WorldWideScience

Sample records for mode-of-action taxonomic distribution

  1. Mode of Action of Glyphosate

    Science.gov (United States)

    Although glyphosate is the most used and studied herbicide in the world, the available information is not enough to fully understand its mode of action. The molecular site of action of glyphosate is the enzyme 5-enolpyruvlyshikimate-3-phosphate synthase (EPSPS). It is the only known compound that ...

  2. [Modes of action of IUDs].

    Science.gov (United States)

    Janaud, A

    1982-05-01

    There are between 14-17 million women in the world, excluding China, who wear an IUD, or about 3-5% of all married women younger than 45. Studies on the mode of action of IUDs have been conducted mostly on laboratory animals; they show that ovulation and fecundation are not inhibited by the presence of an IUD. Contrary to what was generally believed, the latest studies have shown that the principle mode of action of the IUD is not its anti-implantation effect, but it depends on the adjustment inside the uterine cavity between the size of the uterine cavity itself, and the size and shape of the device. Endometrial modifications caused by IUDs include inflammatory phenomena, and inhibition of endometrial maturation. Moreover, copper IUDs act directly on spermatozoa and on endometrial steroid receptors. It is still not clear what role prostaglandins play in the mechanism of action of IUDs. Incidence of ectopic pregnancy is not greater in IUD wearers than in women who do not use contraception. Follicle stimulating hormone and luteinizing hormone levels also are comparable in IUD wearers and in nonwearers. IUD wearers have a shorter luteal phase, which entails an earlier menstrual bleeding due to the antifibrinolytic action of the IUD; progesterone levels are identical in users and in nonusers of IUDs.

  3. Mode of action of insect repellents

    Science.gov (United States)

    The mode of action of DEET and other insect repellents has been a topic of interest since the discovery of DEET in the mid twentieth century. Nearly 60 years have passed since DEET applied topically to the skin was shown to be effective in preventing mosquito bites. With the discovery and characte...

  4. Circular bacteriocins: biosynthesis and mode of action.

    Science.gov (United States)

    Gabrielsen, Christina; Brede, Dag A; Nes, Ingolf F; Diep, Dzung B

    2014-11-01

    Circular bacteriocins are a group of N-to-C-terminally linked antimicrobial peptides, produced by Gram-positive bacteria of the phylum Firmicutes. Circular bacteriocins generally exhibit broad-spectrum antimicrobial activity, including against common food-borne pathogens, such as Clostridium and Listeria spp. These peptides are further known for their high pH and thermal stability, as well as for resistance to many proteolytic enzymes, properties which make this group of bacteriocins highly promising for potential industrial applications and their biosynthesis of particular interest as a possible model system for the synthesis of highly stable bioactive peptides. In this review, we summarize the current knowledge on this group of bacteriocins, with emphasis on the recent progress in understanding circular bacteriocin genetics, biosynthesis, and mode of action; in addition, we highlight the current challenges and future perspectives for the application of these peptides.

  5. (-)-Carvone: antispasmodic effect and mode of action.

    Science.gov (United States)

    Souza, Fábia Valéria M; da Rocha, Marcelly Barbosa; de Souza, Damião P; Marçal, Rosilene Moretti

    2013-03-01

    (-)-Carvone is a monoterpene ketone found in spearmint (Mentha spicata var. crispa) essential oil that is widely used as an odor and flavor additive. An intestinal antispasmodic effect was recently reported for (-)-carvone, and it has been shown to be more potent than its (+)-antipode. The mechanism of (-)-carvone action in the intestines has not been investigated. To gain a better understanding of the (-)-carvone antispasmodic effect, we investigated its pharmacological effects in the guinea pig ileum. Terminal portions of the ileum were mounted for isotonic contraction recordings. The effect of (-)-carvone was compared with that of the classical calcium channel blocker (CCB) verapamil. In isolated ileal smooth muscle, (-)-carvone did not produce direct contractile or relaxation responses and did not modify electrically elicited contractions or low K(+)-evoked contractions. The submaximal contractions induced by histamine (p<0.001), BaCl2 (p<0.05), and carbachol (p<0.01) were significantly reduced by (-)-carvone. The contractile response elicited by high concentrations of carbachol was reduced but not abolished by (-)-carvone. No additive action was detected with co-incubation of (-)-carvone and verapamil on carbachol-induced contraction. (-)-Carvone reduced the contraction induced by high K(+) and was almost 100 times more potent than verapamil. Thus, (-)-carvone showed a typical and potent CCB-like action. Many effects described for both (-)-carvone and spearmint oil can be explained as a CCB-like mode of action.

  6. Kyleo ® - mode of action under examination

    Directory of Open Access Journals (Sweden)

    Heibertshausen, Dagmar

    2014-02-01

    Full Text Available Kyleo® with two known active substances (ai is an innovative, modern herbicide for resistance management. Kyleo® contains 160 g/l 2,4-D and 240 g/l glyphosate. With an application rate of 5,0 l/ha, it shows a far better, faster effect on weeds such as field horsetail (Equisetum arvense, volunteer oilseed rape (Brassica napus and couch grass (Agropyron repens compared to a tank mix or the reference products (RP. This is explained by an unique new formulation technology that for the first time combines 2,4-D as acid and glyphosate as MIPA salt together with FHS. The new form of 2,4-D is lipophilic with better leaf absorption and greater photolytic degradation in the upper layers of soil. Tests with radioactive marked substances have verified the systemic properties of both ai compared to RP. The displacement of 2,4-D into the plant roots was demonstrated 48 h after application (hpt. 98% glyphosate absorption was observed in rape and couch grass – 10% (rape respectively 25% (couch grass greater than with RP. Higher absorption of the ai is characterised by a swifter effect, with stronger, visible symptoms after 24 h in rape and 96 h in couch grass. The rainfastness of Kyleo® was tested in greenhouse (GH trials with rape. Comparability of the test objects was simulated with a uniform glyphosate quantity of 360 g/ha and 10 l/m² simulated precipitation. 24% improved effect compared to RP was verified for 1 hpt rainfall, while 4% improved effect was recorded for rain simulation after 6 hpt. GH trials with wheat and a comparable glyphosate application quantity of 290 g/ha revealed differences of 23% and 22% compared to RP for rain simulation of 1 hpt and 6 hpt. Kyleo® stands out with a swift effect and better rainfastness. The results presented here prove a systemic mode of action, good rainfastness and swift effect of Kyleo.

  7. Mini Review: Mode of Action of Mosquito Repellents

    Science.gov (United States)

    2013-01-01

    Mini review: Mode of action of mosquito repellents Joseph C. Dickens ⇑, Jonathan D. Bohbot United States Department of Agriculture, Agricultural...Modulation a b s t r a c t The mode of action of mosquito repellents remains a controversial topic. However, electrophysiological studies and molecular...annoyance that can disrupt outdoor activities. The use of repellents decreases contacts between mosquitoes and their hosts, and may even lower the rate of

  8. Glycosides from Marine Sponges (Porifera, Demospongiae: Structures, Taxonomical Distribution, Biological Activities and Biological Roles

    Directory of Open Access Journals (Sweden)

    Valentin A. Stonik

    2012-08-01

    Full Text Available Literature data about glycosides from sponges (Porifera, Demospongiae are reviewed. Structural diversity, biological activities, taxonomic distribution and biological functions of these natural products are discussed.

  9. Glycosides from marine sponges (Porifera, Demospongiae): structures, taxonomical distribution, biological activities and biological roles.

    Science.gov (United States)

    Kalinin, Vladimir I; Ivanchina, Natalia V; Krasokhin, Vladimir B; Makarieva, Tatyana N; Stonik, Valentin A

    2012-08-01

    Literature data about glycosides from sponges (Porifera, Demospongiae) are reviewed. Structural diversity, biological activities, taxonomic distribution and biological functions of these natural products are discussed.

  10. Effect and mode of action of some systemic nematicides

    NARCIS (Netherlands)

    Bunt, J.A.

    1975-01-01

    In this study, nematicidal effects, mode of action and specific characters of some systemic nematicides were studied, in search of substitutes for the widely used soil fumigants that require high dosages. The thesis comprises:- a review of literature,- development of techniques,- a test for nematici

  11. Mode of action of the 2-nitroimidazole derivative benznidazole.

    Science.gov (United States)

    Polak, A; Richle, R

    1978-02-01

    Using cultures of Trypanosoma cruzi cells in a liquid medium, the mode of action of the 2-nitroimidazole derivative benznidazole was examined. Benznidazole inhibits protein synthesis and RNA synthesis in T. cruzy. The DNA synthesis is only slightly decreased and no effect on the aerobic respiration of T. cruzi was observed.

  12. Untargeted Metabolomics To Ascertain Antibiotic Modes of Action.

    Science.gov (United States)

    Vincent, Isabel M; Ehmann, David E; Mills, Scott D; Perros, Manos; Barrett, Michael P

    2016-04-01

    Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also collect data on off-target effects and drug modifications. Here, we present data from an untargeted liquid chromatography-mass spectrometry approach to identify the modes of action of eight compounds: 1-[3-fluoro-4-(5-methyl-2,4-dioxo-pyrimidin-1-yl)phenyl]-3-[2-(trifluoromethyl)phenyl]urea (AZ1), 2-(cyclobutylmethoxy)-5'-deoxyadenosine, triclosan, fosmidomycin, CHIR-090, carbonyl cyanidem-chlorophenylhydrazone (CCCP), 5-chloro-2-(methylsulfonyl)-N-(1,3-thiazol-2-yl)-4-pyrimidinecarboxamide (AZ7), and ceftazidime. Data analysts were blind to the compound identities but managed to identify the target as thymidylate kinase for AZ1, isoprenoid biosynthesis for fosmidomycin, acyl-transferase for CHIR-090, and DNA metabolism for 2-(cyclobutylmethoxy)-5'-deoxyadenosine. Changes to cell wall metabolites were seen in ceftazidime treatments, although other changes, presumably relating to off-target effects, dominated spectral outputs in the untargeted approach. Drugs which do not work through metabolic pathways, such as the proton carrier CCCP, have no discernible impact on the metabolome. The untargeted metabolomics approach also revealed modifications to two compounds, namely, fosmidomycin and AZ7. An untreated control was also analyzed, and changes to the metabolome were seen over 4 h, highlighting the necessity for careful controls in these types of studies. Metabolomics is a useful tool in the analysis of drug modes of action and can complement other technologies already in use.

  13. Global nutritional profiling for mutant and chemical mode-of-action analysis in filamentous fungi.

    Science.gov (United States)

    Tanzer, Matthew M; Arst, Herbert N; Skalchunes, Amy R; Coffin, Marie; Darveaux, Blaise A; Heiniger, Ryan W; Shuster, Jeffrey R

    2003-12-01

    We describe a method for gene function discovery and chemical mode-of-action analysis via nutrient utilization using a high throughput Nutritional Profiling platform suitable for filamentous microorganisms. We have optimized the growth conditions for each fungal species to produce reproducible optical density growth measurements in microtiter plates. We validated the Nutritional Profiling platform using a nitrogen source utilization assay to analyze 21 Aspergillus nidulans strains with mutations in the master nitrogen regulatory gene, areA. Analysis of these data accurately reproduced expected results and provided new data to demonstrate that this platform is suitable for fine level phenotyping of filamentous fungi. Next, we analyzed the differential responses of two fungal species to a glutamine synthetase inhibitor, illustrating chemical mode-of-action analysis. Finally, a comparative phenotypic study was performed to characterize carbon catabolite repression in four fungal species using a carbon source utilization assay. The results demonstrate differentiation between two Aspergillus species and two diverse plant pathogens and provide a wealth of new data on fungal nutrient utilization. Thus, these assays can be used for gene function and chemical mode-of-action analysis at the whole organism level as well as interspecies comparisons in a variety of filamentous fungi. Additionally, because uniform distribution of growth within wells is maintained, comparisons between yeast and filamentous forms of a single organism can be performed.

  14. Partial migration in fishes: definitions, methodologies and taxonomic distribution

    DEFF Research Database (Denmark)

    Chapman, B B; Skov, C; Hulthén, K

    2012-01-01

    published. In addition, previous work and synthesis has been hampered by a varied lexicon associated with this phenomenon in fishes. In this review, definitions and important concepts in partial migration research are discussed, and a classification system of the different forms of partial migration...... in fishes introduced. Next, a detailed taxonomic overview of partial migration in this group is considered. Finally, methodological approaches that ichthyologists can use to study this fascinating phenomenon are reviewed. Partial migration is more widespread amongst fishes than previously thought, and given...

  15. Genotoxic potential of glyphosate formulations: mode-of-action investigations.

    Science.gov (United States)

    Heydens, William F; Healy, Charles E; Hotz, Kathy J; Kier, Larry D; Martens, Mark A; Wilson, Alan G E; Farmer, Donna R

    2008-02-27

    A broad array of in vitro and in vivo assays has consistently demonstrated that glyphosate and glyphosate-containing herbicide formulations (GCHF) are not genotoxic. Occasionally, however, related and contradictory data are reported, including findings of mouse liver and kidney DNA adducts and damage following intraperitoneal (ip) injection. Mode-of-action investigations were therefore undertaken to determine the significance of these contradictory data while concurrently comparing results from ip and oral exposures. Exposure by ip injection indeed produced marked hepatic and renal toxicity, but oral administration did not. The results suggest that ip injection of GCHF may induce secondary effects mediated by local toxicity rather than genotoxicity. Furthermore, these results continue to support the conclusion that glyphosate and GCHF are not genotoxic under exposure conditions that are relevant to animals and humans.

  16. Genomic tools to profile antibiotic mode of action.

    Science.gov (United States)

    Cardona, Silvia T; Selin, Carrie; Gislason, April S

    2015-01-01

    The increasing emergence of antimicrobial multiresistant bacteria is of great concern to public health. While these bacteria are becoming an ever more prominent cause of nosocomial and community-acquired infections worldwide, the antibiotic discovery pipeline has been stalled in the last few years with very few efforts in the research and development of novel antibacterial therapies. Some of the root causes that have hampered current antibiotic drug development are the lack of understanding of the mode of action (MOA) of novel antibiotic molecules and the poor characterization of the bacterial physiological response to antibiotics that ultimately causes resistance. Here, we review how bacterial genetic tools can be applied at the genomic level with the goal of profiling resistance to antibiotics and elucidating antibiotic MOAs. Specifically, we highlight how chemical genomic detection of the MOA of novel antibiotic molecules and antibiotic profiling by next-generation sequencing are leveraging basic antibiotic research to unprecedented levels with great opportunities for knowledge translation.

  17. Mosquitocidal bacterial toxins: diversity, mode of action and resistance phenomena

    Directory of Open Access Journals (Sweden)

    Charles Jean-François

    2000-01-01

    Full Text Available Bacteria active against dipteran larvae (mosquitoes and black flies include a wide variety of Bacillus thuringiensis and B. sphaericus strains, as well as isolates of Brevibacillus laterosporus and Clostridium bifermentans. All display different spectra and levels of activity correlated with the nature of the toxins, mainly produced during the sporulation process. This paper describes the structure and mode of action of the main mosquitocidal toxins, in relationship with their potential use in mosquito and/or black fly larvae control. Investigations with laboratory and field colonies of mosquitoes that have become highly resistant to the B. sphaericus Bin toxin have shown that several mechanisms of resistance are involved, some affecting the toxin/receptor binding step, others unknown.

  18. Perfluoroalkyl acids and related chemistries--toxicokinetics and modes of action.

    Science.gov (United States)

    Andersen, Melvin E; Butenhoff, John L; Chang, Shu-Ching; Farrar, David G; Kennedy, Gerald L; Lau, Christopher; Olsen, Geary W; Seed, Jennifer; Wallace, Kendall B

    2008-03-01

    The perfluoroalkyl acid salts (both carboxylates and sulfonates, hereafter designated as PFAAs) and their derivatives are important chemicals that have numerous consumer and industrial applications. However, recent discoveries that some of these compounds have global distribution, environmental persistence, presence in humans and wildlife, as well as toxicity in laboratory animal models, have generated considerable scientific, regulatory, and public interest on an international scale. The Society of Toxicology Contemporary Concepts in Toxicology Symposium, entitled "Perfluoroalkyl Acids and Related Chemistries: Toxicokinetics and Modes-of-Action Workshop" was held February 14-16, 2007 at the Westin Arlington Gateway, Arlington, VA. In addition to the Society of Toxicology, this symposium was sponsored by 3M Company, DuPont, Plastics Europe, and the U.S. Environmental Protection Agency. The objectives of this 3-day meeting were to (1) provide an overview of PFAA toxicity and description of recent findings with the sulfonates, carboxylates, and telomer alcohols; (2) address the toxicokinetic profiles of various PFAAs among animal models and humans, and the biological processes that are responsible for these observations; (3) examine the possible modes of action that determine the PFAA toxicities observed in animal models, and their relevance to human health risks; and (4) identify the critical research needs and strategies to fill the existing informational gaps that hamper risk assessment of these chemicals. This report summarizes the discourse that occurred during the symposium.

  19. A Critical Review of Mode of Action (MOA) Assignment ...

    Science.gov (United States)

    There are various structure-based classification schemes to categorize chemicals based on mode of action (MOA) which have been applied for both eco and human health toxicology. With increasing calls to assess thousands of chemicals, some of which have little available information other than structure, clear understanding how each of these MOA schemes was devised, what information they are based on, and the limitations of each approach is critical. Several groups are developing low-tier methods to more easily classify or assess chemicals, using approaches such as the ecological threshold of concern (eco-TTC) and chemical-activity. Evaluation of these approaches and determination of their domain of applicability is partly dependent on the MOA classification that is used. The most commonly used MOA classification schemes for ecotoxicology include Verhaar and Russom (included in ASTER), both of which are used to predict acute aquatic toxicity MOA. Verhaar is a QSAR-based system that classifies chemicals into one of 4 classes, with a 5th class specified for those chemicals that are not classified in the other 4. ASTER/Russom includes 8 classifications: narcotics (3 groups), oxidative phosphorylation uncouplers, respiratory inhibitors, electrophiles/proelectrophiles, AChE inhibitors, or CNS seizure agents. Other methodologies include TEST (Toxicity Estimation Software Tool), a computational chemistry-based application that allows prediction to one of 5 broad MOA

  20. Taxonomic revalidation and potential distribution of Armatocereus brevispinus Madsen (Cactaceae

    Directory of Open Access Journals (Sweden)

    Christian R. Loaiza S.

    2016-05-01

    Full Text Available We report the first confirmed record for northern Peru of Armatocereus brevispinus Madsen, a species of cactus regarded as endemic to the province of Loja, in the southern region of Ecuador. The record corresponds to a locality placed near the km 18 of the route to Ayabaca (04º42’21.0”S and 79º48’51.0”W, in the district of Ayabaca, within the province of Ayabaca, in the Department of Piura. This records represents an extension of the distributional range known for this species in Ecuador. We analyze its taxonomy and the distribution and conservation status and comments on its biogeography in the Andean region.

  1. Main functions and taxonomic distribution of virulence genes in Brucella melitensis 16 M.

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    Aniel Jessica Leticia Brambila-Tapia

    Full Text Available Many virulence genes have been detected in attenuated mutants of Brucella melitensis 16 M; nevertheless, a complete report of these genes, including the main Cluster of Orthologous Groups (COG represented as well as the taxonomical distribution among all complete bacterial and archaeal genomes, has not been analyzed. In this work a total of 160 virulence genes that have been reported in attenuated mutants in B. melitensis were included and analyzed. Additionally, we obtained 250 B. melitensis randomly selected genes as a reference group for the taxonomical comparisons. The COGs and the taxonomical distribution profile for 789 nonredundant bacterial and archaeal genomes were obtained and compared with the whole-genome COG distribution and with the 250 randomly selected genes, respectively. The main COGs associated with virulence genes corresponded to the following: intracellular trafficking, secretion and vesicular transport (U; cell motility (N; nucleotide transport and metabolism (F; transcription (K; and cell wall/membrane/envelope biogenesis (M. In addition, we found that virulence genes presented a higher proportion of orthologs in the Euryarchaeota and Proteobacteria phyla, with a significant decrease in Chlamydiae, Bacteroidetes, Tenericutes, Firmicutes and Thermotogae. In conclusion, we found that genes related to specific functions are more relevant to B. melitensis virulence, with the COG U the most significant. Additionally, the taxonomical distribution of virulence genes highlights the importance of these genes in the related Proteobacteria, being less relevant in distant groups of organisms with the exception of Euryarchaeota.

  2. On the antifungal mode of action of tridemorph

    NARCIS (Netherlands)

    Kerkenaar, A.; Barug, D.; Kaars Sijpesteijn, A.

    1979-01-01

    Tridemorph (2,6-dimethyl-N-tridecylmorpholine) was active against representative of nearly all taxonomic groups of fungi; gram-positive bacteria were also sensitive although gram-negative were not. Tridemorph, 3–10 μg/ml, inhibited the multiplication of sporidia of Ustilago maydis more strongly than

  3. On the antifungal mode of action of tridemorph

    NARCIS (Netherlands)

    Kerkenaar, A.; Barug, D.; Kaars Sijpesteijn, A.

    1979-01-01

    Tridemorph (2,6-dimethyl-N-tridecylmorpholine) was active against representative of nearly all taxonomic groups of fungi; gram-positive bacteria were also sensitive although gram-negative were not. Tridemorph, 3–10 μg/ml, inhibited the multiplication of sporidia of Ustilago maydis more strongly than

  4. Ocean Acidification Has Multiple Modes of Action on Bivalve Larvae

    Science.gov (United States)

    Waldbusser, George G.; Hales, Burke; Langdon, Chris J.; Haley, Brian A.; Schrader, Paul; Brunner, Elizabeth L.; Gray, Matthew W.; Miller, Cale A.; Gimenez, Iria; Hutchinson, Greg

    2015-01-01

    Ocean acidification (OA) is altering the chemistry of the world’s oceans at rates unparalleled in the past roughly 1 million years. Understanding the impacts of this rapid change in baseline carbonate chemistry on marine organisms needs a precise, mechanistic understanding of physiological responses to carbonate chemistry. Recent experimental work has shown shell development and growth in some bivalve larvae, have direct sensitivities to calcium carbonate saturation state that is not modulated through organismal acid-base chemistry. To understand different modes of action of OA on bivalve larvae, we experimentally tested how pH, PCO2, and saturation state independently affect shell growth and development, respiration rate, and initiation of feeding in Mytilus californianus embryos and larvae. We found, as documented in other bivalve larvae, that shell development and growth were affected by aragonite saturation state, and not by pH or PCO2. Respiration rate was elevated under very low pH (~7.4) with no change between pH of ~ 8.3 to ~7.8. Initiation of feeding appeared to be most sensitive to PCO2, and possibly minor response to pH under elevated PCO2. Although different components of physiology responded to different carbonate system variables, the inability to normally develop a shell due to lower saturation state precludes pH or PCO2 effects later in the life history. However, saturation state effects during early shell development will carry-over to later stages, where pH or PCO2 effects can compound OA effects on bivalve larvae. Our findings suggest OA may be a multi-stressor unto itself. Shell development and growth of the native mussel, M. californianus, was indistinguishable from the Mediterranean mussel, Mytilus galloprovincialis, collected from the southern U.S. Pacific coast, an area not subjected to seasonal upwelling. The concordance in responses suggests a fundamental OA bottleneck during development of the first shell material affected only by

  5. Ocean Acidification Has Multiple Modes of Action on Bivalve Larvae.

    Science.gov (United States)

    Waldbusser, George G; Hales, Burke; Langdon, Chris J; Haley, Brian A; Schrader, Paul; Brunner, Elizabeth L; Gray, Matthew W; Miller, Cale A; Gimenez, Iria; Hutchinson, Greg

    2015-01-01

    Ocean acidification (OA) is altering the chemistry of the world's oceans at rates unparalleled in the past roughly 1 million years. Understanding the impacts of this rapid change in baseline carbonate chemistry on marine organisms needs a precise, mechanistic understanding of physiological responses to carbonate chemistry. Recent experimental work has shown shell development and growth in some bivalve larvae, have direct sensitivities to calcium carbonate saturation state that is not modulated through organismal acid-base chemistry. To understand different modes of action of OA on bivalve larvae, we experimentally tested how pH, PCO2, and saturation state independently affect shell growth and development, respiration rate, and initiation of feeding in Mytilus californianus embryos and larvae. We found, as documented in other bivalve larvae, that shell development and growth were affected by aragonite saturation state, and not by pH or PCO2. Respiration rate was elevated under very low pH (~7.4) with no change between pH of ~ 8.3 to ~7.8. Initiation of feeding appeared to be most sensitive to PCO2, and possibly minor response to pH under elevated PCO2. Although different components of physiology responded to different carbonate system variables, the inability to normally develop a shell due to lower saturation state precludes pH or PCO2 effects later in the life history. However, saturation state effects during early shell development will carry-over to later stages, where pH or PCO2 effects can compound OA effects on bivalve larvae. Our findings suggest OA may be a multi-stressor unto itself. Shell development and growth of the native mussel, M. californianus, was indistinguishable from the Mediterranean mussel, Mytilus galloprovincialis, collected from the southern U.S. Pacific coast, an area not subjected to seasonal upwelling. The concordance in responses suggests a fundamental OA bottleneck during development of the first shell material affected only by

  6. Ocean Acidification Has Multiple Modes of Action on Bivalve Larvae.

    Directory of Open Access Journals (Sweden)

    George G Waldbusser

    Full Text Available Ocean acidification (OA is altering the chemistry of the world's oceans at rates unparalleled in the past roughly 1 million years. Understanding the impacts of this rapid change in baseline carbonate chemistry on marine organisms needs a precise, mechanistic understanding of physiological responses to carbonate chemistry. Recent experimental work has shown shell development and growth in some bivalve larvae, have direct sensitivities to calcium carbonate saturation state that is not modulated through organismal acid-base chemistry. To understand different modes of action of OA on bivalve larvae, we experimentally tested how pH, PCO2, and saturation state independently affect shell growth and development, respiration rate, and initiation of feeding in Mytilus californianus embryos and larvae. We found, as documented in other bivalve larvae, that shell development and growth were affected by aragonite saturation state, and not by pH or PCO2. Respiration rate was elevated under very low pH (~7.4 with no change between pH of ~ 8.3 to ~7.8. Initiation of feeding appeared to be most sensitive to PCO2, and possibly minor response to pH under elevated PCO2. Although different components of physiology responded to different carbonate system variables, the inability to normally develop a shell due to lower saturation state precludes pH or PCO2 effects later in the life history. However, saturation state effects during early shell development will carry-over to later stages, where pH or PCO2 effects can compound OA effects on bivalve larvae. Our findings suggest OA may be a multi-stressor unto itself. Shell development and growth of the native mussel, M. californianus, was indistinguishable from the Mediterranean mussel, Mytilus galloprovincialis, collected from the southern U.S. Pacific coast, an area not subjected to seasonal upwelling. The concordance in responses suggests a fundamental OA bottleneck during development of the first shell material

  7. Testosterone and the Male Skeleton: A Dual Mode of Action

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    Mieke Sinnesael

    2011-01-01

    Full Text Available Testosterone is an important hormone for both bone gain and maintenance in men. Hypogonadal men have accelerated bone turnover and increased fracture risk. In these men, administration of testosterone inhibits bone resorption and maintains bone mass. Testosterone, however, is converted into estradiol via aromatization in many tissues including male bone. The importance of estrogen receptor alpha activation as well of aromatization of androgens into estrogens was highlighted by a number of cases of men suffering from an inactivating mutation in the estrogen receptor alpha or in the aromatase enzyme. All these men typically had low bone mass, high bone turnover and open epiphyses. In line with these findings, cohort studies have confirmed that estradiol contributes to the maintenance of bone mass after reaching peak bone mass, with an association between estradiol and fractures in elderly men. Recent studies in knock-out mice have increased our understanding of the role of androgens and estrogens in different bone compartments. Estrogen receptor activation, but not androgen receptor activation, is involved in the regulation of male longitudinal appendicular skeletal growth in mice. Both the androgen and the estrogen receptor can independently mediate the cancellous bone-sparing effects of sex steroids in male mice. Selective KO studies of the androgen receptor in osteoblasts in male mice suggest that the osteoblast in the target cell for androgen receptor mediated maintenance of trabecular bone volume and coordination of bone matrix synthesis and mineralization. Taken together, both human and animal studies suggest that testosterone has a dual mode of action on different bone surfaces with involvement of both the androgen and estrogen receptor.

  8. Enhancing pressure ulcer prevention using wound dressings: what are the modes of action?

    Science.gov (United States)

    Call, Evan; Pedersen, Justin; Bill, Brian; Black, Joyce; Alves, Paulo; Brindle, C Tod; Dealey, Carol; Santamaria, Nick; Clark, Michael

    2015-08-01

    Recent clinical research has generated interest in the use of sacral wound dressings as preventive devices for patients at risk of ulceration. This study was conducted to identify the modes of action through which dressings can add to pressure ulcer prevention, for example, shear and friction force redistribution and pressure distribution. Bench testing was performed using nine commercially available dressings. The use of dressings can reduce the amplitude of shear stress and friction reaching the skin of patients at risk. They can also effectively redirect these forces to wider areas which minimises the mechanical loads upon skeletal prominences. Dressings can redistribute pressure based upon their effective Poisson ratio and larger deflection areas, providing greater load redistribution.

  9. Combining Taxonomic and Functional Approaches to Unravel the Spatial Distribution of an Amazonian Butterfly Community.

    Science.gov (United States)

    Graça, Márlon B; Morais, José W; Franklin, Elizabeth; Pequeno, Pedro A C L; Souza, Jorge L P; Bueno, Anderson Saldanha

    2016-04-01

    This study investigated the spatial distribution of an Amazonian fruit-feeding butterfly assemblage by linking species taxonomic and functional approaches. We hypothesized that: 1) vegetation richness (i.e., resources) and abundance of insectivorous birds (i.e., predators) should drive changes in butterfly taxonomic composition, 2) larval diet breadth should decrease with increase of plant species richness, 3) small-sized adults should be favored by higher abundance of birds, and 4) communities with eyespot markings should be able to exploit areas with higher predation pressure. Fruit-feeding butterflies were sampled with bait traps and insect nets across 25 km(2) of an Amazonian ombrophilous forest in Brazil. We measured larval diet breadth, adult body size, and wing marking of all butterflies. Our results showed that plant species richness explained most of the variation in butterfly taxonomic turnover. Also, community average diet breadth decreased with increase of plant species richness, which supports our expectations. In contrast, community average body size increased with the abundance of birds, refuting our hypothesis. We detected no influence of environmental gradients on the occurrence of species with eyespot markings. The association between butterfly taxonomic and functional composition points to a mediator role of the functional traits in the environmental filtering of butterflies. The incorporation of the functional approach into the analyses allowed for the detection of relationships that were not observed using a strictly taxonomic perspective and provided an extra insight into comprehending the potential adaptive strategies of butterflies. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. The taxonomic distribution of asteroids from multi-filter all-sky photometric surveys

    CERN Document Server

    DeMeo, Francesca

    2013-01-01

    The distribution of asteroids across the Main Belt has been studied for decades to understand the compositional distribution and what that tells us about the formation and evolution of our solar system. All-sky surveys now provide orders of magnitude more data than targeted surveys. We present a method to bias-correct the asteroid population observed in the Sloan Digital Sky Survey (SDSS) according to size, distance, and albedo. We taxonomically classify this dataset consistent with the Bus and Bus-DeMeo systems and present the resulting taxonomic distribution. The dataset includes asteroids as small as 5 km, a factor of three in diameter smaller than in previous works. Because of the wide range of sizes in our sample, we present the distribution by number, surface area, volume, and mass whereas previous work was exclusively by number. While the distribution by number is a useful quantity and has been used for decades, these additional quantities provide new insights into the distribution of total material. W...

  11. Stratum corneum hydration : mode of action of moisturizers on a molecular level

    NARCIS (Netherlands)

    Caussin, Julia

    2009-01-01

    In this thesis, the mode of action of stratum corneum moisturizers is studied using a variety of techniques: cryo-scanning electron microscopy, freeze fracture transmission electron microscopy, small angle X-ray diffraction and Fourier transform infrared spectroscopy.

  12. Mode of Action for Reproductive and Hepatic Toxicity Inferred from a Genomic Study of Triazole Antifungals

    Science.gov (United States)

    The mode of action for the reproductive toxicity of triazole antifungals have been previously characterized by an observed increased in serum testosterone, hepatotoxicity, and reduced insemination and fertility indices. In order to refine our mechanistic understanding of these m...

  13. Stratum corneum hydration : mode of action of moisturizers on a molecular level

    NARCIS (Netherlands)

    Caussin, Julia

    2009-01-01

    In this thesis, the mode of action of stratum corneum moisturizers is studied using a variety of techniques: cryo-scanning electron microscopy, freeze fracture transmission electron microscopy, small angle X-ray diffraction and Fourier transform infrared spectroscopy.

  14. Mixture toxicity of three toxicants with similar and dissimilar modes of action to Daphnia magna.

    Science.gov (United States)

    Syberg, Kristian; Elleby, Anders; Pedersen, Henrik; Cedergreen, Nina; Forbes, Valery E

    2008-03-01

    Mixture toxicity of similar- and dissimilar-acting toxicants can be predicted by the models concentration addition (CA) and independent action (IA) using single substance toxicity data. Knowledge of the toxicants mode of action is thus required in order to use the models. In order to test the predictive capability of the models, we conducted Daphnia magna 48 h immobilization experiments with three toxicants with known modes of action (dimethoate, pirimicarb and linear alkyl benzene sulfonate) singly, and in binary and ternary mixtures. Our results indicate that CA and IA predict binary mixtures of similar- and dissimilar-acting toxicants equally well. CA and IA also equally predicted the ternary mixture consisting of both similar- and dissimilar-acting chemicals. The paper discusses the concept of mode of action and the implications the definition of mode of action has on the choice of reference model for mixture toxicity studies.

  15. [Study progress on the mode of action of praziquantel against schistosomes].

    Science.gov (United States)

    Xiao, Shu-Hua

    2007-12-01

    Praziquantel is the only effective drug of choice against five human species of schistosomes. Main advantages of praziquantel include convenient oral administration, high safety and efficacy as well as short treatment course. To better understand the mode of action of praziquantel against schistosomes would be helpful for further development of new broad-spectrum anthelminthics. This paper summarizes the 30 years' research progress on the mode of action of the drug against schistosomes proceeded by domestic and abroad laboratories.

  16. The Bias-Corrected Taxonomic Distribution of Mission-Accessible Small Near-Earth Objects

    Science.gov (United States)

    Hinkle, Mary L.; Moskovitz, Nicholas; Trilling, David; Binzel, Richard P.; Thomas, Cristina; Christensen, Eric; DeMeo, Francesca; Person, Michael J.; Polishook, David; Willman, Mark

    2015-11-01

    Although they are thought to compose the majority of the Near-Earth object (NEO) population, the small (d GMOS at Gemini North & South observatories as well as the DeVeny spectrograph at Lowell Observatory's Discovery Channel Telescope. Archival data of 43 objects from the MIT-UH-IRTF Joint Campaign for NEO Spectral Reconnaissance (PI R. Binzel) were also used. Taxonomic classifications were obtained by fitting our spectra to the mean reflectance spectra of the Bus asteroid taxonomy (Bus & Binzel 2002). Small NEAs are the likely progenitors of meteorites; an improved understanding of the abundance of meteorite parent body types in the NEO population improves understanding of how the two populations are related as well as the biases Earth's atmosphere imposes upon the meteorite collection.We present classifications for these objects as well as results for the debiased distribution of taxa(as a proxy for composition) as a function of object size and compare to the observed fractions of ordinary chondritemeteorites and asteroids with d > 1 km. Amongst the smallest NEOs we find an unexpected distribution of taxonomic types that differs from both large NEOs and meteorites.We acknowledge funding support from NASA NEOO grant number NNX14AN82G.

  17. Taxonomic revision and distribution of herbaceous Paramollugo (Molluginaceae in the Eastern Hemisphere

    Directory of Open Access Journals (Sweden)

    Alexander P. Sukhorukov

    2016-10-01

    Full Text Available The genus Paramollugo with the type species Paramollugo nudicaulis (≡Mollugo nudicaulis has recently been described after molecular investigations. Here we report two new endemic Malagasy species: Paramollugo simulans and P. elliotii, and transfer a forgotten New Caledonian endemic Mollugo digyna to Paramollugo (P. digyna. Consequently, the number of Paramollugo species in the Eastern Hemisphere is increased from three to six. Almost all genus representatives (except P. nudicaulis, which has a wide distribution in Southern Asia, Arabia and tropical Africa are endemic to Madagascar, Somalia, or New Caledonia. Since the type of seed coat ornamentation is crucial for species delimitation, a diagnostic key with new taxonomically significant carpological characters and other new traits is provided for all the herbaceous Paramollugo. The distribution patterns of P. nudicaulis s.str., P. simulans and P. elliotii are presented.

  18. Definition of primary mode of action of a combination product. Final rule.

    Science.gov (United States)

    2005-08-25

    The Food and Drug Administration (FDA) is amending its combination product regulations to define "mode of action'' (MOA) and "primary mode of action" (PMOA). Along with these definitions, the final rule sets forth an algorithm the agency will use to assign combination products to an agency component for regulatory oversight when the agency cannot determine with reasonable certainty which mode of action provides the most important therapeutic action of the combination product. Finally, the final rule will require a sponsor to base its recommendation of the agency component with primary jurisdiction for regulatory oversight of its combination product by using the PMOA definition and, if appropriate, the assignment algorithm. The final rule is intended to promote the public health by codifying the agency's criteria for the assignment of combination products in transparent, consistent, and predictable terms.

  19. The taxonomic distribution of asteroids from multi-filter all-sky photometric surveys

    Science.gov (United States)

    DeMeo, F. E.; Carry, B.

    2013-09-01

    The distribution of asteroids across the main belt has been studied for decades to understand the current compositional distribution and what that tells us about the formation and evolution of our Solar System. All-sky surveys now provide orders of magnitude more data than targeted surveys. We present a method to bias-correct the asteroid population observed in the Sloan Digital Sky Survey (SDSS) according to size, distance, and albedo. We taxonomically classify this dataset consistent with the Bus and Binzel (Bus, S.J., Binzel, R.P. [2002]. Icarus 158, 146-177) and Bus-DeMeo et al. (DeMeo, F.E., Binzel, R.P., Slivan, S.M., Bus, S.J. [2009]. Icarus 202(July), 160-180) systems and present the resulting taxonomic distribution. The dataset includes asteroids as small as 5 km, a factor of three in diameter smaller than in previous work such as by Mothé-Diniz et al. (Mothé-Diniz, T., Carvano, J.M.Á., Lazzaro, D. [2003]. Icarus 162(March), 10-21). Because of the wide range of sizes in our sample, we present the distribution by number, surface area, volume, and mass whereas previous work was exclusively by number. While the distribution by number is a useful quantity and has been used for decades, these additional quantities provide new insights into the distribution of total material. We find evidence for D-types in the inner main belt where they are unexpected according to dynamical models of implantation of bodies from the outer Solar System into the inner Solar System during planetary migration (Levison, H.F., Bottke, W.F., Gounelle, M., Morbidelli, A., Nesvorný, D., Tsiganis, K. [2009]. Nature 460(July), 364-366). We find no evidence of S-types or other unexpected classes among Trojans and Hildas, albeit a bias favoring such a detection. Finally, we estimate for the first time the total amount of material of each class in the inner Solar System. The main belt’s most massive classes are C, B, P, V and S in decreasing order. Excluding the four most massive

  20. Mode of action of Chrysosporium lucknowense C1 a-l-arabinohydrolases

    NARCIS (Netherlands)

    Kuhnel, S.; Westphal, Y.; Hinz, S.W.A.; Schols, H.A.; Gruppen, H.

    2011-01-01

    The mode of action of four Chrysosporium lucknowense C1 a-l-arabinohydrolases was determined to enable controlled and effective degradation of arabinan. The active site of endoarabinanase Abn1 has at least six subsites, of which the subsites -1 to +2 have to be occupied for hydrolysis. Abn1 was able

  1. Computational Chemistry-based Acute Aquatic Toxicity Mode of Action Assignment

    Science.gov (United States)

    The ability to determine the mode of action (MOA) for a diverse group of chemicals is a critical part of ecological risk assessment and chemical regulation. However, existing MOA assignment approaches in ecotoxicology have been limited to a relatively few MOAs, have high uncertai...

  2. Mode of Action (MOA) Assignment Classifications for Ecotoxicology: Evaluation of Available Methods

    Science.gov (United States)

    There are various structure-based classification schemes to categorize chemicals based on mode of action (MOA) which have been applied for both eco and human toxicology. With increasing calls to assess 1000s of chemicals, some of which have little available information other tha...

  3. Prediction of aquatic toxicity mode of action using linear discriminant and random forest models

    Science.gov (United States)

    The ability to determine the mode of action (MOA) for a diverse group of chemicals is a critical part of ecological risk assessment and chemical regulation. However, existing MOA assignment approaches in ecotoxicology have been limited to a relatively few MOAs, have high uncertai...

  4. How benthic diatoms within natural communities respond to eight common herbicides with different modes of action.

    Science.gov (United States)

    Wood, Rebecca J; Mitrovic, Simon M; Lim, Richard P; Kefford, Ben J

    2016-07-01

    Herbicides are common pollutants of rivers in agricultural regions. These contaminants include various types of chemicals with different modes of toxic action. Herbicides can have toxic effects on freshwater benthic diatoms, the base of the aquatic food web. We examined the effects of (non-mixture) herbicide exposure to the health of diatoms for eight common herbicides with three different modes of action; the photosystem II (PSII) inhibitors: atrazine, simazine, hexazinone, tebuthiuron and diuron; two auxinic herbicides: MCPA and 2,4-D; and the EPSP synthase inhibitor: glyphosate. Benthic diatoms within riverine communities were exposed to each herbicide in rapid toxicity tests at concentrations of 50, 200 and 500μgL(-1). The most sensitive taxa were Gomphonema spp. and Encyonema gracilis. Navicula cryptotenella was the most tolerant to herbicide exposure. There was no significant effect of the different herbicide modes of action at the community level. Herbicide mode of action did not alter which taxa were most sensitive within the community and sensitivity rankings of the dominant diatom taxa were similar for each of the eight herbicides. The consistency of the results between herbicides suggests that freshwater benthic diatoms may be suitable in situ indicators for detecting the toxicity of herbicides with differing modes of action. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Odorant receptor modulation: Ternary paradigm for mode of action of insect repellents

    Science.gov (United States)

    The modulation of insect behavior for the purpose of controlling the spread of infectious diseases has been the task of a few insect repellents for which the mechanistic modes of action on odorant receptors (ORs) are unclear. Here, we study the effects of the repellents DEET and IR3535, and a novel ...

  6. Study of the mode of action of a polygalacturonase from the phytopathogen Burkholderia cepacia

    DEFF Research Database (Denmark)

    Massa, C.; Clausen, Mads Hartvig; Stojan, J.

    2007-01-01

    of pectins. The mode of action of BcPeh28A on different substrates has been investigated and its enzymatic mechanism elucidated. The hydrolysis of polygalacturonate indicates that BcPeh28A is a non-processive enzyme that releases oligomers with chain lengths ranging from two to eight. By inspection...

  7. Mode of Action Profiles for Pesticide Compounds with Rodent Liver Tumor Outcomes

    Science.gov (United States)

    Mode of action (MOA) provides a central framework for assessing human relevance of adverse health outcomes observed in nonclinical safety studies. The goal of this study was to characterize MOA profiles for known rodent liver tumorigens identified from a database of pesticides as...

  8. Triclosan Decreases Rat Thyroxine: Mode-of-Action, Developmental Susceptibility and Human Relevance

    Science.gov (United States)

    Triclosan (TCS) decreases serum thyroxine (T4) in the rat. In vivo and in vitro approaches were used to address three uncertainties: by what mode-of-action (MOA) does TCS decrease T4; does TCS decrease T4 developmentally; and, are effects observed in rats relevant to humans? To t...

  9. Mixture toxicity of three toxicants with similar and dissimilar modes of action to Daphnia magna

    DEFF Research Database (Denmark)

    Syberg, K.; Engell-Kofoed, Anders Elleby; Pedersen, H.;

    2008-01-01

    Mixture toxicity of similar- and dissimilar-acting toxicants can be predicted by the models concentration addition (CA) and independent action (IA) using single substance toxicity data. Knowledge of the toxicants mode of action is thus required in order to use the models. In order to test the pre...

  10. A Critical Review of Mode of Action (MOA) Assignment Classifications for Ecotoxicology

    Science.gov (United States)

    There are various structure-based classification schemes to categorize chemicals based on mode of action (MOA) which have been applied for both eco and human health toxicology. With increasing calls to assess thousands of chemicals, some of which have little available informatio...

  11. Mode of Action (MOA) Assignment Classifications for Ecotoxicology: Evaluation of Available Methods

    Science.gov (United States)

    There are various structure-based classification schemes to categorize chemicals based on mode of action (MOA) which have been applied for both eco and human toxicology. With increasing calls to assess 1000s of chemicals, some of which have little available information other tha...

  12. Application of mass spectrometric techniques to delineate the modes-of-action of anticancer metallodrugs

    NARCIS (Netherlands)

    Hartinger, Christian G.; Groessl, Michael; Meier, Samuel M.; Casini, Angela; Dyson, Paul J.

    2013-01-01

    Mass spectrometry (MS) has emerged as an important tool for studying anticancer metallodrugs in complex biological samples and for characterising their interactions with biomolecules and potential targets on a molecular level. The exact modes-of-action of these coordination compounds and especially

  13. Mode of action of the phenylpyrrole fungicide fenpiclonil in Fusarium sulphureum.

    NARCIS (Netherlands)

    Jespers, A.B.K.

    1994-01-01

    In the last few decades, plant disease control has become heavily dependent on fungicides. Most modem fungicides were discovered by random synthesis and empirical optimization of lead structures. In general, these fungicides have specific modes of action and meet modem enviromnental criteria. A disa

  14. Mode of Action of Polyamine Analogues on the Growth and Biochemistry of Leishmanial Cells.

    Science.gov (United States)

    1981-09-15

    information on the biochemical properties of parasites has hampered the development of new drugs and indeed no revolutionary new therapeutic approaches...of the parasites and the elucidation of the mode of action of known drugs are prerequisites for the development of new drugs . It would be ideal to

  15. Computational Chemistry-based Acute Aquatic Toxicity Mode of Action Assignment

    Science.gov (United States)

    The ability to determine the mode of action (MOA) for a diverse group of chemicals is a critical part of ecological risk assessment and chemical regulation. However, existing MOA assignment approaches in ecotoxicology have been limited to a relatively few MOAs, have high uncertai...

  16. Prediction of aquatic toxicity mode of action using linear discriminant and random forest models

    Science.gov (United States)

    The ability to determine the mode of action (MOA) for a diverse group of chemicals is a critical part of ecological risk assessment and chemical regulation. However, existing MOA assignment approaches in ecotoxicology have been limited to a relatively few MOAs, have high uncertai...

  17. Innovative mode of action based in vitro assays for detection of marine neurotoxins

    NARCIS (Netherlands)

    Nicolas, J.A.Y.

    2015-01-01

    Innovative mode of action based in vitro assays for detection of marine neurotoxins J. Nicolas, P.J.M. Hendriksen, T.F.H. Bovee, I.M.C.M. Rietjens Marine biotoxins are naturally occurring compounds produced by particular phytoplankton species. These toxins often accumulate in seafood and thereby

  18. Exposure assessment of the cumulative intake of pesticides with dissimilar mode of action

    DEFF Research Database (Denmark)

    Jensen, Bodil Hamborg; Petersen, Annette; Christiansen, Sofie

    . In this study the effects of combined exposure from four endocrine disrupting pesticides have been investigated (procymidone, mancozeb, tebuconazole, and prochloraz). The four pesticides have dissimilar mode of actions. On the background of the potency for each pesticide to a given effect, a relative potency...

  19. Toxicity of mixtures of nephrotoxicants with similar or dissimilar mode of action

    NARCIS (Netherlands)

    Jonker, D.; Woutersen, R.A.; Feron, V.J.

    1996-01-01

    The toxicity of mixtures of chemicals with the same target organ was examined in rats using nephrotoxicants with similar or dissimilar modes of action. In a 4-wk feeding study, lysinoalanine, mercuric chloride, hexachloro-1,3-butadiene and d-limonene, each affecting renal proximal tubular cells but

  20. Revising the taxonomic distribution, origin and evolution of ribosome inactivating protein genes.

    Science.gov (United States)

    Lapadula, Walter J; Sánchez Puerta, María Virginia; Juri Ayub, Maximiliano

    2013-01-01

    Ribosome inactivating proteins are enzymes that depurinate a specific adenine residue in the alpha-sarcin-ricin loop of the large ribosomal RNA, being ricin and Shiga toxins the most renowned examples. They are widely distributed in plants and their presence has also been confirmed in a few bacterial species. According to this taxonomic distribution, the current model about the origin and evolution of RIP genes postulates that an ancestral RIP domain was originated in flowering plants, and later acquired by some bacteria via horizontal gene transfer. Here, we unequivocally detected the presence of RIP genes in fungi and metazoa. These findings, along with sequence and phylogenetic analyses, led us to propose an alternative, more parsimonious, hypothesis about the origin and evolutionary history of the RIP domain, where several paralogous RIP genes were already present before the three domains of life evolved. This model is in agreement with the current idea of the Last Universal Common Ancestor (LUCA) as a complex, genetically redundant organism. Differential loss of paralogous genes in descendants of LUCA, rather than multiple horizontal gene transfer events, could account for the complex pattern of RIP genes across extant species, as it has been observed for other genes.

  1. Revising the taxonomic distribution, origin and evolution of ribosome inactivating protein genes.

    Directory of Open Access Journals (Sweden)

    Walter J Lapadula

    Full Text Available Ribosome inactivating proteins are enzymes that depurinate a specific adenine residue in the alpha-sarcin-ricin loop of the large ribosomal RNA, being ricin and Shiga toxins the most renowned examples. They are widely distributed in plants and their presence has also been confirmed in a few bacterial species. According to this taxonomic distribution, the current model about the origin and evolution of RIP genes postulates that an ancestral RIP domain was originated in flowering plants, and later acquired by some bacteria via horizontal gene transfer. Here, we unequivocally detected the presence of RIP genes in fungi and metazoa. These findings, along with sequence and phylogenetic analyses, led us to propose an alternative, more parsimonious, hypothesis about the origin and evolutionary history of the RIP domain, where several paralogous RIP genes were already present before the three domains of life evolved. This model is in agreement with the current idea of the Last Universal Common Ancestor (LUCA as a complex, genetically redundant organism. Differential loss of paralogous genes in descendants of LUCA, rather than multiple horizontal gene transfer events, could account for the complex pattern of RIP genes across extant species, as it has been observed for other genes.

  2. Biochemical properties of ectoine hydroxylases from extremophiles and their wider taxonomic distribution among microorganisms.

    Directory of Open Access Journals (Sweden)

    Nils Widderich

    Full Text Available Ectoine and hydroxyectoine are well-recognized members of the compatible solutes and are widely employed by microorganisms as osmostress protectants. The EctABC enzymes catalyze the synthesis of ectoine from the precursor L-aspartate-β-semialdehyde. A subgroup of the ectoine producers can convert ectoine into 5-hydroxyectoine through a region-selective and stereospecific hydroxylation reaction. This compatible solute possesses stress-protective and function-preserving properties different from those of ectoine. Hydroxylation of ectoine is carried out by the EctD protein, a member of the non-heme-containing iron (II and 2-oxoglutarate-dependent dioxygenase superfamily. We used the signature enzymes for ectoine (EctC and hydroxyectoine (EctD synthesis in database searches to assess the taxonomic distribution of potential ectoine and hydroxyectoine producers. Among 6428 microbial genomes inspected, 440 species are predicted to produce ectoine and of these, 272 are predicted to synthesize hydroxyectoine as well. Ectoine and hydroxyectoine genes are found almost exclusively in Bacteria. The genome context of the ect genes was explored to identify proteins that are functionally associated with the synthesis of ectoines; the specialized aspartokinase Ask_Ect and the regulatory protein EctR. This comprehensive in silico analysis was coupled with the biochemical characterization of ectoine hydroxylases from microorganisms that can colonize habitats with extremes in salinity (Halomonas elongata, pH (Alkalilimnicola ehrlichii, Acidiphilium cryptum, or temperature (Sphingopyxis alaskensis, Paenibacillus lautus or that produce hydroxyectoine very efficiently over ectoine (Pseudomonas stutzeri. These six ectoine hydroxylases all possess similar kinetic parameters for their substrates but exhibit different temperature stabilities and differ in their tolerance to salts. We also report the crystal structure of the Virgibacillus salexigens EctD protein in its

  3. Biochemical properties of ectoine hydroxylases from extremophiles and their wider taxonomic distribution among microorganisms.

    Science.gov (United States)

    Widderich, Nils; Höppner, Astrid; Pittelkow, Marco; Heider, Johann; Smits, Sander H J; Bremer, Erhard

    2014-01-01

    Ectoine and hydroxyectoine are well-recognized members of the compatible solutes and are widely employed by microorganisms as osmostress protectants. The EctABC enzymes catalyze the synthesis of ectoine from the precursor L-aspartate-β-semialdehyde. A subgroup of the ectoine producers can convert ectoine into 5-hydroxyectoine through a region-selective and stereospecific hydroxylation reaction. This compatible solute possesses stress-protective and function-preserving properties different from those of ectoine. Hydroxylation of ectoine is carried out by the EctD protein, a member of the non-heme-containing iron (II) and 2-oxoglutarate-dependent dioxygenase superfamily. We used the signature enzymes for ectoine (EctC) and hydroxyectoine (EctD) synthesis in database searches to assess the taxonomic distribution of potential ectoine and hydroxyectoine producers. Among 6428 microbial genomes inspected, 440 species are predicted to produce ectoine and of these, 272 are predicted to synthesize hydroxyectoine as well. Ectoine and hydroxyectoine genes are found almost exclusively in Bacteria. The genome context of the ect genes was explored to identify proteins that are functionally associated with the synthesis of ectoines; the specialized aspartokinase Ask_Ect and the regulatory protein EctR. This comprehensive in silico analysis was coupled with the biochemical characterization of ectoine hydroxylases from microorganisms that can colonize habitats with extremes in salinity (Halomonas elongata), pH (Alkalilimnicola ehrlichii, Acidiphilium cryptum), or temperature (Sphingopyxis alaskensis, Paenibacillus lautus) or that produce hydroxyectoine very efficiently over ectoine (Pseudomonas stutzeri). These six ectoine hydroxylases all possess similar kinetic parameters for their substrates but exhibit different temperature stabilities and differ in their tolerance to salts. We also report the crystal structure of the Virgibacillus salexigens EctD protein in its apo

  4. A reverse taxonomic approach to assess macrofaunal distribution patterns in abyssal Pacific polymetallic nodule fields.

    Directory of Open Access Journals (Sweden)

    Annika Janssen

    Full Text Available Heightened interest in the exploitation of deep seafloor minerals is raising questions on the consequences for the resident fauna. Assessing species ranges and determination of processes underlying current species distributions are prerequisites to conservation planning and predicting faunal responses to changing environmental conditions. The abyssal central Pacific nodule belt, located between the Clarion and Clipperton Fracture Zones (CCZ, is an area prospected for mining of polymetallic nodules. We examined variations in genetic diversity and broad-scale connectivity of isopods and polychaetes across the CCZ. Faunal assemblages were studied from two mining claims (the eastern German and French license areas located 1300 km apart and influenced by different productivity regimes. Using a reverse taxonomy approach based on DNA barcoding, we tested to what extent distance and large-scale changes in environmental parameters lead to differentiation in two macrofaunal taxa exhibiting different functions and life-history patterns. A fragment of the mitochondrial gene Cytochrome Oxidase Subunit 1 (COI was analyzed. At a 97% threshold the molecular operational taxonomic units (MOTUs corresponded well to morphological species. Molecular analyses indicated high local and regional diversity mostly because of large numbers of singletons in the samples. Consequently, variation in composition of genotypic clusters between sites was exceedingly large partly due to paucity of deep-sea sampling and faunal patchiness. A higher proportion of wide-ranging species in polychaetes was contrasted with mostly restricted distributions in isopods. Remarkably, several cryptic lineages appeared to be sympatric and occurred in taxa with putatively good dispersal abilities, whereas some brooding lineages revealed broad distributions across the CCZ. Geographic distance could explain variation in faunal connectivity between regions and sites to some extent, while assumed

  5. Discovery of drug mode of action and drug repositioning from transcriptional responses

    OpenAIRE

    Iorio, Francesco; Bosotti, Roberta; Scacheri, Emanuela; Belcastro, Vincenzo; Mithbaokar, Pratibha; Ferriero, Rosa; Murino, Loredana; Tagliaferri, Roberto; Brunetti-Pierri, Nicola; Isacchi, Antonella; di Bernardo, Diego

    2010-01-01

    A bottleneck in drug discovery is the identification of the molecular targets of a compound (mode of action, MoA) and of its off-target effects. Previous approaches to elucidate drug MoA include analysis of chemical structures, transcriptional responses following treatment, and text mining. Methods based on transcriptional responses require the least amount of information and can be quickly applied to new compounds. Available methods are inefficient and are not able to support network pharmac...

  6. Dual mode of action of Bt proteins: protoxin efficacy against resistant insects

    OpenAIRE

    2015-01-01

    Transgenic crops that produce Bacillus thuringiensis (Bt) proteins for pest control are grown extensively, but insect adaptation can reduce their effectiveness. Established mode of action models assert that Bt proteins Cry1Ab and Cry1Ac are produced as inactive protoxins that require conversion to a smaller activated form to exert toxicity. However, contrary to this widely accepted paradigm, we report evidence from seven resistant strains of three major crop pests showing that Cry1Ab and Cry1...

  7. Anti-tumour cytotoxin produced by human monocytes: studies on its mode of action.

    OpenAIRE

    Matthews, N.

    1983-01-01

    Human monocytes can be induced to synthesize a cytotoxin which affects certain tumour cell lines. The interaction of monocyte cytotoxin with a susceptible cell line (L929) has been studied to obtain clues to the mode of action of the cytotoxin. The cytotoxin acts directly on the cells rather than on the culture medium and is cytotoxic at higher concentrations and cytostatic at lower concentrations. First signs of cell damage appear about 20 h after contact with the cytotoxin which must be pre...

  8. Competitive exclusion as a mode of action of a novel Bacillus cereus aquaculture biological agent

    CSIR Research Space (South Africa)

    Lalloo, R

    2010-01-01

    Full Text Available (Kumar et al. 2006; Newaj-Fyzul et al. 2007). Potential mechanisms of biological agents against 7 pathogens include competition for adhesion sites, production of enzymes, immune stimulation, 8 synthesis of antimicrobials, competitive exclusion..., the ability 20 to reduce the concentration of waste ions in reticulated aquaculture, physiological tolerance to 21 environmental conditions and bio-safety (Lalloo et al. 2007; Lalloo et al. 2008) renders the B. 22 Mode of action B. cereus 14 cereus isolate...

  9. Why have no new herbicide modes of action appeared in recent years?

    Science.gov (United States)

    Duke, Stephen O

    2012-04-01

    Herbicides with new modes of action are badly needed to manage the evolution of resistance of weeds to existing herbicides. Yet no major new mode of action has been introduced to the market place for about 20 years. There are probably several reasons for this. New potential products may have remained dormant owing to concerns that glyphosate-resistant (GR) crops have reduced the market for a new herbicide. The capture of a large fraction of the herbicide market by glyphosate with GR crops led to significantly diminished herbicide discovery efforts. Some of the reduced herbicide discovery research was also due to company consolidations and the availability of more generic herbicides. Another problem might be that the best herbicide molecular target sites may have already been discovered. However, target sites that are not utilized, for which there are inhibitors that are highly effective at killing plants, suggests that this is not true. Results of modern methods of target site discovery (e.g. gene knockout methods) are mostly not public, but there is no evidence of good herbicides with new target sites coming from these approaches. In summary, there are several reasons for a long dry period for new herbicide target sites; however, the relative magnitude of each is unclear. The economic stimulus to the herbicide industry caused by the evolution of herbicide-resistant weeds, especially GR weeds, may result in one or more new modes of action becoming available in the not too distant future. Copyright © 2011 Society of Chemical Industry.

  10. A preliminary operational classification system for nonmutagenic modes of action for carcinogenesis.

    Science.gov (United States)

    Hattis, D; Chu, M; Rahmioglu, N; Goble, R; Verma, P; Hartman, K; Kozlak, M

    2009-01-01

    This article proposes a system of categories for nonmutagenic modes of action for carcinogenesis. The classification is of modes of action rather than individual carcinogens, because the same compound can affect carcinogenesis in more than one way. Basically, we categorize modes of action as: (1) co-initiation (facilitating the original mutagenic changes in stem and progenitor cells that start the cancer process) (e.g. induction of activating enzymes for other carcinogens); (2) promotion (enhancing the relative growth vs differentiation/death of initiated clones (e.g. inhibition of growth-suppressing cell-cell communication); (3) progression (enhancing the growth, malignancy, or spread of already developed tumors) (e.g. suppression of immune surveillance, hormonally mediated growth stimulation for tumors with appropriate receptors by estrogens); and (4) multiphase (e.g., "epigenetic" silencing of tumor suppressor genes). A priori, agents that act at relatively early stages in the process are expected to manifest greater relative susceptibility in early life, whereas agents that act via later stage modes will tend to show greater susceptibility for exposures later in life.

  11. Toxicity of 13 different antibiotics towards freshwater green algae Pseudokirchneriella subcapitata and their modes of action.

    Science.gov (United States)

    Fu, Ling; Huang, Tao; Wang, Shuo; Wang, Xiaohong; Su, Limin; Li, Chao; Zhao, Yuanhui

    2017-02-01

    Although modes of action (MOAs) play a key role in the understanding of the toxic mechanism of chemicals, the MOAs have not been investigated for antibiotics to green algae. This paper is to discriminate excess toxicity from baseline level and investigate the MOAs of 13 different antibiotics to algae by using the determined toxicity values. Comparison of the toxicities shows that the inhibitors of protein synthesis to bacteria, such as azithromycin, doxycycline, florfenicol and oxytetracycline, exhibit significantly toxic effects to algae. On the other hand, the cell wall synthesis inhibitors, such as cefotaxime and amoxicillin, show relatively low toxic effects to the algae. The concentrations determined by HPLC indicate that quinocetone and amoxicillin can be easily photodegraded or hydrolyzed during the toxic tests. The toxic effects of quinocetone and amoxicillin to the algae are attributed to not only their parent compounds, but also their metabolites. Investigation on the mode of action shows that, except rifampicin, all the tested antibiotics exhibit excess toxicity to Pseudokirchneriella subcapitata (P. subcapitata). These antibiotics can be identified as reactive modes of action to the algae. They act as electrophilic mechanism of action to P. subcapitata. These results are valuable for the understanding of the toxic mechanism to algae.

  12. Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control.

    Science.gov (United States)

    Bravo, Alejandra; Gill, Sarjeet S; Soberón, Mario

    2007-03-15

    Bacillus thuringiensis Crystal (Cry) and Cytolitic (Cyt) protein families are a diverse group of proteins with activity against insects of different orders--Lepidoptera, Coleoptera, Diptera and also against other invertebrates such as nematodes. Their primary action is to lyse midgut epithelial cells by inserting into the target membrane and forming pores. Among this group of proteins, members of the 3-Domain Cry family are used worldwide for insect control, and their mode of action has been characterized in some detail. Phylogenetic analyses established that the diversity of the 3-Domain Cry family evolved by the independent evolution of the three domains and by swapping of domain III among toxins. Like other pore-forming toxins (PFT) that affect mammals, Cry toxins interact with specific receptors located on the host cell surface and are activated by host proteases following receptor binding resulting in the formation of a pre-pore oligomeric structure that is insertion competent. In contrast, Cyt toxins directly interact with membrane lipids and insert into the membrane. Recent evidence suggests that Cyt synergize or overcome resistance to mosquitocidal-Cry proteins by functioning as a Cry-membrane bound receptor. In this review we summarize recent findings on the mode of action of Cry and Cyt toxins, and compare them to the mode of action of other bacterial PFT. Also, we discuss their use in the control of agricultural insect pests and insect vectors of human diseases.

  13. Non-Membrane Permeabilizing Modes of Action of Antimicrobial Peptides on Bacteria.

    Science.gov (United States)

    Scocchi, Marco; Mardirossian, Mario; Runti, Giulia; Benincasa, Monica

    2016-01-01

    Antimicrobial peptides (AMPs) are a large class of innate immunity effectors with a remarkable capacity to inactivate microorganisms. Their ability to kill bacteria by membranolytic effects has been well established. However, a lot of evidence points to alternative, non-lytic modes of action for a number of AMPs, which operate through interactions with specific molecular targets. It has been reported that non-membrane-permeabilizing AMPs can bind to and inhibit DNA, RNA or protein synthesis processes, inactivate essential intracellular enzymes, or affect membrane septum formation and cell wall synthesis. This minireview summarizes recent findings on these alternative, non-lytic modes of antimicrobial action with an emphasis to the experimental approaches used to clarify each step of their intracellular action, i.e. the cell penetration mechanism, intracellular localization and molecular mechanisms of antibacterial action. Despite the fact that such data exists for a large number of peptides, our analysis indicates that only for a small number of AMPs sufficient data have been collected to support a mode of action with an authentic and substantial contribution by intracellular targeting. In most cases, peptides with non-lytic features have not been thoroughly analyzed, or only a single aspect of their mode of action has been taken into consideration and therefore their mechanism of action can only be hypothesized. A more detailed knowledge of this class of AMPs would be important in the design of novel antibacterial agents against unexploited targets, endowed with the capacity to penetrate into pathogen cells and kill them from within.

  14. Taxonomic distribution and origins of the extended LHC (light-harvesting complex antenna protein superfamily

    Directory of Open Access Journals (Sweden)

    Brinkmann Henner

    2010-07-01

    Full Text Available Abstract Background The extended light-harvesting complex (LHC protein superfamily is a centerpiece of eukaryotic photosynthesis, comprising the LHC family and several families involved in photoprotection, like the LHC-like and the photosystem II subunit S (PSBS. The evolution of this complex superfamily has long remained elusive, partially due to previously missing families. Results In this study we present a meticulous search for LHC-like sequences in public genome and expressed sequence tag databases covering twelve representative photosynthetic eukaryotes from the three primary lineages of plants (Plantae: glaucophytes, red algae and green plants (Viridiplantae. By introducing a coherent classification of the different protein families based on both, hidden Markov model analyses and structural predictions, numerous new LHC-like sequences were identified and several new families were described, including the red lineage chlorophyll a/b-binding-like protein (RedCAP family from red algae and diatoms. The test of alternative topologies of sequences of the highly conserved chlorophyll-binding core structure of LHC and PSBS proteins significantly supports the independent origins of LHC and PSBS families via two unrelated internal gene duplication events. This result was confirmed by the application of cluster likelihood mapping. Conclusions The independent evolution of LHC and PSBS families is supported by strong phylogenetic evidence. In addition, a possible origin of LHC and PSBS families from different homologous members of the stress-enhanced protein subfamily, a diverse and anciently paralogous group of two-helix proteins, seems likely. The new hypothesis for the evolution of the extended LHC protein superfamily proposed here is in agreement with the character evolution analysis that incorporates the distribution of families and subfamilies across taxonomic lineages. Intriguingly, stress-enhanced proteins, which are universally found in the

  15. Pursuing the quest for better understanding the taxonomic distribution of the system of doubly uniparental inheritance of mtDNA

    Directory of Open Access Journals (Sweden)

    Arthur Gusman

    2016-12-01

    Full Text Available There is only one exception to strict maternal inheritance of mitochondrial DNA (mtDNA in the animal kingdom: a system named doubly uniparental inheritance (DUI, which is found in several bivalve species. Why and how such a radically different system of mitochondrial transmission evolved in bivalve remains obscure. Obtaining a more complete taxonomic distribution of DUI in the Bivalvia may help to better understand its origin and function. In this study we provide evidence for the presence of sex-linked heteroplasmy (thus the possible presence of DUI in two bivalve species, i.e., the nuculanoid Yoldia hyperborea(Gould, 1841and the veneroid Scrobicularia plana(Da Costa,1778, increasing the number of families in which DUI has been found by two. An update on the taxonomic distribution of DUI in the Bivalvia is also presented.

  16. Pursuing the quest for better understanding the taxonomic distribution of the system of doubly uniparental inheritance of mtDNA

    Science.gov (United States)

    Gusman, Arthur; Lecomte, Sophia; Stewart, Donald T.; Passamonti, Marco

    2016-01-01

    There is only one exception to strict maternal inheritance of mitochondrial DNA (mtDNA) in the animal kingdom: a system named doubly uniparental inheritance (DUI), which is found in several bivalve species. Why and how such a radically different system of mitochondrial transmission evolved in bivalve remains obscure. Obtaining a more complete taxonomic distribution of DUI in the Bivalvia may help to better understand its origin and function. In this study we provide evidence for the presence of sex-linked heteroplasmy (thus the possible presence of DUI) in two bivalve species, i.e., the nuculanoid Yoldia hyperborea(Gould, 1841)and the veneroid Scrobicularia plana(Da Costa,1778), increasing the number of families in which DUI has been found by two. An update on the taxonomic distribution of DUI in the Bivalvia is also presented. PMID:27994972

  17. Essential oils in food preservation: mode of action, synergies, and interactions with food matrix components

    Directory of Open Access Journals (Sweden)

    Morten eHyldgaard

    2012-01-01

    Full Text Available Essential oils are aromatic and volatile liquids extracted from plants. The chemicals in essential oils are secondary metabolites, which play an important role in plant defence as they often possess antimicrobial properties. The interest in essential oils and their application in food preservation has been amplified in recent years by an increasingly negative consumer perception of synthetic preservatives. Furthermore, food-borne diseases are a growing public health problem worldwide, calling for more effective preservation strategies. The antibacterial properties of essential oils and their constituents have been documented extensively. Pioneering work has also elucidated the mode of action of a few essential oil constituents, but detailed knowledge about most of the compounds' mode of action is still lacking. This knowledge is particularly important to predict their effect on different microorganisms, how they interact with food matrix components, and how they work in combination with other antimicrobial compounds. The main obstacle for using essential oil constituents as food preservatives is that they are most often not potent enough as single components, and they cause negative organoleptic effects when added in sufficient amounts to provide an antimicrobial effect. Exploiting synergies between several compounds has been suggested as a solution to this problem. However, little is known about which interactions lead to synergistic, additive, or antagonistic effects. Such knowledge could contribute to design of new and more potent antimicrobial blends, and to understand the interplay between the constituents of crude essential oils. The purpose of this review is to provide an overview of current knowledge about the antibacterial properties and antibacterial mode of action of essential oils and their constituents, and to identify research avenues that can facilitate implementation of essential oils as natural preservatives in foods.

  18. Essential oils in food preservation: mode of action, synergies, and interactions with food matrix components.

    Science.gov (United States)

    Hyldgaard, Morten; Mygind, Tina; Meyer, Rikke Louise

    2012-01-01

    Essential oils are aromatic and volatile liquids extracted from plants. The chemicals in essential oils are secondary metabolites, which play an important role in plant defense as they often possess antimicrobial properties. The interest in essential oils and their application in food preservation has been amplified in recent years by an increasingly negative consumer perception of synthetic preservatives. Furthermore, food-borne diseases are a growing public health problem worldwide, calling for more effective preservation strategies. The antibacterial properties of essential oils and their constituents have been documented extensively. Pioneering work has also elucidated the mode of action of a few essential oil constituents, but detailed knowledge about most of the compounds' mode of action is still lacking. This knowledge is particularly important to predict their effect on different microorganisms, how they interact with food matrix components, and how they work in combination with other antimicrobial compounds. The main obstacle for using essential oil constituents as food preservatives is that they are most often not potent enough as single components, and they cause negative organoleptic effects when added in sufficient amounts to provide an antimicrobial effect. Exploiting synergies between several compounds has been suggested as a solution to this problem. However, little is known about which interactions lead to synergistic, additive, or antagonistic effects. Such knowledge could contribute to design of new and more potent antimicrobial blends, and to understand the interplay between the constituents of crude essential oils. The purpose of this review is to provide an overview of current knowledge about the antibacterial properties and antibacterial mode of action of essential oils and their constituents, and to identify research avenues that can facilitate implementation of essential oils as natural preservatives in foods.

