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Sample records for jakub ko priit

  1. [Jakub Barner (1640-1683) and his Chymia philosophica (1698): side notes on the publication of the Polish translation].

    PubMed

    Prinke, Rafat T

    2014-01-01

    The translation of Chymiaphilosophica by Jakub Barner is the second publication in Polish historiography of a printed source work on early modem chemistry (alchemy) written by a Polish citizen, well known and influencial across Europe (the first such translation comprised the treatises of Michael Sendivogius). This admirable initiative of unquestionable value to Polish historians of science resulted in an elegantly published volume, with an extensive introduction and useful appendices. The language of the translation is pleasant to read, retaining the spirit of the original by means of a moderate use of archaisms and generally accurate selection of proper terminology. A closer comparison of some fragments of the translation reveals, however, that it omits essential words, phrases and even entire sentences. The translation itself is occasionally incorrect as well, completely changing the meaning of the author's text and distorting his intentions, thereby undermining the reliability of the Polish translation as a whole. In the factual layer, identifying both chemical substances and (especially) the names of the authors cited by Barner often appear to be doubtful or problematic. Apart from numerous obvious mistakes, as well as leaving many surnames unidentified even when it was very difficult, the translators and/or editors of the Polish text created some non-existent authors as a result of errors produced while copying their surnames from the original text or due to unfounded assumptions that some chemical or botanical terms are names of chemical authors. There is also no consistency in the spelling of surnames (usually left in the Latin form, sometimes spelled with wrong inflection, but also modernised). In the biographical introduction there are also numerous factual errors and some bizarre mistranslations. Not only did its author fail to correct invalid information of earlier biographers of Barner, relying only on the most obvious and accessible publications, but

  2. Ko Displacement Theory for Structural Shape Predictions

    NASA Technical Reports Server (NTRS)

    Ko, William L.

    2010-01-01

    The development of the Ko displacement theory for predictions of structure deformed shapes was motivated in 2003 by the Helios flying wing, which had a 247-ft (75-m) wing span with wingtip deflections reaching 40 ft (12 m). The Helios flying wing failed in midair in June 2003, creating the need to develop new technology to predict in-flight deformed shapes of unmanned aircraft wings for visual display before the ground-based pilots. Any types of strain sensors installed on a structure can only sense the surface strains, but are incapable to sense the overall deformed shapes of structures. After the invention of the Ko displacement theory, predictions of structure deformed shapes could be achieved by feeding the measured surface strains into the Ko displacement transfer functions for the calculations of out-of-plane deflections and cross sectional rotations at multiple locations for mapping out overall deformed shapes of the structures. The new Ko displacement theory combined with a strain-sensing system thus created a revolutionary new structure- shape-sensing technology.

  3. Phasic Oscillations of Extracellular Potassium (Ko) in Pregnant Rat Myometrium

    PubMed Central

    Young, Roger C.; Goloman, Gabriela

    2013-01-01

    K-sensitive microelectrodes were used to measure K+ within the extracellular space (Ko) of pregnant rat myometrium. Contractile activity was monitored by measuring either force or bioelectrical signals. Single and double-barreled electrodes were used. Double-barreled electrodes allowed monitoring of electrical activity 15 microns from the site of Ko measurement. From double-barreled electrode experiments, the bioelectrical burst started first, and then Ko began to rise 0.6 ± 0.1 seconds later. This delay indicates that K+ leaves the cells in response to local electrical activity rather than vice versa. Four control experiments were performed to assess the influence of electrical artifacts caused by tissue motion on Ko values. When observed, artifacts were negative and transient, and hence would result in an underestimation of Ko rises. Artifacts were minimized when tissue motion was minimized by fixing the tissue at both ends. At 37°C, 7 single barreled experiments and 45 contractions were analyzed. Resting Ko was within 1 mM of bath K+ (5 mM) at the beginning and end of the experiments. Ko rose during the contraction, fell after the completion of the contraction, and normalized before the next contraction began. Peak Ko values observed during force production were 18.8 ± 5.9 mM, a value high enough to modulate tissue-level electrical activity. Ko required 15.7 ± 2.8 seconds to normalize halfway (t50). Six experiments expressing 38 contractions were performed at 24°C. The contraction period was longer at 24°C. Values for peak Ko (26.2 ± 9.9 mM) and t50 (29.8±16.2 sec) were both larger than at 37°C (p<0.0003 for both). The direct relationships between peak Ko, t50 and the contraction period, suggest elevations in Ko may modulate contraction frequency. The myometrial interstitial space appears to be functionally important, and Ko metabolism may participate in cell-cell interactions. PMID:23724127

  4. The Inhibitor Ko143 Is Not Specific for ABCG2

    PubMed Central

    Zoghbi, Sami S.; Lu, Shuiyu; Shukla, Suneet; Ambudkar, Suresh V.; Pike, Victor W.; Mulder, Jan; Gottesman, Michael M.; Innis, Robert B.; Hall, Matthew D.

    2015-01-01

    Imaging ATP-binding cassette (ABC) transporter activity in vivo with positron emission tomography requires both a substrate and a transporter inhibitor. However, for ABCG2, there is no inhibitor proven to be specific to that transporter alone at the blood-brain barrier. Ko143 [[(3S,6S,12aS)-1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1′,2′:1,6]pyrido[3,4- b]indole-3-propanoic acid 1,1-dimethylethyl ester], a nontoxic analog of fungal toxin fumitremorgin C, is a potent inhibitor of ABCG2, although its specificity in mouse and human systems is unclear. This study examined the selectivity of Ko143 using human embryonic kidney cell lines transfected with ABCG2, ABCB1, or ABCC1 in several in vitro assays. The stability of Ko143 in rat plasma was measured using high performance liquid chromatography. Our results show that, in addition to being a potent inhibitor of ABCG2, at higher concentrations (≥1 μM) Ko143 also has an effect on the transport activity of both ABCB1 and ABCC1. Furthermore, Ko143 was found to be unstable in rat plasma. These findings indicate that Ko143 lacks specificity for ABCG2 and this should be taken into consideration when using Ko143 for both in vitro and in vivo experiments. PMID:26148857

  5. The Inhibitor Ko143 Is Not Specific for ABCG2.

    PubMed

    Weidner, Lora D; Zoghbi, Sami S; Lu, Shuiyu; Shukla, Suneet; Ambudkar, Suresh V; Pike, Victor W; Mulder, Jan; Gottesman, Michael M; Innis, Robert B; Hall, Matthew D

    2015-09-01

    Imaging ATP-binding cassette (ABC) transporter activity in vivo with positron emission tomography requires both a substrate and a transporter inhibitor. However, for ABCG2, there is no inhibitor proven to be specific to that transporter alone at the blood-brain barrier. Ko143 [[(3S,6S,12aS)-1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4- b]indole-3-propanoic acid 1,1-dimethylethyl ester], a nontoxic analog of fungal toxin fumitremorgin C, is a potent inhibitor of ABCG2, although its specificity in mouse and human systems is unclear. This study examined the selectivity of Ko143 using human embryonic kidney cell lines transfected with ABCG2, ABCB1, or ABCC1 in several in vitro assays. The stability of Ko143 in rat plasma was measured using high performance liquid chromatography. Our results show that, in addition to being a potent inhibitor of ABCG2, at higher concentrations (≥1 μM) Ko143 also has an effect on the transport activity of both ABCB1 and ABCC1. Furthermore, Ko143 was found to be unstable in rat plasma. These findings indicate that Ko143 lacks specificity for ABCG2 and this should be taken into consideration when using Ko143 for both in vitro and in vivo experiments. PMID:26148857

  6. Age of Kōko Seamount, Emperor Seamount chain

    USGS Publications Warehouse

    Clague, David A.; Dalrymple, G. Brent

    1973-01-01

    KAr ages obtained by the conventional isotope-dilution and the 40Ar/39Ar techniques on two sanidine trachytes, four basalts, and a phonolite dredged from the top of Ko¯ko Seamount, 300 km north of the Hawaiian-Emperor bend, show that the seamount is 46.4 ± 1.1 my old. These data indicate that the volcanoes in the Hawaiian-Emperor chain continue to increase in age to the west and north beyond Midway Atoll, as predicted by the melting-spot hypothesis for the origin of the chain, and that the rate of volcanic migration along the chain was nonlinear between the time of formation of the island of Hawaii and Ko¯ko Seamount.

