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Sample records for active group showed

  1. Ovalbumin with Glycated Carboxyl Groups Shows Membrane-Damaging Activity

    PubMed Central

    Tang, Ching-Chia; Shi, Yi-Jun; Chen, Ying-Jung; Chang, Long-Sen

    2017-01-01

    The aim of the present study was to investigate whether glycated ovalbumin (OVA) showed novel activity at the lipid-water interface. Mannosylated OVA (Man-OVA) was prepared by modification of the carboxyl groups with p-aminophenyl α-dextro (d)-mannopyranoside. An increase in the number of modified carboxyl groups increased the membrane-damaging activity of Man-OVA on cell membrane-mimicking vesicles, whereas OVA did not induce membrane permeability in the tested phospholipid vesicles. The glycation of carboxyl groups caused a notable change in the gross conformation of OVA. Moreover, owing to their spatial positions, the Trp residues in Man-OVA were more exposed, unlike those in OVA. Fluorescence quenching studies suggested that the Trp residues in Man-OVA were located on the interface binds with the lipid vesicles, and their microenvironment was abundant in positively charged residues. Although OVA and Man-OVA showed a similar binding affinity for lipid vesicles, the lipid-interacting feature of Man-OVA was distinct from that of OVA. Chemical modification studies revealed that Lys and Arg residues, but not Trp residues, played a crucial role in the membrane-damaging activity of Man-OVA. Taken together, our data suggest that glycation of carboxyl groups causes changes in the structural properties and membrane-interacting features of OVA, generating OVA with membrane-perturbing activities at the lipid-water interface. PMID:28264493

  2. Bovine serum albumin with glycated carboxyl groups shows membrane-perturbing activities.

    PubMed

    Yang, Shin-Yi; Chen, Ying-Jung; Kao, Pei-Hsiu; Chang, Long-Sen

    2014-12-15

    The aim of the present study aimed to investigate whether glycated bovine serum albumin (BSA) showed novel activities on the lipid-water interface. Mannosylated BSA (Man-BSA) was prepared by modification of the carboxyl groups with p-aminophenyl α-d-mannopyranoside. In contrast to BSA, Man-BSA notably induced membrane permeability of egg yolk phosphatidylcholine (EYPC)/egg yolk sphingomyelin (EYSM)/cholesterol (Chol) and EYPC/EYSM vesicles. Noticeably, Man-BSA induced the fusion of EYPC/EYSM/Chol vesicles, but not of EYPC/EYSM vesicles. Although BSA and Man-BSA showed similar binding affinity for lipid vesicles, the lipid-bound conformation of Man-BSA was distinct from that of BSA. Moreover, Man-BSA adopted distinct structure upon binding with the EYPC/EYSM/Chol and EYPC/EYSM vesicles. Man-BSA could induce the fusion of EYPC/EYSM/Chol vesicles with K562 and MCF-7 cells, while Man-BSA greatly induced the leakage of Chol-depleted K562 and MCF-7 cells. The modified BSA prepared by conjugating carboxyl groups with p-aminophenyl α-d-glucopyranoside also showed membrane-perturbing activities. Collectively, our data indicate that conjugation of carboxyl groups with monosaccharide generates functional BSA with membrane-perturbing activities on the lipid-water interface.

  3. Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon.

    PubMed

    Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

    2015-08-25

    Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities.

  4. Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon

    PubMed Central

    Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

    2015-01-01

    Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities. PMID:26304458

  5. 17. DINING ROOM INTERIOR SHOWING GROUP OF THREE 1 LIGHT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. DINING ROOM INTERIOR SHOWING GROUP OF THREE 1 LIGHT OVER 1 LIGHT WINDOWS, AND DOORWAY INTO KITCHEN. VIEW TO EAST. - Big Creek Hydroelectric System, Powerhouse 8, Operator Cottage, Big Creek, Big Creek, Fresno County, CA

  6. 25. SECOND FLOOR EAST SIDE APARTMENT KITCHEN INTERIOR SHOWING GROUP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. SECOND FLOOR EAST SIDE APARTMENT KITCHEN INTERIOR SHOWING GROUP OF THREE 6-LIGHT WOOD-FRAME CASEMENT WINDOWS OVER THE SINK, AND OPEN DOORWAY TO TOP OF EXTERIOR STAIR LANDING AND WALKWAY AT REAR OF HOUSE. WALKWAY IS VISIBLE THROUGH KITCHEN WINDOWS. VIEW TO SOUTH. - Lee Vining Creek Hydroelectric System, Triplex Cottage, Lee Vining Creek, Lee Vining, Mono County, CA

  7. Wild chimpanzees show group differences in selection of agricultural crops

    PubMed Central

    McLennan, Matthew R.; Hockings, Kimberley J.

    2014-01-01

    The ability of wild animals to respond flexibly to anthropogenic environmental changes, including agriculture, is critical to survival in human-impacted habitats. Understanding use of human foods by wildlife can shed light on the acquisition of novel feeding habits and how animals respond to human-driven land-use changes. Little attention has focused on within-species variation in use of human foods or its causes. We examined crop-feeding in two groups of wild chimpanzees – a specialist frugivore – with differing histories of exposure to agriculture. Both groups exploited a variety of crops, with more accessible crops consumed most frequently. However, crop selection by chimpanzees with long-term exposure to agriculture was more omnivorous (i.e., less fruit-biased) compared to those with more recent exposure, which ignored most non-fruit crops. Our results suggest chimpanzees show increased foraging adaptations to cultivated landscapes over time; however, local feeding traditions may also contribute to group differences in crop-feeding in this species. Understanding the dynamic responses of wildlife to agriculture can help predict current and future adaptability of species to fast-changing anthropogenic landscapes. PMID:25090940

  8. Tetrahydrobiopterin shows chaperone activity for tyrosine hydroxylase.

    PubMed

    Thöny, Beat; Calvo, Ana C; Scherer, Tanja; Svebak, Randi M; Haavik, Jan; Blau, Nenad; Martinez, Aurora

    2008-07-01

    Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of catecholamine neurotransmitters. Primary inherited defects in TH have been associated with l-DOPA responsive and non-responsive dystonia and infantile parkinsonism. In this study, we show that both the cofactor (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)) and the feedback inhibitor and catecholamine product dopamine increase the kinetic stability of human TH isoform 1 in vitro. Activity measurements and synthesis of the enzyme by in vitro transcription-translation revealed a complex regulation by the cofactor including both enzyme inactivation and conformational stabilization. Oral BH(4) supplementation to mice increased TH activity and protein levels in brain extracts, while the Th-mRNA level was not affected. All together our results indicate that the molecular mechanisms for the stabilization are a primary folding-aid effect of BH(4) and a secondary effect by increased synthesis and binding of catecholamine ligands. Our results also establish that orally administered BH(4) crosses the blood-brain barrier and therapeutic regimes based on BH(4) supplementation should thus consider the effect on TH. Furthermore, BH(4) supplementation arises as a putative therapeutic agent in the treatment of brain disorders associated with TH misfolding, such as for the human TH isoform 1 mutation L205P.

  9. Garnet: featured mineral group at the 1993 Tucson Show

    USGS Publications Warehouse

    Modreski, P.J.

    1993-01-01

    The garnets are a common but complex group of minerals. They are perhaps the mineral kingdom's best example of solid solution: a relationship in which minerals have chemical compositions that are intermediate between two or more ideal end-member species. In garnet, we deal with a complex group of solid-solution series between as many as 14 end-member minerals. The varying intergradations of solid solution between these different end-members help to explain the garnet group's variety of color, environment of occurrence, gem use, and variation in such physical properties as specific gravity, refractive index, and hardness. -from Author

  10. Serving Up Activities for TV Cooking Shows.

    ERIC Educational Resources Information Center

    Katchen, Johanna E.

    This paper documents a presentation given on the use of English-language television cooking shows in English-as-a-Second-Language (ESL) and English-as-a-Foreign-Language (EFL) classrooms in Taiwan. Such shows can be ideal for classroom use, since they have a predictable structure consisting of short segments, are of interest to most students,…

  11. Surveys show support for green 'activities'.

    PubMed

    Baillie, Jonathan

    2012-03-01

    Two independently conducted surveys on sustainability - one into the 'views and values' of NHS 'leaders', and the other questioning the public about the importance of the 'green agenda' in the NHS, and their opinions on how the service might most effectively reduce its carbon footprint, form the basis of Sustainability in the NHS: Health Check 2012, a new NHS Sustainable Development Unit (NHS SDU) publication. As HEJ editor Jonathan Baillie reports, the new document also presents updated data on the 'size' of the carbon footprint of the NHS in England, showing that, although good work by a number of Trusts in the past two years has seen healthcare-generated carbon emissions start to 'level off', the biggest contributors have been the current health service spending review, and the increased national availability of renewable energy.

  12. Mouse models for xeroderma pigmentosum group A and group C show divergent cancer phenotypes.

    PubMed

    Melis, Joost P M; Wijnhoven, Susan W P; Beems, Rudolf B; Roodbergen, Marianne; van den Berg, Jolanda; Moon, Hojin; Friedberg, Errol; van der Horst, Gijsbertus T J; Hoeijmakers, Jan H J; Vijg, Jan; van Steeg, Harry

    2008-03-01

    The accumulation of DNA damage is a slow but hazardous phenomenon that may lead to cell death, accelerated aging, and cancer. One of the most versatile defense mechanisms against the accumulation of DNA damage is nucleotide excision repair, in which, among others, the Xeroderma pigmentosum group C (XPC) and group A (XPA) proteins are involved. To elucidate differences in the functions of these two proteins, comprehensive survival studies with Xpa(-/-), Xpc(-/-) and wild-type control female mice in a pure C57BL/6J background were done. The median survival of Xpc(-/-) mice showed a significant decrease, whereas the median survival of Xpa(-/-) mice did not. Strikingly, Xpa(-/-) and Xpc(-/-) mice also showed a phenotypical difference in terms of tumor spectrum. Xpc(-/-) mice displayed a significant increase in lung tumors and a trend toward increased liver tumors compared with Xpa-deficient or wild-type mice. Xpa(-/-) mice showed a significant elevation in liver tumors. Additionally, Xpc-deficient mice exhibited a strong increase in mutant frequency in lung compared with Xpa(-/-) mice, whereas in both models mutant frequency is increased in liver. Our in vitro data displayed an elevated sensitivity to oxygen in Xpc(-/-) in mouse embryonic fibroblasts (MEF) when compared with Xpa(-/-) and wild-type fibroblasts. We believe that XPC plays a role in the removal of oxidative DNA damage and that, therefore, Xpc(-/-) mice display a significant increase in lung tumors and a significant elevation in mutant frequency in lung, and Xpc-deficient MEFs show greater sensitivity to oxygen when compared with Xpa(-/-) and wild-type mice.

  13. I won't tell: Young children show loyalty to their group by keeping group secrets.

    PubMed

    Misch, Antonia; Over, Harriet; Carpenter, Malinda

    2016-02-01

    Group loyalty is highly valued. However, little is known about young children's loyal behavior. This study tested whether 4- and 5-year-olds (N=96) remain loyal to their group even when betraying it would be materially advantageous. Children and four puppets were allocated to novel groups. Two of these puppets (either in-group or out-group members) then told children a group secret and urged them not to disclose the secret. Another puppet (not assigned to either group) then bribed children with stickers to tell the secret. Across ages, children were significantly less likely to reveal the secret in the in-group condition than in the out-group condition. Thus, even young children are willing to pay a cost to be loyal to their group.

  14. Group Activities for Math Enthusiasts

    ERIC Educational Resources Information Center

    Holdener, J.; Milnikel, R.

    2016-01-01

    In this article we present three group activities designed for math students: a balloon-twisting workshop, a group proof of the irrationality of p, and a game of Math Bingo. These activities have been particularly successful in building enthusiasm for mathematics and camaraderie among math faculty and students at Kenyon College.

  15. Activities of the WASVSO Group

    NASA Astrophysics Data System (ADS)

    Simonsen, Michael A.; van Poucker, Joseph F.; Greene, Stephen M.

    2001-04-01

    This poster outlines the goals, activities, and achievements of the Warren Astronomical Society Variable Star Observers (WASVSO), a special-interest sub-group of the Warren Astronomical Society in Michigan. The WASVSO holds monthly meetings to discuss variable star behavior, terminology, current events, observing techniques, Internet resources, software, and of course, the weather. Ongoing projects include monitoring cataclysmic variables, active galactic nuclei, and stars that need more observations from the AAVSO "News Flashes" and "Alert Notices". We are also actively involved in "spreading the word" about AAVSO and variable star observing through presentations at star parties and a speaker exchange program with other astronomy clubs throughout the Midwest and Canada. The WASVSO also maintains an impressive website featuring member areas, upcoming events, articles on variable stars and observing techniques, charts for obscure cataclsmic variables, utilities for observing, and links to variable star organizations and observers throughout the world. Members of the WASVSO contributed 94% of all variable star observations submitted to the AAVSO from Michigan in the fiscal year 2000-2001, and our enthusiasm has catapulted Michigan from 20th place to 11th in overall numbers of US observations submitted to AAVSO in one year.

  16. Your Library--Greatest Show of All! Activity Manual.

    ERIC Educational Resources Information Center

    Jackson, Mary, Ed.

    Intended as a companion volume for librarians planning a children's summer reading program, this activity manual provides ideas for games, puzzles, puppet shows, story reading, and more, all based on the theme of "Circus Summer." The manual suggests ways to promote the program, such as visits to schools, and provides directions for…

  17. Croton grewioides Baill. (Euphorbiaceae) Shows Antidiarrheal Activity in Mice

    PubMed Central

    da Silva, Anne Dayse Soares; de Melo e Silva, Karoline; Neto, José Clementino; Costa, Vicente Carlos de Oliveira; Pessôa, Hilzeth de Luna F.; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Cavalcante, Fabiana de Andrade

    2016-01-01

    Based on chemotaxonomy, we decided to investigate the possible antidiarrheal activity in mice of a crude ethanolic extract obtained from aerial parts of Croton grewioides (CG-EtOH). We tested for any possible toxicity in rat erythrocytes and acute toxicity in mice. Antidiarrheal activity was assessed by determining the effect of CG-EtOH on defecation frequency, liquid stool, intestinal motility and intestinal fluid accumulation. CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females. CG-EtOH produced a significant and equipotent antidiarrheal activity, both in defecation frequency (ED50 = 106.0 ± 8.1 mg/kg) and liquid stools (ED50 = 105.0 ± 9.2 mg/kg). However, CG-EtOH (125 mg/kg) decreased intestinal motility by only 22.7% ± 4.4%. Moreover, extract markedly inhibited the castor oil-induced intestinal contents (ED50 = 34.6 ± 5.4 mg/kg). We thus conclude that CG-EtOH is not orally lethal and contains active principles with antidiarrheal activity, and this effect seems to involve mostly changes in intestinal secretion. SUMMARY CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females.CG-EtOH probably contains active metabolites with antidiarrheal activity.CG-EtOH reduced the frequency and number of liquid stools.Metabolites presents in the CG-EtOH act mainly by reducing intestinal fluid and, to a lesser extent, reducing intestinal motility. Abbreviations Used: CG-EtOH: crude ethanolic extract obtained from the aerial parts of C. grewioides; WHO: World Health Organization; ED50: dose of a drug that produces 50% of its maximum effect; Emax: maximum effect PMID:27365990

  18. 42. VIEW SHOWING A GROUP OF TRAINEES DURING 50LB PRESSURE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    42. VIEW SHOWING A GROUP OF TRAINEES DURING 50-LB PRESSURE TEST IN RECOMPRESSION CHAMBER IN EQUIPMENT HOUSE No date - U.S. Naval Submarine Base, New London Submarine Escape Training Tank, Albacore & Darter Roads, Groton, New London County, CT

  19. Group photo to show NASA GRC's collaboration with Goodyear tires; The facility is called the

    NASA Technical Reports Server (NTRS)

    2007-01-01

    Group photo to show NASA GRC's collaboration with Goodyear tires; The facility is called the Simulated Lunar Operations (SLOPE) Laboratory and the test-vehicle is called Modular Mobility-Technology Demonstrator (MMTD)

  20. Tetrahdroxysqualene from Rhus taitensis Shows Antimycobacterial Activity Against Mycobacterium tuberculosis

    PubMed Central

    Noro, Jeffrey C.; Barrows, Louis R.; Gideon, Osia G.; Ireland, Chris M.; Koch, Michael; Matainaho, Teatulohi; Piskaut, Pius; Pond, Christopher D.; Bugni, Tim S.

    2010-01-01

    Tuberculosis has become a major health problem, in particular with the emergence of extremely drug resistant tuberculosis (XDRTB). In our search for new therapeutic leads against TB, we isolated a new triterpene (1) from the plant Rhus taitensis collected in Papua New Guinea. Tetrahydroxysqualene (1) was isolated using bioassay-guided fractionation of the methanolic extract of R. taitensis leaves and twigs. The structure of tetrahydroxysqualene (1) was elucidated on the basis of HRESIMS and 1D and 2D NMR spectra. Tetrahydroxysqualene (1) exhibited anti–tuberculosis activity with an MIC of 10.0 μg/mL while showing only modest cytotoxicity. PMID:18710283

  1. Extracts of marine algae show inhibitory activity against osteoclast differentiation.

    PubMed

    Koyama, Tomoyuki

    2011-01-01

    Osteoclasts are multinucleated cells that play a crucial role in bone resorption. The imbalance between bone resorption and bone formation results in osteoporosis. Therefore, substances that can suppress osteoclast formation are potential candidate materials for drug development or functional foods. There have been reports that extracts or purified compounds from marine micro- and macroalgae can suppress osteoclast differentiation. Symbioimine, isolated from the cultured dinoflagellate Symbiodinium sp., had suppressive effects against osteoclast differentiation in osteoclast-like cells. Norzoanthamine, isolated from the colonial zoanthid Zoanthas sp., has been shown to have antiosteoporosis activity in ovariectomized mice. With regard to marine extracts, the fucoxanthin-rich component from brown algae has been shown to have suppressive effects against osteoclast differentiation. An extract of Sargassum fusiforme has recently been shown to have antiosteoporosis activity. This extract suppressed both osteoclast differentiation and accelerated osteoblast formation in separate in vitro experiments. It also showed antiosteoporosis activity in ovariectomized mice by regulating the balance between bone resorption and bone formation. These marine algae and their extracts may be sources of marine medicinal foods for the prevention of osteoporosis.

  2. Common marmosets show social plasticity and group-level similarity in personality

    PubMed Central

    Koski, Sonja E.; Burkart, Judith M.

    2015-01-01

    The social environment influences animal personality on evolutionary and immediate time scales. However, studies of animal personality rarely assess the effects of the social environment, particularly in species that live in stable groups with individualized relationships. We assessed personality experimentally in 17 individuals of the common marmoset, living in four groups. We found their personality to be considerably modified by the social environment. Marmosets exhibited relatively high plasticity in their behaviour, and showedgroup-personality’, i.e. group-level similarity in the personality traits. In exploratory behaviour this was maintained only in the social environment but not when individuals were tested alone, suggesting that exploration tendency is subjected to social facilitation. Boldness, in contrast, showed higher consistency across the social and solitary conditions, and the group-level similarity in trait scores was sustained also outside of the immediate social environment. The ‘group-personality’ was not due to genetic relatedness, supporting that it was produced by social effects. We hypothesize that ‘group-personality’ may be adaptive for highly cooperative animals through facilitating cooperation among individuals with similar behavioural tendency. PMID:25743581

  3. Common marmosets show social plasticity and group-level similarity in personality.

    PubMed

    Koski, Sonja E; Burkart, Judith M

    2015-03-06

    The social environment influences animal personality on evolutionary and immediate time scales. However, studies of animal personality rarely assess the effects of the social environment, particularly in species that live in stable groups with individualized relationships. We assessed personality experimentally in 17 individuals of the common marmoset, living in four groups. We found their personality to be considerably modified by the social environment. Marmosets exhibited relatively high plasticity in their behaviour, and showed 'group-personality', i.e. group-level similarity in the personality traits. In exploratory behaviour this was maintained only in the social environment but not when individuals were tested alone, suggesting that exploration tendency is subjected to social facilitation. Boldness, in contrast, showed higher consistency across the social and solitary conditions, and the group-level similarity in trait scores was sustained also outside of the immediate social environment. The 'group-personality' was not due to genetic relatedness, supporting that it was produced by social effects. We hypothesize that 'group-personality' may be adaptive for highly cooperative animals through facilitating cooperation among individuals with similar behavioural tendency.

  4. The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei

    PubMed Central

    Carvalho, Luis; Martínez-García, Marta; Pérez-Victoria, Ignacio; Manzano, José Ignacio; Yardley, Vanessa

    2015-01-01

    The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, or sleeping sickness, a neglected tropical disease that requires new, safer, and more effective treatments. Repurposing oral drugs could reduce both the time and cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral antimalarial drug belonging to the 8-aminoquinoline family which is currently in clinical phase III. We show here that TFQ efficiently kills different T. brucei spp. in the submicromolar concentration range. Our results suggest that TFQ accumulates into acidic compartments and induces a necrotic process involving cell membrane disintegration and loss of cytoplasmic content, leading to parasite death. Cell lysis is preceded by a wide and multitarget drug action, affecting the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of the mitochondrial membrane potential, elevation of intracellular Ca2+, and production of reactive oxygen species. This is the first report of an 8-aminoquinoline demonstrating significant in vitro activity against T. brucei. PMID:26195527

  5. A novel nucleic acid analogue shows strong angiogenic activity

    SciTech Connect

    Tsukamoto, Ikuko; Sakakibara, Norikazu; Maruyama, Tokumi; Igarashi, Junsuke; Kosaka, Hiroaki; Kubota, Yasuo; Tokuda, Masaaki; Ashino, Hiromi; Hattori, Kenichi; Tanaka, Shinji; Kawata, Mitsuhiro; Konishi, Ryoji

    2010-09-03

    Research highlights: {yields} A novel nucleic acid analogue (2Cl-C.OXT-A, m.w. 284) showed angiogenic potency. {yields} It stimulated the tube formation, proliferation and migration of HUVEC in vitro. {yields} 2Cl-C.OXT-A induced the activation of ERK1/2 and MEK in HUVEC. {yields} Angiogenic potency in vivo was confirmed in CAM assay and rabbit cornea assay. {yields} A synthesized small angiogenic agent would have great clinical therapeutic value. -- Abstract: A novel nucleic acid analogue (2Cl-C.OXT-A) significantly stimulated tube formation of human umbilical endothelial cells (HUVEC). Its maximum potency at 100 {mu}M was stronger than that of vascular endothelial growth factor (VEGF), a positive control. At this concentration, 2Cl-C.OXT-A moderately stimulated proliferation as well as migration of HUVEC. To gain mechanistic insights how 2Cl-C.OXT-A promotes angiogenic responses in HUVEC, we performed immunoblot analyses using phospho-specific antibodies as probes. 2Cl-C.OXT-A induced robust phosphorylation/activation of MAP kinase ERK1/2 and an upstream MAP kinase kinase MEK. Conversely, a MEK inhibitor PD98059 abolished ERK1/2 activation and tube formation both enhanced by 2Cl-C.OXT-A. In contrast, MAP kinase responses elicited by 2Cl-C.OXT-A were not inhibited by SU5416, a specific inhibitor of VEGF receptor tyrosine kinase. Collectively these results suggest that 2Cl-C.OXT-A-induces angiogenic responses in HUVEC mediated by a MAP kinase cascade comprising MEK and ERK1/2, but independently of VEGF receptor tyrosine kinase. In vivo assay using chicken chorioallantoic membrane (CAM) and rabbit cornea also suggested the angiogenic potency of 2Cl-C.OXT-A.

  6. Fluvoxamine, a new antidepressant drug, fails to show antiserotonin activity.

    PubMed

    Maj, J; Rogóz, Z; Skuza, G

    1982-07-09

    Fluvoxamine, (E)-5-methoxy-4'-(trifluoromethyl)valerophenone O-2(2-aminoethyl)oxime, a new antidepressant drug inhibiting serotonin (5-HT) uptake, was studied in rats and mice in order to check whether it has any central anti-5-HT activity, as do some tricyclic antidepressants, e.g. amitriptyline and doxepin. Fluvoxamine did not influence either the 5-hydroxytryptophan-induced head twitch response in mice or the tryptamine convulsions in rats. In the hind limb flexor reflex of the spinal rat the stimulation induced by fenfluramine was inhibited, that induced by LSD was not changed. Fluvoxamine also antagonized the hyperthermia (at ambient temperature of 28 degrees C), induced in rats by fenfluramine or p-chloroamphetamine. The hyperthermia caused by m-chlorophenylpiperazine was not inhibited. Fluvoxamine did not antagonize the 5-HT pressor effect in pithed rats. It has no effect on the immobility time in the behavioural despair test in rats. The results indicate that fluvoxamine fails to show anti-5-HT activity.

  7. High-Resolution Observations of a Filament showing Activated Barb

    NASA Astrophysics Data System (ADS)

    Joshi, Anand; Martin, Sara F.; Mathew, Shibu; Srivastava, Nandita

    2012-07-01

    Analysis of a filament showing an activated barb using observations from the Dutch Open Telescope (DOT) on 2010 August 20 are presented. The DOT takes Doppler images in Hα, among other wavelengths, in a region about 110 × 110 arcsec^{2} in area, at a cadence of 30~seconds. The offline image restoration technique of speckle reconstruction is applied to obtain diffraction limited images. The filament developed a new barb in 10~minutes, which disappeared within the next 35~minutes. Such a rapid formation and disappearance of a filament barb is unusual, and has not been reported earlier. Line-of-sight velocity maps were constructed from the Doppler images of the target filament. We observe flows in the filament spine towards the barb location prior to its formation, and flows in the barb towards the spine during its disappearance. Photospheric magnetograms from Heliospheric Magnetic Imager on board the Solar Dynamics Observatory, at a cadence of 45~seconds, were used to determine the changes in magnetic flux in the region surrounding the barb location. The variation of magnetic flux in this duration supports the view that barbs are rooted in minor magnetic polarity. Our analysis shows that barbs can be short-lived and formation and disappearance of the barb was associated with cancellation of magnetic flux.

  8. Silver nanoparticles synthesised using plant extracts show strong antibacterial activity.

    PubMed

    Kumari, Avnesh; Guliani, Anika; Singla, Rubbel; Yadav, Ramdhan; Yadav, Sudesh Kumar

    2015-06-01

    In this study, three plants Populus alba, Hibiscus arboreus and Lantana camara were explored for the synthesis of silver nanoparticles (SNPs). The effect of reaction temperature and leaf extract (LE) concentration of P. alba, H. arboreus and L. camara was evaluated on the synthesis and size of SNPs. The SNPs were characterised by ultra-violet-visible spectroscopy, scanning electron microscopy and atomic force microscopy. The synthesis rate of SNPs was highest with LE of L. camara followed by H. arboreus and P. alba under similar conditions. L. camara LE showed maximum potential of smaller size SNPs synthesis, whereas bigger particles were formed by H. arboreous LE. The size and shape of L. camara LE synthesised SNPs were analysed by transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). TEM analysis revealed the formation of SNPs of average size 17±9.5 nm with 5% LE of L. camara. The SNPs synthesised by LE of L. camara showed strong antibacterial activity against Escherichia coli. The results document that desired size SNPs can be synthesised using these plant LEs at a particular temperature for applications in the biomedical field.

  9. Teaching Interpersonal Skills through Group Activities.

    ERIC Educational Resources Information Center

    McGrew, Linda G.; Lewis, Stephen D.

    1998-01-01

    Indicates the importance of interpersonal skills in the workplace and suggests that the business curricula offers many opportunities for incorporation of group activities. Offers steps for planning student group activities. (JOW)

  10. NASA's Fermi Shows How Active Galaxies Can Be

    NASA Video Gallery

    Active galaxies called blazars make up the largest class of objects detected by Fermi's Large Area Telescope (LAT). Massive black holes in the hearts of these galaxies fire particle jets in our dir...

  11. Psychopaths Show Enhanced Amygdala Activation during Fear Conditioning.

    PubMed

    Schultz, Douglas H; Balderston, Nicholas L; Baskin-Sommers, Arielle R; Larson, Christine L; Helmstetter, Fred J

    2016-01-01

    Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into "primary" and "secondary" psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional "fearlessness," while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC) for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths.

  12. Psychopaths Show Enhanced Amygdala Activation during Fear Conditioning

    PubMed Central

    Schultz, Douglas H.; Balderston, Nicholas L.; Baskin-Sommers, Arielle R.; Larson, Christine L.; Helmstetter, Fred J.

    2016-01-01

    Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into “primary” and “secondary” psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional “fearlessness,” while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC) for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths. PMID:27014154

  13. This group view shows propellant preparation buidling 4241/E42, 4242/E43, and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    This group view shows propellant preparation buidling 4241/E-42, 4242/E-43, and northwest (314 degrees). Note warning lights at the extreme left of the view, and the use of lightning rods on structures. Building 4241/E-42 housed solid rocket motors after they were cast and awaiting curing. Building 4241/E-42 was the Preparation Control center which housed remote controls for operations in the other two buildings. Building 4243/E-44 housed a remotely controlled mandrel puller for pulling mandrels (casting cores) from cured grain, and a vertical lathe for trimming grain to shape and size. - Jet Propulsion Laboratory Edwards Facility, Edwards Air Force Base, Boron, Kern County, CA

  14. Chemically-related Groups of Active Ingredients

    EPA Pesticide Factsheets

    Many pesticide active ingredients affect pests in similar ways, and we re-evaluate them together as a group. Groups include carbamate insecticides, neonicotinoids, organochlorines, organophosphates, pyrethrins, and pyrethroids.

  15. Show and Tell: An Appreciation of "Making" Activities.

    ERIC Educational Resources Information Center

    Kozolanka, Karne

    This paper describes the incorporation of a "making" activity as part of a course for education majors at Queen's Faculty of Education of the University of Regina (Saskatchewan, Canada). The course was an introductory one in which students explored the methods and merits of outdoor and experiential education. Each student was given a…

  16. Conjugation of ovotransferrin with catechin shows improved antioxidant activity.

    PubMed

    You, Juan; Luo, Yongkang; Wu, Jianping

    2014-03-26

    Ovotransferrin (OTF), representing 12-13% of the total egg white, is a member of transferrin family with antimicrobial and antioxidant activities. Catechin is a polyphenolic antioxidant found in green tea. The objective of the study was to conjugate ovotransferrin with catechin to improve the antioxidant activity of OTF. Conjugates were prepared either by the free radical method using hydrogen peroxide-ascorbic acid as the initiator or by the alkaline method at pH of 9.0. The oxygen-radical-scavenging effect was increased from 3.95 mol trolox equivalent (TE)/mol of ovotransferrin to 22.80 and 17.14 mol TE/mol sample, respectively, in radical and alkaline prepared conjugates, which indicated that conjugation with catechin is an effective way to improve antioxidant activity of the protein. Conjugation between ovotransferrin and catechin was analyzed by fluorescence analyses, ultra performance liquid chromatography, matrix-assisted laser desorption ionization time-of-flight mass spectrometry and liquid chromatography coupled online to a tandem mass spectrometer. Catechin was covalently bound to lysine (residues 327) and glutamic acid (residues 186) in ovotransferrin. The ovotransferrin-catechin conjugate may have a potential application as a functional food and nutraceutical ingredient.

  17. Insurance Applications of Active Fault Maps Showing Epistemic Uncertainty

    NASA Astrophysics Data System (ADS)

    Woo, G.

    2005-12-01

    Insurance loss modeling for earthquakes utilizes available maps of active faulting produced by geoscientists. All such maps are subject to uncertainty, arising from lack of knowledge of fault geometry and rupture history. Field work to undertake geological fault investigations drains human and monetary resources, and this inevitably limits the resolution of fault parameters. Some areas are more accessible than others; some may be of greater social or economic importance than others; some areas may be investigated more rapidly or diligently than others; or funding restrictions may have curtailed the extent of the fault mapping program. In contrast with the aleatory uncertainty associated with the inherent variability in the dynamics of earthquake fault rupture, uncertainty associated with lack of knowledge of fault geometry and rupture history is epistemic. The extent of this epistemic uncertainty may vary substantially from one regional or national fault map to another. However aware the local cartographer may be, this uncertainty is generally not conveyed in detail to the international map user. For example, an area may be left blank for a variety of reasons, ranging from lack of sufficient investigation of a fault to lack of convincing evidence of activity. Epistemic uncertainty in fault parameters is of concern in any probabilistic assessment of seismic hazard, not least in insurance earthquake risk applications. A logic-tree framework is appropriate for incorporating epistemic uncertainty. Some insurance contracts cover specific high-value properties or transport infrastructure, and therefore are extremely sensitive to the geometry of active faulting. Alternative Risk Transfer (ART) to the capital markets may also be considered. In order for such insurance or ART contracts to be properly priced, uncertainty should be taken into account. Accordingly, an estimate is needed for the likelihood of surface rupture capable of causing severe damage. Especially where a

  18. Trajectory Hunting: Analysis of UARS Measurements showing Rapid Chlorine Activation

    NASA Technical Reports Server (NTRS)

    Danilin, M.Y.; Santee, M. L.; Rodriquez, J. M.; Ko, M. K. W.; Mergenthaler, J. M.; Kumer, J. B.; Tabazadeh, A.

    1998-01-01

    Trajectory hunting (i.e., a technique to find air parcels sampled at least twice over the course of a few days) is applied to analyze Upper Atmosphere Research Satellite (UARS) measurements in conjunction with the AER photochemical box model. In this study, we investigate rapid chlorine activation in the Arctic lower stratosphere on 29 Dec 1992 associated with a polar stratospheric cloud (PSC) event. Six air parcels that have been sampled twice were followed along 5-day trajectories at the 465 K (approximately 46 mb) and 585 K (approximately 22 mb) levels. A detailed sensitivity study with the AER. photochemical box model along these trajectories leads to the following conclusions for the episode considered: (1) model results are in better agreement with UARS measurements at these levels if the UKMO temperature is decreased by at least 1-2 K; (2) the NAT (nitric acid trihydrate) PSC formation scheme produces results in better agreement with observations than the STS (supercooled ternary solution) scheme; (3) the model can explain the UARS measurements at 585 K, but under-estimates the ClO abundance at 465 K, suggesting some inconsistency between the UARS measurements at this level.

  19. Trajectory Hunting: Analysis of UARS Measurements Showing Rapid Chlorine Activation

    NASA Technical Reports Server (NTRS)

    Danilin, M. Y.; Santee, M. L.; Rodriquez, J. M.; Ko, M. K. W.; Mergenthaler, J. M.; Kumer, J. B.; Tabazadeh, A.

    1998-01-01

    Trajectory hunting (i.e., a technique to find air parcels sampled at least twice over the course of a few days) is applied to analyze Upper Atmosphere Research Satellite (UARS) measurements in conjunction with the AER photochemical box model. In this study, we investigate rapid chlorine activation in the Arctic lower stratosphere on 29 Dec. 1992 associated with a polar stratospheric cloud (PSC) event. Six air parcels that have been sampled twice were followed along 5-day trajectories at the 465 K (approx. 46 mb) and 585 K (approxi. 22 mb) levels. A detailed sensitivity study with the AER photochemical box model along these trajectories leads to the following conclusions for the episode considered: 1) model results are in better agreement with UARS measurements at these levels if the U.K. Meteorological Office (UKMO) temperature is decreased by at least 1-2 K; 2) the NAT (nitric acid trihydrate) PSC formation scheme produces results in better agreement with observations than the STS (supercooled ternary solution) scheme; 3) the model can explain the UARS measurements at 585 K, but under-estimates the ClO abundance at 465 K, suggesting some inconsistency between the UARS measurements at this level.

  20. Sulfur dioxide - Episodic injection shows evidence for active Venus volcanism

    NASA Astrophysics Data System (ADS)

    Esposito, L. W.

    1984-03-01

    Pioneer Venus ultraviolet spectra from the first 5 years of operation show a decline (by more than a factor of 10) in sulfur dioxide abundance at the cloud tops and in the amount of submicron haze above the clouds. At the time of the Pioneer Venus encounter, the values for both parameters greatly exceeded earlier upper limits. However, Venus had a similar appearance in the late 1950's, implying the episodic injection of sulfur dioxide possibly caused by episodic volcanism. The amount of haze in the Venus middle atmosphere is about ten times that found in earth's stratosphere after the most recent major volcanic eruptions, and the thermal energy required for this injection on Venus is greater by about an order of magnitude than the largest of these recent earth eruptions and about as large as the Krakatoa eruption of 1883. The episodic behavior of sulfur dioxide implies that steady-state models of the chemistry and dynamics of cloud-top regions may be of limited use.

  1. Sulfur dioxide - Episodic injection shows evidence for active Venus volcanism

    NASA Technical Reports Server (NTRS)

    Esposito, L. W.

    1984-01-01

    Pioneer Venus ultraviolet spectra from the first 5 years of operation show a decline (by more than a factor of 10) in sulfur dioxide abundance at the cloud tops and in the amount of submicron haze above the clouds. At the time of the Pioneer Venus encounter, the values for both parameters greatly exceeded earlier upper limits. However, Venus had a similar appearance in the late 1950's, implying the episodic injection of sulfur dioxide possibly caused by episodic volcanism. The amount of haze in the Venus middle atmosphere is about ten times that found in earth's stratosphere after the most recent major volcanic eruptions, and the thermal energy required for this injection on Venus is greater by about an order of magnitude than the largest of these recent earth eruptions and about as large as the Krakatoa eruption of 1883. The episodic behavior of sulfur dioxide implies that steady-state models of the chemistry and dynamics of cloud-top regions may be of limited use.

  2. Emetic toxin-producing strains of Bacillus cereus show distinct characteristics within the Bacillus cereus group.

    PubMed

    Carlin, Frédéric; Fricker, Martina; Pielaat, Annemarie; Heisterkamp, Simon; Shaheen, Ranad; Salonen, Mirja Salkinoja; Svensson, Birgitta; Nguyen-the, Christophe; Ehling-Schulz, Monika

    2006-05-25

    One hundred representative strains of Bacillus cereus were selected from a total collection of 372 B. cereus strains using two typing methods (RAPD and FT-IR) to investigate if emetic toxin-producing hazardous B. cereus strains possess characteristic growth and heat resistance profiles. The strains were classified into three groups: emetic toxin (cereulide)-producing strains (n=17), strains connected to diarrheal foodborne outbreaks (n=40) and food-environment strains (n=43), these latter not producing the emetic toxin. Our study revealed a shift in growth limits towards higher temperatures for the emetic strains, regardless of their origin. None of the emetic toxin-producing strains were able to grow below 10 degrees Celsius. In contrast, 11% (9 food-environment strains) out of the 83 non-emetic toxin-producing strains were able to grow at 4 degrees Celsius and 49% at 7 degrees Celsius (28 diarrheal and 13 food-environment strains). non-emetic toxin-producing strains. All emetic toxin-producing strains were able to grow at 48 degrees Celsius, but only 39% (16 diarrheal and 16 food-environment strains) of the non-emetic toxin-producing strains grew at this temperature. Spores from the emetic toxin-producing strains showed, on average, a higher heat resistance at 90 degrees Celsius and a lower germination, particularly at 7 degrees Celsius, than spores from the other strains. No difference between the three groups in their growth kinetics at 24 degrees Celsius, 37 degrees Celsius, and pH 5.0, 7.0, and 8.0 was observed. Our survey shows that emetic toxin-producing strains of B. cereus have distinct characteristics, which could have important implication for the risk assessment of the emetic type of B. cereus caused food poisoning. For instance, emetic strains still represent a special risk in heat-processed foods or preheated foods that are kept warm (in restaurants and cafeterias), but should not pose a risk in refrigerated foods.

  3. Pleistocene footprints show intensive use of lake margin habitats by Homo erectus groups

    PubMed Central

    Roach, Neil T.; Hatala, Kevin G.; Ostrofsky, Kelly R.; Villmoare, Brian; Reeves, Jonathan S.; Du, Andrew; Braun, David R.; Harris, John W. K.; Behrensmeyer, Anna K.; Richmond, Brian G.

    2016-01-01

    Reconstructing hominin paleoecology is critical for understanding our ancestors’ diets, social organizations and interactions with other animals. Most paleoecological models lack fine-scale resolution due to fossil hominin scarcity and the time-averaged accumulation of faunal assemblages. Here we present data from 481 fossil tracks from northwestern Kenya, including 97 hominin footprints attributed to Homo erectus. These tracks are found in multiple sedimentary layers spanning approximately 20 thousand years. Taphonomic experiments show that each of these trackways represents minutes to no more than a few days in the lives of the individuals moving across these paleolandscapes. The geology and associated vertebrate fauna place these tracks in a deltaic setting, near a lakeshore bordered by open grasslands. Hominin footprints are disproportionately abundant in this lake margin environment, relative to hominin skeletal fossil frequency in the same deposits. Accounting for preservation bias, this abundance of hominin footprints indicates repeated use of lakeshore habitats by Homo erectus. Clusters of very large prints moving in the same direction further suggest these hominins traversed this lakeshore in multi-male groups. Such reliance on near water environments, and possibly aquatic-linked foods, may have influenced hominin foraging behavior and migratory routes across and out of Africa. PMID:27199261

  4. Control groups in paediatric epilepsy research: do first-degree cousins show familial effects?

    PubMed

    Hanson, Melissa; Morrison, Blaise; Jones, Jana E; Jackson, Daren C; Almane, Dace; Seidenberg, Michael; Zhao, Qianqian; Rathouz, Paul J; Hermann, Bruce P

    2017-03-01

    To determine whether first-degree cousins of children with idiopathic focal and genetic generalized epilepsies show any association across measures of cognition, behaviour, and brain structure. The presence/absence of associations addresses the question of whether and to what extent first-degree cousins may serve as unbiased controls in research addressing the cognitive, psychiatric, and neuroimaging features of paediatric epilepsies. Participants were children (aged 8-18) with epilepsy who had at least one first-degree cousin control enrolled in the study (n=37) and all enrolled cousin controls (n=100). Participants underwent neuropsychological assessment and brain imaging (cortical, subcortical, and cerebellar volumes), and parents completed the Child Behaviour Checklist (CBCL). Data (based on 42 outcome measures) from cousin controls were regressed on the corresponding epilepsy cognitive, behavioural, and imaging measures in a linear mixed model and case/control correlations were examined. Of the 42 uncorrected correlations involving cognitive, behavioural, and neuroimaging measures, only two were significant (p<0.05). The median correlation was 0.06. A test for whether the distribution of p values deviated from the null distribution under no association was not significant (p>0.25). Similar results held for the cognition/behaviour and brain imaging measures separately. Given the lack of association between cases and first-degree cousin performances on measures of cognition, behaviour, and neuroimaging, the results suggest a non-significant genetic influence on control group performance. First-degree cousins appear to be unbiased controls for cognitive, behavioural, and neuroimaging research in paediatric epilepsy.

  5. Small Group Activities for Introductory Business Classes.

    ERIC Educational Resources Information Center

    Mundrake, George

    1999-01-01

    Describes numerous small-group activities for the following areas of basic business education: consumer credit, marketing, business organization, entrepreneurship, insurance, risk management, economics, personal finance, business careers, global markets, and government regulation. (SK)

  6. Plant crude extracts could be the solution: extracts showing in vivo antitumorigenic activity.

    PubMed

    Amara, A A; El-Masry, M H; Bogdady, H H

    2008-04-01

    Screening active compounds from plants lead to discover new medicinal drugs which have efficient protection and treatment roles against various diseases including cancer. In our study, extracts from different plants represent seeds of: Gossypium barbadense, Ricinus communis, Sesamum indicum, Nigella sativa, Vinca rosea and Melia azedarah; fruits of: Xanthium occidental; flowers of: Atriplex nummularia; barks of: Cinnamomum zeylanicum; latex of: Ficus carica and rhizomes of: Curcuma longa and Zingiber officinale were tested in vivo using three subsequent bioassays: the BST (Brine Shrimp Toxicity bioassay), AWD (Agar well diffusion antimicrobial bioassay) and AtPDT (Agrobacterium tumefaciens Potato Disc Tumor bioassay). AWD technique omitted any extracts have antimicrobial activities while BST omitted any extract did not has physiological activity and determined the various LC(50) of each plant extract. For the first time, using a range of concentrations in the AtPDT modified protocol allowed the detection of tumor promotion caused by extract represented by A. nummularia. Using cluster analysis leads to classifying the different plant extracts activities to six groups regarding to their toxicity, antitumor activities and both of them. The extracts from edible plants represent 50% of the first and the second group which have the highest antitumor activities represented in F. caraica (group 1) and C. longa (group 2) as well as the non-edible plant extracts of Gossypium barbadense and Ricinus communis. A comparison study between the edible and herbaceous plants different extracts for their antitumor activities was performed. We recommended using the modified protocols used in this study for investigating more plants and using crude plant extracts which have antitumor activities in cancer treatment. Edible plants, which show in vivo antitumor activities, are recommended as save sources for antitumor compounds.

  7. Adolescent earthquake survivors' show increased prefrontal cortex activation to masked earthquake images as adults.

    PubMed

    Du, Xue; Wei, Dongtao; Ganzel, Barbara L; Kim, Pilyoung; Zhang, Qinglin; Qiu, Jiang

    2015-03-01

    The great Sichuan earthquake in China on May 12, 2008 was a traumatic event to many who live near the earthquake area. However, at present, there are few studies that explore the long-term impact of the adolescent trauma exposure on adults' brain function. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the brain activation evoked by masked trauma-related stimuli (earthquake versus neutral images) in 14 adults who lived near the epicenter of the great Sichuan earthquake when they were adolescents (trauma-exposed group) and 14 adults who lived farther from the epicenter of the earthquake when they were adolescents (control group). Compared with the control group, the trauma-exposed group showed significant elevation of activation in the right anterior cingulate cortex (ACC) and the medial prefrontal cortex (MPFC) in response to masked earthquake-related images. In the trauma-exposed group, the right ACC activation was negatively correlated with the frequency of symptoms of post-traumatic stress disorder (PTSD). These findings differ markedly from the long-term effects of trauma exposure in adults. This suggests that trauma exposure during adolescence may have a unique long-term impact on ACC/MPFC function, top-down modulation of trauma-related information, and subsequent symptoms of PTSD.

  8. Disturbance gradient shows logging affects plant functional groups more than fire.

    PubMed

    Blair, David P; McBurney, Lachlan M; Blanchard, Wade; Banks, Sam C; Lindenmayer, David B

    2016-10-01

    Understanding the impacts of natural and human disturbances on forest biota is critical for improving forest management. Many studies have examined the separate impacts on fauna and flora of wildfire, conventional logging, and salvage logging, but empirical comparisons across a broad gradient of simultaneous disturbances are lacking. We quantified species richness and frequency of occurrence of vascular plants, and functional group responses, across a gradient of disturbances that occurred concurrently in 2009 in the mountain ash forests of southeastern Australia. Our study encompassed replicated sites in undisturbed forest (~70 yr post fire), forest burned at low severity, forest burned at high severity, unburned forest that was clearcut logged, and forest burned at high severity that was clearcut salvage logged post-fire. All sites were sampled 2 and 3 yr post fire. Mean species richness decreased across the disturbance gradient from 30.1 species/site on low-severity burned sites and 28.9 species/site on high-severity burned sites, to 25.1 species/site on clearcut sites and 21.7 species/site on salvage logged sites. Low-severity burned sites were significantly more species-rich than clearcut sites and salvage logged sites; high-severity burned sites supported greater species richness than salvage logged sites. Specific traits influenced species' sensitivity to disturbance. Resprouting species dominated undisturbed mountain ash forests, but declined significantly across the gradient. Fern and midstory trees decreased significantly in frequency of occurrence across the gradient. Ferns (excluding bracken) decreased from 34% of plants in undisturbed forest to 3% on salvage logged sites. High-severity burned sites supported a greater frequency of occurrence and species richness of midstory trees compared to clearcut and salvage logged sites. Salvage logging supported fewer midstory trees than any other disturbance category, and were distinctly different from

  9. Task Control Signals in Pediatric Tourette Syndrome Show Evidence of Immature and Anomalous Functional Activity

    PubMed Central

    Church, Jessica A.; Wenger, Kristin K.; Dosenbach, Nico U. F.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

    2009-01-01

    Tourette Syndrome (TS) is a pediatric movement disorder that may affect control signaling in the brain. Previous work has proposed a dual-networks architecture of control processing involving a task-maintenance network and an adaptive control network (Dosenbach et al., 2008). A prior resting-state functional connectivity MRI (rs-fcMRI) analysis in TS has revealed functional immaturity in both putative control networks, with “anomalous” correlations (i.e., correlations outside the typical developmental range) limited to the adaptive control network (Church et al., 2009). The present study used functional MRI (fMRI) to study brain activity related to adaptive control (by studying start-cues signals), and to task-maintenance (by studying signals sustained across a task set). Two hypotheses from the previous rs-fcMRI results were tested. First, adaptive control (i.e., start-cue) activity will be altered in TS, including activity inconsistent with typical development (“anomalous”). Second, group differences found in task-maintenance (i.e., sustained) activity will be consistent with functional immaturity in TS. We examined regions found through a direct comparison of adolescents with and without TS, as well as regions derived from a previous investigation that showed differences between unaffected children and adults. The TS group showed decreased start-cue signal magnitude in regions where start-cue activity is unchanged over typical development, consistent with anomalous adaptive control. The TS group also had higher magnitude sustained signals in frontal cortex regions that overlapped with regions showing differences over typical development, consistent with immature task-maintenance in TS. The results demonstrate task-related fMRI signal differences anticipated by the atypical functional connectivity found previously in adolescents with TS, strengthening the evidence for functional immaturity and anomalous signaling in control networks in adolescents with TS

  10. DOING Physics--Physics Activities for Groups.

    ERIC Educational Resources Information Center

    Green, Glenn; Insley, Peter

    1985-01-01

    Explains two activities: (1) a "rotator demonstration" (a turntable, pendulum, chalk, and other materials), which can be used in many activities to demonstrate rotational concepts; and (2) an "Eskimo yo-yo," consisting of two balls (plus long strings and a glass tube) which rotate in opposite directions to show centripetal force. (JN)

  11. Advanced Extravehicular Activity Breakout Group Summary

    NASA Technical Reports Server (NTRS)

    Kosmo, Joseph J.; Perka, Alan; Walz, Carl; Cobb, Sharon; Hanford, Anthony; Eppler, Dean

    2005-01-01

    This viewgraph document summarizes the workings of the Advanced Extravehicular Activity (AEVA) Breakout group in a Martian environment. The group was tasked with: identifying potential contaminants and pathways for AEVA systems with respect to forward and backward contamination; identifying plausible mitigation alternatives and obstacles for pertinent missions; identifying topics that require further research and technology development and discuss development strategies with uncertain Planetary Protection (PP) requirements; Identifying PP requirements that impose the greatest mission/development costs; Identifying PP requirements/topics that require further definition;

  12. Satellite microglia show spontaneous electrical activity that is uncorrelated with activity of the attached neuron.

    PubMed

    Wogram, Emile; Wendt, Stefan; Matyash, Marina; Pivneva, Tatyana; Draguhn, Andreas; Kettenmann, Helmut

    2016-06-01

    Microglia are innate immune cells of the brain. We have studied a subpopulation of microglia, called satellite microglia. This cell type is defined by a close morphological soma-to-soma association with a neuron, indicative of a direct functional interaction. Indeed, ultrastructural analysis revealed closely attached plasma membranes of satellite microglia and neurons. However, we found no apparent morphological specializations of the contact, and biocytin injection into satellite microglia showed no dye-coupling with the apposed neurons or any other cell. Likewise, evoked local field potentials or action potentials and postsynaptic potentials of the associated neuron did not lead to any transmembrane currents or non-capacitive changes in the membrane potential of the satellite microglia in the cortex and hippocampus. Both satellite and non-satellite microglia, however, showed spontaneous transient membrane depolarizations that were not correlated with neuronal activity. These events could be divided into fast-rising and slow-rising depolarizations, which showed different characteristics in satellite and non-satellite microglia. Fast-rising and slow-rising potentials differed with regard to voltage dependence. The frequency of these events was not affected by the application of tetrodotoxin, but the fast-rising event frequency decreased after application of GABA. We conclude that microglia show spontaneous electrical activity that is uncorrelated with the activity of adjacent neurons.

  13. Antibodies to meningococcal H.8 (Lip) antigen fail to show bactericidal activity.

    PubMed

    Bhattacharjee, A K; Moran, E E; Zollinger, W D

    1990-02-01

    Purified H.8 (Lip) antigen was coupled to tresyl-activated Sepharose 4B and used in affinity columns to purify anti-Lip antibodies from convalescent patient sera and from immune rabbit sera. Affinity-purified anti-Lip antibodies isolated from two convalescent patient sera contained 1000 and 1280 ELISA units of antibody and included antibodies of IgG, IgA, and IgM isotypes. An anti-Lip mouse monoclonal ascites (2-1-CA2) had 28,400 ELISA units of antibody. Bactericidal assays were performed using three different case strains of Neisseria meningitidis group B, namely 44/76, 8532, and 8047. Neither preparation of purified human anti-Lip antibodies had detectable bactericidal activity against strains 44/76 and 8532, but one of the two had a titer of 1:4 against strain 8047. Anti-Lip antibodies that were purified from immune rabbit serum and contained 1600 ELISA units of anti-Lip antibodies also failed to show detectable bactericidal activity. The rabbits were immunized with purified Lip antigen and showed specific antibody levels of 2000-2200 units by ELISA, but even the unfractionated sera had little or no bactericidal activity against the test strains. The high titer mouse monoclonal ascites had no bactericidal activity against the test strains. The poor bactericidal activity associated with monoclonal and polyclonal antibodies to the Lip antigen suggest that in spite of other attractive properties it may not be useful as a meningococcal vaccine.

  14. An active principle of Nigella sativa L., thymoquinone, showing significant antimicrobial activity against anaerobic bacteria

    PubMed Central

    Randhawa, Mohammad Akram; Alenazy, Awwad Khalaf; Alrowaili, Majed Gorayan; Basha, Jamith

    2017-01-01

    Aim/Background: Thymoquinone (TQ) is the major active principle of Nigella sativa seed (black seed) and is known to control many fungi, bacteria, and some viruses. However, the activity of TQ against anaerobic bacteria is not well demonstrated. Anaerobic bacteria can cause severe infections, including diarrhea, aspiration pneumonia, and brain abscess, particularly in immunodeficient individuals. The present study aimed to investigate the in vitro antimicrobial activity of TQ against some anaerobic pathogens in comparison to metronidazole. Methods: Standard, ATCC, strains of four anaerobic bacteria (Clostridium difficile, Clostridium perfringens, Bacteroides fragilis, and Bacteroides thetaiotaomicron), were initially isolated on special Brucella agar base (with hemin and vitamin K). Then, minimum inhibitory concentrations (MICs) of TQ and metronidazole were determined against these anaerobes when grown in Brucella agar, using serial agar dilution method according to the recommended guidelines for anaerobic organisms instructed by the Clinical and Laboratory Standards Institute. Results: TQ showed a significant antimicrobial activity against anaerobic bacteria although much weaker than metronidazole. MICs of TQ and metronidazole against various anaerobic human pathogens tested were found to be between 10-160 mg/L and 0.19-6.25 mg/L, respectively. Conclusions: TQ controlled the anaerobic human pathogenic bacteria, which supports the use of N. sativa in the treatment of diarrhea in folk medicine. Further investigations are in need for determination of the synergistic effect of TQ in combination with metronidazole and the activity of derivatives of TQ against anaerobic infections. PMID:28163966

  15. A Paradox of Syntactic Priming: Why Response Tendencies Show Priming for Passives, and Response Latencies Show Priming for Actives

    PubMed Central

    Segaert, Katrien; Menenti, Laura; Weber, Kirsten; Hagoort, Peter

    2011-01-01

    Speakers tend to repeat syntactic structures across sentences, a phenomenon called syntactic priming. Although it has been suggested that repeating syntactic structures should result in speeded responses, previous research has focused on effects in response tendencies. We investigated syntactic priming effects simultaneously in response tendencies and response latencies for active and passive transitive sentences in a picture description task. In Experiment 1, there were priming effects in response tendencies for passives and in response latencies for actives. However, when participants' pre-existing preference for actives was altered in Experiment 2, syntactic priming occurred for both actives and passives in response tendencies as well as in response latencies. This is the first investigation of the effects of structure frequency on both response tendencies and latencies in syntactic priming. We discuss the implications of these data for current theories of syntactic processing. PMID:22022352

  16. The left occipitotemporal cortex does not show preferential activity for words.

    PubMed

    Vogel, Alecia C; Petersen, Steven E; Schlaggar, Bradley L

    2012-12-01

    Regions in left occipitotemporal (OT) cortex, including the putative visual word form area, are among the most commonly activated in imaging studies of single-word reading. It remains unclear whether this part of the brain is more precisely characterized as specialized for words and/or letters or contains more general-use visual regions having properties useful for processing word stimuli, among others. In Analysis 1, we found no evidence of greater activity in left OT regions for words or letter strings relative to other high-spatial frequency high-contrast stimuli, including line drawings and Amharic strings (which constitute the Ethiopian writing system). In Analysis 2, we further investigated processing characteristics of OT cortex potentially useful in reading. Analysis 2 showed that a specific part of OT cortex 1) is responsive to visual feature complexity, measured by the number of strokes forming groups of letters or Amharic strings and 2) processes learned combinations of characters, such as those in words and pseudowords, as groups but does not do so in consonant and Amharic strings. Together, these results indicate that while regions of left OT cortex are not specialized for words, at least part of OT cortex has properties particularly useful for processing words and letters.

  17. Design, synthesis, and properties of phthalocyanine complexes with main-group elements showing main absorption and fluorescence beyond 1000 nm.

    PubMed

    Furuyama, Taniyuki; Satoh, Koh; Kushiya, Tomofumi; Kobayashi, Nagao

    2014-01-15

    We present a comprehensive description of the unique properties of newly developed phthalocyanines (Pcs) containing main-group elements that absorb and emit in the near-IR region. Group 16 (S, Se, and Te) elements and group 15 (P, As, and Sb) elements were used as peripheral and central (core) substituents. With the introduction of group 16 elements into free-base Pc, a red-shift of the Q-band was observed, as a result of the electron-donating ability of group 16 elements particularly at the α positions. An X-ray crystallographic analysis of α-ArS-, ArSe-, and ArTe-linked free-base Pcs was also successfully performed, and the relationship between structure and optical properties was clarified. When a group 15 element ion was introduced into the center of the Pc ring, the resulting Pcs showed a single Q-band peak beyond 1000 nm (up to 1056 nm in CH2Cl2). In particular, [(ArS)8PcP(OMe)2](+) and [(ArS)8PcAs(OMe)2](+) exhibited a distinct fluorescence in the 960-1400 nm region with moderate quantum yields. The atomic radius of the group 15 element is important for determining the Pc structure, so that this can be controlled by the choice of group 15 elements. Electrochemical data revealed, while MO calculations suggested, that the red-shift of the Q-band is attributable to a decrease of the HOMO-LUMO gap due to significant and moderate stabilization of the LUMO and HOMO, respectively. The effect of peripheral substutuents and a central P(V) ion on the Q-band shift was independently predicted by MO calculations, while the magnitude of the total calculated shift was in good agreement with the experimental observations. The combination of spectral, electrochemical, and theoretical considerations revealed that all of the central group 15 elements, peripheral group 16 elements, and their positions are necessary to shift the Q-band beyond 1000 nm, indicating that the substitution effects of group 15 and 16 elements act synergistically. The Pcs having Q-bands beyond 1000 nm

  18. Alkaloids from the seeds of Peganum harmala showing antiplasmodial and vasorelaxant activities.

    PubMed

    Astulla, Adil; Zaima, Kazumasa; Matsuno, Yosuke; Hirasawa, Yusuke; Ekasari, Wiwied; Widyawaruyanti, Aty; Zaini, Noor Cholies; Morita, Hiroshi

    2008-10-01

    Bioassay-guided purification from the seeds of Peganum harmala led to the isolation of harmine (1), harmaline (2), vasicinone (3), and deoxyvasicinone (4). Harmine (1) and harmaline (2) showed a moderate in vitro antiplasmodial activity against Plasmodium falciparum. Quinazoline alkaloid, vasicinone (3), showed a vasorelaxant activity against phenylephrine-induced contraction of isolated rat aorta.

  19. Computationally designed variants of Escherichia coli chorismate mutase show altered catalytic activity.

    PubMed

    Lassila, Jonathan Kyle; Keeffe, Jennifer R; Oelschlaeger, Peter; Mayo, Stephen L

    2005-04-01

    Computational protein design methods were used to predict five variants of monofunctional Escherichia coli chorismate mutase expected to maintain catalytic activity. The variants were tested experimentally and three active site mutants exhibited catalytic activity similar to or greater than the wild-type enzyme. One mutant, Ala32Ser, showed increased catalytic efficiency.

  20. Activity/inactivity circadian rhythm shows high similarities between young obesity-induced rats and old rats.

    PubMed

    Bravo Santos, R; Delgado, J; Cubero, J; Franco, L; Ruiz-Moyano, S; Mesa, M; Rodríguez, A B; Uguz, C; Barriga, C

    2016-03-01

    The objective of the present study was to compare differences between elderly rats and young obesity-induced rats in their activity/inactivity circadian rhythm. The investigation was motivated by the differences reported previously for the circadian rhythms of both obese and elderly humans (and other animals), and those of healthy, young or mature individuals. Three groups of rats were formed: a young control group which was fed a standard chow for rodents; a young obesity-induced group which was fed a high-fat diet for four months; and an elderly control group with rats aged 2.5 years that was fed a standard chow for rodents. Activity/inactivity data were registered through actimetry using infrared actimeter systems in each cage to detect activity. Data were logged on a computer and chronobiological analysis were performed. The results showed diurnal activity (sleep time), nocturnal activity (awake time), amplitude, acrophase, and interdaily stability to be similar between the young obesity-induced group and the elderly control group, but different in the young control group. We have concluded that obesity leads to a chronodisruption status in the body similar to the circadian rhythm degradation observed in the elderly.

  1. Group Work vs. Whole Class Activity

    ERIC Educational Resources Information Center

    Tanveer, Asma

    2008-01-01

    Group work has only been recently introduced in the education system of Pakistan but many primary teachers, especially in the public schools, are still not aware of how different kinds of strategies that is group work and whole class teaching facilitate learning among students. This paper aims to provide an overview of teaching strategies to…

  2. Evolution and flare activity of a group in July 1978

    SciTech Connect

    Sattarov, I.

    1983-03-01

    The evolution of a sunspot group with a delta configuration which passed over the solar disk on July 8--21, 1978, is studied on the basis of original materials consisting of photoheliograms, H..cap alpha.. filtergrams, and wide-band photographs obtained in Tashkent. More than 160 H..cap alpha.. flares, including 22 flares of importance 1 and 10 flares of importance 2, were observed in the active region (AR) containing this group according to Solar-Geophysical Data. As a result of a comparison of the evolutionary changes of the group with the flare activity of the AR it was found that the flare activity is connected with the formation of a new sunspot group within an old one, with its maximum falling at the time of formation of the first nuclei, and new nuclei are formed along the zero line of the longitudinal field of the old group; the nodes of the majority of flares are located near new nuclei, symmetrical relative to the zero line; the area of the new nuclei increases impulsively; the total area of the entire group varies, fluctuating about its average value, and flares happen during the slowing and cessation of the increase in area; some nuclei show proper motion at a velocity of approx.0.5 km/sec while others show intermittent motion, like pulsation, directed outside the old group; as a result of the development of new nuclei near old ones the small nuclei break up, while the boundary of the large nucleus is deformed on the side of the new nuclei and bright points shine within it.

  3. Tl(+) showed negligible interaction with inner membrane sulfhydryl groups of rat liver mitochondria, but formed complexes with matrix proteins.

    PubMed

    Korotkov, Sergey M; Brailovskaya, Irina V; Kormilitsyn, Boris N; Furaev, Viktor V

    2014-04-01

    The effects of Tl(+) on protein sulfhydryl (SH) groups, swelling, and respiration of rat liver mitochondria (RLM) were studied in a medium containing TlNO3 and sucrose, or TlNO3 and KNO3 as well as glutamate plus malate, or succinate plus rotenone. Detected with Ellman's reagent, an increase in the content of the SH groups was found in the inner membrane fraction, and a simultaneous decline was found in the content of the matrix-soluble fraction for RLM, incubated and frozen in 25-75 mM TlNO3 . This increase was greater in the medium containing KNO3 regardless of the presence of Ca(2+) . It was eliminated completely for RLM injected in the medium containing TlNO3 and then washed and frozen in the medium containing KNO3 . Calcium-loaded RLM showed increased swelling and decreased respiration. These results suggest that a ligand interaction of Tl(+) with protein SH groups, regardless of the presence of calcium, may underlie the mechanism of thallium toxicity.

  4. In-Group and Out-Group Membership Mediates Anterior Cingulate Activation to Social Exclusion

    PubMed Central

    Krill, Austen; Platek, Steven M.

    2009-01-01

    Functional magnetic resonance imaging was employed to examine sensitivity to social exclusion in three conditions: same-race, other-race, and self-resembling faces. The anterior cingulate cortex (ACC), specifically the dorsal ACC, has been targeted as a key substrate in the physical and social pain matrix and was hypothesized to regulate activation response to various facial conditions. We show that participants demonstrated greatest ACC activation when being excluded by self-resembling and same-race faces, relative to other-race faces. Additionally, participants expressed greater distress and showed increased ACC activation as a result of exclusion in the same-race condition relative to the other-race condition. A positive correlation between implicit racial bias and activation in the amygdala was also evident. Implicit attitude about other-race faces partly explains levels of concern about exclusion by out-group individuals. These findings suggest that individuals are more distressed and their brain (i.e. neural alarm system) responds with greater activation when being excluded by individuals whom they are more likely to share group membership with. PMID:19597546

  5. Polymorphism of CRISPR shows separated natural groupings of Shigella subtypes and evidence of horizontal transfer of CRISPR.

    PubMed

    Yang, Chaojie; Li, Peng; Su, Wenli; Li, Hao; Liu, Hongbo; Yang, Guang; Xie, Jing; Yi, Shengjie; Wang, Jian; Cui, Xianyan; Wu, Zhihao; Wang, Ligui; Hao, Rongzhang; Jia, Leili; Qiu, Shaofu; Song, Hongbin

    2015-01-01

    Clustered, regularly interspaced, short palindromic repeats (CRISPR) act as an adaptive RNA-mediated immune mechanism in bacteria. They can also be used for identification and evolutionary studies based on polymorphisms within the CRISPR locus. We amplified and analyzed 6 CRISPR loci from 237 Shigella strains belonging to the 4 species groups, as well as 13 Escherichia coli strains. The CRISPR-associated (cas) gene sequence arrays of these strains were screened and compared. The CRISPR sequences from Shigella were conserved among subtypes, suggesting that CRISPR may represent a new identification tool for the detection and discrimination of Shigella species. Secondary structure analysis showed a different stem-loop structure at the terminal repeat, suggesting a distinct recognition mechanism in the formation of crRNA. In addition, the presence of "self-target" spacers and polymorphisms within CRISPR in Shigella indicated a selective pressure for inhibition of this system, which has the potential to damage "self DNA." Homology analysis of spacers showed that CRISPR might be involved in the regulation of virulence transmission. Phylogenetic analysis based on CRISPR sequences from Shigella and E. coli indicated that although phenotypic properties maintain convergent evolution, the 4 Shigella species do not represent natural groupings. Surprisingly, comparative analysis of Shigella repeats with other species provided new evidence for CRISPR horizontal transfer. Our results suggested that CRISPR analysis is applicable for the detection of Shigella species and for investigation of evolutionary relationships.

  6. DOING Physics--Physics Activities for Groups.

    ERIC Educational Resources Information Center

    Zwicker, Earl, Ed.

    1984-01-01

    Describes an activity which demonstrates standing waves in air generated by a loudspeaker driven by an audio oscillator. The waves are detected by cool spots on a glowing nichrome wire contained in an inexpensive piece of equipment. Also describes activities involving analysis of kinematics through data taking and graphing. (JM)

  7. Exploring Group Activity Therapy with Ethnically Diverse Adolescents

    ERIC Educational Resources Information Center

    Paone, Tina R.; Malott, Krista M.; Maldonado, Jose M.

    2008-01-01

    Group activity therapy has been promoted as an effective means of providing growth opportunities for adolescents through the use of structured, developmentally appropriate activities in a group setting. This article qualitatively explores outcomes of 12 sessions of group activity therapy with ethnically diverse adolescents in a school setting. The…

  8. Adherence to physical activity guidelines among cancer support group participants.

    PubMed

    Stevinson, C; Lydon, A; Amir, Z

    2014-03-01

    Physical activity is recommended after cancer diagnosis for physical function, quality of life and survival benefits. This study provided preliminary data on the prevalence of physical activity among adult men and women with cancer in the UK. As part of a national survey of cancer support group participation, questionnaires including items on leisure-time physical activity and demographic information were completed by 748 cancer survivors. Overall, 395 (52.8%) participants reported no weekly moderate or vigorous intensity physical activity, 221 (29.5%) reported some activity but below minimum recommendations and 132 (17.6%) were meeting published guidelines. Gender, health status and socio-economic status were independently associated with meeting guidelines. Among participants in good or fair health who were not meeting guidelines, 59.9% thought that they ought to be more physically active. In conclusion, overall levels of physical activity are low among cancer survivors in the UK. However, the majority of insufficiently active participants showed awareness of the need to increase their activity, and may be receptive to interventions for promoting physical activity in this population.