  19. Cyclic Ketoenols – Acaricides and Insecticides with a Novel Mode of Action

    Directory of Open Access Journals (Sweden)

    Dejan Marčić

    2011-01-01

    Full Text Available Modern crop protection industry puts great efforts into the investigation and development of pesticides (insecticides, acaricides with a novel mode of action, primarily because of increasingly important problem of resistance of pest organisms to pesticides.Resistance of many pest arthropod species (insects and mites to insecticides and/or acaricides became a global phenomenon in the last decades. Therefore, pest management heavily relies on constant introduction of novel active ingredients in use, i.e. onthe alternative use of a number of compounds with different modes of action in order to save the longevity of newly developed products. Among pest arthropods, according to the potential for resistance development and a number of documented cases, spider mites (Acari: Tetranychidae, especially species Tetranychus urticae and Panonychusulmi, as well as certain species of whiteflies and leaf aphids (Homoptra: Aleyrodidae,Aphididae stand out. In 2002, the company Bayer CropScience introduced spirodiclofen, a tetronic acid derivative and the first cyclic ketoenol, acaricide with a wide spectrum and a novel mode of action – inhibition of acetyl-CoA-carboxylase. Soon after, spiromesifen was introduced, also a derivative of tetronic acid, acaricide and insecticide intended for control of phytophagous mites and whiteflies. Spirotetramat, a tetramic acid derivative, and the third member of the ketoenol group, was recently commercialised as an insecticide efficient against whiteflies,leaf aphids and other harmful Homoptera. In this paper are presented the most significant properties of cyclic ketoenols, aiming at pointing to the possibilities and prospects of their use, but also to potential problems and limitations.

  20. Essential Oils in Food Preservation: Mode of Action, Synergies, and Interactions with Food Matrix Components

    Science.gov (United States)

    Hyldgaard, Morten; Mygind, Tina; Meyer, Rikke Louise

    2012-01-01

    Essential oils are aromatic and volatile liquids extracted from plants. The chemicals in essential oils are secondary metabolites, which play an important role in plant defense as they often possess antimicrobial properties. The interest in essential oils and their application in food preservation has been amplified in recent years by an increasingly negative consumer perception of synthetic preservatives. Furthermore, food-borne diseases are a growing public health problem worldwide, calling for more effective preservation strategies. The antibacterial properties of essential oils and their constituents have been documented extensively. Pioneering work has also elucidated the mode of action of a few essential oil constituents, but detailed knowledge about most of the compounds’ mode of action is still lacking. This knowledge is particularly important to predict their effect on different microorganisms, how they interact with food matrix components, and how they work in combination with other antimicrobial compounds. The main obstacle for using essential oil constituents as food preservatives is that they are most often not potent enough as single components, and they cause negative organoleptic effects when added in sufficient amounts to provide an antimicrobial effect. Exploiting synergies between several compounds has been suggested as a solution to this problem. However, little is known about which interactions lead to synergistic, additive, or antagonistic effects. Such knowledge could contribute to design of new and more potent antimicrobial blends, and to understand the interplay between the constituents of crude essential oils. The purpose of this review is to provide an overview of current knowledge about the antibacterial properties and antibacterial mode of action of essential oils and their constituents, and to identify research avenues that can facilitate implementation of essential oils as natural preservatives in foods. PMID:22291693

  1. Meeting Report: Mode(s) of Action of Asbestos and Related Mineral Fibers

    OpenAIRE

    Gwinn, Maureen R.; DeVoney, Danielle; Jarabek, Annie M.; Sonawane, Babasaheb; Wheeler, John; Weissman, David N.; Masten, Scott; Thompson, Claudia

    2011-01-01

    Background: Although asbestos in general is well known to cause a range of neoplastic and non-neoplastic human health effects, not all asbestos fiber types have the same disease-causing potential, and the mode of action (MOA) of specific types of asbestos and related fibers for various health outcomes are not well understood. Objectives: A workshop was held to discuss the state of the science of the MOA for asbestos-related disease. The objective was to review the range of asbestos-induced he...

  2. Mode of action of antimicrobial proteins, pore-forming toxins and biologically active

    Directory of Open Access Journals (Sweden)

    O Schmidt

    2005-07-01

    Full Text Available Antimicrobial peptides and pore-forming toxins are important effectors in innate immune defencereactions. But their mode of action, comprising the insertion into cholesterol-containing membranes isnot known. Here we explore the mechanical implications of pore-formation by extracellular proteinassemblies that drive cellular uptake reactions by leverage-mediated (LM processes, whereoligomeric adhesion molecules bent membrane-receptors around ‘hinge’-like lipophorin particles. Theinteractions of antimicrobial peptides, pore-forming toxins and biologically active proteins with LMassembliesprovide a new paradigm for the configurational specificity and sterical selectivity ofbiologically active peptides.

  3. Search for aflatoxin and trichothecene production inhibitors and analysis of their modes of action.

    Science.gov (United States)

    Sakuda, Shohei; Yoshinari, Tomoya; Furukawa, Tomohiro; Jermnak, Usuma; Takagi, Keiko; Iimura, Kurin; Yamamoto, Toshiyoshi; Suzuki, Michio; Nagasawa, Hiromichi

    2015-01-01

    Mycotoxin contamination of crops is a serious problem throughout the world because of its impact on human and animal health as well as economy. Inhibitors of mycotoxin production are useful not only for developing effective methods to prevent mycotoxin contamination, but also for investigating the molecular mechanisms of secondary metabolite production by fungi. We have been searching for mycotoxin production inhibitors among natural products and investigating their modes of action. In this article, we review aflatoxin and trichothecene production inhibitors, including our works on blasticidin S, methyl syringate, cyclo(L-Ala-L-Pro), respiration inhibitors, and precocene II.

  4. Exposure assessment of the cumulative intake of pesticides with dissimilar mode of action

    DEFF Research Database (Denmark)

    Jensen, Bodil Hamborg; Petersen, Annette; Christiansen, Sofie

    Risk assessment of pesticides is currently based on the no observed adverse effect levels (NOAELs) for effects of single compounds. However, humans might be exposed to a mixture of pesticides at the same time and the exposure could occur from more pesticides with endocrine disrupting effects....... In this study the effects of combined exposure from four endocrine disrupting pesticides have been investigated (procymidone, mancozeb, tebuconazole, and prochloraz). The four pesticides have dissimilar mode of actions. On the background of the potency for each pesticide to a given effect, a relative potency...... factor and the cumulative acute exposure of the pesticides have been estimated....

  5. Evaluation of carcinogenic modes of action for pesticides in fruit on the Swedish market using a text-mining tool

    OpenAIRE

    Silins, Ilona; Korhonen, Anna; Stenius, Ulla

    2014-01-01

    Toxicity caused by chemical mixtures has emerged as a significant challenge for toxicologists and risk assessors. Information on individual chemicals' modes of action is an important part of the hazard identification step. In this study, an automatic text mining-based tool was employed as a method to identify the carcinogenic modes of action of pesticides frequently found in fruit on the Swedish market. The current available scientific literature on the 26 most common pesticides found in appl...

  6. Mode of Action for Natural Products Isolated From Essential Oils of Two Trees Is Different From Available Mosquito Adulticides

    Science.gov (United States)

    2010-01-01

    chemicals currently used in mosquito control. KEY WORDS mode of action, mosquitoes, nookatone, thymoquinone, carvacrol Commercial insecticides used in...food (Tetra Holding, Blacksburg, VA). Pupae produced in a single day were separated from larvae in cohorts of 600 and put into 35- by 35- by 35-cm...ofAedes aegypti, Culex quinquefasciatusSay, andAnopheles quadri- maculatus Say to 19 pesticides with different modes of action. J. Med. Entomol. 45: 82Ð87

  7. A quantitative weight of evidence assessment of confidence in modes-of-action and their human relevance.

    Science.gov (United States)

    Dekant, Wolfgang; Bridges, James; Scialli, Anthony R

    2017-08-22

    A quantitative weight of evidence (QWoE) methodology was developed to assess confidence in postulated mode(s) of action for adverse effects in animal toxicity studies. The QWoE is appropriate for assessing adverse effects as relevant endpoints for classification and labeling purposes. The methodology involves definition of mode of actions and scoring supporting data for all key steps using predefined criteria for quality and relevance/strength of effects. Scores for all key steps are summarized, and the summary score is compared to the maximal achievable score for the mode of action. The ratio of the summary score to the maximal achievable scores gives an indication of confidence in a specific mode of action in animals. The mode of action in animals with highest confidence is then taken forward to assess appropriateness to humans. If one of the key steps cannot occur in humans, the mode of action is not relevant to humans. The methodology developed is applied to four case studies. Copyright © 2017. Published by Elsevier Inc.

  8. Research strategy for developing key information on bromate's mode of action.

    Science.gov (United States)

    Bull, Richard J; Cottruvo, Joseph A

    2006-04-17

    Bromate is produced when ozone is used to treat waters that contain trace amounts of bromide ion. It is also a contaminant of hypochlorite solutions produced by electrolysis of salt that contains bromide. Both ozone and hypochlorite are extensively used to disinfect drinking water, a process that is credited with reducing the incidence of waterborne infections diseases around the world. In studies on experimental animals, bromate has been consistently demonstrated to induce cancer, although there is evidence of substantial species differences in sensitivity (rat>mouse>hamster). There are no data to indicate bromate is carcinogenic in humans. An issue that is critical to the continued use of ozone as a disinfectant for drinking water in bromide-containing waters depends heavily on whether current predictions of carcinogenic risk based on carcinogenic responses in male rats treated with bromate are accurate at the much lower exposure levels of humans. Thiol-dependent oxidative damage to guanine in DNA is a plausible mode of action for bromate-induced cancer. However, other mechanisms may contribute to the response, including the accumulation of alpha2u-globulin in the kidney of the male rat. To provide direction to institutions that have an interest in clarifying the toxicological risks that bromate in drinking water might pose, a workshop funded by the Awwa Research Foundation was convened to lay out a research strategy that, if implemented, could clarify this important public health issue. The technical issues that underlie the deliberations of the workshop are provided in a series of technical papers. The present manuscript summarizes the conclusions of the workgroup with respect to the type and timing of research that should be conducted. The research approach is outlined in four distinct phases that lay out alternative directions as the research plan is implemented. Phase I is designed to quantify pre-systemic degradation, absorption, distribution, and

  9. Understanding the cellular mode of action of vernakalant using a computational model: answers and new questions

    Directory of Open Access Journals (Sweden)

    Loewe Axel

    2015-09-01

    Full Text Available Vernakalant is a new antiarrhythmic agent for the treatment of atrial fibrillation. While it has proven to be effective in a large share of patients in clinical studies, its underlying mode of action is not fully understood. In this work, we aim to link experimental data from the subcellular, tissue, and system level using an in-silico approach. A Hill’s equation-based drug model was extended to cover the frequency dependence of sodium channel block. Two model variants were investigated: M1 based on subcellular data and M2 based on tissue level data. 6 action potential (AP markers were evaluated regarding their dose, frequency and substrate dependence. M1 comprising potassium, sodium, and calcium channel block reproduced the reported prolongation of the refractory period. M2 not including the effects on potassium channels reproduced reported AP morphology changes on the other hand. The experimentally observed increase of ERP accompanied by a shortening of APD90 was not reproduced. Thus, explanations for the drug-induced changes are provided while none of the models can explain the effects in their entirety. These results foster the understanding of vernakalant’s cellular mode of action and point out relevant gaps in our current knowledge to be addressed in future in-silico and experimental research on this aspiring antiarrhythmic agent.

  10. Mode of Action of the Natural Insecticide, Decaleside Involves Sodium Pump Inhibition

    Science.gov (United States)

    Rajashekar, Yallappa; Shivanandappa, Thimmappa

    2017-01-01

    Decalesides are a new class of natural insecticides which are toxic to insects by contact via the tarsal gustatory chemosensilla. The symptoms of their toxicity to insects and the rapid knockdown effect suggest neurotoxic action, but the precise mode of action and the molecular targets for decaleside action are not known. We have presented experimental evidence for the involvement of sodium pump inhibition in the insecticidal action of decaleside in the cockroach and housefly. The knockdown effect of decaleside is concomitant with the in vivo inhibition of Na+, K+ -ATPase in the head and thorax. The lack of insecticidal action by experimental ablation of tarsi or blocking the tarsal sites with paraffin correlated with lack of inhibition of Na+- K+ ATPase in vivo. Maltotriose, a trisaccharide, partially rescued the toxic action of decaleside as well as inhibition of the enzyme, suggesting the possible involvement of gustatory sugar receptors. In vitro studies with crude insect enzyme preparation and purified porcine Na+, K+ -ATPase showed that decaleside competitively inhibited the enzyme involving the ATP binding site. Our study shows that the insecticidal action of decaleside via the tarsal gustatory sites is causally linked to the inhibition of sodium pump which represents a unique mode of action. The precise target(s) for decaleside in the tarsal chemosensilla and the pathway linked to inhibition of sodium pump and the insecticidal action remain to be understood. PMID:28125742

  11. EFFICACY AND MODES OF ACTION OF RESISTANCE INDUCERS ON TWO WHEAT SPECIES AGAINST MYCOSPHAERELLA GRAMINICOLA.

    Science.gov (United States)

    Somai-Jemmali, L; Randoux, B; Siah, A; Ors, M; Halama, P; Reignault, Ph; Hamada, W

    2014-01-01

    Plant resistance inducers could be an alternative to conventional fungicides to control in a more durable and environmentally friendly manner fungal pathogens. Here, we tested the protection efficacy and the modes of action of four resistance inducers (R1, R2, R3 and R4) against the causal agent of Septoria tritici blotch, Mycosphaerella graminicola, the most frequently occurring pathogen on wheat crops worldwide. The four inducers were tested on two wheat cultivars, Premio (a French bread wheat cultivar) and Karim (a Tunisian durum wheat cultivar), each inoculated with a bread-wheat or a durum-wheat adapted isolate; respectively. All inducers exhibited in the greenhouse a significant protection level on both cultivars regarding disease symptoms (necrosis and chlorosis) and sporulation (pycnidium density). The most efficient inducer was R3 which showed 84% symptom reduction, while the less efficient one was R2 with only a 39% reduction. None of the studied inducers showed direct biocide effect against the fungus, except R4 which displayed a significant in planta inhibition of spore germination. Further investigations revealed that all inducers elicited the plant defence enzymes peroxidase and lipoxygenase, but the activity levels varied depending on the considered inducer. In addition, the effect of resistance inducers on the infection process and the fungal cell-wall degrading enzymes xylanases and glucanases was also investigated. Our study allowed us to find out four efficient resistance inducers on wheat against M. graminicola and to establish data about the modes of action of these inducers.

  12. Analysis of genotoxicity and the carcinogenic mode of action for ortho-phenylphenol.

    Science.gov (United States)

    Brusick, David

    2005-06-01

    Ortho-phenylphenol (OPP) and its sodium salt (SOPP) are commercial products that have wide human exposure and have been shown in several studies to be rodent carcinogens. Genetic toxicology data were assessed in an attempt to understand the carcinogenic mode of action of OPP and SOPP. More than 130 studies were evaluated to determine if OPP, SOPP, or any of their enzymatic or nonenzymatic breakdown products react directly with DNA to induce mutation, changes in chromosome structure or number, DNA repair, or nonspecific DNA damage including strand breakage or covalent binding. The genotoxicity databases for OPP and SOPP are not only large but heterogeneous, requiring weight-of-evidence methods to arrive at a conclusion regarding their genotoxic properties and potential. Evidence derived from the available studies leads to the conclusion that study results showing OPP/SOPP directly interacting with DNA are equivocal. Clastogenicity was the most consistent type of genetic toxicity produced by OPP/SOPP (and their break-down products) and was consistently associated with other intracellular preneoplastic toxicity produced at super-threshold concentrations. The weight of evidence from the combined database supports the hypothesis that OPP/SOPP-induced DNA damage is a threshold-dependent response associated with target tissue toxicity, most likely induced by their breakdown products phenylhydroquinone and phenylbenzoquinone. It is possible that this threshold-dependent clastogenicity could contribute to the carcinogenic mode of action for OPP or SOPP.

  13. Synergy and Mode of Action of Ceftazidime plus Quercetin or Luteolin on Streptococcus pyogenes

    Directory of Open Access Journals (Sweden)

    Supatcharee Siriwong

    2015-01-01

    Full Text Available Streptococcus pyogenes causes streptococcal toxic shock syndrome. The recommended therapy has been often failure through the interfering of beta-lactamase-producing bacteria (BLPB. The present study was to investigate antibacterial activity, synergy, and modes of action of luteolin and quercetin using alone and plus ceftazidime against S. pyogenes. The MICs of ceftazidime, luteolin, and quercetin against all S. pyogenes were 0.50, 128, and 128 µg mL−1, respectively. A synergistic effect was exhibited on luteolin and quercetin plus ceftazidime against these strains at fractional inhibitory concentration indices 0.37 and 0.27, respectively, and was confirmed by the viable count. These combinations increased cytoplasmic membrane (CM permeability, caused irregular cell shape, peptidoglycan, and CM damage, and decreased nucleic acid but increased proteins in bacterial cells. Enzyme assay demonstrated that these flavonoids had an inhibitory activity against β-lactamase. In summary, this study provides evidence that the inhibitory mode of action of luteolin and quercetin may be mediated via three mechanisms: (1 inhibiting of peptidoglycan synthesis, (2 increasing CM permeability, and (3 decreasing nucleic acid but increasing the protein contents of bacterial cells. So, luteolin and quercetin propose the high potential to develop adjunct to ceftazidime for the treatment of coexistence of the BLPB and S. pyogenes infections.

  14. Mode of action of lactococcin R produced by Lactococcus lactis R.

    Science.gov (United States)

    Yildirim, Zeliha; Yildirim, Metin; Johnson, Michael G

    2004-04-01

    We investigated the mode of action and factors affecting adsorption of lactoccocin R produced by Lactococcus lactis R. It was found that lactococcin R adsorbed to all Gram-positive but not to the Gram-negative bacteria tested and its adsorption was dependent on pH. It was observed that the binding of lactococcin R was prevented by anions of several salts (Cl-, PO4(-3)) and lipoteichoic acid. Pretreatments of sensitive cells and cell walls with detergents, organic solvents or enzymes did not reduce subsequent binding of lactococcin R. However, treatment of cell wall preparations with methanol:chloroform and hot 20% trichloroacetic acid (TCA) caused such walls to lose their ability to adsorb lactococcin R. Sensitive cells treated with lactococcin R lost high amounts of intracellular K+ ions, UV-absorbing materials and became more permeable to o-nitrophenol-beta-D-glactopyranoside (ONPG). In addition, different lactococcin R concentrations (0-2560 AU/mL) decreased the colony counts of Listeria monocytogenes by 99% and also a reduction in the absorbance values. These results show that the mode of action of lactococcin R is bactericidal rather than bacteriostatic.

  15. Mode of action and functional significance of 7alpha-hydroxypregnenolone stimulating locomotor activity

    Directory of Open Access Journals (Sweden)

    Shogo eHaraguchi

    2011-08-01

    Full Text Available Previous studies over the past two decades have demonstrated that the brain and other nervous systems possess key steroidogenic enzymes and produces pregnenolone and other various neurosteroids in vertebrates in general. Recently, 7alpha-hydroxypregnenolone, a novel bioactive neurosteroid, was identified in the brain of newts and quail. Importantly, this novel neurosteroid is produced from pregnenolone through the enzymatic activity of cytochrome P4507alpha and acts on brain tissue as a neuronal modulator to stimulate locomotor activity in these vertebrates. Subsequently, the mode of action of 7alpha-hydroxypregnenolone was demonstrated. 7alpha-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7alpha-hydroxypregnenolone in the regulation of locomotor activity, diurnal and seasonal changes in 7alpha-hydroxypregnenolone synthesis were further characterized. Melatonin derived from the pineal gland and eyes regulates 7alpha-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7alpha-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7alpha-hydroxypregnenolone mediates corticosterone action to modulate locomotor activity under stress. This review summarizes the current knowledge regarding the mode of action and functional significance of 7alpha-hydroxypregnenolone, a newly identified bioactive neurosteroid stimulating locomotor activity.

  16. Acetylcholinesterase in Biofouling Species: Characterization and Mode of Action of Cyanobacteria-Derived Antifouling Agents.

    Science.gov (United States)

    Almeida, Joana R; Freitas, Micaela; Cruz, Susana; Leão, Pedro N; Vasconcelos, Vitor; Cunha, Isabel

    2015-07-24

    Effective and ecofriendly antifouling (AF) compounds have been arising from naturally produced chemicals. The objective of this study is to use cyanobacteria-derived agents to investigate the role of acetylcholinesterase (AChE) activity as an effect and/or mode of action of promising AF compounds, since AChE inhibitors were found to inhibit invertebrate larval settlement. To pursue this objective, in vitro quantification of AChE activity under the effect of several cyanobacterial strain extracts as potential AF agents was performed along with in vivo AF (anti-settlement) screening tests. Pre-characterization of different cholinesterases (ChEs) forms present in selected tissues of important biofouling species was performed to confirm the predominance of AChE, and an in vitro AF test using pure AChE activity was developed. Eighteen cyanobacteria strains were tested as source of potential AF and AChE inhibitor agents. Results showed effectiveness in selecting promising eco-friendly AF agents, allowing the understanding of the AF biochemical mode of action induced by different compounds. This study also highlights the potential of cyanobacteria as source of AF agents towards invertebrate macrofouling species.

  17. Multiple Modes of Action of the Squamocin in the Midgut Cells of Aedes aegypti Larvae

    Science.gov (United States)

    de Paula, Sérgio Oliveira; Martins, Gustavo Ferreira; Zanuncio, José Cola

    2016-01-01

    Annonaceous acetogenins are botanical compounds with good potential for use as insecticides. In the vector, Aedes aegypti (L.) (Diptera: Culicidae), squamocin (acetogenin) has been reported to be a larvicide and cytotoxic, but the modes of action of this molecule are still poorly understood. This study evaluated the changes in the cell morphology, and in the expression of genes, for autophagy (Atg1 and Atg8), for membrane ion transporter V-ATPase, and for water channel aquaporin-4 (Aqp4) in the midgut of A. aegypti larvae exposed to squamocin from Annona mucosa Jacq. (Annonaceae). Squamocin showed cytotoxic action with changes in the midgut epithelium and digestive cells of A. aegypti larvae, increase in the expression for autophagy gene Atg1 and Atg8, decrease in the expression of V-ATPase, decrease in the expression of Aqp4 gene in LC20 and inhibition of Apq4 genes in the midgut of this vector in LC50. These multiple modes of action for squamocin are described for the first time in insects, and they are important because different sites of action of squamocin from A. mucosa may reduce the possibility of resistance of A. aegypti to this molecule. PMID:27532504

  18. Mode of Action of Lactoperoxidase as Related to Its Antimicrobial Activity: A Review

    Directory of Open Access Journals (Sweden)

    F. Bafort

    2014-01-01

    Full Text Available Lactoperoxidase is a member of the family of the mammalian heme peroxidases which have a broad spectrum of activity. Their best known effect is their antimicrobial activity that arouses much interest in in vivo and in vitro applications. In this context, the proper use of lactoperoxidase needs a good understanding of its mode of action, of the factors that favor or limit its activity, and of the features and properties of the active molecules. The first part of this review describes briefly the classification of mammalian peroxidases and their role in the human immune system and in host cell damage. The second part summarizes present knowledge on the mode of action of lactoperoxidase, with special focus on the characteristics to be taken into account for in vitro or in vivo antimicrobial use. The last part looks upon the characteristics of the active molecule produced by lactoperoxidase in the presence of thiocyanate and/or iodide with implication(s on its antimicrobial activity.

  19. Membrane Active Peptides: Modes-of-Action, Phase Transitions, and Supramolecular Assemblies

    Science.gov (United States)

    Huang, Huey W.

    1997-03-01

    Recent discoveries showed that 20-40 amino-acid peptides are used as very effective antimicrobials in the host-defense systems throughout the animal kingdom, including human. What distinguishes these peptide antimicrobials from the conventional antibiotics is that they attack the lipid matrix of the cytoplasmic membranes rather than protein targets. So the central questions are what are their modes-of-action and how do their distinguish the bacterial cell membranes from the host-cell membranes? Many of these peptides have very simple structures--they are helices with amphiphilic side chains. Despite such simplicities, their interactions with membranes are complex and interesting. The talk will discuss the optical, x-ray and neutron techniques for studying such systems and the experimental as well as theoretical results. The mode-of-action is a phase transition controlled by the concentration of the peptide bound to the membrane. The specificities with respect to membranes are achieved by having different critical concentrations for different lipid composistions of the membrane.

  20. Probiotics as beneficial microbes in aquaculture: an update on their multiple modes of action: a review.

    Science.gov (United States)

    Zorriehzahra, Mohammad Jalil; Delshad, Somayeh Torabi; Adel, Milad; Tiwari, Ruchi; Karthik, K; Dhama, Kuldeep; Lazado, Carlo C

    2016-12-01

    Wide and discriminate use of antibiotics has resulted in serious biological and ecological concerns, especially the emergence of antibiotic resistance. Probiotics, known as beneficial microbes, are being proposed as an effective and eco-friendly alternative to antibiotics. They were first applied in aquaculture species more than three decades ago, but considerable attention had been given only in the early 2000s. Probiotics are defined as live or dead, or even a component of the microorganisms that act under different modes of action in conferring beneficial effects to the host or to its environment. Several probiotics have been characterized and applied in fish and a number of them are of host origin. Unlike some disease control alternatives being adapted and proposed in aquaculture where actions are unilateral, the immense potential of probiotics lies on their multiple mechanisms in conferring benefits to the host fish and the rearing environment. The staggering number of probiotics papers in aquaculture highlights the multitude of advantages from these microorganisms and conspicuously position them in the dynamic search for health-promoting alternatives for cultured fish. This paper provides an update on the use of probiotics in finfish aquaculture, particularly focusing on their modes of action. It explores the contemporary understanding of their spatial and nutritional competitiveness, inhibitory metabolites, environmental modification capability, immunomodulatory potential and stress-alleviating mechanism. This timely update affirms the importance of probiotics in fostering sustainable approaches in aquaculture and provides avenues in furthering its research and development.

  1. A Comprehensive Survey of Pelagic Megafauna: Their Distribution, Densities, and Taxonomic Richness in the Tropical Southwest Indian Ocean

    Directory of Open Access Journals (Sweden)

    Sophie Laran

    2017-05-01

    Full Text Available The distribution and density of pelagic megafauna (marine mammals, seabirds, elasmobranches, and sea turtles are important indicators of marine biodiversity, reflecting the condition of the underlying ecosystems. A dedicated aerial survey was conducted in the tropical Southwest Indian Ocean to map their distribution, the taxonomic diversity, and to estimate their densities to serve as a baseline for the area. This large survey across three ecological sub-regions revealed contrasting spatial distributions: maps of taxonomic richness of marine mammals and seabirds revealed different “hotspots” in the area. Densities were estimated for eight cetacean taxa with small and large Delphininae, or small Globicephalinae dominating, and for seven seabird taxa, with terns and noddies dominating. At the community level, the Southwest Indian Ocean megafauna was structured by the marine environment with strong differences between the Mozambique Channel and the Mascarene Islands, or between shelf and slope/oceanic habitats. Our results illustrate how multi-taxa aerial surveys are relevant and cost-effective monitoring tools for marine megafauna, allowing a community-wide approach.

  2. Heteroploid reticulate evolution and taxonomic status of an endemic species with bicentric geographical distribution.

    Science.gov (United States)

    Uwe Nierbauer, Kai; Paule, Juraj; Zizka, Georg

    2017-01-24

    Reticulate evolution is considered to be among the main mechanisms of plant evolution, often leading to the establishment of new species. However, complex evolutionary scenarios result in a challenging definition of evolutionary and taxonomic units. In the present study, we aimed to examine the evolutionary origin and revise the species status of Campanula baumgartenii, a rare endemic species from the polyploid complex Campanula section Heterophylla. Morphometry, flow cytometric ploidy estimation, AFLPs, as well as chloroplast and nuclear DNA sequence markers were used to assess the morphological and genetic differentiation among C. baumgartenii, C. rotundifolia and other closely related taxa. Tetra- and hexaploid C. baumgartenii is morphologically and molecularly (AFLP) differentiated from sympatric C. rotundifolia. Contrasting signals from nuclear (ITS) and chloroplast (trnL-rpl32) markers suggest a hybrid origin of C. baumgartenii with C. rotundifolia and a taxon related to the alpine C. scheuchzeri as ancestors. Additionally, hexaploid C. baumgartenii currently hybridizes with co-occurring tetraploid C. rotundifolia resulting in pentaploid hybrids, for which C. baumgartenii serves as both seed and pollen donor. Based on the molecular and morphological differentiation, we propose to keep C. baumgartenii as a separate species. This study exemplifies that detailed population genetic studies can provide a solid basis for taxonomic delimitation within Campanula section Heterophylla as well as for sound identification of conservation targets.

  3. Plant endemics to Sierra de Gredos (central Spain: taxonomic, distributional, and evolutionary aspects

    Directory of Open Access Journals (Sweden)

    García, Bernardo

    2008-12-01

    Full Text Available Causes related to a low number of endemics to Sierra de Gredos (central Iberian Peninsula are poorly understood. Taxonomic, distributional and genetic aspects of the 12 endemic taxa (species and subspecies are herein discussed. New populations found in the last years provide new chorological reports and taxa to science. As a result, we extend the distribution range of Pseudomisopates rivas-martinezii and describe a new subspecies (Teucrium oxylepis subsp. Gredense. Genetic variation was investigated by sequencing the ITS (Internal Transcribed Sequence region, which is a widespread nuclear DNA region used to detect significant sequence divergence at the species and population levels. At the species level, only eight endemics to this large mountain range (c. 4,800 km2 indicates both limited speciation events coupled with their persistence, despite the high species richness of the flora of Sierra de Gredos (>2,500. According to the levels of ITS sequence divergence, significant isolation processes may have predated the Quaternary in Sierra de Gredos to account for divergence of the monotypic genus Pseudomisopates from its closest relatives (Misopates, Acanthorrhinum. Isolation of the other seven endemic species from their closest relatives has been a more recent process, as revealed by the limited ITS sequence variation obtained in this study. At the population level, no net nucleotide substitutions were observed between distant populations of the endemic species: Antirrhinum grosii, Astragalus devesae, Centaurea avilae, Dianthus gredensis, Echinospartum barnadesii, Pseudomisopates rivas-martinezii, Santolina oblongifolia. In contrast, the three populations of Sedum lagascae displayed a relatively high number (4 of nucleotide substitutions. These results, together with limited morphological differentiation, may reflect insufficient population isolation of seven of the eight endemic species of Sierra de Gredos in the Quaternary. Recurrent population

  4. Reconsidering the nature and mode of action of metabolite retrograde signals from the chloroplast

    Directory of Open Access Journals (Sweden)

    Gonzalo Martín Estavillo

    2013-01-01

    Full Text Available Plant organelles produce retrograde signals to alter nuclear gene expression in order to coordinate their biogenesis, maintain homeostasis or optimize their performance under adverse conditions. Many signals of different chemical nature have been described in the past decades, including chlorophyll intermediates, reactive oxygen species and adenosine derivatives. While the effects of retrograde signalling on gene expression are well understood, the initiation and transport of the signals and their mode of action have either not been resolved, or are a matter of speculation. Moreover, retrograde signalling should be consider as part of a broader cellular network, instead of as separate pathways, required to adjust to changing physiologically relevant conditions. Here we summarize current plastid retrograde signalling models in plants, with a focus on new signalling pathways, SAL1-PAP, MEcPP and β- cyclocitral, and outline missing links or future areas of research that we believe need to be addressed to have a better understanding of plant intracellular signalling networks.

  5. Sulfoxaflor and the sulfoximine insecticides: chemistry, mode of action and basis for efficacy on resistant insects.

    Science.gov (United States)

    Sparks, Thomas C; Watson, Gerald B; Loso, Michael R; Geng, Chaoxian; Babcock, Jon M; Thomas, James D

    2013-09-01

    The sulfoximines, as exemplified by sulfoxaflor ([N-[methyloxido[1-[6-(trifluoromethyl)-3-pyridinyl]ethyl]-λ(4)-sulfanylidene] cyanamide] represent a new class of insecticides. Sulfoxaflor exhibits a high degree of efficacy against a wide range of sap-feeding insects, including those resistant to neonicotinoids and other insecticides. Sulfoxaflor is an agonist at insect nicotinic acetylcholine receptors (nAChRs) and functions in a manner distinct from other insecticides acting at nAChRs. The sulfoximines also exhibit structure activity relationships (SAR) that are different from other nAChR agonists such as the neonicotinoids. This review summarizes the sulfoximine SAR, mode of action and the biochemistry underlying the observed efficacy on resistant insect pests, with a particular focus on sulfoxaflor.

  6. Dual mode of action of Bt proteins: protoxin efficacy against resistant insects.

    Science.gov (United States)

    Tabashnik, Bruce E; Zhang, Min; Fabrick, Jeffrey A; Wu, Yidong; Gao, Meijing; Huang, Fangneng; Wei, Jizhen; Zhang, Jie; Yelich, Alexander; Unnithan, Gopalan C; Bravo, Alejandra; Soberón, Mario; Carrière, Yves; Li, Xianchun

    2015-10-12

    Transgenic crops that produce Bacillus thuringiensis (Bt) proteins for pest control are grown extensively, but insect adaptation can reduce their effectiveness. Established mode of action models assert that Bt proteins Cry1Ab and Cry1Ac are produced as inactive protoxins that require conversion to a smaller activated form to exert toxicity. However, contrary to this widely accepted paradigm, we report evidence from seven resistant strains of three major crop pests showing that Cry1Ab and Cry1Ac protoxins were generally more potent than the corresponding activated toxins. Moreover, resistance was higher to activated toxins than protoxins in eight of nine cases evaluated in this study. These data and previously reported results support a new model in which protoxins and activated toxins kill insects via different pathways. Recognizing that protoxins can be more potent than activated toxins against resistant insects may help to enhance and sustain the efficacy of transgenic Bt crops.

  7. Modes of action of fraxinellone against the tobacco budworm,Heliothis virescens

    Institute of Scientific and Technical Information of China (English)

    Zhi Long Liu; Shuit Hung Ho; Swee Hock Goh

    2009-01-01

    Fraxinellone significantly reduced the relative growth rate, food consumption rate as well as the efficiency of conversion of ingested food into biomass of Heliothis virescens when incorporated into artificial diets at concentrations of 4.31 × 10-5 mol/L and above. After being fed with fraxinellone-treated diets for 24 h, the larval midguts of H. virescens possess significantly lower activities of a-amylase and non-specific proteases and higher activities ofcytochrome P450s. In vitro, the compound did not inhibit the activities of α-amylase and non-specific proteases extracted from the larval midguts. Clear evidence of post-ingestive toxicity of fraxinellone to midgut cells was observed under an electron microscope. The modes of action of the compound against insects were discussed.

  8. Probiotics as beneficial microbes in aquaculture: an update on their multiple modes of action: a review

    DEFF Research Database (Denmark)

    Zorriehzahra, Mohammad Jalil; Delshad, Somayeh Torabi; Adel, Milad

    2016-01-01

    Wide and discriminate use of antibiotics has resulted in serious biological and ecological concerns, especially the emergence of antibiotic resistance. Probiotics, known as beneficial microbes, are being proposed as an effective and eco-friendly alternative to antibiotics. They were first applied...... in aquaculture species more than three decades ago, but considerable attention had been given only in the early 2000s. Probiotics are defined as live or dead, or even a component of the microorganisms that act under different modes of action in conferring beneficial effects to the host or to its environment....... Several probiotics have been characterized and applied in fish and a number of them are of host origin. Unlike some disease control alternatives being adapted and proposed in aquaculture where actions are unilateral, the immense potential of probiotics lies on their multiple mechanisms in conferring...

  9. Antibiotic resistance modulation and modes of action of (--α-pinene in Campylobacter jejuni.

    Directory of Open Access Journals (Sweden)

    Jasna Kovač

    Full Text Available The aim of the study was to investigate the mode of action of (--α-pinene in terms of its modulation of antibiotic resistance in Campylobacter jejuni. Broth microdilution and ethidium bromide accumulation assays were used to evaluate the (--α-pinene antimicrobial activity, modulation of antimicrobial resistance, and inhibition of antimicrobial efflux. The target antimicrobial efflux systems were identified using an insertion mutagenesis approach, and C. jejuni adaptation to (--α-pinene was evaluated using DNA microarrays. Knock-out mutants of the key up-regulated transcriptional regulators hspR and hrcA were constructed to investigate their roles in C. jejuni adaptation to several stress factors, including osmolytes, and pH, using Biolog phenotypical microarrays. Our data demonstrate that (--α-pinene efficiently modulates antibiotic resistance in C. jejuni by decreasing the minimum inhibitory concentrations of ciprofloxacin, erythromycin and triclosan by up to 512-fold. Furthermore, (--α-pinene promotes increased expression of cmeABC and another putative antimicrobial efflux gene, Cj1687. The ethidium bromide accumulation was greater in the wild-type strain than in the antimicrobial efflux mutant strains, which indicates that these antimicrobial efflux systems are a target of action of (--α-pinene. Additionally, (--α-pinene decreases membrane integrity, which suggests that enhanced microbial influx is a secondary mode of action of (--α-pinene. Transcriptomic analysis indicated that (--α-pinene disrupts multiple metabolic pathways, and particularly those involved in heat-shock responses. Thus, (--α-pinene has significant activity in the modulation of antibiotic resistance in C. jejuni, which appears to be mediated by multiple mechanisms that include inhibition of microbial efflux, decreased membrane integrity, and metabolic disruption. These data warrant further studies on (--α-pinene to develop its use in the control of antibiotic

  10. Nanovesicle encapsulation of antimicrobial peptide P34: physicochemical characterization and mode of action on Listeria monocytogenes

    Science.gov (United States)

    da Silva Malheiros, Patrícia; Sant'Anna, Voltaire; Micheletto, Yasmine Miguel Serafini; da Silveira, Nadya Pesce; Brandelli, Adriano

    2011-08-01

    Antimicrobial peptide P34, a substance showing antibacterial activity against pathogenic and food spoilage bacteria, was encapsulated in liposomes prepared from partially purified soybean phosphatidylcholine, and their physicochemical characteristics were evaluated. The antimicrobial activity was estimated by agar diffusion assay using Listeria monocytogenes ATCC 7644 as indicator strain. A concentration of 3,200 AU/mL of P34 was encapsulated in nanovesicles and stocked at 4 °C. No significant difference ( p > 0.05) in the biological activity of free and encapsulated P34 was observed through 24 days. Size and PDI of liposomes, investigated by light scattering analysis, were on average 150 nm and 0.22 respectively. Zeta potential was -27.42 mV. There was no significant change ( p > 0.05) in the physicochemical properties of liposomes during the time of evaluation. The liposomes presented closed spherical morphology as visualized by transmission electron microscopy (TEM). The mode of action of liposome-encapsulated P34 under L. monocytogenes cells was investigated by TEM. Liposomes appeared to adhere but not fuse with the bacterial cell wall, suggesting that the antimicrobial is released from nanovesicles to act against the microorganism. The effect of free and encapsulated P34 was tested against L. monocytogenes, showing that free bacteriocin inhibited the pathogen more quickly than the encapsulated P34. Liposomes prepared with low-cost lipid showed high encapsulation efficiency for a new antimicrobial peptide and were stable during storage. The mode of action against the pathogen L. monocytogenes was characterized.

  11. Effectiveness and mode of action of whitening dentifrices on enamel extrinsic stains.

    Science.gov (United States)

    Alshara, Salem; Lippert, Frank; Eckert, George J; Hara, Anderson T

    2014-01-01

    This study was conducted in order to investigate the mode of action and the whitening effect of whitening dentifrices. Two hundred fifty-six bovine enamel specimens (10 × 10 mm(2)) were prepared, partially stained, and assigned into eight groups (n = 32): six whitening dentifrices, one nonwhitening and deionized water (negative control), and further divided in two subgroups (n = 16), according to the test model: chemical (dentifrice slurry treatment only) or chemo-mechanical (slurry + toothbrushing). Specimens were treated with dentifrice slurries 2 ×/day for 1 min and toothbrushed or not, according to each model. In between dentifrice treatments, specimens were artificially stained for 5 h. This protocol was repeated for 5 days and enamel color changes (∆E) were measured after each day (days 1-5). The abrasive level of the dentifrices was determined following the ISO11609 guidelines. In the chemo-mechanical model, the whitening action of all dentifrices was observed after day 1, being higher than the negative control group (p 0.05). Differences on ∆E among dentifrices were observed, and they seemed to correlate well with their abrasive level (r(2) = 0.80). In the chemical model, no significant differences were observed among groups (p > 0.05), with ∆E remaining constant throughout the study. Higher ∆E values were observed in the chemo-mechanical model compared to the chemical (p dentifrices were effective in whitening stained enamel and their mode of action showed to be mainly mechanical (toothbrushing abrasion). The abrasive level of dentifrices seems to determine its whitening effectiveness.

  12. EEG alpha activity reflects motor preparation rather than the mode of action selection.

    Science.gov (United States)

    Deiber, Marie-Pierre; Sallard, Etienne; Ludwig, Catherine; Ghezzi, Catherine; Barral, Jérôme; Ibañez, Vicente

    2012-01-01

    Alpha-band activity (8-13 Hz) is not only suppressed by sensory stimulation and movements, but also modulated by attention, working memory and mental tasks, and could be sensitive to higher motor control functions. The aim of the present study was to examine alpha oscillatory activity during the preparation of simple left or right finger movements, contrasting the external and internal mode of action selection. Three preparation conditions were examined using a precueing paradigm with S1 as the preparatory and S2 as the imperative cue: Full, laterality instructed by S1; Free, laterality freely selected and None, laterality instructed by S2. Time-frequency (TF) analysis was performed in the alpha frequency range during the S1-S2 interval, and alpha motor-related amplitude asymmetries (MRAA) were also calculated. The significant MRAA during the Full and Free conditions indicated effective external and internal motor response preparation. In the absence of specific motor preparation (None), a posterior alpha event-related desynchronization (ERD) dominated, reflecting the main engagement of attentional resources. In Full and Free motor preparation, posterior alpha ERD was accompanied by a midparietal alpha event-related synchronization (ERS), suggesting a concomitant inhibition of task-irrelevant visual activity. In both Full and Free motor preparation, analysis of alpha power according to MRAA amplitude revealed two types of functional activation patterns: (1) a motor alpha pattern, with predominantly midparietal alpha ERS and large MRAA corresponding to lateralized motor activation/visual inhibition and (2) an attentional alpha pattern, with dominating right posterior alpha ERD and small MRAA reflecting visuospatial attention. The present results suggest that alpha oscillatory patterns do not resolve the selection mode of action, but rather distinguish separate functional strategies of motor preparation.

  13. Unraveling the antibacterial mode of action of a clay from the Colombian Amazon.

    Science.gov (United States)

    Londono, Sandra Carolina; Williams, Lynda B

    2016-04-01

    Natural antibacterial clays can inhibit growth of human pathogens; therefore, understanding the antibacterial mode of action may lead to new applications for health. The antibacterial modes of action have shown differences based on mineralogical constraints. Here we investigate a natural clay from the Colombian Amazon (AMZ) known to the Uitoto natives as a healing clay. The physical and chemical properties of the AMZ clay were compared to standard reference materials: smectite (SWy-1) and kaolinite (API #5) that represent the major minerals in AMZ. We tested model Gram-negative (Escherichia coli ATCC #25922) and Gram-positive (Bacillus subtilis ATCC #6633) bacteria to assess the clay's antibacterial effectiveness against different bacterial types. The chemical and physical changes in the microbes were examined using bioimaging and mass spectrometry of clay digests and aqueous leachates. Results indicate that a single dose of AMZ clay (250 mg/mL) induced a 4-6 order of magnitude reduction in cell viability, unlike the reference clays that did not impact bacterial survival. AMZ clay possesses a relatively high specific surface area (51.23 m(2)/g) and much higher total surface area (278.82 m(2)/g) than the reference clays. In aqueous suspensions (50 mg clay/mL water), soluble metals are released and the minerals buffer fluid pH between 4.1 and 4.5. We propose that the clay facilitates chemical interactions detrimental to bacteria by absorbing nutrients (e.g., Mg, P) and potentially supplying metals (e.g., Al) toxic to bacteria. This study demonstrates that native traditional knowledge can direct scientific studies.

  14. EEG alpha activity reflects motor preparation rather than the mode of action selection

    Directory of Open Access Journals (Sweden)

    Marie-Pierre eDeiber

    2012-08-01

    Full Text Available Alpha-band activity (8-13 Hz is suppressed by sensory stimulation and movements, modulated by attention, working memory and mental tasks and may be sensitive to higher motor control functions. The aim of the present study was to examine alpha oscillatory activity during the preparation of simple left or right finger movements, contrasting the external and internal mode of action selection. Three preparation conditions were examined using a precueing paradigm with S1 as the preparatory and S2 as the imperative cue: Full, laterality instructed by S1; Free, laterality freely selected and None, laterality instructed by S2. Time-frequency analysis was performed in the alpha frequency range during the S1-S2 interval, and alpha motor-related amplitude asymmetries (MRAA were also calculated. The significant MRAA during the Full and Free conditions indicated effective external and internal motor response preparation. In the absence of specific motor preparation (None, a posterior alpha power decrease (event-related desynchronization, ERD dominated, reflecting the main engagement of attentional resources. In Full and Free motor preparation, posterior alpha ERD was accompanied by a midparietal alpha power increase (event-related synchronization, ERS, suggesting a concomitant inhibition of task-irrelevant visual activity. In both Full and Free motor preparation, analysis of alpha power according to MRAA amplitude revealed two types of functional activation patterns: 1 a motor alpha pattern, with predominantly midparietal alpha ERS and large MRAA corresponding to lateralized motor activation/visual inhibition and 2 an attentional alpha pattern, with dominating right posterior alpha ERD and small MRAA reflecting visuospatial attention. The present results suggest that alpha oscillatory patterns do not resolve the selection mode of action, but rather distinguish separate functional strategies of motor preparation. 

  15. Evaluation of carcinogenic modes of action for pesticides in fruit on the Swedish market using a text-mining tool.

    Science.gov (United States)

    Silins, Ilona; Korhonen, Anna; Stenius, Ulla

    2014-01-01

    Toxicity caused by chemical mixtures has emerged as a significant challenge for toxicologists and risk assessors. Information on individual chemicals' modes of action is an important part of the hazard identification step. In this study, an automatic text mining-based tool was employed as a method to identify the carcinogenic modes of action of pesticides frequently found in fruit on the Swedish market. The current available scientific literature on the 26 most common pesticides found in apples and oranges was evaluated. The literature was classified according to a taxonomy that specifies the main type of scientific evidence used for determining carcinogenic properties of chemicals. The publication profiles of many pesticides were similar, containing evidence for both genotoxic and non-genotoxic modes of action, including effects such as oxidative stress, chromosomal changes and cell proliferation. We also found that 18 of the 26 pesticides studied here had previously caused tumors in at least one animal species, findings which support the mode of action data. This study shows how a text-mining tool could be used to identify carcinogenic modes of action for a group of chemicals in large quantities of text. This strategy could support the risk assessment process of chemical mixtures.

  16. Evaluation of carcinogenic modes of action for pesticides in fruit on the Swedish market using a text-mining tool

    Directory of Open Access Journals (Sweden)

    Ilona eSilins

    2014-06-01

    Full Text Available Toxicity caused by chemical mixtures has emerged as a significant challenge for toxicologists and risk assessors. Information on individual chemicals’ modes of action is an important part of the hazard identification step. In this study, an automatic text mining-based tool was employed as a method to identify the carcinogenic modes of action of pesticides frequently found in fruit on the Swedish market. The current available scientific literature on the 26 most common pesticides found in apples and oranges was evaluated. The literature was classified according to a taxonomy that specifies the main type of scientific evidence used for determining carcinogenic properties of chemicals. The publication profiles of many pesticides were similar, containing evidence for both genotoxic and non-genotoxic modes of action, including effects such as oxidative stress, chromosomal changes and cell proliferation. We also found that 18 of the 26 pesticides studied here had previously caused tumors in at least one animal species, findings which support the mode of action data. This study demonstrates how a text-mining tool could be used to identify carcinogenic modes of action for a group of chemicals in large quantities of text. The strategy could support the risk assessment process of chemical mixtures.

  17. Relating belowground microbial composition to the taxonomic, phylogenetic, and functional trait distributions of trees in a tropical forest.

    Science.gov (United States)

    Barberán, Albert; McGuire, Krista L; Wolf, Jeffrey A; Jones, F Andrew; Wright, Stuart Joseph; Turner, Benjamin L; Essene, Adam; Hubbell, Stephen P; Faircloth, Brant C; Fierer, Noah

    2015-12-01

    The complexities of the relationships between plant and soil microbial communities remain unresolved. We determined the associations between plant aboveground and belowground (root) distributions and the communities of soil fungi and bacteria found across a diverse tropical forest plot. Soil microbial community composition was correlated with the taxonomic and phylogenetic structure of the aboveground plant assemblages even after controlling for differences in soil characteristics, but these relationships were stronger for fungi than for bacteria. In contrast to expectations, the species composition of roots in our soil core samples was a poor predictor of microbial community composition perhaps due to the patchy, ephemeral, and highly overlapping nature of fine root distributions. Our ability to predict soil microbial composition was not improved by incorporating information on plant functional traits suggesting that the most commonly measured plant traits are not particularly useful for predicting the plot-level variability in belowground microbial communities.

  18. Mode of action of a family 75 chitosanase from Streptomyces avermitilis.

    Science.gov (United States)

    Heggset, Ellinor B; Tuveng, Tina R; Hoell, Ingunn A; Liu, Zhanliang; Eijsink, Vincent G H; Vårum, Kjell M

    2012-06-11

    Chitooligosaccharides (CHOS) are oligomers composed of glucosamine and N-acetylglucosamine with several interesting bioactivities that can be produced from enzymatic cleavage of chitosans. By controlling the degree of acetylation of the substrate chitosan, the enzyme, and the extent of enzyme degradation, CHOS preparations with limited variation in length and sequence can be produced. We here report on the degradation of chitosans with a novel family 75 chitosanase, SaCsn75A from Streptomyces avermitilis . By characterizing the CHOS preparations, we have obtained insight into the mode of action and subsite specificities of the enzyme. The degradation of a fully deacetylated and a 31% acetylated chitosan revealed that the enzyme degrade these substrates according to a nonprocessive, endo mode of action. With the 31% acetylated chitosan as substrate, the kinetics of the degradation showed an initial rapid phase, followed by a second slower phase. In the initial faster phase, an acetylated unit (A) is productively bound in subsite -1, whereas deacetylated units (D) are bound in the -2 subsite and the +1 subsite. In the slower second phase, D-units bind productively in the -1 subsite, probably with both acetylated and deacetylated units in the -2 subsite, but still with an absolute preference for deacetylated units in the +1 subsite. CHOS produced in the initial phase are composed of deacetylated units with an acetylated reducing end. In the slower second phase, higher amounts of low DP fully deacetylated oligomers (dimer and trimer) are produced, while the higher DP oligomers are dominated by compounds with acetylated reducing ends containing increasing amounts of internal acetylated units. The degradation of chitosans with varying degrees of acetylation to maximum extents of degradation showed that increasingly longer oligomers are produced with increasing degree of acetylation, and that the longer oligomers contain sequences of consecutive acetylated units

  19. IDENTIFICATION AND MODE OF ACTION OF ANTIBACTERIAL COMPONENTS FROM MELASTOMA MALABATHRICUM LINN LEAVES

    Directory of Open Access Journals (Sweden)

    Mourouge Saadi Alwash

    2013-01-01

    Full Text Available The present study aimed to assess the antibacterial activity of the methanol extract of Melastoma Malabathricum Leaves (MMML, active fraction of M. Malabathricum Leaves (ML5 and isolated kaempferol-3-O-(2",6"-di-O-p-trans-coumaroyl-β-glucopyranoside (Kf and to describe the preliminary mode of action against Gram-positive and Gram-negative bacteria. The MMML extract was fractionated by Vacuum Liquid Chromatography (VLC to afford M. malabathricum Leaves fractions (ML1-ML6 of increasing polarities. Bioassay-guided fractionation (direct-TLC bioautography revealed that fraction of M. Malabathricum Leaves (ML5 had the highest antibacterial activity. Therefore, the ML5 was further subjected to Column Chromatography (CC to afford Kaempferol-3-O-(2",6"-di-O-p-trans-coumaroyl-β-glucopyranoside (Kf. The compound structure was elucidated using data obtained from 1H NMR and 13C NMR spectra. Antibacterial activity of MMML, ML5 and bioactive constituents Kf against Staphylococcus aureus reference strain, Methicillin-Resistant S. aureus reference strain (MRSA, 11 clinical MRSA isolates, 3 clinical Pseudomonas aeruginosa isolates and P. aeruginosa reference strain was evaluated through disk diffusion method and Minimum Inhibitory Concentration (MIC. The time kill assay and field emission scanning electron microscopy was used to determine the preliminary mode of action. The data obtained from disk diffusion method and MIC showed that the MMML, ML5 and Kf showed antibacterial activity against all test bacteria with various values. Generally, the ML5 and Kf exhibited the highest antibacterial activity with the largest zones of inhibition and lowest MIC values against S. aureus and all tested MRSA. The MMML exerted the strongest killing effect against all tested bacteria while the overall performance of ML5 and Kf were significantly more effective against S. aureus and MRSA than P. aeruginosa. Field emission scanning electron microscopy revealed irregular

  20. Phylogenetic distribution of extracellular guanyl-preferring ribonucleases renews taxonomic status of two Bacillus strains.

    Science.gov (United States)

    Ulyanova, Vera; Shah Mahmud, Raihan; Dudkina, Elena; Vershinina, Valentina; Domann, Eugen; Ilinskaya, Olga

    2016-09-12

    The potential of microbial ribonucleases as promising antitumor and antiviral agents, determines today's directions of their study. One direction is connected with biodiversity of RNases. We have analyzed completed and drafted Bacillus genomes deposited in GenBank for the presence of coding regions similar to the gene of an extracellular guanyl-preferring RNase of Bacillus amyloliquefaciens (barnase). Orthologues of the barnase gene were detected in 9 species out of 83. All of these belong to "B. subtilis" group within the genus. B. subtilis itself, as well as some other species within this group, lack such types of RNases. RNases similar to barnase were also found in species of "B. cereus" group as a part of plasmid-encoded S-layer toxins. It was also found that taxonomic states of culture collection strains, which were initially described based on a limited set of phenotypic characteristics, can be misleading and need to be confirmed. Using several approaches such as matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), sequencing of genes for 16S ribosomal RNA and RNA polymerase subunit beta followed by reconstruction of phylogenetic trees, we have re-identified two RNase-secreting Bacillus strains: B. thuringiensis B-388 which should be assigned as B. altitudinis B388 and B. intermedius 7P which should be renamed as B. pumilus 7P. Therefore, small secreted guanyl-preferring RNases are the feature of "B. subtilis" group only, which is characterized by distinctive lifestyle and adaptation strategies to environment.

  1. Taxonomic distribution of defensive alkaloids in Nearctic oribatid mites (Acari, Oribatida).

    Science.gov (United States)

    Saporito, Ralph A; Norton, Roy A; Garraffo, Martin H; Spande, Thomas F

    2015-11-01

    The opisthonotal (oil) glands of oribatid mites are the source of a wide diversity of taxon-specific defensive chemicals, and are likely the location for the more than 90 alkaloids recently identified in oribatids. Although originally recognized in temperate oribatid species, alkaloids have also been detected in related lineages of tropical oribatids. Many of these alkaloids are also present in a worldwide radiation of poison frogs, which are known to sequester these defensive chemicals from dietary arthropods, including oribatid mites. To date, most alkaloid records involve members of the superfamily Oripodoidea (Brachypylina), although few species have been examined and sampling of other taxonomic groups has been highly limited. Herein, we examined adults of more than 60 species of Nearctic oribatid mites, representing 46 genera and 33 families, for the presence of alkaloids. GC-MS analyses of whole body extracts led to the detection of 15 alkaloids, but collectively they occur only in members of the genera Scheloribates (Scheloribatidae) and Protokalumma (Parakalummidae). Most of these alkaloids have also been detected previously in the skin of poison frogs. All examined members of the oripodoid families Haplozetidae and Oribatulidae were alkaloid-free, and no mites outside the Oripodoidea contained alkaloids. Including previous studies, all sampled species of the cosmopolitan oripodoid families Scheloribatidae and Parakalummidae, and the related, mostly tropical families Mochlozetidae and Drymobatidae contain alkaloids. Our findings are consistent with a generalization that alkaloid presence is widespread, but not universal in Oripodoidea. Alkaloid presence in tropical, but not temperate members of some non-oripodoid taxa (in particular Galumnidae) deserves further study.

  2. Fluensulfone is a nematicide with a mode of action distinct from anticholinesterases and macrocyclic lactones.

    Science.gov (United States)

    Kearn, James; Ludlow, Elizabeth; Dillon, James; O'Connor, Vincent; Holden-Dye, Lindy

    2014-02-01

    Plant parasitic nematodes infest crops and present a threat to food security worldwide. Currently available chemical controls e.g. methyl bromide, organophosphates and carbamates have an unacceptable level of toxicity to non-target organisms and are being withdrawn from use. Fluensulfone is a new nematicide of the fluoroalkenyl thioether group that has significantly reduced environmental impact with low toxicity to non-target insects and mammals. Here, we show that the model genetic organism Caenorhabditis elegans is susceptible to the irreversible nematicidal effects of fluensulfone. Whilst the dose required is higher than that which has nematicidal activity against Meloidogyne spp. the profile of effects on motility, egg-hatching and survival is similar to that reported for plant parasitic nematodes. C. elegans thus provides a tractable experimental paradigm to analyse the effects of fluensulfone on nematode behaviour. We find that fluensulfone has pleiotropic actions and inhibits development, egg-laying, egg-hatching, feeding and locomotion. In the case of feeding and locomotion, an early excitation precedes the gross inhibition. The profile of these effects is notably distinct from other classes of anthelmintic and nematicide: the inhibition of motility caused by fluensulfone is not accompanied by the hypercontraction which is characteristic of organophosphates and carbamates and C. elegans mutants that are resistant to the carbamate aldicarb and the macrocyclic lactone ivermectin retain susceptibility to fluensulfone. These data indicate fluensulfone's mode of action is distinct from currently available nematicides and it therefore presents a promising new chemical entity for crop protection.

  3. Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs.

    Science.gov (United States)

    Shoop, Wesley L; Hartline, Eric J; Gould, Brandon R; Waddell, Molly E; McDowell, Richard G; Kinney, John B; Lahm, George P; Long, Jeffrey K; Xu, Ming; Wagerle, Ty; Jones, Gail S; Dietrich, Robert F; Cordova, Daniel; Schroeder, Mark E; Rhoades, Daniel F; Benner, Eric A; Confalone, Pat N

    2014-04-02

    Afoxolaner is an isoxazoline compound characterized by a good safety profile and extended effectiveness against fleas and ticks on dogs following a single oral administration. In vitro membrane feeding assay data and in vivo pharmacokinetic studies in dogs established an afoxolaner blood concentration of 0.1-0.2 μg/ml to be effective against both fleas (Ctenocephalides felis) and ticks (Dermacentor variabilis). Pharmacokinetic profiles in dogs following a 2.5mg/kg oral dosage demonstrated uniform and predictable afoxolaner plasma concentrations above threshold levels required for efficacy for more than one month. Dose ranging and a 5-month multi-dose experimental study in dogs, established that the 2.5mg/kg oral dosage was highly effective against fleas and ticks, and produced predictable and reproducible pharmacokinetics following repeated dosing. Mode of action studies showed that afoxolaner blocked native and expressed insect GABA-gated chloride channels with nanomolar potency. Afoxolaner has comparable potency between wild type channels and channels possessing the A302S (resistance-to-dieldrin) mutation. Lack of cyclodiene cross-resistance for afoxolaner was confirmed in comparative Drosophila toxicity studies, and it is concluded that afoxolaner blocked GABA-gated chloride channels via a site distinct from the cyclodienes.

  4. The possible role of quinate in the mode of action of glyphosate and acetolactate synthase inhibitors.

    Science.gov (United States)

    Orcaray, Luis; Igal, María; Marino, Daniel; Zabalza, Ana; Royuela, Mercedes

    2010-03-01

    The herbicide glyphosate inhibits the biosynthesis of aromatic amino acids by blocking the shikimate pathway. Imazethapyr and chlorsulfuron are two herbicides that act by inhibiting branched-chain amino acid biosynthesis. These herbicides stimulate secondary metabolism derived from the aromatic amino acids. The aim of this study was to test if they cause any cross-effect in the amino acid content and if they have similar effects on the shikimate pathway. The herbicides inhibiting two different amino acid biosynthesis pathways showed a common pattern in general content of free amino acids. There was a general increase in total free amino acid content, with a transient decrease in the proportion of amino acids whose pathways were specifically inhibited. Afterwards, an increase in these inhibited amino acids was detected; this was probably related to proteolysis. All herbicides caused quinate accumulation. Exogenous application of quinate arrested growth, decreased net photosynthesis and stomatal conductance and was ultimately lethal, similarly to glyphosate and imazethapyr. Quinate accumulation was a common effect of the two different classes of herbicide. Moreover, exogenous quinate application had phytotoxic effects, showing that this plant metabolite can trigger the toxic effects of the herbicides. This ability to mimic the herbicide effects suggests a possible link between the mode of action of these herbicides and the potential role of quinate as a natural herbicide.

  5. Mode of action and human relevance of THF-induced mouse liver tumors.

    Science.gov (United States)

    Choi, Christopher J; Rushton, Erik K; Vardy, Audrey; Higgins, Larry; Augello, Andrea; Parod, Ralph J

    2017-07-05

    In a National Toxicology Program (NTP) bioassay, inhalation of tetrahydrofuran (THF) induced liver tumors in female B6C3F1 mice but not in male mice or rats of either sex. Since THF is not genotoxic, the NTP concluded this carcinogenic activity was likely mediated via non-genotoxic modes of action (MOA). Based on evidence that THF and phenobarbital share a similar MOA, female Car/Pxr knock-out mice were orally exposed to THF to evaluate the potential role of CAR activation in the MOA for THF-induced liver tumors. Because data from this oral study with Car/Pxr knock-out mice (C57Bl/6) and the inhalation studies with wild type mice (B6C3F1) reported by NTP and others were derived from different strains, oral studies with wild type B6C3F1 and C57Bl/6 mice were conducted to ensure THF responses in both strains were comparable. As seen in inhalation studies with THF, oral exposure of wild type female mice to a maximum tolerated dose of THF increased total P450 content, CAR-related P450 activities, and hepatocyte proliferation; these effects were not observed in Car/Pxr knock-out female mice. This finding supports the hypothesis THF-induced carcinogenicity is likely mediated via CAR activation that has limited, if any, relevance to humans. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Toward an understanding of the mode of action of fluoroquinolone drugs

    Science.gov (United States)

    Neugebauer, U.; Schmid, U.; Baumann, K.; Holzgrabe, U.; Schmitt, M.; Popp, J.

    2007-07-01

    Fluoroquinolones are important antibacterial drugs. They were found to interfere with the gyrase-DNA complex which causes cell death. However, the detailed mode of action on a molecular level is so far not understood. In this contribution Raman spectroscopy is chosen as a non-invasive technique to first characterize the individual involved components: fluoroquinolone drugs, and the biological targets DNA and gyrase; and second to study the influence of the fluoroquinolones on bacteria in in-vivo experiments. The use of UV resonance Raman spectroscopy with excitation at 244 nm allows the investigation of the drugs and the biological targets in aqueous solution at biological low concentrations (a few μM). Raman bands associated with the action of the enzyme gyrase could be identified in in-vitro mixing experiments. In-vivo experiments with bacteria experiencing varying drug concentrations revealed changes in the vibrational bands of the protein and DNA components within the bacterial cell caused by the action of the drug. Due to the complexity of the bacterial spectra advanced multivariate statistics in combination with variable selection methods proved to be useful in the data analysis.

  7. Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance

    Directory of Open Access Journals (Sweden)

    Auda A. Eltahla

    2015-09-01

    Full Text Available The hepatitis C virus (HCV is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp has been targeted for antiviral development, and direct-acting antivirals (DAA have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.

  8. New insights into the mode of action of the lantibiotic salivaricin B

    Science.gov (United States)

    Barbour, Abdelahhad; Tagg, John; Abou-Zied, Osama K.; Philip, Koshy

    2016-01-01

    Salivaricin B is a 25 amino acid polycyclic peptide belonging to the type AII lantibiotics and first shown to be produced by Streptococcus salivarius. In this study we describe the bactericidal mode of action of salivaricin B against susceptible Gram-positive bacteria. The killing action of salivaricin B required micro-molar concentrations of lantibiotic whereas the prototype lantibiotic nisin A was shown to be potent at nano-molar levels. Unlike nisin A, salivaricin B did not induce pore formation or dissipate the membrane potential in susceptible cells. This was established by measuring the fluorescence of the tryptophan residue at position 17 when salivaricin B interacted with bacterial membrane vesicles. The absence of a fluorescence blue shift indicates a failure of salivaricin B to penetrate the membranes. On the other hand, salivaricin B interfered with cell wall biosynthesis, as shown by the accumulation of the final soluble cell wall precursor UDP-MurNAc-pentapeptide which is the backbone of the bacterial peptidoglycan. Transmission electron microscopy of salivaricin B-treated cells showed a reduction in cell wall thickness together with signs of aberrant septum formation in the absence of visible changes to cytoplasmic membrane integrity. PMID:27526944

  9. Hypothetical mode of action of earthworm extract with hepatoprotective and antioxidant properties

    Institute of Scientific and Technical Information of China (English)

    Mariappan BALAMURUGAN; Kasi PARTHASARATHI; Lalpet Souri RANGANATHAN; Edwin L. COOPER

    2008-01-01

    The hepatoprotective potential of earthworm extract (EE) (Lampito mauritii, Kinberg) was evaluated against paracetamol-induced liver injury in Wistar albino rat, in comparison with silymarin, the standard hepatoprotective drug. We observed a reduction in liver antioxidants, such as glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx),and catalase (CAT) and in serum total protein, and an increase in serum alkaline phosphatase (ALP), serum aspertate aminotranferase (AST), serum alanine aminotranferase (ALT), bilirubin and liver thiobarbituric acid reactive substances (TBARS) due to liver injury in the paracetamol-administered rats (2 g/kg). On the contrary, increased activities of liver GSH, SOD, GPx,CAT and serum total protein level, and decrease in the contents of serum ALP, AST, ALT, bilirubin and liver TBARS were observed in rats administered with different doses of EE (100, 200 and 300 mg/kg), which are similar to the activities of hepatoprotective drug silymarin (150 mg/kg). The mode of action of EE as evidenced by the above parameters may suggest that EE, on the one hand, prevents the formation of the reactive oxygen groups, or scavenges these groups, thereby preventing the damage on the hepatic cells, and, on the other hand, modulates the genes responsible for synthesis of antioxidant enzymes such as GPx, CAT and SOD in liver tissue and decreases the serum enzymatic activities such as ALP, AST and ALT.

  10. Modes of action for biological control of Botrytis cinerea by antagonistic bacteria

    Directory of Open Access Journals (Sweden)

    Rana HAIDAR

    2017-01-01

    Full Text Available The role of beneficial bacteria in biocontrol of plant diseases, particularly those caused by the necrotrophic fungus Botrytis cinerea, has been investigated by testing many bacteria under laboratory and field conditions. Bacteria may protect plants against B. cinerea by direct antagonistic interactions between biocontrol agents and this pathogen, as well as indirect effects through the induction of host resistance. This review focuses on various bacteria that act as biological control agents (BCAs of B. cinerea and their associated mechanisms. The modes of action (MoAs include: i synthesis of anti-fungal metabolites, such as antibiotics, cell wall-degrading enzymes and volatile organic compounds (VOCs; ii competition for nutrients and/or a niche; and iii induction of host resistance. The challenge for development of BCAs is to reduce the variability of efficiency and to prove persistence under a large range of conditions. We discuss the advantages and drawbacks of MoA for future applications of bacteria in the field and in post-harvest storage, as well as combination of different MoAs as a strategy to achieve a more regular efficacy.

  11. Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance.

    Science.gov (United States)

    Ghannoum, M A; Rice, L B

    1999-10-01

    The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles. Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to prevent and control the emergence and spread of resistance. In this review, the mode of action of antifungals and their mechanisms of resistance are discussed. Additionally, an attempt is made to discuss the correlation between fungal and bacterial resistance. Antifungals can be grouped into three classes based on their site of action: azoles, which inhibit the synthesis of ergosterol (the main fungal sterol); polyenes, which interact with fungal membrane sterols physicochemically; and 5-fluorocytosine, which inhibits macromolecular synthesis. Many different types of mechanisms contribute to the development of resistance to antifungals. These mechanisms include alteration in drug target, alteration in sterol biosynthesis, reduction in the intercellular concentration of target enzyme, and overexpression of the antifungal drug target. Although the comparison between the mechanisms of resistance to antifungals and antibacterials is necessarily limited by several factors defined in the review, a correlation between the two exists. For example, modification of enzymes which serve as targets for antimicrobial action and the involvement of membrane pumps in the extrusion of drugs are well characterized in both the eukaryotic and prokaryotic cells.

  12. Current models of the mode of action of Bacillus thuringiensis insecticidal crystal proteins: a critical review.

    Science.gov (United States)

    Vachon, Vincent; Laprade, Raynald; Schwartz, Jean-Louis

    2012-09-15

    Bacillus thuringiensis (Bt) Cry toxins constitute the active ingredient in the most widely used biological insecticides and insect-resistant transgenic crops. A clear understanding of their mode of action is necessary for improving these products and ensuring their continued use. Accordingly, a long history of intensive research has established that their toxic effect is due primarily to their ability to form pores in the plasma membrane of the midgut epithelial cells of susceptible insects. In recent years, a rather elaborate model involving the sequential binding of the toxins to different membrane receptors has been developed to describe the events leading to membrane insertion and pore formation. However, it was also proposed recently that, in contradiction with this mechanism, Bt toxins function by activating certain intracellular signaling pathways which lead to the necrotic death of their target cells without the need for pore formation. Because work in this field has largely focused, for several years, on the elaboration and promotion of these two models, the present revue examines in detail the experimental evidence on which they are based. It is concluded that the presently available information still supports the notion that Bt Cry toxins act by forming pores, but most events leading to their formation, following binding of the activated toxins to their receptors, remain relatively poorly understood.