  7. Sociophonetic Variations in Korean Constituent Final "-Ko" and "-To"

    ERIC Educational Resources Information Center

    Yi, So Young L.

    2015-01-01

    The purpose of this dissertation is to examine (i) linguistic and extralinguistic factors that influence vowel raising of /o/ in constituent-final "-ko" and "-to" in Seoul Korean and (ii) listeners' perceptions of this vowel raising and social meanings of the raised variant. The analyses are based on production data collected…

  8. Organ Correlation with Tryptophan Metabolism Obtained by Analyses of TDO-KO and QPRT-KO Mice.

    PubMed

    Shibata, Katsumi; Fukuwatari, Tsutomu

    2016-01-01

    The aim of this article is to report the organ-specific correlation with tryptophan (Trp) metabolism obtained by analyses of tryptophan 2,3-dioxygenase knockout (TDO-KO) and quinolinic acid phosphoribosyltransferase knockout (QPRT-KO) mice models. We found that TDO-KO mice could biosynthesize the necessary amount of nicotinamide (Nam) from Trp, resulting in the production of key intermediate, 3-hydroxyanthranilic acid. Upstream metabolites, such as kynurenic acid and xanthurenic acid, in the urine were originated from nonhepatic tissues, and not from the liver. In QPRT-KO mice, the Trp to quinolinic acid conversion ratio was 6%; this value was higher than expected. Furthermore, we found that QPRT activity in hetero mice was half of that in wild-type (WT) mice. Urine quinolinic acid levels remain unchanged in both hetero and WT mice, and the conversion ratio of Trp to Nam was also unaffected. Collectively, these findings show that QPRT was not the rate-limiting enzyme in the conversion. In conclusion, the limiting factors in the conversion of Trp to Nam are the substrate amounts of 3-hydroxyanthranilic acid and activity of 3-hydroxyanthranilic acid 3,4-dioxygenase in the liver. PMID:27147825

  9. Organ Correlation with Tryptophan Metabolism Obtained by Analyses of TDO-KO and QPRT-KO Mice

    PubMed Central

    Shibata, Katsumi; Fukuwatari, Tsutomu

    2016-01-01

    The aim of this article is to report the organ-specific correlation with tryptophan (Trp) metabolism obtained by analyses of tryptophan 2,3-dioxygenase knockout (TDO-KO) and quinolinic acid phosphoribosyltransferase knockout (QPRT-KO) mice models. We found that TDO-KO mice could biosynthesize the necessary amount of nicotinamide (Nam) from Trp, resulting in the production of key intermediate, 3-hydroxyanthranilic acid. Upstream metabolites, such as kynurenic acid and xanthurenic acid, in the urine were originated from nonhepatic tissues, and not from the liver. In QPRT-KO mice, the Trp to quinolinic acid conversion ratio was 6%; this value was higher than expected. Furthermore, we found that QPRT activity in hetero mice was half of that in wild-type (WT) mice. Urine quinolinic acid levels remain unchanged in both hetero and WT mice, and the conversion ratio of Trp to Nam was also unaffected. Collectively, these findings show that QPRT was not the rate-limiting enzyme in the conversion. In conclusion, the limiting factors in the conversion of Trp to Nam are the substrate amounts of 3-hydroxyanthranilic acid and activity of 3-hydroxyanthranilic acid 3,4-dioxygenase in the liver. PMID:27147825

  10. Lack of antiviral antibody response in koalas infected with koala retroviruses (KoRV).

    PubMed

    Fiebig, Uwe; Keller, Martina; Möller, Annekatrin; Timms, Peter; Denner, Joachim

    2015-02-16

    Many wild koalas are infected with the koala retrovirus, KoRV, some of which suffer from lymphoma and chlamydial disease. Three subgroups, KoRV-A, KoRV-B and KoRV-J, have so far been described. It is well known that other closely related gammaretroviruses can induce tumours and severe immunodeficiencies in their respective hosts and a possible role for KoRV infection in lymphoma and chlamydial disease in koalas has been suggested. In many wild koalas, KoRV-A has become endogenised, i.e., it is integrated in the germ-line and is passed on with normal cellular genes. In this study, sera from koalas in European zoos and from wild animals in Australia were screened for antibodies against KoRV-A. These naturally infected animals all carry endogenous KoRV-A and two zoo animals are also infected with KoRV-B. The antibody response is generally an important diagnostic tool for detecting retrovirus infections. However, when Western blot analyses were performed using purified virus or recombinant proteins corresponding to KoRV-A, none of the koalas tested positive for specific antibodies, suggesting a state of tolerance. These results have implications for koala vaccination, as they suggest that therapeutic immunisation of animals carrying and expressing endogenous KoRV-A will not be successful. However, it remains unclear whether these animals can be immunised against KoRV-B and immunisation of uninfected koalas could still be worthwhile. PMID:25596496

  11. Results of Life-Supporting GalT-KO kidneys in Cynomolgus Monkeys Using Two Different Sources of GalT-KO Swine

    PubMed Central

    Sekijima, Mitsuhiro; Waki, Shiori; Sahara, Hisashi; Tasaki, Masayuki; Wilkinson, Robert A.; Villani, Vincenzo; Shimatsu, Yoshiki; Nakano, Kazuaki; Matsunari, Hitomi; Nagashima, Hiroshi; Fishman, Jay A.; Shimizu, Akira; Yamada, Kazuhiko

    2014-01-01

    Background Various durations of survival have been observed in the xenotransplantation of life-supporting alpha-1,3-galactosyltransferase knockout (GalT-KO) porcine kidneys into nonhuman primates (NHPs). While others have demonstrated loss of GalT-KO transplanted kidneys within two weeks, we have reported an average survival of 51 days with the co-transplantation of the kidney and vascularized thymus and an average of 29 days with the kidney alone. In order to determine the factors responsible for this difference in survival time, we performed xenogeneic kidney transplantations into cynomolgus monkeys with an anti-CD40L-based regimen using two different strains of GalT-KO swine, one derived from MGH-Miniature swine and the other obtained from Meji University. Materials and Methods Eight cynomolgus moneys received GalT-KO kidneys. Three kidney grafts were from MGH/NIBS GalT-KO pigs and 5 GalT-KO grafts were from MEIJI GalT-KO swine. All cynomolgus recipients were treated identically. Results Recipients of kidneys from the MGH GalT-KO swine, produced by nuclear transfer in Japan, survived an average of 28.7 days, while recipients of MEIJI GalT-KO swine survived an average of 9.2 days. Among the differences between these two groups, one potentially revealing disparity was that the MEIJI swine were positive for porcine-CMV, while the MGH-derived swine were negative. Conclusions This is the first study comparing renal xenotransplantation from two different sources of GalT-KO swine into NHPs at a single center. The results demonstrate that porcine-CMV may be responsible for early loss of GalTKO swine kidney xenografts. PMID:25243512

  12. In memoriam Professor Ko Saito (1941-2004)

    NASA Astrophysics Data System (ADS)

    Koike, Tohru

    2005-06-01

    Professor Ko Saito of Hiroshima University suffering from hepatic cancer passed away on May 20, 2004 at the age of 63, one year before his planned retirement in March 2005. He graduated from Hiroshima University in 1964, supervised by Professor Yamamura, and started his career in high-temperature chemical reaction and was appointed to be a Research Associate of the Department of Chemistry at Hiroshima University in 1967. He received a Doctor of Science Degree in chemistry in 1973 and spent his study leave from May 1980 to March 1981 at the University of Essex UK and worked with Professor JN Bradley. He was promoted to Associate Professor in 1986 and then to Professor of the Hiroshima University in 1990.

  13. Košice meteorite - overview of analyses

    NASA Astrophysics Data System (ADS)

    Porubcan, V.; Toth, J.; Borovicka, J.; Igaz, A.; Spurny, P.; Kornos, L.; Haloda, J.; Ozdin, D.; Uher, P.; Povinec, P. P.; Sykora, I.; Veis, P.; Kohout, T.; Svoren, J.; Husarik, M.