  9. Group Learning as Relational Economic Activity

    ERIC Educational Resources Information Center

    Saito, Eisuke; Atencio, Matthew

    2014-01-01

    The purpose of this paper is to discuss group learning in line with economic perspectives of embeddedness and integration emanating from the work of Karl Polanyi. Polanyi's work defines economy as a necessary interaction among human beings for survival; the economy is considered inextricably linked from broader society and social relations rather…

  10. Doing Physics--Physics Activities for Groups.

    ERIC Educational Resources Information Center

    Zwicker, Earl, Ed.

    1984-01-01

    Materials needed and procedures for conducting two activities are provided. The first investigates drops of a liquid which float on water in a watchglass resting on top of a loudspeaker. The second investigates electromagnetic phenomena. (JN)

  11. Active microwave users working group program planning

    NASA Technical Reports Server (NTRS)

    Ulaby, F. T.; Bare, J.; Brown, W. E., Jr.; Childs, L. F.; Dellwig, L. F.; Heighway, J. E.; Joosten, R.; Lewis, A. J.; Linlor, W.; Lundien, J. R.

    1978-01-01

    A detailed programmatic and technical development plan for active microwave technology was examined in each of four user activities: (1) vegetation; (2) water resources and geologic applications, and (4) oceanographic applications. Major application areas were identified, and the impact of each application area in terms of social and economic gains were evaluated. The present state of knowledge of the applicability of active microwave remote sensing to each application area was summarized and its role relative to other remote sensing devices was examined. The analysis and data acquisition techniques needed to resolve the effects of interference factors were reviewed to establish an operational capability in each application area. Flow charts of accomplished and required activities in each application area that lead to operational capability were structured.

  12. DOING Physics--Physics Activities for Groups.

    ERIC Educational Resources Information Center

    Zwicker, Earl, Ed.

    1984-01-01

    Describes an activity in which two pulleys are connected by a wire loop; when the bottom pulley is dipped into hot water, the pulleys rotate. Also suggests that students design/build a machine to propel a bean; the machine must use materials including one bean, two plastic straws, and two rubber bands. (JN)

  13. DOING Physics--Physics Activities for Groups.

    ERIC Educational Resources Information Center

    Zwicker, Earl, Ed.

    1985-01-01

    Describes three demonstrations/activities that involve forces: (1) a canoe-like boat made from copper window screen; (2) magnetic forces with a paper clip and ceramic magnetic; and (3) an "icemobile" machine that cuts ice cubes without an obvious source of energy. (DH)

  14. Individual and group dynamics in purchasing activity

    NASA Astrophysics Data System (ADS)

    Gao, Lei; Guo, Jin-Li; Fan, Chao; Liu, Xue-Jiao

    2013-01-01

    As a major part of the daily operation in an enterprise, purchasing frequency is in constant change. Recent approaches on the human dynamics can provide some new insights into the economic behavior of companies in the supply chain. This paper captures the attributes of creation times of purchase orders to an individual vendor, as well as to all vendors, and further investigates whether they have some kind of dynamics by applying logarithmic binning to the construction of distribution plots. It’s found that the former displays a power-law distribution with approximate exponent 2.0, while the latter is fitted by a mixture distribution with both power-law and exponential characteristics. Obviously, two distinctive characteristics are presented for the interval time distribution from the perspective of individual dynamics and group dynamics. Actually, this mixing feature can be attributed to the fitting deviations as they are negligible for individual dynamics, but those of different vendors are cumulated and then lead to an exponential factor for group dynamics. To better describe the mechanism generating the heterogeneity of the purchase order assignment process from the objective company to all its vendors, a model driven by product life cycle is introduced, and then the analytical distribution and the simulation result are obtained, which are in good agreement with the empirical data.

  15. DOING Physics--Physics Activities for Groups.

    ERIC Educational Resources Information Center

    Zwicker, Earl, Ed.

    1985-01-01

    Shows how an electric stud finder (available from hardware stores for $15-20) is used to detect changes in capacitance produced by changes in thickness of a medium or in dielectric constant. Also describes how to construct an inexpensive motor from a battery, rubber bands, ceramic magnet, and copper wire. (DH)

  16. A humanized anti-M2 scFv shows protective in vitro activity against influenza

    SciTech Connect

    Bradbury, Andrew M; Velappan, Nileena; Schmidt, Jurgen G

    2008-01-01

    M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.

  17. Overview of MSFC's Applied Fluid Dynamics Analysis Group Activities

    NASA Technical Reports Server (NTRS)

    Garcia, Roberto; Griffin, Lisa; Williams, Robert

    2003-01-01

    TD64, the Applied Fluid Dynamics Analysis Group, is one of several groups with high-fidelity fluids design and analysis expertise in the Space Transportation Directorate at Marshall Space Flight Center (MSFC). TD64 assists personnel working on other programs. The group participates in projects in the following areas: turbomachinery activities, nozzle activities, combustion devices, and the Columbia accident investigation.

  18. Activities of the Boom and Chassis Group

    NASA Technical Reports Server (NTRS)

    Dell, Jason Scott; Meeks, Thomas Bayne; Merkel, Kelly; Nelson, Brent; Winchell, Tom

    1992-01-01

    Group One of the NASA Lunar Enabler Project has designed the primary chassis and boom structures for the lunar vehicle. Both components also feature V-clamps that were adapted to interface connections within the structure. The chassis features a front end, rear end section, middle cross-section, and face plate. The rear section contains an extra compartment for the engine, hydraulic pump, fuel bottles, and oil reservoir necessary for the wheel drives. Each section consists of tubular aluminum 6061-T6. The boom features four degrees of freedom system, where the minimum factor of safety of any part is 1.5 (but, normally much higher). It consists of a tapered upper boom, lower boom, and three elbows that complement the articulation joints. Each section of the boom has been constructed from aluminum 6061-T6. There are four joints and eight V-clamps in the boom assembly. The V-clamps feature support rings that prevent axial rotation. They provide easy adaptability and assembly.

  19. Space station group activities habitability module study

    NASA Technical Reports Server (NTRS)

    Nixon, David

    1986-01-01

    This study explores and analyzes architectural design approaches for the interior of the Space Station Habitability Module (originally defined as Habitability Module 1 in Space Station Reference Configuration Decription, JSC-19989, August 1984). In the Research Phase, architectural program and habitability design guidelines are specified. In the Schematic Design Phase, a range of alternative concepts is described and illustrated with drawings, scale-model photographs and design analysis evaluations. Recommendations are presented on the internal architectural, configuration of the Space Station Habitability Module for such functions as the wardroom, galley, exercise facility, library and station control work station. The models show full design configurations for on-orbit performance.

  20. Group Dynamics and Initiative Activities with Outdoor Programs.

    ERIC Educational Resources Information Center

    Zwaagstra, Lynn

    This paper focuses on group dynamics and introduces the use of initiative activities as a means of facilitating a more cohesive group experience in outdoor programs. Specific topics addressed and defined include: (1) curative factors of groups (universality, didactic learning, altruism, socialization, peer learning, group cohesiveness); (2) stages…

  1. Discovery of SMP-304, a novel benzylpiperidine derivative with serotonin transporter inhibitory activity and 5-HT1A weak partial agonistic activity showing the antidepressant-like effect.

    PubMed

    Yoshinaga, Hidefumi; Masumoto, Shuji; Koyama, Koji; Kinomura, Naoya; Matsumoto, Yuji; Kato, Taro; Baba, Satoko; Matsumoto, Kenji; Horisawa, Tomoko; Oki, Hitomi; Yabuuchi, Kazuki; Kodo, Toru

    2017-01-01

    We report the discovery of a novel benzylpiperidine derivative with serotonin transporter (SERT) inhibitory activity and 5-HT1A receptor weak partial agonistic activity showing the antidepressant-like effect. The 3-methoxyphenyl group and the phenethyl group of compound 1, which has weak SERT binding activity, but potent 5-HT1A binding activity, were optimized, leading to compound 35 with potent and balanced dual SERT and 5-HT1A binding activity, but also potent CYP2D6 inhibitory activity. Replacement of the methoxy group in the left part of compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy-ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate. SMP-304 with serotonin uptake inhibitory activity and 5-HT1A weak partial agonistic activity, which could work as a 5-HT1A antagonist, displayed faster onset of antidepressant-like effect than a representative SSRI paroxetine in an animal model.

  2. Distributive Education--Fashion Show. Kit No. 88. Instructor's Manual [and] Student Learning Activity Guide.

    ERIC Educational Resources Information Center

    Walters, Brenda B.

    An instructor's manual and student activity guide on fashion shows are provided in this set of prevocational education materials which focuses on the vocational area of distributive education. (This set of materials is one of ninety-two prevocational education sets arranged around a cluster of seven vocational offerings: agriculture, home…

  3. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... purpose of the sponsoring organization in conducting the show is the education of its members, or the promotion and stimulation of interest in, and demand for, the products or services of the industry (or... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  4. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... purpose of the sponsoring organization in conducting the show is the education of its members, or the promotion and stimulation of interest in, and demand for, the products or services of the industry (or... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  5. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... purpose of the sponsoring organization in conducting the show is the education of its members, or the promotion and stimulation of interest in, and demand for, the products or services of the industry (or... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  6. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... purpose of the sponsoring organization in conducting the show is the education of its members, or the promotion and stimulation of interest in, and demand for, the products or services of the industry (or... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  7. 26 CFR 1.513-3 - Qualified convention and trade show activity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... purpose of the sponsoring organization in conducting the show is the education of its members, or the promotion and stimulation of interest in, and demand for, the products or services of the industry (or... interest in, and demand for such products or services; (ii) Activities designed to educate persons in...

  8. New Eugenol Glucoside-based Derivative Shows Fungistatic and Fungicidal Activity against Opportunistic Candida glabrata.

    PubMed

    de Souza, Thiago Belarmino; Brito, Keila Mercês de Oliveira; Silva, Naiara Chaves; Rocha, Raissa Prado; de Sousa, Grasiely Faria; Duarte, Lucienir Pains; Coelho, Luiz Felipe Leomil; Dias, Amanda Latércia Tranches; Veloso, Marcia Paranho; Carvalho, Diogo Teixeira; Dias, Danielle Ferreira

    2016-01-01

    A new series of glucosides modified in their saccharide units were synthesized, evaluated against Candida sp., and compared to prototype 1, an eugenol tetracetyl glucoside previously synthesized and shown to be active against Candida glabrata. Among the new glucosides, benzyl derivative 5 was the most promising, showing fungistatic activity at IC50 18.1 μm against Candida glabrata (threefold higher than fluconazole) and fungicidal activity with a low IC90 value of 36.2 μm. Moreover, the cytotoxic activity of compound 5 (CC50 : 580.9 μm), tested in peripheral blood mononuclear cells, suggests its potential as an agent to treat Candida glabrata infections, with a selectivity index of 32. The new eugenol glucoside 5 may be considered as a novel structural pattern in the development of new anti-Candida drugs.

  9. Group Cognitive Behavioural Therapy Program Shows Potential in Reducing Symptoms of Depression and Stress among Young People with ASD

    ERIC Educational Resources Information Center

    McGillivray, J. A.; Evert, H. T.

    2014-01-01

    We examined the efficacy of cognitive behavioural therapy (CBT) delivered in groups on the reduction of symptoms of depression, anxiety and stress in young people on the autism spectrum. Utilising a quasi-experimental design, comparisons were made between individuals allocated to a group intervention program and individuals allocated to a…

  10. Isolation of Lactic Acid Bacteria Showing Antioxidative and Probiotic Activities from Kimchi and Infant Feces.

    PubMed

    Ji, Keunho; Jang, Na Young; Kim, Young Tae

    2015-09-01

    The purpose of this study was to investigate lactic acid bacteria with antioxidative and probiotic activities isolated from Korean healthy infant feces and kimchi. Isolates A1, A2, S1, S2, and S3 were assigned to Lactobacillus sp. and isolates A3, A4, E1, E2, E3, and E4 were assigned to Leuconostoc sp. on the basis of their physiological properties and 16S ribosomal DNA sequence analysis. Most strains were confirmed as safe bioresources through nonhemolytic activities and non-production of harmful enzymes such as β-glucosidase, β- glucuronidase and tryptophanase. The 11 isolates showed different resistance to acid and bile acids. In addition, they exhibited antibacterial activity against foodborne bacteria, especially Bacillus cereus, Listeria monocytogenes, and Escherichia coli. Furthermore, all strains showed significantly high levels of hydrophobicity. The antioxidant effects of culture filtrates of the 11 strains included 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging capacity, 2.2'- azino-bis (2-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation scavenging activity, and superoxide dismutase activity. The results revealed that most of the culture filtrates have effective scavenging activity for DPPH and ABTS radicals. All strains appeared to have effective superoxide dismutase activity. In conclusion, the isolated strains A1, A3, S1, and S3 have significant probiotic activities applicable to the development of functional foods and health-related products. These strains might also contribute to preventing and controlling several diseases associated with oxidative stress, when used as probiotics.

  11. Arginine kinase shows nucleoside diphosphate kinase-like activity toward deoxythymidine diphosphate.

    PubMed

    Lopez-Zavala, Alonso A; Sotelo-Mundo, Rogerio R; Hernandez-Flores, Jose M; Lugo-Sanchez, Maria E; Sugich-Miranda, Rocio; Garcia-Orozco, Karina D

    2016-06-01

    Arginine kinase (AK) (ATP: L-arginine phosphotransferase, E.C. 2.7.3.3) catalyzes the reversible transfer of ATP γ-phosphate group to L-arginine to synthetize phospho-arginine as a high-energy storage. Previous studies suggest additional roles for AK in cellular processes. Since AK is found only in invertebrates and it is homologous to creatine kinase from vertebrates, the objective of this work was to demonstrate nucleoside diphosphate kinase-like activity for shrimp AK. For this, AK from marine shrimp Litopenaeus vannamei (LvAK) was purified and its activity was assayed for phosphorylation of TDP using ATP as phosphate donor. Moreover, by using high-pressure liquid chromatography (HPLC) the phosphate transfer reaction was followed. Also, LvAK tryptophan fluorescence emission changes were detected by dTDP titration, suggesting that the hydrophobic environment of Trp 221, which is located in the top of the active site, is perturbed upon dTDP binding. The kinetic constants for both substrates Arg and dTDP were calculated by isothermal titration calorimetry (ITC). Besides, docking calculations suggested that dTDP could bind LvAK in the same cavity where ATP bind, and LvAK basic residues (Arg124, 126 and 309) stabilize the dTDP phosphate groups and the pyrimidine base interact with His284 and Ser122. These results suggest that LvAK bind and phosphorylate dTDP being ATP the phosphate donor, thus describing a novel alternate nucleoside diphosphate kinase-like activity for this enzyme.

  12. Systematic Review Shows Only Few Reliable Studies of Physical Activity Intervention in Adolescents

    PubMed Central

    Soares, Nara Michelle Moura; Leão, Arley Santos; Santos, Josivan Rosa; Monteiro, Glauber Rocha; dos Santos, Jorge Rollemberg; Thomazzi, Sara Maria; Silva, Roberto Jerônimo dos Santos

    2014-01-01

    Introduction. Several studies have pointed to the high prevalence of low levels of physical activity in adolescents, suggesting the need for more effective interventions for this group. The aim of this study was to present evidence of intervention programs for efficacy of physical activity for adolescents. Methods. Surveys in PubMed, SportDiscus, LiLacs, and SciELO databases were conducted using keywords to identify population, intervention, and outcome, as well as DeCS and MeSH terms in English, Portuguese, and Spanish, whenever appropriate. The review included observational studies with minimal intervention of six months, minimum sample size of 100 adolescents, written in any language, and those who have reached STROBE score greater than 70%. Results. Only seven studies met all inclusion criteria. Of these, five were pre- and postintervention and two had n > 2000 participants. Interventions were of several types, durations, and strategies for physical activity implementation. Behavior change was assessed in 43% of studies and three reported success in some way. Conclusion. Due to heterogeneity in their contents and methodologies, as well as the lack of jobs that accompany adolescents after the intervention period, one cannot draw conclusions about the actual effects of the intervention programs of physical activity on the behavior of young people. PMID:25152903

  13. Bovine chromaffin cells in culture show carboxylesterase activities sensitive to organophosphorus compounds.

    PubMed

    Sogorb, M A; Vilanova, E; Quintanar, J L; Viniegra, S

    1996-09-01

    Carboxylesterase activities are widely distributed in a great variety of tissues; however, the biological function of these enzymes remains unclear. Some organophosphorus compounds induce a neurodegenarative syndrome related to the covalent modification of a carboxylesterase known as neuropathy target esterase. We investigated the expression of neuropathy target esterase and related carboxylesterase in bovine chromaffin cells with the aim of developing a potential in vitro model for studying the cellular function of carboxylesterase enzymes and toxic effects of organophosphorus compounds. Total phenyl valerate esterase exhibited an activity of 1.27 +/- 0.19 mU/10(5) cells (SD, n = 15). From the phenyl valerate esterase paraoxon and mipafox inhibition curves the following activities have been determined: B-activity (resistant to 40 microM paraoxon), 1.05 +/- 0.08 mU/10(5) cells (n = 8); C-activity (resistant to 40 microM paraoxon plus 250 microM mipafox), 0.12 +/- 0.05 mU/10(5) cells (n = 8); and neuropathy target esterase, calculated by the difference between B- and C-activities, 0.93 +/- 0.08 mU/10(5) cells (n = 8). All of these activities increased linearly with the number of cells and time of incubation with the substrate. Most of the phenol product of the reaction was released and detected in the extracellular medium. None of the components of the reaction were shown to affect cell viability when assessed by trypan blue exclusion. The study shows that bovine chromaffin cells possess carboxylesterase activities and respond to inhibition by paraoxon and mipafox, thus facilitating the discrimination of neuropathy target esterase. In conclusion, bovine chromaffin cells are appropriate as an in vitro cell model for studying toxic effects of organophosphorus compounds.

  14. Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating activity.

    PubMed

    Dhanasekaran, Muralikrishnan; Tharakan, Binu; Manyam, Bala V

    2008-01-01

    Parkinson's disease is a neurodegenerative disorder for which no neurorestorative therapeutic treatment is currently available. Oxidative stress plays an important role in the pathophysiology of Parkinson's disease. The ancient Indian medical system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's disease. In our earlier studies, Mucuna pruriens has been shown to possess antiparkinson and neuroprotective effects in animal models of Parkinson's disease. The antioxidant activity of Mucuna pruriens was demonstrated by its ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species. Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest that the neuroprotective and neurorestorative effect of Mucuna pruriens may be related to its antioxidant activity independent of the symptomatic effect. In addition, the drug appears to be therapeutically safe in the treatment of patients with Parkinson's disease.

  15. Cytorhabdovirus phosphoprotein shows RNA silencing suppressor activity in plants, but not in insect cells.

    PubMed

    Mann, Krin S; Johnson, Karyn N; Dietzgen, Ralf G

    2015-02-01

    RNA silencing in plants and insects provides an antiviral defense and as a countermeasure most viruses encode RNA silencing suppressors (RSS). For the family Rhabdoviridae, no detailed functional RSS studies have been reported in plant hosts and insect vectors. In agroinfiltrated Nicotiana benthamiana leaves we show for the first time for a cytorhabdovirus, lettuce necrotic yellows virus (LNYV), that one of the nucleocapsid core proteins, phosphoprotein (P) has relatively weak local RSS activity and delays systemic silencing of a GFP reporter. Analysis of GFP small RNAs indicated that the P protein did not prevent siRNA accumulation. To explore RSS activity in insects, we used a Flock House virus replicon system in Drosophila S2 cells. In contrast to the plant host, LNYV P protein did not exhibit RSS activity in the insect cells. Taken together our results suggest that P protein may target plant-specific components of RNA silencing post siRNA biogenesis.

  16. Collagen-Immobilized Lipases Show Good Activity and Reusability for Butyl Butyrate Synthesis.

    PubMed

    Dewei, Song; Min, Chen; Haiming, Cheng

    2016-11-01

    Candida rugosa lipases were immobilized onto collagen fibers through glutaraldehyde cross-linking method. The immobilization process has been optimized. Under the optimal immobilization conditions, the activity of the collagen-immobilized lipase reached 340 U/g. The activity was recovered of 28.3 % by immobilization. The operational stability of the obtained collagen-immobilized lipase for hydrolysis of olive oil emulsion was determined. The collagen-immobilized lipase showed good tolerance to temperature and pH variations in comparison to free lipase. The collagen-immobilized lipase was also applied as biocatalyst for synthesis of butyl butyrate from butyric acid and 1-butanol in n-hexane. The conversion yield was 94 % at the optimal conditions. Of its initial activity, 64 % was retained after 5 cycles for synthesizing butyl butyrate in n-hexane.

  17. Functional characterization of a Plagiochasma appendiculatum flavone synthase I showing flavanone 2-hydroxylase activity.

    PubMed

    Han, Xiao-Juan; Wu, Yi-Feng; Gao, Shuai; Yu, Hai-Na; Xu, Rui-Xue; Lou, Hong-Xiang; Cheng, Ai-Xia

    2014-06-27

    FNS I is a 2-oxoglutarate dependent dioxygenase (2-ODD) found mainly in species of the Apiaceae family. Here, an FNS I cDNA sequence was isolated from the liverwort Plagiochasma appendiculatum (Aytoniaceae) and characterized. The recombinant protein exhibited high FNS I activity catalyzing the conversion of naringenin to apigenin and 2-hydroxynaringenin. The critical residue for flavanone-2-hydroxylation activity was Tyr240, as identified from homology modeling and site-directed mutagenesis. The recombinant protein also showed some flavonol synthase activity, as it can convert dihydrokaempferol to kaempferol. When the Leu311 residue was mutated to Phe, the enzyme's capacity to convert dihydrokaempferol to kaempferol was substantially increased. PaFNS I represents a 2-ODD in which a hydrophobic π-stacking interaction between the key residue and the naringenin A-ring determines 2-hydroxyflavanone formation.

  18. Antibodies to Meningococcal H.8 (Lip) Antigen Fail to Show Bactericidal Activity

    DTIC Science & Technology

    1990-01-01

    monoclonaux n’avaient pas non plus d’activit6 bactericide contre ces souches. La faible activitt bactdricide associee aux anticorps monoclonaux et...MENINGOCOCCAL H.8 (Lip) ANTIGEN FAILTO SHOW BACTERICIDAL ACTIVITY. 12. PERSONAL. DUTHOR(S AK BHATTACHARJEE, EE MORAN, & WD ZOLLINGER. lb. TMP OP REPORT DATE...isotypes. An anti-Lip mouse monoclonal ascites (2-1-CA2) had 28 400 ELISA units of antibody. Bactericidal assays were performed using three different

  19. The three catalases in Deinococcus radiodurans: Only two show catalase activity.

    PubMed

    Jeong, Sun-Wook; Jung, Jong-Hyun; Kim, Min-Kyu; Seo, Ho Seong; Lim, Heon-Man; Lim, Sangyong

    2016-01-15

    Deinococcus radiodurans, which is extremely resistant to ionizing radiation and oxidative stress, is known to have three catalases (DR1998, DRA0146, and DRA0259). In this study, to investigate the role of each catalase, we constructed catalase mutants (Δdr1998, ΔdrA0146, and ΔdrA0259) of D. radiodurans. Of the three mutants, Δdr1998 exhibited the greatest decrease in hydrogen peroxide (H2O2) resistance and the highest increase in intracellular reactive oxygen species (ROS) levels following H2O2 treatments, whereas ΔdrA0146 showed no change in its H2O2 resistance or ROS level. Catalase activity was not attenuated in ΔdrA0146, and none of the three bands detected in an in-gel catalase activity assay disappeared in ΔdrA0146. The purified His-tagged recombinant DRA0146 did not show catalase activity. In addition, the phylogenetic analysis of the deinococcal catalases revealed that the DR1998-type catalase is common in the genus Deinococcus, but the DRA0146-type catalase was found in only 4 of 23 Deinococcus species. Taken together, these results indicate that DR1998 plays a critical role in the anti-oxidative system of D. radiodurans by detoxifying H2O2, but DRA0146 does not have catalase activity and is not involved in the resistance to H2O2 stress.

  20. Water-soluble extracts from defatted sesame seed flour show antioxidant activity in vitro.

    PubMed

    Ben Othman, Sana; Katsuno, Nakako; Kanamaru, Yoshihiro; Yabe, Tomio

    2015-05-15

    Defatted white and gold sesame seed flour, recovered as a byproduct after sesame oil extraction, was extracted with 70% ethanol to obtain polar-soluble crude extracts. The in vitro antioxidant activity of the extract was evaluated by DPPH free radical scavenging activity and oxygen radical absorbing capacity (ORAC). The polar-soluble crude extracts of both sesame seed types exhibited good antioxidant capacity, especially by the ORAC method with 34,720 and 21,700 μmol Trolox equivalent/100g of white and gold sesame seed extract, respectively. HPLC, butanol extraction, and UPLC-MS analyses showed that different compounds contributed to the antioxidant activity of the polar-soluble crude extracts. Sesaminol glycosides were identified in the butanol-soluble fractions; whereas, purified water-soluble fraction contained ferulic and vanillic acids. This study shows that hydrophilic antioxidants in the purified water-soluble fraction contributed to the antioxidant activity of white and gold sesame seed polar-soluble crude extracts.

  1. Sterols from Mytilidae show anti-aging and neuroprotective effects via anti-oxidative activity.

    PubMed

    Sun, Yujuan; Lin, Yanfei; Cao, Xueli; Xiang, Lan; Qi, Jianhua

    2014-11-25

    For screening anti-aging samples from marine natural products, K6001 yeast strain was employed as a bioassay system. The active mussel extract was separated to give an active sterol fraction (SF). SF was further purified, and four sterol compounds were obtained. Their structures were determined to be cholesterol (CHOL), brassicasterol, crinosterol, and 24-methylenecholesterol. All compounds showed similar anti-aging activity. To understand the action mechanism involved, anti-oxidative experiments, reactive oxygen species (ROS) assays, and malondialdehyde (MDA) tests were performed on the most abundant compound, CHOL. Results indicated that treatment with CHOL increases the survival rate of yeast under oxidative stress and decreases ROS and MDA levels. In addition, mutations of uth1, skn7, sod1, and sod2, which feature a K6001 background, were employed and the lifespans of the mutations were not affected by CHOL. These results demonstrate that CHOL exerts anti-aging effects via anti-oxidative stress. Based on the connection between neuroprotection and anti-aging, neuroprotective experiments were performed in PC12 cells. Paraquat was used to induce oxidative stress and the results showed that the CHOL and SF protect the PC12 cells from the injury induced by paraquat. In addition, these substance exhibited nerve growth factor (NGF) mimic activities again confirmed their neuroprotective function.

  2. A test of the intergenerational conflict model in Indonesia shows no evidence of earlier menopause in female-dispersing groups

    PubMed Central

    Snopkowski, Kristin; Moya, Cristina; Sear, Rebecca

    2014-01-01

    Menopause remains an evolutionary puzzle, as humans are unique among primates in having a long post-fertile lifespan. One model proposes that intergenerational conflict in patrilocal populations favours female reproductive cessation. This model predicts that women should experience menopause earlier in groups with an evolutionary history of patrilocality compared with matrilocal groups. Using data from the Indonesia Family Life Survey, we test this model at multiple timescales: deep historical time, comparing age at menopause in ancestrally patrilocal Chinese Indonesians with ancestrally matrilocal Austronesian Indonesians; more recent historical time, comparing age at menopause in ethnic groups with differing postmarital residence within Indonesia and finally, analysing age at menopause at an individual-level, assuming a woman facultatively adjusts her age at menopause based on her postmarital residence. We find a significant effect only at the intermediate timescale where, contrary to predictions, ethnic groups with a history of multilocal postnuptial residence (where couples choose where to live) have the slowest progression to menopause, whereas matrilocal and patrilocal ethnic groups have similar progression rates. Multilocal residence may reduce intergenerational conflicts between women, thus influencing reproductive behaviour, but our results provide no support for the female-dispersal model of intergenerational conflict as an explanation of menopause. PMID:24966311

  3. A test of the intergenerational conflict model in Indonesia shows no evidence of earlier menopause in female-dispersing groups.

    PubMed

    Snopkowski, Kristin; Moya, Cristina; Sear, Rebecca

    2014-08-07

    Menopause remains an evolutionary puzzle, as humans are unique among primates in having a long post-fertile lifespan. One model proposes that intergenerational conflict in patrilocal populations favours female reproductive cessation. This model predicts that women should experience menopause earlier in groups with an evolutionary history of patrilocality compared with matrilocal groups. Using data from the Indonesia Family Life Survey, we test this model at multiple timescales: deep historical time, comparing age at menopause in ancestrally patrilocal Chinese Indonesians with ancestrally matrilocal Austronesian Indonesians; more recent historical time, comparing age at menopause in ethnic groups with differing postmarital residence within Indonesia and finally, analysing age at menopause at an individual-level, assuming a woman facultatively adjusts her age at menopause based on her postmarital residence. We find a significant effect only at the intermediate timescale where, contrary to predictions, ethnic groups with a history of multilocal postnuptial residence (where couples choose where to live) have the slowest progression to menopause, whereas matrilocal and patrilocal ethnic groups have similar progression rates. Multilocal residence may reduce intergenerational conflicts between women, thus influencing reproductive behaviour, but our results provide no support for the female-dispersal model of intergenerational conflict as an explanation of menopause.

  4. Vv-AMP1, a ripening induced peptide from Vitis vinifera shows strong antifungal activity

    PubMed Central

    de Beer, Abré; Vivier, Melané A

    2008-01-01

    Background Latest research shows that small antimicrobial peptides play a role in the innate defense system of plants. These peptides typically contribute to preformed defense by developing protective barriers around germinating seeds or between different tissue layers within plant organs. The encoding genes could also be upregulated by abiotic and biotic stimuli during active defense processes. The peptides display a broad spectrum of antimicrobial activities. Their potent anti-pathogenic characteristics have ensured that they are promising targets in the medical and agricultural biotechnology sectors. Results A berry specific cDNA sequence designated Vv-AMP1, Vitis vinifera antimicrobial peptide 1, was isolated from Vitis vinifera. Vv-AMP1 encodes for a 77 amino acid peptide that shows sequence homology to the family of plant defensins. Vv-AMP1 is expressed in a tissue specific, developmentally regulated manner, being only expressed in berry tissue at the onset of berry ripening and onwards. Treatment of leaf and berry tissue with biotic or abiotic factors did not lead to increased expression of Vv-AMP1 under the conditions tested. The predicted signal peptide of Vv-AMP1, fused to the green fluorescent protein (GFP), showed that the signal peptide allowed accumulation of its product in the apoplast. Vv-AMP1 peptide, produced in Escherichia coli, had a molecular mass of 5.495 kDa as determined by mass spectrometry. Recombinant Vv-AMP1 was extremely heat-stable and showed strong antifungal activity against a broad spectrum of plant pathogenic fungi, with very high levels of activity against the wilting disease causing pathogens Fusarium oxysporum and Verticillium dahliae. The Vv-AMP1 peptide did not induce morphological changes on the treated fungal hyphae, but instead strongly inhibited hyphal elongation. A propidium iodide uptake assay suggested that the inhibitory activity of Vv-AMP1 might be associated with altering the membrane permeability of the fungal

  5. Subunits of the Snf1 kinase heterotrimer show interdependence for association and activity.

    PubMed

    Elbing, Karin; Rubenstein, Eric M; McCartney, Rhonda R; Schmidt, Martin C

    2006-09-08

    The Snf1 kinase and its mammalian orthologue, the AMP-activated protein kinase (AMPK), function as heterotrimers composed of a catalytic alpha-subunit and two non-catalytic subunits, beta and gamma. The beta-subunit is thought to hold the complex together and control subcellular localization whereas the gamma-subunit plays a regulatory role by binding to and blocking the function of an auto-inhibitory domain (AID) present in the alpha-subunit. In addition, catalytic activity requires phosphorylation by a distinct upstream kinase. In yeast, any one of three Snf1-activating kinases, Sak1, Tos3, or Elm1, can fulfill this role. We have previously shown that Sak1 is the only Snf1-activating kinase that forms a stable complex with Snf1. Here we show that the formation of the Sak1.Snf1 complex requires the beta- and gamma-subunits in vivo. However, formation of the Sak1.Snf1 complex is not necessary for glucose-regulated phosphorylation of the Snf1 activation loop. Snf1 kinase purified from cells lacking the beta-subunits do not contain any gamma-subunit, indicating that the Snf1 kinase does not form a stable alphagamma dimer in vivo. In vitro kinase assays using purified full-length and truncated Snf1 proteins demonstrate that the kinase domain, which lacks the AID, is significantly more active than the full-length Snf1 protein. Addition of purified beta- and gamma-subunits could stimulate the kinase activity of the full-length alpha-subunit but only when all three subunits were present, suggesting an interdependence of all three subunits for assembly of a functional complex.

  6. Supporting "Learning by Design" Activities Using Group Blogs

    ERIC Educational Resources Information Center

    Fessakis, Georgios; Tatsis, Konstantinos; Dimitracopoulou, Angelique

    2008-01-01

    The paper presents a case study of the educational exploitation of group blogging for the implementation of a "learning by design" activity. More specifically, a group of students used a blog as a communication and information management tool in the University course of ICT-enhanced Geometry learning activities. The analysis of the designed…

  7. PEGASUS: Designing a System for Supporting Group Activity

    ERIC Educational Resources Information Center

    Kyprianidou, Maria; Demetriadis, Stavros; Pombortsis, Andreas; Karatasios, George

    2009-01-01

    Purpose: The purpose of this paper is to present the design and first results of the integration of a web-based system person-centred group-activity support system (PEGASUS) in university instruction, as a means for advancing person-centred learning by supporting group activity. The PEGASUS is expected to help students and teachers in two distinct…

  8. Teacher Educators' Design and Implementation of Group Learning Activities

    ERIC Educational Resources Information Center

    De Hei, Miranda S. A.; Sjoer, Ellen; Admiraal, Wilfried; Strijbos, Jan-Willem

    2016-01-01

    The aim of this study was to describe how teacher educators design and implement group learning activities (GLAs). We used the Group Learning Activities Instructional Design (GLAID) framework to analyse their descriptions. The GLAID framework includes eight components: (1) interaction, (2) learning objectives and outcomes, (3) assessment, (4) task…

  9. Negatively charged liposomes show potent adjuvant activity when simply admixed with protein antigens

    PubMed Central

    Yanasarn, Nijaporn; Sloat, Brian R.; Cui, Zhengrong

    2011-01-01

    Liposomes have been investigated extensively as a vaccine delivery system. Herein the adjuvant activities of liposomes with different net surface charges (neutral, positive, or negative) were evaluated when admixed with protein antigens, ovalbumin (OVA, pI = 4.7), Bacillus anthracis protective antigen protein (PA, pI = 5.6), or cationized OVA (cOVA). Mice immunized subcutaneously with OVA admixed with different liposomes generated different antibody responses. Interestingly, OVA admixed with net negatively charged liposomes prepared with DOPA was as immunogenic as OVA admixed with positively charged liposomes prepared with DOTAP. Immunization of mice with the anthrax PA protein admixed with the net negatively charged DOPA liposomes also induced a strong and functional anti-PA antibody response. When the cationized OVA was used as a model antigen, liposomes with net neutral, negative, or positive charges showed comparable adjuvant activities. Immunization of mice with the OVA admixed with DOPA liposomes also induced OVA-specific CD8+ cytotoxic T lymphocyte responses and significantly delayed the growth of OVA-expressing B16-OVA tumors in mice. However, not all net negatively charged liposomes showed a strong adjuvant activity. The adjuvant activity of the negatively charged liposomes may be related to the liposome’s ability (i) to up-regulate the expression of molecules related to the activation and maturation of antigen-presenting cells and (ii) to slightly facilitate the uptake of the antigens by antigen-presenting cells. Simply admixing certain negatively charged liposomes with certain protein antigens of interest may represent a novel platform for vaccine development. PMID:21615153

  10. A novel cathelicidin from Bufo bufo gargarizans Cantor showed specific activity to its habitat bacteria.

    PubMed

    Sun, Tongyi; Zhan, Bo; Gao, Yuanyuan

    2015-10-25

    Toad Bufo bufo gargarizans Cantor is still used in China as traditional Chinese medicine. However, present investigations on its skin secretions were mainly focused on the bufadienolides, the proteins/peptides contained in the secretions are largely unknown. A cDNA encoding a novel cathelicidin termed BG-CATH was identified by analysis of the toad skin transcriptome. The BG-CATH precursor was predicted to have 2 possible cleavage sites following dibasic cleavage signals at its C-terminal, which will generate two mature peptides, BG-CATH37 and BG-CATH(5-37). Phylogenetic analysis suggests that amphibian cathelicidins might evolve from common ancestors. The two predicted mature cathelicidins from B. bufo gargarizans were synthesized and both of them showed weak antimicrobial activities against human pathogenic bacteria Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus (MIC ≥ 200 μg/mL). However, BG-CATH37 and BG-CATH(5-37) had strong antimicrobial activities against aquatic bacteria of Vibrio splendidus, Streptococcus iniae and Aeromorus hydrophila, which were common microorganisms in the habitat of B. bufo gargarizans (MIC 3.125-40 μg/mL). BG-CATH37 and BG-CATH(5-37) showed no hemolytic activity even at high concentrations (400 μg/mL). CD spectra analysis suggested that structure rigidity of BG-CATH37 and BG-CATH(5-37) might play an important role to regulate their biological activities. Selective antimicrobial activity against habitat microorganisms might reflect the adaptation of amphibians to their living environments.

  11. Student expectations in a group learning activity on harmonic motion

    NASA Astrophysics Data System (ADS)

    Kaczynski, Adam; Wittmann, Michael C.

    2013-01-01

    Students in a sophomore-level mechanics course participated in a new group learning activity that was intended to support model-building and finding coherence between multiple representations in the context of an underdamped harmonic system. Not all of the student groups framed the activity in the same way, and many attempted tasks that existed outside of the prompts of the activity. For one group, this meant that instead of providing a rich verbal description, they framed the activity as finding a mathematical expression.

  12. Newly derived GH43 gene from compost metagenome showing dual xylanase and cellulase activities.

    PubMed

    Sae-Lee, Ritthironk; Boonmee, Atcha

    2014-09-01

    A metagenomic fosmid library was constructed from compost microbial communities that were collected from various farms throughout the Khon Kaen province, Thailand. The library was enriched in carboxymethylcellulose (CM-cellulose)--containing media prior to the screening of clones capable of degrading cellulosic materials. Two clones were selected for further subcloning and sequencing based on different patterns from restriction analysis. Deduced amino acid analysis of possible ORFs revealed one novel gene encoding an enzyme belonging to glycosyl hydrolase family 43 (GH43), which is a GH family rarely found in metagenomic studies. The most notable finding is that this enzyme, designated as Biof1_09, shows dual activities, namely endocellulase and endoxylanase activities. Biof1_09 showed greater than 50% of its activity under acidic conditions ranging from pH 3.5 to 5.5 with a pH optimum of 4.5. The optimum temperature of this enzyme was between 45 and 55 °C with an optimum of 50 °C. The properties of Biof1_09 make this enzyme an attractive candidate for large-scale expression for use in lignocellulose degradation for various bioprocess applications, including bioethanol fermentation.

  13. Brain potentials show rapid activation of implicit attitudes towards young and old people.

    PubMed

    van der Lugt, Arie H; Banfield, Jane F; Osinsky, Roman; Münte, Thomas F

    2012-01-06

    While previous behavioural research suggests that attitudes, for example towards elderly people, may be activated automatically, this type of research does not provide information about the detailed time-course of such processing in the brain. We investigated the impact of age related attitude information in a Go/NoGo association task that paired photographs of elderly or young faces with positive or negative words. Event related brain potentials showed an N200 (NoGo) component, which appeared earlier in runs which required similar responses for congruent stimulus pairings (e.g. respond to pictures of elderly faces or negative words) than for incongruent pairings (e.g. respond to elderly faces or positive words). As information processing leading to a certain attitude must precede differential brain activity according to the congruence of the paired words and faces, we show that this type of information is activated almost immediately following the structural encoding of the face, between 170 and 230 ms after onset of the face.

  14. Variegation of comet 67P/Churyumov-Gerasimenko in regions showing activity

    NASA Astrophysics Data System (ADS)

    Oklay, N.; Vincent, J.-B.; Fornasier, S.; Pajola, M.; Besse, S.; Davidsson, B. J. R.; Lara, L. M.; Mottola, S.; Naletto, G.; Sierks, H.; Barucci, A. M.; Scholten, F.; Preusker, F.; Pommerol, A.; Masoumzadeh, N.; Lazzarin, M.; Barbieri, C.; Lamy, P. L.; Rodrigo, R.; Koschny, D.; Rickman, H.; A'Hearn, M. F.; Bertaux, J.-L.; Bertini, I.; Bodewits, D.; Cremonese, G.; Da Deppo, V.; Debei, S.; De Cecco, M.; Fulle, M.; Groussin, O.; Gutiérrez, P. J.; Güttler, C.; Hall, I.; Hofmann, M.; Hviid, S. F.; Ip, W.-H.; Jorda, L.; Keller, H. U.; Knollenberg, J.; Kovacs, G.; Kramm, J.-R.; Kührt, E.; Küppers, M.; Lin, Z.-Y.; Lopez Moreno, J. J.; Marzari, F.; Moreno, F.; Shi, X.; Thomas, N.; Toth, I.; Tubiana, C.

    2016-02-01

    Aims.We carried out an investigation of the surface variegation of comet 67P/Churyumov-Gerasimenko, the detection of regions showing activity, the determination of active and inactive surface regions of the comet with spectral methods, and the detection of fallback material. Methods: We analyzed multispectral data generated with Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) narrow angle camera (NAC) observations via spectral techniques, reflectance ratios, and spectral slopes in order to study active regions. We applied clustering analysis to the results of the reflectance ratios, and introduced the new technique of activity thresholds to detect areas potentially enriched in volatiles. Results: Local color inhomogeneities are detected over the investigated surface regions. Active regions, such as Hapi, the active pits of Seth and Ma'at, the clustered and isolated bright features in Imhotep, the alcoves in Seth and Ma'at, and the large alcove in Anuket, have bluer spectra than the overall surface. The spectra generated with OSIRIS NAC observations are dominated by cometary emissions of around 700 nm to 750 nm as a result of the coma between the comet's surface and the camera. One of the two isolated bright features in the Imhotep region displays an absorption band of around 700 nm, which probably indicates the existence of hydrated silicates. An absorption band with a center between 800-900 nm is tentatively observed in some regions of the nucleus surface. This absorption band can be explained by the crystal field absorption of Fe2+, which is a common spectral feature seen in silicates.

  15. Coadministration of doxorubicin and etoposide loaded in camel milk phospholipids liposomes showed increased antitumor activity in a murine model.

    PubMed

    Maswadeh, Hamzah M; Aljarbou, Ahmed N; Alorainy, Mohammed S; Rahmani, Arshad H; Khan, Masood A

    2015-01-01

    Small unilamellar vesicles from camel milk phospholipids (CML) mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were prepared, and anticancer drugs doxorubicin (Dox) or etoposide (ETP) were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98%) in liposomes (Lip) prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip. Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP)-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP). Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).

  16. Two chitinase-like proteins abundantly accumulated in latex of mulberry show insecticidal activity

    PubMed Central

    2010-01-01

    Background Plant latex is the cytoplasm of highly specialized cells known as laticifers, and is thought to have a critical role in defense against herbivorous insects. Proteins abundantly accumulated in latex might therefore be involved in the defense system. Results We purified latex abundant protein a and b (LA-a and LA-b) from mulberry (Morus sp.) and analyzed their properties. LA-a and LA-b have molecular masses of approximately 50 and 46 kDa, respectively, and are abundant in the soluble fraction of latex. Western blotting analysis suggested that they share sequence similarity with each other. The sequences of LA-a and LA-b, as determined by Edman degradation, showed chitin-binding domains of plant chitinases at the N termini. These proteins showed small but significant chitinase and chitosanase activities. Lectin RCA120 indicated that, unlike common plant chitinases, LA-a and LA-b are glycosylated. LA-a and LA-b showed insecticidal activities when fed to larvae of the model insect Drosophila melanogaster. Conclusions Our results suggest that the two LA proteins have a crucial role in defense against herbivorous insects, possibly by hydrolyzing their chitin. PMID:20109180

  17. Children who stutter show reduced action-related activity in the rostral cingulate zone.

    PubMed

    Harrewijn, A; Schel, M A; Boelens, H; Nater, C M; Haggard, P; Crone, E A

    2017-02-01

    Previous studies have indicated that children who stutter show not only speech-related problems, but also wider difficulties in self-control. In this study we test the novel hypothesis that children who stutter may experience difficulties with inhibitory control over voluntary actions. We used functional MRI to compare brain activity between children who stutter and children who do not stutter in a task that captures key cognitive aspects of voluntary action control. Participants performed a rolling marble task, in which they were instructed to press a key to stop a rolling marble from crashing on some of the trials (instructed action condition). They were also asked to choose voluntarily whether to execute or inhibit this prepotent response in other trials (volition condition). Children who stutter reported less motor and cognitive impulsivity and had shorter stop-signal reaction times when controlled for IQ, consistent with greater inhibition, compared to children who do not stutter. At the neural level, children who stutter showed decreased activation in the rostral cingulate zone during voluntary action selection compared to children who do not stutter. This effect was more pronounced for children who were rated as showing more stuttered syllables in the stutter screening, and was furthermore correlated with stop-signal reaction times and impulsivity ratings. These findings suggest that stuttering in childhood could reflect wider difficulties in self-control, also in the non-verbal domain. Understanding these neural mechanisms could potentially lead to more focused treatments of stuttering.

  18. Two Analogues of Fenarimol Show Curative Activity in an Experimental Model of Chagas Disease

    PubMed Central

    2013-01-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compounds, 6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10 mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are noncytotoxic, show no adverse effects in vivo following repeat dosing, are prepared by a short synthetic route, and have druglike properties suitable for preclinical development. PMID:24304150

  19. Overview of MSFC's Applied Fluid Dynamics Analysis Group Activities

    NASA Technical Reports Server (NTRS)

    Garcia, Roberto; Griffin, Lisa; Williams, Robert

    2002-01-01

    This viewgraph report presents an overview of activities and accomplishments of NASA's Marshall Space Flight Center's Applied Fluid Dynamics Analysis Group. Expertise in this group focuses on high-fidelity fluids design and analysis with application to space shuttle propulsion and next generation launch technologies. Topics covered include: computational fluid dynamics research and goals, turbomachinery research and activities, nozzle research and activities, combustion devices, engine systems, MDA development and CFD process improvements.

  20. Biofunctional constituent isolated from Citrullus colocynthis fruits and structure-activity relationships of its analogues show acaricidal and insecticidal efficacy.

    PubMed

    Jeon, Ju-Hyun; Lee, Hoi-Seon

    2014-08-27

    The acaricidal and insecticidal potential of the active constituent isolated from Citrullus colocynthis fruits and its structurally related analogues was evaluated by performing leaf disk, contact toxicity, and fumigant toxicity bioassays against Tetranychus urticae, Sitophilus oryzae, and Sitophilus zeamais adults. The active constituent of C. colocynthis fruits was isolated by chromatographic techniques and was identified as 4-methylquinoline on the basis of spectroscopic analyses. To investigate the structure-activity relationships, 4-methylquinoline and its structural analogues were tested against mites and two insect pests. On the basis of the LC50 values, 7,8-benzoquinoline was the most effective against T. urticae. Quinoline, 8-hydroxyquinoline, 2-methylquinoline, 4-methylquinoline, 6-methylquinoline, 8-methylquinoline, and 7,8-benzoquinoline showed high insecticidal activities against S. oryzae and S. zeamais regardless of the application method. These results indicate that introduction of a functional group into the quinoline skeleton and changing the position of the group have an important influence on the acaricidal and insecticidal activities. Furthermore, 4-methylquinoline isolated from C. colocynthis fruits, along with its structural analogues, could be effective natural pesticides for managing spider mites and stored grain weevils.

  1. Endolymphatic Sac Tumor Showing Increased Activity on 68Ga DOTATATE PET/CT.

    PubMed

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-10-01

    Endolymphatic sac tumors (ELSTs) are rare tumors arising from the epithelium of the endolymphatic sac and duct that can be either sporadic or associated with von Hippel-Lindau (VHL) disease. We report a case of a VHL patient with histologically proven residual ELST who underwent Ga DOTATATE PET/CT showing increased activity (SUVmax, 6.29) by the ELST. The presented case of a VHL-associated ELST with increased Ga DOTATATE uptake indicates cell-surface expression of somatostatin receptors by this tumor, suggesting the potential application of somatostatin receptor imaging using Ga DOTA-conjugated peptides in the workup and management of these patients.

  2. Environmental distribution, abundance and activity of the Miscellaneous Crenarchaeotal Group

    NASA Astrophysics Data System (ADS)

    Lloyd, K. G.; Biddle, J.; Teske, A.

    2011-12-01

    Many marine sedimentary microbes have only been identified by 16S rRNA sequences. Consequently, little is known about the types of metabolism, activity levels, or relative abundance of these groups in marine sediments. We found that one of these uncultured groups, called the Miscellaneous Crenarchaeotal Group (MCG), dominated clone libraries made from reverse transcribed 16S rRNA, and 454 pyrosequenced 16S rRNA genes, in the White Oak River estuary. Primers suitable for quantitative PCR were developed for MCG and used to show that 16S rRNA DNA copy numbers from MCG account for nearly all the archaeal 16S rRNA genes present. RT-qPCR shows much less MCG rRNA than total archaeal rRNA, but comparisons of different primers for each group suggest bias in the RNA-based work relative to the DNA-based work. There is no evidence of a population shift with depth below the sulfate-methane transition zone, suggesting that the metabolism of MCG may not be tied to sulfur or methane cycles. We classified 2,771 new sequences within the SSU Silva 106 database that, along with the classified sequences in the Silva database was used to make an MCG database of 4,646 sequences that allowed us to increase the named subgroups of MCG from 7 to 19. Percent terrestrial sequences in each subgroup is positively correlated with percent of the marine sequences that are nearshore, suggesting that membership in the different subgroups is not random, but dictated by environmental selective pressures. Given their high phylogenetic diversity, ubiquitous distribution in anoxic environments, and high DNA copy number relative to total archaea, members of MCG are most likely anaerobic heterotrophs who are integral to the post-depositional marine carbon cycle.

  3. Minimized natural versions of fungal ribotoxins show improved active site plasticity.

    PubMed

    Maestro-López, Moisés; Olombrada, Miriam; García-Ortega, Lucía; Serrano-González, Daniel; Lacadena, Javier; Oñaderra, Mercedes; Gavilanes, José G; Martínez-Del-Pozo, Álvaro

    2017-04-01

    Fungal ribotoxins are highly specific extracellular RNases which cleave a single phosphodiester bond at the ribosomal sarcin-ricin loop, inhibiting protein biosynthesis by interfering with elongation factors. Most ribotoxins show high degree of conservation, with similar sizes and amino acid sequence identities above 85%. Only two exceptions are known: hirsutellin A and anisoplin, produced by the entomopathogenic fungi Hirsutella thompsonii and Metarhizium anisopliae, respectively. Both proteins are similar but smaller than the other known ribotoxins (130 vs 150 amino acids), displaying only about 25% sequence identity with them. They can be considered minimized natural versions of their larger counterparts, best represented by α-sarcin. The conserved α-sarcin active site residue Tyr48 has been replaced by the geometrically equivalent Asp, present in the minimized ribotoxins, to produce and characterize the corresponding mutant. As a control, the inverse anisoplin mutant (D43Y) has been also studied. The results show how the smaller versions of ribotoxins represent an optimum compromise among conformational freedom, stability, specificity, and active-site plasticity which allow these toxic proteins to accommodate the characteristic abilities of ribotoxins into a shorter amino acid sequence and more stable structure of intermediate size between that of other nontoxic fungal RNases and previously known larger ribotoxins.

  4. Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

    PubMed

    Orlowski, Piotr; Tomaszewska, Emilia; Gniadek, Marianna; Baska, Piotr; Nowakowska, Julita; Sokolowska, Justyna; Nowak, Zuzanna; Donten, Mikolaj; Celichowski, Grzegorz; Grobelny, Jaroslaw; Krzyzowska, Malgorzata

    2014-01-01

    The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

  5. Children with High Functioning Autism show increased prefrontal and temporal cortex activity during error monitoring

    PubMed Central

    Goldberg, Melissa C.; Spinelli, Simona; Joel, Suresh; Pekar, James J.; Denckla, Martha B.; Mostofsky, Stewart H.

    2010-01-01

    Evidence exists for deficits in error monitoring in autism. These deficits may be particularly important because they may contribute to excessive perseveration and repetitive behavior in autism. We examined the neural correlates of error monitoring using fMRI in 8–12-year-old children with high-functioning autism (HFA, n=11) and typically developing children (TD, n=15) during performance of a Go/No-Go task by comparing the neural correlates of commission errors versus correct response inhibition trials. Compared to TD children, children with HFA showed increased BOLD fMRI signal in the anterior medial prefrontal cortex (amPFC) and the left superior temporal gyrus (STempG) during commission error (versus correct inhibition) trials. A follow-up region-of-interest analysis also showed increased BOLD signal in the right insula in HFA compared to TD controls. Our findings of increased amPFC and STempG activity in HFA, together with the increased activity in the insula, suggest a greater attention towards the internally-driven emotional state associated with making an error in children with HFA. Since error monitoring occurs across different cognitive tasks throughout daily life, an increased emotional reaction to errors may have important consequences for early learning processes. PMID:21151713

  6. CpG oligodeoxynucleotides with double stem-loops show strong immunostimulatory activity.

    PubMed

    Yang, Liang; Wu, Xiuli; Wan, Min; Yu, Yue; Yu, Yongli; Wang, Liying

    2013-01-01

    Based on the current understanding of TLR9 recognition of CpG ODN, we have tried to design a series of CpG ODNs that display double stem-loops when being analyzed for their secondary structures using 'mfold web server'. Proliferation of human PBMC and bioassay for IFN production were used as technical platforms in primary screening. Interestingly, two of them, designated as DSL01 and D-SL03, belonging to B class CpG ODN and C class CpG ODN respectively, showed vigorous immunostimulatory activity and were chosen for further tests. Flow cytometry analysis showed that both of them could activate human B cells, NK cells, mononuclear cells and T cells and up-regulate expression of CD80, CD86 and HLA-DR on the surface of subsets in human PBMCs. Furthermore, we demonstrated that those two ODNs potently stimulated proliferation of PBMC/splenocytes obtained from diverse vertebrate species. Noticeably, both of them displayed anti-breast cancer effect in mice when administered by peritumoral injection.

  7. Tannic Acid Modified Silver Nanoparticles Show Antiviral Activity in Herpes Simplex Virus Type 2 Infection

    PubMed Central

    Orlowski, Piotr; Tomaszewska, Emilia; Gniadek, Marianna; Baska, Piotr; Nowakowska, Julita; Sokolowska, Justyna; Nowak, Zuzanna; Donten, Mikolaj; Celichowski, Grzegorz; Grobelny, Jaroslaw; Krzyzowska, Malgorzata

    2014-01-01

    The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections. PMID:25117537

  8. Staurosporine shows insecticidal activity against Mythimna separata Walker (Lepidoptera: Noctuidae) potentially via induction of apoptosis.

    PubMed

    Zhang, Yang; Liu, Songlin; Yang, Xing; Yang, Mingjun; Xu, Wenping; Li, Yaxiao; Tao, Liming

    2016-03-01

    Staurosporine (STS), a wide-spectrum kinase inhibitor, is widely used in studies of apoptosis in mammalian cells. However, its physiological and mechanistic effects have never been clearly defined in insect cells, and other applications of STS have rarely been reported. The present study reveals the insecticidal activity of STS on larvae of Mythimna separata Walker, and the apoptotic mechanism induced by STS on lepidopteran Sf9 cell lines. We demonstrate that the viability of Sf9 cells is inhibited by STS in a time- and concentration-dependent manner. Intracellular biochemical assays show that STS-induced apoptosis of Sf9 cells coincides with a decrease in the mitochondrial membrane potential, the release of cytochrome c into the cytosol, a significant increase of the Bax/Bcl-2 ratio, and a marked activation of caspase-9 and caspase-3. These results indicate that a mitochondrial-dependent intrinsic pathway contributes to STS induced caspase-3 activation and apoptosis in Sf9 cells which is homologous to the mechanisms in mammalian cells. This study contributes to our understanding of the mechanism of insect cell apoptosis and suggests a possible new application of STS as a potential insecticide against Lepidopteran insect pests in agriculture.

  9. Men and women show distinct brain activations during imagery of sexual and emotional infidelity.

    PubMed

    Takahashi, Hidehiko; Matsuura, Masato; Yahata, Noriaki; Koeda, Michihiko; Suhara, Tetsuya; Okubo, Yoshiro

    2006-09-01

    Jealousy-related behaviors such as intimate partner violence and morbid jealousy are more common in males. Principal questionnaire studies suggest that men and women have different modules to process cues of sexual and emotional infidelity. We aimed to elucidate the neural response to sentences depicting sexual and emotional infidelity in men and women using functional magnetic resonance imaging. Although there was no sex difference in the self-rating score of jealousy for sexual and emotional infidelity, men and women showed different brain activation patterns in response to the two types of infidelity. During jealous conditions, men demonstrated greater activation than women in the brain regions involved in sexual/aggressive behaviors such as the amygdala and hypothalamus. In contrast, women demonstrated greater activation in the posterior superior temporal sulcus. Our fMRI results are in favor of the notion that men and women have different neuropsychological modules to process sexual and emotional infidelity. Our findings might contribute to a better understanding of the neural basis of the jealousy-related behaviors predominantly observed in males.

  10. An inhibitory RNA aptamer against the lambda cI repressor shows transcriptional activator activity in vivo.

    PubMed

    Ohuchi, Shoji; Suess, Beatrix

    2017-04-13

    An RNA aptamer is one of the promising components for constructing artificial genetic circuits. In this study, we developed a transcriptional activator based on an RNA aptamer against one of the most frequently applied repressor proteins, lambda phage cI. In vitro selection (SELEX), followed by in vivo screening identified an RNA aptamer with the intended transcriptional activator activity from an RNA pool containing a 40-nucleotide long random region. Quantitative analysis showed 35-fold elevation of reporter expression upon aptamer expression. These results suggest that the diversity of artificial transcriptional activators can be extended by employing RNA aptamers against repressor proteins to broaden the tools available for constructing genetic circuits. This article is protected by copyright. All rights reserved.

  11. BRAIN REWARD ACTIVITY TO MASKED IN-GROUP SMILING FACES PREDICTS FRIENDSHIP DEVELOPMENT

    PubMed Central

    Chen, Pin-Hao A.; Whalen, Paul J.; Freeman, Jonathan B.; Taylor, James M.; Heatherton, Todd F.

    2015-01-01

    This study examined whether neural responses in the ventral striatum (VS) to in-group facial expressions—presented without explicit awareness—could predict friendship patterns in newly arrived individuals from China six months later. Individuals who initially showed greater VS activity in response to in-group happy expressions during functional neuroimaging later made considerably more in-group friends, suggesting that VS activity might reflect reward processes that drive in-group approach behaviors. PMID:26185595

  12. In Vitro Assays of BciC Showing C132-Demethoxycarbonylase Activity Requisite for Biosynthesis of Chlorosomal Chlorophyll Pigments.

    PubMed

    Teramura, Misato; Harada, Jiro; Mizoguchi, Tadashi; Yamamoto, Ken; Tamiaki, Hitoshi

    2016-05-01

    A BciC enzyme is related to the removal of the C13(2)-methoxycarbonyl group in biosynthesis of bacteriochlorophylls (BChls) c, d and e functioning in green sulfur bacteria, filamentous anoxygenic phototrophs and phototrophic acidobacteria. These photosynthetic bacteria have the largest and the most efficient light-harvesting antenna systems, called chlorosomes, containing unique self-aggregates of BChl c, d or e pigments, that lack the C13(2)-methoxycarbonyl group which disturbs chlorosomal self-aggregation. In this study, we characterized the BciC derived from the green sulfur bacterium Chlorobaculum tepidum, and examined the in vitro enzymatic activities of its recombinant protein. The BciC-catalyzing reactions of various substrates showed that the enzyme recognized chlorophyllide (Chlide) a and 3,8-divinyl(DV)-Chlide a as chlorin substrates to give 3-vinyl-bacteriochlorophyllide (3V-BChlide) d and DV-BChlide d, respectively. Since the BciC afforded a higher activity with Chlide a than that with DV-Chlide a and no activity with (DV-)protoChlides a (porphyrin substrates) and 3V-BChlide a (a bacteriochlorin substrate), this enzyme was effective for diverting the chlorosomal pigment biosynthetic pathway at the stage of Chlide a away from syntheses of other pigments such as BChl a and Chl a The addition of methanol to the reaction mixture did not prevent the BciC activity, and we identified this enzyme as Chlide a demethoxycarbonylase, not methylesterase.

  13. Male mice housed in groups engage in frequent fighting and show a lower response to additional bone loading than females or individually housed males that do not fight.

    PubMed

    Meakin, Lee B; Sugiyama, Toshihiro; Galea, Gabriel L; Browne, William J; Lanyon, Lance E; Price, Joanna S

    2013-05-01

    Experiments to investigate bone's physiological adaptation to mechanical loading frequently employ models that apply dynamic loads to bones in vivo and assess the changes in mass and architecture that result. It is axiomatic that bones will only show an adaptive response if the applied artificial loading environment differs in a significant way from that to which the bones have been habituated by normal functional loading. It is generally assumed that this normal loading is similar between experimental groups. In the study reported here we found that this was not always the case. Male and female 17-week-old C57BL/6 mice were housed in groups of six, and a single episode (40 cycles) of non-invasive axial loading, engendering 2,200 με on the medial surface of the proximal tibiae in sample mice, was applied to right tibiae on alternate days for two weeks. This engendered an adaptive increase in bone mass in females, but not males. Observation revealed the main difference in behaviour between males and females was that males were involved in fights 1.3 times per hour, whereas the females never fought. We therefore housed all mice individually. In females, there was a similar significant osteogenic response to loading in cortical and trabecular bone of both grouped and individual mice. In contrast, in males, adaptive increases in the loaded compared with non-loaded control bones was only apparent in animals housed individually. Our interpretation of these findings is that the frequent vigorous fighting that occurs between young adult males housed in groups could be sufficient to engender peak strains and strain rates that equal or exceed the stimulus derived from artificial loading. This indicates the importance of ensuring that physical activity is consistent between groups. Reducing the background level of the naturally engendered strain environment allows adaptive responses to artificial loading to be demonstrated at lower loads.

  14. The metastasis-promoting phosphatase PRL-3 shows activity toward phosphoinositides.

    PubMed

    McParland, Victoria; Varsano, Giulia; Li, Xun; Thornton, Janet; Baby, Jancy; Aravind, Ajay; Meyer, Christoph; Pavic, Karolina; Rios, Pablo; Köhn, Maja

    2011-09-06

    Phosphatase of regenerating liver 3 (PRL-3) is suggested as a biomarker and therapeutic target in several cancers. It has a well-established causative role in cancer metastasis. However, little is known about its natural substrates, pathways, and biological functions, and only a few protein substrates have been suggested so far. To improve our understanding of the substrate specificity and molecular determinants of PRL-3 activity, the wild-type (WT) protein, two supposedly catalytically inactive mutants D72A and C104S, and the reported hyperactive mutant A111S were tested in vitro for substrate specificity and activity toward phosphopeptides and phosphoinositides (PIPs), their structural stability, and their ability to promote cell migration using stable HEK293 cell lines. We discovered that WT PRL-3 does not dephosphorylate the tested phosphopeptides in vitro. However, as shown by two complementary biochemical assays, PRL-3 is active toward the phosphoinositide PI(4,5)P(2). Our experimental results substantiated by molecular docking studies suggest that PRL-3 is a phosphatidylinositol 5-phosphatase. The C104S variant was shown to be not only catalytically inactive but also structurally destabilized and unable to promote cell migration, whereas WT PRL-3 promotes cell migration. The D72A mutant is structurally stable and does not dephosphorylate the unnatural substrate 3-O-methylfluorescein phosphate (OMFP). However, we observed residual in vitro activity of D72A against PI(4,5)P(2), and in accordance with this, it exhibits the same cellular phenotype as WT PRL-3. Our analysis of the A111S variant shows that the hyperactivity toward the unnatural OMFP substrate is not apparent in dephosphorylation assays with phosphoinositides: the mutant is completely inactive against PIPs. We observed significant structural destabilization of this variant. The cellular phenotype of this mutant equals that of the catalytically inactive C104S mutant. These results provide a possible

  15. Etoposide incorporated into camel milk phospholipids liposomes shows increased activity against fibrosarcoma in a mouse model.

    PubMed

    Maswadeh, Hamzah M; Aljarbou, Ahmad N; Alorainy, Mohammed S; Alsharidah, Mansour S; Khan, Masood A

    2015-01-01

    Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS). Anticancer drug etoposide (ETP) was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP) and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes) and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes). The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs.

  16. Cysteamine, the natural metabolite of pantetheinase, shows specific activity against Plasmodium.

    PubMed

    Min-Oo, Gundula; Ayi, Kodjo; Bongfen, Silayuv E; Tam, Mifong; Radovanovic, Irena; Gauthier, Susan; Santiago, Helton; Rothfuchs, Antonio Gigliotti; Roffê, Ester; Sher, Alan; Mullick, Alaka; Fortin, Anny; Stevenson, Mary M; Kain, Kevin C; Gros, Philippe

    2010-08-01

    In mice, loss of pantetheinase activity causes susceptibility to infection with Plasmodium chabaudi AS. Treatment of mice with the pantetheinase metabolite cysteamine reduces blood-stage replication of P. chabaudi and significantly increases survival. Similarly, a short exposure of Plasmodium to cysteamine ex vivo is sufficient to suppress parasite infectivity in vivo. This effect of cysteamine is specific and not observed with a related thiol (dimercaptosuccinic acid) or with the pantethine precursor of cysteamine. Also, cysteamine does not protect against infection with the parasite Trypanosoma cruzi or the fungal pathogen Candida albicans, suggesting cysteamine acts directly against the parasite and does not modulate host inflammatory response. Cysteamine exposure also blocks replication of P. falciparum in vitro; moreover, these treated parasites show higher levels of intact hemoglobin. This study highlights the in vivo action of cysteamine against Plasmodium and provides further evidence for the involvement of pantetheinase in host response to this infection.

  17. First multigene analysis of Archamoebae (Amoebozoa: Conosa) robustly reveals its phylogeny and shows that Entamoebidae represents a deep lineage of the group.

    PubMed

    Pánek, Tomáš; Zadrobílková, Eliška; Walker, Giselle; Brown, Matthew W; Gentekaki, Eleni; Hroudová, Miluše; Kang, Seungho; Roger, Andrew J; Tice, Alexander K; Vlček, Čestmír; Čepička, Ivan

    2016-05-01

    Archamoebae is an understudied group of anaerobic free-living or endobiotic protists that constitutes the major anaerobic lineage of the supergroup Amoebozoa. Hitherto, the phylogeny of Archamoebae was based solely on SSU rRNA and actin genes, which did not resolve relationships among the main lineages of the group. Because of this uncertainty, several different scenarios had been proposed for the phylogeny of the Archamoebae. In this study, we present the first multigene phylogenetic analysis that includes members of Pelomyxidae, and Rhizomastixidae. The analysis clearly shows that Mastigamoebidae, Pelomyxidae and Rhizomastixidae form a clade of mostly free-living, amoeboid flagellates, here called Pelobiontida. The predominantly endobiotic and aflagellated Entamoebidae represents a separate, deep-branching lineage, Entamoebida. Therefore, two unique evolutionary events, horizontal transfer of the nitrogen fixation system from bacteria and transfer of the sulfate activation pathway to mitochondrial derivatives, predate the radiation of recent lineages of Archamoebae. The endobiotic lifestyle has arisen at least three times independently during the evolution of the group. We also present new ultrastructural data that clarifies the primary divergence among the family Mastigamoebidae which had previously been inferred from phylogenetic analyses based on SSU rDNA.

  18. Activity Group Therapy for Emotionally Disturbed Pre-School Children.

    ERIC Educational Resources Information Center

    Plenk, Agnes M.

    1978-01-01

    The article discusses the comprehensive services offered emotionally disturbed preschool children by a voluntary social agency (the Childrens Center in Salt Lake City, Utah), focusing on activity group therapy, the major therapeutic tool used there. (Author/DLS)

  19. Acidophilic actinobacteria synthesised silver nanoparticles showed remarkable activity against fungi-causing superficial mycoses in humans.

    PubMed

    Anasane, N; Golińska, P; Wypij, M; Rathod, D; Dahm, H; Rai, M

    2016-03-01

    Superficial mycoses are limited to the most external part of the skin and hair and caused by Malassezia sp., Trichophyton sp. and Candida sp. We report extracellular biosynthesis of silver nanoparticles (AgNPs) by acidophilic actinobacteria (SF23, C9) and its in vitro antifungal activity against fungi-causing superficial mycoses. The phylogenetic analysis based on the 16S rRNA gene sequence of strains SF23 and C9 showed that they are most closely related to Pilimelia columellifera subsp. pallida GU269552(T). The detection of AgNPs was confirmed by visual observation of colour changes from colourless to brown, and UV-vis spectrophotometer analysis, which showed peaks at 432 and 427 nm, respectively. These AgNPs were further characterised by nanoparticle tracking analysis (NTA), Zeta potential, Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The FTIR analysis exhibited the presence of proteins as capping agents. The TEM analysis revealed the formation of spherical and polydispersed nanoparticles in the size range of 4-36 nm and 8-60 nm, respectively. The biosynthesised AgNPs were screened against fungi-causing superficial mycoses viz., Malassezia furfur, Trichophyton rubrum, Candida albicans and C. tropicalis. The highest antifungal activity of AgNPs from SF23 and C9 against T. rubrum and the least against M. furfur and C. albicans was observed as compared to other tested fungi. The biosynthesised AgNPs were found to be potential anti-antifungal agent against fungi-causing superficial mycoses.