  13. The plant cell wall integrity maintenance mechanism-concepts for organization and mode of action.

    Science.gov (United States)

    Hamann, Thorsten

    2015-02-01

    One of the main differences between plant and animal cells are the walls surrounding plant cells providing structural support during development and protection like an adaptive armor against biotic and abiotic stress. During recent years it has become widely accepted that plant cells use a dedicated system to monitor and maintain the functional integrity of their walls. Maintenance of integrity is achieved by modifying the cell wall and cellular metabolism in order to permit tightly controlled changes in wall composition and structure. While a substantial amount of evidence supporting the existence of the mechanism has been reported, knowledge regarding its precise mode of action is still limited. The currently available evidence suggests similarities of the plant mechanism with respect to both design principles and molecular components involved to the very well characterized system active in the model organism Saccharomyces cerevisiae. There the system has been implicated in cell morphogenesis as well as response to abiotic stresses such as osmotic challenges. Here the currently available knowledge on the yeast system will be reviewed initially to provide a framework for the subsequent discussion of the plant cell wall integrity maintenance mechanism. The review will then end with a discussion on possible design principles for the cell wall integrity maintenance mechanism and the function of the plant turgor pressure in this context. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Coral snake venoms: mode of action and pathophysiology of experimental envenomation

    Directory of Open Access Journals (Sweden)

    Oswald Vital Brazil

    1987-06-01

    Full Text Available Coral snakes, the New World Elapidae, are included in the genera Micniroides and Micrurus. The genus Mlcrurus comprises nearly all coral snake species and those which are responsible for human snake-bite accidents. The following generalizations concerning the effects induced by their venoms, and their venom-properties can be made. Coral snake venoms are neurotoxic, producing loss of muscle strenght and death by respiratory paralysis. Local edema and necrosis are not induced nor blood coagulation or hemorrhages. Proteolysis activity is absent or of very low grade. They display phospholipase A2 activity. Nephrotoxic effects are not evoked. The main toxins from elapid venoms are postsynaptic and presynaptic neurotoxins and cardiotoxins. Phospholipases A2 endowed with myonecrotic or cardiotoxin-like properties are important toxic components from some elapid venoms. The mode of action of Micrurus frontalis, M. lemniscatus, M. corallinus and M. fulvius venoms has been investigated in isolated muscle preparations and is here discussed. It is shown that while M. frontalis and M. lemniscatus venoms must contain only neurotoxins that act at the cholinergic end-plate receptor (postsynaptic neurotoxins, M. corallinus venom also inhibits evoked acetylcholine release by the motor nerve endings (presynaptic neurotoxin-like effect and M. fulvius induces muscle fiber membrane depolarization (cardiotoxin-like effect. The effects produced by M. corallinus and M. fulvius venoms in vivo in dogs and M. frontalis venom in dogs and monkeys are also reported.

  15. A Bayesian network model for predicting aquatic toxicity mode of action using two dimensional theoretical molecular descriptors-abstract

    Science.gov (United States)

    The mode of toxic action (MoA) has been recognized as a key determinant of chemical toxicity but MoA classification in aquatic toxicology has been limited. We developed a Bayesian network model to classify aquatic toxicity mode of action using a recently published dataset contain...

  16. MODE OF ACTION: NEUROTOXICITY INDUCED BY THYROID HORMONE DISRUPTION DURING DEVELOPMENT - HEARING LOSS RESULTING FROM EXPOSURE TO PHAHS.

    Science.gov (United States)

    A manuscript summarizes a workshop aimed at developing a framework to determine the relevancy of animal modes-of-action for extrapolation to humans. This specific report used animal data on the neurodevelopmental effects of hypothyroidism to test the framework. Propylthiouracil,...

  17. Role of membrane disturbance and oxidative stress in the mode of action underlying the toxicity of differently charged polystyrene nanoparticles

    NARCIS (Netherlands)

    Bhattacharjee, S.; Ershov, D.S.; Islam, M.A.; Kämpfer, A.M.; Maslowska, K.A.; Gucht, van der J.; Alink, G.M.; Marcelis, A.T.M.; Zuilhof, H.; Rietjens, I.M.C.M.

    2014-01-01

    Surface charge is often hypothesized to influence toxicity of nanoparticles (NPs) including polymeric nanoparticles (PNPs) while oxidative stress is considered to be an important mode of action (MOA) for such toxicity. In order to investigate the role of membrane disturbance and oxidative stress in

  18. Maggot therapy´s modes of action : effect of maggot secretions on microbiological, haematological and immunological processes

    NARCIS (Netherlands)

    Plas, Maartje Jeriena Adriana van der

    2009-01-01

    The work described in this thesis focussed on the modes of action of maggot therapy in chronic wounds, especially related to the inflammatory phase of wound healing. For this purpose, the effect of maggot excretions and/or secretions on microbiological, haematological and immunological processes was

  19. Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

    Energy Technology Data Exchange (ETDEWEB)

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

    2011-12-15

    Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

  20. Insecticidal spectrum and mode of action of the Bacillus thuringiensis Vip3Ca insecticidal protein.

    Science.gov (United States)

    Gomis-Cebolla, Joaquín; Ruiz de Escudero, Iñigo; Vera-Velasco, Natalia Mara; Hernández-Martínez, Patricia; Hernández-Rodríguez, Carmen Sara; Ceballos, Tomás; Palma, Leopoldo; Escriche, Baltasar; Caballero, Primitivo; Ferré, Juan

    2017-01-01

    The Vip3Ca protein, discovered in a screening of Spanish collections of Bacillus thuringiensis, was known to be toxic to Chrysodeixis chalcites, Mamestra brassicae and Trichoplusia ni. In the present study, its activity has been tested with additional insect species and we found that Cydia pomonella is moderately susceptible to this protein. Vip3Ca (of approximately 90kDa) was processed to an approximately 70kDa protein when incubated with midgut juice in all tested species. The kinetics of proteolysis correlated with the susceptibility of the insect species to Vip3Ca. The activation was faster to slower in the following order: M. brassicae (susceptible), Spodoptera littoralis (moderately susceptible), Agrotis ipsilon and Ostrinia nubilalis (slightly susceptible). Processing Vip3Ca by O. nubilalis or M. brassicae midgut juice did not significantly changed its toxicity to either insect species, indicating that the low susceptibility of O. nubilalis is not due to a problem in the midgut processing of the toxin. M. brassicae larvae fed with Vip3Ca showed binding of this toxin to the apical membrane of the midgut epithelial cells. Histopathological inspection showed sloughing of the epithelial cells with further disruption, which suggests that the mode of action of Vip3Ca is similar to that described for Vip3Aa. Biotin-labeled Vip3Ca and Vip3Aa bound specifically to M. brassicae brush border membrane vesicles and both toxins competed for binding sites. This result suggests that insects resistant to Vip3A may also be cross-resistant to Vip3C, which has implications for Insect Resistance Management (IRM).

  1. Studies on the mode of action of the antifungal hexapeptide PAF26.

    Science.gov (United States)

    Muñoz, Alberto; López-García, Belén; Marcos, Jose F

    2006-11-01

    The small antimicrobial peptide PAF26 (Ac-RKKWFW-NH(2)) has been identified by a combinatorial approach and shows preferential activity toward filamentous fungi. In this work, we investigated the mode of action and inhibitory effects of PAF26 on the fungus Penicillium digitatum. The dye Sytox Green was used to demonstrate that PAF26 induced cell permeation. However, microscopic observations showed that sub-MIC concentrations of PAF26 produced both alterations of hyphal morphology (such as altered polar growth and branching) and chitin deposition in areas of no detectable permeation. Analysis of dose-response curves of inhibition and permeation suggested that growth inhibition is not solely a consequence of permeation. In order to shed light on the mode of PAF26 action, its antifungal properties were compared with those of melittin, a well-known pore-forming peptide that kills through cytolysis. While the 50% inhibitory concentrations and MICs of the two peptides against P. digitatum mycelium were comparable, they differed markedly in their fungicidal activities toward conidia and their hemolytic activities toward human red blood cells. Kinetic studies showed that melittin quickly induced Penicillium cell permeation, while PAF26-induced Sytox Green uptake was significantly slower and less efficient. Therefore, the ultimate growth inhibition and morphological alterations induced by PAF26 for P. digitatum are not likely a result of conventional pore formation. Fluorescently labeled PAF26 was used to demonstrate its specific in vivo interaction and translocation inside germ tubes and hyphal cells, at concentrations as low as 0.3 muM (20 times below the MIC), at which no inhibitory, morphological, or permeation effects were observed. Interestingly, internalized PAF26 could bind to cellular RNAs, since in vitro nonspecific RNA binding activity of PAF26 was demonstrated by electrophoretic mobility shift assays. We propose that PAF26 is a short, de novo-designed penetratin

  2. Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi

    Science.gov (United States)

    Papademetrio, Daniela; Batlle, Alcira; Martino, Virginia S.; Frank, Fernanda M.; Lombardo, María E.

    2016-01-01

    Trypanosoma cruzi is the causative agent of Chagas’ disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin accomplished its

  3. Machine learning algorithms for mode-of-action classification in toxicity assessment.

    Science.gov (United States)

    Zhang, Yile; Wong, Yau Shu; Deng, Jian; Anton, Cristina; Gabos, Stephan; Zhang, Weiping; Huang, Dorothy Yu; Jin, Can

    2016-01-01

    Real Time Cell Analysis (RTCA) technology is used to monitor cellular changes continuously over the entire exposure period. Combining with different testing concentrations, the profiles have potential in probing the mode of action (MOA) of the testing substances. In this paper, we present machine learning approaches for MOA assessment. Computational tools based on artificial neural network (ANN) and support vector machine (SVM) are developed to analyze the time-concentration response curves (TCRCs) of human cell lines responding to tested chemicals. The techniques are capable of learning data from given TCRCs with known MOA information and then making MOA classification for the unknown toxicity. A novel data processing step based on wavelet transform is introduced to extract important features from the original TCRC data. From the dose response curves, time interval leading to higher classification success rate can be selected as input to enhance the performance of the machine learning algorithm. This is particularly helpful when handling cases with limited and imbalanced data. The validation of the proposed method is demonstrated by the supervised learning algorithm applied to the exposure data of HepG2 cell line to 63 chemicals with 11 concentrations in each test case. Classification success rate in the range of 85 to 95 % are obtained using SVM for MOA classification with two clusters to cases up to four clusters. Wavelet transform is capable of capturing important features of TCRCs for MOA classification. The proposed SVM scheme incorporated with wavelet transform has a great potential for large scale MOA classification and high-through output chemical screening.

  4. Neurotoxicity and mode of action of N, N-diethyl-meta-toluamide (DEET.

    Directory of Open Access Journals (Sweden)

    Daniel R Swale

    Full Text Available Recent studies suggest that N, N-diethyl-meta-toluamide (DEET is an acetylcholinesterase inhibitor and that this action may result in neurotoxicity and pose a risk to humans from its use as an insect repellent. We investigated the mode of action of DEET neurotoxicity in order to define the specific neuronal targets related to its acute toxicity in insects and mammals. Although toxic to mosquitoes (LD50 ca. 1.5 µg/mg, DEET was a poor acetylcholinesterase inhibitor (<10% inhibition, even at a concentration of 10 mM. IC50 values for DEET against Drosophila melanogaster, Musca domestica, and human acetylcholinesterases were 6-12 mM. Neurophysiological recordings showed that DEET had excitatory effects on the housefly larval central nervous system (EC50: 120 µM, but was over 300-fold less potent than propoxur, a standard anticholinesterase insecticide. Phentolamine, an octopamine receptor antagonist, completely blocked the central neuroexcitation by DEET and octopamine, but was essentially ineffective against hyperexcitation by propoxur and 4-aminopyridine, a potassium channel blocker. DEET was found to illuminate the firefly light organ, a tissue utilizing octopamine as the principal neurotransmitter. Additionally, DEET was shown to increase internal free calcium via the octopamine receptors of Sf21 cells, an effect blocked by phentolamine. DEET also blocked Na(+ and K(+ channels in patch clamped rat cortical neurons, with IC50 values in the micromolar range. These findings suggest DEET is likely targeting octopaminergic synapses to induce neuroexcitation and toxicity in insects, while acetylcholinesterase in both insects and mammals has low (mM sensitivity to DEET. The ion channel blocking action of DEET in neurons may contribute to the numbness experienced after inadvertent application to the lips or mouth of humans.

  5. Understanding the mode of action of a pterostilbene derivative as anti-inflammatory agent.

    Science.gov (United States)

    Nikhil, Kumar; Sharan, Shruti; Palla, Srinivasa Rao; Sondhi, Sham M; Peddinti, Rama Krishna; Roy, Partha

    2015-09-01

    Inflammatory response plays an important role not only in the normal physiology, but also in the pathology of certain diseases such as cancers. In our previous study, we found a novel derivative of pterostilbene (PTER), to be an effective inducer of apoptosis in human breast and prostate cancer cells affecting various cellular targets. Herein, we further attempted to investigate its anti-inflammatory potential followed by its probable mode of action. The newly developed compound was tested for its anti-inflammatory actions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and carrageenan induced rat paw edema models. Our data showed that the derivative inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the downstream products like nitric oxide (NO) and PGE2, at much lower doses as compared to PTER. This effect was found to be associated with the inhibition of phosphorylation/degradation of IκB-α and nuclear translocation of the p-NFκB p65. Moreover, inhibition of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) was also observed. In addition, the newly developed compound also reduced the paw edema, the tissue content of NO, PGE2 and expression of iNOS and COX-2 proteins within the tissues after λ-carrageenan stimulation. Taken together, our findings provide the possibility that the PTER derivative might have enhanced cancer chemopreventive potential based on its stronger anti-NFκB and anti-inflammatory activities as compared to its natural counterpart, i.e., PTER. Thus, this compound can be used towards the development of an effective anti-inflammatory agent.

  6. Dual Mode of Action for Plusbacin A3 in Staphylococcus aureus.

    Science.gov (United States)

    O'Connor, Robert D; Singh, Manmilan; Chang, James; Kim, Sung Joon; VanNieuwenhze, Michael; Schaefer, Jacob

    2017-02-23

    We have used C{F}, N{F}, and N{P} rotational-echo double resonance NMR to determine the location and conformation of (19)F and (15)N double-labeled plusbacin A3 and of double-labeled deslipo-plusbacin A3, each bound to the cell walls of whole cells of Staphyloccocus aureus grown in media containing [1-(13)C]glycine. The (31)P is primarily in wall teichoic acid. Approximately 25% of plusbacin headgroups (the cyclic depsipeptide backbone) are in a closed conformation (N-F separation of 6 Å), while 75% are in a more open conformation (N-F separation of 12 Å). The closed headgroups have no contact with wall teichoic acid, whereas the open headgroups have a strong contact. This places the closed headgroups in hydrophobic regions of the cell wall and the open headgroups in hydrophilic regions. None of the plusbacin tails have contact with the (31)P of either wall teichoic acid or the cell membrane and thus are in hydrophobic regions of the cell wall. In addition, both heads and tails of plusbacin A3 have contact with the glycyl (13)C incorporated in cell-wall peptidoglycan pentaglycyl bridges and with (13)C-labeled purines near the membrane surface. We interpret these results in terms of a dual mode of action for plusbacin A3: first, disruption of the peptidoglycan layer nearest to the membrane surface by closed-conformation plusbacin A3 leading to an inhibition of chain extension by transglycosylation; second, thinning and disruption of the membrane (possibly including disruption of ATP-binding cassette transporters embedded in the membrane) by open-conformation plusbacin A3, thereby leading to release of ATP to the hydrophilic regions of the cell wall and subsequent binding by plusbacin A3.

  7. Modulation of human GABAA receptor function: a novel mode of action of drugs of abuse.

    Science.gov (United States)

    Hondebrink, L; Meulenbelt, J; van Kleef, R G D M; van den Berg, M; Westerink, R H S

    2011-12-01

    Drugs of abuse are known to mainly affect the dopaminergic and serotonergic system, although behavioral studies indicated that the GABA-ergic system also plays a role. We therefore investigated the acute effects of several commonly used drugs of abuse (methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and meta-chlorophenylpiperazine (mCPP)) on the function of the human α(1)β(2)γ(2) GABA(A) receptor (hGABA(A)-R), expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique. Although none of the tested drugs acted as full agonist on the hGABA(A)-R, some drugs induced differential modulation of hGABA(A)-R function, depending on the degree of receptor occupancy. Methamphetamine did not affect the GABA-evoked current at high receptor occupancy, but induced a minor inhibition at low receptor occupancy. Its metabolite amphetamine slightly potentiated the GABA-evoked current. MDMA and its metabolite MDA both inhibited the current at low receptor occupancy. However, MDMA did not affect the current at high occupancy, whereas MDA induced a potentiation. mCPP induced a strong inhibition (max. ∼ 80%) at low receptor occupancy, but ∼ 25% potentiation at high receptor occupancy. Competitive binding to one of the GABA-binding sites could explain the drug-induced inhibitions observed at low receptor occupancy, whereas an additional interaction with a positive allosteric binding site may play a role in the observed potentiations at high receptor occupancy. This is the first study to identify direct modulation of hGABA(A)-Rs as a novel mode of action for several drugs of abuse. Consequently, hGABA(A)-Rs should be considered as target for psychiatric pharmaceuticals and in developing treatment for drug intoxications.

  8. Some insights into the mode of action of butadiene by examining the genotoxicity of its metabolites.

    Science.gov (United States)

    Kligerman, A D; Hu, Y

    2007-03-20

    1,3-Butadiene (BTD) is an important commodity chemical and air pollutant that has been shown to be a potent carcinogen in mice, and to a lesser extent, a carcinogen in rats. To better assess butadiene's carcinogenic risk to humans, it is important to understand its mode of action and how this relates to differences in responses among species. In a series of in vitro experiments, lymphocytes from rats, mice, and humans were exposed to 3,4-epoxy-1-butene (EB) or 1,2:3,4-diepoxybutane (DEB) for 1h at the G(0) stage of the cell cycle, stimulated to divide, and cultured to assess the ability of these metabolites to induce sister chromatid exchange (SCE) and chromosome aberrations (CAs). EB induced no increases in SCEs or CAs in the cells from the three species. DEB was a potent SCE- and CA-inducer, with the results being similar in each rodent species. The response for SCEs seen in the human cells was more complex, with genetic polymorphism for glutathione-S-transferases (GST) possibly modulating the response. The single cell gel electrophoresis assay was used on genetically engineered V79 cell lines to investigate a possible influence of GST status. Experiments were also conducted to investigate the reason for EB's failure to induce SCEs or CAs in G(0) cells. The results indicate that EB-induced DNA damage was repaired before DNA synthesis in unstimulated lymphocytes, but EB caused a large increase in SCEs if actively cycling cells were treated. Thus, the results indicate that DEB damage is persistent in G(0) cells, and DEB is a much more potent genotoxicant than EB. The carcinogenic effect of butadiene will most likely depend on the degree to which DEB is produced and reaches target tissues, and to a lesser extent on the ability of EB to reach actively dividing or repair deficient cells.

  9. The Two-Peptide (Class-IIb) Bacteriocins: Genetics, Biosynthesis, Structure, and Mode of Action

    Science.gov (United States)

    Nissen-Meyer, Jon; Oppegård, Camilla; Rogne, Per; Haugen, Helen Sophie; Kristiansen, Per Eugen

    The two-peptide (class-IIb) bacteriocins consist of two different peptides, both of which are required to obtain high antimicrobial activity. These bacteriocins kill target-cells by inducing membrane-leakage and they seem to display some specificity with respect to the molecules they transfer across membranes. The genes encoding the two peptides of two-peptide bacteriocins are next to each other on the same operon. In the same or a nearby operon are genes encoding (i) the immunity protein that protects the bacteriocin-producer from its own bacteriocin, (ii) a dedicated ABC-transporter that exports the bacteriocin from cells and cleaves off the N-terminal bacteriocin leader sequence, and (iii) an accessory protein whose exact function has not been fully clarified. Some two-peptide bacteriocins appear to be produced constitutively, whereas the production of other two-peptide bacteriocins is regulated through a three-component regulatory system that consists of a peptide pheromone, a membrane-associated histidine protein kinase, and response regulators. It has recently been proposed that the two peptides of (some) two-peptide bacteriocins may form a membrane-penetrating helix-helix structure involving helix-helix interacting GxxxG-motifs present in all currently characterized two-peptide bacteriocins. It has also been suggested that the helix-helix structure interacts with an integrated membrane (transport) protein, thus inducing a conformational change in the protein, which in turn causes membrane-leakage. This proposed mode-of-action is similar to that of the pediocin-like (class-IIa) bacteriocins and lactococcin A, which bind to a part of the mannose phosphotransferase permease that is embedded in the cell membrane, thereby altering the conformation of the ­permease in a manner that causes membrane-leakage and cell death.

  10. The Interference of Selected Cytotoxic Alkaloids with the Cytoskeleton: An Insight into Their Modes of Action

    Directory of Open Access Journals (Sweden)

    Xiaojuan Wang

    2016-07-01

    Full Text Available Alkaloids, the largest group among the nitrogen-containing secondary metabolites of plants, usually interact with several molecular targets. In this study, we provide evidence that six cytotoxic alkaloids (sanguinarine, chelerythrine, chelidonine, noscapine, protopine, homoharringtonine, which are known to affect neuroreceptors, protein biosynthesis and nucleic acids, also interact with the cellular cytoskeleton, such as microtubules and actin filaments, as well. Sanguinarine, chelerythrine and chelidonine depolymerized the microtubule network in living cancer cells (Hela cells and human osteosarcoma U2OS cells and inhibited tubulin polymerization in vitro with IC50 values of 48.41 ± 3.73, 206.39 ± 4.20 and 34.51 ± 9.47 μM, respectively. However, sanguinarine and chelerythrine did not arrest the cell cycle while 2.5 μM chelidonine arrested the cell cycle in the G2/M phase with 88.27% ± 0.99% of the cells in this phase. Noscapine and protopine apparently affected microtubule structures in living cells without affecting tubulin polymerization in vitro, which led to cell cycle arrest in the G2/M phase, promoting this cell population to 73.42% ± 8.31% and 54.35% ± 11.26% at a concentration of 80 μM and 250.9 μM, respectively. Homoharringtonine did not show any effects on microtubules and cell cycle, while the known microtubule-stabilizing agent paclitaxel was found to inhibit tubulin polymerization in the presence of MAPs in vitro with an IC50 value of 38.19 ± 3.33 μM. Concerning actin filaments, sanguinarine, chelerythrine and chelidonine exhibited a certain effect on the cellular actin filament network by reducing the mass of actin filaments. The interactions of these cytotoxic alkaloids with microtubules and actin filaments present new insights into their molecular modes of action.

  11. Challenges in assigning endocrine-specific modes of action: Recommendations for researchers and regulators.

    Science.gov (United States)

    Mihaich, Ellen M; Schäfers, Christoph; Dreier, David A; Hecker, Markus; Ortego, Lisa; Kawashima, Yukio; Dang, Zhi-Chao; Solomon, Keith

    2017-03-01

    As regulatory programs evaluate substances for their endocrine-disrupting properties, careful study design and data interpretation are needed to distinguish between responses that are truly endocrine specific and those that are not. This is particularly important in regulatory environments where criteria are under development to identify endocrine-disrupting properties to enable hazard-based regulation. Irrespective of these processes, most jurisdictions use the World Health Organization/International Programme on Chemical Safety definition of an endocrine disruptor, requiring that a substance is demonstrated to cause a change in endocrine function that consequently leads to an adverse effect in an intact organism. Such a definition is broad, and at its most cautious might capture many general mechanisms that would not specifically denote an endocrine disruptor. In addition, endocrine responses may be adaptive in nature, designed to maintain homeostasis rather than induce an irreversible adverse effect. The likelihood of indirect effects is increased in (eco)toxicological studies that require the use of maximum tolerated concentrations or doses, which must produce some adverse effect. The misidentification of indirect effects as truly endocrine mediated has serious consequences for prompting animal- and resource-intensive testing and regulatory consequences. To minimize the risk for misidentification, an objective and transparent weight-of-evidence procedure based on biological plausibility, essentiality, and empirical evidence of key events in an adverse outcome pathway is recommended to describe the modes of action that may be involved in toxic responses in nontarget organisms. Confounding factors such as systemic toxicity, general stress, and infection can add complexity to such an evaluation and should be considered in the weight of evidence. A recommended set of questions is proffered to help guide researchers and regulators in discerning endocrine and

  12. Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi.

    Science.gov (United States)

    Sülsen, Valeria P; Puente, Vanesa; Papademetrio, Daniela; Batlle, Alcira; Martino, Virginia S; Frank, Fernanda M; Lombardo, María E

    2016-01-01

    Trypanosoma cruzi is the causative agent of Chagas' disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin accomplished its antiparasitic

  13. Cardiac and Hemodynamic Benefits: Mode of Action of Ivabradine in Heart Failure.

    Science.gov (United States)

    Pereira-Barretto, Antonio Carlos

    2015-10-01

    Heart failure has seen a number of therapeutic advances in recent years. Despite this, heart failure is still related to increasing rates of morbidity, repeated hospitalizations, and mortality. Ivabradine is a recent treatment option for heart failure. It has a mode of action that includes reduction in heart rate, and leads to improvement in outcomes related to heart failure mortality and morbidity, as demonstrated by the results of the SHIFT trial in patients with systolic heart failure, functional classes II and III on the New York Heart Association classification, and left ventricular ejection fraction ≤ 35%. These results are intriguing since many heart failure drugs reduce heart rate without such benefits, or with quite different effects, making it more difficult to understand the novelty of ivabradine in this setting. Many of the drugs used in heart failure modify heart rate, but most have other pathophysiological effects beyond their chronotropic action, which affect their efficacy in preventing morbidity and mortality outcomes. For instance, heart rate reduction at rest or exercise with ivabradine prolongs diastolic perfusion time, improves coronary blood flow, and increases exercise capacity. Another major difference is the increase in stroke volume observed with ivabradine, which may underlie its beneficial cardiac effects. Finally, there is mounting evidence from both preclinical and clinical studies that ivabradine has an anti-remodeling effect, improving left ventricular structures and functions. All together, these mechanisms have a positive impact on the prognosis of ivabradine-treated patients with heart failure, making a compelling argument for use of ivabradine in combination with other treatments.

  14. Modes of action, resistance and toxicity of insecticides targeting nicotinic acetylcholine receptors.

    Science.gov (United States)

    Ihara, Makoto; Buckingham, Steven D; Matsuda, Kazuhiko; Sattelle, David B

    2017-02-06

    Nicotinic acetylcholine receptors (nAChRs) are members of the cys-loop superfamily of ligand-gated ion channels (cys-loop LGICs) and mediate fast cholinergic synaptic transmission in the nervous system of insects. The completion of many insect genome projects has greatly enhanced our understanding of the individual subunits that make up nAChR gene families from an insect genetic model organism (Drosophila melanogaster), crop pests, disease vectors and beneficial (pollinator) species. In addition to considerable insect nAChR subunit diversity, individual subunits can be subject to alternative splicing and RNA editing and these post-transcriptional modifications can add significantly to the diversity of nAChR receptor subtypes. The actions of insecticides targeting nAChRs, notably cartap, neonicotinoids, sulfoximines, flupyradifurone, spinosyns and triflumezopyrim are reviewed. Structural studies obtained using an acetylcholine binding protein (AChBP) co-crystallised with neonicotinoids have yielded important new insights into the requirements for neonicotinoid insecticide - nAChR interactions. The persistent application of insecticides to crop pests leads to the onset of resistance and several examples of resistance to insecticides targeting nAChRs have been documented. Understanding the molecular basis of resistance can inform our understanding of the mechanism of insecticide action. It also provides an important driver for the development of new chemistry, diagnostic tests for resistance and the adoption of application strategies designed to attenuate such problems. Finally, we consider toxicity issues relating to nAChR-active insecticides, with particular reference to beneficial insect species (pollinators) as well as mammalian and avian toxicity. This review is part of the special issue "Insecticide Mode of Action: From Insect to Mammalian Toxicity.".

  15. Distribution, vocalization and taxonomic status of hypsiboas roraima and h. angelicus (Amphibia: Anura: Hylidae

    Directory of Open Access Journals (Sweden)

    César L. Barrio-Amorós

    2011-01-01

    Full Text Available The distribution of the poorly known hylid frog Hypsiboas roraima Duellman & Hoogmoed, on the Guiana Shield is redefined, including new records from Venezuela. The advertisement call of this species is analyzed and Hypsiboas angelicus Myers & Donnelly is associated as a junior synonym of H. roraima.

  16. Taxonomic key for the genera of Elmidae (Coleoptera, Byrrhoidea occurring in Goiás State, Brazil, including new records and distributional notes

    Directory of Open Access Journals (Sweden)

    Felipe F. Barbosa

    2013-06-01

    Full Text Available A taxonomic key for the genera of Elmidae (Coleoptera, Byrrhoidea occurring in Goiás State, Brazil, including new records and distributional notes. Despite their great diversity and high abundance in Neotropical aquatic environments, the fauna of Elmidae remains practically unknown in some areas and even entire biomes in this region. In this work we bring, for the first time, faunistic data for the Elmidae of central Brazil. The aim of this work was to inventory the Elmidae fauna in central, southwestern and southeastern Goiás State, Brazil and to produce a taxonomic key, at genus level, for adults from the studied region. The taxonomic key presented herein offers means for the identification of all the 13 genera known to occur in Goiás, 11 of them being new records for the State. Moreover, the number of named species registered for Goiás increased from one to nine.

  17. An integrated approach for prospectively investigating a mode-of-action for rodent liver effects

    Energy Technology Data Exchange (ETDEWEB)

    LeBaron, Matthew J., E-mail: MJLeBaron@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Geter, David R., E-mail: dave.geter@gmail.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Rasoulpour, Reza J. [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Gollapudi, B. Bhaskar, E-mail: BBGollapudi@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Thomas, Johnson, E-mail: JThomas4@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Murray, Jennifer, E-mail: AMurray@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Kan, H. Lynn, E-mail: HLKan@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Wood, Amanda J., E-mail: AJWood@dow.com [Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, 48674 (United States); Elcombe, Cliff, E-mail: CliffElcombe@cxrbiosciences.com [CXR Biosciences, 2 James Lindsay Place, Dundee Technopole, Dundee, DD1 5JJ, Scotland (United Kingdom); Vardy, Audrey, E-mail: audrey_vardy@europe.bd.com [CXR Biosciences, 2 James Lindsay Place, Dundee Technopole, Dundee, DD1 5JJ, Scotland (United Kingdom); McEwan, Jillian, E-mail: jillian.mcewan@rtmcewan.co.uk [CXR Biosciences, 2 James Lindsay Place, Dundee Technopole, Dundee, DD1 5JJ, Scotland (United Kingdom); Terry, Claire, E-mail: CTerry@dow.com [Dow AgroSciences, Abingdon, Oxfordshire (United Kingdom); Billington, Richard, E-mail: RBillington@dow.com [Dow AgroSciences, Abingdon, Oxfordshire (United Kingdom)

    2013-07-15

    Registration of new plant protection products (e.g., herbicide, insecticide, or fungicide) requires comprehensive mammalian toxicity evaluation including carcinogenicity studies in two species. The outcome of the carcinogenicity testing has a significant bearing on the overall human health risk assessment of the substance and, consequently, approved uses for different crops across geographies. In order to understand the relevance of a specific tumor finding to human health, a systematic, transparent, and hypothesis-driven mode of action (MoA) investigation is, appropriately, an expectation by the regulatory agencies. Here, we describe a novel approach of prospectively generating the MoA data by implementing additional end points to the standard guideline toxicity studies with sulfoxaflor, a molecule in development. This proactive MoA approach results in a more robust integration of molecular with apical end points while minimizing animal use. Sulfoxaflor, a molecule targeting sap-feeding insects, induced liver effects (increased liver weight due to hepatocellular hypertrophy) in an initial palatability probe study for selecting doses for subsequent repeat-dose dietary studies. This finding triggered the inclusion of dose-response investigations of the potential key events for rodent liver carcinogenesis, concurrent with the hazard assessment studies. As predicted, sulfoxaflor induced liver tumors in rats and mice in the bioassays. The MoA data available by the time of the carcinogenicity finding supported the conclusion that the carcinogenic potential of sulfoxaflor was due to CAR/PXR nuclear receptor activation with subsequent hepatocellular proliferation. This MoA was not considered to be relevant to humans as sulfoxaflor is unlikely to induce hepatocellular proliferation in humans and therefore would not be a human liver carcinogen. - Highlights: • We prospectively generated MoA data into standard guideline toxicity studies. • A proactive MoA approach

  18. Ruby laser-assisted depilation: The mode of action and potential ways of improved outcome

    Science.gov (United States)

    Topping, Adam Partington

    Aim - To improve efficacy and lessen side effects resulting from normal mode ruby laser (NMRL)-assisted depilation via a greater understanding of its mode of action and the development of novel methods of reducing associated epidermal damage. Employing a thermal imaging camera and ex vivo hair-bearing skin, the targets for the NMRL (pulse duration 900 musec and spot size 7 mm) were defined, the temperatures reached and the heat dissipation rates determined. Production of heat was confined to the hair follicles, with the peak temperatures reached varying considerably between hairs within the same treatment area and also between individuals. Histological assessment for a known indicator of cellular damage (p53 expression) identified the sites and extent of damage, which correlated with the peak temperatures measured. An energy meter was used to detect the penetration of NMRL light through ex vivo skin, which was found to be deeper than previously theorised. The black-haired mouse (C57B1/10) was assessed both macroscopically and histologically and found to be an acceptable animal model of NMRL depilation and associated epidermal damage. Attempts to reduce the epidermal damage by simply stopping the light reaching the epidermis using a chromophore block were assessed. Chromophore did indeed reduce the amount of epidermal damage detected in laser-irradiated ex vivo human skin, whereas in contrast it increased the wounding seen in the much thinner skin of the mouse. Nevertheless the mouse model showed that this technique did not affect the depilation efficacy. An alternative method of reducing epidermal damage using induction of the cells' intrinsic protective mechanisms (heat shock proteins, HSP) was assessed using cultured keratinocytes and the mouse model. Primarily, the sub-lethal temperature optimum for HSP expression in human keratinocytes was determined, then an in vitro model of NMRL-associated epidermal damage was established and the heat pre-treatment assessed

  19. Using Mode of Action to Assess Health Risks from Mixtures of Chemical/Physical Agents

    Energy Technology Data Exchange (ETDEWEB)

    Bull, Richard J.; Lei, Xingye C.; Sasser, Lyle B.

    2003-01-20

    Interactions between tumor promoters with differing mechanisms of action were examined in male B6C3F1 mice treated with mixtures of dichloroacetate (DCA), trichloroacetate (TCA), and tetrachloride (CT), each of which acts by a different mode of action. Mice were initiated by vinyl carbamate (VC), and then promoted by DCA, TCA, CT, or the pair-wised combinations of the three compounds. The effect of each treatment or treatment combination on tumor number/animal and tumor size was individually assessed at 18, 24, 30 or 36 weeks of treatment. Dose-related increases in tumor size were observed with 20 & 50 mg/kg CT, but each produced equal number of tumors at 36 weeks with the main distinction being a decrease in tumor latency at the higher dose. Overall TCA treatment produced dose-related increases in tumor number at 36 weeks of treatment. Thus, the lower doses of CT and TCA treatments apparently affected tumor size rather than number. Results with DCA were not as clear as a true maximum tumor number was not clearly observed within the experimental period. Treatment of mice receiving a high dose of TCA (2 g/L of drinking water) combined with varying doses of DCA (0.1, 0.5 and 2 g/L) produced increased numbers of tumors at 24 weeks and 36 weeks. However, at 36 weeks of treatment DCA produced a dose-related decrease in the size of tumors promoted by TCA. The low dose of TCA (0.1 g/L) decreased the number of tumors produced by a high dose of DCA, however, higher doses of TCA produced the same number as observed with DCA alone. Since these two chemicals produce lesions with differing phenotypes, the combination would have been expected to be additive with respect to number, but this was obviously not the case. These data suggest that the induction of liver cancer from mixtures of solvents may have predictable outcomes. The major conclusion is that these interactions are generally no more than additive. It was most interesting to note that additivity was only observed when

  20. Plant adaptogens. III. Earlier and more recent aspects and concepts on their mode of action.

    Science.gov (United States)

    Panossian, A; Wikman, G; Wagner, H

    1999-10-01

    Stimulus-response coupling systems responsible for defence and adaptation of organism to stressors are multi-target and very complicated pharmacological systems, including the neuroendocrine (stress) and immune system. The mode of action of adaptogens is basically associated with the stress-system (neuroendocrine-immune complex) and can be directed on the various targets of the system involved in regulation (activation and inhibition) of stimulus-response coupling. However, clinical studies performed according to the most modern standards are quite limited. On the other hand there is an extensive amount of clinical experience and also established use in self care etc. These aspects are planned to be dealt within a subsequent article which will be devoted to the application in three areas: self care, adjuvants in medicine and curative action in some diseases. At this stage, nevertheless, it seems possible to define some most important "stress-markers" for evaluation of efficiency of adaptogens in experimental and clinical pharmacological studies. They can be both activating (catecholamines, LT-s, cytokines, NO, etc.--"switch on" system--which activates energetic and other resources of the organism), and deactivating (corticosteroids and PGE2-endogenous mediators of cellular communications, which protect cells and whole organism from overreacting to the activating messengers--"switch off" system) stress-messengers. The balance between the activities of the "switch on" and "switch off" systems reflects the well being of the organism. It could be established on different levels of the homeostasis (heterostasis) with different levels of the sensitivity to stressors (Figure 8). The response of stress system--"reactivity" is different at the various levels of heterostasis and depends on adaptation--capacity of the organism (or a cell) to protect itself. In the process of adaptation to stressor's effects the basal levels mediators of switch on (e.g. NO) and switch of (e

  1. Global network analysis of drug tolerance, mode of action and virulence in methicillin-resistant S. aureus

    Directory of Open Access Journals (Sweden)

    Shirran Sally

    2011-05-01

    Full Text Available Abstract Background Staphylococcus aureus is a major human pathogen and strains resistant to existing treatments continue to emerge. Development of novel treatments is therefore important. Antimicrobial peptides represent a source of potential novel antibiotics to combat resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA. A promising antimicrobial peptide is ranalexin, which has potent activity against Gram-positive bacteria, and particularly S. aureus. Understanding mode of action is a key component of drug discovery and network biology approaches enable a global, integrated view of microbial physiology, including mechanisms of antibiotic killing. We developed a systems-wide functional association network approach to integrate proteome and transcriptome profiles, enabling study of drug resistance and mode of action. Results The functional association network was constructed by Bayesian logistic regression, providing a framework for identification of antimicrobial peptide (ranalexin response modules from S. aureus MRSA-252 transcriptome and proteome profiling. These signatures of ranalexin treatment revealed multiple killing mechanisms, including cell wall activity. Cell wall effects were supported by gene disruption and osmotic fragility experiments. Furthermore, twenty-two novel virulence factors were inferred, while the VraRS two-component system and PhoU-mediated persister formation were implicated in MRSA tolerance to cationic antimicrobial peptides. Conclusions This work demonstrates a powerful integrative approach to study drug resistance and mode of action. Our findings are informative to the development of novel therapeutic strategies against Staphylococcus aureus and particularly MRSA.

  2. Taxonomical and ecological characteristics of the desmids placoderms in reservoir: analyzing the spatial and temporal distribution

    Directory of Open Access Journals (Sweden)

    Sirlene Aparecida Felisberto

    2014-12-01

    Full Text Available AIM: This study aimed to evaluate the influence of river-dam axis and abiotic factors on the composition of Closteriaceae, Gonatozygaceae, Mesotaeniaceae and Peniaceae in a tropical reservoir METHODS: Water samples for physical, chemical and periphyton analysis were collected in April and August 2002 in different regions along the axis of the river-dam of Rosana Reservoir, River Basin Paranapanema. The substrates collected, always in the litoranea region, were petioles of Eichhornia azurea (Swartz Kunth. To examine the relationship of abiotic variables with reservoir zones and between the floristic composition of desmids, we used principal component analysis (PCA and canonical correspondence analysis (CCA RESULTS: The results of the PCA explained 81.3% of the total variability in the first two axes. In the first axis, the variables of conductivity, water temperature and the pH were related to the sampling regions of April with higher values, while for the month of August, nitrate, total phosphorus and dissolved oxygen showed higher values. We identified 20 taxa, distributed in the genera Closterium (14, Gonatozygon (4, Netrium (1 and Penium (1. Spatially, the higher taxa were recorded in the lacustrine region for both collection periods. The canonical correspondence analysis (CCA summarized 62.2% of total data variability of taxa in the first two axes, and in August, Closterium incurvum Brébisson, C. cornu Ehrenberg ex Ralfs and Gonatozygon monotaenium De Bary, were related to higher values of turbidity and nitrate to the lacustrine and intermediate regions CONCLUSION: Thus, the formation of groups was due to the regions along the longitudinal axis, then the seasonal period, which must be related to the low current velocity, the higher values of temperature and the water transparency, especially in late summer

  3. A classification scheme for alternative oxidases reveals the taxonomic distribution and evolutionary history of the enzyme in angiosperms.

    Science.gov (United States)

    Costa, José Hélio; McDonald, Allison E; Arnholdt-Schmitt, Birgit; Fernandes de Melo, Dirce

    2014-11-01

    A classification scheme based on protein phylogenies and sequence harmony method was used to clarify the taxonomic distribution and evolutionary history of the alternative oxidase (AOX) in angiosperms. A large data set analyses showed that AOX1 and AOX2 subfamilies were distributed into 4 phylogenetic clades: AOX1a-c/1e, AOX1d, AOX2a-c and AOX2d. High diversity in AOX family compositions was found. While the AOX2 subfamily was not detected in monocots, the AOX1 subfamily has expanded (AOX1a-e) in the large majority of these plants. In addition, Poales AOX1b and 1d were orthologous to eudicots AOX1d and then renamed as AOX1d1 and 1d2. AOX1 or AOX2 losses were detected in some eudicot plants. Several AOX2 duplications (AOX2a-c) were identified in eudicot species, mainly in the asterids. The AOX2b originally identified in eudicots in the Fabales order (soybean, cowpea) was divergent from AOX2a-c showing some specific amino acids with AOX1d and then it was renamed as AOX2d. AOX1d and AOX2d seem to be stress-responsive, facultative and mutually exclusive among species suggesting a complementary role with an AOX1(a) in stress conditions. Based on the data collected, we present a model for the evolutionary history of AOX in angiosperms and highlight specific areas where further research would be most beneficial. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Evidence-based modeling of mode-of-action for functional ingredients influencing Alzheimer’s disease through neurotrophin pathway

    Directory of Open Access Journals (Sweden)

    Erfan Younesi

    2014-08-01

    Full Text Available Background: Brain-derived neurotrophic factor (BDNF is the most widely expressed member of the neurotrophin family in the human brain and is crucially involved in the development of neural circuits, modulation of synaptic plasticity, and regulation of cognitive functions, including learning and memory. Many studies have shown the association of altered BDNF levels with neurodegenerative and neuropsychiatric disorders. However, BDNF is not able to cross the blood-brain barrier and, thus, its delivery to the nervous system is a challenge. Therefore, functional diets with the ability to induce production of BDNF in the brain may offer an alternative route. The objective of this study was three-fold: first, to find out diets that are causally linked to the agonistic activity of BDNF in the neurotrophin signaling pathway; second and mainly, to investigate mode-of-action of these functional diets through systems-based mechanistic modeling in the context of Alzheimer’s disease; and third, to demonstrate the proof-of-concept application of systems biology methods, that are well established in the pharmaceutical sector, to the emerging field of functional food. Methods: In the first step, two cause-and-effect models of BDNF signaling in two states, i.e. normal state and Alzheimer’s disease state, were constructed using published knowledge in scientific literature and pathway databases. A “differential model analysis” between the two states was performed by which mechanistic mode-of-action of BDNF in neurotrophin signaling pathway could be explained with a high molecular resolution in both normal and disease states. The BDNF mode-of-action model was further validated using the “biomarkerguided validation” approach. In the second step, scientific evidence on the effect of various functional diets on BDNF levels and BDNF-related biological processes or outcomes was harvested from biomedical literature using a disease-specific semantic search

  5. Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites.

    Science.gov (United States)

    Simon-Delso, N; Amaral-Rogers, V; Belzunces, L P; Bonmatin, J M; Chagnon, M; Downs, C; Furlan, L; Gibbons, D W; Giorio, C; Girolami, V; Goulson, D; Kreutzweiser, D P; Krupke, C H; Liess, M; Long, E; McField, M; Mineau, P; Mitchell, E A D; Morrissey, C A; Noome, D A; Pisa, L; Settele, J; Stark, J D; Tapparo, A; Van Dyck, H; Van Praagh, J; Van der Sluijs, J P; Whitehorn, P R; Wiemers, M

    2015-01-01

    doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts.

  6. Proposed mode of action of benzene-induced leukemia: Interpreting available data and identifying critical data gaps for risk assessment.

    Science.gov (United States)

    Meek, M E Bette; Klaunig, James E

    2010-03-19

    Mode of action is defined as a series of key biological events leading to an observed toxicological effect (for example, metabolism to a toxic entity, cell death, regenerative repair and tumors). It contrasts with mechanism of action, which generally involves a detailed understanding of the molecular basis for an effect. A framework to consider the weight of evidence for hypothesized modes of action in animals and their relevance to humans, has been widely adopted and used by government agencies and international organizations. The framework, developed and refined through its application in case studies for principally non-DNA-reactive carcinogens, has more recently been extended to DNA-reactive carcinogens, non-cancer endpoints and different life stages. In addition to increasing transparency, use of the framework promotes consistency in decision-making concerning adequacy of weight of evidence, facilitates peer input and review and identifies critical research needs. The framework provides an effective tool to facilitate discussion between the research and risk assessment communities on critical data gaps, which if filled, would permit more refined estimates of risk. As a basis for additionally coordinating and focusing research on critical data gaps in a risk assessment context, five key events in the mode of action for benzene-induced leukemia are proposed: (1) benzene metabolism via Cytochrome P450, (2) the interaction of benzene metabolites with target cells in the bone marrow, (3) formation of initiated, mutated target cells, (4) selective proliferation of the mutated cells and (5) production of leukemia. These key events are considered in a framework analysis of human relevance as a basis to consider appropriate next steps in developing research strategies.

  7. Bioavailability links mode of action can improve the long-term field risk assessment for tilapia exposed to arsenic.

    Science.gov (United States)

    Tsai, Jeng-Wei; Chen, Wei-Yu; Ju, Yun-Ru; Liao, Chung-Min

    2009-05-01

    The objective of this paper was to develop a mechanistic-based framework to explicitly incorporate the factors controlling the bioavailability, toxicodynamics and mode of action to enhance predictive ability of arsenic (As) toxicity to protect the health of farmed tilapia Oreochromis mossambicus. We linked the biotic ligand model and damage assessment model to develop a toxicokinetic model for elucidating the site-specific temporal changes of As bioavailability and to characterize how the fish regulate the metal toxicity. We built a bioavailability-mode of action-based growth toxicity model by linking a bioenergetic growth model and damage assessment model to predict how the As affects on the tilapia growth in the entire life span in site-specific field ecosystems. Here we show that the proposed model well describes the water-chemistry-dependent toxicokinetics and toxicodynamics variations of As to tilapia. We selected two local tilapia farms with different water chemistries located at southwestern Taiwan coast region to implement the proposed algorithm to predict the risk of As exposure. Results indicate that the growth toxicity of O. mossambicus in Taihsi is more sensitive than that in Peimen. We found that the effect of ion competition on the As bioavailability and their ecotoxicological effects on tilapia are more obvious in Taihsi comparing with that in Peimen. We suggested that the proposed bioavailability- and mode of action-based framework can be used to capture the biological response and regulation of tilapia to As exposures. It is applicable for a site-specific and long-term ecotoxicological risk assessment.

  8. Geographic and taxonomic distribution of a positive interaction: ant-tended homopterans indirectly benefit figs across southern Africa.

    Science.gov (United States)

    Cushman, J Hall; Compton, Stephen G; Zachariades, Costas; Ware, Anthony B; Nefdt, Rory J C; Rashbrook, Vanessa K

    1998-09-01

    Although species pairs and assemblages often occur across geographic regions, ecologists know very little about the outcome of their interactions on such large spatial scales. Here, we assess the geographic distribution and taxonomic diversity of a positive interaction involving ant-tended homopterans and fig trees in the genus Ficus. Previous experimental studies at a few locations in South Africa indicated that Ficus sur indirectly benefited from the presence of a homopteran (Hilda patruelis) because it attracted ants (primarily Pheidole megacephala) that reduced the effects of both pre-dispersal ovule gallers and parasitoids of pollinating wasps. Based on this work, we evaluated three conditions that must be met in order to support the hypothesis that this indirect interaction involves many fig species and occurs throughout much of southern Africa and Madagascar. Data on 429 trees distributed among five countries indicated that 20 of 38 Ficus species, and 46% of all trees sampled, had ants on their figs. Members of the Sycomorus subgenus were significantly more likely to attract ants than those in the Urostigma subgenus, and ant-colonization levels on these species were significantly greater than for Urostigma species. On average, each ant-occupied F.sur tree had 37% of its fig crop colonized by ants, whereas the value was 24% for other Ficus species. H. patruelis was the most common source for attracting ants, although figs were also attacked by a range of other ant-tended homopterans. P. megacephala was significantly more common on figs than other ant species, being present on 58% of sampled trees. Ant densities commonly exceeded 4.5 per fig, which a field experiment indicated was sufficient to provide protection from ovule gallers and parasitoids of pollinators. Forty-nine percent of all colonized F. sur trees sampled had ant densities equal to or greater than 4.5 per fig, whereas this value was 23% for other Ficus species. We conclude that there is

  9. Karyotype reorganisation in the subtilis group of birch mice (Rodentia, Dipodidae, Sicista): unexpected taxonomic diversity within a limited distribution.

    Science.gov (United States)

    Kovalskaya, Y M; Aniskin, V M; Bogomolov, P L; Surov, A V; Tikhonov, I A; Tikhonova, G N; Robinson, T J; Volobouev, V T

    2011-01-01

    Conventional cytogenetic studies of Sicista subtilis and S. severtzovi (Dipodidae, Sicistinae), both attributable to the subtilis group of birch mice, revealed extensive karyotype diversity with 2n = 16-26 and NFa values of 26-46 indicating the overwhelming non-Robertsonian nature of chromosomal reorganization in these species. The numerical and structural chromosome variability was principally found in specimens located within a confined region of the East European (Russian) Plain. The approximately 135,000-km(2) area occurs in the vicinity of the Don River bend between 49°13'N/43°46'E and 51°32'N/36°16'E. The detection of cytotypes sharing similar 2n and NF values, but having morphologically distinct chromosomes, suggests that these may result from polymorphisms present both within recognized species and in cryptic taxa not hitherto described. We conducted a comprehensive, comparative chromosome banding analysis of 52 birch mice (21 localities) referable to the subtilis group and report the presence of 5 distinct karyotypes, each characterized by a combination of stable, variable, and partly overlapping 2n/NFa values. These karyotypes differed from each other by 10-29 structural chromosomal rearrangements (18.1 ± 6.3) that comprised Rb fusions/fissions (42.2%), pericentric inversions (31.1%), and tandem translocations (22.2%). The composition, and the high numbers of these chromosomal changes, is likely to provide an effective means of post-mating isolation, suggesting that taxonomic diversity within the subtilis group is larger than currently accepted. Additionally, we report the frequent fixation of tandem translocations in sample populations, one of which was found in a polymorphic state representing, as far as we are aware, the first case of an in statu nascendi tandem fusion in wild populations. Moreover, our data revealed that bi-armed chromosomes were involved in fusions detected in some of the subtilis taxa. In each instance, however, fusions were

  10. Efficacy and Mode of Action of Kaolin in the Control of Empoasca vitis and Zygina rhamni (Hemiptera: Cicadellidae) in Vineyards.

    Science.gov (United States)

    Tacoli, Federico; Pavan, Francesco; Cargnus, Elena; Tilatti, Elisabetta; Pozzebon, Alberto; Zandigiacomo, Pietro

    2017-06-01

    During 2015, the influence of kaolin applications and bunch-zone leaf removal on the grapevine leafhoppers, Empoasca vitis (Göthe) and Zygina rhamni Ferrari, and their egg parasitoids (Anagrus spp.) was tested in four vineyards of northeastern Italy. The mode of action of kaolin on E. vitis nymphs was also investigated in the laboratory. In the treated plots, kaolin was applied at a rate of 2% w/v on two occasions separated by 5-6 d. In two vineyards, it was applied either on the whole canopy or the bunch zone at the beginning of the E. vitis second generation (preventive criterion), and in the other two vineyards, it was applied to the whole canopy at the peak of the E. vitis third generation (curative criterion). Both the preventive and curative kaolin applications caused a significant decrease in the populations of E. vitis and Z. rhamni nymphs. The effect of the preventive applications was persistent and was associated with reduced E. vitis leaf symptoms. Kaolin did not influence the activity of Anagrus spp. Bunch-zone leaf removal did not affect leafhopper populations. Laboratory experiments showed that inhibition of feeding was the main mode of action through which kaolin affected nymph populations. Based on these outcomes, kaolin could be a valuable alternative to synthetic insecticides in controlling grapevine leafhoppers. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. A Flow Cytometry Method for Rapidly Assessing Mycobacterium tuberculosis Responses to Antibiotics with Different Modes of Action.

    Science.gov (United States)

    Hendon-Dunn, Charlotte Louise; Doris, Kathryn Sarah; Thomas, Stephen Richard; Allnutt, Jonathan Charles; Marriott, Alice Ann Neville; Hatch, Kim Alexandra; Watson, Robert James; Bottley, Graham; Marsh, Philip David; Taylor, Stephen Charles; Bacon, Joanna

    2016-07-01

    Current methods for assessing the drug susceptibility of Mycobacterium tuberculosis are lengthy and do not capture information about viable organisms that are not immediately culturable under standard laboratory conditions as a result of antibiotic exposure. We have developed a rapid dual-fluorescence flow cytometry method using markers for cell viability and death. We show that the fluorescent marker calcein violet with an acetoxy-methyl ester group (CV-AM) can differentiate between populations of M. tuberculosis growing at different rates, while Sytox green (SG) can differentiate between live and dead mycobacteria. M. tuberculosis was exposed to isoniazid or rifampin at different concentrations over time and either dual stained with CV-AM and SG and analyzed by flow cytometry or plated to determine the viability of the cells. Although similar trends in the loss of viability were observed when the results of flow cytometry and the plate counting methods were compared, there was a lack of correlation between these two approaches, as the flow cytometry analysis potentially captured information about cell populations that were unable to grow under standard conditions. The flow cytometry approach had an additional advantage in that it could provide insights into the mode of action of the drug: antibiotics targeting the cell wall gave a flow cytometry profile distinct from those inhibiting intracellular processes. This rapid drug susceptibility testing method could identify more effective antimycobacterials, provide information about their potential mode of action, and accelerate their progress to the clinic.

  12. Antibacterial Effects and Mode of Action of Selected Essential Oils Components against Escherichia coli and Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Julio Cesar Lopez-Romero

    2015-01-01

    Full Text Available Bacterial resistance has been increasingly reported worldwide and is one of the major causes of failure in the treatment of infectious diseases. Natural-based products, including plant secondary metabolites (phytochemicals, may be used to surpass or reduce this problem. The objective of this study was to determine the antibacterial effect and mode of action of selected essential oils (EOs components: carveol, carvone, citronellol, and citronellal, against Escherichia coli and Staphylococcus aureus. The minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC were assessed for the selected EOs components. Moreover, physicochemical bacterial surface characterization, bacterial surface charge, membrane integrity, and K+ leakage assays were carried out to investigate the antimicrobial mode of action of EOs components. Citronellol was the most effective molecule against both pathogens, followed by citronellal, carveol, and carvone. Changes in the hydrophobicity, surface charge, and membrane integrity with the subsequent K+ leakage from E. coli and S. aureus were observed after exposure to EOs. This study demonstrates that the selected EOs have significant antimicrobial activity against the bacteria tested, acting on the cell surface and causing the disruption of the bacterial membrane. Moreover, these molecules are interesting alternatives to conventional antimicrobials for the control of microbial infections.

  13. Investigations of the mode of action and resistance development of cadazolid, a new antibiotic for treatment of Clostridium difficile infections.

    Science.gov (United States)

    Locher, Hans H; Caspers, Patrick; Bruyère, Thierry; Schroeder, Susanne; Pfaff, Philippe; Knezevic, Andreja; Keck, Wolfgang; Ritz, Daniel

    2014-01-01

    Cadazolid is a new oxazolidinone-type antibiotic currently in clinical development for the treatment of Clostridium difficile-associated diarrhea. Here, we report investigations on the mode of action and the propensity for spontaneous resistance development in C. difficile strains. Macromolecular labeling experiments indicated that cadazolid acts as a potent inhibitor of protein synthesis, while inhibition of DNA synthesis was also observed, albeit only at substantially higher concentrations of the drug. Strong inhibition of protein synthesis was also obtained in strains resistant to linezolid, in agreement with low MICs against such strains. Inhibition of protein synthesis was confirmed in coupled transcription/translation assays using extracts from different C. difficile strains, including strains resistant to linezolid, while inhibitory effects in DNA topoisomerase assays were weak or not detectable under the assay conditions. Spontaneous resistance frequencies of cadazolid were low in all strains tested (generally cadazolid retained potent activity against strains resistant or nonsusceptible to linezolid, fluoroquinolones, and the new antibiotic fidaxomicin. In conclusion, the data presented here indicate that cadazolid acts primarily by inhibition of protein synthesis, with weak inhibition of DNA synthesis as a potential second mode of action, and suggest a low potential for spontaneous resistance development.

  14. Inhibition of Listeria monocytogenes on Ready-to-Eat Meats Using Bacteriocin Mixtures Based on Mode-of-Action

    Directory of Open Access Journals (Sweden)

    Paul Priyesh Vijayakumar

    2017-03-01

    Full Text Available Bacteriocin-producing (Bac+ lactic acid bacteria (LAB comprising selected strains of Lactobacillus curvatus, Lactococcus lactis, Pediococcus acidilactici, and Enterococcus faecium and thailandicus were examined for inhibition of Listeria monocytogenes during hotdog challenge studies. The Bac+ strains, or their cell-free supernatants (CFS, were grouped according to mode-of-action (MOA as determined from prior studies. Making a mixture of as many MOAs as possible is a practical way to obtain a potent natural antimicrobial mixture to address L. monocytogenes contamination of RTE meat products (i.e., hotdogs. The heat resistance of the bacteriocins allowed the use of pasteurization to eliminate residual producer cells for use as post-process surface application or their inclusion into hotdog meat emulsion during cooking. The use of Bac+ LAB comprising 3× MOAs directly as co-inoculants on hotdogs was not effective at inhibiting L. monocytogenes. However, the use of multiple MOA Bac+ CFS mixtures in a variety of trials demonstrated the effectiveness of this approach by showing a >2-log decrease of L. monocytogenes in treatment samples and 6–7 log difference vs. controls. These data suggest that surface application of multiple mode-of-action bacteriocin mixtures can provide for an Alternative 2, and possibly Alternative 1, process category as specified by USDA-FSIS for control of L. monocytogenes on RTE meat products.

  15. Proposed mechanism of antibacterial mode of action of Caesalpinia bonducella seed oil against food-borne pathogens

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    Shruti Shukla

    2016-03-01

    Full Text Available The antibacterial mechanism of action of Caesalpinia bonducella seed oil on membrane permeability of Listeria monocytogenes NCIM 24563 (MIC: 2 mg/mL and Escherichia coli ATCC 25922 (MIC: 4 mg/mL was determined by measuring the extracellular ATP concentration, release of 260-nm absorbing materials, leakage of potassium ions and measurement of relative electrical conductivity of the bacterial cells treated at MIC concentration. Its mode of action on membrane integrity was confirmed by release of extracellular ATP (1.42 and 1.33 pg/mL, loss of 260-nm absorbing materials (4.36 and 4.19 optical density, leakage of potassium ions (950 and 1000 mmol/L and increase in relative electrical conductivity (12.6 and 10.5% against food-borne pathogenic bacteria L. monocytogenes and E. coli, respectively. These findings propose that C. bonducella oil compromised its mode of action on membrane integrity, suggesting its enormous food and pharmacological potential.

  16. Investigating Potential Modes of Actions of Mimusops kummel Fruit Extract and Solvent Fractions for Their Antidiarrheal Activities in Mice.

    Science.gov (United States)

    Molla, Mulugeta; Gemeda, Negero; Abay, Solomon M

    2017-01-01

    Fruits of Mimusops kummel A. DC. (Sapotaceae) are traditionally used for the treatment of diarrhea. The present study aimed at investigating modes of actions of this fruits for antidiarrheal action to guide future drug development process. Fractions of chloroform, n-butanol, and water were obtained from 80% methanol extract, which was prepared by maceration. Antidiarrheal activities and the modes of actions were investigated in mice. In castor oil induced diarrheal model, the extract delayed onset of diarrhea and reduced number and weight of feces at all tested doses significantly. In this model all fractions significantly delayed onset of diarrhea at all tested doses. Charcoal meal test showed that the extract and all the fractions produced a significant antimotility effect at all tested doses. Enteropooling test showed that the extract as well as n-butanol and aqueous fractions at all tested doses produced a significant decline in volume and weight of intestinal contents, whereas chloroform fraction had substantial effect only at high dose. This study demonstrated that the extract and solvent fractions produced antidiarrheal activities due to dual inhibitory effect, intestinal motility, and fluid secretion, with the aqueous fraction being the most active among fractions in three models.

  17. Investigating Potential Modes of Actions of Mimusops kummel Fruit Extract and Solvent Fractions for Their Antidiarrheal Activities in Mice

    Directory of Open Access Journals (Sweden)

    Mulugeta Molla

    2017-01-01

    Full Text Available Background. Fruits of Mimusops kummel A. DC. (Sapotaceae are traditionally used for the treatment of diarrhea. The present study aimed at investigating modes of actions of this fruits for antidiarrheal action to guide future drug development process. Methods. Fractions of chloroform, n-butanol, and water were obtained from 80% methanol extract, which was prepared by maceration. Antidiarrheal activities and the modes of actions were investigated in mice. Results. In castor oil induced diarrheal model, the extract delayed onset of diarrhea and reduced number and weight of feces at all tested doses significantly. In this model all fractions significantly delayed onset of diarrhea at all tested doses. Charcoal meal test showed that the extract and all the fractions produced a significant antimotility effect at all tested doses. Enteropooling test showed that the extract as well as n-butanol and aqueous fractions at all tested doses produced a significant decline in volume and weight of intestinal contents, whereas chloroform fraction had substantial effect only at high dose. Conclusion. This study demonstrated that the extract and solvent fractions produced antidiarrheal activities due to dual inhibitory effect, intestinal motility, and fluid secretion, with the aqueous fraction being the most active among fractions in three models.

  18. Classification, mode of action and production strategy of xylanase and its application for biofuel production from water hyacinth.

    Science.gov (United States)

    Uday, Uma Shankar Prasad; Choudhury, Payel; Bandyopadhyay, Tarun Kanti; Bhunia, Biswanath

    2016-01-01

    Xylanases are classified under glycoside hydrolase families which represent one of the largest groups of commercial enzymes. Depolymerizing xylan molecules into monomeric pentose units involves the synergistic action of mainly two key enzymes which are endo-β-xylanase and β-xylosidase. Xylanases are different with respect to their mode of action, substrate specificities, biochemical properties, 3D structure and are widely produced by a spectrum of bacteria and fungi. Currently, large scale production of xylanase can be produced through the application of genetic engineering tool which allow fast identification of novel xylanase genes and their genetic variations makes it an ideal enzymes. Due to depletion of fossil fuel, there is urgent need to find out environment friendly and sustainable energy sources. Therefore, utilisation of cheap lignocellulosic materials along with proper optimisation of process is most important for cost efficient ethanol production. Among, various types of lignocellulosic substances, water hyacinth, a noxious aquatic weed, has been found in many tropical. Therefore, the technological development for biofuel production from water hyacinth is becoming commercially worthwhile. In this review, the classification and mode of action of xylanase including genetic regulation and strategy for robust xylanase production have been critically discussed from recent reports. In addition various strategies for cost effective biofuel production from water hyacinth including chimeric proteins design has also been critically evaluated.

  19. Potential of plant essential oils and their components in animal agriculture – in vitro studies on antibacterial mode of action

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    Corliss A. O'bryan

    2015-09-01

    Full Text Available The broad field of agriculture is currently undergoing major changes in practices, with new catch phrases including organic and sustainable. Consumers are more aware than ever before of the food that they eat and they want food free of toxic chemicals, antibiotics and the like. The antimicrobial activity of essential oils and their components has been recognized for several years. Recent research has demonstrated that many of these essential oils have beneficial effects for livestock, including reduction of foodborne pathogens in these animals. Essential oils as natural antimicrobials offer the opportunity to help maintain the safety of our food supply and minimize consumers’ concerns about consumption of synthetic chemicals. Numerous studies have been made into the mode of action of essential oils and the resulting elucidation of bacterial cell targets have contributed to new perspectives on countering antimicrobial resistance and pathogenicity of these bacteria. In this review, after a brief discussion of the uses essential oils in agriculture as antimicrobials, we give an overview of the current knowledge about the antibacterial mode of action of essential oils and their constituents as determined in vitro.

  20. Inhibition of voltage-gated calcium channels as common mode of action for (mixtures of) distinct classes of insecticides.

    Science.gov (United States)

    Meijer, Marieke; Dingemans, Milou M L; van den Berg, Martin; Westerink, Remco H S

    2014-09-01

    Humans are exposed to distinct structural classes of insecticides with different neurotoxic modes of action. Because calcium homeostasis is essential for proper neuronal function and development, we investigated the effects of insecticides from different classes (pyrethroid: (α-)cypermethrin; organophosphate: chlorpyrifos; organochlorine: endosulfan; neonicotinoid: imidacloprid) and mixtures thereof on the intracellular calcium concentration ([Ca(2+)]i). Effects of acute (20 min) exposure to (mixtures of) insecticides on basal and depolarization-evoked [Ca(2+)]i were studied in vitro with Fura-2-loaded PC12 cells and high resolution single-cell fluorescence microscopy. The data demonstrate that cypermethrin, α-cypermethrin, endosulfan, and chlorpyrifos concentration-dependently decreased depolarization-evoked [Ca(2+)]i, with 50% (IC50) at 78nM, 239nM, 250nM, and 899nM, respectively. Additionally, acute exposure to chlorpyrifos or endosulfan (10μM) induced a modest increase in basal [Ca(2+)]i, amounting to 68 ± 8nM and 53 ± 8nM, respectively. Imidacloprid did not disturb basal or depolarization-evoked [Ca(2+)]i at 10μM. Following exposure to binary mixtures, effects on depolarization-evoked [Ca(2+)]i were within the expected effect additivity range, whereas the effect of the tertiary mixture was less than this expected additivity effect range. These results demonstrate that different types of insecticides inhibit depolarization-evoked [Ca(2+)]i in PC12 cells by inhibiting voltage-gated calcium channels (VGCCs) in vitro at concentrations comparable with human occupational exposure levels. Moreover, the effective concentrations in this study are below those for earlier described modes of action. Because inhibition of VGCCs appears to be a common and potentially additive mode of action of several classes of insecticides, this target should be considered in neurotoxicity risk assessment studies. © The Author 2014. Published by Oxford University Press on behalf

  1. Evaluation of acute toxicity, antibacterial activity, and mode of action of the hydroethanolic extract of Piper umbellatum L.

    Science.gov (United States)

    da Silva, Iberê Ferreira; de Oliveira, Ruberlei Godinho; Mendes Soares, Ilsamar; da Costa Alvim, Tarso; Donizeti Ascêncio, Sérgio; de Oliveira Martins, Domingos Tabajara

    2014-01-01

    Piper umbellatum L., Piperaceae, is a shrub that grows up to 3m high. It is commonly known as "capeba" or "pariparoba" in Brazil. Tea prepared using the leaves of this plant is employed in the treatment of infections and inflammatory processes in different countries. Approximately 50 compounds, notably from the flavonoid, alkaloid, terpene, and sterol classes, have been isolated from the leaves of Piper umbellatum. To evaluate the acute toxicity, antibacterial activity, and mode of action of the hydroethanolic extract of Piper umbellatum leaves (HEPu). Acute toxicity of HEPu against CHO-K1 cells was evaluated using a cytotoxicity assay with Alamar Blue and that against mice was assessed by the Hippocratic test. Antibacterial activity of HEPu was tested using the broth microdilution method using a panel of clinically relevant bacteria, and the effects of HEPu on the bacterial membrane were analyzed in detail. A preliminary phytochemical analysis based on coloration/precipitation was performed according to procedure described in the literature. Secondary metabolites detected were analyzed and confirmed by thin layer chromatography (TLC), spectrophotometry, and high performance liquid chromatography (HPLC). Piper umbellatum did not appear to be toxic in the in vitro (IC50>200 µg/mL) cytotoxicity test. When administered in vivo at doses up to 2000 mg/kg p.o., HEPu did not cause any signs or symptoms of toxicity in mice. It demonstrated a good spectrum of antibacterial activity and its mode of action appeared to be associated with changes in the permeability of bacterial membranes; it led to increased entry of hydrophobic antibiotics, efflux of K(+), and nucleotide leakage. Preliminary phytochemical analysis revealed the presence of flavonoids, alkaloids, terpenes, and sterols in the extract. Spectrophotometric and HPLC analysis revealed the presence of the flavonoids rutin and quercetin. In summary, HEPu has antibacterial activity and low acute toxicity in vitro and

  2. Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.

    Science.gov (United States)

    Matsuda, Hisashi; Ninomiya, Kiyofumi; Morikawa, Toshio; Yasuda, Daisuke; Yamaguchi, Itadaki; Yoshikawa, Masayuki

    2009-10-15

    The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.

  3. Combined effects of estrogenic chemicals with the same mode of action using an estrogen receptor binding bioassay.

    Science.gov (United States)

    Yang, Rong; Li, Na; Ma, Mei; Wang, Zijian

    2014-11-01

    The increasing amounts of various estrogenic chemicals coexisting in the aquatic environment may pose environmental risks. While the concept of estradiol equivalent (EEQ) has been frequently applied in studying estrogenic mixtures, few experiments have been done to prove its reliability. In this study, the reliability of EEQ and the related model concentration addition (CA) was verified based on the two-hybrid recombinant yeast bioassay when all mixture components had the same mode of action and target of action. Our results showed that the measured estrogenic effects could be well predicted by CA and EEQ for all laboratory-made mixtures using two designs, despite the varying estrogenic activity, concentration levels and ratios of the test chemicals. This suggests that when an appropriate endpoint and its relevant bioassay are chosen, CA should be valid and the application of EEQ in predicting the effect of non-equi-effect mixtures is feasible.

  4. Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action.

    Science.gov (United States)

    McKelvie, Jennifer R; Wolfe, David M; Celejewski, Magda A; Alaee, Mehran; Simpson, André J; Simpson, Myrna J

    2011-12-01

    Nuclear magnetic resonance (NMR)--based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms.

  5. New strigolactone mimics: structure-activity relationship and mode of action as germinating stimulants for parasitic weeds.

    Science.gov (United States)

    Zwanenburg, Binne; Nayak, Sandip K; Charnikhova, Tatsiana V; Bouwmeester, Harro J

    2013-09-15

    Strigolactones (SLs) are new plant hormones with varies important bio-functions. This Letter deals with germination of seeds of parasitic weeds. Natural SLs have a too complex structure for synthesis. Therefore, there is an active search for SL analogues and mimics with a simpler structure with retention of activity. SL analogues all contain the D-ring connected with an enone moiety through an enol ether unit. A new mechanism for the hydrolysis SL analogues involving bidentate bound water and an α,β-hydrolase with a Ser-His-Asp catalytic triad has been proposed. Newly discovered SL mimics only have the D-ring with an appropriate leaving group at C-5. A mode of action for SL mimics was proposed for which now supporting evidence is provided. As predicted an extra methyl group at C-4 of the D-ring blocks the germination of seeds of parasitic weeds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Dermcidin-derived peptides show a different mode of action than the cathelicidin LL-37 against Staphylococcus aureus.

