit and a step filter set (slip step-wedge camera) can be used in each pulse to monitor the x-ray emission from the X pinch(es) and arrays in several spectral bands.

  8. COBRA ARRA Subsidies: Was the Carrot Enticing Enough?

    PubMed Central

    Graetz, Ilana; Reed, Mary; Fung, Vicki; Dow, William H; Newhouse, Joseph P; Hsu, John

    2012-01-01

    Objective To help preserve continuity of health insurance coverage during the recent recession, the American Recovery and Reinvestment Act provided a 65 percent Consolidated Omnibus Budget Reconciliation Act (COBRA) premium subsidy for workers laid off in 2008–2010. We examined COBRA enrollment levels with the subsidy and the health, access, and financial consequences of enrollment decisions. Study Design/Data Collection Telephone interviews linked with health system databases for 561 respondents who were laid off in 2009 and eligible for the COBRA subsidy (80 percent response rate). Principal Findings Overall, 38 percent reported enrolling in COBRA and 54 percent reported having some gaps in insurance coverage since being laid off. After adjustments, we found that those who had higher cost-sharing, who had higher incomes, were older, or were sicker were more likely to enroll in COBRA. COBRA enrollees less frequently reported access problems or that their health suffered because of poor access, but they reported greater financial stress due to health care spending. Conclusion Despite the substantial subsidy, a majority of eligible individuals did not enroll in COBRA, and many reported insurance coverage gaps. Nonenrollees reported more access problems and that their health worsened. Without a mandate, subsidies may need to be widely publicized and larger to encourage health insurance enrollment among individuals who suffer a negative income shock. PMID:22515835

  9. The COBRA-1B irradiation experiment in EBR-II

    SciTech Connect

    Tsai, H.; Hins, A.G.; Strain, R.V.; Smith, D.L.

    1994-09-01

    The objective of the forthcoming COBRA-1B experiment in EBR-II is to evaluate the effects of fast neutron irradiation on the physical and mechanical properties of candidate fusion structural materials. Of special interest in this experiment will be ITER-relevant temperature and exposure for the test specimens. Approximately 50% of the irradiation test volume will be devoted to vanadium-alloy specimens. Design of the COBRA-1B irradiation experiment began in this reporting period and is in progress. The target reactor insertion date for COBRA-1B is September 1994. Technical and programmatic feasibility approval for the experiment has been granted by EBR-II Operations.

  10. Triggered Reconnection at 1 MA on COBRA

    NASA Astrophysics Data System (ADS)

    Greenly, John; Blesener, Kate; Seyler, Charles; Zhao, Xuan

    2013-10-01

    We present new results in the study of magnetic reconnection of flux generated by two parallel currents in exploding Al wires driven to 1 MA by the Cornell COBRA pulser. Magnetic and thermal energy are stored in the system as the current rises in 200 ns. The stored energy is then dissipated in reconnection and outflows triggered at the time of voltage reversal and the decline of external magnetic pressure. Data are presented from a new optical spectroscopy diagnostic with high spatial and spectral resolution. The flows are supersonic. Strongly radiating shocks are associated with the current sheet and outflow boundaries. PERSEUS MHD and XMHD simulations are presented to compare with experiment and characterize the reconnection regime. Work supported by US DOE.

  11. Status and Perspectives of the COBRA Experiment

    NASA Astrophysics Data System (ADS)

    Wonsak, Björn

    COBRA is a neutrinoless double beta decay (0νββ) experiment using an array of Cadmium-Zinc-Telluride semiconductor detectors, the isotope of interest being 116Cd with a Q-value of 2814 keV. To investigate the experimental challenges of operating CdZnTe detectors in low background mode and to identify potential background components, a demonstrator setup is operated at the Gran Sasso underground laboratory (LNGS) in Italy, while additional studies are proceeding in surface laboratories. The experiment consists of monolithic, calorimetric detectors of coplanar grid design (CPG de- tectors). These detectors have a size of 1×1×1 cm3 and are arranged in four layers of 4×4 detectors. An overview of the current status and of future perspectives is given. Results of pulse shape analyses are presented as well as background estimates using the data collected so far.

  12. COBRA - Neutrinoless Double Beta Decay Experiment

    NASA Astrophysics Data System (ADS)

    Heidrich, Nadine

    2012-08-01

    The COBRA experiment is searching for neutrinoless double beta decay using CdZnTe semiconductor detectors. The main focus is on Cd-116, with a decay energy of 2814keV well above the highest naturally occurring gamma lines. Furthermore, Te-130, with a high natural abundance, and Cd-106, a double β+ emitter, are under investigation. Advantageous is the possibility to operate the detectors at room temperature. Besides coplanar grid detectors, pixelised detectors are considered. The latter ones would allow for particle discrimination, therefore providing efficient background reduction. The current status of the experiment is described, including the upgrade of the R&D set-up in spring 2011 at the LNGS underground laboratory, the different detector concepts and the latest half -life limits. Furthermore, studies on the use of liquid scintillator for background suppression and Monte-Carlo simulations are presented.

  13. Nested X Pinches on the COBRA Generator

    NASA Astrophysics Data System (ADS)

    Hammer, David; Shelkovenko, Tatiana; Pikuz, Sergei; McBride, Ryan; Knapp, Patrick; Wilhelm, Harold; Sinars, Daniel

    2008-11-01

    Recent results of X pinch studies on the COBRA generator at Cornell University (peak current up to 1.2 MA and rise time of 100 ns) are presented. Increasing of the pulser current requires the use of loads with higher mass per unit length. Such loads can be made by increasing the number of wires or the wire diameters, which leads to increasing the size and complexity of the wire crossing region. Using an initial configuration of wires (before their twisting), similar to nested arrays enables the assembly of a more-nearly symmetric configuration at the X pinch crossing region. It also enables an investigation of multilayered X pinches. We will present experimental results obtained from X pinches with different configurations, including X pinches with different materials in the inner and outer wire layers.

  14. Study of Ion Back Flow suppression with thick COBRA GEM

    NASA Astrophysics Data System (ADS)

    Terasaki, K.

    2014-03-01

    Ion Back Flow (IBF) suppression is essential to avoid a space-charge distortion of the electric field under a high rate condition in the Time Projection Chamber (TPC). A GEM technology is one possible solution to achieve a small IBF and to keep a good performance in terms of particle tracking and particle identification at high rates in TPC. We developed Thick COBRA GEMs to investigate the capability of further IBF suppression. It was found that the COBRA GEM can suppress IBF more effectively compared to a standard GEM. IBF reaches about 0.1-0.5% with a stack configuration consisting of one standard GEM facing to the drift field and two COBRA GEMs. In this paper, the current status of development of COBRA GEM is described.

  15. INGEN: A COBRA-NC input generator user's manual

    SciTech Connect

    Wheeler, C.L.; Dodge, R.E.

    1986-12-01

    The INGEN (INput GENerator) computer program has been developed as a preprocessor to simplify input generation for the COBRA-NC computer program. INGEN uses several empirical correlations and geometric assumptions to simplify the data input requirements for the COBRA-NC computer code. The simplified input scheme is obtained at the expense of much flexibility provided by COBRA-NC. For more complex problems requiring additional flexibility however, INGEN may be used to provide a skeletal input file to which the more detailed input may be added. This report describes the input requirements for INGEN and describes the algorithms and correlations used to generate the COBRA-NC input. 9 refs., 3 figs., 6 tabs.

  16. Assessment of the computer code COBRA/CFTL

    SciTech Connect

    Baxi, C. B.; Burhop, C. J.

    1981-07-01

    The COBRA/CFTL code has been developed by Oak Ridge National Laboratory (ORNL) for thermal-hydraulic analysis of simulated gas-cooled fast breeder reactor (GCFR) core assemblies to be tested in the core flow test loop (CFTL). The COBRA/CFTL code was obtained by modifying the General Atomic code COBRA*GCFR. This report discusses these modifications, compares the two code results for three cases which represent conditions from fully rough turbulent flow to laminar flow. Case 1 represented fully rough turbulent flow in the bundle. Cases 2 and 3 represented laminar and transition flow regimes. The required input for the COBRA/CFTL code, a sample problem input/output and the code listing are included in the Appendices.

  17. The Cobra helmet mounted display system for Gripen

    NASA Astrophysics Data System (ADS)

    Larsson, Jörgen; Blomqvist, Tommy

    2008-04-01

    Selected to meet the stringent requirements of the Gripen swing-role combat aircraft, the Cobra Helmet Mounted Display System, has been integrated as a key component to the Gripen weapon delivery system. Saab Aerosystems has since 2003 together with BAE System been developing the Cobra HMD and in parallel integrating the system in Gripen for South Africa. Work is currently done to prepare other customer for the Cobra HMDS. This paper will highlight some technical challenges and experiences with integrating a HMDS in a small cockpit environment as in Gripen and present an overview of the Cobra HMD design and installation. Furthermore the paper will discuss the importance of having the pilots and users involved during the design phase and throughout the development.

  18. COBRA-SFS. Thermal Analysis Spent Fuel Storage

    SciTech Connect

    Rector, D.R.

    1986-11-01

    COBRA-SFS is used for steady-state and transient thermal hydraulic analysis of spent fuel storage systems as well as other heat transfer and fluid flow problems. It is designed to predict flow and temperature distributions under a wide range of flow conditions, including mixed and natural convection. Two auxiliary programs, RADX1 and RADGEN, generate blackbody view factors and calculate radiation exchange factors for unconsolidated spent fuel assemblies to be supplied as input to COBRA-SFS.

  19. COBRA-Seq: Sensitive and Quantitative Methylome Profiling

    PubMed Central

    Varinli, Hilal; Statham, Aaron L.; Clark, Susan J.; Molloy, Peter L.; Ross, Jason P.

    2015-01-01

    Combined Bisulfite Restriction Analysis (COBRA) quantifies DNA methylation at a specific locus. It does so via digestion of PCR amplicons produced from bisulfite-treated DNA, using a restriction enzyme that contains a cytosine within its recognition sequence, such as TaqI. Here, we introduce COBRA-seq, a genome wide reduced methylome method that requires minimal DNA input (0.1–1.0 μg) and can either use PCR or linear amplification to amplify the sequencing library. Variants of COBRA-seq can be used to explore CpG-depleted as well as CpG-rich regions in vertebrate DNA. The choice of enzyme influences enrichment for specific genomic features, such as CpG-rich promoters and CpG islands, or enrichment for less CpG dense regions such as enhancers. COBRA-seq coupled with linear amplification has the additional advantage of reduced PCR bias by producing full length fragments at high abundance. Unlike other reduced representative methylome methods, COBRA-seq has great flexibility in the choice of enzyme and can be multiplexed and tuned, to reduce sequencing costs and to interrogate different numbers of sites. Moreover, COBRA-seq is applicable to non-model organisms without the reference genome and compatible with the investigation of non-CpG methylation by using restriction enzymes containing CpA, CpT, and CpC in their recognition site. PMID:26512698

  20. COBRA-SFS. Thermal Hydraulic Analysis of Spent Fuel Casks

    SciTech Connect

    Michener, T.E.; Rector, D.R.; Cuta, J.M.; Enderlin, C.W.

    1995-09-01

    COBRA-SFS (Spent Fuel Storage) is a code for thermal-hydraulic analysis of multi-assembly spent fuel storage and transportation systems. It uses a lumped parameter finite difference approach to predict flow and temperature distributions in spent fuel storage systems and fuel assemblies, under forced and natural convection heat transfer conditions. Derived from the COBRA family of codes, which have been extensively evaluated against in-pile and out-of-pile data, COBRA-SFS retains all the important features of the COBRA codes for single phase fluid analysis, and extends the range application to include problems with two-dimensional radiative and three-dimensional conductive heat transfer. COBRA-SFS has been used to analyze various single- and multi-assembly spent fuel storage systems containing unconsolidated and consolidated fuel rods, with a variety of fill media, including air, helium and vacuum. Cycle 0 of COBRA-SFS was released in 1986. Subsequent applications of the code led to development of additional capabilities, which resulted in the release of Cycle 1 in February 1989. Since then, the code has undergone an independent technical review as part of a submittal to the Nuclear Regulatory Commission for a generic license to apply the code to spent fuel storage system analysis. Modifications and improvements to the code have been combined to form the latest release of the code, Cycle 2.

  1. The functional morphology of hooding in cobras.

    PubMed

    Young, Bruce A; Kardong, Kenneth V

    2010-05-01

    Many snakes, particularly cobras, form as part of a defensive display, a hood, an active lateral expansion of their neck skin and underlying musculature and ribs. We identified muscle groups possibly involved in hooding based on their attachments on the specialized ribs of the neck. We then used a combination of morphology, kinematic analysis, morphometrics, electromyography and muscle stimulation to test hypotheses about the functional basis of hooding. We confirmed that hood protraction and erection is an active process that begins cranially and extends caudally, often in stages, through the combined action of several sets of muscles. One set of axial muscles (levator costae and supracostalis lateralis superior) coursing along a line of action to rib displacement are the prime erectors acting to lift the hood. However, a second set of muscles connecting ribs to skin primarily keep the skin taut, rather than to displace the ribs relative to the vertebrae. A third set of muscles coursing between ribs function primarily to transmit forces between adjacent ribs rather than to move ribs. The maintenance of the erect hood requires continued muscle activity. Hood relaxation is due to both active muscle contraction of a fourth set of axial muscles and to passive recoil events in the costovertebral ligaments. The shape of the fully erect hood is reflective of the morphometrics of the underlying ribs, while the duration and kinematics of hood erection and relaxation are related to the behavioral context of the display. PMID:20400637

  2. Verification and validation of COBRA-SFS transient analysis capability

    SciTech Connect

    Rector, D.R.; Michener, T.E.; Cuta, J.M.

    1998-05-01

    This report provides documentation of the verification and validation testing of the transient capability in the COBRA-SFS code, and is organized into three main sections. The primary documentation of the code was published in September 1995, with the release of COBRA-SFS, Cycle 2. The validation and verification supporting the release and licensing of COBRA-SFS was based solely on steady-state applications, even though the appropriate transient terms have been included in the conservation equations from the first cycle. Section 2.0, COBRA-SFS Code Description, presents a capsule description of the code, and a summary of the conservation equations solved to obtain the flow and temperature fields within a cask or assembly model. This section repeats in abbreviated form the code description presented in the primary documentation (Michener et al. 1995), and is meant to serve as a quick reference, rather than independent documentation of all code features and capabilities. Section 3.0, Transient Capability Verification, presents a set of comparisons between code calculations and analytical solutions for selected heat transfer and fluid flow problems. Section 4.0, Transient Capability Validation, presents comparisons between code calculations and experimental data obtained in spent fuel storage cask tests. Based on the comparisons presented in Sections 2.0 and 3.0, conclusions and recommendations for application of COBRA-SFS to transient analysis are presented in Section 5.0.

  3. Shed king cobra and cobra skins as model membranes for in-vitro nicotine permeation studies.

    PubMed

    Pongjanyakul, Thaned; Prakongpan, Sompol; Panomsuk, Suwannee; Puttipipatkhachorn, Satit; Priprem, Aroonsri

    2002-10-01

    Shed king cobra skin (SKCS) and shed cobra skin (SCS) were investigated for use as barrier membranes, including some pre-hydration factors, for in-vitro nicotine permeation. Inter-specimen variations in nicotine fluxes using shed snake skin were compared with those using human epidermis. Nicotine in the form of 1% w/v aqueous buffer solution at pH 5 and transdermal patches (dose 14 mg day(-1)) were used. The nicotine fluxes across the shed snake skin were not significantly affected (P > 0.05) by temperature and duration of hydration pre-treatment. Scanning electron micrographs of SKCS and SCS revealed a remarkable difference in surface morphology, but the nicotine fluxes using both shed skins were not significantly different (P > 0.05). When compared with the results obtained using human epidermis, there were similarities in fluxes and permeation profiles of nicotine. Using nicotine solution, the nicotine permeation profiles of all membranes followed zero order kinetics. The amount of nicotine permeated provided good linearity with the square root of time over 24 h (R(2) > 0.98) when using nicotine patches. The nicotine fluxes using SKCS and SCS had less inter-specimen variation than those using human epidermis. The results suggest a potential use for SKCS or SCS as barrier membranes for in-vitro nicotine permeation studies. PMID:12396295

  4. 26 CFR 54.4980B-6 - Electing COBRA continuation coverage.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 17 2014-04-01 2014-04-01 false Electing COBRA continuation coverage. 54.4980B... (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-6 Electing COBRA continuation coverage. The following questions-and-answers address the manner in which COBRA...

  5. 26 CFR 54.4980B-7 - Duration of COBRA continuation coverage.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 17 2011-04-01 2011-04-01 false Duration of COBRA continuation coverage. 54... (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-7 Duration of COBRA continuation coverage. The following questions-and-answers address the duration of COBRA continuation...

  6. 26 CFR 54.4980B-8 - Paying for COBRA continuation coverage.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 17 2011-04-01 2011-04-01 false Paying for COBRA continuation coverage. 54... (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-8 Paying for COBRA continuation coverage. The following questions-and-answers address paying for COBRA continuation coverage:...

  7. 26 CFR 54.4980B-8 - Paying for COBRA continuation coverage.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 17 2013-04-01 2013-04-01 false Paying for COBRA continuation coverage. 54... (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-8 Paying for COBRA continuation coverage. The following questions-and-answers address paying for COBRA continuation coverage:...

  8. 26 CFR 54.4980B-8 - Paying for COBRA continuation coverage.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 17 2014-04-01 2014-04-01 false Paying for COBRA continuation coverage. 54... (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-8 Paying for COBRA continuation coverage. The following questions-and-answers address paying for COBRA continuation coverage:...

  9. 26 CFR 54.4980B-6 - Electing COBRA continuation coverage.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 17 2011-04-01 2011-04-01 false Electing COBRA continuation coverage. 54.4980B... (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-6 Electing COBRA continuation coverage. The following questions-and-answers address the manner in which COBRA...

  10. 26 CFR 54.4980B-7 - Duration of COBRA continuation coverage.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 17 2014-04-01 2014-04-01 false Duration of COBRA continuation coverage. 54... (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-7 Duration of COBRA continuation coverage. The following questions-and-answers address the duration of COBRA continuation...

  11. Cobra venom cytotoxins; apoptotic or necrotic agents?

    PubMed

    Ebrahim, Karim; Shirazi, Farshad H; Mirakabadi, Abbas Zare; Vatanpour, Hossein

    2015-12-15

    Organs homeostasis is controlled by a dynamic balance between cell proliferation and apoptosis. Failure to induction of apoptosis has been implicated in tumor development. Cytotoxin-I (CTX-I) and cytotoxin-II (CTX-II) are two physiologically active polypeptides found in Caspian cobra venom. Anticancer activity and mechanism of cell death induced by these toxins have been studied. The toxins were purified by different chromatographic steps and their cytotoxicity and pattern of cell death were determined by MTT, LDH release, acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis, caspase-3 activity and neutral red assays. The IC50 of CTX-II in MCF-7, HepG2, DU-145 and HL-60 was 4.1 ± 1.3, 21.2 ± 4.4, 9.4 ± 1.8 μg/mL and 16.3 ± 1.9 respectively while the IC50 of this toxin in normal MDCK cell line was 54.5 ± 3.9 μg/mL. LDH release suddenly increase after a specific toxins concentrations in all cell lines. AO/EtBr double staining, flow cytometric analysis and caspase-3 activity assay confirm dose and time-dependent induction of apoptosis by both toxins. CTX-I and CTX-II treated cells lost their lysosomal membrane integrity and couldn't uptake neutral red day. CTX-I and CTX-II showed significant anticancer activity with minimum effects on normal cells and better IC50 compared to current anticancer drug; cisplatin. They induce their apoptotic effect via lysosomal pathways and release of cathepsins to cytosol. These effects were seen in limited rage of toxins concentrations and pattern of cell death rapidly changes to necrosis by increase in toxin's concentration. In conclusion, significant apoptogenic effects of these toxins candidate them as a possible anticancer agent. PMID:26482932

  12. 26 CFR 54.4980B-1 - COBRA in general.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... for topics not addressed in §§ 54.4980B-1 through 54.4980B-10? A-2: For purposes of section 4980B, for topics relating to the COBRA continuation coverage requirements of section 4980B that are not...

  13. 26 CFR 54.4980B-5 - COBRA continuation coverage.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... employee and spouse who have no children divorce on May 1, 2001, and the spouse elects COBRA continuation... children who do not remain in the employee's custody. An employee and spouse with three dependent children... is a child born to or placed for adoption with a covered employee during a period of...

  14. 26 CFR 54.4980B-5 - COBRA continuation coverage.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... employee and spouse who have no children divorce on May 1, 2001, and the spouse elects COBRA continuation... children who do not remain in the employee's custody. An employee and spouse with three dependent children... is a child born to or placed for adoption with a covered employee during a period of...

  15. 26 CFR 54.4980B-5 - COBRA continuation coverage.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... employee and spouse who have no children divorce on May 1, 2001, and the spouse elects COBRA continuation... children who do not remain in the employee's custody. An employee and spouse with three dependent children... is a child born to or placed for adoption with a covered employee during a period of...

  16. Target tracking during venom ‘spitting’ by cobras

    PubMed Central

    Westhoff, Guido; Boetig, Melissa; Bleckmann, Horst; Young, Bruce A.

    2010-01-01

    Spitting cobras, which defend themselves by streaming venom towards the face and/or eyes of a predator, must be highly accurate because the venom they spit is only an effective deterrent if it lands on the predator's cornea. Several factors make this level of accuracy difficult to achieve; the target is moving, is frequently >1 m away from the snake and the venom stream is released in approximately 50 ms. In the present study we show that spitting cobras can accurately track the movements of a potentially threatening vertebrate, and by anticipating its subsequent (short-term) movements direct their venom to maximize the likelihood of striking the target's eye. Unlike other animals that project material, in spitting cobras the discharge orifice (the fang) is relatively fixed so directing the venom stream requires rapid movements of the entire head. The cobra's ability to track and anticipate the target's movement, and to perform rapid cephalic oscillations that coordinate with the target's movements suggest a level of neural processing that has not been attributed to snakes, or other reptiles, previously. PMID:20472765

  17. Evidence for existence of venom 5' nucleotidase in multiple forms through inhibition of concanavalin A.

    PubMed

    Dhananjaya, B L; Gowda, T V; D'Souza, Cletus J M

    2010-10-01

    Pharmacologically active 5' nucleotidase is a ubiquitously distributed enzyme in snake venoms. In this study the effect of concanavalin A (Con-A) on different snake venoms 5' nucleotidase activity is tested in order to know the protein nature which will ultimately help in purification of the enzyme with high yield. Con-A inhibited Naja naja, Naja kauthia, Naja melanoleuca, Naja naja sputatrix, Agistrodon halys blomhoffii, Bothrops asper and Oxyranus scutellas venom 5' nucleotidase activity at different concentrations. This indicates the presence of glycopart in the protein, thus glycoprotein in nature. Vipera russellii, Vipera plaestenae, Agistrodon contratrix, Bitis orientis, Echis carinatus and Trimeresures malabaricus was not inhibited by Con-A, indicating absence of glycopart in the protein. This study for the first time shows existence of 5' nucleotidase in multimeric forms. PMID:20941753

  18. AN/FPS-108 COBRA DANE Space Surveillance Mission Evolution

    NASA Astrophysics Data System (ADS)

    Chorman, P.; Boggs, J.

    2013-09-01

    It has been ten years since the COBRA DANE radar was restored to continuous full power operations in a more dedicated role of space debris tracking. Over this time, the satellite catalog population has grown and the overall average RCS value of cataloged objects has decreased dramatically, due to a combination of breakups and collisions together with the increased sensitivity offered by COBRA DANE's support to the network. This shift in catalog composition places new challenges on COBRA DANE and other debris tracking radars (PARCS and Eglin/FPS-85) to consistently track the ever-increasing number of small objects. Space Surveillance Network radars now operate at the limits of their detection performance, tracking several thousand new objects in a size category that only the most powerful and sensitive radars can observe (i.e., < 10 cm diameter). However, for much of the last decade, COBRA DANE's inherent Spacetrack mission software functionality remained better tuned for its original support role against the larger (known) orbital objects than for its more modern role in acquiring and reporting small debris in an appreciable number -- that is, until now. Several newly-identified software changes offer promise of significantly increased data yield that will make COBRA DANE an even more important asset for this evolving mission. In the course of assisting JSpOC, AFSPC, and USSTRATCOM with the ongoing challenges of lost satellite management, it was discovered that the radar's performance is being artificially restricted by mission software, rather than by the system's overall architectural design (power-aperture envelope and radar resources). This paper captures specific opportunities to improve COBRA DANE's Spacetrack mission performance, several of which are currently implemented and slated to become operational with the next two software releases. With one of the more prominent enhancements, COBRA DANE will be capable of autonomously 'fence tasking' all newly

  19. COBRA-PI: an extension of the COBRA-3M code dynamically dimensioned to accept pin bundles of any size. [LMFBR

    SciTech Connect

    Froehle, P.H.; Bauer, T.H.

    1983-03-28

    COBRA, in general, performs a thermal-hydraulic analysis of an actual pin bundle by subdividing the bundle cross-section into coolant subchannels, pin sectors, duct wall sectors. Its calculation includes heat convected axially upward through coolant mass flow, heat flow between pin sectors and adjoining subchannels, and heat and mass flow between coolant subchannels. COBRA-3M is a version of COBRA built for LMFBR applications, that includes a sophisticated thermal model of fuel pins and duct wall. COBRA-3M that can explicitly model a wider variety of pin bundle configurations than 3M would allow and includes significant improvements to its thermal modeling. COBRA-PI is currently being used for thermal-hydraulic analysis of hypothetical LMFBR accident transients in both power and flow. Pin bundles currently being analyzed explicitly range from 7 to 37 pins of axial lengths ranging from approx. 0.3-2.0 meters.

  20. MagLev Cobra: Test Facilities and Operational Experiments

    NASA Astrophysics Data System (ADS)

    Sotelo, G. G.; Dias, D. H. J. N.; de Oliveira, R. A. H.; Ferreira, A. C.; De Andrade, R., Jr.; Stephan, R. M.

    2014-05-01

    The superconducting MagLev technology for transportation systems is becoming mature due to the research and developing effort of recent years. The Brazilian project, named MagLev-Cobra, started in 1998. It has the goal of developing a superconducting levitation vehicle for urban areas. The adopted levitation technology is based on the diamagnetic and the flux pinning properties of YBa2Cu3O7-δ (YBCO) bulk blocks in the interaction with Nd-Fe-B permanent magnets. A laboratory test facility with permanent magnet guideway, linear induction motor and one vehicle module is been built to investigate its operation. The MagLev-Cobra project state of the art is presented in the present paper, describing some construction details of the new test line with 200 m.

  1. Status of the COBRA double beta decay experiment

    NASA Astrophysics Data System (ADS)

    Zuber, Kai

    2010-01-01

    The current status of the COBRA experiment is described. Results on the 4-fold forbidden beta decay of 113Cd and a variety of double beta decay limits of Cd, Zn and Te isotopes are presented based on 18 kg × days of exposure with an array of sixteen CdZnTe semiconductor detectors. A short description on the activities with pixelated detectors for tracking is given.

  2. Status of the COBRA double beta decay experiment

    NASA Astrophysics Data System (ADS)

    Janutta, B.; Cobra Collaboration

    2011-08-01

    COBRA is an R&D project, using CdZnTe (CZT) semiconductor detectors to search for the 0νββ decay. CZT is a room temperature semiconductor detector with good energy resolution. The experiment is located at the Laboratori Nazionali del Gran Sasso (LNGS). In addition to pure energy measurements, pixelated detectors allow for tracking, further reducing the background significantly. The current status of the experiment is presented, including the latest analysis results.

  3. The status of the COBRA double-beta-decay experiment

    NASA Astrophysics Data System (ADS)

    Zuber, K.

    2010-04-01

    The current status of the COBRA experiment is described. Results on the fourfold-forbidden beta decay of 113Cd and a variety of double-beta-decay limits for Cd, Zn and Te isotopes are presented, based on 18 kg× days of exposure with an array of sixteen CdZnTe semiconductor detectors. A short description of the activities with pixelated detectors for tracking is given.

  4. The Arabidopsis COBRA Protein Facilitates Cellulose Crystallization at the Plasma Membrane*

    PubMed Central

    Sorek, Nadav; Sorek, Hagit; Kijac, Aleksandra; Szemenyei, Heidi J.; Bauer, Stefan; Hématy, Kian; Wemmer, David E.; Somerville, Chris R.

    2014-01-01

    Mutations in the Arabidopsis COBRA gene lead to defects in cellulose synthesis but the function of COBRA is unknown. Here we present evidence that COBRA localizes to discrete particles in the plasma membrane and is sensitive to inhibitors of cellulose synthesis, suggesting that COBRA and the cellulose synthase complex reside in close proximity on the plasma membrane. Live-cell imaging of cellulose synthesis indicated that, once initiated, cellulose synthesis appeared to proceed normally in the cobra mutant. Using isothermal calorimetry, COBRA was found to bind individual β1–4-linked glucan chains with a KD of 3.2 μm. Competition assays suggests that COBRA binds individual β1–4-linked glucan chains with higher affinity than crystalline cellulose. Solid-state nuclear magnetic resonance studies of the cell wall of the cobra mutant also indicated that, in addition to decreases in cellulose amount, the properties of the cellulose fibrils and other cell wall polymers differed from wild type by being less crystalline and having an increased number of reducing ends. We interpret the available evidence as suggesting that COBRA facilitates cellulose crystallization from the emerging β1–4-glucan chains by acting as a “polysaccharide chaperone.” PMID:25331944

  5. The Arabidopsis COBRA protein facilitates cellulose crystallization at the plasma membrane.

    PubMed

    Sorek, Nadav; Sorek, Hagit; Kijac, Aleksandra; Szemenyei, Heidi J; Bauer, Stefan; Hématy, Kian; Wemmer, David E; Somerville, Chris R

    2014-12-12

    Mutations in the Arabidopsis COBRA gene lead to defects in cellulose synthesis but the function of COBRA is unknown. Here we present evidence that COBRA localizes to discrete particles in the plasma membrane and is sensitive to inhibitors of cellulose synthesis, suggesting that COBRA and the cellulose synthase complex reside in close proximity on the plasma membrane. Live-cell imaging of cellulose synthesis indicated that, once initiated, cellulose synthesis appeared to proceed normally in the cobra mutant. Using isothermal calorimetry, COBRA was found to bind individual β1-4-linked glucan chains with a KD of 3.2 μm. Competition assays suggests that COBRA binds individual β1-4-linked glucan chains with higher affinity than crystalline cellulose. Solid-state nuclear magnetic resonance studies of the cell wall of the cobra mutant also indicated that, in addition to decreases in cellulose amount, the properties of the cellulose fibrils and other cell wall polymers differed from wild type by being less crystalline and having an increased number of reducing ends. We interpret the available evidence as suggesting that COBRA facilitates cellulose crystallization from the emerging β1-4-glucan chains by acting as a "polysaccharide chaperone." PMID:25331944

  6. COBRA-IV PC: A personal computer version of COBRA-IV-I for thermal-hydraulic analysis of rod bundle nuclear fuel elements and cores

    SciTech Connect

    Webb, B.J.

    1988-01-01

    COBRA-IV PC is a modified version of COBRA-IV-I, adapted for use with most IBM PC and PC-compatible desktop computers. Like COBRA-IV-I, COBRA-IV PC uses the subchannel analysis approach to determine the enthalpy and flow distribution in rod bundles for both steady-state and transient conditions. The steady-state and transient solution schemes used in COBRA-IIIC are still available in COBRA-IV PC as the implicit solution scheme option. An explicit solution scheme is also available, allowing the calculation of severe transients involving flow reversals, recirculations, expulsions, and reentry flows, with a pressure or flow boundary condition specified. In addition, several modifications have been incorporated into COBRA-IV PC to allow the code to run on the PC. These include a reduction in the array dimensions, the removal of the dump and restart options, and the inclusion of several code modifications by Oregon State University, most notably, a critical heat flux correlation for boiling water reactor fuel and a new solution scheme for cross-flow distribution calculations. 7 refs., 8 figs., 1 tab.

  7. 26 CFR 54.4980B-6 - Electing COBRA continuation coverage.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 17 2012-04-01 2012-04-01 false Electing COBRA continuation coverage. 54.4980B-6 Section 54.4980B-6 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-6 Electing COBRA continuation coverage. The following...

  8. Developing engineering model Cobra fiber positioners for the Subaru Telescope's prime focus spectrometer

    NASA Astrophysics Data System (ADS)

    Fisher, Charles; Morantz, Chaz; Braun, David; Seiffert, Michael; Aghazarian, Hrand; Partos, Eamon; King, Matthew; Hovland, Larry E.; Schwochert, Mark; Kaluzny, Joel; Capocasale, Christopher; Houck, Andrew; Gross, Johannes; Reiley, Daniel; Mao, Peter; Riddle, Reed; Bui, Khanh; Henderson, David; Haran, Todd; Culhane, Robert; Piazza, Daniele; Walkama, Eric

    2014-07-01

    The Cobra fiber positioner is being developed by the California Institute of Technology (CIT) and the Jet Propulsion Laboratory (JPL) for the Prime Focus Spectrograph (PFS) instrument that will be installed at the Subaru Telescope on Mauna Kea, Hawaii. PFS is a fiber fed multi-object spectrometer that uses an array of Cobra fiber positioners to rapidly reconfigure 2394 optical fibers at the prime focus of the Subaru Telescope that are capable of positioning a fiber to within 5μm of a specified target location. A single Cobra fiber positioner measures 7.7mm in diameter and is 115mm tall. The Cobra fiber positioner uses two piezo-electric rotary motors to move a fiber optic anywhere in a 9.5mm diameter patrol area. In preparation for full-scale production of 2550 Cobra positioners an Engineering Model (EM) version was developed, built and tested to validate the design, reduce manufacturing costs, and improve system reliability. The EM leveraged the previously developed prototype versions of the Cobra fiber positioner. The requirements, design, assembly techniques, development testing, design qualification and performance evaluation of EM Cobra fiber positioners are described here. Also discussed is the use of the EM build and test campaign to validate the plans for full-scale production of 2550 Cobra fiber positioners scheduled to begin in late-2014.

  9. 26 CFR 54.4980B-7 - Duration of COBRA continuation coverage.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Duration of COBRA continuation coverage. 54.4980B-7 Section 54.4980B-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-7 Duration of COBRA continuation coverage. The...

  10. 26 CFR 54.4980B-7 - Duration of COBRA continuation coverage.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 17 2012-04-01 2012-04-01 false Duration of COBRA continuation coverage. 54.4980B-7 Section 54.4980B-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4980B-7 Duration of COBRA continuation coverage. The...

  11. Antihemorrhagin in the blood serum of king cobra (Ophiophagus hannah): purification and characterization.

    PubMed

    Chanhome, Lawan; Khow, Orawan; Omori-Satoh, Tamotsu; Sitprija, Visith

    2003-06-01

    King cobra (Ophiophagus hannah) serum was found to possess antihemorrhagic activity against king cobra hemorrhagin. The activity was stronger than that in commercial king cobra antivenom. An antihemorrhagin has been purified by ion exchange chromatography, affinity chromatography and gel filtration with a 22-fold purification and an overall yield of 12% of the total antihemorrhagic activity contained in crude serum. The purified antihemorrhagin was homogeneous in disc-PAGE and SDS-PAGE. Its apparent molecular weight determined by SDS-PAGE was 120 kDa. The antihemorrhagin was also active against other hemorrhagic snake venoms obtained in Thailand and Japan such as Calloselasma rhodostoma, Trimeresurus albolabris, Trimeresurus macrops and Trimeresurus flavoviridis (Japanese Habu). It inhibited the proteolytic activity of king cobra venom. It is an acid- and thermolabile protein and does not form precipitin lines against king cobra venom. PMID:12875876

  12. Data package addendum for COBRA-1A2 life extension to 400 EFPD

    SciTech Connect

    Hecht, S.L.; Ermi, A.M.

    1994-08-29

    The COBRA-1A experiment was originally designed for irradiations up to 350 effective full power days (EFPD) in EBR-II. Three of the seven B7A test capsules were discharged after 88.6 EFPD (COBRA-1A1; EBR-II designation X516), while the remaining four capsules continued to be irradiated to a goal exposure of 300 EFPD (COBRA-1A2; EBR-II designation X516A). However, it was recently decided that COBRA-1A2 was to remain in the reactor during Run 170, giving and nominal end-of-life (EOL) exposure of 375 EFPD. Since the revised test exposure exceeds the design basis given in supporting analyses, amended analyses are provided herein, giving the technical bases for the extended irradiation. This report describes the safety analysis for the extension of the COBRA-1A2 test (X516A) to 400 effective full power days in FBR-II.

  13. COBRA accelerator for Sandia ICF diode research at Cornell University

    SciTech Connect

    Smith, D.L.; Ingwersen, P.; Bennett, L.F.; Boyes, J.D.; Anderson, D.E.; Greenly, J.B.; Sudan, R.N.

    1995-05-01

    The new COBRA accelerator is being built in stages at the Laboratory of Plasma Studies in Cornell University where its applications will include extraction diode and ion beam research in support of the light ion inertial confinement fusion (ICF) program at Sandia National Laboratories. The 4- to 5-MV, 125- to 250-kA accelerator is based on a four-cavity inductive voltage adder (IVA) design. It is a combination of new ferromagnetically-isolated cavities and self magnetically insulated transmission line (MITL) hardware and components from existing Sandia and Cornell facilities: Marx generator capacitors, hardware, and power supply from the DEMON facility; water pulse forming lines (PFL) and gas switch from the Subsystem Test Facility (STF); a HERMES-III intermediate store capacitor (ISC); and a modified ion diode from Cornell`s LION. The present accelerator consists of a single modified cavity similar to those of the Sandia SABRE accelerator and will be used to establish an operating system for the first stage initial lower voltage testing. Four new cavities will be fabricated and delivered in the first half of FY96 to complete the COBRA accelerator. COBRA is unique in the sense that each cavity is driven by a single pulse forming line, and the IVA output polarity may be reversed by rotating the cavities 180{degrees} about their vertical axis. The site preparations, tank construction, and diode design and development are taking place at Cornell with growing enthusiasm as this machine becomes a reality. Preliminary results with the single cavity and short positive inner cylinder MITL configuration will soon be available.

  14. COBRA accelerator for Sandia ICF diode research at Cornell University

    NASA Astrophysics Data System (ADS)

    Smith, David L.; Ingwersen, Pete; Bennett, Lawrence F.; Boyes, John D.; Anderson, David E.; Greenly, John B.; Sudan, Ravi N.

    The new COBRA accelerator is being built in stages at the Laboratory of Plasma Studies in Cornell University where its applications will include extraction diode and ion beam research in support of the light ion inertial confinement fusion (ICF) program at Sandia National Laboratories. The 4- to 5-MV, 125- to 250-kA accelerator is based on a four-cavity inductive voltage adder (IVA) design. It is a combination of new ferromagnetically-isolated cavities and self magnetically insulated transmission line (MITL) hardware and components from existing Sandia and Cornell facilities: Marx generator capacitors, hardware, and power supply from the DEMON facility; water pulse forming lines (PFL) and gas switch from the Subsystem Test Facility (STF); a HERMES-3 intermediate store capacitor (ISC); and a modified ion diode from Cornell's LION. The present accelerator consists of a single modified cavity similar to those of the Sandia SABRE accelerator and will be used to establish an operating system for the first stage initial lower voltage testing. Four new cavities will be fabricated and delivered in the first half of FY96 to complete the COBRA accelerator. COBRA is unique in the sense that each cavity is driven by a single pulse forming line, and the IVA output polarity may be reversed by rotating the cavities 180(degrees) about their vertical axis. The site preparations, tank construction, and diode design and development are taking place at Cornell with growing enthusiasm as this machine becomes a reality. Preliminary results with the single cavity and short positive inner cylinder MITL configuration will soon be available.

  15. Structural and functional insights into lipid-bound nerve growth factors.

    PubMed

    Tong, Qiong; Wang, Feng; Zhou, Hong-Zhe; Sun, Han-Li; Song, Hui; Shu, Yu-Yan; Gong, Yong; Zhang, Wen-Ting; Cai, Tan-Xi; Yang, Fu-Quan; Tang, Jie; Jiang, Tao

    2012-09-01

    Nerve growth factor (NGF) is a dimeric molecule that modulates the survival, proliferation, and differentiation of nervous cells and is also known to act on cells of the immune system and endocrine system. NGFs extracted from mouse submaxillary gland and cobra venom have different immunological behaviors, yet the underlying mechanism remains unclear. Here we report the crystal structure of the NGF purified from Chinese cobra Naja naja atra (cNGF), which unexpectedly reveals a 2-tailed lipid molecule that is embedded between the two protomers of the NGF homodimer. In addition, crystallographic analysis indicated that the purified mouse NGF(mNGF) is free from lipid but can bind lysophosphatidylserine (lyso-PS) in the same pocket as cNGF. Bioassays indicated that the binding of lipid molecules to cNGF and mNGF are essential for their mast cell activation activity and abates their p75(NTR) binding capacity. Taken together, these results suggest a new mechanism for the regulation of the function of NGF. PMID:22649032

  16. Binding and inhibition studies on lipocortins using phosphatidylcholine vesicles and phospholipase A2 from snake venom, pancreas, and a macrophage-like cell line.

    PubMed

    Davidson, F F; Lister, M D; Dennis, E A

    1990-04-01

    Studies are reported on the inhibition of phospholipase A2 (PLA2) from porcine pancreas, cobra (Naja naja) venom, and the P388D1 macrophage-like cell line by human recombinant lipocortin I and bovine lung calpactin I. Membrane vesicles prepared from 1-stearoyl,2-arachidonoyl phosphatidylcholine (PC) and other PCs were utilized as substrate. Binding studies using sucrose flotation gradients showed that both lipocortin I and calpactin I bind to these vesicles although less tightly than to vesicles prepared from anionic phospholipids or fatty acids. Binding to PC was somewhat enhanced by Ca2+. Inhibition of cobra venom PLA2 was not observed when PC vesicles were used as substrate but was when dipalmitoyl phosphatidylethanolamine was used. Both the pancreatic and macrophage enzymes were inhibited when acting on PC. Interestingly, the inhibition of the macrophage enzyme toward PC depended on the fatty acid attached to the sn-2 position of PC with arachidonate greater than oleate greater than palmitate. Inhibition was also highest at low [PC]; these inhibition results can be explained by the "substrate depletion model" (Davidson, F. F., Dennis, E. A., Powell, M., and Glenney, J. (1987) J. Biol. Chem. 262, 1698-1705). Experimental and theoretical considerations suggest that the in vitro inhibition by lipocortins of this macrophage PLA2 from a cell that makes lipocortin and is active in prostaglandin production is due to effects on substrate availability rather than direct inhibition. PMID:2138608

  17. Status and perspectives of the COBRA double beta decay experiment

    NASA Astrophysics Data System (ADS)

    Kiel, Henning; COBRA Collaboration

    2006-05-01

    The COBRA experiment is going to use a large amount of CdZnTe semiconductor detectors to perform a search for various double beta decay modes. The current status of the experiment is presented, as well as first results. A half-life measurement of the 4-fold forbidden non-unique beta-decay of 113Cd has been performed. Improved half-life limits for the ground state transitions of 64Zn for 0νβ+/EC and 0νEC/EC have been obtained. A short outlook on future activities is given.

  18. Tritium analyses of COBRA-1A2 beryllium pebbles

    SciTech Connect

    Baldwin, D.L.

    1998-03-01

    Selected tritium measurements have been completed for the COBRA-1A2 experiment C03 and D03 beryllium pebbles. The completed results, shown in Tables 1, 2, and 3, include the tritium assay results for the 1-mm and 3-mm C03 pebbles, and the 1-mm D03 pebbles, stepped anneal test results for both types of 1-mm pebbles, and the residual analyses for the stepped-anneal specimens. All results have been reported with date-of-count and are not corrected for decay. Stepped-anneal tritium release response is provided in addenda.

  19. Dermatophilus chelonae in a king cobra (Ophiophagus hannah).

    PubMed

    Wellehan, James F X; Turenne, Christine; Heard, Darryl J; Detrisac, Carol J; O'Kelley, Jeffrey J

    2004-12-01

    A mass was removed from the left flank of a 10-yr-old male king cobra (Ophiophagus hannah), and histologic examination revealed granulomatous dermatitis with intralesional gram-positive cocci and filamentous bacteria. Fourteen months later, a histologically similar subcutaneous mass was removed from a different site. One year later, a large subcutaneous mass at the first surgical site was removed, and histopathologic examination revealed multiloculated granulomas with intralesional gram-positive cocci. An organism was cultured and identified by 16S ribosomal RNA gene sequencing as Dermatophilus chelonae. After a course of antibiotic therapy, no further lesions were seen for 5 mo. PMID:15732601

  20. COBRA System Engineering Processes to Achieve SLI Strategic Goals

    NASA Technical Reports Server (NTRS)

    Ballard, Richard O.

    2003-01-01

    The COBRA Prototype Main Engine Development Project was an endeavor conducted as a joint venture between Pratt & Whitney and Aerojet to conduct risk reduction in LOX/LH2 main engine technology for the NASA Space Launch Initiative (SLI). During the seventeen months of the project (April 2001 to September 2002), approximately seventy reviews were conducted, beginning with the Engine Systems Requirements Review (SRR) and ending with the Engine Systems Interim Design Review (IDR). This paper discusses some of the system engineering practices used to support the reviews and the overall engine development effort.

  1. Study of gas-puff Z-pinches on COBRA

    NASA Astrophysics Data System (ADS)

    Qi, N.; Rosenberg, E. W.; Gourdain, P. A.; de Grouchy, P. W. L.; Kusse, B. R.; Hammer, D. A.; Bell, K. S.; Shelkovenko, T. A.; Potter, W. M.; Atoyan, L.; Cahill, A. D.; Evans, M.; Greenly, J. B.; Hoyt, C. L.; Pikuz, S. A.; Schrafel, P. C.; Kroupp, E.; Fisher, A.; Maron, Y.

    2014-11-01

    Gas-puff Z-pinch experiments were conducted on the 1 MA, 200 ns pulse duration Cornell Beam Research Accelerator (COBRA) pulsed power generator in order to achieve an understanding of the dynamics and instability development in the imploding and stagnating plasma. The triple-nozzle gas-puff valve, pre-ionizer, and load hardware are described. Specific diagnostics for the gas-puff experiments, including a Planar Laser Induced Fluorescence system for measuring the radial neutral density profiles along with a Laser Shearing Interferometer and Laser Wavefront Analyzer for electron density measurements, are also described. The results of a series of experiments using two annular argon (Ar) and/or neon (Ne) gas shells (puff-on-puff) with or without an on- (or near-) axis wire are presented. For all of these experiments, plenum pressures were adjusted to hold the radial mass density profile as similar as possible. Initial implosion stability studies were performed using various combinations of the heavier (Ar) and lighter (Ne) gasses. Implosions with Ne in the outer shell and Ar in the inner were more stable than the opposite arrangement. Current waveforms can be adjusted on COBRA and it was found that the particular shape of the 200 ns current pulse affected on the duration and diameter of the stagnated pinched column and the x-ray yield.

  2. [CO2 Budget and Atmospheric Rectification (COBRA) Over North America

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The purpose of the CO2 Budget and Rectification Airborne (COBRA) study was to assess terrestrial sources and sinks of carbon dioxide using an air-borne study. The study was designed to address the measurement gap between plot-scale direct flux measurements and background hemispheric-scale constraints and to refine techniques for measuring terrestrial fluxes at regional to continental scales. The initial funded effort (reported on here) was to involve two air-borne campaigns over North America, one in summer and one in winter. Measurements for COBRA (given the acronym C02BAR in the initial proposal) were conducted from the University of North Dakota Citation 11, a twin-engine jet aircraft capable of profiling from the surface to 12 km and cruising for up to 4 hours and 175m/s. Onboard instrumentation measured concentrations of CO2, CO, and H2O, and meteorological parameters at high rates. In addition, two separate flask sampling systems collected discrete samples for laboratory analysis of CO2,CO, CH4, N2O, SF6, H2, 13CO2, C18O16O,O2/N2, and Ar/N2. The project involved a collaboration between a number of institutions, including (but not limited to) Harvard, NOAA-CMDL, the University of North Dakota, and Scripps.

  3. Study of gas-puff Z-pinches on COBRA

    SciTech Connect

    Qi, N.; Rosenberg, E. W.; Gourdain, P. A.; Grouchy, P. W. L. de; Kusse, B. R.; Hammer, D. A.; Bell, K. S.; Shelkovenko, T. A.; Potter, W. M.; Atoyan, L.; Cahill, A. D.; Evans, M.; Greenly, J. B.; Hoyt, C. L.; Pikuz, S. A.; Schrafel, P. C.; Kroupp, E.; Fisher, A.; Maron, Y.

    2014-11-15

    Gas-puff Z-pinch experiments were conducted on the 1 MA, 200 ns pulse duration Cornell Beam Research Accelerator (COBRA) pulsed power generator in order to achieve an understanding of the dynamics and instability development in the imploding and stagnating plasma. The triple-nozzle gas-puff valve, pre-ionizer, and load hardware are described. Specific diagnostics for the gas-puff experiments, including a Planar Laser Induced Fluorescence system for measuring the radial neutral density profiles along with a Laser Shearing Interferometer and Laser Wavefront Analyzer for electron density measurements, are also described. The results of a series of experiments using two annular argon (Ar) and/or neon (Ne) gas shells (puff-on-puff) with or without an on- (or near-) axis wire are presented. For all of these experiments, plenum pressures were adjusted to hold the radial mass density profile as similar as possible. Initial implosion stability studies were performed using various combinations of the heavier (Ar) and lighter (Ne) gasses. Implosions with Ne in the outer shell and Ar in the inner were more stable than the opposite arrangement. Current waveforms can be adjusted on COBRA and it was found that the particular shape of the 200 ns current pulse affected on the duration and diameter of the stagnated pinched column and the x-ray yield.