  20. DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae

    PubMed Central

    Yamaguchi, Tomoyuki; Yokoyama, Kazumasa; Nakajima, Chie

    2016-01-01

    Background Fluoroquinolones are a class of antibacterial agents used for leprosy treatment. Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. For example, DC-159a, a recently developed 8-methoxy fluoroquinolone, has been found to be highly potent against various bacterial species. Nonetheless, the efficacy of DC-159a against Mycobacterium leprae is yet to be examined. Methodology/Principal Findings To gather data that can support highly effective fluoroquinolones as candidates for new remedies for leprosy treatment, we conducted in vitro assays to assess and compare the inhibitory activities of DC-159a and two fluoroquinolones that are already known to be more effective against M. leprae than ofloxacin. The fluoroquinolone-inhibited DNA supercoiling assay using recombinant DNA gyrases of wild type and ofloxacin-resistant M. leprae revealed that inhibitory activities of DC-159a and sitafloxacin were at most 9.8- and 11.9-fold higher than moxifloxacin. Also the fluoroquinolone–mediated cleavage assay showed that potencies of those drugs were at most 13.5- and 9.8-fold higher than moxifloxacin. In addition, these two drugs retained their inhibitory activities even against DNA gyrases of ofloxacin-resistant M. leprae. Conclusions/Significance The results indicated that DC-159a and sitafloxacin are more effective against wild type and mutant M. leprae DNA gyrases than moxifloxacin, suggesting that these antibacterial drugs can be good candidates that may supersede current fluoroquinolone remedies. DC-159a in particular is very promising because it is classified in a subgroup of fluoroquinolones that is known to be less likely to cause adverse effects. Our results implied that DC-159a is well worth further investigation to ascertain its in vivo effectiveness and clinical safety for humans. PMID:27681932

  1. Physically active men show better semen parameters and hormone values than sedentary men.

    PubMed

    Vaamonde, Diana; Da Silva-Grigoletto, Marzo Edir; García-Manso, Juan Manuel; Barrera, Natalibeth; Vaamonde-Lemos, Ricardo

    2012-09-01

    Physical exercise promotes many health benefits. The present study was undertaken to assess possible semen and hormone differences among physically active (PA) subjects and sedentary subjects (SE). The analyzed qualitative sperm parameters were: volume, sperm count, motility, and morphology; where needed, additional testing was performed. The measured hormones were: follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), cortisol (C), and the ratio between T and C (T/C). Maximum oxygen consumption was also assessed to check for differences in fitness level. Statistically significant differences were found for several semen parameters such as total progressive motility (PA: 60.94 ± 5.03; SE: 56.07 ± 4.55) and morphology (PA: 15.54 ± 1.38, SE: 14.40 ± 1.15). The seminological values observed were supported by differences in hormones, with FSH, LH, and T being higher in PA than in SE (5.68 ± 2.51 vs. 3.14 ± 1.84; 5.95 ± 1.11 vs. 5.08 ± 0.98; 7.68 ± 0.77 vs. 6.49 ± 0.80, respectively). Likewise, the T/C ratio, index of anabolic versus catabolic status, was also higher in PA (0.46 ± 0.11 vs. 0.32 ± 0.07), which further supports the possibility of an improved hormonal environment. The present study shows that there are differences in semen and hormone values of physically active subjects and sedentary subjects. Physically active subjects seem to have a more anabolic hormonal environment and a healthier semen production.

  2. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase

    PubMed Central

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2016-01-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 μM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl− and the decreased HCO3− concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na–K–2Cl electroneutral cotransporter or Cl−/HCO3− anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells. PMID:25868554

  3. Novel, potent and selective inhibitors of protein kinase C show oral anti-inflammatory activity.

    PubMed

    Nixon, J S; Bishop, J; Bradshaw, D; Davis, P D; Hill, C H; Elliott, L H; Kumar, H; Lawton, G; Lewis, E J; Mulqueen, M

    1991-01-01

    Clarification of the precise role of protein kinase C (PKC) in cellular functional responses has been hampered by a lack of potent, selective inhibitors. The structural lead provided by staurosporine, a potent but non-selective protein kinase (PK) inhibitor, was used to derive a series of bis(indolyl)maleimides of which the most potent, Ro 31-8425 (I50: PKC = 8 nM) showed 350-fold selectivity for PKC over cAMP-dependent protein kinase. Ro 31-8425 antagonised cellular processes triggered by phorbol esters (potent, specific PKC activators) and inhibited the allogeneic mixed lymphocyte reaction, suggesting a role for PKC in T-cell activation. Methylation of the primary amine in Ro 31-8425 produced an analogue. Ro 31-8830 which, when administered orally, produced a dose-dependent inhibition of a phorbol ester-induced paw oedema in mice (minimum effective dose = 15 mg/kg). Ro 31-8830 also selectively inhibited the secondary inflammation in a developing adjuvant arthritis model in the rat. The results presented here suggest that these selective inhibitors of PKC may have therapeutic value in the treatment of T-cell-mediated autoimmune diseases.

  4. Aluminum hydroxide nanoparticles show a stronger vaccine adjuvant activity than traditional aluminum hydroxide microparticles.

    PubMed

    Li, Xinran; Aldayel, Abdulaziz M; Cui, Zhengrong

    2014-01-10

    Aluminum hydroxide is used as a vaccine adjuvant in various human vaccines. Unfortunately, despite its favorable safety profile, aluminum hydroxide can only weakly or moderately potentiate antigen-specific antibody responses. When dispersed in an aqueous solution, aluminum hydroxide forms particulates of 1-20μm. There is increasing evidence that nanoparticles around or less than 200nm as vaccine or antigen carriers have a more potent adjuvant activity than large microparticles. In the present study, we synthesized aluminum hydroxide nanoparticles of 112nm. Using ovalbumin and Bacillus anthracis protective antigen protein as model antigens, we showed that protein antigens adsorbed on the aluminum hydroxide nanoparticles induced a stronger antigen-specific antibody response than the same protein antigens adsorbed on the traditional aluminum hydroxide microparticles of around 9.3μm. The potent adjuvant activity of the aluminum hydroxide nanoparticles was likely related to their ability to more effectively facilitate the uptake of the antigens adsorbed on them by antigen-presenting cells. Finally, the local inflammation induced by aluminum hydroxide nanoparticles in the injection sites was milder than that induced by microparticles. Simply reducing the particle size of the traditional aluminum hydroxide adjuvant into nanometers represents a novel and effective approach to improve its adjuvanticity.

  5. Boehmenan, a lignan from Hibiscus ficulneus, showed Wnt signal inhibitory activity.

    PubMed

    Shono, Takumi; Ishikawa, Naoki; Toume, Kazufumi; Arai, Midori A; Ahmed, Firoj; Sadhu, Samir K; Ishibashi, Masami

    2015-07-15

    The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels.

  6. Water Extract of Fructus Hordei Germinatus Shows Antihyperprolactinemia Activity via Dopamine D2 Receptor

    PubMed Central

    Wang, Xiong; Ma, Li; Zhang, En-jing; Zou, Ji-li; Guo, Hao; Peng, Si-wei; Wu, Jin-hu

    2014-01-01

    Objective. Fructus Hordei Germinatus is widely used in treating hyperprolactinemia (hyperPRL) as a kind of Chinese traditional herb in China. In this study, we investigated the anti-hyperPRL activity of water extract of Fructus Hordei Germinatus (WEFHG) and mechanism of action. Methods. Effect of WEFHG on serum prolactin (PRL), estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and hypothalamus protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) levels of hyperPRL rats were investigated. And effect of WEFHG on PRL secretion, D2 receptors, and dopamine transporters (DAT) was studied in MMQ, GH3, and PC12 cells, respectively. Results. WEFHG reduced the secretion of PRL in hyperPRL rats effectively. In MMQ cell, treatment with WEFHG at 1–5 mg/mL significantly suppressed PRL secretion and synthesis. Consistent with a D2-action, WEFHG did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D2 receptor expression but significantly increased the expression of D2 receptors and DAT in PC12 cells. In addition, WEFHG reduced the cAMP and PKA levels of hypothalamus in hyperPRL rats significantly. Conclusions. WEFHG showed anti-hyperPRL activity via dopamine D2 receptor, which was related to the second messenger cAMP and PKA. PMID:25254056

  7. Overview of MSFC's Applied Fluid Dynamics Analysis Group Activities

    NASA Technical Reports Server (NTRS)

    Garcia, Roberto; Wang, Tee-See; Griffin, Lisa; Turner, James E. (Technical Monitor)

    2001-01-01

    This document is a presentation graphic which reviews the activities of the Applied Fluid Dynamics Analysis Group at Marshall Space Flight Center (i.e., Code TD64). The work of this group focused on supporting the space transportation programs. The work of the group is in Computational Fluid Dynamic tool development. This development is driven by hardware design needs. The major applications for the design and analysis tools are: turbines, pumps, propulsion-to-airframe integration, and combustion devices.

  8. Effects of Collaborative Activities on Group Identity in Virtual World

    ERIC Educational Resources Information Center

    Park, Hyungsung; Seo, Sumin

    2013-01-01

    The purpose of this study was to analyze the effects of collaborative activities on group identity in a virtual world such as "Second Life." To achieve this purpose, this study adopted events that promoted participants' interactions using tools inherent in "Second Life." The interactive tools given to the control group in this…

  9. Neural activation in the "reward circuit" shows a nonlinear response to facial attractiveness.

    PubMed

    Liang, Xiaoyun; Zebrowitz, Leslie A; Zhang, Yi

    2010-01-01

    Positive behavioral responses to attractive faces have led neuroscientists to investigate underlying neural mechanisms in a "reward circuit" that includes brain regions innervated by dopamine pathways. Using male faces ranging from attractive to extremely unattractive, disfigured ones, this study is the first to demonstrate heightened responses to both rewarding and aversive faces in numerous areas of this putative reward circuit. Parametric analyses employing orthogonal linear and nonlinear regressors revealed positive nonlinear effects in anterior cingulate cortex, lateral orbital frontal cortex (LOFC), striatum (nucleus accumbens, caudate, putamen), and ventral tegmental area, in addition to replicating previously documented linear effects in medial orbital frontal cortex (MOFC) and LOFC and nonlinear effects in amygdala and MOFC. The widespread nonlinear responses are consistent with single cell recordings in animals showing responses to both rewarding and aversive stimuli, and with some human fMRI investigations of non-face stimuli. They indicate that the reward circuit does not process face valence with any simple dissociation of function across structures. Perceiver gender modulated some responses to our male faces: Women showed stronger linear effects, and men showed stronger nonlinear effects, which may have functional implications. Our discovery of nonlinear responses to attractiveness throughout the reward circuit echoes the history of amygdala research: Early work indicated a linear response to threatening stimuli, including faces; later work also revealed a nonlinear response with heightened activation to affectively salient stimuli regardless of valence. The challenge remains to determine how such dual coding influences feelings, such as pleasure and pain, and guides goal-related behavioral responses, such as approach and avoidance.

  10. Blood group isoantibody stimulation in man by feeding blood group-active bacteria

    PubMed Central

    Springer, Georg F.; Horton, Richard E.

    1969-01-01

    It was investigated whether or not the human blood group isoantibodies A and B could be induced by immunogenic stimuli via natural routes with a kind of antigenic substance to which all humans are commonly exposed, or if the appearance of these antibodies is independent of antigenic stimuli as has long been believed. Escherichia coli O86, which possess high human blood group B and faint A activity in vitro, were fed to healthy humans and those with intestinal disorders. 80% of the sick individuals of blood group O and A responded with a significant rise of anti-B antibodies which was frequently de novo in infants; significant increase of anti-A isoantibodies among blood group O individuals was less frequent. Over one-third of the healthy individuals also had a significant isoantibody increase. Intestinal lesions favor isoantibody stimulation by intestinal bacteria; this view was supported by the study of control infants. Persons of blood group A responded more frequently with anti-B and anti-E. coli O86 antibody production than those of blood group O. Isoantibody increase was accompanied with antibody rise against E. coli O86. Inhalation of E. coli O86 or blood group AH(O)-specific hog mucin also evoked isoantibodies. The induced isoantibodies were specifically inhibited by small amounts of human blood group substances. E. coli O86-induced anti-blood group antibodies in germ-free chickens and preexisting blood group antibodies in ordinary chickens were neutralized by intravenous injection of E. coli O86 lipopolysaccharide. This study demonstrates that human isoantibodies A and B are readily elicited via physiological routes, by blood group-active E. coli, provided the genetically determined apparatus of the host is responsive. Antibodies against a person's own blood group were not formed. Interpretation of these results permits some careful generalizations as to the origin of so-called natural antibodies. PMID:4893685

  11. HATS-2b: A transiting extrasolar planet orbiting a K-type star showing starspot activity

    NASA Astrophysics Data System (ADS)

    Mohler-Fischer, M.; Mancini, L.; Hartman, J. D.; Bakos, G. Á.; Penev, K.; Bayliss, D.; Jordán, A.; Csubry, Z.; Zhou, G.; Rabus, M.; Nikolov, N.; Brahm, R.; Espinoza, N.; Buchhave, L. A.; Béky, B.; Suc, V.; Csák, B.; Henning, T.; Wright, D. J.; Tinney, C. G.; Addison, B. C.; Schmidt, B.; Noyes, R. W.; Papp, I.; Lázár, J.; Sári, P.; Conroy, P.

    2013-10-01

    We report the discovery of HATS-2b, the second transiting extrasolar planet detected by the HATSouth survey. HATS-2b is moving on a circular orbit around a V = 13.6 mag, K-type dwarf star (GSC 6665-00236), at a separation of 0.0230 ± 0.0003 AU and with a period of 1.3541 days. The planetary parameters have been robustly determined using a simultaneous fit of the HATSouth, MPG/ESO 2.2 m/GROND, Faulkes Telescope South/Spectral transit photometry, and MPG/ESO 2.2 m/FEROS, Euler 1.2 m/CORALIE, AAT 3.9 m/CYCLOPS radial-velocity measurements. HATS-2b has a mass of 1.37 ± 0.16 MJ, a radius of 1.14 ± 0.03 RJ, and an equilibrium temperature of 1567 ± 30 K. The host star has a mass of 0.88 ± 0.04 M⊙ and a radius of 0.89 ± 0.02 R⊙, and it shows starspot activity. We characterized the stellar activity by analyzing two photometric follow-up transit light curves taken with the GROND instrument, both obtained simultaneously in four optical bands (covering the wavelength range of 3860-9520 Å). The two light curves contain anomalies compatible with starspots on the photosphere of the host star along the same transit chord. Tables of the individual photometric measurements are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/558/A55

  12. Total alkaloids of Rubus alceifolius Poir shows anti-angiogenic activity in vivo and in vitro.

    PubMed

    Zhao, Jinyan; Lin, Wei; Zhuang, Qunchuan; Zhong, Xiaoyong; Cao, Zhiyun; Hong, Zhenfeng; Peng, Jun

    2014-11-01

    Total alkaloids is an active ingredient of the natural plant Rubus alceifolius Poir, commonly used for the treatment of various cancers. Antitumor effects may be mediated through anti-angiogenic mechanisms. As such, the goal of the present study was to investigate and evaluate the effect of total alkaloids in Rubus alceifolius Poir (TARAP) on tumor angiogenesis and investigate the underlying molecular mechanisms of TARAP action in vivo and in vitro. A chick embryo chorioallantoic membrane (CAM) assay was used to assess angiogenesis in vivo. An MTT assay was performed to determine the viability of human umbilical vein endothelial cells (HUVECs) with and without treatment. Cell cycle progression of HUVECs was examined by FACS analysis with propidium iodide staining. HUVEC migration was determined using a scratch wound method. Tube formation of HUVECs was assessed with an ECMatrix gel system, and mRNA and protein expression of VEGF-A in both HUVECs and HepG2 human hepatocellular carcinoma cells were examined by RT-PCR and ELISA, respectively. Our results showed that TARAP inhibited angiogenesis in the CAM model in vivo and inhibited HUVEC proliferation via blocking cell cycle G1 to S progression in a dose- and time-dependent manners in vitro. Moreover, TARAP inhibited HUVEC migration and tube formation and downregulated mRNA and protein expression of VEGF-A in both HepG2 cells and HUVECs. Our findings suggest that the anti-angiogenic activity of TARAP may partly contribute to its antitumor properties and may be valuable for the treatment of diseases involving pathologic angiogenesis such as cancer.

  13. Applying an Activity System to Online Collaborative Group Work Analysis

    ERIC Educational Resources Information Center

    Choi, Hyungshin; Kang, Myunghee

    2010-01-01

    This study determines whether an activity system provides a systematic framework to analyse collaborative group work. Using an activity system as a unit of analysis, the research examined learner behaviours, conflicting factors and facilitating factors while students engaged in collaborative work via asynchronous computer-mediated communication.…

  14. Overview af MSFC's Applied Fluid Dynamics Analysis Group Activities

    NASA Technical Reports Server (NTRS)

    Garcia, Roberto; Griffin, Lisa; Williams, Robert

    2004-01-01

    This paper presents viewgraphs on NASA Marshall Space Flight Center's Applied Fluid Dynamics Analysis Group Activities. The topics include: 1) Status of programs at MSFC; 2) Fluid Mechanics at MSFC; 3) Relevant Fluid Dynamics Activities at MSFC; and 4) Shuttle Return to Flight.

  15. Mobilizing and Activating Group Demands: The American Agriculture Movement.

    ERIC Educational Resources Information Center

    Browne, William P.

    1983-01-01

    An analysis of the American agriculture movement begun in 1977 provides insight into group behavior, mobilization, and activation. Leaders who had recruited participants and organized local and state activities were interviewed. Problems of organizing, specifically when protest is involved, are also discussed. (KC)

  16. Trithorax group proteins: switching genes on and keeping them active.

    PubMed

    Schuettengruber, Bernd; Martinez, Anne-Marie; Iovino, Nicola; Cavalli, Giacomo

    2011-11-23

    Cellular memory is provided by two counteracting groups of chromatin proteins termed Trithorax group (TrxG) and Polycomb group (PcG) proteins. TrxG proteins activate transcription and are perhaps best known because of the involvement of the TrxG protein MLL in leukaemia. However, in terms of molecular analysis, they have lived in the shadow of their more famous counterparts, the PcG proteins. Recent advances have improved our understanding of TrxG protein function and demonstrated that the heterogeneous group of TrxG proteins is of critical importance in the epigenetic regulation of the cell cycle, senescence, DNA damage and stem cell biology.

  17. Using analogy role-play activity in an undergraduate biology classroom to show central dogma revision.

    PubMed

    Takemura, Masaharu; Kurabayashi, Mario

    2014-01-01

    For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego® blocks (Lego System A/S, Denmark). Students were studying in the course of mathematics, physics, or chemistry, so biology was not among their usual studies. In this exercise, students perform the central dogma role-play and respectively act out nuclear matrix proteins, a transcription factor, an RNA polymerase II, an mRNA transport protein, nuclear pore proteins, a large ribosomal subunit, a small ribosomal subunit, and several amino-acyl tRNA synthetases. Questionnaire results obtained after the activity show that this central dogma role-play analogy holds student interest in the practical molecular biological processes of transcription and translation.

  18. Novel Peptides from Skins of Amphibians Showed Broad-Spectrum Antimicrobial Activities.

    PubMed

    Wang, Ying; Zhang, Yue; Lee, Wen-Hui; Yang, Xinwang; Zhang, Yun

    2016-03-01

    Peptide agents are often considered as potential biomaterials for developing new drugs that can overcome the rising resistance of pathogenic micro-organisms to classic antibiotic treatments. One key source of peptide agents is amphibian skin, as they provide a great deal of naturally occurring antimicrobial peptide (AMP) templates awaiting further exploitation and utilization. In this study, 12 novel AMPs from the skins of 3 ranid frogs, Rana limnocharis, R. exilispinosa, and Amolops afghanus, were identified using a 5' PCR primer. A total of 11 AMPs exhibited similarities with currently known AMP families, including brevinin-1, brevinin-2, esculentin-1, and nigrocin, besides, one AMP, named as Limnochariin, represented a novel AMP family. All 12 AMPs contain a C-terminus cyclic motif and most of them show obvious antimicrobial activities against 18 standard and clinically isolated strains of bacteria, including 4 Gram-positive bacteria, 11 Gram-negative bacteria, and 3 fungus. These findings provide helpful insight that will be useful in the design of anti-infective peptide agents.

  19. Discriminative Latent Models for Recognizing Contextual Group Activities

    PubMed Central

    Lan, Tian; Wang, Yang; Yang, Weilong; Robinovitch, Stephen N.; Mori, Greg

    2012-01-01

    In this paper, we go beyond recognizing the actions of individuals and focus on group activities. This is motivated from the observation that human actions are rarely performed in isolation; the contextual information of what other people in the scene are doing provides a useful cue for understanding high-level activities. We propose a novel framework for recognizing group activities which jointly captures the group activity, the individual person actions, and the interactions among them. Two types of contextual information, group-person interaction and person-person interaction, are explored in a latent variable framework. In particular, we propose three different approaches to model the person-person interaction. One approach is to explore the structures of person-person interaction. Differently from most of the previous latent structured models, which assume a predefined structure for the hidden layer, e.g., a tree structure, we treat the structure of the hidden layer as a latent variable and implicitly infer it during learning and inference. The second approach explores person-person interaction in the feature level. We introduce a new feature representation called the action context (AC) descriptor. The AC descriptor encodes information about not only the action of an individual person in the video, but also the behavior of other people nearby. The third approach combines the above two. Our experimental results demonstrate the benefit of using contextual information for disambiguating group activities. PMID:22144516

  20. Discriminative latent models for recognizing contextual group activities.

    PubMed

    Lan, Tian; Wang, Yang; Yang, Weilong; Robinovitch, Stephen N; Mori, Greg

    2012-08-01

    In this paper, we go beyond recognizing the actions of individuals and focus on group activities. This is motivated from the observation that human actions are rarely performed in isolation; the contextual information of what other people in the scene are doing provides a useful cue for understanding high-level activities. We propose a novel framework for recognizing group activities which jointly captures the group activity, the individual person actions, and the interactions among them. Two types of contextual information, group-person interaction and person-person interaction, are explored in a latent variable framework. In particular, we propose three different approaches to model the person-person interaction. One approach is to explore the structures of person-person interaction. Differently from most of the previous latent structured models, which assume a predefined structure for the hidden layer, e.g., a tree structure, we treat the structure of the hidden layer as a latent variable and implicitly infer it during learning and inference. The second approach explores person-person interaction in the feature level. We introduce a new feature representation called the action context (AC) descriptor. The AC descriptor encodes information about not only the action of an individual person in the video, but also the behavior of other people nearby. The third approach combines the above two. Our experimental results demonstrate the benefit of using contextual information for disambiguating group activities.

  1. Syzyguim guineense Extracts Show Antioxidant Activities and Beneficial Activities on Oxidative Stress Induced by Ferric Chloride in the Liver Homogenate.

    PubMed

    Pieme, Constant Anatole; Ngoupayo, Joseph; Nkoulou, Claude Herve Khou-Kouz; Moukette, Bruno Moukette; Nono, Borgia Legrand Njinkio; Moor, Vicky Jocelyne Ama; Minkande, Jacqueline Ze; Ngogang, Jeanne Yonkeu

    2014-09-19

    The aim of this study was to determine the in vitro antioxidant activity, free radical scavenging property and the beneficial effects of extracts of various parts of Syzygium guineense in reducing oxidative stress damage in the liver. The effects of extracts on free radicals were determined on radicals DPPH, ABTS, NO and OH followed by the antioxidant properties using Ferric Reducing Antioxidant Power assay (FRAP) and hosphomolybdenum (PPMB). The phytochemical screening of these extracts was performed by determination of the phenolic content. The oxidative damage inhibition in the liver was determined by measuring malondialdehyde (MDA) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase. Overall, the bark extract of the ethanol/water or methanol showed the highest radical scavenging activities against DPPH, ABTS and OH radicals compared to the other extracts. This extract also contained the highest phenolic content implying the potential contribution of phenolic compounds towards the antioxidant activities. However, the methanol extract of the root demonstrated the highest protective effects of SOD and CAT against ferric chloride while the hydro-ethanol extract of the leaves exhibited the highest inhibitory effects on lipid peroxidation. These findings suggest that antioxidant properties of S. guineense extracts could be attributed to phenolic compounds revealed by phytochemical studies. Thus, the present results indicate clearly that the extracts of S. guineense possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants. The antioxidant properties of the bark extract may thus sustain its various biological activities.

  2. Syzyguim guineense Extracts Show Antioxidant Activities and Beneficial Activities on Oxidative Stress Induced by Ferric Chloride in the Liver Homogenate

    PubMed Central

    Pieme, Constant Anatole; Ngoupayo, Joseph; Khou-Kouz Nkoulou, Claude Herve; Moukette Moukette, Bruno; Njinkio Nono, Borgia Legrand; Ama Moor, Vicky Jocelyne; Ze Minkande, Jacqueline; Yonkeu Ngogang, Jeanne

    2014-01-01

    The aim of this study was to determine the in vitro antioxidant activity, free radical scavenging property and the beneficial effects of extracts of various parts of Syzygium guineense in reducing oxidative stress damage in the liver. The effects of extracts on free radicals were determined on radicals DPPH, ABTS, NO and OH followed by the antioxidant properties using Ferric Reducing Antioxidant Power assay (FRAP) and hosphomolybdenum (PPMB). The phytochemical screening of these extracts was performed by determination of the phenolic content. The oxidative damage inhibition in the liver was determined by measuring malondialdehyde (MDA) as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase. Overall, the bark extract of the ethanol/water or methanol showed the highest radical scavenging activities against DPPH, ABTS and OH radicals compared to the other extracts. This extract also contained the highest phenolic content implying the potential contribution of phenolic compounds towards the antioxidant activities. However, the methanol extract of the root demonstrated the highest protective effects of SOD and CAT against ferric chloride while the hydro-ethanol extract of the leaves exhibited the highest inhibitory effects on lipid peroxidation. These findings suggest that antioxidant properties of S. guineense extracts could be attributed to phenolic compounds revealed by phytochemical studies. Thus, the present results indicate clearly that the extracts of S. guineense possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants. The antioxidant properties of the bark extract may thus sustain its various biological activities. PMID:26785075

  3. Mice lacking brain-type creatine kinase activity show defective thermoregulation

    PubMed Central

    Streijger, Femke; Pluk, Helma; Oerlemans, Frank; Beckers, Gaby; Bianco, Antonio C.; Ribeiro, Miriam O.; Wieringa, Bé; Van der Zee, Catharina E.E.M.

    2010-01-01

    The cytosolic brain-type creatine kinase and mitochondrial ubiquitous creatine kinase (CK-B and UbCKmit) are expressed during the prepubescent and adult period of mammalian life. These creatine kinase (CK) isoforms are present in neural cell types throughout the central and peripheral nervous system and in smooth muscle containing tissues, where they have an important role in cellular energy homeostasis. Here, we report on the coupling of CK activity to body temperature rhythm and adaptive thermoregulation in mice. With both brain-type CK isoforms being absent, the body temperature reproducibly drops ~1.0°C below normal during every morning (inactive) period in the daily cycle. Facultative non-shivering thermogenesis is also impaired, since CK−−/−− mice develop severe hypothermia during 24 h cold exposure. A relationship with fat metabolism was suggested because comparison of CK−−/−− mice with wildtype controls revealed decreased weight gain associated with less white and brown fat accumulation and smaller brown adipocytes. Also, circulating levels of glucose, triglycerides and leptin are reduced. Extensive physiological testing and uncoupling protein1 analysis showed, however, that the thermogenic problems are not due to abnormal responsiveness of brown adipocytes, since noradrenaline infusion produced a normal increase of body temperature. Moreover, we demonstrate that the cyclic drop in morning temperature is also not related to altered rhythmicity with reduced locomotion, diminished food intake or increased torpor sensitivity. Although several integral functions appear altered when CK is absent in the brain, combined findings point into the direction of inefficient neuronal transmission as the dominant factor in the thermoregulatory defect. PMID:19419668

  4. SYNTHESIS AND BIOLOGICAL ACTIVITY OF SULFUR COMPOUNDS SHOWING STRUCTURAL ANALOGY WITH COMBRETASTATIN A-4

    PubMed Central

    dos Santos, Edson dos A.; Prado, Paulo C.; de Carvalho, Wanderley R.; de Lima, Ricardo V.; Beatriz e, Adilson; de Lima, Dênis P.; Hamel, Ernest; Dyba, Marzena A.; Albuquerque, Sergio

    2013-01-01

    We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15). PMID:23766547

  5. SYNTHESIS AND BIOLOGICAL ACTIVITY OF SULFUR COMPOUNDS SHOWING STRUCTURAL ANALOGY WITH COMBRETASTATIN A-4.

    PubMed

    Dos Santos, Edson Dos A; Prado, Paulo C; de Carvalho, Wanderley R; de Lima, Ricardo V; Beatriz E, Adilson; de Lima, Dênis P; Hamel, Ernest; Dyba, Marzena A; Albuquerque, Sergio

    2013-02-01

    We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15).

  6. Residue organic mixtures from drinking water show in vitro mutagenic and transforming activity.

    PubMed

    Loper, J C; Lang, D R; Schoeny, R S; Richmond, B B; Gallagher, P M; Smith, C C

    1978-01-01

    Indications of possible health effects of residue organics in drinking water have been sought using short-term tests of mutagenic and transforming activity. Ten percent or less of the total organic material in drinking water has been identified; the remainder is believed to include thousands of unknown nonvolatile compounds. Residual organics were concentrated from drinking water from representative U.S. cities by reverse osmosis followed by liquid-liquid extraction [yielding the reverse osmosis concentrate-organic extract (ROC-OE) fraction] and sorption-desorption on XAD-2 resin. Samples of these residue organics were provided by the Environmental Protection Agency for bioassay. They were examined for mutagenic activity by using Salmonella tester strains (primarily TA98 and TA100) and for transforming activity by using mouse fibroblasts (BALB/3T3 clone 1-13). City-specific patterns of dose-dependent bacterial mutagenesis and of bacterial toxicity were observed for these samples and for subfractions generated by sequential extractions with hexane, ethyl ether, and acetone. Mutagenic effects were essentially independent of a microsome activation system prepared from liver of Aroclor 1254-induced rats. On the basis of strain-specific effects in mutagenesis and differential distributions of mutagenic activity during liquid-liquid extraction, at least some of the active compounds are thought to be acidic, frameshift mutagens. The ROC-OE fraction of a New Orleans sample transformed BALB/3T3 cells in replicate experiments. By comparison with the bacterial mutagenesis data, cell transformation is a relatively sensitive method for detecting possible mutagenic and carcinogenic activity in this sample. The appropriateness of these systems for the assay of complex mixtures and the degree to which reverse osmosis concentrates contain the unaltered organic compounds in the original samples are discussed.

  7. Characterization of inhibitory mechanism and antifungal activity between group-1 and group-2 phytocystatins from taro (Colocasia esculenta).

    PubMed

    Wang, Ke-Ming; Kumar, Senthil; Cheng, Yi-Sheng; Venkatagiri, Shripathi; Yang, Ai-Hwa; Yeh, Kai-Wun

    2008-10-01

    Tarocystatin from Colocasia esculenta, a group-2 phytocystatin, is a defense protein against phytopathogenic nematodes and fungi. It is composed of a highly conserved N-terminal region, which is homological to group-1 cystatin, and a repetitive peptide at the C-terminus. The purified recombinant proteins of tarocystatin, such as full-length (FL), N-terminus (Nt) and C-terminus (Ct) peptides, were produced and their inhibitory activities against papain as well as their antifungal effects were investigated. Kinetic analysis revealed that FL peptide exhibited mixed type inhibition (K(ia) = 0.098 microM and K(ib) = 0.252 microM) and Nt peptide showed competitive inhibition (K(i) = 0.057 microM), whereas Ct peptide possessed weak papain activation properties. A shift in the inhibitory pattern from competitive inhibition of Nt peptide alone to mixed type inhibition of FL peptide implied that the Ct peptide has an regulatory effect on the function of FL peptide. Based on the inhibitory kinetics of FL (group-2) and Nt (group-1) peptides on papain activity, an inhibitory mechanism of group-2 phytocystatins and a regulatory mechanism of extended Ct peptide have each been proposed. By contrast, the antifungal activity of Nt peptide appeared to be greater than that of FL peptide, and the Ct peptide showed no effect on antifungal activity, indicating that the antifungal effect is not related to proteinase inhibitory activity. The results are valid for most phytocystatins with respect to the inhibitory mechanism against cysteine proteinase.

  8. Forestry Activities. A Guide for Youth Group Leaders.

    ERIC Educational Resources Information Center

    Forest Service (USDA), Washington, DC.

    Twenty-six activities related to forestry, conservation, and outdoor education comprise the content of this leader's guide. Designed for use with youth groups, ideas and techniques range from forest conservation mobiles, locating forest fires, and Christmas tree uses to litterbug campaigns, watershed experiments, and crossword puzzles. Activities…

  9. Active Classroom Participation in a Group Scribbles Primary Science Classroom

    ERIC Educational Resources Information Center

    Chen, Wenli; Looi, Chee-Kit

    2011-01-01

    A key stimulus of learning efficacy for students in the classroom is active participation and engagement in the learning process. This study examines the nature of teacher-student and student-student discourse when leveraged by an interactive technology--Group Scribbles (GS) in a Primary 5 Science classroom in Singapore which supports rapid…

  10. A Boronic Acid Conjugate of Angiogenin that Shows ROS-Responsive Neuroprotective Activity.

    PubMed

    Hoang, Trish T; Smith, Thomas P; Raines, Ronald T

    2017-03-01

    Angiogenin (ANG) is a human ribonuclease that is compromised in patients with amyotrophic lateral sclerosis (ALS). ANG also promotes neovascularization, and can induce hemorrhage and encourage tumor growth. The causal neurodegeneration of ALS is associated with reactive oxygen species, which are also known to elicit the oxidative cleavage of carbon-boron bonds. We have developed a synthetic boronic acid mask that restrains the ribonucleolytic activity of ANG. The masked ANG does not stimulate endothelial cell proliferation but protects astrocytes from oxidative stress. By differentiating between the two dichotomous biological activities of ANG, this strategy could provide a viable pharmacological approach for the treatment of ALS.

  11. Water Works: A Great Show on Earth. Classroom Activities for Third and Fourth Grades.

    ERIC Educational Resources Information Center

    McClure, Judy; Clark, Neil

    This curriculum guide is divided into five lessons, each containing several activities that reflect the natural path of inquiry that third or fourth grade students might take in considering the water that arrives in their bathroom sinks each morning. Starting from the familiar faucet, the students are encouraged to reflect on their own habits and…

  12. A novel solubility-enhanced curcumin formulation showing stability and maintenance of anticancer activity.

    PubMed

    Zhang, Fang; Koh, Gar Yee; Jeansonne, Duane P; Hollingsworth, Javoris; Russo, Paul S; Vicente, Graca; Stout, Rhett W; Liu, Zhijun

    2011-07-01

    Curcumin (CUR) is an active food compound, but its insolubility and instability in water contributes to low bioavailability. In this study, the solubility of CUR was enhanced by utilizing the solubilizing properties of rubusoside (RUB). The solubility of CUR in water increased linearly from 61 μg/mL to 2.318 mg/mL in the presence of RUB ranging from 1% to 10% (w/v). Dynamic light scattering and transmission electron microscopy studies found that CUR and RUB formed CUR-RUB nanoparticle (∼8 nm) complexes. The RUB-solubilized CUR was stable in physiological conditions and did not precipitate when diluted or degrade when spray-dried to a completely reconstitutable powder. Furthermore, cell viability assays demonstrated the efficacy of RUB-solubilized CUR against human colon, breast, and pancreatic cancer cell lines. The development of this new solubilized, stable, and biologically active CUR formulation lays the foundation for future bioavailability improvement.

  13. Identification of MET and SRC Activation in Melanoma Cell Lines Showing Primary Resistance to PLX403212

    PubMed Central

    Vergani, Elisabetta; Vallacchi, Viviana; Frigerio, Simona; Deho, Paola; Mondellini, Piera; Perego, Paola; Cassinelli, Giuliana; Lanzi, Cinzia; Testi, Maria Adele; Rivoltini, Licia; Bongarzone, Italia; Rodolfo, Monica

    2011-01-01

    PLX4032/vemurafenib is a first-in-class small-molecule BRAFV600E inhibitor with clinical activity in patients with BRAF mutant melanoma. Nevertheless, drug resistance develops in treated patients, and strategies to overcome primary and acquired resistance are required. To explore the molecular mechanisms involved in primary resistance to PLX4032, we investigated its effects on cell proliferation and signaling in a panel of 27 genetically characterized patient-derived melanoma cell lines. Cell sensitivity to PLX4032 was dependent on BRAFV600E and independent from other gene alterations that commonly occur in melanoma such as PTEN loss, BRAF, and MITF gene amplification. Two cell lines lacking sensitivity to PLX4032 and harboring a different set of genetic alterations were studied as models of primary resistance. Treatment with the MEK inhibitor UO126 but not with PLX4032 inhibited cell growth and ERK activation. Resistance to PLX4032 was maintained after CRAF down-regulation by siRNA indicating alternative activation of MEK-ERK signaling. Genetic characterization by multiplex ligation-dependent probe amplification and analysis of phosphotyrosine signaling by MALDI-TOF mass spectrometry analysis revealed the activation of MET and SRC signaling, associated with the amplification of MET and of CTNNB1 and CCND1 genes, respectively. The combination of PLX4032 with drugs or siRNA targeting MET was effective in inhibiting cell growth and reducing cell invasion and migration in melanoma cells with MET amplification; similar effects were observed after targeting SRC in the other cell line, indicating a role for MET and SRC signaling in primary resistance to PLX4032. Our results support the development of classification of melanoma in molecular subtypes for more effective therapies. PMID:22241959

  14. NF-κB dynamics show digital activation and analog information processing in cells

    NASA Astrophysics Data System (ADS)

    Tay, Savas; Hughey, Jake; Lee, Timothy; Lipniacki, Tomasz; Covert, Markus; Quake, Stephen

    2010-03-01

    Cells operate in ever changing environments using extraordinary communication capabilities. Cell-to-cell communication is mediated by signaling molecules that form spatiotemporal concentration gradients, which requires cells to respond to a wide range of signal intensities. We used high-throughput microfluidic cell culture, quantitative gene expression analysis and mathematical modeling to investigate how single mammalian cells respond to different concentrations of the signaling molecule TNF-α via the transcription factor NF-κB. We measured NF-κB activity in thousands of live cells under TNF-α doses covering four orders of magnitude. In contrast to population studies, the activation is a stochastic, switch-like process at the single cell level with fewer cells responding at lower doses. The activated cells respond fully and express early genes independent of the TNF-α concentration, while only high dose stimulation results in the expression of late genes. Cells also encode a set of analog parameters such as the NF-κB peak intensity, response time and number of oscillations to modulate the outcome. We developed a stochastic model that reproduces both the digital and analog dynamics as well as the gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-α induced NF-κB signaling in various types of cells.

  15. Enhanced excitatory synaptic network activity following transient group I metabotropic glutamate activation.

    PubMed

    Pan, Y-Z; Rutecki, P A

    2014-09-05

    Prolonged activation of group I metabotropic glutamate receptors (mGluRs) using the agonist (S)-3,5-dihydroxyphenylglycine (DHPG) produces long-lasting changes in the CA3 region of the hippocampal slice. Changes in CA3 pyramidal neuron excitability that follow DHPG exposure result in abnormal network activity manifest by epileptiform activity that consists of interictal and longer lasting ictal epileptiform discharges. In this study we evaluated changes in synaptic activity of CA3 neurons in rat hippocampal slices that occurred after exposure to DHPG. Whole-cell voltage-clamp recordings were made from visually identified CA3 neurons in control artificial cerebrospinal fluid at times greater than 1h after DHPG exposure. Compared to control slices, neurons from slices exposed to DHPG showed enhanced amplitude and frequency of spontaneously occurring excitatory postsynaptic currents (EPSCs) without a concurrent change in inhibitory postsynaptic current (IPSC) amplitude or frequency. Miniature EPSCs were not affected by DHPG exposure but mIPSCs occurred less frequently and were of reduced amplitude. IPSCs recorded in the presence of ionotropic glutamate receptor blockade occurred less frequently in neurons that had been exposed to DHPG. Monosynaptic-evoked IPSPs were also reduced in amplitude in neurons that had been exposed to DHPG. Taken together, these findings demonstrated an enhanced network excitability of the CA3 region and failure of compensatory synaptic inhibition. We propose that prolonged activation of group I mGluR that may occur under conditions of pathological glutamate release results in long-lasting changes in CA3 synaptic network activity and epileptiform activity driven by excessive synaptic excitation.

  16. Modulation of Group I Ribozyme Activity by Cationic Porphyrins

    PubMed Central

    Matsumura, Shigeyoshi; Ito, Tatsunobu; Tanaka, Takahiro; Furuta, Hiroyuki; Ikawa, Yoshiya

    2015-01-01

    The effects of cationic porphyrins on the catalytic activities of four group I ribozymes were investigated. A cationic porphyrin possessing four pyridinium moieties (pPyP) inhibited two group IC3 ribozymes (Syn Rz and Azo Rz) and a group IC1 ribozyme (Tet Rz). In the case of a group IA2 ribozyme (Td Rz), however, pPyP served not only as an inhibitor but also as an activator, and the effects of pPyP were dependent on its concentration. To analyze the structural and electronic factors determining the effects of pPyP on group I ribozymes, three cationic porphyrins (pPyNCP, pPyF4P, and TMPyP) were also examined. As interactions between small organic molecules and nucleic acids are attractive and important issues in biochemistry and biotechnology, this study contributes to the development of porphyrin-based molecules that can modulate functions of structured RNA molecules. PMID:25811638

  17. [The enzyme activity of bacilli showing promise for incorporation into biopreparations].

    PubMed

    Slabospitskaia, A T; Krymovskaia, S S; Reznik, S R

    1990-01-01

    The enzymic activity (amalyse, protease, lipase, pectolytic and cellulase) has been studied in 5 strains of aerobic spore-forming bacteria (Bacillus subtilis, B. licheniformis, B. coagulans, B. pumilis, B. badius) being of interest for creation of medical and prophylactic biopreparations. The above-mentioned enzymes were found in some studied strains. This may provide participation of bacilli in the degradation processes of a number of substrates in the digestive tract of a human being and animals and is an advantage of preparations from the genus Bacillus bacteria as compared with the available biopreparations of other microbial cultures for prophylaxis and treatment of gastrointestinal diseases.

  18. DHPG Activation of Group 1 mGluRs in BLA Enhances Fear Conditioning

    ERIC Educational Resources Information Center

    Rudy, Jerry W.; Matus-Amat, Patricia

    2009-01-01

    Group 1 metabotropic glutamate receptors are known to play an important role in both synaptic plasticity and memory. We show that activating these receptors prior to fear conditioning by infusing the group 1 mGluR agonist, (R.S.)-3,5-dihydroxyphenylglycine (DHPG), into the basolateral region of the amygdala (BLA) of adult Sprague-Dawley rats…

  19. Need for Cognition and Active Information Search in Small Student Groups

    ERIC Educational Resources Information Center

    Curseu, Petru Lucian

    2011-01-01

    In a sample of 213 students organized in 44 groups this study tests the impact of need for cognition on active information search by using a multilevel analysis. The results show that group members with high need for cognition seek more advice in task related issues than those with low need for cognition and this pattern of information exchange is…

  20. Alcoholic Extract of Eclipta alba Shows In Vitro Antioxidant and Anticancer Activity without Exhibiting Toxicological Effects

    PubMed Central

    Arya, Rakesh Kumar; Dev, Kapil; Sharma, Chetan; Hossain, Zakir; Meena, Sanjeev; Arya, K. R.; Gayen, J. R.

    2017-01-01

    As per WHO estimates, 80% of people around the world use medicinal plants for the cure and prevention of various diseases including cancer owing to their easy availability and cost effectiveness. Eclipta alba has long been used in Ayurveda to treat liver diseases, eye ailments, and hair related disorders. The promising medicinal value of E. alba prompted us to study the antioxidant, nontoxic, and anticancer potential of its alcoholic extract. In the current study, we evaluated the in vitro cytotoxic and antioxidant effect of the alcoholic extract of Eclipta alba (AEEA) in multiple cancer cell lines along with control. We have also evaluated its effect on different in vivo toxicity parameters. Here, we found that AEEA was found to be most active in most of the cancer cell lines but it significantly induced apoptosis in human breast cancer cell lines by disrupting mitochondrial membrane potential and DNA damage. Moreover, AEEA treatment inhibited migration in both MCF 7 and MDA-MB-231 cells in a dose dependent manner. Further, AEEA possesses robust in vitro antioxidant activity along with high total phenolic and flavonoid contents. In summary, our results indicate that Eclipta alba has enormous potential in complementary and alternative medicine for the treatment of cancer. PMID:28250894

  1. Heterocyclic aromatic hydrocarbons show estrogenic activity upon metabolization in a recombinant transactivation assay.

    PubMed

    Brinkmann, Markus; Maletz, Sibylle; Krauss, Martin; Bluhm, Kerstin; Schiwy, Sabrina; Kuckelkorn, Jochen; Tiehm, Andreas; Brack, Werner; Hollert, Henner

    2014-05-20

    Heterocyclic aromatic hydrocarbons (hetero-PAHs) are increasingly studied at contaminated sites; especially at former industrial facilities where coal tar-oil was handled, e.g., wood treatment plants, high concentrations of hetero-PAHs are frequently detected in groundwater plumes. In previous studies, fractions of groundwater with high estrogenic activity contained hetero-PAHs and their hydroxylated metabolites. To evaluate this preliminary evidence, selected hetero-PAHs were screened for their estrogenic activity in lyticase yeast estrogen screen (LYES) and ER CALUX. All tested substances were inactive in the LYES. Hetero-PAHs such as acridine, xanthene, indole, 2-methylbenzofuran, 2,3-dimethylbenzofuran, dibenzofuran, dibenzothiophene, quinoline, and 6-methylquinoline were positive in the ER CALUX, with estradiol equivalence factors (EEFs) from 2.85 × 10(-7) to 3.18 × 10(-5). The EEF values of these substances were comparable to those of other xenoestrogens (e.g., alkylphenols or bisphenol A) that are sometimes found in surface water. Chemical analyses revealed that T47Dluc cells could metabolize most of the substances. Among the metabolites (tentatively) identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were hydroxides and their keto tautomers, sulfates, sulfoxides, and N-oxides. Because of their high concentrations measured in groundwater, we conclude that hetero-PAHs and metabolites may be a potential risk and should be the subject of further research.

  2. X-ray microtomography shows pore structure and tortuosity in alkali-activated binders

    SciTech Connect

    Provis, John L.; Myers, Rupert J.; White, Claire E.; Rose, Volker; Deventer, Jannie S.J. van

    2012-06-15

    Durability of alkali-activated binders is of vital importance in their commercial application, and depends strongly on microstructure and pore network characteristics. X-ray microtomography ({mu}CT) offers, for the first time, direct insight into microstructural and pore structure characteristics in three dimensions. Here, {mu}CT is performed on a set of sodium metasilicate-activated fly ash/slag blends, using a synchrotron beamline instrument. Segmentation of the samples into pore and solid regions is then conducted, and pore tortuosity is calculated by a random walker method. Segmented porosity and diffusion tortuosity are correlated, and vary as a function of slag content (slag addition reduces porosity and increases tortuosity), and sample age (extended curing gives lower porosity and higher tortuosity). This is particularly notable for samples with {>=} 50% slag content, where a space-filling calcium (alumino)silicate hydrate gel provides porosity reductions which are not observed for the sodium aluminosilicate ('geopolymer') gels which do not chemically bind water of hydration.

  3. Medicinal plants and their isolated compounds showing anti-Trichomonas vaginalis- activity.

    PubMed

    Mehriardestani, Mozhgan; Aliahmadi, Atousa; Toliat, Tayebeh; Rahimi, Roja

    2017-04-01

    Trichomonas vaginalis is a major of non-viral sexually-transmitted infection and an important cause of serious obstetrical and gynecological complications. Treatment options for trichomoniasis are limited to nitroimidazole compounds. The increasing resistance and allergic reactions to nitroimidazole and recurrent trichomoniasis make it essential to identify and develop new drugs against trichomoniasis. Medicinal plants are an important source for discovery of new medications. This review discusses the anti-trichomonas effects of medicinal plants and their chemical constituents to find better options against this pathogenic protozoon. Electronic databases were searched to collect all data from the year 2000 through September 2015 for in vitro, in vivo and clinical studies on the effect of medicinal plants on T. vaginalis. A total of 95 in vitro and clinical studies were identified. Only four human studies were found in this review. The Asteracea, Lamiaceae and Myrtaceae families contained the greatest number of plants with anti-trichomonas activity. Persea americana, Ocimum basilicum and Verbascum thapsus were the most efficacious against T. vaginalis. Plant metabolites containing alkaloids, isoflavonoid glucosides, essential oils, lipids, saponins and sesquiterpene lactones were found to possess anti-trichomonas properties. Assessing the structure-activity of highly-potent anti-trichomonas phytochemicals is suggested for finding natural, semisynthetic and synthetic anti-trichomonas compounds. Further clinical studies are necessary for confirmation of natural anti-trichomonas substances and completion of their safety profiles.

  4. Bacillus cereus strain S2 shows high nematicidal activity against Meloidogyne incognita by producing sphingosine

    PubMed Central

    Gao, Huijuan; Qi, Gaofu; Yin, Rong; Zhang, Hongchun; Li, Chenggang; Zhao, Xiuyun

    2016-01-01

    Plant-parasitic nematodes cause serious crop losses worldwidely. This study intended to discover the antagonistic mechanism of Bacillus cereus strain S2 against Meloidogyne incognita. Treatment with B. cereus strain S2 resulted in a mortality of 77.89% to Caenorhabditis elegans (a model organism) and 90.96% to M. incognita. In pot experiment, control efficiency of B. cereus S2 culture or supernatants were 81.36% and 67.42% towards M. incognita, respectively. In field experiment, control efficiency was 58.97% towards M. incognita. Nematicidal substances were isolated from culture supernatant of B. cereus S2 by polarity gradient extraction, silica gel column chromatography and HPLC. Two nematicidal compounds were identified as C16 sphingosine and phytosphingosine by LC-MS. The median lethal concentration of sphingosine was determined as 0.64 μg/ml. Sphingosine could obviously inhibit reproduction of C. elegans, with an inhibition rate of 42.72% for 24 h. After treatment with sphingosine, ROS was induced in intestinal tract, and genital area disappeared in nematode. Furthermore, B. cereus S2 could induce systemic resistance in tomato, and enhance activity of defense-related enzymes for biocontrol of M. incognita. This study demonstrates the nematicidal activity of B. cereus and its product sphingosine, as well provides a possibility for biocontrol of M. incognita. PMID:27338781

  5. Arabidopsis profilin isoforms, PRF1 and PRF2 show distinctive binding activities and subcellular distributions.

    PubMed

    Wang, Feng; Jing, Yanping; Wang, Zhen; Mao, Tonglin; Samaj, Jozef; Yuan, Ming; Ren, Haiyun

    2009-02-01

    Profilin is an actin-binding protein that shows complex effects on the dynamics of the actin cytoskeleton. There are five profilin isoforms in Arabidopsis thaliana L. However, it is still an open question whether these isoforms are functionally different. In the present study, two profilin isoforms from Arabidopsis, PRF1 and PRF2 were fused with green fluorescent protein (GFP) tag and expressed in Escherichia coli and A. thaliana in order to compare their biochemical properties in vitro and their cellular distributions in vivo. Biochemical analysis revealed that fusion proteins of GFP-PRF1 and GFP-PRF2 can bind to poly-L-proline and G-actin showing remarkable differences. GFP-PRF1 has much higher affinities for both poly-L-proline and G-actin compared with GFP-PRF2. Observations of living cells in stable transgenic A. thaliana lines revealed that 35S::GFP-PRF1 formed a filamentous network, while 35S::GFP-PRF2 formed polygonal meshes. Results from the treatment with latrunculin A and a subsequent recovery experiment indicated that filamentous alignment of GFP-PRF1 was likely associated with actin filaments. However, GFP-PRF2 localized to polygonal meshes resembling the endoplasmic reticulum. Our results provide evidence that Arabidopsis profilin isoforms PRF1 and PRF2 have different biochemical affinities for poly-L-proline and G-actin, and show distinctive localizations in living cells. These data suggest that PRF1 and PRF2 are functionally different isoforms.

  6. Helicobacter pylori genotyping from American indigenous groups shows novel Amerindian vacA and cagA alleles and Asian, African and European admixture.

    PubMed

    Camorlinga-Ponce, Margarita; Perez-Perez, Guillermo; Gonzalez-Valencia, Gerardo; Mendoza, Irma; Peñaloza-Espinosa, Rosenda; Ramos, Irma; Kersulyte, Dangeruta; Reyes-Leon, Adriana; Romo, Carolina; Granados, Julio; Muñoz, Leopoldo; Berg, Douglas E; Torres, Javier

    2011-01-01

    It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America.

  7. Helicobacter pylori Genotyping from American Indigenous Groups Shows Novel Amerindian vacA and cagA Alleles and Asian, African and European Admixture

    PubMed Central

    Camorlinga-Ponce, Margarita; Perez-Perez, Guillermo; Gonzalez-Valencia, Gerardo; Mendoza, Irma; Peñaloza-Espinosa, Rosenda; Ramos, Irma; Kersulyte, Dangeruta; Reyes-Leon, Adriana; Romo, Carolina; Granados, Julio; Muñoz, Leopoldo; Berg, Douglas E.; Torres, Javier

    2011-01-01

    It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America. PMID:22073291

  8. γ Sulphate PNA (PNA S): highly selective DNA binding molecule showing promising antigene activity.

    PubMed

    Avitabile, Concetta; Moggio, Loredana; Malgieri, Gaetano; Capasso, Domenica; Di Gaetano, Sonia; Saviano, Michele; Pedone, Carlo; Romanelli, Alessandra

    2012-01-01

    Peptide Nucleic Acids (PNAs), nucleic acid analogues showing high stability to enzyme degradation and strong affinity and specificity of binding toward DNA and RNA are widely investigated as tools to interfere in gene expression. Several studies have been focused on PNA analogues with modifications on the backbone and bases in the attempt to overcome solubility, uptake and aggregation issues. γ PNAs, PNA derivatives having a substituent in the γ position of the backbone show interesting properties in terms of secondary structure and affinity of binding toward complementary nucleic acids. In this paper we illustrate our results obtained on new analogues, bearing a sulphate in the γ position of the backbone, developed to be more DNA-like in terms of polarity and charge. The synthesis of monomers and oligomers is described. NMR studies on the conformational properties of monomers and studies on the secondary structure of single strands and triplexes are reported. Furthermore the hybrid stability and the effect of mismatches on the stability have also been investigated. Finally, the ability of the new analogue to work as antigene, interfering with the transcription of the ErbB2 gene on a human cell line overexpressing ErbB2 (SKBR3), assessed by FACS and qPCR, is described.

  9. Montmorillonite enhanced ciprofloxacin transport in saturated porous media with sorbed ciprofloxacin showing antibiotic activity

    NASA Astrophysics Data System (ADS)

    Chen, Hao; Gao, Bin; Yang, Liu-Yan; Ma, Lena Q.

    2015-02-01

    Antibiotic ciprofloxacin (CIP) is immobile in the subsurface but it has been frequently detected in the aquatic system. Therefore it is important to investigate the factors impacting CIP's mobilization in aquifer. Laboratory columns packed with sand were used to test colloid-facilitated CIP transport by 1) using kaolinite or montmorillonite to mobilize presorbed-CIP in a column or 2) co-transporting with CIP by pre-mixing them before transport. The Langmuir model showed that CIP sorption by montmorillonite (23 g kg- 1) was 100 times more effective than sand or kaolinite. Even with strong CIP complexation ability to Fe/Al coating on sand surface, montmorillonite promoted CIP transport, but not kaolinite. All presorbed-CIP by sand was mobilized by montmorillonite after 3 pore volumes through co-transporting of CIP with montmorillonite. The majority of CIP was fixed onto the montmorillonite interlayer but still showed inhibition of bacteria growth. Our results suggested that montmorillonite with high CIP sorption ability can act as a carrier to enhance CIP's mobility in aquifer.

  10. A nanoporous metallic mat showing excellent and stable surface enhanced Raman spectroscopy activities.

    PubMed

    Kim, Nam-Jung; Lin, Mengshi

    2010-08-01

    A novel nanoporous mat structure was made of gold nanoparticles through a simple, inexpensive self-assembly process as a bottom-up approach to produce an affordable and high-quality SERS substrate. This nanostructure mat shows an excellent SERS reproducibility, physical stability, and strong Raman enhancement, which may satisfy all the criteria as a universal-type SERS substrate. The limit of detection for crystal violet dye on the nanostructured substrates is estimated to reach ppb levels and the SERS enhancement factor is found to be two orders of magnitude higher than that from conventional de-alloy nanoporous films. Mechanical strength of the nano-cluster network can be increased by a post-assembly annealing process. The nanoparticle-based SERS substrate holds promise in practical sensing applications toward a rapid determination of harmful substances or contaminants in food and environment.

  11. Estradiol shows anti-skin cancer activities through decreasing MDM2 expression.

    PubMed

    Li, Li; Feng, Jianguo; Chen, Ying; Li, Shun; Ou, Mengting; Sun, Weichao; Tang, Liling

    2017-01-31

    Estradiol plays important roles in many biological responses inducing tumor genesis and cancer treatment. However, the effects of estradiol on tumors were inconsistent among a lot of researches and the mechanism is not fully understood. Our previous study indicated that splicing factor hnRNPA1 could bind to the human homologue of mouse double minute (MDM2), an oncogene which has been observed to be over-expressed in numerous types of cancers. In this research, we investigated whether and how estradiol correlate to cancer cell behaviors through heterogeneous nuclear ribonucleoprotein (hnRNPA1) and MDM2. Results showed that 10×10-13Mestradiol elevated the expression of hnRNPA1 regardless ER expression in cells, and then down-regulated the expression of MDM2. At the same time, estradiol inhibited cell proliferation, migration and epithelial-mesenchymal transition progression of A375 and GLL19 cells. While, knocking down hnRNPA1 through the transfection of hnRNPA1 siRNA led to the increase of MDM2 at both protein level and gene level In vivo experiment, subcutaneous injection with estradiol every two days near the tumor at doses of 2.5mg/kg/d suppressed tumor growth and reduced MDM2 expression. In a word, via increasing hnRNPA1 level and then reducing the expression of MDM2, estradiol prevented carcinogenesis in melanomas. We confirmed therapeutic effect of estradiol, as well as a new way for estradiol to resist skin cancer.

  12. KefF, the regulatory subunit of the potassium efflux system KefC, shows quinone oxidoreductase activity.

    PubMed

    Lyngberg, Lisbeth; Healy, Jessica; Bartlett, Wendy; Miller, Samantha; Conway, Stuart J; Booth, Ian R; Rasmussen, Tim

    2011-09-01

    Escherichia coli and many other Gram-negative pathogenic bacteria protect themselves from the toxic effects of electrophilic compounds by using a potassium efflux system (Kef). Potassium efflux is coupled to the influx of protons, which lowers the internal pH and results in immediate protection. The activity of the Kef system is subject to complex regulation by glutathione and its S conjugates. Full activation of KefC requires a soluble ancillary protein, KefF. This protein has structural similarities to oxidoreductases, including human quinone reductases 1 and 2. Here, we show that KefF has enzymatic activity as an oxidoreductase, in addition to its role as the KefC activator. It accepts NADH and NADPH as electron donors and quinones and ferricyanide (in addition to other compounds) as acceptors. However, typical electrophilic activators of the Kef system, e.g., N-ethyl maleimide, are not substrates. If the enzymatic activity is disrupted by site-directed mutagenesis while retaining structural integrity, KefF is still able to activate the Kef system, showing that the role as an activator is independent of the enzyme activity. Potassium efflux assays show that electrophilic quinones are able to activate the Kef system by forming S conjugates with glutathione. Therefore, it appears that the enzymatic activity of KefF diminishes the redox toxicity of quinones, in parallel with the protection afforded by activation of the Kef system.

  13. Tryptophan prenyltransferases showing higher catalytic activities for Friedel-Crafts alkylation of o- and m-tyrosines than tyrosine prenyltransferases.

    PubMed

    Fan, Aili; Xie, Xiulan; Li, Shu-Ming

    2015-07-21

    Tryptophan prenyltransferases FgaPT2, 5-DMATS, 6-DMATSSv and 7-DMATS catalyse regiospecific C-prenylations on the indole ring, while tyrosine prenyltransferases SirD and TyrPT catalyse the O-prenylation of the phenolic hydroxyl group. In this study, we report the Friedel-Crafts alkylation of L-o-tyrosine by these enzymes. Surprisingly, no conversion was detected with SirD and three tryptophan prenyltransferases showed significantly higher activity than another tyrosine prenyltransferase TyrPT. C5-prenylated L-o-tyrosine was identified as a unique product of these enzymes. Using L-m-tyrosine as the prenylation substrate, product formation was only observed with the tryptophan prenyltransferases FgaPT2 and 7-DMATS. C4- and C6-prenylated derivatives were identified in the reaction mixture of FgaPT2. These results provided additional evidence for the similarities and differences between these two subgroups within the DMATS superfamily in their catalytic behaviours.

  14. Contralateral delay activity tracks the influence of Gestalt grouping principles on active visual working memory representations.

    PubMed

    Peterson, Dwight J; Gözenman, Filiz; Arciniega, Hector; Berryhill, Marian E

    2015-10-01

    Recent studies have demonstrated that factors influencing perception, such as Gestalt grouping cues, can influence the storage of information in visual working memory (VWM). In some cases, stationary cues, such as stimulus similarity, lead to superior VWM performance. However, the neural correlates underlying these benefits to VWM performance remain unclear. One neural index, the contralateral delay activity (CDA), is an event-related potential that shows increased amplitude according to the number of items held in VWM and asymptotes at an individual's VWM capacity limit. Here, we applied the CDA to determine whether previously reported behavioral benefits supplied by similarity, proximity, and uniform connectedness were reflected as a neural savings such that the CDA amplitude was reduced when these cues were present. We implemented VWM change-detection tasks with arrays including similarity and proximity (Experiment 1); uniform connectedness (Experiments 2a and 2b); and similarity/proximity and uniform connectedness (Experiment 3). The results indicated that when there was a behavioral benefit to VWM, this was echoed by a reduction in CDA amplitude, which suggests more efficient processing. However, not all perceptual grouping cues provided a VWM benefit in the same measure (e.g., accuracy) or of the same magnitude. We also found unexpected interactions between cues. We observed a mixed bag of effects, suggesting that these powerful perceptual grouping benefits are not as predictable in VWM. The current findings indicate that when grouping cues produce behavioral benefits, there is a parallel reduction in the neural resources required to maintain grouped items within VWM.

  15. Contralateral delay activity tracks the influence of Gestalt grouping principles on active visual working memory representations

    PubMed Central

    Peterson, Dwight J.; Gözenman, Filiz; Arciniega, Hector; Berryhill, Marian E.

    2015-01-01

    Recent studies have demonstrated that factors influencing perception, such as Gestalt grouping cues, can influence the storage of information in visual working memory (VWM). In some cases, stationary cues such as stimulus similarity lead to superior VWM performance. However, the neural correlates underlying these benefits to VWM performance remain unclear. One neural index, the contralateral delay activity (CDA) is an event-related potential that shows increased amplitude according to the number of items held in VWM and asymptotes at an individual’s VWM capacity limit. Here, we applied the CDA to determine whether previously reported behavioral benefits supplied by similarity, proximity and uniform connectedness were reflected as a neural savings such that the CDA amplitude was reduced when these cues were present. We implemented VWM change detection tasks with arrays including similarity and proximity (Experiment 1); uniform connectedness (Experiments 2a and 2b); similarity/proximity and uniform connectedness (Experiment 3). The results indicated that when there was a behavioral benefit to VWM, this was echoed by a reduction in CDA amplitude, which suggests more efficient processing. However, not all perceptual grouping cues provided a VWM benefit in the same measure (e.g., accuracy) or of the same magnitude. We also found unexpected interactions between cues. We observed a mixed bag of effects, suggesting that these powerful perceptual grouping benefits are not as predictable in VWM. The current findings indicate that, when grouping cues produce behavioral benefits, there is a parallel reduction in the neural resources required to maintain grouped items within VWM. PMID:26018644

  16. Dynamic regulation of Polycomb group activity during plant development.

    PubMed

    Bemer, Marian; Grossniklaus, Ueli

    2012-11-01

    Polycomb group (PcG) complexes play important roles in phase transitions and cell fate determination in plants and animals, by epigenetically repressing sets of genes that promote either proliferation or differentiation. The continuous differentiation of new organs in plants, such as leaves or flowers, requires a highly dynamic PcG function, which can be induced, modulated, or repressed when necessary. In this review, we discuss the recent advance in understanding PcG function in plants and focus on the diverse molecular mechanisms that have been described to regulate and counteract PcG activity in Arabidopsis.

  17. Enhanced biological activity of carotenoids stabilized by phenyl groups.

    PubMed

    You, Ji Suk; Jeon, Sunhwa; Byun, Youn Jung; Koo, Sangho; Choi, Shin Sik

    2015-06-15

    Carotenoids are lipid soluble food ingredients with multifunction including antioxidant and anticancer activities. However, carotenoids are destructively oxidized upon reaction with radicals resulting in toxic effects on biological systems. Two synthetic carotenoids (BAS and BTS) containing the aromatic phenyl groups with a para-substituent (OMe and Me, respectively) at C-13 and C-13' position were prepared in order to overcome a structural instability of carotenoid. Both BAS and BTS exerted stronger radical scavenging activity than β-carotene in DPPH and ABTS assays. In particular, BTS significantly reduced in vivo ROS (reactive oxygen species) levels and improved body growth and reproduction of Caenorhabditiselegans. BTS has a great potential for the advanced and modified carotenoid material with stability leading to enhanced bioavailability.

  18. Space station group activities habitability module study: A synopsis

    NASA Technical Reports Server (NTRS)

    Nixon, David; Glassman, Terry

    1987-01-01

    Space station habitability was studied by investigating crew activity routines, proximities, ergonomic envelopes, and group volumes. Ten alternative schematic interior designs were proposed. Preliminary conclusions include: (1) in-service interior modifications may be necessary and should be planned for; (2) design complexity will be increased if the module cluster is reduced from five to three; (3) the increased crew circulation attendant upon enhancement of space station activity may produce human traffic bottlenecks and should be planned for; (4) a single- or two-person quiet area may be desirable to provide crew members with needed solitude during waking hours; and (5) the decision to choose a two-shift or three-shift daily cycle will have a significant impact on the design configuration and operational efficiency of the human habitat.

  19. The International Particle Physics Outreach Group (ippog):. Aims and Activities

    NASA Astrophysics Data System (ADS)

    Barney, David

    2012-08-01

    The International Particle Physics Outreach Group, IPPOG, is a network of particle physics communication and education experts. IPPOG's principle aim is to maximize the impact of education and outreach efforts related to particle physics through information exchange and the sharing of expertise. IPPOG has initiated several major European and Worldwide activities, such as the "International Particle Physics Masterclasses" where each year thousands of high school students in more than 20 countries come to one of about 120 nearby universities or research centres for a day in order to unravel the mysteries of particle physics. IPPOG has also initiated a global database of education and outreach materials, aimed at supporting other particle physicists and education professionals. The aims and activities of IPPOG will be described, as well as plans to include more countries & laboratories in the network.

  20. 75 FR 51525 - Railroad Safety Advisory Committee (RSAC); Working Group Activity Update

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... Federal Railroad Administration Railroad Safety Advisory Committee (RSAC); Working Group Activity Update... of Railroad Safety Advisory Committee (RSAC) Working Group Activities. SUMMARY: The FRA is updating its announcement of RSAC's Working Group activities to reflect its current status. FOR...

  1. Psychosocial mediators of group cohesion on physical activity intention of older adults.

    PubMed

    Caperchione, Cristina; Mummery, Kerry

    2007-01-01

    Considerable evidence has indicated that group-based physical activity may be a promising approach to reducing and preventing age-related illness. However, this research has not examined the mechanisms by which cohesion may impact on behaviour. The purpose of the present research was to utilise the theory of planned behaviour to investigate the mechanism by which group cohesion may affect physical activity intention. Participants were recruited from an existing physical activity intervention studying the effects of group cohesion on physical activity behaviour. The outcomes of this intervention are reported elsewhere. This paper presents data from a sub-sample of the intervention population (N=74) that examined the mediating relationships between the theory of planned behaviour and group cohesion on physical activity intention. Analyses showed that attitude and perceived behavioural control mediated the relationship between specific group cohesion concepts and physical activity intention. The direct measure of subjective norm failed to display a mediating relationship. The mediating relationships displayed between attitude and perceived behavioural control and physical activity intention provide insight into potential mechanisms by which group cohesion may affect behaviour.