    Science.gov (United States)

    Senyürek, Ilknur; Paulmann, Maren; Sinnberg, Tobias; Kalbacher, Hubert; Deeg, Martin; Gutsmann, Thomas; Hermes, Marina; Kohler, Thomas; Götz, Fritz; Wolz, Christiane; Peschel, Andreas; Schittek, Birgit

    2009-06-01

    Dermcidin (DCD) is an antimicrobial peptide which is constitutively expressed in eccrine sweat glands. By postsecretory proteolytic processing in sweat, the DCD protein gives rise to anionic and cationic DCD peptides with a broad spectrum of antimicrobial activity. Many antimicrobial peptides induce membrane permeabilization as part of their killing mechanism, which is accompanied by a loss of the bacterial membrane potential. In this study we show that there is a time-dependent bactericidal activity of anionic and cationic DCD-derived peptides which is followed by bacterial membrane depolarization. However, DCD-derived peptides do not induce pore formation in the membranes of gram-negative and gram-positive bacteria. This is in contrast to the mode of action of the cathelicidin LL-37. Interestingly, LL-37 as well as DCD-derived peptides inhibit bacterial macromolecular synthesis, especially RNA and protein synthesis, without binding to microbial DNA or RNA. Binding studies with components of the cell envelope of gram-positive and gram-negative bacteria and with model membranes indicated that DCD-derived peptides bind to the bacterial envelope but show only a weak binding to lipopolysaccharide (LPS) from gram-negative bacteria or to peptidoglycan, lipoteichoic acid, and wall teichoic acid, isolated from Staphylococcus aureus. In contrast, LL-37 binds strongly in a dose-dependent fashion to these components. Altogether, these data indicate that the mode of action of DCD-derived peptides is different from that of the cathelicidin LL-37 and that components of the bacterial cell envelope play a role in the antimicrobial activity of DCD.

  7. Redescription and taxonomic validity of Leptodiaptomus cuauhtemoci (Osorio- Tafall, 1941 (Copepoda, Calanoida, with notes on its known distribution

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    Marcelo SILVA-BRIANO

    2000-02-01

    Full Text Available Within the American freshwater calanoid copepods, Leptodiaptomus includes species whose taxonomical status is still unclear. One of them is L. cuauhtemoci (Osorio-Tafall, for decades considered to be a synonym of L. siciloides (Lilljeborg; another species involved in this problem is L. assiniboiensis (Anderson & Fabris described from Canada, which had been found to be closely related to L. cuauhtemoci. This species remained of uncertain taxonomy because the type material was lost decades ago. In order to disentangle this controversy, type specimens of L. assiniboiensis, topotypic specimens of L. cuauhtemoci from a National Park in central Mexico, and confirmed specimens of L. siciloides from different locations in Mexico and the United States were used to define the status of these species. Leptodiaptomus cuauhtemoci was fully redescribed using SEM. Based on the main characters used to differentiate species of Diaptomidae, L. assiniboiensis (= Diaptomus intermedius Anderson & Fabris turned out to be conspecific and a junior synonym of L. cuauhtemoci, which then becomes the valid name. The latter species shows taxonomically relevant differences with respect to L. siciloides. In the females the main differences is that the lateral spiniform processes on the genital somite are broader-based in L. cuauhtemoci, the genital field is different in both species. In L. cuauhtemoci the fifth leg endopods bear two large, broad, subterminal setae of about the same size, differently built than in L. siciloides. The male L. cuauhtemoci is slenderer, with wings of pediger 5 clearly more developed than those of L. siciloides. The armature of the modified right antennules and the structure of the fifth leg differ in both species. A large coxal spine is present on the right fifth leg of L. siciloides, whereas it is absent in L. cuauhtemoci. These differences were considered to be enough evidence for recognizing L. cuauhtemoci as a separate, valid species

  8. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    Energy Technology Data Exchange (ETDEWEB)

    Franzellitti, Silvia, E-mail: silvia.franzellitti@unibo.it [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy); Buratti, Sara; Capolupo, Marco [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); Du, Bowen; Haddad, Samuel P. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Chambliss, C. Kevin [Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798 (United States); Brooks, Bryan W. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Fabbri, Elena [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy)

    2014-06-01

    Highlights: • Mode of action (MOA) related endpoints and biomarkers of toxicity were assessed in mussels exposed to fluoxetine (FX). • Significant FX bioaccumulation was observed in tissues of mussels exposed to 30 and 300 ng/L FX. • Alterations of cAMP-related cell signaling were observed in exposed mussels as part of the MOA of FX. • FX reduced the health status of mussels inducing lysosomal effects in digestive gland and antioxidant responses in gills. • The importance of considering additional MOAs and adverse outcome pathways for FX impacts on mussels is highlighted. - Abstract: The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03–300 ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300 ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress

  9. Thiamethoxam induced mouse liver tumors and their relevance to humans. Part 1: mode of action studies in the mouse.

    Science.gov (United States)

    Green, Trevor; Toghill, Alison; Lee, Robert; Waechter, Felix; Weber, Edgar; Noakes, James

    2005-07-01

    Thiamethoxam, a neonicotinoid insecticide, which is not mutagenic either in vitro or in vivo, caused an increased incidence of liver tumors in mice when fed in the diet for 18 months at concentrations in the range 500 to 2500 ppm. A number of dietary studies of up to 50 weeks duration have been conducted in order to identify the mode of action for the development of the liver tumors seen at the end of the cancer bioassay. Both thiamethoxam and its major metabolites have been tested in these studies. Over the duration of a 50-week thiamethoxam dietary feeding study in mice, the earliest change, within one week, is a marked reduction (by up to 40%) in plasma cholesterol. This was followed 10 weeks later by evidence of liver toxicity including single cell necrosis and an increase in apoptosis. After 20 weeks there was a significant increase in hepatic cell replication rates. All of these changes persisted from the time they were first observed until the end of the study at 50 weeks. They occurred in a dose-dependent manner and were only observed at doses (500, 1250, 2500 ppm) where liver tumors were increased in the cancer bioassay. There was a clear no-effect level of 200 ppm. The changes seen in this study are consistent with the development of liver cancer in mice and form the basis of the mode of action. When the major metabolites of thiamethoxam, CGA322704, CGA265307, and CGA330050 were tested in dietary feeding studies of up to 20 weeks duration, only metabolite CGA330050 induced the same changes as those seen in the liver in the thiamethoxam feeding study. It was concluded that thiamethoxam is hepatotoxic and hepatocarcinogenic as a result of its metabolism to CGA330050. Metabolite CGA265307 was also shown to be an inhibitor of inducible nitric oxide synthase and to increase the hepatotoxicity of carbon tetrachloride. It is proposed that CGA265307, through its effects on nitric oxide synthase, exacerbates the toxicity of CGA330050 in thiamethoxam treated mice.

  10. A report on Lecanidae (Rotifera: Monogononta from Andhra Pradesh, India, including six new distribution records with notes on their contemporary taxonomic nomenclature

    Directory of Open Access Journals (Sweden)

    S.Z. Siddiqi

    2013-07-01

    Full Text Available The Lecane-species complex taxonomy the world over, witnessed a state of flux, causing confusion and controversies, among world taxonomists over the treatment of various subgenera, taxa and sub and or infraspecific categories of the species rich genus Lecane Nitzsch 1827, on the basis of structure/shape of key, morphological features like foot/toes, lorica, etc. The taxonomic scenario in India, relying heavily on the classical, divergent taxonomic approaches presented a picture of more chaos/confusion, following poor accessibility to contemporary revisionary studies until the recent past. Despite revisionary studies across the world, a few notable Indian studies continued to be burdened with old nomenclature. This short communication reports for the first time ever, 33 valid species of lecanid rotifers (Lecanidae, including six new distributional records from Greater Hyderabad region and the entire state of Andhra Pradesh too with comments on their current nomenclature. Further, limnobiological correlation between five physicochemical parameters and rotifer associations revealed, L. bulla, L. closterocerca, L. hamata, L. ludwigi, L. luna and L. papuana as euryokous species, showing tolerance to a wide range of abiotic factors and habitats too.

  11. Classifying chemical mode of action using gene networks and machine learning: a case study with the herbicide linuron.

    Science.gov (United States)

    Ornostay, Anna; Cowie, Andrew M; Hindle, Matthew; Baker, Christopher J O; Martyniuk, Christopher J

    2013-12-01

    The herbicide linuron (LIN) is an endocrine disruptor with an anti-androgenic mode of action. The objectives of this study were to (1) improve knowledge of androgen and anti-androgen signaling in the teleostean ovary and to (2) assess the ability of gene networks and machine learning to classify LIN as an anti-androgen using transcriptomic data. Ovarian explants from vitellogenic fathead minnows (FHMs) were exposed to three concentrations of either 5α-dihydrotestosterone (DHT), flutamide (FLUT), or LIN for 12h. Ovaries exposed to DHT showed a significant increase in 17β-estradiol (E2) production while FLUT and LIN had no effect on E2. To improve understanding of androgen receptor signaling in the ovary, a reciprocal gene expression network was constructed for DHT and FLUT using pathway analysis and these data suggested that steroid metabolism, translation, and DNA replication are processes regulated through AR signaling in the ovary. Sub-network enrichment analysis revealed that FLUT and LIN shared more regulated gene networks in common compared to DHT. Using transcriptomic datasets from different fish species, machine learning algorithms classified LIN successfully with other anti-androgens. This study advances knowledge regarding molecular signaling cascades in the ovary that are responsive to androgens and anti-androgens and provides proof of concept that gene network analysis and machine learning can classify priority chemicals using experimental transcriptomic data collected from different fish species.

  12. Meleagrin, a new FabI inhibitor from Penicillium chryosogenum with at least one additional mode of action.

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    Chang Ji Zheng

    Full Text Available Bacterial enoyl-acyl carrier protein reductase (FabI is a promising novel antibacterial target. We isolated a new class of FabI inhibitor from Penicillium chrysogenum, which produces various antibiotics, the mechanisms of some of them are unknown. The isolated FabI inhibitor was determined to be meleagrin by mass spectroscopy and nuclear magnetic resonance spectral analyses, and its more active and inactive derivatives were chemically prepared. Consistent with their selective inhibition of Staphylococcus aureus FabI, meleagrin and its more active derivatives directly bound to S. aureus FabI in a fluorescence quenching assay, inhibited intracellular fatty acid biosynthesis and growth of S. aureus, and increased the minimum inhibitory concentration for fabI-overexpressing S. aureus. The compounds that were not effective against the FabK isoform, however, inhibited the growth of Streptococcus pneumoniae that contained only the FabK isoform. Additionally no resistant mutant to the compounds was obtained. Importantly, fabK-overexpressing Escherichia coli was not resistant to these compounds, but was resistant to triclosan. These results demonstrate that the compounds inhibited another target in addition to FabI. Thus, meleagrin is a new class of FabI inhibitor with at least one additional mode of action that could have potential for treating multidrug-resistant bacteria.

  13. Differential scanning fluorometry signatures as indicators of enzyme inhibitor mode of action: case study of glutathione S-transferase.

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    Wendy A Lea

    Full Text Available Differential scanning fluorometry (DSF, also referred to as fluorescence thermal shift, is emerging as a convenient method to evaluate the stabilizing effect of small molecules on proteins of interest. However, its use in the mechanism of action studies has received far less attention. Herein, the ability of DSF to report on inhibitor mode of action was evaluated using glutathione S-transferase (GST as a model enzyme that utilizes two distinct substrates and is known to be subject to a range of inhibition modes. Detailed investigation of the propensity of small molecule inhibitors to protect GST from thermal denaturation revealed that compounds with different inhibition modes displayed distinct thermal shift signatures when tested in the presence or absence of the enzyme's native co-substrate glutathione (GSH. Glutathione-competitive inhibitors produced dose-dependent thermal shift trendlines that converged at high compound concentrations. Inhibitors acting via the formation of glutathione conjugates induced a very pronounced stabilizing effect toward the protein only when GSH was present. Lastly, compounds known to act as noncompetitive inhibitors exhibited parallel concentration-dependent trends. Similar effects were observed with human GST isozymes A1-1 and M1-1. The results illustrate the potential of DSF as a tool to differentiate diverse classes of inhibitors based on simple analysis of co-substrate dependency of protein stabilization.

  14. Jasmine absolute (Jasminum grandiflora L.) and its mode of action on guinea-pig ileum in vitro.

    Science.gov (United States)

    Lis-Balchin, M; Hart, S; Wan Hang Lo, B

    2002-08-01

    Jasmine (Jasminum grandiflorum L.) is used in aromatherapy as a holistic treatment for apathy, hysteria, uterine disorders and childbirth, muscle relaxation and coughs. Its stimulant nature, on inhalation, has been shown both in animals and man. Jasmine has a spasmolytic activity on guinea-pig ileum and rat uterus in vitro. The mechanism of action of the spasmolytic activity, studied in vitro using a guinea-pig ileum smooth muscle preparation, was postsynaptic and not atropine-like. The spasmolytic effect of jasmine absolute was most likely to be mediated through cAMP, and not through cGMP. The mode of action in vitro resembled that of geranium, lavender and peppermint oils. The contradictory effect in vitro and in vivo is probably due to the solely physiological effects of jasmine absolute in vitro (producing a relaxation) compared with that in vivo, where it has a strong psychological input, producing a stimulant effect in man and enhanced movement in animals. Copyright 2002 John Wiley & Sons, Ltd.

  15. Using mode of action information to improve regulatory decision-making: an ECETOC/ILSI RF/HESI workshop overview.

    Science.gov (United States)

    Carmichael, Neil; Bausen, Melanie; Boobis, Alan R; Cohen, Samuel M; Embry, Michelle; Fruijtier-Pölloth, Claudia; Greim, Helmut; Lewis, Richard; Bette Meek, M E; Mellor, Howard; Vickers, Carolyn; Doe, John

    2011-03-01

    The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), the International Life Sciences Institute (ILSI) Research Foundation (RF), and the ILSI Health and Environmental Sciences Institute (HESI) hosted a workshop in November 2009 to review current practice in the application of mode of action (MOA) considerations in chemical risk assessment. The aim was to provide a rationale for a more general, but flexible approach and to propose steps to facilitate broader uptake and use of the MOA concept. There was consensus amongst the workshop participants that it will require substantial effort and cooperation from the multiple disciplines involved to embrace a common, consistent, and transparent approach. Setting up a repository of accepted MOAs and associated guidance concerning appropriate data to support specific MOAs for critical effects would facilitate categorization of chemicals and allow predictions of toxicity outcomes by read-across. This should in future contribute to the reduction of toxicity testing in animals. The workshop participants also acknowledged the value and importance of human data and the importance of integrating information from biological pathway analyses into current MOA/human relevance frameworks.

  16. The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus.

    Science.gov (United States)

    Iimura, Kurin; Furukawa, Tomohiro; Yamamoto, Toshiyoshi; Negishi, Lumi; Suzuki, Michio; Sakuda, Shohei

    2017-07-12

    Cyclo(l-Ala-l-Pro) inhibits aflatoxin production in aflatoxigenic fungi without affecting fungal growth. The mode of action of cyclo(l-Ala-l-Pro) in inhibiting aflatoxin production of Aspergillus flavus was investigated. A glutathione S-transferase (GST) of the fungus, designated AfGST, was identified as a binding protein of cyclo(l-Ala-l-Pro) in an experiment performed using cyclo(l-Ala-l-Pro)-immobilized Sepharose beads. Cyclo(l-Ala-l-Pro) specifically bound to recombinant AfGST and inhibited its GST activity. Ethacrynic acid, a known GST inhibitor, inhibited the GST activity of recombinant AfGST and aflatoxin production of the fungus. Ethacrynic acid reduced the expression level of AflR, a key regulatory protein for aflatoxin production, similar to cyclo(l-Ala-l-Pro). These results suggest that cyclo(l-Ala-l-Pro) inhibits aflatoxin production by affecting GST function in A. flavus, and that AfGST inhibitors are possible candidates as selective aflatoxin production inhibitors.

  17. Three toxins, two receptors, one mechanism: Mode of action of Cry1A toxins from Bacillus thuringiensis in Heliothis virescens.

    Science.gov (United States)

    Bretschneider, Anne; Heckel, David G; Pauchet, Yannick

    2016-09-01

    Insecticidal crystal (Cry) proteins from Bacillus thuringiensis (Bt) are highly active against Lepidoptera. However, field-evolved resistance to Bt toxins is on the rise. The 12-cadherin domain protein HevCaLP and the ABC transporter HevABCC2 are both genetically linked to Cry toxin resistance in Heliothis virescens. We investigated their interaction using stably expressing non-lytic clonal Sf9 cell lines expressing either protein or both together. Untransfected Sf9 cells are innately sensitive to Cry1Ca toxin, but not to Cry1A toxins; and quantitative PCR revealed negligible expression of genes involved in Cry1A toxicity such as cadherin, ABCC2, alkaline phosphatase (ALP) and aminopeptidase N (APN). Cry1Aa, Cry1Ab or Cry1Ac caused swelling of Sf9 cells expressing HevABCC2, and caused faster swelling, lysis and up to 86% mortality in cells expressing both proteins. No such effect was observed in control Sf9 cells or in cells expressing only HevCaLP. The results of a mixing experiment demonstrated that both proteins need to be expressed within the same cell for high cytotoxicity, and suggest a novel role for HevCaLP. Binding assays showed that the toxin-receptor interaction is specific. Our findings confirm that HevABCC2 is the central target in Cry1A toxin mode of action, and that HevCaLP plays a supporting role in increasing Cry1A toxicity.

  18. Combining QSAR modeling and text-mining techniques to link chemical structures and carcinogenic modes of action

    Directory of Open Access Journals (Sweden)

    Georgios Papamokos

    2016-08-01

    Full Text Available There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. QSAR, a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

  19. BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action.

    Science.gov (United States)

    Dach, Katharina; Bendt, Farina; Huebenthal, Ulrike; Giersiefer, Susanne; Lein, Pamela J; Heuer, Heike; Fritsche, Ellen

    2017-03-20

    Polybrominated diphenyl ethers (PBDEs) are bioaccumulating flame retardants causing developmental neurotoxicity (DNT) in humans and rodents. Their DNT effects are suspected to involve thyroid hormone (TH) signaling disruption. Here, we tested the hypothesis whether disturbance of neural progenitor cell (NPC) differentiation into the oligodendrocyte lineage (O4(+) cells) by BDE-99 involves disruption of TH action in human and mouse (h,m)NPCs. Therefore, we quantified differentiation of NPCs into O4(+) cells and measured their maturation via expression of myelin-associated genes (hMBP, mMog) in presence and absence of TH and/or BDE-99. T3 promoted O4(+) cell differentiation in mouse, but not hNPCs, and induced hMBP/mMog gene expression in both species. BDE-99 reduced generation of human and mouse O4(+) cells, but there is no indication for BDE-99 interfering with cellular TH signaling during O4(+) cell formation. BDE-99 reduced hMBP expression due to oligodendrocyte reduction, but concentrations that did not affect the number of mouse O4(+) cells inhibited TH-induced mMog transcription by a yet unknown mechanism. In addition, ascorbic acid antagonized only the BDE-99-dependent loss of human, not mouse, O4(+) cells by a mechanism probably independent of reactive oxygen species. These data point to species-specific modes of action of BDE-99 on h/mNPC development into the oligodendrocyte lineage.

  20. Cloning, functional characterization, and mode of action of a novel insecticidal pore-forming toxin, sphaericolysin, produced by Bacillus sphaericus.

    Science.gov (United States)

    Nishiwaki, Hisashi; Nakashima, Kenta; Ishida, Chiharu; Kawamura, Tadayuki; Matsuda, Kazuhiko

    2007-05-01

    An insecticidal protein produced by Bacillus sphaericus A3-2 was purified to elucidate its structure and mode of action. The active principle purified from the culture broth of A3-2 was a protein with a molecular mass of 53 kDa that rapidly intoxicated German cockroaches (Blattela germanica) at a dose of about 100 ng when injected. The insecticidal protein sphaericolysin possessed the undecapeptide motif of cholesterol-dependent cytolysins and had a unique N-terminal sequence. The recombinant protein expressed in Escherichia coli was equally as potent as the native protein. Sphaericolysin-induced hemolysis resulted from the protein's pore-forming action. This activity as well as the insecticidal activity was markedly reduced by a Y159A mutation. Also, coapplication of sphaericolysin with cholesterol abolished the insecticidal action, suggesting that cholesterol binding plays an important role in insecticidal activity. Sphaericolysin-lysed neurons dissociated from the thoracic ganglia of the German cockroaches. In addition, sphaericolysin's activity in ganglia was suppressed by the Y159A mutation. The sphaericolysin-induced damage to the cockroach ganglia was greater than the damage to the ganglia of common cutworms (Spodoptera litura), which accounts, at least in part, for the higher sensitivity to sphaericolysin displayed by the cockroaches than that displayed by cutworms.

  1. Efficacy of combined formulations of fungicides with different modes of action in controlling botrytis gray mold disease in chickpea.

    Science.gov (United States)

    Rashid, M H; Hossain, M Ashraf; Kashem, M A; Kumar, Shiv; Rafii, M Y; Latif, M A

    2014-01-01

    Botrytis gray mold (BGM) caused by Botrytis cinerea Pers. Ex. Fr. is an extremely devastating disease of chickpea (Cicer arietinum L.) and has a regional as well as an international perspective. Unfortunately, nonchemical methods for its control are weak and ineffective. In order to identify an effective control measure, six fungicides with different modes of action were evaluated on a BGM susceptible chickpea variety BARIchhola-1 at a high BGM incidence location (Madaripur) in Bangladesh for three years (2008, 2009, and 2010). Among the six fungicides tested, one was protectant [Vondozeb 42SC, a.i. mancozeb (0.2%)], two systemic [Bavistin 50 WP, a.i. carbendazim (0.2%), and Protaf 250EC, propiconazole (0.05%)], and three combination formulations [Acrobat MZ690, dimethomorph 9% + mancozeb 60%, (0.2%); Secure 600 WG, phenomadone + mancozeb (0.2%); and Companion, mancozeb 63% + carbendazim 12% (0.2%)]. The results showed superiority of combination formulations involving both protectant and systemic fungicides over the sole application of either fungicide separately. Among the combination fungicides, Companion was most effective, resulting in the lowest disease severity (3.33 score on 1-9 scale) and the highest increase (38%) of grain yield in chickpea. Therefore, this product could be preferred over the sole application of either solo protectant or systemic fungicides to reduce yield losses and avoid fungicide resistance.

  2. Mode of action of dopamine in inducing hyperglycemia in the fresh water edible crab, Oziothelphusa senex senex.

    Science.gov (United States)

    Swetha, Ch; Sainath, S B; Reddy, P Sreenivasula

    2014-11-01

    The objective of this study was to investigate the mode of action of dopamine in regulating hemolymph sugar level in the fresh water edible crab, Oziothelphusa senex senex. Injection of dopamine produced hyperglycemia in a dose-dependent manner in intact crabs but not in eyestalkless crabs. Administration of dopamine resulted in a significant decrease in total carbohydrates and glycogen levels with a significant increase in glycogen phosphorylase activity levels in hepatopancreas and muscle of intact crabs, indicating dopamine-induced glycogenolysis resulting in hyperglycemia. Bilateral eyestalk ablation resulted in significant increase in the total carbohydrates and glycogen levels with a significant decrease in the activity levels of phosphorylase in the hepatopancreas and muscle of the crabs. Eyestalk ablation resulted in significant decrease in hemolymph hyperglycemic hormone levels. The levels of hyperglycemic hormone in the hemolymph of dopamine injected crabs were significantly higher than in control crabs. However, no significant changes in the levels of hemolymph hyperglycemic hormone and sugar and tissue carbohydrate and phosphorylase activity were observed in dopamine injected eyestalk ablated crabs when compared with eyestalk ablated crabs. These results support an earlier hypothesis in crustaceans that dopamine acts as a neurotransmitter and induces hyperglycemia by triggering the release of hyperglycemic hormone in the crab, O. senex senex. © 2014 Wiley Periodicals, Inc.

  3. Cadmium and naphthalene-induced hyperglycemia in the fiddler crab, Uca pugilator: Differential modes of action on the neutroendocrine system

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, P.S.; Katyayani, R.V.; Fingerman, M. [Tulane Univ., New Orleans, LA (United States)

    1996-03-01

    Hyperglycemia is a typical response of aquatic organisms to heavy metals. In crustaceans, the medulla terminalis X-organ-sinus gland neuroendocrine complex in the eyestalk is the source of the crustacean hyperglycemic hormone (CHH). The role of CHH in pollutant-induced b1ood glucose changes has only recently begun to be studied. Reddy provided evidence that CHH mediates cadmium-induced hyperglycemia in the red swamp crayfish, Procambarus clarkii. In a study of another hormonally-regulated function, color changes, cadmium exposure resulted in pigment in the melanophores of the fiddler crab, Uca pugilator, becoming less dispersed than in unexposed crabs. Earlier studies showed that, like cadmium, both a PCB, Aroclor 1242, and naphthalene induced black pigment aggregation in Uca poor. In general, when crabs are exposed to a pollutant, hydrocarbon or cadmium, they aggregate the pigment in their melanophores, but apparently by different mechanisms. Hydrocarbons appear to inhibit release of black pigment-dispersing hormone (BDPH), whereas cadmium appears to inhibit its synthesis. These apparent different modes of action of cadmium and naphthalene on the color change mechanism led us to compare the impact of these pollutants on the hormonal regulation of blood glucose in Uca pugilator. The present study was performed to determine (1) whether cadmium and naphthalene induce hyperglycemia in Uca pugilator, (2) whether CH has a role, if naphthalene and cadmium do induce hyperglycemia, and (3) the effects, if any, of cadmium and naphthalene on CHH activity in the eyestalk neuroendocrine complex.

  4. Antibacterial Activities and Possible Modes of Action of Acacia nilotica (L. Del. against Multidrug-Resistant Escherichia coli and Salmonella

    Directory of Open Access Journals (Sweden)

    Muhammad Bilal Sadiq

    2017-01-01

    Full Text Available Medicinal plants are frequently used for the treatment of various infectious diseases. The objective of this study was to evaluate the antibacterial activity and mode of action of Acacia nilotica and the antibiogram patterns of foodborne and clinical strains of Escherichia coli and Salmonella. The mechanism of action of acacia extracts against E. coli and Salmonella was elucidated by observing morphological damages including cell integrity and cell membrane permeability, as well as changes in cell structures and growth patterns in kill-time experiments. The clinical isolates of E. coli and Salmonella were found resistant to more of the tested antibiotics, compared to food isolates. Minimum inhibitory concentration and minimum bactericidal concentration of acacia leaf extracts were in the ranges of 1.56–3.12 mg/mL and 3.12–6.25 mg/mL, respectively, whereas pods and bark extracts showed somewhat higher values of 3.12–6.25 mg/mL and 6.25–12.5 mg/mL, respectively, against all tested pathogens. The release of electrolytes and essential cellular constituents (proteins and nucleic acids indicated that acacia extracts damaged the cellular membrane of the pathogens. These changes corresponded to simultaneous reduction in the growth of viable bacteria. This study indicates that A. nilotica can be a potential source of new antimicrobials, effective against antibiotic-resistant strains of pathogens.

  5. Purification, characterization, and mode of action of a rhamnogalacturonan hydrolase from Irpex lacteus, tolerant to an acetylated substrate.

    Science.gov (United States)

    Normand, Jessica; Ralet, Marie-Christine; Thibault, Jean-François; Rogniaux, Hélène; Delavault, Philippe; Bonnin, Estelle

    2010-03-01

    A novel rhamnogalacturonase (RGase) acting on an acetylated substrate was detected in the commercial preparation Driselase, an enzymatic mixture derived from the basidiomycete Irpex lacteus. The activity was isolated by hydrophobic interaction chromatography, gel filtration, and preparative isoelectric focusing, resulting in the isolation of five different rhamnogalacturonan hydrolases exhibiting various isoelectric points from 6.2 to 7.7. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and mass spectrometry analyses after trypsin cleavage of the five fractions revealed that the five rhamnogalacturonases have a molar mass of 55 kDa without any divergences in the identified peptides. The RGase with a pI of 7.2 exhibited a pH optimum between 4.5 and 5 and a temperature optimum between 40 degrees C and 50 degrees C. Its mode of action was analyzed by mass spectrometry of the oligosaccharides produced after hydrolysis of acetylated and nonacetylated rhamnogalacturonan. Oligomers esterified by an acetyl group on the reducing galacturonic acid residue or fully acetylated were detected in the hydrolysate showing that the novel enzyme is able to bind acetylated galacturonic acid in its active site.

  6. Identification of antifungal natural products via Saccharomyces cerevisiae bioassay: insights into macrotetrolide drug spectrum, potency and mode of action.

    Science.gov (United States)

    Tebbets, Brad; Yu, Zhiguo; Stewart, Douglas; Zhao, Li-Xing; Jiang, Yi; Xu, Li-Hua; Andes, David; Shen, Ben; Klein, Bruce

    2013-04-01

    Since current antifungal drugs have not kept pace with the escalating medical demands of fungal infections, new, effective medications are required. However, antifungal drug discovery is hindered by the evolutionary similarity of mammalian and fungal cells, which results in fungal drug targets having human homologs and drug non-selectivity. The group III hybrid histidine kinases (HHKs) are an attractive drug target since they are conserved in fungi and absent in mammals. We used a Saccharomyces cerevisiae reporter strain that conditionally expresses HHK to establish a high-throughput bioassay to screen microbial extracts natural products for antifungals. We identified macrotetrolides, a group of related ionophores thought to exhibit restricted antifungal activity. In addition to confirming the use of this bioassay for the discovery of antifungal natural products, we demonstrated broader, more potent fungistatic activity of the macrotetrolides against multiple Candida spp., Cryptococcus spp., and Candida albicans in biofilms. Macrotetrolides were also active in an animal model of C. albicans biofilm, but were found to have inconsistent activity against fluconazole-resistant C. albicans, with most isolates resistant to this natural product. The macrotetrolides do not directly target HHKs, but their selective activity against S. cerevisiae grown in galactose (regardless of Drk1 expression) revealed potential new insight into the role of ion transport in the mode of action of these promising antifungal compounds. Thus, this simple, high-throughput bioassay permitted us to screen microbial extracts, identify natural products as antifungal drugs, and expand our understanding of the activity of macrotetrolides.

  7. Bacillus thuringiensis insecticidal three-domain Cry toxins: mode of action, insect resistance and consequences for crop protection.

    Science.gov (United States)

    Pardo-López, Liliana; Soberón, Mario; Bravo, Alejandra

    2013-01-01

    Bacillus thuringiensis bacteria are insect pathogens that produce different Cry and Cyt toxins to kill their hosts. Here we review the group of three-domain Cry (3d-Cry) toxins. Expression of these 3d-Cry toxins in transgenic crops has contributed to efficient control of insect pests and a reduction in the use of chemical insecticides. The mode of action of 3d-Cry toxins involves sequential interactions with several insect midgut proteins that facilitate the formation of an oligomeric structure and induce its insertion into the membrane, forming a pore that kills midgut cells. We review recent progress in our understanding of the mechanism of action of these Cry toxins and focus our attention on the different mechanisms of resistance that insects have evolved to counter their action, such as mutations in cadherin, APN and ABC transporter genes. Activity of Cry1AMod toxins, which are able to form toxin oligomers in the absence of receptors, against different resistant populations, including those affected in the ABC transporter and the role of dominant negative mutants as antitoxins, supports the hypothesis that toxin oligomerization is a limiting step in the Cry insecticidal activity. Knowledge of the action of 3d-Cry toxin and the resistance mechanisms to these toxins will set the basis for a rational design of novel toxins to overcome insect resistance, extending the useful lifespan of Cry toxins in insect control programs.

  8. Mode of Action and Specificity of Bacillus thuringiensis Toxins in the Control of Caterpillars and Stink Bugs in Soybean Culture.

    Science.gov (United States)

    Schünemann, Rogério; Knaak, Neiva; Fiuza, Lidia Mariana

    2014-01-01

    The bacterium Bacillus thuringiensis (Bt) produces delta-endotoxins that possess toxic properties and can be used as biopesticides, as well as a source of genes for the construction of transgenic plants resistant to insects. In Brazil, the introduction of Bt soybean with insecticidal properties to the velvetbean caterpillar, the main insect pest of soybean, has been seen a promising tool in the management of these agroecosystems. However, the increase in stink bug populations in this culture, in various regions of the country, which are not susceptible to the existing genetically modified plants, requires application of chemicals that damage the environment. Little is known about the actual toxicity of Bt to Hemiptera, since these insects present sucking mouthparts, which hamper toxicity assays with artificial diets containing toxins of this bacterium. In recent studies of cytotoxicity with the gut of different hemipterans, susceptibility in the mechanism of action of delta-endotoxins has been demonstrated, which can generate promising subsidies for the control of these insect pests in soybean. This paper aims to review the studies related to the selection, application and mode of action of Bt in the biological control of the major pest of soybean, Anticarsia gemmatalis, and an analysis of advances in research on the use of Bt for control hemipterans.

  9. Efficacy of Combined Formulations of Fungicides with Different Modes of Action in Controlling Botrytis Gray Mold Disease in Chickpea

    Directory of Open Access Journals (Sweden)

    M. H. Rashid

    2014-01-01

    Full Text Available Botrytis gray mold (BGM caused by Botrytis cinerea Pers. Ex. Fr. is an extremely devastating disease of chickpea (Cicer arietinum L. and has a regional as well as an international perspective. Unfortunately, nonchemical methods for its control are weak and ineffective. In order to identify an effective control measure, six fungicides with different modes of action were evaluated on a BGM susceptible chickpea variety BARIchhola-1 at a high BGM incidence location (Madaripur in Bangladesh for three years (2008, 2009, and 2010. Among the six fungicides tested, one was protectant [Vondozeb 42SC, a.i. mancozeb (0.2%], two systemic [Bavistin 50 WP, a.i. carbendazim (0.2%, and Protaf 250EC, propiconazole (0.05%], and three combination formulations [Acrobat MZ690, dimethomorph 9% + mancozeb 60%, (0.2%; Secure 600 WG, phenomadone + mancozeb (0.2%; and Companion, mancozeb 63% + carbendazim 12% (0.2%]. The results showed superiority of combination formulations involving both protectant and systemic fungicides over the sole application of either fungicide separately. Among the combination fungicides, Companion was most effective, resulting in the lowest disease severity (3.33 score on 1–9 scale and the highest increase (38% of grain yield in chickpea. Therefore, this product could be preferred over the sole application of either solo protectant or systemic fungicides to reduce yield losses and avoid fungicide resistance.

  10. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

  11. Unraveling the role of fermentation in the mode of action of acetolactate synthase inhibitors by metabolic profiling.

    Science.gov (United States)

    Zabalza, Ana; Orcaray, Luis; Igal, María; Schauer, Nicolas; Fernie, Alisdair R; Geigenberger, Peter; van Dongen, Joost T; Royuela, Mercedes

    2011-09-01

    Herbicides that inhibit branched chain amino acid biosynthesis induce aerobic fermentation. The role of fermentation in the mode of action of these herbicides is not known, nor is the importance of this physiological response in the growth inhibition and the lethality caused by them. Metabolic profiling was used to compare the effects of the herbicide imazethapyr (IM) on pea plants with two other treatments that also induce fermentation: hypoxia and the exogenous supply pyruvate for seven days. While hypoxic roots did not show internal anoxia, feeding pyruvate or applying IM to the roots led to internal anoxia, probably related to the respiratory burst detected. The three treatments induced ethanol fermentation, but fermentation induced following herbicide treatment was earlier than that following pyruvate supply and was not associated with a decrease in the energy status. No striking changes were detected in the metabolic profiling of hypoxic roots, indicating that metabolism was only slightly impaired. Feeding pyruvate resulted in marked succinate accumulation and a general amino acid accumulation. IM-treated roots showed a general accumulation of glycolytic metabolites upstream of pyruvate, a decrease in some TCA intermediates and an increase in the free amino acid pool sizes. All treatments caused GABA and putrescine accumulation. Our results indicate that IM supply impairs carbon/nitrogen metabolism and this impaired metabolism is likely to be related to the growth arrest detected. As growth is arrested, carbohydrates and glycolytic intermediates accumulate and energy becomes more available.

  12. Developmental Triclosan Exposure Decreases Maternal,Fetal, and Early Neonatal Thyroxine: Dynamic and Kinetic Data Support for a Mode-of-Action

    Science.gov (United States)

    This work tests the mode-of-action (MOA) hypothesis that perinatal triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via activation of pregnane X and/or constitutive androstane receptors (PXR, CAR), resulting in up-regulation of hepatic catabolism and e...

  13. Use of Electroencephalography (EEG) to Assess CNS Changes Produced by Pesticides with different Modes of Action: Effects of Permethrin, Deltamethrin, Fipronil, Imidacloprid, Carbaryl, and Triadimefon

    Science.gov (United States)

    The electroencephalogram (EEG) is an apical measure, capable of detecting changes in brain neuronal activity produced by internal or external stimuli. We assessed whether pesticides with different modes of action produced different changes in the EEG of adult male Long-Evans rats...

  14. Use of Electroencephalography (EEG) to Assess CNS Changes Produced by Pesticides with different Modes of Action: Effects of Permethrin, Deltamethrin, Fipronil, Imidacloprid, Carbaryl, and Triadimefon

    Science.gov (United States)

    The electroencephalogram (EEG) is an apical measure, capable of detecting changes in brain neuronal activity produced by internal or external stimuli. We assessed whether pesticides with different modes of action produced different changes in the EEG of adult male Long-Evans rats...

  15. DIFFICULTY OF MODE OF ACTION DETERMINATION FOR TRICHLOROETHYLENE: AN EXAMPLE OF COMPLEX INTERACTIONS OF METABOLITES AND OTHER CHEMICAL EXPOSURES (Journal Article)

    Science.gov (United States)

    The mode(s) of action (MOA) of a pollutant for adverse health effects may be dependent on the mixture of metabolites resulting from exposure to a single agent and may also be affected by co-exposure to pollutants that have similar targets or affected pathways. Trichloroethylene ...

  16. DOSE RESPONSE FROM HIGH THROUGHPUT GENE EXPRESSION STUDIES AND THE INFLUENCE OF TIME AND CELL LINE ON INFERRED MODE OF ACTION BY ONTOLOGIC ENRICHMENT (SOT)

    Science.gov (United States)

    Gene expression with ontologic enrichment and connectivity mapping tools is widely used to infer modes of action (MOA) for therapeutic drugs. Despite progress in high-throughput (HT) genomic systems, strategies suitable to identify industrial chemical MOA are needed. The L1000 is...

  17. Spontaneous bacteriocin resistance in Listeria monocytogenes as a susceptibility screen for identifying different mechanisms of resistance and modes of action by bacteriocins of lactic acid bacteria.

    Science.gov (United States)

    Macwana, Sunita; Muriana, Peter M

    2012-01-01

    A practical system was devised for grouping bacteriocins of lactic acid bacteria (LAB) based on mode of action as determined by changes in inhibitory activity to spontaneously-acquired bacteriocin resistance (Bac(R)). Wild type Listeria monocytogenes 39-2 was sensitive to five bacteriocins produced by 3 genera of LAB: pediocin PA-1 and pediocin Bac3 (Pediococcus), lacticin FS97 and lacticin FS56 (Lactococcus), and curvaticin FS47 (Lactobacillus). A spontaneous Bac(R) derivative of L. monocytogenes 39-2 obtained by selective recovery against lacticin FS56 provided complete resistance to the bacteriocin made by Lactococcus lactis FS56. The lacticin FS56-resistant strain of L. monocyotgenes 39-2 was also cross-resistant to curvaticin FS47 and pediocin PA-1, but not to lacticin FS97 or pediocin Bac3. The same pattern of cross-resistance was also observed with Bac(R) isolates obtained with L. monocytogenes Scott A-2. A spontaneous mutation that renders a strain cross-resistant to different bacteriocins indicates that they share a common mechanism of resistance due to similar modes of action of the bacteriocins. Spontaneous resistance was acquired to other bacteriocins (in aggregate) by following the same procedure against which the Bac(R) strain was still sensitive. In subsequent challenge assays, mixtures of bacteriocins of different modes of action provided greater inhibition than mixtures of bacteriocins of the same mode of action (as determined by our screening method). This study identifies a methodical approach to classify bacteriocins into functional groups based on mechanism of resistance (i.e., mode of action) that could be used for identifying the best mixture of bacteriocins for use as biopreservatives.

  18. The genus Macrostemum Kolenati 1859 (Trichoptera: Hydropsychidae) in the Neotropical Region: Description of two new species, taxonomic notes, distributional records and key to males.

    Science.gov (United States)

    França, Diogo; Paprocki, Henrique; Calor, Adolfo R

    2013-01-01

    The genus Macrostemum Kolenati contains 105. described species, with 15 valid species in the Neotropical region. The Adults are recognized principally by wing membranes strongly marked with dark and light colors. The Neotropical species Of Macrostemum were described based on the wing colors patterns and body morphology. In this paper we present a taxonomic study of the Neotropical species, descriptions of two new species from Brazil, distributional records and a key to males. The male of Macrostemum negrense Flint 1978 is described for the first time, Names of three Neotropical species, M. ramosum (Navás 1916), M. trigramma (Navás 1916), and M. triste (Navás 1916) are designated nomina dubia.

  19. Synergistic anti-candidal activity and mode of action of Mentha piperita essential oil and its major components.

    Science.gov (United States)

    Samber, Neha; Khan, Amber; Varma, Ajit; Manzoor, Nikhat

    2015-01-01

    Mentha piperita L. (Lamiaceae) has been used in folk medicine since antiquity. Its essential oil (mint EO) and major bioactive components have antimicrobial properties but their mechanism of action is still not clear. The present work aims to elucidate M. piperita's anti-Candida activity and mode of action. Chemical constituents of mint EO were identified by GC-MS by injecting 0.1 ml sample in a splitless mode. MIC was determined by the broth dilution method. Synergy with fluconazole (FLC) was evaluated by checkerboard assay and FICI. Mid log phase cells harvested from YPD media were used for proton extrusion measurement and the rate of glucose-induced H(+) efflux gives PM-ATPase activity. Cell membrane integrity was estimated by total ergosterol content and scanning microscopy at respective MIC and sub-MIC values. In vitro hemolytic activity was performed to rule out possible cytotoxicity of the test compounds. The MIC value of mint EO, carvone, menthol, and menthone was 225, 248, 500, and 4200 µg/ml, respectively. At their respective MICs, these compounds showed 47, 42, 35, and 29% decrease in PM-ATPase activity besides showing synergy with FLC. In case of FLC-resistant strains, the decrease in H(+) efflux was by 52, 48, 32, and 30%, a trend similar to the susceptible cases. Exposed Candida cells showed a 100% decrease in the ergosterol content, cell membrane breakage, and alterations in morphology. Our studies suggest that mint EO and its lead compounds exert antifungal activity by reducing ergosterol levels, inhibiting PM-ATPase leading to intracellular acidification, and ultimately cell death. Our results suggest that mint EO and its constituents are potential antifungal agents and need to be further investigated.

  20. Resistance mutation conserved between insects and mites unravels the benzoylurea insecticide mode of action on chitin biosynthesis.

    Science.gov (United States)

    Douris, Vassilis; Steinbach, Denise; Panteleri, Rafaela; Livadaras, Ioannis; Pickett, John Anthony; Van Leeuwen, Thomas; Nauen, Ralf; Vontas, John

    2016-12-20

    Despite the major role of chitin biosynthesis inhibitors such as benzoylureas (BPUs) in the control of pests in agricultural and public health for almost four decades, their molecular mode of action (MoA) has in most cases remained elusive. BPUs interfere with chitin biosynthesis and were thought to interact with sulfonylurea receptors that mediate chitin vesicle transport. Here, we uncover a mutation (I1042M) in the chitin synthase 1 (CHS1) gene of BPU-resistant Plutella xylostella at the same position as the I1017F mutation reported in spider mites that confers etoxazole resistance. Using a genome-editing CRISPR/Cas9 approach coupled with homology-directed repair (HDR) in Drosophila melanogaster, we introduced both substitutions (I1056M/F) in the corresponding fly CHS1 gene (kkv). Homozygous lines bearing either of these mutations were highly resistant to etoxazole and all tested BPUs, as well as buprofezin-an important hemipteran chitin biosynthesis inhibitor. This provides compelling evidence that BPUs, etoxazole, and buprofezin share in fact the same molecular MoA and directly interact with CHS. This finding has immediate effects on resistance management strategies of major agricultural pests but also on mosquito vectors of serious human diseases such as Dengue and Zika, as diflubenzuron, the standard BPU, is one of the few effective larvicides in use. The study elaborates on how genome editing can directly, rapidly, and convincingly elucidate the MoA of bioactive molecules, especially when target sites are complex and hard to reconstitute in vitro.

  1. Coexpression of nuclear receptors and histone methylation modifying genes in the testis: implications for endocrine disruptor modes of action.

    Directory of Open Access Journals (Sweden)

    Alison M Anderson

    Full Text Available BACKGROUND: Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. METHODOLOGY/PRINCIPAL FINDINGS: The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. CONCLUSIONS/SIGNIFICANCE: This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods.

  2. Cardiac disorders and mode of action of the Egyptian scorpion venom Androctonus bicolor on isolated toad’s heart

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    Mohamed A. Abdel-Rahman

    2015-10-01

    Full Text Available Scorpion venom is a complex mixture of components with various pharmacological and toxicological effects. It is characterized by the presence of a large number of toxins that specifically interact with ion channels of excitable cells. The Egyptian scorpion Androctonus bicolor belongs to the family of Buthidae and until now no information is available about the effect of its venom on cardiac muscles. Using an in vitro approach, cardiotoxicity and mode of action of A. bicolor venom on isolated toad’s heart were investigated. Direct application of scorpion venom (0.5 μg/ml into isolated toad’s heart induced a remarkable bradycardia concomitant with a protraction in the conduction time (P–R interval. In the meantime, a significant increase in the R-wave amplitude (ventricular contraction was noticed after 5 min of venom perfusion. Various cases of cardiac disorders were recorded such as sinus arrhythmias, ectopic beats and different degrees of heart block. Through using different autonomic and ion channel blockers, the possible mechanism of action of A. bicolor venom on isolated toad’s heart was revealed. The application of both atropine (4 μg/ml and verapamil (5 μg/ml could not alleviate the pronounced negative chronotropic and positive inotropic effects. Meanwhile, a significant decrease in the R-wave amplitude was observed after propranolol (5 μg/ml application. In conclusion, our findings indicate that the venom of A. bicolor directly influenced the cardiac electrical activity of toads through β-adrenergic receptors. The direct effect of this venom on cardiac tissues may significantly contribute in the development of several cardiotoxic effects following scorpion sting.

  3. Mode of action and variability in efficacy of plant essential oils showing toxicity against the poultry red mite, Dermanyssus gallinae.

    Science.gov (United States)

    George, D R; Smith, T J; Shiel, R S; Sparagano, O A E; Guy, J H

    2009-05-12

    This paper describes a series of experiments to examine the mode of action and toxicity of three plant essential oils (thyme, manuka and pennyroyal) to the poultry red mite, Dermanyssus gallinae (De Geer), a serious ectoparasitic pest of laying hens. All three oils were found to be toxic to D. gallinae in laboratory tests with LC(50), LC(90) and LC(99) values below 0.05, 0.20 and 0.30mg/cm(3), respectively, suggesting that these products may make for effective acaricides against this pest. Further experiments demonstrated that when mites were exposed to only the vapour phase of the essential oil without contact with the oil itself, mortality was consistently higher in closed arenas than in arenas open to the surrounding environment, or in control arenas. This suggests that all three essential oils were toxic to D. gallinae by fumigant action. In addition, in an experiment where mites were allowed contact with the essential oil in either open or closed arenas, mortality was always reduced in the open arenas where this was comparable to control mortality for thyme and pennyroyal essential oil treatments. This supports the findings of the previous experiment and also suggests that, with the possible exception of manuka, the selected essential oils were not toxic to D. gallinae on contact. Statistical comparisons were made between the toxicity of the selected essential oils to D. gallinae in the current work and in a previous study conducted in the same laboratory. The results demonstrated considerable variation in LC(50), LC(90) and LC(99) values. Since both the essential oils and the mites were obtained from identical sources in the two studies, it is hypothesized that this variation resulted from the use of different 'batches' of essential oil, which could have varied in chemistry and hence acaricidal activity.

  4. Evidence for a central mode of action for etoricoxib (COX-2 inhibitor) in patients with painful knee osteoarthritis.

    Science.gov (United States)

    Arendt-Nielsen, Lars; Egsgaard, Line Lindhardt; Petersen, Kristian Kjær

    2016-08-01

    The COX-2 inhibitor etoricoxib modulates the peripheral and central nociceptive mechanisms in animals. This interaction has not been studied in patients with pain. This randomized, double-blind, placebo-controlled, 2-way crossover, 4-week treatment study investigated the pain mechanisms modulated by etoricoxib in patients with painful knee osteoarthritis. Patients were randomized to group A (60 mg/d etoricoxib followed by placebo) or B (placebo followed by 60 mg/d etoricoxib). The quantitative, mechanistic pain biomarkers were pressure pain thresholds, temporal summation (TS), and conditioning pain modulation. Clinical readouts were Brief Pain Inventory, WOMAC, painDETECT questionnaire (PD-Q), and time and pain intensity during walking and stair climbing. Etoricoxib as compared with placebo significantly modulated the pressure pain thresholds (P = 0.012, localized sensitization) at the knee and leg (control site) (P = 0.025, spreading sensitization) and TS assessed from the knee (P = 0.038) and leg (P = 0.045). Conditioning pain modulation was not modulated. The Brief Pain Inventory (pain scores), PD-Q, WOMAC, and walking and stair climbing tests were all significantly improved by etoricoxib. Based on a minimum of 30% or 50% pain alleviation (day 0-day 28), responders and nonresponders were defined. The nonresponders showed a significant association between increased facilitation of TS and increased pain alleviation. None of the other parameters predicted the degree of pain alleviation. Generally, a responder to etoricoxib has the most facilitated TS. In conclusion, etoricoxib (1) modulated central pain modulatory mechanisms and (2) improved pain and function in painful osteoarthritis. Stronger facilitation of TS may indicate a better response to etoricoxib, supporting the central mode-of-action of the drug.

  5. Anticancer drug mithramycin interacts with core histones: An additional mode of action of the DNA groove binder

    Directory of Open Access Journals (Sweden)

    Amrita Banerjee

    2014-01-01

    Full Text Available Mithramycin (MTR is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of osteosarcoma. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of MTR with the integral component of chromatin – histone proteins – as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode or both histones and chromosomal DNA (dual binding mode. The present report shows that besides DNA, MTR also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the MTR–DNA interaction, association of MTR with histones does not require obligatory presence of bivalent metal ion like Mg2+. As a consequence of its ability to interact with core histones, MTR inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo. Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon MTR treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of MTR with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies.

  6. Mutant analysis in Arabidopsis provides insight into the molecular mode of action of the auxinic herbicide dicamba.

    Directory of Open Access Journals (Sweden)

    Cynthia Gleason

    Full Text Available Herbicides that mimic the natural auxin indole-3-acetic acid are widely used in weed control. One common auxin-like herbicide is dicamba, but despite its wide use, plant gene responses to dicamba have never been extensively studied. To further understand dicamba's mode of action, we utilized Arabidopsis auxin-insensitive mutants and compared their sensitivity to dicamba and the widely-studied auxinic herbicide 2,4-dichlorophenoxyacetic acid (2,4-D. The mutant axr4-2, which has disrupted auxin transport into cells, was resistant to 2,4-D but susceptible to dicamba. By comparing dicamba resistance in auxin signalling F-box receptor mutants (tir1-1, afb1, afb2, afb3, and afb5, only tir1-1 and afb5 were resistant to dicamba, and this resistance was additive in the double tir1-1/afb5 mutant. Interestingly, tir1-1 but not afb5 was resistant to 2,4-D. Whole genome analysis of dicamba-induced gene expression showed that 10 hours after application, dicamba stimulated many stress-responsive and signalling genes, including those involved in biosynthesis or signalling of auxin, ethylene, and abscisic acid (ABA, with TIR1 and AFB5 required for the dicamba-responsiveness of some genes. Research into dicamba-regulated gene expression and the selectivity of auxin receptors has provided molecular insight into dicamba-regulated signalling and could help in the development of novel herbicide resistance in crop plants.

  7. Mechanistic insights into mode of action of potent natural antagonists of BACE-1 for checking Alzheimer’s plaque pathology

    Energy Technology Data Exchange (ETDEWEB)

    Dhanjal, Jaspreet Kaur [School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067 (India); Goyal, Sukriti [Apaji Institute of Mathematics and Applied Computer Technology, Banasthali University, Tonk 304022, Rajasthan (India); Sharma, Sudhanshu [Department of Biotechnology, Delhi Technological University, New Delhi 110042 (India); Hamid, Rabia [Department of Biochemistry, University of Kashmir, Srinagar 190006 (India); Grover, Abhinav, E-mail: abhinavgr@gmail.com [School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067 (India)

    2014-01-17

    Highlights: •Accumulation of Aβ plaques is one of the major pathology associated with Alzheimer’s disease. •Inhibition of β-Secretase or BACE-1 offers a viable prospect to check the growth of these plaques. •A large virtual dataset of natural compounds was screened against BACE-1. •Top two hits were analyzed for thermodynamic and structural stability using MD simulations. •Their detailed binding mode of actions were elucidated. -- Abstract: Alzheimer’s is a neurodegenerative disorder resulting in memory loss and decline in cognitive abilities. Accumulation of extracellular beta amyloidal plaques is one of the major pathology associated with this disease. β-Secretase or BACE-1 performs the initial and rate limiting step of amyloidic pathway in which 37–43 amino acid long peptides are generated which aggregate to form plaques. Inhibition of this enzyme offers a viable prospect to check the growth of these plaques. Numerous efforts have been made in recent years for the generation of BACE-1 inhibitors but many of them failed during the preclinical or clinical trials due to drug related or drug induced toxicity. In the present work, we have used computational methods to screen a large dataset of natural compounds to search for small molecules having BACE-1 inhibitory activity with low toxicity to normal cells. Molecular dynamics simulations were performed to analyze molecular interactions between the screened compounds and the active residues of the enzyme. Herein, we report two natural compounds of inhibitory nature active against β-secretase enzyme of amyloidic pathway and are potent lead molecules against Alzheimer’s disease.

  8. Antifungal activity, mode of action and anti-biofilm effects of Laurus nobilis Linnaeus essential oil against Candida spp.

    Science.gov (United States)

    Peixoto, Larissa Rangel; Rosalen, Pedro Luiz; Ferreira, Gabriela Lacet Silva; Freires, Irlan Almeida; de Carvalho, Fabíola Galbiatti; Castellano, Lúcio Roberto; de Castro, Ricardo Dias

    2017-01-01

    The present study demonstrated the antifungal potential of the chemically characterized essential oil (EO) of Laurus nobilis L. (bay laurel) against Candida spp. biofilm adhesion and formation, and further established its mode of action on C. albicans. L. nobilis EO was obtained and tested for its minimum inhibitory and fungicidal concentrations (MIC/MFC) against Candida spp., as well as for interaction with cell wall biosynthesis and membrane ionic permeability. Then we evaluated its effects on the adhesion, formation, and reduction of 48hC. albicans biofilms. The EO phytochemical profile was determined by gas chromatography coupled to mass spectrometry (GC/MS). The MIC and MFC values of the EO ranged from (250 to 500) μg/mL. The MIC values increased in the presence of sorbitol (osmotic protector) and ergosterol, which indicates that the EO may affect cell wall biosynthesis and membrane ionic permeability, respectively. At 2 MIC the EO disrupted initial adhesion of C. albicans biofilms (p0.05). When applied for 1min, every 8h, for 24h and 48h, the EO reduced the amount of C. albicans mature biofilm with no difference in relation to nystatin (p>0.05). The phytochemical analysis identified isoeugenol as the major compound (53.49%) in the sample. L. nobilis EO has antifungal activity probably due to monoterpenes and sesquiterpenes in its composition. This EO may affect cell wall biosynthesis and membrane permeability, and showed deleterious effects against C. albicans biofilms. Copyright © 2016. Published by Elsevier Ltd.

  9. A Microplate Growth Inhibition Assay for Screening Bacteriocins against Listeria monocytogenes to Differentiate Their Mode-of-Action.

    Science.gov (United States)

    Vijayakumar, Paul Priyesh; Muriana, Peter M

    2015-06-11

    Lactic acid bacteria (LAB) have historically been used in food fermentations to preserve foods and are generally-recognized-as-safe (GRAS) by the FDA for use as food ingredients. In addition to lactic acid; some strains also produce bacteriocins that have been proposed for use as food preservatives. In this study we examined the inhibition of Listeria monocytogenes 39-2 by neutralized and non-neutralized bacteriocin preparations (Bac+ preps) produced by Lactobacillus curvatus FS47; Lb. curvatus Beef3; Pediococcus acidilactici Bac3; Lactococcus lactis FLS1; Enterococcus faecium FS56-1; and Enterococcus thailandicus FS92. Activity differences between non-neutralized and neutralized Bac+ preps in agar spot assays could not readily be attributed to acid because a bacteriocin-negative control strain was not inhibitory to Listeria in these assays. When neutralized and non-neutralized Bac+ preps were used in microplate growth inhibition assays against L. monocytogenes 39-2 we observed some differences attributed to acid inhibition. A microplate growth inhibition assay was used to compare inhibitory reactions of wild-type and bacteriocin-resistant variants of L. monocytogenes to differentiate bacteriocins with different modes-of-action (MOA) whereby curvaticins FS47 and Beef3, and pediocin Bac3 were categorized to be in MOA1; enterocins FS92 and FS56-1 in MOA2; and lacticin FLS1 in MOA3. The microplate bacteriocin MOA assay establishes a platform to evaluate the best combination of bacteriocin preparations for use in food applications as biopreservatives against L. monocytogenes.

  10. The mode of action of isocyanide in three aquatic organisms, Balanus amphitrite, Bugula neritina and Danio rerio.

    Directory of Open Access Journals (Sweden)

    Yi-Fan Zhang

    Full Text Available Isocyanide is a potential antifouling compound in marine environments. In this study, we investigated its mode of action in three aquatic organisms. Two of them, the bryozoan Bugula neritina and the barnacle Balanus amphitrite, are major marine fouling invertebrates, and the other organism is the non-target species zebrafish Danio rerio. In the swimming larvae of B. neritina, isocyanide did not affect the total attachment rate (≤50 µg ml(-1, but it did change the attachment site by increasing the percentage of attachment on the bottom of the container rather than on the wall or air-water inter-surface. Isocyanide binds several proteins in B. neritina as identified via SDS-PAGE-LC-MS/MS: 1 a 30 kD protein band containing two proteins similar to voltage dependent anion channels (VDAC, which control the direct coupling of the mitochondrial matrix to the energy maintenance of the cytosol and the release of apoptogenic factors from mitochondria of mammalian cells; and 2 an unknown 39 kD protein. In B. amphitrite cyprids, the isocyanide binding protein were 1 a protein similar to NADH-ubiquinone oxidoreductase, which is the "entry enzyme" of oxidative phosphorylation in mitochondria; and 2 cytochrome P450. In Danio rerio embryos, isocyanide caused "wavy" notochords, hydrocephalus, pericardial edema, poor blood circulation, and defects in pigmentation and hematopoiesis, which phenocopied copper deficiency. This is the first report on isocyanide binding proteins in fouling organisms, as well as the first description of its phenotype and potential toxicology in zebrafish.

  11. The dual role of serotonin in defense and the mode of action of antidepressants on generalized anxiety and panic disorders.

    Science.gov (United States)

    Graeff, Frederico G; Zangrossi, Hélio

    2010-09-01

    Antidepressants are widely used to treat several anxiety disorders, among which generalized anxiety disorder (GAD) and panic disorder (PD). Serotonin (5-HT) is believed to play a key role in the mode of action of these agents, a major question being which pathways and receptor subtypes are involved in each type of anxiety disorder. The dual role of 5-HT in defense hypothesis assumes that 5-HT facilitates defensive responses to potential threat, like inhibitory avoidance, related to anxiety, whereas it inhibits defensive responses to proximal danger, like one-way escape, related to panic. The former action would be exerted at the forebrain, chiefly the amygdala and medial prefrontal cortex (PFC), while the latter would be exerted at the dorsal periaqueductal gray (DPAG) matter of the midbrain. The present review is focused on studies designed to test this hypothesis, performed in animal models of anxiety and panic, as well as in human experimental anxiety tests. The reviewed results suggest that chronic, but not acute, administration of antidepressants suppress panic attacks by increasing the release of 5-HT and enhancing the responsivity of post-synaptic 5-HT1A and 5-HT2A receptors in the DPAG. The attenuation of generalized anxiety, also caused by the same drug treatment, would be due to the desensitization of 5-HT2C receptors and, less certainly, to increased stimulation of 5-HT1A receptors in forebrain structures. This action would result in less activation of the amygdala, medial PFC and insula by warning signals, as shown by the reviewed results obtained with functional neuroimaging in healthy volunteers and patients with anxiety disorders.

  12. Differential Gel Electrophoresis (DIGE) Evaluation of Naphthoimidazoles Mode of Action: A Study in Trypanosoma cruzi Bloodstream Trypomastigotes

    Science.gov (United States)

    Brunoro, Giselle Villa Flor; Faça, Vitor Marcel; Caminha, Marcelle Almeida; Ferreira, André Teixeira da Silva; Trugilho, Monique; de Moura, Kelly Cristina Gallan; Perales, Jonas; Valente, Richard Hemmi; Menna-Barreto, Rubem Figueiredo Sadok

    2016-01-01

    Background The obligate intracellular protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected illness affecting millions of people in Latin America that recently entered non-endemic countries through immigration, as a consequence of globalization. The chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. Our group has been studying the trypanocidal effects of naturally occurring quinones and their derivatives, and naphthoimidazoles derived from β-lapachone N1, N2 and N3 were the most active. To assess the molecular mechanisms of action of these compounds, we applied proteomic techniques to analyze treated bloodstream trypomastigotes, which are the clinically relevant stage of the parasite. Methodology/Principal Findings The approach consisted of quantification by 2D-DIGE followed by MALDI-TOF/TOF protein identification. A total of 61 differentially abundant protein spots were detected when comparing the control with each N1, N2 or N3 treatment, for 34 identified spots. Among the differentially abundant proteins were activated protein kinase C receptor, tubulin isoforms, asparagine synthetase, arginine kinase, elongation factor 2, enolase, guanine deaminase, heat shock proteins, hypothetical proteins, paraflagellar rod components, RAB GDP dissociation inhibitor, succinyl-CoA ligase, ATP synthase subunit B and methionine sulfoxide reductase. Conclusion/Significance Our results point to different modes of action for N1, N2 and N3, which indicate a great variety of metabolic pathways involved and allow for novel perspectives on the development of trypanocidal agents. PMID:27551855

  13. A novel mode-of-action mediated by the fetal muscle nicotinic acetylcholine receptor resulting in developmental toxicity in rats.

    Science.gov (United States)

    Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Terry, Claire; Millar, Neil S; Zablotny, Carol L; Gibb, Alasdair; Marshall, Valerie; Collins, Toby; Carney, Edward W; Billington, Richard

    2012-06-01

    Sulfoxaflor (X11422208), a novel agricultural molecule, induced fetal effects (forelimb flexure, hindlimb rotation, and bent clavicle) and neonatal death in rats at high doses (≥ 400 ppm in diet); however, no such effects occurred in rabbit dietary studies despite achieving similar maternal and fetal plasma exposure levels. Mode-of-action (MoA) studies were conducted to test the hypothesis that the effects in rats had a single MoA induced by sulfoxaflor agonism on the fetal rat muscle nicotinic acetylcholine receptor (nAChR). The studies included cross-fostering and critical windows of exposure studies in rats, fetal ((α1)(2)β1γδ) and adult ((α1)(2)β1δε) rat and human muscle nAChR in vitro agonism experiments, and neonatal rat phrenic nerve-hemidiaphragm contracture studies. The weight of evidence from these studies supported a novel MoA where sulfoxaflor is an agonist to the fetal, but not adult, rat muscle nAChR and that prolonged agonism on this receptor in fetal/neonatal rats causes sustained striated muscle contracture resulting in concomitant reduction in muscle responsiveness to physiological nerve stimulation. Fetal effects were inducible with as little as 1 day of exposure at the end of gestation, but were rapidly reversible after birth, consistent with a pharmacological MoA. With respect to human relevance, sulfoxaflor was shown to have no agonism on human fetal or adult muscle nAChRs. Taken together, the data support the hypothesis that the developmental effects of sulfoxaflor in rats are mediated via sustained agonism on the fetal muscle nAChR during late fetal development and are considered not relevant to humans.

  14. The Mode of Action of Isocyanide in Three Aquatic Organisms, Balanus amphitrite, Bugula neritina and Danio rerio

    KAUST Repository

    Zhang, Yi-Fan

    2012-09-18

    Isocyanide is a potential antifouling compound in marine environments. In this study, we investigated its mode of action in three aquatic organisms. Two of them, the bryozoan Bugula neritina and the barnacle Balanus amphitrite, are major marine fouling invertebrates, and the other organism is the non-target species zebrafish Danio rerio. In the swimming larvae of B. neritina, isocyanide did not affect the total attachment rate (≤50 µg ml^(−1)), but it did change the attachment site by increasing the percentage of attachment on the bottom of the container rather than on the wall or air-water inter-surface. Isocyanide binds several proteins in B. neritina as identified via SDS-PAGE-LC-MS/MS: 1) a 30 kD protein band containing two proteins similar to voltage dependent anion channels (VDAC), which control the direct coupling of the mitochondrial matrix to the energy maintenance of the cytosol and the release of apoptogenic factors from mitochondria of mammalian cells; and 2) an unknown 39 kD protein. In B. amphitrite cyprids, the isocyanide binding protein were 1) a protein similar to NADH-ubiquinone oxidoreductase, which is the “entry enzyme” of oxidative phosphorylation in mitochondria; and 2) cytochrome P450. In Danio rerio embryos, isocyanide caused “wavy” notochords, hydrocephalus, pericardial edema, poor blood circulation, and defects in pigmentation and hematopoiesis, which phenocopied copper deficiency. This is the first report on isocyanide binding proteins in fouling organisms, as well as the first description of its phenotype and potential toxicology in zebrafish.

  15. Iodine and disinfection: theoretical study on mode of action, efficiency, stability, and analytical aspects in the aqueous system.

    Science.gov (United States)

    Gottardi, W

    1999-05-01

    Although they have been in use for nearly 170 years, the mode of action of iodine-based disinfectants is not yet clearly understood, as is manifested, for example, in diverging judgements about the relevance of the individual iodine species. Although studies based on calculated equilibrium concentrations in pure iodine solutions have already been done, there is a lack of knowledge about iodine solutions in the presence of additional iodide which would be of intrinsic importance for disinfection practice. Therefore, a re-calculation was undertaken considering variations of this parameter in the pH range 0-14. The presented calculations concern fresh iodine solutions not affected by disproportionation (iodate formation) and provide information about the equilibrium concentrations of the species I, I2, I3, I5-, I6(2-), HOI, O1-, HI2O-, IO2- and H2OI+. Additional iodide and the pH value have a very pronounced influence on the individual equilibrium concentrations (several powers of ten); hence, conditions can be indicated where the number of species of virtual importance is drastically reduced. In the most common case with iodine in the presence of additional iodide at pH iodine cation H2OI+, frequently quoted as an active agent in disinfection, is without any relevance under the conditions occurring in practice, as are IO- and HI2O- which become important only at pH > 10. The stability problem (i.e. rate of iodate formation) arising at pH > 6 can be reduced to hypoiodous acid, as manifested in the simple rate law d[IO3]/dt = 0.25 [HOI]3/[H+] which allows an estimation of stability under weakly alkaline conditions. The results of this study allow us to deduce general qualities of aqueous iodine solutions, such as reactivity, stability, and analytical aspects, and to estimate major disinfection-orientated properties such as microbicidal activity, irritation, and incorporation effects. Though the calculations consider primarily preparations devoid of polymeric organic

  16. Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Stein, Jürgen [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Department of Internal Medicine, Sachsenhausen Hospital, Frankfurt am Main (Germany); Fürst, Robert [Institute of Pharmaceutical Biology, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Steinhilber, Dieter [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Ulrich-Rückert, Sandra, E-mail: sandra.ulrich@em.uni-frankfurt.de [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany)

    2015-08-15

    (Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC{sub 50} values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G{sub 2}/M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like

  17. Determining the mode of action of anti-mycobacterial C17 diyne natural products using expression profiling: evidence for fatty acid biosynthesis inhibition

    OpenAIRE

    Li, Haoxin; Cowie, Andrew; JOHNSON, JOHN A.; Webster, Duncan; Martyniuk, Christopher J.; Gray, Christopher A.

    2016-01-01

    Background The treatment of microbial infections is becoming increasingly challenging because of limited therapeutic options and the growing number of pathogenic strains that are resistant to current antibiotics. There is an urgent need to identify molecules with novel modes of action to facilitate the development of new and more effective therapeutic agents. The anti-mycobacterial activity of the C17 diyne natural products falcarinol and panaxydol has been described previously; however, thei...

  18. Thymus vulgaris essential oil and thymol against Alternaria alternata (Fr.) Keissler: effects on growth, viability, early infection and cellular mode of action.

    Science.gov (United States)

    Perina, Fabiano J; Amaral, Douglas C; Fernandes, Rafael S; Labory, Claudia Rg; Teixeira, Glauco A; Alves, Eduardo

    2015-10-01

    In initial assays, Thymus vulgaris essential oil (TEO) has demonstrated activity against several plant-pathogenic fungi and has reduced the fungal diseases to levels comparable with commercial fungicides. Thus, the goal of this work was to identify the mode of action in fungi of TEO and its major compound thymol (TOH) at the cellular level using an ultrastructure approach. TEO from leaves and TOH had minimum inhibitory concentrations (MICs) of 500 and 250 µg mL(-1) respectively against A. alternata; under the same conditions, MIC for a commercial fungicide was 1250 µg mL(-1) . Ultrastructure analysis showed that TOH phenolic substance prevented fungal growth, reduced fungal viability and prevented the penetration in fruits by a cell wall/plasma membrane interference mode of action with organelles targeted for destruction in the cytoplasm. Such mode of action differs from protective and preventive-curative commercial fungicides used as pattern control. These findings suggest that TOH was responsible for the antifungal activity of TEO. Therefore, both the essential oil and its major substance have potential for use in the development of new phenolic structures and analogues to control Alternaria brown spot disease caused by Alternaria alternata. © 2014 Society of Chemical Industry.

  19. Structure-Activity Relationships of the Antimicrobial Peptide Arasin 1 — And Mode of Action Studies of the N-Terminal, Proline-Rich Region

    Science.gov (United States)

    Paulsen, Victoria S.; Blencke, Hans-Matti; Benincasa, Monica; Haug, Tor; Eksteen, Jacobus J.; Styrvold, Olaf B.; Scocchi, Marco; Stensvåg, Klara

    2013-01-01

    Arasin 1 is a 37 amino acid long proline-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. In this work the active region of arasin 1 was identified through structure-activity studies using different peptide fragments derived from the arasin 1 sequence. The pharmacophore was found to be located in the proline/arginine-rich NH2 terminus of the peptide and the fragment arasin 1(1–23) was almost equally active to the full length peptide. Arasin 1 and its active fragment arasin 1(1–23) were shown to be non-toxic to human red blood cells and arasin 1(1–23) was able to bind chitin, a component of fungal cell walls and the crustacean shell. The mode of action of the fully active N-terminal arasin 1(1–23) was explored through killing kinetic and membrane permeabilization studies. At the minimal inhibitory concentration (MIC), arasin 1(1–23) was not bactericidal and had no membrane disruptive effect. In contrast, at concentrations of 5×MIC and above it was bactericidal and interfered with membrane integrity. We conclude that arasin 1(1–23) has a different mode of action than lytic peptides, like cecropin P1. Thus, we suggest a dual mode of action for arasin 1(1–23) involving membrane disruption at peptide concentrations above MIC, and an alternative mechanism of action, possibly involving intracellular targets, at MIC. PMID:23326415

  20. Structure-activity relationships of the antimicrobial peptide arasin 1 - and mode of action studies of the N-terminal, proline-rich region.