    2012-09-01

    On February 28, 2010 at 22:25 UT a very bright bolide has flown over Slovakia accompained with cannon-like burst sounds and a series of low frequency blasts. Due to bad weather, cloudy skies and scatter showers no optical records by the Central European Fireball Network (operated by Pavel Spurný) and the Slovak Video Meteor Network (operated by Juraj Tóth) could not be taken However, thanks to three video records by the surveillance cameras in Northern Hungery, were was clear sky, the trajectory and impact area western of the city of Košice in Eastern Slovakia could be calculated and the meteorite could be recovered [1].

  14. Nqrs Data for C8H9KO6 [C8H5KO4·2(H2O)] (Subst. No. 1092)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C8H9KO6 [C8H5KO4·2(H2O)] (Subst. No. 1092)

  15. Sarcocystis neurona infection in gamma interferon gene knockout (KO) mice: comparative infectivity of sporocysts in two strains of KO mice, effect of trypsin digestion on merozoite viability, and infectivity of bradyzoites to KO mice and cell culture.

    PubMed

    Dubey, J P; Sundar, N; Kwok, O C H; Saville, W J A

    2013-09-01

    The protozoan Sarcocystis neurona is the primary cause of Equine Protozoal Myeloencephalitis (EPM). EPM or EPM-like illness has been reported in horses, sea otters, and several other mammals. The gamma interferon gene knockout (KO) mouse is often used as a model to study biology and discovery of new therapies against S. neurona because it is difficult to induce clinical EPM in other hosts, including horses. In the present study, infectivity of three life cycle stages (merozoites, bradyzoites, sporozoites) to KO mice and cell culture was studied. Two strains of KO mice (C57-black, and BALB/c-derived, referred here as black or white) were inoculated orally graded doses of S. neurona sporocysts; 12 sporocysts were infective to both strains of mice and all infected mice died or became ill within 70 days post-inoculation. Although there was no difference in infectivity of sporocysts to the two strains of KO mice, the disease was more severe in black mice. S. neurona bradyzoites were not infectious to KO mice and cell culture. S. neurona merozoites survived 120 min incubation in 0.25% trypsin, indicating that trypsin digestion can be used to recover S. neurona from tissues of acutely infected animals. PMID:23375195

  16. Skeletal effects of a gastrin receptor antagonist in H+/K+ATPase beta subunit KO mice.

    PubMed

    Aasarød, Kristin M; Ramezanzadehkoldeh, Masoud; Shabestari, Maziar; Mosti, Mats P; Stunes, Astrid K; Reseland, Janne E; Beisvag, Vidar; Eriksen, Erik Fink; Sandvik, Arne K; Erben, Reinhold G; Schüler, Christiane; Boyce, Malcolm; Skallerud, Bjørn H; Syversen, Unni; Fossmark, Reidar

    2016-08-01

    Epidemiological studies suggest an increased fracture risk in patients taking proton pump inhibitors (PPIs) for long term. The underlying mechanism, however, has been disputed. By binding to the gastric proton pump, PPIs inhibit gastric acid secretion. We have previously shown that proton pump (H(+)/K(+)ATPase beta subunit) KO mice exhibit reduced bone mineral density (BMD) and inferior bone strength compared with WT mice. Patients using PPIs as well as these KO mice exhibit gastric hypoacidity, and subsequently increased serum concentrations of the hormone gastrin. In this study, we wanted to examine whether inhibition of the gastrin/CCK2 receptor influences bone quality in these mice. KO and WT mice were given either the gastrin/CCK2 receptor antagonist netazepide dissolved in polyethylene glycol (PEG) or only PEG for 1year. We found significantly lower bone mineral content and BMD, as well as inferior bone microarchitecture in KO mice compared with WT. Biomechanical properties by three-point bending test also proved inferior in KO mice. KO mice receiving netazepide exhibited significantly higher cortical thickness, cortical area fraction, trabecular thickness and trabecular BMD by micro-CT compared with the control group. Three-point bending test also showed higher Young's modulus of elasticity in the netazepide KO group compared with control mice. In conclusion, we observed that the gastrin receptor antagonist netazepide slightly improved bone quality in this mouse model, suggesting that hypergastrinemia may contribute to deteriorated bone quality during acid inhibition. PMID:27325243

  17. Requirements and tasks of cohorts and registers, the German KoRegIT project.

    PubMed

    Michalik, Claudia; Dress, Jochen; Ngouongo, Sylvie; Stäubert, Sebastian; Weber, Ulrike; Brockmeyer, Norbert; Paulus, Ursula; Stausberg, Jürgen

    2014-01-01

    Epidemiological cohorts and registers (KoReg) are long lasting and complex research projects, which need systematic and extensive planning and steering. The aim of the KoRegIT project was to develop a generic catalogue of requirements to support the organisational- and IT-structure of KoReg. The catalogue of requirements comprises the top level (TL) tasks of the core processes. All TL were classified into the following project phases: 1. Development, 2. Operation, 3. Completion. According to the defined TL tasks, the appropriate use cases (UC) were identified. The catalogue currently specifies 45 TL tasks and 207 UC. The UC were elaborated by a short and standardized description of the task, the involved actors (human or external systems), the preconditions, which have to be fulfilled in order to realize this task, the normal flow of the task and the post conditions. The developed catalogue was reviewed by representatives of different KoReg in Germany. The draft catalogue of requirements was revised according to the reviewer's feedback and discussion. The revised and complete catalogue with all elaborated UC was reviewed again by further experts. The developed KoRegIT catalogue of requirements offers a supporting tool to set-up the organisational structures and processes of KoReg as well as the definition of the needed IT-infrastructure. In addition it can be used to optimize or to expand these structures. PMID:25160356

  18. Košice meteorite - recovery and the strew field

    NASA Astrophysics Data System (ADS)

    Toth, J.; Porubčan, V.; Borovička, J.; Igaz, A.; Spurný, P.; Svoreň, J.; Husárik, M.; Kornoš, L.; Vereš, P.; Zigo, P.; Koza, J.; Kučera, A.; Gajdoš, S.; Világi, J.; Čapek, D.; Šilha, J.; Schunová, E.; Krišandová, Z.; Tomko, D.; Bodnárová, M.; Búzová, D.; Krejčová, T.

    2012-09-01

    The glare of the bolide on the night of February 28, 2010, illuminated streets and interior of apartments, at some places in Eastern Slovakia and Northern Hungary and cannon-like burst or series of low frequency blasts were heard. Due to bad weather, cloudy skies and scatter showers the Central European Fireball Network (operated by Pavel Spurný of the Czech Academy of Sciences) did not take direct optical records of the bolide and also the Slovak Video Meteor Network (operated by Juraj Tóth of Comenius University in Bratislava) did not operate that night so that at first moment it seemed that there were no scientific records available of this event. Fortunately, fast photoelectric sensors on 7 automated fireball stations in the Czech Republic (6) and Austria (1) worked also under cloudy sky and recorded the light curve of the bolide. It enabled to determine the exact time and duration of the event and to estimate its brightness as well. The bolide reached the maximum brightness of at least -18 magnitudes in one huge flare. This light curve was used also for modeling of meteoroid atmospheric fragmentation. Later, several surveillance cameras data were published showing the moment when the night became a day. Three videos from Hungary (Örkény village, Fazzi Daniella and Vass Gábor; Telki village, contact persons Sárneczky Krisztián, Kiss László and Budapest) actually captured the fireball itself. Thanks to calibration of videos by several members of the Hungarian Astronomical Association (MCSE - www.mcse.hu, namely by Igaz Antal) and the trajectory analysis done by Jiří Borovička gave the hope that significant number of meteorite fragments reached the surface. He also calculated the impact area western of the city of Košice in Eastern Slovakia. The data from the Local Seismic Network of Eastern Slovakia (Peter Moczo of the Comenius University) analyzed by Pavel Kalenda confirmed the atmospheric trajectory as well [1].

  19. Region-Specific Defects of Respiratory Capacities in the Ndufs4(KO) Mouse Brain

    PubMed Central

    Kayser, Ernst-Bernhard; Sedensky, Margaret M.; Morgan, Philip G.