  2. The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target.

    PubMed

    Wilkinson, Craig; McPhillie, Martin J; Zhou, Ying; Woods, Stuart; Afanador, Gustavo A; Rawson, Shaun; Khaliq, Farzana; Prigge, Sean T; Roberts, Craig W; Rice, David W; McLeod, Rima; Fishwick, Colin W; Muench, Stephen P

    2014-02-01

    The enoyl acyl-carrier protein reductase (ENR) enzyme of the apicomplexan parasite family has been intensely studied for antiparasitic drug design for over a decade, with the most potent inhibitors targeting the NAD(+) bound form of the enzyme. However, the higher affinity for the NADH co-factor over NAD(+) and its availability in the natural environment makes the NADH complex form of ENR an attractive target. Herein, we have examined a benzimidazole family of inhibitors which target the NADH form of Francisella ENR, but despite good efficacy against Toxoplasma gondii, the IC50 for T. gondii ENR is poor, with no inhibitory activity at 1 μM. Moreover similar benzimidazole scaffolds are potent against fungi which lack the ENR enzyme and as such we believe that there may be significant off target effects for this family of inhibitors.

  3. Record of two species of Culicoides (Diptera, Ceratopogonidae) new for Madagascar and molecular study showing the paraphylies of the subgenus Oecacta and the Schultzei group.

    PubMed

    Augot, D; Randrianambinintsoa, F J; Gasser, A; Depaquit, J

    2013-08-01

    Culicoides are vectors of diseases of Veterinary Medicine importance (bluetongue, African horse sickness, Schmallenberg virus) all over the world. In the present study, we report two species new for Madagascar: C. nevilli and C. enderleini. They belong to the Schultzei group which is sometimes classified in the subgenus Oecacta and sometimes in the subgenus Remmia, depending on authors. Consequently, we carried out a molecular cladistics of these groups based on cytochrome C oxidase subunit I mtDNA sequences. We processed the Malagasy specimens and some C. furens (the Oecacta type-species) caught in Florida and we analyzed their sequences and those available in Genbank: C. schultzei, C. oxystoma, C. festivipennis, C. brunnicans, C. kibunensis, C. truncorum and C. vexans. C. (Avaritia) imicola have been selected as an outgroup. The maximum parsimony analysis showed the paraphylies of the Schultzei group (=Remmia) and of the subgenus Oecacta if the first group is excluded from the latter. Our results underline the doubtful current classification and need to be validated by other molecular markers in the future.

  4. Neural activity reveals perceptual grouping in working memory.

    PubMed

    Rabbitt, Laura R; Roberts, Daniel M; McDonald, Craig G; Peterson, Matthew S

    2017-03-01

    There is extensive evidence that the contralateral delay activity (CDA), a scalp recorded event-related brain potential, provides a reliable index of the number of objects held in visual working memory. Here we present evidence that the CDA not only indexes visual object working memory, but also the number of locations held in spatial working memory. In addition, we demonstrate that the CDA can be predictably modulated by the type of encoding strategy employed. When individual locations were held in working memory, the pattern of CDA modulation mimicked previous findings for visual object working memory. Specifically, CDA amplitude increased monotonically until working memory capacity was reached. However, when participants were instructed to group individual locations to form a constellation, the CDA was prolonged and reached an asymptote at two locations. This result provides neural evidence for the formation of a unitary representation of multiple spatial locations.

  5. Photovoltaic Reliability Group activities in USA and Brazil (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Dhere, Neelkanth G.; Cruz, Leila R. O.

    2015-09-01

    Recently prices of photovoltaic (PV) systems have been reduced considerably and may continue to be reduced making them attractive. If these systems provide electricity over the stipulated warranty period, it would be possible attain socket parity within the next few years. Current photovoltaic module qualifications tests help in minimizing infant mortality but do not guarantee useful lifetime over the warranty period. The PV Module Quality Assurance Task Force (PVQAT) is trying to formulate accelerated tests that will be useful towards achieving the ultimate goal of assuring useful lifetime over the warranty period as well as to assure manufacturing quality. Unfortunately, assuring the manufacturing quality may require 24/7 presence. Alternatively, collecting data on the performance of fielded systems would assist in assuring manufacturing quality. Here PV systems installed by home-owners and small businesses can constitute as an important untapped source of data. The volunteer group, PV - Reliable, Safe and Sustainable Quality! (PVRessQ!) is providing valuable service to small PV system owners. Photovoltaic Reliability Group (PVRG) is initiating activities in USA and Brazil to assist home owners and small businesses in monitoring photovoltaic (PV) module performance and enforcing warranty. It will work in collaboration with small PV system owners, consumer protection agencies. Brazil is endowed with excellent solar irradiance making it attractive for installation of PV systems. Participating owners of small PV systems would instruct inverter manufacturers to copy the daily e-mails to PVRG and as necessary, will authorize the PVRG to carry out review of PV systems. The presentation will consist of overall activities of PVRG in USA and Brazil.

  6. Bacillus subtilis from Soybean Food Shows Antimicrobial Activity for Multidrug-Resistant Acinetobacter baumannii by Affecting the adeS Gene.

    PubMed

    Wang, Tieshan; Su, Jianrong

    2016-12-28

    Exploring novel antibiotics is necessary for multidrug-resistant pathogenic bacteria. Because the probiotics in soybean food have antimicrobial activities, we investigated their effects on multidrug-resistant Acinetobacter baumannii. Nineteen multidrug-resistant A. baumannii strains were clinifcally isolated as an experimental group and 11 multidrug-sensitive strains as controls. The growth rates of all bacteria were determined by using the analysis for xCELLigence Real-Time Cell. The combination of antibiotics showed synergistic effects on the strains in the control group but no effect on the strains in the experimental group. Efflux pump gene adeS was absent in all the strains from the control group, whereas it exists in all the strains from the experimental group. Furthermore, all the strains lost multidrug resistance when an adeS inhibitor was used. One strain of probiotics isolated from soybean food showed high antimicrobial activity for multidrug-resistant A. baumannii. The isolated strain belongs to Bacillus subtilis according to 16S RNA analysis. Furthermore, E. coli showed multidrug resistance when it was transformed with the adeS gene from A. baumannii whereas the resistant bacteria could be inhibited completely by isolated Bacillus subtilis. Thus, probiotics from soybean food provide potential antibiotics against multidrug-resistant pathogenic bacteria.

  7. An Update on the VAMOS Extremes Working Group Activities

    NASA Technical Reports Server (NTRS)

    Schubert, Siegfried; Cavalcanti, Iracema

    2011-01-01

    We review here the progress of the Variability of the American MOnsoon Systems (VAMOS) extremes working group since it was formed in February of 2010. The goals of the working group are to 1) develop an atlas of warm-season extremes over the Americas, 2) evaluate existing and planned simulations, and 3) suggest new model runs to address mechanisms and predictability of extremes. Substantial progress has been made in the development of an extremes atlas based on gridded observations and several reanalysis products including Modern Era Retrospective-Analysis for Research and Applications (MERRA) and Climate Forecast System Reanalysis (CFSR). The status of the atlas, remaining issues and plans for its expansion to include model data will be discussed. This includes the possibility of adding a companion atlas based on station observations based on the software developed under the World Climate Research Programme (WCRP) Expert Team on Climate Change. Detection and Indices (ETCCDI) activity. We will also review progress on relevant research and plans for the use and validation of the atlas results.

  8. Structure-antifungal activity relationships of polyene antibiotics of the amphotericin B group.

    PubMed

    Tevyashova, Anna N; Olsufyeva, Evgenia N; Solovieva, Svetlana E; Printsevskaya, Svetlana S; Reznikova, Marina I; Trenin, Aleksei S; Galatenko, Olga A; Treshalin, Ivan D; Pereverzeva, Eleonora R; Mirchink, Elena P; Isakova, Elena B; Zotchev, Sergey B; Preobrazhenskaya, Maria N

    2013-08-01

    A comprehensive comparative analysis of the structure-antifungal activity relationships for the series of biosynthetically engineered nystatin analogues and their novel semisynthetic derivatives, as well as amphotericin B (AMB) and its semisynthetic derivatives, was performed. The data obtained revealed the significant influence of the structure of the C-7 to C-10 polyol region on the antifungal activity of these polyene antibiotics. Comparison of positions of hydroxyl groups in the antibiotics and in vitro antifungal activity data showed that the most active are the compounds in which hydroxyl groups are in positions C-8 and C-9 or positions C-7 and C-10. Antibiotics with OH groups at both C-7 and C-9 had the lowest activity. The replacement of the C-16 carboxyl with methyl group did not significantly affect the in vitro antifungal activity of antibiotics without modifications at the amino group of mycosamine. In contrast, the activity of the N-modified derivatives was modulated both by the presence of CH3 or COOH group in the position C-16 and by the structure of the modifying substituent. The most active compounds were tested in vivo to determine the maximum tolerated doses and antifungal activity on the model of candidosis sepsis in leukopenic mice (cyclophosphamide-induced). Study of our library of semisynthetic polyene antibiotics led to the discovery of compounds, namely, N-(L-lysyl)-BSG005 (compound 3n) and, especially, L-glutamate of 2-(N,N-dimethylamino)ethyl amide of S44HP (compound 2j), with high antifungal activity that were comparable in in vitro and in vivo tests to AMB and that have better toxicological properties.

  9. Genome Sequence of Lactobacillus salivarius SMXD51, a Potential Probiotic Strain Isolated from Chicken Cecum, Showing Anti-Campylobacter Activity

    PubMed Central

    Kergourlay, Gilles; Messaoudi, Soumaya; Dousset, Xavier

    2012-01-01

    We report the draft genome sequence of Lactobacillus salivarius SMXD51, isolated from the cecum of healthy chickens showing an activity against Campylobacter—the food-borne pathogen that is the most common cause of gastroenteritis in the European Union (EU)—and potentially interesting features for a probiotic strain, explaining our interest in it. PMID:22582370

  10. Magnetosomes extracted from Magnetospirillum magneticum strain AMB-1 showed enhanced peroxidase-like activity under visible-light irradiation.

    PubMed

    Li, Kefeng; Chen, Chuanfang; Chen, Changyou; Wang, Yuzhan; Wei, Zhao; Pan, Weidong; Song, Tao

    2015-05-01

    Magnetosomes are intracellular structures produced by magnetotactic bacteria and are magnetic nanoparticles surrounded by a lipid bilayer membrane. Magnetosomes reportedly possess intrinsic enzyme mimetic activity similar to that found in horseradish peroxidase (HRP) and can scavenge reactive oxygen species depending on peroxidase activity. Our previous study has demonstrated the phototaxis characteristics of Magnetospirillum magneticum strain AMB-1 cells, but the mechanism is not well understood. Therefore, we studied the relationship between visible-light irradiation and peroxidase-like activity of magnetosomes extracted from M. magneticum strain AMB-1. We then compared this characteristic with that of HRP, iron ions, and naked magnetosomes using 3,3',5,5'-tetramethylbenzidine as a peroxidase substrate in the presence of H2O2. Results showed that HRP and iron ions had different activities from those of magnetosomes and naked magnetosomes when exposed to visible-light irradiation. Magnetosomes and naked magnetosomes had enhanced peroxidase-like activities under visible-light irradiation, but magnetosomes showed less affinity toward substrates than naked magnetosomes under visible-light irradiation. These results suggested that the peroxidase-like activity of magnetosomes may follow an ordered ternary mechanism rather than a ping-pong mechanism. This finding may provide new insight into the function of magnetosomes in the phototaxis in magnetotactic bacteria.

  11. Cocaine users with comorbid Cluster B personality disorders show dysfunctional brain activation and connectivity in the emotional regulation networks during negative emotion maintenance and reappraisal.

    PubMed

    Albein-Urios, Natalia; Verdejo-Román, Juan; Soriano-Mas, Carles; Asensio, Samuel; Martínez-González, José Miguel; Verdejo-García, Antonio

    2013-12-01

    Cocaine dependence often co-occurs with Cluster B personality disorders. Since both disorders are characterized by emotion regulation deficits, we predicted that cocaine comorbid patients would exhibit dysfunctional patterns of brain activation and connectivity during reappraisal of negative emotions. We recruited 18 cocaine users with comorbid Cluster B personality disorders, 17 cocaine users without comorbidities and 21 controls to be scanned using functional magnetic resonance imaging (fMRI) during performance on a reappraisal task in which they had to maintain or suppress the emotions induced by negative affective stimuli. We followed region of interest (ROI) and whole-brain approaches to investigate brain activations and connectivity associated with negative emotion experience and reappraisal. Results showed that cocaine users with comorbid personality disorders had reduced activation of the subgenual anterior cingulate cortex during negative emotion maintenance and increased activation of the lateral orbitofrontal cortex and the amygdala during reappraisal. Amygdala activation correlated with impulsivity and antisocial beliefs in the comorbid group. Connectivity analyses showed that in the cocaine comorbid group the subgenual cingulate was less efficiently connected with the amygdala and the fusiform gyri and more efficiently connected with the anterior insula during maintenance, whereas during reappraisal the left orbitofrontal cortex was more efficiently connected with the amygdala and the right orbitofrontal cortex was less efficiently connected with the dorsal striatum. We conclude that cocaine users with comorbid Cluster B personality disorders have distinctive patterns of brain activation and connectivity during maintenance and reappraisal of negative emotions, which correlate with impulsivity and dysfunctional beliefs.

  12. Predicted group II intron lineages E and F comprise catalytically active ribozymes.

    PubMed

    Nagy, Vivien; Pirakitikulr, Nathan; Zhou, Katherine Ismei; Chillón, Isabel; Luo, Jerome; Pyle, Anna Marie

    2013-09-01

    Group II introns are self-splicing, retrotransposable ribozymes that contribute to gene expression and evolution in most organisms. The ongoing identification of new group II introns and recent bioinformatic analyses have suggested that there are novel lineages, which include the group IIE and IIF introns. Because the function and biochemical activity of group IIE and IIF introns have never been experimentally tested and because these introns appear to have features that distinguish them from other introns, we set out to determine if they were indeed self-splicing, catalytically active RNA molecules. To this end, we transcribed and studied a set of diverse group IIE and IIF introns, quantitatively characterizing their in vitro self-splicing reactivity, ionic requirements, and reaction products. In addition, we used mutational analysis to determine the relative role of the EBS-IBS 1 and 2 recognition elements during splicing by these introns. We show that group IIE and IIF introns are indeed distinct active intron families, with different reactivities and structures. We show that the group IIE introns self-splice exclusively through the hydrolytic pathway, while group IIF introns can also catalyze transesterifications. Intriguingly, we observe one group IIF intron that forms circular intron. Finally, despite an apparent EBS2-IBS2 duplex in the sequences of these introns, we find that this interaction plays no role during self-splicing in vitro. It is now clear that the group IIE and IIF introns are functional ribozymes, with distinctive properties that may be useful for biotechnological applications, and which may contribute to the biology of host organisms.

  13. Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes.

    PubMed

    Siska, Peter J; Kim, Bumki; Ji, Xiangming; Hoeksema, Megan D; Massion, Pierre P; Beckermann, Kathryn E; Wu, Jianli; Chi, Jen-Tsan; Hong, Jiyong; Rathmell, Jeffrey C

    2016-11-01

    T and B lymphocytes undergo metabolic re-programming upon activation that is essential to allow bioenergetics, cell survival, and intermediates for cell proliferation and function. To support changes in the activity of signaling pathways and to provide sufficient and necessary intracellular metabolites, uptake of extracellular nutrients increases sharply with metabolic re-programming. One result of increased metabolic activity can be reactive oxygen species (ROS), which can be toxic when accumulated in excess. Uptake of cystine allows accumulation of cysteine that is necessary for glutathione synthesis and ROS detoxification. Cystine uptake is required for T cell activation and function but measurements based on radioactive labeling do not allow analysis on single cell level. Here we show the critical role for cystine uptake in T cells using a method for measurement of cystine uptake using a novel CystineFITC probe. T cell receptor stimulation lead to upregulation of the cystine transporter xCT (SLC7a11) and increased cystine uptake in CD4+ and CD8+ human T cells. Similarly, lipopolysaccharide stimulation increased cystine uptake in human B cells. The CystineFITC probe was not toxic and could be metabolized to prevent cystine starvation induced cell death. Furthermore, blockade of xCT or competition with natural cystine decreased uptake of CystineFITC. CystineFITC is thus a versatile tool that allows measurement of cystine uptake on single cell level and shows the critical role for cystine uptake for T cell ROS regulation and activation.

  14. Malten, a new synthetic molecule showing in vitro antiproliferative activity against tumour cells and induction of complex DNA structural alterations

    PubMed Central

    Amatori, S; Bagaloni, I; Macedi, E; Formica, M; Giorgi, L; Fusi, V; Fanelli, M

    2010-01-01

    Background: Hydroxypyrones represent several classes of molecules known for their high synthetic versatility. This family of molecules shows several interesting pharmaceutical activities and is considered as a promising source of new antineoplastic compounds. Methods: In the quest to identify new potential anticancer agents, a new maltol (3-hydroxy-2-methyl-4-pyrone)-derived molecule, named malten (N,N′-bis((3-hydroxy-4-pyron-2-yl)methyl)-N,N′-dimethylethylendiamine), has been synthesised and analysed at both biological and molecular levels for its antiproliferative activity in eight tumour cell lines. Results: Malten exposure led to a dose-dependent reduction in cell survival in all the neoplastic models studied. Sublethal concentrations of malten induce profound cell cycle changes, particularly affecting the S and/or G2-M phases, whereas exposure to lethal doses causes the induction of programmed cell death. The molecular response to malten was also investigated in JURKAT and U937 cells. It showed the modulation of genes having key roles in cell cycle progression and apoptosis. Finally, as part of the effort to clarify the action mechanism, we showed that malten is able to impair DNA electrophoretic mobility and drastically reduce both PCR amplificability and fragmentation susceptibility of DNA. Conclusion: Taken together, these results show that malten may exert its antiproliferative activity through the induction of complex DNA structural modifications. This evidence, together with the high synthetic versatility of maltol-derived compounds, makes malten an interesting molecular scaffold for the future design of new potential anticancer agents. PMID:20571494

  15. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models.

    PubMed

    Li, Zhimin; Qiu, Yushi; Personett, David; Huang, Peng; Edenfield, Brandy; Katz, Jason; Babusis, Darius; Tang, Yang; Shirely, Michael A; Moghaddam, Mehran F; Copland, John A; Tun, Han W

    2013-01-01

    Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS

  16. Incorporating More Individual Accountability in Group Activities in General Chemistry

    ERIC Educational Resources Information Center

    Cox, Charles T., Jr.

    2015-01-01

    A modified model of cooperative learning known as the GIG model (for group-individual-group) designed and implemented in a large enrollment freshman chemistry course. The goal of the model is to establish a cooperative environment while emphasizing greater individual accountability using both group and individual assignments. The assignments were…

  17. Quantity, Quality, and Variety of Pupil Responses during an Open-Communication Structured Group Directed Reading-Thinking Activity and a Closed Communication Structured Group Directed Reading Activity.

    ERIC Educational Resources Information Center

    Petre, Richard M.

    The quality, quantity, and variety of pupil responses while using two different group directed reading activities, the Directed Reading Activity (DRA), and the Directed Reading-Thinking Activity (DRTA) were investigated in this study. The subjects, all fourth graders in two nearby communities, were grouped into above-grade-level, at-grade-level,…

  18. Backbone cyclised peptides from plants show molluscicidal activity against the rice pest Pomacea canaliculata (golden apple snail).

    PubMed

    Plan, Manuel Rey R; Saska, Ivana; Cagauan, Arsenia G; Craik, David J

    2008-07-09

    Golden apple snails ( Pomacea canaliculata) are serious pests of rice in South East Asia. Cyclotides are backbone cyclized peptides produced by plants from Rubiaceae and Violaceae. In this study, we investigated the molluscicidal activity of cyclotides against golden apple snails. Crude cyclotide extracts from both Oldenlandia affinis and Viola odorata plants showed molluscicidal activity comparable to the synthetic molluscicide metaldehyde. Individual cyclotides from each extract demonstrated a range of molluscicidal activities. The cyclotides cycloviolacin O1, kalata B1, and kalata B2 were more toxic to golden apple snails than metaldehyde, while kalata B7 and kalata B8 did not cause significant mortality. The toxicity of the cyclotide kalata B2 on a nontarget species, the Nile tilapia ( Oreochromis niloticus), was three times lower than the common piscicide rotenone. Our findings suggest that the existing diversity of cyclotides in plants could be used to develop natural molluscicides.

  19. Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus

    PubMed Central

    Padilla, Marina Aiello; Rodrigues, Rodney Alexandre Ferreira; Bastos, Juliana Cristina Santiago; Martini, Matheus Cavalheiro; Barnabé, Ana Caroline de Souza; Kohn, Luciana Konecny; Uetanabaro, Ana Paula Trovatti; Bomfim, Getúlio Freitas; Afonso, Rafael Sanches; Fantinatti-Garboggini, Fabiana; Arns, Clarice Weis

    2015-01-01

    Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV). Two bacterial strains were identified as active, with percentages of inhibition (IP) equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s) responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s) that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection. PMID:26579205

  20. Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus.

    PubMed

    Padilla, Marina Aiello; Rodrigues, Rodney Alexandre Ferreira; Bastos, Juliana Cristina Santiago; Martini, Matheus Cavalheiro; Barnabé, Ana Caroline de Souza; Kohn, Luciana Konecny; Uetanabaro, Ana Paula Trovatti; Bomfim, Getúlio Freitas; Afonso, Rafael Sanches; Fantinatti-Garboggini, Fabiana; Arns, Clarice Weis

    2015-01-01

    Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV). Two bacterial strains were identified as active, with percentages of inhibition (IP) equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s) responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s) that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection.

  1. The novel HSP90 inhibitor NVP-AUY922 shows synergistic anti-leukemic activity with cytarabine in vivo.

    PubMed

    Wendel, Torunn; Zhen, Yan; Suo, Zenhe; Bruheim, Skjalg; Wiedlocha, Antoni

    2016-01-15

    HSP90 is a molecular chaperone essential for stability, activity and intracellular sorting of many proteins, including oncoproteins, such as tyrosine kinases, transcription factors and cell cycle regulatory proteins. Therefore, inhibitors of HSP90 are being investigated for their potential as anti-cancer drugs. Here we show that the HSP90 inhibitor NVP-AUY922 induced degradation of the fusion oncoprotein FOP2-FGFR1 in a human acute myeloid leukemia (AML) cell line, KG-1a. Concordantly, downstream signaling cascades, such as STAT1, STAT3 and PLCγ were abrogated. At concentrations that caused FOP2-FGFR1 degradation and signaling abrogation, NVP-AUY922 treatment caused significant cell death and inhibition of proliferation of KG-1a cells in vitro. In an animal model for AML, NVP-AUY922 administrated alone showed no anti-leukemic activity. However, when NVP-AUY922 was administered in combination with cytarabine, the two compounds showed significant synergistic anti-leukemic activity in vivo. Thus NVP-AUY922 and cytarabine combination therapy might be a prospective strategy for AML treatment.

  2. Circadian activity rhythm in pre-pubertal and pubertal marmosets (Callithrix jacchus) living in family groups.

    PubMed

    Melo, Paula R; Gonçalves, Bruno S B; Menezes, Alexandre A L; Azevedo, Carolina V M

    2016-03-01

    In marmosets, a phase advance was observed in activity onset in pubertal animals living in captivity under semi-natural conditions which had stronger correlation with the times of sunrise over the course of the year than the age of the animal. In order to evaluate the effect of puberty on the circadian activity rhythm in male and female marmosets living in family groups in controlled lighting conditions, the activity of 5 dyads of twins (4 ♀/♂ and 1 ♂/♂) and their respective parents was continuously monitored by actiwatches between the 4th and 12th months of age. The families were kept under LD 12:12 h with constant humidity and temperature. The onset of puberty was identified by monitoring fecal steroids. Juveniles showed higher totals of daily activity and differences in the daily distribution of activity in relation to parents, in which the bimodal profile was characterized by higher levels in evening activity in relation to morning activity. Regarding the phase, the activity onset and offset, occurred later in relation to parents. After entering puberty, the activity onset and offset occurred later and there was an increase in total daily activity. On the other hand, when assessing the effect of sex, only females showed a delay in the activity offset and an increase in total daily activity. Therefore, the circadian activity rhythm in marmosets has peculiar characteristics in the juvenile stage in relation to the total of daily activity, the onset and offset of the active phase, and the distribution of activity during this phase. Besides, the entering puberty was associated with a phase delay and increase on total daily activity, with differences between sexes, possibly due to hormonal influences and/or social modulation on rhythm.

  3. Pazopanib, a novel multi-kinase inhibitor, shows potent antitumor activity in colon cancer through PUMA-mediated apoptosis.

    PubMed

    Zhang, Lingling; Wang, Huanan; Li, Wei; Zhong, Juchang; Yu, Rongcheng; Huang, Xinfeng; Wang, Honghui; Tan, Zhikai; Wang, Jiangang; Zhang, Yingjie

    2017-01-10

    Colon cancer is still the third most common cancer which has a high mortality but low five-year survival rate. Novel tyrosine kinase inhibitors (TKI) such as pazopanib become effective antineoplastic agents that show promising clinical activity in a variety of carcinoma, including colon cancer. However, the precise underlying mechanism against tumor is unclear. Here, we demonstrated that pazopanib promoted colon cancer cell apoptosis through inducing PUMA expression. Pazopanib induced p53-independent PUMA activation by inhibiting PI3K/Akt signaling pathway, thereby activating Foxo3a, which subsequently bound to the promoter of PUMA to activate its transcription. After induction, PUMA activated Bax and triggered the intrinsic mitochondrial apoptosis pathway. Furthermore, administration of pazopanib highly suppressed tumor growth in a xenograft model. PUMA deletion in cells and tumors led to resistance of pazopanib, indicating PUMA-mediated pro-apoptotic and anti-tumor effects in vitro and in vivo. Combing pazopanib with some conventional or novel drugs, produced heightened and synergistic antitumor effects that were associated with potentiated PUMA induction via different pathways. Taken together, these results establish a critical role of PUMA in mediating the anticancer effects of pazopanib in colon cancer cells and provide the rationale for clinical evaluation.

  4. The Use of a Group Blog to Actively Support Learning Activities

    ERIC Educational Resources Information Center

    Duarte, Paulo

    2015-01-01

    Despite the widespread use of blogs in higher education, there remains a lack of knowledge and consensus about the use and value of blogging in higher education, particularly when used for long periods. This article investigates the use of a group blog to assist traditional teaching activities and foster collaborative learning through the…

  5. Quercetin and quercetin 3-O-glycosides from Bauhinia longifolia (Bong.) Steud. show anti-Mayaro virus activity

    PubMed Central

    2014-01-01

    Background The arthropod-borne Mayaro virus (MAYV) causes ‘Mayaro fever’, a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. Currently, there are no licensed drugs against most mosquito-transmitted viruses. Here, we investigated the in vitro anti-MAYV activity of the flavonoids quercetin and its derivatives from the Brazilian shrub Bauhinia longifolia (Bong.) Steud. Methods Flavonoids were purified by chromatographic fractionation from leaf extracts of B. longifolia and chemically identified as quercetin and quercetin glycosides using spectroscopic techniques. Cytotoxicity of purified flavonoids and of EtOAc- and n-BuOH-containing flavonoid mixtures was measured by the dye-uptake assay while their antiviral activity was evaluated by a virus yield inhibition assay. Results The following flavonoids were purified from B. longifolia leaves: non-glycosylated quercetin and its glycosides guaijaverin, quercitrin, isoquercitrin, and hyperin. EtOAc and n-BuOH fractions containing these flavonoids demonstrated the highest antiviral activity of all tested substances, while quercetin had the highest antiviral activity amongst purified flavonoids. Quercetin, EtOAc, or n-BuOH fractions inhibited MAYV production by more than 90% at 25 μg/mL, displaying a stronger antiviral effect than the licensed antiviral ribavirin. A mixture of the isomers isoquercitrin and hyperin had a modest antiviral effect (IC90 = 104.9), while guaijaverin and quercitrin did not show significant antiviral activity. Conclusions B. longifolia is a good source of flavonoids with anti-Mayaro virus activity. This is the first report of the activity of quercetin and its derivatives against an alphavirus. PMID:24678592

  6. Group D prothrombin activators from snake venom are structural homologues of mammalian blood coagulation factor Xa.

    PubMed Central

    Rao, Veena S; Joseph, Jeremiah S; Kini, R Manjunatha

    2003-01-01

    Procoagulant venoms of several Australian elapids contain proteinases that specifically activate prothrombin; among these, Group D activators are functionally similar to coagulation factor Xa (FXa). Structural information on this class of prothrombin activators will contribute significantly towards understanding the mechanism of FXa-mediated prothrombin activation. Here we present the purification of Group D prothrombin activators from three Australian snake venoms (Hoplocephalus stephensi, Notechis scutatus scutatus and Notechis ater niger) using a single-step method, and their N-terminal sequences. The N-terminal sequence of the heavy chain of hopsarin D (H. stephensi) revealed that a fully conserved Cys-7 was substituted with a Ser residue. We therefore determined the complete amino acid sequence of hopsarin D. Hopsarin D shows approximately 70% similarity with FXa and approximately 98% similarity with trocarin D, a Group D prothrombin activator from Tropidechis carinatus. It possesses the characteristic Gla domain, two epidermal growth factor-like domains and a serine proteinase domain. All residues important for catalysis are conserved, as are most regions involved in interactions with factor Va and prothrombin. However, there are some structural differences. Unlike FXa, hopsarin D is glycosylated in both its chains: in light-chain residue 52 and heavy-chain residue 45. The glycosylation on the heavy chain is a large carbohydrate moiety adjacent to the active-site pocket. Overall, hopsarin D is structurally and functionally similar to mammalian coagulation FXa. PMID:12403650

  7. T cells conditioned with MDSC show an increased anti-tumor activity after adoptive T cell based immunotherapy.

    PubMed

    Raber, Patrick L; Sierra, Rosa A; Thevenot, Paul T; Shuzhong, Zhang; Wyczechowska, Dorota D; Kumai, Takumi; Celis, Esteban; Rodriguez, Paulo C

    2016-04-05

    The success of adoptive T cell-based immunotherapy (ACT) in cancer is limited in part by the accumulation of myeloid-derived suppressor cells (MDSC), which block several T cell functions, including T cell proliferation and the expression of various cytotoxic mediators. Paradoxically, the inhibition of CD8+ T cell differentiation into cytotoxic populations increased their efficacy after ACT into tumor-bearing hosts. Therefore, we aimed to test the impact of conditioning CD8+ T cells with MDSC on their differentiation potential and ACT efficacy. Our results indicate that MDSC impaired the progression of CD8+ T cells into effector populations, without altering their activation status, production of IL-2, or signaling through the T cell receptor. In addition, culture of CD8+ T cells with MDSC resulted in an increased ACT anti-tumor efficacy, which correlated with a higher frequency of the transferred T cells and elevated IFNγ production. Interestingly, activated CD62L+ CD8+ T cells were responsible for the enhanced anti-tumor activity showed by MDSC-exposed T cells. Additional results showed a decreased protein synthesis rate and lower activity of the mammalian/mechanistic target of rapamycin (mTOR) in T cells conditioned with MDSC. Silencing of the negative mTOR regulator tuberous sclerosis complex-2 in T cells co-cultured with MDSC restored mTOR activity, but resulted in T cell apoptosis. These results indicate that conditioning of T cells with MDSC induces stress survival pathways mediated by a blunted mTOR signaling, which regulated T cell differentiation and ACT efficacy. Continuation of this research will enable the development of better strategies to increase ACT responses in cancer.

  8. Repressible extracellular phosphodiesterases showing cyclic 2',3'- and cyclic 3',5'-nucleotide phosphodiesterase activities in Neurospora crassa.

    PubMed Central

    Hasunuma, K

    1983-01-01

    Two molecular species of repressible extracellular phosphodiesterases showing cyclic 2',3'- and cyclic 3',5'-nucleotide phosphodiesterase activities were detected in mycelial culture media of wild-type Neurospora crassa and purified. The two molecular species were found to be monomeric and polymeric forms of an enzyme constituted of identical subunits having molecular weights of 50,000. This enzyme had the same electrophoretic mobility as repressible acid phosphatase. The enzyme designated repressible cyclic phosphodiesterase showed pH optima of 3.2 to 4.0 with a cyclic 3',5'-AMP substrate and 5.0 to 5.6 with a cyclic 2',3'-AMP substrate. Repressible cyclic phosphodiesterase was activated by MnCl2 and CoCl2 with cyclic 2',3'-AMP as substrate and was slightly activated by MnCl2 with cyclic 3',5'-AMP. The enzyme hydrolyzed cyclic 3',5'- and cyclic 2',3'-nucleotides, in addition to bis-rho-nitrophenyl phosphate, but not certain 5' -and 3'-nucleotides. 3'-GMP and 3'-CMP were hydrolyzed less efficiently. Mutant strains A1 (nuc-1) and B1 (nuc-2), which cannot utilize RNA or DNA as a sole source of phosphorus, were unable to produce repressible cyclic phosphodiesterase. The wild type (74A) and a heterocaryon between strains A1 and B1 produced the enzyme and showed growth on orthophosphate-free media containing cyclic 2',3'-AMP or cyclic 3',5'-AMP, whereas both mutants showed little or no growth on these media. Images PMID:6311798

  9. The Fantastic Facilitator: Engaging Activities for Leading Groups.

    ERIC Educational Resources Information Center

    Duttweiler, Patricia Cloud

    This document is designed to help facilitators with the formation and development of effective teams of people who have no previous history as a team and no training in group processes. Part 1 provides a narrative explanation of the stages of group development (investing in membership, forming attachments to subgroups, confronting/debating issues,…

  10. An Activity Group Experience for Disengaged Elderly Persons.

    ERIC Educational Resources Information Center

    Harris, John Ewing; Bodden, Jack L.

    1978-01-01

    Tested the activity theory (which proposes that elderly persons remain in active contact with their environment) and disengagement theory (which suggests adjustment comes through reduction of activity and social contact). Disengaged elderly were identified. Subjects demonstrated significant improvement over the untreated control subjects. Results…

  11. BO-1055, a novel DNA cross-linking agent with remarkable low myelotoxicity shows potent activity in sarcoma models

    PubMed Central

    Ambati, Srikanth R.; Shieh, Jae-Hung; Pera, Benet; Lopes, Eloisi Caldas; Chaudhry, Anisha; Wong, Elissa W.P.; Saxena, Ashish; Su, Tsann-Long; Moore, Malcolm A.S.

    2016-01-01

    DNA damaging agents cause rapid shrinkage of tumors and form the basis of chemotherapy for sarcomas despite significant toxicities. Drugs having superior efficacy and wider therapeutic windows are needed to improve patient outcomes. We used cell proliferation and apoptosis assays in sarcoma cell lines and benign cells; γ-H2AX expression, comet assay, immunoblot analyses and drug combination studies in vitro and in patient derived xenograft (PDX) models. BO-1055 caused apoptosis and cell death in a concentration and time dependent manner in sarcoma cell lines. BO-1055 had potent activity (submicromolar IC50) against Ewing sarcoma and rhabdomyosarcoma, intermediate activity in DSRCT (IC50 = 2-3μM) and very weak activity in osteosarcoma (IC50 >10μM) cell lines. BO-1055 exhibited a wide therapeutic window compared to other DNA damaging drugs. BO-1055 induced more DNA double strand breaks and γH2AX expression in cancer cells compared to benign cells. BO-1055 showed inhibition of tumor growth in A673 xenografts and caused tumor regression in cyclophosphamide resistant patient-derived Ewing sarcoma xenografts and A204 xenografts. Combination of BO-1055 and irinotecan demonstrated synergism in Ewing sarcoma PDX models. Potent activity on sarcoma cells and its relative lack of toxicity presents a strong rationale for further development of BO-1055 as a therapeutic agent. PMID:27248664

  12. Platinum-based complexes of bioactive 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-Trypanosoma cruzi activity.

    PubMed

    Vieites, Marisol; Otero, Lucía; Santos, Diego; Olea-Azar, Claudio; Norambuena, Ester; Aguirre, Gabriela; Cerecetto, Hugo; González, Mercedes; Kemmerling, Ulrike; Morello, Antonio; Diego Maya, Juan; Gambino, Dinorah

    2009-03-01

    Eight new platinum(II) complexes with 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-trypanosomal activity were synthesized, characterized and in vitro evaluated. Most of the complexes showed IC(50) values in the micromolar range against two different strains of Trypanosoma cruzi, causative agent of Chagas disease (American Trypanosomiasis). In addition, most of the newly developed complexes, together with the analogous platinum 5-nitrofuraldehyde containing thiosemicarbazones previously reported, resulted more active than the reference trypanocidal drug nifurtimox on the infective trypomastigote form of the parasite. Their capacity to produce free radicals that could lead to parasite death was evaluated by ESR experiments in the parasite and by respiration measurements. Compounds were tested for their DNA interaction ability. Results showed that some of the compounds could act as dual inhibitors in the parasite, through production of toxic free radicals and interaction with DNA. All the results were compared with those previously reported for the free ligands, the analogous palladium(II) compounds and the previously reported series of platinum(II) compounds.

  13. Map showing recently active breaks along the San Andreas Fault between Pt. Delgada and Bolinas Bay, California

    USGS Publications Warehouse

    Brown, Robert D.; Wolfe, Edward W.

    1970-01-01

    This strip map is one of a series of maps showing recently active fault breaks along the San Andreas and other active faults in California. It is designed to inform persons who are concerned with land use near the fault of the location of those fault breaks that have moved recently. The lines on the map are lines of rupture and creep that can be identified by field evidence and that clearly affect the present surface of the land. Map users should keep in mind that these lines are intended primarily as guides to help locate the fault; the mapped lines are not necessarily shown with the precision demanded by some engineering or land utilization needs.

  14. Silk gland-specific proteinase inhibitor serpin16 from the Bombyx mori shows cysteine proteinase inhibitory activity.

    PubMed

    Guo, Peng-Chao; Dong, Zhaoming; Xiao, Li; Li, Tao; Zhang, Yan; He, Huawei; Xia, Qingyou; Zhao, Ping

    2015-01-30

    Serpins (serine proteinase inhibitors) are widely distributed in different species and are well known for their inhibitory activities towards serine proteinases. Here, we report the functional characterization of Bombyx mori serpin16. Expression analysis showed that serpin16 was specifically expressed at high levels in the silk gland at both the transcriptional and translational levels. Moreover, homology modeling and multi-sequence alignment suggested that serpin16 had a canonical serpin fold, but it contained a unique reactive center loop, which was obviously shorter than that of typical serpins. Inhibitory activity analyses revealed that the target proteinase of serpin18 is a cysteine proteinase, rather than a serine proteinase. Furthermore, a Michaelis complex model of serpin16 with its target proteinase was constructed to explain the structural basis of how serpin16 recognizes the cysteine proteinase and its target specificity.

  15. Group Problem Solving as a Zone of Proximal Development activity

    NASA Astrophysics Data System (ADS)

    Brewe, Eric

    2006-12-01

    Vygotsky described learning as a process, intertwined with development, which is strongly influenced by social interactions with others that are at differing developmental stages.i These interactions create a Zone of Proximal Development for each member of the interaction. Vygotsky’s notion of social constructivism is not only a theory of learning, but also of development. While teaching introductory physics in an interactive format, I have found manifestations of Vygotsky’s theory in my classroom. The source of evidence is a paired problem solution. A standard mechanics problem was solved by students in two classes as a homework assignment. Students handed in the homework and then solved the same problem in small groups. The solutions to both the group and individual problem were assessed by multiple reviewers. In many cases the group score was the same as the highest individual score in the group, but in some cases, the group score was higher than any individual score. For this poster, I will analyze the individual and group scores and focus on three groups solutions and video that provide evidence of learning through membership in a Zone of Proximal Development. Endnotes i L. Vygotsky -Mind and society: The development of higher mental processes. Cambridge, MA: Harvard University Press. (1978).

  16. DNA sequence-selective C8-linked pyrrolobenzodiazepine-heterocyclic polyamide conjugates show anti-tubercular-specific activities.

    PubMed

    Brucoli, Federico; Guzman, Juan D; Basher, Mohammad A; Evangelopoulos, Dimitrios; McMahon, Eleanor; Munshi, Tulika; McHugh, Timothy D; Fox, Keith R; Bhakta, Sanjib

    2016-12-01

    New chemotherapeutic agents with novel mechanisms of action are in urgent need to combat the tuberculosis pandemic. A library of 12 C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-heterocyclic polyamide conjugates (1-12) was evaluated for anti-tubercular activity and DNA sequence selectivity. The PBD conjugates were screened against slow-growing Mycobacterium bovis Bacillus Calmette-Guérin and M. tuberculosis H37Rv, and fast-growing Escherichia coli, Pseudomonas putida and Rhodococcus sp. RHA1 bacteria. DNase I footprinting and DNA thermal denaturation experiments were used to determine the molecules' DNA recognition properties. The PBD conjugates were highly selective for the mycobacterial strains and exhibited significant growth inhibitory activity against the pathogenic M. tuberculosis H37Rv, with compound 4 showing MIC values (MIC=0.08 mg l(-1)) similar to those of rifampin and isoniazid. DNase I footprinting results showed that the PBD conjugates with three heterocyclic moieties had enhanced sequence selectivity and produced larger footprints, with distinct cleavage patterns compared with the two-heterocyclic chain PBD conjugates. DNA melting experiments indicated a covalent binding of the PBD conjugates to two AT-rich DNA-duplexes containing either a central GGATCC or GTATAC sequence, and showed that the polyamide chains affect the interactions of the molecules with DNA. The PBD-C8 conjugates tested in this study have a remarkable anti-mycobacterial activity and can be further developed as DNA-targeted anti-tubercular drugs.

  17. Influence of ethylene-oxy spacer group on the activity of linezolid: synthesis of potent antibacterials possessing a thiocarbonyl group.

    PubMed

    Selvakumar, N; Raheem, Mohammed A; Khera, Manoj Kumar; Rajale, Trideep V; Kumar, Magadi Sitaram; Kandepu, Sreenivas; Das, Jagattaran; Rajagopalan, R; Iqbal, Javed; Trehan, Sanjay

    2003-12-01

    The influence of an ethylene-oxy spacer element between the heterocycle and the aromatic ring in linezolid is reported. The introduction of such spacer group generated compounds with inferior antibacterial activity. However, the conversion of the acetamide group present in the linezolid analogues to either thiocarbamate or thioacetamide functionality restored the activity. The synthesis of linezolid analogues possessing the ethylene-oxy spacer group along with SAR studies with different heterocycles and preparation of some thiocarbonyl compounds possessing potent antibacterial property are presented.

  18. Distribution and characterization of hemolytic activity by an oral anaerobe from the Streptococcus milleri group.

    PubMed

    Yamaguchi, T; Koreeda, H

    2004-04-01

    Some oral anaerobes from the Streptococcus milleri strain group were found to secrete human specific hemolytic toxin, which was detected when bacteria were cultured in Todd-Hewitt broth and Brain Heart Infusion broth. The toxin elicited by the Streptococcus intermedius strain was partially fractionated by ammonium sulfate precipitation. Preincubation with glutathione or cysteine showed significant inhibiting effects; however, no effects were seen with dithiothreitol or beta-mercaptoethanol, and cholesterol was a weak inhibitor. Five kinds of protease inhibitor had no effect on the hemolytic activity, and rabbit preimmune and immune sera against the bacterial cells showed weak inhibition at a similar level. Digestion with trypsin, chymotrypsin, proteinase-K, subtilisin and pronase-P brought about a rise in activity, followed by a decrease during long-term incubation. Other enzymes tested showed no effects. Further, the presence of the intermedilysin gene in the portion with hemolytic activity was not identified by polymerase chain reaction.

  19. PCR DGGE and RT-PCR DGGE show diversity and short-term temporal stability in the Clostridium coccoides-Eubacterium rectale group in the human intestinal microbiota.

    PubMed

    Maukonen, Johanna; Mättö, Jaana; Satokari, Reetta; Söderlund, Hans; Mattila-Sandholm, Tiina; Saarela, Maria

    2006-12-01

    As the Clostridium coccoides-Eubacterium rectale (Erec; clostridial phylogenetic cluster XIVa) group is one of the major groups of the human intestinal microbiota, DNA- and RNA-based population analysis techniques (denaturing gradient gel electrophoresis; DGGE) were developed and applied to assess the diversity and temporal stability (6 months-2 years) of this faecal clostridial microbiota in 12 healthy adults. The stability of the Erec group was compared with the stability of the predominant bacterial microbiota, which was also assessed with PCR-DGGE. In addition, the Erec group was quantified with a hybridization-based method. According to our results, the Erec group was diverse in each subject, but interindividual uniqueness was not as clear as that of the predominant bacteria. The Erec group was found to be temporally as stable as the predominant bacteria. Over 200 clones obtained from two samples proved the developed method to be specific. However, the amount of bacteria belonging to the Erec group was not related to the diversity of that same bacterial group. In conclusion, the newly developed DGGE method proved to be a valuable and specific tool for the direct assessment of the stability of the Erec group, demonstrating diversity in addition to short-term stability in most of the subjects studied.

  20. Epididymal Cystadenomas in von Hippel-Lindau Disease Showing Increased Activity on 68Ga DOTATATE PET/CT.

    PubMed

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-10-01

    von Hippel-Lindau (VHL) disease is a familial cancer syndrome characterized by the development of a variety of malignant and benign tumors, including epididymal cystadenomas. We report a case of a VHL patient with bilateral epididymal cystadenomas who was evaluated with Ga DOTATATE PET/CT, showing intensely increased activity (SUVmax, 21.6) associated with the epididymal cystadenomas, indicating cell-surface overexpression of somatostatin receptors. The presented case supports the usefulness of somatostatin receptor imaging using Ga DOTA-conjugated peptides for detection and follow-up of VHL manifestations, as well as surveillance of asymptomatic gene carriers.

  1. Dyslexic Children Show Atypical Cerebellar Activation and Cerebro-Cerebellar Functional Connectivity in Orthographic and Phonological Processing.

    PubMed

    Feng, Xiaoxia; Li, Le; Zhang, Manli; Yang, Xiujie; Tian, Mengyu; Xie, Weiyi; Lu, Yao; Liu, Li; Bélanger, Nathalie N; Meng, Xiangzhi; Ding, Guosheng

    2017-04-01

    Previous neuroimaging studies have found atypical cerebellar activation in individuals with dyslexia in either motor-related tasks or language tasks. However, studies investigating atypical cerebellar activation in individuals with dyslexia have mostly used tasks tapping phonological processing. A question that is yet unanswered is whether the cerebellum in individuals with dyslexia functions properly during orthographic processing of words, as growing evidence shows that the cerebellum is also involved in visual and spatial processing. Here, we investigated cerebellar activation and cerebro-cerebellar functional connectivity during word processing in dyslexic readers and typically developing readers using tasks that tap orthographic and phonological codes. In children with dyslexia, we observed an abnormally higher engagement of the bilateral cerebellum for the orthographic task, which was negatively correlated with literacy measures. The greater the reading impairment was for young dyslexic readers, the stronger the cerebellar activation was. This suggests a compensatory role of the cerebellum in reading for children with dyslexia. In addition, a tendency for higher cerebellar activation in dyslexic readers was found in the phonological task. Moreover, the functional connectivity was stronger for dyslexic readers relative to typically developing readers between the lobule VI of the right cerebellum and the left fusiform gyrus during the orthographic task and between the lobule VI of the left cerebellum and the left supramarginal gyrus during the phonological task. This pattern of results suggests that the cerebellum compensates for reading impairment through the connections with specific brain regions responsible for the ongoing reading task. These findings enhance our understanding of the cerebellum's involvement in reading and reading impairment.

  2. Brain Correlates of Cognitive Remediation in Schizophrenia: Activation Likelihood Analysis Shows Preliminary Evidence of Neural Target Engagement

    PubMed Central

    Ramsay, Ian S.; MacDonald, Angus W.

    2015-01-01

    Cognitive remediation training (CRT) for schizophrenia has been found to improve cognitive functioning and influence neural plasticity. However, with various training approaches and mixed findings, the mechanisms driving generalization of cognitive skills from CRT are unclear. In this meta-analysis of extant imaging studies examining CRT’s effects, we sought to clarify whether varying approaches to CRT suggest common neural changes and whether such mechanisms are restorative or compensatory. We conducted a literature search to identify studies appropriate for inclusion in an activation likelihood estimation (ALE) meta-analysis. Our criteria required studies to consist of training-based interventions designed to improve patients’ cognitive or social functioning, including generalization to untrained circumstances. Studies were also required to examine changes in pre- vs posttraining functional activation using functional magnetic resonance imaging or positron emission tomography. The literature search identified 162 articles, 9 of which were appropriate for inclusion. ALE analyses comparing pre- and posttraining brain activation showed increased activity in the lateral and medial prefrontal cortex (PFC), parietal cortex, insula, and the caudate and thalamus. Notably, activation associated with CRT in the left PFC and thalamus partially overlapped with previous meta-analytically identified areas associated with deficits in working memory, executive control, and facial emotion processing in schizophrenia. We conclude that CRT interventions from varying theoretic modalities elicit plasticity in areas that support cognitive and socioemotional processes in this early set of studies. While preliminary, these changes appear to be both restorative and compensatory, though thalamocortical areas previously associated with dysfunction may be common sources of plasticity for cognitive remediation in schizophrenia. PMID:25800249

  3. OTX2 Activity at Distal Regulatory Elements Shapes the Chromatin Landscape of Group 3 Medulloblastoma.

    PubMed

    Boulay, Gaylor; Awad, Mary E; Riggi, Nicolo; Archer, Tenley C; Iyer, Sowmya; Boonseng, Wannaporn E; Rossetti, Nikki E; Naigles, Beverly; Rengarajan, Shruthi; Volorio, Angela; Kim, James C; Mesirov, Jill P; Tamayo, Pablo; Pomeroy, Scott L; Aryee, Martin J; Rivera, Miguel N

    2017-02-17

    Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1. These sites are responsive to OTX2 and NEUROD1 knockdown and could also be generated de novo upon ectopic OTX2 expression in primary cells, showing that OTX2 cooperates with NEUROD1 and plays a major role in maintaining and possibly establishing regulatory elements as a pioneer factor. Among OTX2 target genes, we identified the kinase NEK2, whose knockdown and pharmacologic inhibition decreased cell viability. Our studies thus show that OTX2 controls the regulatory landscape of Group 3 medulloblastoma through cooperative activity at enhancer elements and contributes to the expression of critical target genes.SIGNIFICANCE: The gene regulation mechanisms that drive medulloblastoma are not well understood. Using chromatin profiling, we find that the transcription factor OTX2 acts as a pioneer factor and, in cooperation with NEUROD1, controls the Group 3 medulloblastoma active enhancer landscape. OTX2 itself or its target genes, including the mitotic kinase NEK2, represent attractive targets for future therapies. Cancer Discov; 7(3); 1-14. ©2017 AACR.

  4. Syntheses and Characterization of Chiral Arm Liquid Crystals--Containing Active Group

    NASA Astrophysics Data System (ADS)

    Jia, Ying; Zhang, Fang-Di; He, Xiao-Zhi

    2016-05-01

    A new series of chiral two-arm dopant containg active group were first synthesized. Four precursors of C1~C4 were obtained at first and then were esterized separately with isosorbide and got four two-arm liquid crystals (MC1~MC4). The chemical structures and LC properties of the liquid crystalline molecule were measured by spectrum and thermal analysis techniques. XRD curves of MC1~MC4 samples only showed broad peaks at wide-angle, no sharp peak was seen for all the samples. The results showed that MC1~MC4 appeared cholesteric phase with oily streak texture or lined texture and finger print texture. Cholesteric phase was successfully induced by isosorbide. The different active group of two arm liquid crystal and chiral core had effects on their liquid crystalline properties.

  5. Effects of sulfate group in red seaweed polysaccharides on anticoagulant activity and cytotoxicity.

    PubMed

    Liang, Wanai; Mao, Xuan; Peng, Xiaohui; Tang, Shunqing

    2014-01-30

    In this paper, the structural effects of two main red seaweed polysaccharides (agarose and carrageenan) and their sulfated derivatives on the anticoagulant activity and cytotoxicity were investigated. The substitution position rather than the substitution degree of sulfate groups shows the biggest impact on both the anticoagulant activity and the cell proliferation. Among them, C-2 of 3,6-anhydro-α-d-Galp is the most favorable position for substitution, whereas C-6 of β-d-Galp is the most disadvantageous. Moreover, the secondary structures of glycans also play a key role in biological activities. These demonstrations warrant that the red seaweed polysaccharides should be seriously considered in biomedical applications after carefully tailoring the sulfate groups.

  6. [Preparation, characterization and adsorption performance of mesoporous activated carbon with acidic groups].

    PubMed

    Li, Kun-Quan; Li, Ye; Zheng, Zheng; Zhang, Yu-Xuan

    2013-06-01

    Mesoporous activated carbons containing acidic groups were prepared with cotton stalk based fiber as raw materials and H3PO4 as activating agent by one step carbonization method. Effects of impregnation ratio, carbonization temperature and heat preservation time on the yield, elemental composition, oxygen-containing acid functional groups and adsorptive capacity of activated carbon were studied. The adsorption capacity of the prepared activated carbon AC-01 for p-nitroaniline and Pb(II) was studied, and the adsorption mechanism was also suggested according to the equilibrium experimental results. The maximum yield of activated carbons prepared from cotton stalk fiber reached 35.5% when the maximum mesoporous volume and BET surface area were 1.39 cm3 x g(-1) and 1 731 m2 x g(-1), respectively. The activated carbon AC-01 prepared under a H3 PO4/precursor ratio of 3:2 and activated at 900 degrees C for 90 min had a total pore volume of 1.02 cm3 x g(-1), a micoporous ratio of 31%, and a mesoporous ratio of 65%. The pore diameter of the mesoporous activated carbon was mainly distributed in the range of 2-5 nm. The Langmuir maximum adsorption capacities of Pb(II) and p-nitroaniline on cotton stalk fiber activated carbon were 123 mg x g(-1) and 427 mg x g(-1), respectively, which were both higher than those for commercial activated carbon fiber ACF-CK. The equilibrium adsorption experimental data showed that mesopore and oxygen-containing acid functional groups played an important role in the adsorption.

  7. Portosystemic hepatic encephalopathy model shows reversal learning impairment and dysfunction of neural activity in the prefrontal cortex and regions involved in motivated behavior.

    PubMed

    Méndez, M; Méndez-López, M; López, L; Aller, M A; Arias, J; Arias, J L

    2011-05-01

    Hepatic encephalopathy (HE) is a neurological complication that affects attention and memory. Experimental animal models have been used to study HE, the most frequent being the portacaval shunt (PCS). In order to investigate learning impairment and brain functional alterations in this model, we assessed reversal learning and neural metabolic activity in a PCS rat model. PCS and sham-operated rats were tested for reversal learning in the Morris water maze. Brains were then processed for cytochrome oxidase (CO) histochemistry. The PCS group had reversal learning impairment and a reduction in CO activity in the prefrontal cortex, ventral tegmental area and accumbens shell nucleus. These results suggest that this model of portosystemic HE shows learning impairments that could be linked to dysfunction in neural activity in the prefrontal cortex and regions involved in motivated behavior.

  8. Epigallocatechin-3-gallate shows anti-proliferative activity in HeLa cells targeting tubulin-microtubule equilibrium.

    PubMed

    Chakrabarty, Subhendu; Ganguli, Arnab; Das, Amlan; Nag, Debasish; Chakrabarti, Gopal

    2015-12-05

    In this study our main objective was to find out a novel target of the major bioactive green tea polyphenol, Epigallocatechin-3-gallate (EGCG), in cervical carcinoma HeLa cells. We found that EGCG showed antiproliferative activity against HeLa cells through depolymerization of cellular microtubule. EGCG also prevented the reformation of the cellular microtubule network distorted by cold treatment and inhibited polymerization of tubulin in cell-free system with IC50 of 39.6 ± 0.63 μM. Fluorescence spectroscopic analysis showed that EGCG prevented colchicine binding to tubulin and in silico study revealed that EGCG bound to the α-subunit of tubulin at the interphase of the α-and β-heterodimers and very close to colchicine binding site. The binding is entropy driven (ΔS(0) was 18.75 ± 1.48 cal K(-1) mol(-1)) with Kd value of 3.50 ± 0.40 μM. This is a novel mechanism of antipriliferative activity of EGCG.

  9. Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells.

    PubMed

    Amatori, Stefano; Mazzoni, Luca; Alvarez-Suarez, Josè Miguel; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Yuliett; Afrin, Sadia; Errico Provenzano, Alfredo; Persico, Giuseppe; Mezzetti, Bruno; Amici, Augusto; Fanelli, Mirco; Battino, Maurizio

    2016-08-08

    We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the "Alba" variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy.

  10. Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

    PubMed Central

    Amatori, Stefano; Mazzoni, Luca; Alvarez-Suarez, Josè Miguel; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Yuliett; Afrin, Sadia; Errico Provenzano, Alfredo; Persico, Giuseppe; Mezzetti, Bruno; Amici, Augusto; Fanelli, Mirco; Battino, Maurizio

    2016-01-01

    We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the “Alba” variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy. PMID:27498973

  11. C(5) modified uracil derivatives showing antiproliferative and erythroid differentiation inducing activities on human chronic myelogenous leukemia K562 cells

    PubMed Central

    Brognara, Eleonora; Lampronti, Ilaria; Breveglieri, Giulia; Accetta, Alessandro; Corradini, Roberto; Manicardi, Alex; Borgatti, Monica; Canella, Alessandro; Multineddu, Chiara; Marchelli, Rosangela; Gambari, Roberto

    2011-01-01

    The K562 cell line has been proposed as a useful experimental system to identify anti-tumor compounds acting by inducing terminal erythroid differentiation. K562 cells exhibit a low proportion of hemoglobin-synthesizing cells under standard cell growth conditions, but are able to undergo terminal erythroid differentiation when treated with a variety of anti-tumor compounds. In this paper we report a screening study on a set of different modified C(5) uracil derivatives for the evaluation of their antiproliferative effect in connection with erythroid differentiation pathways, and for defining a new class of drug candidates for the treatment of chronic myelogenous leukemia. Activity of the derivatives tested can be classified in two effect: an antiproliferative effect linked to a high level of erythroid differentiation activity and an antiproliferative effect without activation of gamma globin genes The highest antiproliferative effect and erythroid induction was shown by compound 9, a thymine derivative bearing a n-octyl chain on nitrogen N(1), whereas thymine did not show any effect, suggesting the importance of the linear alkyl chain in position N(1). To our knowledge this compound should be considered among the most efficient inducers of erythroid differentiation of K562 cells. This work is the starting point for the quest of more effective and specific drugs for the induction of terminal erythroid differentiation, for leading new insights in the treatment of neoplastic diseases with molecules acting by inducing differentiation rather than by simply exerting cytotoxic effects. PMID:21958870

  12. Simple dialkyl pyrazole-3,5-dicarboxylates show in vitro and in vivo activity against disease-causing trypanosomatids.

    PubMed

    Reviriego, Felipe; Olmo, Francisco; Navarro, Pilar; Marín, Clotilde; Ramírez-Macías, Inmaculada; García-España, Enrique; Albelda, María Teresa; Gutiérrez-Sánchez, Ramón; Sánchez-Moreno, Manuel; Arán, Vicente J

    2017-04-03

    The synthesis and antiprotozoal activity of some simple dialkyl pyrazole-3,5-dicarboxylates (compounds 2-6) and their sodium salts (pyrazolates) (compounds 7-9) against Trypanosoma cruzi, Leishmania infantum and Leishmania braziliensis are reported. In most cases the studied compounds showed, especially against the clinically significant amastigote forms, in vitro activities higher than those of the reference drugs (benznidazole for T. cruzi and glucantime for Leishmania spp.); furthermore, the low non-specific cytotoxicities against Vero cells and macrophages shown by these compounds led to good selectivity indexes, which are 8-72 times higher for T. cruzi amastigotes and 15-113 times higher for Leishmania spp. amastigotes than those of the respective reference drugs. The high efficiency of diethyl ester 3 and its sodium salt 8 against the mentioned protozoa was confirmed by further in vitro assays on infection rates and by an additional in vivo study in a murine model of acute and chronic Chagas disease. The inhibitory capacity of compounds 3 and 8 on the essential iron superoxide dismutase of the aforementioned parasites may be related to the observed anti-trypanosomatid activity. The low acute toxicity of compounds 3 and 8 in mice is also reported in this article.

  13. Blood group ABO and Lewis antigens in bladder tumors: correlation between glycosyltransferase activity and antigen expression.

    PubMed

    Orntoft, T F; Wolf, H

    1988-01-01

    Pronounced changes in the expression of ABO and Lewis antigens have been observed in transitional cell carcinomas compared with normal urothelium. These changes are associated with changes in the activity of blood-group gene-encoded glycosyltransferases. This paper describes the correlation between blood-group antigen expression and the activity of glycosyltransferases in transitional cell carcinomas. Examined individuals were A1A2BO, Lewis, and secretor typed by the use of blood and saliva. The activity of alpha-2-, and alpha-4-L-fucosyltransferases as well as the alpha-3-N-acetyl-D-galactosaminyltransferase were determined as p-moles of labelled sugar incorporated by Lacto-N-biose I and 2'-fucosyllactose, respectively, per 100,000 carcinoma cells. In 3 non-secretors whose erythrocytes types as Le(a+b-), the alpha-2-L-fucosyltransferase activity was similar to that in 3 secretors, and the Leb antigen could be demonstrated to be present by monoclonal antibodies, both by immunohistological and immunochemical means. In 11 tumors from A individuals, the A1-transferase was severely reduced in 9 individuals who showed a loss of A antigen expression, and present in 2 individuals with A antigen expression in cytoplasmic vesicles. In conclusion, we demonstrate a good correlation between individual glycosyltransferase activity and expression of blood group Leb and loss of expression of blood group A in transitional cell carcinomas. Immunostaining of neutral glycolipids separated by TLC showed the Leb-active glycolipids to be simple hexa-saccharides in both secretors and non-secretors.

  14. Formation of nanostructured Group IIA metal activated sensors: The transformation of Group IIA metal compound sites

    NASA Astrophysics Data System (ADS)

    Tune, Travis C.; Baker, Caitlin; Hardy, Neil; Lin, Arthur; Widing, Timothy J.; Gole, James L.

    2015-05-01

    Trends in the Group IIA metal oxides and hydroxides of magnesium, calcium, and barium are unique in the periodic table. In this study we find that they display novel trends as decorating nanostructures for extrinsic semiconductor interfaces. The Group IIA metal ions are strong Lewis acids. We form these M2+ ions in aqueous solution and bring these solutions in contact with a porous silicon interface to form interfaces for conductometric measurements. Observed responses are consistent with the formation of MgO whereas the heavier elements display behaviors which suggest the effect of their more basic nature. Mg(OH)2, when formed, represents a weak base whereas the heavier metal hydroxides of Ca, Sr, and Ba are strong bases. However, the hydroxides tend to give up hydrogen and act as Brönsted acids. For the latter elements, the reversible interaction response of nanostructures deposited to the porous silicon (PS) interface is modified, as the formation of more basic sites appears to compete with M2+ Lewis acidity and hydroxide Brönsted acidity. Mg2+ forms an interface whose response to the analytes NH3 and NO is consistent with MgO and well explained by the recently developing Inverse Hard/Soft Acid/Base model. The behavior of the Ca2+ and Ba2+ decorated interfaces as they interact with the hard base NH3 follows a reversal of the model, indicating a decrease in acidic character as the observed conductometric response suggests the interaction with hydroxyl groups. A change from oxide-like to hydroxide-like constituents is supported by XPS studies. The changes in conductometric response is easily monitored in contrast to changes associated with the Group IIA oxides and hydroxides observed in XPS, EDAX, IR, and NMR measurements.

  15. Mono- and dinuclear manganese(III) complexes showing efficient catechol oxidase activity: syntheses, characterization and spectroscopic studies.

    PubMed

    Banu, Kazi Sabnam; Chattopadhyay, Tanmay; Banerjee, Arpita; Mukherjee, Madhuparna; Bhattacharya, Santanu; Patra, Goutam Kumar; Zangrando, Ennio; Das, Debasis

    2009-10-28

    Four side-off compartmental ligands L1-L4 [L1 = N,N'-ethylenebis(3-formyl-5-methyl-salicylaldimine), L2 = N,N'-1-methylethylenebis(3-formyl-5-methylsalicylaldimine), L3 = N,N'-1,1-dimethylethylenebis(3-formyl-5-methylsalicylaldimine) and L4= N,N'-cyclohexenebis(3-formyl-5-methylsalicylaldimine)] having two binding sites, N2O2 and O4, have been chosen to synthesize mononuclear and dinuclear manganese(III) complexes with the aim to study their catecholase activity using 3,5-di-tert-butylcatechol (3,5-DTBC) as substrate in the presence of molecular oxygen. In all cases only mononuclear manganese complexes (1-4) were obtained, with manganese coordination taking place at the N2O2 binding site only, irrespective of the amount of manganese salt used. All these complexes have been characterized by routine physico-chemical techniques. Complex MnL2Cl.4H2O (2) has further been structurally characterized by X-ray single crystal structure analysis. Four dinuclear manganese complexes, 5-8, were obtained after condensing the two pending formyl groups on each ligand (L1-L4) with aniline followed by reaction with MnCl2 to put the second Mn atom onto another N2O2 site. The catalytic activity of all complexes 1-8 has been investigated following the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert-butylbenzoquinone (3,5-DTBQ) with molecular oxygen in two different solvents, methanol and acetonitrile. The study reveals that the catalytic activity is influenced by the solvent and to a significant extent by the backbone of the diamine and the behavior seems to be related mainly to steric rather than electronic factors. Experimental data suggest that a correlation, the lower the E(1/2) value the higher the catalytic activity, can be drawn between E(1/2) and Vmax of the complexes in a particular solvent. The EPR measurements suggest that the catalytic property of the complexes is related to the metal center(s) participation rather than to a radical mechanism.

  16. Phosphoinositide 5- and 3-phosphatase activities of a voltage-sensing phosphatase in living cells show identical voltage dependence

    PubMed Central

    Keum, Dongil; Kim, Dong-Il; Suh, Byung-Chang

    2016-01-01

    Voltage-sensing phosphatases (VSPs) are homologs of phosphatase and tensin homolog (PTEN), a phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] 3-phosphatase. However, VSPs have a wider range of substrates, cleaving 3-phosphate from PI(3,4)P2 and probably PI(3,4,5)P3 as well as 5-phosphate from phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and PI(3,4,5)P3 in response to membrane depolarization. Recent proposals say these reactions have differing voltage dependence. Using Förster resonance energy transfer probes specific for different PIs in living cells with zebrafish VSP, we quantitate both voltage-dependent 5- and 3-phosphatase subreactions against endogenous substrates. These activities become apparent with different voltage thresholds, voltage sensitivities, and catalytic rates. As an analytical tool, we refine a kinetic model that includes the endogenous pools of phosphoinositides, endogenous phosphatase and kinase reactions connecting them, and four exogenous voltage-dependent 5- and 3-phosphatase subreactions of VSP. We show that apparent voltage threshold differences for seeing effects of the 5- and 3-phosphatase activities in cells are not due to different intrinsic voltage dependence of these reactions. Rather, the reactions have a common voltage dependence, and apparent differences arise only because each VSP subreaction has a different absolute catalytic rate that begins to surpass the respective endogenous enzyme activities at different voltages. For zebrafish VSP, our modeling revealed that 3-phosphatase activity against PI(3,4,5)P3 is 55-fold slower than 5-phosphatase activity against PI(4,5)P2; thus, PI(4,5)P2 generated more slowly from dephosphorylating PI(3,4,5)P3 might never accumulate. When 5-phosphatase activity was counteracted by coexpression of a phosphatidylinositol 4-phosphate 5-kinase, there was accumulation of PI(4,5)P2 in parallel to PI(3,4,5)P3 dephosphorylation

  17. Cephalosporin-NO-donor prodrug PYRRO-C3D shows β-lactam-mediated activity against Streptococcus pneumoniae biofilms.

    PubMed

    Allan, Raymond N; Kelso, Michael J; Rineh, Ardeshir; Yepuri, Nageshwar R; Feelisch, Martin; Soren, Odel; Brito-Mutunayagam, Sanjita; Salib, Rami J; Stoodley, Paul; Clarke, Stuart C; Webb, Jeremy S; Hall-Stoodley, Luanne; Faust, Saul N

    2017-05-01

    Bacterial biofilms show high tolerance towards antibiotics and are a significant problem in clinical settings where they are a primary cause of chronic infections. Novel therapeutic strategies are needed to improve anti-biofilm efficacy and support reduction in antibiotic use. Treatment with exogenous nitric oxide (NO) has been shown to modulate bacterial signaling and metabolic processes that render biofilms more susceptible to antibiotics. We previously reported on cephalosporin-3'-diazeniumdiolates (C3Ds) as NO-donor prodrugs designed to selectively deliver NO to bacterial infection sites following reaction with β-lactamases. With structures based on cephalosporins, C3Ds could, in principal, also be triggered to release NO following β-lactam cleavage mediated by transpeptidases/penicillin-binding proteins (PBPs), the antibacterial target of cephalosporin antibiotics. Transpeptidase-reactive C3Ds could potentially show both NO-mediated anti-biofilm properties and intrinsic (β-lactam-mediated) antibacterial effects. This dual-activity concept was explored using Streptococcus pneumoniae, a species that lacks β-lactamases but relies on transpeptidases for cell-wall synthesis. Treatment with PYRRO-C3D (a representative C3D containing the diazeniumdiolate NO donor PYRRO-NO) was found to significantly reduce viability of planktonic and biofilm pneumococci, demonstrating that C3Ds can elicit direct, cephalosporin-like antibacterial activity in the absence of β-lactamases. While NO release from PYRRO-C3D in the presence of pneumococci was confirmed, the anti-pneumococcal action of the compound was shown to arise exclusively from the β-lactam component and not through NO-mediated effects. The compound showed similar potency to amoxicillin against S. pneumoniae biofilms and greater efficacy than azithromycin, highlighting the potential of C3Ds as new agents for treating pneumococcal infections.