    Directory of Open Access Journals (Sweden)

    Victoria S Paulsen

    Full Text Available Arasin 1 is a 37 amino acid long proline-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. In this work the active region of arasin 1 was identified through structure-activity studies using different peptide fragments derived from the arasin 1 sequence. The pharmacophore was found to be located in the proline/arginine-rich NH(2 terminus of the peptide and the fragment arasin 1(1-23 was almost equally active to the full length peptide. Arasin 1 and its active fragment arasin 1(1-23 were shown to be non-toxic to human red blood cells and arasin 1(1-23 was able to bind chitin, a component of fungal cell walls and the crustacean shell. The mode of action of the fully active N-terminal arasin 1(1-23 was explored through killing kinetic and membrane permeabilization studies. At the minimal inhibitory concentration (MIC, arasin 1(1-23 was not bactericidal and had no membrane disruptive effect. In contrast, at concentrations of 5×MIC and above it was bactericidal and interfered with membrane integrity. We conclude that arasin 1(1-23 has a different mode of action than lytic peptides, like cecropin P1. Thus, we suggest a dual mode of action for arasin 1(1-23 involving membrane disruption at peptide concentrations above MIC, and an alternative mechanism of action, possibly involving intracellular targets, at MIC.

  1. Structure-activity relationships of the antimicrobial peptide arasin 1 - and mode of action studies of the N-terminal, proline-rich region.

    Science.gov (United States)

    Paulsen, Victoria S; Blencke, Hans-Matti; Benincasa, Monica; Haug, Tor; Eksteen, Jacobus J; Styrvold, Olaf B; Scocchi, Marco; Stensvåg, Klara

    2013-01-01

    Arasin 1 is a 37 amino acid long proline-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. In this work the active region of arasin 1 was identified through structure-activity studies using different peptide fragments derived from the arasin 1 sequence. The pharmacophore was found to be located in the proline/arginine-rich NH(2) terminus of the peptide and the fragment arasin 1(1-23) was almost equally active to the full length peptide. Arasin 1 and its active fragment arasin 1(1-23) were shown to be non-toxic to human red blood cells and arasin 1(1-23) was able to bind chitin, a component of fungal cell walls and the crustacean shell. The mode of action of the fully active N-terminal arasin 1(1-23) was explored through killing kinetic and membrane permeabilization studies. At the minimal inhibitory concentration (MIC), arasin 1(1-23) was not bactericidal and had no membrane disruptive effect. In contrast, at concentrations of 5×MIC and above it was bactericidal and interfered with membrane integrity. We conclude that arasin 1(1-23) has a different mode of action than lytic peptides, like cecropin P1. Thus, we suggest a dual mode of action for arasin 1(1-23) involving membrane disruption at peptide concentrations above MIC, and an alternative mechanism of action, possibly involving intracellular targets, at MIC.

  2. Insecticidal genes of Yersinia spp.: taxonomical distribution, contribution to toxicity towards Manduca sexta and Galleria mellonella, and evolution

    Directory of Open Access Journals (Sweden)

    Schachtner Joachim

    2008-12-01

    Full Text Available Abstract Background Toxin complex (Tc proteins termed TcaABC, TcdAB, and TccABC with insecticidal activity are present in a variety of bacteria including the yersiniae. Results The tc gene sequences of thirteen Yersinia strains were compared, revealing a high degree of gene order conservation, but also remarkable differences with respect to pseudogenes, sequence variability and gene duplications. Outside the tc pathogenicity island (tc-PAIYe of Y. enterocolitica strain W22703, a pseudogene (tccC2'/3' encoding proteins with homology to TccC and similarity to tyrosine phosphatases at its C-terminus was identified. PCR analysis revealed the presence of the tc-PAIYe and of tccC2'/3'-homologues in all biotype 2–5 strains tested, and their absence in most representatives of biotypes 1A and 1B. Phylogenetic analysis of 39 TccC sequences indicates the presence of the tc-PAIYe in an ancestor of Yersinia. Oral uptake experiments with Manduca sexta revealed a higher larvae lethality of Yersinia strains harbouring the tc-PAIYe in comparison to strains lacking this island. Following subcutaneous infection of Galleria mellonella larvae with five non-human pathogenic Yersinia spp. and four Y. enterocolitica strains, we observed a remarkable variability of their insecticidal activity ranging from 20% (Y. kristensenii to 90% (Y. enterocolitica strain 2594 dead larvae after five days. Strain W22703 and its tcaA deletion mutant did not exhibit a significantly different toxicity towards G. mellonella. These data confirm a role of TcaA upon oral uptake only, and suggest the presence of further insecticidal determinants in Yersinia strains formerly unknown to kill insects. Conclusion This study investigated the tc gene distribution among yersiniae and the phylogenetic relationship between TccC proteins, thus contributing novel aspects to the current discussion about the evolution of insecticidal toxins in the genus Yersinia. The toxic potential of several Yersinia

  3. Asteroid taxonomic signatures from photometric phase curves

    CERN Document Server

    Oszkiewicz, D A; Wasserman, L H; Muinonen, K; Penttilä, A; Pieniluoma, T; Trilling, D E; Thomas, C A

    2012-01-01

    We explore the correlation between an asteroid's taxonomy and photometric phase curve using the H, G12 photometric phase function, with the shape of the phase function described by the single parameter G12. We explore the usability of G12 in taxonomic classification for individual objects, asteroid families, and dynamical groups. We conclude that the mean values of G12 for the considered taxonomic complexes are statistically different, and also discuss the overall shape of the G12 distribution for each taxonomic complex. Based on the values of G12 for about half a million asteroids, we compute the probabilities of C, S, and X complex membership for each asteroid. For an individual asteroid, these probabilities are rather evenly distributed over all of the complexes, thus preventing meaningful classification. We then present and discuss the G12 distributions for asteroid families, and predict the taxonomic complex preponderance for asteroid families given the distribution of G12 in each family. For certain ast...

  4. A report on Lecanidae (Rotifera: Monogononta) from Andhra Pradesh, India, including six new distribution records with notes on their contemporary taxonomic nomenclature

    OpenAIRE

    S. Z. Siddiqi; M. Paingankar; M. Karuthapandi

    2013-01-01

    The Lecane-species complex taxonomy the world over, witnessed a state of flux, causing confusion and controversies, among world taxonomists over the treatment of various subgenera, taxa and sub and or infraspecific categories of the species rich genus Lecane Nitzsch 1827, on the basis of structure/shape of key, morphological features like foot/toes, lorica, etc. The taxonomic scenario in India, relying heavily on the classical, divergent taxonomic approaches presented a picture of more chaos/...

  5. The Mode of Action of the Bacillus thuringiensis Vegetative Insecticidal Protein Vip3A Differs from That of Cry1Ab δ-Endotoxin

    OpenAIRE

    Lee, Mi Kyong; Walters, Frederick S.; Hart, Hope; Palekar, Narendra; Chen, Jeng-Shong

    2003-01-01

    The Vip3A protein, secreted by Bacillus spp. during the vegetative stage of growth, represents a new family of insecticidal proteins. In our investigation of the mode of action of Vip3A, the 88-kDa Vip3A full-length toxin (Vip3A-F) was proteolytically activated to an approximately 62-kDa core toxin either by trypsin (Vip3A-T) or lepidopteran gut juice extracts (Vip3A-G). Biotinylated Vip3A-G demonstrated competitive binding to lepidopteran midgut brush border membrane vesicles (BBMV). Further...

  6. Partial Purification and Characterization of the Mode of Action of Enterocin S37: A Bacteriocin Produced by Enterococcus faecalis S37 Isolated from Poultry Feces

    Directory of Open Access Journals (Sweden)

    Y. Belguesmia

    2010-01-01

    Full Text Available The aim of this research was to purify and characterize the mode of action of enterocin S37, a bacteriocin produced by Enterococcus faecalis S37, a strain recently isolated from the chicken feces. Enterocin S37 has a molecular weight comprised between 4 and 5 kDa. It remained active after 1 h at 80oC and at pH values ranging from 4.0 to 9.0. Furthermore, cell-free supernatant of Enterococcus faecalis S37 and purified enterocin S37 were active against Gram-positive bacteria including Listeria monocytogenes EGDe, L. innocua F, Enterococcus faecalis JH2-2, and Lactobacillus brevis F145. The purification of enterocin S37 was performed by ammonium sulfate precipitation followed up by hydrophobic-interaction chromatography procedures. Treatment of enterocin S37 with proteinase K, -chymotrypsin, and papain confirmed its proteinaceous nature, while its treatment with lysozyme and lipase resulted in no alteration of activity. Enterocin S37 is hydrophobic, anti-Listeria and likely acting by depletion of intracellular K+ ions upon action on KATP channels. This study contributed to gain more insights into the mode of action of enterocins.

  7. Biological control of the cucurbit powdery mildew pathogen Podosphaera xanthii by means of the epiphytic fungus Pseudozyma aphidis and parasitism as a mode of action.

    Science.gov (United States)

    Gafni, Aviva; Calderon, Claudia E; Harris, Raviv; Buxdorf, Kobi; Dafa-Berger, Avis; Zeilinger-Reichert, Einat; Levy, Maggie

    2015-01-01

    Epiphytic yeasts, which colonize plant surfaces, may possess activity that can be harnessed to help plants defend themselves against various pathogens. Due to their unique characteristics, epiphytic yeasts belonging to the genus Pseudozyma hold great potential for use as biocontrol agents. We identified a unique, biologically active isolate of the epiphytic yeast Pseudozyma aphidis that is capable of inhibiting Botrytis cinerea via a dual mode of action, namely induced resistance and antibiosis. Here, we show that strain L12 of P. aphidis can reduce the severity of powdery mildew caused by Podosphaera xanthii on cucumber plants with an efficacy of 75%. Confocal and scanning electron microscopy analyses demonstrated P. aphidis proliferation on infected tissue and its production of long hyphae that parasitize the powdery mildew hyphae and spores as an ectoparasite. We also show that crude extract of P. aphidis metabolites can inhibit P. xanthii spore germination in planta. Our results suggest that in addition to its antibiosis as mode of action, P. aphidis may also act as an ectoparasite on P. xanthii. These results indicate that P. aphidis strain L12 has the potential to control powdery mildew.

  8. Biological control of the cucurbit powdery mildew pathogen Podosphaera xanthii by means of the epiphytic fungus Pseudozyma aphidis and parasitism as a mode of action

    Directory of Open Access Journals (Sweden)

    Aviva eGafni

    2015-03-01

    Full Text Available Epiphytic yeasts, which colonize plant surfaces, may possess activity that can be harnessed to help plants defend themselves against various pathogens. Due to their unique characteristics, epiphytic yeasts belonging to the genus Pseudozyma hold great potential for use as biocontrol agents. We identified a unique, biologically active isolate of the epiphytic yeast Pseudozyma aphidis that is capable of inhibiting Botrytis cinerea via a dual mode of action, namely induced resistance and antibiosis. Here, we show that strain L12 of P. aphidis can reduce the severity of powdery mildew caused by Podosphaera xanthii on cucumber plants with an efficacy of 75%. Confocal and scanning electron microscopy analyses demonstrated P. aphidis proliferation on infected tissue and its production of long hyphae that parasitize the powdery mildew hyphae and spores as an ectoparasite. We also show that crude extract of P. aphidis metabolites can inhibit P. xanthii spore germination in planta. Our results suggest that in addition to its antibiosis mode of action, P. aphidis may also act as an ectoparasite on P. xanthii. These results indicate that P. aphidis strain L12 has the potential to control powdery mildew.

  9. Mode of Action: Oxalate Crystal-Induced Renal Tubule Degeneration and Glycolic Acid-Induced Dysmorphogenesis—Renal and Developmental Effects of Ethylene Glycol

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; Meek, M E.; Carney, E W.

    2005-10-01

    Ethylene glycol can cause both renal and developmental toxicity, with metabolism playing a key role in the mode of action (MOA) for each form of toxicity. Renal toxicity is ascribed to the terminal metabolite oxalic acid, which precipitates in the kidney in the form of calcium oxalate crystals and is believed to cause physical damage to the renal tubules. The human relevance of the renal toxicity of ethylene glycol is indicated by the similarity between animals and humans of metabolic pathways, the observation of renal oxalate crystals in toxicity studies in experimental animals and human poisonings, and cases of human kidney and bladder stones related to dietary oxalates and oxalate precursors. High-dose gavage exposures to ethylene glycol also cause axial skeletal defects in rodents (but not rabbits), with the intermediary metabolite, glycolic acid, identified as the causative agent. However, the mechanism by which glycolic acid perturbs development has not been investigated sufficiently to develop a plausible hypothesis of mode of action, nor have any cases of ethylene glycol-induced developmental effects been reported in humans. Given this, and the variations in sensitivity between animal species in response, the relevance to humans of ethylene glycol-induced developmental toxicity in animals is unknown at this time.

  10. The economic importance of acaricides in the control of phytophagous mites and an update on recent acaricide mode of action research.

    Science.gov (United States)

    Van Leeuwen, Thomas; Tirry, Luc; Yamamoto, Atsushi; Nauen, Ralf; Dermauw, Wannes

    2015-06-01

    Acaricides are one of the cornerstones of an efficient control program for phytophagous mites. An analysis of the global acaricide market reveals that spider mites such as Tetranychus urticae, Panonychus citri and Panonychus ulmi are by far the most economically important species, representing more than 80% of the market. Other relevant mite groups are false spider mites (mainly Brevipalpus), rust and gall mites and tarsonemid mites. Acaricides are most frequently used in vegetables and fruits (74% of the market), including grape vines and citrus. However, their use is increasing in major crops where spider mites are becoming more important, such as soybean, cotton and corn. As revealed by a detailed case study of the Japanese market, major shifts in acaricide use are partially driven by resistance development and the commercial availability of compounds with novel mode of action. The importance of the latter cannot be underestimated, although some compounds are successfully used for more than 30 years. A review of recent developments in mode of action research is presented, as such knowledge is important for devising resistance management programs. This includes spirocyclic keto-enols as inhibitors of acetyl-CoA carboxylase, the carbazate bifenazate as a mitochondrial complex III inhibitor, a novel class of complex II inhibitors, and the mite growth inhibitors hexythiazox, clofentezine and etoxazole that interact with chitin synthase I.

  11. Partial Purification and Characterization of the Mode of Action of Enterocin S37: A Bacteriocin Produced by Enterococcus faecalis S37 Isolated from Poultry Feces

    Science.gov (United States)

    Belguesmia, Y.; Choiset, Y.; Prévost, H.; Dalgalarrondo, M.; Chobert, J.-M.; Drider, D.

    2010-01-01

    The aim of this research was to purify and characterize the mode of action of enterocin S37, a bacteriocin produced by Enterococcus faecalis S37, a strain recently isolated from the chicken feces. Enterocin S37 has a molecular weight comprised between 4 and 5 kDa. It remained active after 1 h at 80oC and at pH values ranging from 4.0 to 9.0. Furthermore, cell-free supernatant of Enterococcus faecalis S37 and purified enterocin S37 were active against Gram-positive bacteria including Listeria monocytogenes EGDe, L. innocua F, Enterococcus faecalis JH2-2, and Lactobacillus brevis F145. The purification of enterocin S37 was performed by ammonium sulfate precipitation followed up by hydrophobic-interaction chromatography procedures. Treatment of enterocin S37 with proteinase K, α-chymotrypsin, and papain confirmed its proteinaceous nature, while its treatment with lysozyme and lipase resulted in no alteration of activity. Enterocin S37 is hydrophobic, anti-Listeria and likely acting by depletion of intracellular K+ ions upon action on KATP channels. This study contributed to gain more insights into the mode of action of enterocins. PMID:20811593

  12. Assessment of the mode of action of polyhexamethylene biguanide against Listeria innocua by Fourier transformed infrared spectroscopy and fluorescence anisotropy analysis.

    Science.gov (United States)

    Chadeau, Elise; Dumas, Emilie; Adt, Isabelle; Degraeve, Pascal; Noël, Claude; Girodet, Christophe; Oulahal, Nadia

    2012-12-01

    Polyhexamethylene biguanide (PHMB) is a cationic biocide. The antibacterial mode of action of PHMB (at concentrations not exceeding its minimal inhibitory concentration) upon Listeria innocua LRGIA 01 was investigated by Fourier transformed infrared spectroscopy and fluorescence anisotropy analysis. Fourier transformed infrared spectra of bacteria treated with or without PHMB presented some differences in the lipids region: the CH(2)/CH(3) (2924 cm(-1)/2960 cm(-1)) band areas ratio significantly increased in the presence of PHMB. Since this ratio generally reflects membrane phospholipids and membrane microenvironment of the cells, these results suggest that PHMB molecules interact with membrane phospholipids and, thus, affect membrane fluidity and conformation. To assess the hypothesis of PHMB interaction with L. innocua membrane phospholipids and to clarify the PHMB mode of action, we performed fluorescence anisotropy experiments. Two probes, 1,6-diphenyl-1,3,5-hexatriene (DPH) and its derivative 1-[4-(trimethyl-amino)-phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH), were used. DPH and TMA-DPH incorporate inside and at the surface of the cytoplasmic membrane, respectively. When PHMB was added, an increase of TMA-DPH fluorescence anisotropy was observed, but no changes of DPH fluorescence anisotropy occurred. These results are consistent with the hypothesis that PHMB molecules perturb L. innocua LRGIA 01 cytoplasmic membrane by interacting with the first layer of the membrane lipid bilayer.

  13. Use of mode of action data to inform a dose-response assessment for bladder cancer following exposure to inorganic arsenic.

    Science.gov (United States)

    Gentry, P R; Yager, J W; Clewell, R A; Clewell, H J

    2014-10-01

    In the recent National Research Council report on conducting a dose-response assessment for inorganic arsenic, the committee remarked that mode of action data should be used, to the extent possible, to extrapolate below the observed range for epidemiological studies to inform the shape of the dose-response curve. Recent in vitro mode of action studies focused on understanding the development of bladder cancer following exposure to inorganic arsenic provide data to inform the dose-response curve. These in vitro data, combined with results of bladder cancer epidemiology studies, inform the dose-response curve in the low-dose region, and include values for both pharmacokinetic and pharmacodynamic variability. Integration of these data provides evidence of a range of concentrations of arsenic for which no effect on the bladder would be expected. Specifically, integration of these results suggest that arsenic exposures in the range of 7-43 ppb in drinking water are exceedingly unlikely to elicit changes leading to key events in the development of cancer or noncancer effects in bladder tissue. These findings are consistent with the lack of evidence for bladder cancer following chronic ingestion of arsenic water concentrations <100 ppb in epidemiological studies.

  14. The first toxicological study of the antiozonant and research tool ethylene diurea (EDU) using a Lemna minor L. bioassay: Hints to its mode of action.

    Science.gov (United States)

    Agathokleous, Eugenios; Mouzaki-Paxinou, Akrivi-Chara; Saitanis, Costas J; Paoletti, Elena; Manning, William J

    2016-06-01

    The antiozonant and research tool ethylene diurea (EDU) is widely studied as a phytoprotectant against the widespread pollutant ground-surface ozone. Although it has been extensively used, its potential toxicity in the absence of ozone is unknown and its mode of action is unclear. The purpose of this research was to toxicologically assess EDU and to further investigate its mode of action using Lemna minor L. as a model organism. Application of EDU concentrations greater than 593 mg L(-1) (practically 600 mg L(-1)) resulted in adverse inhibition of colony growth. As no-observed-toxic-effects concentration (NOEL) we recommend a concentration of 296 mg L(-1) (practically 300 mg L(-1)). A hormetic response was detected, i.e. stimulatory effects of low EDU concentrations, which may indicate overcompensation in response to disruption in homeostasis. Growth inhibition and suppressed biomass were associated with impacted chlorophyll a fluorescence (ΦPSII, qP and ETR). Furthermore, EDU increased mesophyll thickness, as indicated by frond succulence index. Applications of concentrations ≥593 mg L(-1) to uncontrolled environments should be avoided due to potential toxicity to sensitive organisms and the environment.

  15. Identifying the Enzymatic Mode of Action for Cellulase Enzymes by Means of Docking Calculations and a Machine Learning Algorithm

    Directory of Open Access Journals (Sweden)

    Somisetti V. Sambasivarao

    2014-01-01

    Full Text Available Docking calculations have been conducted on 36 cellulase enzymes and the results were evaluated by a machine learning algorithm to determine the nature of the enzyme (i.e. endo- or exo- enzymatic activity. The docking calculations have also been used to identify crucial substrate-enzyme interactions, and establish structure-function relationships. The use of carboxymethyl cellulose as a docking substrate is found to correctly identify the endo- or exo- behavior of cellulase enzymes with 92% accuracy while cellobiose docking calculations resulted in an 86% predictive accuracy. The binding distributions for cellobiose have been classified into two distinct types; distributions with a single maximum or distributions with a bi-modal structure. It is found that the uni-modal distributions correspond to exo- type enzyme while a bi-modal substrate docking distribution corresponds to endo- type enzyme. These results indicate that the use of docking calculations and machine learning algorithms are a fast and computationally inexpensive method for predicting if a cellulase enzyme possesses primarily endo- or exo- type behavior, while also revealing critical enzyme-substrate interactions.

  16. Use of electroencephalography (EEG) to assess CNS changes produced by pesticides with different modes of action: Effects of permethrin, deltamethrin, fipronil, imidacloprid, carbaryl, and triadimefon

    Energy Technology Data Exchange (ETDEWEB)

    Freeborn, Danielle L., E-mail: Freeborn.danielle@epa.gov; McDaniel, Katherine L., E-mail: McDaniel.kathy@epa.gov; Moser, Virginia C., E-mail: Moser.ginger@epa.gov; Herr, David W., E-mail: Herr.david@epa.gov

    2015-01-15

    The electroencephalogram (EEG) is an apical measure, capable of detecting changes in brain neuronal activity produced by internal or external stimuli. We assessed whether pesticides with different modes of action produced different changes in the EEG of adult male Long–Evans rats. The EEG was recorded using two montages (visual cortex referenced to the cerebellum and to the frontal cortex) in unrestrained rats at the time of peak behavioral effects. Pesticides included: permethrin and deltamethrin (Type I and Type II pyrethroids; 2 h), fipronil (single and repeated doses; phenylpyrazole; 6 h), imidacloprid (neonicotinoid; 2 h), carbaryl (carbamate; 0.5 h), and triadimefon (triazole; 1 h), using dosages that produced approximately an ED{sub 30} or an ED{sub 50}–ED{sub 80} change in motor activity. Permethrin (43, 100 mg/kg) increased amplitudes or areas (delta, alpha, or gamma bands) in the EEG. Deltamethrin (2.5, 5.5 mg/kg) reduced the amplitudes or areas of the delta, theta, alpha, beta, and gamma bands, but the changes were not dose-related. A single treatment with fipronil (25, 50 mg/kg, but not 5, 10 mg/kg) decreased gamma band area. Additional changes in the delta, theta, and gamma bands were observed when fipronil (5, 10 mg/kg) was administered for 14 days. Imidacloprid (50, 100 mg/kg) did not alter the EEG. Carbaryl (10, 50 mg/kg) decreased theta area, and decreased delta and increased beta frequency. Triadimefon (75, 150 mg/kg) produced minimal changes in the EEG. The results show that the EEG is affected differently by approximately equipotent doses of pesticides with different modes of action. - Highlights: • Pesticides with different modes of action have different effects on in vivo rodent EEG. • The EEG was also changed differently after single vs. repeated treatment with fipronil. • The data suggest that EEG may be used as an apical measure for detecting chemical effects on the central nervous system.

  17. Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action?

    Science.gov (United States)

    Dalhoff, A

    2015-04-01

    This review summarizes evidence that commercially available fluoroquinolones used for the treatment of bacterial infections are active against other non-bacterial infectious agents as well. Any of these fluoroquinolones exerts, in parallel to its antibacterial action, antiviral, antifungal, and antiparasitic actions at clinically achievable concentrations. This broad range of anti-infective activities is due to one common mode of action, i.e., the inhibition of type II topoisomerases or inhibition of viral helicases, thus maintaining the selective toxicity of fluoroquinolones inhibiting microbial topoisomerases at low concentrations but mammalian topoisomerases at much higher concentrations. Evidence suggests that standard doses of the fluoroquinolones studied are clinically effective against viral and parasitic infections, whereas higher doses administered topically were active against Candida spp. causing ophthalmological infections. Well-designed clinical studies should be performed to substantiate these findings.

  18. Use of the antiozonant ethylenediurea (EDU) in Italy: verification of the effects of ambient ozone on crop plants and trees and investigation of EDU's mode of action.

    Science.gov (United States)

    Paoletti, Elena; Contran, Nicla; Manning, William J; Ferrara, Anna M

    2009-05-01

    Twenty-four experiments where EDU was used to protect plants from ozone (O(3)) in Italy are reviewed. Doses of 150 and 450 ppm EDU at 2-3 week intervals were successfully applied to alleviate O(3)-caused visible injury and growth reductions in crop and forest species respectively. EDU was mainly applied as soil drench to crops and by stem injection or infusion into trees. Visible injury was delayed and reduced but not completely. In investigations on mode of action, EDU was quickly (8 days), as it cannot move via phloem. EDU did not enter cells, suggesting it does not directly affect cell metabolism. EDU delayed senescence, did not affect photosynthesis and foliar nitrogen content, and stimulated antioxidant responses to O(3) exposure. Preliminary results suggest developing an effective soil application method for forest trees is warranted.

  19. 新颖杀螨剂Pyflubumide的合成和作用机制%The Synthesis and Mode of Action of Novel Acaricide Pyflubumidera

    Institute of Scientific and Technical Information of China (English)

    邓建玲

    2015-01-01

    Pyflubumide是新颖的杀螨剂,具有独特的化学结构,其苯胺部分上有甲氧基取代的六氟异丙基基团.其结构与琥珀酸脱氢酶抑制剂型杀菌剂相似.主要介绍了pyflubumide的发现过程、合成和构效关系;以及作用机制.Pyflubumide在蛛螨体内很快脱酰代谢为NH-物,后者与腈吡螨酯的OH-物作用于线粒体复合体Ⅱ的同一酶,但其结合点和/或结合方式不同,应属于不同的类别.%Pyflubumide is a novel acaricide with a unique chemical structure that contains a methoxy-substituted hexafluoroisopropyl group on the anilino moiety. Its structure is similar to that of succinate-dehydrogenase inhibitor(SDHI) fungicides. This paper introduces the discovery, synthesis and structure-activity relationship of pyflubumide, and its mode of action. Pyflubumide is quickly metabolized to its NH-form in the homogenate of spider mites and NH-form acts on the same enzyme with OH-form of cyenopyrafen. But the two compounds act the different binding sites on mitochondrial complexⅡand/or with the different manners of binding, and should be classified into different groups in terms of their mode of action.

  20. Probable neuro sexual mode of action of Casimiroa edulis seed extract versus [correction of verses] sildenafil citrate (Viagra(tm)) on mating behavior in normal male rats.

    Science.gov (United States)

    Ali, Syed Tabrez; Rakkah, Nabeeh I

    2008-01-01

    The present study deals with the aphrodisiac actions of the aqueous extract of the seeds of the hypotensive plant Casimiroa edulis on the sexual behavior of normal male rats. In this investigation 30 healthy male Wister strain white albino rats showing the brisk sexual activity age 15 weeks, weighing 400-450 grams were included. Female rats were artificially brought into estrous by hormonal treatment. Receptivity was checked by exposing them to the male rats and the most receptive females were selected for the stud The mating responses including Mounting Frequency (MF), Intromission Frequency (IF), Mounting Latency (ML), Intromission Latency (IL), Ejaculatory Latency in first and second series (EL1 and EL2) and Post Ejaculatory Interval (PEI) were recorded after treating the animals with 250 mg/kg casimiroa edulis extract (test reference) and 5 mg/kg sildenafil citrate (standard reference) respectively orally per day for 7 days. Both the groups exhibited a significant increase in Mounting Frequency, Intromission Frequency, and first and second ejaculatory latencies, where as Mounting and Intromission latencies and the Post Ejaculatory Interval showed a significant reduction than the controls. Although a similar pattern of mating behavior was observed among the test and the standard groups, however in all the cases as expected, sildenafil produced greater activity than the casimiroa edulis extract. These results suggest the possibility of a similar mode of action of casimiroa edulis and sildenafil citrate on mating behavior in these animals. Our work reported in this research thus provide preliminary evidence that the aqueous seed extract of casimiroa edulis possesses alphrodisiac activity and may be used as an alternative drug therapy to restore sexual functions probably via a neurogenic mode of action.

  1. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

    Science.gov (United States)

    Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

    2014-01-01

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

  2. Incretin therapies: highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors.

    Science.gov (United States)

    Nauck, M

    2016-03-01

    Over the last few years, incretin-based therapies have emerged as important agents in the treatment of type 2 diabetes (T2D). These agents exert their effect via the incretin system, specifically targeting the receptor for the incretin hormone glucagon-like peptide 1 (GLP-1), which is partly responsible for augmenting glucose-dependent insulin secretion in response to nutrient intake (the 'incretin effect'). In patients with T2D, pharmacological doses/concentrations of GLP-1 can compensate for the inability of diabetic β cells to respond to the main incretin hormone glucose-dependent insulinotropic polypeptide, and this is therefore a suitable parent compound for incretin-based glucose-lowering medications. Two classes of incretin-based therapies are available: GLP-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1RAs promote GLP-1 receptor (GLP-1R) signalling by providing GLP-1R stimulation through 'incretin mimetics' circulating at pharmacological concentrations, whereas DPP-4 inhibitors prevent the degradation of endogenously released GLP-1. Both agents produce reductions in plasma glucose and, as a result of their glucose-dependent mode of action, this is associated with low rates of hypoglycaemia; however, there are distinct modes of action resulting in differing efficacy and tolerability profiles. Furthermore, as their actions are not restricted to stimulating insulin secretion, these agents have also been associated with additional non-glycaemic benefits such as weight loss, improvements in β-cell function and cardiovascular risk markers. These attributes have made incretin therapies attractive treatments for the management of T2D and have presented physicians with an opportunity to tailor treatment plans. This review endeavours to outline the commonalities and differences among incretin-based therapies and to provide guidance regarding agents most suitable for treating T2D in individual patients.

  3. Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink.

    Science.gov (United States)

    Wilson, Maxwell Z; Wang, Rurun; Gitai, Zemer; Seyedsayamdost, Mohammad R

    2016-02-09

    While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal-bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA's cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed.

  4. Coriandrum sativum L. (Coriander essential oil: antifungal activity and mode of action on Candida spp., and molecular targets affected in human whole-genome expression.

    Directory of Open Access Journals (Sweden)

    Irlan de Almeida Freires

    Full Text Available Oral candidiasis is an opportunistic fungal infection of the oral cavity with increasingly worldwide prevalence and incidence rates. Novel specifically-targeted strategies to manage this ailment have been proposed using essential oils (EO known to have antifungal properties. In this study, we aim to investigate the antifungal activity and mode of action of the EO from Coriandrum sativum L. (coriander leaves on Candida spp. In addition, we detected the molecular targets affected in whole-genome expression in human cells. The EO phytochemical profile indicates monoterpenes and sesquiterpenes as major components, which are likely to negatively impact the viability of yeast cells. There seems to be a synergistic activity of the EO chemical compounds as their isolation into fractions led to a decreased antimicrobial effect. C. sativum EO may bind to membrane ergosterol, increasing ionic permeability and causing membrane damage leading to cell death, but it does not act on cell wall biosynthesis-related pathways. This mode of action is illustrated by photomicrographs showing disruption in biofilm integrity caused by the EO at varied concentrations. The EO also inhibited Candida biofilm adherence to a polystyrene substrate at low concentrations, and decreased the proteolytic activity of Candida albicans at minimum inhibitory concentration. Finally, the EO and its selected active fraction had low cytotoxicity on human cells, with putative mechanisms affecting gene expression in pathways involving chemokines and MAP-kinase (proliferation/apoptosis, as well as adhesion proteins. These findings highlight the potential antifungal activity of the EO from C. sativum leaves and suggest avenues for future translational toxicological research.

  5. Coriandrum sativum L. (Coriander) essential oil: antifungal activity and mode of action on Candida spp., and molecular targets affected in human whole-genome expression.

    Science.gov (United States)

    Freires, Irlan de Almeida; Murata, Ramiro Mendonça; Furletti, Vivian Fernandes; Sartoratto, Adilson; Alencar, Severino Matias de; Figueira, Glyn Mara; de Oliveira Rodrigues, Janaina Aparecida; Duarte, Marta Cristina Teixeira; Rosalen, Pedro Luiz

    2014-01-01

    Oral candidiasis is an opportunistic fungal infection of the oral cavity with increasingly worldwide prevalence and incidence rates. Novel specifically-targeted strategies to manage this ailment have been proposed using essential oils (EO) known to have antifungal properties. In this study, we aim to investigate the antifungal activity and mode of action of the EO from Coriandrum sativum L. (coriander) leaves on Candida spp. In addition, we detected the molecular targets affected in whole-genome expression in human cells. The EO phytochemical profile indicates monoterpenes and sesquiterpenes as major components, which are likely to negatively impact the viability of yeast cells. There seems to be a synergistic activity of the EO chemical compounds as their isolation into fractions led to a decreased antimicrobial effect. C. sativum EO may bind to membrane ergosterol, increasing ionic permeability and causing membrane damage leading to cell death, but it does not act on cell wall biosynthesis-related pathways. This mode of action is illustrated by photomicrographs showing disruption in biofilm integrity caused by the EO at varied concentrations. The EO also inhibited Candida biofilm adherence to a polystyrene substrate at low concentrations, and decreased the proteolytic activity of Candida albicans at minimum inhibitory concentration. Finally, the EO and its selected active fraction had low cytotoxicity on human cells, with putative mechanisms affecting gene expression in pathways involving chemokines and MAP-kinase (proliferation/apoptosis), as well as adhesion proteins. These findings highlight the potential antifungal activity of the EO from C. sativum leaves and suggest avenues for future translational toxicological research.

  6. Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models.

    Science.gov (United States)

    Villain, Jonathan; Minguez, Laetitia; Halm-Lemeille, Marie-Pierre; Durrieu, Gilles; Bureau, Ronan

    2016-02-01

    The acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure-activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water).

  7. Bacteriocins from Lactobacillus plantarum - production, genetic organization and mode of action: produção, organização genética e modo de ação.

    Science.gov (United States)

    Todorov, Svetoslav D

    2009-04-01

    Bacteriocins are biologically active proteins or protein complexes that display a bactericidal mode of action towards usually closely related species. Numerous strains of bacteriocin producing Lactobacillus plantarum have been isolated in the last two decades from different ecological niches including meat, fish, fruits, vegetables, and milk and cereal products. Several of these plantaricins have been characterized and the aminoacid sequence determined. Different aspects of the mode of action, fermentation optimization and genetic organization of the bacteriocin operon have been studied. However, numerous of bacteriocins produced by different Lactobacillus plantarum strains have not been fully characterized. In this article, a brief overview of the classification, genetics, characterization, including mode of action and production optimization for bacteriocins from Lactic Acid Bacteria in general, and where appropriate, with focus on bacteriocins produced by Lactobacillus plantarum, is presented.

  8. A toxicological review of the ethylene glycol series: Commonalities and differences in toxicity and modes of action.

    Science.gov (United States)

    Fowles, Jeff; Banton, Marcy; Klapacz, Joanna; Shen, Hua

    2017-08-15

    This review summarizes the hazards, exposure and risk that are associated with ethylene glycols (EGs) in their intended applications. Ethylene glycol (EG; CAS RN 107-21-1) and its related oligomers include mono-, di-, tri-, tetra-, and penta-EG. All of the EGs are quickly and extensively absorbed following ingestion and inhalation, but not by the dermal route. Metabolism involves oxidation to the mono- and dicarboxylic acids. Elimination is primarily through the urine as the parent compound or the monoacid, and, in the case of EG, also as exhaled carbon dioxide. All EGs exert acute toxicity in a similar manner, characterized by CNS depression and metabolic acidosis in humans and rodents; the larger molecules being proportionally less acutely toxic on a strict mg/kg basis. Species differences exist in the metabolism and distribution of toxic metabolites, particularly with the formation of glycolic acids and oxalates (OX) from EG and diethylene glycol (DEG); OX are not formed to a significant degree in higher ethylene glycols. Among rodents, rats are more sensitive than mice, and males more sensitive than females to the acute and repeated-dose toxicity of EG. The metabolic formation of glycolic acid (GA), diglycolic acid (DGA), and OX are associated with nephrotoxicity in humans and rodents following single and repeated exposures. However, physiological and metabolic differences in the rate of formation of GA, DGA and OX and their distribution result in EG and DEG causing embryotoxicity in rats, but not rabbits. This rodent-specific sensitivity indicates that EG and its higher oligomers are not anticipated to be embryotoxic in humans at environmentally relevant doses. None of the compounds present developmental toxicity concerns at doses that do not also cause significant maternal toxicity, nor do any of the EGs cause adverse effects on fertility. The EGs are neither genotoxic nor carcinogenic. A read-across matrix is presented, which considers the common and

  9. Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera against Multidrug-Resistant Tumor Cells

    Directory of Open Access Journals (Sweden)

    Onat Kadioglu

    2017-05-01

    Full Text Available Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (Nelumbo nucifera Gaertn, has been previously shown to have various anti-cancer effects. In the present study, we evaluated the effect of neferine in terms of P-glycoprotein (P-gp inhibition via in vitro cytotoxicity assays, R123 uptake assays in drug-resistant cancer cells, in silico molecular docking analysis on human P-gp and in silico absorption, distribution, metabolism, and excretion (ADME, quantitative structure activity relationships (QSAR and toxicity analyses. Lipinski rule of five were mainly considered for the ADME evaluation and the preset descriptors including number of hydrogen bond donor, acceptor, hERG IC50, logp, logD were considered for the QSAR analyses. Neferine revealed higher toxicity toward paclitaxel- and doxorubicin-resistant breast, lung or colon cancer cells, implying collateral sensitivity of these cells toward neferine. Increased R123 uptake was observed in a comparable manner to the control P-gp inhibitor, verapamil. Molecular docking analyses revealed that neferine still interacts with P-gp, even if R123 was pre-bound. Bioinformatical ADME and toxicity analyses revealed that neferine possesses the druggability parameters with no predicted toxicity. In conclusion, neferine may allocate the P-gp drug-binding pocket and prevent R123 binding in agreement with P-gp inhibition experiments, where neferine increased R123 uptake.

  10. Intracellular Diagnostics: Hunting for the Mode of Action of Redox-Modulating Selenium Compounds in Selected Model Systems

    Directory of Open Access Journals (Sweden)

    Dominika Mániková

    2014-08-01

    Full Text Available Redox-modulating compounds derived from natural sources, such as redox active secondary metabolites, are currently of considerable interest in the field of chemoprevention, drug and phytoprotectant development. Unfortunately, the exact and occasionally even selective activity of such products, and the underlying (bio-chemical causes thereof, are often only poorly understood. A combination of the nematode- and yeast-based assays provides a powerful platform to investigate a possible biological activity of a new compound and also to explore the “redox link” which may exist between its activity on the one side and its chemistry on the other. Here, we will demonstrate the usefulness of this platform for screening several selenium and tellurium compounds for their activity and action. We will also show how the nematode-based assay can be used to obtain information on compound uptake and distribution inside a multicellular organism, whilst the yeast-based system can be employed to explore possible intracellular mechanisms via chemogenetic screening and intracellular diagnostics. Whilst none of these simple and easy-to-use assays can ultimately substitute for in-depth studies in human cells and animals, these methods nonetheless provide a first glimpse on the possible biological activities of new compounds and offer direction for more complicated future investigations. They may also uncover some rather unpleasant biochemical actions of certain compounds, such as the ability of the trace element supplement selenite to induce DNA strand breaks.

  11. Effects of chronic exposure to sodium arsenite on hypothalamo-pituitary-testicular activities in adult rats: possible an estrogenic mode of action

    Directory of Open Access Journals (Sweden)

    Jana Subarna

    2006-02-01

    Full Text Available Abstract Background Inorganic arsenic is a major water pollutant and a known human carcinogen that has a suppressive influence on spermatogenesis and androgenesis in male reproductive system. However, the actual molecular events resulting in male reproductive dysfunctions from exposure to arsenic remain unclear. In this context, we evaluated the mode of action of chronic oral exposure of sodium arsenite on hypothalamo-pituitary- testicular activities in mature male albino rats. Methods The effect of chronic oral exposure to sodium arsenite (5 mg/kg body weight/day via drinking water without or with hCG (5 I.U./kg body weight/day and oestradiol (25 micrograms oestradiol 3-benzoate suspended in 0.25 ml olive oil/rat/day co-treatments for 6 days a week for 4 weeks (about the duration of two spermatogenic cycle was evaluated in adult male rats. Changes in paired testicular weights, quantitative study of different varieties of germ cells at stage VII of spermatogenic cycle, epididymal sperm count, circulatory concentrations of hormones (LH, FSH, testosterone and corticosterone, testicular activities of delta 5, 3beta-hydroxysteroid dehydrogenase (delta 5, 3beta-HSD, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD, sorbitol dehydrogenase (SDH, acid phosphatase (ACP, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH, as well as the levels of biogenic amines (dopamine, noradrenaline and 5-hydroxytryptamine (5-HT in the hypothalamus and pituitary were monitored in this study. Hormones were assayed by radioimmuno- assay or enzyme- linked immunosorbent assay and the enzymes were estimated after spectrophotometry as well as the biogenic amines by HPLC electrochemistry. Results Sodium arsenite treatment resulted in: decreased paired testicular weights; epididymal sperm count; plasma LH, FSH, testosterone and testicular testosterone concentrations; and increased plasma concentration of corticosterone. Testicular enzymes such as delta 5, 3 beta

  12. The mode of action of the Bacillus thuringiensis vegetative insecticidal protein Vip3A differs from that of Cry1Ab delta-endotoxin.

    Science.gov (United States)

    Lee, Mi Kyong; Walters, Frederick S; Hart, Hope; Palekar, Narendra; Chen, Jeng-Shong

    2003-08-01

    The Vip3A protein, secreted by Bacillus spp. during the vegetative stage of growth, represents a new family of insecticidal proteins. In our investigation of the mode of action of Vip3A, the 88-kDa Vip3A full-length toxin (Vip3A-F) was proteolytically activated to an approximately 62-kDa core toxin either by trypsin (Vip3A-T) or lepidopteran gut juice extracts (Vip3A-G). Biotinylated Vip3A-G demonstrated competitive binding to lepidopteran midgut brush border membrane vesicles (BBMV). Furthermore, in ligand blotting experiments with BBMV from the tobacco hornworm, Manduca sexta (Linnaeus), activated Cry1Ab bound to 120-kDa aminopeptidase N (APN)-like and 250-kDa cadherin-like molecules, whereas Vip3A-G bound to 80-kDa and 100-kDa molecules which are distinct from the known Cry1Ab receptors. In addition, separate blotting experiments with Vip3A-G did not show binding to isolated Cry1A receptors, such as M. sexta APN protein, or a cadherin Cry1Ab ecto-binding domain. In voltage clamping assays with dissected midgut from the susceptible insect, M. sexta, Vip3A-G clearly formed pores, whereas Vip3A-F was incapable of pore formation. In the same assay, Vip3A-G was incapable of forming pores with larvae of the nonsusceptible insect, monarch butterfly, Danaus plexippus (Linnaeus). In planar lipid bilayers, both Vip3A-G and Vip3A-T formed stable ion channels in the absence of any receptors, supporting pore formation as an inherent property of Vip3A. Both Cry1Ab and Vip3A channels were voltage independent and highly cation selective; however, they differed considerably in their principal conductance state and cation specificity. The mode of action of Vip3A supports its use as a novel insecticidal agent.

  13. Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Kostov, Rumen V.; Knatko, Elena V.; McLaughlin, Lesley A.; Henderson, Colin J. [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Zheng, Suqing [Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, 11794 (United States); Huang, Jeffrey T.-J. [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Honda, Tadashi [Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, 11794 (United States); Dinkova-Kostova, Albena T., E-mail: a.dinkovakostova@dundee.ac.uk [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States); Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States)

    2015-09-25

    The acetylenic tricyclic bis(cyanoenone) TBE-31 is a highly potent cysteine targeting compound with a reversible covalent mode of action; its best-characterized target being Kelch-like ECH-associated protein-1 (Keap1), the cellular sensor for oxidants and electrophiles. TBE-31 reacts with cysteines of Keap1, impairing its ability to target nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) for degradation. Consequently, Nrf2 accumulates and orchestrates cytoprotective gene expression. In this study we investigated the pharmacokinetic and pharmacodynamic properties of TBE-31 in C57BL/6 mice. After a single oral dose of 10 μmol/kg (∼200 nmol/animal), the concentration of TBE-31 in blood exhibited two peaks, at 22.3 nM and at 15.5 nM, 40 min and 4 h after dosing, respectively, as determined by a quantitative stable isotope dilution LC-MS/MS method. The AUC{sub 0–24h} was 195.5 h/nmol/l, the terminal elimination half-life was 10.2 h, and the k{sub el} was 0.068 h{sup −1}. To assess the pharmacodynamics of Nrf2 activation by TBE-31, we determined the enzyme activity of its prototypic target, NAD(P)H:quinone oxidoreductase 1 (NQO1) and found it elevated by 2.4- and 1.5-fold in liver and heart, respectively. Continuous feeding for 18 days with diet delivering the same daily doses of TBE-31 under conditions of concurrent treatment with the immunosuppressive agent azathioprine had a similar effect on Nrf2 activation without any indications of toxicity. Together with previous reports showing the cytoprotective effects of TBE-31 in animal models of carcinogenesis, our results demonstrate the high potency, efficacy and suitability for chronic administration of cysteine targeting reversible covalent drugs. - Highlights: • TBE-31 is a cysteine targeting compound with a reversible covalent mode of action. • After a single oral dose, the blood concentration of TBE-31 exhibits two peaks. • Oral TBE-31 is a potent activator of Nrf2-dependent enzymes in

  14. QSAR-analysis and mixture toxicity as diagnostic tools: Influence of degradation on the toxicity and mode of action of diuron in algae and daphnids.

    Science.gov (United States)

    Neuwoehner, Judith; Zilberman, Tobias; Fenner, Kathrin; Escher, Beate I

    2010-04-01

    Even though the environmental occurrence of pesticide transformation products is well established, ecotoxicological data for transformation products are often lacking. Therefore, it remains an open question for regulators how to handle transformation products in the process of authorization and risk assessment. Transformation products may (1) possess a similar mode of toxic action as the parent compound, (2) exhibit unexpected effects towards non-target organisms or (3) contribute to overall mixture toxicity through baseline toxicity even if the specific activity of the parent compound is lost. In the present study, a systematic and integrated approach is presented to differentiate between these three options with the goal of identifying transformation products that significantly add to the risk posed by the parent compound. Quantitative structure-activity relationships (QSAR) and a toxic ratio (TR) analysis were used to evaluate the toxicity and mode of toxic action of the transformation products relative to the parent compound. In addition, mixture toxicity experiments were used as diagnostic tools to underpin the mode of action analysis and to elucidate whether the transformation products possess a similar risk potential as the parent compound. As an illustrative example, the phenylurea herbicide diuron was chosen since a sound basis of ecotoxicological data was available not only for diuron itself but also for most of its transformation products. Effects were investigated using the most sensitive species, algae, and the non-target organism Daphnia magna, for which a previous QSAR-analysis of literature data suggested a specific hazard. In the present study the primary transformation products 1-(3,4-dichlorophenyl)-3-methlyurea (DCPMU), 3-(3-chlorophenyl)-1,1-dimethylurea (MCPDMU), and 1-(3,4-dichlorophenyl)urea (DCPU) were identified as specific toxicants in algae, but as baseline toxicants in daphnids. The subsequent loss of the methylurea group during

  15. Some notes on taxonomic methodology

    NARCIS (Netherlands)

    Hammen, van der L.

    1986-01-01

    The present paper constitutes an introduction to taxonomic methodology. After an analysis of taxonomic practice, and a brief survey of kinds of attributes, the paper deals with observation, description, comparison, arrangement and classification, hypothesis construction, deduction, model, experiment

  16. Antibacterial Mode of Action of the Essential Oil Obtained from Chamaecyparis obtusa Sawdust on the Membrane Integrity of Selected Foodborne Pathogens

    Directory of Open Access Journals (Sweden)

    Vivek K. Bajpai

    2014-01-01

    Full Text Available The present study examines the possible antibacterial mechanism of action of the essential oil obtained from Chamaecyparis obtusa (COEO sawdust against foodborne pathogenic bacteria. The COEO was obtained by microwave-assisted hydrodistillation of C. obtusa sawdust. The minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC values of COEO against the tested foodborne pathogens including Bacillus cereus ATCC 13061, Listeria monocytogenes ATCC 7644, Staphylococcus aureus ATCC 12600, Salmonella Typhimurium ATCC 43174 and Escherichia coli ATCC 43889 were found in the range from 62.5 to 500 μg/mL and from 125 to 1000 μg/mL, respectively. At the MIC concentrations, the COEO had potential inhibitory effect on the cell viability of the tested bacteria. In addition, the scanning electron microscopic analysis confirmed the inhibitory effect of COEO by revealing significant morphological alterations or rupture of the cell membranes of B. cereus ATCC 13061 and E. coli ATCC 43889. Moreover, the mode of action of COEO on the cell membrane of both Gram-positive B. cereus ATCC 13061 and Gram-negative E. coli ATCC 43889 bacteria was confirmed by marked release of extracellular adenosine 5’-triphosphate (ATP and cellular material that absorbs at 260 nm, and by efflux of potassium ions. These findings suggest that COEO holds a broad-spectrum antibacterial efficacy, confirming its influence on the membrane integrity and morphological characteristics of tested foodborne pathogens.

  17. Case study: an evaluation of the human relevance of the synthetic pyrethroid metofluthrin-induced liver tumors in rats based on mode of action.

    Science.gov (United States)

    Yamada, Tomoya; Uwagawa, Satoshi; Okuno, Yasuyoshi; Cohen, Samuel M; Kaneko, Hideo

    2009-03-01

    In recent years, mode of action (MOA) frameworks have been developed through the International Life Sciences Institute Risk Science Institute and the International Programme on Chemical Safety, including an evaluation of the human relevance of the animal MOA data. In the present paper, the MOA for rat liver tumors induced by Metofluthrin is first analyzed through this framework based on data from studies on Metofluthrin and information on related chemicals from the literature. The human relevance of the rat liver carcinogenic response is then discussed based upon the human relevance framework. Two-year treatment with high dose of Metofluthrin produced hepatocellular tumors in both sexes of the Wistar rats. Metofluthrin induced CYP2B (increased smooth endoplasmic reticulum), resulted in increased liver weights which were associated with centrilobular hepatocyte hypertrophy, and induction of increased hepatocellular DNA replications. The above parameters related to the key events in Metofluthrin-induced liver tumors were observed at or below tumorigenic dose levels. Furthermore, CYP2B induction by Metofluthrin was shown to involve activation of the constitutive androstane receptor in rat hepatocytes. Based on the evidence, including a comparison with the results with another chemical, phenobarbital, acting by a similar MOA, it is reasonable to conclude that Metofluthrin will not have any hepatocarcinogenic activity in humans.

  18. Evaluation of Antifungal Activity and Mode of Action of New Coumarin Derivative, 7-Hydroxy-6-nitro-2H-1-benzopyran-2-one, against Aspergillus spp.

    Directory of Open Access Journals (Sweden)

    Felipe Queiroga Sarmento Guerra

    2015-01-01

    Full Text Available Aspergillus spp. produce a wide variety of diseases. For the treatment of such infections, the azoles and Amphotericin B are used in various formulations. The treatment of fungal diseases is often ineffective, because of increases in azole resistance and their several associated adverse effects. To overcome these problems, natural products and their derivatives are interesting alternatives. The aim of this study was to examine the effects of coumarin derivative, 7-hydroxy-6-nitro-2H-1-benzopyran-2-one (Cou-NO2, both alone and with antifungal drugs. Its mode of action against Aspergillus spp. Cou-NO2 was tested to evaluate its effects on mycelia growth and germination of fungal conidia of Aspergillus spp. We also investigated possible Cou-NO2 action on cell walls (0.8 M sorbitol and on Cou-NO2 to ergosterol binding in the cell membrane. The study shows that Cou-NO2 is capable of inhibiting both the mycelia growth and germination of conidia for the species tested, and that its action affects the structure of the fungal cell wall. At subinhibitory concentration, Cou-NO2 enhanced the in vitro effects of azoles. Moreover, in combination with azoles (voriconazole and itraconazole Cou-NO2 displays an additive effect. Thus, our study supports the use of coumarin derivative 7-hydroxy-6-nitro-2H-1-benzopyran-2-one as an antifungal agent against Aspergillus species.

  19. Antimicrobial activity of cationic antimicrobial peptides against gram-positives: Current progress made in understanding the mode of action and the response of bacteria

    Directory of Open Access Journals (Sweden)

    Soraya Omardien

    2016-10-01

    Full Text Available Antimicrobial peptides (AMPs have been proposed as a novel class of antimicrobials that could aid the fight against antibiotic resistant bacteria. The mode of action of AMPs as acting on the bacterial cytoplasmic membrane has often been presented as an enigma and there are doubts whether the membrane is the sole target of AMPs. Progress has been made in clarifying the possible targets of these peptides, which is reported in this review with as focus gram-positive vegetative cells and spores. Numerical estimates are discussed to evaluate the possibility that targets, other than the membrane, could play a role in susceptibility to AMPs. Concerns about possible resistance that bacteria might develop to AMPs are addressed. Proteomics, transcriptomics and other molecular techniques are reviewed in the context of explaining the response of bacteria to the presence of AMPs and to predict what resistance strategies might be. Emergent mechanisms are cell envelope stress responses as well as enzymes able to degrade and/or specifically bind (and thus inactivate AMPs. Further studies are needed to address the broadness of the AMP resistance and stress responses observed.

  20. IARC use of oxidative stress as key mode of action characteristic for facilitating cancer classification: Glyphosate case example illustrating a lack of robustness in interpretative implementation.

    Science.gov (United States)

    Bus, James S

    2017-06-01

    The International Agency for Research on Cancer (IARC) has formulated 10 key characteristics of human carcinogens to incorporate mechanistic data into cancer hazard classifications. The analysis used glyphosate as a case example to examine the robustness of IARC's determination of oxidative stress as "strong" evidence supporting a plausible cancer mechanism in humans. The IARC analysis primarily relied on 14 human/mammalian studies; 19 non-mammalian studies were uninformative of human cancer given the broad spectrum of test species and extensive use of formulations and aquatic testing. The mammalian studies had substantial experimental limitations for informing cancer mechanism including use of: single doses and time points; cytotoxic/toxic test doses; tissues not identified as potential cancer targets; glyphosate formulations or mixtures; technically limited oxidative stress biomarkers. The doses were many orders of magnitude higher than human exposures determined in human biomonitoring studies. The glyphosate case example reveals that the IARC evaluation fell substantially short of "strong" supporting evidence of oxidative stress as a plausible human cancer mechanism, and suggests that other IARC monographs relying on the 10 key characteristics approach should be similarly examined for a lack of robust data integration fundamental to reasonable mode of action evaluations. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. In Vitro Evaluation of CBR-2092, a Novel Rifamycin-Quinolone Hybrid Antibiotic: Studies of the Mode of Action in Staphylococcus aureus▿

    Science.gov (United States)

    Robertson, Gregory T.; Bonventre, Eric J.; Doyle, Timothy B.; Du, Qun; Duncan, Leonard; Morris, Timothy W.; Roche, Eric D.; Yan, Dalai; Lynch, A. Simon

    2008-01-01

    Rifamycins have proven efficacy in the treatment of persistent bacterial infections. However, the frequency with which bacteria develop resistance to rifamycin agents restricts their clinical use to antibiotic combination regimens. In a program directed toward the synthesis of rifamycins with a lower propensity to elicit resistance development, a series of compounds were prepared that covalently combine rifamycin and quinolone pharmacophores to form stable hybrid antibacterial agents. We describe mode-of-action studies with Staphylococcus aureus of CBR-2092, a novel hybrid that combines the rifamycin SV and 4H-4-oxo-quinolizine pharmacophores. In biochemical studies, CBR-2092 exhibited rifampin-like potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant. Macromolecular biosynthesis studies confirmed that CBR-2092 has rifampin-like effects on RNA synthesis in rifampin-susceptible strains and quinolone-like effects on DNA synthesis in rifampin-resistant strains. Studies of mutant strains that exhibited reduced susceptibility to CBR-2092 further substantiated RNA polymerase as the primary cellular target of CBR-2092, with DNA gyrase and DNA topoisomerase IV being secondary and tertiary targets, respectively, in strains exhibiting preexisting rifampin resistance. In contrast to quinolone comparator agents, no strains with altered susceptibility to CBR-2092 were found to exhibit changes consistent with altered efflux properties. The combined data indicate that CBR-2092 may have potential utility in monotherapy for the treatment of persistent S. aureus infections. PMID:18443108

  2. Bioefficacy and mode-of-action of some limonoids of salannin group from Azadirachta indica A. Juss and their role in a multicomponent system against lepidopteran larvae

    Indian Academy of Sciences (India)

    Opender Koul; Gurmeet Singh; Rajwinder Singh; Jasbir Singh; W M Daniewski; Stanislaw Berlozecki

    2004-12-01

    Biological activities of the salannin type of limonoids isolated from Azadirachta indica A. Juss were assessed using the gram pod borer Helicoverpa armigera (Hubner) and the tobacco armyworm Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae). Inhibition of larval growth was concomitant with reduced feeding by neonate and third instar larvae. All three compounds exhibited strong antifeedant activity in a choice leaf disc bioassay with 2.0, 2.3 and 2.8 g/cm2 of 3-O-acetyl salannol, salannol and salannin, respectively deterring feeding by 50% in S. litura larvae. In nutritional assays, all three compounds reduced growth and consumption when fed to larvae without any effect on efficiency of conversion of ingested food (ECI), suggesting antifeedant activity alone. No toxicity was observed nor was there any significant affect on nutritional indices following topical application, further suggesting specific action as feeding deterrents. When relative growth rates were plotted against relative consumption rates, growth efficiency of the H. armigera fed diet containing 3-O-acetyl salannol, salannol or salannin did not differ from that of starved control larvae (used as calibration curve), further confirming the specific antifeedant action of salannin type of limonoids. Where the three compounds were co-administered, no enhancement in activity was observed. Non-azadirachtin limonoids having structural similarities and explicitly similar modes of action, like feeding deterrence in the present case, have no potentiating effect in any combination.

  3. Evaluation of Antifungal Activity and Mode of Action of New Coumarin Derivative, 7-Hydroxy-6-nitro-2H-1-benzopyran-2-one, against Aspergillus spp.

    Science.gov (United States)

    Guerra, Felipe Queiroga Sarmento; de Araújo, Rodrigo Santos Aquino; de Sousa, Janiere Pereira; Pereira, Fillipe de Oliveira; Mendonça-Junior, Francisco J B; Barbosa-Filho, José M; de Oliveira Lima, Edeltrudes

    2015-01-01

    Aspergillus spp. produce a wide variety of diseases. For the treatment of such infections, the azoles and Amphotericin B are used in various formulations. The treatment of fungal diseases is often ineffective, because of increases in azole resistance and their several associated adverse effects. To overcome these problems, natural products and their derivatives are interesting alternatives. The aim of this study was to examine the effects of coumarin derivative, 7-hydroxy-6-nitro-2H-1-benzopyran-2-one (Cou-NO2), both alone and with antifungal drugs. Its mode of action against Aspergillus spp. Cou-NO2 was tested to evaluate its effects on mycelia growth and germination of fungal conidia of Aspergillus spp. We also investigated possible Cou-NO2 action on cell walls (0.8 M sorbitol) and on Cou-NO2 to ergosterol binding in the cell membrane. The study shows that Cou-NO2 is capable of inhibiting both the mycelia growth and germination of conidia for the species tested, and that its action affects the structure of the fungal cell wall. At subinhibitory concentration, Cou-NO2 enhanced the in vitro effects of azoles. Moreover, in combination with azoles (voriconazole and itraconazole) Cou-NO2 displays an additive effect. Thus, our study supports the use of coumarin derivative 7-hydroxy-6-nitro-2H-1-benzopyran-2-one as an antifungal agent against Aspergillus species.

  4. How the mode of action affects evidence of planning and movement kinematics in aging: End-state comfort in older adults.

    Science.gov (United States)

    Scharoun, Sara M; Gonzalez, Dave A; Roy, Eric A; Bryden, Pamela J

    2016-05-01

    Motor deficits are commonly observed with age; however, it has been argued that older adults are more adept when acting in natural tasks and do not differ from young adults in these contexts. This study assessed end-state comfort and movement kinematics in a familiar task to examine this further. Left- and right-handed older adults picked up a glass (upright or overturned) as if to pour water in four modes of action (pantomime, pantomime with image/cup as a guide, actual grasping). With increasing age, a longer deceleration phase (in pantomime without a stimulus) and less end-state comfort (in pantomime without a stimulus and image as a guide) was displayed as the amount of contextual information available to guide movement decreased. Changes in movement strategies likely reflect an increased reliance on feedback control and demonstration of a more cautious movement. A secondary aim of this study was to assess hand preference and performance, considering conflicting reports of manual asymmetries with age. Performance differences in the Grooved Pegboard place task indicate left handers may display a shift towards right handedness in some, but not all cases. Summarizing, this study supports age-related differences in planning and control processes in a familiar task, and changes in manual asymmetries with age in left handers.

  5. Further evidences for the mode of action of the larvicidal m-pentadecadienyl-phenol isolated from Myracrodruon urundeuva seeds against Aedes aegypti.

    Science.gov (United States)

    Souza, Terezinha M; Menezes, Erika S Bezerra; Oliveira, Rodrigo V; Almeida Filho, Luiz Carlos P; Martins, Jorge M; Moreno, Frederico B; Monteiro-Moreira, Ana Cristina O; Moura, Arlindo A Araripe; Carvalho, Ana F Urano

    2015-12-01

    Nowadays, dengue fever is considered the most important arbovirosis worldwide and its control is still based upon combating the vector Aedes aegypti. Besides monitoring of mosquito populations resistant to conventional insecticides, the search for new environmentally safe insecticides and conduction of molecular studies focusing on the elucidation of mode of action and possible resistance mechanisms are considered the key for a sustainable management of the mosquito vector. Thus, the present work aimed to assess changes in protein expression of 3rd-instar larvae of Ae. aegypti after exposure to the natural insecticide m-pentadecadienyl-phenol. Bidimensional electrophoresis followed by mass spectrometry resulted in identification of 12 proteins differentially expressed between control and treated groups. Larvae exposed to the toxic compound for 24h showed elevated detoxification response (glutathione-S-transferase), increased levels of stress-related proteins (HSP70) as well as evidence of lysosome stabilization to enable survival. Furthermore, expression of proteins involved in protection of peritrophic membrane and metabolism of lipids indicated systemic effect of toxic effects in treated larvae.

  6. Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPARγ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Merilin Al Sharif

    2014-01-01

    Full Text Available Comprehensive understanding of the precise mode of action/adverse outcome pathway (MoA/AOP of chemicals becomes a key step towards superseding the current repeated dose toxicity testing methodology with new generation predictive toxicology tools. The description and characterization of the toxicological MoA leading to non-alcoholic fatty liver disease (NAFLD are of specific interest, due to its increasing incidence in the modern society. Growing evidence stresses on the PPARγ ligand-dependent dysregulation as a key molecular initiating event (MIE for this adverse effect. The aim of this work was to analyze and systematize the numerous scientific data about the steatogenic role of PPARγ. Over 300 papers were ranked according to preliminary defined criteria and used as reliable and significant sources of data about the PPARγ-dependent prosteatotic MoA. A detailed analysis was performed regarding proteins which PPARγ-mediated expression changes had been confirmed to be prosteatotic by most experimental evidence. Two probable toxicological MoAs from PPARγ ligand binding to NAFLD were described according to the Organisation for Economic Cooperation and Development (OECD concepts: (i PPARγ activation in hepatocytes and (ii PPARγ inhibition in adipocytes. The possible events at different levels of biological organization starting from the MIE to the organ response and the connections between them were described in details.

  7. Consensus diagnoses and mode of action for the formation of gastric tumors in rats treated with the chloroacetanilide herbicides alachlor and butachlor.

    Science.gov (United States)

    Furukawa, Satoshi; Harada, Takanori; Thake, Daryl; Iatropoulos, Michael J; Sherman, James H

    2014-01-01

    A panel of pathologists (Panel) was formed to evaluate the pathogenesis and human relevance of tumors that developed in the fundic region of rat stomachs in carcinogenicity and mechanistic studies with alachlor and butachlor. The Panel evaluated stomach sections stained with hematoxylin and eosin, neuron-specific enolase, and chromogranin A to determine the presence and relative proportion of enterochromaffin-like (ECL) cells in the tumors and concluded all tumors were derived from ECL cells. Biochemical and pathological data demonstrated the tumor formation involved a nongenotoxic threshold mode of action (MOA) initially characterized by profound atrophy of the glandular fundic mucosa that affected gastric glands, but not surface epithelium. This resulted in a substantial loss of parietal cells and a compensatory mucosal cell proliferation. The loss of parietal cells caused a marked increase in gastric pH (hypochlorhydria), leading to sustained and profound hypergastrinemia. The mucosal atrophy, together with the increased gastrin, stimulated cell growth in one or more ECL cell populations, resulting in neoplasia. ECL cell autocrine and paracrine effects led to dedifferentiation of ECL cell tumors. The Panel concluded the tumors develop via a threshold-dependent nongenotoxic MOA, under conditions not relevant to humans.

  8. Cancer mode of action, weight of evidence, and proposed cancer reference value for hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).

    Science.gov (United States)

    Sweeney, Lisa M; Okolica, Michelle R; Gut, Chester P; Gargas, Michael L

    2012-11-01

    Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX, CAS No. 121-82-4) is a component of munitions formulations, and has been detected in groundwater samples collected at various US military sites. Clean up target levels for RDX may be derived based on consideration of acceptable cumulative human exposure as expressed in toxicity reference values. Evaluations of the cancer weight of evidence and possible modes of action (MOA) for RDX-induced cancer were conducted. It was concluded that the available data provide suggestive evidence of human carcinogenic potential for RDX. While a mutagenic/genotoxic MOA for RDX is unlikely, no alterative MOA is strongly supported by the available data. A nonlinear (threshold) approach to the assessment of human cancer risk was recommended, and a recommended chronic cancer reference dose of 0.08mg/kg/day was derived. For comparison only, computations using a linear approach were also conducted, yielding a cancer risk specific dose of 0.000235mg/kg/day for 1 in 10(5) risk; this value is 2.6-fold higher the current US EPA risk specific dose for 1 in 10(5) risk. Thus, cleanup standards based on human health risk from RDX exposure could potentially depend on the willingness of risk managers to accept a nonlinear MOA and nonlinear toxicity risk value derivation. Published by Elsevier Inc.

  9. Mode of Action Temu Kunci (Kaempferia pandurata Essential Oil on E. coli K1.1 Cell Determined by Leakage of Material Cell and Salt Tolerance Assays

    Directory of Open Access Journals (Sweden)

    MIKSUSANTI

    2008-06-01

    Full Text Available The essential oil of Kaempferia pandurata consist of terpen and oxygenated terpen that exhibits broad-spectrum antimicrobial activity. It’s mode of action against the gram-negative bacterium E. coli K1.1 has been investigated using a range of treatments. The mode action of the essential oil were analyzed by it’s ability to leakage E. coli K1.1 cell, to change permeability of the cell, and to alter salt tolerance of the cell. Ion leakage from the cell were analyzed by atomic absorption spectrophotometer. Salt tolerance assays was conducted by investigating the ability of E. coli K1.1 treated with temu kunci essential oil to grow on NA supplemented with NaCl. Protein and acid nucleic leakage were analyzed by UV spectrophotometer. There were inorganic compound leakage (potassium, calcium ion and organic compound leakage (nucleic acid, protein from cytoplasmic membrane, after exposing this organism to essential oil of Kaempferia pandurata. The more concentration of oil added, the more leakage was observed due to the loss of absorbing material such as nucleic acid (260 nm and protein (280 nm, the loss of potassium and calcium ion, and loss of the salt tolerance of E. coli K1.1.

  10. In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus.

    Science.gov (United States)

    Robertson, Gregory T; Bonventre, Eric J; Doyle, Timothy B; Du, Qun; Duncan, Leonard; Morris, Timothy W; Roche, Eric D; Yan, Dalai; Lynch, A Simon

    2008-07-01

    Rifamycins have proven efficacy in the treatment of persistent bacterial infections. However, the frequency with which bacteria develop resistance to rifamycin agents restricts their clinical use to antibiotic combination regimens. In a program directed toward the synthesis of rifamycins with a lower propensity to elicit resistance development, a series of compounds were prepared that covalently combine rifamycin and quinolone pharmacophores to form stable hybrid antibacterial agents. We describe mode-of-action studies with Staphylococcus aureus of CBR-2092, a novel hybrid that combines the rifamycin SV and 4H-4-oxo-quinolizine pharmacophores. In biochemical studies, CBR-2092 exhibited rifampin-like potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant. Macromolecular biosynthesis studies confirmed that CBR-2092 has rifampin-like effects on RNA synthesis in rifampin-susceptible strains and quinolone-like effects on DNA synthesis in rifampin-resistant strains. Studies of mutant strains that exhibited reduced susceptibility to CBR-2092 further substantiated RNA polymerase as the primary cellular target of CBR-2092, with DNA gyrase and DNA topoisomerase IV being secondary and tertiary targets, respectively, in strains exhibiting preexisting rifampin resistance. In contrast to quinolone comparator agents, no strains with altered susceptibility to CBR-2092 were found to exhibit changes consistent with altered efflux properties. The combined data indicate that CBR-2092 may have potential utility in monotherapy for the treatment of persistent S. aureus infections.

  11. Microwave synthesis of ZnO@mSiO₂ for detailed antifungal mode of action study: understanding the insights into oxidative stress.

    Science.gov (United States)

    Mitra, Shouvik; Patra, Prasun; Pradhan, Saheli; Debnath, Nitai; Dey, Kushal Kumar; Sarkar, Sampad; Chattopadhyay, Dhrubajyoti; Goswami, Arunava

    2015-04-15

    A simple chemical method has been devised for deliberate incorporation of zinc oxide nanoparticles (ZNPs) within mesoporous nanosilica (mSiO2) matrix to yield zinc oxide nanoparticles embedded in mesoporous nanosilica (ZnO@mSiO2). ZnO@mSiO2 inhibited the growth of four strains of fungi in a dose dependant manner. A series of biochemical assays revealed generation of oxidative stress from ZnO@mSiO2 for such biocidal response. We proposed transient superoxide and its subsequent conversion to H2O2 played a pivotal role behind such biocidal response as revealed from our systematic evaluation. This resulted morphological alteration of fungi through increase in number of facets, in correlation we found up-regulation in oxidative stress related genes. Bioavailability within the fungal sample was confirmed from microscopic, spectroscopic, biophysical techniques. Protein carbonylation of fungal species was the chemical outcome of such above mentioned stress and quantified by high performance liquid chromatography (HPLC) via subsequent hydrazone derivatization. Several in vitro and in vivo evaluations revealed the biocompatibility of ZnO@mSiO2. Altogether this report claims a new biocidal agent with a detailed mode of action focusing on the origin and quantification of oxidative stress through biophysical and biochemical techniques for the first time for real time applications.