  4. Radiative Properties of Argon Gas-Puff Implosions on COBRA

    NASA Astrophysics Data System (ADS)

    Ouart, Nicholas; Qi, Niansheng; de Grouchy, Phil; Shelkovenko, Tatiana; Pikuz, Sergei; Giuliani, John; Dasgupta, Arati; Apruzese, John; Clark, Robert; Hammer, David; Kusse, Bruce

    2015-11-01

    Gas-puff Z-pinch experiments were performed on the 1 MA COBRA pulsed power generator at Cornell University. The gas puffs were injected into the load region from a triple nozzle. The load region had an anode-cathode gap of 2.5 cm. The standard diagnostics on COBRA include time-integrated pinhole cameras, a time-integrated axially resolved x-ray spectrometer, filtered photo-conducting detectors, and time-gated XUV cameras. We will focus mainly on results from pinhole images and x-ray spectra from argon gas puffs including some with a SO2 dopant. The x-ray time-integrated pinhole images feature a tight axially uniform plasma column with a diameter of approximately 1 mm for argon gas implosion. The x-ray spectrometer used mica crystals (2d =19.84 Å) and captured the argon K-shell radiation from different crystal reflections. A 1-D multi-zone argon and sulfur non-LTE kinetics code with radiation transport is used to model the K-shell emission for the purpose of inferring the plasma conditions and the interaction of gas from the inner annulus with the central jet. This work is supported by DOE/NNSA.

  5. Generation and characterization of transgenic mice expressing cobra venom factor.

    PubMed

    Andrä, Jörg; Halter, Roman; Kock, Michael A; Niemann, Heiner; Vogel, Carl-Wilhelm; Paul, Dieter

    2002-10-01

    Cobra venom factor (CVF), the anticomplementary protein in cobra venom, activates the alternative complement pathway, eventually leading to complement consumption. Here, we describe the development of a transgenic mouse model for CVF. We generated a DNA construct containing the full-length cDNA for single-chain pre-pro-CVF. Expression of CVF was controlled by the alpha(1)-antitrypsin promoter to achieve liver-specific expression. Linearized DNA was microinjected into murine ovary cells (strain CD(2)F(1) (BALB/cxDBA/2J)) and the newborn mice were analyzed for stable integration of CVF DNA. After establishing the transgene, mice were propagated in a BALB/c background. The CVF mRNA was detected in the liver and, in some animals, in the kidney. CVF protein was detected in small amounts in the serum. Serum complement hemolytic activity in CVF-transgenic mice was virtually absent. The concentration of plasma C3 was significantly reduced. The CVF-transgenic animals show no unusual phenotype. They provide an animal model to study the effect of long-term complement depletion by continued activation, as well as the role of complement in host immune response and pathogenesis of disease. PMID:12220893

  6. Humanized cobra venom factor decreases myocardial ischemia reperfusion injury

    PubMed Central

    Gorsuch, W. Brian; Guikema, Benjamin J.; Fritzinger, David C.; Vogel, Carl-Wilhelm; Stahl, Gregory L.

    2009-01-01

    Cobra venom factor (CVF) is a complement activating protein in cobra venom, which functionally resembles C3b, and has been used for decades for decomplementation of serum to investigate the role of complement in many model systems of disease. The use of CVF for clinical practice is considered impractical because of immunogenicity issues. Humanization of CVF was recently demonstrated to yield a potent CVF-like molecule. In the present study, we demonstrate that mice treated with recombinant humanized CVF (HC3-1496) are protected from myocardial ischemia-reperfusion (MI/R) injuries with resultant preservation of cardiac function. Also, C3 deposition in the myocardium following MI/R was not observed following treatment with HC3-1496. HC3-1496 led to complement activation and depletion of C3, but preserved C5 titers. These data suggest, unlike CVF, HC3-1496 does not form a C5 convertase in the mouse, similar to recent studies in human sera/plasma. These results suggest that humanized CVF (HC3-1496) protects the ischemic myocardium from reperfusion injuries induced by complement activation and represents a novel anti-complement therapy for potential clinical use. PMID:19747734

  7. A fatal cobra-bite in a snake expert.

    PubMed

    Hossain, M Z; Atiqullah, S; Saha, A C; Chowdhury, A J; Jahangir, K M; Faiz, M A

    2010-04-01

    A 35-year-old so called snake-expert from Thakurgaon district was admitted in Medicine department of Rangpur Medical College Hospital (RpMCH), Rangpur, Bangladesh on 2nd November 2007 with history of bites by a cobra snake. He was famous for his outstanding works to establish a snake farm first ever in Bangladesh. He had a collection of more than one hundred snakes of different species. He used to hatch eggs of the snakes, feed the young-snakes, collect venoms and sell those. Everyday many visitors used to visit his farm to watch exciting games with poisonous snakes. Several satellite television (TV) channels and some daily newspapers had covered him on different occasions. He was accidentally bitten by a newly caught hungry cobra snake while recording for a satellite TV channel. Following bites he was brought to the hospital three and a half hours later. By that time, neurotoxicity developed. Repeated doses of Anti Snake Venom (ASV) along with respiratory support and other supportive cares were provided. Despite utmost care feasible at RpMCH, patient expired around 49 hours later. PMID:20395931

  8. COBRA-SFS CYCLE 3. Thermal Hydraulic Analysis of Spent Fuel Casks

    SciTech Connect

    Rector, D.R.; Cuta, J.M.; Enderlin, C.W.

    1995-09-01

    COBRA-SFS (Spent Fuel Storage) is a code for thermal-hydraulic analysis of multi-assembly spent fuel storage and transportation systems. It uses a lumped parameter finite difference approach to predict flow and temperature distributions in spent fuel storage systems and fuel assemblies, under forced and natural convection heat transfer conditions. Derived from the COBRA family of codes, which have been extensively evaluated against in-pile and out-of-pile data, COBRA-SFS retains all the important features of the COBRA codes for single phase fluid analysis, and extends the range application to include problems with two-dimensional radiative and three-dimensional conductive heat transfer. COBRA-SFS has been used to analyze various single- and multi-assembly spent fuel storage systems containing unconsolidated and consolidated fuel rods, with a variety of fill media, including air, helium and vacuum. Cycle 0 of COBRA-SFS was released in 1986. Subsequent applications of the code led to development of additional capabilities, which resulted in the release of Cycle 1 in February 1989. Since then, the code has undergone an independent technical review as part of a submittal to the Nuclear Regulatory Commission for a generic license to apply the code to spent fuel storage system analysis. Modifications and improvements to the code have been combined to form Cycle 2. Cycle 3., the newest version of COBRA-SFS, has been validated and verified for transient applications, such as a storage cask thermal response to a pool fire.

  9. Synchronization and an application of a novel fractional order King Cobra chaotic system.

    PubMed

    Muthukumar, P; Balasubramaniam, P; Ratnavelu, K

    2014-09-01

    In this paper, we design a new three dimensional King Cobra face shaped fractional order chaotic system. The multi-scale synchronization scheme of two fractional order chaotic systems is described. The necessary conditions for the multi-scale synchronization of two identical fractional order King Cobra chaotic systems are derived through feedback control. A new cryptosystem is proposed for an image encryption and decryption by using synchronized fractional order King Cobra chaotic systems with the supports of multiple cryptographic assumptions. The security of the proposed cryptosystem is analyzed by the well known algebraic attacks. Numerical simulations are given to show the effectiveness of the proposed theoretical results. PMID:25273185

  10. Synchronization and an application of a novel fractional order King Cobra chaotic system

    SciTech Connect

    Muthukumar, P. Balasubramaniam, P.; Ratnavelu, K.

    2014-09-01

    In this paper, we design a new three dimensional King Cobra face shaped fractional order chaotic system. The multi-scale synchronization scheme of two fractional order chaotic systems is described. The necessary conditions for the multi-scale synchronization of two identical fractional order King Cobra chaotic systems are derived through feedback control. A new cryptosystem is proposed for an image encryption and decryption by using synchronized fractional order King Cobra chaotic systems with the supports of multiple cryptographic assumptions. The security of the proposed cryptosystem is analyzed by the well known algebraic attacks. Numerical simulations are given to show the effectiveness of the proposed theoretical results.

  11. First molecular characterization of enteric protozoa and the human pathogenic microsporidian, Enterocytozoon bieneusi, in captive snakes in China.

    PubMed

    Karim, Md Robiul; Yu, Fuchang; Li, Jian; Li, Junqiang; Zhang, Longxian; Wang, Rongjun; Rume, Farzana Islam; Jian, Fuchun; Zhang, Sumei; Ning, Changshen

    2014-08-01

    Enteric protozoa are frequently found in snakes. Nevertheless, few studies regarding genetic characterization of these parasites have been carried out. We describe here the first molecular survey of protozoan pathogens from snakes in China and the first report on Enterocytozoon bieneusi genotyping in snakes in the world. Here, 240 fecal specimens were collected from two species of captive snakes, Naja naja (Indian cobra) and Ptyas mucosus (Oriental rat snake), in Guangxi Province, China, and examined by PCR amplification of the small subunit-ribosomal RNA of enteric protozoa and the internal transcribed spacer of ribosomal RNA of E. bieneusi. Cryptosporidium serpentis was identified in three specimens (2.1%) of Oriental rat snakes. Caryospora was found in 5.4% specimens, including eight from cobras (8.1%) and five from rat snakes (3.6%), and represented six new species-Caryospora sp. SKC-2014a to Caryospora sp. SKC-2014 f. Three new Eimeria species, Eimeria sp. SKE-2014a to Eimeria sp. SKE-2014c, were detected in three specimens (2.1%) from rat snakes. Additionally, Sarcocystis sp. SKS-2014 was detected in one specimen from a cobra. The infection rates of E. bieneusi were 3.0% in cobras and 5.7% in rat snakes. Sequence analysis of 11 PCR products revealed the presence of six E. bieneusi genotypes-two known genotypes (type IV and Henan V) and four new genotypes (CRep-1 to CRep-4). All six E. bieneusi genotypes belonged to the zoonotic group (group 1). This result raised the possibility that E. bieneusi could be present in animals consumed by snakes. This should be taken into consideration to better understand the diversity of the parasite, its transmission through the predator-prey relationship, and public health implications. PMID:24906991

  12. Parallel X pinches on the 1 MA COBRA pulser

    NASA Astrophysics Data System (ADS)

    Pikuz, S. A.; Shelkovenko, T. A.; Knapp, P. F.; Hoyt, C. L.; Greenly, J. B.; Wilhelm, H.; Hammer, D. A.

    2009-11-01

    Two standard and nested X pinches have been tested in parallel as the load on the 1MA, 100 ns risetime COBRA pulsed power generator at Cornell University. The spatial, temporal, and spectral parameters of the X pinches were studied using laser-based imaging, time gated XUV-sensitive cameras, a slit-step-wedge and pinhole cameras, X-ray spectroscopy and x-ray radiography. The latter includes testing a new method of point-projection quasi-monochromatic radiography. Electrical cross-talk of the X pinches was studied using very small B-dot probes placed in the space between X-pinches. The experiments show that the parallel nested x-pinches produce smaller, brighter and more stable x-ray source points than the standard configuration.

  13. The COBRA demonstrator at the LNGS underground laboratory

    NASA Astrophysics Data System (ADS)

    Ebert, J.; Fritts, M.; Gehre, D.; Gößling, C.; Göpfert, T.; Hagner, C.; Heidrich, N.; Klingenberg, R.; Köttig, T.; Kröninger, K.; Michel, T.; Neddermann, T.; Nitsch, C.; Oldorf, C.; Quante, T.; Rajek, S.; Rebber, H.; Reinecke, O.; Rohatsch, K.; Schulz, O.; Sörensen, A.; Stekl, I.; Tebrügge, J.; Temminghoff, R.; Theinert, R.; Timm, J.; Wester, T.; Wonsak, B.; Zatschler, S.; Zuber, K.

    2016-01-01

    The COBRA demonstrator, a prototype for a large-scale experiment searching for neutrinoless double beta-decay, was built at the underground laboratory Laboratori Nazionali del Gran Sasso (LNGS) in Italy. It consists of an array of 64 monolithic, calorimetric CdZnTe semiconductor detectors with a coplanar-grid design and a total mass of 380 g. It is used to investigate the experimental challenges faced when operating CdZnTe detectors in low-background mode, to identify potential background sources and to show the long-term stability of the detectors. The first data-taking period started in 2011 with a subset of the detectors, while the demonstrator was completed in November 2013. To date, more than 250 kg d of data have been collected. This paper describes the technical details of the experimental setup and the hardware components.

  14. COBRA-SFS modifications and cask model optimization

    SciTech Connect

    Rector, D.R.; Michener, T.E.

    1989-01-01

    Spent-fuel storage systems are complex systems and developing a computational model for one can be a difficult task. The COBRA-SFS computer code provides many capabilities for modeling the details of these systems, but these capabilities can also allow users to specify a more complex model than necessary. This report provides important guidance to users that dramatically reduces the size of the model while maintaining the accuracy of the calculation. A series of model optimization studies was performed, based on the TN-24P spent-fuel storage cask, to determine the optimal model geometry. Expanded modeling capabilities of the code are also described. These include adding fluid shear stress terms and a detailed plenum model. The mathematical models for each code modification are described, along with the associated verification results. 22 refs., 107 figs., 7 tabs.

  15. Multiwire X Pinches on the COBRA Pulsed Power Generator

    SciTech Connect

    Shelkovenko, Tatiana A.; Pikuz, Sergey A.; Douglass, Jonathan D.; McBride, Ryan D.; Hammer, David A.

    2006-01-05

    The rebuilt COBRA pulsed power generator, which has a variable current pulse waveform and amplitude (90-150 ns rise time, 0.6 - 1 MA) has extended the range of current pulse parameters that can be used to study X pinches. X pinches with 2 to 12 wires with diameters from 25 to 75 {mu}m of several different wire materials (from Al to W) have been studied. The influence of different current shapes on X pinch plasma formation and pinch implosion dynamics has been studied using a set of diagnostics with spatial and/or temporal resolution. Multiwire X pinches were placed in the diode center and/or two four wire X pinches were places in one of four parallel return current circuits of the diode. Radiographic images of different test objects, wires in the array and the X pinches, themselves, were obtained with {mu}m scale spatial resolution.

  16. Use of Cobra Lily (Darlingtonia californica) & Drosophila for Investigating Predator-Prey Relationships.

    ERIC Educational Resources Information Center

    Pratt, Carl R.

    1994-01-01

    Describes an experiment that uses the cobra lily (Darlingtonia californica) and fruit flies (Drosophila virilis) to investigate predator-prey relationships in a classroom laboratory. Suggestions for classroom extension of this experimental system are provided. (ZWH)

  17. COBRA/TRAC analysis of the PKL reflood test K9. [PWR

    SciTech Connect

    Wilkins, C.A.; Thurgood, M.J.

    1982-08-01

    Experiments at the Primaerkreislaeufe (PKL) test facility in Erlangen, Germany, simulated the refill and reflood procedure after a loss-of-coolant accident (LOCA) in the primary coolant system of a 1300-MW pressurized water reactor (PWR). COBRA/TRAC, a thermal-hydraulics analysis code developed at the Pacific Northwest Laboratory, was used to model experiment K9 of the PKL test series (completed December 1979). The COBRA/TRAC code, which utilizes COBRA-TF as the vessel module and TRAC-P1A for the remaining components, was designed to analyze LOCAs in PWRs. PKL-K9 was characterized by a double-ended guillotine break in the cold leg with emergency core cooling water injected into the cold legs. COBRA/TRAC was able to successfully predict lower-core temperature profiles and quench times, upper-core temperature profiles until the quench, upper plenum and break pressures, and correct trends in collapsed water levels.

  18. 26 CFR 54.4980B-6 - Electing COBRA continuation coverage.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... a divorce or legal separation of a covered employee. The group health plan is not required to offer... election period. Revocation of the waiver is an election of COBRA continuation coverage. However, if...

  19. COBRA-SFS CYCLE 3: Code System for Thermal Hydraulic Analysis of Spent Fuel Casks

    Energy Science and Technology Software Center (ESTSC)

    2003-11-01

    COBRA-SFS (Spent Fuel Storage) is a code for thermal-hydraulic analysis of multi-assembly spent fuel storage and transportation systems. It uses a lumped parameter finite difference approach to predict flow and temperature distributions in spent fuel storage systems and fuel assemblies, under forced and natural convection heat transfer conditions. Derived from the COBRA family of codes, which have been extensively evaluated against in-pile and out-of-pile data, COBRA-SFS retains all the important features of the COBRA codesmore » for single phase fluid analysis and extends the range application to include problems with two-dimensional radiative and three-dimensional conductive heat transfer. COBRA-SFS has been used to analyze various single- and multi-assembly spent fuel storage systems containing unconsolidated and consolidated fuel rods, with a variety of fill media, including air, helium and vacuum. Cycle 0 of COBRA-SFS was released in 1986. Subsequent applications of the code led to development of additional capabilities, which resulted in the release of Cycle 1 in February 1989. Since then, the code has undergone an independent technical review as part of a submittal to the Nuclear Regulatory Commission for a generic license to apply the code to spent fuel storage system analysis. Modifications and improvements to the code have been combined to form Cycle 2. Cycle 3., the newest version of COBRA-SFS, has been validated and verified for transient applications, such as a storage cask thermal response to a pool fire.« less

  20. Wire Array Dynamics with Varied Current Risetime on COBRA

    NASA Astrophysics Data System (ADS)

    Greenly, John; Chandler, Katherine; Chalenski, David; Douglass, Jon; Hammer, David; Kusse, Bruce; Pikuz, Sergei; McBride, Ryan; Shelkovenko, Tatiana

    2006-10-01

    The 1 MA COBRA accelerator is used to drive wire array loads with current risetimes from 95 to 220 ns. The dynamics of 8 x 12 micron Al arrays show a clearly different character when driven by the fast and slow current pulses. The fast (˜100 ns, 1 MA) drive produces a hot pinch, high total x-ray energy in a long-duration, slowly rising x-ray pulse, multiple hot spots in the pinch, a relatively small load voltage that stays up after x-ray peak, and a large inferred current radius at x-ray peak. In contrast, the slow (˜200 ns, 900 kA drive) produces a cooler pinch with lower total x-ray energy in a short, fast-rising x-ray pulse, absence of hot spots but clear evidence of high-energy ``electron beam,'' large load voltage that drops fast after x-ray peak, and small inferred current radius at x-ray peak. The diagnostic evidence of these characteristics especially x-ray imaging and spectral information, will be presented and the dynamics underlying these phenomena will be discussed.

  1. Instability studies in radial foil configurations on the COBRA generator

    NASA Astrophysics Data System (ADS)

    Gourdain, P.-A.; Greenly, J. B.; Hammer, D. A.; Knapp, P. F.; Kusse, B. R.; Pikuz, S. A.; Schrafel, P. C.; Shelkovenko, T. C.

    2010-11-01

    Radial foil configurations prove to be a very simple experimental set up to study high energy density plasmas. A 5-micron thin metallic foil lies flat over a stretcher which is connected to the anode of a pulsed power generator such as COBRA (1MA, 100 ns current rise time). The cathode contacts the foil at its geometrical center using a hollow stainless steel pin. As the foil ablates, JxB forces lift the foil leading to the formation a plasma bubble surrounding a central plasma column, which is a z-pinch. Force densities on this column should increase considerably as the initial pin diameter is diminished and we expect plasma properties to change accordingly. Based only on pin diameter considerations, radial foil explosions could produce magnetic pressures ranging from 160 kbar (for 2-mm pins) to 2.5 Mbar (for 0.5-mm pins). However, as the cathode diameter diminishes, instabilities appear earlier in the discharge, preventing the z-pinch implosion to occur at maximum current, de facto limiting plasma parameters. We investigate the cause of these instabilities, the possible means to reduce plasma instabilities and to improve plasma performances.

  2. Performance Evaluation of the COBRA GEM for the Application of the TPC

    NASA Astrophysics Data System (ADS)

    Terasaki, Kohei; Hamagaki, Hideki; Gunji, Taku; Yamaguchi, Yorito

    2014-09-01

    Suppression of the back-drifting ions from avalanche region to drift space (IBF: Ion Backflow) is the key for a Time Projection Chamber (TPC) since IBF easily distorts the drift field. To suppress IBF, Gating Grid system is widely used for the TPC but this limits the data taking rate. Gas Electron Multiplier (GEM) has advantages in the reduction of IBF and high rate capability. By adopting GEM, it is possible to run a TPC continuously under high rate and high multiplicity conditions. Motivated by the study of IBF reduction for RICH with Thick COBRA, which has been developed by F. A. Amero et al., we developed COBRA GEMs for the application of a TPC. With a stack configuration, IBF reaches about 0.1 ~ 0.5%, which is ×5--10 better IBF than the standard GEMs. However, the measured energy resolution with COBRA is 20% (σ) and this is much worse than the resolution with standard GEMs. Measurement of long-time stability of gain indicates that gain of COBRA varies significantly due to charging up effect. Simulation studies based on Garfield++ are performed for understanding quantitatively the reasons of worse energy resolution and instability of gain. In this presentation, we will report the simulation studies together with the measured performance of the COBRA GEM.

  3. The dependence receptor TrkC triggers mitochondria-dependent apoptosis upon Cobra-1 recruitment.

    PubMed

    Ichim, Gabriel; Genevois, Anne-Laure; Ménard, Marie; Yu, Li-Ying; Coelho-Aguiar, Juliana M; Llambi, Fabien; Jarrosson-Wuilleme, Loraine; Lefebvre, Jonathan; Tulasne, David; Dupin, Elisabeth; Le Douarin, Nicole; Arumäe, Urmas; Tauszig-Delamasure, Servane; Mehlen, Patrick

    2013-09-12

    The neurotrophin receptor TrkC was recently identified as a dependence receptor, and, as such, it triggers apoptosis in the absence of its ligand, NT-3. The molecular mechanism for apoptotic engagement involves the double cleavage of the receptor's intracellular domain, leading to the formation of a proapoptotic "killer" fragment (TrkC KF). Here, we show that TrkC KF interacts with Cobra1, a putative cofactor of BRCA1, and that Cobra1 is required for TrkC-induced apoptosis. We also show that, in the developing chick neural tube, NT-3 silencing is associated with neuroepithelial cell death that is rescued by Cobra1 silencing. Cobra1 shuttles TrkC KF to the mitochondria, where it promotes Bax activation, cytochrome c release, and apoptosome-dependent apoptosis. Thus, we propose that, in the absence of NT-3, the proteolytic cleavage of TrkC leads to the release of a killer fragment that triggers mitochondria-dependent apoptosis via the recruitment of Cobra1. PMID:24034695

  4. Identification of MEDIATOR16 as the Arabidopsis COBRA suppressor MONGOOSE1

    PubMed Central

    Sorek, Nadav; Szemenyei, Heidi; Sorek, Hagit; Landers, Abigail; Knight, Heather; Bauer, Stefan; Wemmer, David E.; Somerville, Chris R.

    2015-01-01

    We performed a screen for genetic suppressors of cobra, an Arabidopsis mutant with defects in cellulose formation and an increased ratio of unesterified/esterified pectin. We identified a suppressor named mongoose1 (mon1) that suppressed the growth defects of cobra, partially restored cellulose levels, and restored the esterification ratio of pectin to wild-type levels. mon1 was mapped to the MEDIATOR16 (MED16) locus, a tail mediator subunit, also known as SENSITIVE TO FREEZING6 (SFR6). When separated from the cobra mutation, mutations in MED16 caused resistance to cellulose biosynthesis inhibitors, consistent with their ability to suppress the cobra cellulose deficiency. Transcriptome analysis revealed that a number of cell wall genes are misregulated in med16 mutants. Two of these genes encode pectin methylesterase inhibitors, which, when ectopically expressed, partially suppressed the cobra phenotype. This suggests that cellulose biosynthesis can be affected by the esterification levels of pectin, possibly through modifying cell wall integrity or the interaction of pectin and cellulose. PMID:26655738

  5. Effect of cyclosporine, total lymphoid irradiation, and cobra venom factor on hyperacute rejection

    SciTech Connect

    Knechtle, S.J.; Halperin, E.C.; Murphy, C.E.; Saad, T.; Abernethy, K.; Miller, D.; Bollinger, R.R.

    1985-09-01

    Transplantation into sensitized recipients is contraindicated due to the potential for hyperacute rejection. In order to study the mechanism of hyperacute rejection and the role of immunosuppression in the face of presensitization, we evaluated the effect of total lymphoid irradiation, cyclosporine, and cobra venom factor, alone and in combination, on hyperacute rejection of heterotopic rat heart allografts. Lewis rats were sensitized to strongly RT-1-incompatible ACI rats by three successive skin grafts. Heart allografts were then performed, and survived for a mean period of 15.7 +/- 7.4 hours. Neither preoperative treatment of hypersensitized rats with total lymphoid irradiation alone nor with cyclosporine (5 mg/kg/day) resulted in a prolongation of survival (20.4 +/- 16.6 hours and 35.6 +/- 6.2 hours, respectively). However, complement depletion using cobra venom factor significantly prolonged mean graft survival time to 114.4 +/- 31.0 hours (p less than 0.05). Cyclosporine (10 mg/kg/day) also significantly prolonged survival to 149 +/- 29 hours (p less than 0.01), but did not lower the antibody or complement levels. The addition of total lymphoid irradiation or cyclosporine to treatment with cobra venom factor did not result in longer survival than cobra venom factor alone. In conclusion, cobra venom factor and cyclosporine delay but do not prevent hyperacute rejection, while total lymphoid irradiation has no observable effect on hyperacute rejection.

  6. Identification of MEDIATOR16 as the Arabidopsis COBRA suppressor MONGOOSE1.

    PubMed

    Sorek, Nadav; Szemenyei, Heidi; Sorek, Hagit; Landers, Abigail; Knight, Heather; Bauer, Stefan; Wemmer, David E; Somerville, Chris R

    2015-12-29

    We performed a screen for genetic suppressors of cobra, an Arabidopsis mutant with defects in cellulose formation and an increased ratio of unesterified/esterified pectin. We identified a suppressor named mongoose1 (mon1) that suppressed the growth defects of cobra, partially restored cellulose levels, and restored the esterification ratio of pectin to wild-type levels. mon1 was mapped to the MEDIATOR16 (MED16) locus, a tail mediator subunit, also known as SENSITIVE TO FREEZING6 (SFR6). When separated from the cobra mutation, mutations in MED16 caused resistance to cellulose biosynthesis inhibitors, consistent with their ability to suppress the cobra cellulose deficiency. Transcriptome analysis revealed that a number of cell wall genes are misregulated in med16 mutants. Two of these genes encode pectin methylesterase inhibitors, which, when ectopically expressed, partially suppressed the cobra phenotype. This suggests that cellulose biosynthesis can be affected by the esterification levels of pectin, possibly through modifying cell wall integrity or the interaction of pectin and cellulose. PMID:26655738

  7. Treatment of the first known case of king cobra envenomation in the United Kingdom, complicated by severe anaphylaxis.

    PubMed

    Veto, T; Price, R; Silsby, J F; Carter, J A

    2007-01-01

    We report the first known case of envenomation following snake bite by a king cobra in the UK. The patient required tracheal intubation and ventilation. Treatment with king cobra antivenom resulted in anaphylaxis (bronchospasm and hypotension), requiring adrenaline infusion. The patient's trachea was extubated 11 h after administration of antivenom. PMID:17156231

  8. Use of Molecular Diagnostic Tools for the Identification of Species Responsible for Snakebite in Nepal: A Pilot Study

    PubMed Central

    Sharma, Sanjib Kumar; Kuch, Ulrich; Höde, Patrick; Bruhse, Laura; Pandey, Deb P.; Ghimire, Anup; Chappuis, François; Alirol, Emilie

    2016-01-01

    Snakebite is an important medical emergency in rural Nepal. Correct identification of the biting species is crucial for clinicians to choose appropriate treatment and anticipate complications. This is particularly important for neurotoxic envenoming which, depending on the snake species involved, may not respond to available antivenoms. Adequate species identification tools are lacking. This study used a combination of morphological and molecular approaches (PCR-aided DNA sequencing from swabs of bite sites) to determine the contribution of venomous and non-venomous species to the snakebite burden in southern Nepal. Out of 749 patients admitted with a history of snakebite to one of three study centres, the biting species could be identified in 194 (25.9%). Out of these, 87 had been bitten by a venomous snake, most commonly the Indian spectacled cobra (Naja naja; n = 42) and the common krait (Bungarus caeruleus; n = 22). When both morphological identification and PCR/sequencing results were available, a 100% agreement was noted. The probability of a positive PCR result was significantly lower among patients who had used inadequate “first aid” measures (e.g. tourniquets or local application of remedies). This study is the first to report the use of forensic genetics methods for snake species identification in a prospective clinical study. If high diagnostic accuracy is confirmed in larger cohorts, this method will be a very useful reference diagnostic tool for epidemiological investigations and clinical studies. PMID:27105074

  9. Snakes of medical importance in India: is the concept of the "Big 4" still relevant and useful?

    PubMed

    Simpson, Ian D; Norris, Robert L

    2007-01-01

    Snakebites continue to be a major medical concern in India. However, there is very little hard evidence of a numerical nature to enable us to understand which species are responsible for mortality and morbidity. For many decades, the concept of the "Big 4" Snakes of Medical Importance has reflected the view that 4 species are responsible for Indian snakebite mortality--the Indian cobra (Naja naja), the common krait (Bungarus caeruleus), the Russell's viper (Daboia russelii) and the saw-scaled viper (Echis carinatus). However, a recent discovery that another species, the hump-nosed pit viper (Hypnale hypnale), is capable of causing lethal envenomation, and that this problem was being concealed by systematic misidentification of this species as the saw-scaled viper, has necessitated a review of the concept of the "Big 4." The concept of the "Big 4" snakes is reviewed to demonstrate its failure to include all currently known snakes of medical significance in India, and its negative effects related to clinical management of snakebite. The emergence of the hump-nosed pit viper (Hypnale hypnale) as a snake of medical significance has rendered the "Big 4" obsolete in terms of completeness. The concept of the "Big 4" is restricting sound epidemiological work and the development of effective snake antivenoms. It should be replaced by the model introduced in the 1980s by the World Health Organization, which has not received adequate circulation and implementation. PMID:17447706

  10. Carbonothioate phospholipids as substrate for a spectrophotometric assay of phospholipase A2.

    PubMed

    Yu, L; Ternansky, R J; Crisologo, J F; Chang, J; Baker, B L; Coutts, S M

    1998-12-01

    A continuous spectrophotometric assay for phospholipase A2 (PLA2) was developed using novel carbonothioate phospholipids. These phospholipid analogues contain a carbonothioate bond in the place of the sn-2 ester of the natural substrates of phospholipase A2 and were synthesized in a one-pot two-step reaction. Phospholipase A2 from cobra venom (Naja naja atra) hydrolyzes carbonothioate phospholipids and liberates a free thiol, alkylmercaptan, which is reacted with 5,5'-dithiobis(2-nitrobenzoic acid) to yield a product that absorbs at 412 nm. The kinetic studies on PLA2 hydrolysis of carbonothioate phospholipids were carried out in pure phospholipid forms and in Triton X-100 mixed micelles. The hydrolysis of pure carbonothioate phospholipids exhibits an interfacial activation phenomenon. The hydrolysis of phospholipid in mixed Triton X-100 micelles follows classical Michaelis-Menten kinetics. In a mixed micellar system, the catalytic efficiency observed with this series of substrates is two orders of magnitude lower than that of the hydrolysis of the natural substrate dipalmitoyl phosphocholine. However, these substrates bind to the enzyme over 10 times tighter than does the natural substrate. Application of this carbonothioate assay to screen both reversible and irreversible enzyme inhibitors of phospholipase A2 is also demonstrated. PMID:9866705

  11. Prey transport in "palatine-erecting" elapid snakes.

    PubMed

    Deufel, Alexandra; Cundall, David

    2003-12-01

    Cobras and mambas are members of a group of elapid snakes supposedly united by the morphology and inferred behavior of their palatine bone during prey transport (palatine erectors). The palatine erectors investigated (Dendroaspis polylepis, Naja pallida, Ophiophagus hannah, Aspidelaps scutatus, A. lubricus) show differences in the morphology of their feeding apparatus that do not affect the overall behavior of the system. We delineated the structures directly involved in producing palatine erection during prey transport. Palatine erection can be achieved by a colubroid muscle contraction pattern acting on a palato-pterygoid bar with a movable palato-pterygoid joint and a palatine that is stabilized against the snout. The palatine characters originally proposed to cause palatine erection are not required to produce the behavior and actually impede it in Naja pallida. Palatine-erecting elapids share a fundamental design of the palato-maxillary apparatus with all higher snakes. A set of plesiomorphic core characters is functionally integrated to function in prey transport using the pterygoid walk. Variant characters are either part of a structural periphery unrelated to the core structures that define function or patterns of variation are subordinate character sets operating within functional thresholds of a single system. PMID:14584037

  12. Cardiotoxin III Inhibits Proliferation and Migration of Oral Cancer Cells through MAPK and MMP Signaling

    PubMed Central

    Yen, Ching-Yu; Liang, Shih-Shin; Han, Lo-Yi; Chou, Han-Lin; Chou, Chon-Kit; Lin, Shinne-Ren

    2013-01-01

    Cardiotoxin III (CTXIII), isolated from the snake venom of Formosan cobra Naja naja atra, has previously been found to induce apoptosis in many types of cancer. Early metastasis is typical for the progression of oral cancer. To modulate the cell migration behavior of oral cancer is one of the oral cancer therapies. In this study, the possible modulating effect of CTXIII on oral cancer migration is addressed. In the example of oral squamous carcinoma Ca9-22 cells, the cell viability was decreased by CTXIII treatment in a dose-responsive manner. In wound-healing assay, the cell migration of Ca9-22 cells was attenuated by CTXIII in a dose- and time-responsive manner. After CTXIII treatment, the MMP-2 and MMP-9 protein expressions were downregulated, and the phosphorylation of JNK and p38-MAPK was increased independent of ERK phosphorylation. In conclusion, CTXIII has antiproliferative and -migrating effects on oral cancer cells involving the p38-MAPK and MMP-2/-9 pathways. PMID:23710144

  13. Use of Molecular Diagnostic Tools for the Identification of Species Responsible for Snakebite in Nepal: A Pilot Study.

    PubMed

    Sharma, Sanjib Kumar; Kuch, Ulrich; Höde, Patrick; Bruhse, Laura; Pandey, Deb P; Ghimire, Anup; Chappuis, François; Alirol, Emilie

    2016-04-01

    Snakebite is an important medical emergency in rural Nepal. Correct identification of the biting species is crucial for clinicians to choose appropriate treatment and anticipate complications. This is particularly important for neurotoxic envenoming which, depending on the snake species involved, may not respond to available antivenoms. Adequate species identification tools are lacking. This study used a combination of morphological and molecular approaches (PCR-aided DNA sequencing from swabs of bite sites) to determine the contribution of venomous and non-venomous species to the snakebite burden in southern Nepal. Out of 749 patients admitted with a history of snakebite to one of three study centres, the biting species could be identified in 194 (25.9%). Out of these, 87 had been bitten by a venomous snake, most commonly the Indian spectacled cobra (Naja naja; n = 42) and the common krait (Bungarus caeruleus; n = 22). When both morphological identification and PCR/sequencing results were available, a 100% agreement was noted. The probability of a positive PCR result was significantly lower among patients who had used inadequate "first aid" measures (e.g. tourniquets or local application of remedies). This study is the first to report the use of forensic genetics methods for snake species identification in a prospective clinical study. If high diagnostic accuracy is confirmed in larger cohorts, this method will be a very useful reference diagnostic tool for epidemiological investigations and clinical studies. PMID:27105074

  14. Particle fluxes and condensational uptake over sea ice during COBRA

    NASA Astrophysics Data System (ADS)

    Whitehead, J. D.; Dorsey, J. R.; Gallagher, M. W.; Flynn, M. J.; McFiggans, G.; Carpenter, L. J.

    2012-08-01

    Particle fluxes were measured over sea ice at Hudson Bay, Canada, during the COBRA experiment in February and March, 2008. Eddy covariance particle fluxes were measured using a condensation particle counter and an ultrasonic anemometer on a 2.5 m mast on the sea ice. After applying appropriate corrections and filtering, the mean net deposition velocity was 0.12 ± 0.11 mm s-1 for particles measured with a CPC 3776 (lower size threshold, Dp50 = 2.5 nm) and was at the detection limit of the measurement system. No evidence of nucleation events was seen. Two optical particle counters (at heights 0.2 and 1.35 m on the mast) allowed size segregated fluxes of particles in the accumulation and coarse mode diameter range 0.3-20 μm to be derived using the aerodynamic flux gradient method. Strong net emission fluxes were observed around midday, 3rd March, when winds increased to around 10 m s-1, suggesting ice particle resuspension. The fluxes during this period had a significant influence on the derived condensational loss rate to the available particle surfaces, kt. Number fluxes were greatest in the smallest size channels, while the largest sizes dominated the mass flux. Number fluxes also increased with wind speed, and this relationship was strongest for the smaller sizes. Particle mass size distributions showed an enhanced mode around 400 nm (dry size). Values of kt were well approximated by the molecular regime and were found to be much smaller and less variable than values derived for marine air.

  15. Structure-function relationship of king cobra cathelicidin.

    PubMed

    Zhang, Yong; Zhao, Hui; Yu, Guo-Yu; Liu, Xiao-Dong; Shen, Ji-Hong; Lee, Wen-Hui; Zhang, Yun

    2010-08-01

    King cobra cathelicidin (OH-CATH) is composed of 34 amino acid residues having strong antibacterial and very weak hemolytic activities as reported by us recently. OH-CATH can be served as a valuable template to develop novel therapeutic drugs. In this study, OH-CATH and six of its analogs were synthesized to explore their structure-function relationships based on their bactericidal and hemolytic activities. Experimental results of OH-CATH(3-34) and OH-CATH(5-34) indicated that the N-terminal 4 amino acid residues of OH-CATH played an important role on its hemolytic activity but had weak effects on its bactericidal activity. Among OH-CATH and its analogs, OH-CATH(5-34) had the lowest hemolytic activity while maintained strong antimicrobial activity. To evaluate its potential usage, the biological activities of OH-CATH(5-34) were compared with those of pexiganan. The bactericidal activity of OH-CATH(5-34) against 5 different species (11 laboratory strains) was 2-4 times stronger than that of pexiganan (4-16 microg/ml vs 8-32 microg/ml). Hemolytic activity of OH-CATH(5-34) against human erythrocytes was 0.69% while that of pexiganan was 16.5% at the dosage of 200 microg/ml. OH-CATH(5-34) showed very weak cytotoxic activities against primary rabbit ventricular endothelial cells and four human cancer cell lines whereas pexiganan showed strong cytotoxic activity against these five cell lines (IC(50)=20-90 microg/ml). The intravenous LD(50) value of OH-CATH(5-34) on mice was 7-fold higher than that of pexiganan (175 mg/kg vs 25mg/kg). Taken together, our results suggested that OH-CATH(5-34) should be considered as an excellent candidate for developing therapeutic drugs. PMID:20576537

  16. Improvements, enhancements, and optimizations of COBRA-TF

    SciTech Connect

    Salko, R. K.; Avramova, M. N.; Hooper, R.; Palmtag, S.; Popov, E.; Turner, J.

    2013-07-01

    The Reactor Dynamics and Fuel Management Group (RDFMG) at The Pennsylvania State University (PSU) has become active in the Consortium for Advanced Simulation of Light Water Reactors (CASL) program by delivering, supporting, and further developing CTF, the PSU version of the Coolant Boiling in Rod Arrays - Two Fluids (COBRA-TF) Thermal/Hydraulic (T/H), sub-channel program. New development work on CTF was primarily geared towards decreasing the execution time of the code so that it may eventually be used for performing pin-by-pin, full-core simulations. Great gains have been made through targeting sections of source code for optimization. For example, wall clock time has been reduced for a one-assembly, three-dimensional model, containing {approx}9,400 mesh cells, from 9.2 min to 1 min. A further improvement has been reduction in code memory usage, which was previously prohibitive for large models. In conjunction with the run time speedups, this has enabled the simulation of a refined quarter-core model ({approx}460,000 mesh cells), which saw a reduction in memory usage from over 130 GB to less than 3 GB. In addition to the optimization work, RDFMG has also created a preprocessor utility for the fast and less error-prone generation of CTF input decks. Furthermore, basic post-processing capabilities have been implemented by creating a CTF subroutine for producing Visualization Tool-Kit (VTK) files that output mesh data and associated simulation results. These VTK files can be opened with visualization software. (authors)

  17. COBRA/TRAC analysis of the PKL reflood test K9

    SciTech Connect

    Wilkins, C.A.

    1982-03-01

    Experiments simulating the refill and reflood procedure after a loss-of-coolant accident (LOCA) in a 1300 MW PWR primary coolant system were performed at the KWU test facility in Erlangen, Germany. COBRA/TRAC was used to model experiment K9 of the PKL series (completed December 1979). PKL-K9 was characterized by a double-ended guillotine break in the cold leg with emergency core cooling water injected into the cold legs. COBRA/TRAC was able to successfully predict lower core temperature profiles and quench times, upper core temperature profiles until quench, upper plenum and break pressures and correct trends in collapsed water levels.

  18. Improvements and applications of COBRA-TF for stand-alone and coupled LWR safety analyses

    SciTech Connect

    Avramova, M.; Cuervo, D.

    2006-07-01

    The advanced thermal-hydraulic subchannel code COBRA-TF has been recently improved and applied for stand-alone and coupled LWR core calculations at the Pennsylvania State Univ. in cooperation with AREVA NP GmbH (Germany)) and the Technical Univ. of Madrid. To enable COBRA-TF for academic and industrial applications including safety margins evaluations and LWR core design analyses, the code programming, numerics, and basic models were revised and substantially improved. The code has undergone through an extensive validation, verification, and qualification program. (authors)

  19. COBRA-SFS predictions of single assembly spent fuel heat transfer data

    SciTech Connect

    Lombardo, N.J.; Michener, T.E.; Wheeler, C.L.; Rector, D.R.

    1986-04-01

    The study reported here is one of several efforts to evaluate and qualify the COBRA-SFS computer code for use in spent fuel storage system thermal analysis. The ability of COBRA-SFS to predict the thermal response of two single assembly spent fuel heat transfer tests was investigated through comparisons of predictions with experimental test data. From these comparisons, conclusions regarding the computational treatment of the physical phenomena occurring within a storage system can be made. This objective was successfully accomplished as reasonable agreement between predictions and data were obtained for the 21 individual test cases of the two experiments.

  20. Genetic suppression reveals DNA repair-independent antagonism between BRCA1 and COBRA1 in mammary gland development.

    PubMed

    Nair, Sreejith J; Zhang, Xiaowen; Chiang, Huai-Chin; Jahid, Md Jamiul; Wang, Yao; Garza, Paula; April, Craig; Salathia, Neeraj; Banerjee, Tapahsama; Alenazi, Fahad S; Ruan, Jianhua; Fan, Jian-Bing; Parvin, Jeffrey D; Jin, Victor X; Hu, Yanfen; Li, Rong

    2016-01-01

    The breast cancer susceptibility gene BRCA1 is well known for its function in double-strand break (DSB) DNA repair. While BRCA1 is also implicated in transcriptional regulation, the physiological significance remains unclear. COBRA1 (also known as NELF-B) is a BRCA1-binding protein that regulates RNA polymerase II (RNAPII) pausing and transcription elongation. Here we interrogate functional interaction between BRCA1 and COBRA1 during mouse mammary gland development. Tissue-specific deletion of Cobra1 reduces mammary epithelial compartments and blocks ductal morphogenesis, alveologenesis and lactogenesis, demonstrating a pivotal role of COBRA1 in adult tissue development. Remarkably, these developmental deficiencies due to Cobra1 knockout are largely rescued by additional loss of full-length Brca1. Furthermore, Brca1/Cobra1 double knockout restores developmental transcription at puberty, alters luminal epithelial homoeostasis, yet remains deficient in homologous recombination-based DSB repair. Thus our genetic suppression analysis uncovers a previously unappreciated, DNA repair-independent function of BRCA1 in antagonizing COBRA1-dependent transcription programme during mammary gland development. PMID:26941120

  1. Genetic suppression reveals DNA repair-independent antagonism between BRCA1 and COBRA1 in mammary gland development

    PubMed Central

    Nair, Sreejith J.; Zhang, Xiaowen; Chiang, Huai-Chin; Jahid, Md Jamiul; Wang, Yao; Garza, Paula; April, Craig; Salathia, Neeraj; Banerjee, Tapahsama; Alenazi, Fahad S.; Ruan, Jianhua; Fan, Jian-Bing; Parvin, Jeffrey D.; Jin, Victor X.; Hu, Yanfen; Li, Rong

    2016-01-01

    The breast cancer susceptibility gene BRCA1 is well known for its function in double-strand break (DSB) DNA repair. While BRCA1 is also implicated in transcriptional regulation, the physiological significance remains unclear. COBRA1 (also known as NELF-B) is a BRCA1-binding protein that regulates RNA polymerase II (RNAPII) pausing and transcription elongation. Here we interrogate functional interaction between BRCA1 and COBRA1 during mouse mammary gland development. Tissue-specific deletion of Cobra1 reduces mammary epithelial compartments and blocks ductal morphogenesis, alveologenesis and lactogenesis, demonstrating a pivotal role of COBRA1 in adult tissue development. Remarkably, these developmental deficiencies due to Cobra1 knockout are largely rescued by additional loss of full-length Brca1. Furthermore, Brca1/Cobra1 double knockout restores developmental transcription at puberty, alters luminal epithelial homoeostasis, yet remains deficient in homologous recombination-based DSB repair. Thus our genetic suppression analysis uncovers a previously unappreciated, DNA repair-independent function of BRCA1 in antagonizing COBRA1-dependent transcription programme during mammary gland development. PMID:26941120

  2. Optimization Studies for the COBRA Neutrinoless Double-Beta Decay Experiment and Results from a Prototype

    NASA Astrophysics Data System (ADS)

    Martin, Jerrad Wayne

    The COBRA experiment uses Cadmium Zinc Telluride (CZT) room-temperature semiconductor detectors to search for the neutrinoless double-beta decay of cadmium-116. While the experiment has produced globally competitive half-life limits with data from coplanar-grid CZT detectors, a future ton-scale iteration could set limits constraining the effective Majorana neutrino mass to less than 100 meV. The aim of this work is to determine the optimal CZT detector type for such an experiment. First, an overview of the relevant neutrino physics as well as an introduction to the COBRA experiment is presented. The performance characteristics and design criteria for CZT detectors are then covered, both in general and as they relate to COBRA. Simulations and prototype experiments have been performed using two of the detector design candidates. The method and results are discussed in detail. Finally, the prototype is compared with other CZT detector designs in the context of performance and scalability for a 420 kg COBRA experiment.

  3. Thermal ramp tritium release in COBRA-1A2 C03 beryllium pebbles

    SciTech Connect

    Baldwin, D.L.

    1998-03-01

    Tritium release kinetics, using the method of thermal ramp heating at three linear ramp rates, were measured on the COBRA-1A2 C03 1-mm beryllium pebbles. This report includes a brief discussion of the test, and the test data in graph format.

  4. 26 CFR 54.4980B-8 - Paying for COBRA continuation coverage.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... continuation coverage. The following questions-and-answers address paying for COBRA continuation coverage: Q-1... not exceed 102 percent of the applicable premium for that period. (See paragraph (b) of this Q&A-1 for... payment is not made to the plan with respect to that qualified beneficiary (see Q&A-1 of §...

  5. 26 CFR 54.4980B-7 - Duration of COBRA continuation coverage.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... a child born to or placed for adoption with a covered employee during a period of COBRA continuation... continuation coverage during which the child was born or placed for adoption. Paragraph (b) of this Q&A-4... dependent child of the retired covered employee ends on the earlier of— (1) The date of the...

  6. 76 FR 18750 - Humble Gas Pipeline Company; Cobra Pipeline Ltd.; Notice of Baseline Filings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Humble Gas Pipeline Company; Cobra Pipeline Ltd.; Notice of Baseline Filings Take notice that on March 28, 2011, the applicants listed above submitted a revised baseline filing...

  7. Cloning and purification of alpha-neurotoxins from king cobra (Ophiophagus hannah).

    PubMed

    He, Ying-Ying; Lee, Wei-Hui; Zhang, Yun

    2004-09-01

    Thirteen complete and three partial cDNA sequences were cloned from the constructed king cobra (Ophiophagus hannah) venom gland cDNA library. Phylogenetic analysis of nucleotide sequences of king cobra with those from other snake venoms revealed that obtained cDNAs are highly homologous to snake venom alpha-neurotoxins. Alignment of deduced mature peptide sequences of the obtained clones with those of other reported alpha-neurotoxins from the king cobra venom indicates that our obtained 16 clones belong to long-chain neurotoxins (seven), short-chain neurotoxins (seven), weak toxin (one) and variant (one), respectively. Up to now, two out of 16 newly cloned king cobra alpha-neurotoxins have identical amino acid sequences with CM-11 and Oh-6A/6B, which have been characterized from the same venom. Furthermore, five long-chain alpha-neurotoxins and two short-chain alpha-neurotoxins were purified from crude venom and their N-terminal amino acid sequences were determined. The cDNAs encoding the putative precursors of the purified native peptide were also determined based on the N-terminal amino acid sequencing. The purified alpha-neurotoxins showed different lethal activities on mice. PMID:15302536

  8. From the Kiss of a Cobra: A Sidelong View of Snakebite, Antivenin, and Serum Sickness.

    ERIC Educational Resources Information Center

    Graham, Douglas H.