  18. Parents' Networking Strategies: Participation of Formal and Informal Parent Groups in School Activities and Decisions

    ERIC Educational Resources Information Center

    Wanat, Carolyn L.

    2010-01-01

    This case study examined parent groups' involvement in school activities and their participation in decision making. Research questions included the following: (1) What is the nature of parent groups in schools? (2) What activities and issues gain parent groups' attention and participation? (3) How do parent groups communicate concerns about…

  19. An alpha2,6-sialyltransferase cloned from Photobacterium leiognathi strain JT-SHIZ-119 shows both sialyltransferase and neuraminidase activity.

    PubMed

    Mine, Toshiki; Katayama, Sakurako; Kajiwara, Hitomi; Tsunashima, Masako; Tsukamoto, Hiroshi; Takakura, Yoshimitsu; Yamamoto, Takeshi

    2010-02-01

    We cloned, expressed, and characterized a novel beta-galactoside alpha2,6-sialyltransferase from Photobacterium leiognathi strain JT-SHIZ-119. The protein showed 56-96% identity to the marine bacterial alpha2,6-sialyltransferases classified into glycosyltransferase family 80. The sialyltransferase activity of the N-terminal truncated form of the recombinant enzyme was 1477 U/L of Escherichia coli culture. The truncated recombinant enzyme was purified as a single band by sodium dodecyl sulfate polyacrylamide gel electrophoresis through 3 column chromatography steps. The enzyme had distinct activity compared with known marine bacterial alpha2,6-sialyltransferases. Although alpha2,6-sialyltransferases cloned from marine bacteria, such as Photobacterium damselae strain JT0160, P. leiognathi strain JT-SHIZ-145, and Photobacterium sp. strain JT-ISH-224, show only alpha2,6-sialyltransferase activity, the recombinant enzyme cloned from P. leiognathi strain JT-SHIZ-119 showed both alpha2,6-sialyltransferase and alpha2,6-linkage-specific neuraminidase activity. Our results provide important information toward a comprehensive understanding of the bacterial sialyltransferases belonging to the group 80 glycosyltransferase family in the CAZy database.

  20. Indonesian fire activity and smoke pollution in 2015 show persistent nonlinear sensitivity to El Niño-induced drought

    NASA Astrophysics Data System (ADS)

    Field, Robert D.; van der Werf, Guido R.; Fanin, Thierry; Fetzer, Eric J.; Fuller, Ryan; Jethva, Hiren; Levy, Robert; Livesey, Nathaniel J.; Luo, Ming; Torres, Omar; Worden, Helen M.

    2016-08-01

    The 2015 fire season and related smoke pollution in Indonesia was more severe than the major 2006 episode, making it the most severe season observed by the NASA Earth Observing System satellites that go back to the early 2000s, namely active fire detections from the Terra and Aqua Moderate Resolution Imaging Spectroradiometers (MODIS), MODIS aerosol optical depth, Terra Measurement of Pollution in the Troposphere (MOPITT) carbon monoxide (CO), Aqua Atmospheric Infrared Sounder (AIRS) CO, Aura Ozone Monitoring Instrument (OMI) aerosol index, and Aura Microwave Limb Sounder (MLS) CO. The MLS CO in the upper troposphere showed a plume of pollution stretching from East Africa to the western Pacific Ocean that persisted for 2 mo. Longer-term records of airport visibility in Sumatra and Kalimantan show that 2015 ranked after 1997 and alongside 1991 and 1994 as among the worst episodes on record. Analysis of yearly dry season rainfall from the Tropical Rainfall Measurement Mission (TRMM) and rain gauges shows that, due to the continued use of fire to clear and prepare land on degraded peat, the Indonesian fire environment continues to have nonlinear sensitivity to dry conditions during prolonged periods with less than 4 mm/d of precipitation, and this sensitivity appears to have increased over Kalimantan. Without significant reforms in land use and the adoption of early warning triggers tied to precipitation forecasts, these intense fire episodes will reoccur during future droughts, usually associated with El Niño events.

  1. Indonesian fire activity and smoke pollution in 2015 show persistent nonlinear sensitivity to El Niño-induced drought.

    PubMed

    Field, Robert D; van der Werf, Guido R; Fanin, Thierry; Fetzer, Eric J; Fuller, Ryan; Jethva, Hiren; Levy, Robert; Livesey, Nathaniel J; Luo, Ming; Torres, Omar; Worden, Helen M

    2016-08-16

    The 2015 fire season and related smoke pollution in Indonesia was more severe than the major 2006 episode, making it the most severe season observed by the NASA Earth Observing System satellites that go back to the early 2000s, namely active fire detections from the Terra and Aqua Moderate Resolution Imaging Spectroradiometers (MODIS), MODIS aerosol optical depth, Terra Measurement of Pollution in the Troposphere (MOPITT) carbon monoxide (CO), Aqua Atmospheric Infrared Sounder (AIRS) CO, Aura Ozone Monitoring Instrument (OMI) aerosol index, and Aura Microwave Limb Sounder (MLS) CO. The MLS CO in the upper troposphere showed a plume of pollution stretching from East Africa to the western Pacific Ocean that persisted for 2 mo. Longer-term records of airport visibility in Sumatra and Kalimantan show that 2015 ranked after 1997 and alongside 1991 and 1994 as among the worst episodes on record. Analysis of yearly dry season rainfall from the Tropical Rainfall Measurement Mission (TRMM) and rain gauges shows that, due to the continued use of fire to clear and prepare land on degraded peat, the Indonesian fire environment continues to have nonlinear sensitivity to dry conditions during prolonged periods with less than 4 mm/d of precipitation, and this sensitivity appears to have increased over Kalimantan. Without significant reforms in land use and the adoption of early warning triggers tied to precipitation forecasts, these intense fire episodes will reoccur during future droughts, usually associated with El Niño events.

  2. Indonesian fire activity and smoke pollution in 2015 show persistent nonlinear sensitivity to El Niño-induced drought

    PubMed Central

    Field, Robert D.; van der Werf, Guido R.; Fanin, Thierry; Fetzer, Eric J.; Fuller, Ryan; Jethva, Hiren; Levy, Robert; Livesey, Nathaniel J.; Luo, Ming; Torres, Omar; Worden, Helen M.

    2016-01-01

    The 2015 fire season and related smoke pollution in Indonesia was more severe than the major 2006 episode, making it the most severe season observed by the NASA Earth Observing System satellites that go back to the early 2000s, namely active fire detections from the Terra and Aqua Moderate Resolution Imaging Spectroradiometers (MODIS), MODIS aerosol optical depth, Terra Measurement of Pollution in the Troposphere (MOPITT) carbon monoxide (CO), Aqua Atmospheric Infrared Sounder (AIRS) CO, Aura Ozone Monitoring Instrument (OMI) aerosol index, and Aura Microwave Limb Sounder (MLS) CO. The MLS CO in the upper troposphere showed a plume of pollution stretching from East Africa to the western Pacific Ocean that persisted for 2 mo. Longer-term records of airport visibility in Sumatra and Kalimantan show that 2015 ranked after 1997 and alongside 1991 and 1994 as among the worst episodes on record. Analysis of yearly dry season rainfall from the Tropical Rainfall Measurement Mission (TRMM) and rain gauges shows that, due to the continued use of fire to clear and prepare land on degraded peat, the Indonesian fire environment continues to have nonlinear sensitivity to dry conditions during prolonged periods with less than 4 mm/d of precipitation, and this sensitivity appears to have increased over Kalimantan. Without significant reforms in land use and the adoption of early warning triggers tied to precipitation forecasts, these intense fire episodes will reoccur during future droughts, usually associated with El Niño events. PMID:27482096

  3. Physical activity and beverage consumption in preschoolers: focus groups with parents and teachers

    PubMed Central

    2013-01-01

    Background Qualitative research is a method in which new ideas and strategies can be discovered. This qualitative study aimed to investigate parents’ and teachers’ opinions on physical activity and beverage consumption of preschool children. Through separate, independent focus groups, they expressed their perceptions on children’s current physical activity and beverage consumption levels, factors that influence and enhance these behaviours, and anticipated barriers to making changes. Methods Multi-cultural and multi-geographical focus groups were carried out in six European countries (Belgium, Bulgaria, Germany, Greece, Poland and Spain). In total, twenty-four focus groups with 122 parents and eighteen focus groups with 87 teachers were conducted between October 2010 and January 2011. Based on a semi-structured interview guide, questions on preschoolers’ physical activity (opinions on preschoolers’ physical activity, how to increase physical activity, facilitators and barriers of physical activity) and beverage consumption (rules and policies, factors influencing promotion of healthy drinking, recommendations for future intervention development) were asked. The information was analyzed using qualitative data analysis software (NVivo8). Results The focus group results indicated misperceptions of caregivers on preschoolers’ physical activity and beverage consumption levels. Caregivers perceived preschoolers as sufficiently active; they argue that children need to learn to sit still in preparation for primary school. At most preschools, children can drink only water. In some preschools sugar-sweetened beverages like chocolate milk or fruit juices, are also allowed. It was mentioned that sugar-sweetened beverages can be healthy due to mineral and vitamin content, although according to parents their daily intake is limited. These opinions resulted in low perceived needs to change behaviours. Conclusions Although previous research shows need of change in

  4. Design, synthesis, and antifungal activities of novel triazole derivatives containing the benzyl group

    PubMed Central

    Xu, Kehan; Huang, Lei; Xu, Zheng; Wang, Yanwei; Bai, Guojing; Wu, Qiuye; Wang, Xiaoyan; Yu, Shichong; Jiang, Yuanying

    2015-01-01

    In previous studies undertaken by our group, a series of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols (1a–r), which were analogs of fluconazole, was designed and synthesized by click chemistry. In the study reported here, the in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi. Compounds 1a, 1q, and 1r showed the more antifungal activity than the others. PMID:25792806

  5. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

    For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the…

  6. Rat supraoptic magnocellular neurones show distinct large conductance, Ca2+-activated K+ channel subtypes in cell bodies versus nerve endings

    PubMed Central

    Dopico, Alejandro M; Widmer, Hélène; Wang, Gang; Lemos, José R; Treistman, Steven N

    1999-01-01

    Large conductance, Ca2+-activated K+ (BK) channels were identified in freshly dissociated rat supraoptic neurones using patch clamp techniques. The single channel conductance of cell body BK channels, recorded from inside-out patches in symmetric 145 mM K+, was 246.1 pS, compared with 213 pS in nerve ending BK channels (P < 0.01). At low open probability (Po), the reciprocal of the slope in the ln(NPo)-voltage relationship (N, number of available channels in the patch) for cell body and nerve ending channels were similar: 11 vs. 14 mVper e-fold change in NPo, respectively. At 40 mV, the [Ca2+]i producing half-maximal activation was 273 nM, as opposed to > 1.53 μM for the neurohypophysial channel, indicating the higher Ca2+ sensitivity of the cell body isochannel. Cell body BK channels showed fast kinetics (open time constant, 8.5 ms; fast closed time constant, 1.6 and slow closed time constant, 12.7 ms), identifying them as ‘type I’ isochannels, as opposed to the slow gating (type II) of neurohypophysial BK channels. Cell body BK activity was reduced by 10 nM charybdotoxin (NPo, 37 % of control), or 10 nM iberiotoxin (NPo, 5 % of control), whereas neurohypophysial BK channels are insensitive to charybdotoxin at concentrations as high as 360 nM. Whilst blockade of nerve ending BK channels markedly slowed the repolarization of evoked single spikes, blockade of cell body channels was without effect on repolarization of evoked single spikes. Ethanol reversibly increased neurohypophysial BK channel activity (EC50, 22 mM; maximal effect, 100 mM). In contrast, ethanol (up to 100 mM) failed to increase cell body BK channel activity. In conclusion, we have characterized BK channels in supraoptic neuronal cell bodies, and demonstrated that they display different electrophysiological and pharmacological properties from their counterparts in the nerve endings. PMID:10432342

  7. Epidihydropinidine, the main piperidine alkaloid compound of Norway spruce (Picea abies) shows promising antibacterial and anti-Candida activity.

    PubMed

    Fyhrquist, Pia; Virjamo, Virpi; Hiltunen, Eveliina; Julkunen-Tiitto, Riitta

    2017-03-01

    This study reports for the first time promising antibacterial and antifungal effects of epidihydropinidine, the major piperidine alkaloid in the needles and bark of Norway spruce, Picea abies (L.) Karsten. Epidihydropinidine was growth inhibitory against all bacterial and fungal strains used in our investigation, showing the lowest MIC value of 5.37μg/mL against Pseudomonas aeruginosa, Enterococcus faecalis, Candida glabrata and C. albicans. Epidihydropinidine was nearly three times more active than tetracycline against P. aeruginosa and E. faecalis. Promising antibacterial effects were also recorded against Staphylococcus aureus and Bacillus cereus (MIC 10.75μg/mL) as well as against Salmonella enterica (MIC and MBC 43μg/mL). Our preliminary results suggest that epidihydropinidine as well related alkaloids of Norway spruce could be powerful candidates for new antibiotics and for preventing food spoilage.

  8. Novel triterpenoid saponins from residual seed cake of Camellia oleifera Abel. show anti-proliferative activity against tumor cells.

    PubMed

    Zong, Jianfa; Wang, Ruilong; Bao, Guanhu; Ling, Tiejun; Zhang, Liang; Zhang, Xinfu; Hou, Ruyan

    2015-07-01

    Four oleanane-type triterpenoid saponins were isolated from the seed cake of Camellia oleifera Abel.: camelliasaponin B1 and three new saponins, oleiferasaponin C1-C3 (1-3). Their structures were identified as 22-O-angeloyl-camelliagenin B 3-O-[β-d-galactopyranosyl-(1→2)]-[β-d-galactopyranosyl-(1→2)-α-l-arabinopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (1); 22-O-angeloyl-camelliagenin A 3-O-[β-d-galactopyranosyl-(1→2)]-[β-d-glucopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (2); and 28-O-cinnamoyl-camelliagenin B 3-O-[β-d-galactopyranosylz-(1→2)] [β-d-galactopyranosyl(1→2)-α-l-arabinopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (3) through 1D and 2D NMR, HR-ESI-MS, as well as GC-MS spectroscopic methods. The anti-proliferative activities of these four compounds were investigated on five human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB). Compounds 1 and 2 and camelliasaponin B1 showed significant cytotoxic activities.

  9. Governance - Alignment and Configuration of Business Activities Task Group Report

    DTIC Science & Technology

    2006-05-01

    governance level and the Enterprise Model as a way of ensuring integration at the management and work/execution levels 3. Ensure shared services (i.e...Management Framework o QDR Organizational Model o Secretary of Defense 2006-2008 Priorities o Shared Services Defense Business Board...support for horizontal and vertical organizations • Move “supporting” organizations to shared services model May 2006 "Team Defense" 18 Task Group

  10. Graphene Oxide Catalyzed C-H Bond Activation: The Importance Oxygen Functional Groups for Biaryl Construction

    SciTech Connect

    Gao, Yongjun; Tang, Pei; Zhou, Hu; Zhang, Wei; Yang, Hanjun; Yan, Ning; Hu, Gang; Mei, Donghai; Wang, Jianguo; Ma, Ding

    2016-02-24

    A heterogeneous, inexpensive and environment-friendly carbon catalytic system was developed for the C-H bond arylation of benzene resulting in the subsequent formation of biaryl compounds. The oxygen-containing groups on these graphene oxide sheets play an essential role in the observed catalytic activity. The catalytic results of model compounds and DFT calculations show that these functional groups promote this reaction by stabilization and activation of K ions at the same time of facilitating the leaving of I. And further mechanisms studies show that it is the charge induced capabilities of oxygen groups connected to specific carbon skeleton together with the giant π-reaction platform provided by the π-domain of graphene that played the vital roles in the observed excellent catalytic activity. D. Mei acknowledges the support from the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory (PNNL) is a multiprogram national laboratory operated for DOE by Battelle. Computing time was granted by the grand challenge of computational catalysis of the William R. Wiley Environmental Molecular Sciences Laboratory.

  11. Poly(amidoamine) dendrimers show carbonic anhydrase inhibitory activity against α-, β-, γ- and η-class enzymes.

    PubMed

    Carta, Fabrizio; Osman, Sameh M; Vullo, Daniela; AlOthman, Zeid; Del Prete, Sonia; Capasso, Clemente; Supuran, Claudiu T

    2015-11-01

    Four generations of poly(amidoamine) (PAMAM) dendrimers incorporating benzenesulfonamide moieties were investigated as inhibitors of carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α-, β-, γ- and η-classes which are present in pathogenic bacteria, fungi or protozoa. The following bacterial, fungal and protozoan organisms were included in the study: Vibrio cholerae, Trypanosoma cruzi, Leishmania donovani chagasi, Porphyromonas gingivalis, Cryptococcus neoformans, Candida glabrata, and Plasmodium falciparum. The eight pathozymes present in these organisms were efficiently inhibited by the four generations PAMAM-sulfonamide dendrimers, but multivalency effects were highly variable among the different enzyme classes. The Vibrio enzyme VchCA was best inhibited by the G3 dendrimer incorporating 32 sulfamoyl moieties. The Trypanosoma enzyme TcCA on the other hand was best inhibited by the first generation dendrimer G0 (with 4 sulfamoyl groups), whereas for other enzymes the optimal inhibitory power was observed for the G1 or G2 dendrimers, with 8 and 16 sulfonamide functionalities. This study thus proves that the multivalency may be highly relevant for enzyme inhibition for some but not all CAs from pathogenic organisms. On the other hand, some dendrimers investigated here showed a better inhibitory power compared to acetazolamide for enzymes from widespread pathogens, such as the η-CA from Plasmodium falciparum. Overall, the main conclusion is that this class of molecules may lead to important developments in the field of anti-infective CA inhibitors.

  12. Working Group 5: Measurements technology and active experiments

    NASA Technical Reports Server (NTRS)

    Whipple, E.; Barfield, J. N.; Faelthammar, C.-G.; Feynman, J.; Quinn, J. N.; Roberts, W.; Stone, N.; Taylor, W. L.

    1986-01-01

    Technology issues identified by working groups 5 are listed. (1) New instruments are needed to upgrade the ability to measure plasma properties in space. (2) Facilities should be developed for conducting a broad range of plasma experiments in space. (3) The ability to predict plasma weather within magnetospheres should be improved and a capability to modify plasma weather developed. (4) Methods of control of plasma spacecraft and spacecraft plasma interference should be upgraded. (5) The space station laboratory facilities should be designed with attention to problems of flexibility to allow for future growth. These issues are discussed.

  13. Crack users show high rates of antisocial personality disorder, engagement in illegal activities and other psychosocial problems.

    PubMed

    Paim Kessler, Felix Henrique; Barbosa Terra, Mauro; Faller, Sibele; Ravy Stolf, Anderson; Carolina Peuker, Ana; Benzano, Daniela; Pechansky, Flavio

    2012-01-01

    The aim of this study was to compare three groups of Brazilian psychoactive substance (PAS) abuse patients (crack cocaine users, cocaine snorters, and non-cocaine PAS users) in terms of psychiatric comorbidities and severity of psychosocial problems. A cross-sectional, multi-center study was conducted at five Brazilian research centers. A total of 738 current PAS abusers seeking specialized treatment (outpatient and inpatient clinics) were assessed using the sixth version of the Addiction Severity Index (ASI-6): 293 patients using crack cocaine were compared with 126 using powder cocaine and 319 using non-cocaine PAS (mostly alcohol and marijuana). Psychiatric comorbidities were assessed in a smaller sample (290 cases), originating from three of the centers, using the Mini International Neuropsychiatric Interview Plus (MINI-Plus). Crack and powder cocaine users were significantly younger than non-cocaine PAS users (31.1 ± 8.1 and 32.9 ± 8.8 vs. 42.4 ± 12, respectively; p < .001). Crack users presented a higher rate of antisocial personality disorder (25%) than powder cocaine (9%) and non-cocaine PAS users (9%), even when adjusted for confounding factors (Pr = 2.6; 95% CI 1.10-6.40). According to ASI-6 summary scores, crack users presented a significantly higher rate of occupational, family, and legal problems and reported more illegal and violent activities such as burglary and theft (23%) and threatening or assaulting (32%) than non-cocaine PAS users. Our findings, combined with the recent increase observed in the prevalence of crack use in Brazil, highlight the severity of psychiatric symptoms and psychosocial problems related to this powerful drug and corroborate the already suggested association between crack/cocaine, violence, and legal problems. Treatment programs for crack users should routinely consider the possibility of associated psychiatric comorbidities, such as antisocial personality disorder, which may affect treatment outcomes.

  14. Polysaccharides from the Medicinal Mushroom Cordyceps taii Show Antioxidant and Immunoenhancing Activities in a D-Galactose-Induced Aging Mouse Model

    PubMed Central

    Xiao, Jian-Hui; Xiao, Dai-Min; Chen, Dai-Xiong; Xiao, Yu; Liang, Zong-Qi; Zhong, Jian-Jiang

    2012-01-01

    Cordyceps taii, an edible medicinal mushroom native to south China, is recognized as an unparalleled resource of healthy foods and drug discovery. In the present study, the antioxidant pharmacological properties of C. taii were systematically investigated. In vitro assays revealed the scavenging activities of the aqueous extract and polysaccharides of C. taii against various free radicals, that is, 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, and superoxide anion radical. The EC50 values for superoxide anion-free radical ranged from 2.04 mg/mL to 2.49 mg/mL, which was at least 2.6-fold stronger than that of antioxidant thiourea. The polysaccharides also significantly enhanced the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) and markedly decreased the malondialdehyde production of lipid peroxidation in a D-galactose-induced aging mouse model. Interestingly, the immune function of the administration group was significantly boosted compared with the D-galactose-induced aging model group. Therefore, the C. taii polysaccharides possessed potent antioxidant activity closely associated with immune function enhancement and free radical scavenging. These findings suggest that the polysaccharides are a promising source of natural antioxidants and antiaging drugs. Consequently, a preliminary chemical investigation was performed using gas chromatography-mass spectroscopy and revealed that the polysaccharides studied were mainly composed of glucose, mannose, and galactose. Fourier-transform infrared spectra also showed characteristic polysaccharide absorption bands. PMID:22536281

  15. Patients with idiopathic recurrent miscarriage show higher levels of DR+ activated T-cells that are less responsive to mitogens.

    PubMed

    Kuon, R J; Schaumann, J; Goeggl, T; Strowitzki, T; Sadeghi, M; Opelz, G; Daniel, V; Toth, B

    2015-11-01

    In 50% of recurrent miscarriages (RM) the cause remains unknown and standardized immunological diagnosis and treatment of idiopathic RM (iRM) is yet not established. In this prospective case-control study, out of 220 RM patients screened, 97 iRM patients were identified and compared to 26 healthy controls without a previous pregnancy or blood transfusion in order to identify deregulated immunological parameters. Blood levels of lymphocyte subpopulations, cytokines and neopterin were determined by FACS, ELISA, and Luminex technique. Lymphocyte function was studied by in-vitro lympocyte proliferation tests. As compared to controls, patients had significantly higher proportions of activated CD3+DR+, CD4+DR+ and CD8+DR+ lymphocytes, elevated levels of neopterin and a lower in-vitro proliferation of lymphocytes (all p<0.05). Within the iRM patients higher proportions of CD3+DR+ T-lymphocytes correlated with higher proportions and absolute numbers of CD4+DR+ and CD8+DR+ T-lymphocytes and lower CD16+CD56+ NK-cells. Further, it was associated with lower absolute numbers of CD19+ B-lymphocytes, CD3+CD25+ T-lymphocytes and CD45+ total lymphocytes (all p<0.05). In addition we found decreased in-vitro lymphocyte proliferation in iRM patients with high CD3+DR+ T-lymphocytes (p<0.05). In summary patients with iRM showed increased activated T-cells that are less responsive to mitogens in-vitro. The inverse relationship of increased DR but decreased CD25 expression on CD3+ T-cells and the decreased in-vitro proliferation characterize an immunological disorder with similarities to T-cell exhaustion in patients with HIV and cancer. These abnormalities potentially contribute to the pathogenesis of iRM and might be a target for future immunomodulatory therapies.

  16. The Isothiocyanate Isolated from Moringa oleifera Shows Potent Anti-Inflammatory Activity in the Treatment of Murine Subacute Parkinson's Disease.

    PubMed

    Giacoppo, Sabrina; Rajan, Thangavelu Soundara; De Nicola, Gina Rosalinda; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

    2017-02-01

    The present study was aimed at estimating a possible neuroprotective effect of glucomoringin (GMG) [4-(α-L-rhamnopyranosyloxy)benzyl glucosinolate] bioactivated with the enzyme myrosinase to form the corresponding isothiocyanate [4-(α-L-rhamnopyranosyloxy)benzyl C; moringin] in the treatment or prevention of Parkinson's disease (PD). In this study, the beneficial effects of moringin were compared with those of pure GMG, not enzymatically activated, in an in vivo experimental mouse model of subacute PD. Subacute PD was induced in C57BL/6 mice by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were pretreated daily for 1 week with moringin (10 mg/kg +5 μL myrosinase/mouse) and with GMG (10 mg/kg). Behavioral evaluations were also performed to assess motor deficits and bradykinesia in MPTP mice. Besides, assuming that pretreatment with moringin could modulate the triggering of inflammatory cascade with a correlated response, we tested its in vitro anti-inflammatory activity by using a model of RAW 264.7 macrophages stimulated with lipopolysaccharide. Achieved results in vivo showed a higher efficacy of moringin compared with GMG not only to modulate the inflammatory pathway but also oxidative stress and apoptotic pathways. In addition, the greater effectiveness of moringin in countering mainly the inflammatory pathway has been corroborated by the results obtained in vitro. The relevance and innovation of the present study lie in the possible use of a safe formulation of a bioactive compound, resulting from exogenous myrosinase hydrolysis of the natural phytochemical GMG, which can be used in clinical practice as a useful drug for the treatment or prevention of PD.

  17. PASylated Coversin, a C5-Specific Complement Inhibitor with Extended Pharmacokinetics, Shows Enhanced Anti-Hemolytic Activity in Vitro.

    PubMed

    Kuhn, Nadine; Schmidt, Christoph Q; Schlapschy, Martin; Skerra, Arne

    2016-10-19

    The Ornithodoros moubata Complement Inhibitor (OmCI) binds complement component 5 (C5) with high affinity and, thus, selectively prevents proteolytic activation of the terminal lytic complement pathway. A recombinant version of OmCI (also known as Coversin and rEV576) has proven efficacious in several animal models of complement-mediated diseases and successfully completed a phase Ia clinical trial. Coversin is a small 17 kDa lipocalin protein which has a very short plasma half-life if not bound to C5; therefore, the drug requires frequent dosing. We have improved the pharmacokinetics of Coversin by N-terminal translational conjugation with a 600 residue polypeptide composed of Pro, Ala, and Ser (PAS) residues. To this end, PAS-Coversin as well as the unmodified Coversin were functionally expressed in the cytoplasm of E. coli and purified to homogeneity. Both versions showed identical affinity to human C5, as determined by surface plasmon resonance measurements, and revealed similar complement inhibitory activity, as measured in ELISAs with human serum. In line with the PEG-like biophysical properties, PASylation dramatically prolonged the plasma half-life of uncomplexed Coversin by a factor ≥50 in mice. In a clinically relevant in vitro model of the complement-mediated disease paroxysmal nocturnal hemoglobinuria (PNH) both versions of Coversin effectively reduced erythrocyte lysis. Unexpectedly, while the IC50 values were comparable, PAS-Coversin reached a substantially lower plateau of residual lysis at saturating inhibitor concentrations. Taken together, our data demonstrate two clinically relevant improvements of PASylated Coversin: markedly increased plasma half-life and considerably reduced background hemolysis of erythrocytes with PNH-induced phenotype.

  18. Sequence analysis of the non-recurring C-terminal domains shows that insect lipoprotein receptors constitute a distinct group of LDL receptor family members.

    PubMed

    Rodenburg, Kees W; Smolenaars, Marcel M W; Van Hoof, Dennis; Van der Horst, Dick J

    2006-04-01

    Lipoprotein-mediated delivery of lipids in mammals involves endocytic receptors of the low density lipoprotein (LDL) receptor (LDLR) family. In contrast, in insects, the lipoprotein, lipophorin (Lp), functions as a reusable lipid shuttle in lipid delivery, and these animals, therefore, were not supposed to use endocytic receptors. However, recent data indicate additional endocytic uptake of Lp, mediated by a Lp receptor (LpR) of the LDLR family. The two N-terminal domains of LDLR family members are involved in ligand binding and dissociation, respectively, and are composed of a mosaic of multiple repeats. The three C-terminal domains, viz., the optional O-linked glycosylation domain, the transmembrane domain, and the intracellular domain, are of a non-repetitive sequence. The present classification of newly discovered LDLR family members, including the LpRs, bears no relevance to physiological function. Therefore, as a novel approach, the C-terminal domains of LDLR family members across the entire animal kingdom were used to perform a sequence comparison analysis in combination with a phylogenetic tree analysis. The LpRs appeared to segregate into a specific group distinct from the groups encompassing the other family members, and each of the three C-terminal domains of the insect receptors is composed of unique set of sequence motifs. Based on conservation of sequence motifs and organization of these motifs in the domains, LpR resembles most the groups of the LDLRs, very low density lipoprotein (VLDL) receptors, and vitellogenin receptors. However, in sequence aspects in which LpR deviates from these three receptor groups, it most notably resembles LDLR-related protein-2, or megalin. These features might explain the functional differences disclosed between insect and mammalian lipoprotein receptors.

  19. The sorting of blood group active proteins during enucleation.

    PubMed

    Satchwell, Timothy J; Bell, Amanda J; Toye, Ashley M

    2015-04-01

    Enucleation represents the critical stage during red blood cell development when the nucleus is extruded from an orthochromatic erythroblast in order to generate a nascent immature reticulocyte. Extrusion of the nucleus results in loss of a proportion of the erythroblast plasma membrane, which surrounds the nucleus, the bulk of the endoplasmic reticulum and a small region of cytoplasm. For this reason enucleation provides an important point in erythroblast differentiation at which proteins not required for the function of the erythrocyte can be lost, whilst those that are important for the structure-function properties of the mature erythrocyte must be efficiently retained in the reticulocyte plasma membrane. Disturbances in protein distribution during enucleation are envisaged to occur during human diseases such as Hereditary Spherocytosis. This article will discuss the current knowledge of erythroblast enucleation in the context of retention and loss of proteins that display antigenic blood group sites and that exist within multiprotein complexes within the erythrocyte membrane.

  20. Current activities of the Atmospheric Composition Sub-Group of the CEOS Working Group on Calibration and Validation

    NASA Astrophysics Data System (ADS)

    Bojkov, Bojan

    The Atmospheric Sub-Group of the CEOS Calibration and Validation Working Group (CEOS WGCV/ASCG) was established in November 2001 with mission to ensure accurate and traceable calibration of remotely-sensed atmospheric chemistry radiance data and validation of higher level products, for application to atmospheric chemistry and climate research. This working-group, consisting of 15 members from space agencies and other relevant agencies and organizations with broad experience in calibration, modeling, algorithm development and validation, meet on an annual basis to promote international collaboration and technical exchanges, encourage interactions between mission scientists and data users, recommend network validation sites, develop comprehensive validation methodologies involving ground-based and space-borne assets, and specify comprehensive and consistent multi-mission validation datasets. Recent activities of the ACSG, including the recent ground-based intercomparisons, the ongoing NASA-ESA-NDACC validation data sharing activities, and the planned multi-agency CO2 validation efforts, will be presented.

  1. Endophytic Bacteria Isolated from Common Bean (Phaseolus vulgaris) Exhibiting High Variability Showed Antimicrobial Activity and Quorum Sensing Inhibition.

    PubMed

    Lopes, Ralf Bruno Moura; Costa, Leonardo Emanuel de Oliveira; Vanetti, Maria Cristina Dantas; de Araújo, Elza Fernandes; de Queiroz, Marisa Vieira

    2015-10-01

    Endophytic bacteria play a key role in the biocontrol of phytopathogenic microorganisms. In this study, genotypic diversity was analyzed via repetitive element PCR (rep-PCR) of endophytic isolates of the phylum Actinobacteria that were previously collected from leaves of cultivars of common bean (Phaseolus vulgaris). Considerable variability was observed, which has not been reported previously for this phylum of endophytic bacteria of the common bean. Furthermore, the ethanol extracts from cultures of various isolates inhibited the growth of pathogenic bacteria in vitro, especially Gram-positive pathogens. Extracts from cultures of Microbacterium testaceum BAC1065 and BAC1093, which were both isolated from the 'Talismã' cultivar, strongly inhibited most of the pathogenic bacteria tested. Bean endophytic bacteria were also demonstrated to have the potential to inhibit the quorum sensing of Gram-negative bacteria. This mechanism may regulate the production of virulence factors in pathogens. The ability to inhibit quorum sensing has also not been reported previously for endophytic microorganisms of P. vulgaris. Furthermore, M. testaceum with capacity to inhibit quorum sensing appears to be widespread in common bean. The genomic profiles of M. testaceum were also analyzed via pulsed-field gel electrophoresis, and greater differentiation was observed using this method than rep-PCR; in general, no groups were formed based on the cultivar of origin. This study showed for the first time that endophytic bacteria from common bean plants exhibit high variability and may be useful for the development of strategies for the biological control of diseases in this important legume plant.

  2. Exploring the transferase activity of Ffase from Schwanniomyces occidentalis, a β-fructofuranosidase showing high fructosyl-acceptor promiscuity.

    PubMed

    Piedrabuena, David; Míguez, Noa; Poveda, Ana; Plou, Francisco J; Fernández-Lobato, María

    2016-10-01

    The β-fructofuranosidase from the yeast Schwanniomyces occidentalis (Ffase) produces the prebiotic sugars 6-kestose and 1-kestose by transfructosylation of sucrose, which makes it of biotechnological interest. In this study, the hydrolase and transferase activity of this enzyme was kinetically characterized and its potential to synthesize new fructosylated products explored. A total of 40 hydroxylated compounds were used as potential fructosyl-acceptor alternatives to sucrose. Only 17 of them, including some monosaccharides, disaccharides, and oligosaccharides as well as alditols and glycosides were fructosylated. The best alternative acceptors were the alditols. The major transfer product of the reaction including mannitol was purified and characterized as 1-O-β-D-fructofuranosyl-D-mannitol, whose maximum concentration reached 44 g/L, representing about 7.3 % of total compounds in the mixture and 89 % of all products generated by transfructosylation. The reactions including erythritol produced 35 g/L of an isomer mixture comprising 1- and 4-O-β-D-fructofuranosyl-D-erythritol. In addition, Ffase produced 24 g/L of the disaccharide blastose by direct fructosylation of glucose, which makes it the first enzyme characterized from yeast showing this ability. Thus, novel fructosylated compounds with potential applications in food and pharmaceutical industries can be obtained due to the Ffase fructosyl-acceptor promiscuity.

  3. Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models.

    PubMed

    Wang, Ying; Li, Xiaojie; Yang, Meifeng; Wu, Chunyun; Zou, Zhirong; Tang, Jing; Yang, Xinwang

    2017-03-01

    Pain is a major symptom of many diseases and results in enormous pressures on human body or society. Currently, clinically used analgesic drugs, including opioids and nonsteroidal anti-inflammatory drugs, have adverse reactions, and thus, the development of new types of analgesic drug candidates is urgently needed. Animal venom peptides have proven to have potential as new types of analgesic medicine. In this research, we describe the isolation and characterization of an analgesic peptide from the crude venom of centipede, Scolopendra subspinipes mutilans. The amino acid sequence of this peptide was identical with SsmTX-I that was previously reported as a specific Kv2.1 ion channel blocker. Our results revealed that SsmTX-I was produced by posttranslational processing of a 73-residue prepropeptide. The intramolecular disulfide bridge motifs of SsmTX-I was Cys1-Cys3 and Cys2-Cys4. Functional assay revealed that SsmTX-I showed potential analgesic activities in formalin-induced paw licking, thermal pain, and acetic acid-induced abdominal writhing mice models. Our research provides the first report of cDNA sequences, disulfide motif, successful synthesis, and analgesic potential of SsmTX-I for the development of pain-killing drugs. It indicates that centipede peptide toxins could be a treasure trove for the search of novel analgesic drug candidates. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

  4. AGN physics - A Chandra-Swift Census of AGN activity in Compact Groups

    NASA Astrophysics Data System (ADS)

    Tzanavaris, Panayiotis

    2012-09-01

    We present a missing link in the study of AGN activity in compact groups of galaxies. The level of this activity in compact groups remains controversial, but has only been studied with optical and infrared diagnostics. We present the first systematic study of 40 compact group galaxies in 9 groups, combining Chandra and Swift data, and providing the first X-ray/UV view of galactic nuclei in compact groups. Our results provide independent evidence that the level of AGN activity in compact groups is representative of their unique environment, which is distinct to that of rich clusters and the field.

  5. Meta-Analysis of Group Learning Activities: Empirically Based Teaching Recommendations

    ERIC Educational Resources Information Center

    Tomcho, Thomas J.; Foels, Rob

    2012-01-01

    Teaching researchers commonly employ group-based collaborative learning approaches in Teaching of Psychology teaching activities. However, the authors know relatively little about the effectiveness of group-based activities in relation to known psychological processes associated with group dynamics. Therefore, the authors conducted a meta-analytic…

  6. Engager and Avoider Behaviour in Types of Activities Performed by Out-of-Class Learning Groups

    ERIC Educational Resources Information Center

    Yan, Louisa; Kember, David

    2004-01-01

    This study examines the out-of-class learning activities undertaken, at the students' volition, by groups of students. Data were gathered through 57 individual and 15 focus group interviews with university students in Hong Kong. Group activities reported included: copying, sharing material, consulting peers, consulting teachers, studying and…

  7. Antitumor activities and interaction with DNA of oxaliplatin-type platinum complexes with linear or branched alkoxyacetates as leaving groups.

    PubMed

    Yin, Runting; Gou, Shaohua; Liu, Xia; Lou, Liguang

    2011-08-01

    Five oxaliplatin-typed platinum complexes containing trans-1R, 2R-diaminocyclohexane chelating platinum cores, characteristic of linear or branched alkoxycarboxylates as leaving groups, were biologically evaluated. These compounds showed higher antitumor activity, lower toxicity in vivo than cisplatin or oxaliplatin. And the results revealed that the antitumor activity and interaction with DNA of these compounds were highly related to the nature of leaving groups. Among these complexes, 5a, cis-(trans-1R, 2R-diaminocyclohexane) bis (2-tert-butoxyacetate) platinum(II), showed the highest antitumor activity and the lowest toxicity.

  8. Healthy co-twins of patients with affective disorders show reduced risk-related activation of the insula during a monetary gambling task

    PubMed Central

    Macoveanu, Julian; Miskowiak, Kamilla; Kessing, Lars Vedel; Vinberg, Maj; Siebner, Hartwig Roman

    2016-01-01

    Background Healthy first-degree relatives of patients with affective disorders are at increased risk for affective disorders and express discrete structural and functional abnormalities in the brain reward system. However, value-based decision making is not well understood in these at-risk individuals. Methods We investigated healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorders (high-risk and low-risk groups, respectively) using functional MRI during a gambling task. We assessed group differences in activity related to gambling risk over the entire brain. Results We included 30 monozygotic and 37 dizygotic twins in our analysis. Neural activity in the anterior insula and ventral striatum increased linearly with the amount of gambling risk in the entire cohort. Individual neuroticism scores were positively correlated with the neural response in the ventral striatum to increasing gambling risk and negatively correlated with individual risk-taking behaviour. Compared with low-risk twins, the high-risk twins showed a bilateral reduction of risk-related activity in the middle insula extending into the temporal cortex with increasing gambling risk. Post hoc analyses revealed that this effect was strongest in dizygotic twins. Limitations The relatively old average age of the mono- and dizygotic twin cohort (49.2 yr) may indicate an increased resilience to affective disorders. The size of the monozygotic high-risk group was relatively small (n = 13). Conclusion The reduced processing of risk magnitude in the middle insula may indicate a deficient integration of exteroceptive information related to risk-related cues with interoceptive states in individuals at familial risk for affective disorders. Impaired risk processing might contribute to increased vulnerability to affective disorders. PMID:26395812

  9. Peer groups and substance use: examining the direct and interactive effect of leisure activity.

    PubMed

    Thorlindsson, Thorolfur; Bernburg, Jon Gunnar

    2006-01-01

    This paper explores the relationships among adolescent leisure activities, peer behavior, and substance use. We suggest that peer group interaction can have a differential effect on adolescent deviant behavior depending on the type of leisure pattern adolescents engage in. We analyze data from a representative national sample of Icelandic adolescents, exploring the variations in the use of alcohol and illegal drugs among three different patterns of leisure activity, controlling for parental ties and school commitment. The findings show that alcohol and substance use varies significantly across the three leisure patterns. Moreover, it was found that the well-known relationship between adolescent substance use and having substance-using friends is significantly contingent on the type of leisure pattern. Our findings suggest that it is important to take into account different peer leisure activities in order to understand adolescent substance use. Finally, we discuss the implications of the findings for prevention work with adolescents.

  10. The temperate Burkholderia phage AP3 of the Peduovirinae shows efficient antimicrobial activity against B. cenocepacia of the IIIA lineage.

    PubMed

    Roszniowski, Bartosz; Latka, Agnieszka; Maciejewska, Barbara; Vandenheuvel, Dieter; Olszak, Tomasz; Briers, Yves; Holt, Giles S; Valvano, Miguel A; Lavigne, Rob; Smith, Darren L; Drulis-Kawa, Zuzanna

    2017-02-01

    Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholderia cenocepacia lineage IIIA strains commonly isolated from cystic fibrosis patients. AP3 exhibits high pairwise nucleotide identity (61.7 %) to Burkholderia phage KS5, specific to the same B. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of Burkholderia. The lysis cassette of these related phages has a similar organization (putative antiholin, putative holin, endolysin, and spanins) and shows 29-98 % homology between specific lysis genes, in contrast to Enterobacteria phage P2, the hallmark phage of this genus. The AP3 and KS5 lysis genes have conserved locations and high amino acid sequence similarity. The AP3 bacteriophage particles remain infective up to 5 h at pH 4-10 and are stable at 60 °C for 30 min, but are sensitive to chloroform, with no remaining infective particles after 24 h of treatment. AP3 lysogeny can occur by stable genomic integration and by pseudo-lysogeny. The lysogenic bacterial mutants did not exhibit any significant changes in virulence compared to wild-type host strain when tested in the Galleria mellonella moth wax model. Moreover, AP3 treatment of larvae infected with B. cenocepacia revealed a significant increase (P < 0.0001) in larvae survival in comparison to AP3-untreated infected larvae. AP3 showed robust lytic activity, as evidenced by its broad host range, the absence of increased virulence in lysogenic isolates, the lack of bacterial gene disruption conditioned by bacterial tRNA downstream integration site, and the absence of detected toxin sequences. These data suggest that the AP3 phage is a promising potent agent against bacteria belonging to the most common B. cenocepacia IIIA lineage strains.

  11. B-Ring-Aryl Substituted Luotonin A Analogues with a New Binding Mode to the Topoisomerase 1-DNA Complex Show Enhanced Cytotoxic Activity

    PubMed Central

    González-Ruiz, Víctor; Pascua, Irene; Fernández-Marcelo, Tamara; Ribelles, Pascual; Bianchini, Giulia; Sridharan, Vellaisamy; Iniesta, Pilar; Ramos, M. Teresa; Olives, Ana I.; Martín, M. Antonia; Menéndez, J. Carlos

    2014-01-01

    Topoisomerase 1 inhibition is an important strategy in targeted cancer chemotherapy. The drugs currently in use acting on this enzyme belong to the family of the camptothecins, and suffer severe limitations because of their low stability, which is associated with the hydrolysis of the δ-lactone moiety in their E ring. Luotonin A is a natural camptothecin analogue that lacks this functional group and therefore shows a much-improved stability, but at the cost of a lower activity. Therefore, the development of luotonin A analogues with an increased potency is important for progress in this area. In the present paper, a small library of luotonin A analogues modified at their A and B rings was generated by cerium(IV) ammonium nitrate-catalyzed Friedländer reactions. All analogues showed an activity similar or higher than the natural luotonin A in terms of topoisomerase 1 inhibition and some compounds had an activity comparable to that of camptothecin. Furthermore, most compounds showed a better activity than luotonin A in cell cytotoxicity assays. In order to rationalize these results, the first docking studies of luotonin-topoisomerase 1-DNA ternary complexes were undertaken. Most compounds bound in a manner similar to luotonin A and to standard topoisomerase poisons such as topotecan but, interestingly, the two most promising analogues, bearing a 3,5-dimethylphenyl substituent at ring B, docked in a different orientation. This binding mode allows the hydrophobic moiety to be shielded from the aqueous environment by being buried between the deoxyribose belonging to the G(+1) guanine and Arg364 in the scissile strand and the surface of the protein and a hydrogen bond between the D-ring carbonyl and the basic amino acid. The discovery of this new binding mode and its associated higher inhibitory potency is a significant advance in the design of new topoisomerase 1 inhibitors. PMID:24830682

  12. Enhancement of CA3 hippocampal network activity by activation of group II metabotropic glutamate receptors.

    PubMed

    Ster, Jeanne; Mateos, José María; Grewe, Benjamin Friedrich; Coiret, Guyllaume; Corti, Corrado; Corsi, Mauro; Helmchen, Fritjof; Gerber, Urs

    2011-06-14

    Impaired function or expression of group II metabotropic glutamate receptors (mGluRIIs) is observed in brain disorders such as schizophrenia. This class of receptor is thought to modulate activity of neuronal circuits primarily by inhibiting neurotransmitter release. Here, we characterize a postsynaptic excitatory response mediated by somato-dendritic mGluRIIs in hippocampal CA3 pyramidal cells and in stratum oriens interneurons. The specific mGluRII agonists DCG-IV or LCCG-1 induced an inward current blocked by the mGluRII antagonist LY341495. Experiments with transgenic mice revealed a significant reduction of the inward current in mGluR3(-/-) but not in mGluR2(-/-) mice. The excitatory response was associated with periods of synchronized activity at theta frequency. Furthermore, cholinergically induced network oscillations exhibited decreased frequency when mGluRIIs were blocked. Thus, our data indicate that hippocampal responses are modulated not only by presynaptic mGluRIIs that reduce glutamate release but also by postsynaptic mGluRIIs that depolarize neurons and enhance CA3 network activity.

  13. Surface modification with multiphilic ligands at detectable well defined active positions of nano-object of giant wheel shaped molybdenum blue showing third-order nonlinear optical properties

    NASA Astrophysics Data System (ADS)

    Zhang, Lijuan; Li, Yuhao; Zhou, Yunshan

    2010-04-01

    The reaction of an aqueous solution of sodium molybdate with L-tyrosine in the presence of reducing agent results in the formation of a new compound of the formula of Na 8Co 3[Mo VI126 Mo V28O 462H 14(H 2O) 46(HOC 6H 4CH 2CH( NH3+)COO -) 12]·ca. 200H 2O. The compound contains nanosized ring-shaped clusters with tyrosine ligands possessing different types of functional groups (one -CO 2, one -NH3+ and one -ArOH) coordinated through the carboxylate groups at the active sites of the inner cavity. Importantly, the result demonstrates that not only active sites/areas of the cluster surface under a specified condition can be directly monitored and detected but also novel type surfaces within the cavity of a nano-structured ring-shaped cluster can be generated simultaneously. The nonlinear optical properties of the new cluster are studied using the well-known Z-scan technique at a wavelength of 532 nm with laser pulse duration of 18 ps. The results show that the new cluster exhibits interesting self-focusing nonlinear optical response with the real and imaginary parts of the third-order nonlinear optical susceptibility χ(3) being 1.069 × 10 -13(esu) and 2.529 × 10 -15(esu), respectively, which may find application in material science.

  14. Active Learning Facilitated by Using a Game-Show Format or Who Doesn't Want to Be a Millionaire?

    ERIC Educational Resources Information Center

    Sarason, Yolanda; Banbury, Catherine

    2004-01-01

    University faculty are increasingly called on to be less of a sage on the stage and more a guide on the side. This discussion introduces the underlying philosophy and assumptions of active learning theory. With this shift in pedagogical philosophy, there has been an increasing call for tools that actively engage students in the learning process. A…

  15. Physical Activity in the Life of a Woman with Severe Cerebral Palsy: Showing Competence and Being Socially Connected

    ERIC Educational Resources Information Center

    Gaskin, Cadeyrn J.; Andersen, Mark B.; Morris, Tony

    2009-01-01

    We used a life-history approach to investigate the meanings and experiences of physical activity in the life of a 25-year-old woman with severe cerebral palsy (Amy). Amy and her mother were interviewed about Amy's life and her involvement in physical activity. The conversation was audio-recorded and transcribed verbatim. We interpreted Amy's story…

  16. Cell-penetrating peptide TP10 shows broad-spectrum activity against both Plasmodium falciparum and Trypanosoma brucei brucei.

    PubMed

    Arrighi, Romanico B G; Ebikeme, Charles; Jiang, Yang; Ranford-Cartwright, Lisa; Barrett, Michael P; Langel, Ulo; Faye, Ingrid

    2008-09-01

    Malaria and trypanosomiasis are diseases which afflict millions and for which novel therapies are urgently required. We have tested two well-characterized cell-penetrating peptides (CPPs) for antiparasitic activity. One CPP, designated TP10, has broad-spectrum antiparasitic activity against Plasmodium falciparum, both blood and mosquito stages, and against blood-stage Trypanosoma brucei brucei.

  17. Imidazopyridine-Based Fatty Acid Synthase Inhibitors That Show Anti-HCV Activity and in Vivo Target Modulation

    PubMed Central

    2012-01-01

    Potent imidazopyridine-based inhibitors of fatty acid synthase (FASN) are described. The compounds are shown to have antiviral (HCV replicon) activities that track with their biochemical activities. The most potent analogue (compound 19) also inhibits rat FASN and inhibits de novo palmitate synthesis in vitro (cell-based) as well as in vivo. PMID:24900571

  18. Healthy children show gender differences in correlations between nonverbal cognitive ability and brain activation during visual perception.

    PubMed

    Asano, Kohei; Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Thyreau, Benjamin; Asano, Michiko; Takeuchi, Hikaru; Kawashima, Ryuta

    2014-08-08

    Humans perceive textual and nontextual information in visual perception, and both depend on language. In childhood education, students exhibit diverse perceptual abilities, such that some students process textual information better and some process nontextual information better. These predispositions involve many factors, including cognitive ability and learning preference. However, the relationship between verbal and nonverbal cognitive abilities and brain activation during visual perception has not yet been examined in children. We used functional magnetic resonance imaging to examine the relationship between nonverbal and verbal cognitive abilities and brain activation during nontextual visual perception in large numbers of children. A significant positive correlation was found between nonverbal cognitive abilities and brain activation in the right temporoparietal junction, which is thought to be related to attention reorienting. This significant positive correlation existed only in boys. These findings suggested that male brain activation differed from female brain activation, and that this depended on individual cognitive processes, even if there was no gender difference in behavioral performance.

  19. Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations

    PubMed Central

    2010-01-01

    Background Intracranial pediatric germ cell tumors (GCTs) are rare and heterogeneous neoplasms and vary in histological differentiation, prognosis and clinical behavior. Germinoma and mature teratoma are GCTs that have a good prognosis, while other types of GCTs, termed nongerminomatous malignant germ cell tumors (NGMGCTs), are tumors with an intermediate or poor prognosis. The second group of tumors requires more extensive drug and irradiation treatment regimens. The mechanisms underlying the differences in incidence and prognosis of the various GCT subgroups are unclear. Results We identified a distinct mRNA profile correlating with GCT histological differentiation and prognosis, and also present in this study the first miRNA profile of pediatric primary intracranial GCTs. Most of the differentially expressed miRNAs were downregulated in germinomas, but miR-142-5p and miR-146a were upregulated. Genes responsible for self-renewal (such as POU5F1 (OCT4), NANOG and KLF4) and the immune response were abundant in germinomas, while genes associated with neuron differentiation, Wnt/β-catenin pathway, invasiveness and epithelial-mesenchymal transition (including SNAI2 (SLUG) and TWIST2) were abundant in NGMGCTs. Clear transcriptome segregation based on patient survival was observed, with malignant NGMGCTs being closest to embryonic stem cells. Chromosome copy number variations (CNVs) at cytobands 4q13.3-4q28.3 and 9p11.2-9q13 correlated with GCT malignancy and clinical risk. Six genes (BANK1, CXCL9, CXCL11, DDIT4L, ELOVL6 and HERC5) within 4q13.3-4q28.3 were more abundant in germinomas. Conclusions Our results integrate molecular profiles with clinical observations and provide insights into the underlying mechanisms causing GCT malignancy. The genes, pathways and microRNAs identified have the potential to be novel therapeutic targets. PMID:20178649

  20. Four TFL1/CEN-like genes on distinct linkage groups show different expression patterns to regulate vegetative and reproductive development in apple (Malus x domestica Borkh.).

    PubMed

    Mimida, Naozumi; Kotoda, Nobuhiro; Ueda, Takanori; Igarashi, Megumi; Hatsuyama, Yoshimichi; Iwanami, Hiroshi; Moriya, Shigeki; Abe, Kazuyuki

    2009-02-01

    Recent molecular analyses in several plant species revealed that TERMINAL FLOWER1 (TFL1) and CENTRORADIALIS (CEN) homologs are involved in regulating the flowering time and/or maintaining the inflorescence meristem. In apple (Malusxdomestica Borkh.), four TFL1/CEN-like genes, MdTFL1, MdTFL1a, MdCENa and MdCENb, were found and mapped by a similar position on putatively homoeologous linkage groups. Apple TFL1/CEN-like genes functioned equivalently to TFL1 when expressed constitutively in transgenic Arabidopsis plants, suggesting that they have a potential to complement the TFL1 function. Because MdTFL1 and MdTFL1a were expressed in the vegetative tissues in both the adult and juvenile phases, they could function redundantly as a flowering repressor and a regulator of vegetative meristem identity. On the other hand, MdCENa was mainly expressed in fruit receptacles, cultured tissues and roots, suggesting that it is involved in the development of proliferating tissues but not in the control of the transition from the juvenile to the adult phase. In contrast, MdCENb was silenced in most organs probably due to gene duplication by the polyploid origin of apple. The expression patterns of MdTFL1 and MdCENa in apple were also supported by the heterologous expression of beta-glucuronidase fused with their promoter regions in transgenic Arabidopsis. Our results suggest that functional divergence of the roles in the regulation of vegetative meristem identity may have occurred among four TFL1/CEN-like genes during evolution in apple.

  1. A novel inhibitor of fatty acid synthase shows activity against HER2+ breast cancer xenografts and is active in anti-HER2 drug-resistant cell lines

    PubMed Central

    2011-01-01

    Introduction Inhibiting the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of breast carcinoma cells, and this is linked to human epidermal growth factor receptor 2 (HER2) signaling pathways in models of simultaneous expression of FASN and HER2. Methods In a xenograft model of breast carcinoma cells that are FASN+ and HER2+, we have characterised the anticancer activity and the toxicity profile of G28UCM, the lead compound of a novel family of synthetic FASN inhibitors. In vitro, we analysed the cellular and molecular interactions of combining G28UCM with anti-HER drugs. Finally, we tested the cytotoxic ability of G28UCM on breast cancer cells resistant to trastuzumab or lapatinib, that we developed in our laboratory. Results In vivo, G28UCM reduced the size of 5 out of 14 established xenografts. In the responding tumours, we observed inhibition of FASN activity, cleavage of poly-ADPribose polymerase (PARP) and a decrease of p-HER2, p- protein kinase B (AKT) and p-ERK1/2, which were not observed in the nonresponding tumours. In the G28UCM-treated animals, no significant toxicities occurred, and weight loss was not observed. In vitro, G28UCM showed marked synergistic interactions with trastuzumab, lapatinib, erlotinib or gefitinib (but not with cetuximab), which correlated with increases in apoptosis and with decreases in the activation of HER2, extracellular signal-regulated kinase (ERK)1/2 and AKT. In trastuzumab-resistant and in lapatinib-resistant breast cancer cells, in which trastuzumab and lapatinib were not effective, G28UCM retained the anticancer activity observed in the parental cells. Conclusions G28UCM inhibits fatty acid synthase (FASN) activity and the growth of breast carcinoma xenografts in vivo, and is active in cells with acquired resistance to anti-HER2 drugs, which make it a candidate for further pre-clinical development. PMID:22177475

  2. Virome analysis of antiretroviral-treated HIV patients shows no correlation between T-cell activation and anelloviruses levels

    PubMed Central

    Li, Linlin; Deng, Xutao; Da Costa, Antonio Charlys; Bruhn, Roberta; Deeks, Steven G.; Delwart, Eric

    2015-01-01

    Background Abnormally high levels of T-cell activation can persist in HIV-infected subjects despite effective anti-retroviral therapy (ART) and has been associated with negative health outcomes. The nature of the antigenic drivers or other causes of this residual T-cell activation remain uncertain. Anelloviruses are universally acquired soon after birth, resulting in persistent viremia, and considered part of the commensal human virome. Reduced immunocompetence results in increased anellovirus levels. Objectives To test whether increased levels of anelloviruses or other viruses in plasma are associated with higher levels of persistent T-cell activation during ART. Study design Two amplification methods combined with next generation sequencing were used to detect all viruses and estimate relative anellovirus levels in plasma from 19 adults on effective ART who exhibited a wide range of T-cell activation levels. Results Nucleic acids from HBV and HCV were detected in one patient each while pegivirus A (GBV-C) was found in three patients. Anellovirus DNA was detected in all patients with some individuals carrying up to eight different genotypes. Specific anellovirus genotypes or higher level of co-infections were not detected in subjects with higher levels of T-cell activation. No association was detected between relative plasma anellovirus DNA levels and the percentage of activated CD4 or CD8 T cells. Conclusions Human anelloviruses were detected in all HIV suppressed subjects, exhibited a wide range of viremia levels, and were genetically highly diverse. The level of persistent T-cell activation was not correlated with the level of viremia or genotypes present indicating that anellovirus antigens are unlikely to be a dominant source of antigens driving chronic T-cell activation. PMID:26479202

  3. Forebrain-specific constitutively active CaMKKα transgenic mice show deficits in hippocampus-dependent long-term memory.

    PubMed

    Kaitsuka, Taku; Li, Sheng-Tian; Nakamura, Kenji; Takao, Keizo; Miyakawa, Tsuyoshi; Matsushita, Masayuki

    2011-09-01

    The Ca(2+)/calmodulin (CaM) kinase cascade is activated by Ca(2+) influx through the voltage-dependent Ca(2+) channels and the NMDA receptor. CaM kinase kinase (CaMKK), the most upstream kinase of the CaM kinase cascade, phosphorylates and activates both CaM kinase I (CaMKI) and CaMKIV, resulting in activation of cyclic AMP-responsive element binding protein (CREB)-dependent gene transcription. Using transgenic techniques, we created mutant mice in which a constitutively active form of CaMKK1, the autoinhibitory domain truncated protein, is over-expressed specifically in the forebrain. In these mice, although performance was normal in basal activity and short-term memory, specific impairments were shown in hippocampus-dependent long-term memory after training in spatial memory tasks and after contextual fear conditioning. In cultured neurons of these mice, phosphorylation of CaMKI was significantly increased in basal states, whereas the activity range of CaMKI phosphorylation by brain-derived neurotrophic factor (BDNF) and KCl stimulation was significantly diminished in mutant mice. Our results define a critical role for CaMKKα in synaptic plasticity and the retention of hippocampus-dependent long-term memory.

  4. Synthesis and antitumor activity of new amphiphilic alkylglycerolipids substituted with a polar head group, 2-(2-trimethylammonioethoxy)ethyl or a congeneric oligo(ethyleneoxy)ethyl group.

    PubMed

    Ukawa, K; Imamiya, E; Yamamoto, H; Aono, T; Kozai, Y; Okutani, T; Nomura, H; Honma, Y; Hozumi, M; Kudo, I

    1989-12-01

    A new series of amphiphilic 1-octadecyl glycerolipids (eleven compounds, 1a-k) were designed and synthesized, in which the 3-phosphocholine portion of platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) was replaced by the 2-(2-trimethylammonioethoxy)ethyl group and congeneric groups having oligo(ethyleneoxy)ethyl bridges of various lengths at position 3, together with modification at position 2 (lower alkyl, acetonyl, acetoacetyl, carboxymethyl and pyrimidin-2-yl groups). These ether lipids, characterized by a nonphosphorus lysoglycerolipid structure, showed potent antitumor activity in vitro (human promyelocytic leukemia cells, HL-60, and human epidermoid carcinoma cells, KB) and in vivo (mouse sarcoma S180 and mouse mammary carcinoma MM46). Maximal in vitro potency was obtained with 1-O-octadecyl-2-O-(2-pyrimidinyl)-3-O-[2-(2-trimethylammonioethoxy )ethyl] glycerol (1g; IC50 values for both HL-60 and KB were 0.32 microgram/ml, indicating a higher activity than alkyl-lysophospholipid, ET18-OMe). Several appropriately 2-substituted 1-octadecylglycerolipids with the 3-[2-(2-trimethylammonioethoxy)ethyl] group (e.g., methyl, 1b; butyl, 1f; 2,2,2-trifluoroethyl, 1j; and acetonyl, 1k) showed a potent life-span-prolonging effect on mice with ascites sarcoma S180 and on those with mammary carcinoma MM46, when administered intraperitoneally at 16.5 and 12.5 mg/kg/d, respectively. Compounds 1b and 1k showed definite tumor growth inhibition against solid sarcoma S180 in mice, whether given p.o. or i.v. at 16.5 mg/kg/d. Studies on the structure-activity relationships indicate that the metabolic stability to phospholipase C or related enzymes is at least partly responsible for the potent antitumor activity of this series of ether lipids.

  5. Acculturation and psychosocial stress show differential relationships to insulin resistance (HOMA) and body fat distribution in two groups of blacks living in the US Virgin Islands.

    PubMed

    Tull, Eugene S; Thurland, Anne; LaPorte, Ronald E; Chambers, Earle C

    2003-07-01

    The objective of this study was to determine whether acculturation and psychosocial stress exert differential effects on body fat distribution and insulin resistance among native-born African Americans and African-Caribbean immigrants living in the US Virgin Islands (USVI). Data collected from a non-diabetic sample of 183 USVI-born African Americans and 296 African-Caribbean immigrants age > 20 on the island of St. Croix, USVI were studied. Information on demographic characteristics, acculturation and psychosocial stress was collected by questionnaire. Anthropometric measurements were taken, and serum glucose and insulin were measured from fasting blood samples. Insulin resistance was estimated by the homeostasis model assessment (HOMA) method. The results showed that in multivariate regression analyses, controlling for age, education, gender, BMI, waist circumference, family history of diabetes, smoking and alcohol consumption, acculturation was independently related to logarithm of HOMA (InHOMA) scores among USVI-born African Americans, but not among African-Caribbean immigrants. In contrast, among USVI-born African Americans psychosocial stress was not significantly related to InHOMA, while among African-Caribbean immigrants psychosocial stress was independently related to InHOMA in models that included BMI, but not in those which included waist circumference. This study suggests that acculturation and psychosocial stress may have a differential effect on body fat distribution and insulin resistance among native-born and immigrant blacks living in the US Virgin Islands.

  6. A New Calibrated Sunspot Group Series Since 1749: Statistics of Active Day Fractions

    NASA Astrophysics Data System (ADS)

    Usoskin, I. G.; Kovaltsov, G. A.; Lockwood, M.; Mursula, K.; Owens, M.; Solanki, S. K.

    2016-11-01

    Although sunspot-number series have existed since the mid-nineteenth century, they are still the subject of intense debate, with the largest uncertainty being related to the "calibration" of the visual acuity of individual observers in the past. A daisy-chain regression method is usually applied to inter-calibrate the observers, which may lead to significant bias and error accumulation. Here we present a novel method for calibrating the visual acuity of the key observers to the reference data set of Royal Greenwich Observatory sunspot groups for the period 1900 - 1976, using the statistics of the active-day fraction. For each observer we independently evaluate their observational thresholds [SS] defined such that the observer is assumed to miss all of the groups with an area smaller than SS and report all the groups larger than SS. Next, using a Monte-Carlo method, we construct a correction matrix for each observer from the reference data set. The correction matrices are significantly non-linear and cannot be approximated by a linear regression or proportionality. We emphasize that corrections based on a linear proportionality between annually averaged data lead to serious biases and distortions of the data. The correction matrices are applied to the original sunspot-group records reported by the observers for each day, and finally the composite corrected series is produced for the period since 1748. The corrected series is provided as supplementary material in electronic form and displays secular minima around 1800 (Dalton Minimum) and 1900 (Gleissberg Minimum), as well as the Modern Grand Maximum of activity in the second half of the twentieth century. The uniqueness of the grand maximum is confirmed for the last 250 years. We show that the adoption of a linear relationship between the data of Wolf and Wolfer results in grossly inflated group numbers in the eighteenth and nineteenth centuries in some reconstructions.

  7. Saraca indica Bark Extract Shows In Vitro Antioxidant, Antibreast Cancer Activity and Does Not Exhibit Toxicological Effects

    PubMed Central

    Yadav, Navneet Kumar; Saini, Karan Singh; Hossain, Zakir; Omer, Ankur; Sharma, Chetan; Gayen, Jiaur R.; Singh, Poonam; Arya, K. R.; Singh, R. K.

    2015-01-01

    Medicinal plants are used as a complementary and alternative medicine in treatment of various diseases including cancer worldwide, because of their ease of accessibility and cost effectiveness. Multicomposed mixture of compounds present in a plant extract has synergistic activity, increases the therapeutic potential many folds, compensates toxicity, and increases bioavailability. Saraca indica (family Caesalpiniaceae) is one of the most ancient sacred plants with medicinal properties, exhibiting a number of pharmacological effects. Antioxidant, antibreast cancer activity and toxicological evaluation of Saraca indica bark extract (SIE) were carried out in the present study. The results of the study indicated that this herbal preparation has antioxidant and antibreast cancer activity. Toxicological studies suggest that SIE is safer to use and may have a potential to be used as complementary and alternative medicine for breast cancer therapy. PMID:25861411

  8. A new class of peroxisome proliferator-activated receptor agonists with a novel binding epitope shows antidiabetic effects.

    PubMed

    Ostberg, Tove; Svensson, Stefan; Selén, Göran; Uppenberg, Jonas; Thor, Markus; Sundbom, Maj; Sydow-Bäckman, Mona; Gustavsson, Anna-Lena; Jendeberg, Lena

    2004-09-24

    The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the NR1 subfamily of nuclear receptors. The PPARs play key roles in the control of glucose and lipid homeostasis, and the synthetic isoform-specific PPAR agonists are used clinically to improve insulin sensitivity and to lower serum triglyceride levels. All of the previously reported PPAR agonists form the same characteristic interactions with the receptor, which have been postulated to be important for the induction of agonistic activity. Here we describe a new class of PPARalpha/gamma modulators, the 5-substituted 2-benzoylaminobenzoic acids (2-BABAs). As shown by x-ray crystallography, the representative compounds BVT.13, BVT.762, and BVT.763, utilize a novel binding epitope and lack the agonist-characteristic interactions. Despite this, some compounds within the 2-BABA family are potent agonists in a cell-based reporter gene assay. Furthermore, BVT.13 displays antidiabetic effects in ob/ob mice. We concluded that the 2-BABA binding mode can be used to design isoform-specific PPAR modulators with biological activity in vivo.

  9. Individuals with low working memory spans show greater interference from irrelevant information because of poor source monitoring, not greater activation.

    PubMed

    Lilienthal, Lindsey; Rose, Nathan S; Tamez, Elaine; Myerson, Joel; Hale, Sandra

    2015-04-01

    Although individuals with high and low working memory (WM) span appear to differ in the extent to which irrelevant information interferes with their performance on WM tasks, the locus of this interference is not clear. The present study investigated whether, when performing a WM task, high- and low-span individuals differ in the activation of formerly relevant, but now irrelevant items, and/or in their ability to correctly identify such irrelevant items. This was done in two experiments, both of which used modified complex WM span tasks. In Experiment 1, the span task included an embedded lexical decision task designed to obtain an implicit measure of the activation of both currently and formerly relevant items. In Experiment 2, the span task included an embedded recognition judgment task designed to obtain an explicit measure of both item and source recognition ability. The results of these experiments indicate that low-span individuals do not hold irrelevant information in a more active state in memory than high-span individuals, but rather that low-span individuals are significantly poorer at identifying such information as irrelevant at the time of retrieval. These results suggest that differences in the ability to monitor the source of information, rather than differences in the activation of irrelevant information, are the more important determinant of performance on WM tasks.

  10. Glycosynthase Mutants of Endoglycosidase S2 Show Potent Transglycosylation Activity and Remarkably Relaxed Substrate Specificity for Antibody Glycosylation Remodeling.

    PubMed

    Li, Tiezheng; Tong, Xin; Yang, Qiang; Giddens, John P; Wang, Lai-Xi

    2016-08-05

    Glycosylation can exert a profound impact on the structures and biological functions of antibodies. Glycosylation remodeling using the endoglycosidase-catalyzed deglycosylation and transglycosylation approach is emerging as a promising platform to produce homogeneous glycoforms of antibodies, but the broad application of this method will require the availability of highly efficient glycosynthase mutants. We describe in this paper a systematic site-directed mutagenesis of an endoglycosidase from Streptococcus pyogenes of serotype M49 (Endo-S2) and the evaluation of the resulting mutants for their hydrolysis and transglycosylation activities. We found that mutations at the Asp-184 residue gave mutants that demonstrated significantly different properties, some possessed potent transglycosylation activity with diminished hydrolysis activity but others did not, which would be otherwise difficult to predict without the comparative study. In contrast to the previously reported Endo-S mutants that are limited to action on complex type N-glycans, the Endo-S2 glycosynthases described here, including D184M and D184Q, were found to have remarkably relaxed substrate specificity and were capable of transferring three major types (complex, high-mannose, and hybrid type) of N-glycans for antibody glycosylation remodeling. In addition, the Endo-S2 glycosynthase mutants were found to be much more active in general than the Endo-S mutants for transglycosylation. The usefulness of these Endo-S2 glycosynthase mutants was exemplified by an efficient glycosylation remodeling of two therapeutic monoclonal antibodies, rituximab and trastuzumab (Herceptin).