    2016-01-01

    Background Lack of NDUFS4, a subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase), causes Leigh syndrome (LS), a progressive encephalomyopathy. Knocking out Ndufs4, either systemically or in brain only, elicits LS in mice. In patients as well as in KO mice distinct regions of the brain degenerate while surrounding tissue survives despite systemic complex I dysfunction. For the understanding of disease etiology and ultimately for the development of rationale treatments for LS, it appears important to uncover the mechanisms that govern focal neurodegeneration. Results Here we used the Ndufs4(KO) mouse to investigate whether regional and temporal differences in respiratory capacity of the brain could be correlated with neurodegeneration. In the KO the respiratory capacity of synaptosomes from the degeneration prone regions olfactory bulb, brainstem and cerebellum was significantly decreased. The difference was measurable even before the onset of neurological symptoms. Furthermore, neither compensating nor exacerbating changes in glycolytic capacity of the synaptosomes were found. By contrast, the KO retained near normal levels of synaptosomal respiration in the degeneration-resistant/resilient “rest” of the brain. We also investigated non-synaptic mitochondria. The KO expectedly had diminished capacity for oxidative phosphorylation (state 3 respiration) with complex I dependent substrate combinations pyruvate/malate and glutamate/malate but surprisingly had normal activity with α-ketoglutarate/malate. No correlation between oxidative phosphorylation (pyruvate/malate driven state 3 respiration) and neurodegeneration was found: Notably, state 3 remained constant in the KO while in controls it tended to increase with time leading to significant differences between the genotypes in older mice in both vulnerable and resilient brain regions. Neither regional ROS damage, measured as HNE-modified protein, nor regional complex I stability, assessed by blue

  20. Adaptive thermogenesis and thermal conductance in wild-type and UCP1-KO mice

    PubMed Central

    Willershäuser, Monja; Jastroch, Martin; Rourke, Bryan C.; Fromme, Tobias; Oelkrug, Rebecca; Heldmaier, Gerhard; Klingenspor, Martin

    2010-01-01

    We compared maximal cold-induced heat production (HPmax) and cold limits between warm (WA; 27°C), moderate cold (MCA; 18°C), or cold acclimated (CA; 5°C) wild-type and uncoupling-protein 1 knockout (UCP1-KO) mice. In wild-type mice, HPmax was successively increased after MCA and CA, and the cold limit was lowered to −8.3°C and −18.0°C, respectively. UCP1-KO mice also increased HPmax in response to MCA and CA, although to a lesser extent. Direct comparison revealed a maximal cold-induced recruitment of heat production by +473 mW and +227 mW in wild-type and UCP1-KO mice, respectively. The increase in cold tolerance of UCP1-KO mice from −0.9°C in MCA to −10.1°C in CA could not be directly related to changes in HPmax, indicating that UCP1-KO mice used the dissipated heat more efficiently than wild-type mice. As judged from respiratory quotients, acutely cold-challenged UCP1-KO mice showed a delayed transition toward lipid oxidation, and 5-h cold exposure revealed diminished physical activity and less variability in the control of metabolic rate. We conclude that BAT is required for maximal adaptive thermogenesis but also allows metabolic flexibility and a rapid switch toward sustained lipid-fuelled thermogenesis as an acute response to cold. In both CA groups, expression of contractile proteins (myosin heavy-chain isoforms) showed minor training effects in skeletal muscles, while cardiac muscle of UCP1-KO mice had novel expression of beta cardiac isoform. Neither respiration nor basal proton conductance of skeletal muscle mitochondria were different between genotypes. In subcutaneous white adipose tissue of UCP1-KO mice, cold exposure increased cytochrome-c oxidase activity and expression of the cell death-inducing DFFA-like effector A by 3.6-fold and 15-fold, respectively, indicating the recruitment of mitochondria-rich brown adipocyte-like cells. Absence of functional BAT leads to remodeling of white adipose tissue, which may significantly contribute

  1. GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance.

    PubMed

    Wang, Jinghong; Pan, Zheng; Baribault, Helene; Chui, Danny; Gundel, Caroline; Véniant, Murielle

    2016-01-01

    Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice. PMID:27081476

  2. GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance

    PubMed Central

    Wang, Jinghong; Pan, Zheng; Baribault, Helene; Chui, Danny; Gundel, Caroline; Véniant, Murielle

    2016-01-01

    Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice. PMID:27081476

  3. Heavy metal characteristics in Kočani Field soil-plant system (Republic of Macedonia)

    NASA Astrophysics Data System (ADS)

    Rogan Šmuc, Nastja; Dolenec, Tadej; Serafimovski, Todor; Tasev, Goran; Dolenec, Matej; Komar, Darja; Vrhovnik, Petra

    2014-05-01

    Contamination of soils with heavy metals is globally widespread and induces a long-term risk to ecosystem health. This research focuses on the heavy metal contamination, transfer values and health risk assessment in the Kočani Field soil-plant system (Republic of Macedonia). To identify the heavy metal concentrations in Kočani soils and crops (rice and maize) the geochemical analysis were performed by inductive coupled plasma mass spectrometer (ICP-MS), thereupon the transfer factor (TF) and estimated daily intake amount (EDIA) values in Kočani crops were calculated. Heavy metal contamination status of Kočani soils was also assessed by using sequential extraction procedure and by several environmental indexes: geoaccumulation index, contamination factor and contamination degree. The detected total concentrations of As, Cu, Cd, Pb and Zn in soil samples were highly above the threshold values considered to be phytotoxically excessive for the surface soils. The results of the applied indexes confirmed a very high contamination status for Kočani soils. According to the sum of the water soluble (1) and exchangeable (2) fractions for Ag, As, Cd, Cu, Mo, Ni, Pb, Sb and Zn measured in the soils, the mobility and bioavailability potential of the heavy metals studied declined in the following order: Cd > Mo > Sb > Zn > Cu > As > Pb > Ni > Ag. The highest As, Cd, Mo, Pb and Zn values were determined in the rice samples grown in the paddy fields near the Zletovska River. The highest Pb and Mo concentrations measured in the maize samples were from the maize fields near the Zletovska River and Ciflik city. High transfer factor values for Mo, Zn, Cd and Cu revealed a strong accumulation of Mo, Zn and Cd by rice and Mo and Zn by maize crops. The results of the estimated dialy intake showed that the regular consumption of rice and maize crops containing the highest Cd, Mo, Pb and Zn concentrations could pose a serious threat to human health, because the daily intake of Cd, Mo

  4. Ethanol production from marine algal hydrolysates using Escherichia coli KO11.

    PubMed

    Kim, Nag-Jong; Li, Hui; Jung, Kwonsu; Chang, Ho Nam; Lee, Pyung Cheon

    2011-08-01

    Algae biomass is a potential raw material for the production of biofuels and other chemicals. In this study, biomass of the marine algae, Ulva lactuca, Gelidium amansii,Laminaria japonica, and Sargassum fulvellum, was treated with acid and commercially available hydrolytic enzymes. The hydrolysates contained glucose, mannose, galactose, and mannitol, among other sugars, at different ratios. The Laminaria japonica hydrolysate contained up to 30.5% mannitol and 6.98% glucose in the hydrolysate solids. Ethanogenic recombinant Escherichia coli KO11 was able to utilize both mannitol and glucose and produced 0.4g ethanol per g of carbohydrate when cultured in L. japonica hydrolysate supplemented with Luria-Bertani medium and hydrolytic enzymes. The strategy of acid hydrolysis followed by simultaneous enzyme treatment and inoculation with E. coli KO11 could be a viable strategy to produce ethanol from marine alga biomass. PMID:21640583

  5. Regional brain volumes changes in adult male FMR1-KO mouse on the FVB strain.

    PubMed

    Lai, J K Y; Lerch, J P; Doering, L C; Foster, J A; Ellegood, J

    2016-03-24

    Fragile X Syndrome (FXS) is the most common heritable single gene cause of autism spectrum disorder (ASD). FMR1-KO mice mimic the etiology and phenotypic manifestations of FXS. Neuroanatomical changes in specific brain regions have been reported in clinical settings and in preclinical models. FMR1-KO mice have been generated in different strains including C57Bl/6 (B6) and FVB. Mice on different genetic backgrounds have stable yet distinct behavioral phenotypes that may lead to unique gene-strain interactions on brain structure. Previous magnetic resonance imaging (MRI) studies have examined FMR1 knockout male mice on a B6 and found few differences compared to wild-type mice. Here, we examine brain volumes in FMR1 knockout male mice on a FVB background using high resolution (multi-channel 7.0Tesla) MRI. We observe multiple differences in the neuroanatomy of male FMR1-/y mice on a FVB background. Significantly larger relative volume (% total brain volume) differences were found in major white matter structures throughout the brain. In addition, there were changes in areas associated with fronto-striatal circuitry and other regions. Functional and structural connectivity differences are often seen in human ASD, and therefore, this increased white matter seen in the FMR1-KO-FVB could be highlighting a structural over-connectivity, which could lead to some of the behavioral abnormalities seen with the FMR1-KO-FVB mice. Furthermore, these results highlight the importance of genetic strain contribution to brain structure. PMID:26794591