    1992-01-01

    Article tells the story of how a New York City customs man was bit by a King Cobra from Thailand and the medical treatment he received. Describes three types of snake venoms: hemotoxins, cytotoxins, and neurotoxins. Explains how horses are used to produce antitoxins and side effects of the antitoxins on humans. (PR)

  9. Construction and Initial Validation of the Color-Blind Racial Attitudes Scale (CoBRAS).

    ERIC Educational Resources Information Center

    Neville, Helen A.; Lilly, Roderick L.; Duran, Georgia; Lee, Richard M.; Browne, LaVonne

    2000-01-01

    Describes development of a conceptually grounded scale to assess cognitive aspects of color-blind racial attitudes. Factor analysis suggests that the 3-factor model is a good fit of data. States that CoBRAS was positively related to other indexes of racial attitudes indicating that greater endorsement of color-blind racial attitudes was related to…

  10. The Content-based Reading Approaches (COBRA) Model in the ELL and LD Classroom

    ERIC Educational Resources Information Center

    Lee, Pei-Yi

    2010-01-01

    The Content-based Reading Approaches (COBRA) framework, constructed by Heerman (2002), was made up of the instructional goals designed for reading-learning integrations in subject matter classrooms. ELL and LD students often fail to have sufficient reading skills to succeed within their different academic subjects, consequently it is important for…

  11. Comparisons of COBRA-SFS calculations with data from simulated sections of unconsolidated and consolidated BWR spent fuel. Final report

    SciTech Connect

    Cuta, J.M.; Creer, J.M.

    1986-08-01

    The COBRA-SFS code was used to calculate temperatures in test sections modeling consolidated and unconsolidated spent fuel rods. The test sections were two-feet long, oriented horizontally, and designed so that the predominate direction of heat flow was in the radial direction. The data consisted of temperature measurements obtained on the electrically heated rods in the test assemblies, and on the boundary walls of the test sections. The COBRA-SFS calculations were in excellent agreement with the measured data from the consolidated test sections. The temperature calculated for the unconsolidated tests were somewhat higher than the measured values. Sensitivity studies on the models for the various modes of heat transfer available in the test sections show that for the consolidated geometry, the COBRA-SFS results are in agreement with the data, and well within experimental error. For the unconsolidated geometry, the COBRA-SFS results are conservative due to an idealized representation of the actual geometry.

  12. Direct nephrotoxicity of Russell's viper venom demonstrated in the isolated perfused rat kidney.

    PubMed

    Ratcliffe, P J; Pukrittayakamee, S; Ledingham, J G; Warrell, D A

    1989-03-01

    Envenoming by Russell's Viper (Vipera russelli) is an important cause of acute renal failure. The mechanism of renal damage is unresolved. It is difficult to obtain evidence of a direct nephrotoxic action because of the coincidental disturbance to the systemic circulation. We studied the action of Russell's Viper venom on the function of the isolated perfused rat kidney. Direct nephrotoxic action was indicated by a dose dependent decrease in inulin clearance and an increase in fractional excretion of sodium seen at venom concentrations down to 50 ng/ml, a concentration likely to be achieved in the human circulation after envenoming. The isolated perfused kidney was also used to assess the efficiency of antivenom and for a comparison with snake venoms from the Thai cobra (Naja kauothia) and the Nigerian Saw-Scaled Viper (Echis ocellatus). PMID:2929855

  13. Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0.

    PubMed

    Schellenberger, Jan; Que, Richard; Fleming, Ronan M T; Thiele, Ines; Orth, Jeffrey D; Feist, Adam M; Zielinski, Daniel C; Bordbar, Aarash; Lewis, Nathan E; Rahmanian, Sorena; Kang, Joseph; Hyduke, Daniel R; Palsson, Bernhard Ø

    2011-09-01

    Over the past decade, a growing community of researchers has emerged around the use of constraint-based reconstruction and analysis (COBRA) methods to simulate, analyze and predict a variety of metabolic phenotypes using genome-scale models. The COBRA Toolbox, a MATLAB package for implementing COBRA methods, was presented earlier. Here we present a substantial update of this in silico toolbox. Version 2.0 of the COBRA Toolbox expands the scope of computations by including in silico analysis methods developed since its original release. New functions include (i) network gap filling, (ii) (13)C analysis, (iii) metabolic engineering, (iv) omics-guided analysis and (v) visualization. As with the first version, the COBRA Toolbox reads and writes systems biology markup language-formatted models. In version 2.0, we improved performance, usability and the level of documentation. A suite of test scripts can now be used to learn the core functionality of the toolbox and validate results. This toolbox lowers the barrier of entry to use powerful COBRA methods. PMID:21886097

  14. Implosion dynamics of wire-array z-pinches on the COBRA accelerator

    NASA Astrophysics Data System (ADS)

    McBride, R. D.; Bell, K. S.; Blesener, I. C.; Chalenski, D. A.; Douglass, J. D.; Greenly, J. B.; Knapp, P. F.; Pikuz, S. A.; Shelkovenko, T. A.; Blanchard, T.; Wilhelm, H.; Hammer, D. A.; Kusse, B. R.

    2007-11-01

    Experimental results characterizing wire-array z-pinch implosion dynamics on the 1-MA, 100-ns rise time COBRA pulsed power generator are presented. Diagnostics fielded include an optical streak camera, a time-gated XUV framing camera, a laser shadowgraph system, filtered time-integrated pinhole cameras, a focusing x-ray spectrometer with spatial resolution (FSSR), a load voltage monitor, a faraday cup, a bolometer, silicon diodes and diamond photoconducting detectors (PCDs). The load geometries investigated in this set of experiments include cylindrical arrays ranging from 6 to 16 mm in diameter, and consisting of 8, 16, or 32 wires of either aluminum (Al) or tungsten (W). The data produced by the entire suite of diagnostics are analyzed and presented to provide an overall picture of implosion dynamics and timing on COBRA. In particular, data fitting to various implosion trajectory models, as well as x-ray pulse shape dependencies on various loads and implosion characteristics are presented and discussed.

  15. The COBRA accelerator pulsed-power driver for Cornell/Sandia ICF research

    SciTech Connect

    Smith, D.L.; Ingwersen, P.; Bennett, L.F.; Boyes, J.D.; Anderson, D.E.; Greenly, J.B.; Sudan, R.N.; Hammer, D.A.

    1995-07-01

    This paper introduces and describes the new Cornell Beam Research Accelerator, COBRA, the result of a three and one-half year collaboration. The flexible 4 to 5-MV, 100 to 250-kA, 46-ns pulse width accelerator is based on a four-cavity Inductive Voltage Adder (IVA) design. In addition to being a mix of new and existing components, COBRA is unique in the sense that each cavity is driven by a single pulse forming line, and the IVA output polarity may be reversed by rotating the cavities 1800 about their vertical axis. Our tests with negative high voltage on the inner MITL stalk indicate that the vacuum power flow has established reasonable azimuthal symmetry within about 2 ns (or 0.6 m) after the cavity output cap. Preliminary results with the accelerator, single cavity, and MITL are presented alone, with the design details and circuit model predictions.

  16. Ophthalmia Due to Spitting Cobra Venom in an Urban Setting - A Report of Three Cases

    PubMed Central

    Ang, Leslie Jonathan; Sanjay, Srinivasan; Sangtam, Tiakumzuk

    2014-01-01

    To describe three presentations of spitting cobra venom induced ophthalmia in urban Singapore. Case notes and photographs of three patients with venom ophthalmia who presented to our clinic between 2007 and 2012 were reviewed. Two patients encountered the spitting cobra while working at a job site while the third patient had caught the snake and caged it. The venom entered the eyes in all 3 cases. Immediate irrigation with tap water was carried out before presenting to the Accident and Emergency department. All patients were treated medically with topical antibiotic prophylaxis and copious lubricants. The use of anti-venom was not required in any case. All eyes recovered with no long-term sequelae. If irrigation is initiated early, eyes can recover with no significant complications or sequelae. PMID:25100912

  17. Updates on activities since the Durham meeting and status of the COBRA experiment

    NASA Astrophysics Data System (ADS)

    Zuber, Kai

    2007-10-01

    This article consists of two parts. The first one is an update on activities since the Durham meeting. The aim of this meeting was to investigate experiments which should or could be performed to provide viable input for the nuclear matrix element calculations. The second part describes the status of the COBRA double beta decay experiment, using CdZnTe semiconductor detectors for the search.

  18. Production of {sup 4}He and tritium from Be in the COBRA-1A2 irradiation

    SciTech Connect

    Greenwood, L.R.

    1998-03-01

    The production of {sup 4}He and tritium has been calculated for beryllium irradiated in the COBRA-1A2 experiment in the Experimental Breeder Reactor II. Reaction rates were based on adjusted neutron spectra determined from reactor dosimetry measurements at three different elevations in the region of the beryllium capsules. Equations are given so that gas production can be calculated for any specific capsule elevation.

  19. Temperature Distributions in LMR Fuel Pin Bundles as Modeled by COBRA-IV-I

    NASA Astrophysics Data System (ADS)

    Wright, Steven A.; Stout, Sherry

    2005-02-01

    Most pin type reactor designs for space power or terrestrial applications group the fuel pins into a number of relatively large fuel pin bundles or subassemblies. Fuel bundles for terrestrial liquid metal fast breeders reactors typically use 217 - 271 pins per sub-assembly, while some SP100 designs use up to 331 pins in a central subassembly that was surrounded by partial assemblies. Because thermal creep is exponentially related to temperature, small changes in fuel pin cladding temperature can make large differences in the lifetime in a high temperature liquid metal reactor (LMR). This paper uses the COBRA-IV-I computer code to determine the temperature distribution within LMR fuel bundles. COBRA-IV-I uses the sub-channel analysis approach to determine the enthalpy (or temperature) and flow distribution in rod bundles for both steady-state and transient conditions. The COBRA code runs in only a few seconds and has been benchmarked and tested extensively over a wide range of flow conditions. In this report the flow and temperature distributions for two types of lithium cooled space reactor core designs were calculated. One design uses a very tight fuel pin packing that has a pitch to diameter ratio of 1.05 (small wire wrap with a diameter of 392 μm) as proposed in SP100. The other design uses a larger pitch to diameter ratio of 1.09 with a larger more conventional sized wire wrap diameter of 1 mm. The results of the COBRA pin bundle calculations show that the larger pitch-to-diameter fuel bundle designs are more tolerant to local flow blockages, and in addition they are less sensitive to mal-flow distributions that occur near the edges of the subassembly.

  20. Neutron dosimetry and damage calculations for the EBRII COBRA-1A irradiations

    SciTech Connect

    Greenwood, L.R.; Ratner, R.T.

    1997-04-01

    Neutron fluence measurements and radiation damage calculations are reported for the joint U.S. and Japanese COBRA-1A1 and 1A2 irradiations in the Experimental Breeder Reactor II. The maximum total neutron fluences at midplane were 2.0E+22 and 7.5E+22 n/cm{sup 2}, for the 1A1 and 1A2 irradiations, respectively, resulting in about 8.0 and 30.3 dpa in stainless steel.

  1. 26 CFR 54.4980B-10 - Interaction of FMLA and COBRA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 825.213. Even if recovery of premiums is permitted under 29 CFR 825.213, the right to COBRA... CFR Part 825 (§§ 825.100-825.800).) The maximum coverage period (see Q&A-4 of § 54.4980B-7) is... later, on September 28, 2001, that C will not be returning to work. Under the FMLA regulations, 29...

  2. 26 CFR 54.4980B-10 - Interaction of FMLA and COBRA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 825.213. Even if recovery of premiums is permitted under 29 CFR 825.213, the right to COBRA... CFR Part 825 (§§ 825.100-825.800).) The maximum coverage period (see Q&A-4 of § 54.4980B-7) is... later, on September 28, 2001, that C will not be returning to work. Under the FMLA regulations, 29...

  3. Temperature Distributions in LMR Fuel Pin Bundles as Modeled by COBRA-IV-I

    SciTech Connect

    Wright, Steven A.; Stout, Sherry

    2005-02-06

    Most pin type reactor designs for space power or terrestrial applications group the fuel pins into a number of relatively large fuel pin bundles or subassemblies. Fuel bundles for terrestrial liquid metal fast breeders reactors typically use 217 - 271 pins per sub-assembly, while some SP100 designs use up to 331 pins in a central subassembly that was surrounded by partial assemblies. Because thermal creep is exponentially related to temperature, small changes in fuel pin cladding temperature can make large differences in the lifetime in a high temperature liquid metal reactor (LMR). This paper uses the COBRA-IV-I computer code to determine the temperature distribution within LMR fuel bundles. COBRA-IV-I uses the sub-channel analysis approach to determine the enthalpy (or temperature) and flow distribution in rod bundles for both steady-state and transient conditions. The COBRA code runs in only a few seconds and has been benchmarked and tested extensively over a wide range of flow conditions. In this report the flow and temperature distributions for two types of lithium cooled space reactor core designs were calculated. One design uses a very tight fuel pin packing that has a pitch to diameter ratio of 1.05 (small wire wrap with a diameter of 392 {mu}m) as proposed in SP100. The other design uses a larger pitch to diameter ratio of 1.09 with a larger more conventional sized wire wrap diameter of 1 mm. The results of the COBRA pin bundle calculations show that the larger pitch-to-diameter fuel bundle designs are more tolerant to local flow blockages, and in addition they are less sensitive to mal-flow distributions that occur near the edges of the subassembly.

  4. 26 CFR 54.4980B-10 - Interaction of FMLA and COBRA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 825.213. Even if recovery of premiums is permitted under 29 CFR 825.213, the right to COBRA... CFR Part 825 (§§ 825.100-825.800).) The maximum coverage period (see Q&A-4 of § 54.4980B-7) is... later, on September 28, 2001, that C will not be returning to work. Under the FMLA regulations, 29...

  5. 26 CFR 54.4980B-10 - Interaction of FMLA and COBRA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 825.213. Even if recovery of premiums is permitted under 29 CFR 825.213, the right to COBRA... CFR Part 825 (§§ 825.100-825.800).) The maximum coverage period (see Q&A-4 of § 54.4980B-7) is... later, on September 28, 2001, that C will not be returning to work. Under the FMLA regulations, 29...

  6. Updates on activities since the Durham meeting and status of the COBRA experiment

    SciTech Connect

    Zuber, Kai

    2007-10-12

    This article consists of two parts. The first one is an update on activities since the Durham meeting. The aim of this meeting was to investigate experiments which should or could be performed to provide viable input for the nuclear matrix element calculations. The second part describes the status of the COBRA double beta decay experiment, using CdZnTe semiconductor detectors for the search.

  7. COBRA: a computational brewing application for predicting the molecular composition of organic aerosols.

    PubMed

    Fooshee, David R; Nguyen, Tran B; Nizkorodov, Sergey A; Laskin, Julia; Laskin, Alexander; Baldi, Pierre

    2012-06-01

    Atmospheric organic aerosols (OA) represent a significant fraction of airborne particulate matter and can impact climate, visibility, and human health. These mixtures are difficult to characterize experimentally due to their complex and dynamic chemical composition. We introduce a novel Computational Brewing Application (COBRA) and apply it to modeling oligomerization chemistry stemming from condensation and addition reactions in OA formed by photooxidation of isoprene. COBRA uses two lists as input: a list of chemical structures comprising the molecular starting pool and a list of rules defining potential reactions between molecules. Reactions are performed iteratively, with products of all previous iterations serving as reactants for the next. The simulation generated thousands of structures in the mass range of 120-500 Da and correctly predicted ∼70% of the individual OA constituents observed by high-resolution mass spectrometry. Select predicted structures were confirmed with tandem mass spectrometry. Esterification was shown to play the most significant role in oligomer formation, with hemiacetal formation less important, and aldol condensation insignificant. COBRA is not limited to atmospheric aerosol chemistry; it should be applicable to the prediction of reaction products in other complex mixtures for which reasonable reaction mechanisms and seed molecules can be supplied by experimental or theoretical methods. PMID:22568707

  8. Comparing the Laryngeal Mask Airway, Cobra Perilaryngeal Airway and Face Mask in Children Airway Management

    PubMed Central

    Tekin, Beyza; Hatipoğlu, Zehra; Türktan, Mediha; Özcengiz, Dilek

    2016-01-01

    Objective We compared the effects of the laryngeal mask airway (LMA), face mask and Cobra perilaryngeal airway (PLA) in the airway management of spontaneously breathing paediatric patients undergoing elective inguinal surgery. Methods In this study, 90 cases of 1–14-year-old children undergoing elective inguinal surgery were scheduled. The patients were randomly divided into three groups. Anaesthesia was provided with sevoflurane and 50%–50% nitrous oxide and oxygen. After providing an adequate depth of anaesthesia, supraglottic airway devices were inserted in the group I and II patients. The duration and number of insertion, haemodynamic parameters, plateau and peak inspiratory pressure and positive end-expiratory pressure of the patients were recorded preoperatively, after induction and at 5, 10, 15 and 30 min peroperatively. Results There were no statistical differences between the groups in terms of haemodynamic parameters (p>0.05). In group II, instrumentation success was higher and instrumentation time was shorter than group II. The positive end-expiratory pressure and plateau and peak inspiratory pressure values were statistically lower in group II (p<0.05). Conclusion We concluded that for airway safety and to avoid possible complications, LMA and Cobra PLA could be alternatives to face mask and that the Cobra PLA provided lower airway pressure and had a faster and more easy placement than LMA. PMID:27366563

  9. COBRA: A Computational Brewing Application for Predicting the Molecular Composition of Organic Aerosols

    SciTech Connect

    Fooshee, David R.; Nguyen, Tran B.; Nizkorodov, Sergey A.; Laskin, Julia; Laskin, Alexander; Baldi, Pierre

    2012-05-08

    Atmospheric organic aerosols (OA) represent a significant fraction of airborne particulate matter and can impact climate, visibility, and human health. These mixtures are difficult to characterize experimentally due to the enormous complexity and dynamic nature of their chemical composition. We introduce a novel Computational Brewing Application (COBRA) and apply it to modeling oligomerization chemistry stemming from condensation and addition reactions of monomers pertinent to secondary organic aerosol (SOA) formed by photooxidation of isoprene. COBRA uses two lists as input: a list of chemical structures comprising the molecular starting pool, and a list of rules defining potential reactions between molecules. Reactions are performed iteratively, with products of all previous iterations serving as reactants for the next one. The simulation generated thousands of molecular structures in the mass range of 120-500 Da, and correctly predicted ~70% of the individual SOA constituents observed by high-resolution mass spectrometry (HR-MS). Selected predicted structures were confirmed with tandem mass spectrometry. Esterification and hemiacetal formation reactions were shown to play the most significant role in oligomer formation, whereas aldol condensation was shown to be insignificant. COBRA is not limited to atmospheric aerosol chemistry, but is broadly applicable to the prediction of reaction products in other complex mixtures for which reasonable reaction mechanisms and seed molecules can be supplied by experimental or theoretical methods.

  10. Development in High-Density Cobra Fiber Positioners for the Subaru Telescope's Prime Focus Spectrometer

    NASA Technical Reports Server (NTRS)

    Fisher, Charles D.; Braun, David F.; Kaluzny, Joel V.; Seiffert, Mic D.; Dekany, Richard G.; Ellis, Richard S.; Smith, Roger S.

    2012-01-01

    The Prime Focus Spectrograph (PFS) is a fiber fed multi-object spectrometer for the Subaru Telescope that will conduct a variety of targeted surveys for studies of dark energy, galaxy evolution, and galactic archaeology. The key to the instrument is a high density array of fiber positioners placed at the prime focus of the Subaru Telescope. The system, nicknamed "Cobra", will be capable of rapidly reconfiguring the array of 2394 optical fibers to the image positions of astronomical targets in the focal plane with high accuracy. The system uses 2394 individual "SCARA robot" mechanisms that are 7.7mm in diameter and use 2 piezo-electric rotary motors to individually position each of the optical fibers within its patrol region. Testing demonstrates that the Cobra positioner can be moved to within 5 micrometers of an astronomical target in 6 move iterations with a success rate of 95%. The Cobra system is a key aspect of PFS that will enable its unprecedented combination of high-multiplex factor and observing efficiency on the Subaru telescope. The requirements, design, and prototyping efforts for the fiber positioner system for the PFS are described here as are the plans for modular construction, assembly, integration, functional testing, and performance validation.

  11. COBRA: A Computational Brewing Application for Predicting the Molecular Composition of Organic Aerosols

    PubMed Central

    Fooshee, David R.; Nguyen, Tran B.; Nizkorodov, Sergey A.; Laskin, Julia; Laskin, Alexander; Baldi, Pierre

    2012-01-01

    Atmospheric organic aerosols (OA) represent a significant fraction of airborne particulate matter and can impact climate, visibility, and human health. These mixtures are difficult to characterize experimentally due to their complex and dynamic chemical composition. We introduce a novel Computational Brewing Application (COBRA) and apply it to modeling oligomerization chemistry stemming from condensation and addition reactions in OA formed by photooxidation of isoprene. COBRA uses two lists as input: a list of chemical structures comprising the molecular starting pool, and a list of rules defining potential reactions between molecules. Reactions are performed iteratively, with products of all previous iterations serving as reactants for the next. The simulation generated thousands of structures in the mass range of 120–500 Da, and correctly predicted ~70% of the individual OA constituents observed by high-resolution mass spectrometry. Select predicted structures were confirmed with tandem mass spectrometry. Esterification was shown to play the most significant role in oligomer formation, with hemiacetal formation less important, and aldol condensation insignificant. COBRA is not limited to atmospheric aerosol chemistry; it should be applicable to the prediction of reaction products in other complex mixtures for which reasonable reaction mechanisms and seed molecules can be supplied by experimental or theoretical methods. PMID:22568707

  12. SO{sub 2} control in low emissions boiler systems with the COBRA process

    SciTech Connect

    Breault, R.W.; Litka, A.F.; Beittel, R.

    1995-06-01

    The COBRA process is an advanced embodiment of the chemically well proven copper oxide process. COBRA stands for Copper Oxide Bed Regenerative Adsorber, a moving bed - cross flow configuration which is ideally suited for SO{sub 2} control and NO{sub x}, reduction through its SCR capabilities. The moving bed adsorber provides low sorbent attrition and allows the use of larger sorbent particle sizes for an overall more economical design. The location of the COBRA process between the economizer and the air heater enhances low temperature heat recovery by removing SO{sub 3} in addition to SO{sub 2}, thereby allowing for very low flue gas temperatures. This paper presents the results of a sensitivity analysis aimed at optimizing the design of a 400 Mw system and integration into a low emissions boiler system. It will identify the benefits of the technology, showing how it is possible to achieve a 99% reduction of SO{sub 2} with very low power consumption and produce a salable by-product - either sulfuric acid or elemental sulfur.

  13. COBRA-LIKE2, a member of the glycosylphosphatidylinositol-anchored COBRA-LIKE family, plays a role in cellulose deposition in arabidopsis seed coat mucilage secretory cells.

    PubMed

    Ben-Tov, Daniela; Abraham, Yael; Stav, Shira; Thompson, Kevin; Loraine, Ann; Elbaum, Rivka; de Souza, Amancio; Pauly, Markus; Kieber, Joseph J; Harpaz-Saad, Smadar

    2015-03-01

    Differentiation of the maternally derived seed coat epidermal cells into mucilage secretory cells is a common adaptation in angiosperms. Recent studies identified cellulose as an important component of seed mucilage in various species. Cellulose is deposited as a set of rays that radiate from the seed upon mucilage extrusion, serving to anchor the pectic component of seed mucilage to the seed surface. Using transcriptome data encompassing the course of seed development, we identified COBRA-LIKE2 (COBL2), a member of the glycosylphosphatidylinositol-anchored COBRA-LIKE gene family in Arabidopsis (Arabidopsis thaliana), as coexpressed with other genes involved in cellulose deposition in mucilage secretory cells. Disruption of the COBL2 gene results in substantial reduction in the rays of cellulose present in seed mucilage, along with an increased solubility of the pectic component of the mucilage. Light birefringence demonstrates a substantial decrease in crystalline cellulose deposition into the cellulosic rays of the cobl2 mutants. Moreover, crystalline cellulose deposition into the radial cell walls and the columella appears substantially compromised, as demonstrated by scanning electron microscopy and in situ quantification of light birefringence. Overall, the cobl2 mutants display about 40% reduction in whole-seed crystalline cellulose content compared with the wild type. These data establish that COBL2 plays a role in the deposition of crystalline cellulose into various secondary cell wall structures during seed coat epidermal cell differentiation. PMID:25583925

  14. Assessment of the Antimicrobial Activity of Few Saudi Arabian Snake Venoms

    PubMed Central

    Al-Asmari, Abdulrahman K.; Abbasmanthiri, Rajamohamed; Abdo Osman, Nasreddien M.; Siddiqui, Yunus; Al-Bannah, Faisal Ahmed; Al-Rawi, Abdulgadir M.; Al-Asmari, Sarah A.

    2015-01-01

    Background Venoms of two cobras, four vipers, a standard antibiotic and an antimycotic, were evaluated comparatively, as antimicrobials. Methods: Six venom concentrations and three of the standard antibiotic and the antimycotic were run in micro-dilution and diffusion plates against the microorganisms. RESULTS: Echis pyramidum, Echis coloratus and Cerastes cerastes gasperettii highest venom concentrations gave significant growth inhibition zones (GIZ) with respect to a negative control, except Bitis arietans, whose concentrations were significant. The cobra Walterinnesia aegyptia had significant venom concentrations more than Naja haje arabica. The Staphylococcus aureus Methicillin Resistant (MRSA) bacterium was the most susceptible, with a highly (P < 0.001) significant GIZ mean difference followed by the Gram positive Staphylococcus aureus, (P < 0.001), Escherichia coli (P < 0.001), Enterococcus faecalis (P < 0.001) and Pseudomonas aeruginosa which, had the least significance (P < 0.05). The fungus Candida albicans was resistant to both viper and cobra venoms (P > 0.05). The antibiotic Vancomycin was more effective than snake venoms though, they were more efficient in inhibiting growth of the resistant Pseudomonas aeruginosa. This antibiotic was also inactive against the fungus, whilst its specific antifungal Fungizone was highly efficient with no antibacterial activity. Conclusions: These findings showed that snake venoms had antibacterial activity comparable to antibiotics, with a directly proportional relationship of venom concentration and GIZ, though, they were more efficient in combatting resistant types of bacteria. Both venoms and the standard antibiotic, showed no antifungal benefits. PMID:26668657

  15. COBRA-SFS (Spent Fuel Storage): A thermal-hydraulic analysis computer code: Volume 2, User's manual

    SciTech Connect

    Rector, D.R.; Cuta, J.M.; Lombardo, N.J.; Michener, T.E.; Wheeler, C.L.

    1986-11-01

    COBRA-SFS (Spent Fuel Storage) is a general thermal-hydraulic analysis computer code used to predict temperatures and velocities in a wide variety of systems. The code was refined and specialized for spent fuel storage system analyses for the US Department of Energy's Commercial Spent Fuel Management Program. The finite-volume equations governing mass, momentum, and energy conservation are written for an incompressible, single-phase fluid. The flow equations model a wide range of conditions including natural circulation. The energy equations include the effects of solid and fluid conduction, natural convection, and thermal radiation. The COBRA-SFS code is structured to perform both steady-state and transient calculations; however, the transient capability has not yet been validated. This volume contains the input instructions for COBRA-SFS and an auxiliary radiation exchange factor code, RADX-1. It is intended to aid the user in becoming familiar with the capabilities and modeling conventions of the code.

  16. NASA TechPort Entry for Coiled Brine Recovery Assembly (CoBRA) CL IR&D Project

    NASA Technical Reports Server (NTRS)

    Pensinger, Stuart

    2014-01-01

    The Coiled Brine Recovery Assembly (CoBRA) project will result in a proof-of-concept demonstration for a lightweight, compact, affordable, regenerable and disposable solution to brine water recovery. The heart of CoBRA is an evaporator that produces water vapor from brine. This evaporator leverages a novel design that enables passive transport of brine from place to place within the system. While it will be necessary to build or modify a system for testing the CoBRA concept, the emphasis of this project will be on developing the evaporator itself. This project will utilize a “test early, test often” approach, building at least one trial evaporator to guide the design of the final product.

  17. Thermal-hydraulic/heat transfer code development for sphere-pac-fueled LMFBRs. [COBRA-3SP code

    SciTech Connect

    Morris, D.G.

    1980-06-01

    Sphere-pac fuel has received much attention recently in light of the development of proliferation-resistant fuel cycles for the Fast Breeder Reactor Program in the United States. However, for sphere-pac fuel to be a viable alternative to conventional pellet fuel, a means to analyze the thermal behavior of sphere-pac-fueled pin bundles is needed. To meet this need, a thermal-hydraulic/heat transfer computer code has been developed for sphere-pac-fueled fast breeder reactors. The code, COBRA-3SP, is a modified version of COBRA-3M incorporating a three-region sphere-pac fuel pin model which permits fuel restructuring. With COBRA-3SP, steady-state and transient analysis of sphere-pac-fueled pin bundles is possible. The validity of the sphere-pac fuel pin model has been verified using experimental results of irradiated sphere-pac fuel.

  18. Cobra-IE Evaluation by Simulation of the NUPEC BWR Full-Size Fine-Mesh Bundle Test (BFBT)

    SciTech Connect

    Burns, C. J. and Aumiler, D. L.

    2006-04-26

    The COBRA-IE computer code is a thermal-hydraulic subchannel analysis program capable of simulating phenomena present in both PWRs and BWRs. As part of ongoing COBRA-IE assessment efforts, the code has been evaluated against experimental data from the NUPEC BWR Full-Size Fine-Mesh Bundle Tests (BFBT). The BFBT experiments utilized an 8 x 8 rod bundle to simulate BWR operating conditions and power profiles, providing an excellent database for investigation of the capabilities of the code. Benchmarks performed included steady-state and transient void distribution, single-phase and two-phase pressure drop, and steady-state and transient critical power measurements. COBRA-IE effectively captured the trends seen in the experimental data with acceptable prediction error. Future sensitivity studies are planned to investigate the effects of enabling and/or modifying optional code models dealing with void drift, turbulent mixing, rewetting, and CHF.

  19. Coiled Brine Recovery Assembly (CoBRA): A New Approach to Recovering Water from Wastewater Brines

    NASA Technical Reports Server (NTRS)

    Pensinger, Stuart J.

    2015-01-01

    Brine water recovery represents a current technology gap in water recycling for human spaceflight. The role of a brine processor is to take the concentrated discharge from a primary wastewater processor, called brine, and recover most of the remaining water from it. The current state-of-the-art primary processor is the ISS Urine Processor Assembly (UPA) that currently achieves 70% water recovery. Recent advancements in chemical pretreatments are expected to increase this to 85% in the near future. This is a welcome improvement, yet is still not high enough for deep space transit. Mission architecture studies indicate that at least 95% is necessary for a Mars mission, as an example. Brine water recovery is the technology that bridges the gap between 85% and 95%, and moves life support systems one step closer to full closure of the water loop. Several brine water recovery systems have been proposed for human spaceflight, most of them focused on solving two major problems: operation in a weightless environment, and management and containment of brine residual. Brine residual is the leftover byproduct of the brine recovery process, and is often a viscous, sticky paste, laden with crystallized solid particles. Due to the chemical pretreatments added to wastewater prior to distillation in a primary processor, these residuals are typically toxic, which further complicates matters. Isolation of crewmembers from these hazardous materials is paramount. The Coiled Brine Recovery Assembly (CoBRA) is a recently developed concept from the Johnson Space Center that offers solutions to these challenges. CoBRA is centered on a softgoods evaporator that enables a passive fill with brine, and regeneration by discharging liquid brine residual to a collection bag. This evaporator is meant to be lightweight, which allows it to be discarded along with the accumulated brine solids contained within it. This paper discusses design and development of a first CoBRA prototype, and reports

  20. Purification of native and recombinant cobra venom factor using thiophilic adsorption chromatography.

    PubMed

    Kölln, Johanna; Braren, Ingke; Bredehorst, Reinhard; Spillner, Edzard

    2007-01-01

    The complement activating venom component Cobra Venom Factor (CVF) forms a stable CVF-dependent C3 convertase complex, which initiates continuous activation of the complement system, consumes all downstream complement components and obliterates functional complement. Therefore, native CVF is routinely used as decomplementing agent in vivo and in vitro. However, in most countries, CVF and even unfractionated cobra venom are now becoming unavailable due to the CITES agreement. Although CVF is a complex molecule with three disulfide linked polypeptide chains and pronounced glycosylation, recombinant expression of the active molecule in eukaryotic host cells may provide an alternative source. In this study we describe a strategy for the production and efficient isolation of recombinant CVF from supernatant of mammalian cells. Thiophilic adsorption chromatography (TAC), an efficient procedure for purification of the human homologue C3, was evaluated for its suitability regarding purification of both native as well as recombinant CVF. Native CVF could be purified by TAC in a one-step procedure from cobra venom with yields of 92% compared to 35% by conventional approaches. After establishment of stably transfected mammalian cells recombinant CVF could be obtained and enriched from CHO supernatants by TAC to a purity of 73%, and up to 90% if an additional affinity chromatography step was included. Subsequent characterization revealed comparable hemolytic and bystander lysis activity and of rCVF and nCVF. These data demonstrate that the functional expression in mammalian cells in combination with TAC for purification renders rCVF a highly attractive substitute for its native counterpart. PMID:17584174

  1. Antiproliferative activity of king cobra (Ophiophagus hannah) venom L-amino acid oxidase.

    PubMed

    Li Lee, Mui; Chung, Ivy; Yee Fung, Shin; Kanthimathi, M S; Hong Tan, Nget

    2014-04-01

    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (LAAO), a heat-stable enzyme, is an extremely potent antiproliferative agent against cancer cells when compared with LAAO isolated from other snake venoms. King cobra venom LAAO was shown to exhibit very strong antiproliferative activities against MCF-7 (human breast adenocarcinoma) and A549 (human lung adenocarcinoma) cells, with an IC50 value of 0.04±0.00 and 0.05±0.00 μg/mL, respectively, after 72-hr treatment. In comparison, its cytotoxicity was about 3-4 times lower when tested against human non-tumourigenic breast (184B5) and lung (NL 20) cells, suggesting selective antitumour activity. Furthermore, its potency in MCF-7 and A549 cell lines was greater than the effects of doxorubicin, a clinically established cancer chemotherapeutic agent, which showed an IC50 value of 0.18±0.03 and 0.63±0.21 μg/mL, respectively, against the two cell lines. The selective cytotoxic action of the LAAO was confirmed by phycoerythrin (PE) annexin V/7-amino-actinomycin (AAD) apoptotic assay, in which a significant increase in apoptotic cells was observed in LAAO-treated tumour cells than in their non-tumourigenic counterparts. The ability of LAAO to induce apoptosis in tumour cells was further demonstrated using caspase-3/7 and DNA fragmentation assays. We also determined that this enzyme may target oxidative stress in its killing of tumour cells, as its cytotoxicity was significantly reduced in the presence of catalase (a H2O2 scavenger). In view of its heat stability and selective and potent cytotoxic action on cancer cells, king cobra venom LAAO can be potentially developed for treating solid tumours. PMID:24118879

  2. Status and perspectives of the COBRA double-beta decay experiment

    NASA Astrophysics Data System (ADS)

    Wilson, J. R.; Cobra Collaboration

    2006-05-01

    The COBRA experiment is going to use a large amount of CdZnTe semiconductor detectors to perform a search for various double-beta-decay modes. The current status of the experiment is presented, as well as first results. Improved half-life limits for the ground-state transitions of 64Zn and 120Te for 0νβ +/EC and 0νECEC have been obtained and the rate of the 4-fold forbidden 113Cd decays has been measured. A short outlook on future activities is also given.

  3. Studies of Hot Spots in Imploding Wire Arrays at 1 MA on COBRA

    NASA Astrophysics Data System (ADS)

    Pikuz, Sergey A.; Shelkovenko, Tatiana A.; McBride, Ryan D.; Hammer, David A.

    2009-01-01

    We present recent results from hot spot investigations in imploding Al wire array z-pinches on the COBRA generator at Cornell University using x-ray diagnostics. Measurements of the temporal and spatial distribution of hot spots in stagnating plasmas by an x-ray streak-camera are included. Experiments show that hot spots have nanosecond lifetime and appear randomly along the array axis after plasma stagnation in secondary pinches in 8 mm diameter and during plasma stagnation in the arrays with 4 mm diameter.

  4. A parallelization approach to the COBRA-TF thermal-hydraulic subchannel code

    NASA Astrophysics Data System (ADS)

    Ramos, Enrique; Abarca, Agustín; Roman, Jose E.; Miró, Rafael

    2014-06-01

    In order to reduce the response time when simulating large reactors in detail, we have developed a parallel version of the thermal-hydraulic subchannel code COBRA-TF, with standard message passing technology (MPI). The parallelization is oriented to reactor cells, so it is best suited for models consisting of many cells. The generation of the Jacobian is parallelized, in such a way that each processor is in charge of generating the data associated to a subset of cells. Also, the solution of the linear system of equations is done in parallel, using the PETSc toolkit.

  5. Studies of Hot Spots in Imploding Wire Arrays at 1 MA on COBRA

    SciTech Connect

    Pikuz, Sergey A.; Shelkovenko, Tatiana A.; McBride, Ryan D.; Hammer, David A.

    2009-01-21

    We present recent results from hot spot investigations in imploding Al wire array z-pinches on the COBRA generator at Cornell University using x-ray diagnostics. Measurements of the temporal and spatial distribution of hot spots in stagnating plasmas by an x-ray streak-camera are included. Experiments show that hot spots have nanosecond lifetime and appear randomly along the array axis after plasma stagnation in secondary pinches in 8 mm diameter and during plasma stagnation in the arrays with 4 mm diameter.

  6. EM experiments for computational model validation for AH-1S Cobra Helicopter

    SciTech Connect

    Nelson, S.D.

    1997-04-06

    The effort described here describes a set of outdoor experiments performed on the AH-1S Cobra helicopter in order to validate and compare to the computational electromagnetic models of the bulk structure of the airframe in the frequency bands up to 4 GHz. Also included in this were coupling measurements to wires and cables inside of the airframe and various cavity to HPM pulse in this frequency range as part of other activities. Additionally, the low power modeling compression will be completed in this time frame.

  7. ATWS Analysis with an Advanced Boiling Curve Approach within COBRA 3-CP

    SciTech Connect

    Gensler, A.; Knoll, A.; Kuehnel, K.

    2007-07-01

    In 2005 the German Reactor Safety Commission issued specific requirements on core coolability demonstration for PWR ATWS (anticipated transients without scram). Thereupon AREVA NP performed detailed analyses for all German PWRs. For a German KONVOI plant the results of an ATWS licensing analysis are presented. The plant dynamic behavior is calculated with NLOOP, while the hot channel analysis is performed with the thermal hydraulic computer code COBRA 3-CP. The application of the fuel rod model included in COBRA 3-CP is essential for this type of analysis. Since DNB (departure from nucleate boiling) occurs, the advanced post DNB model (advanced boiling curve approach) of COBRA 3-CP is used. The results are compared with those gained with the standard BEEST model. The analyzed ATWS case is the emergency power case 'loss of main heat sink with station service power supply unavailable'. Due to the decreasing coolant flow rate during the transient the core attains film boiling conditions. The results of the hot channel analysis strongly depend on the performance of the boiling curve model. The BEEST model is based on pool boiling conditions whereas typical PWR conditions - even in most transients - are characterized by forced flow for which the advanced boiling curve approach is particularly suitable. Compared with the BEEST model the advanced boiling curve approach in COBRA 3-CP yields earlier rewetting, i.e. a shorter period in film boiling. Consequently, the fuel rod cladding temperatures, that increase significantly due to film boiling, drop back earlier and the high temperature oxidation is significantly diminished. The Baker-Just-Correlation was used to calculate the value of equivalent cladding reacted (ECR), i.e. the reduction of cladding thickness due to corrosion throughout the transient. Based on the BEEST model the ECR value amounts to 0.4% whereas the advanced boiling curve only leads to an ECR value of 0.2%. Both values provide large margins to the 17

  8. Monochromatic X-Ray Imaging by X pinches on the COBRA Accelerator

    NASA Astrophysics Data System (ADS)

    Douglass, J. D.; Hammer, D. A.; Pikuz, S. A.; Shelkovenko, T. A.

    2006-10-01

    The COBRA accelerator is a pulsed power generator capable of producing up to 1 MA current pulses with a typical rise time of 100 ns and pulse width of about 200 ns. Time-gated x-ray imaging is an important diagnostic for the study of imploding dense z-pinches. These plasmas must be studied on the nanosecond time scale, and they generally radiate strongly in the soft x-ray range. As such, they require short, intense x-ray sources to illuminate them. Monochromatic x-ray imaging using an X pinch is a way that has been used successfully in the past [1,2] to image single exploding wires and various static objects. Experiments have been performed to investigate x-ray source parameters for various materials and configurations. Of these materials aluminum (6.6343å) and zinc (9.815å) have the most potential for use as a monochromatic source on COBRA. Data presented includes x-ray spectra (˜1-10 å) along with source size estimates and results from initial imaging experiments. This research was supported by the Stewardship Sciences Academic Alliances program of the National Nuclear Security Administration under DOE Cooperative agreement DE-FC03-02NA00057. [1] S. A. Pikuz, et al., Rev. Sci. Instrum., 68, 740 (1997). [2] D. B. Sinars, et al., Phys. Plasmas 13, 042704 (2006).

  9. Developments in high-density Cobra fiber positioners for the Subaru Telescope's Prime Focus Spectrometer

    NASA Astrophysics Data System (ADS)

    Fisher, Charles D.; Braun, David F.; Kaluzny, Joel V.; Seiffert, Michael D.; Dekany, Richard G.; Ellis, Richard S.; Smith, Roger M.

    2012-09-01

    The Prime Focus Spectrograph (PFS) is a fiber fed multi-object spectrometer for the Subaru Telescope that will conduct a variety of targeted surveys for studies of dark energy, galaxy evolution, and galactic archaeology. The key to the instrument is a high density array of fiber positioners placed at the prime focus of the Subaru Telescope. The system, nicknamed “Cobra”, will be capable of rapidly reconfiguring the array of 2394 optical fibers to the image positions of astronomical targets in the focal plane with high accuracy. The system uses 2394 individual “SCARA robot” mechanisms that are 7.7mm in diameter and use 2 piezo-electric rotary motors to individually position each of the optical fibers within its patrol region. Testing demonstrates that the Cobra positioner can be moved to within 5μm of an astronomical target in 6 move iterations with a success rate of 95%. The Cobra system is a key aspect of PFS that will enable its unprecedented combination of high-multiplex factor and observing efficiency on the Subaru telescope. The requirements, design, and prototyping efforts for the fiber positioner system for the PFS are described here as are the plans for modular construction, assembly, integration, functional testing, and performance validation.

  10. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system

    PubMed Central

    Vonk, Freek J.; Casewell, Nicholas R.; Henkel, Christiaan V.; Heimberg, Alysha M.; Jansen, Hans J.; McCleary, Ryan J. R.; Kerkkamp, Harald M. E.; Vos, Rutger A.; Guerreiro, Isabel; Calvete, Juan J.; Wüster, Wolfgang; Woods, Anthony E.; Logan, Jessica M.; Harrison, Robert A.; Castoe, Todd A.; de Koning, A. P. Jason; Pollock, David D.; Yandell, Mark; Calderon, Diego; Renjifo, Camila; Currier, Rachel B.; Salgado, David; Pla, Davinia; Sanz, Libia; Hyder, Asad S.; Ribeiro, José M. C.; Arntzen, Jan W.; van den Thillart, Guido E. E. J. M.; Boetzer, Marten; Pirovano, Walter; Dirks, Ron P.; Spaink, Herman P.; Duboule, Denis; McGlinn, Edwina; Kini, R. Manjunatha; Richardson, Michael K.

    2013-01-01

    Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection. PMID:24297900

  11. CoBRA: Cone beam Computed Tomography (CT) reconstruction code in Interactive Data Language (IDL)

    SciTech Connect

    Sheats, M.J.; Stupin, D.M.

    1997-10-01

    In support of stockpile stewardship and other important missions, Los Alamos is continually looking for fast and effective ways of inspecting and evaluating industrial parts. Thus, Los Alamos is continually striving to improve our radiography and computed tomography (CT) capabilities. Cormack and Hounsfield received the Nobel Prize in 1979 for their pioneering work in computed tomography that led to the development of medical scanners. Copley et al. provides a good history of the development of industrial CT systems. The early systems collect data via a single detector or linear detector array. While CT offers greatly increased spatial resolutions over radiography, CT inspections with a linear array are slow and costly. To improve the viability of CT for NDT applications, Feldkamp, Davis, and Kress reported a cone beam reconstruction technique that speeds up the CT process by using image data rather than data collected by a linear array. Because it potentially offers processing speeds up to 10 times faster than CT systems that use a linear array, we are building a cone beam CT for use with our 20 MV x-ray source and Los Alamos Neutron Science Center (LANSCE) neutron sources. Our software, called CoBRA, is a portable cone beam reconstruction code for CT applications that efficiently and rapidly reconstructs large data sets. CoBRA applications include both x-ray and neutron inspections using x-ray phosphor screens coupled to either a CCD camera or flat-panel amorphous silicon arrays. Photographs of two amorphous silicon arrays.

  12. COBRAS/SAMBA: the ESA Medium Size Mission for measurements of CBR anisotropy

    NASA Astrophysics Data System (ADS)

    Mandolesi, N.; Bersanelli, M.; Cesarsky, C.; Danese, L.; Efstathiou, G.; Griffin, M.; Lamarre, J. M.; Norgaard-Nielsen, H. U.; Pace, O.; Puget, J. L.; Raisanen, A.; Smoot, G. F.; Tauber, J.; Volonte, S.

    1995-02-01

    The COBRAS/SAMBA mission is designed for extensive, accurate mapping of the anisotropy of the Cosmic Background Radiation. with angular sensitivity from scales of a few arcminutes up to and overlapping with the > 7° COBE-DMR resolution. This will allow a full identification of the primordial density perturbations which grew to Corm the large-scale structures observed in the present universe. The COBRAS/SAMBA maps will provide a major source of information relevant to several cosmological and astrophysical issues, such as testing theories of the early universe and the origin of cosmic structure. One of the main diffuse foreground emissions will be from interstellar dust, and the mission will provide relevant information on its components and emission properties. A combination of bolometric and radiometric detection techniques will ensure the sensitivity and wide spectral coverage required for accurate foreground discrimination. A far-Earth orbit has been selected to minimize the unwanted emission from the Earth as a source of contamination. The project is currently undergoing a feasibility study within the European Space Agency M3 programme.

  13. Ohanin, a novel protein from king cobra venom: its cDNA and genomic organization.

    PubMed

    Pung, Yuh Fen; Kumar, Sanjeed Vijaya; Rajagopalan, Nandhakishore; Fry, Bryan G; Kumar, Prakash P; Kini, R Manjunatha

    2006-04-26

    Ohanin, from king cobra venom, is a novel protein which induces hypolocomotion and hyperalgesia in mice [Pung, Y.F., Wong, P.T.H., Kumar, P.P., Hodgson W.C., Kini, R.M., 2005. Ohanin, a novel protein from king cobra venom induces hypolocomotion and hyperalgesia in mice. J. Biol. Chem. 280, 13137-13147.]. It is weakly similar to PRY-SPRY domains (B30.2-like domain). Here we report the complete cDNA and genomic organization of ohanin. Interestingly, cDNA sequence does not show significant sequence similarity to any known sequences, including those of B30.2-like domain-containing proteins. Its full-length cDNA sequence of 1558 bp encodes for prepro-ohanin with a propeptide segment at the C-terminal. Ohanin is the first member of a new subfamily of proteins containing B30.2-like domain with short N-terminal segment. We named this subfamily as vespryns. There are two mRNA subtypes differing in their 5'-untranslated regions. Southern hybridization study shows that ohanin is encoded by a single gene. Its genomic sequence is 7086 bp with five exons and four introns, and the two types of mRNAs are generated by alternative splicing of exon 2. Our results indicate that ohanin and vespryns may have evolved from the same ancestral gene as B30.2 domain. PMID:16472942

  14. COBRA-SFS: A thermal-hydraulic analysis code for spent fuel storage and transportation casks

    SciTech Connect

    Michener, T.E.; Rector, D.R.; Cuta, J.M.; Dodge, R.E.; Enderlin, C.W.

    1995-09-01

    COBRA-SFS is a general thermal-hydraulic analysis computer code for prediction of material temperatures and fluid conditions in a wide variety of systems. The code has been validated for analysis of spent fuel storage systems, as part of the Commercial Spent Fuel Management Program of the US Department of Energy. The code solves finite volume equations representing the conservation equations for mass, moment, and energy for an incompressible single-phase heat transfer fluid. The fluid solution is coupled to a finite volume solution of the conduction equation in the solid structure of the system. This document presents a complete description of Cycle 2 of COBRA-SFS, and consists of three main parts. Part 1 describes the conservation equations, constitutive models, and solution methods used in the code. Part 2 presents the User Manual, with guidance on code applications, and complete input instructions. This part also includes a detailed description of the auxiliary code RADGEN, used to generate grey body view factors required as input for radiative heat transfer modeling in the code. Part 3 describes the code structure, platform dependent coding, and program hierarchy. Installation instructions are also given for the various platform versions of the code that are available.

  15. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system.

    PubMed

    Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Heimberg, Alysha M; Jansen, Hans J; McCleary, Ryan J R; Kerkkamp, Harald M E; Vos, Rutger A; Guerreiro, Isabel; Calvete, Juan J; Wüster, Wolfgang; Woods, Anthony E; Logan, Jessica M; Harrison, Robert A; Castoe, Todd A; de Koning, A P Jason; Pollock, David D; Yandell, Mark; Calderon, Diego; Renjifo, Camila; Currier, Rachel B; Salgado, David; Pla, Davinia; Sanz, Libia; Hyder, Asad S; Ribeiro, José M C; Arntzen, Jan W; van den Thillart, Guido E E J M; Boetzer, Marten; Pirovano, Walter; Dirks, Ron P; Spaink, Herman P; Duboule, Denis; McGlinn, Edwina; Kini, R Manjunatha; Richardson, Michael K

    2013-12-17

    Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection. PMID:24297900

  16. Merit Pay in Arkansas: An Evaluation of the Cobra Pride Incentive Program in the Fountain Lake School District

    ERIC Educational Resources Information Center

    Jensen, Nathan C.