  11. Oral Therapy with Amlodipine and Lacidipine, 1,4-Dihydropyridine Derivatives Showing Activity against Experimental Visceral Leishmaniasis.

    PubMed

    Palit, Partha; Ali, Nahid

    2008-01-01

    Amlodipine and lacidipine, conventional antihypertensive drugs, inhibited Leishmania donovani infection in vitro and in BALB/c mice when administered orally. These 1,4-dihydropyridine derivatives functioned through dose-dependent inhibition of oxygen consumption, triggering caspase 3-like activation-mediated programmed cell death of the parasites.

  12. Nonplanar tertiary amides in rigid chiral tricyclic dilactams. Peptide group distortions and vibrational optical activity.

    PubMed

    Pazderková, Markéta; Profant, Václav; Hodačová, Jana; Sebestík, Jaroslav; Pazderka, Tomáš; Novotná, Pavlína; Urbanová, Marie; Safařík, Martin; Buděšínský, Miloš; Tichý, Miloš; Bednárová, Lucie; Baumruk, Vladimír; Maloň, Petr

    2013-08-22

    We investigate amide nonplanarity in vibrational optical activity (VOA) spectra of tricyclic spirodilactams 5,8-diazatricyclo[6,3,0,0(1,5)]undecan-4,9-dione (I) and its 6,6',7,7'-tetradeuterio derivative (II). These rigid molecules constrain amide groups to nonplanar geometries with twisted pyramidal arrangements of bonds to amide nitrogen atoms. We have collected a full range vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra including signals of C-H and C-D stretching vibrations. We report normal-mode analysis and a comparison of calculated to experimental VCD and ROA. The data provide band-to-band assignment and offer a possibility to evaluate roles of constrained nonplanar tertiary amide groups and rigid chiral skeletons. Nonplanarity shows as single-signed VCD and ROA amide I signals, prevailing the couplets expected to arise from the amide-amide interaction. Amide-amide coupling dominates amide II (mainly C'-N stretching, modified in tertiary amides by the absence of a N-H bond) transitions (strong couplet in VCD, no significant ROA) probably due to the close proximity of amide nitrogen atoms. At lower wavenumbers, ROA spectra exhibit another likely manifestation of amide nonplanarity, showing signals of amide V (δ(oop)(N-C) at ~570 cm(-1)) and amide VI (δ(oop)(C'═O) at ~700 cm(-1) and ~650 cm(-1)) vibrations.

  13. Exploring Group Dynamics of Primary 6 Students Engaged in Mathematical Modelling Activities

    ERIC Educational Resources Information Center

    Eric, Chan Chun Ming

    2014-01-01

    This paper explores the group dynamics among three groups of students involved in collaborative learning in mathematical modelling activities. It reports how group dynamics were established and their influence on the students' mathematical problem-solving endeavours. Through video analyses, discourse structures were identified to suggest the…

  14. The Effect of Science Activities on Concept Acquisition of Age 5-6 Children Groups

    ERIC Educational Resources Information Center

    Dogru, Mustafa; Seker, Fatih

    2012-01-01

    Present research aims to determine the effect of science activities on concept development of preschool period age 5-6 children groups. Parallel to research objective, qualitative research pattern has been the selected method. Study group comprises of collectively 48 children from 5-6 age group attending to a private education institution in city…

  15. A statistical algorithm showing coenzyme Q10 and citrate synthase as biomarkers for mitochondrial respiratory chain enzyme activities.

    PubMed

    Yubero, D; Adin, A; Montero, R; Jou, C; Jiménez-Mallebrera, C; García-Cazorla, A; Nascimento, A; O'Callaghan, M M; Montoya, J; Gort, L; Navas, P; Ribes, A; Ugarte, M D; Artuch, R

    2016-12-01

    Laboratory data interpretation for the assessment of complex biological systems remains a great challenge, as occurs in mitochondrial function research studies. The classical biochemical data interpretation of patients versus reference values may be insufficient, and in fact the current classifications of mitochondrial patients are still done on basis of probability criteria. We have developed and applied a mathematic agglomerative algorithm to search for correlations among the different biochemical variables of the mitochondrial respiratory chain in order to identify populations displaying correlation coefficients >0.95. We demonstrated that coenzyme Q10 may be a better biomarker of mitochondrial respiratory chain enzyme activities than the citrate synthase activity. Furthermore, the application of this algorithm may be useful to re-classify mitochondrial patients or to explore associations among other biochemical variables from different biological systems.

  16. Adrenal cryptococcosis in an immunosuppressed patient showing intensely increased metabolic activity on (18)F-FDG PET/CT.

    PubMed

    Papadakis, Georgios Z; Holland, Steven M; Quezado, Martha; Patronas, Nicholas J

    2016-12-01

    Disseminated cryptococcosis most commonly occurs in immunosuppressed patients and can rarely affect the adrenal glands. We report on a patient with biopsy proven bilateral adrenal cryptococcosis resulting in primary adrenal insufficiency, which was evaluated with whole-body positron emission tomography/computed tomography scan using (18)F-FDG. Both enlarged adrenal glands presented intensely increased (18)F-FDG activity in the periphery, while central necrotic regions were photopenic. Although diagnosis was established by adrenal gland biopsy, (18)F-FDG positron emission tomography/computed tomography scan can significantly contribute to the assessment of disease activity and monitoring of treatment response. Furthermore, fungal infections should always be considered when encountering hypermetabolic adrenal masses, especially in the setting of immunodeficient patients.

  17. Group cognitive behavioural therapy and group recreational activity for adults with autism spectrum disorders: a preliminary randomized controlled trial.

    PubMed

    Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne

    2014-08-01

    Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This preliminary randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive behavioural therapy and recreational activity. Both interventions comprised 36 weekly 3-h sessions led by two therapists in groups of 6-8 patients. A total of 68 psychiatric patients with autism spectrum disorders participated in the study. Outcome measures were Quality of Life Inventory, Sense of Coherence Scale, Rosenberg Self-Esteem Scale and an exploratory analysis on measures of psychiatric health. Participants in both treatment conditions reported an increased quality of life at post-treatment (d = 0.39, p < 0.001), with no difference between interventions. No amelioration of psychiatric symptoms was observed. The dropout rate was lower with cognitive behavioural therapy than with recreational activity, and participants in cognitive behavioural therapy rated themselves as more generally improved, as well as more improved regarding expression of needs and understanding of difficulties. Both interventions appear to be promising treatment options for adults with autism spectrum disorder. The interventions' similar efficacy may be due to the common elements, structure and group setting. Cognitive behavioural therapy may be additionally beneficial in terms of increasing specific skills and minimizing dropout.

  18. Group cognitive behavioural therapy and group recreational activity for adults with autism spectrum disorders: A preliminary randomized controlled trial

    PubMed Central

    Plenty, Stephanie; Bejerot, Susanne

    2014-01-01

    Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This preliminary randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive behavioural therapy and recreational activity. Both interventions comprised 36 weekly 3-h sessions led by two therapists in groups of 6–8 patients. A total of 68 psychiatric patients with autism spectrum disorders participated in the study. Outcome measures were Quality of Life Inventory, Sense of Coherence Scale, Rosenberg Self-Esteem Scale and an exploratory analysis on measures of psychiatric health. Participants in both treatment conditions reported an increased quality of life at post-treatment (d = 0.39, p < 0.001), with no difference between interventions. No amelioration of psychiatric symptoms was observed. The dropout rate was lower with cognitive behavioural therapy than with recreational activity, and participants in cognitive behavioural therapy rated themselves as more generally improved, as well as more improved regarding expression of needs and understanding of difficulties. Both interventions appear to be promising treatment options for adults with autism spectrum disorder. The interventions’ similar efficacy may be due to the common elements, structure and group setting. Cognitive behavioural therapy may be additionally beneficial in terms of increasing specific skills and minimizing dropout. PMID:24089423

  19. Evaluation of Work Place Group and Internet Based Physical Activity Interventions on Psychological Variables Associated with Exercise Behavior Change

    PubMed Central

    Dawson, Kimberley A.; Tracey, Jill; Berry, Tanya

    2008-01-01

    The purpose of this research was to compare group-based and internet-based physical activity interventions in terms of desirability, participant characteristics, exercise self-efficacy, and barrier self-efficacy. Pretest questionnaires were completed prior to voluntary enrollment into either of the ten-week physical activity interventions. Both interventions were based on Social Cognitive Theory and the Transtheoretical Model. Interventions were followed with posttest questionnaires. Results demonstrated that the internet intervention attracted more participants, but only the group-based participants showed significant increases in exercise and barrier self-efficacy. At pretest, participants who selected the internet intervention were significantly lower in life and job satisfaction than those who selected the group intervention. Results suggest that traditional group-based exercise interventions are helpful for improving cognitions associated with exercise behavior change (e.g., exercise self-efficacy) and that the internet intervention may help employees who fall into an “unhappy employee ”typology. Key pointsGroup-based physical activity interventions are capable of improving exercise self-efficacy and barrier self-efficacy.At pretest, participants who selected the internet physical activity intervention were significantly lower in job and life satisfaction than those who selected the group-intervention.While the internet intervention attracted more participants, the group-based physical activity intervention was more successful at changing cognitions associated with successful exercise behavior change. PMID:24149963

  20. Group II p21-activated kinases as therapeutic targets in gastrointestinal cancer

    PubMed Central

    Shao, Yang-Guang; Ning, Ke; Li, Feng

    2016-01-01

    P21-activated kinases (PAKs) are central players in various oncogenic signaling pathways. The six PAK family members are classified into group I (PAK1-3) and group II (PAK4-6). Focus is currently shifting from group I PAKs to group II PAKs. Group II PAKs play important roles in many fundamental cellular processes, some of which have particular significance in the development and progression of cancer. Because of their important functions, group II PAKs have become popular potential drug target candidates. However, few group II PAKs inhibitors have been reported, and most do not exhibit satisfactory kinase selectivity and “drug-like” properties. Isoform- and kinase-selective PAK inhibitors remain to be developed. This review describes the biological activities of group II PAKs, the importance of group II PAKs in the development and progression of gastrointestinal cancer, and small-molecule inhibitors of group II PAKs for the treatment of cancer. PMID:26811660

  1. Antimicrobial peptides expressed in medicinal maggots of the blow fly Lucilia sericata show combinatorial activity against bacteria.

    PubMed

    Pöppel, Anne-Kathrin; Vogel, Heiko; Wiesner, Jochen; Vilcinskas, Andreas

    2015-05-01

    The larvae of the common green bottle fly (Lucilia sericata) produce antibacterial secretions that have a therapeutic effect on chronic and nonhealing wounds. Recent developments in insect biotechnology have made it possible to use these larvae as a source of novel anti-infectives. Here, we report the application of next-generation RNA sequencing (RNA-Seq) to characterize the transcriptomes of the larval glands, crop, and gut, which contribute to the synthesis of antimicrobial peptides (AMPs) and proteins secreted into wounds. Our data confirm that L. sericata larvae have adapted in order to colonize microbially contaminated habitats, such as carrion and necrotic wounds, and are protected against infection by a diverse spectrum of AMPs. L. sericata AMPs include not only lucifensin and lucimycin but also novel attacins, cecropins, diptericins, proline-rich peptides, and sarcotoxins. We identified 47 genes encoding putative AMPs and produced 23 as synthetic analogs, among which some displayed activities against a broad spectrum of microbial pathogens, including Pseudomonas aeruginosa, Proteus vulgaris, and Enterococcus faecalis. Against Escherichia coli (Gram negative) and Micrococcus luteus (Gram positive), we found mostly additive effects but also synergistic activity when selected AMPs were tested in combination. The AMPs that are easy to synthesize are currently being produced in bulk to allow their evaluation as novel anti-infectives that can be formulated in hydrogels to produce therapeutic wound dressings and adhesive bandages.

  2. Antimicrobial Peptides Expressed in Medicinal Maggots of the Blow Fly Lucilia sericata Show Combinatorial Activity against Bacteria

    PubMed Central

    Pöppel, Anne-Kathrin; Vogel, Heiko; Wiesner, Jochen

    2015-01-01

    The larvae of the common green bottle fly (Lucilia sericata) produce antibacterial secretions that have a therapeutic effect on chronic and nonhealing wounds. Recent developments in insect biotechnology have made it possible to use these larvae as a source of novel anti-infectives. Here, we report the application of next-generation RNA sequencing (RNA-Seq) to characterize the transcriptomes of the larval glands, crop, and gut, which contribute to the synthesis of antimicrobial peptides (AMPs) and proteins secreted into wounds. Our data confirm that L. sericata larvae have adapted in order to colonize microbially contaminated habitats, such as carrion and necrotic wounds, and are protected against infection by a diverse spectrum of AMPs. L. sericata AMPs include not only lucifensin and lucimycin but also novel attacins, cecropins, diptericins, proline-rich peptides, and sarcotoxins. We identified 47 genes encoding putative AMPs and produced 23 as synthetic analogs, among which some displayed activities against a broad spectrum of microbial pathogens, including Pseudomonas aeruginosa, Proteus vulgaris, and Enterococcus faecalis. Against Escherichia coli (Gram negative) and Micrococcus luteus (Gram positive), we found mostly additive effects but also synergistic activity when selected AMPs were tested in combination. The AMPs that are easy to synthesize are currently being produced in bulk to allow their evaluation as novel anti-infectives that can be formulated in hydrogels to produce therapeutic wound dressings and adhesive bandages. PMID:25666157

  3. Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain.

    PubMed

    Webster, J C; Francis, M M; Porter, J K; Robinson, G; Stokes, C; Horenstein, B; Papke, R L

    1999-07-01

    We show that a portion of the TM2 domain regulates the sensitivity of beta subunit-containing rat neuronal nicotinic AChR to the ganglionic blocker mecamylamine, such that the substitution of 4 amino acids of the muscle beta subunit sequence into the neuronal beta4 sequence decreases the potency of mecamylamine by a factor of 200 and eliminates any long-term effects of this drug on receptor function. The same exchange of sequence that decreases inhibition by mecamylamine produces a comparable potentiation of long-term inhibition by nicotine. Inhibition by mecamylamine is voltage-dependent, suggesting a direct interaction of mecamylamine with sequence elements within the membrane field. We have previously shown that sensitivity to TMP (tetramethylpiperidine) inhibitors is controlled by the same sequence elements that determine mecamylamine sensitivity. However, inhibition by bis-TMP compounds is independent of voltage. Our experiments did not show any influence of voltage on the inhibition of chimeric receptors by nicotine, suggesting that the inhibitory effects of nicotine are mediated by binding to a site outside the membrane's electric field. An analysis of point mutations indicates that the residues at the 6' position within the beta subunit TM2 domain may be important for determining the effects of both mecamylamine and nicotine in a reciprocal manner. Single mutations at the 10' position are not sufficient to produce effects, but 6' 10' double mutants show more effect than do the 6' single mutants.

  4. Reduced Expression of the Retinoblastoma Protein Shows That the Related Signaling Pathway Is Essential for Mediating the Antineoplastic Activity of Erufosine

    PubMed Central

    Zaharieva, Maya M.; Kirilov, Milen; Chai, Minquang; Berger, Stefan M.; Konstantinov, Spiro; Berger, Martin R.

    2014-01-01

    Erufosine is a new antineoplastic agent of the group of alkylphosphocholines, which interferes with signal transduction and induces apoptosis in various leukemic and tumor cell lines. The present study was designed to examine for the first time the mechanism of resistance to erufosine in malignant cells with permanently reduced expression of the retinoblastoma (Rb) protein. Bearing in mind the high number of malignancies with reduced level of this tumor-suppressor, this investigation was deemed important for using erufosine, alone or in combination, in patients with compromised RB1 gene expression. For this purpose, clones of the leukemic T-cell line SKW-3 were used, which had been engineered to constantly express differently low Rb levels. The alkylphosphocholine induced apoptosis, stimulated the expression of the cyclin dependent kinase inhibitor p27Kip1 and inhibited the synthesis of cyclin D3, thereby causing a G2 phase cell cycle arrest and death of cells with wild type Rb expression. In contrast, Rb-deficiency impeded the changes induced by eru-fosine in the expression of these proteins and abrogated the induction of G2 arrest, which was correlated with reduced antiproliferative and anticlonogenic activities of the compound. In conclusion, analysis of our results showed for the first time that the Rb signaling pathway is essential for mediating the antineoplastic activity of erufosine and its efficacy in patients with malignant diseases may be predicted by determining the Rb status. PMID:24987858

  5. In Vitro and In Vivo Antimalarial Activity Assays of Seeds from Balanites aegyptiaca: Compounds of the Extract Show Growth Inhibition and Activity against Plasmodial Aminopeptidase

    PubMed Central

    Kusch, Peter; Deininger, Susanne; Specht, Sabine; Maniako, Rudeka; Haubrich, Stefanie; Pommerening, Tanja; Lin, Paul Kong Thoo; Hoerauf, Achim; Kaiser, Annette

    2011-01-01

    Balanites aegyptiaca (Balanitaceae) is a widely grown desert plant with multiuse potential. In the present paper, a crude extract from B. aegyptiaca seeds equivalent to a ratio of 1 : 2000 seeds to the extract was screened for antiplasmodial activity. The determined IC50 value for the chloroquine-susceptible Plasmodium falciparum NF54 strain was 68.26 μg/μL ± 3.5. Analysis of the extract by gas chromatography-mass spectrometry detected 6-phenyl-2(H)-1,2,4-triazin-5-one oxime, an inhibitor of the parasitic M18 Aspartyl Aminopeptidase as one of the compounds which is responsible for the in vitro antiplasmodial activity. The crude plant extract had a Ki of 2.35 μg/μL and showed a dose-dependent response. After depletion of the compound, a significantly lower inhibition was determined with a Ki of 4.8 μg/μL. Moreover, two phenolic compounds, that is, 2,6-di-tert-butyl-phenol and 2,4-di-tert-butyl-phenol, with determined IC50 values of 50.29 μM ± 3 and 47.82 μM ± 2.5, respectively, were detected. These compounds may contribute to the in vitro antimalarial activity due to their antioxidative properties. In an in vivo experiment, treatment of BALB/c mice with the aqueous Balanite extract did not lead to eradication of the parasites, although a reduced parasitemia at day 12 p.i. was observed. PMID:21687598

  6. Map showing recent and historic landslide activity on coastal bluffs of Puget Sound between Shilshole Bay and Everett, Washington

    USGS Publications Warehouse

    Baum, R.L.; Harp, E.L.; Hultman, W.A.

    2000-01-01

    Many landslides occurred on the coastal bluffs between Seattle and Everett, Washington during the winters of 1996 and 1997. Shallow earth slides and debris flows were the most common, but a few deep-seated rotational earth slides also occurred. The landslides caused significant property damage and interfered with rail traffic; future landslides in the area pose significant hazards to property and public safety. Field observations indicate that ground-water seepage, runoff concentration, and dumping at the tops of the bluffs all contributed to instability of the bluffs. Most landslides in the study area occurred in colluvium, residuum, and landslide deposits derived from the Vashon Drift, particularly the advance outwash. In the northern part of the area, colluvium derived from the Pleistocene Whidbey Formation was also involved in shallow landslides. Comparison of recent activity with historic records in the southern part of the map area indicates that landslides tend to occur in many of the same areas as previous landslides.

  7. 2,8-bis(trifluoromethyl)quinoline analogs show improved anti-Zika virus activity, compared to mefloquine.

    PubMed

    Barbosa-Lima, Giselle; Moraes, Adriana M; Araújo, Adriele da S; da Silva, Emerson T; de Freitas, Caroline S; Vieira, Yasmine R; Marttorelli, Andressa; Neto, José Cerbino; Bozza, Patrícia T; de Souza, Marcus V N; Souza, Thiago Moreno L

    2017-02-15

    Zika virus (ZIKV), an arthropod-born Flavivirus, has been associated with a wide range of neurological diseases in adults, foetuses and neonates. Since no vaccine is available, repurposing of antiviral drugs currently in medical use is necessary. Mefloquine has confirmed anti-ZIKV activity. We used medicinal chemistry-driven approaches to synthesize and evaluate the ability of a series of new 2,8-bis(trifluoromethyl)quinoline derivatives to inhibit ZIKV replication in vitro, in order to improve the potency of mefloquine. We found that quinoline derivatives 3a and 4 were the most potent compounds within this series, both with mean EC50 values of 0.8 μM, which represents a potency 5 times that of mefloquine. These results indicate that new 2,8-bis(trifluoromethyl)quinoline chemical structures may be promising for the development of novel anti-ZIKV drugs.

  8. Mucin-depleted foci are modulated by dietary treatments and show deregulation of proliferative activity in carcinogen-treated rodents.

    PubMed

    Femia, Angelo Pietro; Caderni, Giovanna; Bottini, Consuelo; Salvadori, Maddalena; Dolara, Piero; Tessitore, Luciana

    2007-06-01

    The correlation between mucin-depleted foci (MDF) and colon carcinogenesis was studied in F344 rats initiated with 1,2-dimethylhydrazine and treated with a chemopreventive regimen (polyethylene glycol, PEG) or with a promoting diet (high-corn oil). High corn oil diet increased MDF, while PEG reduced them. The expression of p27 and p16, inhibitors of cyclin-dependent kinases, which inhibit the progression of the cell cycle, was studied by immunohistochemistry in MDF and in aberrant crypt foci (ACF) of control rats. In both MDF and ACF, the nuclear expression of p27 was markedly reduced, while p16 was reduced to a lower extent. Mitotic activity was higher in MDF and ACF than in normal mucosa of control rats. MDF were also identified in azoxymethane-initiated SWR/J mice. These results further confirm that MDF are preneoplastic lesions and could be useful biomarkers of colon carcinogenesis.

  9. Synthesis of analogues of the Des-Phe-NH2 C-terminal hexapeptide of cholecystokinin showing gastrin antagonist activity.

    PubMed

    Laur, J; Rodriguez, M; Aumelas, A; Bali, J P; Martinez, J

    1986-04-01

    Four analogues of Z-CCK-27-32-NH2, Z-Tyr(SO3-)-Met-Gly-Trp-Met-Asp-NH2, a cholecystokinin receptor antagonist have been synthesized by solution methodology. In these analogues, Z-Tyr(SO3-)-Nle-Gly-Trp-Met-Asp-NH2 16, Z-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-NH2 17, BOC-Tyr(SO3-)-Met-Gly-Trp-Met-Asp-NH2 24 and Boc-Tyr(SO3-)-Met-Gly-Trp-Nle-Asp-NH2 25 methionyl residues were replaced by norleucyl residues. Preliminary biological activity on gastrin-induced acid secretion, in rat, are reported. These derivatives proved to antagonize the action of gastrin, with ED 50 of between 0.5 and 3 mg/kg.

  10. The adult pituitary shows stem/progenitor cell activation in response to injury and is capable of regeneration.

    PubMed

    Fu, Qiuli; Gremeaux, Lies; Luque, Raul M; Liekens, Daisy; Chen, Jianghai; Buch, Thorsten; Waisman, Ari; Kineman, Rhonda; Vankelecom, Hugo

    2012-07-01

    The pituitary gland constitutes, together with the hypothalamus, the regulatory core of the endocrine system. Whether the gland is capable of cell regeneration after injury, in particular when suffered at adult age, is unknown. To investigate the adult pituitary's regenerative capacity and the response of its stem/progenitor cell compartment to damage, we constructed a transgenic mouse model to conditionally destroy pituitary cells. GHCre/iDTR mice express diphtheria toxin (DT) receptor after transcriptional activation by Cre recombinase, which is driven by the GH promoter. Treatment with DT for 3 d leads to gradual GH(+) (somatotrope) cell obliteration with a final ablation grade of 80-90% 1 wk later. The stem/progenitor cell-clustering side population promptly expands after injury, concordant with the immediate increase in Sox2(+) stem/progenitor cells. In addition, folliculo-stellate cells, previously designated as pituitary stem/progenitor cells and significantly overlapping with Sox2(+) cells, also increase in abundance. In situ examination reveals expansion of the Sox2(+) marginal-zone niche and appearance of remarkable Sox2(+) cells that contain GH. When mice are left after the DT-provoked lesion, GH(+) cells considerably regenerate during the following months. Double Sox2(+)/GH(+) cells are observed throughout the regenerative period, suggesting recovery of somatotropes from stem/progenitor cells, as further supported by 5-ethynyl-2'-deoxyuridine (EdU) pulse-chase lineage tracing. In conclusion, our study demonstrates that the adult pituitary gland holds regenerative competence and that tissue repair follows prompt activation and plausible involvement of the stem/progenitor cells.

  11. Hedgehog Signaling Pathway Is Active in GBM with GLI1 mRNA Expression Showing a Single Continuous Distribution Rather than Discrete High/Low Clusters

    PubMed Central

    Biswas, Nidhan K.; Rote, Sarang; Chatterjee, Uttara; Ghosh, Samarendra N.; Deb, Sumit; Saha, Suniti K.; Chowdhury, Anup K.; Ghosh, Subhashish; Rudin, Charles M.; Mukherjee, Ankur; Basu, Analabha; Dhara, Surajit

    2015-01-01

    Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression—as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution—unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the “high-Hh” cluster of MB but 5.6 fold higher than that of the “low-Hh” cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them. PMID:25775002

  12. The challenge of "teaching" large groups of learners: strategies to increase active participation and learning.

    PubMed

    Nierenberg, D W

    1998-01-01

    While teaching in a tutorial, seminar, or problem-based learning group format may be the most fun and most active/interactive for both learner and faculty mentor, there are situations in medical student education in which various constraints require the use of the "lecture" format. Similar constraints may occur in the field of continuing medical education, or graduate medical education, as well. When this occurs, the faculty mentor can increase the active participation of the learners in the audience by continuously stressing seven key pedagogical (androgogical) principles. These include: 1) begin the learning exercise with a clinical example or anecdote to show the relevance of the material to the student; 2) frequently ask the students whether they have ever seen examples of what you describe in their previous experience with patients, personal experience, experience with relatives, etc.; 3) ask students frequently whether they have heard similar material presented differently in other courses; 4) recruit students to help solve "mystery cases"; 5) show examples of similar material from real life (e.g., patient descriptions, or even excerpts from favorite TV shows); 6) ask students to help summarize key points at the end of the session; and 7) allow, or even encourage, whispering during the class. Using some or all of these techniques can help turn a "lecture format" into a much more fun, interactive, and valuable session that emphasizes "learning" rather than "teaching."

  13. Nanorods of a new metal-biomolecule coordination polymer showing novel bidirectional electrocatalytic activity and excellent performance in electrochemical sensing.

    PubMed

    Yang, Jiao; Zhou, Bo; Yao, Jie; Jiang, Xiao-Qing

    2015-05-15

    Metal organic coordination polymers (CPs), as most attractive multifunctional materials, have been studied extensively in many fields. However, metal-biomolecule CPs and CPs' electrochemical properties and applications were studied much less. We focus on this topic aiming at electrochemical biosensors with excellent performance and high biocompatibility. A new nanoscaled metal-biomolecule CP, Mn-tyr, containing manganese and tyrosine, was synthesized hydrothermally and characterized by various techniques, including XRD, TEM, EDS, EDX mapping, elemental analysis, XPS, and IR. Electrode modified with Mn-tyr showed novel bidirectional electrocatalytic ability toward both reduction and oxidation of H2O2, which might be due to Mn. With the assistance of CNTs, the sensing performance of Mn-tyr/CNTs/GCE was improved to a much higher level, with high sensitivity of 543 mA mol(-1) L cm(-2) in linear range of 1.00×10(-6)-1.02×10(-4) mol L(-1), and detection limit of 3.8×10(-7) mol L(-1). Mn-tyr/CNTs/GCE also showed fast response, high selectivity, high steadiness and reproducibility. The excellent performance implies that the metal-biomolecule CPs are promising candidates for using in enzyme-free electrochemical biosensing.

  14. "We Are in This Together": Common Group Identity Predicts Majority Members' Active Acculturation Efforts to Integrate Immigrants.

    PubMed

    Kunst, Jonas R; Thomsen, Lotte; Sam, David L; Berry, John W

    2015-10-01

    Although integration involves a process of mutual accommodation, the role of majority groups is often downplayed to passive tolerance, leaving immigrants with the sole responsibility for active integration. However, we show that common group identity can actively involve majority members in this process across five studies. Study 1 showed that common identity positively predicted support of integration efforts; Studies 2 and 3 extended these findings, showing that it also predicted real behavior such as monetary donations and volunteering. A decrease in modern racism mediated the relations across these studies, and Studies 4 and 5 further demonstrated that it indeed mediated these effects over and above acculturation expectations and color-blindness, which somewhat compromised integration efforts. Moreover, the last two studies also demonstrated that common, but not dual, groups motivated integration efforts. Common identity appears crucial for securing majorities' altruistic efforts to integrate immigrants and, thus, for achieving functional multiculturalism.

  15. Immobilized MAS1 lipase showed high esterification activity in the production of triacylglycerols with n-3 polyunsaturated fatty acids.

    PubMed

    Wang, Xiumei; Li, Daoming; Qu, Man; Durrani, Rabia; Yang, Bo; Wang, Yonghua

    2017-02-01

    Immobilization of lipase MAS1 from marine Streptomyces sp. strain W007 and its application in catalyzing esterification of n-3 polyunsaturated fatty acids (PUFA) with glycerol were investigated. The resin XAD1180 was selected as a suitable support for the immobilization of lipase MAS1, and its absorption ability was 75mg/g (lipase/resin ratio) with initial buffer pH value of 8.0. The thermal stability of immobilized MAS1 was improved significantly compared with that of the free lipase. Immobilized MAS1 had no regiospecificity in the hydrolysis of triolein. The highest esterification degree (99.31%) and TAG content (92.26%) by immobilized MAS1-catalyzed esterification were achieved under the optimized conditions, which were significantly better than those (82.16% and 47.26%, respectively) by Novozym 435. More than 92% n-3 PUFA was incorporated into TAG that had similar fatty acids composition to the substrate (n-3 PUFA). The immobilized MAS1 exhibited 50% of its initial activity after being used for five cycles.

  16. Ecotoxicological assessment of solar cell leachates: Copper indium gallium selenide (CIGS) cells show higher activity than organic photovoltaic (OPV) cells.

    PubMed

    Brun, Nadja Rebecca; Wehrli, Bernhard; Fent, Karl

    2016-02-01

    Despite the increasing use of photovoltaics their potential environmental risks are poorly understood. Here, we compared ecotoxicological effects of two thin-film photovoltaics: established copper indium gallium selenide (CIGS) and organic photovoltaic (OPV) cells. Leachates were produced by exposing photovoltaics to UV light, physical damage, and exposure to environmentally relevant model waters, representing mesotrophic lake water, acidic rain, and seawater. CIGS cell leachates contained 583 μg L(-1) molybdenum at lake water, whereas at acidic rain and seawater conditions, iron, copper, zinc, molybdenum, cadmium, silver, and tin were present up to 7219 μg L(-1). From OPV, copper (14 μg L(-1)), zinc (87 μg L(-1)) and silver (78 μg L(-1)) leached. Zebrafish embryos were exposed until 120 h post-fertilization to these extracts. CIGS leachates produced under acidic rain, as well as CIGS and OPV leachates produced under seawater conditions resulted in a marked hatching delay and increase in heart edema. Depending on model water and solar cell, transcriptional alterations occurred in genes involved in oxidative stress (cat), hormonal activity (vtg1, ar), metallothionein (mt2), ER stress (bip, chop), and apoptosis (casp9). The effects were dependent on the concentrations of cationic metals in leachates. Addition of ethylenediaminetetraacetic acid protected zebrafish embryos from morphological and molecular effects. Our study suggests that metals leaching from damaged CIGS cells, may pose a potential environmental risk.

  17. An Agrobacterium tumefaciens Strain with Gamma-Aminobutyric Acid Transaminase Activity Shows an Enhanced Genetic Transformation Ability in Plants

    PubMed Central

    Nonaka, Satoko; Someya, Tatsuhiko; Zhou, Sha; Takayama, Mariko; Nakamura, Kouji; Ezura, Hiroshi

    2017-01-01

    Agrobacterium tumefaciens has the unique ability to mediate inter-kingdom DNA transfer, and for this reason, it has been utilized for plant genetic engineering. To increase the transformation frequency in plant genetic engineering, we focused on gamma-aminobutyric acid (GABA), which is a negative factor in the Agrobacterium-plant interaction. Recent studies have shown contradictory results regarding the effects of GABA on vir gene expression, leading to the speculation that GABA inhibits T-DNA transfer. In this study, we examined the effect of GABA on T-DNA transfer using a tomato line with a low GABA content. Compared with the control, the T-DNA transfer frequency was increased in the low-GABA tomato line, indicating that GABA inhibits T-DNA transfer. Therefore, we bred a new A. tumefaciens strain with GABA transaminase activity and the ability to degrade GABA. The A. tumefaciens strain exhibited increased T-DNA transfer in two tomato cultivars and Erianthus arundinacues and an increased frequency of stable transformation in tomato. PMID:28220841

  18. A major EBNA1 variant from Asian EBV isolates shows enhanced transcriptional activity compared to prototype B95.8.

    PubMed

    Do, Nguyen-Van; Ingemar, Ernberg; Phi, Phan-Thi Phi; Jenny, Almqvist; Chinh, Tran-Thi; Zeng, Yixin; Hu, Lifu

    2008-03-01

    Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) has an instrumental role in maintaining EBV latent infection by controlling EBV episome replication and regulating viral transcription. It is a ubiquitously expressed protein during latent viral infection and in EBV-associated tumors. The EBNA1 C-terminus interacts functionally with the Qp and Cp that control viral gene expression in latency I/II and III, respectively. EBNA1 has been classified into five subtypes due to sequence variation in the DNA-interacting C-terminus. By DNA sequence analysis of its C-terminus, we detected a main sub-variant (V-val-v1) of EBNA1 with valine located in both positions 487 and 528 from matched samples including NPC biopsies and peripheral blood taken from Vietnamese (9), Chinese (12) NPC patients and healthy donors (5). In the FR-region of oriP from nine NPC biopsies from Vietnam we also frequently found substitutions, deletions and variable numbers of repeats. Using a luciferase reporter system, EBNA1 and FR both derived from Asian isolates induced higher transcriptional activity than those from B95-8 virus.

  19. The physical activity profiles of South Asian ethnic groups in England

    PubMed Central

    Bhatnagar, Prachi; Townsend, Nick; Shaw, Alison; Foster, Charlie

    2016-01-01

    Background To identify what types of activity contribute to overall physical activity in South Asian ethnic groups and how these vary according to sex and age. We used the White British ethnic group as a comparison. Methods Self-reported physical activity was measured in the Health Survey for England 1999 and 2004, a nationally representative, cross-sectional survey that boosted ethnic minority samples in these years. We merged the two survey years and analysed data from 19 476 adults. The proportions of total physical activity achieved through walking, housework, sports and DIY activity were calculated. We stratified by sex and age group and used analysis of variances to examine differences between ethnic groups, adjusted for the socioeconomic status. Results There was a significant difference between ethnic groups for the contributions of all physical activity domains for those aged below 55 years, with the exception of walking. In women aged 16–34 years, there was no significant difference in the contribution of walking to total physical activity (p=0.38). In the 35–54 age group, Bangladeshi males have the highest proportion of total activity from walking (30%). In those aged over 55 years, the proportion of activity from sports was the lowest in all South Asian ethnic groups for both sexes. Conclusions UK South Asians are more active in some ways that differ, by age and sex, from White British, but are similarly active in other ways. These results can be used to develop targeted population level interventions for increasing physical activity levels in adult UK South Asian populations. PMID:26677257

  20. The Pervasive Problem With Placebos in Psychology: Why Active Control Groups Are Not Sufficient to Rule Out Placebo Effects.

    PubMed

    Boot, Walter R; Simons, Daniel J; Stothart, Cary; Stutts, Cassie

    2013-07-01

    To draw causal conclusions about the efficacy of a psychological intervention, researchers must compare the treatment condition with a control group that accounts for improvements caused by factors other than the treatment. Using an active control helps to control for the possibility that improvement by the experimental group resulted from a placebo effect. Although active control groups are superior to "no-contact" controls, only when the active control group has the same expectation of improvement as the experimental group can we attribute differential improvements to the potency of the treatment. Despite the need to match expectations between treatment and control groups, almost no psychological interventions do so. This failure to control for expectations is not a minor omission-it is a fundamental design flaw that potentially undermines any causal inference. We illustrate these principles with a detailed example from the video-game-training literature showing how the use of an active control group does not eliminate expectation differences. The problem permeates other interventions as well, including those targeting mental health, cognition, and educational achievement. Fortunately, measuring expectations and adopting alternative experimental designs makes it possible to control for placebo effects, thereby increasing confidence in the causal efficacy of psychological interventions.

  1. A Group Contingency plus Self-Management Intervention Targeting At-Risk Secondary Students' Class-Work and Active Engagement

    ERIC Educational Resources Information Center

    Trevino-Maack, Sylvia I.; Kamps, Debra; Wills, Howard

    2015-01-01

    The purpose of the present study is to show that an independent group contingency (GC) combined with self-management strategies and randomized-reinforcer components can increase the amount of written work and active classroom responding in high school students. Three remedial reading classes and a total of 15 students participated in this study.…

  2. The structure-anticoagulant activity relationships of sulfated lacquer polysaccharide: effect of carboxyl group and position of sulfation.

    PubMed

    Yang, Jianhong; Du, Yumin; Huang, Ronghua; Wan, Yunyang; Wen, Yan

    2005-07-01

    Regiospecific oxidation of the primary hydroxyl groups in lacquer polysaccharide (LPL, Mw 6.85 x 10(4)) and its NaIO4 oxidation derivatives (LPLde) to C-6 carboxy groups was achieved with NaOCl in the presence of Tempo and NaBr. Sulfate groups were incorporated into the oxidated polysaccharides using Py.SO3 complex as a reagent. Reactivity of polysaccharide hydroxyl group was C-6 > C-2 > C-4. Sulfate groups were mainly linked to the second hydroxy at C-2 in the products. The results of APTT assay showed after incorporation of carboxyl groups into lacquer polysaccharides, the intrinsic coagulation pathway was promoted, and all sulfated polysaccharides had very weak anticoagulant activity within the scope of studied DS (0.39-1.11). These indicated that carboxyl groups and sulfate groups had the synergistic action. At the same time, the anticoagulant activity increased very slowly with the DS in the second hydroxy. This indicated that 6-O-SO3- in the side chains took an important role in the anticoagulant activity.

  3. Two sulfhydryl groups near the active site of soybean beta-amylase.

    PubMed

    Mikami, B; Nomura, K; Morita, Y

    1994-01-01

    The less reactive SH groups of soybean beta-amylase, SH4, SH5, and SH6, were modified with p-chloromercuribenzoic acid or N-ethylmaleimide, after the reactive SH groups, SH1, SH2, and SH3, were blocked with 5,5'-dithiobis-(2-nitrobenzoic acid) and cyanide. The enzyme activity decreased, accompanied by the modification of SH4. alpha-Cyclodextrin protected SH4 from the modification more effectively than maltose. The SH4-modified enzyme still bound to glucose, maltose, and alpha-cyclodextrin. SH4 was concerned with neither the catalysis nor substrate binding but its large substituent affected the substrate binding site. The sequencing of the 5-(iodoacetoamidoethyl)-aminoaphthalene-1-sulfonate-labeled peptides showed that SH4, SH5, and SH6 are Cys343, Cys82, and Cys208, respectively. Comparison of the primary structure of beta-amylases also showed that the sequence around SH4 (Cys343), as well as SH2 (Cys95), is strongly conserved between higher plant and bacterial beta-amylases. These results agree with the structure model deduced from X-ray crystallography of soybean beta-amylase.

  4. An Echinococcus multilocularis Antigen B3 Proteoform That Shows Specific Antibody Responses to Active-Stage Alveolar Echinococcosis

    PubMed Central

    Ahn, Chun-Seob; Cai, Huixia; Kim, Jeong-Geun; Han, Xiumin; Ma, Xiao; Bae, Young-An; Yang, Hyun-Jong; Kang, Insug; Wang, Hu

    2015-01-01

    Alveolar echinococcosis (AE), caused by the Echinococcus multilocularis metacestode, represents one of the most frequently fatal zoonoses. Early diagnosis significantly reduces morbidity and mortality associated with AE. Diagnosis of AE largely depends on a combination of imaging and serological tests due to its minimal clinical manifestations. Several antigens derived from the whole worm and protoscolex have been targeted for AE serodiagnosis, while the antigenic properties of E. multilocularis hydatid fluid (EmHF) are unclear. We observed two AE-specific 6- and 8-kDa antigen proteoforms through an immunoproteome array of the EmHF. We identified these proteins as representing an E. multilocularis antigen B3 (EmAgB3) isoform, and the proteins were shown to be encoded by the same gene. We cloned the gene and expressed the recombinant EmAgB3 protein (rEmAgB3) in Escherichia coli. rEmAgB3 exhibited sensitivity of 90.9% (80/88 cases) and specificity of 98.5% (597/606 samples) by immunoblotting. The positive and negative predictive values were 89.9% and 98.6%, respectively. The protein did not show antibody responses to 33 AE sera collected during posttreatment follow-up monitoring. Mouse sera experimentally infected with AE protoscoleces began to demonstrate specific antibody responses to native and recombinant EmAgB3 6 months after infection. At that stage, fully mature metacestode vesicles that harbored the brood capsule, primary cell, and protoscolex were observed within an AE mass(es). The response declined along with worm degeneration. Our results demonstrate that the immune responses to this EmAgB3 isoform were highly correlated with worm viability accompanied with AE progression. rEmAgB3 is a promising biomarker for serological assessment of AE patients. PMID:26269620

  5. Virus infection and interferon can activate gene expression through a single synthetic element, but endogenous genes show distinct regulation.

    PubMed

    Raj, N B; Engelhardt, J; Au, W C; Levy, D E; Pitha, P M

    1989-10-05

    Virus inducible elements (IE) in promoters of mouse alpha-interferon and human beta 1-interferon genes contain multiple copies of the hexanucleotide sequence AGT-GAA or its variants which are also found in the interferon-stimulated response element of genes transcriptionally induced by interferon. We have examined the similarities between virus and interferon induction of gene expression and the role of AGTGAA and AAT-GAA hexamers in these responses. Hybrid plasmids were constructed by inserting the IE region, the alpha 4 promoter, or the multiple copies of AGTGAA or AAT-GAA 5' to the inactive-45 human immunodeficiency-chloramphenicol acetyltransferase hybrid gene, and their inducible expression was studied in a transient expression assay. In L-cells, multiple hexamers were efficiently induced both by infection with Newcastle disease virus and by interferon treatment; while the alpha 4 promoter and the IE inducible region were induced predominantly by virus rather than by interferon. In order to dissociate the effect of virus and endogenous interferon on the induction process, we examined the gene expression in Vero cells, which have undergone homozygous deletion of type 1 interferon genes, and in VNPT-159 cells, which were derived from Vero cells by insertion of an inducible human interferon beta 1 gene. The results show that while the alpha 4 promoter was efficiently induced only by virus in both cell types, the constructs containing shorter segments of the IE were induced by both virus and interferon in Vero cells. However, the inducibility by interferon was not detected in VNPT-159 cells, suggesting that the presence of endogenous interferon suppresses interferon-induced expression of hexanucleotide repeats and the short inducible region. In contrast, virus inducibility of endogenous interferon-stimulated genes, ISG-15 and ISG-54, was about 100-fold more efficient in VNPT-159 cells than in Vero cells, suggesting that this induction is largely mediated through

  6. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    NASA Astrophysics Data System (ADS)

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; Watts, Benjamin; Kaneno, Ramon; Zambuzzi, Willian F.; Daemen, Luke; Saeki, Margarida J.; Bordallo, Heloisa N.

    2016-03-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells.

  7. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    SciTech Connect

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; Watts, Benjamin; Kaneno, Ramon; Zambuzzi, Willian F.; Daemen, Luke; Saeki, Margarida J.; Bordallo, Heloisa N.

    2016-03-02

    Here, the most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. In conclusion, from these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells.

  8. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    DOE PAGES

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; ...

    2016-03-02

    Here, the most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigatemore » the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. In conclusion, from these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells.« less

  9. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    PubMed Central

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; Watts, Benjamin; Kaneno, Ramon; Zambuzzi, Willian F.; Daemen, Luke; Saeki, Margarida J.; Bordallo, Heloisa N.

    2016-01-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells. PMID:26932808

  10. Specialization of the DNA-Cleaving Activity of a Group I Ribozyme Through In Vitro Evolution

    NASA Technical Reports Server (NTRS)

    Tsang, Joyce; Joyce, Gerald F.

    1996-01-01

    In an earlier study, an in vitro evolution procedure was applied to a large population of variants of the Tetrahymena group 1 ribozyme to obtain individuals with a 10(exp 5)-fold improved ability to cleave a target single-stranded DNA substrate under simulated physiological conditions. The evolved ribozymes also showed a twofold improvement, compared to the wild-type, in their ability to cleave a single-stranded RNA substrate. Here, we report continuation of the in vitro evolution process using a new selection strategy to achieve both enhanced DNA and diminished RNA-cleavage activity. Our strategy combines a positive selection for DNA cleavage with a negative selection against RNA binding. After 36 "generations" of in vitro evolution, the evolved population showed an approx. 100-fold increase in the ratio of DNA to RNA-cleavage activity. Site-directed mutagenesis experiment confirmed the selective advantage of two covarying mutations within the catalytic core of ribozyme that are largely responsible for this modified behavior. The population of ribozymes has now undergone a total of 63 successive generations of evolution, resulting in an average 28 mutations relative to the wild-type that are responsible for the altered phenotype.

  11. Highly active oxygen reduction non-platinum group metal electrocatalyst without direct metal-nitrogen coordination.

    PubMed

    Strickland, Kara; Miner, Elise; Jia, Qingying; Tylus, Urszula; Ramaswamy, Nagappan; Liang, Wentao; Sougrati, Moulay-Tahar; Jaouen, Frédéric; Mukerjee, Sanjeev

    2015-06-10

    Replacement of noble metals in catalysts for cathodic oxygen reduction reaction with transition metals mostly create active sites based on a composite of nitrogen-coordinated transition metal in close concert with non-nitrogen-coordinated carbon-embedded metal atom clusters. Here we report a non-platinum group metal electrocatalyst with an active site devoid of any direct nitrogen coordination to iron that outperforms the benchmark platinum-based catalyst in alkaline media and is comparable to its best contemporaries in acidic media. In situ X-ray absorption spectroscopy in conjunction with ex situ microscopy clearly shows nitrided carbon fibres with embedded iron particles that are not directly involved in the oxygen reduction pathway. Instead, the reaction occurs primarily on the carbon-nitrogen structure in the outer skin of the nitrided carbon fibres. Implications include the potential of creating greater active site density and the potential elimination of any Fenton-type process involving exposed iron ions culminating in peroxide initiated free-radical formation.

  12. A Relaxed Active Site After Exon Ligation by the Group I Intron

    SciTech Connect

    Lipchock,S.; Strobel, S.

    2008-01-01

    During RNA maturation, the group I intron promotes two sequential phosphorotransfer reactions resulting in exon ligation and intron release. Here, we report the crystal structure of the intron in complex with spliced exons and two additional structures that examine the role of active-site metal ions during the second step of RNA splicing. These structures reveal a relaxed active site, in which direct metal coordination by the exons is lost after ligation, while other tertiary interactions are retained between the exon and the intron. Consistent with these structural observations, kinetic and thermodynamic measurements show that the scissile phosphate makes direct contact with metals in the ground state before exon ligation and in the transition state, but not after exon ligation. Despite no direct exonic interactions and even in the absence of the scissile phosphate, two metal ions remain bound within the active site. Together, these data suggest that release of the ligated exons from the intron is preceded by a change in substrate-metal coordination before tertiary hydrogen bonding contacts to the exons are broken.

  13. Highly active oxygen reduction non-platinum group metal electrocatalyst without direct metal–nitrogen coordination

    PubMed Central

    Strickland, Kara; Miner, Elise; Jia, Qingying; Tylus, Urszula; Ramaswamy, Nagappan; Liang, Wentao; Sougrati, Moulay-Tahar; Jaouen, Frédéric; Mukerjee, Sanjeev

    2015-01-01

    Replacement of noble metals in catalysts for cathodic oxygen reduction reaction with transition metals mostly create active sites based on a composite of nitrogen-coordinated transition metal in close concert with non-nitrogen-coordinated carbon-embedded metal atom clusters. Here we report a non-platinum group metal electrocatalyst with an active site devoid of any direct nitrogen coordination to iron that outperforms the benchmark platinum-based catalyst in alkaline media and is comparable to its best contemporaries in acidic media. In situ X-ray absorption spectroscopy in conjunction with ex situ microscopy clearly shows nitrided carbon fibres with embedded iron particles that are not directly involved in the oxygen reduction pathway. Instead, the reaction occurs primarily on the carbon–nitrogen structure in the outer skin of the nitrided carbon fibres. Implications include the potential of creating greater active site density and the potential elimination of any Fenton-type process involving exposed iron ions culminating in peroxide initiated free-radical formation. PMID:26059552

  14. Phosphatase activity of the voltage-sensing phosphatase, VSP, shows graded dependence on the extent of activation of the voltage sensor.

    PubMed

    Sakata, Souhei; Okamura, Yasushi

    2014-03-01

    The voltage-sensing phosphatase (VSP) consists of a voltage sensor and a cytoplasmic phosphatase region, and the movement of the voltage sensor is coupled to the phosphatase activity. However, its coupling mechanisms still remain unclear. One possible scenario is that the phosphatase is activated only when the voltage sensor is in a fully activated state. Alternatively, the enzymatic activity of single VSP proteins could be graded in distinct activated states of the voltage sensor, and partial activation of the voltage sensor could lead to partial activation of the phosphatase. To distinguish between these two possibilities, we studied a voltage sensor mutant of zebrafish VSP, where the voltage sensor moves in two steps as evidenced by analyses of charge movements of the voltage sensor and voltage clamp fluorometry. Measurements of the phosphatase activity toward phosphatidylinositol 4,5-bisphosphate revealed that both steps of voltage sensor activation are coupled to the tuning of phosphatase activities, consistent with the idea that the phosphatase activity is graded by the magnitude of the movement of the voltage sensor.

  15. The Relationship between Students' Small Group Activities, Time Spent on Self-Study, and Achievement

    ERIC Educational Resources Information Center

    Kamp, Rachelle J. A.; Dolmans, Diana H. J. M.; van Berkel, Henk J. M.; Schmidt, Henk G.

    2012-01-01

    The purpose of this study was to investigate the relationship between the contributions students make to the problem-based tutorial group process as observed by their peers, self-study time and achievement. To that end, the Maastricht Peer Activity Rating Scale was administered to students participating in Problem-Based Learning tutorial groups.…

  16. Alpha casein micelles show not only molecular chaperone-like aggregation inhibition properties but also protein refolding activity from the denatured state.

    PubMed

    Sakono, Masafumi; Motomura, Konomi; Maruyama, Tatsuo; Kamiya, Noriho; Goto, Masahiro

    2011-01-07

    Casein micelles are a major component of milk proteins. It is well known that casein micelles show chaperone-like activity such as inhibition of protein aggregation and stabilization of proteins. In this study, it was revealed that casein micelles also possess a high refolding activity for denatured proteins. A buffer containing caseins exhibited higher refolding activity for denatured bovine carbonic anhydrase than buffers including other proteins. In particular, a buffer containing α-casein showed about a twofold higher refolding activity compared with absence of α-casein. Casein properties of surface hydrophobicity, a flexible structure and assembly formation are thought to contribute to this high refolding activity. Our results indicate that casein micelles stabilize milk proteins by both chaperone-like activity and refolding properties.

  17. What Do We Want Small Group Activities For? Voices from EFL Teachers in Japan

    ERIC Educational Resources Information Center

    Kato, Yoshitaka

    2016-01-01

    This paper discusses the fundamental issue of why small group activities are utilized in the language learning classroom. Although these activities have gained popularity in the field of Teaching English as a Second Language (TESL), supported by a sound theoretical base, few studies have so far examined the reasons why language teachers are…

  18. Fostering an Active Learning Environment for Undergraduates: Peer-to-Peer Interactions in a Research Group

    ERIC Educational Resources Information Center

    Long, Christopher E.; Matthews, Michael A.; Thompson, Nancy S.

    2007-01-01

    The benefits of active learning in the traditional classroom setting are well established among engineering educators; however, this learning model can thrive in other settings, namely in a research group. This work presents findings from an educational research project specifically designed to foster active learning among undergraduates and…

  19. Work group IV: Future directions for measures of the food and physical activity environments.

    PubMed

    Story, Mary; Giles-Corti, Billie; Yaroch, Amy Lazarus; Cummins, Steven; Frank, Lawrence Douglas; Huang, Terry T-K; Lewis, LaVonna Blair

    2009-04-01

    Much progress has been made in the past 5 to 10 years in measuring and understanding the impact of the food and physical activity environments on behavioral outcomes. Nevertheless, this research is in its infancy. A work group was convened to identify current evidence gaps and barriers in food and physical activity environments and policy research measures, and develop recommendations to guide future directions for measurement and methodologic research efforts. A nominal group process was used to determine six priority areas for food and physical activity environments and policy measures to move the field forward by 2015, including: (1) identify relevant factors in the food and physical activity environments to measure, including those most amenable to change; (2) improve understanding of mechanisms for relationships between the environment and physical activity, diet, and obesity; (3) develop simplified measures that are sensitive to change, valid for different population groups and settings, and responsive to changing trends; (4) evaluate natural experiments to improve understanding of food and physical activity environments and their impact on behaviors and weight; (5) establish surveillance systems to predict and track change over time; and (6) develop standards for adopting effective health-promoting changes to the food and physical activity environments. The recommendations emanating from the work group highlight actions required to advance policy-relevant research related to food and physical activity environments.

  20. Integration of Structured Expressive Activities within a Humanistic Group Play Therapy Format for Preadolescents

    ERIC Educational Resources Information Center

    Bratton, Sue C.; Ceballos, Peggy L.; Ferebee, Kelly Webb

    2009-01-01

    The integration of expressive activities in play groups with preadolescents encourages them to reach more deeply into their own resources, enabling them to handle future challenges more effectively. Developmental and therapeutic rationale, along with research support, is given for the integration of creative activities into a humanistic play group…

  1. Upper Elementary Boys' Participation during Group Singing Activities in Single-Sex and Coeducational Classes

    ERIC Educational Resources Information Center

    Bazzy, Zadda M.

    2010-01-01

    As boys in the upper elementary grades become increasingly influenced by peer pressure, many are less likely to participate in singing activities because singing is considered a "feminine" activity. The purpose of this research was to explore if there was an effect on upper elementary boys' level of participation during group singing activities…

  2. IMPORTANCE OF ACTIVATED CARBON'S OXYGEN SURFACE FUNCTIONAL GROUPS ON ELEMENTAL MERCURY ADSORPTION

    EPA Science Inventory

    The effect of varying physical and chemical properties of activated carbons on adsorption of elemental mercury [Hg(0)] was studied by treating two activated carbons to modify their surface functional groups and pore structures. Heat treatment (1200 K) in nitrogen (N2), air oxidat...

  3. Group cohesion and between session homework activities predict self-reported cognitive-behavioral skill use amongst participants of SMART Recovery groups.

    PubMed

    Kelly, Peter J; Deane, Frank P; Baker, Amanda L

    2015-04-01

    SMART Recovery groups are cognitive-behaviorally oriented mutual support groups for individuals with addictions. The aim of the study was to assess the extent to which the quality of group facilitation, group cohesion and the use of between session homework activities contribute to self-rated use of cognitive-behavioral skills amongst group participants. Participants attending SMART Recovery groups in Australia completed a cross sectional survey (N=124). The survey included measures of cognitive and behavioral skill utilization, group cohesion, quality of group facilitation and a rating of how frequently participants leave group meetings with an achievable between session homework plan. On average, participants had been attending SMART Recovery meetings for 9 months. Participants were most likely to attend SMART Recovery for problematic alcohol use. Regression analyses indicated that group cohesion significantly predicted use of cognitive restructuring, but that only provision of homework at the end of each group session predicted self-reported behavioral activation. Both group cohesion and leaving a group with an achievable homework plan predicted participant use of cognitive behavioral skills. The concrete actions associated with homework activities may facilitate behavioral activation. There is a need for longitudinal research to examine the relationship between the utilization of cognitive and behavioral skills and participant outcomes (e.g. substance use, mental health) for people attending SMART Recovery groups.

  4. Unique lead adsorption behavior of activated hydroxyl group in two-dimensional titanium carbide.

    PubMed

    Peng, Qiuming; Guo, Jianxin; Zhang, Qingrui; Xiang, Jianyong; Liu, Baozhong; Zhou, Aiguo; Liu, Riping; Tian, Yongjun

    2014-03-19

    The functional groups and site interactions on the surfaces of two-dimensional (2D) layered titanium carbide can be tailored to attain some extraordinary physical properties. Herein a 2D alk-MXene (Ti3C2(OH/ONa)(x)F(2-x)) material, prepared by chemical exfoliation followed by alkalization intercalation, exhibits preferential Pb(II) sorption behavior when competing cations (Ca(II)/Mg(II)) coexisted at high levels. Kinetic tests show that the sorption equilibrium is achieved in as short a time as 120 s. Attractively, the alk-MXene presents efficient Pb(II) uptake performance with the applied sorption capacities of 4500 kg water per alk-MXene, and the effluent Pb(II) contents are below the drinking water standard recommended by the World Health Organization (10 μg/L). Experimental and computational studies suggest that the sorption behavior is related to the hydroxyl groups in activated Ti sites, where Pb(II) ion exchange is facilitated by the formation of a hexagonal potential trap.

  5. covR Mediated Antibiofilm Activity of 3-Furancarboxaldehyde Increases the Virulence of Group A Streptococcus

    PubMed Central

    Ashwinkumar Subramenium, Ganapathy; Viszwapriya, Dharmaprakash; Iyer, Prasanth Mani; Balamurugan, Krishnaswamy; Karutha Pandian, Shunmugiah

    2015-01-01

    Background Group A streptococcus (GAS, Streptococcus pyogenes), a multi-virulent, exclusive human pathogen responsible for various invasive and non-invasive diseases possesses biofilm forming phenomenon as one of its pathogenic armaments. Recently, antibiofilm agents have gained prime importance, since inhibiting the biofilm formation is expected to reduce development of antibiotic resistance and increase their susceptibility to the host immune cells. Principal Findings The current study demonstrates the antibiofilm activity of 3Furancarboxaldehyde (3FCA), a floral honey derived compound, against GAS biofilm, which was divulged using crystal violet assay, light microscopy, and confocal laser scanning microscopy. The report is extended to study its effect on various aspects of GAS (morphology, virulence, aggregation) at its minimal biofilm inhibitory concentration (132μg/ml). 3FCA was found to alter the growth pattern of GAS in solid and liquid medium and increased the rate of auto-aggregation. Electron microscopy unveiled the increase in extra polymeric substances around cell. Gene expression studies showed down-regulation of covR gene, which is speculated to be the prime target for the antibiofilm activity. Increased hyaluronic acid production and down regulation of srtB gene is attributed to the enhanced rate of auto-aggregation. The virulence genes (srv, mga, luxS and hasA) were also found to be over expressed, which was manifested with the increased susceptibility of the model organism Caenorhabditis elegans to 3FCA treated GAS. The toxicity of 3FCA was ruled out with no adverse effect on C. elegans. Significance Though 3FCA possess antibiofilm activity against GAS, it was also found to increase the virulence of GAS. This study demonstrates that, covR mediated antibiofilm activity may increase the virulence of GAS. This also emphasizes the importance to analyse the acclimatization response and virulence of the pathogen in the presence of antibiofilm compounds

  6. [Cellulase and xylanase activities of Fusarium Lk:Fr. genus fungi of different trophic groups].

    PubMed

    Kurchenko, I M; Sokolova, O V; Zhdanova, N M; Iarynchyn, A M; Iovenko, O M

    2008-01-01

    A comparative analysis of cellulase and xylanase activities of 26 fungal strains of phytopathogenic, saprophytic and endophytic Fusarium species has been realized using the qualitative reactions. The rare of their linear growth on the media with carboxymethyl cellulose or xylane has been studied. It was shown that the fungi of genus Fusarium belonging to different trophic groups possessed low activities of investigated enzymes as a whole, but in endophytic strains their levels were lower than in phytopathogenic ones. At the same time the distinct strain dependence of cellulase and xylanase activities was fixed in the fungi of different trophic groups. As far as the cellulase and xylanase activities in phytopathogenic isolates varied from complete absence to high levels, and since the activity maximum for each of the investigated strains was observed in different growth terms the conclusion was made that the cellulase and xylanase activities could not be considered as possible markers of the fungal isolate pathogenicity on the strain level.

  7. Variant for estimating the activity of tropical cyclone groups in the world ocean

    NASA Astrophysics Data System (ADS)

    Yaroshevich, M. I.

    2016-12-01

    It is especially important to know the character and the intensity level of tropical cyclone (TC) activity when the system for estimating the cyclonic danger and risk is formed. During seasons of increased cyclonic activity, when several TCs are simultaneously active, the total energy effect of the cyclone group joint action is not estimated numerically. Cyclonic activity is as a rule characterized by the number of TCs that occur in the considered zone. A variant of the criterion, according to which relative cyclonic activity is estimated, is presented.

  8. Mutualistic Benefits Generate an Unequal Distribution of Risky Activities Among Unrelated Group Members

    NASA Astrophysics Data System (ADS)

    Kukuk, Penelope F.; Ward, Seamus A.; Jozwiak, Amy

    Recent studies provide a new challenge to the adequacy of theories concerning the evolution of cooperation among nonrelatives: some individuals perform high-risk activities while others do not. We examined a communal hymenopteran species, Lasioglossum(Chilalictus)hemichalceum, to determine why group members engaged in demonstrably risky activities (foraging) tolerate the selfish behavior (remaining in the nest) of unrelated nestmates. Experimental removal of adult females indicated that their presence is required for the protection of brood from ant predators. Nonforagers ensure the continued presence of adults in the nest if the risk-taking foragers die, thereby safeguarding the survival of forager offspring. This results in an unequal distribution of risky activities within social groups in which avoidance of risky activities by some group members is ultimately beneficial to risk takers.

  9. Synergistic effect between defect sites and functional groups on the hydrolysis of cellulose over activated carbon.

    PubMed

    Foo, Guo Shiou; Sievers, Carsten

    2015-02-01

    The chemical oxidation of activated carbon by H2 O2 and H2 SO4 is investigated, structural and chemical modifications are characterized, and the materials are used as catalysts for the hydrolysis of cellulose. Treatment with H2 O2 enlarges the pore size and imparts functional groups such as phenols, lactones, and carboxylic acids. H2 SO4 treatment targets the edges of carbon sheets primarily, and this effect is more pronounced with a higher temperature. Adsorption isotherms demonstrate that the adsorption of oligomers on functionalized carbon is dominated by van der Waals forces. The materials treated chemically are active for the hydrolysis of cellulose despite the relative weakness of most of their acid sites. It is proposed that a synergistic effect between defect sites and functional groups enhances the activity by inducing a conformational change in the glucan chains if they are adsorbed at defect sites. This activates the glycosidic bonds for hydrolysis by in-plane functional groups.

  10. Minimizing within-experiment and within-group effects in Activation Likelihood Estimation meta-analyses.

    PubMed

    Turkeltaub, Peter E; Eickhoff, Simon B; Laird, Angela R; Fox, Mick; Wiener, Martin; Fox, Peter

    2012-01-01

    Activation Likelihood Estimation (ALE) is an objective, quantitative technique for coordinate-based meta-analysis (CBMA) of neuroimaging results that has been validated for a variety of uses. Stepwise modifications have improved ALE's theoretical and statistical rigor since its introduction. Here, we evaluate two avenues to further optimize ALE. First, we demonstrate that the maximum contribution of an experiment makes to an ALE map is related to the number of foci it reports and their proximity. We present a modified ALE algorithm that eliminates these within-experiment effects. However, we show that these effects only account for 2-3% of cumulative ALE values, and removing them has little impact on thresholded ALE maps. Next, we present an alternate organizational approach to datasets that prevents subject groups with multiple experiments in a dataset from influencing ALE values more than others. This modification decreases cumulative ALE values by 7-9%, changes the relative magnitude of some clusters, and reduces cluster extents. Overall, differences between results of the standard approach and these new methods were small. This finding validates previous ALE reports against concerns that they were driven by within-experiment or within-group effects. We suggest that the modified ALE algorithm is theoretically advantageous compared with the current algorithm, and that the alternate organization of datasets is the most conservative approach for typical ALE analyses and other CBMA methods. Combining the two modifications minimizes both within-experiment and within-group effects, optimizing the degree to which ALE values represent concordance of findings across independent reports.

  11. Theory of divalent main group H2 activation: electronics and quasiclassical trajectories.

    PubMed

    Devarajan, Deepa; Doubleday, Charles E; Ess, Daniel H

    2013-08-05

    Density functional theory (DFT), absolutely localized molecular orbital (ALMO) analysis, and quasiclassical trajectories (QCTs) were used to study the structure, barrier heights, thermodynamics, electronic properties, and dynamics of dihydrogen (H2) activation by singlet divalent main group compounds (ER2; E = C, Si, Ge). ALMO energy and charge decomposition calculations reveal that in the transition state CR2 acts as an ambiphile toward H2 because of equal forward-bonding and back-bonding orbital stabilization while SiR2 and GeR2 act as nucleophiles with dominant orbital energy stabilization arising from ER2 to H2 donation. Frontier molecular orbital (FMO) energy gaps do not provide a reasonable estimate of energy stabilization gained between the ER2 and H2 in the transition state or an accurate description of the nucleophilic versus electrophilic character because of electron repulsion and orbital overlap influences that are neglected. In CR2 transition states, forward-bonding and back-bonding are maximized in the nonleast motion geometry. In contrast, SiR2/GeR2 transition states have side-on geometries to avoid electron-electron repulsion. Electron repulsion, rather than orbital interactions, also determines the relative barrier heights of CR2 versus SiR2/GeR2 reactions. Examination of barrier heights and reaction energies shows a clear kinetic-thermodynamic relationship for ER2 activation of H2. A computational survey of R groups on ER2 divalent atom centers was performed to explore the possibility for H2 activation to occur with a low barrier and thermodynamically reversible. QCTs show that dihydrogen approach and reaction with CR2 may involve geometries significantly different than the static transition-state structure. In contrast, trajectories for dihydrogen addition to SiR2 involve geometries close to the side-on approach suggested by the static transition-state structure. QCTs also demonstrate that addition of H2 to CR2 and SiR2 is dynamically concerted

  12. Anatomically-adapted graph wavelets for improved group-level fMRI activation mapping.

    PubMed

    Behjat, Hamid; Leonardi, Nora; Sörnmo, Leif; Van De Ville, Dimitri

    2015-12-01

    A graph based framework for fMRI brain activation mapping is presented. The approach exploits the spectral graph wavelet transform (SGWT) for the purpose of defining an advanced multi-resolutional spatial transformation for fMRI data. The framework extends wavelet based SPM (WSPM), which is an alternative to the conventional approach of statistical parametric mapping (SPM), and is developed specifically for group-level analysis. We present a novel procedure for constructing brain graphs, with subgraphs that separately encode the structural connectivity of the cerebral and cerebellar gray matter (GM), and address the inter-subject GM variability by the use of template GM representations. Graph wavelets tailored to the convoluted boundaries of GM are then constructed as a means to implement a GM-based spatial transformation on fMRI data. The proposed approach is evaluated using real as well as semi-synthetic multi-subject data. Compared to SPM and WSPM using classical wavelets, the proposed approach shows superior type-I error control. The results on real data suggest a higher detection sensitivity as well as the capability to capture subtle, connected patterns of brain activity.

  13. Control of abdominal and expiratory intercostal muscle activity during vomiting - Role of ventral respiratory group expiratory neurons

    NASA Technical Reports Server (NTRS)

    Miller, Alan D.; Tan, L. K.; Suzuki, Ichiro

    1987-01-01

    The role of ventral respiratory group (VRG) expiratory (E) neurons in the control of abdominal and internal intercostal muscle activity during vomiting was investigated in cats. Two series of experiments were performed: in one, the activity of VRG E neurons was recorded during fictive vomiting in cats that were decerebrated, paralyzed, and artificially ventilated; in the second, the abdominal muscle activity during vomiting was compared before and after sectioning the axons of descending VRG E neurons in decerebrate spontaneously breathing cats. The results show that about two-thirds of VRG E neurons that project at least as far caudally as the lower thoracic cord contribute to internal intercostal muscle activity during vomiting. The remaining VRG E neurons contribute to abdominal muscle activation. As shown by severing the axons of the VRG E neurons, other, as yet unidenified, inputs (either descending from the brain stem or arising from spinal reflexes) can also produce abdominal muscle activation.