  12. Diclofenac can exhibit estrogenic modes of action in male Xenopus laevis, and affects the hypothalamus-pituitary-gonad axis and mating vocalizations.

    Science.gov (United States)

    Efosa, Norah Johanna; Kleiner, Wibke; Kloas, Werner; Hoffmann, Frauke

    2017-04-01

    Diclofenac (DCF) is a non-steroidal analgesic and antiphlogistic. Due to its tremendous use, DCF can be found in the environment, especially in sewage, but also surface waters, ground and drinking water. Previous studies indicated that DCF can modulate the reproductive physiology of fish by altering the expression of important key enzymes of the hypothalamus-pituitary-gonad-axis (HPG-axis) and might act as an estrogenic endocrine disrupting chemical (EDC). Other studies, however, demonstrated that DCF does not exhibit any estrogenicity. Thus, in the present study we investigated whether an exposure to DCF can affect reproductive behavior and physiology of adult male X. laevis by analyzing DCF effects on the mate calling behavior of the frogs and on gene expression patterns of key biomarkers of the HPG-axis. In addition, plasma sex steroid levels were determined to gain detailed insights into the mechanisms of DCF action. We could demonstrate that DCF can act as EDC by exhibiting slight estrogenic modes of action. In addition, pharmacological impacts on gonadal steroidogenesis could be revealed leading to imbalances in sex steroid levels and ratios. DCF furthermore altered the calling behavior of exposed males, potentially reducing the mating and reproductive success of the frogs, possibly leading to severe population effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. MODE OF ACTION OF LANTANA CAMARA EXTRACTS ON ENZYMES ASPARTATE AMINO TRANSFERASE AND ALANINE AMINO TRANSFERASE ACTIVITY IN TARGET AND NONTARGET ORGANISMS

    Directory of Open Access Journals (Sweden)

    DIVYA RAJAN

    2013-01-01

    Full Text Available The plant Lantana camara on the basis of study conducted found to show effective larvicidal activity. The presentstudy deals with the mode of action of Lantana camara extract on enzymes, Aspartate Amino Transferase andAlanine Amino Transferase activity in target and non-target organisms. The major transaminase system of the bodysuch as AsAT and AlAT were significantly inhibited by the plant extract. A significant decrease in the activity ofabove two enzyme systems were observed from the fourth h of incubation onwards. The transaminase system ofmosquito larvae was more sensitive to Lantana camara extract than that of vertebrate system such as Anabastestudineus and Rana hexadactyla which are the non-target organisms seen in the aquatic habitat. The majortransaminase systems of the body such as AsAT and AlAT were inhibited in a dose dependent manner under bothinvitro and invivo conditions. The change of pH from alkaline (normal larvae to acidic (intoxicated larvae, mayalso be sufficient for inhibiting or blocking most of the enzymatic reactions leading to the death of the organisms.The results of this experiment indicated that the shrub Lantana camara could be studied further in detail and itsbenificial effects to the control of vector bron diseases could be utilised for healthy environments

  14. Mode of action and in vitro susceptibility of mastitis pathogens to macedocin ST91KM and preparation of a teat seal containing the bacteriocin

    Directory of Open Access Journals (Sweden)

    Renee Pieterse

    2010-03-01

    Full Text Available Mastitis is considered to be the most economically costly disease affecting the dairy industry. Regular dosage of animals with antibiotics, including use of prophylactic concentrations, may select for resistant strains. The purpose of this study was to determine the mode of action of a new bacteriocin (macedocin ST91KM, to evaluate the antimicrobial resistance of mastitis pathogens to antibiotics commonly used in treatment remedies, and to introduce the possible use of an alternative antimicrobial agent. The bacteriocin macedocin ST91KM, produced by Streptococcus gallolyticus subsp. macedonicus ST91KM, is bactericidal to Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis and Staphylococcus aureus associated with mastitis infections, including strains resistant to methicillin and oxacillin. Sensitive cells were deformed and secreted nucleotides, K+ and β-galactosidase when exposed to macedocin ST91KM. Adsorption of the peptide to target cells decreased in the presence of solvents, suggesting that receptors on the cell surfaces have lipid moieties. No adsorption was recorded in the presence of MgCl2, KI and Na2CO3, suggesting that ionic strength plays an important role. A teat seal preparation containing macedocin ST91KM effectively released the peptide and inhibited the growth of S. agalactiae. Macedocin ST91KM could form the basis for alternative dry cow therapy to prevent mastitis infections in dairy cows as it is effective against pathogens that display resistance to conventional antibiotic therapy.

  15. Antimicrobial Activity of Cationic Antimicrobial Peptides against Gram-Positives: Current Progress Made in Understanding the Mode of Action and the Response of Bacteria

    Science.gov (United States)

    Omardien, Soraya; Brul, Stanley; Zaat, Sebastian A. J.

    2016-01-01

    Antimicrobial peptides (AMPs) have been proposed as a novel class of antimicrobials that could aid the fight against antibiotic resistant bacteria. The mode of action of AMPs as acting on the bacterial cytoplasmic membrane has often been presented as an enigma and there are doubts whether the membrane is the sole target of AMPs. Progress has been made in clarifying the possible targets of these peptides, which is reported in this review with as focus gram-positive vegetative cells and spores. Numerical estimates are discussed to evaluate the possibility that targets, other than the membrane, could play a role in susceptibility to AMPs. Concerns about possible resistance that bacteria might develop to AMPs are addressed. Proteomics, transcriptomics, and other molecular techniques are reviewed in the context of explaining the response of bacteria to the presence of AMPs and to predict what resistance strategies might be. Emergent mechanisms are cell envelope stress responses as well as enzymes able to degrade and/or specifically bind (and thus inactivate) AMPs. Further studies are needed to address the broadness of the AMP resistance and stress responses observed.

  16. Sources and modes of action of invasive knotweed allelopathy: the effects of leaf litter and trained soil on the germination and growth of native plants

    Directory of Open Access Journals (Sweden)

    Madalin Parepa

    2012-05-01

    Full Text Available Invasive knotweeds, native to Eastern Asia, are among the most dominant plant invaders of European and North American temperate ecosystems. Recent studies indicate that one cause of this dominance might be allelopathy, but the possible sources and modes of action of this allelopathy are insufficiently understood. Here, we asked whether the invasive knotweed Fallopia × bohemica can exert allelopathic effects on native plants also through its leaf litter, or through persistent soil contaminants, and whether these affect the germination or growth of native plants. In a germination experiment with nine native species neither litter leachate, an aqueous extract of knotweed leaves added to the soil, nor trained soil with a history of Fallopia pre-cultivation suppressed the germination or early growth of natives. A mesocosm study with experimental native communities showed that the presence of F. × bohemica, although not a dominant in these communities, caused significant shifts of life-history strategy in two dominant natives, and that similar effects could be elicited through litter leachates or trained soil alone. However, there were hardly any effects on the biomass of natives. Our study indicates that knotweed allelopathy acts on the growth rather than germination of natives, and that soil contamination through persistent allelochemicals may not be a significant problem in habitat restoration. It also shows that allelopathic effects can sometimes be subtle changes in life-history and allocation patterns of the affected species.

  17. Taxonomic Study on a Naturalized Plant,Euphorbia dentate Michx. and Its New Distribution in Hebei Province%齿裂大戟的分类学研究及其在河北省的新分布

    Institute of Scientific and Technical Information of China (English)

    牛玉璐

    2011-01-01

    The specimen of naturalized plant Euphorbia dentate Michx.collected from Yi County and Luquan County was a newly geographical distribution in Hebei Province.A description of this species,as well as its taxonomic features and distributions,was presented in%首次报道了归化植物齿裂大戟在河北省易县和鹿泉县的新分布;详细描述了该种的分类学特征和地理分布,并总结出该种的识别特征;对该种与其相近种进行了比较.最后,对该种扩散范围与趋势进行了讨论.

  18. Tissue Distribution of Polychlorinated Biphenyls and Organochlorine Pesticides and Potential Toxicity to Alaskan Northern Fur Seals Assessed Using PCBs Congener Specific Mode of Action Schemes

    Science.gov (United States)

    The concentrations of 145 polychlorinated biphenyl (PCB) congeners were measured using gas chromatography-ion trap mass spectrometry in 8 different tissues (blubber, brain, heart, kidney, liver, lung, muscle, and reproductive tissues) of 10 Alaskan northern fur seals. The mean concentrations of bot...

  19. Studies on the mode of action of calciferol. XIII. Development of a radioimmunoassay for vitamin D-dependent chick intestinal calcium-binding protein and tissue distribution

    Energy Technology Data Exchange (ETDEWEB)

    Christakos, S.; Friedlander, E.J.; Frandsen, B.R.; Norman, A.W.

    1979-05-01

    A RIA for chick intestinal calcium-binding protein (CaBP) has been developed with a sensitivity of 1 ng. The antiserum was generated in rabbits injected with highly purified vitamin D-dependent chick intestinal CaBP. The assay employs the double antibody technique, and /sup 125/I-labeled CaBP was prepared using chloramine T. Low molecular weight peptide hormones and normal rabbit, rat, and human serum proteins show no cross-reactivity in the assay. Measurements of chick intestinal and kidney CaBP by RIA showed a good correlation with measurements of CaBP by the radial immunodiffusion method. The assay is reproducible (interassay variability, 16.3%) and precise (intraassay variability, 4.0%). The concentration of immunoreactive CaBP (iCaBP) in chick serum (2.7 ng/ml serum) can now be measured as early as 8 h after the administration of 6.5 nmol 1,25-dihydroxyvitamin D/sub 3/; a maximum of 11 ng/ml is reached at 20 h. The level of CaBP in chick serum was found to be dependent on the dose of vitamin D/sub 3/ or 1,25-dihydroxyvitamin D/sub 3/ administered to the animal.

  20. New insights into the structure and mode of action of Mo-CBP3, an antifungal chitin-binding protein of Moringa oleifera seeds.

    Directory of Open Access Journals (Sweden)

    Adelina B Batista

    Full Text Available Mo-CBP3 is a chitin-binding protein purified from Moringa oleifera Lam. seeds that displays inhibitory activity against phytopathogenic fungi. This study investigated the structural properties and the antifungal mode of action of this protein. To this end, circular dichroism spectroscopy, antifungal assays, measurements of the production of reactive oxygen species and microscopic analyses were utilized. Mo-CBP3 is composed of 30.3% α-helices, 16.3% β-sheets, 22.3% turns and 30.4% unordered forms. The Mo-CBP3 structure is highly stable and retains its antifungal activity regardless of temperature and pH. Fusarium solani was used as a model organism for studying the mechanisms by which this protein acts as an antifungal agent. Mo-CBP3 significantly inhibited spore germination and mycelial growth at 0.05 mg.mL-1. Mo-CBP3 has both fungistatic and fungicidal effects, depending on the concentration used. Binding of Mo-CBP3 to the fungal cell surface is achieved, at least in part, via electrostatic interactions, as salt was able to reduce its inhibitory effect. Mo-CBP3 induced the production of ROS and caused disorganization of both the cytoplasm and the plasma membrane in F. solani cells. Based on its high stability and specific toxicity, with broad-spectrum efficacy against important phytopathogenic fungi at low inhibitory concentrations but not to human cells, Mo-CBP3 has great potential for the development of new antifungal drugs or transgenic crops with enhanced resistance to phytopathogens.

  1. Mode of action analysis for the synthetic pyrethroid metofluthrin-induced rat liver tumors: evidence for hepatic CYP2B induction and hepatocyte proliferation.

    Science.gov (United States)

    Deguchi, Yoshihito; Yamada, Tomoya; Hirose, Yukihiro; Nagahori, Hirohisa; Kushida, Masahiko; Sumida, Kayo; Sukata, Tokuo; Tomigahara, Yoshitaka; Nishioka, Kazuhiko; Uwagawa, Satoshi; Kawamura, Satoshi; Okuno, Yasuyoshi

    2009-03-01

    Two-year treatment with high doses of Metofluthrin produced hepatocellular tumors in both sexes of Wistar rats. To understand the mode of action (MOA) by which the tumors are produced, a series of studies examined the effects of Metofluthrin on hepatic microsomal cytochrome P450 (CYP) content, hepatocellular proliferation, hepatic gap junctional intercellular communication (GJIC), oxidative stress and apoptosis was conducted after one or two weeks of treatment. The global gene expression profile indicated that most genes with upregulated expression with Metofluthrin were metabolic enzymes that were also upregulated with phenobarbital. Metofluthrin induced CYP2B and increased liver weights associated with centrilobular hepatocyte hypertrophy (increased smooth endoplasmic reticulum [SER]), and induction of increased hepatocellular DNA replication. CYP2B1 mRNA induction by Metofluthrin was not observed in CAR knockdown rat hepatocytes using the RNA interference technique, demonstrating that Metofluthrin induces CYP2B1 through CAR activation. Metofluthrin also suppressed hepatic GJIC and induced oxidative stress and increased antioxidant enzymes, but showed no alteration in apoptosis. The above parameters related to the key events in Metofluthrin-induced liver tumors were observed at or below tumorigenic dose levels. All of these effects were reversible upon cessation of treatment. Metofluthrin did not cause cytotoxicity or peroxisome proliferation. Thus, it is highly likely that the MOA for Metofluthrin-induced liver tumors in rats is through CYP induction and increased hepatocyte proliferation, similar to that seen for phenobarbital. Based on analysis with the International Life Sciences Institute/Risk Science Institute MOA framework, it is reasonable to conclude that Metofluthrin will not have any hepatocarcinogenic activity in humans, at least at expected levels of exposure.

  2. Development of linear and threshold no significant risk levels for inhalation exposure to titanium dioxide using systematic review and mode of action considerations.

    Science.gov (United States)

    Thompson, Chad M; Suh, Mina; Mittal, Liz; Wikoff, Daniele S; Welsh, Brian; Proctor, Deborah M

    2016-10-01

    Titanium dioxide (TiO2) has been characterized as a poorly soluble particulate (PSP) with low toxicity. It is well accepted that low toxicity PSPs such as TiO2 induce lung tumors in rats when deposition overwhelms particle clearance mechanisms. Despite the sensitivity of rats to PSPs and questionable relevance of PSP-induced tumors to humans, TiO2 is listed as a possible human carcinogen by some agencies and regulators. Thus, environmental toxicity criteria for TiO2 are needed for stakeholders to evaluate potential risks from environmental exposure and regulatory compliance. A systematic review of the literature was conducted to characterize the available data and identify candidate datasets upon which toxicity values could be derived. Key to this assessment, a survey of mechanistic data relevant for lung cancer was used to support quantitative inhalation risk assessment approaches. A total of 473 human studies were identified, 7 of which were epidemiological studies that met inclusion criteria to quantitatively characterize carcinogenic endpoints in humans. None of these studies supported derivation of toxicity criteria; therefore, animal data were used to derived safety values for TiO2 using different dose-metrics (regional deposited dose ratios, TiO2 particle surface area lung burden, and volumetric overload of alveolar macrophages), benchmark dose modeling, and different low-dose extrapolation approaches. Based on empirical evidence and mechanistic support for nonlinear mode of action involving particle overload, chronic inflammation and cell proliferation, a no significant risk level (NSRL) of 300 μg/day was derived. By comparison, low-dose linear extrapolation from tumor incidence in the rat lung resulted in an NSRL value of 44 μg/day. These toxicity values should be useful for stakeholders interested in assessing risks from environmental exposure to respirable TiO2.

  3. Contractility of isolated bovine ventricular myocytes is enhanced by intracellular injection of cardioactive glycosides. Evidence for an intracellular mode of action.

    Science.gov (United States)

    Isenberg, G

    1984-01-01

    The contractions of isolated bovine left ventricular myocytes were evaluated by optically measuring the extent of unloaded shortening (ES), the maximal rate of shortening (MRS) and the maximal rate of re-lengthening (MRL). Ouabain, digoxin or digitoxin were intracellularly injected by 2 sec long pressure pulses via the microelectrodes. Their i.c. concentration was estimated to be 2-5 nM. Within 1-4 min after the injection, ES, MRS and MRL increased by more than 2-fold. The contractility renormalized within the following 20 min. Injection of solutions without glycosides did not increase the contractility. An interaction of the injected glycoside with the e.c. ouabain receptor could be largely excluded because a) the amount of the released glycoside was too small for e.c. effects, b) 500 nM e.c. antidigoxin, c) 20 mM [K]o or d) covalent binding of digoxin to HSA did not prevent the increase in contractility due to the i.c. injections. Since contractility also increased when the injections were performed at Na-free conditions, [Na]i-load is not necessary for the effect of i.e. glycosides. The increased contractility due to the injected glycosides was not observed when the contractility prior to the injection was already potentiated, e.g. by greater than 3.6 mM [Ca]o or by stimulation at frequencies greater than 1.25 Hz. The results are interpreted by the hypothesis that the i.c. glycosides facilitate the release of activator calcium from the SR. The possible i.c. modes of action are discussed as well as the idea that e.c. applied glycosides internalize and mediate inotropy via the i.e. mechanism.

  4. Mode of action of human pharmaceuticals in fish: the effects of the 5-alpha-reductase inhibitor, dutasteride, on reproduction as a case study.

    Science.gov (United States)

    Margiotta-Casaluci, Luigi; Hannah, Robert E; Sumpter, John P

    2013-03-15

    In recent years, a growing number of human pharmaceuticals have been detected in the aquatic environment, generally at low concentrations (sub-ng/L-low μg/L). In most cases, these compounds are characterised by highly specific modes of action, and the evolutionary conservation of drug targets in wildlife species suggests the possibility that pharmaceuticals present in the environment may cause toxicological effects by acting through the same targets as they do in humans. Our research addressed the question of whether or not dutasteride, a pharmaceutical used to treat benign prostatic hyperplasia, may cause adverse effects in a teleost fish, the fathead minnow (Pimephales promelas), by inhibiting the activity of both isoforms of 5α-reductase (5αR), the enzyme that converts testosterone into dihydrotestosterone (DHT). Mammalian pharmacological and toxicological information were used to guide the experimental design and the selection of relevant endpoints, according to the so-called "read-across approach", suggesting that dutasteride may affect male fertility and steroid hormone dynamics. Therefore, a 21-day reproduction study was conducted to determine the effects of dutasteride (10, 32 and 100 μg/L) on fish reproduction. Exposure to dutasteride significantly reduced fecundity of fish and affected several aspects of reproductive endocrine functions in both males and females. However, none of the observed adverse effects occurred at concentrations of exposure lower than 32 μg/L; this, together with the low volume of drug prescribed every year (10.34 kg in the UK in 2011), and the extremely low predicted environmental concentration (0.03 ng/L), suggest that, at present, the potential presence of dutasteride in the environment does not represent a threat to wild fish populations.

  5. Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

    Science.gov (United States)

    Labib, Sarah; Bourdon-Lacombe, Julie; Kuo, Byron; Buick, Julie K.; Lemieux, France; Williams, Andrew; Halappanavar, Sabina; Malik, Amal; Luijten, Mirjam; Aubrecht, Jiri; Hyduke, Daniel R.; Fornace, Albert J.; Swartz, Carol D.; Recio, Leslie; Yauk, Carole L.

    2015-01-01

    Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lung 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work. PMID:25605026

  6. A medium-term gpt delta rat model as an in vivo system for analysis of renal carcinogenesis and the underlying mode of action.

    Science.gov (United States)

    Matsushita, Kohei; Ishii, Yuji; Takasu, Shinji; Kuroda, Ken; Kijima, Aki; Tsuchiya, Takuma; Kawaguchi, Hiroaki; Miyoshi, Noriaki; Nohmi, Takehiko; Ogawa, Kumiko; Nishikawa, Akiyoshi; Umemura, Takashi

    2015-01-01

    The kidney is a major target site of chemical carcinogenesis. However, a reliable in vivo assay for rapid identification of renal carcinogens has not been established. The purpose of this study was to develop a new medium-term gpt delta rat model (the GNP model) to facilitate identification of renal carcinogens. In this model, we carried out an in vivo mutation assay using unilaterally nephrectomized kidney tissue and a tumor-promoting assay using residual kidney tissue, with diethylnitrosamine (DEN) as the renal tumor initiator. To clarify the optimal time of DEN injection after nephrectomy, time-dependent changes in bromodeoxyuridine-labeling indices in the tubular epithelium of nephrectomized rats were examined. The optimal dose of DEN injection and sufficient duration of subsequent nitrilotriacetic acid treatment were determined for detection of renal preneoplastic lesions. The standard protocol for the GNP model was determined as follows. Six-week-old female gpt delta rats were treated with test chemicals for 4 weeks, followed by a 2-week washout period, and 40 mg/kg DEN was administered intraperitoneally to initiate renal carcinogenesis. Unilateral nephrectomy was performed 48 h before DEN injection, followed by gpt assays using excised kidney tissues. One week after DEN injection, rats were further exposed to test chemicals for 12 weeks, and histopathological analysis of renal preneoplastic lesions was performed as an indicator of tumor-promoting activity in residual kidney tissue. Validation studies using aristolochic acid, potassium dibasic phosphate, phenylbutazone, and d-limonene indicated the reliability of the GNP model for predicting renal carcinogens and the underlying mode of action.

  7. Toxicity assessment of four insecticides with different modes of action on pupae and adults of Eriopis connexa (Coleoptera: Coccinellidae), a relevant predator of the Neotropical Region.

    Science.gov (United States)

    Fogel, Marilina Noelia; Schneider, Marcela Inés; Rimoldi, Federico; Ladux, Lorena Sabrina; Desneux, Nicolas; Ronco, Alicia Estela

    2016-08-01

    Pesticides can be toxic to nontarget organisms including the natural enemies of agricultural pests, thus reducing the biodiversity of agroecosystems. The lethal and sublethal effects of four insecticides with different modes of action-pyriproxyfen, teflubenzuron, acetamiprid, and cypermethrin-were evaluated on pupae and adults of Eriopis connexa, an effective predator in horticultural crops. Pupal survival was reduced by pyriproxyfen (26 %) and cypermethrin (41 %). Malformations in adults emerged from treated pupae were observed after acetamiprid (82.7 and 100 % for 100 and 200 mg a.i./l, respectively), pyriproxyfen (48.6 %), and cypermethrin (13.3 %) treatments. A longer mean oviposition time was also observed in adults emerged from pupae treated with cypermethrin. Moreover, the latter insecticide as well as teflubenzuron did not reduce reproductive parameters, whereas females emerged from pyriproxyfen-treated pupae were not be able to lay eggs even when females showed large abdomens. Upon exposure of adults, survival was reduced to approximately 90 % by acetamiprid, but no reduction occurred with pyriproxyfen, teflubenzuron, or cypermethrin though the fecundity at fifth oviposition time of the female survivors was reduced. Pyriproxyfen decreased the hatching at all the oviposition times tested, whereas fertility was reduced in the fourth and fifth ovipositions by teflubenzuron and in the first and third ovipositions by cypermethrin. In conclusion, all four insecticides tested exhibited lethal or sublethal effects, or both, on E. connexa. The neurotoxic insecticides were more harmful than the insect-growth regulators, and pupae were more susceptible than adults. The toxicity of insecticides on the conservation of predators in agroecosystems of the Neotropical Region is discussed.

  8. New insights into the structure and mode of action of Mo-CBP3, an antifungal chitin-binding protein of Moringa oleifera seeds.

    Science.gov (United States)

    Batista, Adelina B; Oliveira, José T A; Gifoni, Juliana M; Pereira, Mirella L; Almeida, Marina G G; Gomes, Valdirene M; Da Cunha, Maura; Ribeiro, Suzanna F F; Dias, Germana B; Beltramini, Leila M; Lopes, José Luiz S; Grangeiro, Thalles B; Vasconcelos, Ilka M

    2014-01-01

    Mo-CBP3 is a chitin-binding protein purified from Moringa oleifera Lam. seeds that displays inhibitory activity against phytopathogenic fungi. This study investigated the structural properties and the antifungal mode of action of this protein. To this end, circular dichroism spectroscopy, antifungal assays, measurements of the production of reactive oxygen species and microscopic analyses were utilized. Mo-CBP3 is composed of 30.3% α-helices, 16.3% β-sheets, 22.3% turns and 30.4% unordered forms. The Mo-CBP3 structure is highly stable and retains its antifungal activity regardless of temperature and pH. Fusarium solani was used as a model organism for studying the mechanisms by which this protein acts as an antifungal agent. Mo-CBP3 significantly inhibited spore germination and mycelial growth at 0.05 mg.mL-1. Mo-CBP3 has both fungistatic and fungicidal effects, depending on the concentration used. Binding of Mo-CBP3 to the fungal cell surface is achieved, at least in part, via electrostatic interactions, as salt was able to reduce its inhibitory effect. Mo-CBP3 induced the production of ROS and caused disorganization of both the cytoplasm and the plasma membrane in F. solani cells. Based on its high stability and specific toxicity, with broad-spectrum efficacy against important phytopathogenic fungi at low inhibitory concentrations but not to human cells, Mo-CBP3 has great potential for the development of new antifungal drugs or transgenic crops with enhanced resistance to phytopathogens.

  9. FTIR Metabolomic Fingerprint Reveals Different Modes of Action Exerted by Structural Variants of N-Alkyltropinium Bromide Surfactants on Escherichia coli and Listeria innocua Cells

    Science.gov (United States)

    Corte, Laura; Tiecco, Matteo; Roscini, Luca; De Vincenzi, Sergio; Colabella, Claudia; Germani, Raimondo; Tascini, Carlo; Cardinali, Gianluigi

    2015-01-01

    Surfactants are extremely important agents to clean and sanitize various environments. Their biocidal activity is a key factor determined by the interactions between amphiphile structure and the target microbial cells. The object of this study was to analyze the interactions between four structural variants of N-alkyltropinium bromide surfactants with the Gram negative Escherichia coli and the Gram positive Listeria innocua bacteria. Microbiological and conductometric methods with a previously described FTIR bioassay were used to assess the metabolomic damage exerted by these compounds. All surfactants tested showed more biocidal activity in L. innocua than in E. coli. N-tetradecyltropinium bromide was the most effective compound against both species, while all the other variants had a reduced efficacy as biocides, mainly against E. coli cells. In general, the most prominent metabolomic response was observed for the constituents of the cell envelope in the fatty acids (W1) and amides (W2) regions and at the wavenumbers referred to peptidoglycan (W2 and W3 regions). This response was particularly strong and negative in L. innocua, when cells were challenged by N-tetradecyltropinium bromide, and by the variant with a smaller head and a 12C tail (N-dodecylquinuclidinium bromide). Tail length was critical for microbial inhibition especially when acting against E. coli, maybe due the complex nature of Gram negative cell envelope. Statistical analysis allowed us to correlate the induced mortality with the metabolomic cell response, highlighting two different modes of action. In general, gaining insights in the interactions between fine structural properties of surfactants and the microbial diversity can allow tailoring these compounds for the various operative conditions. PMID:25588017

  10. A Reexamination of the PPAR-α Activation Mode of Action as a Basis for Assessing Human Cancer Risks of Environmental Contaminants

    Science.gov (United States)

    Guyton, Kathryn Z.; Chiu, Weihsueh A.; Bateson, Thomas F.; Jinot, Jennifer; Scott, Cheryl Siegel; Brown, Rebecca C.; Caldwell, Jane C.

    2009-01-01

    Background Diverse environmental contaminants, including the plasticizer di(2-ethylhexyl)phthalate (DEHP), are hepatocarcinogenic peroxisome proliferators in rodents. Peroxisome proliferator–activated receptor-α (PPAR-α) activation and its sequelae have been proposed to constitute a mode of action (MOA) for hepatocarcinogenesis by such agents as a sole causative factor. Further, based on a hypothesized lower sensitivity of humans to this MOA, prior reviews have concluded that rodent hepatocarcinogenesis by PPAR-α agonists is irrelevant to human carcinogenic risk. Data synthesis Herein, we review recent studies that experimentally challenge the PPAR-α activation MOA hypothesis, providing evidence that DEHP is hepatocarcinogenic in PPAR-α–null mice and that the MOA but not hepatocarcinogenesis is evoked by PPAR-α activation in a transgenic mouse model. We further examine whether relative potency for PPAR-α activation or other steps in the MOA correlates with tumorigenic potency. In addition, for most PPAR-α agonists of environmental concern, available data are insufficient to characterize relative human sensitivity to this rodent MOA or to induction of hepatocarcinogenesis. Conclusions Our review and analyses raise questions about the hypothesized PPAR-α activation MOA as a sole explanation for rodent hepatocarcinogenesis by PPAR-α agonists and therefore its utility as a primary basis for assessing human carcinogenic risk from the diverse compounds that activate PPAR-α. These findings have broad implications for how MOA hypotheses are developed, tested, and applied in human health risk assessment. We discuss alternatives to the current approaches to these key aspects of mechanistic data evaluation. PMID:20049115

  11. Control of postharvest soft rot caused by Erwinia carotovora of vegetables by a strain of Bacillus amyloliquefaciens and its potential modes of action.

    Science.gov (United States)

    Zhao, Yancun; Li, Pengxia; Huang, Kaihong; Wang, Yuning; Hu, Huali; Sun, Ya

    2013-03-01

    Erwinia carotovora subsp. carotovora (Ecc), the causal agent of bacterial soft rot, is one of the destructive pathogens of postharvest vegetables. In this study, a bacterial isolate (BGP20) from the vegetable farm soil showed strong antagonistic activity against Ecc in vitro, and its twofold cell-free culture filtrate showed excellent biocontrol effect in controlling the postharvest bacterial soft rot of potatoes at 25 °C. The anti-Ecc metabolites produced by the isolate BGP20 had a high resistance to high temperature, UV-light and protease K. Based on the colonial morphology, cellular morphology, sporulation, and partial nucleotide sequences of 16S rRNA and gyrB gene, the isolate BGP20 was identified as Bacillus amyloliquefaciens subsp. plantarum. Further in vivo assays showed that the BGP20 cell culture was more effective in controlling the postharvest bacterial soft rot of green peppers and Chinese cabbages than its twofold cell-free culture filtrate. In contrast, the biocontrol effect and safety of the BGP20 cell culture were very poor on potatoes. In the wounds of potatoes treated with both the antagonist BGP20 and the pathogen Ecc, the viable count of Ecc was 31,746 times that of BGP20 at 48 h of incubation at 25 °C. But in the wounds of green peppers, the viable count of BGP20 increased 182.3 times within 48 h, and that of Ecc increased only 51.3 %. In addition, the treatment with both BGP20 and Ecc induced higher activity of phenylalanine ammonia-lyase (PAL) than others in potatoes. But the same treatment did not induce an increase of PAL activity in green peppers. In conclusion, the present study demonstrated that the isolate BGP20 is a promising candidate in biological control of postharvest bacterial soft rot of vegetables, but its main mode of action is different among various vegetables.

  12. Evaluating genotoxicity data to identify a mode of action and its application in estimating cancer risk at low doses: A case study involving carbon tetrachloride.

    Science.gov (United States)

    Eastmond, David A

    2008-03-01

    In the new USEPA cancer risk assessment guidelines, mode of action (MoA) information, combined with a determination of whether or not a chemical is mutagenic, plays an important role in determining whether a linear or nonlinear approach should be used to estimate cancer risks at low doses. In this article, carbon tetrachloride (CT) is used as an example to illustrate how mixed genotoxicity data can be evaluated and used to identify a likely MoA. CT is essentially negative in inducing gene mutations in Salmonella, but is consistently positive in inducing recombination and aneuploidy in fungi. Negative or equivocal results were seen in most in vitro and in vivo studies in mammals, including mutation studies in transgenic mice. However, DNA adducts, primarily those derived from oxidation- and lipid-peroxidation-derived products as well as DNA double-strand breaks and micronucleated cells, have been seen repeatedly in the liver of CT-treated animals. On the basis of the weight of evidence, CT should not be considered a directly mutagenic agent. Mutagenic as well as other genotoxic effects, as they occur, will most likely be generated through indirect mechanisms resulting from oxidative and lipid peroxidative damage and/or damage occurring during necrosis or apoptosis. As key events in this process are expected to occur in a nonlinear fashion, the expected relationship between CT dose and carcinogenic response in the liver is likely to be nonlinear with a steep dose response. This conclusion is consistent with rodent cancer bioassay results in which steep nonlinear dose responses have been seen.

  13. Toxicity ranking and toxic mode of action evaluation of commonly used agricultural adjuvants on the basis of bacterial gene expression profiles.

    Directory of Open Access Journals (Sweden)

    Ingrid Nobels

    used agricultural adjuvants based on toxicity and toxic mode of action data.

  14. Taxonomic distribution, repeats, and functions of the S1 domain-containing proteins as members of the OB-fold family.

    Science.gov (United States)

    Deryusheva, Evgeniia I; Machulin, Andrey V; Selivanova, Olga M; Galzitskaya, Oxana V

    2017-04-01

    Proteins of the nucleic acid-binding proteins superfamily perform such functions as processing, transport, storage, stretching, translation, and degradation of RNA. It is one of the 16 superfamilies containing the OB-fold in protein structures. Here, we have analyzed the superfamily of nucleic acid-binding proteins (the number of sequences exceeds 200,000) and obtained that this superfamily prevalently consists of proteins containing the cold shock DNA-binding domain (ca. 131,000 protein sequences). Proteins containing the S1 domain compose 57% from the cold shock DNA-binding domain family. Furthermore, we have found that the S1 domain was identified mainly in the bacterial proteins (ca. 83%) compared to the eukaryotic and archaeal proteins, which are available in the UniProt database. We have found that the number of multiple repeats of S1 domain in the S1 domain-containing proteins depends on the taxonomic affiliation. All archaeal proteins contain one copy of the S1 domain, while the number of repeats in the eukaryotic proteins varies between 1 and 15 and correlates with the protein size. In the bacterial proteins, the number of repeats is no more than 6, regardless of the protein size. The large variation of the repeat number of S1 domain as one of the structural variants of the OB-fold is a distinctive feature of S1 domain-containing proteins. Proteins from the other families and superfamilies have either one OB-fold or change slightly the repeat numbers. On the whole, it can be supposed that the repeat number is a vital for multifunctional activity of the S1 domain-containing proteins. Proteins 2017; 85:602-613. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Distributional data and taxonomic notes on the flea Strepsylla (Siphonaptera: Ctenophthalmidae: Neopsyllinae: Phalacropsyllini Datos de distribución y notas taxonómicas de las especies de Strepsylla (Siphonaptera: Ctenophthalmidae: Neopsyllinae: Phalacropsyllini

    Directory of Open Access Journals (Sweden)

    Roxana Acosta

    2011-12-01

    Full Text Available Strepsylla Traub, 1950 is considered a New World flea genus, parasitizing, in most cases, species of Muridae, particularly peromyscines. Thirteen species of Strepsylla are addressed with respect to their taxonomic characters, host preferences and geographic distribution. A detailed list of material is included.Strepsylla Traub, 1950 es considerado un género de pulgas del nuevo mundo, que en la mayoría de los casos parasitan múridos, particularmente peromisinos. Se comentan algunos de los caracteres taxonómicos, preferencia de huéspedes, distribución geográfica y el material examinado de las 13 especies del género.

  16. Taxonomic abstraction in psychobiology.

    Science.gov (United States)

    Evans, S H; Chafetz, M D; Gage, F H

    1984-10-01

    If a body of knowledge in a scientific discipline is to be extended beyond empirical observation and into the realm of laws and principles, one of the fundamental requirements is a taxonomy which supports the systematic integration of observations. Psychobiology benefits from taxonomies provided by biology and chemistry, which include not only object oriented taxonomies such as species or chemical elements, but also process oriented taxonomies, such as oxidation, metabolism, phototaxis, or predation. Psychobiology has yet to provide equivalent taxonomies for its behavioral observations, although the common use of terms such as fear, anger, arousal, stress, and memory might lead one to suppose that these are based on a well established taxonomy of behavioral measures. In this report the logical and quantitative requirements for treating behavioral measures in terms of taxonomic classes are reviewed. A sample of studies representing recent research in psychobiology was examined to assess interest in such a taxonomy and to identify elements of current practice which might contribute to its development. Recent practice displays some evidence of interest in behavioral classes, in choice of language, and in frequent use of multiple dependent measures. Multivariate methods, which might elicit from such data evidence contributing to the development of a taxonomy, are rarely used. Recommendations are given on some appropriate analytic methods for data resulting from current practice and for new exploratory paradigms which could aim directly at the establishment of taxonomic classes for behaviors.

  17. 基于代谢组学的杀菌剂作用机理研究%Study on Antifungal Modes-of-Action Based on Metabolomics

    Institute of Scientific and Technical Information of China (English)

    陈溪; 纪明山

    2013-01-01

    Metabolomics had so far been a valuable high-throughput screening tool for bioactive substances, and it was widely applied to life science and showed a promising perspective. The concept, empirical method, analytical method, data processing, application of metabolomics was summarized, and its potentials in biology, medicine, pesticide sphere were prospected. In this foundation, the development direction through the studies on antifungal metabolomics was rised. Through high-throughput screening and data processing as device, metabolic fingerprint library was established, and a method which can quickly screen unknown modes-of-action antifungal was set up. Metabolomics has important future trends in new drug research, drug toxicology analysis and assessment, and it might be a important breakthrough in pesticide study.%目前代谢组学是生物活性物质高效筛选的重要工具,在生命科学领域得到了越来越广泛的应用并展现出良好的前景.综述了代谢组学的概念、实验方法、分析方法、数据处理以及在生物、医药领域的应用及农药学领域的研究前景.并在此基础上,提出了利用代谢组学研究杀菌剂作用机理可能的发展方向.以高通量检测和数据处理为手段,建立代谢指纹图谱库,创建一个可以快速筛查未知杀菌剂作用机理的方法,在新型农药的研制、毒理学分析、安全评价等领域具有广阔的前景,将成为农药现代研究的一个重要突破口.

  18. Cytotoxicity and modes of action of four Cameroonian dietary spices ethno-medically used to treat cancers: Echinops giganteus, Xylopia aethiopica, Imperata cylindrica and Piper capense.

    Science.gov (United States)

    Kuete, Victor; Sandjo, Louis P; Wiench, Benjamin; Efferth, Thomas

    2013-08-26

    Echinops giganteus, Imperata cylindrica, Piper capense and Xylopia aethiopica are four medicinal spices used in Cameroon to treat cancers. The above plants previously displayed cytotoxicity against leukemia CCRF-CEM and CEM/ADR5000 cell lines as well as human pancreatic MiaPaCa-2 cells. The present study aims at emphasizing the study of the cytotoxicity and the modes of action of the above plants on a panel of ten cancer cell lines including various sensitive and drug-resistant phenotypes. The study has been extended to the isolation of the bioactive constituents from Echinops giganteus. The cytotoxicity of the extracts was determined using a resazurin reduction assay, whereas the caspase-Glo assay was used to detect the activation of caspases 3/7, caspase 8 and caspase 9 in cells treated with the four extracts. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells, analysis of mitochondrial membrane potential (MMP) as well as measurement of reactive oxygen species (ROS). The four tested extracts inhibited the proliferation of all tested cancer cell lines including sensitive and drug-resistant phenotypes. Collateral sensitivity of cancer cells to the extract of Echinops giganteus was generally better than to doxorubicin. The recorded IC50 ranges were 3.29 µg/mL [against human knockout clones HCT116 (p53(-/-)) colon cancer cells] to 14.32 µg/mL (against human liver hepatocellular carcinoma HepG2 cells) for the crude extract from Echinops giganteus, 4.17 µg/mL (against breast cancer cells transduced with control vector MDA-MB231 cells) to 19.45 µg/mL (against MDA-MB-231 BCRP cells) for that of Piper capense, 4.11 µg/mL (against leukemia CCRF-CEM cells) to 30.60 µg/mL (against leukemia HL60AR cells) for Xylopia aethiopica, 3.28 µg/mL [against HCT116 (p53(-/-)) cells] to 33.43 µg/mL (against HepG2 cells) for Imperata cylindica and 0.11 µg/mL (against CCRF-CEM cells) to 132.47 µg/mL (against HL60AR cells) for doxorubicin. The four

  19. Repeated inhalation exposure of rats to an anionic high molecular weight polymer aerosol: application of prediction models to better understand pulmonary effects and modes of action.

    Science.gov (United States)

    Pauluhn, Jürgen

    2014-08-01

    Opposed to the wealth of information available for kinetic lung overload-related effects of poorly-soluble, low-toxicity particles (PSP), only limited information is available on biodegradable high molecular weight (HMW) organic polymers (molecular weight >20,000 Da). It is hypothesized that such types of polymers may exert a somewhat similar volume displacement-related mode of action in alveolar macrophages as PSP; however, with a differing biokinetics of the material retained in the lung. This polyurethane polymer was examined in single and 2-/13-week repeated exposure rat inhalation bioassays. The design of studies was adapted to that commonly applied for PSP. Rats were nose-only exposed for 6h/day for the respective study duration, followed by 1-, 2- and 4-week postexposure periods in the single, 2- and 13-week studies, respectively. While the findings in bronchoalveolar lavage (BAL) and histopathology were consistent with those typical of PSP, they appear to be superimposed by pulmonary phospholipidosis and a much faster reversibility of pulmonary inflammation. Kinetic modeling designed to estimate the accumulated lung burden of biopersistent PSP was also suitable to simulate the overload-dependent outcomes of this biodegradable polymer as long as the faster than normal elimination kinetics was observed and an additional 'void space volume' was added to adjust for the phagocytosed additional fraction of pulmonary phospholipids. The changes observed following repeated inhalation exposure appear to be consistent with a retention-related etiopathology (kinetic overload). In summary, this study did not reveal evidence of any polymer-specific pulmonary irritation or parenchymal injury. Taking all findings into account, 7 mg polymer/m(3) (exposure 6h/day, 5-days/week on 13 consecutive weeks) constitutes the point of departure for lower respiratory tract findings that represent a transitional state from effects attributable to an overload-dependent pulmonary

  20. Review of new Nearctic mosquito distributional records north of Mexico, with notes on additions and taxonomic changes of the fauna, 1982-89.

    Science.gov (United States)

    Darsie, R F; Ward, R A

    1989-12-01

    During the past 7 years, 24 species of Nearctic mosquitoes have had extensions to their known distribution in the form of 32 new state and province records in the United States and Canada. They are included in this report along with relevant references. Additionally, 3 new United States country records have been established, 3 species have had name changes, a new species of Anopheles and sibling species of another anopheline have been described. Details of these occurrences are covered.

  1. A Taxonomic Search Engine: Federating taxonomic databases using web services

    Directory of Open Access Journals (Sweden)

    Page Roderic DM

    2005-03-01

    Full Text Available Abstract Background The taxonomic name of an organism is a key link between different databases that store information on that organism. However, in the absence of a single, comprehensive database of organism names, individual databases lack an easy means of checking the correctness of a name. Furthermore, the same organism may have more than one name, and the same name may apply to more than one organism. Results The Taxonomic Search Engine (TSE is a web application written in PHP that queries multiple taxonomic databases (ITIS, Index Fungorum, IPNI, NCBI, and uBIO and summarises the results in a consistent format. It supports "drill-down" queries to retrieve a specific record. The TSE can optionally suggest alternative spellings the user can try. It also acts as a Life Science Identifier (LSID authority for the source taxonomic databases, providing globally unique identifiers (and associated metadata for each name. Conclusion The Taxonomic Search Engine is available at http://darwin.zoology.gla.ac.uk/~rpage/portal/ and provides a simple demonstration of the potential of the federated approach to providing access to taxonomic names.

  2. Anonymous nuclear markers reveal taxonomic incongruence and long-term disjunction in a cactus species complex with continental-island distribution in South America.

    Science.gov (United States)

    Perez, Manolo F; Carstens, Bryan C; Rodrigues, Gustavo L; Moraes, Evandro M

    2016-02-01

    The Pilosocereus aurisetus complex consists of eight cactus species with a fragmented distribution associated to xeric enclaves within the Cerrado biome in eastern South America. The phylogeny of these species is incompletely resolved, and this instability complicates evolutionary analyses. Previous analyses based on both plastid and microsatellite markers suggested that this complex contained species with inherent phylogeographic structure, which was attributed to recent diversification and recurring range shifts. However, limitations of the molecular markers used in these analyses prevented some questions from being properly addressed. In order to better understand the relationship among these species and make a preliminary assessment of the genetic structure within them, we developed anonymous nuclear loci from pyrosequencing data of 40 individuals from four species in the P. aurisetus complex. The data obtained from these loci were used to identify genetic clusters within species, and to investigate the phylogenetic relationship among these inferred clusters using a species tree methodology. Coupled with a palaeodistributional modelling, our results reveal a deep phylogenetic and climatic disjunction between two geographic lineages. Our results highlight the importance of sampling more regions from the genome to gain better insights on the evolution of species with an intricate evolutionary history. The methodology used here provides a feasible approach to develop numerous genealogical molecular markers throughout the genome for non-model species. These data provide a more robust hypothesis for the relationship among the lineages of the P. aurisetus complex.

  3. Composición taxonómica, distribución y bionomía de la familia Noteridae (Coleoptera: Adephaga en Cuba Taxonomic composition, distribution and bionomics of the family Noteridae (Coleoptera: Adephaga in Cuba

    Directory of Open Access Journals (Sweden)

    Yoandri S. Megna

    2006-07-01

    Full Text Available La presente investigación analiza la composición taxonómica, distribución y bionomía de los notéridos registrados en Cuba, y se brinda una clave para su identificación. El estudio se realizó sobre la base de datos bibliográficos a nivel regional y nacional, así como del material colectado en diferentes localidades del país. Este trabajo permitió definir la lista de especies, su distribución por distritos fitogeográficos y los aspectos más generales de su bionomía. Se determinó que la familia Noteridae está compuesta por cinco géneros ( Hydrocanthus Say, Mesonoterus Sharp , Suphis Aubé , Suphisellus Crotch y Notomicrus Sharp y 10 especies, de las cuales Suphisellus tenuicornis (Chevrolat es endémica, e Hydrocanthus advena Sharp no está confirmada. Las especies registradas están distribuidas en 11 (28,2% de los 39 distritos fitogeográficos establecidos. El distrito de mayor riqueza de especies es el Nº 15 (Planicie Centro-Occidental, con ocho especies. La especie más ampliamente distribuida es Notomicrus sharpi J. Balfour-Browne, reportada para seis (15,4% distritos. Los datos bionómicos muestran que los notéridos tienen preferencia por los hábitats lénticos y permanentes, de aguas dulces y turbias, ubicados en zonas bajas y soleadas con abundante vegetación acuática.The present work deals with the taxonomic composition, distribution, and bionomics of noterids from Cuba . Our research is based both on local and regional references on this family found in the literature, and on the identification of specimens collected from several localities of the country. We present a taxonomical list and a key to identify the species occurring in Cuba , along with their distribution regarding phytogeographic districts, and bionomical information. In Cuba , the family Noteridae is composed of five genera ( Hydrocanthus Say, Mesonoterus Sharp, Suphis Aubé , Suphisellus Crotch, and Notomicrus Sharp and 10 species, of which

  4. Metabonomic strategy for the investigation of the mode of action of the phytotoxin (5S,8R,13S,16R)-(-)-pyrenophorol using 1H nuclear magnetic resonance fingerprinting.

    Science.gov (United States)

    Aliferis, Konstantinos A; Chrysayi-Tokousbalides, Maria

    2006-03-08

    The biochemical mode of action of (5S,8R,13S,16R)-(-)-pyrenophorol isolated from a Drechslera avenae pathotype was investigated by using metabolic fingerprinting. (1)H NMR spectra of crude leaf extracts from untreated Avena sterilis seedlings and A. sterilis seedlings treated with pyrenophorol were compared with those obtained from treatments with the herbicides diuron, glyphosate, mesotrione, norflurazon, oxadiazon, and paraquat. Multivariate analysis was carried out to group treatments according to the mode of action of the phytotoxic substances applied. Analysis results revealed that none of the herbicide treatments fitted the pyrenophorol model and indicate that the effect of the phytotoxin on A. sterilis differs than those caused by glyphosate, mesotrione, norflurazon, oxadiazon, paraquat, and diuron, which inhibit 5-enolpyruvylshikimate-3-phosphate synthase, 4-hydroxyphenyl-pyruvate-dioxygenase, phytoene desaturase, protoporphyrinogen oxidase, photosystem I, and photosystem II, respectively. The method applied, combined with appropriate data preprocessing and analysis, was found to be rapid for the screening of phytotoxic substances for metabolic effects.

  5. Bacteriocins from Lactobacillus plantarum production, genetic organization and mode of action: produção, organização genética e modo de ação Bacteriocinas de Lactobacillus plantarum

    Directory of Open Access Journals (Sweden)

    Svetoslav D. Todorov

    2009-06-01

    Full Text Available Bacteriocins are biologically active proteins or protein complexes that display a bactericidal mode of action towards usually closely related species. Numerous strains of bacteriocin producing Lactobacillus plantarum have been isolated in the last two decades from different ecological niches including meat, fish, fruits, vegetables, and milk and cereal products. Several of these plantaricins have been characterized and the aminoacid sequence determined. Different aspects of the mode of action, fermentation optimization and genetic organization of the bacteriocin operon have been studied. However, numerous of bacteriocins produced by different Lactobacillus plantarum strains have not been fully characterized. In this article, a brief overview of the classification, genetics, characterization, including mode of action and production optimization for bacteriocins from Lactic Acid Bacteria in general, and where appropriate, with focus on bacteriocins produced by Lactobacillus plantarum, is presented.Bacteriocinas são proteínas ou complexos protéicos biologicamente ativos que apresentam atividade bactericida contra espécies relacionadas. Nas ultimas duas décadas, várias cepas de Lactobacillus plantarum produtoras de bacteriocinas foram isoladas de diferentes nichos ecológicos como carnes, peixes, frutas, vegetais e produtos lácteos e de cereais. Várias plantaricinas foram caracterizadas e suas seqüências de aminoácidos determinadas. Diferentes aspectos do modo de ação, otimização da fermentação e organização genética já foram estudados. Entretanto, muitas bacteriocinas produzidas por diferentes cepas de Lactobacillus plantarum ainda não foram completamente caracterizadas.Nesse artigo, apresenta-se uma breve revisão sobre a classificação, genética, caracterização, modo de ação, e otimização da produção de bacteriocinas de bactérias láticas em geral, e, quando apropriado, de bacteriocinas de Lactobacillus plantarum.

  6. Nanostructural modification of a model homogalacturonan with a novel pectin methylesterase: Effects of pH on nanostructure, enzyme mode of action and substrate functionality

    Science.gov (United States)

    A pectin methylesterase (CpL-PME) present in a commercial papain preparation was used to modify the amount and distribution of charge in a model pectic homogalacturonan (HG) at pH 4.5 and pH 7.5. Introduced negatively charged demethylesterified blocks (DMB) were excised as oligomers with a limited e...

  7. Nacellidae limpets of the southern end of South America: taxonomy and distribution Lapas Nacellidae del extremo sur de Sudamérica: taxonomía y distribución

    Directory of Open Access Journals (Sweden)

    CLAUDIO VALDOVINOS

    2005-09-01

    Full Text Available Taxonomically, the Mollusca of the southern end of South America are moderately well known, but the literature is scattered, there is little information on their habitats, and distributional records are scarce for the Chilean archipelago lying between Chiloé Island (42° S and Tierra del Fuego (55° S. Although much is known about the biology and ecology of of some species of Nacellidae, the taxonomy of the group have been partially neglected, particularly in remote areas of the world such as the Chilean fjords. Therefore, this study aims to clarify the nomenclatural status, and establish the morphological characteristics and distribution of the Chilean Nacellidae. Especially, the following three objectives are pursued: (i to clarify the correct identity of existing species; (ii to describe of morphological details, highlighting the clear diagnostic characters of each species, and (iii to delimitate and discuss their geographical range in Chile. The examination of the Nacellidae of the Chilean fiords has resulted in the recognition of one species of Nacella (Nacella and seven species of Nacella (Patinigera, wherein the principal specific differences are in the shell (shape, thickness and color and in radular teeth morphology. The genus Nacella and its subgenus Patinigera are cold-water limpets, and are exclusively inhabitants of Subantarctic and Antarctic waters. The greater part of their range being subantarctic, but extending to the Antarctic by way of the Scotia Arc, and also ranging northward up the Chilean coast to at least Valparaiso at 33° S (only N. (P. clypeater. They apparently have their centre of distribution in the Magellanic Province of southern South America, corresponding to an area with a high degree of diversification (N. (N. mytilina, N. (P. chiloensis, N. (P. deaurata, N. (P. delicatissima, N. (P. flammea, N. (P. magellanica, N. (P. venosa, wherefrom the species tends to spread eastward, with a larval transport probably

  8. A taxonomic revision of Germainia (Andropogoneae: Poaceae) in Thailand

    NARCIS (Netherlands)

    Teerawatananon, A.; Sungkaew, S.; Boontia, V.; Hodkinson, T.R.

    2012-01-01

    A taxonomic revision of the genus Germainia (Andropogoneae, Poaceae) in Thailand is presented based on herbarium and field studies, including evidence from morphology, habitats and geographical distribution. Six of the nine recognized Germainia species are found in Thailand. We include a key to the

  9. A taxonomic revision of Germainia (Andropogoneae: Poaceae) in Thailand

    NARCIS (Netherlands)

    Teerawatananon, A.; Sungkaew, S.; Boontia, V.; Hodkinson, T.R.

    2012-01-01

    A taxonomic revision of the genus Germainia (Andropogoneae, Poaceae) in Thailand is presented based on herbarium and field studies, including evidence from morphology, habitats and geographical distribution. Six of the nine recognized Germainia species are found in Thailand. We include a key to the

  10. NODC Standard Product: NODC Taxonomic Code on CD-ROM (NODC Accession 0050418)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The content of the NODC Taxonomic Code, Version 8 CD-ROM (CD-ROM NODC-68) distributed by NODC is archived in this accession. Version 7 of the NODC Taxonomic Code...

  11. Global taxonomic diversity of living reptiles.

    Science.gov (United States)

    Pincheira-Donoso, Daniel; Bauer, Aaron M; Meiri, Shai; Uetz, Peter

    2013-01-01

    Reptiles are one of the most ecologically and evolutionarily remarkable groups of living organisms, having successfully colonized most of the planet, including the oceans and some of the harshest and more environmentally unstable ecosystems on earth. Here, based on a complete dataset of all the world's diversity of living reptiles, we analyse lineage taxonomic richness both within and among clades, at different levels of the phylogenetic hierarchy. We also analyse the historical tendencies in the descriptions of new reptile species from Linnaeus to March 2012. Although (non-avian) reptiles are the second most species-rich group of amniotes after birds, most of their diversity (96.3%) is concentrated in squamates (59% lizards, 35% snakes, and 2% amphisbaenians). In strong contrast, turtles (3.4%), crocodilians (0.3%), and tuataras (0.01%) are far less diverse. In terms of species discoveries, most turtles and crocodilians were described early, while descriptions of lizards, snakes and amphisbaenians are multimodal with respect to time. Lizard descriptions, in particular, have reached unprecedented levels during the last decade. Finally, despite such remarkably asymmetric distributions of reptile taxonomic diversity among groups, we found that the distributions of lineage richness are consistently right-skewed, with most clades (monophyletic families and genera) containing few lineages (monophyletic genera and species, respectively), while only a few have radiated greatly (notably the families Colubridae and Scincidae, and the lizard genera Anolis and Liolaemus). Therefore, such consistency in the frequency distribution of richness among clades and among phylogenetic levels suggests that the nature of reptile biodiversity is fundamentally fractal (i.e., it is scale invariant). We then compared current reptile diversity with the global reptile diversity and taxonomy known in 1980. Despite substantial differences in the taxonomies (relative to 2012), the patterns of

  12. Exploring historical trends using taxonomic name metadata

    Directory of Open Access Journals (Sweden)

    Schenk Ryan

    2008-05-01

    Full Text Available Abstract Background Authority and year information have been attached to taxonomic names since Linnaean times. The systematic structure of taxonomic nomenclature facilitates the ability to develop tools that can be used to explore historical trends that may be associated with taxonomy. Results From the over 10.7 million taxonomic names that are part of the uBio system 4, approximately 3 million names were identified to have taxonomic authority information from the years 1750 to 2004. A pipe-delimited file was then generated, organized according to a Linnaean hierarchy and by years from 1750 to 2004, and imported into an Excel workbook. A series of macros were developed to create an Excel-based tool and a complementary Web site to explore the taxonomic data. A cursory and speculative analysis of the data reveals observable trends that may be attributable to significant events that are of both taxonomic (e.g., publishing of key monographs and societal importance (e.g., world wars. The findings also help quantify the number of taxonomic descriptions that may be made available through digitization initiatives. Conclusion Temporal organization of taxonomic data can be used to identify interesting biological epochs relative to historically significant events and ongoing efforts. We have developed an Excel workbook and complementary Web site that enables one to explore taxonomic trends for Linnaean taxonomic groupings, from Kingdoms to Families.

  13. Exploring historical trends using taxonomic name metadata.

    Science.gov (United States)

    Sarkar, Indra Neil; Schenk, Ryan; Norton, Catherine N

    2008-05-13

    Authority and year information have been attached to taxonomic names since Linnaean times. The systematic structure of taxonomic nomenclature facilitates the ability to develop tools that can be used to explore historical trends that may be associated with taxonomy. From the over 10.7 million taxonomic names that are part of the uBio system 4, approximately 3 million names were identified to have taxonomic authority information from the years 1750 to 2004. A pipe-delimited file was then generated, organized according to a Linnaean hierarchy and by years from 1750 to 2004, and imported into an Excel workbook. A series of macros were developed to create an Excel-based tool and a complementary Web site to explore the taxonomic data. A cursory and speculative analysis of the data reveals observable trends that may be attributable to significant events that are of both taxonomic (e.g., publishing of key monographs) and societal importance (e.g., world wars). The findings also help quantify the number of taxonomic descriptions that may be made available through digitization initiatives. Temporal organization of taxonomic data can be used to identify interesting biological epochs relative to historically significant events and ongoing efforts. We have developed an Excel workbook and complementary Web site that enables one to explore taxonomic trends for Linnaean taxonomic groupings, from Kingdoms to Families.

  14. Significando o risco sanitário: modos de atuação sobre o risco na vigilância sanitária / Meaning the health risk: modes of action on the risk in health surveillance

    Directory of Open Access Journals (Sweden)

    Ana Valesca Fernandes GIlson Silva

    2014-05-01

    Full Text Available Este estudo qualitativo, que utiliza o Interacionismo Simbólico como referencial teórico e a Teoria Fundamentada nos Dados como método, buscou compreender os modos de atuação sobre o risco. Sintetiza os significados do risco para os profissionais da Vigilância Sanitária (VISA e analisa os modos de atuação para o seu controle. A síntese é a sistematização das interpretações e significados do risco. A análise apresenta a existência de dois modos de atuação, permitindo empreender a aplicação do significado de risco no âmbito do domínio de um saber específico. Entre a identificação do risco e a intervenção existem processos que mesclam a racionalidade à subjetividade, a autoridade ao controle, a experiência ao conhecimento formal adquirido. O agir do profissional da VISA é constituído por conhecimentos, pela experiência adquirida, pelos contextos socioculturais e pelas interações que definem e redefinem os modos de atuar. As ações são baseadas nos significados do risco que se deslocam no plano da objetividade e da subjetividade, e a legislação é um importante instrumento de decisão e de persuasão. Embora ocorra um deslocamento para o uso do conhecimento e da experiência, é o arcabouço legal que imprime o que deve ou não ser controlado. ------------------------------------------------------------------------- This qualitative study that utilizes Symbolic Interactionism as a theoretical background and Grounded Theory as a method, sought to understand the modes of action about risk. It summarizes the meanings of risk to the professionals of Health Surveillance (HS, and analyses the modes of action to control it. The summary is the systematization of the in-terpretations and meanings of risk. The analysis shows the existence of two modes of ac-tion, allowing to undertake the application of the meaning of risk in the scope of domain of an specific knowledge. Between the risk identification and the

  15. Mode-of-Action Uncertainty for Dual-Mode Carcinogens: A Bounding Approach for Naphthalene-Induced Nasal Tumors in Rats Based on PBPK and 2-Stage Stochastic Cancer Risk Models

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K T

    2007-05-11

    A relatively simple, quantitative approach is proposed to address a specific, important gap in the appr approach recommended by the USEPA Guidelines for Cancer Risk Assessment to oach address uncertainty in carcinogenic mode of action of certain chemicals when risk is extrapolated from bioassay data. These Guidelines recognize that some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate 'linear' (genotoxic) vs. 'nonlinear' (nongenotoxic) approaches to low low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient t to parameterize a biologically based model that reliably o extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach - similar to that used in reference dose procedures for classic toxicity endpoints - can address MOA uncertainty in a way that avoids explicit modeling of low low-dose risk as a function of administere administered or internal dose. Even when a 'nonlinear' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was i illustrated llustrated for a likely DMOA rodent carcinogen naphthalene, specifically to the issue of risk extrapolation from bioassay data on naphthalene naphthalene-induced nasal tumors in rats. Bioassay data, supplemental toxicokinetic data, and related physiologically based p

  16. Azelaic acid: Properties and mode of action.

    Science.gov (United States)

    Sieber, M A; Hegel, J K E

    2014-01-01

    Acne is a common skin disorder that can be problematic for adults as well as for adolescents. It has several key pathophysiological features such as follicular hyperkeratosis, elevated Propionibacterium acnes proliferation, and reactive inflammation, all of which should be targeted for an optimal outcome. Azelaic acid (AzA) has profound anti-inflammatory, antioxidative effects, and is bactericidal against a range of Gram-negative and Gram-positive microorganisms as well, including antibiotic-resistant bacterial strains. In addition, AzA's antikeratinizing effects are inhibitory toward comedones. AzA is effective overall in targeting multiple causes of acne and has been proven to be well tolerated in numerous clinical trials.

  17. GHB for cataplexy: Possible mode of action.

    Science.gov (United States)

    Szabadi, Elemer

    2015-06-01

    The sleep disorder narcolepsy is caused by the loss of orexinergic neurones in the lateral hypothalamus. A troublesome symptom of narcolepsy is cataplexy, the sudden loss of muscle tone in response to strong emotions. It can be alleviated by antidepressants and sodium oxybate (γ-hydroxybutyric acid (GHB)). It is likely that the noradrenergic nucleus locus coeruleus (LC) is involved since it is essential for the maintenance of muscle tone, and ceases to fire during cataplectic attacks. Furthermore, alpha-2 adrenoceptors proliferate in the LC in cataplexy, probably due to 'heterologous denervation supersensitivity' resulting from the loss/weakening of the orexinergic input to the LC. This would lead to the sensitization of the autoinhibition mechanism of LC neurones mediated by inhibitory alpha-2 adrenoceptors ('autoreceptors'). Thus the excitatory input from the amygdala to the LC, activated by an emotional stimulus, would lead to the 'switching off' of LC activity via the supersensitive auto-inhibition mechanism. GHB is an agonist at both γ-aminobutyric acid (GABA) GABA (B) and GHB receptors that may be a subtype of an extrasynaptic GABA(A) receptor. GHB may prevent a cataplectic attack by dampening the tone of LC neurones via the stimulation of inhibitory extrasynaptic GABA receptors in the LC, and thus increasing the threshold for autoinhibition.

  18. Lactococcal bacteriocins : mode of action and immunity

    NARCIS (Netherlands)

    Venema, Koen; Venema, Gerard; Kok, Jan

    1995-01-01

    Bacteriocins are antimicrobial peptides produced by bacteria. Some of those synthesized by Lactococcus lactis have been characterized in great detail recently. The lactococcal bacteriocins are hydrophobic cationic peptides, which form pores in the cytoplasmic membrane of sensitive cells.

  19. LACTOCOCCAL BACTERIOCINS - MODE OF ACTION AND IMMUNITY

    NARCIS (Netherlands)

    VENEMA, K; KOK, J; Venema, Gerhardus

    1995-01-01

    Bacteriocins are antimicrobial peptides produced by bacteria. Some of those synthesized by Lactococcus lactis have been characterized in great detail recently. The lactococcal bacteriocins are hydrophobic cationic peptides, which form pores in the cytoplasmic membrane of sensitive cells.

  20. Lactococcins : Mode of action, immunity and secretion

    NARCIS (Netherlands)

    Venema, K; Kok, J; Venema, Gerhardus

    1995-01-01

    Lactococcus lactis subsp. cremoris 9B4 produces three small (around 5kDa), heat-stable, non-lanthionine containing, membrane active bacteriocins. Amino acid uptake experiments and proton motive force measurements have indicated that these peptides most probably form pores in the cytoplasmic membrane

  1. The mode of action of immunological adjuvants.

    Science.gov (United States)

    Allison, A C

    1998-01-01

    Adjuvants augment immune responses to antigens and influence the balance between cell-mediated and humoral responses, as well as the isotypes of antibodies formed. New adjuvant formulations include antigen-carrying vehicles and small molecules with immunomodulating activity. Widely used two-phase vehicles comprise liposomes and microfluidized squalene or squalane emulsions. These are believed to target antigens to antigen-presenting cells, including dendritic cells (DC), follicular dendritic cells (FDC) and B-lymphocytes. Activation of complement generates C3d, which binds CR2 (CD21) on FDC and B-lymphocytes, thereby stimulating the proliferation of the latter and the generation of B-memory. Targeting of antigens to DC may favour cell-mediated immunity. Immunomodulating agents induce the production of cytokine cascades. In a primary cascade at injection sites TNF-alpha, GM-CSF and IL-1 are produced. TNF-alpha promotes migration of DC to lymphoid tissues, while GM-CSF and IL-1 accelerate the maturation of DC into efficient antigen-presenting cells for T-lymphocytes. In a secondary cytokine cascade in draining lymph nodes, DC produce IL-12, which induces Th1 responses with the production of IFN-gamma. The cytokines elicit cell-mediated immune responses and the formation of antibodies of protective isotypes, such as IgG2a in the mouse and IgG1 in humans. Antibodies of these isotypes activate complement and collaborate with antibody-dependent effector cells in protective immune responses.

  2. mode of action (Part 2 of 4)

    African Journals Online (AJOL)

    Inlrodiu lion. Probiotic preparations are usually defined as live microbial dietary adjuvants which by improving nutritional and .... used in the treatment of oral pathogens, should be .... relapsing Clostridium difficile colitis with Lactobacillus. GG.

  3. [Mode of action of terrazoleon Mucor mucedo].

    Science.gov (United States)

    Lyr, H; Casperson, G; Laussmann, B

    1977-01-01

    It is assumed that the fungistatic effect of terrazol in Mucor mucedo is induced by a liberation of phospholipases within within the mitochondria and perhaps at other membranes. In isolated mitochondria a rapid formation of lysolecithin can be demonstrated at low concentrations of terrazol. This would explain the lytic symptoms in mitochondria visible by electron microscopy. Lipid peroxidation could not be demonstrated. The only antidots at present known for the growth inhibiting effect of terrazol and on its ultrastructural effects are impure saccharose, which seems to contain an unknown factor, and procain hydrochloride or to a lesser extent lidocain, which are well-known inhibitors of phospholipases. The pathological thickening of the cell wall induced by terazol seems to be an unspecific side effect reflecting a diminished phosphorylating activity of the mitochondria.

  4. Intracervical tents: usage and mode of action.

    Science.gov (United States)

    Johnson, N

    1989-06-01

    Topical prostaglandins and intracervical tents at present comprise the most widely used methods for priming of the cervix before surgery. While tents and prostaglandins are comparable in terms of shortening the time interval between labor induction and delivery, tents do not initiate powerful myometrial contractions and thus are not associated with the complication of uterine hypertonus. In early abortion, tents are regarded as superior to prostaglandins, estrogen, and relaxin. In the midtrimester abortion, however, best results are achieved through the combined use of tents and prostaglandins. This approach facilitates a shorter abortion time, a lesser risk of sepsis, and use of a lower dose of prostaglandin. The effect of the particular type of tent selected--Clamicel, Dilapan, or Laminaria--is related to the initial state of the cervix, with the best results achieved in the soft patulous cervix of young pregnant women. Laminaria tents are declining in popularity as a result of their lengthy duration of action, unreliability, pain, or insertion and as the tent expands, and need for several insertions of multiple tents. The synthetic Dilapan tent does not share the disadvantages of inconsistency, long duration of action, and risk of sepsis, but tends to fragment and fracture so that the distal portion remains within the uterus. Lamicel, a polyvinyl alcohol sponge impregnated with magnesium sulfate, has a less impressive speed of action than Dilapan (3 hours and 2 hours, respectively), yet its softness makes it easy to withdraw without fragmentation or fracture. Lamicel has been used successfully in 1st-trimester abortion, before induction of labor or IUD insertion, for hysteroscopy and removal of lost IUDs, and in formal diagnostic curettage.

  5. Flexible taxonomic assignment of ambiguous sequencing reads

    Directory of Open Access Journals (Sweden)

    Jansson Jesper

    2011-01-01

    Full Text Available Abstract Background To characterize the diversity of bacterial populations in metagenomic studies, sequencing reads need to be accurately assigned to taxonomic units in a given reference taxonomy. Reads that cannot be reliably assigned to a unique leaf in the taxonomy (ambiguous reads are typically assigned to the lowest common ancestor of the set of species that match it. This introduces a potentially severe error in the estimation of bacteria present in the sample due to false positives, since all species in the subtree rooted at the ancestor are implicitly assigned to the read even though many of them may not match it. Results We present a method that maps each read to a node in the taxonomy that minimizes a penalty score while balancing the relevance of precision and recall in the assignment through a parameter q. This mapping can be obtained in time linear in the number of matching sequences, because LCA queries to the reference taxonomy take constant time. When applied to six different metagenomic datasets, our algorithm produces different taxonomic distributions depending on whether coverage or precision is maximized. Including information on the quality of the reads reduces the number of unassigned reads but increases the number of ambiguous reads, stressing the relevance of our method. Finally, two measures of performance are described and results with a set of artificially generated datasets are discussed. Conclusions The assignment strategy of sequencing reads introduced in this paper is a versatile and a quick method to study bacterial communities. The bacterial composition of the analyzed samples can vary significantly depending on how ambiguous reads are assigned depending on the value of the q parameter. Validation of our results in an artificial dataset confirm that a combination of values of q produces the most accurate results.

  6. Nanoscaled boehmites' modes of action in a polymer and its carbon fiber reinforced plastic under compression load; Wirkungsweisen nanoskaliger Boehmite in einem Polymer und seinem Kohlenstofffaserverbund unter Druckbelastung

    Energy Technology Data Exchange (ETDEWEB)

    Arlt, Christine

    2011-07-01

    Increasing ecological awareness as well as quality and safety demands, which are present, for instance, in the aerospace and automotive sectors, lead to the need to use more sophisticated and more effective materials. For that purpose, laminates of carbon fiber reinforced plastic (CFRP), which are manufactured by injection technology, are reinforced with boehmite particles. This doping strengthens the laminates, whose original properties are weaker than prepregs. Besides the shear strength, compression strength and the damage tolerance, the mode of action of the nanoparticles in resin and in CRFP is also analyzed. It thereby reveals that the hydroxyl groups and even more a taurine modification of the boehmites' surface after the elementary polymer morphology. Consequently a new flow and reaction comportment, lower glass transition temperatures and shrinkage, as well as a changed mechanical behavior occur. Due to a structural upgrading of the matrix (higher shear stiffness, reduced residual stress), a better fiber-matrix adhesion, and differing crack paths, the boehmite nanoparticles move the degradation barrier of the material to higher loadings, thus resulting in considerably upgraded new CFRP. (orig.)