    2012-01-01

    Starting in the 2010-11, administrators at the Fountain Lake School District implemented the Cobra Pride Incentive Program (CPIP), a merit pay program designed to financially reward all school employees with year-end bonuses primarily for significant improvements in student achievement. At the conclusion of the 2010-11 school year, over $800,000…

  17. Studies of the Dynamics of Ablation Stream development in Wire Arrays on COBRA

    NASA Astrophysics Data System (ADS)

    Greenly, John; Martin, Matthew; Seyler, Charles

    2007-11-01

    Wire-array simulations with the 3D GORGON code (see adjoining poster by Martin et al.) show a characteristic evolution in the development of streams of ablated material ejected from the wires toward the array axis. In simulations of aluminum arrays, the fundamental behavior occurs in two steps. The first is the development of coronal plasma that is trapped around the wire core in closed ``local'' magnetic flux. This coronal plasma, together with the closed flux, is then accelerated inward after a certain ``dwell'' time, leaving behind a radially distributed current density with entirely open ``global'' magnetic field lines, producing smooth, distributed acceleration of ablated plasma inward from the wire core until the onset of the final implosion. Interpretation of these dynamics in terms of simple physical modeling will be discussed, and experimental evidence of these phenomena from imaging and magnetic field diagnostics on arrays on the COBRA facility at Cornell will be presented.

  18. The Thick-COBRA: a new gaseous electron multiplier for radiation detectors

    NASA Astrophysics Data System (ADS)

    Amaro, F. D.; Santos, C.; Veloso, J. F. C. A.; Breskin, A.; Chechik, R.; dos Santos, J. M. F.

    2010-10-01

    The operation principle and preliminary results of a novel gas-avalanche patterned hole electron multiplier, the Thick-COBRA (THCOBRA), are presented. This micro-hole structure is derived from the THGEM and MHSP. Sub-millimeter diameter holes are mechanically drilled in a thin G10 plate, Cu-clad on both faces; on one of the faces the Cu is etched to produce additional anode strips winding between circular cathode strips. Primary avalanches occurring within the holes are followed by additional ones at the anode-strips vicinity. Gains in excess of 5*104were reached with 22.1 keV x-rays in Ar, Ne and Ar-10%CH4, with 12.2 % FWHM energy resolution in Ar-10%CH4. Higher gains were measured with single photoelectrons. This robust multiplier may have numerous potential applications.

  19. Exploration of Pixelated detectors for double beta decay searches within the COBRA experiment

    NASA Astrophysics Data System (ADS)

    Schwenke, M.; Zuber, K.; Janutta, B.; He, Z.; Zeng, F.; Anton, G.; Michel, T.; Durst, J.; Lück, F.; Gleixner, T.; Gössling, C.; Schulz, O.; Köttig, T.; Krawczynski, H.; Martin, J.; Stekl, I.; Cermak, P.

    2011-09-01

    The aim of the COBRA experiment is the search for neutrinoless double beta decay events in Cadmium Zinc Telluride (CdZnTe) room temperature semiconductor detectors. The development of pixelated detectors provides the potential for clear event identification and thus major background reduction. The tracking option of a semiconductor is a unique approach in this field. For initial studies, several possible detector systems are considered with a special regard for low background applications: the large volume system Polaris with a pixelated CdZnTe sensor, Timepix detectors with Si and enriched CdTe sensor material and a CdZnTe pixel system developed at the Washington University in St. Louis, USA. For all detector systems first experimental background measurements taken at underground laboratories (Gran Sasso Underground Laboratory in Italy, LNGS and the Niederniveau Messlabor Felsenkeller in Dresden, Germany) and additionally for the Timepix detectors simulation results are presented.

  20. The High-Redshift Clusters Occupied by Bent Radio AGN (COBRA) Survey

    NASA Astrophysics Data System (ADS)

    Paterno-Mahler, Rachel; Blanton, Elizabeth L.; Wing, Joshua; Ashby, M. L. N.; Brodwin, Mark; Golden-Marx, Emmet

    2015-08-01

    The number of confirmed, high-redshift galaxy clusters is very low compared to the number of well-studied clusters nearby. Bent, double-lobed radio sources are frequently found in galaxy clusters, and thus can be used as tracers for efficiently locating high-redshift clusters. Using our Spitzer Snapshot Survey, we have identified approximately 300 potential new clusters with redshifts 0.7COBRA) survey. We have created color-magnitude diagrams using infrared and optical data. Using the colors of the radio source host and the red sequence we can estimate redshifts for our clusters, as well as examine the evolution of the cluster galaxies over a large range of cosmic time.

  1. The neutrinoless double beta decay experiment COBRA: Status and future plans

    NASA Astrophysics Data System (ADS)

    Martin, Jerrad

    2009-10-01

    The COBRA experiment uses Cadmium Zinc Telluride (CZT) room-temperature solid-state detectors to search for neutrinoless double beta decays of the isotope ^116Cd as well as for rare decays from several other Cd and Te isotopes. A prototype experiment is currently taking data in the Gran Sasso underground laboratory. In this contribution, recent results from the prototype will be presented. Furthermore, the on-going detector R&D will be described and two detector options for a large-scale experiment made of 420 kg of CZT detectors will be discussed. The first option uses ``calorimetric coplanar grid detector units". Alternatively, finely pixelated detectors may be used with pixel pitches of between 200 and 350 microns. The pixelated detectors would afford the possibility of tracking beta particles inside the detector and distinguishing them from background events.

  2. Embedding magnetic field lines in the plasma jet of an exploding radial foil on COBRA

    NASA Astrophysics Data System (ADS)

    Schrafel, Peter; Gourdain, Pierre; Greenly, John; Kusse, Bruce

    2009-11-01

    Previous investigations of exploding radial foils have shown the formation of an axial plasma jet in the early stages of the foil explosion. In this case a thin load foil was pressed at an outer annulus held at ground, and contacted in the center by a small straight rod cathode driven by the 1MA COBRA accelerator. The present experiments look at the effects of inducing a transient magnetic field in the region containing the plasma jet. This induced magnetic field is created in one of two ways: twisting the rod cathode to have a helical coil segment near the foil, or putting an inductive current path in parallel to the straight rod cathode. Of great interest is whether this applied magnetic field can be embedded into the plasma jet and influence its development. The jet is diagnosed visually with laser shadowgraphy and observation of XUV emission. B-dot probes measure the magnetic field strength in the region near the jet.

  3. Evidence for the emission of reactive halocarbons from open leads in Arctic seaice during COBRA

    NASA Astrophysics Data System (ADS)

    Carpenter, L. J.; Shaw, M. D.; Hornsby, K. E.; Chance, R. J.; Atkinson, H. E.; Roscoe, H.

    2009-04-01

    Recent observations of reactive iodine in the Antarctic boundary layer show that polar sources of iodine must be significant. The nature and formation of such iodine precursors are currently unknown. Very short lived halocarbons (mono-, di- and tri- halogenated organics) containing iodine are one possibility - these are rapidly photolysed (290-350nm) within the polar boundary layer. Current research suggests both biotic and abiotic sources of halocarbons in polar regions. During the COBRA (Impact of COmbined Bromine and Iodine Release on the Arctic atmosphere) campaign at Kuujjuarapik on the east coast of Hudson bay (55.30°N, 77.73°W), measurements during Feb-Mar 2008 in air and throughout the sea-ice suggest that biological production of reactive halocarbons on the bottom of sea-ice is significant, and that these gaseous emissions are predominantly vented from open leads. Here we discuss the implications of these results.

  4. A lethal neurotoxic protein from Indian king cobra (Ophiophagus hannah) venom.

    PubMed

    De, Pallabi; Dasgupta, S C; Gomes, A

    2002-12-01

    A lethal neurotoxin protein (Toxin CM36) was isolated and purified from the Indian King Cobra (Ophiophagus hannah) venom by CM-Sephadex ion exchange chromatography and HPLC. The purified toxin had a SDS-molecular weight of 15 +/- 0.5 kD. The UV absorption spectra of Toxin CM36 showed a peak at 280 nm and an Emax at 343.8 nm, when excited at 280 nm fluorescence. Toxin CM36 had an LD50 of 3.5 microg/20 g (i.v.) in male albino mice. It exhibited neurotoxicity and produced irreversible blockade of isolated chick biventer cervicis and rat phrenic nerve diaphragm. The neurotoxicity was found to be Ca2+ dependent. Toxin CM36 had no significant effect on isolated guineapig heart and auricle. It also had no effect on blood pressure of cat and rat but produced respiratory apnoea in rat and guineapig. Toxin CM36 lacked phospholipase activity. PMID:12974397

  5. Preliminary crystallographic study of an acidic phospholipase A2 from Ophiophagus hannah (king cobra).

    PubMed

    Xu, Sujuan; Gu, Lichuan; Wang, Qiuyan; Shu, Yuyan; Lin, Zhengjiong

    2002-10-01

    An acidic phospholipase A(2) (OH APLA(2)-II) with an isoelectric point (pI) of 4.0 was recently isolated from Ophiophagus hannah (king cobra) from Guangxi province, China. Comparison of this enzyme to a previously reported homologous phospholipase A(2) from the same venom shows that it lacks toxicity and exhibits a greater phospholipase activity. OH APLA(2)-II has been crystallized by the hanging-drop vapour-diffusion method using 1,6-hexanediol and magnesium chloride as precipitants. The crystal belongs to space group P6(3), with unit-cell parameters a = b = 98.06, c = 132.39 A. The diffraction data were collected under cryoconditions (100 K) and reduced to 2.1 A resolution. A molecular-replacement solution has been determined and shows that there are six molecules in one asymmetric unit. PMID:12351830

  6. Reduced gravity boiling and condensing experiments simulated with the COBRA/TRAC computer code

    NASA Technical Reports Server (NTRS)

    Cuta, Judith M.; Krotiuk, William

    1988-01-01

    A series of reduced-gravity two-phase flow experiments has been conducted with a boiler/condenser apparatus in the NASA KC-135 aircraft in order to obtain basic thermal-hydraulic data applicable to analytical design tools. Several test points from the KC-135 tests were selected for simulation by means of the COBRA/TRAC two-fluid, three-field thermal-hydraulic computer code; the points were chosen for a 25-90 percent void-fraction range. The possible causes for the lack of agreement noted between simulations and experiments are explored, with attention to the physical characteristics of two-phase flow in one-G and near-zero-G conditions.

  7. Maintaining health insurance during a recession: likely COBRA eligibility: an updated analysis using the Commonwealth Fund 2007 Biennial Health Insurance Survey.

    PubMed

    Doty, Michelle; Rustgi, Sheila D; Schoen, Cathy; Collins, Sara R

    2009-01-01

    As the U.S. economic downturn continues and job losses mount, more working Americans are likely to lose access to affordable health benefits subsidized by their employers. Analysis of the 2007 Commonwealth Fund Biennial Health Insurance Survey finds that two of three working adults would be eligible to extend job-based coverage, under the 1985 Consolidated Omnibus Budget Reconciliation Act (COBRA) if they became unemployed. Under COBRA, however, unemployed workers would have to pay four to six times their current contribution at a time of sharply reduced income. In fact, the latest national figures indicate that, because of high premiums, only 9 percent of unemployed workers have COBRA coverage. Substantial financial assistance of 75 percent to 85 percent of premiums could help laid-off workers maintain coverage. In addition, expansion of Medicaid and the State Children's Health Insurance Program would benefit low-income, laid-off workers and their families who are ineligible for COBRA. PMID:19288628

  8. Novel Cross-Band Relative Absorption (CoBRA) technique For Measuring Atmospheric Species

    NASA Astrophysics Data System (ADS)

    Prasad, N. S.; Pliutau, D.

    2013-12-01

    We describe a methodology called Cross-Band Relative Absorption (CoBRA) we have implemented to significantly reduce interferences due to variations in atmospheric temperature and pressure in molecular mixing ration measurements [1-4]. The interference reduction is achieved through automatic compensation based on selecting spectral line pairs exhibiting similar evolution behavior under varying atmospheric conditions. The method is applicable to a wide range of molecules including CO2 and CH4 which can be matched with O2 or any other well-mixed atmospheric molecule. Such matching results in automatic simultaneous adjustments of the spectral line shapes at all times with a high precision under varying atmospheric conditions of temperature and pressure. We present the results of our selected CoBRA analysis based on line-by-line calculations and the Modern Era Retrospective Analysis for Research and Applications (MERRA) dataset including more recent evaluation of the error contributions due to water vapor interference effects. References: 1) N. S. Prasad, D. Pliutau, 'Cross-band relative absorption technique for the measurement of molecular mixing ratios.', Optics Express, Vol. 21, Issue 11, pp. 13279-13292 (2013) 2) D. Pliutau and N. S. Prasad, "Cross-band Relative Absorption Technique for Molecular Mixing Ratio Determination," in CLEO: 2013, OSA Technical Digest (online) (Optical Society of America, 2013), paper CW3L.4. 3) Denis Pliutau; Narasimha S. Prasad; 'Semi-empirical validation of the cross-band relative absorption technique for the measurement of molecular mixing ratios',.Proc. SPIE 8731, Laser Radar Technology and Applications XVIII, 87310L (May 20, 2013); doi:10.1117/12.2016661. 4) Denis Pliutau,; Narasimha S. Prasad; 'Comparative analysis of alternative spectral bands of CO2 and O2 for the sensing of CO2 mixing ratios' Proc. SPIE 8718, Advanced Environmental, Chemical, and Biological Sensing Technologies X, 87180L (May 31, 2013); doi:10.1117/12.2016337.

  9. COBRA-SFS (Spent Fuel Storage): A thermal-hydraulic analysis computer code: Volume 1, Mathematical models and solution method

    SciTech Connect

    Rector, D.R.; Wheeler, C.L.; Lombardo, N.J.

    1986-11-01

    COBRA-SFS (Spent Fuel Storage) is a general thermal-hydraulic analysis computer code used to predict temperatures and velocities in a wide variety of systems. The code was refined and specialized for spent fuel storage system analyses for the US Department of Energy's Commercial Spent Fuel Management Program. The finite-volume equations governing mass, momentum, and energy conservation are written for an incompressible, single-phase fluid. The flow equations model a wide range of conditions including natural circulation. The energy equations include the effects of solid and fluid conduction, natural convection, and thermal radiation. The COBRA-SFS code is structured to perform both steady-state and transient calculations: however, the transient capability has not yet been validated. This volume describes the finite-volume equations and the method used to solve these equations. It is directed toward the user who is interested in gaining a more complete understanding of these methods.

  10. COBRA-SFS (Spent Fuel Storage): A thermal-hydraulic analysis computer code: Volume 3, Validation assessments

    SciTech Connect

    Lombardo, N.J.; Cuta, J.M.; Michener, T.E.; Rector, D.R.; Wheeler, C.L.

    1986-12-01

    This report presents the results of the COBRA-SFS (Spent Fuel Storage) computer code validation effort. COBRA-SFS, while refined and specialized for spent fuel storage system analyses, is a lumped-volume thermal-hydraulic analysis computer code that predicts temperature and velocity distributions in a wide variety of systems. Through comparisons of code predictions with spent fuel storage system test data, the code's mathematical, physical, and mechanistic models are assessed, and empirical relations defined. The six test cases used to validate the code and code models include single-assembly and multiassembly storage systems under a variety of fill media and system orientations and include unconsolidated and consolidated spent fuel. In its entirety, the test matrix investigates the contributions of convection, conduction, and radiation heat transfer in spent fuel storage systems. To demonstrate the code's performance for a wide variety of storage systems and conditions, comparisons of code predictions with data are made for 14 runs from the experimental data base. The cases selected exercise the important code models and code logic pathways and are representative of the types of simulations required for spent fuel storage system design and licensing safety analyses. For each test, a test description, a summary of the COBRA-SFS computational model, assumptions, and correlations employed are presented. For the cases selected, axial and radial temperature profile comparisons of code predictions with test data are provided, and conclusions drawn concerning the code models and the ability to predict the data and data trends. Comparisons of code predictions with test data demonstrate the ability of COBRA-SFS to successfully predict temperature distributions in unconsolidated or consolidated single and multiassembly spent fuel storage systems.

  11. [A case of favourable outcome of severe acute intoxication with an animal poison after a bite by the monocled cobra].

    PubMed

    Livanov, G A; Batotsyrenkov, B V; Lodiagin, A N; Andrianov, A Iu; Kuznetsov, O A; Loladze, A T; Baranov, D V

    2014-01-01

    This paper reports a case of severe acute intoxication with an animal poison after a bite by the monocled cobra. Combined treatment including artificial lung ventilation, infusion-detoxication and desensitizing (hormonal) therapy, hemosorption, correction of metabolic disorders with cytoflavin, antibacterial therapy had positive effect on the patient's condition and ensured the favourable outcome ofpotentially lethal poisoning without the use ofa specific anti-snake venom serum. PMID:25790716

  12. Interaction of toxic venoms with the complement system

    PubMed Central

    Birdsey, Vanessa; Lindorfer, Jean; Gewurz, H.

    1971-01-01

    Thirty-nine venoms from various vertebrate and invertebrate species were tested for their ability to consume haemolytic complement (C) activity upon incubation in fresh guinea-pig serum. Nineteen had `anti-complementary' activity, and these were provisionally sorted into the following groups: Pattern I—exemplified by the Naja haje (Egyptian cobra) and six other Elapidae species (all cobras), which induced selective consumption of C3—C9, and led to formation of a stable C3—C9-consuming intermediate; Pattern II—exemplified by the Agkistrodon rhodostoma (Malayan pit viper), Bitis arietans (puff adder), Bothrops jararaca (South American pit viper), Bothrops atrox (Fer de Lance) and three other species, which induced marked consumption of C4 and C2, as well as C3—C9, but did not form a stable C3—C9-consuming intermediate; and individual animals, e.g. the Lachesis muta (bushmaster), which induced other patterns (III—VI) of complement component consumption. Active fractions of representative venoms were partially purified by ion exchange and gel filtration chromatography and their interactions with the complement system characterized further. It is anticipated that these enzymes, with a capacity to activate the complement system in unique ways, will prove to be of further experimental usefulness. PMID:4398349

  13. New and already known acanthocephalans from amphibians and reptiles in Vietnam, with keys to species of Pseudoacanthocephalus Petrochenko, 1956 (Echinorhynchidae) and Sphaerechinorhynchus Johnston and Deland, 1929 (Plagiorhynchidae).

    PubMed

    Amin, Omar M; Ha, Ngyuen Van; Heckmann, Richard A

    2008-02-01

    Adults of 2 new species in 2 orders of acanthocephalans obtained from the intestines of terrestrial amphibians and reptiles collected between 1998 and 2004 in Vietnam are described here. Pseudoacanthocephalus nguyenthileae n. sp. (Palaeacnthocephala: Echinorhynchidae) was collected from 5 species of terrestrial amphibians: (1) the common Sunda toad Bufo melanostictus Schneider (Bufonidae); (2) Paa verucospinosa (Bourret); (3) Gunther's Amoy frog Rana guentheri Boulenger; (4) Taipei frog R. taipehensis Denburgh (Ranidae), and (5) the Burmese whipping frog Polypedates mutus (Smith) (Racophoridae); as well as from the Chinese cobra Naja atra Cantor (Reptilia: Elapidae) and house gecko Hemidactylus frenatus Dumeril and Bibron (Reptilia: Gekkonidae). Sphaerechinorhynchus maximesospinus n. sp. (Plagiorhynchidae: Sphaerechinorhynchinae) was isolated from a king cobra Ophiophagus hannah (cantor) (Reptilia: Elapidae). Cystacanths of Porrorchis houdemeri (Joyeux and Baer, 1935) Schmidt and Kuntz, 1967 (Plagiorhynchidae: Porrorchinae) obtained from the mesenteries of banded krait Bungarus fasciatus (Schneider) (Reptilia: Elapidae), a paratenic host, are reported for the first time. Keys to the species of Pseudoacanthocephalus and Sphaerechinorhynchus are included. Characteristic features distinguishing the new species from related taxa include: P. nguyenthileae has 15-19 (usually 16-18) proboscis hook rows, each with 5-6 hooks that progressively increase in length and size posteriorly. The largest, intermediate, and smallest proboscis hooks of S. maximesospinus are the middle, anterior, and posterior hooks, respectively; the proboscis and neck are enclosed in a membrane. Morphometric characteristics of P. nguyenthileae show host-related variability. PMID:18372639

  14. Protease inhibitor homologues from mamba venoms: facilitation of acetylcholine release and interactions with prejunctional blocking toxins.

    PubMed

    Harvey, A L; Karlsson, E

    1982-09-01

    1 Five polypeptides, which were isolated from elapid snake venoms and which are structurally related to protease inhibitors, were tested for action on isolated biventer cervicis nerve-muscle preparations of the chick. 2 Dendrotoxin from the Eastern green mamba (Dendroaspis angusticeps) and toxins K and I from the black mamba (Dendroaspis polylepis polylepis) increased to indirect stimulation without affecting responses to exogenous acetylcholine, carbachol of KCl. 3 The two other protease inhibitor homologues, HHV-II from Ringhals cobra (Hemachatus haemachatus) and NNV-II from Cape cobra (Naja nivea) did not increase responses to nerve stimulation. Trypsin inhibitor from bovine pancreas also had no facilitatory effects on neuromuscular transmission. 4 The facilitatory toxins from mamba venoms interacted with the prejunctional blocking toxins, beta-bungarotoxin, crotoxin and notexin, but not with taipoxin. The blocking effects of beta-bungarotoxin were reduced by pretreatment with the mamba toxins, whereas the blocking actions of crotoxin and notexin were enhanced. 5 The results indicate that protease inhibitor homologues from mamba venoms form a new class of neurotoxin, which acts to increase the release of acetylcholine in response to motor nerve stimulation. 6 From the interaction studies it is concluded that the facilitatory toxins bind to motor nerve terminals at sites related to those occupied by the prejunctional blocking toxins. However, differences in interactions with individual toxins suggest that there must be several related binding sites on the nerve terminals. PMID:6751453

  15. Cross-reactivity and neutralization of Indian King cobra (Ophiophagus hannah) venom by polyvalent and monovalent antivenoms.

    PubMed

    Gowtham, Yashonandana J; Mahadeswaraswamy, Y H; Girish, K S; K, Kemparaju

    2014-07-01

    The venom of the largest venomous snake, the king cobra (Ophiophagus hannah), is still out of league for the production of therapeutic polyvalent antivenom nor it is characterized immunologically in the Indian subcontinent. In the present study, the king cobra venom is comparatively studied for the cross-reactivity/reactivity and toxicity neutralization by the locally available equine therapeutic polyvalent BSV and VB antivenoms, and monovalent antivenom (OH-IgG) prepared in rabbit. None of the two therapeutic antivenoms procured from two different firms showed any signs of cross-reactivity in terms of antigen-antibody precipitin lines in immunodouble diffusion assay; however, a weak and an insignificant cross-reactivity pattern was observed in ELISA and Western blot studies. Further, both BSV and VB antivenoms failed to neutralize proteolytic, hyaluronidase and phospholipase activities as well as toxic properties such as edema, myotoxicity and lethality of the venom. As expected, OH-IgG showed strong reactivity in immunodouble diffusion, ELISA and in Western blot analysis and also neutralized both enzyme activities as well as the toxic properties of the venom. Thus, the study provides insight into the likely measures that are to be taken in cases of accidental king cobra bites for which the Indian subcontinent is still not prepared for. PMID:24815989

  16. [Immobilization of phospholipase A2 from Central Asian cobra venom on polyamide sorbents].

    PubMed

    Akhmedzhanov, R A; Salikhova, Z T; Aripov, T F; Rakhimov, M M

    1988-01-01

    The effect of the immobilization technique and the ligand nature on catalytic properties of phospholipase A2 from the cobra venom was studied. Preparations of phospholipase A2 adsorbed on and covalently bound to polyamide sorbents were obtained. The enzyme was coupled to polyamide beads modified with glutaraldehyde. In this case only 9% of the enzyme activity was retained. The enzyme adsorbed on polyamide modified with phosphatidylethanolamine retained up to 20% of the initial activity. The binding selectivity of phospholipase A2 was maximum in case of the sorbent with a binary ligand, e. g. phosphatidylethanolamine+cytotoxin, the sorbent capacity for the bound enzyme increased 2-3 times (460-600 units/g sorbent. The specific activity of the adsorbed phospholipase A2 was 17-40 units/g sorbent in contrast to 8.6 units/g sorbent for the covalently bound enzyme. Immobilization of the enzyme on polyamide sorbents resulted in changes of the pH-optimum, sensitivity to Ca2+ ions and the character of the enzyme-substrate interactions. Heart stability of the adsorbed phospholipase A2 was lower than that of the covalently bound enzyme. However, the adsorbed enzyme can be used, for example, in affinity chromatography due to its higher specific activity, selectivity and reversibility of the sorption. PMID:3244675

  17. Gas puff Z-pinch implosions with external Bz field on COBRA

    NASA Astrophysics Data System (ADS)

    Qi, N.; de Grouchy, P.; Schrafel, P. C.; Atoyan, L.; Potter, W. M.; Cahill, A. D.; Gourdain, P.-A.; Greenly, J. B.; Hammer, D. A.; Hoyt, C. L.; Kusse, B. R.; Pikuz, S. A.; Shelkovenko, T. A.

    2014-12-01

    We present preliminary experimental results on mitigating Magneto-Rayleigh-Taylor (MRT) instabilities by applying an external Bz field. The experiments were conducted on the 1-MA, 200-ns COBRA generator at Cornell University. In the experiments, a triple-nozzle was used to produce z-pinch loads from concentric outer and inner annular gas puffs and a center gas puff column. A single coil was used to produce a Bz field in the pinch region. We have used two 4-frame 2-ns gated EUV cameras to obtain images of the imploding plasmas, in which the MRT instabilities were observed. The MRT instabilities can grow when the plasma accelerates toward the axis. With a triple gas puff (outer, inner and center puff), reduced acceleration or de-acceleration of the imploding plasma occurred when the outer puff plasma imploded onto the inner annular puff plasma resulting a relatively stable implosion. In the absent of the inner annular gas puff, the imploding outer annular plasma continued to accelerate toward the axis. Large turbulent flares at the edge of the implosion or pinch plasma were observed. The implosion was not stable. To stabilize the implosion without the inner gas puff, a Bz field was applied. This external Bz field was compressed by the outer imploding plasma shell. A relatively stable implosion was observed. Increasing the Bz field to 2-kG resulted in a relatively fatter pinch plasma.

  18. Energy Deposition before Voltage Collapse in Cylindrical Wire Arrays on COBRA

    NASA Astrophysics Data System (ADS)

    Qamar, Shaan; Greenly, John; Kusse, Bruce

    2006-10-01

    The COBRA pulsed power generator at Cornell produces 1MA pulses with 100 nsec rise times and has been used to implode cylindrical wire arrays with 8-16 wires.. Because of the design of this machine it has been possible to install an inductive voltage monitor to measure the voltage applied to the load. Upon close examination of this signal, early in the pulse, it is possible to see a precipitous drop in the voltage characteristic of the classic collapse that has been observed in single wire initiation experiments. The resistive component of this voltage signal can be extracted and coupled with load current to estimate the energy deposited in the array wires before the current is diverted from the wire cores to the coronal plasma. Results will be presented for cylindrical arrays with 8 to 16 Tungsten or Aluminum wires of several different diameters. This research was supported by DOE grant DE-FG03-98ER54496, by Sandia National Laboratories contract AO258, and by the NNSA Stockpile Stewardship Academic Alliances program under DOE Cooperative Agreement DE-FC03-02NA00057.

  19. Characterization of the COBRA triple-nozzle gas-puff valve using planar laser induced fluorescence

    NASA Astrophysics Data System (ADS)

    de Grouchy, P. W. L.; Rosenberg, E.; Qi, N.; Kusse, B. R.; Kroupp, E.; Fisher, A.; Maron, Y.; Hammer, D. A.

    2014-12-01

    We present neutral density measurements of argon (Ar) injected into the 70 mm outer diameter, 24 mm axial length, outflow region of the triple-nozzle gas-puff valve fielded for gas-puff z-pinch experiments on the (1 MA, 100-200 ns) COBRA generator at Cornell University. Measurements are obtained by planar laser induced fluorescence of (λ = 266 nm, E = 80 mJ, Δt = 3 ns) frequency-quadrupled Nd:YAG laser light, absorbed by acetone dopant introduced into the Ar at 7% by pressure. Results are acquired 500μs after valve opening, the time of current initiation during z-pinch experiments. Number density plots are obtained across the Outer (O), Inner (I) and Center (C) puffs, with nozzle backing pressures {O:I:C} = {1:3:8}psia and {4:0:10}psia, delivering `uniform' and `hollow' profiles respectively. The total mass per unit length in these puffs is 22±0.4 μgcm-1 and 47±1 μgcm-1. Density measurement precision is ±5×1015 cm-3.

  20. The COBRA experiment - Status and prospects on the search of neutrinoless double beta-decay

    NASA Astrophysics Data System (ADS)

    Zatschler, S.

    2015-10-01

    The Cadmium-Zinc-Telluride 0-ν Double Beta Research Apparatus (COBRA) [1] is a next-generation experiment searching for the existence of neutrinoless double beta-decay (0νββ-decay). The observation of 0νββ-decay would be an unambiguous sign for physics beyond the Standard Model such as lepton number violating processes and would prove the Majorana character of neutrinos. Furthermore, the study of 0νββ-decay could probe the absolute neutrino mass and allows for the identification of the neutrino mass hierarchy realized in nature assuming light Majorana neutrino exchange. Currently a demonstrator setup at the underground facility LNGS (Italy) built of 4×4×4 coplanar grid (CPG) detectors collects high quality low background physics data with FADC pulse shape sampling. The detectors are made of natural abundant CdZnTe (CZT), which is a commercially available room temperature semiconductor. It contains several double beta isotopes, the most promising of which is 116Cd with a Q-value of 2813.5 keV - which is well above the highest naturally occurring prominent γ-lines.

  1. Gas Puff Z-Pinches at 1-MA and 200-ns on COBRA

    NASA Astrophysics Data System (ADS)

    Hammer, David; Qi, Niansheng; Rosenberg, Elliott; Atoyan, Levon; Potter, William; Blesener, Kate; Cahill, Adam; Gourdain, Pierre-Alexandre; Greenly, John; Hoyt, Cad; Kusse, Bruce; Pikuz, Sergei; Schrafel, Peter; Shelkovenko, Tatiana

    2013-10-01

    We report 6-cm diameter, double-shell gas puff Z-pinch experiments at 1 MA on the COBRA pulsed power generator, in which the implosion dynamics in puff-on-puff load configurations with and without a wire on the pinch axis were studied. Diagnostics used included: Planar Laser Induced Fluorescence Analyzer for measuring initial density profiles of the gas puff; a Laser Shearing Interferometer and a Laser Wavefront Analyzer for density profiles in the implosion and pinch phases; fiber-coupled, gated visible-light spectrometers for radially resolved imploding plasma spectra; gated XUV cameras for implosion dynamics; filtered pinhole x-ray cameras for imaging x-ray emission; and a double-crystal x-ray spectrometer for axially resolved pinch plasma densities and temperatures. From these, we derived the implosion velocity, ion charge states and then the imploding plasma temperatures, obtained the time evolution of the imploding plasma sheath structure and Magnetic Rayleigh-Taylor instability, and observed the most stable implosion with light-ions (Ne) imploding on heavy-ions (Ar), unstable implosions with heavy-ions (Ar) imploding on light-ions (Ne), and tighter, denser and less hot pinch plasma with a wire on axis. Details of the results will be presented. Supported by NNSA under DOE Coop. Agreement DE- NA0001836.

  2. Double cathode experiments using radial foil configurations on the COBRA generator

    NASA Astrophysics Data System (ADS)

    Pang, B. H.; Gorenstein, A. Y.; Kim, J. E.; Gourdain, P.-A.; Hammer, D. A.; Kusse, B. R.

    2010-11-01

    As part of the Laboratory of Plasma Studies at Cornell University, our research group has been investigating the dynamics and the collision of plasma bubbles formed by the explosion of metallic foils. A 100-ns rise time 1MA current runs through an aluminum foil, five micron thick, stretched horizontally onto the anode of the COBRA pulsed power generator. Cathode contacts consist of two hollow stainless pins equally spaced about the center of the foil. The parameters of this experiment include the spacing (3 mm) and inclination of the cathode pins (parallel or at a 45 degree angle). During the explosion, plasma bubbles are formed around each pin. As the bubbles grow and collide, interesting features appear in both experiments. For the parallel cathode configuration, a plasma plume forms above the center between the two bubbles before collision occurs. The plume resembles a twisted helix. For the slanted cathode configuration a plasma sheet forms when the two bubbles collide, and possibly a shock front is formed after the collision. The sheet extends inside a vertical plane just above the foil geometrical center. The electron density of this plasma sheet is approximately 5x10^18 cm-3, and its velocity is below 150 km/s.

  3. Local envenomation from the bite of a juvenile false water cobra (Hydrodynastes gigas; Dipsadidae).

    PubMed

    Keyler, D E; Richards, D P; Warrell, D A; Weinstein, S A

    2016-03-01

    The false water cobra (Hydrodynastes gigas) is a non-front-fanged colubroid snake frequently exhibited in zoos, and maintained by amateur collectors. Little detailed documentation regarding the time-course of symptoms development and the consequences of their bites to humans has been published. Reported here is a case of envenoming in a 25 yo male that occurred after the bite of a juvenile H. gigas. The victim was bitten on the fourth digit of the left hand while processing the snake for sex determination, and the snake remained attached to the digit for approximately 30 s; there was no jaw advancement. Within 5 min, intense local pain developed, and at 4hr post bite the entire dorsal aspect of the hand was significantly edematous, The local effects progressed and involved the entire forearm, and the local pain referred to the axillary region. Mild paresthesia and local blanching ("pallor") were noted in the affected digit, but resolved within 7 days. The clinical course in the patient showed that moderate localized symptoms may result from the bite of a juvenile H.gigas. PMID:26743113

  4. Results of a search for neutrinoless double-β decay using the COBRA demonstrator

    NASA Astrophysics Data System (ADS)

    Ebert, Joachim; Fritts, M.; Gehre, Daniel; Gößling, Claus; Hagner, Caren; Heidrich, Nadine; Klingenberg, Reiner; Kröninger, Kevin; Nitsch, Christian; Oldorf, Christian; Quante, Thomas; Rajek, Silke; Rebber, Henning; Rohatsch, Katja; Tebrügge, Jan; Temminghoff, Robert; Theinert, Robert; Timm, Jan; Wonsak, Björn; Zatschler, Stefan; Zuber, Kai; Cobra Collaboration

    2016-08-01

    Neutrinoless double-β decay (0 ν β β decay) is a hypothetical process that can occur if the neutrino is its own antiparticle. The COBRA Collaboration operates a demonstrator to search for these decays at the Laboratori Nazionali del Gran Sasso in Italy using CdZnTe semiconductor detectors. The exposure of 234.7 kg d considered in this analysis was collected between September 2011 and February 2015. The analysis focuses on the decay of the nuclides 114Cd,128Te,70Zn,130Te, and 116Cd. A Bayesian analysis is performed to estimate the signal strength of 0 ν β β decay. No signal is observed for any of these nuclides. Therefore, the following half-life limits at 90% credibility are set: T1/2 0 ν>1.6 ×1021yr (114Cd),T1/2 0 ν>1.9 ×1021yr (128Te),T1/2 0 ν>6.8 ×1018yr (70Zn),T1/2 0 ν>6.1 ×1021yr (130Te), and T1/2 0 ν>1.1 ×1021yr (116Cd).

  5. Plasma Density Measurements within Tungsten Wire-Array Z-Pinches on the COBRA Accelerator

    NASA Astrophysics Data System (ADS)

    Douglass, Jon; McBride, Ryan; Bell, Kate; Knapp, Patrick; Greenly, John; Pikuz, Sergei; Shelkovenko, Tanya; Hammer, David

    2007-11-01

    The COBRA pulsed-power generator, with a nominal peak current of 1.1 MA and a minimum zero-to-peak rise-time of about 100ns, is being used to study the early phases of wire-array z-pinch development with a variety of diagnostics. Here we present the results of applying point-projection x-ray radiography to make accurate, high-resolution spatial and temporal measurements of the plasma density distributions in tungsten (W) wire-array z-pinch implosions. Density measurements are quantified by comparing x-ray transmission recorded on photographic films to transmission through W calibration steps of known thicknesses. Plasma density distributions as a function of time are presented for the coronal (10^18-10^20/cm^3), ablation (<10^18/cm^3) and on-axis (<10^19/cm^3) plasmas during the pre-stagnation phases of z-pinch dynamics (70-170 ns after the start of the current pulse). With this data set the time dependence of ablation velocity and corresponding mass ablation rate are addressed.

  6. Early time studies of cylindrical liner implosions at 1 MA on COBRA

    SciTech Connect

    Atoyan, L. Byvank, T. Cahill, A. D. Hoyt, C. L. Grouchy, P. W. L. de Potter, W. M. Kusse, B. R. Hammer, D. A.

    2014-12-15

    Tests of the magnetized liner inertial fusion (MagLIF) concept will make use of the 27 MA Z machine at Sandia National Laboratories, Albuquerque, to implode a cylindrical metal liner to compress and heat preheated, magnetized plasma contained within it. While most pulsed power machines produce much lower currents than the Z-machine, there are issues that can still be addressed on smaller scale facilities. Recent work on the Cornell Beam Research Accelerator (COBRA) has made use of 10 mm long and 4 mm diameter metal liners having different wall thicknesses to study the initiation of plasma on the liner’s surface as well as axial magnetic field compression [P.-A. Gourdain et al., Nucl. Fusion 53, 083006 (2013)]. This report presents experimental results with non-imploding liners, investigating the impact the liner’s surface structure has on initiation and ablation. Extreme ultraviolet (XUV) imaging and optical 12 frame camera imaging were used to observe and assess emission non-uniformities as they developed. Axial and side-on interferometry was used to determine the distribution of plasma near the liner surface, including the impact of non-uniformities during the plasma initiation and ablation phases of the experiments.

  7. Ice clouds optical properties in the Far Infrared from the ECOWAR-COBRA Experiment

    NASA Astrophysics Data System (ADS)

    Rizzi, Rolando; Tosi, Ennio

    ECOWAR-COBRA (Earth COoling by WAter vapouR emission -Campagna di Osservazioni della Banda Rotazionale del vapor d'Acqua) field campaign took place in Italy from 3 to 17 March 2007 with the main goal of studying the scarcely sensed atmospheric emission occurring beyond 17 microns. Instrumentation involved in the campaign included two different Fourier Transforms Spectrometers (FTS) : REFIR-PAD (at Testa Grigia Station, 3500 m a.s.l.) and FTIR-ABB (at Cervinia Station, 1990 m a.s.l.). In this work cloudy sky data have been ana-lyzed. A cloud properties retrieval methodology (RT-RET), based on high spectral resolution measurements in the atmospheric window (800-1000 cm-1), is applied to both FTS sensors. Cloud properties determined from the infrared retrievals are compared with those obtained from Raman lidar taken by the BASIL Lidar system that was operating at Cervinia station. Cloud microphysical and optical properties retrieved by RT-RET are used to perform forward simulations over the entire FTSs measurements spectral interval. Results are compared to FTS data to test the ability of single scattering ice crystals models to reproduce cloudy sky radiances in the Far Infra-Red (FIR) part of the spectrum. New methods to retrieve cloud optical and microphysical properties exploiting high spectral resolution FIR measurements are also investigated.

  8. The COBRA experiment – Status and prospects on the search of neutrinoless double beta-decay

    SciTech Connect

    Zatschler, S.

    2015-10-28

    The Cadmium-Zinc-Telluride 0-ν Double Beta Research Apparatus (COBRA) [1] is a next-generation experiment searching for the existence of neutrinoless double beta-decay (0νββ-decay). The observation of 0νββ-decay would be an unambiguous sign for physics beyond the Standard Model such as lepton number violating processes and would prove the Majorana character of neutrinos. Furthermore, the study of 0νββ-decay could probe the absolute neutrino mass and allows for the identification of the neutrino mass hierarchy realized in nature assuming light Majorana neutrino exchange. Currently a demonstrator setup at the underground facility LNGS (Italy) built of 4×4×4 coplanar grid (CPG) detectors collects high quality low background physics data with FADC pulse shape sampling. The detectors are made of natural abundant CdZnTe (CZT), which is a commercially available room temperature semiconductor. It contains several double beta isotopes, the most promising of which is {sup 116}Cd with a Q-value of 2813.5 keV – which is well above the highest naturally occurring prominent γ-lines.

  9. Functional analysis of Cobra Venom Factor/human C3 chimeras transiently expressed in mammalian cells.

    PubMed

    Kölln, Johanna; Matzas, Mark; Jänner, Nathalie; Mix, Thorsten; Klensang, Katrin; Bredehorst, Reinhard; Spillner, Edzard

    2004-05-01

    The complement activating venom component Cobra Venom Factor (CVF), a functional and structural homologue of the human complement component C3, forms a stable CVF-dependent C3 convertase complex, which, in contrast to C3-dependent convertase effects continuous activation of the complement and, thereby, decomplementation. In order to elucidate the mechanism underlying the enhanced activity of CVF compared to human C3, we generated two CVF/C3 chimeras and established different affinity-based assay systems for functional analysis of these constructs. To allow for convenient expression and subsequent functional characterisation, the CVF/C3 chimeras as well as CVF and C3 were transiently expressed in mammalian cells. Problems due to the low concentration of the recombinant proteins in the supernatants of transient expressions were circumvented by fusion to peptide tags enabling their efficient immobilisation onto suitable surfaces and subsequent characterisation. In an alternative approach monoclonal antibody fragments generated from a semisynthetic phage display scFv library were employed for concentrating the recombinant proteins by immunoprecipitation. Utilising both approaches all transiently expressed proteins could be characterised for their complement consumption activity. The data obtained with the CVF/C3 chimeras demonstrate that the increased stability of the CVFBb complex is independent of the domains in CVF corresponding to binding sites of factor B and H and the cleavage sites of factor I in the human C3 molecule. PMID:15140572

  10. Ohanin, a novel protein from king cobra venom, induces hypolocomotion and hyperalgesia in mice.

    PubMed

    Pung, Yuh Fen; Wong, Peter T H; Kumar, Prakash P; Hodgson, Wayne C; Kini, R Manjunatha

    2005-04-01

    We have identified, purified, and determined the complete amino acid sequence of a novel protein, ohanin from Ophiophagus hannah (king cobra) venom. It is a small protein containing 107 amino acid residues with a molecular mass of 11951.47 +/- 0.67 Da as assessed by electrospray ionization-mass spectrometry. It does not show similarity to any known families of snake venom proteins and hence is the first member of a new family of snake venom proteins. It shows similarity to PRY and SPRY domain proteins. It is nontoxic up to 10 mg/kg when injected intraperitoneally in mice. Ohanin produced statistically significant and dose-dependent hypolocomotion in mice. In a pain threshold assay, it showed dose-dependent hyperalgesic effect. The ability of the protein to elicit a response at greatly reduced doses when injected intracerebroventricularly as compared with intraperitoneal administration in both the locomotion and hot plate experiments strongly suggests that ohanin acts on the central nervous system. Since the natural abundance of the protein in the venom is low (approximately 1 mg/g), a synthetic gene was constructed and expressed. The recombinant protein, which was obtained in the insoluble fraction in Escherichia coli, was purified under denaturing condition and was refolded. Recombinant ohanin is structurally and functionally similar to native protein as determined by circular dichroism and hot plate assay, suggesting that it will be useful in future structure-function relationship studies. PMID:15668253

  11. Structure of a king cobra phospholipase A2 determined from a hemihedrally twinned crystal.

    PubMed

    Xu, Sujuan; Gu, Lichuan; Wang, Qiuyan; Shu, Yuyan; Song, Shiying; Lin, Zhengjiong

    2003-09-01

    An acidic PLA(2) (OH APLA(2)-II) from the venom of Ophiophagus hannah (king cobra) shows greater phospholipase A(2) activity and weaker cardiotoxic and myotoxic activity than a homologous acidic PLA(2) from the same venom. The crystal of the enzyme belongs to space group P6(3). The crystals are invariably hemihedrally twinned, exhibiting perfect 622 Laue symmetry. The structure was determined by molecular replacement and refined using a hemihedral twinning program at 2.1 A resolution. The final model has reasonable stereochemistry and a crystallographic R factor of 19.5% (R(free) = 21.5%). The structure reveals the molecular arrangement and the mode of twinning. There are six independent molecules in the asymmetric unit. Owing to the presence of a non-crystallographic twofold parallel to the hemihedral twinning twofold, the molecular packing in the twinned crystal is extremely similar to that in an untwinned crystal for four of the molecules. This unique molecular arrangement may be related to the difficulty in recognizing the twinning. The structure was compared with the previously determined structure of a homologous acidic PLA(2) from the same source. The comparison shows structural changes that might be implicated in the increased catalytic activity and weakened toxicity. PMID:12925787

  12. [Sequencing and analysis of the complete mitochondrial genome of the King Cobra, Ophiophagus hannah (Serpents: Elapidae)].

    PubMed

    Chen, Nian; Lai, Xiao-Ping

    2010-07-01

    We obtained the complete mitochondrial genome of King Cobra(GenBank accession number: EU_921899) by Ex Taq-PCR, TA-cloning and primer-walking methods. This genome is very similar to other vertebrate, which is 17 267 bp in length and encodes 38 genes (including 13 protein-coding, 2 ribosomal RNA and 23 transfer RNA genes) and two long non-coding regions. The duplication of tRNA-Ile gene forms a new mitochondrial gene rearrangement model. Eight tRNA genes and one protein genes were transcribed from L strand, and the other genes were transcribed genes from H strand. Genes on the H strand show a fairly similar content of Adenosine and Thymine respectively, whereas those on the L strand have higher proportion of A than T. Combined rDNA sequence data (12S+16S rRNA) were used to reconstruct the phylogeny of 21 snake species for which complete mitochondrial genome sequences were available in the public databases. This large data set and an appropriate range of outgroup taxa demonstrated that Elapidae is more closely related to colubridae than viperidae, which supports the traditional viewpoints. PMID:20650853

  13. Early time studies of cylindrical liner implosions at 1 MA on COBRA

    NASA Astrophysics Data System (ADS)

    Atoyan, L.; Byvank, T.; Cahill, A. D.; Hoyt, C. L.; de Grouchy, P. W. L.; Potter, W. M.; Kusse, B. R.; Hammer, D. A.

    2014-12-01

    Tests of the magnetized liner inertial fusion (MagLIF) concept will make use of the 27 MA Z machine at Sandia National Laboratories, Albuquerque, to implode a cylindrical metal liner to compress and heat preheated, magnetized plasma contained within it. While most pulsed power machines produce much lower currents than the Z-machine, there are issues that can still be addressed on smaller scale facilities. Recent work on the Cornell Beam Research Accelerator (COBRA) has made use of 10 mm long and 4 mm diameter metal liners having different wall thicknesses to study the initiation of plasma on the liner's surface as well as axial magnetic field compression [P.-A. Gourdain et al., Nucl. Fusion 53, 083006 (2013)]. This report presents experimental results with non-imploding liners, investigating the impact the liner's surface structure has on initiation and ablation. Extreme ultraviolet (XUV) imaging and optical 12 frame camera imaging were used to observe and assess emission non-uniformities as they developed. Axial and side-on interferometry was used to determine the distribution of plasma near the liner surface, including the impact of non-uniformities during the plasma initiation and ablation phases of the experiments.

  14. Studies of Cylindrical Liner Z-Pinches at 1 MA on COBRA

    NASA Astrophysics Data System (ADS)

    Atoyan, Levon; Byvank, Tom; Cahill, Adam; Potter, William; de Grouchy, Philip; Kusse, Bruce; Hammer, David

    2014-10-01

    Tests of the magnetized liner inertial fusion (MagLIF) concept will make use of the 27 MA Z-machine to implode a cylindrical metal liner onto a preheated plasma contained within it. While most pulsed power machines produce much lower currents than the Z-machine, there are questions that can be addressed on smaller scale facilities. Recent work on the 1 MA Cornell Beam Research Accelerator (COBRA) has made use of 10 mm long cylindrical metal liners having a 4 mm diameter and a varying wall thickness to study the initiation of plasma on the liner's outer surface as well as axial magnetic field compression. We will present experimental results with both imploding and non-imploding liners, investigating the impact the liner's external surface structure has on initiation, outer surface ablation, and implosion. The effect of a uniform axial external magnetic field on observed surface striations will also be discussed. This research is supported by the National Nuclear Security Administration Stewardship Sciences Academic Programs under Department of Energy Cooperative Agreement DE-NA0001836.

  15. High-Z Pusher Experiments on the Cobra Triple Nozzle Gas-Puff Z-Pinch

    NASA Astrophysics Data System (ADS)

    de Grouchy, Philip; Qi, Niansheng; Kusse, Bruce; Seyler, Charles; Atoyan, Levon; Byvank, Tom; Cahill, Adam; Greenly, John; Hoyt, Cad; Pikuz, Sergei; Shelkovenko, Tania; Hammer, David

    2014-10-01

    For inertial confinement fusion application and as efficient hard x-ray sources, the imploding sheath of a gas-puff z-pinch or thin liner must be accelerated to the highest possible velocity before hydrodynamic instabilities significantly disrupt the implosion symmetry. Much recent work has focused on increasing implosion stability using radially structured mass-density profiles produced by multi-nozzle gas-puff valves. The introduction of a high-Z element such as xenon into the outer gas shells in such experiments can modify radiation output during the implosion phase as well as at stagnation. In these experiments xenon is introduced into the triple-nozzle gas valve fielded on the (1 MA, 200 ns) COBRA z-pinch machine at Cornell University. The xenon is introduced only in the outer shell, only in the inner shell or in both, to investigate the radiative effects on implosion hydrodynamics and x-ray yield. Results are compared to those obtained during pure argon implosions with the same mass-density profile. Sheath thicknesses and stability are recorded using laser interferometry (532 nm) and multi-frame imaging systems. The distribution of flow velocities and of high-Z material across the pinch is investigated using a (5 GW, 527 nm) Thomson scattering probe. Work supported by DOE Grant No. DE-NA0001836.