  14. Genome-Wide Identification of Mitogen-Activated Protein Kinase Gene Family across Fungal Lineage Shows Presence of Novel and Diverse Activation Loop Motifs

    PubMed Central

    Mohanta, Tapan Kumar; Mohanta, Nibedita; Parida, Pratap; Panda, Sujogya Kumar; Ponpandian, Lakshmi Narayanan; Bae, Hanhong

    2016-01-01

    The mitogen-activated protein kinase (MAPK) is characterized by the presence of the T-E-Y, T-D-Y, and T-G-Y motifs in its activation loop region and plays a significant role in regulating diverse cellular responses in eukaryotic organisms. Availability of large-scale genome data in the fungal kingdom encouraged us to identify and analyse the fungal MAPK gene family consisting of 173 fungal species. The analysis of the MAPK gene family resulted in the discovery of several novel activation loop motifs (T-T-Y, T-I-Y, T-N-Y, T-H-Y, T-S-Y, K-G-Y, T-Q-Y, S-E-Y and S-D-Y) in fungal MAPKs. The phylogenetic analysis suggests that fungal MAPKs are non-polymorphic, had evolved from their common ancestors around 1500 million years ago, and are distantly related to plant MAPKs. We are the first to report the presence of nine novel activation loop motifs in fungal MAPKs. The specificity of the activation loop motif plays a significant role in controlling different growth and stress related pathways in fungi. Hence, the presences of these nine novel activation loop motifs in fungi are of special interest. PMID:26918378

  15. Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the β-globin locus control region in vivo

    PubMed Central

    Gillemans, Nynke; Tewari, Rita; Lindeboom, Fokke; Rottier, Robbert; de Wit, Ton; Wijgerde, Mark; Grosveld, Frank; Philipsen, Sjaak

    1998-01-01

    The locus control region of the β-globin cluster contains five DNase I hypersensitive sites (5′HS1–5) required for locus activation. 5′HS3 contains six G-rich motifs that are essential for its activity. Members of a protein family, characterized by three zinc fingers highly homologous to those found in transcription factor Sp1, interact with these motifs. Because point mutagenesis cannot distinguish between family members, it is not known which protein activates 5′HS3. We show that the function of such closely related proteins can be distinguished in vivo by matching point mutations in 5′HS3 with amino acid changes in the zinc fingers of Sp1 and EKLF. Testing their activity in transgenic mice shows that EKLF is a direct activator of 5′HS3. PMID:9744863

  16. Group 14 hydrides with low valent elements for activation of small molecules.

    PubMed

    Mandal, Swadhin K; Roesky, Herbert W

    2012-02-21

    Transition metal compounds are well known as activators of small molecules, and they serve as efficient catalysts for a variety of homogeneous and heterogeneous transformations. In contrast, there is a general feeling that main group compounds cannot act as efficient catalysts because of their inability to activate small molecules. Traditionally, the activation of small molecules is considered one of the key steps during a catalytic cycle with transition metals. As a consequence, researchers have long neglected the full range of possibilities in harnessing main group elements for the design of efficient catalysts. Recent developments, however, have made it possible to synthesize main group compounds with low-valent elements capable of activating small molecules. In particular, the judicious use of sterically appropriate ligands has been successful in preparing and stabilizing a variety of Group 14 hydrides with low-valent elements. In this Account, we discuss recent advances in the synthesis of Group 14 hydrides with low-valent elements and assess their potential as small-molecule activators. Group 14, which comprises the nonmetal C, the semimetals Si and Ge, and the metals Sn and Pb, was for years a source of hydrides with the Group 14 element almost exclusively in tetravalent form. Synthetic difficulties and the low stability of Group 14 hydrides in lower oxidation states were difficult to overcome. But in 2000, a divalent Sn(II) hydride was prepared as a stable compound through the incorporation of sterically encumbered aromatic ligands. More recently, the stabilization of GeH(2) and SnH(2) complexes using an N-heterocyclic carbene (NHC) as a donor and BH(3) or a metal carbonyl complex as an acceptor was reported. A similar strategy was also employed to synthesize the Si(II) hydride. This class of hydrides may be considered coordinatively saturated, with the lone pair of electrons on the Group 14 elements taking part in coordination. We discuss the large

  17. Promoting healthy diets and active lives to hard-to-reach groups: market research study.

    PubMed

    White, S L; Maloney, S K

    1990-01-01

    Continued progress over the next decade in reducing premature morbidity and mortality from chronic disease will require that health communication efforts target a significant proportion of the American public that has not been influenced by the health promotion efforts of the 1980s. Focus groups conducted with members of the hard-to-reach American public showed that while being healthy seemed to be important to participants, and they were generally aware of what to do to stay healthy, they had a different operational definition of health than that used in health promotion programs. Participants seemed to believe that better health behaviors would build their resistance to acute illnesses, that is, keep them healthy, but that chronic diseases, such as cancer and diabetes, were due to fate and heredity and beyond their individual control. The focus group results show that participants had not made the link between chronic disease prevention and the importance of diet, exercise, and weight control. Although most of them seemed to express a genuine interest in "doing better," they were not able to supply more than superficial examples of how such changes might be made. Surprisingly, there were more similarities than differences in participants' attitudes and beliefs, with the similarities cutting across boundaries of race-ethnicity, age, and sex. Interest in changing behaviors was only slightly more pronounced among female rather than male, and older rather than younger, participants. However, there was not much evidence from the participants that they were actively seeking health information or trying to reconcile conflicting knowledge and beliefs.

  18. Potentiation of acid-sensing ion channel activity by peripheral group I metabotropic glutamate receptor signaling.

    PubMed

    Gan, Xiong; Wu, Jing; Ren, Cuixia; Qiu, Chun-Yu; Li, Yan-Kun; Hu, Wang-Ping

    2016-05-01

    Glutamate activates peripheral group I metabotropic glutamate receptors (mGluRs) and contributes to inflammatory pain. However, it is still not clear the mechanisms are involved in group I mGluR-mediated peripheral sensitization. Herein, we report that group I mGluRs signaling sensitizes acid-sensing ion channels (ASICs) in dorsal root ganglion (DRG) neurons and contributes to acidosis-evoked pain. DHPG, a selective group I mGluR agonist, can potentiate the functional activity of ASICs, which mediated the proton-induced events. DHPG concentration-dependently increased proton-gated currents in DRG neurons. It shifted the proton concentration-response curve upwards, with a 47.3±7.0% increase of the maximal current response to proton. Group I mGluRs, especially mGluR5, mediated the potentiation of DHPG via an intracellular cascade. DHPG potentiation of proton-gated currents disappeared after inhibition of intracellular Gq/11 proteins, PLCβ, PKC or PICK1 signaling. Moreover, DHPG enhanced proton-evoked membrane excitability of rat DRG neurons and increased the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, peripherally administration of DHPG dose-dependently exacerbated nociceptive responses to intraplantar injection of acetic acid in rats. Potentiation of ASIC activity by group I mGluR signaling in rat DRG neurons revealed a novel peripheral mechanism underlying group I mGluRs involvement in hyperalgesia.

  19. Benign hormone-secreting adenoma within a larger adrenocortical mass showing intensely increased activity on (18)F-FDG PET/CT.

    PubMed

    Papadakis, Georgios Z; Millo, Corina; Stratakis, Constantine A

    2016-10-01

    Adrenal adenomas usually show (18)F-FDG activity less than that of the liver parenchyma. However, lipid-poor and hormone-secreting adenomas have been reported to show mild (18)F-FDG avidity. We report on a 51-year-old female with clinical symptoms of hypercortisolemia and a large right adrenal mass detected on CT. Post-contrast CT images showed an enhancing focus in the lower pole of the mass, with corresponding markedly increased activity on (18)F-FDG PET/CT. Right adrenalectomy was performed and histology revealed a benign adenoma, indicating that functioning benign adenomas can show intensely increased metabolic activity on (18)F-FDG mimicking malignancy.

  20. Promoting Physical Activity With Group Pictures. Affiliation-Based Visual Communication for High-Risk Populations.

    PubMed

    Reifegerste, Doreen; Rossmann, Constanze

    2017-02-01

    Past research in social and health psychology has shown that affiliation motivation is associated with health behavior, especially for high-risk populations, suggesting that targeting this motivation could be a promising strategy to promote physical activity. However, the effects that affiliation appeals (e.g., pictures depicting companionship during physical activities) and accompanying slogans have on motivating physical activity have been largely unexplored. Hence, our two studies experimentally tested the effects of exposure to affiliation-based pictures for overweight or less active people, as well as the moderating effect of affiliation motivation. The results of these two studies give some indication that group pictures (with or without an accompanying slogan) can be an effective strategy to improve high-risk populations' attitudes, self-efficacy, and intentions to engage in physical activity. Affiliation motivation as a personality trait did not interact with these effects, but was positively associated with attitudes, independent of the group picture effect.

  1. How to lead a group--practical principles and experiences of conducting a promotional group in health-related physical activity.

    PubMed

    Rinne, M; Toropainen, E

    1998-04-01

    In this article the different roles and styles of instruction for the leader of a promotional group in physical activity are described. The promotional group is defined as one in which group dynamics is used to its maximum in order to facilitate permanent change in the members' health-related physical activities. Thus e.g., the group forms its own goals on the basis of its members' individual needs and aspirations and the group members provide feedback, behavioural models and encouragement to each other in their pursuit of change. The leader-instructor works in a stepwise fashion from assessment to evaluation to reformulation of plans made and monitors closely the stages of adoption of physical activity in his or her group. As the group advances the instructor should be ready to transfer more and more responsibility to the members.

  2. [Phytase activity in some groups of bacteria. Search for and cloning of genes for bacterial phytases].

    PubMed

    Shedova, E N; Berezina, O V; Khmel', I A; Lipasova, V A; Borriss, R; Velikodvorskaia, G A

    2004-01-01

    A search for phytase genes in 9 Bacillus strains from the collection of IMGAN was implemented. The growth optimum of strains IX-22, IX-12B, K17-2, K18, IMG I, IMG II, M4 and M8 was 50-60 degrees C; the optimal growth temperature for Bacillus sp. 790 was 45-47 degrees C. According to the sequence data of 16S RNA genes, Bacillus sp. 790 belongs to the B. subtilis/amyloliquefaciens group. The other 8 strains were identified as B. licheniformis. Selection of Bacillus strains, potentially containing the phytase genes, was performed via PCR with primers designed on the basis of the conserved sequence regions of the phyA gene from B. amyloliquefaciens FZB45 with chromosomal DNA being used as the template. The nucleotide sequences of all PCR fragments showed a high level of homology to the known Bacillus phytase genes. The gene libraries of B. licheniformis M8 and B. amyloliquefaciens 790 in E. coli were constructed and phytase-containing clones were selected from them. Twenty-four Pseudomonas strains of different species, 5 Xanthomonas maltophilia strains and 1 Xanthomonas malvacearum (all from the mentioned collection) were tested for phytase activity. Such activity was found in 13 Pseudomonas strains and in 6 Xanthomonas strains. The accumulation of phytase in Pseudomonas was shown to take place at later (over 2 days') growth stages. The optimum pH for phytase from 3 Pseudomonas strains were established. The enzymes were found to be most active at pH 5.5.

  3. Seismicity characteristics of a potentially active Quaternary volcano: The Tatun Volcano Group, northern Taiwan

    NASA Astrophysics Data System (ADS)

    Konstantinou, Konstantinos I.; Lin, Cheng-Horng; Liang, Wen-Tzong

    2007-02-01

    The Tatun Volcano Group (TVG) is located at the northern tip of Taiwan, near the capital Taipei and close to two nuclear power plants. Because of lack of any activity in historical times it has been classified as an extinct volcano, even though more recent studies suggest that TVG might have been active during the last 20 ka. In May 2003 a seismic monitoring project at the TVG area was initiated by deploying eight three-component seismic stations some of them equipped with both short-period and broadband sensors. During the 18 months observation period local seismicity mainly consisted of high frequency earthquakes either occurring as isolated events, or as a continuous sequence in the form of spasmodic bursts. Mixed and low frequency events were also present during the same period, even though they occurred only rarely. Arrival times from events with clear P-/S-wave phases were inverted in order to obtain a minimum 1D velocity model with station corrections. Probabilistic nonlinear earthquake locations were calculated for all these events using the newly derived velocity model. Most high frequency seismicity appeared to be concentrated near the areas of hydrothermal activity, forming tight clusters at depths shallower than 4 km. Relative locations, calculated using the double-difference method and utilising catalogue and cross-correlation differential traveltimes, showed insignificant differences when compared to the nonlinear probabilistic locations. In general, seismicity in the TVG area seems to be primarily driven by circulation of hydrothermal fluids as indicated by the occurrence of spasmodic bursts, mixed/low frequency events and a b-value (1.17 ± 0.1) higher than in any other part of Taiwan. These observations, that are similar to those reported in other dormant Quaternary volcanoes, indicate that a magma chamber may still exist beneath TVG and that a future eruption or period of unrest should not be considered unlikely.

  4. Work group I: Measures of the food and physical activity environment: instruments.

    PubMed

    Saelens, Brian E; Glanz, Karen

    2009-04-01

    A work group was convened to identify the core challenges, content gaps, and corresponding possible solutions for improving food- and physical activity-environment instrumentation. Identified challenges included instrument proliferation, the scaling or grain of instruments and appropriate aggregation to the neighborhood or community level, and unknown sensitivity to change of most instruments. Solutions for addressing these challenges included establishing an interactive and real-time instrument repository, developing and enforcing high standards for instrument reporting, increasing community-researcher collaborations, and implementing surveillance of food and physical activity environment. Solid instrumentation will accelerate a better understanding of food- and physical activity-environment effects on eating and physical activity behaviors.

  5. Industrial Hygiene Group: 1986 Annual report on research and special activities

    SciTech Connect

    Ettinger, H.J.

    1987-11-01

    This report details all the 1986 research activities and some selected operational programs of the Industrial Hygiene Group. During 1986, research studies were directed at: respiratory protection, personal protective clothing, applied industrial hygiene, and aerosols and air cleaning. In several instances, the transfer of technology, previously developed by the Industrial Hygiene Group, is described together with the application of research developments to operational health protection programs.

  6. Salivary alpha amylase activity in human beings of different age groups subjected to psychological stress.

    PubMed

    Sahu, Gopal K; Upadhyay, Seema; Panna, Shradha M

    2014-10-01

    Salivary alpha-amylase (sAA) has been proposed as a sensitive non-invasive biomarker for stress-induced changes in the body that reflect the activity of the sympathetic nervous system. Though several experiments have been conducted to determine the validity of this salivary component as a reliable stress marker in human subjects, the effect of stress induced changes on sAA level in different age groups is least studied. This article reports the activity of sAA in human subjects of different age groups subjected to psychological stress induced through stressful video clip. Differences in sAA level based on sex of different age groups under stress have also been studied. A total of 112 subjects consisting of both the male and female subjects, divided into two groups on basis of age were viewed a video clip of corneal transplant surgery as stressor. Activity of sAA from saliva samples of the stressed subjects were measured and compared with the activity of the samples collected from the subjects before viewing the clip. The age ranges of subjects were 18-25 and 40-60 years. The sAA level increased significantly in both the groups after viewing the stressful video. The increase was more pronounced in the younger subjects. The level of sAA was comparatively more in males than females in the respective groups. No significant change in sAA activity was observed after viewing the soothed video clip. Significant increase of sAA level in response to psychological stress suggests that it might act as a reliable sympathetic activity biochemical marker in different stages of human beings.

  7. Site-restricted plasminogen activation mediated by group A streptococcal streptokinase variants.

    PubMed

    Cook, Simon M; Skora, Amanda; Walker, Mark J; Sanderson-Smith, Martina L; McArthur, Jason D

    2014-02-15

    SK (streptokinase) is a secreted plasminogen activator and virulence factor of GAS (group A Streptococcus). Among GAS isolates, SK gene sequences are polymorphic and are grouped into two sequence clusters (cluster type-1 and cluster type-2) with cluster type-2 being further classified into subclusters (type-2a and type-2b). In the present study, we examined the role of bacterial and host-derived cofactors in SK-mediated plasminogen activation. All SK variants, apart from type-2b, can form an activator complex with Glu-Plg (Glu-plasminogen). Specific ligand-binding-induced conformational changes in Glu-Plg mediated by fibrinogen, PAM (plasminogen-binding group A streptococcal M protein), fibrinogen fragment D or fibrin, were required for type-2b SK to form a functional activator complex with Glu-Plg. In contrast with type-1 and type-2a SK, type-2b SK activator complexes were inhibited by α2-antiplasmin unless bound to fibrin or to the GAS cell-surface via PAM in combination with fibrinogen. Taken together, these data suggest that type-2b SK plasminogen activation may be restricted to specific microenvironments within the host such as fibrin deposits or the bacterial cell surface through the action of α2-antiplasmin. We conclude that phenotypic SK variation functionally underpins a pathogenic mechanism whereby SK variants differentially focus plasminogen activation, leading to specific niche adaption within the host.

  8. Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations.

    PubMed

    Felipo, Vicente; Piedrafita, Blanca; Barios, Juan A; Agustí, Ana; Ahabrach, Hanan; Romero-Vives, María; Barrio, Luis C; Rey, Beatriz; Gaztelu, Jose M; Llansola, Marta

    2015-01-01

    Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light.

  9. The working group ``Science with the SRT'': tasks, activities, and results

    NASA Astrophysics Data System (ADS)

    Prandoni, I.; Felli, M.

    The Working Group Science with the SRT was formed in May 2004, with the aim of providing scientific input to the Board of the SRT, in order to plan the focal plane instrumentation development of the SRT. In the present contribution, tasks and activities of the Working Group are outlined, and the main indications and results are briefly summarized. For a detailed discussion we refer to the IRA Internal Report ``The Sardinia Radio Telescope (SRT). Science and Technical Requirements'' produced by the members of the Working Group.

  10. A Disease-associated Mutant of NLRC4 Shows Enhanced Interaction with SUG1 Leading to Constitutive FADD-dependent Caspase-8 Activation and Cell Death.

    PubMed

    Raghawan, Akhouri Kishore; Sripada, Anand; Gopinath, Gayathri; Pushpanjali, Pendyala; Kumar, Yatender; Radha, Vegesna; Swarup, Ghanshyam

    2017-01-27

    Nod-like receptor family card containing 4 (NLRC4)/Ipaf is involved in recognition of pathogen-associated molecular patterns leading to caspase-1 activation and cytokine release, which mediate protective innate immune response. Point mutations in NLRC4 cause autoinflammatory syndromes. Although all the mutations result in constitutive caspase-1 activation, their phenotypic presentations are different, implying that these mutations cause different alterations in properties of NLRC4. NLRC4 interacts with SUG1 and induces caspase-8-mediated cell death. Here, we show that one of the autoinflammatory syndrome-causing mutants of NLRC4, H443P, but not T337A and V341A, constitutively activates caspase-8 and induces apoptotic cell death in human lung epithelial cells. Compared with wild type NLRC4, the H443P mutant shows stronger interaction with SUG1 and with ubiquitinated cellular proteins. Phosphorylation of NLRC4 at Ser(533) plays a crucial role in caspase-8 activation and cell death. However, H443P mutant does not require Ser(533) phosphorylation for caspase-8 activation and cell death. Caspase-8 activation by NLRC4 and its H443P mutant are dependent on the adaptor protein FADD. A phosphomimicking mutant of NLRC4, S533D does not require SUG1 activity for inducing cell death. Ubiquitin-tagged NLRC4 could induce cell death and activate caspase-8 independent of Ser(533) phosphorylation. Our work suggests that SUG1-mediated signaling results in enhanced ubiquitination and regulates FADD-dependent caspase-8 activation by NLRC4. We show that the autoinflammation-associated H443P mutant is altered in interaction with SUG1 and ubiquitinated proteins, triggering constitutive caspase-8-mediated cell death dependent on FADD but independent of Ser(533) phosphorylation.

  11. In-vehicle group activity modeling and simulation in sensor-based virtual environment

    NASA Astrophysics Data System (ADS)

    Shirkhodaie, Amir; Telagamsetti, Durga; Poshtyar, Azin; Chan, Alex; Hu, Shuowen

    2016-05-01

    Human group activity recognition is a very complex and challenging task, especially for Partially Observable Group Activities (POGA) that occur in confined spaces with limited visual observability and often under severe occultation. In this paper, we present IRIS Virtual Environment Simulation Model (VESM) for the modeling and simulation of dynamic POGA. More specifically, we address sensor-based modeling and simulation of a specific category of POGA, called In-Vehicle Group Activities (IVGA). In VESM, human-alike animated characters, called humanoids, are employed to simulate complex in-vehicle group activities within the confined space of a modeled vehicle. Each articulated humanoid is kinematically modeled with comparable physical attributes and appearances that are linkable to its human counterpart. Each humanoid exhibits harmonious full-body motion - simulating human-like gestures and postures, facial impressions, and hands motions for coordinated dexterity. VESM facilitates the creation of interactive scenarios consisting of multiple humanoids with different personalities and intentions, which are capable of performing complicated human activities within the confined space inside a typical vehicle. In this paper, we demonstrate the efficiency and effectiveness of VESM in terms of its capabilities to seamlessly generate time-synchronized, multi-source, and correlated imagery datasets of IVGA, which are useful for the training and testing of multi-source full-motion video processing and annotation. Furthermore, we demonstrate full-motion video processing of such simulated scenarios under different operational contextual constraints.

  12. Identification and biological activity of antifungal saponins from shallot ( Allium cepa L. Aggregatum group).

    PubMed

    Teshima, Yoshiki; Ikeda, Tsuyoshi; Imada, Kiyoshi; Sasaki, Kazunori; El-Sayed, Magdi A; Shigyo, Masayoshi; Tanaka, Shuhei; Ito, Shin-Ichi

    2013-08-07

    The n-butanol extract of shallot basal plates and roots showed antifungal activity against plant pathogenic fungi. The purified compounds from the extract were examined for antifungal activity to determine the predominant antifungal compounds in the extract. Two major antifungal compounds purified were determined to be alliospiroside A (ALA) and alliospiroside B. ALA had prominent antifungal activity against a wide range of fungi. The products of acid hydrolysis of ALA showed a reduced antifungal activity, suggesting that the compound's sugar chain is essential for its antifungal activity. Fungal cells treated with ALA showed rapid production of reactive oxygen species. The fungicidal action of ALA was partially inhibited by a superoxide scavenger, Tiron, suggesting that superoxide anion generation in the fungal cells may be related to the compound's action. Inoculation experiments showed that ALA protected strawberry plants against Colletotrichum gloeosporioides , indicating that ALA has the potential to control anthracnose of the plant.

  13. Activation of group IVC phospholipase A2 by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells

    PubMed Central

    Richards, Sean M.; Elgayyar, Mona A.; Menn, Fu-Minn; Vulava, Vijay M.; McKay, Larry; Sanseverino, John; Sayler, Gary; Tucker, Dawn E.; Leslie, Christina C.; Lu, Kim P.; Ramos, Kenneth S.

    2016-01-01

    Exposure to environmental pollutants, such as polycyclic aromatic hydrocarbons (PAHs) found in coal tar mixtures and tobacco sources, is considered a significant risk factor for the development of heart disease in humans. The goal of this study was to determine the influence of PAHs present at a Superfund site on human coronary artery endothelial cell (HCAEC) phospholipase A2 (PLA2) activity and apoptosis. Extremely high levels of 12 out of 15 EPA high-priority PAHs were present in both the streambed and floodplain sediments at a site where an urban creek and its adjacent floodplain were extensively contaminated by PAHs and other coal tar compounds. Nine of the 12 compounds and a coal tar mixture (SRM 1597A) activated group IVC PLA2 in HCAECs, and activation of this enzyme was associated with histone fragmentation and poly (ADP) ribose polymerase (PARP) cleavage. Genetic silencing of group IVC PLA2 inhibited both 3H-fatty acid release and histone fragmentation by PAHs and SRM 1597A, indicating that individual PAHs and a coal tar mixture induce apoptosis of HCAECs via a mechanism that involves group IVC PLA2. Western blot analysis of aortas isolated from feral mice (Peromyscus leucopus) inhabiting the Superfund site showed increased PARP and caspase-3 cleavage when compared to reference mice. These data suggest that PAHs induce apoptosis of HCAECs via activation of group IVC PLA2. PMID:21132278

  14. Weapons in disguise--activating mechanisms and protecting group chemistry in nature.

    PubMed

    Kwan, Jason C; Luesch, Hendrik

    2010-11-22

    Bioactive natural products often possess uniquely functionalized structures with unusual modes of action; however, the natural product itself is not always the active species. We discuss molecules that draw on protecting group chemistry or else require activation to unmask reactive centers, illustrating that nature is not only a source of complex structures but also a guide for elegant chemical transformations which provides ingenious chemical solutions for drug delivery.

  15. Fusion peptide P15-CSP shows antibiofilm activity and pro-osteogenic activity when deposited as a coating on hydrophilic but not hydrophobic surfaces.

    PubMed

    Li, Xian; Contreras-Garcia, Angel; LoVetri, Karen; Yakandawala, Nandadeva; Wertheimer, Michael R; De Crescenzo, Gregory; Hoemann, Caroline D

    2015-12-01

    In the context of porous bone void filler for oral bone reconstruction, peptides that suppress microbial growth and promote osteoblast function could be used to enhance the performance of a porous bone void filler. We tested the hypothesis that P15-CSP, a novel fusion peptide containing collagen-mimetic osteogenic peptide P15, and competence-stimulating peptide (CSP), a cationic antimicrobial peptide, has emerging properties not shared by P15 or CSP alone. Peptide-coated surfaces were tested for antimicrobial activity toward Streptoccocus mutans, and their ability to promote human mesenchymal stem cell (MSC) attachment, spreading, metabolism, and osteogenesis. In the osteogenesis assay, peptides were coated on tissue culture plastic and on thin films generated by plasma-enhanced chemical vapor deposition to have hydrophilic or hydrophobic character (water contact angles 63°, 42°, and 92°, respectively). S. mutans planktonic growth was specifically inhibited by CSP, whereas biofilm formation was inhibited by P15-CSP. MSC adhesion and actin stress fiber formation was strongly enhanced by CSP, P15-CSP, and fibronectin coatings and modestly enhanced by P15 versus uncoated surfaces. Metabolic assays revealed that CSP was slightly cytotoxic to MSCs. MSCs developed alkaline phosphatase activity on all surfaces, with or without peptide coatings, and consistently deposited the most biomineralized matrix on hydrophilic surfaces coated with P15-CSP. Hydrophobic thin films completely suppressed MSC biomineralization, consistent with previous findings of suppressed osteogenesis on hydrophobic bioplastics. Collective data in this study provide new evidence that P15-CSP has unique dual capacity to suppress biofilm formation, and to enhance osteogenic activity as a coating on hydrophilic surfaces.

  16. A Model for Aryl Hydrocarbon Receptor-Activated Gene Expression Shows Potency and Efficacy Changes and Predicts Squelching Due to Competition for Transcription Co-Activators

    PubMed Central

    Simon, Ted W.; Budinsky, Robert A.; Rowlands, J. Craig

    2015-01-01

    A stochastic model of nuclear receptor-mediated transcription was developed based on activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and subsequent binding the activated AHR to xenobiotic response elements (XREs) on DNA. The model was based on effects observed in cells lines commonly used as in vitro experimental systems. Following ligand binding, the AHR moves into the cell nucleus and forms a heterodimer with the aryl hydrocarbon nuclear translocator (ARNT). In the model, a requirement for binding to DNA is that a generic coregulatory protein is subsequently bound to the AHR-ARNT dimer. Varying the amount of coregulator available within the nucleus altered both the potency and efficacy of TCDD for inducing for transcription of CYP1A1 mRNA, a commonly used marker for activation of the AHR. Lowering the amount of available cofactor slightly increased the EC50 for the transcriptional response without changing the efficacy or maximal response. Further reduction in the amount of cofactor reduced the efficacy and produced non-monotonic dose-response curves (NMDRCs) at higher ligand concentrations. The shapes of these NMDRCs were reminiscent of the phenomenon of squelching. Resource limitations for transcriptional machinery are becoming apparent in eukaryotic cells. Within single cells, nuclear receptor-mediated gene expression appears to be a stochastic process; however, intercellular communication and other aspects of tissue coordination may represent a compensatory process to maintain an organism’s ability to respond on a phenotypic level to various stimuli within an inconstant environment. PMID:26039703

  17. Novel method for the preparation of polymethacrylates with nonlinear optically active side groups

    NASA Astrophysics Data System (ADS)

    Strohriegl, Peter; Mueller, Harry; Nuyken, Oskar

    1993-01-01

    Because of their excellent optical properties, a variety of polymethacrylates with pendant NLO-chromophores has been prepared and investigated by different research groups. The method normally used for the synthesis of these polymers is the free radical polymerization of the corresponding methacrylates with NLO-active side groups. However, the NLO- chromophores, usually large conjugated molecules with an electron donor and an electron acceptor substituent, often contain a number of functional groups, e.g., nitro- or azo groups. These may act as retarders or inhibitors in a free radical polymerization. So in many cases the yields are not quantitative and the molecular weights are quite low. We present an alternative method for the preparation of polymethacrylates with pendant NLO-chromophores, the polymeranalogous esterification of poly(methacryloyl chloride). In a first step, reactive prepolymers are prepared by the free radical polymerization of methacryloyl chloride (MAC1) or by copolymerization of MAC1 with methyl methacrylate (MMA). These prepolymers are esterified using NLO-active side groups with a hydroxy-terminated spacer. Well defined, high molecular weight polymethacrylates with high dye contents can be prepared by this method. A copolymer with 19 mole% of azochromophores exhibits an electro-optical coefficient of 9 pm/V at 1300 mm after poling, whereas 19 pm/V (1500 nm) were measured for a polymer with 90 mole% of NLO active azobenzene side groups. In addition, the novel method provides easy access to some novel copolymers with both NLO-active azobenzene units and photocrosslinkable cinnamoyl groups.

  18. A method to quantify movement activity of groups of animals using automated image analysis

    NASA Astrophysics Data System (ADS)

    Xu, Jianyu; Yu, Haizhen; Liu, Ying

    2009-07-01

    Most physiological and environmental changes are capable of inducing variations in animal behavior. The behavioral parameters have the possibility to be measured continuously in-situ by a non-invasive and non-contact approach, and have the potential to be used in the actual productions to predict stress conditions. Most vertebrates tend to live in groups, herds, flocks, shoals, bands, packs of conspecific individuals. Under culture conditions, the livestock or fish are in groups and interact on each other, so the aggregate behavior of the group should be studied rather than that of individuals. This paper presents a method to calculate the movement speed of a group of animal in a enclosure or a tank denoted by body length speed that correspond to group activity using computer vision technique. Frame sequences captured at special time interval were subtracted in pairs after image segmentation and identification. By labeling components caused by object movement in difference frame, the projected area caused by the movement of every object in the capture interval was calculated; this projected area was divided by the projected area of every object in the later frame to get body length moving distance of each object, and further could obtain the relative body length speed. The average speed of all object can well respond to the activity of the group. The group activity of a tilapia (Oreochromis niloticus) school to high (2.65 mg/L) levels of unionized ammonia (UIA) concentration were quantified based on these methods. High UIA level condition elicited a marked increase in school activity at the first hour (P<0.05) exhibiting an avoidance reaction (trying to flee from high UIA condition), and then decreased gradually.

  19. Involving postgraduate's students in undergraduate small group teaching promotes active learning in both

    PubMed Central

    Kalra, Ruchi; Modi, Jyoti Nath; Vyas, Rashmi

    2015-01-01

    Background: Lecture is a common traditional method for teaching, but it may not stimulate higher order thinking and students may also be hesitant to express and interact. The postgraduate (PG) students are less involved with undergraduate (UG) teaching. Team based small group active learning method can contribute to better learning experience. Aim: To-promote active learning skills among the UG students using small group teaching methods involving PG students as facilitators to impart hands-on supervised training in teaching and managerial skills. Methodology: After Institutional approval under faculty supervision 92 UGs and 8 PGs participated in 6 small group sessions utilizing the jigsaw technique. Feedback was collected from both. Observations: Undergraduate Feedback (Percentage of Students Agreed): Learning in small groups was a good experience as it helped in better understanding of the subject (72%), students explored multiple reading resources (79%), they were actively involved in self-learning (88%), students reported initial apprehension of performance (71%), identified their learning gaps (86%), team enhanced their learning process (71%), informal learning in place of lecture was a welcome change (86%), it improved their communication skills (82%), small group learning can be useful for future self-learning (75%). Postgraduate Feedback: Majority performed facilitation for first time, perceived their performance as good (75%), it was helpful in self-learning (100%), felt confident of managing students in small groups (100%), as facilitator they improved their teaching skills, found it more useful and better identified own learning gaps (87.5%). Conclusions: Learning in small groups adopting team based approach involving both UGs and PGs promoted active learning in both and enhanced the teaching skills of the PGs. PMID:26380201

  20. The Use of Group Activities in Introductory Biology Supports Learning Gains and Uniquely Benefits High-Achieving Students.

    PubMed

    Marbach-Ad, Gili; Rietschel, Carly H; Saluja, Neeti; Carleton, Karen L; Haag, Eric S

    2016-12-01

    This study describes the implementation and effectiveness of small-group active engagement (GAE) exercises in an introductory biology course (BSCI207) taught in a large auditorium setting. BSCI207 (Principles of Biology III-Organismal Biology) is the third introductory core course for Biological Sciences majors. In fall 2014, the instructors redesigned one section to include GAE activities to supplement lecture content. One section (n = 198) employed three lectures per week. The other section (n = 136) replaced one lecture per week with a GAE class. We explored the benefits and challenges associated with implementing GAE exercises and their relative effectiveness for unique student groups (e.g., minority students, high- and low-grade point average [GPA] students). Our findings show that undergraduates in the GAE class exhibited greater improvement in learning outcomes than undergraduates in the traditional class. Findings also indicate that high-achieving students experienced the greatest benefit from GAE activities. Some at-risk student groups (e.g., two-year transfer students) showed comparably low learning gains in the course, despite the additional support that may have been afforded by active learning. Collectively, these findings provide valuable feedback that may assist other instructors who wish to revise their courses and recommendations for institutions regarding prerequisite coursework approval policies.

  1. The Use of Group Activities in Introductory Biology Supports Learning Gains and Uniquely Benefits High-Achieving Students†

    PubMed Central

    Marbach-Ad, Gili; Rietschel, Carly H.; Saluja, Neeti; Carleton, Karen L.; Haag, Eric S.

    2016-01-01

    This study describes the implementation and effectiveness of small-group active engagement (GAE) exercises in an introductory biology course (BSCI207) taught in a large auditorium setting. BSCI207 (Principles of Biology III—Organismal Biology) is the third introductory core course for Biological Sciences majors. In fall 2014, the instructors redesigned one section to include GAE activities to supplement lecture content. One section (n = 198) employed three lectures per week. The other section (n = 136) replaced one lecture per week with a GAE class. We explored the benefits and challenges associated with implementing GAE exercises and their relative effectiveness for unique student groups (e.g., minority students, high- and low-grade point average [GPA] students). Our findings show that undergraduates in the GAE class exhibited greater improvement in learning outcomes than undergraduates in the traditional class. Findings also indicate that high-achieving students experienced the greatest benefit from GAE activities. Some at-risk student groups (e.g., two-year transfer students) showed comparably low learning gains in the course, despite the additional support that may have been afforded by active learning. Collectively, these findings provide valuable feedback that may assist other instructors who wish to revise their courses and recommendations for institutions regarding prerequisite coursework approval policies. PMID:28101262

  2. Prediction of cloud condensation nuclei activity for organic compounds using functional group contribution methods

    DOE PAGES

    Petters, M. D.; Kreidenweis, S. M.; Ziemann, P. J.

    2016-01-19

    A wealth of recent laboratory and field experiments demonstrate that organic aerosol composition evolves with time in the atmosphere, leading to changes in the influence of the organic fraction to cloud condensation nuclei (CCN) spectra. There is a need for tools that can realistically represent the evolution of CCN activity to better predict indirect effects of organic aerosol on clouds and climate. This work describes a model to predict the CCN activity of organic compounds from functional group composition. Following previous methods in the literature, we test the ability of semi-empirical group contribution methods in Köhler theory to predict themore » effective hygroscopicity parameter, kappa. However, in our approach we also account for liquid–liquid phase boundaries to simulate phase-limited activation behavior. Model evaluation against a selected database of published laboratory measurements demonstrates that kappa can be predicted within a factor of 2. Simulation of homologous series is used to identify the relative effectiveness of different functional groups in increasing the CCN activity of weakly functionalized organic compounds. Hydroxyl, carboxyl, aldehyde, hydroperoxide, carbonyl, and ether moieties promote CCN activity while methylene and nitrate moieties inhibit CCN activity. The model can be incorporated into scale-bridging test beds such as the Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) to evaluate the evolution of kappa for a complex mix of organic compounds and to develop suitable parameterizations of CCN evolution for larger-scale models.« less

  3. Prediction of cloud condensation nuclei activity for organic compounds using functional group contribution methods

    NASA Astrophysics Data System (ADS)

    Petters, M. D.; Kreidenweis, S. M.; Ziemann, P. J.

    2016-01-01

    A wealth of recent laboratory and field experiments demonstrate that organic aerosol composition evolves with time in the atmosphere, leading to changes in the influence of the organic fraction to cloud condensation nuclei (CCN) spectra. There is a need for tools that can realistically represent the evolution of CCN activity to better predict indirect effects of organic aerosol on clouds and climate. This work describes a model to predict the CCN activity of organic compounds from functional group composition. Following previous methods in the literature, we test the ability of semi-empirical group contribution methods in Köhler theory to predict the effective hygroscopicity parameter, kappa. However, in our approach we also account for liquid-liquid phase boundaries to simulate phase-limited activation behavior. Model evaluation against a selected database of published laboratory measurements demonstrates that kappa can be predicted within a factor of 2. Simulation of homologous series is used to identify the relative effectiveness of different functional groups in increasing the CCN activity of weakly functionalized organic compounds. Hydroxyl, carboxyl, aldehyde, hydroperoxide, carbonyl, and ether moieties promote CCN activity while methylene and nitrate moieties inhibit CCN activity. The model can be incorporated into scale-bridging test beds such as the Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) to evaluate the evolution of kappa for a complex mix of organic compounds and to develop suitable parameterizations of CCN evolution for larger-scale models.

  4. In vitro anti-mycobacterial activity of nine medicinal plants used by ethnic groups in Sonora, Mexico

    PubMed Central

    2013-01-01

    Background Sonoran ethnic groups (Yaquis, Mayos, Seris, Guarijíos, Pimas, Kikapúes and Pápagos) use mainly herbal based preparations as their first line of medicinal treatment. Among the plants used are those with anti-tuberculosis properties; however, no formal research is available. Methods Organic extracts were obtained from nine medicinal plants traditionally used by Sonoran ethnic groups to treat different kinds of diseases; three of them are mainly used to treat tuberculosis. All of the extracts were tested against Mycobacterium tuberculosis H37Rv using the Alamar Blue redox bioassay. Results Methanolic extracts from Ambrosia confertiflora, Ambrosia ambrosioides and Guaiacum coulteri showed minimal inhibitory concentration (MIC) values of 200, 790 and 1000 μg/mL, respectively, whereas no effect was observed with the rest of the methanolic extracts at the concentrations tested. Chloroform, dichloromethane, and ethyl acetate extracts from Ambrosia confertiflora showed a MIC of 90, 120 and 160 μg/mL, respectively. Conclusions A. confertiflora and A. ambrosioides showed the best anti-mycobacterial activity in vitro. The activity of Guaiacum coulteri is consistent with the traditional use by Sonoran ethnic groups as anti-tuberculosis agent. For these reasons, it is important to investigate a broader spectrum of medicinal plants in order to find compounds active against Mycobacterium tuberculosis. PMID:24267469

  5. 75 FR 49913 - Active Duty Service Determinations For Civilian or Contractual Groups

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ... Department of the Air Force Active Duty Service Determinations For Civilian or Contractual Groups SUMMARY: On July 30, 2010, the Secretary of the Air Force, acting as Executive Agent of the Secretary of Defense...'' for purposes of all laws administered by the Department of Veterans Affairs (VA). FOR...

  6. Bill Gates' Great-Great-Granddaughter's Honeymoon: An Astronomy Activity for Several Different Age Groups

    ERIC Educational Resources Information Center

    Fraknoi, Andrew

    2009-01-01

    When students finish a unit or course on the planets these days, they are often overwhelmed with facts, comparisons, and images. A good culminating activity, to help them organize their thinking (and review), is to have them divide into small groups (travel agencies) and come up with their top ten solar system "tourist sights" for future space…

  7. Active Group Learning: A Selective Study of Effective Public Humanities Programs.

    ERIC Educational Resources Information Center

    Cole, Charles C., Jr.

    A study of active group learning that occurred during 61 state humanities programs in 35 states is discussed, and 11 recommendations to state humanities councils are offered. Information was obtained from a mail survey and review of state council proposals and narrative reports. Definitions of learning and information on the following learning…

  8. Effects of Cooperative Group Work Activities on Pre-School Children's Pattern Recognition Skills

    ERIC Educational Resources Information Center

    Tarim, Kamuran

    2015-01-01

    The aim of this research is twofold; to investigate the effects of cooperative group-based work activities on children's pattern recognition skills in pre-school and to examine the teachers' opinions about the implementation process. In line with this objective, for the study, 57 children (25 girls and 32 boys) were chosen from two private schools…

  9. When Talking Won't Work: Implementing Experiential Group Activities with Addicted Clients

    ERIC Educational Resources Information Center

    Hagedorn, W. Bryce; Hirshhorn, Meredith A.

    2009-01-01

    Traditional talk therapy, particularly cognitive behavioral techniques, are often ineffective when working with addicted clients for many reasons. By tapping into the power of the group modality, experiential activities can serve as a powerful facilitator of insight and behavior change. The authors provide a brief review of the literature followed…

  10. Peer Interactions among Children with Profound Intellectual and Multiple Disabilities during Group Activities

    ERIC Educational Resources Information Center

    Nijs, Sara; Penne, Anneleen; Vlaskamp, Carla; Maes, Bea

    2016-01-01

    Background: Children with profound intellectual and multiple disabilities (PIMD) meet other children with PIMD in day care centres or schools. This study explores the peer-directed behaviours of children with PIMD, the peer interaction-influencing behaviour of the direct support workers and the children's positioning. Method: Group activities for…

  11. Activating Group Recycling in Action: A Rhodium-Catalyzed Carbothiolation Route to Substituted Isoquinolines

    PubMed Central

    2013-01-01

    A new rhodium(I) catalyst allows practical and efficient alkyne carbothiolation reactions to be achieved on synthetically useful ketone-bearing aryl methyl sulfides. The carbothiolation adducts, featuring a ‘recycled methyl sulfide’ activating group, are convenient precursors to highly substituted isoquinolines. PMID:24083625

  12. 78 FR 75905 - Credit for Increasing Research Activities: Intra-Group Gross Receipts

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-13

    ...; ] DEPARTMENT OF TREASURY Internal Revenue Service 26 CFR Part 1 RIN 1545-BE14 Credit for Increasing Research Activities: Intra-Group Gross Receipts AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of... under section 41 of the Internal Revenue Code (Code) relating to the treatment of qualified...

  13. Children's Preferences for Group Musical Activities in Child Care Centres: A Cross-Cultural Study

    ERIC Educational Resources Information Center

    Yim, Hoi Yin Bonnie; Ebbeck, Marjory

    2009-01-01

    This paper reports on a cross-cultural research study of children's preferences for group musical activities in child care centres. A total of 228 young children aged 4-5 years in seven child care centres in Hong Kong and in the Adelaide City of South Australia participated in the study. Both qualitative and quantitative data were collected via a…

  14. Information Activities and Appropriation in Teacher Trainees' Digital, Group-Based Learning

    ERIC Educational Resources Information Center

    Hanell, Fredrik

    2016-01-01

    Introduction: This paper reports results from an ethnographic study of teacher trainees' information activities in digital, group-based learning and their relation to the interplay between use and appropriation of digital tools and the learning environment. Method: The participants in the present study are 249 pre-school teacher trainees in…

  15. Use of a Wiki-Based Software to Manage Research Group Activities

    ERIC Educational Resources Information Center

    Wang, Ting; Vezenov, Dmitri V.; Simboli, Brian

    2014-01-01

    This paper discusses use of the wiki software Confluence to organize research group activities and lab resources. Confluence can serve as an electronic lab notebook (ELN), as well as an information management and collaboration tool. The article provides a case study in how researchers can use wiki software in "home-grown" fashion to…

  16. An Investigation of the Structure of Group Activities in ELT Coursebooks.

    ERIC Educational Resources Information Center

    Jacobs, George M.; Ball, Jessica

    1996-01-01

    Reports a study examining the use of group activities in 10 randomly selected English-language teaching coursebooks published since 1990. Results are discussed in light of theory and research on cooperative learning; task-based language teaching; and the roles of learners, teachers, and coursebooks. (26 references) (Author/CK)

  17. Peer Groups and Substance Use: Examining the Direct and Interactive Effect of Leisure Activity

    ERIC Educational Resources Information Center

    Thorlindsson, Thorolfur; Bernburg, Jon Gunnar

    2006-01-01

    This paper explores the relationships among adolescent leisure activities, peer behavior, and substance use. We suggest that peer group interaction can have a differential effect on adolescent deviant behavior depending on the type of leisure pattern adolescents engage in. We analyze data from a representative national sample of Icelandic…

  18. Osteoporosis Knowledge, Calcium Intake, and Weight-Bearing Physical Activity in Three Age Groups of Women.

    ERIC Educational Resources Information Center

    Terrio, Kate; Auld, Garry W.

    2002-01-01

    Determined the extent and integration of osteoporosis knowledge in three age groups of women, comparing knowledge to calcium intake and weight bearing physical activity (WBPA). Overall calcium intake was relatively high. There were no differences in knowledge, calcium intake, or WBPA by age, nor did knowledge predict calcium intake and WBPA. None…

  19. Healthful Eating and Physical Activity in the Home Environment: Results from Multifamily Focus Groups

    ERIC Educational Resources Information Center

    Berge, Jerica M.; Arikian, Aimee; Doherty, William J.; Neumark-Sztainer, Dianne

    2012-01-01

    Objective: To explore multiple family members' perceptions of risk and protective factors for healthful eating and physical activity in the home. Design: Ten multifamily focus groups were conducted with 26 families. Setting and Participants: Community setting with primarily black and white families. Family members (n = 103) were aged 8 to 61…

  20. Communication: Active space decomposition with multiple sites: Density matrix renormalization group algorithm

    SciTech Connect

    Parker, Shane M.; Shiozaki, Toru

    2014-12-07

    We extend the active space decomposition method, recently developed by us, to more than two active sites using the density matrix renormalization group algorithm. The fragment wave functions are described by complete or restricted active-space wave functions. Numerical results are shown on a benzene pentamer and a perylene diimide trimer. It is found that the truncation errors in our method decrease almost exponentially with respect to the number of renormalization states M, allowing for numerically exact calculations (to a few μE{sub h} or less) with M = 128 in both cases. This rapid convergence is because the renormalization steps are used only for the interfragment electron correlation.

  1. A Small-Group Activity Introducing the Use and Interpretation of BLAST †

    PubMed Central

    Newell, Peter D.; Fricker, Ashwana D.; Roco, Constance Armanda; Chandrangsu, Pete; Merkel, Susan M.

    2013-01-01

    As biological sequence data are generated at an ever increasing rate, the role of bioinformatics in biological research also grows. Students must be trained to complete and interpret bioinformatic searches to enable them to effectively utilize the trove of sequence data available. A key bioinformatic tool for sequence comparison and genome database searching is BLAST (Basic Local Alignment Search Tool). BLAST identifies sequences in a database that are similar to the entered query sequence, and ranks them based on the length and quality of the alignment. Our goal was to introduce sophomore and junior level undergraduate students to the basic functions and uses of BLAST with a small group activity lasting a single class period. The activity provides students an opportunity to perform a BLAST search, interpret the data output, and use the data to make inferences about bacterial cell envelope structure. The activity consists of two parts. Part 1 is a handout to be completed prior to class, complete with video tutorial, that reviews cell envelope structure, introduces key terms, and allows students to familiarize themselves with the mechanics of a BLAST search. Part 2 consists of a hands-on, web-based small group activity to be completed during the class period. Evaluation of the activity through student performance assessments suggests that students who complete the activity can better interpret the BLAST output parameters % query coverage and % max identity. While the topic of the activity is bacterial cell wall structure, it could be adapted to address other biological concepts. PMID:24358388

  2. Pre-Session Satiation as a Treatment for Stereotypy During Group Activities.

    PubMed

    Rispoli, Mandy; Camargo, Síglia Hoher; Neely, Leslie; Gerow, Stephanie; Lang, Russell; Goodwyn, Fara; Ninci, Jennifer

    2014-05-01

    Individuals with developmental disabilities may engage in automatically reinforced behaviors that may interfere with learning opportunities. Manipulation of motivating operations has been shown to reduce automatically maintained behavior in some individuals. Considering behavioral indicators of satiation may assist in identifying the point at which an abolishing operation has begun to effect behavior. The purpose of this study was to evaluate the effects of pre-session satiation of automatic reinforcement on subsequent levels of stereotypy and activity engagement during group activities for three males ages 5 to 13 years with developmental disabilities. Following functional analyses with analogue conditions, an alternating treatment design compared a pre-session access to stereotypy condition with a no-pre-session access condition prior to group activity sessions. Results indicated that pre-session satiation of the putative reinforcer produced by stereotypy was effective in decreasing stereotypy and increasing activity engagement during subsequent group activities for all participants. These findings add to the literature supporting the effectiveness of abolishing operations to decrease automatically maintained stereotypy.

  3. Human Activity Dampens the Benefits of Group Size on Vigilance in Khulan (Equus hemionus) in Western China.

    PubMed

    Wang, Mu-Yang; Ruckstuhl, Kathreen E; Xu, Wen-Xuan; Blank, David; Yang, Wei-Kang

    2016-01-01

    Animals receive anti-predator benefits from social behavior. As part of a group, individuals spend less time being vigilant, and vigilance decreases with increasing group size. This phenomenon, called "the many-eyes effect", together with the "encounter dilution effect", is considered among the most important factors determining individual vigilance behavior. However, in addition to group size, other social and environmental factors also influence the degree of vigilance, including disturbance from human activities. In our study, we examined vigilance behavior of Khulans (Equus hemionus) in the Xinjiang Province in western China to test whether and how human disturbance and group size affect vigilance. According to our results, Khulan showed a negative correlation between group size and the percentage time spent vigilant, although this negative correlation depended on the groups' disturbance level. Khulan in the more disturbed area had a dampened benefit from increases in group size, compared to those in the undisturbed core areas. Provision of continuous areas of high-quality habitat for Khulans will allow them to form larger undisturbed aggregations and to gain foraging benefits through reduced individual vigilance, as well as anti-predator benefits through increased probability of predator detection.

  4. Townes Group Activities from 1983-2000: Personal Recollections of William Danchi

    NASA Technical Reports Server (NTRS)

    Danchi, William C.

    2015-01-01

    I arrived in Berkeley in October 1983 as a post-doc, and my appointment was at the Space Sciences Laboratory (SSL). During that time the group was very large, with multiple activities led by Charlie himself and also by Senior Fellows such as John Lacy, Dan Jaffe, and Al Betz at the top of the hill at Space Sciences. Another significant contingent of the Townes group was housed in Birge Hall on campus, led by Reinhard Genzel when he was an Assistant Professor in the Physics Department. Although the group encompassed two separate locations, it functioned as one large group. Either we rode with Charlie up and down the hill, or (if we were concerned about our safety!) we took the bus.

  5. “Convivência” Groups: Building Active and Healthy Communities of Older Adults in Brazil

    PubMed Central

    Benedetti, Tânia R. Bertoldo; d'Orsi, Eleonora; Schwingel, Andiara; Chodzko-Zajko, Wojtek J.

    2012-01-01

    In old age, social groups can be a crucial component for health and well-being. In 2009-2010, a follow-up survey was carried out in Florianópolis, Brazil to understand the impact of a variety of programs established since 2002 that were designed to enhance social activities among the older adult population. This study employed two surveys within the population of older adults in Florianópolis. The first survey interviewed a total of 875 older adults in 2002, and the second survey involved 1,705 older adults between 2009 and 2010. By 2010, many new programs were offered in the community and the enrollment of older adults in social programs followed similar trends. “Convivência” groups stood out as extremely popular social groups among this population. This paper discusses some of the potential outcomes associated with participation in “convivência” groups. PMID:22830022

  6. Activities of the OECD/NEA Expert Group on Assay Data for Spent Nuclear Fuel

    SciTech Connect

    Gauld, Ian C; Rugama, Yolanda

    2009-01-01

    Management of spent nuclear fuel is a key issue for many NEA member countries. In nuclear criticality safety, the decision of many countries to advance burnup credit as part of their licensing strategy has heightened recent interest in experimental data needed to validate computer codes used in burnup credit calculations. This paper discusses recent activities of an Expert Group on assay data, formed under the OECD/NEA/NSC/WPNCS (Working Party on Nuclear Criticality Safety) to help coordinate isotopic assay data activities and facilitate international collaboration between NEA member countries developing or implementing burnup credit methodologies. Recent activities of the Expert Group are described, focusing on the planned expansion of the Spent Fuel Isotopic Composition Database (SFCOMPO), and preparation of a state-of-the-art report on assay data that includes sections on recommended radiochemical analysis methods, techniques, and lessons learned from previous experiments.

  7. The 5'-flanking region of the RP58 coding sequence shows prominent promoter activity in multipolar cells in the subventricular zone during corticogenesis.

    PubMed

    Ohtaka-Maruyama, C; Hirai, S; Miwa, A; Takahashi, A; Okado, H

    2012-01-10

    Pyramidal neurons of the neocortex are produced from progenitor cells located in the neocortical ventricular zone (VZ) and subventricular zone (SVZ) during embryogenesis. RP58 is a transcriptional repressor that is strongly expressed in the developing brain and plays an essential role in corticogenesis. The expression of RP58 is strictly regulated in a time-dependent and spatially restricted manner. It is maximally expressed in E15-16 embryonic cerebral cortex, localized specifically to the cortical plate and SVZ of the neocortex, hippocampus, and parts of amygdala during brain development, and found in glutamatergic but not GABAergic neurons. Identification of the promoter activity underlying specific expression patterns provides important clues to their mechanisms of action. Here, we show that the RP58 gene promoter is activated prominently in multipolar migrating cells, the first in vivo analysis of RP58 promoter activity in the brain. The 5.3 kb 5'-flanking genomic DNA of the RP58 coding region demonstrates promoter activity in neurons both in vitro and in vivo. This promoter is highly responsive to the transcription factor neurogenin2 (Ngn2), which is a direct upstream activator of RP58 expression. Using in utero electroporation, we demonstrate that RP58 gene promoter activity is first detected in a subpopulation of pin-like VZ cells, then prominently activated in migrating multipolar cells in the multipolar cell accumulation zone (MAZ) located just above the VZ. In dissociated primary cultured cortical neurons, RP58 promoter activity mimics in vivo expression patterns from a molecular standpoint that RP58 is expressed in a fraction of Sox2-positive progenitor cells, Ngn2-positive neuronal committed cells, and Tuj1-positive young neurons, but not in Dlx2-positive GABAergic neurons. Finally, we show that Cre recombinase expression under the control of the RP58 gene promoter is a feasible tool for conditional gene switching in post-mitotic multipolar migrating

  8. Motor Skills and Free-Living Physical Activity Showed No Association Among Preschoolers in 2012 U.S. National Youth Fitness Survey.

    PubMed

    Loprinzi, Paul D; Frith, Emily

    2017-04-01

    Albeit limited, some emerging work, using convenience-based samples, has demonstrated that greater motor skill development is associated with higher physical activity among preschool-aged children. The purpose of this study was to evaluate this topic using data from the 2012 National Youth Fitness Survey that included 329 preschool-aged children (3-5 years). Parents proxy-reported their child's physical activity, with motor skill level assessed from the Test of Gross Motor Development-Second Edition (TGMD2). Motor skill levels (Gross Motor Quotient, locomotor or object control) were not associated with preschool free-living physical activity in any analytic model. Thus, in this large sample of preschoolers, contrary to research with older children, motor skill level was not associated with physical activity. Findings are discussed in terms of study limitations of (a) a reliance on parent report of children's physical activity levels and (b) the possibility that physical activity data within the national survey were too limited in range to show possible associations to motor skill development with higher levels of free-living physical activity in preschoolers.

  9. Detection and comparison of neuraminidase activities in human and bovine group B streptococci.

    PubMed

    Ekin, Ismail Hakki; Gurturk, Kemal; Ilhan, Ziya; Ekin, Suat; Borum, Ayse Ebru; Arabaci, Cigdem; Yesilova, Abdullah

    2016-12-01

    Human and bovine group B streptococcus (GBS) isolates were serotyped and amounts of released N-acetylneuraminic acid from N-acetylneuraminyl-lactose by extracellular neuraminidase were colorimetrically assessed. According to serotyping by co-agglutination method, 30 of bovine GBS and 43 of human GBS could be serotyped (ST) by monospecific antisera coated with protein A. The remaining GBS strains were designated as nontypeable (NT). The released N-acetylneuraminic acid was determined in 90.9% of bovine GBS and 47.1% of human GBS isolates. The differences between the total bovine and human GBS isolates were statistically significant (p < 0.001). In comparison with detected N-acetylneuraminic acid level in bovine and human groups, significant decrease was observed in the bovine NT group according to increased human NT (p < 0.01) and bovine ST groups (p < 0.01). However, N-acetylneuraminic acid level in bovine ST and bovine total groups significantly (p < 0.001) increased with respect to the human ST group and human total group. Neuraminidase activity was detected more frequently in bovine GBS isolates. Considerable differentiations were observed between typeable and nontypeable isolates.

  10. Activity related to the carcinogenicity of plastic additives in the benzophenone group.

    PubMed

    Nakajima, Daisuke; Asada, Shin; Kageyama, Shiho; Yamamoto, Takashi; Kuramochi, Hidetoshi; Tanaka, Noriho; Takeda, Ken; Goto, Sumio

    2006-06-01

    This study examines the activities relating to the carcinogenicity of six types of benzophenone derivatives (benzophenone, 2-hydroxy-4-octyloxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone) currently used in plastic products as additives to serve as ultraviolet absorbing agents. The evaluation of the initiation activity used a light absorption umu-test, a luminescent umu-test and the Ames test. The promotion activity was examined by a Bhas assay, a method that uses Bhas 42 cells for the formation of transformation foci. The luminescent umu-test indicated positive initiation activity of 2-hydroxy-4-methoxybenzophenone, and pseudo-positive activity of 2,4-dihydroxybenzophenone and 2,2'-dihydroxy-4-methoxybenzophenone. In the Ames test, 2-hydroxy-4-octyloxybenzophenone showed pseudo-positive initiation activity. Conversely, 2,4-dihydroxybenzophenone indicated weak promotion activity at 10 microg/ml concentration.

  11. Bid chimeras indicate that most BH3-only proteins can directly activate Bak and Bax, and show no preference for Bak versus Bax

    PubMed Central

    Hockings, C; Anwari, K; Ninnis, R L; Brouwer, J; O'Hely, M; Evangelista, M; Hinds, M G; Czabotar, P E; Lee, E F; Fairlie, W D; Dewson, G; Kluck, R M

    2015-01-01

    The mitochondrial pathway of apoptosis is initiated by Bcl-2 homology region 3 (BH3)-only members of the Bcl-2 protein family. On upregulation or activation, certain BH3-only proteins can directly bind and activate Bak and Bax to induce conformation change, oligomerization and pore formation in mitochondria. BH3-only proteins, with the exception of Bid, are intrinsically disordered and therefore, functional studies often utilize peptides based on just their BH3 domains. However, these reagents do not possess the hydrophobic membrane targeting domains found on the native BH3-only molecule. To generate each BH3-only protein as a recombinant protein that could efficiently target mitochondria, we developed recombinant Bid chimeras in which the BH3 domain was replaced with that of other BH3-only proteins (Bim, Puma, Noxa, Bad, Bmf, Bik and Hrk). The chimeras were stable following purification, and each immunoprecipitated with full-length Bcl-xL according to the specificity reported for the related BH3 peptide. When tested for activation of Bak and Bax in mitochondrial permeabilization assays, Bid chimeras were ~1000-fold more effective than the related BH3 peptides. BH3 sequences from Bid and Bim were the strongest activators, followed by Puma, Hrk, Bmf and Bik, while Bad and Noxa were not activators. Notably, chimeras and peptides showed no apparent preference for activating Bak or Bax. In addition, within the BH3 domain, the h0 position recently found to be important for Bax activation, was important also for Bak activation. Together, our data with full-length proteins indicate that most BH3-only proteins can directly activate both Bak and Bax. PMID:25906158

  12. [Identification of catalytically active groups of wheat (Triticum aestivum L.) germ lipase].

    PubMed

    Korneeva, O S; Popova, T N; Kapranchikov, V S; Motina, E A

    2008-01-01

    The active site of wheat germ lipase was studied by the Dixon method and chemical modification. The profile of curve logV = f(pH), pK and ionization heat values, lipase photoinactivation, and lipase inactivation with diethylpyrocarbonate and dicyclohexylcarbodiimide led us to assume that the active site of the enzyme comprises the carboxylic group of aspartic or glutamic acid and the imidazole group of histidine. Apparently, the OH-group of serine plays a key role in catalysis: as a result of incubation for 1 h in the presence of phenylmethylsulfonyl fluoride, the enzyme activity decreased by more than 70%. It is shown that ethylenediamine tetraacetate is a noncompetitive inhibitor of lipase. Wheat germs are very healthful because they are rich in vitamins, essential amino acids, and proteins. For this reason, wheat germs are widely used in food, medical, and feed mill industries [1-3]. However, their use is limited by instability during storage, which is largely determined by the effect of hydrolytic and redox enzymes. Representative enzymes of this group are lipase (glycerol ester hydrolase, EC 3.1.1.3), which hydrolyzes triglycerides of higher fatty acids, and lipoxygenase (EC 1.13.11.13), which oxidizes polyunsaturated higher fatty acids.

  13. Activation of Group I Metabotropic Glutamate Receptors Potentiates Heteromeric Kainate Receptors

    PubMed Central

    Wetherington, Jonathon; Shaw, Renee; Serrano, Geidy; Swanger, Sharon; Dingledine, Raymond

    2013-01-01

    Kainate receptors (KARs), a family of ionotropic glutamate receptors, are widely expressed in the central nervous system and are critically involved in synaptic transmission. KAR activation is influenced by metabotropic glutamate receptor (mGlu) signaling, but the underlying mechanisms are not understood. We undertook studies to examine how mGlu modulation affects activation of KARs. Confocal immunohistochemistry of rat hippocampus and cultured rat cortex revealed colocalization of the high-affinity KAR subunits with group I mGlu receptors. In hippocampal and cortical cultures, the calcium signal caused by activation of native KARs was potentiated by activation of group I mGlu receptors. In Xenopus laevis oocytes, activation of group I mGlu receptors potentiated heteromeric but not homomeric KAR-mediated currents, with no change in agonist potency. The potentiation of heteromeric KARs by mGlu1 activation was attenuated by GDPβS, blocked by an inhibitor of phospholipase C or the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), prolonged by the phosphatase inhibitor okadaic acid, but unaffected by the tyrosine kinase inhibitor lavendustin A. Protein kinase C (PKC) inhibition reduced the potentiation by mGlu1 of GluK2/GluK5, and conversely, direct activation of PKC by phorbol 12-myristate,13-acetate potentiated GluK2/GluK5. Using site-directed mutagenesis, we identified three serines (Ser833, Ser836, and Ser840) within the membrane proximal region of the GluK5 C-terminal domain that, in combination, are required for mGlu1-mediated potentiation of KARs. Together, these data suggest that phosphorylation of key residues in the C-terminal domain changes the overall charge of this domain, resulting in potentiated agonist responses. PMID:23066089

  14. Trabectedin and its C subunit modified analogue PM01183 attenuate nucleotide excision repair and show activity toward platinum-resistant cells.

    PubMed

    Soares, Daniele G; Machado, Miriana S; Rocca, Céline J; Poindessous, Virginie; Ouaret, Djamila; Sarasin, Alain; Galmarini, Carlos M; Henriques, João A P; Escargueil, Alexandre E; Larsen, Annette K

    2011-08-01

    PM01183 is a novel marine-derived covalent DNA binder in clinical development. PM01183 is structurally similar to trabectedin (yondelis, ecteinascidin-743) except for the C subunit, and this modification is accompanied by different pharmacokinetics in cancer patients. We here characterize the interaction of PM01183 with the nucleotide excision repair (NER) pathway in comparison with trabectedin. Our results show for the first time that although neither PM01183 nor trabectedin is repaired by NER, both compounds are able to interfere with the NER machinery thereby attenuating the repair of specific NER substrates. We further show that the NER activity is increased in 3 of 4 cellular models with acquired resistance to cisplatin or oxaliplatin, confirming the involvement of NER in the resistance to platinum derivatives. Importantly, both PM01183 and trabectedin show unchanged or even enhanced activity toward all 4 cisplatin- and oxaliplatin-resistant cell lines. We finally show that combinations of PM01183 and cisplatin were mostly synergistic toward both parental and cisplatin-resistant ovarian carcinoma cells as indicated by Chou and Talalay analysis. These data show that the C subunit of trabectedin can be subjected to at least some structural modifications without loss of activity or NER interaction. While PM01183 and trabectedin appear functionally similar in cellular models, it is likely that the differences in pharmacokinetics may allow different dosing and scheduling of PM01183 in the clinic that could lead to novel and/or increased antitumor activity. Taken together, our results provide a mechanistic basis to support clinical trials of PM01183 alone or in combination with cisplatin.

  15. Assessing Activity and Location of Individual Laying Hens in Large Groups Using Modern Technology

    PubMed Central

    Siegford, Janice M.; Berezowski, John; Biswas, Subir K.; Daigle, Courtney L.; Gebhardt-Henrich, Sabine G.; Hernandez, Carlos E.; Thurner, Stefan; Toscano, Michael J.

    2016-01-01

    Simple Summary Tracking of individual animals within large groups is increasingly possible offering an exciting opportunity to researchers. Whereas previously only relatively indistinguishable groups of individual animals could be observed and combined into pen level data, we can now focus on individual actors and track their activities across time and space with minimal intervention and disturbance. We describe several tracking systems that are currently in use for laying hens and review each, highlighting their strengths and weaknesses, as well as environments or conditions for which they may be most suited, and relevant issues to fit the best technology for the intended purpose. Abstract Tracking individual animals within large groups is increasingly possible, offering an exciting opportunity to researchers. Whereas previously only relatively indistinguishable groups of individual animals could be observed and combined into pen level data, we can now focus on individual actors within these large groups and track their activities across time and space with minimal intervention and disturbance. The development is particularly relevant to the poultry industry as, due to a shift away from battery cages, flock sizes are increasingly becoming larger and environments more complex. Many efforts have been made to track individual bird behavior and activity in large groups using a variety of methodologies with variable success. Of the technologies in use, each has associated benefits and detriments, which can make the approach more or less suitable for certain environments and experiments. Within this article, we have divided several tracking systems that are currently available into two major categories (radio frequency identification and radio signal strength) and review the strengths and weaknesses of each, as well as environments or conditions for which they may be most suitable. We also describe related topics including types of analysis for the data and concerns

  16. Development, Evaluation and Implementation of Chief Complaint Groupings to Activate Data Collection

    PubMed Central

    Bajaj, L.; Hoffman, J.; Alessandrini, E.; Ballard, D. W.; Norris, R.; Tzimenatos, L.; Swietlik, M.; Tham, E.; Grundmeier, R. W.; Kuppermann, N.; Dayan, P. S.

    2015-01-01

    Summary Background Overuse of cranial computed tomography scans in children with blunt head trauma unnecessarily exposes them to radiation. The Pediatric Emergency Care Applied Research Network (PECARN) blunt head trauma prediction rules identify children who do not require a computed tomography scan. Electronic health record (EHR) based clinical decision support (CDS) may effectively implement these rules but must only be provided for appropriate patients in order to minimize excessive alerts. Objectives To develop, implement and evaluate site-specific groupings of chief complaints (CC) that accurately identify children with head trauma, in order to activate data collection in an EHR. Methods As part of a 13 site clinical trial comparing cranial computed tomography use before and after implementation of CDS, four PECARN sites centrally developed and locally implemented CC groupings to trigger a clinical trial alert (CTA) to facilitate the completion of an emergency department head trauma data collection template. We tested and chose CC groupings to attain high sensitivity while maintaining at least moderate specificity. Results Due to variability in CCs available, identical groupings across sites were not possible. We noted substantial variability in the sensitivity and specificity of seemingly similar CC groupings between sites. The implemented CC groupings had sensitivities greater than 90% with specificities between 75–89%. During the trial, formal testing and provider feedback led to tailoring of the CC groupings at some sites. Conclusions CC groupings can be successfully developed and implemented across multiple sites to accurately identify patients who should have a CTA triggered to facilitate EHR data collection. However, CC groupings will necessarily vary in order to attain high sensitivity and moderate-to-high specificity. In future trials, the balance between sensitivity and specificity should be considered based on the nature of the clinical condition

  17. Plasma membrane of Beta vulgaris storage root shows high water channel activity regulated by cytoplasmic pH and a dual range of calcium concentrations.