  6. Decellularized GGTA1-KO pig heart valves do not bind preformed human xenoantibodies.

    PubMed

    Ramm, Robert; Niemann, Heiner; Petersen, Björn; Haverich, Axel; Hilfiker, Andres

    2016-07-01

    Pre-clinical and clinical data have unequivocally demonstrated the usefulness of decellularized heart valve (HV) matrices implanted for HV replacement therapy. However, human donor valves applicable for decellularization are in short supply, which prompts the search for suitable alternatives, such as porcine grafts. Since decellularization might be insufficient to remove all xenoantigens, we analysed the interaction of human preformed antibodies with decellularized porcine HV in vitro to assess potential immune reactions upon implantation. Detergent-decellularized pulmonary HV from German Landrace wild-type (wt) or α1,3-galactosyltransferase knockout (GGTA1-KO) pigs were investigated by inhibition ELISA and GSL I-B4 staining to localize and quantify matrix-bound αGal epitopes, which represent the most prominent xenoantigen. Additionally, preformed human xenoantibodies were affinity purified by perfusing porcine kidneys. Binding of purified human antibodies to decellularized HV was investigated by inhibition ELISA. Furthermore, binding of human plasma proteins to decellularized matrices was determined by western blot. Decellularized human pulmonary artery served as controls. Decellularization of wt HV led to a reduction of αGal epitopes by 70 %. Residual epitopes were associated with the subendothelial extracellular matrix. As expected, no αGal epitopes were found on decellularized GGTA1-KO matrix. The strongest binding of preformed human anti-pig antibodies was found on wt matrices, whereas GGTA1-KO matrices bound similar or even fewer xenoantibodies than human controls. These results demonstrate the suitability of GGTA1-KO pigs as donors for decellularized heart valves for human patients. Besides the presence of αGal antibodies on decellularized heart valves, no further preformed xenoantibodies against porcine matrix were detected in tested human sera. PMID:27154491

  7. Locomotor hyperactivity in 14-3-3ζ KO mice is associated with dopamine transporter dysfunction

    PubMed Central

    Ramshaw, H; Xu, X; Jaehne, E J; McCarthy, P; Greenberg, Z; Saleh, E; McClure, B; Woodcock, J; Kabbara, S; Wiszniak, S; Wang, Ting-Yi; Parish, C; van den Buuse, M; Baune, B T; Lopez, A; Schwarz, Q

    2013-01-01

    Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions that are tightly linked to catecholamine exocytosis and receptor interactions on pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily achieved through reuptake of extracellular DA by the DA transporter (DAT) on presynaptic neurons. Aberrant regulation of DA signalling, and in particular hyperactivation, has been proposed as a key insult in the presentation of schizophrenia and related neuropsychiatric disorders. We recently identified 14-3-3ζ as an essential component of neurodevelopment and a central risk factor in the schizophrenia protein interaction network. Our analysis of 14-3-3ζ-deficient mice now shows that baseline hyperactivity of knockout (KO) mice is rescued by the antipsychotic drug clozapine. 14-3-3ζ KO mice displayed enhanced locomotor hyperactivity induced by the DA releaser amphetamine. Consistent with 14-3-3ζ having a role in DA signalling, we found increased levels of DA in the striatum of 14-3-3ζ KO mice. Although 14-3-3ζ is proposed to modulate activity of the rate-limiting DA biosynthesis enzyme, tyrosine hydroxylase (TH), we were unable to identify any differences in total TH levels, TH localization or TH activation in 14-3-3ζ KO mice. Rather, our analysis identified significantly reduced levels of DAT in the absence of notable differences in RNA or protein levels of DA receptors D1–D5. Providing insight into the mechanisms by which 14-3-3ζ controls DAT stability, we found a physical association between 14-3-3ζ and DAT by co-immunoprecipitation. Taken together, our results identify a novel role for 14-3-3ζ in DA neurotransmission and provide support to the hyperdopaminergic basis of pathologies associated with schizophrenia and related disorders. PMID:24301645

  8. Cosmogenic nuclides in the Košice meteorite: Experimental investigations and Monte Carlo simulations

    NASA Astrophysics Data System (ADS)

    Povinec, Pavel P.; Masarik, Jozef; Sýkora, Ivan; KováčIk, Andrej; BeåO, Juraj; Meier, Matthias M. M.; Wieler, Rainer; Laubenstein, Matthias; PorubčAn, Vladimir

    2015-05-01

    Results of nondestructive gamma-ray analyses of cosmogenic radionuclides (7Be, 22Na, 26Al, 46Sc, 48V, 54Mn, 56Co, 57Co, 58Co, and 60Co) in 19 fragments of the Košice meteorite are presented and discussed. The activities varied mainly with position of fragments in the meteoroid body, and with fluxes of cosmic-ray particles in the space affecting radionuclides with different half-lives. Monte Carlo simulations of the production rates of 60Co and 26Al compared with experimental data indicate that the pre-atmospheric radius of the meteoroid was 50 ± 5 cm. In two Košice fragments, He, Ne, and Ar concentrations and isotopic compositions were also analyzed. The noble-gas cosmic-ray exposure age of the Košice meteorite is 5-7 Myr, consistent with the conspicuous peak (or doublet peak) in the exposure age histogram of H chondrites. One sample likely contains traces of implanted solar wind Ne, suggesting that Košice is a regolith breccia. The agreement between the simulated and observed 26Al activities indicate that the meteoroid was mostly irradiated by a long-term average flux of galactic cosmic rays of 4.8 particles cm-2 s-1, whereas the short-lived radionuclide activities are more consistent with a flux of 7.0 protons cm-2 s-1 as a result of the low solar modulation of the galactic cosmic rays during the last few years before the meteorite fall.

  9. Elementary model of severe plastic deformation by KoBo process

    SciTech Connect

    Gusak, A.; Storozhuk, N.; Danielewski, M. Korbel, A.; Bochniak, M.

    2014-01-21

    Self-consistent model of generation, interaction, and annihilation of point defects in the gradient of oscillating stresses is presented. This model describes the recently suggested method of severe plastic deformation by combination of pressure and oscillating rotations of the die along the billet axis (KoBo process). Model provides the existence of distinct zone of reduced viscosity with sharply increased concentration of point defects. This zone provides the high extrusion velocity. Presented model confirms that the Severe Plastic Deformation (SPD) in KoBo may be treated as non-equilibrium phase transition of abrupt drop of viscosity in rather well defined spatial zone. In this very zone, an intensive lateral rotational movement proceeds together with generation of point defects which in self-organized manner make rotation possible by the decrease of viscosity. The special properties of material under KoBo version of SPD can be described without using the concepts of nonequilibrium grain boundaries, ballistic jumps and amorphization. The model can be extended to include different SPD processes.