  16. Improvement of COBRA-TF for modeling of PWR cold- and hot-legs during reactor transients

    NASA Astrophysics Data System (ADS)

    Salko, Robert K.

    COBRA-TF is a two-phase, three-field (liquid, vapor, droplets) thermal-hydraulic modeling tool that has been developed by the Pacific Northwest Laboratory under sponsorship of the NRC. The code was developed for Light Water Reactor analysis starting in the 1980s; however, its development has continued to this current time. COBRA-TF still finds wide-spread use throughout the nuclear engineering field, including nuclear-power vendors, academia, and research institutions. It has been proposed that extension of the COBRA-TF code-modeling region from vessel-only components to Pressurized Water Reactor (PWR) coolant-line regions can lead to improved Loss-of-Coolant Accident (LOCA) analysis. Improved modeling is anticipated due to COBRA-TF's capability to independently model the entrained-droplet flow-field behavior, which has been observed to impact delivery to the core region[1]. Because COBRA-TF was originally developed for vertically-dominated, in-vessel, sub-channel flow, extension of the COBRA-TF modeling region to the horizontal-pipe geometries of the coolant-lines required several code modifications, including: • Inclusion of the stratified flow regime into the COBRA-TF flow regime map, along with associated interfacial drag, wall drag and interfacial heat transfer correlations, • Inclusion of a horizontal-stratification force between adjacent mesh cells having unequal levels of stratified flow, and • Generation of a new code-input interface for the modeling of coolant-lines. The sheer number of COBRA-TF modifications that were required to complete this work turned this project into a code-development project as much as it was a study of thermal-hydraulics in reactor coolant-lines. The means for achieving these tasks shifted along the way, ultimately leading the development of a separate, nearly completely independent one-dimensional, two-phase-flow modeling code geared toward reactor coolant-line analysis. This developed code has been named CLAP, for

  17. Improvement of COBRA-TF for modeling of PWR cold- and hot-legs during reactor transients

    NASA Astrophysics Data System (ADS)

    Salko, Robert K.

    COBRA-TF is a two-phase, three-field (liquid, vapor, droplets) thermal-hydraulic modeling tool that has been developed by the Pacific Northwest Laboratory under sponsorship of the NRC. The code was developed for Light Water Reactor analysis starting in the 1980s; however, its development has continued to this current time. COBRA-TF still finds wide-spread use throughout the nuclear engineering field, including nuclear-power vendors, academia, and research institutions. It has been proposed that extension of the COBRA-TF code-modeling region from vessel-only components to Pressurized Water Reactor (PWR) coolant-line regions can lead to improved Loss-of-Coolant Accident (LOCA) analysis. Improved modeling is anticipated due to COBRA-TF's capability to independently model the entrained-droplet flow-field behavior, which has been observed to impact delivery to the core region[1]. Because COBRA-TF was originally developed for vertically-dominated, in-vessel, sub-channel flow, extension of the COBRA-TF modeling region to the horizontal-pipe geometries of the coolant-lines required several code modifications, including: • Inclusion of the stratified flow regime into the COBRA-TF flow regime map, along with associated interfacial drag, wall drag and interfacial heat transfer correlations, • Inclusion of a horizontal-stratification force between adjacent mesh cells having unequal levels of stratified flow, and • Generation of a new code-input interface for the modeling of coolant-lines. The sheer number of COBRA-TF modifications that were required to complete this work turned this project into a code-development project as much as it was a study of thermal-hydraulics in reactor coolant-lines. The means for achieving these tasks shifted along the way, ultimately leading the development of a separate, nearly completely independent one-dimensional, two-phase-flow modeling code geared toward reactor coolant-line analysis. This developed code has been named CLAP, for

  18. Spectroscopy and implosion dynamics of low wire number nested arrays on the 1 MA COBRA generator

    NASA Astrophysics Data System (ADS)

    Safronova, A. S.; Kantsyrev, V. L.; Esaulov, A. A.; Ouart, N. D.; Yilmaz, M. F.; Williamson, K. M.; Shrestha, I.; Osborne, G. C.; Greenly, J. B.; Chandler, K. M.; McBride, R. D.; Chalenski, D. A.; Hammer, D. A.; Kusse, B. R.; LePell, P. D.

    2008-03-01

    Low wire number nested array Z-pinch experiments have been carried out with wires made of aluminum, stainless steel (uniform), and combinations of these two materials (mixed) on the 1MA COBRA generator at Cornell University [J. D. Douglass, J. B. Greenly, D. A. Hammer et al., in Proceedings of the 15th IEEE International Pulsed Power Conference (IEEE, Piscataway, NJ, 2005)]. The outer array consisted of eight wires, whereas the inner array had four or eight wires. The 10μm Al wires were alloy 5056 and the 6.25μm stainless steel wires were alloy SS304. The diagnostic suite included fast-x-ray and extreme ultraviolet (EUV) detectors, a time-gated x-ray pinhole camera, x-ray spectrometers, and laser shadow imaging. The main focus was made on the spectroscopic study of plasma evolution after the main x-ray burst though the data from photoconducting detector (PCD) and EUV signals over the whole period of current, and in addition laser shadowgraphy images before the main x-ray burst were analyzed. Modeling of the time-gated spectra recorded after the main x-ray burst indicates that the electron temperature Te either follows the PCD signals and peaks at times of the second (and the third if present) x-ray burst or has the higher value at the first frame (closest to the main x-ray burst), then slightly changes and increases at the last frame, which coincides with the second maximum of the current. It was also found that the values of Te never drop below 150eV, and the EUV signal remains intense even when the PCD signal is almost zero.

  19. COBRA: A prospective multimodal imaging study of dopamine, brain structure and function, and cognition.

    PubMed

    Nevalainen, N; Riklund, K; Andersson, M; Axelsson, J; Ögren, M; Lövdén, M; Lindenberger, U; Bäckman, L; Nyberg, L

    2015-07-01

    Cognitive decline is a characteristic feature of normal human aging. Previous work has demonstrated marked interindividual variability in onset and rate of decline. Such variability has been linked to factors such as maintenance of functional and structural brain integrity, genetics, and lifestyle. Still, few, if any, studies have combined a longitudinal design with repeated multimodal imaging and a comprehensive assessment of cognition as well as genetic and lifestyle factors. The present paper introduces the Cognition, Brain, and Aging (COBRA) study, in which cognitive performance and brain structure and function are measured in a cohort of 181 older adults aged 64 to 68 years at baseline. Participants will be followed longitudinally over a 10-year period, resulting in a total of three equally spaced measurement occasions. The measurement protocol at each occasion comprises a comprehensive set of behavioral and imaging measures. Cognitive performance is evaluated via computerized testing of working memory, episodic memory, perceptual speed, motor speed, implicit sequence learning, and vocabulary. Brain imaging is performed using positron emission tomography with [(11)C]-raclopride to assess dopamine D2/D3 receptor availability. Structural magnetic resonance imaging (MRI) is used for assessment of white and gray-matter integrity and cerebrovascular perfusion, and functional MRI maps brain activation during rest and active task conditions. Lifestyle descriptives are collected, and blood samples are obtained and stored for future evaluation. Here, we present selected results from the baseline assessment along with a discussion of sample characteristics and methodological considerations that determined the design of the study. This article is part of a Special Issue entitled SI: Memory & Aging. PMID:25239478

  20. Viper and Cobra Venom Neutralization by Alginate Coated Multicomponent Polyvalent Antivenom Administered by the Oral Route

    PubMed Central

    Bhattacharya, Sourav; Chakraborty, Mousumi; Mukhopadhyay, Piyasi; Kundu, P. P.; Mishra, Roshnara

    2014-01-01

    Background Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals. Methodology/Principal Findings To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom. Conclusions/Significance Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra

  1. Atmospheric Oxidation of Squalene: Molecular Study Using COBRA Modeling and High-Resolution Mass Spectrometry

    SciTech Connect

    Fooshee, David R.; Aiona, Paige K.; Laskin, Alexander; Laskin, Julia; Nizkorodov, Sergey; Baldi, Pierre

    2015-10-22

    Squalene is a major component of skin and plant surface lipids, and is known to be present at high concentrations in indoor dust. Its high reactivity toward ozone makes it an important ozone sink and a natural protectant against atmospheric oxidizing agents. While the volatile products of squalene ozonolysis are known, the condensed-phase products have not been characterized. We present an analysis of condensed-phase products resulting from an extensive oxidation of squalene by ozone probed by electrospray ionization (ESI) high-resolution mass spectrometry (HR-MS). A complex distribution of nearly 1,300 peaks assignable to molecular formulas is observed in direct infusion positive ion mode ESI mass spectra. The distribution of peaks in the mass spectra suggests that there are extensive cross-coupling reactions between hydroxy-carbonyl products of squalene ozonolysis. To get additional insights into the mechanism, we apply a Computational Brewing Application (COBRA) to simulate the oxidation of squalene in the presence of ozone, and compare predicted results with those observed by the HR-MS experiments. The system predicts over one billion molecular structures between 0-1450 Da, which correspond to about 27,000 distinct elemental formulas. Over 83% of the squalene oxidation products inferred from the mass spectrometry data are matched by the simulation. Simulation indicates a prevalence of peroxy groups, with hydroxyl and ether groups being the second-most important O-containing functional groups formed during squalene oxidation. These highly oxidized products of squalene ozonolysis may accumulate on indoor dust and surfaces, and contribute to their redox capacity.

  2. Atmospheric Oxidation of Squalene: Molecular Study Using COBRA Modeling and High-Resolution Mass Spectrometry.

    PubMed

    Fooshee, David R; Aiona, Paige K; Laskin, Alexander; Laskin, Julia; Nizkorodov, Sergey A; Baldi, Pierre F

    2015-11-17

    Squalene is a major component of skin and plant surface lipids and is known to be present at high concentrations in indoor dust. Its high reactivity toward ozone makes it an important ozone sink and a natural protectant against atmospheric oxidizing agents. While the volatile products of squalene ozonolysis are known, the condensed-phase products have not been characterized. We present an analysis of condensed-phase products resulting from an extensive oxidation of squalene by ozone probed by electrospray ionization (ESI) high-resolution mass spectrometry (HR-MS). A complex distribution of nearly 1300 peaks assignable to molecular formulas is observed in direct infusion positive ion mode ESI mass spectra. The distribution of peaks in the mass spectra suggests that there are extensive cross-coupling reactions between hydroxy-carbonyl products of squalene ozonolysis. To get additional insights into the mechanism, we apply a Computational Brewing Application (COBRA) to simulate the oxidation of squalene in the presence of ozone, and compare predicted results with those observed by the HR-MS experiments. The system predicts over one billion molecular structures between 0 and 1450 Da, which correspond to about 27 000 distinct elemental formulas. Over 83% of the squalene oxidation products inferred from the mass spectrometry data are matched by the simulation. The simulation indicates a prevalence of peroxy groups, with hydroxyl and ether groups being the second-most important O-containing functional groups formed during squalene oxidation. These highly oxidized products of squalene ozonolysis may accumulate on indoor dust and surfaces and contribute to their redox capacity. PMID:26492333

  3. Brittle Culm1, a COBRA-Like Protein, Functions in Cellulose Assembly through Binding Cellulose Microfibrils

    PubMed Central

    Zhang, Baocai; Liu, Xiangling; Yan, Meixian; Zhang, Lanjun; Shi, Yanyun; Zhang, Mu; Qian, Qian; Li, Jiayang; Zhou, Yihua

    2013-01-01

    Cellulose represents the most abundant biopolymer in nature and has great economic importance. Cellulose chains pack laterally into crystalline forms, stacking into a complicated crystallographic structure. However, the mechanism of cellulose crystallization is poorly understood. Here, via functional characterization, we report that Brittle Culm1 (BC1), a COBRA-like protein in rice, modifies cellulose crystallinity. BC1 was demonstrated to be a glycosylphosphatidylinositol (GPI) anchored protein and can be released into cell walls by removal of the GPI anchor. BC1 possesses a carbohydrate-binding module (CBM) at its N-terminus. In vitro binding assays showed that this CBM interacts specifically with crystalline cellulose, and several aromatic residues in this domain are essential for binding. It was further demonstrated that cell wall-localized BC1 via the CBM and GPI anchor is one functional form of BC1. X-ray diffraction (XRD) assays revealed that mutations in BC1 and knockdown of BC1 expression decrease the crystallite width of cellulose; overexpression of BC1 and the CBM-mutated BC1s caused varied crystallinity with results that were consistent with the in vitro binding assay. Moreover, interaction between the CBM and cellulose microfibrils was largely repressed when the cell wall residues were pre-stained with two cellulose dyes. Treating wild-type and bc1 seedlings with the dyes resulted in insensitive root growth responses in bc1 plants. Combined with the evidence that BC1 and three secondary wall cellulose synthases (CESAs) function in different steps of cellulose production as revealed by genetic analysis, we conclude that BC1 modulates cellulose assembly by interacting with cellulose and affecting microfibril crystallinity. PMID:23990797

  4. Spectroscopy and implosion dynamics of low wire number nested arrays on the 1 MA COBRA generator

    SciTech Connect

    Safronova, A. S.; Kantsyrev, V. L.; Esaulov, A. A.; Ouart, N. D.; Yilmaz, M. F.; Williamson, K. M.; Shrestha, I.; Osborne, G. C.; Greenly, J. B.; Chandler, K. M.; McBride, R. D.; Chalenski, D. A.; Hammer, D. A.; Kusse, B. R.; LePell, P. D.

    2008-03-15

    Low wire number nested array Z-pinch experiments have been carried out with wires made of aluminum, stainless steel (uniform), and combinations of these two materials (mixed) on the 1 MA COBRA generator at Cornell University [J. D. Douglass, J. B. Greenly, D. A. Hammer et al., in Proceedings of the 15th IEEE International Pulsed Power Conference (IEEE, Piscataway, NJ, 2005)]. The outer array consisted of eight wires, whereas the inner array had four or eight wires. The 10 {mu}m Al wires were alloy 5056 and the 6.25 {mu}m stainless steel wires were alloy SS304. The diagnostic suite included fast-x-ray and extreme ultraviolet (EUV) detectors, a time-gated x-ray pinhole camera, x-ray spectrometers, and laser shadow imaging. The main focus was made on the spectroscopic study of plasma evolution after the main x-ray burst though the data from photoconducting detector (PCD) and EUV signals over the whole period of current, and in addition laser shadowgraphy images before the main x-ray burst were analyzed. Modeling of the time-gated spectra recorded after the main x-ray burst indicates that the electron temperature Te either follows the PCD signals and peaks at times of the second (and the third if present) x-ray burst or has the higher value at the first frame (closest to the main x-ray burst), then slightly changes and increases at the last frame, which coincides with the second maximum of the current. It was also found that the values of Te never drop below 150 eV, and the EUV signal remains intense even when the PCD signal is almost zero.

  5. Pulse-shape discrimination of surface events in CdZnTe detectors for the COBRA experiment

    NASA Astrophysics Data System (ADS)

    Fritts, M.; Tebrügge, J.; Durst, J.; Ebert, J.; Gößling, C.; Göpfert, T.; Gehre, D.; Hagner, C.; Heidrich, N.; Homann, M.; Köttig, T.; Neddermann, T.; Oldorf, C.; Quante, T.; Rajek, S.; Reinecke, O.; Schulz, O.; Timm, J.; Wonsak, B.; Zuber, K.

    2014-06-01

    Events near the cathode and anode surfaces of a coplanar grid CdZnTe detector are identifiable by means of the interaction depth information encoded in the signal amplitudes. However, the amplitudes cannot be used to identify events near the lateral surfaces. In this paper a method is described to identify lateral surface events by means of their pulse shapes. Such identification allows for discrimination of surface alpha particle interactions from more penetrating forms of radiation, which is particularly important for rare event searches. The effectiveness of the presented technique in suppressing backgrounds due to alpha contamination in the search for neutrinoless double beta decay with the COBRA experiment is demonstrated.

  6. [Localization of binding sites in rat muscles and brain for cobra neurotoxin and serum immunoglobulins from patients with myasthenia].

    PubMed

    Smirnov, V A; Vladeeva, N V; Lobzin, V S; Paniukov, A N

    1986-09-01

    Using the immunohistochemical technique, it was revealed that serum immunoglobulins of patients with myasthenia gravis (Ig) were irreversibly attached to the myoneuronal connections of the rat intercostal muscles like the marker of the nicotin cholinireceptors--the cobra venom neurotoxin (CT). In addition, Ig differs from CT in the binding to nervous cells of the claustrum and diencephalon reticular formation and with certain cells of the nucleus caudatus and hemispheric cerebral cortex. It is suggested that the autoimmune processes in patients with myasthenia gravis do not only involve myoneuronal connection but also participate in central mechanisms of the disease genesis. PMID:3756323

  7. Effect of oral supplementation of vitamin E on the hemolysis and erythrocyte phospholipid-splitting action of cobra and viper venoms.

    PubMed

    Mukherjee, A K; Ghosal, S K; Maity, C

    1998-04-01

    In the present investigation, it was found that oral supplementation of graded amounts of vitamin E to volunteers increased the alpha-tocopherol content of the erythrocytes and decreased the susceptibility of the latter to the hemolytic action of cobra and viper venoms. Further, exogenous addition of graded amounts of alpha-tocopherol to the red cells, prior to the addition of either venoms, minimizes the venom-induced lysis and erythrocyte phospholipid splitting. It may thus be inferred that vitamin E, a fat-soluble antioxidant, plays an important role in reducing the hemolytic action of cobra and viper venoms. PMID:9643479

  8. A case report of the new Polyzene™-F COBRA PzF™ Nanocoated Coronary Stent System (NCS): Addressing an unmet clinical need.

    PubMed

    Styllou, Panorea; Silber, Sigmund

    2016-01-01

    Because of anticipated antiplatelet medication risks, patients who are not DES candidates or who are at particularly high risk for bleeding events have been targeted initially for treatment with the COBRA PzF Coronary Stent System. We report the case of a successful experience with a new, Polyzene™-F COBRA PzF™ Coronary Stent System, designed to impart thrombo-resistance and reduce inflammation, to achieve shorter dual antiplatelet therapy duration while reducing restenosis incidence in a high risk patient with atrial fibrillation. PMID:26944851

  9. COBRA-LIKE2, a Member of the Glycosylphosphatidylinositol-Anchored COBRA-LIKE Family, Plays a Role in Cellulose Deposition in Arabidopsis Seed Coat Mucilage Secretory Cells1,2[OPEN

    PubMed Central

    Ben-Tov, Daniela; Abraham, Yael; Stav, Shira; Thompson, Kevin; Loraine, Ann; Elbaum, Rivka; de Souza, Amancio; Pauly, Markus; Kieber, Joseph J.; Harpaz-Saad, Smadar

    2015-01-01

    Differentiation of the maternally derived seed coat epidermal cells into mucilage secretory cells is a common adaptation in angiosperms. Recent studies identified cellulose as an important component of seed mucilage in various species. Cellulose is deposited as a set of rays that radiate from the seed upon mucilage extrusion, serving to anchor the pectic component of seed mucilage to the seed surface. Using transcriptome data encompassing the course of seed development, we identified COBRA-LIKE2 (COBL2), a member of the glycosylphosphatidylinositol-anchored COBRA-LIKE gene family in Arabidopsis (Arabidopsis thaliana), as coexpressed with other genes involved in cellulose deposition in mucilage secretory cells. Disruption of the COBL2 gene results in substantial reduction in the rays of cellulose present in seed mucilage, along with an increased solubility of the pectic component of the mucilage. Light birefringence demonstrates a substantial decrease in crystalline cellulose deposition into the cellulosic rays of the cobl2 mutants. Moreover, crystalline cellulose deposition into the radial cell walls and the columella appears substantially compromised, as demonstrated by scanning electron microscopy and in situ quantification of light birefringence. Overall, the cobl2 mutants display about 40% reduction in whole-seed crystalline cellulose content compared with the wild type. These data establish that COBL2 plays a role in the deposition of crystalline cellulose into various secondary cell wall structures during seed coat epidermal cell differentiation. PMID:25583925

  10. COBRA-SFS thermal analysis of a sealed storage cask for the Monitored Retrievable Storage of spent fuel

    SciTech Connect

    Rector, D.R.; Wheeler, C.L.

    1986-01-01

    The COBRA-SFS (Spent Fuel Storage) computer code was used to predict temperature distributions in a concrete Sealed Storage Cask (SSC). This cask was designed for the Department of Energy in the Monitored Retrievable Storage (MRS) program for storage of spent fuel from commercial power operations. Analytical results were obtained for nominal operation of the SSC with spent fuel from 36 PWR fuel assemblies consolidated in 12 cylindrical canisters. Each canister generates 1650 W of thermal power. A parametric study was performed to assess the effects on cask thermal performance of thermal conductivity of the concrete, the fin material, and the amount of radial reinforcing steel bars (rebar). Seven different cases were modeled. The results of the COBRA-SFS analysis of the current cask design predict that the peak fuel cladding temperature in the SSC will not exceed the 37/sup 0/C design limit for the maximum spent fuel load of 19.8 kW and a maximum expected ambient temperature of 37.8/sup 0/C (100/sup 0/F). The results of the parametric analyses illustrate the importance of material selection and design optimization with regard to the SSC thermal performance.

  11. Occurrence of non-protein low molecular weight cardiotoxin in Indian King Cobra (Ophiophagus hannah) Cantor 1836, venom.

    PubMed

    Saha, Archita; Gomes, Aparna; Giri, B; Chakravarty, A K; Biswas, A K; Dasgupta, S C; Gomes, A

    2006-04-01

    Pathophysiology due to snakebite is a combined effect of various actions of the complex venom constituents. Importance of protein toxins in snake envenomation is well known. The present investigation reports the existence of nonprotein/nonpetide low molecular weight toxin in Indian King Cobra venom, which plays an important role in envenomation consequences in experimental animal models. A group of non-peptidic toxins (OH-NPT1) was isolated from Indian King Cobra Ophiophagus hannah by thin layer chromatography and silica gel column chromatography. UV, IR, NMR and (ESI) TOF-MS studies characterized the OH-NPT1 as a mixture of aliphatic acids having molecular weights 256, 326 and 340Da. The minimum lethal dose of OH-NPT1 was found to be 2.5 microg/20g (iv) and 4microg/20g (ip) in male albino mice. The cardiotoxic property of OH-NPT1 was established through studies on isolated guinea pig heart and auricle preparations, ECG studies in albino rat and estimation of LDH1/LDH and CPK-MB/CPK ratio in Swiss albino mice. Commercial antiserum failed to neutralize the lethality and cardiotoxicity of the toxin. However, calcium and magnesium effectively neutralized the lethal action. PMID:16629369

  12. Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics.

    PubMed

    Melani, Rafael D; Skinner, Owen S; Fornelli, Luca; Domont, Gilberto B; Compton, Philip D; Kelleher, Neil L

    2016-07-01

    Characterizing whole proteins by top-down proteomics avoids a step of inference encountered in the dominant bottom-up methodology when peptides are assembled computationally into proteins for identification. The direct interrogation of whole proteins and protein complexes from the venom of Ophiophagus hannah (king cobra) provides a sharply clarified view of toxin sequence variation, transit peptide cleavage sites and post-translational modifications (PTMs) likely critical for venom lethality. A tube-gel format for electrophoresis (called GELFrEE) and solution isoelectric focusing were used for protein fractionation prior to LC-MS/MS analysis resulting in 131 protein identifications (18 more than bottom-up) and a total of 184 proteoforms characterized from 14 protein toxin families. Operating both GELFrEE and mass spectrometry to preserve non-covalent interactions generated detailed information about two of the largest venom glycoprotein complexes: the homodimeric l-amino acid oxidase (∼130 kDa) and the multichain toxin cobra venom factor (∼147 kDa). The l-amino acid oxidase complex exhibited two clusters of multiproteoform complexes corresponding to the presence of 5 or 6 N-glycans moieties, each consistent with a distribution of N-acetyl hexosamines. Employing top-down proteomics in both native and denaturing modes provides unprecedented characterization of venom proteoforms and their complexes. A precise molecular inventory of venom proteins will propel the study of snake toxin variation and the targeted development of new antivenoms or other biotherapeutics. PMID:27178327

  13. Venom Proteomics of Indonesian King Cobra, Ophiophagus hannah: Integrating Top-Down and Bottom-Up Approaches.

    PubMed

    Petras, Daniel; Heiss, Paul; Süssmuth, Roderich D; Calvete, Juan J

    2015-06-01

    We report on the first application of top-down mass spectrometry in snake venomics. De novo sequence tags generated by, and ProSight Lite supported analysis of, combined collisional based dissotiations (CID and HCD) recorded in a hybrid LTQ Orbitrap instrument in data-dependent mode identified a number of proteins from different toxin families, namely, 11 three-finger toxins (7-7.9 kDa), a Kunitz-type inhibitor (6.3 kDa), ohanin (11.9 kDa), a novel phospholipase A2 molecule (13.8 kDa), and the cysteine-rich secretory protein (CRISP) ophanin (25 kDa) from Indonesian king cobra venom. Complementary bottom-up MS/MS analyses contributed to the completion of a locus-resolved venom phenotypic map for Ophiophagus hannah, the world's longest venomous snake and a species of medical concern across its wide distribution range in forests from India to Southeast Asia. Its venom composition, comprising 32-35 proteins/peptides from 10 protein families, is dominated by α-neurotoxins and convincingly explains the main neurotoxic effects of human envenoming caused by king cobra bite. The integration of efficient chromatographic separation of the venom's components and locus-resolved toxin identification through top-down and bottom-up MS/MS-based species-specific database searching and de novo sequencing holds promise that the future will be bright for the field of venom research. PMID:25896403

  14. Mad, bad and dangerous to know: the biochemistry, ecology and evolution of slow loris venom

    PubMed Central

    2013-01-01

    Only seven types of mammals are known to be venomous, including slow lorises (Nycticebus spp.). Despite the evolutionary significance of this unique adaptation amongst Nycticebus, the structure and function of slow loris venom is only just beginning to be understood. Here we review what is known about the chemical structure of slow loris venom. Research on a handful of captive samples from three of eight slow loris species reveals that the protein within slow loris venom resembles the disulphide-bridged heterodimeric structure of Fel-d1, more commonly known as cat allergen. In a comparison of N. pygmaeus and N. coucang, 212 and 68 compounds were found, respectively. Venom is activated by combining the oil from the brachial arm gland with saliva, and can cause death in small mammals and anaphylactic shock and death in humans. We examine four hypotheses for the function of slow loris venom. The least evidence is found for the hypothesis that loris venom evolved to kill prey. Although the venom’s primary function in nature seems to be as a defense against parasites and conspecifics, it may also serve to thwart olfactory-orientated predators. Combined with numerous other serpentine features of slow lorises, including extra vertebra in the spine leading to snake-like movement, serpentine aggressive vocalisations, a long dark dorsal stripe and the venom itself, we propose that venom may have evolved to mimic cobras (Naja sp.). During the Miocene when both slow lorises and cobras migrated throughout Southeast Asia, the evolution of venom may have been an adaptive strategy against predators used by slow lorises as a form of Müllerian mimicry with spectacled cobras. PMID:24074353

  15. Mad, bad and dangerous to know: the biochemistry, ecology and evolution of slow loris venom.

    PubMed

    Nekaris, K Anne-Isola; Moore, Richard S; Rode, E Johanna; Fry, Bryan G

    2013-01-01

    Only seven types of mammals are known to be venomous, including slow lorises (Nycticebus spp.). Despite the evolutionary significance of this unique adaptation amongst Nycticebus, the structure and function of slow loris venom is only just beginning to be understood. Here we review what is known about the chemical structure of slow loris venom. Research on a handful of captive samples from three of eight slow loris species reveals that the protein within slow loris venom resembles the disulphide-bridged heterodimeric structure of Fel-d1, more commonly known as cat allergen. In a comparison of N. pygmaeus and N. coucang, 212 and 68 compounds were found, respectively. Venom is activated by combining the oil from the brachial arm gland with saliva, and can cause death in small mammals and anaphylactic shock and death in humans. We examine four hypotheses for the function of slow loris venom. The least evidence is found for the hypothesis that loris venom evolved to kill prey. Although the venom's primary function in nature seems to be as a defense against parasites and conspecifics, it may also serve to thwart olfactory-orientated predators. Combined with numerous other serpentine features of slow lorises, including extra vertebra in the spine leading to snake-like movement, serpentine aggressive vocalisations, a long dark dorsal stripe and the venom itself, we propose that venom may have evolved to mimic cobras (Naja sp.). During the Miocene when both slow lorises and cobras migrated throughout Southeast Asia, the evolution of venom may have been an adaptive strategy against predators used by slow lorises as a form of Müllerian mimicry with spectacled cobras. PMID:24074353

  16. Development of uncertainty methodology for COBRA-TF void distribution and critical power predictions

    NASA Astrophysics Data System (ADS)

    Aydogan, Fatih

    specimens among the sample with a bias lower than the experimental uncertainty. Besides, the rankings of dominant phenomena are observed with the second comparison method (sensitivity analysis). Simple Random Sampling, Order Statistics, Richardson Extrapolation are some of the methods that are in the developed methodology. This uncertainty methodology was implemented for the COBRA-TF predictions. The uncertainty and sensitivity results are presented in the dissertation.

  17. Oxidative stress-induced methemoglobinemia is the silent killer during snakebite: a novel and strategic neutralization by melatonin.

    PubMed

    Sharma, Rachana D; Katkar, Gajanan D; Sundaram, Mahalingam S; Paul, Manoj; NaveenKumar, Somanathapura K; Swethakumar, Basavarajaiah; Hemshekhar, Mahadevappa; Girish, Kesturu S; Kemparaju, Kempaiah

    2015-09-01

    Oxidative stress-induced methemoglobinemia remained an untouched area in venom pharmacology till date. This study for the first time explored the potential of animal venoms to oxidize hemoglobin to methemoglobin. In in vitro whole-blood assay, methemoglobin forming ability of venoms varied as Naja naja > Ophiophagus hannah > Echis carinatus > Daboia russellii > Apis mellifera > Mesobuthus tamulus > Hippasa partita. Being highly potential, N. naja venom was further studied to observe methemoglobin formation in RBCs and in combinations with PMNs and PBMCs, where maximum effect was observed in RBCs + PMNs combination. Naja naja venom/externally added methemoglobin-induced methemoglobin formation was in parallel with ROS generation in whole blood/RBCs/RBCs + PMNs/RBCs + PBMCs. In in vivo studies, the lethal dose (1 mg/kg body weight, i.p.) of N. naja venom readily induced methemoglobin formation, ROS generation, expression of inflammatory markers, and hypoxia-inducible factor-3α. Although the mice administered with three effective doses of antivenom recorded zero mortality; the methemoglobin and ROS levels remained high. However, one effective dose of antivenom when administered along with melatonin (1:50; venom/melatonin, w/w), not only offered 100% survival of experimental mice, but also significantly reduced methemoglobin level, and oxidative stress markers including hypoxia-inducible factor-3α. This study provides strong drive that, complementing melatonin would not only reduce the antivenom load, but for sure greatly increase the success rate of antivenom therapy and drastically minimize the global incidence of snakebite deaths. However, further detailed investigations are needed before translating the combined therapy towards the bed side. PMID:26103459

  18. Evaluation of the Sub-Channel Code COBRA-TF for Prediction of BWR Fuel Assembly Void Fraction Distribution

    SciTech Connect

    Aydogan, Fatih; Hochreiter, Lawrence E.; Ivanov, Kostadin; Rhee, Gene; Sartori, Enrico

    2006-07-01

    Good quality experimental data is needed to refine the thermal hydraulic models for the prediction of rod bundle void distribution and critical heat flux (CHF) or dry-out. The Nuclear Power Engineering Corporation (NUPEC) has provided a valuable database to evaluate the thermal hydraulic codes [1]. Part of this database was selected for the NUPEC BWR Full-size Fine-Mesh Bundle Tests (BFBT) benchmark sponsored by US NRC, METI-Japan, NEA/OECD and Nuclear Engineering Program of the Pennsylvania State University (PSU). Twenty-five organizations from ten countries have confirmed their intention to participate and will provide code predictions to be compared to the measured data for a series of defined exercises within the framework of the BFBT benchmark. This benchmark data includes both the fine-mesh high quality sub-channel void fraction and critical power data. Using a full BWR rod bundle test facility, the void distribution was measured at mesh sizes smaller than the sub-channel by using a state-of-the-art computer tomography (CT) technology [1]. Experiments were performed for different pressures, flow rates, exit qualities, inlet sub-cooling, power distributions, spacer types and assembly designs. There are microscopic and sub-channel averaged void fraction data from the CT scanner at the bundle exit as well as X-ray densitometer void distribution data at different elevation levels in the rod bundle. Each sub-channel's loss coefficient was calculated with using the Rehme method [2,3], and a COBRA-TF sub-channel model was developed for the NUPEC facility. The BWR assembly that was modeled with COBRA-TF includes two water rods at the center. The predicted sub-channel void fraction values from COBRA-TF are compared with the bundle exit void fraction values measured using the CT-scanner void fraction from the BFBT benchmark data. Different plots are used to examine the code prediction of the void distribution at a sub-channel level for the different sub-channels within

  19. Anti-necrosis potential of polyphenols against snake venoms.

    PubMed

    Leanpolchareanchai, Jiraporn; Pithayanukul, Pimolpan; Bavovada, Rapepol

    2009-01-01

    Polyphenols from the extracts of Areca catechu L. and Quercus infectoria Oliv. inhibited phospholipase A(2), proteases, hyaluronidase and L-amino acid oxidase of Naja naja kaouthia Lesson (NK) and Calloselasma rhodostoma Kuhl (CR) venoms by in vitro tests. Both extracts inhibited the hemorrhagic activity of CR venom and the dermonecrotic activity of NK venom by in vivo tests. The inhibitory activity of plant polyphenols against local tissue necrosis induced by snake venoms may be caused by inhibition of inflammatory reactions, hemorrhage, and necrosis. The result implies the therapeutic potential of plant polyphenols against necrosis in snakebite victims. PMID:19874222

  20. Development of burnup dependent fuel rod model in COBRA-TF

    NASA Astrophysics Data System (ADS)

    Yilmaz, Mine Ozdemir

    The purpose of this research was to develop a burnup dependent fuel thermal conductivity model within Pennsylvania State University, Reactor Dynamics and Fuel Management Group (RDFMG) version of the subchannel thermal-hydraulics code COBRA-TF (CTF). The model takes into account first, the degradation of fuel thermal conductivity with high burnup; and second, the fuel thermal conductivity dependence on the Gadolinium content for both UO2 and MOX fuel rods. The modified Nuclear Fuel Industries (NFI) model for UO2 fuel rods and Duriez/Modified NFI Model for MOX fuel rods were incorporated into CTF and fuel centerline predictions were compared against Halden experimental test data and FRAPCON-3.4 predictions to validate the burnup dependent fuel thermal conductivity model in CTF. Experimental test cases from Halden reactor fuel rods for UO2 fuel rods at Beginning of Life (BOL), through lifetime without Gd2O3 and through lifetime with Gd 2O3 and a MOX fuel rod were simulated with CTF. Since test fuel rod and FRAPCON-3.4 results were based on single rod measurements, CTF was run for a single fuel rod surrounded with a single channel configuration. Input decks for CTF were developed for one fuel rod located at the center of a subchannel (rod-centered subchannel approach). Fuel centerline temperatures predicted by CTF were compared against the measurements from Halden experimental test data and the predictions from FRAPCON-3.4. After implementing the new fuel thermal conductivity model in CTF and validating the model with experimental data, CTF model was applied to steady state and transient calculations. 4x4 PWR fuel bundle configuration from Purdue MOX benchmark was used to apply the new model for steady state and transient calculations. First, one of each high burnup UO2 and MOX fuel rods from 4x4 matrix were selected to carry out single fuel rod calculations and fuel centerline temperatures predicted by CTF/TORT-TD were compared against CTF /TORT-TD /FRAPTRAN

  1. Measurements and modelling of tropospheric bromine monoxide for the Canadian Arctic within the COBRA-IPY project

    NASA Astrophysics Data System (ADS)

    Oetjen, H.; Mahajan, A. S.; Plane, J. M. C.; Begoin, M.; Richter, A.

    2009-04-01

    In February and March 2008, a 5 week-long field campaign took place at the Centre d'études nordique research station in Kuujjuarapik (55°N) at the Hudson Bay, Canada. The aim of this project (COBRA) was to study the impact of combined iodine and bromine release on the Arctic atmosphere within the frame of the International Polar Year (IPY) programme. Significantly enhanced BrO concentrations of up to 30 ppt could be observed during a so-called bromine explosion event. Here, ground-based measurements are presented from two differential optical absorption spectroscopy (DOAS) instruments: a long path DOAS and a multi-axis DOAS. The time series of the retrieved BrO column densities, surface concentrations and vertical profiles will be compared to satellite data from SCIAMACHY and GOME-2 as well as to model simulations.

  2. Optical streak camera images of wire-array z-pinches on the 1-MA COBRA pulsed power generator

    NASA Astrophysics Data System (ADS)

    McBride, Ryan; Pikuz, Sergei; Blesener, Isaac; Zhao, Yu Tao; Greenly, John; Hammer, David; Kusse, Bruce

    2006-10-01

    Initial optical streak camera imaging experiments of wire array z-pinches on the 1 MA COBRA pulsed power generator are presented. The imaging system makes use of a Hamamatsu C7700 streak unit, which is coupled to a V7669-06 image intensifier with an MCP, and a C4742-98 CCD camera. A long focal length optical system is employed to relay the z-pinch produced light from the experiment chamber to the input slit of the streak camera -- a total transmission distance of approximately 14 m. The optical streak camera images produced, along with data from other supporting diagnostics, are presented for z-pinch implosions of various wire array geometries and materials.

  3. Experimental r-θ density profiles of wire-array and cylindrical foil Z-pinches on COBRA

    NASA Astrophysics Data System (ADS)

    Blesener, Isaac; Greenly, John; Pikuz, Sergey; Shelkovenko, Tatiana; Kusse, Bruce; Seyler, Charles

    2010-11-01

    Calibrated r-θ ion density profiles from wire-array and cylindrical foil experiments on the 1-MA COBRA machine will be presented. Profiles are axially averaged over the 1-cm height of the array. The data was gathered using an axial X pinch backlighter.ootnotetextI.C. Blesener et al., ``Axial x-ray backlighting of wire-array Z-pinches using X pinches'', Rev. Sci. Instrum. 80, 123505 (2009). Images have better than 5-micron resolution with calibrated ion densities from 10^18 to 10^20 cm-3. The latest data will be presented, comparing the timing and development of ablation streams and precursor formation between wire-arrays and cylindrical foils. Experimental data will also be compared to simulation results.

  4. Experimental Analysis of Steady-State Maneuvering Effects on Transmission Vibration Patterns Recorded in an AH-1 Cobra Helicopter

    NASA Technical Reports Server (NTRS)

    Huff, Edward M.; Dzwonczyk, Mark; Norvig, Peter (Technical Monitor)

    2000-01-01

    Flight experiment was designed primarily to determine the extent to which steady-state maneuvers influence characteristic vibration patterns measured at the input pinion and output annulus gear locations of the main transmission. If results were to indicate that maneuvers systematically influence vibration patterns, more extensive studies would be planned to explore the response surface. It was also designed to collect baseline data for comparison with experimental data to be recorded at a later date from test stands at Glenn Research Center. Finally, because this was the first vibration flight study on the Cobra aircraft, considerable energy was invested in developing an in-flight recording apparatus, as well as exploring acceleration mounting methods, and generally learning about the overall vibratory characteristics of the aircraft itself.

  5. Biobankers: Treat the Poison of Invisibility with CoBRA, a Systematic Way of Citing Bioresources in Journal Articles

    PubMed Central

    Calzolari, Alessia; Cambon-Thomsen, Anne; Mabile, Laurence; Rossi, Anna Maria; De Castro, Paola; Bravo, Elena

    2016-01-01

    Even though an increasing portion of biomedical research today relies on the use of bioresources, at present biobankers are not able to trace this use in scientific literature and measure its impact with a variety of citation metrics. The “BRIF (Bioresource Research Impact Factor) and journal editors” subgroup was created precisely with the aim to study this issue and to build a standardized system to cite bioresources in journal articles. This report aims at presenting a guideline for Citation of BioResources in journal Articles (CoBRA). The guideline offers for the first time a standard for citing bioresources (including biobanks) within journal articles. It will increase their visibility and promote their sharing. PMID:27314833

  6. Biobankers: Treat the Poison of Invisibility with CoBRA, a Systematic Way of Citing Bioresources in Journal Articles.

    PubMed

    Napolitani, Federica; Calzolari, Alessia; Cambon-Thomsen, Anne; Mabile, Laurence; Rossi, Anna Maria; De Castro, Paola; Bravo, Elena

    2016-08-01

    Even though an increasing portion of biomedical research today relies on the use of bioresources, at present biobankers are not able to trace this use in scientific literature and measure its impact with a variety of citation metrics. The "BRIF (Bioresource Research Impact Factor) and journal editors" subgroup was created precisely with the aim to study this issue and to build a standardized system to cite bioresources in journal articles. This report aims at presenting a guideline for Citation of BioResources in journal Articles (CoBRA). The guideline offers for the first time a standard for citing bioresources (including biobanks) within journal articles. It will increase their visibility and promote their sharing. PMID:27314833

  7. Antibacterial action of a heat-stable form of L-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom.

    PubMed

    Lee, Mui Li; Tan, Nget Hong; Fung, Shin Yee; Sekaran, Shamala Devi

    2011-03-01

    The major l-amino acid oxidase (LAAO, EC 1.4.3.2) of king cobra (Ophiophagus hannah) venom is known to be an unusual form of snake venom LAAO as it possesses unique structural features and unusual thermal stability. The antibacterial effects of king cobra venom LAAO were tested against several strains of clinical isolates including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli using broth microdilution assay. For comparison, the antibacterial effects of several antibiotics (cefotaxime, kanamycin, tetracycline, vancomycin and penicillin) were also examined using the same conditions. King cobra venom LAAO was very effective in inhibiting the two Gram-positive bacteria (S. aureus and S. epidermidis) tested, with minimum inhibitory concentration (MIC) of 0.78μg/mL (0.006μM) and 1.56μg/mL (0.012μM) against S. aureus and S. epidermidis, respectively. The MICs are comparable to the MICs of the antibiotics tested, on a weight basis. However, the LAAO was only moderately effective against three Gram-negative bacteria tested (P. aeruginosa, K. pneumoniae and E. coli), with MIC ranges from 25 to 50μg/mL (0.2-0.4μM). Catalase at the concentration of 1mg/mL abolished the antibacterial effect of LAAO, indicating that the antibacterial effect of the enzyme involves generation of hydrogen peroxide. Binding studies indicated that king cobra venom LAAO binds strongly to the Gram-positive S. aureus and S. epidermidis, but less strongly to the Gram-negative E. coli and P. aeruginosa, indicating that specific binding to bacteria is important for the potent antibacterial activity of the enzyme. PMID:21059402

  8. Comparative analysis of the venom proteome of four important Malaysian snake species

    PubMed Central

    2014-01-01

    Background Naja kaouthia, Ophiophagus hannah, Bungarus fasciatus and Calloselasma rhodostoma are four venomous snakes indigenous to Malaysia. In the present study, their proteomic profile by two-dimensional gel electrophoresis (2-DE) have been separated and compared. Results The 2-DE of venoms of the four species snake demonstrated complexity and obvious interspecies differences in proteome profiles. A total of 63 proteins were identified in the four species: C. rhodostoma – 26, N. kaouthia – 16, O. hannah – 15 and B. fasciatus – 6. Conclusions Despite the identifications of major proteins in the four snake species, a large number of protein spots from the 2-DE were unidentified even though the spots displayed high-quality MALDI-TOF-MS spectra. Those identified included phospholipase A2 proteins in all four venoms, long neurotoxins in both cobra species and the C. rhodostoma venom found with the most varied types of peptidases, i.e. metalloproteinase kistomin, halystase and L-amino acid oxidase. PMID:24593956

  9. Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex

    PubMed Central

    Barnwal, Bhaskar; Jobichen, Chacko; Girish, Vallerinteavide Mavelli; Foo, Chun Shin; Sivaraman, J.; Kini, R. Manjunatha

    2016-01-01

    Anticoagulant therapy is used for the prevention and treatment of thromboembolic disorders. Blood coagulation is initiated by the interaction of factor VIIa (FVIIa) with membrane-bound tissue factor (TF) to form the extrinsic tenase complex which activates FX to FXa. Thus, it is an important target for the development of novel anticoagulants. Here, we report the isolation and characterization of a novel anticoagulant ringhalexin from the venom of Hemachatus haemachatus (African Ringhals Cobra). Amino acid sequence of the protein indicates that it belongs to the three-finger toxin family and exhibits 94% identity to an uncharacterized Neurotoxin-like protein NTL2 from Naja atra. Ringhalexin inhibited FX activation by extrinsic tenase complex with an IC50 of 123.8 ± 9.54 nM. It is a mixed-type inhibitor with the kinetic constants, Ki and Ki’ of 84.25 ± 3.53 nM and 152.5 ± 11.32 nM, respectively. Ringhalexin also exhibits a weak, irreversible neurotoxicity on chick biventer cervicis muscle preparations. Subsequently, the three-dimensional structure of ringhalexin was determined at 2.95 Å resolution. This study for the first time reports the structure of an anticoagulant three-finger toxin. Thus, ringhalexin is a potent inhibitor of the FX activation by extrinsic tenase complex and a weak, irreversible neurotoxin. PMID:27173146

  10. The structure and behavior of the NA-CATH antimicrobial peptide with liposomes.

    PubMed

    Du, Haijuan; Samuel, Robin L; Massiah, Michael A; Gillmor, Susan D

    2015-10-01

    Naja atra cathelicidin (NA-CATH) is a 34-amino acid highly cationic peptide identified in Chinese cobras to possess potent toxicity against gram-negative and gram-positive bacteria and low toxicity against host cells. Here, we report the NMR solution structure of the full-length NA-CATH peptide and its interaction with liposomes. The structure shows a well-defined α-helix between residues Phe3 to Lys23, on which one surface is lined by the side-chains of one arginine and 11 lysine residues, while the other side is populated by hydrophobic residues. The last eleven amino acids, which are predominately aromatic and hydrophobic in nature, have no defined structure. NMR data reveal that these residues do not interact with the hydrophobic residues of the helix, indicating that the C-terminal residues have random conformations. Fluorescence requenching experiments, in which liposomes serve as a mimic of the bacterial membranes, result in fluorophore leakage that is consistent with a membrane thinning or transient pore formation mechanism. NMR titration studies of the peptide-liposome interaction reveal that the peptide is in fast exchange with the liposome, consistent with the fluorescent studies. These data indicate that full length NA-CATH possesses a helical segment and unstructured C-terminal tail that disrupts the bilayer to induce leakage and lysing. PMID:26205847

  11. Public health aspects of snakebite care in West Africa: perspectives from Nigeria.

    PubMed

    Habib, Abdulrazaq G

    2013-01-01

    Snakebite envenoming is a major public health problem among rural communities of the Nigerian savanna. The saw-scaled or carpet viper (Echis ocellatus) and, to a lesser extent, the African cobras (Naja spp.) and puff adders (Bitis arietans) have proved to be the most important cause of mortality and morbidity. The main clinical features of E. ocellatus envenoming are systemic hemorrhage, incoagulable blood, shock, local swelling, bleeding and, occasionally, necrosis. Bites may be complicated by amputation, blindness, disability, disfigurement, mutilation, tissue destruction and psychological consequences. Antivenom remains the hallmark and mainstay of envenoming management while studies in Nigeria confirm its protection of over 80% against mortality from carpet-viper bites. However, the availability, distribution and utilization of antivenom remain challenging although two new antivenoms (monospecific EchiTab G and trispecific EchiTab ICP-Plus) derived from Nigerian snake venoms have proven very effective and safe in clinical trials. A hub-and-spoke strategy is suggested for broadening antivenom access to endemic rural areas together with instituting quality assurance, standardization and manpower training. With the advent of antivenomics, national health authorities must be aided in selecting and purchasing antivenoms appropriate to their national needs while manufacturers should be helped in practical ways to improve the safety, efficacy and potential coverage against snake venoms and pricing of their products. PMID:24134780

  12. Public health aspects of snakebite care in West Africa: perspectives from Nigeria

    PubMed Central

    2013-01-01

    Snakebite envenoming is a major public health problem among rural communities of the Nigerian savanna. The saw-scaled or carpet viper (Echis ocellatus) and, to a lesser extent, the African cobras (Naja spp.) and puff adders (Bitis arietans) have proved to be the most important cause of mortality and morbidity. The main clinical features of E. ocellatus envenoming are systemic hemorrhage, incoagulable blood, shock, local swelling, bleeding and, occasionally, necrosis. Bites may be complicated by amputation, blindness, disability, disfigurement, mutilation, tissue destruction and psychological consequences. Antivenom remains the hallmark and mainstay of envenoming management while studies in Nigeria confirm its protection of over 80% against mortality from carpet-viper bites. However, the availability, distribution and utilization of antivenom remain challenging although two new antivenoms (monospecific EchiTab G and trispecific EchiTab ICP-Plus) derived from Nigerian snake venoms have proven very effective and safe in clinical trials. A hub-and-spoke strategy is suggested for broadening antivenom access to endemic rural areas together with instituting quality assurance, standardization and manpower training. With the advent of antivenomics, national health authorities must be aided in selecting and purchasing antivenoms appropriate to their national needs while manufacturers should be helped in practical ways to improve the safety, efficacy and potential coverage against snake venoms and pricing of their products. PMID:24134780

  13. Identification and characterization of novel reptile cathelicidins from elapid snakes.

    PubMed

    Zhao, Hui; Gan, Tong-Xiang; Liu, Xiao-Dong; Jin, Yang; Lee, Wen-Hui; Shen, Ji-Hong; Zhang, Yun

    2008-10-01

    Three cDNA sequences coding for elapid cathelicidins were cloned from constructed venom gland cDNA libraries of Naja atra, Bungarus fasciatus and Ophiophagus hannah. The open reading frames of the cloned elapid cathelicidins were all composed of 576bp and coded for 191 amino acid residue protein precursors. Each of the deduced elapid cathelicidin has a 22 amino acid residue signal peptide, a conserved cathelin domain of 135 amino acid residues and a mature antimicrobial peptide of 34 amino acid residues. Unlike the highly divergent cathelicidins in mammals, the nucleotide and deduced protein sequences of the three cloned elapid cathelicidins were remarkably conserved. All the elapid mature cathelicidins were predicted to be cleaved at Valine157 by elastase. OH-CATH, the deduced mature cathelicidin from king cobra, was chemically synthesized and it showed strong antibacterial activity against various bacteria with minimal inhibitory concentration of 1-20microg/ml in the presence of 1% NaCl. Meanwhile, the synthetic peptide showed no haemolytic activity toward human red blood cells even at a high dose of 200microg/ml. Phylogenetic analysis of cathelicidins from vertebrate suggested that elapid and viperid cathelicidins were grouped together in the tree. Snake cathelicidins were evolutionary closely related to the neutrophilic granule proteins (NGPs) from mouse, rat and rabbit. Snake cathelicidins also showed a close relationship with avian fowlicidins (1-3) and chicken myeloid antimicrobial peptide 27. Elapid cathelicidins might be used as models for the development of novel therapeutic drugs. PMID:18620012

  14. High-affinity selective inhibitor against phospholipase A2 (PLA2): a computational study.

    PubMed

    Chinnasamy, Sathishkumar; Chinnasamy, Selvakkumar; Muthusamy, Karthikeyan

    2016-04-01

    Phospholipase A2 (PLA2) is the most abundant protein found in snake venom. PLA2 induces a variety of pharmacological effects such as neurotoxicity, myotoxicity and cardiotoxicity as well as anticoagulant, hemolytic, anti-platelet, hypertensive, hemorrhagic and edema inducing effects. In this study, the three dimensional structure of PLA2 of Naja sputatrix (Malayan spitting cobra) was modeled by I-TASSER, SWISS-MODEL, PRIME and MODELLER programs. The best model was selected based on overall stereo-chemical quality. Further, molecular dynamics simulation was performed to know the stability of the modeled protein using Gromacs software. Average structure was generated during the simulation period of 10 ns. High throughput virtual screening was employed through different databases (Asinex, Hit finder, Maybridge, TOSLab and ZINC databases) against PLA2. The top seven compounds were selected based on the docking score and free energy binding calculations. These compounds were analyzed by quantum polarized ligand docking, induced fit docking and density functional theory calculation. Furthermore, the stability of lead molecules in the active site of PLA2 was employed by MD simulation. The results show that selected lead molecules were highly stable in the active site of PLA2. PMID:26422703

  15. Epidemiology of snakebite in Eshowe, KwaZulu-Natal, South Africa.

    PubMed

    Blaylock, Roger

    2004-02-01

    Three hundred and thirty-three patients admitted to Eshowe Hospital with snakebite were analysed. Forty-one were non-envenomed, 282 exhibited painful progressive swelling (PPS), seven showed progressive weakness (PW), and there were three cases of minor envenomations that were unclassifiable. Offending dead venomous snakes included Naja mossambica (Mozambique spitting cobra), Bitis arietans (puff adder), Atractaspis bibronii (stiletto snake), Causus rhombeatus (common night adder) and Dendroaspis polylepis (black mamba). Most bites occurred on the leg in the wet summer months during the first three decades of the patients' lives. The majority of patients used a first-aid measure. The snake was most commonly sighted if the patient was bitten on an upper limb or above the ankle. Severe envenomation was associated with quicker arrival at hospital, and multiple bites occurred more frequently in sleeping patients. Non-envenomation following snakebites was more common in winter, in adult females, and if the patient was bitten proximally on a limb or on a hand. Patients with PPS developed bite site complications (42), compartment syndromes (4), femoral vessel entrapment (1), deep vein thrombosis (1), and respiratory complications (4). Severe swelling was associated with spring and early summer, proximal limb bites and children who were most at risk of necrosis. Fingers and hands were most prone to necrosis and permanent disability. Four patients with PW developed respiratory failure. Antivenom was administered to 12 patients, five of whom developed an acute adverse reaction. There was one death. PMID:15019475

  16. Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex.