  7. A taxonomic synopsis of Altingiaceae with nine new combinations

    Directory of Open Access Journals (Sweden)

    Stefanie Ickert-Bond

    2013-12-01

    Full Text Available A taxonomic synopsis of the Altingiaceae is presented, including the taxonomic enumeration and distribution of 15 recognized species based on studies of 1,500 specimens from 24 herbaria throughout the distributional range of the taxa. Previous phylogenetic analyses based on several molecular markers have shown that Altingia and Semiliquidambar are nested within Liquidambar. All Altingia and Semiliquidambar species are now formally transferred to Liquidambar, which has the nomenclatural priority. The following nine new combinations are herein made: Liquidambar cambodiana (Lecomte Ickert-Bond & J. Wen, L. caudata (H. T. Chang Ickert-Bond & J. Wen, L. chingii (Metcalf Ickert-Bond & J. Wen, L. gracilipes (Hemsl. Ickert-Bond & J. Wen, L. multinervis (Cheng Ickert-Bond & J. Wen, L. obovata (Merrill & Chun Ickert-Bond & J. Wen, L. poilanei (Tardieu Ickert-Bond & J. Wen, L. siamensis (Craib Ickert-Bond & J. Wen, and L. yunnanensis (Rehder & Wilson Ickert-Bond & J. Wen.

  8. A taxonomic revision of Germainia (Andropogoneae: Poaceae) in Thailand

    OpenAIRE

    Teerawatananon, A.; Sungkaew, S.; Boontia, V.; Hodkinson, T.R.

    2012-01-01

    A taxonomic revision of the genus Germainia (Andropogoneae, Poaceae) in Thailand is presented based on herbarium and field studies, including evidence from morphology, habitats and geographical distribution. Six of the nine recognized Germainia species are found in Thailand. We include a key to the taxa that are currently known from Thailand or may be expected, lists of species synonymies, species descriptions and lists of representative specimens.

  9. [Taxonomic theory for non-classical systematics].

    Science.gov (United States)

    Pavlinov, I Ia

    2012-01-01

    Outlined briefly are basic principles of construing general taxonomic theory for biological systematics considered in the context of non-classical scientific paradigm. The necessity of such kind of theory is substantiated, and some key points of its elaboration are exposed: its interpretation as a framework concept for the partial taxonomic theories in various schools of systematics; elaboration of idea of cognitive situation including three interrelated components, namely subject, object, and epistemic ones; its construing as a content-wisely interpreted quasi-axiomatics, with strong structuring of its conceptual space including demarcation between axioms and inferring rules; its construing as a "conceptual pyramid" of concepts of various levels of generality; inclusion of a basic model into definition of the taxonomic system (classification) regulating its content. Two problems are indicated as fundamental: definition of taxonomic diversity as a subject domain for the systematics as a whole; definition of onto-epistemological status of taxonomic system (classification) in general and of taxa in particular.

  10. Editor's Highlight: Mode of Action Analysis for Rat Hepatocellular Tumors Produced by the Synthetic Pyrethroid Momfluorothrin: Evidence for Activation of the Constitutive Androstane Receptor and Mitogenicity in Rat Hepatocytes.

    Science.gov (United States)

    Okuda, Yu; Kushida, Masahiko; Sumida, Kayo; Nagahori, Hirohisa; Nakamura, Yoshimasa; Higuchi, Hashihiro; Kawamura, Satoshi; Lake, Brian G; Cohen, Samuel M; Yamada, Tomoya

    2017-08-01

    High dietary levels of momfluorothrin, a nongenotoxic synthetic pyrethroid, induced hepatocellular tumors in male and female Wistar rats in a 2-year bioassay. The mode of action (MOA) for rat hepatocellular tumors was postulated to occur via activation of the constitutive androstane receptor (CAR), as momfluorothrin is a close structural analogue of the pyrethroid metofluthrin, which is known to produce rat liver tumors through a CAR-mediated MOA. To elucidate the MOA for rat hepatocellular tumor formation by momfluorothrin, this study was conducted to examine effects on key and associative events of the CAR-mediated MOA for phenobarbital based on the International Programme on Chemical Safety framework. A 2-week in vivo study in Wistar rats revealed that momfluorothrin induced CYP2B activities, increased liver weights, produced hepatocyte hypertrophy and increased hepatocyte replicative DNA synthesis. These effects correlated with the dose-response relationship for liver tumor formation and also showed reversibility upon cessation of treatment. Moreover, momfluorothrin did not increase CYP2B1/2 mRNA expression and hepatocyte replicative DNA synthesis in CAR knockout rats. Using cultured Wistar rat hepatocytes and the RNA interference technique, knockdown of CAR resulted in a suppression of induction of CYP2B1/2 mRNA levels by momfluorothrin. Alternative MOAs for liver tumor formation were excluded. A global gene expression profile analysis of the liver of male Wistar rats treated with momfluorothrin for 2 weeks also showed similarity to the prototypic CAR activator phenobarbital. Overall, these data strongly support that the postulated MOA for momfluorothrin-induced rat hepatocellular tumors as being mediated by CAR activation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. N(4)-tolyl-2-acetylpyridine thiosemicarbazones and their platinum(II,IV) and gold(III) complexes: cytotoxicity against human glioma cells and studies on the mode of action.

    Science.gov (United States)

    Ferraz, Karina S O; Da Silva, Jeferson G; Costa, Flávia M; Mendes, Bruno M; Rodrigues, Bernardo L; dos Santos, Raquel G; Beraldo, Heloisa

    2013-10-01

    Complexes [Au(2Ac4oT)Cl][AuCl2] (1), [Au(Hpy2Ac4mT)Cl2]Cl·H2O (2), [Au(Hpy2Ac4pT)Cl2]Cl (3), [Pt(H2Ac4oT)Cl]Cl (4), [Pt(2Ac4mT)Cl]·H2O (5), [Pt(2Ac4pT)Cl] (6) and [Pt(L)Cl2OH], L = 2Ac4mT (7), 2Ac4oT (8), 2Ac4pT (9) were prepared with N(4)-ortho- (H2Ac4oT), N(4)-meta- (H2Ac4mT) and N(4)-para- (H2Ac4pT) tolyl-2-acetylpyridine thiosemicarbazone. The cytotoxic activities of all compounds were assayed against U-87 and T-98 human malignant glioma cell lines. Upon coordination cytotoxicity improved in 2, 5 and 8. In general, the gold(III) complexes were more cytotoxic than those with platinum(II,IV). Several of these compounds proved to be more active than cisplatin and auranofin used as controls. The gold(III) complexes probably act by inhibiting the activity of thioredoxin reductase enzyme whereas the mode of action of the platinum(II,IV) complexes involves binding to DNA. Cells treated with the studied compounds presented morphological changes such as cell shrinkage and blebs formation, which indicate cell death by apoptosis induction.

  12. 天然化合物丁香酚抗烟草花叶病毒病作用机制初探%Mode of Action of Natural Compound Eugenol on Tobacco Mosaic Virus Disease

    Institute of Scientific and Technical Information of China (English)

    王春梅; 苏杭; 陈浩; 石志琦; 范永坚

    2012-01-01

    [Aims] The aim of this research was to study mode of action of eugenol on tobacco mosaic virus disease. [Methods] The preventive and therapeutic effect of Eugenol on tobacco mosaic virus disease was determined. The influence of eugenol on TMV virions was observed with electron microscope. The effect of ugenol on polymerization of TMV coat protein was also determined. [Results] The results showed that eugenol had a better preventive and therapeutic effect. The TMV virions treated with Eugenol showed ruptures and abnormality. Eugenol had an inhibition effect on polymerization of TMV coat protein. [Conclusions] Eugenol as a newly reported antiviral compound could be used to control plant virus diseases.%[目的]初步研究丁香酚对植物病毒病的作用机制.[方法]利用盆栽法测定了丁香酚对烟草花叶病毒病的预防和治疗效果;电镜法观察了丁香酚对病毒粒子的影响;体外混合法测定了丁香酚对烟草花叶病毒外壳蛋白体外聚合的影响.[结果]丁香酚对烟草花叶病毒病具有较好的预防和治疗效果;丁香酚与病毒混合处理后,病毒粒子有断裂现象;丁香酚对TMV外壳蛋白体外聚合有一定的抑制作用.[结论]丁香酚可以作为新型抗病毒剂用于防治作物病毒病.

  13. Comparison of the effects of hexavalent chromium in the alimentary canal of F344 rats and B6C3F1 mice following exposure in drinking water: implications for carcinogenic modes of action.

    Science.gov (United States)

    Thompson, Chad M; Proctor, Deborah M; Suh, Mina; Haws, Laurie C; Hébert, Charles D; Mann, Jill F; Shertzer, Howard G; Hixon, J Gregory; Harris, Mark A

    2012-01-01

    Exposure to high concentrations of hexavalent chromium (Cr[VI]) in drinking water is reported to induce oral mucosa tumors in F344 rats and intestinal tumors in B6C3F1 mice. To investigate the modes of action underlying these tumors, 90-day drinking water studies (with interim necropsy at day 8) were conducted with concentrations of 0.1-182 mg/l Cr(VI), administered as 0.3-520 mg/l sodium dichromate dihydrate. Blood and tissue samples were analyzed for chromium content, oxidative stress, iron levels, and gross and microscopic lesions. Results for the F344 rats are described herein and compared with results from B6C3F1 mice published previously. After 90 days of exposure, total chromium concentrations in the rat and mouse oral mucosae were comparable, yet significant dose-dependent decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed only in rats. In the duodenum, changes in GSH/GSSG were only observed in mice. Levels of 8-hydroxydeoxyguanosine were not increased in the oral or duodenal mucosae of either species. Glutathione levels were increased in the duodenum but decreased in the jejunum of both species, indicating potential differential responses in the intestinal segments. Histiocytic infiltration was observed in the duodenum of both species, yet duodenal cytokines were repressed in mice but increased in rats. Serum and bone marrow iron levels were more decreased in rats than mice. Collectively, these data suggest that Cr(VI)-induced carcinogenesis in the rodent alimentary canal involves oxidative stress; however, differences in histopathology, cytokines, and iron status suggest potential contributions from other factors as well.

  14. Mode of action of ethyl tertiary-butyl ether hepatotumorigenicity in the rat: evidence for a role of oxidative stress via activation of CAR, PXR and PPAR signaling pathways.

    Science.gov (United States)

    Kakehashi, Anna; Hagiwara, Akihiro; Imai, Norio; Nagano, Kasuke; Nishimaki, Fukumi; Banton, Marcy; Wei, Min; Fukushima, Shoji; Wanibuchi, Hideki

    2013-12-01

    To elucidate possible mode of action (MOA) and human relevance of hepatotumorigenicity in rats for ethyl tertiary-butyl ether (ETBE), male F344 rats were administered ETBE at doses of 0, 150 and 1000 mg/kg body weight twice a day by gavage for 1 and 2 weeks. For comparison, non-genotoxic carcinogen phenobarbital (PB) was applied at a dose of 500 ppm in diet. Significant increase of P450 total content and hydroxyl radical levels by low, high doses of ETBE and PB treatments at weeks 1 and 2, and 8-OHdG formation at week 2, accompanied accumulation of CYP2B1/2B2, CYP3A1/3A2 and CYP2C6, and downregulation of DNA oxoguanine glycosylase 1, induction of apoptosis and cell cycle arrest in hepatocytes, respectively. Up-regulation of CYP2E1 and CYP1A1 at weeks 1 and 2, and peroxisome proliferation at week 2 were found in high dose ETBE group. Results of proteome analysis predicted activation of upstream regulators of gene expression altered by ETBE including constitutive androstane receptor (CAR), pregnane-X-receptor (PXR) and peroxisome proliferator-activated receptors (PPARs). These results indicate that the MOA of ETBE hepatotumorigenicity in rats may be related to induction of oxidative stress, 8-OHdG formation, subsequent cell cycle arrest, and apoptosis, suggesting regenerative cell proliferation after week 2, predominantly via activation of CAR and PXR nuclear receptors by a mechanism similar to that of PB, and differentially by activation of PPARs. The MOA for ETBE hepatotumorigenicity in rats is unlikely to be relevant to humans.

  15. Taxonomic status of Pelargonium reniforme Curt.

    Directory of Open Access Journals (Sweden)

    Janine E. Victor

    2014-07-01

    Full Text Available Background: Pelargonium reniforme Curt. is a morphologically variable species that many authors have attempted to split or combine. Confusion relating to the differences between the two subspecies currently included under P. reniforme has impeded attempts to assess their conservation status.  Pelargonium reniforme is closely related to  Pelargonium sidoides;  the two species are indistinguishable when not flowering and their distributions overlap in some areas.Objectives: With this study, we aimed to clarify the taxonomic status of the two subspecies of P. reniforme, which has relevance in terms of their conservation status.Method: Leaf shape, petiole length, internode length and flower colour were assessed by studying herbarium specimens of the two subspecies of  P. reniforme and specimens of P. sidoides. Living specimens of the two subspecies were also examined in their natural habitat.Results: The current investigation showed that the morphological characters used to distinguish the two subspecies of P. reniforme are too variable to separate them. Variation in some morphological characters may be related to environmental conditions.Conclusion: The recognition of the two subspecies of P. reniforme as distinct taxa is no longer justified.

  16. Taxonomic names, metadata, and the Semantic Web

    Directory of Open Access Journals (Sweden)

    Roderic D. M. Page

    2006-01-01

    Full Text Available Life Science Identifiers (LSIDs offer an attractive solution to the problem of globally unique identifiers for digital objects in biology. However, I suggest that in the context of taxonomic names, the most compelling benefit of adopting these identifiers comes from the metadata associated with each LSID. By using existing vocabularies wherever possible, and using a simple vocabulary for taxonomy-specific concepts we can quickly capture the essential information about a taxonomic name in the Resource Description Framework (RDF format. This opens up the prospect of using technologies developed for the Semantic Web to add ``taxonomic intelligence" to biodiversity databases. This essay explores some of these ideas in the context of providing a taxonomic framework for the phylogenetic database TreeBASE.

  17. Mode-of-Action Uncertainty for Dual-Mode Carcinogens:Lower Bounds for Naphthalene-Induced Nasal Tumors in Rats Implied byPBPK and 2-Stage Stochastic Cancer Risk Models

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K T

    2007-01-30

    As reflected in the 2005 USEPA Guidelines for Cancer Risk Assessment, some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate ''linear'' (genotoxic) vs. ''nonlinear'' (nongenotoxic) approaches to low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient to parameterize a biologically based model that reliably extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach--similar to that used in reference dose procedures for classic toxicity endpoints--can address MOA uncertainty in a way that avoids explicit modeling of low-dose risk as a function of administered or internal dose. Even when a ''nonlinear'' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was illustrated for the rodent carcinogen naphthalene. Bioassay data, supplemental toxicokinetic data, and related physiologically based pharmacokinetic and 2-stage stochastic carcinogenesis modeling results all clearly indicate that naphthalene is a DMOA carcinogen. Plausibility bounds on rat-tumor-type specific DMOA-related uncertainty were obtained using a 2-stage model adapted to reflect the empirical link between genotoxic and cytotoxic effects of the most potent identified genotoxic naphthalene metabolites, 1,2- and 1,4-naphthoquinone. Resulting

  18. Mode of action of ethyl tertiary-butyl ether hepatotumorigenicity in the rat: Evidence for a role of oxidative stress via activation of CAR, PXR and PPAR signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Kakehashi, Anna, E-mail: anna@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Hagiwara, Akihiro; Imai, Norio [DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113 (Japan); Nagano, Kasuke [Nagano Toxicologic-Pathology Consulting, Ochiai, Hadano, Kanagawa 257-0025 (Japan); Nishimaki, Fukumi [Biofuel Assessment Group, New Fuels Dept., Japan Petroleum Energy Center (JPEC), 4-3-9 Toranomon, Minato-ku, Tokyo 105-0001 (Japan); Banton, Marcy [Toxicology and Risk Assessment, LyondellBasell Industries, LyondellBasell Corporate HSE/Product Safety, One Houston Center, Suite 700, 1221 McKinney Street, Houston, TX 770 10 (United States); Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0011 (Japan); Wanibuchi, Hideki [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2013-12-01

    To elucidate possible mode of action (MOA) and human relevance of hepatotumorigenicity in rats for ethyl tertiary-butyl ether (ETBE), male F344 rats were administered ETBE at doses of 0, 150 and 1000 mg/kg body weight twice a day by gavage for 1 and 2 weeks. For comparison, non-genotoxic carcinogen phenobarbital (PB) was applied at a dose of 500 ppm in diet. Significant increase of P450 total content and hydroxyl radical levels by low, high doses of ETBE and PB treatments at weeks 1 and 2, and 8-OHdG formation at week 2, accompanied accumulation of CYP2B1/2B2, CYP3A1/3A2 and CYP2C6, and downregulation of DNA oxoguanine glycosylase 1, induction of apoptosis and cell cycle arrest in hepatocytes, respectively. Up-regulation of CYP2E1 and CYP1A1 at weeks 1 and 2, and peroxisome proliferation at week 2 were found in high dose ETBE group. Results of proteome analysis predicted activation of upstream regulators of gene expression altered by ETBE including constitutive androstane receptor (CAR), pregnane-X-receptor (PXR) and peroxisome proliferator-activated receptors (PPARs). These results indicate that the MOA of ETBE hepatotumorigenicity in rats may be related to induction of oxidative stress, 8-OHdG formation, subsequent cell cycle arrest, and apoptosis, suggesting regenerative cell proliferation after week 2, predominantly via activation of CAR and PXR nuclear receptors by a mechanism similar to that of PB, and differentially by activation of PPARs. The MOA for ETBE hepatotumorigenicity in rats is unlikely to be relevant to humans. - Highlights: • We focus on MOA and human relevance of hepatotumorigenicity in rats for ETBE. • ETBE was administered to F344 rats for 1 and 2 weeks. • Oxidative stress formation, proliferation and apoptosis in the liver are analyzed. • ETBE-induced changes of gene and protein expression in the liver are examined. • The effects are compared with those induced by non-genotoxic carcinogen PB.

  19. The Mode of Action of D-Pinitol and It's Formulation on Sphaerotheca fuliginea%D-松醇原药及其水剂对黄瓜白粉病的作用方式

    Institute of Scientific and Technical Information of China (English)

    王丹丹; 陈佳; 陈义娟; 张红艳; 贾福丽; 白羡钦; 代光辉

    2012-01-01

    [目的]通过室内试验,验证D-松醇原药及其水剂对黄瓜白粉病的作用方式,为D-松醇的田间应用提供理论支持.[方法]配制不同质量浓度的D-松醇原药及其水剂,在不同时间采用温室喷雾法对黄瓜白粉病进行防治试验,调查其防治效果.[结果]试验表明:接种后第3天,原药和水剂分别处理的防效均优于各接种前5、2 d和接种后1 d处理的效果.原药质量浓度梯度实验显示2000 mg/L时,接菌后7d防效达64.52%,其他处理方式的防效均低于50%.20%(质量分数)水剂稀释至3.3%,接菌后7d,防效为93.07%,同比防效最好.[结论]研究表明:D-松醇对黄瓜白粉病有治疗效果,治疗3d的防效效果最好.原药2000mg/L时防效最好,20%的水剂稀释至3.3%防效最好.水剂在减少D-松醇原药用量的基础上,进一步减轻了黄瓜白粉病发病程度,为D-松醇水剂的开发提供了可行性依据.此外,D-松醇原药及其水剂对黄瓜白粉病作用方式的确定为深入研究D-松醇对黄瓜白粉病菌的作用机制提供了依据.%[Aims] Through the indoor experiment, the mode of action of D-pinitol TC and D-pinitol AS against Sphaerotheca fuliginea were tested to provide theoretical support for their field application. [Methods] The control effects of D-pinitol TC and D-pinitol AS with different concentrations against Sphaerotheca fuliginea were investigated by using spay method in greenhouse at different time. [Results] The results exhibited the control effect was best at the 3rd day after infection treated with D-pinitol TC and D-pinitol AS separately compared with that at the 2nd and 5th day before infection and that at the 1st day after infection. The concentration gradient study showed that D-pinitol TC's control effect reached 64.52% at 2000 mg/L at the 7th day superior to other treatment methods (less than 50%). D-Pinitol 20% AS was diluted to the concentration of 3.3% gave the best control effect of 93

  20. Taxonomic revision of Myrosma (Marantaceae)

    NARCIS (Netherlands)

    Vieira, S.; Maas, P.J.M.; Borchsenius, F.

    2012-01-01

    Myrosma is a genus of rosulate herbs characterized by a compact and strongly monosymmetric inflorescence with conspicuous, white to pale green, mostly membranous bracts, in the axil of which is a single flower pair. The genus is widely distributed throughout Central Brazil, northern South America, a

  1. Converting Taxonomic Descriptions to New Digital Formats

    Directory of Open Access Journals (Sweden)

    Hong Cui

    2008-01-01

    Full Text Available Abstract.--The majority of taxonomic descriptions is currently in print format. The majority of digital descriptions are in formats such as DOC, HTML, or PDF and for human readers. These formats do not convey rich semantics in taxonomic descriptions for computer-aided process. Newer digital formats such as XML and RDF accommodate semantic annotations that allow computers to process the rich semantics on human's behalf, thus open up opportunities for a wide range of innovative usages of taxonomic descriptions, such as searching in more precise and flexible ways, integrating with gnomic and geographic information, generating taxonomic keys automatically, and text data mining and information visualization etc. This paper discusses the challenges in automated conversion of multiple collections of descriptions to XML format and reports an automated system, MARTT. MARTT is a machine-learning system that makes use of training examples to tag new descriptions into XML format. A number of utilities are implemented as solutions to the challenges. The utilities are used to reduce the effort for training example preparation, to facilitate the creation of a comprehensive schema, and to predict system performance on a new collection of descriptions. The system has been tested with several plant and alga taxonomic publications including Flora of China and Flora of North America.

  2. Taxonomic turnover and abundance in Cretaceous to Tertiary wood floras of Antarctica: implications for changes in forest ecology

    NARCIS (Netherlands)

    Cantrill, David J.; Poole, I.J.

    2004-01-01

    Based on the temporal distribution, abundance, and taxonomic composition of wood floras, four phases of vegetation development are recognized through the Cretaceous to Early Tertiary of the Antarctic Peninsula: (1) Aptian to Albian communities dominated by podocarpaceous, araucarian, and minor

  3. Dynamics and Modes of Action of Xylanases fromPenicillium corylophilum on Xylan%顶青霉木聚糖酶的水解动力学与水解模式

    Institute of Scientific and Technical Information of China (English)

    杨瑞金; 许时婴; 王璋

    2001-01-01

    从顶青霉(Penicillium corylophilum)培养液中分离纯化得到的3种木聚糖酶组分(Part A, Part B 和 Part C),对其水解动力学和水解模式的研究结果表明,3种木聚糖酶的动力学常数(桦木木聚糖为底物)分别为:Part A,Km=1.00 mg/mL,Vmax=0.159 U/mL;Part B, Km=1.59 mg/mL, Vmax=0.274 U/mL;Part C,Km=0.85 mg/mL,Vmax=0.200 U/mL. 3种木聚糖酶的水解模式相同,主要从一端(非还原端)水解得到木三糖和木二糖,并且得到木三糖的速度大于得到木二糖的速度;水解会产生木四糖,但木四糖会很快进一步水解成木二糖,木四糖水解成木糖和木三糖的可能性极小;木三糖会进一步水解成木糖和木二糖,但速度不快;木二糖不会进一步水解。粗酶水解玉米芯木聚糖时,阿拉伯糖侧链的水解与木聚糖主链的水解同步进行,粗酶中含有水解阿拉伯糖基侧链的阿拉伯糖苷酶活力.%Dynamics and mode of acting on xylan of three parts of xylanases (Part A, Part B and Part C) separated and purified from a culture filtrate of Penicillium corylophilum No. P-3-31 were investigated. The Km and Vmax of the three purified enzymes with birchwood xylan as a substrate were 1.00 mg/mL and 0.159 U/mL for Part A ( pH 4.0, 50 ℃) , 1.59 mg/mL and 0.274 U/mL for Part B (pH 4.0,50 ℃) and 0.85 mg/mL and 0.200 U/mL for Part C (pH 5.5,50 ℃). Based on the dynamic studies, it was deduced that three purified enzymes had the same mode of action on xylan. Xylotriose and xylobiose were main hydrolysates of long-chain xylan by these enzymes. Xylooligosaccharides upwards from xylotetraose were immediately hydrolyzed, and xylotetraose was mainly hydrolyzed to xylobiose. Xylotriose was slowly hydrolyzed, but xylobiose was unable to be further hydrolyzed by these enzymes. The studies on the hydrolysis dynamics of xylan from corncob with crude enzyme showed that the hydrolysis of arabinose side-chain was almost

  4. A taxonomic revision of Harpullia (Sapindaceae)

    NARCIS (Netherlands)

    Leenhouts, P.W.; Vente, Magda

    1982-01-01

    The present taxonomic revision of Harpullia was started by the second author as the main part of her work for a M. Sc. in biology at Leiden University. She concentrated on a revision of the species occurring in New Guinea, paid only a more superficial attention to the rest of the genus. The first

  5. Relicts of a forested past: Southernmost distribution of the hairy frog genus Trichobatrachus Boulenger, 1900 (Anura: Arthroleptidae) in the Serra do Pingano region of Angola with comments on its taxonomic status.

    Science.gov (United States)

    Ernst, Raffael; Nienguesso, Alvaro Bruno Toto; Lautenschläger, Thea; Barej, Michael F; Schmitz, Andreas; Scmitz, Andreas; Hölting, Monique

    2014-03-14

    The monotypic genus Trichobatrachus, with its sole representative, the hairy frog, Trichobatrachus robustus Boulenger, 1900, could be considered one of the most well-known frogs of Africa. Despite its broad recognition and the fact that it is considered wide-spread and locally common (Amiet & Burger 2004), surprisingly little is known about the actual distribution and the specific occurrence patterns of the species. It was originally described by Boulenger (1900) from the Benito River, previously erroneously stated to be located in Gabon. However, Lötters et al. (2001) clarified that the type locality was actually situated in Equatorial Guinea, then part of French Congo, and subsequently provided the first confirmed country record for Gabon. Hairy frogs were previously included in the herpetofaunal lists of Cameroon (Parker 1936; Perret & Mertens 1957), the Democratic Republic of Congo (Laurent 1956), and Nigeria (Schiøtz 1963). More recently published accounts list them for Cameroon (Euskirchen et al. 1999; Herrmann et al. 2005; Gonwouo & Rödel 2008), Equatorial Guinea (De la Riva 1994; Lasso et al. 2002), Gabon (Lötters et al. 2001; Rödel & Pauwels 2003; Burger et al. 2004; Pauwels & Rödel 2007; Bell et al. 2011), and the Democratic Republic of Congo (DRC, Fretey et al. 2011), and speculate about their potential occurrence in Congo and the Cabinda enclave of Angola (Amiet & Burger 2004). The DRC record so far represented the most southerly distribution, while the most northerly account comes from the Adamaoua Province of northern Cameroon (Tadpole voucher MHNG-AMP/ERPI-1035.006 from Bénoué source, Northern cliff Ngaoundéré, Adamaoua, Cameroon/Adamaoua Province, cf. Perret 1966). Specimens stored in the collection at the Royal Museum of Central Africa, Tervuren (RMCA) under collection numbers RMCA B 90060.0004-11 confirm the occurrence of the species in Congo. To our knowledge, these specimens represent yet unpublished first country records.

  6. Biogeographic Variation in Host Range Phenotypes and Taxonomic Composition of Marine Cyanophage Isolates.

    Science.gov (United States)

    Hanson, China A; Marston, Marcia F; Martiny, Jennifer B H

    2016-01-01

    Despite the important role of phages in marine systems, little is understood about how their diversity is distributed in space. Biogeographic patterns of marine phages may be difficult to detect due to their vast genetic diversity, which may not be accurately represented by conserved marker genes. To investigate the spatial biogeographic structure of marine phages, we isolated over 400 cyanophages on Synechococcus host strain WH7803 at three coastal locations in the United States (Rhode Island, Washington, and southern California). Approximately 90% of the cyanophage isolates were myoviruses, while the other 10% were podoviruses. The diversity of isolates was further characterized in two ways: (i) taxonomically, using conserved marker genes and (ii) phenotypically, by testing isolates for their ability to infect a suite of hosts, or their "host range." Because host range is a highly variable trait even among closely related isolates, we hypothesized that host range phenotypes of cyanophage isolates would vary more strongly among locations than would taxonomic composition. Instead, we found evidence for strong biogeographic variation both in taxonomic composition and host range phenotypes, with little taxonomic overlap among the three coastal regions. For both taxonomic composition and host range phenotypes, cyanophage communities from California and Rhode Island were the most dissimilar, while Washington communities exhibited similarity to each of the other two locations. These results suggest that selection imposed by spatial variation in host dynamics influence the biogeographic distribution of cyanophages.

  7. Taxonomía y distribución del género Leptoscelis en Costa Rica (Hemiptera: Heteroptera: Coreidae: Leptoscelini Taxonomy and distribution of the genus Leptoscelis in Costa Rica (Hemiptera: Heteroptera: Coreidae: Leptoscelini

    Directory of Open Access Journals (Sweden)

    Harry Brailovsky

    2012-03-01

    Full Text Available Se revisa el género Leptoscelis Laporte (Coreidae: Leptoscelini para Costa Rica y se describe una especie nueva, L. conspicuus. Se discuten sus relaciones con L. quadrisignatus (Distant y L. tricolor Westwood. Leptoscelis bisbimaculata Breddin es sinonimizada con L. quadrisignatus. Se cita por primera vez L. tricolor para Costa Rica. El trabajo incluye nuevos datos de distribución para el género, ilustraciones de las especies y de los parámeros y una clave para la identificación de las especies costarricenses.The genus Leptoscelis Laporte (Coreidae: Leptoscelini from Costa Rica is revised. One new species, L. conspicuus, is described and compared with L. quadrisignatus (Distant and L. tricolor Westwood. Leptoscelis bisbimaculata Breddin is synonymized with L. quadrisignatus. Leptoscelis tricolor is recorded for the first time from Costa Rica. New distribution records are presented. Habitus illustrations and drawings of parameres are provided. A key to the known Costarican species is presented.

  8. FANTOM: Functional and taxonomic analysis of metagenomes

    Directory of Open Access Journals (Sweden)

    Sanli Kemal

    2013-02-01

    Full Text Available Abstract Background Interpretation of quantitative metagenomics data is important for our understanding of ecosystem functioning and assessing differences between various environmental samples. There is a need for an easy to use tool to explore the often complex metagenomics data in taxonomic and functional context. Results Here we introduce FANTOM, a tool that allows for exploratory and comparative analysis of metagenomics abundance data integrated with metadata information and biological databases. Importantly, FANTOM can make use of any hierarchical database and it comes supplied with NCBI taxonomic hierarchies as well as KEGG Orthology, COG, PFAM and TIGRFAM databases. Conclusions The software is implemented in Python, is platform independent, and is available at http://www.sysbio.se/Fantom.

  9. Lactobacillus species: taxonomic complexity and controversial susceptibilities.

    Science.gov (United States)

    Goldstein, Ellie J C; Tyrrell, Kerin L; Citron, Diane M

    2015-05-15

    The genus Lactobacillus is a taxonomically complex and is composed of over 170 species that cannot be easily differentiated phenotypically and often require molecular identification. Although they are part of the normal human gastrointestinal and vaginal flora, they can also be occasional human pathogens. They are extensively used in a variety of commercial products including probiotics. Their antimicrobial susceptibilities are poorly defined in part because of their taxonomic complexity and are compounded by the different methods recommended by Clinical Laboratory Standards Institute and International Dairy Foundation. Their use as probiotics for prevention of Clostridium difficile infection is prevalent among consumers worldwide but raises the question of will the use of any concurrent antibiotic effect their ability to survive. Lactobacillus species are generally acid resistant and are able to survive ingestion. They are generally resistant to metronidazole, aminoglycosides and ciprofloxacin with L. acidophilus being susceptible to penicillin and vancomycin, whereas L. rhamnosus and L. casei are resistant to metronidazole and vancomycin.

  10. Phylogenetic analysis and taxonomic revision of Physodactylinae (Coleoptera, Elateridae

    Directory of Open Access Journals (Sweden)

    Simone Policena Rosa

    2014-01-01

    Full Text Available A phylogeny based on male morphological characters and taxonomic revision of the Physodactylinae genera are presented. The phylogenetic analysis based on 66 male characters resulted in the polyphyly of Physodactylinae which comprises four independent lineages. Oligostethius and Idiotropia from Africa were found to be sister groups. Teslasena from Brazil was corroborated as belonging to Cardiophorinae clade. The South American genera Physodactylus and Dactylophysus were found to be sister groups and phylogenetically related to Heterocrepidius species. The Oriental Toxognathus resulted as sister group of that clade plus (Dicrepidius ramicornis (Lissomus sp, Physorhynus erythrocephalus. Taxonomic revisions include diagnoses and redescriptions of genera and distributional records and illustrations of species. Key to species of Teslasena, Toxognathus, Dactylophysus and Physodactylus are also provided. Teslasena lucasi is synonymized with T. femoralis. A new species of Dactylophysus is described, D. hirtus sp. nov., and lectotypes are designated to non-conspecific D. mendax sensu Fleutiaux and Heterocrepidius mendax Candèze. Physodactylus niger is removed from synonymy under P. oberthuri; P. carreti is synonymized with P. niger; P. obesus and P. testaceus are synonymized with P. sulcatus. Nine new species are described in Physodactylus: P. asper sp. nov., P. brunneus sp. nov., P. chassaini sp. nov., P. flavifrons sp. nov., P. girardi sp. nov., P. gounellei sp. nov., P. latithorax sp. nov., P. patens sp. nov. and P. tuberculatus sp. nov.

  11. A Falsification of the Citation Impediment in the Taxonomic Literature

    Science.gov (United States)

    Steiner, Florian M.; Pautasso, Marco; Zettel, Herbert; Moder, Karl; Arthofer, Wolfgang; Schlick-Steiner, Birgit C.

    2015-01-01

    Current science evaluation still relies on citation performance, despite criticisms of purely bibliometric research assessments. Biological taxonomy suffers from a drain of knowledge and manpower, with poor citation performance commonly held as one reason for this impediment. But is there really such a citation impediment in taxonomy? We compared the citation numbers of 306 taxonomic and 2291 non-taxonomic research articles (2009–2012) on mosses, orchids, ciliates, ants, and snakes, using Web of Science (WoS) and correcting for journal visibility. For three of the five taxa, significant differences were absent in citation numbers between taxonomic and non-taxonomic papers. This was also true for all taxa combined, although taxonomic papers received more citations than non-taxonomic ones. Our results show that, contrary to common belief, taxonomic contributions do not generally reduce a journal's citation performance and might even increase it. The scope of many journals rarely featuring taxonomy would allow editors to encourage a larger number of taxonomic submissions. Moreover, between 1993 and 2012, taxonomic publications accumulated faster than those from all biological fields. However, less than half of the taxonomic studies were published in journals in WoS. Thus, editors of highly visible journals inviting taxonomic contributions could benefit from taxonomy's strong momentum. The taxonomic output could increase even more than at its current growth rate if: (i) taxonomists currently publishing on other topics returned to taxonomy and (ii) non-taxonomists identifying the need for taxonomic acts started publishing these, possibly in collaboration with taxonomists. Finally, considering the high number of taxonomic papers attracted by the journal Zootaxa, we expect that the taxonomic community would indeed use increased chances of publishing in WoS indexed journals. We conclude that taxonomy's standing in the present citation-focused scientific landscape could

  12. Phytoliths as Emerging Taxonomic Tools for Identification of Plants: An Overview

    Directory of Open Access Journals (Sweden)

    Sheikh Abdul Shakoor

    2014-01-01

    Full Text Available In the recent advancements in identification of plant species, phytoliths have found an immense role in the identification of plants at different levels of taxonomic hierarchy. Many plant groups are known to accumulate silica in solid form in and between the cells and tissues and hence create the structures commonly known as phytoliths. These phytoliths create replicas of the structures where they are deposited. The shapes of phytolith replicas, their size dimensions (morphometric parameters, surface features (ornamentation, distribution, and orientation pattern in epidermal layers of vegetative and reproductive structures as well as their frequency are highly important for characterization of species. Monocotyledonous families particularly the family Poaceae (Gramineae are known to produce diverse phytolith types that can serve as diagnostic markers for characterization of different taxa at different levels of taxonomic hierarchy. The present paper highlights the importance of phytoliths in taxonomic analysis of plants particularly in the family Poaceae.

  13. Plant DNA barcodes, taxonomic management, and species discovery in tropical forests.

    Science.gov (United States)

    Dick, Christopher W; Webb, Campbell O

    2012-01-01

    DNA barcodes have great potential for species identification and taxonomic discovery in tropical forests. This use of DNA barcodes requires a reference DNA library of known taxa with which to match DNA from unidentified specimens. At an even more basic level, it presupposes that the species in the regional species pool have Latin binomials. This is not the case in species-rich tropical forests in which many species are new to science or members of poorly circumscribed species complexes. This chapter describes a workflow geared toward taxonomic discovery, which includes the discovery of new species, distribution records, and hybrid forms, and to management of taxonomic entities in forest inventory plots. It outlines the roles of laboratory technicians, field workers and herbarium-based taxonomists, and concludes with a discussion of potential multilocus nuclear DNA approaches for identifying species in recently evolved clades.

  14. Taxonomic resolution and Biological Traits Analysis (BTA) approaches in estuarine free-living nematodes

    Science.gov (United States)

    Alves, A. S.; Veríssimo, H.; Costa, M. J.; Marques, J. C.

    2014-02-01

    The taxonomic and functional structure of the subtidal nematode assemblages from a temperate estuary (Mondego estuary, Portugal) was studied, focussing on different taxonomic levels (genus, family and order), on single functional groups and on multiple biological traits. Based on taxonomic levels and on four biological traits (feeding type, life strategy, tail and body shape), the analysis of the nematode assemblage distribution patterns revealed spatial differences but no clear temporal pattern. At the family and genus level, a separation of the upstream sections was observed, while a distinction of polyhaline and euhaline areas was less evident. The use of biological traits added new information regarding the relationships between diversity patterns and the environmental variables. Most nematodes encountered along the estuary were non-selective deposit feeders (1B) and omnivores/predators (2B), colonizer-persisters (score of 2 or 3), with clavate-conicocylindrical tails and slender bodies and with a distribution related essentially to salinity, oxygen and chlorophyll a. Applying a Biological Traits Analysis (BTA) showed the role of oxygen concentration in the distribution of the nematode communities. Although the BTA was no more powerful than the traditional taxonomic approach in detecting spatial differences along the Mondego estuary, it has increased our knowledge of the functional structure and characterization of nematode communities in the estuary.

  15. Dung Beetles along a Tropical Altitudinal Gradient: Environmental Filtering on Taxonomic and Functional Diversity

    Science.gov (United States)

    Nunes, Cássio Alencar; Braga, Rodrigo Fagundes; Figueira, José Eugênio Cortes; Neves, Frederico de Siqueira; Fernandes, G. Wilson

    2016-01-01

    Mountains provide an interesting context in which to study the many facets of biodiversity in response to macroclimate, since environmental conditions change rapidly due to elevation. Although the decrease in biodiversity with increasing elevation is generally accepted, our understanding of the variation of functional diversity along altitudinal gradients is still poorly known. The partitioning of diversity into spatial components can help to understand the processes that influence the distribution of species, and these studies are urgently needed in face of the increasing threats to mountain environments throughout the world. We describe the distribution of dung beetle diversity along an altitudinal gradient on a tropical mountain in southeastern Brazil, including the spatial partitioning of taxonomic and functional diversities. The altitudinal gradient ranged from 800 up to 1400 m a.s.l. and we collected dung beetles at every 100 m of altitude. We used the Rao Index to calculate γ, α and β diversity for taxonomic and functional diversity of dung beetles. Climatic, soil and vegetation variables were used to explain variation in community attributes along the altitudinal gradient. Dung beetle richness declined with altitude and was related to climatic and vegetation variables, but functional diversity did not follow the same pattern. Over 50% of γ taxonomic diversity was caused by among altitudes diversity (β), while almost 100% of functional diversity was due to the α component. Contrasting β taxonomic with β functional diversity, we suggest that there is ecological redundancy among communities and that the environment is filtering species in terms of the Grinnellian niche, rather than the Eltonian niche. β taxonomic diversity is caused mainly by the turnover component, reinforcing the hypothesis of environmental filtering. Global warming may have strong effects on mountain communities due to upslope range shifts and extinctions, and these events will

  16. Dung Beetles along a Tropical Altitudinal Gradient: Environmental Filtering on Taxonomic and Functional Diversity.

    Science.gov (United States)

    Nunes, Cássio Alencar; Braga, Rodrigo Fagundes; Figueira, José Eugênio Cortes; Neves, Frederico de Siqueira; Fernandes, G Wilson

    2016-01-01

    Mountains provide an interesting context in which to study the many facets of biodiversity in response to macroclimate, since environmental conditions change rapidly due to elevation. Although the decrease in biodiversity with increasing elevation is generally accepted, our understanding of the variation of functional diversity along altitudinal gradients is still poorly known. The partitioning of diversity into spatial components can help to understand the processes that influence the distribution of species, and these studies are urgently needed in face of the increasing threats to mountain environments throughout the world. We describe the distribution of dung beetle diversity along an altitudinal gradient on a tropical mountain in southeastern Brazil, including the spatial partitioning of taxonomic and functional diversities. The altitudinal gradient ranged from 800 up to 1400 m a.s.l. and we collected dung beetles at every 100 m of altitude. We used the Rao Index to calculate γ, α and β diversity for taxonomic and functional diversity of dung beetles. Climatic, soil and vegetation variables were used to explain variation in community attributes along the altitudinal gradient. Dung beetle richness declined with altitude and was related to climatic and vegetation variables, but functional diversity did not follow the same pattern. Over 50% of γ taxonomic diversity was caused by among altitudes diversity (β), while almost 100% of functional diversity was due to the α component. Contrasting β taxonomic with β functional diversity, we suggest that there is ecological redundancy among communities and that the environment is filtering species in terms of the Grinnellian niche, rather than the Eltonian niche. β taxonomic diversity is caused mainly by the turnover component, reinforcing the hypothesis of environmental filtering. Global warming may have strong effects on mountain communities due to upslope range shifts and extinctions, and these events will

  17. Extrafloral nectaries in Combretaceae: morphology, anatomy and taxonomic significance

    Directory of Open Access Journals (Sweden)

    P. M. Tilney

    2004-12-01

    Full Text Available Extrafloral nectaries (EFNs in members of the Combretaceae are nectaries not involved with pollination and occurring on vegetative structures; they are believed to attract ants to protect plants against herbivorv by other insects. In the Combretaceae EFNs are reported in species of Terminalia L. and Pteleopsis Engl., putative EFNs in Meiostemon Exell & Stace and Quisqualis L., and an absence of EFNs in Combretum Loefl. and Lumnitzera Willd. EFNs in the family are generally spherical in shape and may be raised, level with the surface or somewhat concave. They are similar in the Terminalia and  Pteleopsis species where they display varying degrees of internal zonation and are composed of small cells; those species observed in the field were all found to have functional EFNs. In Meiostemon tetrandrum (Exell Exell & Stace, Quisqualis indica L.. Q. littorea (Engl. Exell and Q. paviflora Gerrard ex Sond.. apparent EFNs lack internal zonation and are composed of enlarged cells; confirmation is required as to whether these are functional . The formation of EFNs appears to be highly flexible. They are usually essentially associated with new growth but their occurrence is sporadic and they do not appear on every leaf or every' branch of a plant. The distribution of EFNs on leaves, when present, is of taxonomic significance to separate species of Pteleopsis and Terminalia: otherwise the presence or absence and distribution of EFNs are too variable and sporadic in occurrence to be of taxonomic significance at the species level. Indiscriminate use of the terms gland and domatium instead of EFN. and possible confusion with damage caused by other organisms, has probably con­tributed to many of these structures not previously being recorded as EFNs. Floral and extrafloral nectar samples of T. phanerophlebia Engl. & Diels differed in sugar composition.

  18. Taxonomical developments in the family Polyomaviridae.

    Science.gov (United States)

    Johne, Reimar; Buck, Christopher B; Allander, Tobias; Atwood, Walter J; Garcea, Robert L; Imperiale, Michael J; Major, Eugene O; Ramqvist, Torbjorn; Norkin, Leonard C

    2011-09-01

    The Polyomaviridae Study Group of the International Committee on Taxonomy of Viruses (ICTV) has recommended several taxonomical revisions, as follows: The family Polyomaviridae, which is currently constituted as a single genus (Polyomavirus), will be comprised of three genera: two containing mammalian viruses and one containing avian viruses. The two mammalian genera will be designated Orthopolyomavirus and Wukipolyomavirus, and the avian genus will be named Avipolyomavirus. These genera will be created by the redistribution of species from the current single genus (Polyomavirus) and by the inclusion of several new species. In addition, the names of several species will be changed to reflect current usage.

  19. Bacterial phospholipide antigens and their taxonomic significance.

    Science.gov (United States)

    Karalnik, B V; Razbash, M P; Akhmetova, E A

    1981-01-01

    The investigation of interrelationships between the phospholipides of various microorganisms (33 strains of corynebacteria, mycobacteria and staphylococci) using crossed antibody neutralization reactions with phospholipide antigenic erythrocyte diagnostic was used for the assessment of the degree of antigenic propinquity and antigenic differences between the phospholipides of bacteria of the same species, genus, and of different genera. The role of the determinants of the corresponding (their own) and "foreign" genera in the antigenic differences between the phospholipides of the microorganisms investigated was established. On the basis of the results obtained the conclusion has been drawn that the method of assessment of antigenic interrelationships between phospholipides can be used for the study of some taxonomic problems.

  20. Accurate taxonomic assignment of short pyrosequencing reads.

    Science.gov (United States)

    Clemente, José C; Jansson, Jesper; Valiente, Gabriel

    2010-01-01

    Ambiguities in the taxonomy dependent assignment of pyrosequencing reads are usually resolved by mapping each read to the lowest common ancestor in a reference taxonomy of all those sequences that match the read. This conservative approach has the drawback of mapping a read to a possibly large clade that may also contain many sequences not matching the read. A more accurate taxonomic assignment of short reads can be made by mapping each read to the node in the reference taxonomy that provides the best precision and recall. We show that given a suffix array for the sequences in the reference taxonomy, a short read can be mapped to the node of the reference taxonomy with the best combined value of precision and recall in time linear in the size of the taxonomy subtree rooted at the lowest common ancestor of the matching sequences. An accurate taxonomic assignment of short reads can thus be made with about the same efficiency as when mapping each read to the lowest common ancestor of all matching sequences in a reference taxonomy. We demonstrate the effectiveness of our approach on several metagenomic datasets of marine and gut microbiota.

  1. Rotational Study of Ambiguous Taxonomic Classified Asteroids

    Science.gov (United States)

    Linder, Tyler R.; Sanchez, Rick; Wuerker, Wolfgang; Clayson, Timothy; Giles, Tucker

    2017-01-01

    The Sloan Digital Sky Survey (SDSS) moving object catalog (MOC4) provided the largest ever catalog of asteroid spectrophotometry observations. Carvano et al. (2010), while analyzing MOC4, discovered that individual observations of asteroids which were observed multiple times did not classify into the same photometric-based taxonomic class. A small subset of those asteroids were classified as having both the presence and absence of a 1um silicate absorption feature. If these variations are linked to differences in surface mineralogy, the prevailing assumption that an asteroid’s surface composition is predominantly homogenous would need to be reexamined. Furthermore, our understanding of the evolution of the asteroid belt, as well as the linkage between certain asteroids and meteorite types may need to be modified.This research is an investigation to determine the rotational rates of these taxonomically ambiguous asteroids. Initial questions to be answered:Do these asteroids have unique or nonstandard rotational rates?Is there any evidence in their light curve to suggest an abnormality?Observations were taken using PROMPT6 a 0.41-m telescope apart of the SKYNET network at Cerro Tololo Inter-American Observatory (CTIO). Observations were calibrated and analyzed using Canopus software. Initial results will be presented at AAS.

  2. Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action

    DEFF Research Database (Denmark)

    Sanderson, Hans; Thomsen, Marianne

    2009-01-01

    a comprehensive database based on OECD's standardized measured ecotoxicological data and to evaluate if there is generally cause of greater concern with regards to pharmaceutical aquatic toxicological profiles relative to industrial chemicals. Comparisons were based upon aquatic ecotoxicity classification under......Pharmaceuticals have been reported to be ubiquitously present in surface waters prompting concerns of effects of these bioactive substances. Meanwhile, there is a general scarcity of publicly available ecotoxicological data concerning pharmaceuticals. The aim of this paper was to compile...... the United Nations Global Harmonized System for classification and labeling of chemicals (GHS). Moreover, we statistically explored whether the predominant mode-of-action (MOA) for pharmaceuticals is narcosis. We found 275 pharmaceuticals with 569 acute aquatic effect data; 23 pharmaceuticals had chronic...

  3. A novel algorithm for establishing taxonomic relation of Chinese ontology

    Institute of Scientific and Technical Information of China (English)

    PEI Bing-zhen; CHEN Xiao-rong; HU Yi; LU Ru-zhan

    2009-01-01

    Both a general domain-independent bottom-up multi-level model and an algorithm for establishing the taxonomic relation of Chinese ontology are proposed. The model consists of extracting domain vocabularies and establishing taxonomic relation, with the consideration of characteristics unique to Chinese natural language. By establishing the semantic forests of domain vocabularies and then using the existing semantic dictionary or ma-chine-readable dictionary (MRD), the proposed algorithm can integrate these semantic forests together to estab-lish the taxonomic relation. Experimental results show that the proposed algorithm is feasible and effective in es-tablishing the integrated taxonomic relation among domain vocabularies and concepts.

  4. TaxMan: a taxonomic database manager

    Directory of Open Access Journals (Sweden)

    Blaxter Mark

    2006-12-01

    Full Text Available Abstract Background Phylogenetic analysis of large, multiple-gene datasets, assembled from public sequence databases, is rapidly becoming a popular way to approach difficult phylogenetic problems. Supermatrices (concatenated multiple sequence alignments of multiple genes can yield more phylogenetic signal than individual genes. However, manually assembling such datasets for a large taxonomic group is time-consuming and error-prone. Additionally, sequence curation, alignment and assessment of the results of phylogenetic analysis are made particularly difficult by the potential for a given gene in a given species to be unrepresented, or to be represented by multiple or partial sequences. We have developed a software package, TaxMan, that largely automates the processes of sequence acquisition, consensus building, alignment and taxon selection to facilitate this type of phylogenetic study. Results TaxMan uses freely available tools to allow rapid assembly, storage and analysis of large, aligned DNA and protein sequence datasets for user-defined sets of species and genes. The user provides GenBank format files and a list of gene names and synonyms for the loci to analyse. Sequences are extracted from the GenBank files on the basis of annotation and sequence similarity. Consensus sequences are built automatically. Alignment is carried out (where possible, at the protein level and aligned sequences are stored in a database. TaxMan can automatically determine the best subset of taxa to examine phylogeny at a given taxonomic level. By using the stored aligned sequences, large concatenated multiple sequence alignments can be generated rapidly for a subset and output in analysis-ready file formats. Trees resulting from phylogenetic analysis can be stored and compared with a reference taxonomy. Conclusion TaxMan allows rapid automated assembly of a multigene datasets of aligned sequences for large taxonomic groups. By extracting sequences on the basis of

  5. Taxonomic etymology – in search of inspiration

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    Piotr Jozwiak

    2015-07-01

    Full Text Available We present a review of the etymology of zoological taxonomic names with emphasis on the most unusual examples. The names were divided into several categories, starting from the most common – given after morphological features – through inspiration from mythology, legends, and classic literature but also from fictional and nonfictional pop-culture characters (e.g., music, movies or cartoons, science, and politics. A separate category includes zoological names created using word-play and figures of speech such as tautonyms, acronyms, anagrams, and palindromes. Our intention was to give an overview of possibilities of how and where taxonomists can find the inspirations that will be consistent with the ICZN rules and generate more detail afterthought about the naming process itself, the meaningful character of naming, as well as the recognition and understanding of names.

  6. A position paper on the electronic publication of nematode taxonomic manuscripts.

    Science.gov (United States)

    Eyualem-Abebe; Baldwin, James G; Adams, Byron; Hope, Duane; Gardner, Scott; Huettel, Robin; Mullin, Peter; Powers, Topper; Sharma, Jyotsna; Ye, Weimin; Thomas, William K

    2006-09-01

    Several nematode species have now attained 'model organism' status, yet there remain many niches in basic biological inquiry for which nematodes would be ideal model systems of study. However, furthering the model system approach is hindered by lack of information on nematode biodiversity. The shortage of taxonomic resources to inventory and characterize biodiversity hinders research programs in invasion biology, ecosystem functioning, conservation biology, and many others. The disproportion between numbers of species to be described and numbers of available taxonomic specialists is greater for Nematoda than for any other metazoan phylum. A partial solution to the taxonomic impediment is the adoption of recent advances in electronic publishing. Electronic publishing has the potential to increase the rate at which taxonomic papers are published, the breadth of their distribution, and the type, quantity, quality, and accessibility of data. We propose that the Journal of Nematology implement the advantageous aspects of electronic publication as a means to help ameliorate the limitations of an underdeveloped taxonomy and empower the nematological disciplines currently hindered by it.

  7. Taxonomic status and redescription of Magneuptychia nebulosa (Butler, 1867 (Lepidoptera, Nymphalidae, Satyrinae with a lectotype designation

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    Shinichi Nakahara

    2015-05-01

    Full Text Available A redescription of Magneuptychia nebulosa (Butler, 1867, a poorly known euptychiine butterfly, is given here, and accurate distributional data are provided for the first time. Taxonomic status of this taxon has been discussed by comparing its morphology against its possible congeners. In addition, lectotype designation for M. nebulosa is provided in order to objectively establish the identity of this taxon and consequently stabilize the nomenclature.

  8. Taxonomic review of the tribe Junoniini (Lepidoptera: Nymphalidae: Nymphalinae from Myanmar

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    Nan Zarchi Win

    2016-09-01

    Full Text Available This paper provides keys to the genera and species for the butterfly species belonging to the tribe Junoniini (Lepidoptera: Nymphalidae from Myanmar. Species accounts include taxonomic description, synonymic lists, distributional ranges, and adult illustrations of nine species: Junonia hierta (Fabricius, Junonia orithya (Linnaeus, Junonia almana (Linnaeus, Junonia lemonias (Linnaeus, Junonia atlites (Linnaeus, Junonia iphita (Cramer, Yoma sabina (Cramer, Hypolimnas bolina (Linnaeus, and Hypolimnas misippus (Linnaeus.

  9. Taxonomic status and redescription of Magneuptychia nebulosa (Butler, 1867) (Lepidoptera, Nymphalidae, Satyrinae) with a lectotype designation

    OpenAIRE

    Shinichi Nakahara; Mario Marín; Cristóbal Ríos-Málaver

    2015-01-01

    Abstract A redescription of Magneuptychia nebulosa (Butler, 1867), a poorly known euptychiine butterfly, is given here, and accurate distributional data are provided for the first time. Taxonomic status of this taxon has been discussed by comparing its morphology against its possible congeners. In addition, lectotype designation for Magneuptychia nebulosa is provided in order to objectively establish the identity of this taxon and consequently stabilize the nomenclature.

  10. Taxonomic status and redescription of Magneuptychia nebulosa (Butler, 1867) (Lepidoptera, Nymphalidae, Satyrinae) with a lectotype designation

    Science.gov (United States)

    Nakahara, Shinichi; Marín, Mario Alejandro; Ríos-Málaver, Cristóbal

    2015-01-01

    Abstract A redescription of Magneuptychia nebulosa (Butler, 1867), a poorly known euptychiine butterfly, is given here, and accurate distributional data are provided for the first time. Taxonomic status of this taxon has been discussed by comparing its morphology against its possible congeners. In addition, lectotype designation for Magneuptychia nebulosa is provided in order to objectively establish the identity of this taxon and consequently stabilize the nomenclature. PMID:26019673

  11. Global pedodiversity, taxonomic distance, and the World Reference Base

    NARCIS (Netherlands)

    Minasny, B.; McBratney, A.B.; Hartemink, A.E.

    2010-01-01

    This paper discusses the study of taxonomic distance and pedodiversity by (1) deriving taxonomic distances for the World Reference Base for Soil Resources (WRB), (2) calculating pedodiversity indices at the global scale using the soil map of the world at a scale 1:25M, and (3) comparing traditional

  12. Preschool Children's Taxonomic Knowledge of Animal Species

    Science.gov (United States)

    Allen, Michael

    2015-01-01

    Although taxonomic proficiency is a prerequisite for understanding ideas central to biology, previous research has established that learners frequently misclassify animals by not following the tenets of accepted taxonomic rubrics. This has immediate relevance with the recently revised English National Curriculum now requiring concepts of animal…

  13. Taxonomic and chemical assessment of exceptionally abundant rock mine biofilm

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    Karolina Tomczyk-Żak

    2017-08-01

    Full Text Available Background An exceptionally thick biofilm covers walls of ancient gold and arsenic Złoty Stok mine (Poland in the apparent absence of organic sources of energy. Methods and Results We have characterized this microbial community using culture-dependent and independent methods. We sequenced amplicons of the 16S rRNA gene obtained using generic primers and additional primers targeted at Archaea and Actinobacteria separately. Also, we have cultured numerous isolates from the biofilm on different media under aerobic and anaerobic conditions. We discovered very high biodiversity, and no single taxonomic group was dominant. The majority of almost 4,000 OTUs were classified above genus level indicating presence of novel species. Elemental analysis, performed using SEM-EDS and X-ray, of biofilm samples showed that carbon, sulphur and oxygen were not evenly distributed in the biofilm and that their presence is highly correlated. However, the distribution of arsenic and iron was more flat, and numerous intrusions of elemental silver and platinum were noted, indicating that microorganisms play a key role in releasing these elements from the rock. Conclusions Altogether, the picture obtained throughout this study shows a very rich, complex and interdependent system of rock biofilm. The chemical heterogeneity of biofilm is a likely explanation as to why this oligotrophic environment is capable of supporting such high microbial diversity.

  14. Taxonomic significance of trichomes micromorphology in cucurbits

    Science.gov (United States)

    Ali, Mohammad Ajmal; Al-Hemaid, Fahad M.A.

    2010-01-01

    Studies on trichomes micromorphology using Scanning Electron Microscope (SEM) were undertaken in 23 species with one variety under 13 genera of the family Cucurbitaceae (viz., Benincasa hispida (Thunb.) Cogn., Citrullus lanatus (Thunb.) Matsum. & Nakai, Cucumis melo var. agrestis Naudin, Cucumis sativus L., Diplocyclos palmatus (L.) C. Jeffrey, Edgaria dargeelingensis C.B. Clarke, Gynostemma burmanicum King ex Chakr., Gynostemma pentaphyllum (Thunb.) Makino, Gynostemma pubescens (Gagnep.) C.Y. Wu, Hemsleya dipterygia Kuang & A.M. Lu, Lagenaria siceraria (Molina) Standl., Luffa acutangula (L.) Roxb., Luffa cylindrica M. Roem., Luffa echinata Roxb., Melothria heterophylla (Lour.) Cogn., Melothria leucocarpa (Blume) Cogn., Melothria maderspatana (L.) Cogn., Sechium edule (Jacq.) Sw., Thladiantha cordifolia (Blume) Cogn., Trichosanthes cucumerina L., T. cucumerina var. anguina (L.) Haines, Trichosanthes dioica Roxb., Trichosanthes lepiniana (Naudin) Cogn. and T. tricuspidata Lour.). The trichomes in the family Cucurbitaceae vary from unicellular to multicellular, conical to elongated, smooth to ridges, with or without flattened disk at base and cyctolithic appendages, thin to thick walled, curved at apices to blunt. Trichomes micromorphology in the family Cucurbitaceae was found significant taxonomically. PMID:23961108

  15. Karyomorphology of Taiwanese Begonia (Begoniaceae): taxonomic implications.

    Science.gov (United States)

    Oginuma, Kazuo; Peng, Ching-I

    2002-06-01

    The karyomorphology of all 14 species of Taiwanese Begonia was investigated to elucidate their chromosome features and chromosomal evolution. Among all species investigated, differences in chromosome features are found in: (1) chromosome number 2 n = 22, 26, 36, 38, 52, 60, 64, 82, and (2) frequencies of chromosomes with secondary, tertiary, and/or small constrictions of polyploids, ranging from 23% to 63%, which is higher than the expected value of about 9%. It is suggested that after polyploidization from the diploid species (i.e., 2 n = 22 and frequencies of chromosomes with secondary, tertiary, and/or small constrictions of polyploids of about 9%), chromosome translocations occurred, followed by a decrease in chromosome number, and subsequently stabilized genomes were formed in various species in Taiwan. The karyomorphological evidence also suggested that the chromosome morphology has evolved in parallel in the begonias belonging to different sections in Taiwan. The variation in chromosomal features is more complex than the variation in floral and fruit morphologies. Karyomorphological data also supports the recognition of five new species in Taiwan: Begonia bouffordii, B. chuyunshanensis, B. pinglinensis, B. tengchiana, and B. wutaiana. Based on detailed karyomorphological analyses, the taxonomic implications, speciation, and chromosomal evolution in Taiwanese Begoniaare discussed.

  16. Reference databases for taxonomic assignment in metagenomics.

    Science.gov (United States)

    Santamaria, Monica; Fosso, Bruno; Consiglio, Arianna; De Caro, Giorgio; Grillo, Giorgio; Licciulli, Flavio; Liuni, Sabino; Marzano, Marinella; Alonso-Alemany, Daniel; Valiente, Gabriel; Pesole, Graziano

    2012-11-01

    Metagenomics is providing an unprecedented access to the environmental microbial diversity. The amplicon-based metagenomics approach involves the PCR-targeted sequencing of a genetic locus fitting different features. Namely, it must be ubiquitous in the taxonomic range of interest, variable enough to discriminate between different species but flanked by highly conserved sequences, and of suitable size to be sequenced through next-generation platforms. The internal transcribed spacers 1 and 2 (ITS1 and ITS2) of the ribosomal DNA operon and one or more hyper-variable regions of 16S ribosomal RNA gene are typically used to identify fungal and bacterial species, respectively. In this context, reliable reference databases and taxonomies are crucial to assign amplicon sequence reads to the correct phylogenetic ranks. Several resources provide consistent phylogenetic classification of publicly available 16S ribosomal DNA sequences, whereas the state of ribosomal internal transcribed spacers reference databases is notably less advanced. In this review, we aim to give an overview of existing reference resources for both types of markers, highlighting strengths and possible shortcomings of their use for metagenomics purposes. Moreover, we present a new database, ITSoneDB, of well annotated and phylogenetically classified ITS1 sequences to be used as a reference collection in metagenomic studies of environmental fungal communities. ITSoneDB is available for download and browsing at http://itsonedb.ba.itb.cnr.it/.

  17. Taxonomic significance of trichomes micromorphology in cucurbits.

    Science.gov (United States)

    Ali, Mohammad Ajmal; Al-Hemaid, Fahad M A

    2011-01-01

    Studies on trichomes micromorphology using Scanning Electron Microscope (SEM) were undertaken in 23 species with one variety under 13 genera of the family Cucurbitaceae (viz., Benincasa hispida (Thunb.) Cogn., Citrullus lanatus (Thunb.) Matsum. & Nakai, Cucumis melo var. agrestis Naudin, Cucumis sativus L., Diplocyclos palmatus (L.) C. Jeffrey, Edgaria dargeelingensis C.B. Clarke, Gynostemma burmanicum King ex Chakr., Gynostemma pentaphyllum (Thunb.) Makino, Gynostemma pubescens (Gagnep.) C.Y. Wu, Hemsleya dipterygia Kuang & A.M. Lu, Lagenaria siceraria (Molina) Standl., Luffa acutangula (L.) Roxb., Luffa cylindrica M. Roem., Luffa echinata Roxb., Melothria heterophylla (Lour.) Cogn., Melothria leucocarpa (Blume) Cogn., Melothria maderspatana (L.) Cogn., Sechium edule (Jacq.) Sw., Thladiantha cordifolia (Blume) Cogn., Trichosanthes cucumerina L., T. cucumerina var. anguina (L.) Haines, Trichosanthes dioica Roxb., Trichosanthes lepiniana (Naudin) Cogn. and T. tricuspidata Lour.). The trichomes in the family Cucurbitaceae vary from unicellular to multicellular, conical to elongated, smooth to ridges, with or without flattened disk at base and cyctolithic appendages, thin to thick walled, curved at apices to blunt. Trichomes micromorphology in the family Cucurbitaceae was found significant taxonomically.

  18. Controlling the taxonomic variable: Taxonomic concept resolution for a southeastern United States herbarium portal

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    Nico Franz

    2016-09-01

    Full Text Available Overview. Taxonomic names are imperfect identifiers of specific and sometimes conflicting taxonomic perspectives in aggregated biodiversity data environments. The inherent ambiguities of names can be mitigated using syntactic and semantic conventions developed under the taxonomic concept approach. These include: (1 representation of taxonomic concept labels (TCLs: name sec. source to precisely identify name usages and meanings, (2 use of parent/child relationships to assemble separate taxonomic perspectives, and (3 expert provision of Region Connection Calculus articulations (RCC–5: congruence, [inverse] inclusion, overlap, exclusion that specify how data identified to different-sourced TCLs can be integrated. Application of these conventions greatly increases trust in biodiversity data networks, most of which promote unitary taxonomic 'syntheses' that obscure the actual diversity of expert-held views. Better design solutions allow users to control the taxonomic variable and thereby assess the robustness of their biological inferences under different perspectives. A unique constellation of prior efforts – including the powerful Symbiota collections software platform, the Euler/X multi-taxonomy alignment toolkit, and the "Weakley Flora" which entails 7,000 concepts and more than 75,000 RCC–5 articulations – provides the opportunity to build a first full-scale concept resolution service for SERNEC, the SouthEast Regional Network of Expertise and Collections, currently with 60 member herbaria and 2 million occurrence records. Intellectual merit. We have developed a multi-dimensional, step-wise plan to transition SERNEC's data culture from name- to concept-based practices. (1 We will engage SERNEC experts through annual, regional workshops and follow-up interactions that will foster buy-in and ultimately the completion of 12 community-identified use cases. (2. We will leverage RCC–5 data from the Weakley Flora and further development of

  19. Taxonomic indexing--extending the role of taxonomy.

    Science.gov (United States)

    Patterson, David J; Remsen, David; Marino, William A; Norton, Cathy

    2006-06-01

    Taxonomic indexing refers to a new array of taxonomically intelligent network services that use nomenclatural principles and elements of expert taxonomic knowledge to manage information about organisms. Taxonomic indexing was introduced to help manage the increasing amounts of digital information about biology. It has been designed to form a near basal layer in a layered cyberinfrastructure that deals with biological information. Taxonomic Indexing accommodates the special problems of using names of organisms to index biological material. It links alternative names for the same entity (reconciliation), and distinguishes between uses of the same name for different entities (disambiguation), and names are placed within an indefinite number of hierarchical schemes. In order to access all information on all organisms, Taxonomic indexing must be able to call on a registry of all names in all forms for all organisms. NameBank has been developed to meet that need. Taxonomic indexing is an area of informatics that overlaps with taxonomy, is dependent on the expert input of taxonomists, and reveals the relevance of the discipline to a wide audience.

  20. Taxonomic chauvinism revisited: insight from parental care research.

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    Zachary R Stahlschmidt

    Full Text Available Parental care (any non-genetic contribution by a parent that appears likely to increase the fitness of its offspring is a widespread trait exhibited by a broad range of animal taxa. In addition to influencing the fitness of parent(s and offspring, parental care may be inextricably involved in other evolutionary processes, such as sexual selection and the evolution of endothermy. Yet, recent work has demonstrated that bias related to taxonomy is prevalent across many biological disciplines, and research in parental care may be similarly burdened. Thus, I used parental care articles published in six leading journals of fundamental behavioral sciences (Animal Behaviour, Behavioral Ecology, Behavioral Ecology and Sociobiology, Ethology, Hormones and Behavior, and Physiology & Behavior from 2001-2010 (n = 712 to examine the year-to-year dynamics of two types of bias related to taxonomy across animals: (1 taxonomic bias, which exists when research output is not proportional to the frequency of organisms in nature, and (2 taxonomic citation bias, which is a proxy for the breadth of a given article-specifically, the proportion of articles cited that refer solely to the studied taxon. I demonstrate that research on birds likely represents a disproportionate amount of parental care research and, thus, exhibits taxonomic bias. Parental care research on birds and mammals also refers to a relatively narrow range of taxonomic groups when discussing its context and, thus, exhibits taxonomic citation bias. Further, the levels of taxonomic bias and taxonomic citation bias have not declined over the past decade despite cautionary messages about similar bias in related disciplines--in fact, taxonomic bias may have increased. As in Bonnet et al. (2002, my results should not be interpreted as evidence of an 'ornithological Mafia' conspiring to suppress other taxonomic groups. Rather, I generate several rational hypotheses to determine why bias persists and to

  1. Concordant biogeographic patterns among multiple taxonomic groups in the Mexican freshwater biota.

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    Benjamín Quiroz-Martínez

    Full Text Available In this paper we analyse the degree of concordance in species richness and taxonomic distinctness (diversity patterns among different freshwater taxonomic groups in order to test three long held patterns described in Mexican freshwater biogeography: 1. The aquatic biota of Mexico includes two distinct faunas, a rich Neotropical component in the south and a south-eastern region and a less rich Nearctic component towards central and northern latitudes of the country. 2. A hotspot of species richness and diversity has been recorded in the Usumacinta, including the Yucatan Peninsula. 3. The presence of two distinct biotas in Mexico, an eastern one distributed along the Gulf of Mexico slope, and a western one associated to the Pacific versant. We use species richness and taxonomic distinctness to explore patterns of diversity and how these patterns change between zoogeographical regions. This paper points out a clear separation between Neotropical and Nearctic drainage basins but also between eastern (Gulf of Mexico and western (Pacific drainage basins. Present data gives additional empirical support from freshwater biota for three long held beliefs regarding distributional patterns of the Mexican biota. The neotropical basins of Mexico are generally host to a richest and more diversified fauna, that includes more families, genera and species, compared to the less rich and less diverse fauna in the nearctic basins.

  2. Concordant Biogeographic Patterns among Multiple Taxonomic Groups in the Mexican Freshwater Biota

    Science.gov (United States)

    Quiroz-Martínez, Benjamín; Álvarez, Fernando; Espinosa, Héctor; Salgado-Maldonado, Guillermo

    2014-01-01

    In this paper we analyse the degree of concordance in species richness and taxonomic distinctness (diversity) patterns among different freshwater taxonomic groups in order to test three long held patterns described in Mexican freshwater biogeography: 1. The aquatic biota of Mexico includes two distinct faunas, a rich Neotropical component in the south and a south-eastern region and a less rich Nearctic component towards central and northern latitudes of the country. 2. A hotspot of species richness and diversity has been recorded in the Usumacinta, including the Yucatan Peninsula. 3. The presence of two distinct biotas in Mexico, an eastern one distributed along the Gulf of Mexico slope, and a western one associated to the Pacific versant. We use species richness and taxonomic distinctness to explore patterns of diversity and how these patterns change between zoogeographical regions. This paper points out a clear separation between Neotropical and Nearctic drainage basins but also between eastern (Gulf of Mexico) and western (Pacific) drainage basins. Present data gives additional empirical support from freshwater biota for three long held beliefs regarding distributional patterns of the Mexican biota. The neotropical basins of Mexico are generally host to a richest and more diversified fauna, that includes more families, genera and species, compared to the less rich and less diverse fauna in the nearctic basins. PMID:25136979

  3. A taxonomic study on the diversity of Indian Knema Lour. (Myristicaceae

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    Dipanwita Banik

    2016-06-01

    Full Text Available A taxonomic study on the diversity of the genus Knema Lour. belonging to the family Myristicaceae R. Br. in India revealed the distribution of the ten taxa under four series in North East and Peninsular India and Andaman and Nicobar Islands including two endemic species. Knema ser. Obovoideae W.J. de Wilde is synonymised here under ser. Knema. Series Knema is represented by two species and ser. Glaucae W.J. de Wilde by one species in North East India, while ser. Laurinae W.J. de Wilde is represented by three species and two subspecies in North East India and Andaman and Nicobar Island, and ser. Glomeratae W.J. de Wilde by 2 species in South and NE India. This is the first taxonomic study on the genus in India. All the taxa are cited with updated nomenclature, diagnostic characters, distribution, phonological data, vernacular names, line drawings, photo plates and specimens examined in various herbaria. Taxonomic keys are provided for easy identification of these taxa.