  10. KoBaMIN: a knowledge-based minimization web server for protein structure refinement.

    PubMed

    Rodrigues, João P G L M; Levitt, Michael; Chopra, Gaurav

    2012-07-01

    The KoBaMIN web server provides an online interface to a simple, consistent and computationally efficient protein structure refinement protocol based on minimization of a knowledge-based potential of mean force. The server can be used to refine either a single protein structure or an ensemble of proteins starting from their unrefined coordinates in PDB format. The refinement method is particularly fast and accurate due to the underlying knowledge-based potential derived from structures deposited in the PDB; as such, the energy function implicitly includes the effects of solvent and the crystal environment. Our server allows for an optional but recommended step that optimizes stereochemistry using the MESHI software. The KoBaMIN server also allows comparison of the refined structures with a provided reference structure to assess the changes brought about by the refinement protocol. The performance of KoBaMIN has been benchmarked widely on a large set of decoys, all models generated at the seventh worldwide experiments on critical assessment of techniques for protein structure prediction (CASP7) and it was also shown to produce top-ranking predictions in the refinement category at both CASP8 and CASP9, yielding consistently good results across a broad range of model quality values. The web server is fully functional and freely available at http://csb.stanford.edu/kobamin. PMID:22564897

  11. KoBaMIN: a knowledge-based minimization web server for protein structure refinement

    PubMed Central

    Rodrigues, João P. G. L. M.; Levitt, Michael; Chopra, Gaurav

    2012-01-01

    The KoBaMIN web server provides an online interface to a simple, consistent and computationally efficient protein structure refinement protocol based on minimization of a knowledge-based potential of mean force. The server can be used to refine either a single protein structure or an ensemble of proteins starting from their unrefined coordinates in PDB format. The refinement method is particularly fast and accurate due to the underlying knowledge-based potential derived from structures deposited in the PDB; as such, the energy function implicitly includes the effects of solvent and the crystal environment. Our server allows for an optional but recommended step that optimizes stereochemistry using the MESHI software. The KoBaMIN server also allows comparison of the refined structures with a provided reference structure to assess the changes brought about by the refinement protocol. The performance of KoBaMIN has been benchmarked widely on a large set of decoys, all models generated at the seventh worldwide experiments on critical assessment of techniques for protein structure prediction (CASP7) and it was also shown to produce top-ranking predictions in the refinement category at both CASP8 and CASP9, yielding consistently good results across a broad range of model quality values. The web server is fully functional and freely available at http://csb.stanford.edu/kobamin. PMID:22564897

  12. Kdo hydroxylase is an inner core assembly enzyme in the Ko-containing lipopolysaccharide biosynthesis.

    PubMed

    Chung, Hak Suk; Yang, Eun Gyeong; Hwang, Dohyeon; Lee, Ji Eun; Guan, Ziqiang; Raetz, Christian R H

    2014-09-26

    The lipopolysaccharide (LPS) isolated from certain important Gram-negative pathogens including a human pathogen Yersinia pestis and opportunistic pathogens Burkholderia mallei and Burkholderia pseudomallei contains d-glycero-d-talo-oct-2-ulosonic acid (Ko), an isosteric analog of 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo). Kdo 3-hydroxylase (KdoO), a Fe(2+)/α-KG/O2 dependent dioxygenase from Burkholderia ambifaria and Yersinia pestis is responsible for Ko formation with Kdo2-lipid A as a substrate, but in which stage KdoO functions during the LPS biosynthesis has not been established. Here we purify KdoO from B. ambifaria (BaKdoO) to homogeneity for the first time and characterize its substrates. BaKdoO utilizes Kdo2-lipid IVA or Kdo2-lipid A as a substrate, but not Kdo-lipid IVAin vivo as well as in vitro and Kdo-(Hep)kdo-lipid A in vitro. These data suggest that KdoO is an inner core assembly enzyme that functions after the Kdo-transferase KdtA but before the heptosyl-transferase WaaC enzyme during the Ko-containing LPS biosynthesis. PMID:25204504

  13. GAL3 receptor KO mice exhibit an anxiety-like phenotype

    PubMed Central

    Brunner, Susanne M.; Farzi, Aitak; Locker, Felix; Holub, Barbara S.; Drexel, Meinrad; Reichmann, Florian; Lang, Andreas A.; Mayr, Johannes A.; Vilches, Jorge J.; Navarro, Xavier; Lang, Roland; Sperk, Günther; Holzer, Peter; Kofler, Barbara

    2014-01-01

    The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems. It is a modulator of various physiological and pathological processes, and it mediates its effects via three G protein-coupled receptors (GAL1–3 receptors). A role for GAL as a modulator of mood and anxiety was suggested, because GAL and its receptors are highly expressed in limbic brain structures of rodents. In recent years, numerous studies of animal models have suggested an involvement of GAL and GAL1 and GAL2 receptors in anxiety- and depression-related behavior. However, to date, there is sparse literature implicating GAL3 receptors in behavioral functions. Therefore, we studied the behavior of GAL3 receptor-deficient (GAL3-KO) mice to elucidate whether GAL3 receptors are involved in mediating behavior-associated actions of GAL. The GAL3-KO mouse line exhibited normal breeding and physical development. In addition to behavioral tests, phenotypic characterization included analysis of hematology, amino acid profiles, metabolism, and sudomotor function. In contrast to WT littermates, male GAL3-KO mice exhibited an anxiety-like phenotype in the elevated plus maze, open field, and light/dark box tests, and they were less socially affiliated than WT animals to a stranger mouse in a social interaction test. In conclusion, our data suggest involvement of GAL3 receptors in GAL-mediated effects on mood, anxiety, and behavior, making it a possible target for alternative treatment strategies for mood disorders. PMID:24782539

  14. KoFlux: Korean Regional Flux Network in AsiaFlux

    NASA Astrophysics Data System (ADS)

    Kim, J.

    2002-12-01

    AsiaFlux, the Asian arm of FLUXNET, held the Second International Workshop on Advanced Flux Network and Flux Evaluation in Jeju Island, Korea on 9-11 January 2002. In order to facilitate comprehensive Asia-wide studies of ecosystem fluxes, the meeting launched KoFlux, a new Korean regional network of long-term micrometeorological flux sites. For a successful assessment of carbon exchange between terrestrial ecosystems and the atmosphere, an accurate measurement of surface fluxes of energy and water is one of the prerequisites. During the 7th Global Energy and Water Cycle Experiment (GEWEX) Asian Monsoon Experiment (GAME) held in Nagoya, Japan on 1-2 October 2001, the Implementation Committee of the Coordinated Enhanced Observing Period (CEOP) was established. One of the immediate tasks of CEOP was and is to identify the reference sites to monitor energy and water fluxes over the Asian continent. Subsequently, to advance the regional and global network of these reference sites in the context of both FLUXNET and CEOP, the Korean flux community has re-organized the available resources to establish a new regional network, KoFlux. We have built up domestic network sites (equipped with wind profiler and radiosonde measurements) over deciduous and coniferous forests, urban and rural rice paddies and coastal farmland. As an outreach through collaborations with research groups in Japan, China and Thailand, we also proposed international flux sites at ecologically and climatologically important locations such as a prairie on the Tibetan plateau, tropical forest with mixed and rapid land use change in northern Thailand. Several sites in KoFlux already begun to accumulate interesting data and some highlights are presented at the meeting. The sciences generated by flux networks in other continents have proven the worthiness of a global array of micrometeorological flux towers. It is our intent that the launch of KoFlux would encourage other scientists to initiate and

  15. Study on molecular structure and hydration mechanism of Domyoji-ko starch by IR and NIR hetero 2D analysis

    NASA Astrophysics Data System (ADS)

    Katayama, Norihisa; Kondo, Miyuki; Miyazawa, Mitsuhiro

    2010-06-01

    The hydration structure of starch molecule in Domyoji-ko, which is made from gluey rice, was investigated by hetero 2D correlation analysis of IR and NIR spectroscopy. The feature near 1020 cm -1 in the IR spectra of Domyoji-ko is changed by rehydration process, indicating that the molecular structure of amylopectin in the starch has been varied by the hydration without heating. The intensity of a band at 4770 cm -1 in NIR spectra is decreasing with the increasing of either the heating time with water or rehydration time without heating. These results suggest that the hydration of Domyoji-ko has proceeded in similar mechanisms on these processes. The generalized hetero 2D IR-NIR correlation analysis for rehydration of Domyoji-ko has supported the assignments for NIR bands concerning the gelatinization of starch.

  16. Expression pattern of immediate early genes in the cerebellum of D1R KO, D2R KO, and wild type mice under vestibular-controlled activity.