    PubMed

    Barnwal, Bhaskar; Jobichen, Chacko; Girish, Vallerinteavide Mavelli; Foo, Chun Shin; Sivaraman, J; Kini, R Manjunatha

    2016-01-01

    Anticoagulant therapy is used for the prevention and treatment of thromboembolic disorders. Blood coagulation is initiated by the interaction of factor VIIa (FVIIa) with membrane-bound tissue factor (TF) to form the extrinsic tenase complex which activates FX to FXa. Thus, it is an important target for the development of novel anticoagulants. Here, we report the isolation and characterization of a novel anticoagulant ringhalexin from the venom of Hemachatus haemachatus (African Ringhals Cobra). Amino acid sequence of the protein indicates that it belongs to the three-finger toxin family and exhibits 94% identity to an uncharacterized Neurotoxin-like protein NTL2 from Naja atra. Ringhalexin inhibited FX activation by extrinsic tenase complex with an IC50 of 123.8 ± 9.54 nM. It is a mixed-type inhibitor with the kinetic constants, Ki and Ki' of 84.25 ± 3.53 nM and 152.5 ± 11.32 nM, respectively. Ringhalexin also exhibits a weak, irreversible neurotoxicity on chick biventer cervicis muscle preparations. Subsequently, the three-dimensional structure of ringhalexin was determined at 2.95 Å resolution. This study for the first time reports the structure of an anticoagulant three-finger toxin. Thus, ringhalexin is a potent inhibitor of the FX activation by extrinsic tenase complex and a weak, irreversible neurotoxin. PMID:27173146

  17. Inhibition of Nicotinic Acetylcholine Receptors, a Novel Facet in the Pleiotropic Activities of Snake Venom Phospholipases A2

    PubMed Central

    Vulfius, Catherine A.; Kasheverov, Igor E.; Starkov, Vladislav G.; Osipov, Alexey V.; Andreeva, Tatyana V.; Filkin, Sergey Yu.; Gorbacheva, Elena V.; Astashev, Maxim E.; Tsetlin, Victor I.; Utkin, Yuri N.

    2014-01-01

    Phospholipases A2 represent the most abundant family of snake venom proteins. They manifest an array of biological activities, which is constantly expanding. We have recently shown that a protein bitanarin, isolated from the venom of the puff adder Bitis arietans and possessing high phospholipolytic activity, interacts with different types of nicotinic acetylcholine receptors and with the acetylcholine-binding protein. To check if this property is characteristic to all venom phospholipases A2, we have studied the capability of these enzymes from other snakes to block the responses of Lymnaea stagnalis neurons to acetylcholine or cytisine and to inhibit α-bungarotoxin binding to nicotinic acetylcholine receptors and acetylcholine-binding proteins. Here we present the evidence that phospholipases A2 from venoms of vipers Vipera ursinii and V. nikolskii, cobra Naja kaouthia, and krait Bungarus fasciatus from different snake families suppress the acetylcholine- or cytisine-elicited currents in L. stagnalis neurons and compete with α-bungarotoxin for binding to muscle- and neuronal α7-types of nicotinic acetylcholine receptor, as well as to acetylcholine-binding proteins. As the phospholipase A2 content in venoms is quite high, under some conditions the activity found may contribute to the deleterious venom effects. The results obtained suggest that the ability to interact with nicotinic acetylcholine receptors may be a general property of snake venom phospholipases A2, which add a new target to the numerous activities of these enzymes. PMID:25522251

  18. Optical Follow-Up Observations for the High-z COBRA (Clusters Occupied by Bent Radio AGN) Survey

    NASA Astrophysics Data System (ADS)

    Golden-Marx, Emmet; Blanton, Elizabeth L.; Paterno-Mahler, Rachel; Wing, Joshua; Ashby, Matthew; Brodwin, Mark

    2015-01-01

    Galaxy clusters are unique laboratories for exploring galaxy formation and evolution. Relatively few galaxy clusters have been spectroscopically confirmed beyond a redshift of 1. Different methods of searching for galaxy clusters are adding to these numbers, including detecting regions with a high-density of galaxies in the optical and IR regimes, detecting the hot intracluster medium in the X-ray, and measuring the Sunyaev-Zel'dovich effect. Another promising method for discovering high-redshift galaxy clusters uses radio observations of AGN. In particular, we use bent-double lobed radio sources, known often to reside in nearby clusters, as markers for distant galaxy clusters. We present initial results from the high-redshift COBRA (Clusters Occupied by Bent Radio AGN) survey. We have Spitzer IRAC observations of 653 bent-double radio sources with hosts too faint to be detected in the SDSS. Since the host galaxies for these radio sources are usually giant ellipticals, lack of detection in the SDSS means they are likely at z > 0.7. We have begun deep follow-up optical observations using the 4.3 m Discovery Channel Telescope and have determined from these initial optical observations that ~50% of the observed fields are overdense and thus good cluster candidates. Additionally, we have created optical-IR color magnitude diagrams to estimate the redshifts of our cluster candidates by identifying the red sequence. The distribution of galaxies on the red sequence can be used to limit galaxy formation models.

  19. Interfacial Structure, Bonding and Composition of InAs and GaSb Thin Films Determined Using COBRA

    NASA Astrophysics Data System (ADS)

    Cionca, Codrin; Walko, Donald Alan; Yacoby, Yizhak; Dorin, Catalina; Mirecki Millunchick, Joanna; Clarke, Roy

    2007-03-01

    We have used Bragg rod x-ray diffraction and Coherent Bragg Rod Analysis (COBRA) direct phase retrieval method to extract atomic resolution electron density maps of a complementary series of heteroepitaxial III-V semiconductor samples. From the 3D electron density maps we derived the spacing between monolayers, the chemical composition and the distribution of bond lengths for all atomic planes in the film and across the interface with the substrate. InAs films grown on GaSb (001) using different As species (dimer or tetramer form) both showed conformal roughness and mixed GaSb/InSb interfacial bonding character. The tetramer conditions favored InSb bonding at the heterointerface; the percentages corresponding to InSb and GaAs bonding were equal in the case of the dimer. The GaAs film grown on InAs (001) displayed significant In and As interdiffusion and had a significant percentage of GaAs-like bonds at the heterointerface.

  20. Initial magnetic field compression studies using gas-puff Z-pinches and thin liners on COBRA

    NASA Astrophysics Data System (ADS)

    Gourdain, P.-A.; Concepcion, R. J.; Evans, M. T.; Greenly, J. B.; Hammer, D. A.; Hoyt, C. L.; Kroupp, E.; Kusse, B. R.; Maron, Y.; Novick, A. S.; Pikuz, S. A.; Qi, N.; Rondeau, G.; Rosenberg, E.; Schrafel, P. C.; Seyler, C. E.; Shelkovenko, T. C.

    2013-08-01

    This magnetic compression of cylindrical liners filled with DT gas has promise as an efficient way to achieve fusion burn using pulsed-power machines. However, to avoid rapid cooling of the fuel by transfer of heat to the liner an axial magnetic field is required. This field has to be compressed during the implosion since the thermal insulation is more demanding as the compressed DT plasma becomes hotter and its volume smaller. This compression of the magnetic field is driven both by the imploding liner and plasma. To highlight how this magnetic field compression by the plasma and liner evolves we have separately studied Z-pinch implosions generated by gas puff and liner loads. The masses of the gas puff and liner loads were adjusted to match COBRA's current rise times. Our results have shown that Ne gas-puff implosions are well described by a snowplow model where electrical currents are predominately localized to the outer surface of the imploding plasma and the magnetic field is external to the imploding plasma. Liner implosions are dominated by the plasma ablation process on the inside surface of the liner and the electrical currents and magnetic fields are advected into the inner plasma volume; the sharp radial gradient associated with the snowplow process is not present.

  1. Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex

    PubMed Central

    Janssen, Bert J C; Gomes, Lucio; Koning, Roman I; Svergun, Dmitri I; Koster, Abraham J; Fritzinger, David C; Vogel, Carl-Wilhelm; Gros, Piet

    2009-01-01

    Immune protection by the complement system critically depends on assembly of C3 convertases on the surface of pathogens and altered host cells. These short-lived protease complexes are formed through pro-convertases, which for the alternative pathway consist of the complement component C3b and the pro-enzyme factor B (FB). Here, we present the crystal structure at 2.2-Å resolution, small-angle X-ray scattering and electron microscopy (EM) data of the pro-convertase formed by human FB and cobra venom factor (CVF), a potent homologue of C3b that generates more stable convertases. FB is loaded onto CVF through its pro-peptide Ba segment by specific contacts, which explain the specificity for the homologous C3b over the native C3 and inactive products iC3b and C3c. The protease segment Bb binds the carboxy terminus of CVF through the metal-ion dependent adhesion site of the Von Willebrand factor A-type domain. A possible dynamic equilibrium between a ‘loading' and ‘activation' state of the pro-convertase may explain the observed difference between the crystal structure of CVFB and the EM structure of C3bB. These insights into formation of convertases provide a basis for further development of complement therapeutics. PMID:19574954

  2. Effect of complement depletion by cobra venom factor on fowlpox virus infection in chickens and chicken embryos.

    PubMed Central

    Ohta, H; Yoshikawa, Y; Kai, C; Yamanouchi, K; Taniguchi, H; Komine, K; Ishijima, Y; Okada, H

    1986-01-01

    The course of infection with an attenuated strain of fowlpox virus (FPV), which is known to induce antibody-independent activation of complement via the alternative pathway, was investigated in 1- to 3-day-old chickens and 14-day-old chicken embryos by treatment with cobra venom factor (CVF). CVF was found to inhibit complement activity transiently via the alternative pathway but not via the classical pathway. In chickens treated with CVF, virus growth in the skin was enhanced, and pock lesions tended to disseminate, leading to fatal infection in some birds. Histologically, an acute inflammation at an early stage of infection (within 3 days) was inhibited, and virus content in the pock lesion was increased. In chicken embryos with immature immune capacities, CVF treatment caused changes in pock morphology from clear pocks to diffuse ones, an increase in virus content in the pock, and inhibition of cell infiltration. Thus, FPV infection was aggravated in both CVF-treated chickens and chicken embryos. These results are discussed in relation to roles of complement in the elimination of virus at an early stage of FPV infection. Images PMID:3003397

  3. Comprehensive Analysis of the COBRA-Like (COBL) Gene Family in Gossypium Identifies Two COBLs Potentially Associated with Fiber Quality

    PubMed Central

    Niu, Erli; Shang, Xiaoguang; Cheng, Chaoze; Bao, Jianghao; Zeng, Yanda; Cai, Caiping; Du, Xiongming; Guo, Wangzhen

    2015-01-01

    COBRA-Like (COBL) genes, which encode a plant-specific glycosylphosphatidylinositol (GPI) anchored protein, have been proven to be key regulators in the orientation of cell expansion and cellulose crystallinity status. Genome-wide analysis has been performed in A. thaliana, O. sativa, Z. mays and S. lycopersicum, but little in Gossypium. Here we identified 19, 18 and 33 candidate COBL genes from three sequenced cotton species, diploid cotton G. raimondii, G. arboreum and tetraploid cotton G. hirsutum acc. TM-1, respectively. These COBL members were anchored onto 10 chromosomes in G. raimondii and could be divided into two subgroups. Expression patterns of COBL genes showed highly developmental and spatial regulation in G. hirsutum acc. TM-1. Of them, GhCOBL9 and GhCOBL13 were preferentially expressed at the secondary cell wall stage of fiber development and had significantly co-upregulated expression with cellulose synthase genes GhCESA4, GhCESA7 and GhCESA8. Besides, GhCOBL9 Dt and GhCOBL13 Dt were co-localized with previously reported cotton fiber quality quantitative trait loci (QTLs) and the favorable allele types of GhCOBL9 Dt had significantly positive correlations with fiber quality traits, indicating that these two genes might play an important role in fiber development. PMID:26710066

  4. Beta-cardiotoxin: a new three-finger toxin from Ophiophagus hannah (king cobra) venom with beta-blocker activity.

    PubMed

    Rajagopalan, Nandhakishore; Pung, Yuh Fen; Zhu, Yi Zhun; Wong, Peter Tsun Hon; Kumar, Prakash P; Kini, R Manjunatha

    2007-11-01

    Snake venoms have provided a number of novel ligands with therapeutic potential. We have constructed a partial cDNA library from the mRNA of Ophiophagus hannah (king cobra) venom gland tissue and identified five new genes encoding proteins belonging to the three-finger toxin family of snake venom proteins. We have isolated and characterized one of these beta-sheet containing proteins with a mass of 7012.43 +/- 0.91 Da from the venom. The protein was nonlethal up to a dose of 10 mg/kg when injected intraperitoneally into Swiss albino mice. However, it induces labored breathing and death at a dose of 100 mg/kg. It does not show any hemolytic or anticoagulant activity. It caused a dose-dependent decrease of heart rate in vivo (anesthetized Sprague-Dawley rats) and also ex vivo (Langendorff isolated rat heart). This is in contrast to classical cardiotoxins from snake venom that increase the heart rate in animals. Radioligand displacement studies showed that this protein targets beta-adrenergic receptors with a binding affinity (Ki) of 5.3 and 2.3 microM toward beta1 and beta2 subtypes, respectively, to bring about its effect, and hence, it was named as beta-cardiotoxin. This is the first report of a natural exogenous beta-blocker. PMID:17616557

  5. Isolation, expression and characterization of a novel dual serine protease inhibitor, OH-TCI, from king cobra venom.

    PubMed

    He, Ying-Ying; Liu, Shu-Bai; Lee, Wen-Hui; Qian, Jin-Qiao; Zhang, Yun

    2008-10-01

    Snake venom Kunitz/BPTI members are good tools for understanding of structure-functional relationship between serine proteases and their inhibitors. A novel dual Kunitz/BPTI serine proteinase inhibitor named OH-TCI (trypsin- and chymotrypsin-dual inhibitor from Ophiophagus hannah) was isolated from king cobra venom by three chromatographic steps of gel filtration, trypsin affinity and reverse phase HPLC. OH-TCI is composed of 58 amino acid residues with a molecular mass of 6339Da. Successful expression of OH-TCI was performed as the maltose-binding fusion protein in E. coli DH5alpha. Much different from Oh11-1, the purified native and recombinant OH-TCI both had strong inhibitory activities against trypsin and chymotrypsin although the sequence identity (74.1%) between them is very high. The inhibitor constants (K(i)) of recombinant OH-TCI were 3.91 x 10(-7) and 8.46 x10(-8)M for trypsin and chymotrypsin, respectively. To our knowledge, it was the first report of Kunitz/BPTI serine proteinase inhibitor from snake venom that had equivalent trypsin and chymotrypsin inhibitory activities. PMID:18582511

  6. CNS and anticonvulsant activity of a non-protein toxin (KC-MMTx) isolated from King Cobra (Ophiophagus hannah) venom.

    PubMed

    Saha, A; Gomes, A; Chakravarty, A K; Biswas, A K; Giri, B; Dasgupta, S C; Gomes, A

    2006-03-01

    In the present study, King Cobra (Ophiophagus hannah) venom was subjected to TLC followed by column chromatography/HPLC to isolate and purify a non-protein toxin designated as KC-MMTx. (1)H NMR, IR and EIMS studies showed KC-MMTx likely to be a 282 D unsaturated aliphatic acid having molecular formula C18H34O2. The minimum lethal dose of KC-MMTx was 200 microg/kg (i.v.) and 350 microg/kg (i.p.) in Swiss albino male mice. It significantly increased pentobarbitone induced sleeping time and significantly decreased the body temperature of male albino mice. It provided protection against amphetamine aggregate toxicity in mice but failed to protect amphetamine stereotypy in male albino rats. KC-MMTx provided significant protection against drug (strychnine, pentylenetetrazole, yohimbine) induced convulsions in male albino mice. It increased serum Na+ and decreased serum Ca2+ significantly in male mice. MAO activity and brain neurotransmitter levels in male mice were altered significantly. Further detailed study is warranted on the CNS, anticonvulsant potential of KC-MMTx, which may lead to the development of newer therapeutic tools in the near future. PMID:16457861

  7. Structural and functional characterization of a novel homodimeric three-finger neurotoxin from the venom of Ophiophagus hannah (king cobra).

    PubMed

    Roy, Amrita; Zhou, Xingding; Chong, Ming Zhi; D'hoedt, Dieter; Foo, Chun Shin; Rajagopalan, Nandhakishore; Nirthanan, Selvanayagam; Bertrand, Daniel; Sivaraman, J; Kini, R Manjunatha

    2010-03-12

    Snake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of molecular probes and therapeutic agents. Here, we describe the structural and functional characterization of a novel neurotoxin, haditoxin, from the venom of Ophiophagus hannah (King cobra). Haditoxin exhibited novel pharmacology with antagonism toward muscle (alphabetagammadelta) and neuronal (alpha(7), alpha(3)beta(2), and alpha(4)beta(2)) nicotinic acetylcholine receptors (nAChRs) with highest affinity for alpha(7)-nAChRs. The high resolution (1.5 A) crystal structure revealed haditoxin to be a homodimer, like kappa-neurotoxins, which target neuronal alpha(3)beta(2)- and alpha(4)beta(2)-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic short-chain alpha-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain alpha-neurotoxins and kappa-neurotoxins notwithstanding, haditoxin exhibited unique blockade of alpha(7)-nAChRs (IC(50) 180 nm), which is recognized by neither short-chain alpha-neurotoxins nor kappa-neurotoxins. This is the first report of a dimeric short-chain alpha-neurotoxin interacting with neuronal alpha(7)-nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs. PMID:20071329

  8. Development, characterization and anti-tumor effect of a sequential sustained-release preparation containing ricin and cobra venom cytotoxin.

    PubMed

    Zhang, Xiu-Juan; Ke, Li-Ming; Yang, Jing; Lin, Li-Wu; Xue, En-Sheng; Wang, Yan; Yu, Li-Yun; Chen, Zhi-Kui

    2012-07-01

    Cobra venom cytotoxin (CVC) loaded in poly (lactide-co-glycolide) (PLGA) microspheres was mixed with ricin and encapsulated in a thermosensitive PLGA-PEG-PLGA hydrogel for this study. This sequential sustained-release preparation (SSRP) containing ricin and CVC could avoid burst release effect of CVC from microspheres. In addition, in SSRP, the two biotoxins have different drug release rates and antitumor mechanisms, which can be complementary to each other. Ricin has a faster release rate than CVC. It can combine with the tumor cell membrane and enter the cell, inhibiting protein synthesis within 2 weeks. Whereas CVC releases slowly in 5 weeks directly dissolving the tumor cell membrane and killing the cells which are less-sensitive to ricin. The in vivo experiments showed that intratumoral injection of SSRP could inhibit hepatocellular carcinoma growth significantly, and the tumor growth inhibition rate reached 73.5%. It appears that a new medicine preparation for cancer local treatment should be further studied for clinical applications. PMID:22888519

  9. Implementation of the LAX-Wendroff Method in Cobra-TF for Solving Two-Phase Flow Transport Equations

    SciTech Connect

    Salko, Robert K; Wang, Dean; Ren, Kangyu

    2016-01-01

    COBRA-TF (Coolant Boiling in Rod Arrays Two Fluid), or CTF, is a subchannel code used to conduct the reactor core thermal hydraulic (T/H) solution in both standalone and coupled multi-physics applications. CTF applies the first-order upwind spatial discretization scheme for solving two-phase flow conservation equations. In this work, the second-order Lax-Wendroff (L-W) scheme has been implemented in CTF to solve the two-phase flow transport equations to improve numerical accuracy in both temporal and spatial discretization. To avoid the oscillation issue, a non-linear flux limiter VA (Van Albada) is employed for the convective terms in the transport equations. Assessments have been carried out to evaluate the performance and stability of the implemented second-order L-W scheme. It has been found that the L-W scheme performs better than the upwind scheme for the single-phase and two-phase flow problems in terms of numerical accuracy and computational efficiency.

  10. Spectroscopic Studies of the Soft X-Ray Radiation from Gas-Puff Z-Pinches on Cobra

    NASA Astrophysics Data System (ADS)

    Shelkovenko, T. A.; Pikuz, S. A.; de Grouchy, P. W. L.; Qi, N.; Atoyan, L.; Kusse, B. R.; Hammer, D. A.

    2015-11-01

    Gas-puff Z-pinch experiments have been conducted on the 0.8-1.2 MA, 100-240 ns pulse duration COBRA pulsed power generator. Triple nozzle gas-puff loads consisting of Ne, Ar and Kr gases in different combination and pressures with pre-ionization were used in the most recent experiments. Photo-conducting diodes (PCDs) and pinhole cameras with different filters were used to study the X-ray timing, intensity and spatial distribution in different energy bands. Spectrographs with spatial and temporal resolution were used to study the soft x-ray radiation from the gas-puff Z-pinches. One spectrograph with two spherically bent mica crystals was used to study radiation with 200 micron spatial resolution and high spectral resolution. An x-ray streak camera with one spherically bent quartz crystal was used to study the x-ray radiation with up to 10 ps temporal resolution. The x-ray spectra were used to estimate spatial and temporal distributions of plasma parameters and determine the intensity of the line and continuum radiation from the Z-pinches plasma. Work supported by the National Nuclear Security Administration Stewardship Sciences Academic Programs under Department of Energy Cooperative Agreement No. DE-NA0001836.

  11. A study of snake bite among children presenting to a paediatric ward in the main Teaching Hospital of North Central Province of Sri Lanka

    PubMed Central

    2014-01-01

    Background Snake bite is a common problem in the North Central province of Sri Lanka. Common krait (Bungarus careuleus), Ceylon krait (Bungarus ceylonicus), Cobra (Naja naja), Russell’s viper (Daboia russelii), Saw-scaled viper (Echis carinatus) and Hump-nosed pit viper (Hypnale hypnale) are the six species of venomous land snakes in Sri Lanka. A significant number of adults and children are bitten by snakes every year. However, the majority of research studies done in Sri Lanka and other countries show adults bitten by snakes and studies describing children bitten by snakes are very sparse. Methods A descriptive cross sectional study was performed in the Teaching Hospital Anuradhapura in the North Central Province of Sri Lanka from May 2010 to 2011 May to describe the characteristics associated with cases of snake bite. Results There were 24 males and 20 females. The highest numbers of bites (48%) were in the range of ages 6-12 years. The majority of the bites occurred between 6 pm to 6 am (59%).The foot was the most common bitten site (48%). Out of all the venomous bites, the Hump-nosed pit viper (Hypnale hypnale) accounted for the highest number (44%) and Russell’s viper (Daboia ruselii) accounted for the second highest number (27%). A significant number of venomous bites occurred indoors while sleeping (22%). Antivenom serum was given to (39%) of venomous bites. Deaths occurred in (11%) of the venomous bites. Conclusions Hump-nosed pit viper (Hypnale hypnale) accounted for the highest number of venomous bites. Majority of the bites occurred between 6 pm and 6 am. Foot was the most common bitten site. A significant number of venomous bites occurred indoor while sleeping. Antivenom serum was given to a significant number of venomous bites. Educating the public on making their houses snake proof and using a torch when going out during night time will help in the prevention of getting bitten by snakes. PMID:25073710

  12. Photoaffinity labeling and quaternary structure of the acetylcholine receptor from Torpedo californica.

    PubMed Central

    Hucho, F; Layer, P; Kiefer, H R; Bandini, G

    1976-01-01

    Membrane fragments from electric tissue of Torpedo californica containing nicotinic acetylcholine receptor are composed of four different polypeptide chains with molecular weights of 40,000 (alpha), 48,000 (beta), 62,000 (gamma), and 66,000 (delta). The alpha and beta chains are still present in all and gamma and delta in some of the receptor preparations after Triton X-100 extraction and purification by affinity chromatography. All components of the receptor react covalently with the photoaffinity label 4-azido-2-nitrobenzyltrimethylammonium fluoroborate, the delta chain incorporating less of the reagent as compared to the alpha and beta chains. Agonists and antagonists containing a quaternary ammonium group protect all chains against the label; the principal neurotoxin from Naja naja siamensis protects the alpha chain only. We conclude that the alpha chain binds the neurotoxin from Naja naja, the alpha and beta chains are involved in the binding of ligands with quaternary ammonium groups, and the function of the gamma and delta chains remains to be determined. Images PMID:1066671

  13. High mortality from snakebite in south-eastern Senegal.

    PubMed

    Trape, J F; Pison, G; Guyavarch, E; Mane, Y

    2001-01-01

    Over 24 years, from 1976 to 1999, we conducted a prospective study of overall and cause-specific mortality among the population of 42 villages of south-eastern Senegal. Of 4228 deaths registered during this period, 26 were caused by snakebite, 4 by invertebrate stings and 8 by other wild or domestic animals. The average annual mortality rate from snakebite was 14 deaths per 100,000 population. Among persons aged > or = 1 year, 0.9% (26/2880) of deaths were caused by snakebite and this cause represented 28% (26/94) of total deaths by accidents. We also investigated the snake fauna of the area. Of 1280 snakes belonging to 34 species that were collected, one-third were dangerous and the proportion of Viperidae, Elapidae and Atractaspidae was 23%, 11% and 0.6%, respectively. The saw-scaled viper Echis ocellatus was the most abundant species (13.6%). Other venomous species were Causus maculatus (6.5%), Naja katiensis (5.5%), Bitis arietans (2.7%), Elapsoidea trapei (2.4%), Naja nigricollis (1.2%), Naja melanoleuca (1.1%), Atractaspis aterrima (0.4%), Dendroaspis polylepis (0.3%) and Naja haje (0.1%). PMID:11579888

  14. [Mortality from snake bites, wild and domestic animal bites and arthropod stings in the savannah zone of eastern Senegal].

    PubMed

    Trape, J F; Pison, G; Guyavarch, E; Mane, Y

    2002-08-01

    From 1976 to 1999, we conducted a prospective study of overall and cause-specific mortality among the population of 42 villages of south-eastern Senegal. Of 4,228 deaths registered during this period, 26 were brought on by snakebites, 4 by invertebrate stings and 8 by other wild or domestic animals. The average annual mortality rate from snakebite was 14 deaths per 100,000 population. Among persons aged 1 year or more, 0.9% (26/2,880) of deaths were caused by snakebite and this cause represented 28% (26/94) of the total number of deaths by accident. We also investigated the snake fauna of the area. Of 1,280 snakes belonging to 34 species that were collected, one-third were dangerous and the proportion of Viperidae, Elapidae and Atractaspididae was 23%, 11% and 0.6%, respectively. The saw-scaled viper Echis ocellatus was the most abundant species (13.6%). Other venomous species were Causus maculatus (6.5%), Naja katiensis (5.5%), Bitis arietans (2.7%), Elapsoidea trapei (2.4%), Naja nigricollis (1.2%), Naja melanoleuca (1.1%), Atractaspis aterrima (0.4%), Dendroaspis polylepis (0.3%) and Naja haje (0.1%). PMID:12404858

  15. Molecular mechanism of cell death induced by king cobra (Ophiophagus hannah) venom l-amino acid oxidase.

    PubMed

    Fung, Shin Yee; Lee, Mui Li; Tan, Nget Hong

    2015-03-01

    Snake venom LAAOs have been reported to exhibit a wide range of pharmacological activities, including cytotoxic, edema-inducing, platelet aggregation-inducing/platelet aggregation-inhibiting, bactericidal and antiviral activities. A heat-stable form of l-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom (OH-LAAO) has been shown to exhibit very potent cytotoxicity against human tumorigenic cells but not in their non-tumorigenic counterparts, and the cytotoxicity was due to the apoptosis-inducing effect of the enzyme. In this work, the molecular mechanism of cell death induced by OH-LAAO was investigated. The enzyme exerts its apoptosis-inducing effect presumably via both intrinsic and extrinsic pathways as suggested by the increase in caspase-8 and -9 activities. Oligonucleotide microarray analysis showed that the expression of a total of 178 genes was significantly altered as a result of oxidative stress induced by the hydrogen peroxide generated by the enzyme. Of the 178 genes, at least 27 genes are involved in apoptosis and cell death. These alterations of gene expression was presumably caused by the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidative modifications of signaling molecules that eventually lead to apoptosis and cell death. The very substantial up-regulation of cytochrome P450 genes may also contribute to the potent cytotoxic action of OH-LAAO by producing excessive reactive oxygen species (ROS). In conclusion, the potent apoptosis inducing activity of OH-LAAO was likely due to the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidation of signalling molecules. PMID:25615711

  16. Detecting multi-hit events in a CdZnTe coplanar grid detector using pulse shape analysis: A method for improving background rejection in the COBRA 0νββ experiment

    NASA Astrophysics Data System (ADS)

    McGrath, J.; Fulton, B. R.; Joshi, P.; Davies, P.; Muenstermann, D.; Schulz, O.; Zuber, K.; Freer, M.

    2010-03-01

    A number of experiments are underway to search for a rare form of radioactivity, neutrinoless double beta decay, as a measurement of the half-life would enable the neutrino mass to be determined. The COBRA collaboration [1,2] (Zuber, 2001; Dawson, 2009) employs CdZnTe detectors in such a search. This paper describes techniques using pulse shape analysis for identifying two-centre events in a coplanar grid CdZnTe detector. This enables Compton scatter events to be identified and so suppressing the background present within the COBRA detectors.

  17. Evaluation of the lethal potency of scorpion and snake venoms and comparison between intraperitoneal and intravenous injection routes.

    PubMed

    Oukkache, Naoual; El Jaoudi, Rachid; Ghalim, Noreddine; Chgoury, Fatima; Bouhaouala, Balkiss; Mdaghri, Naima El; Sabatier, Jean-Marc

    2014-06-01

    Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD₅₀) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD₅₀ values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD₅₀ values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD₅₀ values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the

  18. Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes

    PubMed Central

    Oukkache, Naoual; Jaoudi, Rachid El; Ghalim, Noreddine; Chgoury, Fatima; Bouhaouala, Balkiss; Mdaghri, Naima El; Sabatier, Jean-Marc

    2014-01-01

    Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins

  19. Modelling of three dimensional equilibrium and stability of MAST plasmas with magnetic perturbations using VMEC and COBRA

    NASA Astrophysics Data System (ADS)

    Ham, C. J.; Chapman, I. T.; Kirk, A.; Saarelma, S.

    2014-10-01

    It is known that magnetic perturbations can mitigate edge localized modes (ELMs) in experiments, for example, MAST [Kirk et al., Nucl. Fusion 53, 043007 (2013)]. One hypothesis is that the magnetic perturbations cause a three dimensional corrugation of the plasma and this corrugated plasma has different stability properties to peeling-ballooning modes compared to an axisymmetric plasma. It has been shown in an up-down symmetric plasma that magnetic perturbations in tokamaks will break the usual axisymmetry of the plasma causing three dimensional displacements [Chapman et al., Plasma Phys. Controlled Fusion 54, 105013 (2012)]. We produce a free boundary three-dimensional equilibrium of a lower single null MAST relevant plasma using VMEC [S. P. Hirshman and J. C. Whitson, Phys. Fluids 26, 3553 (1983)]. The safety factor and pressure profiles used for the modelling are similar to those deduced from axisymmetric analysis of experimental data with ELMs. We focus on the effect of applying n = 3 and n = 6 magnetic perturbations using the resonant magnetic perturbation (RMP) coils. A midplane displacement of over ±1 cm is seen when the full current is applied. The current in the coils is scanned and a linear relationship between coil current and midplane displacement is found. The pressure gradient in real space in different toroidal locations is shown to change when RMPs are applied. This effect should be taken into account when diagnosing plasmas with RMPs applied. The helical Pfirsch-Schlüter currents which arise as a result of the assumption of nested flux surfaces are estimated for this equilibrium. The effect of this non-axisymmetric equilibrium on infinite n ballooning stability is investigated using COBRA [Sanchez et al., J. Comput. Phys. 161, 576-588 (2000)]. The infinite n ballooning stability is analysed for two reasons; it may give an indication of the effect of non-axisymmetry on finite n peeling-ballooning modes, responsible for ELMs; and infinite n

  20. Modelling of three dimensional equilibrium and stability of MAST plasmas with magnetic perturbations using VMEC and COBRA

    SciTech Connect

    Ham, C. J. Chapman, I. T.; Kirk, A.; Saarelma, S.

    2014-10-15

    It is known that magnetic perturbations can mitigate edge localized modes (ELMs) in experiments, for example, MAST [Kirk et al., Nucl. Fusion 53, 043007 (2013)]. One hypothesis is that the magnetic perturbations cause a three dimensional corrugation of the plasma and this corrugated plasma has different stability properties to peeling-ballooning modes compared to an axisymmetric plasma. It has been shown in an up-down symmetric plasma that magnetic perturbations in tokamaks will break the usual axisymmetry of the plasma causing three dimensional displacements [Chapman et al., Plasma Phys. Controlled Fusion 54, 105013 (2012)]. We produce a free boundary three-dimensional equilibrium of a lower single null MAST relevant plasma using VMEC [S. P. Hirshman and J. C. Whitson, Phys. Fluids 26, 3553 (1983)]. The safety factor and pressure profiles used for the modelling are similar to those deduced from axisymmetric analysis of experimental data with ELMs. We focus on the effect of applying n = 3 and n = 6 magnetic perturbations using the resonant magnetic perturbation (RMP) coils. A midplane displacement of over ±1 cm is seen when the full current is applied. The current in the coils is scanned and a linear relationship between coil current and midplane displacement is found. The pressure gradient in real space in different toroidal locations is shown to change when RMPs are applied. This effect should be taken into account when diagnosing plasmas with RMPs applied. The helical Pfirsch-Schlüter currents which arise as a result of the assumption of nested flux surfaces are estimated for this equilibrium. The effect of this non-axisymmetric equilibrium on infinite n ballooning stability is investigated using COBRA [Sanchez et al., J. Comput. Phys. 161, 576–588 (2000)]. The infinite n ballooning stability is analysed for two reasons; it may give an indication of the effect of non-axisymmetry on finite n peeling-ballooning modes, responsible for ELMs; and

  1. Cost and outcome of behavioural activation versus cognitive behaviour therapy for depression (COBRA): study protocol for a randomised controlled trial

    PubMed Central

    2014-01-01

    Background Cognitive behaviour therapy (CBT) is an effective treatment for depression. However, CBT is a complex therapy that requires highly trained and qualified practitioners, and its scalability is therefore limited by the costs of training and employing sufficient therapists to meet demand. Behavioural activation (BA) is a psychological treatment for depression that may be an effective alternative to CBT and, because it is simpler, might also be delivered by less highly trained and specialised mental health workers. Methods/Design COBRA is a two-arm, non-inferiority, patient-level randomised controlled trial, including clinical, economic, and process evaluations comparing CBT delivered by highly trained professional therapists to BA delivered by junior professional or para-professional mental health workers to establish whether the clinical effectiveness of BA is non-inferior to CBT and if BA is cost effective compared to CBT. Four hundred and forty patients with major depressive disorder will be recruited through screening in primary care. We will analyse for non-inferiority in per-protocol and intention-to-treat populations. Our primary outcome will be severity of depression symptoms (Patient Health Questionnaire-9) at 12 months follow-up. Secondary outcomes will be clinically significant change and severity of depression at 18 months, and anxiety (General Anxiety Disorder-7 questionnaire) and health-related quality of life (Short-Form Health Survey-36) at 12 and 18 months. Our economic evaluation will take the United Kingdom National Health Service/Personal Social Services perspective to include costs of the interventions, health and social care services used, plus productivity losses. Cost-effectiveness will explored in terms of quality-adjusted life years using the EuroQol-5D measure of health-related quality of life. Discussion The clinical and economic outcomes of this trial will provide the evidence to help policy makers, clinicians and guideline

  2. Studies of x-ray and XUV radiation from wire-array z-pinches on COBRA using an x-ray streak camera

    NASA Astrophysics Data System (ADS)

    Gourdain, P.-A.; Pikuz, S. A.; Shelkovenko, T. A.; Knapp, P. F.; Hammer, D. A.; Simar, D. B.

    2008-11-01

    Time- and space- resolved short-wavelength radiation from wire-array z-pinches has been studied using a low-magnification Kentech x-ray streak camera in experiments on the 1 MA COBRA pulsed power generator at Cornell University. In the x-ray spectral band, a standard photochode and imaging slit were used to record one-dimensional images in the axial direction. Axial and radial images of wire arrays were recorded in XUV radiaion using an open pinhole and a specially made transparent mesh-type photocathode. The development of the precursor plasma and hot spots in the stagnated plasma have been observed. The images were compared with results obtained with an optical streak camera and 4-frame gated microchannel plate imager.

  3. In-flight measurements of propeller blade deformation on a VUT100 cobra aeroplane using a co-rotating camera system

    NASA Astrophysics Data System (ADS)

    Boden, F.; Stasicki, B.; Szypuła, M.; Ružička, P.; Tvrdik, Z.; Ludwikowski, K.

    2016-07-01

    Knowledge of propeller or rotor blade behaviour under real operating conditions is crucial for optimizing the performance of a propeller or rotor system. A team of researchers, technicians and engineers from Avia Propeller, DLR, EVEKTOR and HARDsoft developed a rotating stereo camera system dedicated to in-flight blade deformation measurements. The whole system, co-rotating with the propeller at its full speed and hence exposed to high centrifugal forces and strong vibration, had been successfully tested on an EVEKTOR VUT 100 COBRA aeroplane in Kunovice (CZ) within the project AIM2—advanced in-flight measurement techniques funded by the European Commission (contract no. 266107). This paper will describe the work, starting from drawing the first sketch of the system up to performing the successful flight test. Apart from a description of the measurement hardware and the applied IPCT method, the paper will give some impressions of the flight test activities and discuss the results obtained from the measurements.

  4. Maize Brittle stalk2 encodes a COBRA-like protein expressed in early organ development but required for tissue flexibility at maturity.

    PubMed

    Sindhu, Anoop; Langewisch, Tiffany; Olek, Anna; Multani, Dilbag S; McCann, Maureen C; Vermerris, Wilfred; Carpita, Nicholas C; Johal, Gurmukh

    2007-12-01

    The maize (Zea mays) brittle stalk2 (bk2) is a recessive mutant, the aerial parts of which are easily broken. The bk2 phenotype is developmentally regulated and appears 4 weeks after planting, at about the fifth-leaf stage. Before this time, mutants are indistinguishable from wild-type siblings. Afterward, all organs of the bk2 mutants turn brittle, even the preexisting ones, and they remain brittle throughout the life of the plant. Leaf tension assays and bend tests of the internodes show that the brittle phenotype does not result from loss of tensile strength but from loss in flexibility that causes the tissues to snap instead of bend. The Bk2 gene was cloned by a combination of transposon tagging and a candidate gene approach and found to encode a COBRA-like protein similar to rice (Oryza sativa) BC1 and Arabidopsis (Arabidopsis thaliana) COBRA-LIKE4. The outer periphery of the stalk has fewer vascular bundles, and the sclerids underlying the epidermis possess thinner secondary walls. Relative cellulose content is not strictly correlated with the brittle phenotype. Cellulose content in mature zones of bk2 mature stems is lowered by 40% but is about the same as wild type in developing stems. Although relative cellulose content is lowered in leaves after the onset of the brittle phenotype, total wall mass as a proportion of dry mass is either unchanged or slightly increased, indicating a compensatory increase in noncellulosic carbohydrate mass. Fourier transform infrared spectra indicated an increase in phenolic ester content in the walls of bk2 leaves and stems. Total content of lignin is unaffected in bk2 juvenile leaves before or after appearance of the brittle phenotype, but bk2 mature and developing stems are markedly enriched in lignin compared to wild-type stems. Despite increased lignin in bk2 stems, loss of staining with phloroglucinol and ultraviolet autofluorescence is observed in vascular bundles and sclerid layers. Consistent with the infrared

  5. Virtual Screening Against α-Cobratoxin

    PubMed Central

    UTSINTONG, MALEERUK; TALLEY, TODD T.; TAYLOR, PALMER W.; OLSON, ARTHUR J.; VAJRAGUPTA, OPA

    2011-01-01

    α-Cobratoxin (Cbtx), the neurotoxin isolated from the venom of the Thai cobra Naja kaouthia, causes paralysis by preventing acetylcholine (ACh) binding to nicotinic acetylcholine receptors (nAChRs). In the current study, the region of the Cbtx molecule that is directly involved in binding to nAChRs is used as the target for anticobratoxin drug design. The crystal structure (1YI5) of Cbtx in complex with the acetylcholine binding protein (AChBP), a soluble homolog of the extracellular binding domain of nAChRs, was selected to prepare an α-cobratoxin active binding site for docking. The amino acid residues (Ser182-Tyr192) of the AChBP structure, the binding site of Cbtx, were used as the positive control to validate the prepared Cbtx active binding site (root mean square deviation < 1.2 Å). Virtual screening of the National Cancer Institute diversity set, a library of 1990 compounds with nonredundant pharmacophore profiles, using AutoDock against the Cbtx active site, revealed 39 potential inhibitor candidates. The adapted in vitro radioligand competition assays using [3H]epibatidine and [125I]bungarotoxin against the AChBPs from the marine species, Aplysia californica (Ac), and from the freshwater snails, Lymnaea stagnalis (Ls) and Bolinus truncates (Bt), revealed 4 compounds from the list of inhibitor candidates that had micromolar to nanomolar interferences for the toxin binding to AChBPs. Three hits (NSC42258, NSC121865, and NSC134754) can prolong the survival time of the mice if administered 30 min before injection with Cbtx, but only NSC121865 and NSC134754 can prolong the survival time if injected immediately after injection with Cbtx. These inhibitors serve as novel templates/scaffolds for the development of more potent and specific anticobratoxin. PMID:19734437

  6. Protective immunity against alpha-cobratoxin following a single administration of a genetic vaccine encoding a non-toxic cobratoxin variant.

    PubMed

    Pergolizzi, Robert G; Dragos, Rachel; Ropper, Alexander E; Menez, André; Crystal, Ronald G

    2005-03-01

    Venomous snakebites result in almost 125,000 deaths per year worldwide. We present a new paradigm for the development of vaccines to protect against snakebite, using knowledge of the structure and action of specific toxins combined with a gene-based strategy to deliver a toxin gene modified to render it non-toxic while maintaining its three-dimensional structure and hence its ability to function as an immunogen. As a model for this approach, we developed a genetic vaccine to protect against alpha-cobratoxin (CTX), a potent, post-synaptic neurotoxin that is the major toxic component of the venom of Naja kaouthia, the monocellate cobra. To develop the vaccine, substitutions in the CTX cDNA were introduced at two residues critical for binding to the nicotinic acetylcholine receptor (Asp27 to Arg, Arg33 to Gly). The mutated CTX expression cassette was delivered in the context of a replication deficient adenovirus vector (AdmCTX). To assess whether expression of the mutated CTX in vivo leads to the development of protective immunity, BALB/c mice were challenged by IV administration of 2 microg of alpha-cobratoxin protein 21 or 63 days after administration of AdmCTX or Ad- Null (as a control; both, 10(9) particle units). Animals receiving AdmCTX but no alpha-cobratoxin challenge suffered no ill effects, but > or =80% of naive animals or those receiving the AdNull control vector died within 10 min from the alpha-cobratoxin challenge. In contrast, 100% of animals receiving a single dose of AdmCTX 21 or 63 days prior to alpha-cobratoxin challenge survived. The data demonstrates that an adenovirus-based vaccine can be developed to protect against lethal challenge with a potent snake venom. The effectiveness of this approach might serve as a basis to consider the development of a global public health program to protect those at risk for death by snakebite. PMID:15812224

  7. Efficacy of Indian polyvalent snake antivenoms against Sri Lankan snake venoms: lethality studies or clinically focussed in vitro studies.

    PubMed

    Maduwage, Kalana; Silva, Anjana; O'Leary, Margaret A; Hodgson, Wayne C; Isbister, Geoffrey K

    2016-01-01

    In vitro antivenom efficacy studies were compared to rodent lethality studies to test two Indian snake antivenoms (VINS and BHARAT) against four Sri Lankan snakes. In vitro efficacy was tested at venom concentrations consistent with human envenoming. Efficacy was compared statistically for one batch from each manufacturer where multiple vials were available. In binding studies EC50 for all VINS antivenoms were less than BHARAT for D. russelii [553 μg/mL vs. 1371 μg/mL;p = 0.016), but were greater for VINS antivenoms compared to BHARAT for N. naja [336 μg/mL vs. 70 μg/mL;p < 0.0001]. EC50 of both antivenoms was only slighty different for E. carinatus and B. caeruleus. For procoagulant activity neutralisation, the EC50 was lower for VINS compared to BHARAT - 60 μg/mL vs. 176 μg/mL (p < 0.0001) for Russell's viper and 357 μg/mL vs. 6906μg/mL (p < 0.0001) for Saw-scaled viper. Only VINS antivenom neutralized in vitro neurotoxicity of krait venom. Both antivenoms partially neutralized cobra and didn't neutralize Russell's viper neurotoxicity. Lethality studies found no statistically significant difference in ED50 values between VINS and BHARAT antivenoms. VINS antivenoms appeared superior to BHARAT at concentrations equivalent to administering 10 vials antivenom, based on binding and neutralisation studies. Lethality studies were inconsistent suggesting rodent death may not measure relevant efficacy outcomes in humans. PMID:27231196

  8. Efficacy of Indian polyvalent snake antivenoms against Sri Lankan snake venoms: lethality studies or clinically focussed in vitro studies

    PubMed Central

    Maduwage, Kalana; Silva, Anjana; O’Leary, Margaret A.; Hodgson, Wayne C.; Isbister, Geoffrey K.