    PubMed

    Alleva, Karina; Niemietz, Christa M; Sutka, Moira; Maurel, Christophe; Parisi, Mario; Tyerman, Stephen D; Amodeo, Gabriela

    2006-01-01

    Plasma membrane vesicles isolated by two-phase partitioning from the storage root of Beta vulgaris show atypically high water permeability that is equivalent only to those reported for active aquaporins in tonoplast or animal red cells (Pf=542 microm s(-1)). The values were determined from the shrinking kinetics measured by stopped-flow light scattering. This high Pf was only partially inhibited by mercury (HgCl2) but showed low activation energy (Ea) consistent with water permeation through water channels. To study short-term regulation of water transport that could be the result of channel gating, the effects of pH, divalent cations, and protection against dephosphorylation were tested. The high Pf observed at pH 8.3 was dramatically reduced by medium acidification. Moreover, intra-vesicular acidification (corresponding to the cytoplasmic face of the membrane) shut down the aquaporins. De-phosphorylation was discounted as a regulatory mechanism in this preparation. On the other hand, among divalent cations, only calcium showed a clear effect on aquaporin activity, with two distinct ranges of sensitivity to free Ca2+ concentration (pCa 8 and pCa 4). Since the normal cytoplasmic free Ca2+ sits between these ranges it allows for the possibility of changes in Ca2+ to finely up- or down-regulate water channel activity. The calcium effect is predominantly on the cytoplasmic face, and inhibition corresponds to an increase in the activation energy for water transport. In conclusion, these findings establish both cytoplasmic pH and Ca2+ as important regulatory factors involved in aquaporin gating.

  18. Rh D blood group conversion using transcription activator-like effector nucleases.

    PubMed

    Kim, Young-Hoon; Kim, Hyun O; Baek, Eun J; Kurita, Ryo; Cha, Hyuk-Jin; Nakamura, Yukio; Kim, Hyongbum

    2015-06-16

    Group O D-negative blood cells are universal donors in transfusion medicine and methods for converting other blood groups into this universal donor group have been researched. However, conversion of D-positive cells into D-negative is yet to be achieved, although conversion of group A or B cells into O cells has been reported. The Rh D blood group is determined by the RHD gene, which encodes a 12-transmembrane domain protein. Here we convert Rh D-positive erythroid progenitor cells into D-negative cells using RHD-targeting transcription activator-like effector nucleases (TALENs). After transfection of TALEN-encoding plasmids, RHD-knockout clones are obtained. Erythroid-lineage cells differentiated from these knockout erythroid progenitor cells do not agglutinate in the presence of anti-D reagents and do not express D antigen, as assessed using flow cytometry. Our programmable nuclease-induced blood group conversion opens new avenues for compatible donor cell generation in transfusion medicine.

  19. Rh D blood group conversion using transcription activator-like effector nucleases

    PubMed Central

    Kim, Young-Hoon; Kim, Hyun O.; Baek, Eun J.; Kurita, Ryo; Cha, Hyuk-Jin; Nakamura, Yukio; Kim, Hyongbum

    2015-01-01

    Group O D-negative blood cells are universal donors in transfusion medicine and methods for converting other blood groups into this universal donor group have been researched. However, conversion of D-positive cells into D-negative is yet to be achieved, although conversion of group A or B cells into O cells has been reported. The Rh D blood group is determined by the RHD gene, which encodes a 12-transmembrane domain protein. Here we convert Rh D-positive erythroid progenitor cells into D-negative cells using RHD-targeting transcription activator-like effector nucleases (TALENs). After transfection of TALEN-encoding plasmids, RHD-knockout clones are obtained. Erythroid-lineage cells differentiated from these knockout erythroid progenitor cells do not agglutinate in the presence of anti-D reagents and do not express D antigen, as assessed using flow cytometry. Our programmable nuclease-induced blood group conversion opens new avenues for compatible donor cell generation in transfusion medicine. PMID:26078220

  20. Towards a common framework for assessing the activity and associations of groups who sexually abuse children

    PubMed Central

    Cockbain, Ella; Brayley, Helen; Sullivan, Joe

    2013-01-01

    Extensive social psychological research emphasises the importance of groups in shaping individuals’ thoughts and actions. Within the child sexual abuse (CSA) literature criminal organisation has been largely overlooked, with some key exceptions. This research was a novel collaboration between academia and the UK's Child Exploitation and Online Protection Centre (CEOP). Starting from the premise that the group is, in itself, a form of social situation affecting abuse, it offers the first systematic situational analysis of CSA groups. In-depth behavioural data from a small sample of convicted CSA group-offenders (n = 3) were analysed qualitatively to identify factors and processes underpinning CSA groups’ activities and associations: group formation, evolution, identity and resources. The results emphasise CSA groups’ variability, fluidity and dynamism. The foundations of a general framework are proposed for researching and assessing CSA groups and designing effective interventions. It is hoped that this work will stimulate discussion and development in this long-neglected area of CSA, helping to build a coherent knowledge-base. PMID:26494978

  1. Indole-2-carboxamide-based MmpL3 Inhibitors Show Exceptional Antitubercular Activity in an Animal Model of Tuberculosis Infection.

    PubMed

    Stec, Jozef; Onajole, Oluseye K; Lun, Shichun; Guo, Haidan; Merenbloom, Benjamin; Vistoli, Giulio; Bishai, William R; Kozikowski, Alan P

    2016-07-14

    Our team had previously identified certain indolecarboxamides that represented a new chemical scaffold that showed promising anti-TB activity at both an in vitro and in vivo level. Based on mutational analysis using bacteria found resistant to one of these indolecarboxamides, we identified the trehalose monomycolate transporter MmpL3 as the likely target of these compounds. In the present work, we now further elaborate on the SAR of these compounds, which has led in turn to the identification of a new analog, 4,6-difluoro-N-((1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)-1H-indole-2-carboxamide (26), that shows excellent activity against drug-sensitive (MIC = 0.012 μM; SI ≥ 16000), multidrug-resistant (MDR), and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains, has superior ADMET properties, and shows excellent activity in the TB aerosol lung infection model. Compound 26 is also shown to work in synergy with rifampin. Because of these properties, we believe that indolecarboxamide 26 is a possible candidate for advancement to human clinical trials.

  2. Human Activity Dampens the Benefits of Group Size on Vigilance in Khulan (Equus hemionus) in Western China

    PubMed Central

    Wang, Mu-Yang; Ruckstuhl, Kathreen E.; Xu, Wen-Xuan; Blank, David; Yang, Wei-Kang

    2016-01-01

    Animals receive anti-predator benefits from social behavior. As part of a group, individuals spend less time being vigilant, and vigilance decreases with increasing group size. This phenomenon, called “the many-eyes effect”, together with the “encounter dilution effect”, is considered among the most important factors determining individual vigilance behavior. However, in addition to group size, other social and environmental factors also influence the degree of vigilance, including disturbance from human activities. In our study, we examined vigilance behavior of Khulans (Equus hemionus) in the Xinjiang Province in western China to test whether and how human disturbance and group size affect vigilance. According to our results, Khulan showed a negative correlation between group size and the percentage time spent vigilant, although this negative correlation depended on the groups’ disturbance level. Khulan in the more disturbed area had a dampened benefit from increases in group size, compared to those in the undisturbed core areas. Provision of continuous areas of high-quality habitat for Khulans will allow them to form larger undisturbed aggregations and to gain foraging benefits through reduced individual vigilance, as well as anti-predator benefits through increased probability of predator detection. PMID:26756993

  3. Group Cognitive Behavioural Therapy and Group Recreational Activity for Adults with Autism Spectrum Disorders: A Preliminary Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne

    2014-01-01

    Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This "preliminary" randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive…

  4. Showing What They Know

    ERIC Educational Resources Information Center

    Cech, Scott J.

    2008-01-01

    Having students show their skills in three dimensions, known as performance-based assessment, dates back at least to Socrates. Individual schools such as Barrington High School--located just outside of Providence--have been requiring students to actively demonstrate their knowledge for years. The Rhode Island's high school graduating class became…

  5. The Ozone Show.

    ERIC Educational Resources Information Center

    Mathieu, Aaron

    2000-01-01

    Uses a talk show activity for a final assessment tool for students to debate about the ozone hole. Students are assessed on five areas: (1) cooperative learning; (2) the written component; (3) content; (4) self-evaluation; and (5) peer evaluation. (SAH)

  6. What Do Maps Show?

    ERIC Educational Resources Information Center

    Geological Survey (Dept. of Interior), Reston, VA.

    This curriculum packet, appropriate for grades 4-8, features a teaching poster which shows different types of maps (different views of Salt Lake City, Utah), as well as three reproducible maps and reproducible activity sheets which complement the maps. The poster provides teacher background, including step-by-step lesson plans for four geography…

  7. Engagement in elderly persons with dementia attending animal-assisted group activity.

    PubMed

    Olsen, Christine; Pedersen, Ingeborg; Bergland, Astrid; Enders-Slegers, Marie-José; Ihlebæk, Camilla

    2016-09-02

    The need for meaningful activities that enhance engagement is very important among persons with dementia (PWDs), both for PWDs still living at home, as well as for PWDs admitted to a nursing home (NH). In this study, we systematically registered behaviours related to engagement in a group animal-assisted activity (AAA) intervention for 21 PWDs in NHs and among 28 home-dwelling PWDs attending a day care centre. The participants interacted with a dog and its handler for 30 minutes, twice a week for 12 weeks. Video-recordings were carried out early (week 2) and late (week 10) during the intervention period and behaviours were categorized by the use of an ethogram. AAA seems to create engagement in PWDs, and might be a suitable and health promoting intervention for both NH residents and participants of a day care centre. Degree of dementia should be considered when planning individual or group based AAA.

  8. Group behavioral activation for patients with severe obesity and binge eating disorder: a randomized controlled trial.

    PubMed

    Alfonsson, Sven; Parling, Thomas; Ghaderi, Ata

    2015-03-01

    The aim of the present study was to assess whether behavioral activation (BA) is an efficacious treatment for decreasing eating disorder symptoms in patients with obesity and binge eating disorder (BED). Ninety-six patients with severe obesity and BED were randomized to either 10 sessions of group BA or wait-list control. The study was conducted at an obesity clinic in a regular hospital setting. The treatment improved some aspects of disordered eating and had a positive effect on depressive symptoms but there was no significant difference between the groups regarding binge eating and most other symptoms. Improved mood but lack of effect on binge eating suggests that dysfunctional eating (including BED) is maintained by other mechanisms than low activation and negative mood. However, future studies need to investigate whether effects of BA on binge eating might emerge later than at post-assessment, as in interpersonal psychotherapy for bulimia nervosa.

  9. Chlorosulfonation of polystyrene substrates for bioanalytical assays: distribution of activated groups at the surface.

    PubMed

    del Prado, Anselmo; Briz, Nerea; Navarro, Rodrigo; Pérez, Mónica; Gallardo, Alberto; Reinecke, Helmut

    2012-12-07

    In this work the activation of transparent PS substrates by chlorosulfonation is described and their distribution in the subsurface region is analyzed. For this purpose XPS, FTIR-ATR and colorimetry have been used. It is shown that the electrophilic aromatic substitution of polystyrene in pure chlorosulfonic acid is extremely quick with complete surface coverage by chlorosulfonic groups achieved after only a 10 minute reaction time at -10 °C. It is further demonstrated that the reaction is very surface selective and that even after reaction times as long as 3 hours, the modification is limited to a layer with a thickness of less than one micron. The activated PS substrates can be further functionalized in a second step with carboxylic groups. Due to the excellent optical transparency that the samples maintain upon modification, the modified systems were successfully probed for use in ELISA assays.

  10. New Horizons in C-F Activation by Main Group Electrophiles

    SciTech Connect

    Ozerov, Oleg V.

    2016-02-13

    This technical report describes progress on the DOE sponsored project "New Horizons in C-F Activation by Main Group Electrophiles" during the period of 09/15/2010 – 08/31/2015. The main goal of this project was to develop improved catalysts for conversion of carbon-fluorine bonds in potentially harmful compounds. The approach involved combining of a highly reactive positively charged main-group compound with a highly unreactive negatively charged species (anions) as a way to access potent catalysts for carbon-fluorine bond activation. This report details progress made in improving synthetic pathways to a variety of new anions with improved properties and analysis of their potential in catalysis.

  11. Control of Surface Functional Groups on Pertechntate Sorption on Activated Carbon

    SciTech Connect

    Y. Wang; H. Gao; R. Yeredla; H. Xu; M. Abrecht; G.D. Stasio

    2006-07-05

    {sup 99}Tc is highly soluble and poorly adsorbed by natural materials under oxidizing conditions, thus being of particular concern for radioactive waste disposal. Activated carbon can potentially be used as an adsorbent for removing Tc from aqueous solutions. We have tested six commercial activated carbon materials for their capabilities for sorption of pertechnetate (TcO{sub 4}{sup -}). The tested materials can be grouped into two distinct types: Type I materials have high sorption capabilities with the distribution coefficients (K{sub d}) varying from 9.5 x 10{sup 5} to 3.2 x 10{sup 3} mL/g as the pH changes from 4.5 to 9.5, whereas type II materials have relatively low sorption capabilities with K{sub d} remaining more or less constant (1.1 x 10{sup 3} - 1.8 x 10{sup 3} mL/g) over a similar pH range. The difference in sorption behavior between the two types of materials is attributed to the distribution of surface functional groups. The predominant surface groups are identified to be carboxylic and phenolic groups. The carboxylic group can be further divided into three subgroups A, B, and C in the order of increasing acidity. The high sorption capabilities of type I materials are found to be caused by the presence of a large fraction of carboxylic subgroups A and B, while the low sorption capabilities of type II materials are due to the exclusive presence of phenolic and carboxylic subgroup C. Therefore, the performance of activated carbon for removing TcO{sub 4}{sup -} can be improved by enhancing the formation of carboxylic subgroups A and B during material processing.

  12. Diffuse large B-cell lymphoma with concurrent high MYC and BCL2 expression shows evidence of active B-cell receptor signaling by quantitative immunofluorescence

    PubMed Central

    Kovach, Alexandra E.; Le, Long P.; Feng, Derek; Baxter, Richard H. G.; Sohani, Aliyah R.

    2017-01-01

    B-cell receptor (BCR)-mediated signaling plays an important role in the pathogenesis of a subset of diffuse large B-cell lymphoma (DLBCL), and novel agents targeting this pathway are now in clinical use. We have previously identified a signature of active BCR signaling on formalin-fixed paraffin-embedded specimens using quantitative immunofluorescence, allowing for identification of patients who might benefit from anti-BCR therapies. We sought to characterize the clinicopathologic significance of active BCR signaling in DLBCL by correlating measures of signaling intensity with clinical features and various tumor cell characteristics. High MYC and concurrent high MYC and BCL2 double-expression was positively correlated with individual markers of active BCR signaling and cases with MYC/BCL2 double-expression showed overall greater BCR activation compared to cases lacking double-expression. Our findings suggest that the BCR signaling pathway may be more active in MYC/BCL2 double-expressor DLBCL and may represent a rational therapeutic target in this aggressive DLBCL subgroup. PMID:28212447

  13. Improving Diet and Physical Activity Practices in Group Homes Serving Residents With Severe Mental Illness

    PubMed Central

    Xiong, Glen; Ziegahn, Linda; Schuyler, Barlow; Rowlett, Al; Cassady, Diana

    2011-01-01

    Background People with severe mental illness (SMI) are at least 50% more likely to be overweight for various reasons, including poor nutrition, sedentary lifestyles, and side effects of antipsychotic medications. Objectives Among residents with SMI who live in group homes, we examined (1) factors that affected the motivations of both group home operators and residents around improvement of residents' diet and physical activity, (2) how operators and residents viewed responsibility for maintaining good health in group homes, and (3) strategies from operators and residents for improving diet and exercise. Methods The research team conducted 6 focus groups—3 with group home operators and 3 with residents, using a community-based participatory research (CBPR) process and qualitative data analysis. Results Both group home operators and residents discussed conflicting feelings about foods they know as healthy and foods they prefer to eat. Operators attributed barriers to better health to the perceived negative attitudes of residents and providers, lack of communication with health care providers, and poor working relationships with the state licensing body that protects individual rights on lifestyle choices. Residents reported barriers of their own negative attitudes, limited menu options, lack of organized activities, existing health problems, and side effects of medications. Conclusion Residents and operators had concrete suggestions for changes they could make individually, as well as recommendations for systemic changes to support healthier lifestyles. These recommendations provide a basis for designing an urgently needed pilot intervention program to address the current epidemic of obesity and diabetes in people with SMI residing in group homes. PMID:21169705

  14. Assessing Activity and Location of Individual Laying Hens in Large Groups Using Modern Technology.

    PubMed

    Siegford, Janice M; Berezowski, John; Biswas, Subir K; Daigle, Courtney L; Gebhardt-Henrich, Sabine G; Hernandez, Carlos E; Thurner, Stefan; Toscano, Michael J

    2016-02-02

    Tracking individual animals within large groups is increasingly possible, offering an exciting opportunity to researchers. Whereas previously only relatively indistinguishable groups of individual animals could be observed and combined into pen level data, we can now focus on individual actors within these large groups and track their activities across time and space with minimal intervention and disturbance. The development is particularly relevant to the poultry industry as, due to a shift away from battery cages, flock sizes are increasingly becoming larger and environments more complex. Many efforts have been made to track individual bird behavior and activity in large groups using a variety of methodologies with variable success. Of the technologies in use, each has associated benefits and detriments, which can make the approach more or less suitable for certain environments and experiments. Within this article, we have divided several tracking systems that are currently available into two major categories (radio frequency identification and radio signal strength) and review the strengths and weaknesses of each, as well as environments or conditions for which they may be most suitable. We also describe related topics including types of analysis for the data and concerns with selecting focal birds.

  15. Synthesis, insecticidal, and acaricidal activities of novel 2-aryl-pyrrole derivatives containing ester groups.

    PubMed

    Zhao, Yu; Li, Yongqiang; Ou, Xiaoming; Zhang, Pengxiang; Huang, Zhiqiang; Bi, Fuchun; Huang, Runqiu; Wang, Qingmin

    2008-11-12

    A series of novel 2-aryl-pyrrole derivatives containing ester groups were synthesized, and their structures were characterized by (1)H NMR spectroscopy and elemental analysis. The insecticidal activities against oriental armyworm, mosquito, diamondback moth, green rice leafhopper, and bean aphids and acaricidal activities against spider mite of these new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal and acaricidal activities. The insecticidal activities against oriental armyworm of compounds IVa, IVd, IVe, IVf, IVg, IVi, IVk, and IVp were equal to commercialized Chlorfenapyr, and the insecticidal activities of most of compounds IVb, IVc, IVd, IVf, IVg, IVj, IVk, IVl, IVs, IVt, IVu, IVw, IVx, IVz, and Chlorfenapyr against mosquito at 0.10 mg kg (-1) were 100%, and the acaricidal activities of compounds IVd, IVe, IVf, IVg, IVh, IVi, and IVk were equal or superior to Chlorfenapyr. Especially, the results indicated that the acaricidal activity of [4-bromo-2-(4-chlorophenyl)-3-cyano-5-(trifluoromethyl)pyrrol-1-yl]methyl 3-methylbutanoate ( IVg) against spider mite was 2.65-fold as high as that of Chlorfenapyr from the value of LC 50.

  16. The 46 kDa dimeric protein from Variovorax paradoxus shows faster methotrexate degrading activity in its nanoform compare to the native enzyme.

    PubMed

    Bayineni, Venkata Krishna; Venkatesh, Krishna; Sahu, Chandan Kumar; Kadeppagari, Ravi-Kumar

    2016-04-01

    Methotrexate degrading enzymes are required to overcome the toxicity of the methotrexate while treating the cancer. The enzyme from Variovorax paradoxus converts the methotrexate in to non toxic products. Methotrexate degrading enzyme from V. paradoxus is a dimeric protein with a molecular mass of 46 kDa and it acts on casein and gelatin. This enzyme is optimally active at pH 7.5 and 40°C and nanoparticles of this enzyme were prepared by desolvation-crosslinking method. Enzyme nanoparticles could degrade methotrexate faster than the native enzyme and they show lower Km compare to the native enzyme. Enzyme nanoparticles show better thermostability and they were stable for much longer time in the serum compare to the native enzyme. Enzyme nanoparticles show better functionality than the native enzyme while clearing the methotrexate added to the serum suggesting their advantage over the native enzyme for the therapeutic and biotechnological applications.

  17. Lysis of typhus-group rickettsia-infected targets by lymphokine activated killers

    SciTech Connect

    Carl, M.; Dasch, G.A.

    1986-03-01

    The authors recently described a subset of OKT8, OKT3-positive lymphocytes from typhus-group rickettsia immune individuals which were capable of lysing autologous PHA-blasts or Epstein-Barr virus transformed B cells (LCL) infected with typhus-group rickettsiae. In order to determine if killing by these effectors was HLA-restricted, they stimulated peripheral blood mononuclear cells (PBMC) from typhus-group rickettsia immune individuals in vitro with typhus-group rickettsia-derived antigen for one week and then measured lysis of autologous LCL or HLA-mismatched LCL in a 4-6 hour Cr/sup 51/-release assay. There was significant lysis of both the autologous and the HLA-mismatched infected targets as compared to the corresponding uninfected targets. Since this suggested that the effectors were lymphokine activated killers (LAK) rather than cytotoxic T lymphocytes, they then tested this hypothesis by stimulating PBMC from both immune and non-immune individuals in vitro for one week with purified interleukin 2 and measuring lysis of infected, autologous LCL. PBMC thus treated, from both immune and non-immune individuals, were capable of significantly lysing autologous, infected LCL as compared to the non-infected control. They therefore conclude that targets infected with typhus-group rickettsiae are susceptible to lysis to LAK.

  18. Novel Antiviral Characteristics of Nanosized Copper(I) Iodide Particles Showing Inactivation Activity against 2009 Pandemic H1N1 Influenza Virus

    PubMed Central

    Sato, Tetsuya; Hayata, Taishi; Nagao, Tomokazu; Nakayama, Mikio; Nakayama, Tsuruo; Sugamata, Ryuichi; Suzuki, Kazuo

    2012-01-01

    We investigated the antiviral activity of nanosized copper(I) iodide (CuI) particles having an average size of 160 nm. CuI particles showed aqueous stability and generated hydroxyl radicals, which were probably derived from monovalent copper (Cu+). We confirmed that CuI particles showed antiviral activity against an influenza A virus of swine origin (pandemic [H1N1] 2009) by plaque titration assay. The virus titer decreased in a dose-dependent manner upon incubation with CuI particles, with the 50% effective concentration being approximately 17 μg/ml after exposure for 60 min. SDS-PAGE analysis confirmed the inactivation of the virus due to the degradation of viral proteins such as hemagglutinin and neuraminidase by CuI. Electron spin resonance (ESR) spectroscopy revealed that CuI generates hydroxyl radicals in aqueous solution, and radical production was found to be blocked by the radical scavenger N-acetylcysteine. Taken together, these findings indicate that CuI particles exert antiviral activity by generating hydroxyl radicals. Thus, CuI may be a useful material for protecting against viral attacks and may be suitable for applications such as filters, face masks, protective clothing, and kitchen cloths. PMID:22156433

  19. Erucin, a new promising cancer chemopreventive agent from rocket salads, shows anti-proliferative activity on human lung carcinoma A549 cells.

    PubMed

    Melchini, A; Costa, C; Traka, M; Miceli, N; Mithen, R; De Pasquale, R; Trovato, A

    2009-07-01

    Erucin (ER) is a dietary isothiocyanate present in cruciferous vegetables, such as rocket salads (Erucasativa Mill., Diplotaxis sp.), that has been recently considered a promising cancer chemopreventive phytochemical. Biological activity of ER was investigated on human lung adenocarcinoma A549 cells, analyzing its effects on molecular pathways involved in apoptosis and cell cycle arrest, such as PARP-1 cleavage, p53 and p21 protein expression. Our results show that ER affects the A549 cell proliferation, enhancing significantly p53 and p21 protein expression in a dose-dependent manner (p<0.001). PARP-1 cleavage occurs only after exposure to high concentrations of ER (50 microM), in accordance to previous studies showing similar bioactivity of other isothiocyanates (ITCs). Our study reports for the first time that the induction of p53, p21 and PARP-1 cleavage may participate in the anti-proliferative activity of ER in human lung adenocarcinoma A549 cells. Comparison of data with those obtained with the isothiocyanate sulforaphane (SF), structurally related to ER, underlines the strong relationship between structural analogy of ITCs and their biological activity. The ability of dietary compounds to modulate molecular mechanisms that affect cancer cell proliferation is certainly a key point of the cancer prevention potential by functional foods.

  20. Sunspot groups with high flare activity: Specific features of magnetic configuration, morphology, and dynamics

    NASA Astrophysics Data System (ADS)

    Fursyak, Yu. A.

    2016-12-01

    Specific features of the magnetic configuration, morphological structure, dynamics, and evolution of sunspot groups of the current (24th) cycle of solar activity with high flare activity are considered. The gradients of longitudinal magnetic fields at places of δ-configuration are calculated. The main finding is a time delay of 24-30 h between the time when the magnetic field gradient reaches a critical level of 0.1 G/km and the time when the first of powerful flares occurs in the active region. The study is based on data from the SDO and GOES-15 spacecrafts and ground-based solar telescopes (TST-2 at the Crimean Astrophysical Observatory of the Russian Academy of Sciences and the 150-foot telescope at the Mount Wilson Observatory).

  1. Recognition of human-vehicle interactions in group activities via multi-attributed semantic message generation

    NASA Astrophysics Data System (ADS)

    Elangovan, Vinayak; Shirkhodaie, Amir

    2015-05-01

    Improved Situational awareness is a vital ongoing research effort for the U.S. Homeland Security for the past recent years. Many outdoor anomalous activities involve vehicles as their primary source of transportation to and from the scene where a plot is executed. Analysis of dynamics of Human-Vehicle Interaction (HVI) helps to identify correlated patterns of activities representing potential threats. The objective of this paper is bi-folded. Primarily, we discuss a method for temporal HVI events detection and verification for generation of HVI hypotheses. To effectively recognize HVI events, a Multi-attribute Vehicle Detection and Identification technique (MVDI) for detection and classification of stationary vehicles is presented. Secondly, we describe a method for identification of pertinent anomalous behaviors through analysis of state transitions between two successively detected events. Finally, we present a technique for generation of HVI semantic messages and present our experimental results to demonstrate the effectiveness of semantic messages for discovery of HVI in group activities.

  2. ABDOMINAL MUSCLE ACTIVATION INCREASES LUMBAR SPINAL STABILITY: ANALYSIS OF CONTRIBUTIONS OF DIFFERENT MUSCLE GROUPS

    PubMed Central

    Stokes, Ian A.F.; Gardner-Morse, Mack G.; Henry, Sharon M.

    2011-01-01

    Background Antagonistic activation of abdominal muscles and raised intra-abdominal pressure are associated with both spinal unloading and spinal stabilization. Rehabilitation regimens have been proposed to improve spinal stability via selective recruitment of certain trunk muscle groups. This biomechanical study used an analytical model to address whether lumbar spinal stability is increased by selective activation of abdominal muscles. Methods The biomechanical model included anatomically realistic three-layers of curved abdominal musculature connected by fascia, rectus abdominis and 77 symmetrical pairs of dorsal muscles. The muscle activations were calculated with the model loaded with either flexion, extension, lateral bending or axial rotation moments up to 60 Nm, along with intra-abdominal pressure up to 5 or 10 kPa (37.5 or 75 mm Hg) and partial bodyweight. After solving for muscle forces, a buckling analysis quantified spinal stability. Subsequently, different patterns of muscle activation were studied by forcing activation of selected abdominal muscles to at least 10% or 20% of maximum. Findings The spinal stability increased by an average factor of 1.8 with doubling of intra-abdominal pressure. Forced activation of obliques or transversus abdominis muscles to at least 10% of maximum increased stability slightly for efforts other than flexion, but forcing at least 20% activation generally did not produce further increase in stability. Forced activation of rectus abdominis did not increase stability. Interpretation Based on predictions from an analytical spinal buckling model, the degree of stability was not substantially influenced by selective forcing of muscle activation. This casts doubt on the supposed mechanism of action of specific abdominal muscle exercise regimens that have been proposed for low back pain rehabilitation. PMID:21571410

  3. PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects

    PubMed Central

    Zazo, Sandra; Arpí, Oriol; Menéndez, Silvia; Manso, Rebeca; Lluch, Ana; Eroles, Pilar; Rovira, Ana; Albanell, Joan; García-Foncillas, Jesús; Madoz-Gúrpide, Juan; Rojo, Federico

    2015-01-01

    The protein phosphatase 2A (PP2A) is a key tumor suppressor which has emerged as a novel molecular target in some human cancers. Here, we show that PP2A inhibition is a common event in breast cancer and identified PP2A phosphorylation and deregulation SET and CIP2A as molecular contributing mechanisms to inactivate PP2A. Interestingly, restoration of PP2A activity after FTY720 treatment reduced cell growth, induced apoptosis and decreased AKT and ERK activation. Moreover, FTY720 led to PP2A activation then enhancing doxorubicin-induced antitumor effects both in vitro and in vivo. PP2A inhibition (CPscore: PP2A phosphorylation and/or CIP2A overexpression) was detected in 27% of cases (62/230), and associated with grade (p = 0.017), relapse (p < 0.001), negative estrogen (p < 0.001) and progesterone receptor expression (p < 0.001), HER2-positive tumors (p = 0.049), Ki-67 expression (p < 0.001), and higher AKT (p < 0.001) and ERK (p < 0.001) phosphorylation. Moreover, PP2A inhibition determined shorter overall (p = 0.006) and event-free survival (p = 0.003), and multivariate analysis confirmed its independent prognostic impact. Altogether, our results indicate that PP2A is frequently inactivated in breast cancer and determines worse outcome, and its restoration using PP2A activators represents an alternative therapeutic strategy in this disease. PMID:25726524

  4. PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects.

    PubMed

    Rincón, Raúl; Cristóbal, Ion; Zazo, Sandra; Arpí, Oriol; Menéndez, Silvia; Manso, Rebeca; Lluch, Ana; Eroles, Pilar; Rovira, Ana; Albanell, Joan; García-Foncillas, Jesús; Madoz-Gúrpide, Juan; Rojo, Federico

    2015-02-28

    The protein phosphatase 2A (PP2A) is a key tumor suppressor which has emerged as a novel molecular target in some human cancers. Here, we show that PP2A inhibition is a common event in breast cancer and identified PP2A phosphorylation and deregulation SET and CIP2A as molecular contributing mechanisms to inactivate PP2A. Interestingly, restoration of PP2A activity after FTY720 treatment reduced cell growth, induced apoptosis and decreased AKT and ERK activation. Moreover, FTY720 led to PP2A activation then enhancing doxorubicin-induced antitumor effects both in vitro and in vivo. PP2A inhibition (CPscore: PP2A phosphorylation and/or CIP2A overexpression) was detected in 27% of cases (62/230), and associated with grade (p = 0.017), relapse (p < 0.001), negative estrogen (p < 0.001) and progesterone receptor expression (p < 0.001), HER2-positive tumors (p = 0.049), Ki-67 expression (p < 0.001), and higher AKT (p < 0.001) and ERK (p < 0.001) phosphorylation. Moreover, PP2A inhibition determined shorter overall (p = 0.006) and event-free survival (p = 0.003), and multivariate analysis confirmed its independent prognostic impact. Altogether, our results indicate that PP2A is frequently inactivated in breast cancer and determines worse outcome, and its restoration using PP2A activators represents an alternative therapeutic strategy in this disease.

  5. AGN POPULATION IN HICKSON COMPACT GROUPS. I. DATA AND NUCLEAR ACTIVITY CLASSIFICATION

    SciTech Connect

    MartInez, M. A.; Del Olmo, A.; Perea, J.; Coziol, R. E-mail: chony@iaa.es E-mail: rcoziol@astro.ugto.mx

    2010-03-15

    We have conducted a new spectroscopic survey to characterize the nature of nuclear activity in Hickson compact group (HCG) galaxies and establish its frequency. We have obtained new intermediate-resolution optical spectroscopy for 200 member galaxies and corrected for underlying stellar population contamination using galaxy templates. Spectra for 11 additional galaxies have been acquired from the ESO and 6dF public archives, and emission-line ratios have been taken from the literature for 59 more galaxies. Here we present the results of our classification of the nuclear activity for 270 member galaxies, which belong to a well-defined sample of 64 HCGs. We found a large fraction of galaxies, 63%, with emission lines. Using standard diagnostic diagrams, 45% of the emission-line galaxies were classified as pure active galactic nuclei (AGNs), 23% as Transition Objects (TOs), and 32% as star-forming nuclei (SFNs). In the HCGs, the AGN activity appears as the most frequent activity type. Adopting the interpretation that in TOs a low-luminosity AGN coexists with circumnuclear star formation, the fraction of galaxies with an AGN could rise to 42% of the whole sample. The low frequency (20%) of SFNs confirms that there is no star formation enhancement in HCGs. After extinction correction, we found a median AGN H{alpha} luminosity of 7.1 x 10{sup 39} erg s{sup -1}, which implies that AGNs in HCG have a characteristically low luminosity. This result added to the fact that there is an almost complete absence of broad-line AGNs in compact groups (CGs) as found by MartInez et al. and corroborated in this study for HCGs, is consistent with very few gas left in these galaxies. In general, therefore, what may characterize the level of activity in CGs is a severe deficiency of gas.

  6. The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose

    SciTech Connect

    Penza, M.; Jeremic, M.; Marrazzo, E.; Maggi, A.; Ciana, P.; Rando, G.; Grigolato, P.G.; Di Lorenzo, D.

    2011-08-15

    Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5 {mu}g/kg). At higher doses (50-500 {mu}g/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ER{alpha} or ER{beta}, TBT (in a dose range of 1-100 nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ER{alpha} in undifferentiated preadipocytic cells and by ER{beta} in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed. - Research Highlights: > The environmental organotin tributyltin chloride shows dose-dependent estrogenic and adipogenic activities in mice. > The duration and extent of these effects depend on the sex and the dose of the compound. > The estrogenic and adipogenic effects of TBT occur at doses closed to

  7. Bronchodilator activity of xanthine derivatives substituted with functional groups at the 1- or 7-position.

    PubMed

    Miyamoto, K; Yamamoto, Y; Kurita, M; Sakai, R; Konno, K; Sanae, F; Ohshima, T; Takagi, K; Hasegawa, T; Iwasaki, N

    1993-05-14

    Xanthine derivatives with several functional groups at the 1- or 7-position were synthesized, and their pharmacological activities in guinea pigs were studied. In general, the in vitro tracheal relaxant action and positive chronotropic action of 3-propylxanthines were increased by substitutions with nonpolar functional groups at the 1-position, but decreased by any substitution at the 7-position. On the other hand, because positive chronotropic actions of substituents with allyl, aminoalkyl, alkoxyalkyl, and normal alkyl groups were much less than tracheal muscle became very high with substitutions of 3'-butenyl, (dimethylamino)ethyl, 2'-ethoxyethyl, 3'-methoxypropyl, and n-propyl groups at the 1-position and of 2'-ethoxyethyl, 2'-oxopropyl, and n-propyl groups at the 7-position, compared with theophylline and the corresponding unsubstituted xanthines, 3-propylxanthine and 1-methyl-3-propylxanthine. When compounds were intraduodenally administered to the guinea pig, 1-(2'-ethoxyethyl)-, 1-(3'-methoxypropyl)-, 1-(3'-butenyl)-, and 1-[(dimethylamino)-ethyl]-3-propylxanthines, 1-methyl-7-(2'-oxopropyl)-3-propylxanthine, and denbufylline (1,3-di-n-butyl-7-(2'-oxopropyl)xanthine) effectively inhibited the acetylcholine-induced bronchospasm without heart stimulation or central nervous system-stimulation at the effective dosage range. Particularly, the bronchodilatory effect of 1-(2'-ethoxyethyl)-3-propylxanthine was much stronger and more continuous than those of theophylline and pentoxifylline. On the other hand, there were certain relationships among the in vitro tracheal relaxant activities of these compounds, their affinities for adenosine (A1) receptors in the brain membrane, and their inhibition of cyclic AMP-phosphodiesterase (PDE) in the tracheal muscle. The affinity for A2 receptors of these compounds was very low or negligible. This suggests that both the action on A1 receptors or interaction with adenosine and the cyclic AMP-PDE inhibitory activity contribute

  8. Structure-activity relationship study of vitamin D analogs with oxolane group in their side chain.

    PubMed

    Belorusova, Anna Y; Martínez, Andrea; Gándara, Zoila; Gómez, Generosa; Fall, Yagamare; Rochel, Natacha

    2017-04-02

    Synthetic analogs of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) have been developed with the goal of improving the biological profile of the natural hormone for therapeutic applications. Derivatives of 1,25(OH)2D3 with the oxolane moiety branched in the side chain at carbon C20, act as Vitamin D nuclear Receptor (VDR) superagonists being several orders of magnitude more active than the natural ligand. Here, we describe the synthesis and biological evaluation of three diastereoisomers of (1S, 3R)-Dihydroxy-(20S)-[(2″-hydroxy-2″-propyl)-tetrahydrofuryl]-22,23,24,25,26,27-hexanor-1α-hydroxyvitamin D3, with different stereochemistry at positions C2 and C5 of the oxolane ring branched at carbon C22 (1, C2RC5S; 2, C2SC5R; 3, C2SC5S). These compounds act as weak VDR agonist in transcriptional assays with compound 3 being the most active. X-ray crystallographic analysis of the VDR ligand-binding domain accommodating the three compounds indicates that the oxolane group branched at carbon C22 is not constrained as in case of compound with oxolane group branched at C20 leading to the loss of interactions of the triene group and increased flexibility of the C/D-rings and of the side chain.

  9. Group planarian sudden mortality: Is the threshold around global geomagnetic activity ≥K6?

    PubMed

    Murugan, Nirosha J; Karbowski, Lukasz M; Mekers, William Ft; Persinger, Michael A

    2015-01-01

    Sudden deaths in groups of animals have been observed by field and laboratory biologists. We have measured mortalities in large group-housed planarian during the infrequent periods of very intense geomagnetic activity. In 13 separate episodes over the last 5 y we have observed the sudden death in our laboratory of hundreds of planarian if their density was about 1 worm per cc and the global geomagnetic activity was K≥6 the day before or the day of the observation of the mortality. Such mortality never occurred in other conditions or days. Both estimates of the "magnetic moment" of a planarian in magnetic fields above this threshold of sustained magnetic flux density as well as the magnetic energy within the planarian volume predict values that could affect phenomenon associated with the total numbers of pH-dependent charges within each worm. These conditions could affect the Levin-Burr bioelectrical signals and networks that affect patterning information and sustainability in whole living systems. The establishment of a central reservoir for the report of these transient events might allow Life Scientists to more fully appreciate the impact of these pervasive global stimuli upon dense groups of animals.

  10. Nonequilibrium dynamics of active matter with correlated noise: A dynamical renormalization group study

    NASA Astrophysics Data System (ADS)

    Kachan, Devin; Levine, Alex; Bruinsma, Robijn

    2014-03-01

    Biology is rife with examples of active materials - soft matter systems driven into nonequilibrium steady states by energy input at the micro scale. For example, solutions of active micron scale swimmers produce active fluids showing phenomena reminiscent of turbulent convection at low Reynolds number; cytoskeletal networks driven by endogenous molecular motors produce active solids whose mechanics and low frequency strain fluctuations depend sensitively on motor activity. One hallmark of these systems is that they are driven at the micro scale by temporally correlated forces. In this talk, we study how correlated noise at the micro scale leads to novel long wavelength and long time scale dynamics at the macro scale in a simple model system. Specifically, we study the fluctuations of a ϕ4 scalar field obeying model A dynamics and driven by noise with a finite correlation time τ. We show that the effective dynamical system at long length and time scales is driven by white noise with a renormalized amplitude and renormalized transport coefficients. We discuss the implications of this result for a broad class of active matter systems driven at the micro scale by colored noise.

  11. Practical tethering of vitamin B1 on a silica surface via its phosphate group and evaluation of its activity.

    PubMed

    Vartzouma, Ch; Louloudi, M; Butler, I S; Hadjiliadis, N

    2002-03-07

    A convenient immobilization of thiamine pyrophosphate molecules on a silica surface through the phosphate group is developed, leading to a very active heterogenized biocatalyst for pyruvate decarboxylation.

  12. Activation of carboxyl group with cyanate: peptide bond formation from dicarboxylic acids.

    PubMed

    Danger, Grégoire; Charlot, Solenne; Boiteau, Laurent; Pascal, Robert

    2012-06-01

    The reaction of cyanate with C-terminal carboxyl groups of peptides in aqueous solution was considered as a potential pathway for the abiotic formation of peptide bonds under the condition of the primitive Earth. The catalytic effect of dicarboxylic acids on cyanate hydrolysis was definitely attributed to intramolecular nucleophilic catalysis by the observation of the 1H-NMR signal of succinic anhydride when reacting succinic acid with KOCN in aqueous solution (pH 2.2-5.5). The formation of amide bonds was noticed when adding amino acids or amino acid derivatives into the solution. The reaction of N-acyl aspartic acid derivatives was observed to proceed similarly and the scope of the cyanate-promoted reaction was analyzed from the standpoint of prebiotic peptide formation. The role of cyanate in activating peptide C-terminus constitutes a proof of principle that intramolecular reactions of adducts of peptides C-terminal carboxyl groups with activating agents represent a pathway for peptide activation in aqueous solution, the relevance of which is discussed in connexion with the issue of the emergence of homochirality.

  13. Transformation of Lettuce with rol ABC Genes: Extracts Show Enhanced Antioxidant, Analgesic, Anti-Inflammatory, Antidepressant, and Anticoagulant Activities in Rats.

    PubMed

    Ismail, Hammad; Dilshad, Erum; Waheed, Mohammad Tahir; Mirza, Bushra

    2017-03-01

    Lettuce is an edible crop that is well known for dietary and antioxidant benefits. The present study was conducted to investigate the effects of rol ABC genes on antioxidant and medicinal potential of lettuce by Agrobacterium-mediated transformation. Transgene integration and expression was confirmed through PCR and real-time RT-PCR, respectively. The transformed plants showed 91-102 % increase in total phenolic contents and 53-65 % increase in total flavonoid contents compared to untransformed plants. Total antioxidant capacity and total reducing power increased up to 112 and 133 % in transformed plants, respectively. Results of DPPH assay showed maximum 51 % increase, and lipid peroxidation assay exhibited 20 % increase in antioxidant activity of transformed plants compared to controls. Different in vivo assays were carried out in rats. The transgenic plants showed up to 80 % inhibition in both hot plate analgesic assay and carrageenan-induced hind paw edema test, while untransformed plants showed only 45 % inhibition. Antidepressant and anticoagulant potential of transformed plants was also significantly enhanced compared to untransformed plants. Taken together, the present work highlights the use of rol genes to enhance the secondary metabolite production in lettuce and improve its analgesic, anti-inflammatory, antidepressant, and anticoagulatory properties.

  14. Mechanistic considerations on contact-active antimicrobial surfaces with controlled functional group densities.

    PubMed

    Bieser, Arno M; Tiller, Joerg C

    2011-04-08

    A series of N-alkyl-N,N-dimethyldeoxyammonium celluloses is synthesized by converting tosyl celluloses with DBA and DDA, respectively. Surface coatings with these water-insoluble derivatives contain well-defined densities of quaternary ammonium functions and nonactive hydrophobic and hydrophilic groups. It is shown that the antimicrobial activity of such surfaces against S. aureus requires a delicate balance between DDA, BDA, and hydrophobic groups. A mechanism is proposed that involves the selective adhesion of anionic phospholipids from the bacterial cell membrane. This so-called phospholipid sponge effect is supported by the fact that all coatings could be deactivated by treatment with SDS or negatively charged phospholipids, but not with neutral phospholipids.

  15. Modified high-density lipoproteins by artificial sweetener, aspartame, and saccharin, showed loss of anti-atherosclerotic activity and toxicity in zebrafish.

    PubMed

    Kim, Jae-Yong; Park, Ki-Hoon; Kim, Jihoe; Choi, Inho; Cho, Kyung-Hyun

    2015-01-01

    Safety concerns have been raised regarding the association of chronic consumption of artificial sweeteners (ASs) with metabolic disorders, especially in the heart and brain. There has been no information on the in vivo physiological effects of AS consumption in lipoprotein metabolism. High-dosage treatment (final 25, 50, and 100 mM) with AS (aspartame, acesulfame K, and saccharin) to human high-density lipoprotein (HDL) induced loss of antioxidant ability along with elevated atherogenic effects. Aspartame-treated HDL3 (final 100 mM) almost all disappeared due to putative proteolytic degradation. Aspartame- and saccharin-treated HDL3 showed more enhanced cholesteryl ester transfer activity, while their antioxidant ability was disappeared. Microinjection of the modified HDL3 exacerbated the inflammatory death in zebrafish embryos in the presence of oxLDL. These results show that AS treatment impaired the beneficial functions of HDL, resulting in loss of antioxidant and anti-atherogenic activities. These results suggest that aspartame and saccharin could be toxic to the human circulation system as well as embryonic development via impairment of lipoprotein function.

  16. C-terminal truncated cannabinoid receptor 1 coexpressed with G protein trimer in Sf9 cells exists in a precoupled state and shows constitutive activity.

    PubMed

    Chillakuri, Chandramouli Reddy; Reinhart, Christoph; Michel, Hartmut

    2007-12-01

    We have investigated the existence of a precoupled form of the distal C-terminal truncated cannabinoid receptor 1 (CB1-417) and heterotrimeric G proteins in a heterologous insect cell expression system. CB1-417 showed higher production levels than the full-length receptor. The production levels obtained in our expression system were double the values reported in the literature. We also observed that at least the distal C-terminus of the receptor was not involved in receptor dimerization, as was predicted in the literature. Using fluorescence resonance energy transfer, we found that CB1-417 and Galpha(i1)beta(1)gamma(2) proteins were colocalized in the cells. GTPgammaS binding assays with the Sf9 cell membranes containing CB1-417 and the G protein trimer showed that the receptor could constitutively activate the Galpha(i1) protein in the absence of agonists. A CB1-specific antagonist (SR 141716A) inhibited this constitutive activity of the truncated receptor. We found that the CB1-417/Galpha(i1)beta(1)gamma(2) complex could be solubilized from Sf9 cell membranes and coimmunoprecipitated. In this study, we have proven that the receptor and G proteins can be coexpressed in higher yields using Sf9 cells, and that the protein complex is stable in detergent solution. Thus, our system can be used to produce sufficient quantities of the protein complex to start structural studies.

  17. Catechins and procyanidins of Ginkgo biloba show potent activities towards the inhibition of β-amyloid peptide aggregation and destabilization of preformed fibrils.

    PubMed

    Xie, Haiyan; Wang, Jing-Rong; Yau, Lee-Fong; Liu, Yong; Liu, Liang; Han, Quan-Bin; Zhao, Zhongzhen; Jiang, Zhi-Hong

    2014-04-22

    Catechins and procyanidins, together with flavonoid glycosides and terpene trilactones, are three important categories of components in the standard extract of Ginkgo biloba leaves (EGb761). In this research, catechins and proanthocyanidins were found to exist in both the extract of Ginkgo leaves and Ginkgo products. By comparing with reference compounds, six of them were identified as (+)-catechin, (-)-epicatechin, (-)-gallocatechin, (-)-epigallocatechin and procyanidins B1 and B3. The activities of these polyphenols in the inhibition of Aβ42 aggregation and the destabilization of preformed fibrils were evaluated using biochemical assays, which showed that all six of the polyphenols, as well as a fraction of the extract of Ginkgo biloba leaves (EGb) containing catechins and procyanidins, exerted potent inhibitory activities towards Aβ42 aggregation and could also destabilize the performed fibrils. Catechins and procyanidins can therefore be regarded as the potent active constituents of EGb761 in terms of their inhibition of Aβ42 aggregation and destabilization of the fibrils. Although quantitative mass spectroscopic analysis revealed that the catechins and procyanidins are only present in low concentrations in EGb761, these components should be studied in greater detail because of their potent inhibitory effects towards Aβ42 aggregation and their ability to destabilize preformed fibrils, especially during the quality control of Ginkgo leaves and the manufacture of Ginkgo products.

  18. Camptothecin analog (CPT-11)-sensitive human pancreatic tumor cell line QGP-1N shows resistance to SN-38, an active metabolite of CPT-11.

    PubMed

    Takeda, S; Shimazoe, T; Kuga, H; Sato, K; Kono, A

    1992-10-15

    In the course of our study to determine the cross-sensitivity between CPT-11 and its active metabolite, SN-38, we found a SN-38-resistant human pancreatic tumor cell line, QGP-1N, which shows sensitivity to CPT-11. The IC50 of SN-38 was 152 times greater for QGP-1N than for SUIT-2, also a human pancreatic tumor cell line, whose IC50 of CPT-11 was similar to that for QGP-1N. The uptakes of CPT-11 and SN-38 and the intracellular conversion of CPT-11 to SN-38 could not explain the difference in sensitivity. DNA synthesis of QGP-1N cells was inhibited by CPT-11 which did not affect that of SUIT-2, while SN-38 inhibited the DNA synthesis of SUIT-2 at lower concentrations than that of QGP-1N. The inhibition test of topoisomerase I catalytic activity by CPT-11 or SN-38 revealed no difference in the biochemical properties of the topoisomerase I enzymes to the compounds between these two cell lines. These results indicate that CPT-11 should have its own inhibitory effect on DNA synthesis through a yet unknown mechanism in QGP-1N cells, although SN-38 plays an essential role in the antitumor activity of CPT-11 in SUIT-2 cells. In some cases, the antitumor effect of CPT-11 might be consequent not only on SN-38 but also on CPT-11 itself.

  19. Cytokinin-Deficient Transgenic Arabidopsis Plants Show Multiple Developmental Alterations Indicating Opposite Functions of Cytokinins in the Regulation of Shoot and Root Meristem Activity

    PubMed Central

    Werner, Tomáš; Motyka, Václav; Laucou, Valérie; Smets, Rafaël; Van Onckelen, Harry; Schmülling, Thomas

    2003-01-01

    Cytokinins are hormones that regulate cell division and development. As a result of a lack of specific mutants and biochemical tools, it has not been possible to study the consequences of cytokinin deficiency. Cytokinin-deficient plants are expected to yield information about processes in which cytokinins are limiting and that, therefore, they might regulate. We have engineered transgenic Arabidopsis plants that overexpress individually six different members of the cytokinin oxidase/dehydrogenase (AtCKX) gene family and have undertaken a detailed phenotypic analysis. Transgenic plants had increased cytokinin breakdown (30 to 45% of wild-type cytokinin content) and reduced expression of the cytokinin reporter gene ARR5:GUS (β-glucuronidase). Cytokinin deficiency resulted in diminished activity of the vegetative and floral shoot apical meristems and leaf primordia, indicating an absolute requirement for the hormone. By contrast, cytokinins are negative regulators of root growth and lateral root formation. We show that the increased growth of the primary root is linked to an enhanced meristematic cell number, suggesting that cytokinins control the exit of cells from the root meristem. Different AtCKX-green fluorescent protein fusion proteins were localized to the vacuoles or the endoplasmic reticulum and possibly to the extracellular space, indicating that subcellular compartmentation plays an important role in cytokinin biology. Analyses of promoter:GUS fusion genes showed differential expression of AtCKX genes during plant development, the activity being confined predominantly to zones of active growth. Our results are consistent with the hypothesis that cytokinins have central, but opposite, regulatory functions in root and shoot meristems and indicate that a fine-tuned control of catabolism plays an important role in ensuring the proper regulation of cytokinin functions. PMID:14555694

  20. The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose.

    PubMed

    Penza, M; Jeremic, M; Marrazzo, E; Maggi, A; Ciana, P; Rando, G; Grigolato, P G; Di Lorenzo, D

    2011-08-15

    Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5μg/kg). At higher doses (50-500μg/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ERα or ERβ, TBT (in a dose range of 1-100nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ERα in undifferentiated preadipocytic cells and by ERβ in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed.

  1. Alpha-momorcharin, a RIP produced by bitter melon, enhances defense response in tobacco plants against diverse plant viruses and shows antifungal activity in vitro.

    PubMed

    Zhu, Feng; Zhang, Ping; Meng, Yan-Fa; Xu, Fei; Zhang, Da-Wei; Cheng, Jian; Lin, Hong-Hui; Xi, De-Hui

    2013-01-01

    Alpha-momorcharin (α-MMC) is type-1 ribosome inactivating proteins (RIPs) with molecular weight of 29 kDa and has lots of biological activity. Our recent study indicated that the α-MMC purified from seeds of Momordica charantia exhibited distinct antiviral and antifungal activity. Tobacco plants pre-treated with 0.5 mg/mL α-MMC 3 days before inoculation with various viruses showed less-severe symptom and less reactive oxygen species (ROS) accumulation compared to that inoculated with viruses only. Quantitative real-time PCR analysis revealed that the replication levels of viruses were lower in the plants treated with the α-MMC than control plants at 15 days post inoculation. Moreover, the coat protein expression of viruses was almost completely inhibited in plants which were treated with the α-MMC compared with control plants. Furthermore, the SA-responsive defense-related genes including non-expressor of pathogenesis-related genes 1 (NPR1), PR1, PR2 were up-regulated and activities of some antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) were increased after the α-MMC treatment. In addition, the α-MMC (500 μg/mL) revealed remarkable antifungal effect against phytopathogenic fungi, in the growth inhibition range 50.35-67.21 %, along with their MIC values ranging from 100 to 500 μg/mL. The α-MMC had also a strong detrimental effect on spore germination of all the tested plant pathogens along with concentration as well as time-dependent kinetic inhibition of Sclerotinia sclerotiorum. The α-MMC showed a remarkable antiviral and antifungal effect and hence could possibly be exploited in crop protection for controlling certain important plant diseases.

  2. Novel Gal3 proteins showing altered Gal80p binding cause constitutive transcription of Gal4p-activated genes in Saccharomyces cerevisiae.

    PubMed Central

    Blank, T E; Woods, M P; Lebo, C M; Xin, P; Hopper, J E

    1997-01-01

    Gal4p-mediated activation of galactose gene expression in Saccharomyces cerevisiae normally requires both galactose and the activity of Gal3p. Recent evidence suggests that in cells exposed to galactose, Gal3p binds to and inhibits Ga180p, an inhibitor of the transcriptional activator Gal4p. Here, we report on the isolation and characterization of novel mutant forms of Gal3p that can induce Gal4p activity independently of galactose. Five mutant GAL3(c) alleles were isolated by using a selection demanding constitutive expression of a GAL1 promoter-driven HIS3 gene. This constitutive effect is not due to overproduction of Gal3p. The level of constitutive GAL gene expression in cells bearing different GAL3(c) alleles varies over more than a fourfold range and increases in response to galactose. Utilizing glutathione S-transferase-Gal3p fusions, we determined that the mutant Gal3p proteins show altered Gal80p-binding characteristics. The Gal3p mutant proteins differ in their requirements for galactose and ATP for their Gal80p-binding ability. The behavior of the novel Gal3p proteins provides strong support for a model wherein galactose causes an alteration in Gal3p that increases either its ability to bind to Gal80p or its access to Gal80p. With the Gal3p-Gal80p interaction being a critical step in the induction process, the Gal3p proteins constitute an important new reagent for studying the induction mechanism through both in vivo and in vitro methods. PMID:9111326

  3. Dual fatty acid synthase and HER2 signaling blockade shows marked antitumor activity against breast cancer models resistant to anti-HER2 drugs.

    PubMed

    Blancafort, Adriana; Giró-Perafita, Ariadna; Oliveras, Glòria; Palomeras, Sònia; Turrado, Carlos; Campuzano, Òscar; Carrión-Salip, Dolors; Massaguer, Anna; Brugada, Ramon; Palafox, Marta; Gómez-Miragaya, Jorge; González-Suárez, Eva; Puig, Teresa

    2015-01-01

    Blocking the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of HER2-positive breast carcinoma cells. The hypothesis is that blocking FASN, in combination with anti-HER2 signaling agents, would be an effective antitumor strategy in preclinical HER2+ breast cancer models of trastuzumab and lapatinib resistance. We developed and molecularly characterized in vitro HER2+ models of resistance to trastuzumab (SKTR), lapatinib (SKLR) and both (SKLTR). The cellular interactions of combining anti-FASN polyphenolic compounds (EGCG and the synthetic G28UCM) with anti-HER2 signaling drugs (trastuzumab plus pertuzumab and temsirolimus) were analyzed. Tumor growth inhibition after treatment with EGCG, pertuzumab, temsirolimus or the combination was evaluated in two in vivo orthoxenopatients: one derived from a HER2+ patient and another from a patient who relapsed on trastuzumab and lapatinib-based therapy. SKTR, SKLR and SKLTR showed hyperactivation of EGFR and p-ERK1/2 and PI3KCA mutations. Dual-resistant cells (SKLTR) also showed hyperactivation of HER4 and recovered levels of p-AKT compared with mono-resistant cells. mTOR, p-mTOR and FASN expression remained stable in SKTR, SKLR and SKLTR. In vitro, anti-FASN compounds plus pertuzumab showed synergistic interactions in lapatinib- and dual- resistant cells and improved the results of pertuzumab plus trastuzumab co-treatment. FASN inhibitors combined with temsirolimus displayed the strongest synergistic interactions in resistant cells. In vivo, both orthoxenopatients showed strong response to the antitumor activity of the combination of EGCG with pertuzumab or temsirolimus, without signs of toxicity. We showed that the simultaneous blockade of FASN and HER2 pathways is effective in cells and in breast cancer models refractory to anti-HER2 therapies.

  4. Dual Fatty Acid Synthase and HER2 Signaling Blockade Shows Marked Antitumor Activity against Breast Cancer Models Resistant to Anti-HER2 Drugs

    PubMed Central

    Blancafort, Adriana; Giró-Perafita, Ariadna; Oliveras, Glòria; Palomeras, Sònia; Turrado, Carlos; Campuzano, Òscar; Carrión-Salip, Dolors; Massaguer, Anna; Brugada, Ramon; Palafox, Marta; Gómez-Miragaya, Jorge; González-Suárez, Eva; Puig, Teresa

    2015-01-01

    Blocking the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of HER2-positive breast carcinoma cells. The hypothesis is that blocking FASN, in combination with anti-HER2 signaling agents, would be an effective antitumor strategy in preclinical HER2+ breast cancer models of trastuzumab and lapatinib resistance. We developed and molecularly characterized in vitro HER2+ models of resistance to trastuzumab (SKTR), lapatinib (SKLR) and both (SKLTR). The cellular interactions of combining anti-FASN polyphenolic compounds (EGCG and the synthetic G28UCM) with anti-HER2 signaling drugs (trastuzumab plus pertuzumab and temsirolimus) were analyzed. Tumor growth inhibition after treatment with EGCG, pertuzumab, temsirolimus or the combination was evaluated in two in vivo orthoxenopatients: one derived from a HER2+ patient and another from a patient who relapsed on trastuzumab and lapatinib-based therapy. SKTR, SKLR and SKLTR showed hyperactivation of EGFR and p-ERK1/2 and PI3KCA mutations. Dual-resistant cells (SKLTR) also showed hyperactivation of HER4 and recovered levels of p-AKT compared with mono-resistant cells. mTOR, p-mTOR and FASN expression remained stable in SKTR, SKLR and SKLTR. In vitro, anti-FASN compounds plus pertuzumab showed synergistic interactions in lapatinib- and dual- resistant cells and improved the results of pertuzumab plus trastuzumab co-treatment. FASN inhibitors combined with temsirolimus displayed the strongest synergistic interactions in resistant cells. In vivo, both orthoxenopatients showed strong response to the antitumor activity of the combination of EGCG with pertuzumab or temsirolimus, without signs of toxicity. We showed that the simultaneous blockade of FASN and HER2 pathways is effective in cells and in breast cancer models refractory to anti-HER2 therapies. PMID:26107737

  5. Synthesis, characterization and catalytic activity of acid-base bifunctional materials through protection of amino groups

    SciTech Connect

    Shao, Yanqiu; Liu, Heng; Yu, Xiaofang; Guan, Jingqi; Kan, Qiubin

    2012-03-15

    Graphical abstract: Acid-base bifunctional mesoporous material SO{sub 3}H-SBA-15-NH{sub 2} was successfully synthesized under low acidic medium through protection of amino groups. Highlights: Black-Right-Pointing-Pointer The acid-base bifunctional material SO{sub 3}H-SBA-15-NH{sub 2} was successfully synthesized through protection of amino groups. Black-Right-Pointing-Pointer The obtained bifunctional material was tested for aldol condensation. Black-Right-Pointing-Pointer The SO{sub 3}H-SBA-15-NH{sub 2} catalyst containing amine and sulfonic acid groups exhibited excellent acid-basic properties. -- Abstract: Acid-base bifunctional mesoporous material SO{sub 3}H-SBA-15-NH{sub 2} was successfully synthesized under low acidic medium through protection of amino groups. X-ray diffraction (XRD), N{sub 2} adsorption-desorption, transmission electron micrographs (TEM), back titration, {sup 13}C magic-angle spinning (MAS) NMR and {sup 29}Si magic-angle spinning (MAS) NMR were employed to characterize the synthesized materials. The obtained bifunctional material was tested for aldol condensation reaction between acetone and 4-nitrobenzaldehyde. Compared with monofunctional catalysts of SO{sub 3}H-SBA-15 and SBA-15-NH{sub 2}, the bifunctional sample of SO{sub 3}H-SBA-15-NH{sub 2} containing amine and sulfonic acid groups exhibited excellent acid-basic properties, which make it possess high activity for the aldol condensation.

  6. Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

    PubMed

    Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

    2014-02-05

    The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production.

  7. X-ray structure of Candida antarctica lipase A shows a novel lid structure and a likely mode of interfacial activation.

    PubMed

    Ericsson, Daniel J; Kasrayan, Alex; Johansson, Patrik; Bergfors, Terese; Sandström, Anders G; Bäckvall, Jan-E; Mowbray, Sherry L

    2008-02-08

    In nature, lipases (EC 3.1.1.3) catalyze the hydrolysis of triglycerides to form glycerol and fatty acids. Under the appropriate conditions, the reaction is reversible, and so biotechnological applications commonly make use of their capacity for esterification as well as for hydrolysis of a wide variety of compounds. In the present paper, we report the X-ray structure of lipase A from Candida antarctica, solved by single isomorphous replacement with anomalous scattering, and refined to 2.2-A resolution. The structure is the first from a novel family of lipases. Contrary to previous predictions, the fold includes a well-defined lid as well as a classic alpha/beta hydrolase domain. The catalytic triad is identified as Ser184, Asp334 and His366, which follow the sequential order considered to be characteristic of lipases; the serine lies within a typical nucleophilic elbow. Computer docking studies, as well as comparisons to related structures, place the carboxylate group of a fatty acid product near the serine nucleophile, with the long lipid tail closely following the path through the lid that is marked by a fortuitously bound molecule of polyethylene glycol. For an ester substrate to bind in an equivalent fashion, loop movements near Phe431 will be required, suggesting the primary focus of the conformational changes required for interfacial activation. Such movements will provide virtually unlimited access to solvent for the alcohol moiety of an ester substrate. The structure thus provides a basis for understanding the enzyme's preference for acyl moieties with long, straight tails, and for its highly promiscuous acceptance of widely different alcohol and amine moieties. An unconventional oxyanion hole is observed in the present structure, although the situation may change during interfacial activation.

  8. [Design, synthesis, and biological activities of histone deacetylase inhibitors with diketo ester as zinc binding group].

    PubMed

    Lu, Hui; Su, Hong; Yang, Bo; You, Qi-Dong

    2011-03-01

    Histone deacetylases (HDACs) inhibition causes hyperacetylation of histones leading to growth arrest, differentiation and apoptosis of tumor cells, representing a new strategy in cancer therapy. Many of previously reported HDACs inhibitors are hydroxamic acid derivatives, which could chelate the zinc ion in the active site in a bidentate fashion. However, hydroxamic acids occasionally have produced problems such as poor pharmacokinetics, severe toxicity and low selectivity. Herein we describe the identification of a new series of non-hydroxamate HDACs inhibitors bearing diketo ester moieties as zinc binding group. HDACs inhibition assay and antiproliferation assays in vitro against multiple cancer cell lines were used for evaluation. These compounds displayed low antiproliferative activity against solid tumor cells, while good antiproliferative activity against human leukemic monocyte lymphoma cell line U937. Compound CPUYS707 is the best with GI50 value of 0.31 micromol x L(-1) against U937 cells, which is more potent than SAHA and MS-275. HDACs inhibition activity of these compounds is lower than that expected, further evaluation is needed.

  9. Structure-activity relationships among the kanamycin aminoglycosides: role of ring I hydroxyl and amino groups.

    PubMed

    Salian, Sumantha; Matt, Tanja; Akbergenov, Rashid; Harish, Shinde; Meyer, Martin; Duscha, Stefan; Shcherbakov, Dmitri; Bernet, Bruno B; Vasella, Andrea; Westhof, Eric; Böttger, Erik C

    2012-12-01

    The kanamycins form an important subgroup of the 4,6-disubstituted 2-deoxystreptamine aminoglycoside antibiotics, comprising kanamycin A, kanamycin B, tobramycin, and dibekacin. These compounds interfere with protein synthesis by targeting the ribosomal decoding A site, and they differ in the numbers and locations of amino and hydroxy groups of the glucopyranosyl moiety (ring I). We synthesized kanamycin analogues characterized by subtle variations of the 2' and 6' substituents of ring I. The functional activities of the kanamycins and the synthesized analogues were investigated (i) in cell-free translation assays on wild-type and mutant bacterial ribosomes to study drug-target interaction, (ii) in MIC assays to assess antibacterial activity, and (iii) in rabbit reticulocyte translation assays to determine activity on eukaryotic ribosomes. Position 2' forms an intramolecular H bond with O5 of ring II, helping the relative orientations of the two rings with respect to each other. This bond becomes critical for drug activity when a 6'-OH substituent is present.

  10. Healthful Eating and Physical Activity in the Home Environment: Results from Multi-Family Focus Groups

    PubMed Central

    Berge, Jerica M.; Arikian, Aimee; Doherty, William J.; Neumark-Sztainer, Dianne

    2012-01-01

    Objective To explore multiple family members’ perceptions of risk and protective factors for healthy eating and physical activity in the home. Design Ten multi-family focus groups were conducted with 26 families. Setting Community setting. Participants Primarily Black and White families. Family members (n = 103) were between the ages of 8–61 years. Analysis A grounded hermeneutic approach. Phenomenon of Interest Risk and protective factors for healthy eating and physical activity in the home environment. Results Ten major themes were identified by family members related to health behaviors in the home environment, including: (a) accessibility to healthy foods and activity, (b) time constraints, (c) stage of youth development, (d) individual investment in health behaviors, (e) family investment in health behaviors, (f) family meals and shared activities, (g) parent modeling, (h) making health behaviors fun, (i) making health behaviors part of the family lifestyle, and (j) community investment in family health behaviors. Conclusions and Implications This study identified the importance of the family system and the reciprocal influences within the home environment on health behaviors. In addition, individual and community-level suggestions were identified. Insights from the families provide leads for future research and ideas for the prevention of youth obesity. PMID:22192951

  11. Group-specific small-subunit rRNA hybridization probes to characterize filamentous foaming in activated sludge systems.

    PubMed Central

    de los Reyes, F L; Ritter, W; Raskin, L

    1997-01-01

    Foaming in activated sludge systems is characterized by the formation of a thick, chocolate brown-colored scum that floats on the surface of aeration basins and secondary clarifiers. These viscous foams have been associated with the presence of filamentous mycolic acid-containing actinomycetes. To aid in evaluating the microbial representation in foam, we developed and characterized group-, genus-, and species-specific oligonucleotide probes targeting the small subunit rRNA of the Mycobacterium complex, Gordona spp., and Gordona (Nocardia) amarae, respectively. The use of a universal base analog, 5-nitroindole, in oligonucleotide probe design was evaluated by comparing the characteristics of two different versions of the Mycobacterium complex probe. The temperature of dissociation of each probe was determined. Probe specificity studies with a diverse collection of 67 target and nontarget rRNAs demonstrated the specificity of the probes to the target groups. Whole-cell hybridizations with fluorescein- and rhodamine-labeled probes were performed with pure cultures of various members of the Mycobacterium complex as well as with environmental samples from a full-scale activated sludge plant which experienced foaming. Quantitative membrane hybridizations with activated sludge and anaerobic digester foam showed that 15.0 to 18.3% of the total small-subunit rRNAs could be attributed to members of the Mycobacterium complex, of which a vast majority consisted of Gordona rRNA. Several G. amarae strains made up only a very small percentage of the Gordona strains present. We demonstrated that group-specific rRNA probes are useful tools for the in situ monitoring and identification of filamentous bacteria in activated sludge systems. PMID:9055425

  12. Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

    PubMed Central

    Zhang, Xiaoling; Shang, Xun; Guo, Fukun; Murphy, Kim; Kirby, Michelle; Kelly, Patrick; Reeves, Lilith; Smith, Franklin O.; Williams, David A.

    2008-01-01

    Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway. PMID:18565850

  13. Final Report: Main Group Element Chemistry in Service of Hydrogen Storage and Activation

    SciTech Connect

    David A. Dixon; Anthony J. Arduengo, III

    2010-09-30

    goal was met in terms of reducing the number of costly experiments and helping to focus the experimental effort on the potentially optimal targets. We have used computational chemistry approaches to predict the thermodynamic properties of a wide range of compounds containing boron, nitrogen, hydrogen, and other elements as appropriate including carbon. These calculations were done in most cases with high level molecular orbital theory methods that have small error bars on the order of ± 1 to 2 kcal/mol. The results were used to benchmark more approximate methods such as density functional theory for larger systems and for database development. We predicted reliable thermodynamics for thousands of compounds for release and regeneration schemes to aid/guide materials design and process design and simulation. These are the first reliable computed values for these compounds and for many represent the only available values. Overall, the computational results have provided us with new insights into the chemistry of main group and organic-base chemical hydrogen systems from the release of hydrogen to the regeneration of spent fuel. A number of experimental acc