    PubMed

    Nakamura, Toru; Sato, Asako; Kitsukawa, Takashi; Sasaoka, Toshikuni; Yamamori, Tetsuo

    2015-01-01

    We previously reported the different motor abilities of D1R knockout (KO), D2R KO and wild-type (WT) mice. To understand the interaction between the cerebellum and the striatal direct and indirect pathways, we examined the expression patterns of immediate early genes (IEG) in the cerebellum of these three genotypes of mice. In the WT naive mice, there was little IEG expression. However, we observed a robust expression of c-fos mRNA in the vermis and hemisphere after running rota-rod tasks. In the vermis, c-fos was expressed throughout the lobules except lobule 7, and also in crus 1 of the ansiform lobule (Crus1), copula of the pyramis (Cop) and most significantly in the flocculus in the hemisphere. jun-B was much less expressed but more preferentially expressed in Purkinje cells. In addition, we observed significant levels of c-fos and jun-B expressions after handling mice, and after the stationary rota-rod task in naive mice. Surprisingly, we observed significant expression of c-fos and jun-B even 30 min after single weighing. Nonetheless, certain additional c-fos and jun-B expressions were observed in three genotypes of the mice that experienced several sessions of motor tasks 24 h after stationary rota-rod task and on days 1 and 5 after rota-rod tasks, but no significant differences in expressions after the running rota-rod tasks were observed among the three genotypes. In addition, there may be some differences 24 h after the stationary rota-rod task between the naive mice and the mice that experienced several sessions of motor tasks. PMID:26137459

  17. Binding Specificities of the Telomere Phage ϕKO2 Prophage Repressor CB and Lytic Repressor Cro.

    PubMed

    Hammerl, Jens Andre; Jäckel, Claudia; Lanka, Erich; Roschanski, Nicole; Hertwig, Stefan

    2016-01-01

    Temperate bacteriophages possess a genetic switch which regulates the lytic and lysogenic cycle. The genomes of the temperate telomere phages N15, PY54, and ϕKO2 harbor a primary immunity region (immB) comprising genes for the prophage repressor (cI or cB), the lytic repressor (cro) and a putative antiterminator (q). The roles of these products are thought to be similar to those of the lambda proteins CI (CI prophage repressor), Cro (Cro repressor), and Q (antiterminator Q), respectively. Moreover, the gene order and the location of several operator sites in the prototype telomere phage N15 and in ϕKO2 are reminiscent of lambda-like phages. We determined binding sites of the ϕKO2 prophage repressor CB and lytic repressor Cro on the ϕKO2 genome in detail by electrophoretic mobility shift assay (EMSA) studies. Unexpectedly, ϕKO2 CB and Cro revealed different binding specificities. CB was bound to three OR operators in the intergenic region between cB and cro, two OL operators between cB and the replication gene repA and even to operators of N15. Cro bound exclusively to the 16 bp operator site OR3 upstream of the ϕKO2 prophage repressor gene. The ϕKO2 genes cB and cro are regulated by several strong promoters overlapping with the OR operators. The data suggest that Cro represses cB transcription but not its own synthesis, as already reported for PY54 Cro. Thus, not only PY54, but also phage ϕKO2 possesses a genetic switch that diverges significantly from the switch of lambda-like phages. PMID:27527206

  18. Binding Specificities of the Telomere Phage ϕKO2 Prophage Repressor CB and Lytic Repressor Cro

    PubMed Central

    Hammerl, Jens Andre; Jäckel, Claudia; Lanka, Erich; Roschanski, Nicole; Hertwig, Stefan

    2016-01-01

    Temperate bacteriophages possess a genetic switch which regulates the lytic and lysogenic cycle. The genomes of the temperate telomere phages N15, PY54, and ϕKO2 harbor a primary immunity region (immB) comprising genes for the prophage repressor (cI or cB), the lytic repressor (cro) and a putative antiterminator (q). The roles of these products are thought to be similar to those of the lambda proteins CI (CI prophage repressor), Cro (Cro repressor), and Q (antiterminator Q), respectively. Moreover, the gene order and the location of several operator sites in the prototype telomere phage N15 and in ϕKO2 are reminiscent of lambda-like phages. We determined binding sites of the ϕKO2 prophage repressor CB and lytic repressor Cro on the ϕKO2 genome in detail by electrophoretic mobility shift assay (EMSA) studies. Unexpectedly, ϕKO2 CB and Cro revealed different binding specificities. CB was bound to three OR operators in the intergenic region between cB and cro, two OL operators between cB and the replication gene repA and even to operators of N15. Cro bound exclusively to the 16 bp operator site OR3 upstream of the ϕKO2 prophage repressor gene. The ϕKO2 genes cB and cro are regulated by several strong promoters overlapping with the OR operators. The data suggest that Cro represses cB transcription but not its own synthesis, as already reported for PY54 Cro. Thus, not only PY54, but also phage ϕKO2 possesses a genetic switch that diverges significantly from the switch of lambda-like phages. PMID:27527206

  19. Effects of the Histamine 1 Receptor Antagonist Cetirizine on the Osteoporotic Phenotype in H(+) /K(+) ATPase Beta Subunit KO Mice.

    PubMed

    Aasarød, Kristin M; Stunes, Astrid K; Mosti, Mats P; Ramezanzadehkoldeh, Masoud; Viggaklev, Bjørn I; Reseland, Janne E; Skallerud, Bjørn H; Fossmark, Reidar; Syversen, Unni

    2016-09-01

    Epidemiological studies suggest increased fracture risk in patients using proton pump inhibitors (PPIs). We have previously shown that the H(+) /K(+) ATPase beta subunit knockout (KO) mouse, which is a model of PPI-use, have lower bone mineral density (BMD) and impaired bone quality compared to wild type (WT) mice. Like PPI users, these KO mice display elevated gastric pH and hypergastrinemia, which in turn stimulates gastric histamine release. Previous studies have suggested a negative effect of histamine on bone, thus, we wanted to study whether a histamine 1 receptor (H1R) antagonist could improve bone quality in KO mice. Female KO and WT mice aged 8 weeks received either an H1R antagonist (cetirizine) or polyethylene glycol (PEG) for 6 months. At the end of the study, KO mice displayed elevated plasma histamine levels compared to WT. As demonstrated previously, the KO mice also exhibited lower whole body BMD, reduced mechanical bone strength, and impaired bone quality assessed by μCT. No significant differences, however, were found between the KO groups receiving cetirizine or PEG for any of the measured bone parameters. In vitro gene expression analyses of histamine receptors revealed the presence of H1R and H2R both in osteoblasts and osteoclasts, and H3R in late stage osteoblasts. In conclusion, administration of the H1R antagonist cetirizine in a concentration of 3 mg/kg did not rescue the osteoporotic phenotype in H(+) /K(+) ATPase beta subunit KO mice. It can, however, not be ruled out that histamine may influence bone via other receptors. J. Cell. Biochem. 117: 2089-2096, 2016. © 2016 Wiley Periodicals, Inc. PMID:26869358

  20. Antiproliferative and Proapoptotic Effects of Labisia pumila Ethanol Extract and Its Active Fraction in Human Melanoma HM3KO Cells

    PubMed Central

    Lope Pihie, Azimahtol Hawariah; Zakaria, Zainul Amiruddin; Othman, Fezah

    2012-01-01

    The present study was to determine the anticancer potential of Labisia pumila in in vitro models. Results from the study revealed that ethanol extract of L. pumila was more cytotoxic against HM3KO cells while having reduced effects on nonmalignant cells as compared to aqueous and hexane extracts. Thus, ethanol extract was selected to be further separated by using the bioassay-guided fractionation method to give an active fraction, SF2Lp. Results obtained from the flow cytometry analysis showed that SF2Lp was able to arrest the HM3KO cell cycle at the G1 phase, while morphological findings from AO-EB nuclear staining assays along with the Apoptotic Index confirmed the induction of apoptosis by SF2Lp in HM3KO cells. Results from the mechanistic study further revealed that SF2Lp treatment was able to concurrently increase the expression level of p53 and pro-apoptotic protein Bax and also reduce the expression level of anti-apoptotic protein BCl-2 in HM3KO cells, directly contributing to the increase in Bax/Bcl-2 ratio. These findings, therefore, suggested that L. pumila was able to inhibit HM3KO cell growth possibly by arresting the cell cycle at G1 phase and inducing apoptosis in HM3KO cells via the up- and down-regulation of Bax/Bcl-2 protein, mediated through a p53-dependent pathway. PMID:22474490

  1. Antiproliferative and Proapoptotic Effects of Labisia pumila Ethanol Extract and Its Active Fraction in Human Melanoma HM3KO Cells.