    2016-01-01

    In vitro antivenom efficacy studies were compared to rodent lethality studies to test two Indian snake antivenoms (VINS and BHARAT) against four Sri Lankan snakes. In vitro efficacy was tested at venom concentrations consistent with human envenoming. Efficacy was compared statistically for one batch from each manufacturer where multiple vials were available. In binding studies EC50 for all VINS antivenoms were less than BHARAT for D. russelii [553 μg/mL vs. 1371 μg/mL;p = 0.016), but were greater for VINS antivenoms compared to BHARAT for N. naja [336 μg/mL vs. 70 μg/mL;p < 0.0001]. EC50 of both antivenoms was only slighty different for E. carinatus and B. caeruleus. For procoagulant activity neutralisation, the EC50 was lower for VINS compared to BHARAT - 60 μg/mL vs. 176 μg/mL (p < 0.0001) for Russell’s viper and 357 μg/mL vs. 6906μg/mL (p < 0.0001) for Saw-scaled viper. Only VINS antivenom neutralized in vitro neurotoxicity of krait venom. Both antivenoms partially neutralized cobra and didn’t neutralize Russell’s viper neurotoxicity. Lethality studies found no statistically significant difference in ED50 values between VINS and BHARAT antivenoms. VINS antivenoms appeared superior to BHARAT at concentrations equivalent to administering 10 vials antivenom, based on binding and neutralisation studies. Lethality studies were inconsistent suggesting rodent death may not measure relevant efficacy outcomes in humans. PMID:27231196

  9. Antimicrobial and antibiofilm activity of cathelicidins and short, synthetic peptides against Francisella.

    PubMed

    Amer, Lilian S; Bishop, Barney M; van Hoek, Monique L

    2010-05-28

    Francisella infects the lungs causing pneumonic tularemia. Focusing on the lung's host defense, we have examined antimicrobial peptides as part of the innate immune response to Francisella infection. Interest in antimicrobial peptides, such as the cathelicidins, has grown due their potential therapeutic applications and the increasing problem of bacterial resistance to commonly used antibiotics. Only one human cathelicidin, LL-37, has been characterized. Helical cathelicidins have also been discovered in snakes including the Chinese King Cobra, Naja atra (NA-CATH). Four synthetic 11-residue peptides (ATRA-1, -2, -1A and -1P) containing variations of a repeated motif within NA-CATH were designed. We hypothesized that these smaller synthetic peptides could have excellent antimicrobial effectiveness with shorter length (and less cost), making them strong potential candidates for development into broad-spectrum antimicrobial compounds. We tested the susceptibility of F. novicida to four ATRA peptides, LL-37, and NA-CATH. Two of the ATRA peptides had high antimicrobial activity (microM), while the two proline-containing ATRA peptides had low activity. The ATRA peptides did not show significant hemolytic activity even at high peptide concentration, indicating low cytotoxicity against host cells. NA-CATH killed Francisella bacteria more quickly than LL-37. However, LL-37 was the most effective peptide against F. novicida (EC50=50 nM). LL-37 mRNA was induced in A549 cells by Francisella infection. We recently demonstrated that F. novicida forms in vitro biofilms. LL-37 inhibited F. novicida biofilm formation at sub-antimicrobial concentrations. Understanding the properties of these peptides, and their endogenous expression in the lung could lead to potential future therapeutic interventions for this lung infection. PMID:20399752

  10. Snake Cathelicidin NA-CATH and Smaller Helical Antimicrobial Peptides Are Effective against Burkholderia thailandensis

    PubMed Central

    Blower, Ryan J.; Barksdale, Stephanie M.; van Hoek, Monique L.

    2015-01-01

    Burkholderia thailandensis is a Gram-negative soil bacterium used as a model organism for B. pseudomallei, the causative agent of melioidosis and an organism classified category B priority pathogen and a Tier 1 select agent for its potential use as a biological weapon. Burkholderia species are reportedly “highly resistant” to antimicrobial agents, including cyclic peptide antibiotics, due to multiple resistance systems, a hypothesis we decided to test using antimicrobial (host defense) peptides. In this study, a number of cationic antimicrobial peptides (CAMPs) were tested in vitro against B. thailandensis for both antimicrobial activity and inhibition of biofilm formation. Here, we report that the Chinese cobra (Naja atra) cathelicidin NA-CATH was significantly antimicrobial against B. thailandensis. Additional cathelicidins, including the human cathelicidin LL-37, a sheep cathelicidin SMAP-29, and some smaller ATRA peptide derivatives of NA-CATH were also effective. The D-enantiomer of one small peptide (ATRA-1A) was found to be antimicrobial as well, with EC50 in the range of the L-enantiomer. Our results also demonstrate that human alpha-defensins (HNP-1 & -2) and a short beta-defensin-derived peptide (Peptide 4 of hBD-3) were not bactericidal against B. thailandensis. We also found that the cathelicidin peptides, including LL-37, NA-CATH, and SMAP-29, possessed significant ability to prevent biofilm formation of B. thailandensis. Additionally, we show that LL-37 and its D-enantiomer D-LL-37 can disperse pre-formed biofilms. These results demonstrate that although B. thailandensis is highly resistant to many antibiotics, cyclic peptide antibiotics such as polymyxin B, and defensing peptides, some antimicrobial peptides including the elapid snake cathelicidin NA-CATH exert significant antimicrobial and antibiofilm activity towards B. thailandensis. PMID:26196513

  11. Interaction of three-finger toxins with phospholipid membranes: comparison of S- and P-type cytotoxins

    PubMed Central

    2004-01-01

    The CTs (cytotoxins) I and II are positively charged three-finger folded proteins from venom of Naja oxiana (the Central Asian cobra). They belong to S- and P-type respectively based on Ser-28 and Pro-30 residues within a putative phospholipid bilayer binding site. Previously, we investigated the interaction of CTII with multilamellar liposomes of dipalmitoylphosphatidylglycerol by wide-line 31P-NMR spectroscopy. To compare interactions of these proteins with phospholipids, we investigated the interaction of CTI with the multilamellar liposomes of dipalmitoylphosphatidylglycerol analogously. The effect of CTI on the chemical shielding anisotropy and deformation of the liposomes in the magnetic field was determined at different temperatures and lipid/protein ratios. It was found that both the proteins do not affect lipid organization in the gel state. In the liquid crystalline state of the bilayer they disturb lipid packing. To get insight into the interactions of the toxins with membranes, Monte Carlo simulations of CTI and CTII in the presence of the bilayer membrane were performed. It was found that both the toxins penetrate into the bilayer with the tips of all the three loops. However, the free-energy gain on membrane insertion of CTI is smaller (by ≈7 kcal/mol; 1 kcal≡4.184 kJ) when compared with CTII, because of the lower hydrophobicity of the membrane-binding site of CTI. These results clearly demonstrate that the P-type cytotoxins interact with membranes stronger than those of the S-type, although the mode of the membrane insertion is similar for both the types. PMID:15584897

  12. Snake Cathelicidin NA-CATH and Smaller Helical Antimicrobial Peptides Are Effective against Burkholderia thailandensis.

    PubMed

    Blower, Ryan J; Barksdale, Stephanie M; van Hoek, Monique L

    2015-01-01

    Burkholderia thailandensis is a Gram-negative soil bacterium used as a model organism for B. pseudomallei, the causative agent of melioidosis and an organism classified category B priority pathogen and a Tier 1 select agent for its potential use as a biological weapon. Burkholderia species are reportedly "highly resistant" to antimicrobial agents, including cyclic peptide antibiotics, due to multiple resistance systems, a hypothesis we decided to test using antimicrobial (host defense) peptides. In this study, a number of cationic antimicrobial peptides (CAMPs) were tested in vitro against B. thailandensis for both antimicrobial activity and inhibition of biofilm formation. Here, we report that the Chinese cobra (Naja atra) cathelicidin NA-CATH was significantly antimicrobial against B. thailandensis. Additional cathelicidins, including the human cathelicidin LL-37, a sheep cathelicidin SMAP-29, and some smaller ATRA peptide derivatives of NA-CATH were also effective. The D-enantiomer of one small peptide (ATRA-1A) was found to be antimicrobial as well, with EC50 in the range of the L-enantiomer. Our results also demonstrate that human alpha-defensins (HNP-1 & -2) and a short beta-defensin-derived peptide (Peptide 4 of hBD-3) were not bactericidal against B. thailandensis. We also found that the cathelicidin peptides, including LL-37, NA-CATH, and SMAP-29, possessed significant ability to prevent biofilm formation of B. thailandensis. Additionally, we show that LL-37 and its D-enantiomer D-LL-37 can disperse pre-formed biofilms. These results demonstrate that although B. thailandensis is highly resistant to many antibiotics, cyclic peptide antibiotics such as polymyxin B, and defensing peptides, some antimicrobial peptides including the elapid snake cathelicidin NA-CATH exert significant antimicrobial and antibiofilm activity towards B. thailandensis. PMID:26196513

  13. Analysis of Compact Cylindrical Wire Array Implosions with Brass and also by Alternating Brass and Al wires on the 1-MA COBRA Generator

    NASA Astrophysics Data System (ADS)

    Ouart, N. D.; Yilmaz, M. F.; Safronova, A. S.; Kantsyrev, V. L.; Esaulov, A. A.; Williamson, K. M.; Osborne, G. C.; Shrestha, I.; Weller, M. E.; McBride, R. D.; Knapp, P. F.; Bell, K. S.; Pikuz, S. A.; Shelkovenko, T. A.; Greenly, J. B.; Hammer, D. A.; Kusse, B. R.

    2009-01-01

    Implosions from compact cylindrical wire arrays (CCWA) with mid-Z and low-Z wires were carried out on the 1-MA COBRA generator at Cornell University. In particular, the CCWA used either Brass 310 (70% Cu, 30% Zn) wires or a combination of Brass 310 and Al 5056 (95% Al, 5% Mg) wires arranged in an alternating pattern. A total of 16 wires were used on either a 6 or 4 mm diameter array. The diagnostic suite included a bolometer, fast x-ray detectors, a time-integrated spectrometer, and a streak camera. A higher energy output was observed from bolometer measurements when alternating the brass and Al wires compared to using only the brass wires. This study will focus mainly on the spectroscopy of the brass and alternating brass and Al CCWA by applying the non-LTE kinetic models of Cu and Zn to account for the L-shell radiation. The resulting plasma parameters, electron density and electron temperature, will be discussed and compared for the CCWA with only brass wires and alternating brass and Al wires. The simulations with the novel Wire Ablation Dynamics Model that account for wire ablation will be performed to analyze the differences in implosion dynamics of the uniform and alternating compact cylindrical arrays.

  14. Emissions of CH4 and N2O over the United States and Canada based on a receptor-oriented modeling framework and COBRA-NA atmospheric observations

    NASA Astrophysics Data System (ADS)

    Kort, Eric A.; Eluszkiewicz, Janusz; Stephens, Britton B.; Miller, John B.; Gerbig, Christoph; Nehrkorn, Thomas; Daube, Bruce C.; Kaplan, Jed O.; Houweling, Sander; Wofsy, Steven C.

    2008-09-01

    We present top-down emission constraints for two non-CO2 greenhouse gases in large areas of the U.S. and southern Canada during early summer. Collocated airborne measurements of methane and nitrous oxide acquired during the COBRA-NA campaign in May-June 2003, analyzed using a receptor-oriented Lagrangian particle dispersion model, provide robust validation of independent bottom-up emission estimates from the EDGAR and GEIA inventories. We find that the EDGAR CH4 emission rates are slightly low by a factor of 1.08 +/- 0.15 (2σ), while both EDGAR and GEIA N2O emissions are significantly too low, by factors of 2.62 +/- 0.50 and 3.05 +/- 0.61, respectively, for this region. Potential footprint bias may expand the statistically retrieved uncertainties. Seasonality of agricultural N2O emissions may help explain the discrepancy. Total anthropogenic U.S. and Canadian emissions would be 49 Tg CH4 and 4.3 Tg N2O annually, if these inventory scaling factors applied to all of North America.

  15. Doppler shift and broadening of H-like and He-like Al lines in imploded arrays on MAGPIE and COBRA pulsers experiments

    NASA Astrophysics Data System (ADS)

    Pikuz, S. A.; Douglass, J. D.; Shelkovenko, T. A.; Hammer, D. A.; Hall, G. N.; Lebedev, S. V.; Bland, S. N.; Bott, S. C.; Chittenden, J. P.

    2006-10-01

    Strong broadening and clearly visible ``red'' and ``blue'' shifts of K-shell spectral lines as a function position along the array axis have been observed in the time-integrated spectra of 8-32 wire Al arrays in experiments on the MAGPIE (1.2 MA, 240 ns risetime) and COBRA (1.1 MA, 100 ns risetime) pulsed-power generators. Spectra were recorded using focusing spectrographs with spherically bent mica crystals (FSSR) in configurations in which the film was positioned out of Rowland circle and the influence of the spatial position on a line position in the spectral direction on the film is not negligible. To separate the spectral and spatial shift of the spectral lines, two wide-band spectrographs with 3 spherically bent crystals each (WB-FSSR) with radius of curvature 182 mm have been used in a mirror-symmetric configuration. The measured Doppler shift of the spectral lines varied along the pinch axis and reached ±0.015 å corresponding to a radial plasma velocity of ±5x10^7 cm/s. This research was sponsored by the NNSA under DOE Cooperative Agreement DE-F03-02NA00057.

  16. Novel genes encoding six kinds of three-finger toxins in Ophiophagus hannah (king cobra) and function characterization of two recombinant long-chain neurotoxins

    PubMed Central

    Li, Jing; Zhang, Huayuan; Liu, Jing; Xu, Kangsen

    2006-01-01

    Three-finger toxins are a family of low-molecular-mass toxins (<10 kDa) having very similar three-dimensional structures. In the present study, 19 novel cDNAs coding three-finger toxins were cloned from the venom gland of Ophiophagus hannah (king cobra). Alignment analysis showed that the putative peptides could be divided into six kinds of three-finger toxins: LNTXs (long-chain neurotoxins), short-chain neurotoxins, cardiotoxins (CTXs), weak neurotoxins, muscarinic toxins and a toxin with a free SH group. Furthermore, a phylogenetic tree was established on the basis of the toxin cDNAs and the previously reported similar nucleotide sequences from the same source venom. It indicated that three-finger-toxin genes in O. hannah diverged early in the course of evolution by long- and short-type pathways. Two LNTXs, namely rLNTX1 (recombinant LNTX1) and rLNTX3, were expressed and showed cytolytic activity in addition to their neurotoxic function. By comparing the functional residues, we offer some possible explanations for the differences in their neurotoxic function. Moreover, a plausible elucidation of the additonal cytolytic activity was achieved by hydropathy-profile analysis. This, to our knowledge, is the first observation that recombinant long chain α-neurotoxins have a CTX-like cytolytic activity. PMID:16689684

  17. Analysis of Compact Cylindrical Wire Array Implosions with Brass and also by Alternating Brass and Al wires on the 1-MA COBRA Generator

    SciTech Connect

    Ouart, N. D.; Yilmaz, M. F.; Safronova, A. S.; Kantsyrev, V. L.; Esaulov, A. A.; Williamson, K. M.; Osborne, G. C.; Shrestha, I.; Weller, M. E.; McBride, R. D.; Knapp, P. F.; Bell, K. S.; Pikuz, S. A.; Shelkovenko, T. A.; Greenly, J. B.; Hammer, D. A.; Kusse, B. R.

    2009-01-21

    Implosions from compact cylindrical wire arrays (CCWA) with mid-Z and low-Z wires were carried out on the 1-MA COBRA generator at Cornell University. In particular, the CCWA used either Brass 310 (70% Cu, 30% Zn) wires or a combination of Brass 310 and Al 5056 (95% Al, 5% Mg) wires arranged in an alternating pattern. A total of 16 wires were used on either a 6 or 4 mm diameter array. The diagnostic suite included a bolometer, fast x-ray detectors, a time-integrated spectrometer, and a streak camera. A higher energy output was observed from bolometer measurements when alternating the brass and Al wires compared to using only the brass wires. This study will focus mainly on the spectroscopy of the brass and alternating brass and Al CCWA by applying the non-LTE kinetic models of Cu and Zn to account for the L-shell radiation. The resulting plasma parameters, electron density and electron temperature, will be discussed and compared for the CCWA with only brass wires and alternating brass and Al wires. The simulations with the novel Wire Ablation Dynamics Model that account for wire ablation will be performed to analyze the differences in implosion dynamics of the uniform and alternating compact cylindrical arrays.

  18. COBRA, an Arabidopsis Extracellular Glycosyl-Phosphatidyl Inositol-Anchored Protein, Specifically Controls Highly Anisotropic Expansion through Its Involvement in Cellulose Microfibril OrientationW⃞

    PubMed Central

    Roudier, François; Fernandez, Anita G.; Fujita, Miki; Himmelspach, Regina; Borner, Georg H.H.; Schindelman, Gary; Song, Shuang; Baskin, Tobias I.; Dupree, Paul; Wasteneys, Geoffrey O.; Benfey, Philip N.

    2005-01-01

    The orientation of cell expansion is a process at the heart of plant morphogenesis. Cellulose microfibrils are the primary anisotropic material in the cell wall and thus are likely to be the main determinant of the orientation of cell expansion. COBRA (COB) has been identified previously as a potential regulator of cellulose biogenesis. In this study, characterization of a null allele, cob-4, establishes the key role of COB in controlling anisotropic expansion in most developing organs. Quantitative polarized-light and field-emission scanning electron microscopy reveal that loss of anisotropic expansion in cob mutants is accompanied by disorganization of the orientation of cellulose microfibrils and subsequent reduction of crystalline cellulose. Analyses of the conditional cob-1 allele suggested that COB is primarily implicated in microfibril deposition during rapid elongation. Immunodetection analysis in elongating root cells revealed that, in agreement with its substitution by a glycosylphosphatidylinositol anchor, COB was polarly targeted to both the plasma membrane and the longitudinal cell walls and was distributed in a banding pattern perpendicular to the longitudinal axis via a microtubule-dependent mechanism. Our observations suggest that COB, through its involvement in cellulose microfibril orientation, is an essential factor in highly anisotropic expansion during plant morphogenesis. PMID:15849274

  19. Spatially-Resolved Argon and Neon K-Shell X-Ray Spectra from Triple-Nozzle Gas-Puff Z-Pinches on Cobra

    NASA Astrophysics Data System (ADS)

    Qi, Niansheng; de Grouchy, Philip; Hoyt, Cad; Shelkovenko, Tania; Pikuz, Sergei; Atoyan, Levon; Potter, William; Cahill, Adam; Greenly, John; Kusse, Bruce; Hammer, David

    2014-10-01

    We present the x-ray spectra obtained during Ar/Ne gas puff z-pinch experiments on the 1MA, 200ns COBRA pulsed power generator at Cornell University. A triple-nozzle gas-puff, which produces two annular (``outer'' and ``inner'') gas puffs and a high density center jet, is used to tailor the radial mass density distribution. Argon and/or neon plasmas are imploded. Filtered x-ray photo-conducting detectors are used for timing the neon and argon K-shell emission and a filtered x-ray pinhole camera images the K-shell x-ray source size. A spectrometer with three spherical mica crystals is used to capture the K-shell x-ray emission. Our objective is to diagnose the Ar and Ne pinch plasma densities (1019-1020 cm-3) and temperatures (0.5-2 keV) with 0.1 mm axial and/or radial spatial resolution from the K-shell X-ray spectra. The He-like resonance to intercombination line ratio will be used to estimate the electron density and the He-like resonance to Li-like satellite line ratio will be used to estimate the electron temperature. We will also add Cl as a dopant in either the center Ar gas jet or inner annular puff for K-shell x-ray spectrum studies. Work supported by DOE Grant No. DE-NA0001836.

  20. Novel genes encoding six kinds of three-finger toxins in Ophiophagus hannah (king cobra) and function characterization of two recombinant long-chain neurotoxins.

    PubMed

    Li, Jing; Zhang, Huayuan; Liu, Jing; Xu, Kangsen

    2006-09-01

    Three-finger toxins are a family of low-molecular-mass toxins (<10 kDa) having very similar three-dimensional structures. In the present study, 19 novel cDNAs coding three-finger toxins were cloned from the venom gland of Ophiophagus hannah (king cobra). Alignment analysis showed that the putative peptides could be divided into six kinds of three-finger toxins: LNTXs (long-chain neurotoxins), short-chain neurotoxins, cardiotoxins (CTXs), weak neurotoxins, muscarinic toxins and a toxin with a free SH group. Furthermore, a phylogenetic tree was established on the basis of the toxin cDNAs and the previously reported similar nucleotide sequences from the same source venom. It indicated that three-finger-toxin genes in O. hannah diverged early in the course of evolution by long- and short-type pathways. Two LNTXs, namely rLNTX1 (recombinant LNTX1) and rLNTX3, were expressed and showed cytolytic activity in addition to their neurotoxic function. By comparing the functional residues, we offer some possible explanations for the differences in their neurotoxic function. Moreover, a plausible elucidation of the additonal cytolytic activity was achieved by hydropathy-profile analysis. This, to our knowledge, is the first observation that recombinant long chain alpha-neurotoxins have a CTX-like cytolytic activity. PMID:16689684

  1. Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)*♦

    PubMed Central

    Roy, Amrita; Zhou, Xingding; Chong, Ming Zhi; D'hoedt, Dieter; Foo, Chun Shin; Rajagopalan, Nandhakishore; Nirthanan, Selvanayagam; Bertrand, Daniel; Sivaraman, J.; Kini, R. Manjunatha

    2010-01-01

    Snake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of molecular probes and therapeutic agents. Here, we describe the structural and functional characterization of a novel neurotoxin, haditoxin, from the venom of Ophiophagus hannah (King cobra). Haditoxin exhibited novel pharmacology with antagonism toward muscle (αβγδ) and neuronal (α7, α3β2, and α4β2) nicotinic acetylcholine receptors (nAChRs) with highest affinity for α7-nAChRs. The high resolution (1.5 Å) crystal structure revealed haditoxin to be a homodimer, like κ-neurotoxins, which target neuronal α3β2- and α4β2-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic short-chain α-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain α-neurotoxins and κ-neurotoxins notwithstanding, haditoxin exhibited unique blockade of α7-nAChRs (IC50 180 nm), which is recognized by neither short-chain α-neurotoxins nor κ-neurotoxins. This is the first report of a dimeric short-chain α-neurotoxin interacting with neuronal α7-nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs. PMID:20071329

  2. Sarcocystis nesbitti infection in human skeletal muscle: possible transmission from snakes.

    PubMed

    Lau, Yee Ling; Chang, Phooi Yee; Tan, Chong Tin; Fong, Mun Yik; Mahmud, Rohela; Wong, Kum Thong

    2014-02-01

    Sarcocystis nesbitti is an intracellular protozoan parasite found as sarcocysts within muscle fibers of intermediate hosts (monkey and baboon). The definitive host is suspected to be the snake. We report two cases from a larger cohort of 89 patients who had fever, headache, and generalized myalgia after a trip to Pangkor Island, Malaysia. Sarcocysts were detected in skeletal muscle biopsy specimens by light and electron microscopy from these two patients. DNA sequencing based on the 18S ribosomal DNA region identified the Sarcocystis species as S. nesbitti. We also identified S. nesbitti sequences in the stools of a snake (Naja naja). Phylogenetic analysis showed that these sequences form a cluster with most of the other known Sarcocystis species for which the snake is a definitive host. We believe these two patients were likely to have symptomatic acute muscular sarcocystosis after S. nesbitti infection that may have originated from snakes. PMID:24420776

  3. Sarcocystis nesbitti Infection in Human Skeletal Muscle: Possible Transmission from Snakes

    PubMed Central

    Lau, Yee Ling; Chang, Phooi Yee; Tan, Chong Tin; Fong, Mun Yik; Mahmud, Rohela; Wong, Kum Thong

    2014-01-01

    Sarcocystis nesbitti is an intracellular protozoan parasite found as sarcocysts within muscle fibers of intermediate hosts (monkey and baboon). The definitive host is suspected to be the snake. We report two cases from a larger cohort of 89 patients who had fever, headache, and generalized myalgia after a trip to Pangkor Island, Malaysia. Sarcocysts were detected in skeletal muscle biopsy specimens by light and electron microscopy from these two patients. DNA sequencing based on the 18S ribosomal DNA region identified the Sarcocystis species as S. nesbitti. We also identified S. nesbitti sequences in the stools of a snake (Naja naja). Phylogenetic analysis showed that these sequences form a cluster with most of the other known Sarcocystis species for which the snake is a definitive host. We believe these two patients were likely to have symptomatic acute muscular sarcocystosis after S. nesbitti infection that may have originated from snakes. PMID:24420776

  4. Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study.

    PubMed

    M, Madhusudan; Zameer, Farhan; Naidu, Akhilender; M N, Nagendra Prasad; Dhananjaya, Bhadrapura Lakkappa; Hegdekatte, Raghavendra

    2016-09-01

    Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation. Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes. Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark). Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC50 value of 13.8 mg/mL on PLA2 from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC50 value of 16.6 mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC50 value of 0.92 mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of -128.96 compared to standard phenidone (-103.61). Thus, the current study validates the application of WS for inflammatory diseases. Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases. PMID:26704448

  5. Update on performance tests from the COBRA Process, a combined SO{sub 2} and NO{sub x} removal system[Copper Oxide Bed Regenerable Adsorber

    SciTech Connect

    Breault, R.W.; Litka, T.

    1999-07-01

    The Low Emission Boiler System (LEBS) Program of the US Department of Energy (DOE) is developing advanced power systems to accelerate the commercialization of affordable, highly efficient, and low-emission pulverized coal-fueled electric generating technologies. DB Riley Inc.'s concept for LEBS includes a dry, regenerable flue gas desulfurization and denitrification process. The COBRA (Copper Oxide Bed Regenerable Adsorber) Process can efficiently remove sulfur dioxide (SO{sub 2}) and sulfur trioxide (SO{sub 3}) and reduce nitrogen oxides (NO{sub x}) from flue gas with no solid or liquid byproducts and at a competitive cost. The sulfur laden flue gas is contacted with copper oxide impregnated alumina substrate in a cross flow moving bed reactor operating at 700 F. Sulfur dioxide reacts with the copper to form copper sulfate and the copper oxide/copper sulfate bed acts as a selective catalyst for NO{sub x} reduction. The sulfated sorbent is transported from the bottom of the moving bed reactors to the regenerator vessels where methane is used to reduce the copper sulfate to copper and SO{sub 2}. The concentrated SO{sub 2} stream resulting from regeneration may be oxidized to SO{sub 3} and condensed to sulfuric acid or can be converted to elemental sulfur in a Claus Plant or scrubbed with ammonia to form an ammonium sulfate. This paper will present the results of performance testing conducted on a 1 MW Pilot Scale Facility located at the Illinois Coal Development Park. This facility was designed and built to demonstrate at a reasonable scale the component configurations to be utilized in a full-scale system and to verify and optimize the operation of the integrated system. The ability of laboratory tests, when combined with a model of the moving bed adsorber, to predict the performance of the pilot system will be shown.

  6. Ophioluxin, a convulxin-like C-type lectin from Ophiophagus hannah (King cobra) is a powerful platelet activator via glycoprotein VI.

    PubMed

    Du, Xiao-Yan; Clemetson, Jeannine M; Navdaev, Alexei; Magnenat, Edith M; Wells, Timothy N C; Clemetson, Kenneth J

    2002-09-20

    Ophioluxin, a potent platelet agonist, was purified from the venom of Ophiophagus hannah (King cobra). Under nonreducing conditions it has a mass of 85 kDa, similar to convulxin, and on reduction gives two subunits with masses of 16 and 17 kDa, slightly larger than those of convulxin. The N-terminal sequences of both subunits are very similar to those of convulxin and other C-type lectins. Ophioluxin induces a pattern of tyrosine-phosphorylated proteins in platelets like that caused by convulxin, when using appropriate concentrations based on aggregation response, because it is about 2-4 times more powerful as agonist than the latter. Ophioluxin and convulxin induce [Ca(2+)](i) elevation both in platelets and in Dami megakaryocytic cells, and each of these C-type lectins desensitizes responses to the other. Convulxin agglutinates fixed platelets at 2 microg/ml, whereas ophioluxin does not, even at 80 microg/ml. Ophioluxin resembles convulxin more than echicetin or alboaggregin B because polyclonal anti-ophioluxin antibodies recognize both ophioluxin and convulxin, but not echicetin, and platelets adhere to and spread on ophioluxin- or convulxin-precoated surfaces in the same way that is clearly different from their behavior on an alboaggregin B surface. Immobilized ophioluxin was used to isolate the glycoprotein VI-Fcgamma complex from resting platelets, which also contained Fyn, Lyn, Syk, LAT, and SLP76. Ophioluxin is the first multiheterodimeric, convulxin-like snake C-type lectin, as well as the first platelet agonist, to be described from the Elapidae snake family. PMID:12130642

  7. Anticancer Activity of Cobra Venom Polypeptide, Cytotoxin-II, against Human Breast Adenocarcinoma Cell Line (MCF-7) via the Induction of Apoptosis

    PubMed Central

    Shirazi, Farshad H.; Vatanpour, Hosein; zare, Abas; Kobarfard, Farzad; Rabiei, Hadi

    2014-01-01

    Purpose Breast cancer is a significant health problem worldwide, accounting for a quarter of all cancer diagnoses in women. Current strategies for breast cancer treatment are not fully effective, and there is substantial interest in the identification of novel anticancer agents especially from natural products including toxins. Cytotoxins are polypeptides found in the venom of cobras and have various physiological effects. In the present study, the anticancer potential of cytotoxin-II against the human breast adenocarcinoma cell line (MCF-7) was investigated. Methods The cytotoxic effects of cytotoxin-II were determined by morphological analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The mode and mechanism of cell death were investigated via acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis of cell death, detection of mitochondrial membrane potential, measurement of intracellular reactive oxygen species (ROS), annexin V/propidium iodide staining, and caspase-9 activity assays. Results The half maximal inhibitory concentration (IC50) of cytotoxin-II in MCF-7 cells was 4.18±1.23 µg/mL, while the value for cisplatin was approximately 28.02±1.87 µg/mL. Morphological analysis and AO/EtBr double staining showed typical manifestations of apoptotic cell death (in doses lower than 8 µg/mL). Dose- and time-dependent ROS generation, loss of mitochondrial membrane potential, caspase-9 activation, and cell cycle arrest were observed in their respective tests. Conclusion In conclusion, cytotoxin-II has potent anticancer effects in the MCF-7 cell line, which are induced via the intrinsic pathways of apoptosis. Based on these findings, cytotoxin-II is a suitable choice for breast cancer treatment. PMID:25548578

  8. Reviews DVD: Nuclear Radiation Books: The Theoretical Minimum and Time Reborn Equipment: Cobra4 Data Logger Book: Stuff Matters Book: Hunting the Higgs Book: My Brief History Apps Web Watch

    NASA Astrophysics Data System (ADS)

    2014-01-01

    WE RECOMMEND Nuclear Radiation DVD is an excellent introduction to nuclear radiation WORTH A LOOK The Theoretical Minimum and Time Reborn Can mathematics be the key to reality? Cobra4 Data Logger Apparatus provides an extensive collection of sensors Stuff Matters Materials book deserves a wide readership Hunting the Higgs Higgs book a bit light on detail but good for visits to CERN My Brief History Hawking's book is readable but inconclusive APPS Using apps to help students visualize fields WEB WATCH Vintage film of Eric Laithwaite ... induction hobs as an example of electromagnetic induction ... the deconstruction of a CRO tube ... the Brocken spectre ... the Square Kilometre Array telescope

  9. The standard aqueous stem bark extract of Mangifera indica L. inhibits toxic PLA2 - NN-XIb-PLA2 of Indian cobra venom.

    PubMed

    Dhananjaya, Bhadrapura Lakkappa; Sudarshan, Shivalingaiah; Dongol, Yashad; More, Sunil S

    2016-05-01

    The aqueous extract of Mangifera indica is known to possess diverse medicinal properties, which also includes anti-snake venom activities. However, its inhibitory potency and mechanism of action on multi-toxic snake venom phospholipases A2s are still unknown. Therefore, the objective of this study was to evaluate the modulatory effect of standard aqueous bark extract of M. indica on NN-XIb-PLA2 of Indian cobra venom. The in vitro sPLA2, in situ hemolytic and in vivo edema inhibition effect were carried out as described. Also the effect of substrate and calcium concentration was carried out. M. indica extract dose dependently inhibited the GIA sPLA2 (NN-XIb-PLA2) activity with an IC50 value of 7.6 μg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ∼40 μg/ml concentration. Further, M. indica extract (0-50 μg/ml) inhibited the edema formed in a dose dependent manner. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect of M. indica extract on the NN-XIb-PLA2. Further, the inhibition was irreversible as evident from binding studies. The in vitro inhibition is well correlated with in situ and in vivo edema inhibiting activities of M. indica. As the inhibition is independent of substrate and calcium and was irreversible, it can be concluded that M. indica extract mode of inhibition could be due to direct interaction of components present in the extract with the PLA2 enzyme. The aqueous extract of M. indica effectively inhibits svPLA2 enzymatic and its associated toxic activities, which substantiate their anti-snake venom properties. Further in-depth studies on the role and mechanism of the principal constituents present in the extract, responsible for the anti-PLA2 activity will be interesting to develop them into potent antisnake component and also as an anti-inflammatory agent. PMID:27275129

  10. King cobra (Ophiophagus hannah) venom L-amino acid oxidase induces apoptosis in PC-3 cells and suppresses PC-3 solid tumor growth in a tumor xenograft mouse model.

    PubMed

    Lee, Mui Li; Fung, Shin Yee; Chung, Ivy; Pailoor, Jayalakshmi; Cheah, Swee Hung; Tan, Nget Hong

    2014-01-01

    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (OH-LAAO), a heat stable enzyme, has been shown to exhibit very potent anti-proliferative activity against human breast and lung tumorigenic cells but not in their non-tumorigenic counterparts. We further examine its in vitro and in vivo anti-tumor activity in a human prostate adenocarcinoma (PC-3) model. OH-LAAO demonstrated potent cytotoxicity against PC-3 cells with IC50 of 0.05 µg/mL after 72 h incubation in vitro. It induced apoptosis as evidenced with an increase in caspase-3/7 cleavages and an increase in annexin V-stained cells. To examine its in vivo anti-tumor activity, we treated PC-3 tumor xenograft implanted subcutaneously in immunodeficient NU/NU (nude) mice with 1 µg/g OH-LAAO given intraperitoneally (i.p.). After 8 weeks of treatment, OH-LAAO treated PC-3 tumors were markedly inhibited, when compared to the control group (P <0.05). TUNEL staining analysis on the tumor sections showed a significantly increase of apoptotic cells in the LAAO-treated animals. Histological examinations of the vital organs in these two groups showed no significant differences with normal tissues, indicating no obvious tissue damage. The treatment also did not cause any significant changes on the body weight of the mice during the duration of the study. These observations suggest that OH-LAAO cytotoxic effects may be specific to tumor xenografts and less to normal organs. Given its potent anti-tumor activities shown in vitro as well as in vivo, the king cobra venom LAAO can potentially be developed to treat prostate cancer and other solid tumors. PMID:24782648

  11. The New MODIS-Terra, and the Proposed COBRA Mission: First Global Aerosol Distribution and Properties Over Land and Ocean, and Plans to Measure Global Black Carbon Absorption Over the Ocean Glint

    NASA Technical Reports Server (NTRS)

    Kaufman, Yoram J.; Tanre, Didier; Remer, Lorraine; Martins, Vanderlei; Schoeberl, Mark; Lau, William K. M. (Technical Monitor)

    2001-01-01

    The MODIS instrument was launched on the NASA Terra satellite in Dec. 1999. Since last Oct, the sensor and the aerosol algorithm reached maturity and provide global daily retrievals of aerosol optical thickness and properties. MODIS has 36 spectral channels in the visible to IR with resolution down to 250 m. This allows accurate cloud screening and multi-spectral aerosol retrievals. We derive the aerosol optical thickness over the ocean and most of the land areas, distinguishing between fine (mainly man-made aerosol) and coarse (mainly natural) aerosol particles. New methods to derive the aerosol absorption of sunlight are also being developed. These measurements are use to track different aerosol sources, transport and the radiative forcing at the top and bottom of the atmosphere. However MODIS or any present satellite sensor cannot measure absorption by Black Carbon over the oceans, a critical component in studying climate change and human health. For this purpose we propose the COBRA mission that observes the ocean at glint and off glint simultaneously measuring the spectral polarized light and deriving precisely the aerosol absorption.

  12. Analysis of camelid antibodies for antivenom development: Neutralisation of venom-induced pathology.

    PubMed

    Cook, Darren A N; Owen, Timothy; Wagstaff, Simon C; Kinne, Joerg; Wernery, Ulrich; Harrison, Robert A

    2010-09-01

    Camelid IgG has been reported to be less immunogenic, less able to activate the complement cascade and more thermostable than IgG from other mammals, and has the ability to bind antigens that are unreactive with other mammalian IgGs. We are investigating whether these attributes of camelid IgG translate into antivenom with immunological and venom-neutralising efficacy advantages over conventional equine and ovine antivenoms. The objective of this study was to determine the preclinical venom-neutralising effectiveness of IgG from camels immunised with venoms, individually or in combination, of the saw-scaled viper, Echis ocellatus, the puff adder, Bitis arietans and the spitting cobra, Naja nigricollis - the most medically-important snake species in West Africa. Neutralisation of the pathological effects of venoms from E. ocellatus, B. arietans and N. nigricollis by IgG from the venom-immunised camels, or commercial antivenom, was compared using assays of venom lethality (ED(50)), haemorrhage (MHD) and coagulopathy (MCD). The E. ocellatus venom ED(50), MHD and MCD results of the E. ocellatus monospecific camel IgG antivenom were broadly equivalent to comparable ovine (EchiTAbG, MicroPharm Ltd, Wales) and equine (SAIMR Echis, South African Vaccine Producer, South Africa) antivenoms, although the equine antivenom required half the amount of IgG. The B. arietans monospecific camel IgG neutralised the lethal effects of B. arietans venom at one fourth the concentration of the SAIMR polyspecific antivenom (a monospecific B. arietans antivenom is not available). The N. nigricollis camel IgG antivenom was ineffective (at the maximum permitted dose, 100 mul) against the lethal effects of N. nigricollis venom. All the equine polyspecific antivenoms required more than 100 microl to be effective against this venom. The polyspecific camel IgG antivenom, prepared from five camels, was effective against the venom-induced effects of E. ocellatus but not against that of B. arietans

  13. Phospholipase A2 as a mechanosensor.

    PubMed Central

    Lehtonen, J Y; Kinnunen, P K

    1995-01-01

    Osmotic swelling of large unilamellar vesicles (LUVs) causes membrane stretching and thus reduces the lateral packing of lipids. This is demonstrated to modulate strongly the catalytic activity of phospholipase A2 (PLA2) toward a fluorescent phospholipid, 1-palmitoyl-2-[(6-pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PPDPC) residing in LUVs composed of different unsaturated and saturated phosphatidylcholines. The magnitude of the osmotic pressure gradient delta omega required for maximal PLA2 activity as well as the extent of activation depend on the degree of saturation of the membrane phospholipid acyl chains. More specifically, delta omega needed for maximal hydrolytic activity increases in the sequence DOPC < SOPC < DMPC in accordance with the increment in the intensity of chain-chain van der Waals interactions. Previous studies on the hydrolysis of substrate monolayers by C. adamanteus and N. naja PLA2 revealed maximal hydrolytic rates for these two enzymes to be achieved at lipid packing densities corresponding to surface pressures of 12 and 18 mN m-1, respectively. In keeping with the above the magnitudes of delta omega producing maximal activity of Crotalus adamanteus and Naja naja toward PPDPC/DMPC LUVs were 40 and 20 mOsm/kg, respectively. Our findings suggest a novel possibility of regulating the activity of PLA2 and perhaps also other lipid packing density-dependent enzymes in vivo by osmotic forces applied on cellular membranes. Importantly, our results reveal serendipitously that the responsiveness of membranes to osmotic stress is modulated by the acyl chain composition of the lipids. PMID:7612831

  14. Flare-up of antigen-induced arthritis in mice after challenge with intravenous antigen: effects of pre-treatment with cobra venom factor and anti-lymphocyte serum.

    PubMed Central

    Lens, J W; van den Berg, W B; van de Putte, L B; Berden, J H; Lems, S P

    1984-01-01

    Intravenous injection of methylated bovine serum albumin (mBSA) into mice with unilateral chronic mBSA-induced arthritis (AIA) causes a flare-up of the joint inflammation without affecting the contralateral non-arthritic knee joint. We studied the mechanism of the flare-up by decomplementation with cobra venom factor (CoVF) and by treatment with anti-lymphocyte serum (ALS) prior to the induction of the flare-up. Treatment of mice with CoVF had no effect on the induction of the flare-up reaction whereas a reversed passive Arthus reaction (RPA) in the ear of similarly treated mice was clearly suppressed. The complement activity in the serum was zero at 2 h after CoVF treatment and remained for 24 h. This indicates that this type of flare-up reaction is not complement-dependent. On the other hand, the flare-up reaction was completely abolished after treatment with ALS. Control experiments revealed that ALS treatment diminished the number of lymphocytes in the peripheral blood and clearly suppressed a delayed hypersensitivity reaction in the ear, but had no effect on an RPA. These results suggest an important role of T lymphocytes in the mechanism of the flare-up of arthritis. T lymphocytes were demonstrated in the synovial tissue of chronically inflamed joints by immunofluorescence and appeared to be diminished after ALS treatment. Interaction between exogenous antigen and antigen reactive T lymphocytes present in chronically inflamed joints, may be an important principle in the exacerbation and propagation of joint inflammation. Images Fig. 3 PMID:6235993

  15. Hydrology, water quality, trophic status, and aquatic plants of Fowler Lake, Wisconsin

    USGS Publications Warehouse

    Hughes, P.E.

    1993-01-01

    The low annual phosphorus input (28 pounds per square mile) to the lake from the Oconomowoc River shows the benefit of upstream lakes on the Oconomowoc River. Fourteen percent of the phosphorus input load to Fowler Lake is deposited in the lake sediments and the rest is transported through the lake by surface-water flow to downstream Lac La Belle. Dense growths of macrophytes in the lake change in composition seasonally; chara sp. (muskgrass) and Myriophyllum sp. (milfoil) are abundant in June and Najas marina and Vallesneria Americana (wild celery) are abundant in August.

  16. Natural phospholipase A(2) myotoxin inhibitor proteins from snakes, mammals and plants.

    PubMed

    Lizano, Sergio; Domont, Gilberto; Perales, Jonas

    2003-12-15

    A renewed interest in the phenomenon of inter- and intra-species resistance towards the toxicity of snake venoms, coupled with the search for new strategies for treatment of snake envenomations, has prompted the discovery of proteins which neutralize the major toxic components of these venoms. Among these emerging groups of proteins are inhibitors of toxic phospholipases A2 (PLA2s), many of which exhibit a wide range of toxic effects including muscle-tissue damage, neurotoxicity, and inflammation. These proteins have been isolated from both venomous and non-venomous snakes, mammals, and most recently from medicinal plant extracts. The snake blood-derived inhibitors have been grouped into three major classes, alpha, beta, and gamma, based on common structural motifs found in other proteins with diverse physiological properties. In mammals, DM64, an anti-myotoxic protein isolated from opossum serum, belongs to the immunoglobulin super gene family and is homologous to human alpha1B-glycoprotein and DM43, a metalloproteinase inhibitor from the same organism. In plants, a short note is made of WSG, a newly described anti-toxic-PLA2 glycoprotein isolated from Withania somnifera (Ashwaganda), a medicinal plant whose aqueous extracts neutralize the PLA2 activity of the Naja naja venom. The implications of these new groups of PLA2 toxin inhibitors in the context of our current understanding of snake biology as well as in the development of novel therapeutic reagents in the treatment of snake envenomations worldwide are discussed. PMID:15019494

  17. Photolabeling reveals the proximity of the alpha-neurotoxin binding site to the M2 helix of the ion channel in the nicotinic acetylcholine receptor.

    PubMed Central

    Machold, J; Utkin, Y; Kirsch, D; Kaufmann, R; Tsetlin, V; Hucho, F

    1995-01-01

    A photoactivatable derivative of neurotoxin II from Naja naja oxiana containing a 125I-labeled p-azidosalicylamidoethyl-1,3'-dithiopropyl label at Lys-25 forms a photo-induced cross-link with the delta subunit of the membrane-bound Torpedo californica nicotinic acetylcholine receptor (AChR). The cross-linked radioactive receptor peptide was isolated by reverse-phase HPLC after tryptic digestion of the labeled delta subunit. The sequence of this peptide, delta-(260-277), and the position of the label at Ala-268 were established by matrix-assisted laser-desorption-ionization mass spectrometry based on the molecular mass and on post-source decay fragment analysis. With the known dimensions of the AChR molecule, of the photolabel, and of alpha-neurotoxin, finding the cross-link at delta Ala-268 (located in the upper part of the channel-forming transmembrane helix M2) means that the center of the alpha-neurotoxin binding site is situated at least approximately 40 A from the extracellular surface of the AChR, proximal to the channel axis. Images Fig. 2 PMID:7543679

  18. Electron microscopy of complexes of isolated acetylcholine receptor, biotinyl-toxin, and avidin

    SciTech Connect

    Holtzman, E.; Wise, D.; Wall, J.; Karlin, A.

    1982-01-01

    The principal curarimimetic toxin of Naja naja siamensis derivatized with biothinyl groups binds specifically both to acetylcholine receptor, isolated from Torpedo californica electric tissue, and to avidin. Isolated complexes of receptor monomer or dimer, biotinyl-toxin, and avidin were negatively stained and examined in the scanning transmission electron microscope. We measured the angle made by the radius to each avidin bound at the periphery of a monomeric unit in dimer to the axis connecting the centers of the monomers, starting at the crosslink between the monomers. We infer from the distribution of these angles that one toxin binding site is located in the range of 45/sup 0/ to 85/sup 0/ and another at about 100/sup 0/ further from the crosslink between the monomers. Because it is known that there are two toxin binding sites per monomer, associated with the two ..cap alpha.. chains, the bound avidins presumably point to portions of the ..cap alpha.. chains, indicating their positions relative to that portion of the delta chain located at the crosslink between monomers in dimer.

  19. Identification of novel inhibitors of Daboia russelli phospholipase A2 using the combined pharmacophore modeling approach.

    PubMed

    Ramakrishnan, Chandrasekaran; Joshi, Vikram; Joseph, Joseph Mavelithuruthel; Vishwanath, Bannikuppe S; Velmurugan, Devadasan

    2014-10-01

    Crystal structures available for Daboia russelli venom PLA(2) confirm that it undergoes dimerization with asymmetry and hence difference in the conformation of active site of the two subunits. The active site of subunit A is open and that of subunit B is closed. Pharmacophore models were generated based on the interaction of different types of inhibitors with their preferred subsites in the active site of subunit A. Particularly, the features responsible for recognizing subsites 1-3 and those of subsites 4-6 were combined as these two are involving in inflammation and anticoagulation processes, respectively. Pharmacophore model was edited to make the geometry suitable for the active site of both the subunits A and B. Final model is validated and subjected for screening a library of druglike compounds. Eight compounds were shortlisted and subjected for molecular docking and dynamics simulation to assess their binding mode with both the subunits. Based on the hydrophobic interactions and binding free energy, four compounds were selected for further biochemical assay. The overall results suggest that two compounds can bind both the subunits of PLA(2) of Daboia russelli venom in spite of its aggregated form and other two inhibit structurally very similar Naja naja PLA(2). PMID:24703201

  20. Protein interactions between the C-terminus of Aβ-peptide and phospholipase A2--a structure biology based approach to identify novel Alzheimer's therapeutics.

    PubMed

    Mirza, Zeenat; Pillai, Vikram G; Kamal, Mohammad A

    2014-01-01

    Amyloid β (Aβ) polypeptide plays a key role in determining the state of protein aggregation in Alzheimer's disease. The hydrophobic C-terminal part of the Aβ peptide is critical in triggering the transformation from α-helical to β- sheet structure. We hypothesized that phospholipase A2 (PLA2) may inhibit the aggregation of Aβ peptide by interacting with the peptide and keeping the two peptide chains apart. In order to examine the nature of interactions between PLA2 and Aβ peptide, we prepared and crystallized complex of Naja naja sagittifera PLA2 with the C-terminal hepta-peptide Val-Gly-Gly-Val-Val-Ile-Ala. The X-ray intensity data were collected to 2.04 A resolution and the structure was determined by molecular replacement and refined to the crystallographic R factor of 0.186. The structural analysis revealed that the peptide binds to PLA2 at the hydrophobic substrate binding cavity forming at least eight hydrogen bonds and approximately a two dozen Van der Waals interactions. The number and nature of interactions indicate that the affinity between PLA2 and the hepta-peptide is greater than the affinity between two Aβ peptide chains. Therefore, PLA2 is proposed as a probable ligand to prevent the aggregation of Aβ peptides. PMID:25230229

  1. A checklist of the snake fauna of Guinea, with taxonomic changes in the genera Philothamnus and Dipsadoboa (Colubridae) and a comparison with the snake fauna of some other West African countries.