  4. Taxonomic review of the Sebastes pachycephalus complex (Scorpaeniformes: Scorpaenidae).

    Science.gov (United States)

    Kai, Yoshiaki; Nakabo, Tetsuji

    2013-01-01

    A taxonomic review of the Sebastes pachycephalus complex established the existence of two valid species, S. pachycephalus and S. nudus. Similarities between them include: cranium armed dorsally with robust preocular, supraocular, postocular, and parietal spines; interorbital space concave; lower jaw lacking scales, shorter than upper jaw; thickened rays in ventral half of pectoral fin; dorsal fin usually with 13 spines and 12 soft-rays; pored lateral line scales 27-35 (usually 29-33). However, S. pachycephalus is distinguishable from the latter in having minute scales below the entire dorsal-fin spine base (vs. lacking minute scales below first to fifth or variously to the posteriormost spine in the latter), dark spots scattered on the dorsal, anal and caudal fins (vs. no distinct dark spots), and lacking distinct colored markings on the dorsum (vs. yellow or reddish-brown markings present). Although both species occur off the southern Korean Peninsula and in the Bohai and Yellow Seas, in Japanese waters, the former is distributed from northern Honshu Is. southward to southern Kyushu Is., whereas the latter extends from southern Hokkaido southward along the Pacific coast of Japan to Kanagawa, and along the Sea of Japan coast to northern Kyushu Is., including the Seto Inland Sea. Sebastes nigricaus, S. nigricans, and S. latus are confirmed as junior synonyms of S. pachycephalus, and S. chalcogrammus as junior synonym of S. nudus, based on the examination of type specimens.

  5. Taxonomic status of the Columbia duskysnail (Truncatelloidea, Amnicolidae, Colligyrus

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    Hsiu-Ping Liu

    2015-07-01

    Full Text Available Undescribed freshwater snails (Amnicolidae: Colligyrus from the Mount Hood region (northwestern United States identified as a new species (commonly known as the Columbia duskysnail in grey literature have been provided federal protection under the “survey and manage” provisions of the Northwest Forest Plan and have been placed on conservation watch lists. However, there are no published studies of the identity of these snails aside from a molecular phylogenetic analysis which delineated a close relationship between the single sampled population and C. greggi, which is distributed more than 750 km to the east of the Mount Hood area. Here we examine the taxonomic status of the Columbia duskysnail based on additional molecular sampling of mitochondrial DNA sequences (COI and morphological evidence. We found that the Columbia duskysnail is not a monophyletic group and forms a strongly supported clade with C. greggi. The COI divergence between these broadly disjunct groups (2.1% was somewhat larger than that within C. greggi (1.0% but considerably less than that among the three currently recognized species of Colligyrus (8.7–12.1%. Additionally we found that the Columbia duskysnail and C. greggi cannot be consistently differentiated by previously reported diagnostic characters (size and shape of shell spire, pigmentation of body and penis and are closely similar in other aspects of morphology. Based on these results we conclude that the Columbia duskysnail is conspecific with C. greggi.

  6. Genome-based Taxonomic Classification of Bacteroidetes

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    Richard L. Hahnke

    2016-12-01

    Full Text Available The bacterial phylum Bacteroidetes, characterized by a distinct gliding motility, occurs in a broad variety of ecosystems, habitats, life styles and physiologies. Accordingly, taxonomic classification of the phylum, based on a limited number of features, proved difficult and controversial in the past, for example, when decisions were based on unresolved phylogenetic trees of the 16S rRNA gene sequence. Here we use a large collection of type-strain genomes from Bacteroidetes and closely related phyla for assessing their taxonomy based on the principles of phylogenetic classification and trees inferred from genome-scale data. No significant conflict between 16S rRNA gene and whole-genome phylogenetic analysis is found, whereas many but not all of the involved taxa are supported as monophyletic groups, particularly in the genome-scale trees. Phenotypic and phylogenomic features support the separation of Balneolaceae as new phylum Balneolaeota from Rhodothermaeota and of Saprospiraceae as new class Saprospiria from Chitinophagia. Epilithonimonas is nested within the older genus Chryseobacterium and without significant phenotypic differences; thus merging the two genera is proposed. Similarly, Vitellibacter is proposed to be included in Aequorivita. Flexibacter is confirmed as being heterogeneous and dissected, yielding six distinct genera. Hallella seregens is a later heterotypic synonym of Prevotella dentalis. Compared to values directly calculated from genome sequences, the G+C content mentioned in many species descriptions is too imprecise; moreover, corrected G+C content values have a significantly better fit to the phylogeny. Corresponding emendations of species descriptions are provided where necessary. Whereas most observed conflict with the current classification of Bacteroidetes is already visible in 16S rRNA gene trees, as expected whole-genome phylogenies are much better resolved.

  7. Genome-Based Taxonomic Classification of Bacteroidetes.

    Science.gov (United States)

    Hahnke, Richard L; Meier-Kolthoff, Jan P; García-López, Marina; Mukherjee, Supratim; Huntemann, Marcel; Ivanova, Natalia N; Woyke, Tanja; Kyrpides, Nikos C; Klenk, Hans-Peter; Göker, Markus

    2016-01-01

    The bacterial phylum Bacteroidetes, characterized by a distinct gliding motility, occurs in a broad variety of ecosystems, habitats, life styles, and physiologies. Accordingly, taxonomic classification of the phylum, based on a limited number of features, proved difficult and controversial in the past, for example, when decisions were based on unresolved phylogenetic trees of the 16S rRNA gene sequence. Here we use a large collection of type-strain genomes from Bacteroidetes and closely related phyla for assessing their taxonomy based on the principles of phylogenetic classification and trees inferred from genome-scale data. No significant conflict between 16S rRNA gene and whole-genome phylogenetic analysis is found, whereas many but not all of the involved taxa are supported as monophyletic groups, particularly in the genome-scale trees. Phenotypic and phylogenomic features support the separation of Balneolaceae as new phylum Balneolaeota from Rhodothermaeota and of Saprospiraceae as new class Saprospiria from Chitinophagia. Epilithonimonas is nested within the older genus Chryseobacterium and without significant phenotypic differences; thus merging the two genera is proposed. Similarly, Vitellibacter is proposed to be included in Aequorivita. Flexibacter is confirmed as being heterogeneous and dissected, yielding six distinct genera. Hallella seregens is a later heterotypic synonym of Prevotella dentalis. Compared to values directly calculated from genome sequences, the G+C content mentioned in many species descriptions is too imprecise; moreover, corrected G+C content values have a significantly better fit to the phylogeny. Corresponding emendations of species descriptions are provided where necessary. Whereas most observed conflict with the current classification of Bacteroidetes is already visible in 16S rRNA gene trees, as expected whole-genome phylogenies are much better resolved.

  8. Taxonomic notes on the genera Brypoctia Schoorl, 1990 and Schreiteriana Fletcher & Nye, 1982 (Lepidoptera, Cossidae).

    Science.gov (United States)

    Penco, Fernando C; Yakovlev, Roman V; Witt, Thomas J

    2016-12-06

    Currently, the Cossidae of South America are rather poorly studied. Data on the distribution and taxonomy of Neotropical carpenter moths are lacking. An exception is the clarification of the taxonomic position of the genus Miacora Dyar, 1905 (Yakovlev 2014), Neotropical Cossidae checklist (Donahue 1995), and a preliminary list of Cossidae  of Argentina (Penco & Yakovlev 2015). The majority of Neotropical Cossidae genera have not been studied and the taxonomic position of some genera remains completely unresolved. Additionally, images of genitalia of the Neotropical genera have not been published, including the genera Brypoctia Schoorl, 1990 and Schreiteriana Fletcher & Nye, 1982 (Cossidae: Zeuzerinae). The taxonomic position of the second genus was questioned by Schoorl (1990).

  9. Lab Practicums: Are We Teaching Sound Taxonomic Principles?

    Science.gov (United States)

    Vogt, Kenneth D.

    1993-01-01

    Presents a series of exercises to help students understand the importance of the limits of taxonomic keys and to identify the appropriate levels. Introductory activities include having students classify screws, "gummy bears," and beans. (PR)

  10. Taxonomic status of the melanistic forms of the Cordylus cordylus ...

    African Journals Online (AJOL)

    1988-10-04

    Oct 4, 1988 ... taxonomic status of the melanistic form lack a sound factual basis. Recently ... interpreted as products of the swamping of small remain- ing melanistic ..... light brown lines along side of neck from ear opening to front limbs.

  11. Primaquine: Modes of Action and Mechanisms of Drug Resistance.

    Science.gov (United States)

    1975-06-30

    dehydrogenase was used as an enzyme marker for the presence of mitochondria, acid phosphatase for lysosomal contamination, and isocitrate dehydrogenase for... dehydrogenase , acid phosphatase and isocitrate dehydrogenase were determined in the supernatants and pellets of the preparative steps for the...Relative Activity() Succinic Acid Isocitrate Fraction Description Dehydrogenase Phosphatase Dehydrogenase I Pellet after first 100 100 100 7000 x

  12. Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner.

    Science.gov (United States)

    Jiang, Shiyao; Tsikolia, Maia; Bernier, Ulrich R; Bloomquist, Jeffrey R

    2017-02-06

    Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality) values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal dose for 50% mortality) values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti. These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA) treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 (half maximal effective concentration) values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl, the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

  13. Mode of action of glyphosate in Candida maltosa.

    Science.gov (United States)

    Bode, R; Melo, C; Birnbaum, D

    1984-11-01

    The broad-spectrum herbicide glyphosate inhibits the growth of Candida maltosa and causes the accumulation of shikimic acid and shikimate-3-phosphate. Glyphosate is a potent inhibitor of three enzymes of aromatic amino acid biosynthesis in this yeast. In relation to tyrosine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase and dehydroquinate synthase, the inhibitory effect appears at concentrations in the mM range, but 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase is inhibited by micromolar concentrations of glyphosate. Inhibition of partially purified EPSP synthase reaction by glyphosate is competitive with respect to phosphoenolpyruvate (PEP) with a Ki-value of 12 microM. The app. Km for PEP is about 5-fold higher and was 62 microM. Furthermore, the presence of glyphosate leads to derepression of many amino acid biosynthetic enzymes.

  14. Hyperthermic radiosensitization : mode of action and clinical relevance

    NARCIS (Netherlands)

    Kampinga, HH; Dikomey, E

    2001-01-01

    Purpose: To provide an update on the recent knowledge about the molecular mechanisms of thermal radiosensitization and its possible relevance to thermoradiotherapy. Summary: Hyperthermia is probably the most potent cellular radiosensitizer known to date. Heat interacts with radiation and potentiates

  15. Antimicrobial activity of GN peptides and their mode of action

    DEFF Research Database (Denmark)

    Godballe, Troels; Mojsoska, Biljana; Nielsen, Hanne M

    2015-01-01

    Increasing prevalence of bacteria that carries resistance towards conventional antibiotics has prompted the investigation into new compounds for bacterial intervention to ensure efficient infection control in the future. One group of potential lead structures for antibiotics is antimicrobial pept...

  16. Studies on the mode of action of lathyrogenic compounds.

    Science.gov (United States)

    LEVENE, C I

    1962-08-01

    The lathyrogenic effect of INAH in the chick embryo may be measured by the increase in the extractibility of collagen from the bones with 1 M NaCl. Incubation of these bones in vitro with carbonyl compounds diminishes the amount of extractible collagen; with D-L-glyceraldehyde the reversal of the INAH effect is complete. This reversal effect is dependent on the time and temperature of incubation and on the quantity of D-L-glyceraldehyde, but is independent of the pH of the incubating medium, the optical form of the glyceraldehyde, or the metabolism of the cells; this suggests that it depends on a simple chemical combination. D-L-glyceraldehyde also reverses completely the extractibility of collagen from the bones of embryos rendered lathyrogenic with BAPN, semicarbazide, and hydrazine hydrate. The hypothesis has been advanced "that lathyrogenic agents act by blocking carbonyl groups on the collagen molecule, thus preventing cross-linking essential to normal maturation; normal maturation may be restored by the addition of carbonyl groups which act by competing either for the lathyrogen or for functional sites on the collagen molecule." In support of this hypothesis, it has been shown that purified lathyritic guinea pig collagen takes up lesser amounts of 2,4-dinitrophenylhydrazine-a compound which combines with carbonyl groups-than does normal collagen; it has been shown that lathyritic collagen still possesses the ability to form segment-long-spacing (SLS) collagen, but that these fibres are much thinner than normal; this is due perhaps to blockade of groups essential for lateral cross-linking of the tropocollagen unit. It has also been shown that normal, purified guinea pig collagen which has been pretreated with INAH, takes up lesser amounts of 2,4-dinitrophenylhydrazine and forms much thinner SLS fibres than the untreated controls.

  17. Systems Biology and Mode of Action Based Risk Assessment.

    Science.gov (United States)

    The application of systems biology approaches has greatly increased in the past decade largely as a consequence of the human genome project and technological advances in genomics and proteomics. Systems approaches have been used in the medical & pharmaceutical realm for diagnost...

  18. 4-Alkynylphenylsilatranes: Insecticidal activity, mammalian toxicity, and mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Horsham, M.A.; Palmer, C.J.; Cole, L.M.; Casida, J.E. (Univ. of California, Berkeley (USA))

    1990-08-01

    4-Ethynyl- and 4-(prop-1-ynyl)phenylsilatranes (N(CH{sub 2}CH{sub 2}O){sub 3}SiR, R = C{sub 6}H{sub 4}-4-C{triple bond}CH or C{sub 6}H{sub 4}-4-C{triple bond}CCH{sub 3}) are highly toxic to houseflies (pretreated with piperonyl butoxide) and milkweed bugs (topical LD{sub 50}s 3-14 {mu}g/g) and to mice (intraperitoneal LD{sub 50}s 0.4-0.9 mg/kg), and they are moderately potent inhibitors of the ({sup 35}S)-tert-butylbicyclophosphorothionate or TBPS binding site (GABA-gated chloride channel) of mouse brain membranes. Scatchard analysis indicates noncompetitive interaction of 4-ethynylphenylsilatrane with the TBPS binding site. Phenylsilatrane analogues with 4-substituents of H, CH{sub 3}, Cl, Br, and C{triple bond}CSi(CH{sub 3}){sub 3} are highly toxic to mice but have little or no activity in the insect and receptor assays. Radioligand binding studies with (4-{sup 3}H)phenylsilatrane failed to reveal a specific binding site in mouse brain. Silatranes with R = H, CH{sub 3}, CH{sub 2}Cl, CH{double bond}CH{sub 2}, OCH{sub 2}CH{sub 3}, and C{sub 6}H{sub 4}-4-CH{sub 2}CH{sub 3} are of little or no activity in the insect and mouse toxicity and TBPS binding site assays as are the trithia and monocyclic analogues of phenylsilatrane. 4-Alkynylphenylsilatranes are new probes to examine the GABA receptor-ionophore complex of insects and mammals.

  19. Neurotoxicological effects and the mode of action of pyrethroid insecticides

    NARCIS (Netherlands)

    Vijverberg, H.P.M.; Bercken, Joep van den

    1990-01-01

    Neuroexcitatory symptoms of acute poisoning of vertebrates by pyrethroids are related to the ability of these insecticides to modify electrical activity in various parts of the nervous system. Repetitive nerve activity, particularly in the sensory nervous system, membrane depolarization, and enhance

  20. Chapter 14. Approaches for Evaluation of Mode of Action.

    Science.gov (United States)

    Cellular and molecular approaches vastly expand the possibilities for revealing the underlying mechanisms of developmental toxicity. The typical teratology screening test examines near-term fetuses after exposure throughout organogenesis and evaluates the potential for an exposur...

  1. The structure and mode of action of the dinoflagellate toxins

    Directory of Open Access Journals (Sweden)

    Akram Najafi

    2016-07-01

    Full Text Available Background: Dinoflagellates are the major causative agents of harmful algal blooms. In different studies, it has been shown that many dinoflagellate species produce various natural toxins. Saxitoxin, brevetoxin, yessotoxin, etc can be considered as the most important neurotoxins. The most important dinoflagellate toxins structures, their origin, structure and mechanisms of action were evaluated in a systematic review. Materials & Methods: Marine dinoflagellates, marine toxins, and their mechanisms of action and structure were keywords for a comprehensive search in online databases including Pubmed, Science Direct, Google Scholar and Scirus. A total of 95 papers were evaluated, however, by omitting similar reports, 68 papers were included in the study. Results: Dinoflagellates toxins are usually polycyclic ether and polyketaide compounds that have distinct mechanisms of action including alteration in different ion channels and/or pumps at cell membrane, effect on the normal functioning of neuronal and other excitable tissues, inhibition of serine/threonine phosphoprotein phosphatases, disrupting major mechanisms of controlling cellular functions, and alteration in cellular cytoskeleton. However, the precise mechanisms of action of few toxins are not determined yet. Conclusion: The clarification of the dinoflagellate toxins structures and their mechanisms of action may be helpful for novel drug design, therapeutic measures and to overcome against marine toxicity. 

  2. STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN

    Science.gov (United States)

    Using tritium-labelled toxin, it was shown that HeLa cells treated with a saturating dose take up less than 2% ( 0.005ug/ml) of the added toxin...of C14-amino acids into protein in extracts of HeLa cells and of rabbit reticulo cytes. It was shown that the toxin interferes with a step involving

  3. Adjuvants for veterinary vaccines--types and modes of action.

    Science.gov (United States)

    Gerdts, Volker

    2015-01-01

    Adjuvants are used to improve the immune response to vaccines. Formulation with adjuvants can result in an earlier onset of immunity, an overall stronger immune response, a specific type of immunity, or a longer duration of immunity to the vaccine. Adjuvants were discovered empirically, and for decades, have been used in both humans and animals without understanding the mechanisms of action. With an improved understanding of the immune system, and in particular the interplay between innate and adaptive immunity, we are now getting better insight into the function of adjuvants. As a result, new adjuvants are being developed that are safe and highly effective for common use in humans and animals, as well as for use in high risk populations such as immunocompromised animals, neonates or very old animals. Furthermore, adjuvants can help to reduce the amount of antigen needed in the vaccine, increase the stability of the vaccine and enable alternatiye administration routes such as needle-free delivery of the vaccine. Here, I will provide an over view of the existing adjuvant technologies for veterinary vaccines and provide an outlook into some of the new technologies in preclinical and clinical development.

  4. Germination inhibitors of fungal spores: identification and mode of action

    NARCIS (Netherlands)

    Chitarra, G.S.

    2003-01-01

    Fungi can be found in a wide variety of environments, such as seeds, plants, soil, water, insects, and food products. Fungi and their toxic metabolites cause losses of food products, and diseases in plants and animals, and may have adverse effects on human health. A crucial step in fungal

  5. Mode of action and clinical studies with alemtuzumab.

    Science.gov (United States)

    Jones, Joanne L; Coles, Alasdair J

    2014-12-01

    The lymphocyte depleting anti-CD52 monoclonal antibody alemtuzumab has been used in Cambridge, UK, as an experimental treatment of multiple sclerosis since 1991. One phase-2 trial (CAMMS-223) and two phase-3 studies (CARE-MS1 and CARE-MS2) have confirmed its efficacy in treatment-naive patients, and have established superiority over interferon beta-1a in patients who continue to relapse in spite of first-line therapy (Cohen et al., 2012; Coles et al., 2008; Coles et al., 2012a; Coles et al., 2012b). Despite causing a prolonged T cell lymphopenia, significant infections have not been an issue following treatment; rather alemtuzumab's primary safety concern is secondary autoimmunity, occurring up to five years after treatment and maximally at two years: 30% of patients develops thyroid autoimmunity, and 1% develops idiopathic thrombocytopenic purpura (ITP). In addition, 4 out of 1486 patients (multiple sclerosis (under the trade name Lemtrada). Lemtrada is now also approved as a treatment of multiple sclerosis in Canada, Australia, Switzerland, Israel, Mexico and Brazil. However, in December 2013, Lemtrada failed to gain approval from the U.S. Food and Drug Administration (FDA), with concerns over trial design and safety stated as the main reasons. In this review we describe our local experience and explain the rationale behind its initial use as a treatment of multiple sclerosis and behind the design of the commercially sponsored trials, summarising their key findings. We also sum up our understanding of its mechanism of action.

  6. Mode of Action and Synergy of Ceftazidime and Baicalein against ...

    African Journals Online (AJOL)

    infrared microspectroscopy were used to investigate the changes in the ... Synergistic activity, Fourier Transform-infrared microspectroscopy, ..... Food. Chem 2009; 113: 1301-1307. 27. Al-Qadiri HM, Al-Holy MA, Lin M, Alami NI, Cavinato AG,.

  7. Actions and mode of actions of FGF19 subfamily members.

    Science.gov (United States)

    Fukumoto, Seiji

    2008-03-01

    Fibroblast growth factors (FGFs) are humoral factors with diverse biological functions. While most FGFs were shown to work as local factors regulating cell growth and differentiation, recent investigations indicated that FGF19 subfamily members, FGF15/19, FGF21 and FGF23 work as systemic factors. FGF15/19 produced by intestine inhibits bile acid synthesis and FGF21from liver is involved in carbohydrate and lipid metabolism. In addition, FGF23 was shown to be produced by bone and regulate phosphate and vitamin D metabolism. Furthermore, these FGFs require klotho or betaklotho for their actions in addition to canonical FGF receptors. It is possible that these FGFs together with their receptor systems might be targets for novel therapeutic measures in the future.

  8. Antibacterial Activity and Mode of Action of Mentha arvensis Ethanol ...

    African Journals Online (AJOL)

    SEM findings revealed that the extract induced potential ... Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International ... China. The plant material was identified by Prof. Jian Zunzhao ...

  9. Allergen immunotherapy: routes, safety,efficacy, and mode of action

    Directory of Open Access Journals (Sweden)

    Hochfelder JL

    2013-07-01

    Full Text Available Jillian Leigh Hochfelder, Punita PondaDivision of Allergy and Immunology, North Shore–Long Island Jewish Health System, New Hyde Park, NY, USAAbstract: Allergic rhinitis, allergic conjunctivitis, and allergic asthma have been steadily increasing in prevalence in recent years. These allergic diseases have a major impact on quality of life and are a major economic burden in the US. Although allergen avoidance and pharmacotherapy are currently the mainstays of therapy, they are not always successful in treating patients’ symptoms effectively. If a patient fails allergen avoidance and medical therapy, immunotherapy may be indicated. Furthermore, immunotherapy is the only therapy that may change the course of the disease and induce long-term remission. Though subcutaneous administration has been the standard route for immunotherapy for many decades, there are several other routes of administration that have been and are currently being studied. The goal of utilizing alternative routes of immunotherapy is to improve safety without decreasing the efficacy of treatment. This paper will review the novel routes of immunotherapy, including sublingual, oral, local nasal, epicutaneous, and intralymphatic.Keywords: immunotherapy, allergic rhinitis, allergic asthma, sublingual, intralymphatic

  10. Ecdysone Agonist: New Insecticides with Novel Mode of Action

    Directory of Open Access Journals (Sweden)

    Y. Andi Trisyono

    2002-12-01

    Full Text Available Development of insect resistance to insecticide has been the major driving force for the development of new insecticides. Awareness and demand from public for more environmentally friendly insecticides have contributed in shifting the trend from using broad spectrum to selective insecticides. As a result, scientists have looked for new target sites beyond the nervous system. Insect growth regulators (IGRs are more selective insecticides than conventional insecticides, and ecdysone agonists are the newest IGRs being commercialized, e.g. tebufenozide, methoxyfenozide, and halofenozide. Ecdysone agonists bind to the ecdysteroid receptors, and they act similarly to the molting hormone 20-hydroxyecdysone. The binding provides larvae or nymphs with a signal to enter a premature and lethal molting cycle. In addition, the ecdysone agonists cause a reduction in the number of eggs laid by female insects. The ecdysone agonists are being developed as selective biorational insecticides. Tebufenozide and methoxyfenozide are used to control lepidopteran insect pests, whereas halofenozide is being used to control coleopteran insect pests. Their selectivity is due to differences in the binding affinity between these compounds to the receptors in insects from different orders. The selectivity of these compounds makes them candidates to be used in combinations with other control strategies to develop integrated pest management programs in agricultural ecosystems. Key words: new insecticides, selectivity, ecdysone agonists

  11. Genetics, Biosynthesis, Structure, and Mode of Action of Lantibiotics

    Science.gov (United States)

    Kuipers, Anneke; Rink, Rick; Moll, Gert N.

    Lantibiotics are lanthionine-containing peptide antibiotics. They are characterized by having meso-lanthionine(s) and/or β-methyllanthionine(s) or both. These intramolecular monosulfide cross-links render the peptide resistant against breakdown by peptidases. Moreover, in several cases, the (methyl)lanthionines are essential for interaction with the so-called docking molecule lipid II. The best known lantibiotic, nisin, highly effectively inhibits growth of target cells via two mechanisms: (1) abduction of the cell wall precursor lipid II from the septum and (2) formation of pores composed of lipid II and nisin. (Methyl)lanthionines result from two enzyme-catalyzed posttranslational modifications: dehydration of serines/threonines and coupling of the resulting dehydro amino acids to cysteines. Besides the localization of the thioether bridges and dehydro amino acids in the lantibiotics, also the three-dimensional structure of some lantibiotics has been resolved by NMR. Genes encoding proteins involved in the biosynthesis of lantibiotics are present in clusters and may comprise combinations of the following genes in varying order: a structural gene that encodes a leader peptide and the lantibiotic propeptide, modification enzyme(s), a transporter responsible for the export of the lantibiotic and in some cases for cleavage of the leader peptide, a leader peptidase, a so-called immunity protein involved in self-protection of the host cell, components of a transporter also involved in self-protection, and two components of an autoinduction system.

  12. Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner

    Directory of Open Access Journals (Sweden)

    Shiyao Jiang

    2017-02-01

    Full Text Available Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal dose for 50% mortality values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti. These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 (half maximal effective concentration values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl, the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

  13. Mode of action of mosquitocidal Bacillus thuringiensis toxins.

    Science.gov (United States)

    Soberón, Mario; Fernández, Luisa E; Pérez, Claudia; Gill, Sarjeet S; Bravo, Alejandra

    2007-04-01

    Cry toxins from Bacillus thuringiensis (Bt) are used for insect control. Their primary action is to lyse midgut epithelial cells. In lepidopteran insects, Cry1A monomeric toxins interact with a first receptor and this interaction triggers toxin oligomerization. The oligomeric structure interacts then with a second GPI-anchored receptor that induces insertion into membrane microdomains and larvae death. In the case of mosquitocidal Bt strains, two different toxins participate, Cry and Cyt. These toxins have a synergistic effect and Cyt1Aa overcomes Cry toxin-resistance. We will summarize recent findings on the identification of Cry receptors in mosquitoes and the mechanism of synergism: Cyt1Aa synergizes or suppresses resistance to Cry toxins by functioning as a Cry membrane-bound receptor.

  14. New Mode of Action for a Knottin Protein Bioinsecticide

    Science.gov (United States)

    Chouabe, Christophe; Eyraud, Vanessa; Da Silva, Pedro; Rahioui, Isabelle; Royer, Corinne; Soulage, Christophe; Bonvallet, Robert; Huss, Markus; Gressent, Frédéric

    2011-01-01

    PA1b (for pea albumin 1 subunit b) is a plant bioinsecticide lethal to several pests that are important in agriculture or human health. PA1b belongs to the inhibitory cystine knot family or knottin family. Originating from a plant (the garden pea) commonly eaten by humans without any known toxic or allergic effects, PA1b is a candidate for transgenic applications and is one of the most promising biopesticides for pest control. Using whole-cell patch-clamp techniques on Sf9 PA1b-sensitive lepidopteran insect cells, we discovered that PA1b reversibly blocked ramp membrane currents in a dose-dependent manner (EC50 = 0.52 μm). PA1b had the same effect as bafilomycin, a specific inhibitor of the vacuolar proton pump (V-type H+-ATPase), and the PA1b-sensitive current depended on the internal proton concentration. Biochemical assays on purified V-ATPase from the lepidopteran model Manduca sexta showed that PA1b inhibited the V1V0-type H+-ATPase holoenzyme activity (IC50 ∼ 70 nm) by interacting with the membrane-bound V0 part of the V-ATPase. V-ATPase is a complex protein that has been studied increasingly because of its numerous physiological roles. In the midgut of insects, V-ATPase activity is essential for energizing nutrient absorption, and the results reported in this work explain the entomotoxic properties of PA1b. Targeting V-ATPase is a promising means of combating insect pests, and PA1b represents the first peptidic V-ATPase inhibitor. The search for V-ATPase inhibitors is currently of great importance because it has been demonstrated that V-ATPase plays a role in so many physiological processes. PMID:21890633

  15. Artemisinin inhibits chloroplast electron transport activity: mode of action.

    Directory of Open Access Journals (Sweden)

    Adyasha Bharati

    Full Text Available Artemisinin, a secondary metabolite produced in Artemisia plant species, besides having antimalarial properties is also phytotoxic. Although, the phytotoxic activity of the compound has been long recognized, no information is available on the mechanism of action of the compound on photosynthetic activity of the plant. In this report, we have evaluated the effect of artemisinin on photoelectron transport activity of chloroplast thylakoid membrane. The inhibitory effect of the compound, under in vitro condition, was pronounced in loosely and fully coupled thylakoids; being strong in the former. The extent of inhibition was drastically reduced in the presence of uncouplers like ammonium chloride or gramicidin; a characteristic feature described for energy transfer inhibitors. The compound, on the other hand, when applied to plants (in vivo, behaved as a potent inhibitor of photosynthetic electron transport. The major site of its action was identified to be the Q(B; the secondary quinone moiety of photosystemII complex. Analysis of photoreduction kinetics of para-benzoquinone and duroquinone suggest that the inhibition leads to formation of low pool of plastoquinol, which becomes limiting for electron flow through photosystemI. Further it was ascertained that the in vivo inhibitory effect appeared as a consequence of the formation of an unidentified artemisinin-metabolite rather than by the interaction of the compound per se. The putative metabolite of artemisinin is highly reactive in instituting the inhibition of photosynthetic electron flow eventually reducing the plant growth.

  16. Una taxonomía de modelos de desarrollo sustentable

    OpenAIRE

    Darcy Tetreault

    2004-01-01

    Este ensayo pretende ayudar a desenmarañar una parte del discurso sobre desarrollo sustentable mediante la construcción de una taxonomía de modelos de desarrollo sustentable. La misma taxonomía se basa en una revisión literaria extensiva que en cierta medida privilegia la experiencia mexicana. De este modo, el ensayo presenta y compara tanto modelos normativos como positivos. Los modelos incluidos son el modelo dominante, el cual corresponde con la estrategia ...

  17. Developing green supply chain management strategies: A taxonomic approach

    OpenAIRE

    Michael Mutingi

    2013-01-01

    Purpose: The objective of this research is to explore the empirical green supply chain activities found in literature, and to develop a taxonomic framework that can be used for formulating appropriate strategies for green supply chains, based on characteristic dimensions for the green supply chain. Design/methodology/approach: The taxonomic framework is developed through (i) analysis of green supply chain activities found in existing empirical work or case studies recorded in literature, (ii)...

  18. Taxonomic diversity and distinctness indices in assessment of weed communities

    Directory of Open Access Journals (Sweden)

    Magdalena Jastrzębska

    2012-12-01

    Full Text Available This paper contains an analysis of taxonomic weed biodiversity in the cultivation of spring barley in the period of 1990-2004, grown in crop rotation after potato with a 25% share of this cereal (potato - spring barley - field pea - winter triticale as well as in crop rotation with its 75% share (potato - spring barley - spring barley - spring barley in which barley was grown once and twice after the same barley crop. No weed control was used in the present experiment. Every year in the spring (at full emergence of the cereal crop and before harvest, the species composition and the numbers of individual weed species were determined, as well as weed biomass before harvest. On this basis, the taxonomic diversity and distinctness indices were calculated. Potato/barley crop rotation with a 25% share of this cereal and growing spring barley once and twice after the same barley crop did not differentiate taxonomic weed biodiversity. However, it was positively correlated with rainfall abundance during the growing season and negatively correlated with mean temperature. The taxonomic diversity indices were positively correlated with species richness and species diversity, whereas the taxonomic distinctness indices did not generally show any relationship with these measures. Spring barley grain yield did not depend on taxonomic biodiversity of weed communities.

  19. Niche partitioning and biogeography of high light adapted Prochlorococcus across taxonomic ranks in the North Pacific.

    Science.gov (United States)

    Larkin, Alyse A; Blinebry, Sara K; Howes, Caroline; Lin, Yajuan; Loftus, Sarah E; Schmaus, Carrie A; Zinser, Erik R; Johnson, Zackary I

    2016-07-01

    The distribution of major clades of Prochlorococcus tracks light, temperature and other environmental variables; yet, the drivers of genomic diversity within these ecotypes and the net effect on biodiversity of the larger community are poorly understood. We examined high light (HL) adapted Prochlorococcus communities across spatial and temporal environmental gradients in the Pacific Ocean to determine the ecological drivers of population structure and diversity across taxonomic ranks. We show that the Prochlorococcus community has the highest diversity at low latitudes, but seasonality driven by temperature, day length and nutrients adds complexity. At finer taxonomic resolution, some 'sub-ecotype' clades have unique, cohesive responses to environmental variables and distinct biogeographies, suggesting that presently defined ecotypes can be further partitioned into ecologically meaningful units. Intriguingly, biogeographies of the HL-I sub-ecotypes are driven by unique combinations of environmental traits, rather than through trait hierarchy, while the HL-II sub-ecotypes appear ecologically similar, thus demonstrating differences among these dominant HL ecotypes. Examining biodiversity across taxonomic ranks reveals high-resolution dynamics of Prochlorococcus evolution and ecology that are masked at phylogenetically coarse resolution. Spatial and seasonal trends of Prochlorococcus communities suggest that the future ocean may be comprised of different populations, with implications for ecosystem structure and function.

  20. Taxonomic distinctness and richness of helminth parasite assemblages of freshwater fishes in Mexican hydrological basins.

    Directory of Open Access Journals (Sweden)

    Benjamín Quiroz-Martínez

    Full Text Available In this paper, we analyse the distributional patterns of adult helminth parasites of freshwater fishes with respect to the main hydrological basins of Mexico. We use the taxonomic distinctness and the variation in taxonomic distinctness to explore patterns of parasite diversity and how these patterns change between zoogeographical regions. We address questions about the factors that determine the variation of observed diversity of helminths between basins. We also investigate patterns of richness, taxonomic distinctness and distance decay of similarity amongst basins. Our analyses suggest that the evolution of the fauna of helminth parasites in Mexico is mostly dominated by independent host colonization events and that intra--host speciation could be a minor factor explaining the origin of this diversity. This paper points out a clear separation between the helminth faunas of northern--nearctic and southern--neotropical components in Mexican continental waters, suggesting the availability of two distinct taxonomic pools of parasites in Mexican drainage basins. Data identifies Mexican drainage basins as unities inhabited by freshwater fishes, hosting a mixture of neotropical and nearctic species, in addition, data confirms neotropical and neartic basins/helminth faunas. The neotropical basins of Mexico are host to a richest and more diversified helminth fauna, including more families, genera and species, compared to the less rich and less diverse helminth fauna in the nearctic basins. The present analysis confirms distance--decay as one of the important factors contributing to the patterns of diversity observed. The hypothesis that helminth diversity could be explained by the ichthyological diversity of the basin received no support from present analysis.

  1. LCA*: an entropy-based measure for taxonomic assignment within assembled metagenomes.

    Science.gov (United States)

    Hanson, Niels W; Konwar, Kishori M; Hallam, Steven J

    2016-12-01

    A perennial problem in the analysis of environmental sequence information is the assignment of reads or assembled sequences, e.g. contigs or scaffolds, to discrete taxonomic bins. In the absence of reference genomes for most environmental microorganisms, the use of intrinsic nucleotide patterns and phylogenetic anchors can improve assembly-dependent binning needed for more accurate taxonomic and functional annotation in communities of microorganisms, and assist in identifying mobile genetic elements or lateral gene transfer events. Here, we present a statistic called LCA* inspired by Information and Voting theories that uses the NCBI Taxonomic Database hierarchy to assign taxonomy to contigs assembled from environmental sequence information. The LCA* algorithm identifies a sufficiently strong majority on the hierarchy while minimizing entropy changes to the observed taxonomic distribution resulting in improved statistical properties. Moreover, we apply results from the order-statistic literature to formulate a likelihood-ratio hypothesis test and P-value for testing the supremacy of the assigned LCA* taxonomy. Using simulated and real-world datasets, we empirically demonstrate that voting-based methods, majority vote and LCA*, in the presence of known reference annotations, are consistently more accurate in identifying contig taxonomy than the lowest common ancestor algorithm popularized by MEGAN, and that LCA* taxonomy strikes a balance between specificity and confidence to provide an estimate appropriate to the available information in the data. The LCA* has been implemented as a stand-alone Python library compatible with the MetaPathways pipeline; both of which are available on GitHub with installation instructions and use-cases (http://www.github.com/hallamlab/LCAStar/). shallam@mail.ubc.caSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  2. Taxonomic distinctness and richness of helminth parasite assemblages of freshwater fishes in Mexican hydrological basins.

    Science.gov (United States)

    Quiroz-Martínez, Benjamín; Salgado-Maldonado, Guillermo

    2013-01-01

    In this paper, we analyse the distributional patterns of adult helminth parasites of freshwater fishes with respect to the main hydrological basins of Mexico. We use the taxonomic distinctness and the variation in taxonomic distinctness to explore patterns of parasite diversity and how these patterns change between zoogeographical regions. We address questions about the factors that determine the variation of observed diversity of helminths between basins. We also investigate patterns of richness, taxonomic distinctness and distance decay of similarity amongst basins. Our analyses suggest that the evolution of the fauna of helminth parasites in Mexico is mostly dominated by independent host colonization events and that intra--host speciation could be a minor factor explaining the origin of this diversity. This paper points out a clear separation between the helminth faunas of northern--nearctic and southern--neotropical components in Mexican continental waters, suggesting the availability of two distinct taxonomic pools of parasites in Mexican drainage basins. Data identifies Mexican drainage basins as unities inhabited by freshwater fishes, hosting a mixture of neotropical and nearctic species, in addition, data confirms neotropical and neartic basins/helminth faunas. The neotropical basins of Mexico are host to a richest and more diversified helminth fauna, including more families, genera and species, compared to the less rich and less diverse helminth fauna in the nearctic basins. The present analysis confirms distance--decay as one of the important factors contributing to the patterns of diversity observed. The hypothesis that helminth diversity could be explained by the ichthyological diversity of the basin received no support from present analysis.

  3. Marine actinomycetes from Madeira Archipelago preliminary taxonomic studies

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    Ilda Santos Sanches

    2014-06-01

    region and suggesting a more globally distribution of this genus than previously supposed (unplublished results. In this study further 82 strains from Madeira Archipelago (out of 421 were selected for taxonomic identification, taking into account small groups of strains (1-4 evidencing very diverse morphological appearances, as exemplified in Figure 2. Using the same experimental microbiology identification tools, 8 genera were identified. However it was perceived that, the genera Streptomyces, Nocardiopsis and Actinomycetospora were predominant (93%, Figure 3. The phylogenetic trees built for the 82 taxonomically identified strains performed in this study are presented in Figures 4, 5 and 6. To date, having into account the present work and previous studies, our research group have identified from the actinomycetes isolated from Madeira´s ocean sediments, genera Streptomyces, Micromonospora, Salinispora, Nocardiopsis, Verrucosispora, Kocuria, Nonomuraea, Nocardia, Brevibacterium, Mycobacterium, Marinobacter, Actinomadura, Micrococcus, Actinomycetospora, Pseudonocardia, Gordonia and Millisia. From which genera Streptomyces, Micromonospora, Salinispora evidence a major representation. Crude extracts were obtained from all 421 strains and tested for their ability to produce natural products with bioactive properties: (i antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA, vancomycin-resistant Enterococcus faecalis (VRE and Candida albicans strains; and (ii cytotoxic activity against the HCT-116 cell line. A screening positive rate of 2.4% for antimicrobial MRSA and VRE assays and 3.2% for cytotoxic HCT-116 assay was obtained (submitted manuscripts. These studies demonstrate that the Macaronesian Atlantic Ocean region is a rich source of marine actinomycete biodiversity with potential industrial applications. Figure 1. Marine actinomycetes sediment sampling locations at Madeira Archipelago. Figure 2. Morphological diversity characteristics of

  4. Taxonomic novelties in the genus Campylospermum (Ochnaceae)

    NARCIS (Netherlands)

    Bissiengou, P.; Chatrou, L.W.; Wieringa, J.J.; Sosef, M.S.M.

    2013-01-01

    Four new species, one with two subspecies, of the genus Campylospermum are described, all endemic or sub-endemic to Gabon. These are C. auriculatum, C. gabonensis, C. gabonensis subsp. australis, C. glaucifolium and C. occidentalis. Distribution maps and scans of the holotypes are provided as well a

  5. Taxonomic Evaluation of Cleveland Harbor Lake Areas

    Science.gov (United States)

    2014-01-01

    studies should include benthic organisms such as microbiota and harvestable shellfish and finfish. Abundance, diversity, and distribution should be...statistical comparisons and determinations of data normality (Kolmogorov-Smirnov test) and homogeneity (Levene’s test) were performed using Sigmastat

  6. Taxonomic novelties in the genus Campylospermum (Ochnaceae)

    OpenAIRE

    Bissiengou, P.; Chatrou, L.W.; Wieringa, J. J.; Sosef, M.S.M.

    2013-01-01

    Four new species, one with two subspecies, of the genus Campylospermum are described, all endemic or sub-endemic to Gabon. These are C. auriculatum, C. gabonensis, C. gabonensis subsp. australis, C. glaucifolium and C. occidentalis. Distribution maps and scans of the holotypes are provided as well as preliminary IUCN Red List assessments. New combinations for nine species formerly assigned to the genus Ouratea and/or Gomphia are proposed: C. andongensis, C. glomeratum, C. longestipulatum, C. ...

  7. Efeito e modo de ação das bacteriocinas produzidas por Lactococcus lactis subsp. lactis ITAL 383, ATCC 11454 e CNRZ 150 contra Listeria innocua LIN 11 Effect and mode of action of the bacterioncin produced by Lactococcus. lactis subsp. lactis ITAL 383, ATCC 11454 e CNRZ 150 against Listeria innocua LIN 11

    Directory of Open Access Journals (Sweden)

    Izildinha MORENO

    1999-01-01

    Full Text Available O efeito e o modo de ação das bacteriocinas produzidas por L. lactis subsp. lactis ITAL 383 e CNRZ 150 são similares à nisina de L. lactis subsp. lactis ATCC 11454. Estas bacteriocinas apresentaram um modo de ação bactericida, causando a lise de células de L. innocua LIN 11, associada ao decréscimo da absorbância e da viabilidade celular. O efeito letal foi maior para células em fase exponencial comparativamente à fase estacionária de crescimento. A adsorção dessas bacteriocinas às células de L. innocua LIN 11 foi muito rápida e influenciada pelo pH do meio de suspensão; adsorção máxima foi verificada a pH 6,0 e logo após o contato inicial. Perda completa de adsorção ocorreu em pH 2,0.The effect and mode of action of the bacteriocin produced by L. lactis subsp. lactis ITAL 383 and CNRZ 150 are similar to the nisin produced by L. lactis subsp. lactis ATCC 11454. It was clearly bactericidal, and caused lysis of a strain of L. innocua LIN 11 detected by the decrease of absorbance values and the cell viability. Their lethal effect was considerably higher during the logarithmic growth when compared to the stationary phase. Adsorption developed rapidly and was influenced by the pH value of the suspension medium. Maximum adsorption was observed at pH 6,0 and immediately after initial contact and loss at pH 2,0.

  8. A taxonomic review of the dry-fruited species of Anemone (Ranunculaceae in southern Africa

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    J. C. Manning

    2013-01-01

    Full Text Available The three dry-fruited species of Anemone sect. Pulsatilloides subsect. Alchemillifoliae (Ranunculaceae from southern Africa are reviewed, with full descriptions and nomenclature, including complete synonomy, taxonomic history with nomenclatural corrections, ecological notes, and distribution. A. tenuifolia (L.f. DC. from the Cape Floristic Region is segregated as ser. Pinnatifoliae from the two summer rainfall species, A. caffra (Eckl. & Zeyh. Harv. and A. fanninnii Harv. ex Masters, which remain in ser. Alchemillifoliae, emphasising the strong vegetative differences between the two series.

  9. Taxonomic study of Festuca L. subgenus Schedonorus (P. Beauv. Peterm. in Iran

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    Sayed Zabihollah Hosseini

    2013-11-01

    Full Text Available This study was based upon a taxonomic review of the subgenus Schedonorus in Iran. A collection of 30 specimens belonging to the herbaria: W, B and HUI (herbarium of the University of Isfahan were studied. Based on the results of this study, this subgenus included three species: Festuca arundinacea, F. gigantea and F. pratensis in Iran. Furthermore, this study showed that F. arundinacea, occured in this country with two subspecies: orientalis (Hack. Tzvelev and fenas (Lag. Arcang. with the greatest area of distribution compared to the other two species. Our examination of the type specimen of F. elatior subsp. pratensis var. elbursiana confirmed its synonymy with F. arundinacea.

  10. [Taxonomic characteristics and physiological properties of microorganisms from the gut of pike (Esox lucius)].

    Science.gov (United States)

    Izveskova, G I; Nemtseva, N V; Plotnikov, A O

    2008-01-01

    The taxonomic composition and distribution of microorganisms differing in the degree of association with the intestinal mucosa of the pike (Lucius lucius) has been studied. Microorgansism of the families Enterobacteriaceae, Aeromonadaceae, and Vibrionaceae dominate in the gut microflora. Numerically prevailing bacterial species are characterized by high proteolytic and amylolytic enzyme activities as well as by high persistence accounted for by antilysozyme and antihistone activities. The results of this study show that Hafnia alvei, Yersinia ruckeri, Vibrio vulnificus, V. furnissii, Aeromonas salmonicida, and Shewanella putrefaciens may be regarded as normal components of the pike gut microflora.

  11. A taxonomic revision of the type section of Pelargonium L’Hérit. (Geraniaceae

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    J. J. A. van der Walt

    1984-12-01

    Full Text Available Twenty four species are recognized in this taxonomic treatment of the section Pelargonium which was last revised by Knuth in 1912, Most species occur in the south-western, southern and eastern Cape where they usually grow in rather moist, semi-shaded habitats, A key to the identification o f the species has been compiled, and at least one illustration as well as a distribution map is presented for each species. The section is considered to be the most primitive section of the genus with a basic chromosome number of x = 11.

  12. Taxonomic notes on Agroeca (Araneae, Liocranidae

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    Kronestedt, Torbjörn

    2009-07-01

    Full Text Available Agroeca gaunitzi Tullgren, 1952 is stated here to be a junior synonym of A. proxima (O. P.-Cambridge, 1871. The illustrations of the male palp attributed to A. proxima in papers by Tullgren of 1946 and 1952 in fact show A. inopina O. P.-Cambridge, 1886. The record of A. inopina from Finland, quite outside its known distribution range, was based on a misidentification. It is argued that the type species of the genus Agroeca Westring, 1861 should be A. proxima (O. P.-Cambridge, 1871, not A. brunnea (Blackwall, 1833 as currently applied. Protagroeca Lohmander, 1944 is placed as an objective synonym of Agroeca Westring, 1861.

  13. A taxonomic study of Bali and Lombok Begonia (Begoniaceae

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    Deden Girmansyah

    2009-12-01

    Full Text Available GIRMANSYAH, DEDEN. 2009. A taxonomic study of Bali and Lombok Begonia (Begoniaceae. Reinwardtia 12(5: 419–434. — A taxonomic study of Bali and Lombok Begonia was based on an investigation of morphological characters from 60 specimens in Herbarium Bogoriense. This study shows that there are 8 species that can be recognized: three species already in the genus (Begonia coriacea, B. longifolia, and B. tenuifolia and five new (Begonia baliensis, B. lempuyangensis, B. pseudomuricata, B. multibracteata, and B. lombokensis.

  14. Hypothesis testing and power calculations for taxonomic-based human microbiome data.

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    Patricio S La Rosa

    Full Text Available This paper presents new biostatistical methods for the analysis of microbiome data based on a fully parametric approach using all the data. The Dirichlet-multinomial distribution allows the analyst to calculate power and sample sizes for experimental design, perform tests of hypotheses (e.g., compare microbiomes across groups, and to estimate parameters describing microbiome properties. The use of a fully parametric model for these data has the benefit over alternative non-parametric approaches such as bootstrapping and permutation testing, in that this model is able to retain more information contained in the data. This paper details the statistical approaches for several tests of hypothesis and power/sample size calculations, and applies them for illustration to taxonomic abundance distribution and rank abundance distribution data using HMP Jumpstart data on 24 subjects for saliva, subgingival, and supragingival samples. Software for running these analyses is available.

  15. Taxonomic review and phylogenetic analysis of Enchodontoidei.

    Science.gov (United States)

    Silva, Hilda M A; Gallo, Valéria

    2011-06-01

    Enchodontoidei are extinct marine teleost fishes with a long temporal range and a wide geographic distribution. As there has been no comprehensive phylogenetic study of this taxon, we performed a parsimony analysis using a data matrix with 87 characters, 31 terminal taxa for ingroup, and three taxa for outgroup. The analysis produced 93 equally parsimonious trees (L = 437 steps; CI = 0. 24; RI = 0. 49). The topology of the majority rule consensus tree was: (Sardinioides + Hemisaurida + (Nardorex + (Atolvorator + (Protostomias + Yabrudichthys ) + (Apateopholis + (Serrilepis + (Halec + Phylactocephalus ) + (Cimolichthys + (Prionolepis + ( (Eurypholis + Saurorhamphus ) + (Enchodus + (Paleolycus + Parenchodus ))))))) + ( (Ichthyotringa + Apateodus ) + (Rharbichthys + (Trachinocephalus + ( (Apuliadercetis + Brazilodercetis ) + (Benthesikyme + (Cyranichthys + Robertichthys ) + (Dercetis + Ophidercetis )) + (Caudadercetis + (Pelargorhynchus + (Nardodercetis + (Rhynchodercetis + (Dercetoides + Hastichthys )))))). The group Enchodontoidei is not monophyletic. Dercetidae form a clade supported by the presence of very reduced neural spines and possess a new composition. Enchodontidae are monophyletic by the presence of middorsal scutes, and Rharbichthys was excluded. Halecidae possess a new composition, with the exclusion of Hemisaurida. This taxon and Nardorex are Aulopiformes incertae sedis.

  16. Taxonomic and functional ecology of montane ants

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    Tom Rhys Bishop

    2017-04-01

    Full Text Available Why is biological diversity distributed in the way that it is? This question has been central to ecology and biogeography for centuries and is of great importance for pure and applied reasons. I use a functional trait view of ecology to complement standard sampling protocols to better understand the distribution and structure of ant (Hymenoptera: Formicidae diversity across mountains. I use a long-term dataset of ant diversity and abundance, combined with a recently collected morphological trait dataset to examine how the alpha and beta diversity of ants responds to changes in temperature along an extensive elevational gradient in southern Africa. In addition, I link morphological thermoregulatory traits to each other and to the environment with a new database of ant elevational abundances from across the globe. Finally, I analyse how physiological thermal tolerances vary and constrain foraging patterns in montane ants. I find that temperature is a strong driver of both alpha and beta diversity patterns. In addition, morphological traits such as colour and body size are found to have a significant relationship to ambient temperatures. This relationship also implies that the relative abundances of different ant species change depending on their thermoregulatory traits (colour and body size and the surrounding thermal environment. Furthermore, the critical thermal minimum (CTmin of the ant species investigated and the lowest environmental temperatures are found to be key in constraining foraging activity patterns. The data presented here strengthen and link existing ideas about how thermoregulation can influence ecological communities and also suggests important ways in which diversity patterns may change in the future.

  17. Taxonomía de la literatura oral kuna

    OpenAIRE

    Prestán, Arnulfo

    2016-01-01

    El presente trabajo trata de descifrar, grosso modo, la taxonomía de la literatura oral kuna denominada ikar que significa tratado o camino y se especifica anteponiendo un sustantivo, por ejemplo, pap ikar que significa tratado de Dios; ina ikar, tratado de medicina, etc.

  18. WEVOTE: Weighted Voting Taxonomic Identification Method of Microbial Sequences

    Science.gov (United States)

    Metwally, Ahmed A.; Dai, Yang; Finn, Patricia W.; Perkins, David L.

    2016-01-01

    Background Metagenome shotgun sequencing presents opportunities to identify organisms that may prevent or promote disease. The analysis of sample diversity is achieved by taxonomic identification of metagenomic reads followed by generating an abundance profile. Numerous tools have been developed based on different design principles. Tools achieving high precision can lack sensitivity in some applications. Conversely, tools with high sensitivity can suffer from low precision and require long computation time. Methods In this paper, we present WEVOTE (WEighted VOting Taxonomic idEntification), a method that classifies metagenome shotgun sequencing DNA reads based on an ensemble of existing methods using k-mer-based, marker-based, and naive-similarity based approaches. Our evaluation on fourteen benchmarking datasets shows that WEVOTE improves the classification precision by reducing false positive annotations while preserving a high level of sensitivity. Conclusions WEVOTE is an efficient and automated tool that combines multiple individual taxonomic identification methods to produce more precise and sensitive microbial profiles. WEVOTE is developed primarily to identify reads generated by MetaGenome Shotgun sequencing. It is expandable and has the potential to incorporate additional tools to produce a more accurate taxonomic profile. WEVOTE was implemented using C++ and shell scripting and is available at www.github.com/aametwally/WEVOTE. PMID:27683082

  19. Developing green supply chain management strategies: A taxonomic approach

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    Michael Mutingi

    2013-06-01

    Full Text Available Purpose: The objective of this research is to explore the empirical green supply chain activities found in literature, and to develop a taxonomic framework that can be used for formulating appropriate strategies for green supply chains, based on characteristic dimensions for the green supply chain. Design/methodology/approach: The taxonomic framework is developed through (i analysis of green supply chain activities found in existing empirical work or case studies recorded in literature, (ii identification of key dimensions that influence green supply chain management strategies, and (iii development of a taxonomic scheme for selecting or developing green strategies. Findings: The paper finds that this study yielded: a set of three characteristic dimensions that influence strategic green supply chain management, and a guided structured approach selecting appropriate green strategies, providing managerial insights. Research limitations/implications: This paper shows that future work includes development of specific performance management indices according to the taxonomy of green strategies developed in this study. Practical implications: This research provided a practical guided approach that enhances appropriate formulation of green strategies for green supply chain management, while providing sound managerial insights for the supply chain decision maker. The choice of supply chain strategy directly impacts the overall environmental, economic and operations performance of the supply chain. Originality/value: This study presents to supply chain decision makers a new taxonomic framework that simplifies and enhances the formulation of green strategies, and to researchers a comparative understanding of various strategies applicable to green supply chains.

  20. Taxonomic scheme for the identification of marine bacteria

    Science.gov (United States)

    Oliver, James D.

    1982-06-01

    A recently developed taxonomic scheme for the identification of marine bacteria is presented. The scheme is based on numerous reviews and monographs on marine bacteria, as well as Bergey's Manual of Determinative Bacteriology. While fairly extensive, the scheme is designed to identify marine bacteria using relatively few tests.

  1. A Taxonomic Approach to the Gestalt Theory of Perls

    Science.gov (United States)

    Raming, Henry E.; Frey, David H.

    1974-01-01

    This study applied content analysis and cluster analysis to the ideas of Fritz Perls to develop a taxonomy of Gestalt processes and goals. Summaries of the typal groups or clusters were written and the implications of taxonomic research in counseling discussed. (Author)

  2. A synopsis of taxonomic changes in Aporosa Blume (Euphorbiaceae)

    NARCIS (Netherlands)

    Schot, Anne M.

    1995-01-01

    Some major nomenclatural and taxonomic changes in Aporosa Blume are treated, i.e., the spelling of the genus name, some new combinations, and descriptions of four new species of from West Malesia, six from New Guinea, and two new varieties from West Malesia. Notes on a number of often misunderstood

  3. Taxonomic revision of the genus Thereianthus (Iridaceae: Crocoideae

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    J. C. Manning

    2011-12-01

    Full Text Available Thereianthus G.J.Lewis is revised, with full descriptions and synonomy, distribution maps, and notes on ecology and taxonomic history. All species are illustrated, and capsule and seed morphology are described for many of the species for the first time. Novel characteristics of the bract, seed, and pollen operculum are used to separate the species into two sections: sect. Brevibracteae Goldblatt & J.C.Manning is distinguished by relatively small bracts, 3–8 mm long and uniformly leathery or soft-textured without thickened veins, seeds with filiform chalazal extension, and pollen grains with 1-banded operculum; and sect. Thereianthus by relatively larger bracts, (7–8–15 mm long with prominently sclerified veins, seeds without any extension to the chalazal crest, and pollen grains with ± 2-banded operculum. Species in sect. Thereianthus are further segregated into ser. Thereianthus, with heavily ribbed leaves and suberect flowers with arcuate or erect stamens, and ser. Bracteolatus, with plane, inconspicuously veined leaves and ± spreading flowers with declinate stamens. Eleven species are recognized in the genus, all restricted to the southwestern portion of Western Cape. Two new species are described in sect. Thereianthus: T. bulbiferus Goldblatt & J.C.Manning, known from three populations along the West Coast, is distinguished by the unique development of cormels in the lower leaf axil, and by its actinomorphic perianth with white marks at the base of each tepal and ± declinate stamens; and T. elandsmontanus Goldblatt & J.C.Manning, known from a single population in Elandsberg Nature Reserve near Wellington, has distinctive cream-coloured, moderately long-tubed flowers with unusually narrow, linear tepals heavily marked with purple near the base. In adddition, T. lapeyrousioides [now T. minutus] var. elatior G.J.Lewis in sect. Brevibracteae is raised to species status as T. intermedius Goldblatt & J.C.Manning, differing from typical T

  4. A taxonomic revision of Acaciella (Leguminosae, Mimosoideae

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    Rico Arce, M. de L.

    2006-12-01

    Full Text Available The genus Acaciella Britton & Rose is reinstated. All species are neotropical with the highest species diversity along the Pacific coast of Mexico. The genus is characterised by three features exceptional in Acacia Miller: unarmed plants, lack extrafloral nectaries and pollen polyads 8-celled. With the exception of the number of stamens, Acaciella shares more features with the genus Piptadenia (tribe Mimoseae than with Acacia. In terms of pollen and free aminoacids it is related to the pantropical Acacia subgen. Aculeiferum. Molecular studies place Acaciella sister to a monophyletic clade comprising elements of the mainly Australian Acacia subgen. Phyllodineae, and the pantropical tribe Ingeae. The 85 validly published names in Acaciella are referred here to 15 accepted species and five varieties. One new species and one variety are described, and two new names and five new combinations proposed. Twenty one names are lectotypified. Keys, descriptions, illustrations, distribution maps and conservationSe restablece el género Acaciella Britton & Rose. Todas las especies son de origen neotropical con su máxima diversidad en la costa del Pacífico de México. El género se caracteriza por tres aspectos morfológicos, que son excepciones del género Acacia Miller: plantas completamente inermes, ausencia de nectarios extraflorales y políades con 8 granos de polen. La única característica que lo mantenía dentro del género Acacia Miller era el número de estambres. Acaciella comparte más caracteres con el género Piptadenia (tribu Mimoseae. En lo que refiere al polen y aminoácidos libres se encuentra emparentado con Acacia subg. Aculeiferum. Los datos moleculares sugieren que Acaciella es grupo hermano del clado formado por los táxones Acacia subgen. Phyllodineae y la tribu pantropical Ingeae. Los 85 nombres publicados como Acaciella son tratados aquí como 15 especies y cinco variedades. Se proponen una nueva especie, una nueva variedad, dos

  5. Evolutionary and Taxonomic Implications of Variation in Nuclear Genome Size: Lesson from the Grass Genus Anthoxanthum (Poaceae).

    Science.gov (United States)

    Chumová, Zuzana; Krejčíková, Jana; Mandáková, Terezie; Suda, Jan; Trávníček, Pavel

    2015-01-01

    The genus Anthoxanthum (sweet vernal grass, Poaceae) represents a taxonomically intricate polyploid complex with large phenotypic variation and its evolutionary relationships still poorly resolved. In order to get insight into the geographic distribution of ploidy levels and assess the taxonomic value of genome size data, we determined C- and Cx-values in 628 plants representing all currently recognized European species collected from 197 populations in 29 European countries. The flow cytometric estimates were supplemented by conventional chromosome counts. In addition to diploids, we found two low (rare 3x and common 4x) and one high (~16x-18x) polyploid levels. Mean holoploid genome sizes ranged from 5.52 pg in diploid A. alpinum to 44.75 pg in highly polyploid A. amarum, while the size of monoploid genomes ranged from 2.75 pg in tetraploid A. alpinum to 9.19 pg in diploid A. gracile. In contrast to Central and Northern Europe, which harboured only limited cytological variation, a much more complex pattern of genome sizes was revealed in the Mediterranean, particularly in Corsica. Eight taxonomic groups that partly corresponded to traditionally recognized species were delimited based on genome size values and phenotypic variation. Whereas our data supported the merger of A. aristatum and A. ovatum, eastern Mediterranean populations traditionally referred to as diploid A. odoratum were shown to be cytologically distinct, and may represent a new taxon. Autopolyploid origin was suggested for 4x A. alpinum. In contrast, 4x A. odoratum seems to be an allopolyploid, based on the amounts of nuclear DNA. Intraspecific variation in genome size was observed in all recognized species, the most striking example being the A. aristatum/ovatum complex. Altogether, our study showed that genome size can be a useful taxonomic marker in Anthoxathum to not only guide taxonomic decisions but also help resolve evolutionary relationships in this challenging grass genus.

  6. Beta Diversity in a Highly Heterogeneous Area: Disentangling Species and Taxonomic Dissimilarity for Terrestrial Vertebrates.

    Science.gov (United States)

    Calderón-Patrón, Jaime M; Goyenechea, Irene; Ortiz-Pulido, Raúl; Castillo-Cerón, Jesús; Manriquez, Norma; Ramírez-Bautista, Aurelio; Rojas-Martínez, Alberto E; Sánchez-Rojas, Gerardo; Zuria, Iriana; Moreno, Claudia E

    2016-01-01

    Quantifying differences in species composition among communities provides important information related to the distribution, conservation and management of biodiversity, especially when two components are recognized: dissimilarity due to turnover, and dissimilarity due to richness differences. The ecoregions in central Mexico, within the Mexican Transition Zone, have outstanding environmental heterogeneity and harbor huge biological richness, besides differences in the origin of the biota. Therefore, biodiversity studies in this area require the use of complementary measures to achieve appropriate information that may help in the design of conservation strategies. In this work we analyze the dissimilarity of terrestrial vertebrates, and the components of turnover and richness differences, among six ecoregions in the state of Hidalgo, central Mexico. We follow two approaches: one based on species level dissimilarity, and the second on taxonomic dissimilarity. We used databases from the project "Biodiversity in the state of Hidalgo". Our results indicate that species dissimilarity is higher than taxonomic dissimilarity, and that turnover contributes more than richness differences, both for species and taxonomic total dissimilarity. Moreover, total dissimilarity, turnover dissimilarity and the dissimilarity due to richness differences were positively related in the four vertebrate groups. Reptiles had the highest values of dissimilarity, followed by mammals, amphibians and birds. For reptiles, birds, and mammals, species turnover was the most important component, while richness differences had a higher contribution for amphibians. The highest values of dissimilarity occurred between environmentally contrasting ecoregions (i.e., tropical and temperate forests), which suggests that environmental heterogeneity and differences in the origin of biotas are key factors driving beta diversity of terrestrial vertebrates among ecoregions in this complex area.

  7. Clarification of the taxonomic relationship of the extant and extinct ovibovids, Ovibos, Praeovibos, Euceratherium and Bootherium

    Science.gov (United States)

    Campos, Paula F.; Sher, Andrei; Mead, Jim I.; Tikhonov, Alexei; Buckley, Michael; Collins, Matthew; Willerslev, Eske; Gilbert, M. Thomas P.

    2010-08-01

    During the late Pleistocene, a large number of species colonized North America from Eurasia through the Bering Land Bridge. At least four different genera within the tribe Ovibovini are known from this time, the holarctically distributed Ovibos moschatus (the extant musk ox) and Praeovibos, and the nearctically distributed Bootherium and Euceratherium. Questions about the taxonomic relationships of the four North American musk oxen arose soon after their description and continue to be unresolved at the present. In this study we present the first DNA and protein analyses, of the four mentioned genera. Phylogenetic analysis at the mitochondrial level indicates that Praeovibos falls within the diversity of modern Ovibos, which might indicate that Praeovibos is simply an earlier morphotype of the extant species O. moschatus. In contrast Euceratherium and Bootherium are clearly distinct genera, in agreement with the findings of previous morphological studies.

  8. Does taxonomic diversity in indicator groups influence their effectiveness in identifying priority areas for species conservation?

    DEFF Research Database (Denmark)

    Bladt, Jesper Stentoft; Larsen, Frank Wugt; Rahbek, Carsten

    2008-01-01

    the taxonomic diversity in species indicator groups influence their effectiveness in the identification of priority areas for species conservation. We tested whether indicator groups comprising a higher taxonomic diversity (i.e. indicator groups consisting of species from many different taxonomic groups...

  9. Quantifying the taxonomic diversity in real species communities

    Energy Technology Data Exchange (ETDEWEB)

    Cartozo, Cecile Caretta [Laboratoire de Biophysique Statistique, ITP-FSB, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne (Switzerland); Garlaschelli, Diego [Department of Physics, University of Siena, Via Roma 56, 53100 Siena (Italy); Ricotta, Carlo [Department of Plant Biology, University of Rome ' La Sapienza' , Piazzale Aldo Moro 5, 00185 Rome (Italy); Barthelemy, Marc [School of Informatics and Biocomplexity Center, Indiana University, Eigenmann Hall, 1900 East Tenth Street, Bloomington, IN 47406 (United States); Caldarelli, Guido [INFM-CNR Centro SMC Department of Physics, University of Rome ' La Sapienza' , Piazzale Aldo Moro 5, 00185 Rome (Italy)], E-mail: cecile.carettacartozo@epfl.ch, E-mail: garlaschelli@unisi.it, E-mail: carlo.ricotta@uniroma1.it, E-mail: mbarthel@indiana.edu, E-mail: guido.caldarelli@roma1.infn.it

    2008-06-06

    We analyze several florae (collections of plant species populating specific areas) in different geographic and climatic regions. For every list of species we produce a taxonomic classification tree and we consider its statistical properties. We find that regardless of the geographical location, the climate and the environment all species collections have universal statistical properties that we show to be also robust in time. We then compare observed data sets with simulated communities obtained by randomly sampling a large pool of species from all over the world. We find differences in the behavior of the statistical properties of the corresponding taxonomic trees. Our results suggest that it is possible to distinguish quantitatively real species assemblages from random collections and thus demonstrate the existence of correlations between species.

  10. A taxonomic catalogue of Japanese nemerteans (phylum Nemertea).

    Science.gov (United States)

    Kajihara, Hiroshi

    2007-04-01

    A literature-based taxonomic catalogue of the nemertean species (Phylum Nemertea) reported from Japanese waters is provided, listing 19 families, 45 genera, and 120 species as valid. Applications of the following species names to forms previously recorded from Japanese waters are regarded as uncertain: Amphiporus cervicalis, Amphiporus depressus, Amphiporus lactifloreus, Cephalothrix filiformis, Cephalothrix linearis, Cerebratulus fuscus, Lineus vegetus, Lineus bilineatus, Lineus gesserensis, Lineus grubei, Lineus longifissus, Lineus mcintoshii, Nipponnemertes pulchra, Oerstedia venusta, Prostoma graecense, and Prostoma grande. The identities of the taxa referred to by the following four nominal species require clarification through future investigations: Cosmocephala japonica, Dicelis rubra, Dichilus obscurus, and Nareda serpentina. The nominal species established from Japanese waters are tabulated. In addition, a brief history of taxonomic research on Japanese nemerteans is reviewed.

  11. Quantifying the taxonomic diversity in real species communities

    CERN Document Server

    Cartozo, C Caretta; Ricotta, C; Barthelemy, M; Caldarelli, G

    2008-01-01

    We analyze several florae (collections of plant species populating specific areas) in different geographic and climatic regions. For every list of species we produce a taxonomic classification tree and we consider its statistical properties. We find that regardless of the geographical location, the climate and the environment all species collections have universal statistical properties that we show to be also robust in time. We then compare observed data sets with simulated communities obtained by randomly sampling a large pool of species from all over the world. We find differences in the behavior of the statistical properties of the corresponding taxonomic trees. Our results suggest that it is possible to distinguish quantitatively real species assemblages from random collections and thus demonstrate the existence of correlations between species.

  12. Data on taxonomic status and phylogenetic relationship of tits

    Directory of Open Access Journals (Sweden)

    Xue-Juan Li

    2017-02-01

    Full Text Available The data in this paper are related to the research article entitled “Taxonomic status and phylogenetic relationship of tits based on mitogenomes and nuclear segments” (X.J. Li et al., 2016 [1]. The mitochondrial genomes and nuclear segments of tits were sequenced to analyze mitochondrial characteristics and phylogeny. In the data, the analyzed results are presented. The data holds the resulting files of mitochondrial characteristics, heterogeneity, best schemes, and trees.

  13. Data on taxonomic status and phylogenetic relationship of tits.

    Science.gov (United States)

    Li, Xue-Juan; Lin, Li-Liang; Cui, Ai-Ming; Bai, Jie; Wang, Xiao-Yang; Xin, Chao; Zhang, Zhen; Yang, Chao; Gao, Rui-Rui; Huang, Yuan; Lei, Fu-Min

    2017-02-01

    The data in this paper are related to the research article entitled "Taxonomic status and phylogenetic relationship of tits based on mitogenomes and nuclear segments" (X.J. Li et al., 2016) [1]. The mitochondrial genomes and nuclear segments of tits were sequenced to analyze mitochondrial characteristics and phylogeny. In the data, the analyzed results are presented. The data holds the resulting files of mitochondrial characteristics, heterogeneity, best schemes, and trees.

  14. La confusa taxonomía de Cryptosporidium

    Directory of Open Access Journals (Sweden)

    Gregorio Pérez-Cordón

    2006-10-01

    Full Text Available Los últimos descubrimientos en la biología y filogenética de Cryptosporidium refuerzan la necesidad de una exhaustiva revisión del ciclo de vida y la taxonomía de este parásito. Tanto futuros estudios de cultivo in vitro e in vivo así como estudios moleculares y genéticos permitirán avanzar en el profundo conocimiento de este interesante parásito.

  15. Insights from Zootaxa on potential trends in zoological taxonomic activity

    Directory of Open Access Journals (Sweden)

    Dubois Alain

    2011-03-01

    Full Text Available Abstract Background An opinion currently shared by taxonomists and non taxonomists alike is that the work of inventorying biodiversity is unbalanced: firstly, i