    PubMed

    Trape, Jean-François; Baldé, Cellou

    2014-01-01

    We present here the results of a study of 4,906 snakes from Guinea belonging to 95 species collected from 2002 to 2013 at 54 localities in all administrative regions of the country. We resurrect Dipsadoboa guineensis from the synonymy of D. brevirostris and consider the latter species a junior synonym of D. duchesnei. In addition we resurrrect Philothamnus pobeguini and P. belli from the synonymy of P. heterodermus. 19 species were not previously collected in this country, including Letheobia coecata, Tricheilostoma bicolor, Myriopholis rouxestevae, Rhinoleptus koniagui, Python regius, Grayia tholloni, Natriciteres fuliginoides, Philothamnus heterolepidotus, Thrasops aethiopissa, Amblyodipsas unicolor, Gonionotophis granti, Mehelya crossi, Prosymna gregeirti, Prosymna meleagris, Rhamphiophis oxyrhynchus, Elapsoidea trapei, Naja katiensis, Naja senegalensis and Echis jogeri. Based on a critical review of literature and our own data, we compare the currently known snake fauna of Guinea (104 species) with that of Sierra Leone (65 species), Liberia (63 species), Ivory Coast (101 species), Ghana (102 species), Togo (93 species), Benin (72 species) and Nigeria (118 species).  PMID:25543742

  2. What Is Your Cobra E.Q.?

    ERIC Educational Resources Information Center

    Anderson, Deborah B.; And Others

    An award winning project for incorporating economics study into the junior high school curriculum is described. As a joint activity of 3 eighth grade social studies classes, 60 students created a videotape program to teach and test 6 basic economic concepts: scarcity and choice, opportunity costs, productive resources, production, supply and…

  3. Alpha-lipoic acid: an inhibitor of secretory phospholipase A2 with anti-inflammatory activity.

    PubMed

    Jameel, Noor Mohamed; Shekhar, Mysore A; Vishwanath, Bannikuppe S

    2006-12-14

    Alpha-lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are powerful antioxidants both in hydrophilic and lipophylic environments with diverse pharmacological properties including anti-inflammatory activity. The mechanism of anti-inflammatory activity of ALA and DHALA is not known. The present study describes the interaction of ALA and DHALA with pro-inflammatory secretory PLA(2) enzymes from inflammatory fluids and snake venoms. In vitro enzymatic inhibition of sPLA(2) from Vipera russellii, Naja naja and partially purified sPLA(2) enzymes from human ascitic fluid (HAF), human pleural fluid (HPF) and normal human serum (HS) by ALA and DHLA was studied using (14)C-oleate labeled Escherichia coli as the substrate. Biophysical interaction of ALA with sPLA(2) was studied by fluorescent spectral analysis and circular dichroism studies. In vivo anti-inflammatory activity was checked using sPLA(2) induced mouse paw edema model. ALA but not DHLA inhibited purified sPLA(2) enzymes from V. russellii, N. naja and partially purified HAF, HPF and HS in a dose dependent manner. This data indicated that ALA is critical for inhibition. IC(50) value calculated for these enzymes ranges from 0.75 to 3.0 microM. The inhibition is independent of calcium and substrate concentration. Inflammatory sPLA(2) enzymes are more sensitive to inhibition by ALA than snake venom sPLA(2) enzymes. ALA quenched the fluorescence intensity of sPLA(2) enzyme in a dose dependent manner. Apparent shift in the far UV-CD spectra of sPLA(2) with ALA indicated change in its alpha-helical confirmation and these results suggest its direct interaction with the enzyme. ALA inhibits the sPLA(2) induced mouse paw edema in a dose dependent manner and confirms the sPLA(2) inhibitory activity in vivo also. These data suggest that ALA may act as an endogenous regulator of sPLA(2) enzyme activity and suppress inflammatory reactions. PMID:17011589

  4. Maintaining the competitiveness of the American fisheries society journals: an assessment based on influence and cost-effectiveness

    USGS Publications Warehouse

    Hewitt, David A.; Link, Jason S.; Steinich, Dave R.; Wahl, David H.; Mather, Martha E.

    2009-01-01

    Recent changes in the landscape of scientific publishing prompted the Publications Overview Committee of the American Fisheries Society (AFS) to review the Society's portfolio of scientific journals. We evaluated journals based on metrics in two categories: (1) citation-based measures of the influence of a journal on the scientific literature, and (2) measures of the cost-effectiveness of a journal (citation rate adjusted for subscription cost). Over the long-term, we found that ecology journals had far stronger citation-based influence than fisheries and aquatic sciences journals, and that journals publishing primarily basic research had stronger influence than journals publishing applied research (including four AFS journals and Fisheries magazine). In evaluating the current status of fisheries and aquatic sciences journals, we found that metrics of influence and cost-effectiveness provided considerably different portrayals of journals relative to their peers. In terms of citation-based influence, we found that the AFS journal Transactions of the American Fisheries Society (TAFS) and Fisheries magazine were competitive with highly regarded peer fisheries journals, but that North American Journal of Aquaculture (NAJA) and Journal of Aquatic Animal Health (JAAH) were less influential than their peers. The citation-based influence of North American Journal of Fisheries Management (NAJFM) was intermediate between TAFS/Fisheries and NAJA/JAAH. For journals like NAJFM and NAJA, we expect that much of the scientific influence on policy and management is not captured by citations in the primary literature, and alternative methods of evaluation may be needed. All of the AFS journals ranked highly with regard to cost-effectiveness because their subscription costs are low, and these rankings are in accordance with membership needs and the strategic mission of AFS to provide broad and timely dissemination of scientific information. We conclude by suggesting

  5. Quantifying Demyelination in NK venom treated nerve using its electric circuit model.

    PubMed

    Das, H K; Das, D; Doley, R; Sahu, P P

    2016-01-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination. PMID:26932543

  6. Comparison of Pasteur and Behringwerke antivenoms in envenoming by the carpet viper (Echis carinatus).

    PubMed Central

    Warrell, D A; Warrell, M J; Edgar, W; Prentice, C R; Mathison, J; Mathison, J

    1980-01-01

    Bites and envenoming by the carpet viper Echis carinatus are common medical emergencies in parts of Nigeria, but the most effective use of the various commercially produced antivenoms in treatment has not been established. Pasteur Paris Echis monospecific and Behringwerke West and North Africa Bitis-Echis-Naja polyspecific antivenoms were compared in two groups of seven patients with incoagulable blood after E carinatus bites. In both groups spontaneous bleeding stopped within a few hours and local swelling subsided within two weeks after the initial antivenom injection. Pasteur antivenom (20-40 ml) restored blood coagulability within 12 hours in all cases, but 60--180 ml of Behringwerke antivenom was effective in only four cases. Persisting venom procoagulant activity was observed in the remaining three cases. Despite its potency in the mouse protection test, Behringwerke antivenom is unreliable and unpredictable in neutralising venom procoagulant in humans bitten by E carinatus. PMID:7370603

  7. Quantifying Demyelination in NK venom treated nerve using its electric circuit model

    NASA Astrophysics Data System (ADS)

    Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

    2016-03-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

  8. Membrane phase characteristics control NA-CATH activity.

    PubMed

    Samuel, Robin; Gillmor, Susan

    2016-09-01

    Our studies presented in this report focus on the behavior of NA-CATH, an α-helical cathelicidin antimicrobial peptide, originally discovered in the Naja atra snake. It has demonstrated high potency against gram-positive and gram-negative bacteria with minimal hemolysis. Here we examine the kinetics, behaviors and potential mechanisms of the peptide in the presence of membrane liposome, modeling Escherichia coli, whose membrane exhibits distinct lipid phases. To understand NA-CATH interactions, the role of lipid phases is critical. We test three different lipid compositions to detangle the effect of phase on NA-CATH's activity using a series of leakage experiments. From these studies, we observe that NA-CATH changes from membrane disruption to pore-based lysing, depending on phases and lipid composition. This behavior also plays a major role in its kinetics. PMID:27216315

  9. Fate of psychoactive compounds in wastewater treatment plant and the possibility of their degradation using aquatic plants.

    PubMed

    Mackuľak, Tomáš; Mosný, Michal; Škubák, Jaroslav; Grabic, Roman; Birošová, Lucia

    2015-03-01

    In this study we analyzed and characterized 29 psychoactive remedies, illicit drugs and their metabolites in single stages of wastewater treatment plants in the capital city of Slovakia. Psychoactive compounds were present within all stages, and tramadol was detected at a very high concentration (706 ng/L). Significant decreases of codeine, THC-COOH, cocaine and buprenorphine concentration were observed in the biological stage. Consequently, we were interested in the possibility of alternative tertiary post-treatment of effluent water with the following aquatic plants: Cabomba caroliniana, Limnophila sessiliflora, Egeria najas and Iris pseudacorus. The most effective plant for tertiary cleansing was I. pseudacorus which demonstrated the best pharmaceutical removal capacity. After 48 h codeine and citalopram was removed with 87% efficiency. After 96 h were all analyzed compounds were eliminated with efficiencies above 58%. PMID:25818110

  10. Distribution of submersed macrophytes in the St. Clair-Detroit River System, 1978

    USGS Publications Warehouse

    Schloesser, Donald W.; Manny, Bruce A.

    1986-01-01

    An extensive survey was conducted in fall 1978 to determine the distribution and abundance of submersed macrophytes through the St. Clair-Detroit River system from Lake Huron to Lake Erie. Submersed macrophytes, representing 19 taxa, were widely distributed in the system, being found on 358 km2 (30%) of the total 1185 km2 of substrate surveyed. Of the 19 taxa identified, 8 common taxa were found on 20 to 121 km2 of substrate. These commonly found taxa, in decreasing order of substrate coverage were Characeae, Vallisneria americana, Najas flexilis, Myriophyllum spicatum, Elodea canadensis, Potamogeton richardsonii, Potamogeton spp. (narrow-leaf forms), andHeteranthera dubia. In general, macrophyte beds of low, medium, and high biomass covered much less area but a higher proportion of the available substrate in the St. Clair and Detroit rivers than in Lake St. Clair.

  11. Secondary structure determination for alpha-neurotoxin from Dendroaspis polylepis polylepis based on sequence-specific 1H-nuclear-magnetic-resonance assignments.

    PubMed

    Labhardt, A M; Hunziker-Kwik, E H; Wüthrich, K

    1988-11-01

    Sequence-specific assignments are presented for the polypeptide backbone protons and a majority of the amino-acid-side-chain protons of alpha-neurotoxin from Dendroaspis polylepis polylepis, and individual amide proton-exchange rates with the solvent are reported. The secondary structure and the hydrogen-bonding patterns in the regular secondary structure elements are deduced from nuclear Overhauser effects and the sequence locations of the slowly exchanging amide protons. The molecule includes a three-stranded antiparallel beta-sheet, and there are indications that two additional short chain segments are arranged in an antiparallel beta-sheet. These structural elements are similar, but not identical, to either the secondary structure reported for erabutoxin b in single crystals, or the solution structure of cytotoxin CTXIIb from Naja mossambica mossambica. PMID:2847926

  12. Quantifying Demyelination in NK venom treated nerve using its electric circuit model

    PubMed Central

    Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

    2016-01-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination. PMID:26932543

  13. Analysis of ligand binding to the synthetic dodecapeptide 185-196 of the acetylcholine receptor alpha subunit.

    PubMed

    Neumann, D; Barchan, D; Fridkin, M; Fuchs, S

    1986-12-01

    A synthetic dodecapeptide corresponding to residues 185-196 of the Torpedo acetylcholine receptor alpha subunit, which contains the adjacent cysteine residues at positions 192 and 193, was recently shown by us to contain the essential elements for alpha-bungarotoxin binding. In the present study, we have used Sepharose-linked peptides for quantitative analysis of the cholinergic binding properties of this and other synthetic peptides. Sepharose-linked peptides corresponding to residues 1-20, 126-143, 143-158, 169-181, 185-196, 193-210, and 394-409 of the alpha subunit of Torpedo acetylcholine receptor, as well as a peptide corresponding to residues 185-196 of the alpha subunit of human acetylcholine receptor, were tested for their toxin-binding capacity. Of these immobilized peptides, only peptide 185-196 of the Torpedo acetylcholine receptor bound toxin significantly, thus verifying that this synthetic peptide contains essential components of the receptor toxin-binding site. Analysis of toxin binding to the peptide yielded a dissociation constant of 3.5 X 10(-5) M. This binding was inhibited by various cholinergic ligands. The inhibition potency obtained was alpha-bungarotoxin greater than Naja naja siamensis toxin greater than d-tubocurarine greater than decamethonium greater than acetylcholine greater than carbamoylcholine. This pharmacological profile resembles that of the nicotinic acetylcholine receptor and therefore suggests that the synthetic dodecapeptide also includes the neurotransmitter binding site. Reduction and carboxymethylation of the cysteine residues on peptide 185-196 inhibit its capacity to bind toxin, demonstrating that an intact disulfide is required for toxin binding. A decrease in toxin binding was also obtained following chemical modification of the tryptophan residue at position 187, thus implying its possible involvement in toxin binding. The failure to detect binding of toxin to the corresponding human sequence 185-196, in which the

  14. Analysis of ligand binding to the synthetic dodecapeptide 185-196 of the acetylcholine receptor alpha subunit.

    PubMed Central

    Neumann, D; Barchan, D; Fridkin, M; Fuchs, S

    1986-01-01

    A synthetic dodecapeptide corresponding to residues 185-196 of the Torpedo acetylcholine receptor alpha subunit, which contains the adjacent cysteine residues at positions 192 and 193, was recently shown by us to contain the essential elements for alpha-bungarotoxin binding. In the present study, we have used Sepharose-linked peptides for quantitative analysis of the cholinergic binding properties of this and other synthetic peptides. Sepharose-linked peptides corresponding to residues 1-20, 126-143, 143-158, 169-181, 185-196, 193-210, and 394-409 of the alpha subunit of Torpedo acetylcholine receptor, as well as a peptide corresponding to residues 185-196 of the alpha subunit of human acetylcholine receptor, were tested for their toxin-binding capacity. Of these immobilized peptides, only peptide 185-196 of the Torpedo acetylcholine receptor bound toxin significantly, thus verifying that this synthetic peptide contains essential components of the receptor toxin-binding site. Analysis of toxin binding to the peptide yielded a dissociation constant of 3.5 X 10(-5) M. This binding was inhibited by various cholinergic ligands. The inhibition potency obtained was alpha-bungarotoxin greater than Naja naja siamensis toxin greater than d-tubocurarine greater than decamethonium greater than acetylcholine greater than carbamoylcholine. This pharmacological profile resembles that of the nicotinic acetylcholine receptor and therefore suggests that the synthetic dodecapeptide also includes the neurotransmitter binding site. Reduction and carboxymethylation of the cysteine residues on peptide 185-196 inhibit its capacity to bind toxin, demonstrating that an intact disulfide is required for toxin binding. A decrease in toxin binding was also obtained following chemical modification of the tryptophan residue at position 187, thus implying its possible involvement in toxin binding. The failure to detect binding of toxin to the corresponding human sequence 185-196, in which the

  15. A single-label fluorescent derivatization method for quantitative determination of neurotoxin in vivo by capillary electrophoresis coupled with laser-induced fluorescence detection.

    PubMed

    Chen, Cuiwei; Hu, Yiqin; Shi, Xiaowei; Tao, Chenghao; Zheng, Hongyue; Fei, Weidong; Han, Shunping; Zhu, Jiazhen; Wei, Yinghui; Li, Fanzhu

    2016-07-21

    Neurotoxin (NT), a short-chain α-neurotoxin, is the main neurotoxic protein identified from the venom of Naja naja atra. As an effective drug for the analgesis of advanced cancer patients, NT lasts longer than morphine and does not cause addiction. However, achieving a sensitive and high-resolution measurement of NT is difficult because of the extra-low content of NT in vivo. Therefore, developing a novel method to quantify NT is essential to study its pharmacokinetics in vivo. Although NT contains four primary amine groups that could react with the thiourea in fluorescein isothiocyanate (FITC), we developed a simple and reproducible single-label fluorescent derivatization method for NT which is related to the reaction of N-terminal α-amino of NT alone under optimized derivatization conditions. Furthermore, neurotoxin labelled with fluorescein isothiocyanate (NT-FITC) was prepared by high-performance liquid chromatography (HPLC) with a purity value higher than 99.29% and identified by MALDI-TOF/TOF-MS. Finally, NT-FITC could be detected at 0.8 nmol L(-1) in rat plasma using capillary electrophoresis coupled with laser induced fluorescence detection (CE-LIF). In this paper, the established method robustly and reliably quantified NT labelled with FITC via intravenous and intramuscular administrations in vivo. In addition, this work fully demonstrated the pharmacokinetic characteristics of NT in vivo, which could reduce the risk of drug accumulation, optimize therapies, and provide sufficient evidence for the rational use of NT in clinical and research laboratories. PMID:27175860

  16. Increase of the cytotoxic effect of Bothrops jararacussu venom on mouse extensor digitorum longus and soleus by potassium channel blockers and by Na(+)/K(+)-ATPase inhibition.

    PubMed

    Tomaz, Marcelo A; Fernandes, Fabrício F A; El-Kik, Camila Z; Moraes, Raphael A M; Calil-Elias, Sabrina; Saturnino-Oliveira, Jeison; Martinez, Ana Maria B; Ownby, Charlotte L; Melo, Paulo A

    2008-09-15

    We investigated the myotoxicity of Bothrops jararacussu crude venom and other cytolytic agents on mouse isolated extensor digitorum longus (EDL) and soleus (SOL) muscles, which present distinct properties: EDL is a fast-twitch, white muscle with predominantly glycolytic fibers, while SOL is slow-twitch, red muscle with predominantly oxidative fibers. Muscles were exposed to B. jararacussu crude venom (25 microg/ml) and other crotaline venoms (Agkistrodon contortrix laticinctus; Crotalus viridis viridis; Crotalus durissus terrificus) at the same concentration. Basal creatine kinase (CK) release to bathing solution was 0.43+/-0.06 for EDL and 0.29+/-0.06 for SOL (U g(-)(1) h(-)(1), n=36 for each muscle). Sixty minutes after exposure to B. jararacussu venom, EDL presented higher increase in the rate of CK release than SOL, respectively, 13.2+/-1.5 and 2.9+/-0.7 U g(-)(1)h(-)(1), n=10-12. Muscle denervation, despite decreasing CK content, did not affect sensitivities to B. jararacussu venom. Ouabain and potassium channel blockers (TEA; clotrimazole; glibenclamide) increased the rate of CK release by B. jararacussu in EDL and SOL muscles, decreasing and almost abolishing the different sensitivity. When we exposed EDL or SOL muscles to Naja naja, Apis mellifera venoms (25 microg/ml), or Triton X-100 (0.01%), they showed similar rate of CK release. Our present data suggest that a mechanism involving intracellular calcium regulation or potassium channels may participate in the different sensitivity of EDL and SOL to B. jararacussu venom. PMID:18675839

  17. Evidence for conformational differences in aqueous and crystalline structures of α-bungarotoxin and cobratoxin

    NASA Astrophysics Data System (ADS)

    Thomas, George J.; Prescott, Betty; Love, Robert; Stroud, Robert M.

    Laser Raman spectroscopy has been employed to investigate the structures of α-bungarotoxin ( Bungarus multicinctus) and cobratoxin ( Naja naja siamensis) in H 2O and D 2O solutions. Structures of the aqueous neurotoxins are compared with one another and with the X-ray crystal structures. The results indicate that the solution and crystal molecular structures of cobratoxin are in substantial agreement with one another, but those of α-bungarotoxin are not. Raman data provide no evidence for strained disulfides in aqueous α-bungarotoxin, although strained CSSC dihedral angles are indicated for the X-ray crystal structure. The data are interpreted as evidence for a strained molecular conformation of α-bungarotoxin in the crystal, which converts to a relaxed, more energetically favorable conformation in aqueous solution. Raman spectra also suggest more β-strand secondary structure in aqueous α-bungarotoxin (47 ± 5%) than in the crystalline form ( < 10%). The high β-strand content measured by Raman spectroscopy could be due to either a secondary structure in solution that is appreciably different than that of the crystal, or to the imprecision of the Raman method in distinguishing peptide configurations that are vibrationally equivalent but conformationally inequivalent. Aqueous α-bungarotoxin and cobratoxin also differ from one another in amino acid side chain orientations and interactions, though not in main chain conformations. Different geometries are indicated for cystine CCSS dihedral angles, and different hydrogen bonding states are indicated for internal tyrosines. Tyrosine-24 of α-bungarotoxin is shown to donate a strong hydrogen bond to a negative acceptor, deduced to be glutamate-41, whereas the equivalently positioned residue of cobratoxin is apparently hydrogen bonded to solvent molecules.

  18. Cobra Strikes! High-Performance Car Inspires Students, Markets Program

    ERIC Educational Resources Information Center

    Jenkins, Bonita

    2008-01-01

    Nestled in the Lower Piedmont region of upstate South Carolina, Piedmont Technical College (PTC) is one of 16 technical colleges in the state. Automotive technology is one of its most popular programs. The program features an instructive, motivating activity that the author describes in this article: building a high-performance car. The Cobra…

  19. 26 CFR 54.4980B-5 - COBRA continuation coverage.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., the older child has incurred no covered expenses, and the younger one has incurred $120 of covered... deductible, and the younger one has no further deductible. Example 2. (i) A group health plan applies...

  20. 26 CFR 54.4980B-1 - COBRA in general.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... added parallel continuation coverage requirements to Part 6 of Subtitle B of Title I of the Employee... ERISA. (c) A group health plan that is subject to section 4980B (or the parallel provisions under ERISA... refers to section 4980B (as amended) and to the parallel provisions of ERISA. Q-2: What standard...

  1. Development of Equine IgG Antivenoms against Major Snake Groups in Mozambique

    PubMed Central

    Guidolin, Felipe Raimondi; Caricati, Celso Pereira; Marcelino, José Roberto; da Silva, Wilmar Dias

    2016-01-01

    Background Snake envenoming is a significant public health problem in underdeveloped and developing countries. In sub-Saharan Africa, it is estimated that 90,000–400,000 envenomations occur each year, resulting in 3,500–32,000 deaths. Envenomings are caused by snakes from the Viperidae (Bitis spp. and Echis spp.) and Elapidae (Naja spp. and Dendroaspis spp.) families. The African continent has been suffering from a severe antivenom crisis and current antivenom production is only sufficient to treat 25% of snakebite cases. Our aim is to develop high-quality antivenoms against the main snake species found in Mozambique. Methods Adult horses primed with the indicated venoms were divided into 5 groups (B. arietans; B. nasicornis + B. rhinoceros; N. melanoleuca; N. mossambica; N. annulifera + D. polylepis + D. angusticeps) and reimmunized two times for antivenom production. Blood was collected, and plasma was separated and subjected to antibody purification using caprylic acid. Plasmas and antivenoms were subject to titration, affinity determination, cross-recognition assays and in vivo venom lethality neutralization. A commercial anti-Crotalic antivenom was used for comparison. Results The purified antivenoms exhibited high titers against B. arietans, B. nasicornis and B. rhinoceros (5.18 x 106, 3.60 x 106 and 3.50 x 106 U-E/mL, respectively) and N. melanoleuca, N. mossambica and N. annulifera (7.41 x 106, 3.07 x 106 and 2.60 x 106 U-E/mL, respectively), but lower titers against the D. angusticeps and D. polylepis (1.87 x 106 and 1.67 x 106 U-E/mL). All the groups, except anti-N. melanoleuca, showed significant differences from the anti-Crotalic antivenom (7.55 x 106 U-E/mL). The affinity index of all the groups was high, ranging from 31% to 45%. Cross-recognition assays showed the recognition of proteins with similar molecular weight in the venoms and may indicate the possibility of paraspecific neutralization. The three monospecific antivenoms were able to

  2. Dreissena polymorpha Pall. postveligers in submersed macrophyte beds of Put-in-Bay, Ohio, as related to rate and density of settlement, macrophyte preference, water depth, and position within beds

    SciTech Connect

    Moore, D.L.

    1995-06-01

    Increased water clarity due in large part to the invasion and spread of Dreissena polymorpha Pall., has allowed reestablishment of nearly continuous beds of submersed macrophytes in Put-in-Bay, Ohio. These beds now serve as sites for settlement by Dreissena veligers. Four transects extending from a maximum depth of 4.0 m to a minimum depth of 0.5 m were established in 1994, to document the time of recruitment, density of postveliger settlement, preferred macrophyte as a substrate, and effects of water depth and location within transects on recruitment. Settlement densities were determined for 100 g wet weight samples of macrophytes harvested along transects by snorkel and scuba. Peak settlement occurred 23 August, 11 days after the second planktonic veliger peak, but continued until early October. Maximum densities were greatest in 1.5-3.5 m water nearer the lakeward end of the transects and decreased in 1.0 m water or shoreward in dense submersed macrophyte beds. A maximum density of 15,150 Dreissena/100 g macrophyte occurred on the perennial Myriophyllum spicatum L., although mean settlement densities were greatest for the perennials M. spicatum, Ceratophyllum demersum L., and the annuals Vallisneria americana Michx. and Najas quadalupensis (Spreng.) Magnus. Macrophyte preference as a settling substrate is most probably a reflection of relative macrophyte abundance and position within dense beds rather than a particular plant architecture. Assessment of densities after autumnal vegetational growth is not yet complete.

  3. GPS & GLONASS mass-market receivers: positioning performances and peculiarities.

    PubMed

    Dabove, Paolo; Manzino, Ambrogio M

    2014-01-01

    Over the last twenty years, positioning with low cost Global Navigation Satellite System (GNSS) sensors have rapidly developed around the world at both a commercial and academic research level. For many years these instruments have only acquired the GPS constellation but are now able to track the Global'naja Navigacionnaja Sputnikovaja Sistema (GLONASS) constellation. This characteristic is very interesting, especially if used in hard-urban environments or in hard conditions where satellite visibility is low. The goal of this research is to investigate the contribution of the GLONASS constellation for mass-market receivers in order to analyse the performance in real time (Network Real Time Kinematic-NRTK positioning) with post-processing approaches. Under these conditions, it is possible to confirm that mass-market sensors could be a valid alternative to a more expensive receiver for a large number of surveying applications, but with low cost hardware the contribution of the GLONASS constellation for fixing ambiguities is useless, if not dangerous. PMID:25429405

  4. Comparative sensitivity of five species of macrophytes and six species of algae to atrazine, metribuzin, alachlor, and metolachlor

    USGS Publications Warehouse

    Fairchild, J.F.; Ruessler, D.S.; Carlson, A.R.

    1998-01-01

    This study determined the relative sensitivity of five species of aquatic macrophytes and six species of algae to four commonly used herbicides (atrazine, metribuzin, alachlor, and metolachlor). Toxicity tests consisted of 96-h (duckweed and algae) or 14-d (submerged macrophytes) static exposures. The triazine herbicides (atrazine and metribuzin) were significantly more toxic to aquatic plants than were the acetanilide herbicides (alachlor and metolachlor). Toxicity studies ranked metribuzin > atrazine > alachlor > metolachlor in decreasing order of overall toxicity to aquatic plants. Relative sensitivities of macrophytes to these herbicides decreased in the order of Ceratophyllum > Najas > Elodea > Lemna > Myriophyllum. Relative sensitivities of algae to herbicides decreased in the order of Selenastrum > Chlorella > Chlamydomonas > Microcystis > Scenedesmus > Anabaena. Algae and macrophytes were of similar overall sensitivities to herbicides. Data indicated that Selenastrum, a commonly tested green alga, was generally more sensitive compared to other plant species. Lemna minor, a commonly tested floating vascular plant, was of intermediate sensitivity, and was fivefold less sensitive than Ceratophyllum, which was the most sensitive species tested. The results indicated that no species was consistently most sensitive, and that a suite of aquatic plant test species may be needed to perform accurate risk assessments of herbicides.

  5. Venomics of the beaked sea snake, Hydrophis schistosus: A minimalist toxin arsenal and its cross-neutralization by heterologous antivenoms.

    PubMed

    Tan, Choo Hock; Tan, Kae Yi; Lim, Sin Ee; Tan, Nget Hong

    2015-08-01

    The venom proteome of Hydrophis schistosus (syn: Enhydrina schistosa) captured in Malaysian waters was investigated using reverse-phase HPLC, SDS-PAGE and high-resolution liquid chromatography-tandem mass spectrometry. The findings revealed a minimalist profile with only 18 venom proteins. These proteins belong to 5 toxin families: three-finger toxin (3FTx), phospholipase A2 (PLA2), cysteine-rich secretory protein (CRISP), snake venom metalloprotease (SVMP) and L-amino acid oxidase (LAAO). The 3FTxs (3 short neurotoxins and 4 long neurotoxins) constitute 70.5% of total venom protein, 55.8% being short neurotoxins and 14.7% long neurotoxins. The PLA2 family consists of four basic (21.4%) and three acidic (6.1%) isoforms. The minor proteins include one CRISP (1.3%), two SVMPs (0.5%) and one LAAO (0.2%). This is the first report of the presence of long neurotoxins, CRISP and LAAO in H. schistosus venom. The neurotoxins and the basic PLA2 are highly lethal in mice with an intravenous median lethal dose of <0.2 μg/g. Cross-neutralization by heterologous elapid antivenoms (Naja kaouthia monovalent antivenom and Neuro polyvalent antivenom) was moderate against the long neurotoxin and basic PLA2, but weak against the short neurotoxin, indicating that the latter is the limiting factor to be overcome for improving the antivenom cross-neutralization efficacy. PMID:26047715

  6. Comparative study of anticoagulant and procoagulant properties of 28 snake venoms from families Elapidae, Viperidae, and purified Russell's viper venom-factor X activator (RVV-X).

    PubMed

    Suntravat, Montamas; Nuchprayoon, Issarang; Pérez, John C

    2010-09-15

    Snake venoms consist of numerous molecules with diverse biological functions used for capturing prey. Each component of venom has a specific target, and alters the biological function of its target. Once these molecules are identified, characterized, and cloned; they could have medical applications. The activated clotting time (ACT) and clot rate were used for screening procoagulant and anticoagulant properties of 28 snake venoms. Crude venoms from Daboia russellii siamensis, Bothrops asper, Bothrops moojeni, and one Crotalus oreganus helleri from Wrightwood, CA, had procoagulant activity. These venoms induced a significant shortening of the ACT and showed a significant increase in the clot rate when compared to the negative control. Factor X activator activity was also measured in 28 venoms, and D. r. siamensis venom was 5-6 times higher than those of B. asper, B. moojeni, and C. o. helleri from Wrightwood County. Russell's viper venom-factor X activator (RVV-X) was purified from D. r. siamensis venom, and then procoagulant activity was evaluated by the ACT and clot rate. Other venoms, Crotalus atrox and two Naja pallida, had anticoagulant activity. A significant increase in the ACT and a significant decrease in the clot rate were observed after the addition of these venoms; therefore, the venoms were considered to have anticoagulant activity. Venoms from the same species did not always have the same ACT and clot rate profiles, but the profiles were an excellent way to identify procoagulant and anticoagulant activities in snake venoms. PMID:20677373

  7. A Lys49-PLA2 myotoxin of Bothrops asper triggers a rapid death of macrophages that involves autocrine purinergic receptor signaling.

    PubMed

    Tonello, F; Simonato, M; Aita, A; Pizzo, P; Fernández, J; Lomonte, B; Gutiérrez, J M; Montecucco, C

    2012-01-01

    Lys49-PLA(2) myotoxins, an important component of various viperid snake venoms, are a class of PLA(2)-homolog proteins deprived of catalytic activity. Similar to enzymatically active PLA(2) (Asp49) and to other classes of myotoxins, they cause severe myonecrosis. Moreover, these toxins are used as tools to study skeletal muscle repair and regeneration, a process that can be very limited after snakebites. In this work, the cytotoxic effect of different myotoxins, Bothrops asper Lys49 and Asp49-PLA(2), Notechis scutatus notexin and Naja mossambica cardiotoxin, was evaluated on macrophages, cells that have a key role in muscle regeneration. Only the Lys49-myotoxin was found to trigger a rapid asynchronous death of mouse peritoneal macrophages and macrophagic cell lines through a process that involves ATP release, ATP-induced ATP release and that is inhibited by various purinergic receptor antagonists. ATP leakage is induced also at sublytical doses of the Lys49-myotoxin, it involves Ca(2+) release from intracellular stores, and is reduced by inhibitors of VSOR and the maxi-anion channel. The toxin-induced cell death is different from that caused by high concentration of ATP and appears to be linked to localized purinergic signaling. Based on present findings, a mechanism of cell death is proposed that can be extended to other cytolytic proteins and peptides. PMID:22764102

  8. Fall and winter foods of northern pintails in the Sacramento Valley, California

    USGS Publications Warehouse

    Miller, M.R.

    1987-01-01

    Food habits of northern pintails (Anas acuta) were investigated on 3 national wildlife refuges in the western portion of the Sacramento Valley, California, from August to March 1979-82. Pintails consumed 97% (aggregate % dry wt) plant food during diurnal foraging on national wildlife refuge rice, summer-irrigated, and summer-dry habitats from August through January. Invertebrate use increased to 28.9-65.6% of the diet in these habitats during February and March. Rice, swamp timothy (Heleochloa schoenoides), flatsedges (Cyperus spp.), common barnyardgrass (Echinochloa crusgalli), southern naiad (Najas guadalupensis), and smartweed (Polygonum spp.) seeds, miscellaneous vegetation, snails (Gastropoda), and midge (Diptera) and water beetle (Coleoptera) larvae were most important. These foods usually were taken proportional to or greater than availability. Rice was the most important food of pintails feeding nocturnally off the refuges in harvested rice fields from October through January (99.7%) and February and March (63%; barnyardgrass formed 31% of the diet). In August and October, some pintails consumed invertebrates or bulrush (Scirpus spp. ) seedlings in marshes soon after feeding in refuge rice (Aug) or harvested commercial rice fields (Oct), thereby increasing dietary protein. In late winter, females and males obtained similar (P > 0.05) percentages of invertebrates from refuge habitats. Important dietary seeds and invertebrates contained high protein or metabolizable energy content. Management should maintain adequate seed production in fall and mid-winter and invertebrate biomass in late winter.

  9. Selenium concentrations in water and plant tissues of a newly formed arid wetland in Las Vegas, Nevada.

    PubMed

    Pollard, James; Cizdziel, James; Stave, Krystyna; Reid, Michelle

    2007-12-01

    There is concern that elevated levels of selenium found in the source water of a newly formed wetland park in Las Vegas, Nevada, may have detrimental effects on local wildlife. In this study, we collected and analyzed water samples monthly for a three year period from the inflow and outflow of the system. We also gathered dominant aquatic plants and selected terrestrial plants and analyzed the water and plant tissues (root, shoot, leaf and flower) for selenium by high resolution Inductively Coupled Plasma Mass Spectrometer. Except for storm events and the introduction of an alternative low selenium content source water during summer low-flow conditions, selenium in the water was relatively stable. The concentration in the outflow tended to be slightly lower than the inflow. Concentrations of selenium in the dominant plant taxa in this wetlands were typical of ecosystems in the western United States and varied by taxa, tissue type, localized conditions (e.g., contact with selenium-laden water), and to a lesser extent, seasons. Selenium in the aquatic plant spiny naiad (Najas marina) was relatively high and may pose an ecological risk to wildlife during the late spring and summer. Additional work is underway investigating aquatic food chain accumulations of selenium as well as mass balance of selenium in the system. PMID:17394092

  10. Evaluation of the mechanism of skin enhancing surfactants on the biomembrane of shed snake skin.

    PubMed

    Wonglertnirant, Nanthida; Ngawhirunpat, Tanasait; Kumpugdee-Vollrath, Mont

    2012-01-01

    The aim of the present work was to investigate the effects of different surfactants at various concentrations as a skin penetration enhancer through the biomembrane of the shed skin of Naja kaouthia. Additionally, the enhancer mechanism(s) of each class of surfactants were evaluated using physical characterization techniques, such as scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, and small and wide angle X-ray scattering (SWAXS). Our results showed that skin permeability increased with increasing concentrations of surfactants and the degree of increase was higher for the model hydrophilic permeant, deuterium dioxide (D(2)O), than the lipophilic permeant, ketoprofen (KP). Ionic surfactants, sodium lauryl sulfate (SLS) and cetyl trimethyl ammonium bromide (CTAB), demonstrated higher enhancement ability than the polyoxyethylene (20) sorbitan mono-oleate (Tween 80) non-ionic surfactant, which was consistent with the results from physical characterization studies. Increasing amounts of permeated drug resulted in an increase in membrane interactions. From our observations, it can be assumed that SLS and CTAB can be localized inside the biomembrane and thereby enhance drug permeation mainly through interactions with intercellular lipids in the stratum corneum (SC) and the creation of a perturbed microenvironment among lipid alkyl chains and polar head groups. PMID:22466556

  11. Last interglacial plant macrofossils and climates from Ziegler Reservoir, Snowmass Village, Colorado, USA

    USGS Publications Warehouse

    Strickland, Laura E.; Baker, Richard G.; Thompson, Robert S.; Miller, Dane M.

    2014-01-01

    Ninety plant macrofossil taxa from the Ziegler Reservoir fossil site near Snowmass Village, Colorado, record environmental changes at high elevation (2705 m asl) in the Rocky Mountains during the Last Interglacial Period. Present-day vegetation is aspen forest (Populus tremuloides) intermixed with species of higher (Picea, Abies) and lower (Artemisia, Quercus) elevations. Stratigraphic units 4–13 contain montane forest taxa found near the site today and several species that today generally live at lower elevations within (Abies concolor, Lycopus americanus) and outside Colorado (Najas flexilis). These data suggest near-modern climatic conditions, with slightly warmer summer and winter temperatures. This montane forest period was succeeded by a shorter treeless interval (Unit 14) representing colder and/or drier conditions. In units 15–16, conifer trees reoccur but deciduous and herb taxa are lacking, suggesting a return to warmer conditions, although cooler than during the earlier forest period. Comparison of these inferred paleoclimatic changes with the site's geochronologic framework indicates that the lower interval of sustained warmth correlates with late MIS 6–early 5b (~ 138–94 ka), the cold interval with MIS 5b (~ 94–87 ka), and the uppermost cool assemblages with MIS 5a (~ 87–77 ka).

  12. Freshwater Plants Synthesize Sulfated Polysaccharides: Heterogalactans from Water Hyacinth (Eicchornia crassipes)

    PubMed Central

    Dantas-Santos, Nednaldo; Gomes, Dayanne Lopes; Costa, Leandro Silva; Cordeiro, Sara Lima; Costa, Mariana Santos Santana Pereira; Trindade, Edvaldo Silva; Franco, Célia Regina Chavichiolo; Scortecci, Kátia Castanho; Leite, Edda Lisboa; Rocha, Hugo Alexandre Oliveira

    2012-01-01

    Sulfated polysaccharides (SP) are found mainly in seaweeds and animals. To date, they have only been found in six plants and all inhabit saline environments. Furthermore, there are no reports of SP in freshwater or terrestrial plants. As such, this study investigated the presence of SP in freshwaters Eichhornia crassipes, Egeria densa, Egeria naja, Cabomba caroliniana, Hydrocotyle bonariensis and Nymphaea ampla. Chemical analysis identified sulfate in N. ampla, H. bonariensis and, more specifically, E. crassipes. In addition, chemical analysis, FT-IR spectroscopy, histological analysis, scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDXA), as well as agarose gel electrophoresis detected SP in all parts of E. crassipes, primarily in the root (epidermis and vascular bundle). Galactose, glucose and arabinose are the main monosaccharides found in the sulfated polysaccharides from E. crassipes. In activated partial thromboplastin time (APTT) test, to evaluate the intrinsic coagulation pathway, SP from the root and rhizome prolonged the coagulation time to double the baseline value, with 0.1 mg/mL and 0.15 mg/mL, respectively. However, SP from the leaf and petiole showed no anticoagulant activity. Eichornia SP demonstrated promising anticoagulant potential and have been selected for further studies on bioguided fractionation; isolation and characterization of pure polysaccharides from this species. Additionally in vivo experiments are needed and are already underway. PMID:22312297

  13. Last interglacial plant macrofossils and climates from Ziegler Reservoir, Snowmass Village, Colorado, USA

    NASA Astrophysics Data System (ADS)

    Strickland, Laura E.; Baker, Richard G.; Thompson, Robert S.; Miller, Dane M.

    2014-11-01

    Ninety plant macrofossil taxa from the Ziegler Reservoir fossil site near Snowmass Village, Colorado, record environmental changes at high elevation (2705 m asl) in the Rocky Mountains during the Last Interglacial Period. Present-day vegetation is aspen forest (Populus tremuloides) intermixed with species of higher (Picea, Abies) and lower (Artemisia, Quercus) elevations. Stratigraphic units 4-13 contain montane forest taxa found near the site today and several species that today generally live at lower elevations within (Abies concolor, Lycopus americanus) and outside Colorado (Najas flexilis). These data suggest near-modern climatic conditions, with slightly warmer summer and winter temperatures. This montane forest period was succeeded by a shorter treeless interval (Unit 14) representing colder and/or drier conditions. In units 15-16, conifer trees reoccur but deciduous and herb taxa are lacking, suggesting a return to warmer conditions, although cooler than during the earlier forest period. Comparison of these inferred paleoclimatic changes with the site's geochronologic framework indicates that the lower interval of sustained warmth correlates with late MIS 6-early 5b (~ 138-94 ka), the cold interval with MIS 5b (~ 94-87 ka), and the uppermost cool assemblages with MIS 5a (~ 87-77 ka).

  14. Molecular barcoding of venomous snakes and species-specific multiplex PCR assay to identify snake groups for which antivenom is available in Thailand.

    PubMed

    Supikamolseni, A; Ngaoburanawit, N; Sumontha, M; Chanhome, L; Suntrarachun, S; Peyachoknagul, S; Srikulnath, K

    2015-01-01

    DNA barcodes of mitochondrial COI and Cytb genes were constructed from 54 specimens of 16 species for species identification. Intra- and interspecific sequence divergence of the COI gene (10 times) was greater than that of the Cytb gene (4 times), which suggests that the former gene may be a better marker than the latter for species delimitation in snakes. The COI barcode cut-off scores differed by more than 3% between most species, and the minimum interspecific divergence was greater than the maximum intraspecific divergence. Clustering analysis indicated that most species fell into monophyletic clades. These results suggest that these species could be reliably differentiated using COI DNA barcodes. Moreover, a novel species-specific multiplex PCR assay was developed to distinguish between Naja spp, Ophiophagus hannah, Trimeresurus spp, Hydrophiinae, Daboia siamensis, Bungarus fasciatus, and Calloselasma rhodostoma. Antivenom for these species is produced and kept by the Thai Red Cross for clinical use. Our novel PCR assay could easily be applied to venom and saliva samples and could be used effectively for the rapid and accurate identification of species during forensic work, conservation study, and medical research. PMID:26535713

  15. GPS & GLONASS Mass-Market Receivers: Positioning Performances and Peculiarities

    PubMed Central

    Dabove, Paolo; Manzino, Ambrogio M.

    2014-01-01

    Over the last twenty years, positioning with low cost Global Navigation Satellite System (GNSS) sensors have rapidly developed around the world at both a commercial and academic research level. For many years these instruments have only acquired the GPS constellation but are now able to track the Global’naja Navigacionnaja Sputnikovaja Sistema (GLONASS) constellation. This characteristic is very interesting, especially if used in hard-urban environments or in hard conditions where satellite visibility is low. The goal of this research is to investigate the contribution of the GLONASS constellation for mass-market receivers in order to analyse the performance in real time (Network Real Time Kinematic—NRTK positioning) with post-processing approaches. Under these conditions, it is possible to confirm that mass-market sensors could be a valid alternative to a more expensive receiver for a large number of surveying applications, but with low cost hardware the contribution of the GLONASS constellation for fixing ambiguities is useless, if not dangerous. PMID:25429405

  16. Identification and phylogeny of Arabian snakes: Comparison of venom chromatographic profiles versus 16S rRNA gene sequences.

    PubMed

    Al Asmari, Abdulrahman; Manthiri, Rajamohammed Abbas; Khan, Haseeb Ahmad

    2014-11-01

    Identification of snake species is important for various reasons including the emergency treatment of snake bite victims. We present a simple method for identification of six snake species using the gel filtration chromatographic profiles of their venoms. The venoms of Echis coloratus, Echis pyramidum, Cerastes gasperettii, Bitis arietans, Naja arabica, and Walterinnesia aegyptia were milked, lyophilized, diluted and centrifuged to separate the mucus from the venom. The clear supernatants were filtered and chromatographed on fast protein liquid chromatography (FPLC). We obtained the 16S rRNA gene sequences of the above species and performed phylogenetic analysis using the neighbor-joining method. The chromatograms of venoms from different snake species showed peculiar patterns based on the number and location of peaks. The dendrograms generated from similarity matrix based on the presence/absence of particular chromatographic peaks clearly differentiated Elapids from Viperids. Molecular cladistics using 16S rRNA gene sequences resulted in jumping clades while separating the members of these two families. These findings suggest that chromatographic profiles of snake venoms may provide a simple and reproducible chemical fingerprinting method for quick identification of snake species. However, the validation of this methodology requires further studies on large number of specimens from within and across species. PMID:25313278

  17. Scales microstructure of snakes from the Egyptian area.

    PubMed

    Allam, Ahmed A; Abo-Eleneen, Rasha E

    2012-11-01

    The morphology of many organisms seems to be related to the environments in which they live. Many snakes are so similar in their morphological patterns that it becomes quite difficult to distinguish any adaptive divergence that may have occurred. Many authors have suggested that the microstructure of the reptile's scales has important functional value. Herein, we investigate variations on the micromorphology of the external surface of dorsal scales on the head, the mid-body region (trunk), and the tail of Rhomphotyphlops braminus (Typhlopidae), Eryx jaculus (Boidae), Psammophis sibilans (Colubridae), Naja haje (Elapidae) and Echis carinatus (Viperidae). The specimens were metallized and analyzed by scanning electron microscopy. All species displayed unique dorsal scale surface microstructures of the investigated regions. The microstructural pattern of the scales of head, trunk, and tail differs in different species of these snakes. In conclusion, we detected ecomorphologic relationships between extant dorsal scale microstructures and snake microhabitat, enabling us to hypothesize that environmental pressures have significant influences not only on these animals' macrostructure, but also on its microstructure as well. PMID:23106563

  18. [Preliminary results of an herpetology investigation in sugar cane plantation in Democratic Republic of Congo].

    PubMed

    Malukisa, J; Collet, M; Bokata, S; Odio, W

    2005-11-01

    Out of the 3,000 species of snakes described in the world, 163 are currently known from D.R. of Congo. We performed a systematic survey in sugar-cane plantations of the Sugar Company of Kwilu-Ngongo (Bas-Congo), located at 160 km South-West from Kinshasa and exploiting nearly 10,000 ha. The plantation is divided into 3 sectors in the middle of which we deposited barrels filled of formaldehyde. All the employees of the Sugar Company of Kwilu-Ngongo were requested to collect encountered snakes and put them in the nearest barrel. Between August 9th and September 21st, 2004, we collected 36 snakes in two different sites, revealing the presence of 3 families and 12 species. The most abundant species in Causus maculatus (47% in the first site--Point 8--and 29% in the second site--Point 13). The most poisonous and dangerous species were captured only in the first site--point 8, and were Dendroaspis jamesoni and Naja melanoleuca, both young. PMID:16402584

  19. Phylogenetic relationship of Hepatozoon blood parasites found in snakes from Africa, America and Asia.

    PubMed

    Haklová, B; Majláthová, V; Majláth, I; Harris, D J; Petrilla, V; Litschka-Koen, T; Oros, M; Peťko, B

    2014-03-01

    The blood parasites from the genus Hepatozoon Miller, 1908 (Apicomplexa: Adeleida: Hepatozoidae) represent the most common intracellular protozoan parasites found in snakes. In the present study, we examined 209 individuals of snakes, from different zoogeographical regions (Africa, America, Asia and Europe), for the occurrence of blood parasites using both molecular and microscopic examination methods, and assess phylogenetic relationships of all Hepatozoon parasites from snakes for the first time. In total, 178 blood smears obtained from 209 individuals, representing 40 species, were examined, from which Hepatozoon unicellular parasites were found in 26 samples (14·6% prevalence). Out of 180 samples tested by molecular method polymerase chain reaction (PCR), the presence of parasites was observed in 21 individuals (prevalence 11·6%): 14 snakes from Africa belonging to six genera (Dendroaspis, Dispholidus, Mehelya, Naja, Philothamnus and Python), five snakes from Asia from the genus Morelia and two snakes from America, from two genera (Coluber and Corallus). The intensity of infection varied from one to 1433 infected cells per 10 000 erythrocytes. Results of phylogenetic analyses (Bayesian and Maximum Likelihood) revealed the existence of five haplotypes divided into four main lineages. The present data also indicate neither geographical pattern of studied Hepatozoon sp., nor congruency in the host association. PMID:24553081

  20. Pioneers of anti-venomous serotherapy: Dr Vital Brazil (1865-1950).

    PubMed

    Hawgood, B J

    1992-01-01

    Dr Vital Brazil was a great humanitarian and pioneer of medical science. His main work arose from his concern with poisonous snakebite accidents to labourers working the land. Vital Brazil estimated that, at the beginning of this century, deaths due to crotaline snakebites in the State of São Paulo, Brazil, were nearly 3000 per year, representing a mortality rate of about 25%, the majority being due to bothropic envenomation. After reading a report of Calmette's anti-Naja serum, Vital Brazil raised monovalent serum against the venom of Bothrops jararaca and the venom of Crotalus durissus terrificus. In 1989 this led to the first demonstration of the specificity of anti-venomous serum and later, the first production of polyvalent serum for therapeutic use. As Director of the newly founded Institute Butantan in São Paulo, Vital Brazil was actively engaged in every aspect of serotherapeutic treatment. This included organizing a unique system of exchanging anti-ophidic serum for snakes as well as a wide-ranging teaching programme. His many outstanding contributions to the fields of immunology, public health, toxinology and herpetology required not only a very high level of observational, deductive and practical ability but also an unswerving vision and sense of duty; this was allied to great administrative skill and exceptional energy. PMID:1519249