    PubMed

    Lope Pihie, Azimahtol Hawariah; Zakaria, Zainul Amiruddin; Othman, Fezah

    2012-01-01

    The present study was to determine the anticancer potential of Labisia pumila in in vitro models. Results from the study revealed that ethanol extract of L. pumila was more cytotoxic against HM3KO cells while having reduced effects on nonmalignant cells as compared to aqueous and hexane extracts. Thus, ethanol extract was selected to be further separated by using the bioassay-guided fractionation method to give an active fraction, SF2Lp. Results obtained from the flow cytometry analysis showed that SF2Lp was able to arrest the HM3KO cell cycle at the G1 phase, while morphological findings from AO-EB nuclear staining assays along with the Apoptotic Index confirmed the induction of apoptosis by SF2Lp in HM3KO cells. Results from the mechanistic study further revealed that SF2Lp treatment was able to concurrently increase the expression level of p53 and pro-apoptotic protein Bax and also reduce the expression level of anti-apoptotic protein BCl-2 in HM3KO cells, directly contributing to the increase in Bax/Bcl-2 ratio. These findings, therefore, suggested that L. pumila was able to inhibit HM3KO cell growth possibly by arresting the cell cycle at G1 phase and inducing apoptosis in HM3KO cells via the up- and down-regulation of Bax/Bcl-2 protein, mediated through a p53-dependent pathway. PMID:22474490

  2. [Effect of midazolam on mantle cell lymphoma JeKo-1 cell line and its relevant mechanisms].

    PubMed

    Hong, Jin-Quan; Wu, Shan-Hu; Chen, Zhi-Yuan; Zhuang, Wei-Huang; Gao, Hong-Zhi

    2013-12-01

    This study was aimed to explore the effect of midazolam on mantle cell lymphoma cell line JeKo-1 and the relevant mechanisms. Effects of midazolam on the proliferation and apoptosis of JeKo-1 cells were observed by CCK8 assay and flow cytometry, respectively. Effect of midazolam on the expression of BCL-2, cytochrome C (Cyto-C), pro-caspase-9, pro-caspase-8 and pro-caspase-3 protein were detected by Western blot. The results showed that midazolam could inhibit the growth of JeKo-1 cells significantly and the concentration of 50% growth inhibition (IC50) at 48 hours was approximately 40 µmol/L. After treatment with 20, 40, 80 µmol/L midazolam for 48 hours, a dose-dependent apoptosis of JeKo-1 cells could be observed. Meanwhile, a dose-dependent reduction of BCL-2, pro-caspase-9 and pro-caspase-3 protein expression and increase of Cyto-C protein expression in JeKo-1 cells were found, but the expression of pro-caspase-8 protein did not change. It is concluded that midazolam possibly initiates the mitochondrial pathway, not the death receptor pathway, by reducing the expression of BCL-2, leading in turn to the releasing of Cyto-C in mitochondria, then activating caspase-9 and caspase-3 protein, triggers the caspase cascade, and induces the apoptosis of JeKo-1 cells ultimately. PMID:24370029

  3. The Idea of an Innovated Concept of the Košice Geothermal Project

    NASA Astrophysics Data System (ADS)

    Bujanská, Alena; Böszörményi, László

    2015-11-01

    Slovakia has very limited amounts of fossil resources. However, it has a relatively high potential of geothermal energy which use is far below its possibilities. The most abundant geothermal resource, not only in Slovakia but throughout the central Europe, is Košice basin. Since the publication of the first ideas about the ambitious goal to exploit the geothermal potential of this site, 20 years has passed and three geothermal wells has been made but without any progress. In the article the authors present the idea of a fundamental change in the approach to improve the energy and economic efficiency of the project.

  4. Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS deficient ApoE ko mice

    PubMed Central

    Kuhlencordt, Peter J.; Padmapriya, P.; Rützel, S.; Schödel, J.; Hu, K.; Schäfer, A.; Huang, P.L.; Ertl, G.; Bauersachs, J.

    2013-01-01

    Objective Hypercholesterolemia is associated with decreased vascular nitric oxide bioavailability and deletion of endothelial nitric oxide synthase (eNOS) markedly accelerates atherosclerosis development in apolipoprotein E knockout (apoE ko) mice. The current study tests whether atheroprotection provided by a lipid lowering therapy with Ezetimibe depends on eNOS. Methods/Results ApoE ko and apoE/eNOS double ko (dko) mice received a high fat diet with or without 0.05% Ezetimibe. Ezetimibe significantly reduced plasma cholesterol concentrations and atherogenic lipoproteins in both genotypes to a similar extent. Moreover, the drug reduced vascular inflammation, as it significantly reduced Vascular Cell Adhesion Molecule-1 (VCAM-1) expression and vascular CD14 expression, a marker for mononuclear cell infiltration, in both genotypes. Neither NOS protein expression nor vascular reactivity of aortic rings were changed in apoE ko mice following Ezetimibe treatment. Significant lesion reduction was seen in Ezetimibe treated male and female apoE ko and apoE/eNOS dko animals (p≤0.05). Interestingly, the drug mediated additional atheroprotection in male apoE ko, compared to male eNOS dko mice, suggesting that lipid lowering does provide additional eNOS dependent atheroprotection in this experimental group. Conclusion Lipid lowering with Ezetimibe potently reduces atherosclerosis and vascular inflammation independent of eNOS. Moreover, Ezetimibe did not exert any effects on eNOS protein expression or enzyme activity. However, additional atheroprotection by Ezetimibe was observed in eNOS competent apoE ko mice, suggesting that some of the drug's antiatherosclerotic effects are mediated by the eNOS pathway. PMID:18479686

  5. Copepod community succession during warm season in Lagoon Notoro-ko, northeastern Hokkaido, Japan

    NASA Astrophysics Data System (ADS)

    Nakagawa, Yoshizumi; Ichikawa, Hideaki; Kitamura, Mitsuaki; Nishino, Yasuto; Taniguchi, Akira

    2015-06-01

    Lagoon Notoro-ko, located on the northeastern coast of Hokkaido, Japan, and connected to the Okhotsk Sea by a human-made channel, is strongly influenced by local hydrography, as water masses in the lagoon are seasonally influenced by the Soya Warm Current and the East Sakhalin Current. We here report on the succession of copepod communities during the warm season in relation to water mass exchange. Copepods were categorized into four seasonal communities (spring/early-summer, mid-summer, late-summer/fall, and early-winter) via a cluster analysis based on Bray-Curtis similarities. Spring/early-summer and early-winter communities were characterized by the temperate-boreal calanoid Pseudocalanus newmani, comprising 34.9%-77.6% of the total abundance of copepods during times of low temperature/salinity, as influenced by the prevailing East Sakhalin Current. Late-summer/fall communities were characterized by the neritic warm-water calanoid Paracalanus parvus s.l., comprising 63.9%-96.3% of the total abundance, as influenced by the Soya Warm Current. Mid-summer communities comprised approximately equal abundances of P. parvus, Eurytemora herdmani, Scolecithricella minor, and Centropages abdominalis (12.8%-28.2%); this community is transitional between those of the spring/early-summer and late-summer/fall. Copepod community succession in Lagoon Notoro-ko can be largely explained by seasonal changes in water masses.

  6. Further Development of Ko Displacement Theory for Deformed Shape Predictions of Nonuniform Aerospace Structures

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Fleischer, Van Tran

    2009-01-01

    The Ko displacement theory previously formulated for deformed shape predictions of nonuniform beam structures is further developed mathematically. The further-developed displacement equations are expressed explicitly in terms of geometrical parameters of the beam and bending strains at equally spaced strain-sensing stations along the multiplexed fiber-optic sensor line installed on the bottom surface of the beam. The bending strain data can then be input into the displacement equations for calculations of local slopes, deflections, and cross-sectional twist angles for generating the overall deformed shapes of the nonuniform beam. The further-developed displacement theory can also be applied to the deformed shape predictions of nonuniform two-point supported beams, nonuniform panels, nonuniform aircraft wings and fuselages, and so forth. The high degree of accuracy of the further-developed displacement theory for nonuniform beams is validated by finite-element analysis of various nonuniform beam structures. Such structures include tapered tubular beams, depth-tapered unswept and swept wing boxes, width-tapered wing boxes, and double-tapered wing boxes, all under combined bending and torsional loads. The Ko displacement theory, combined with the fiber-optic strain-sensing system, provide a powerful tool for in-flight deformed shape monitoring of unmanned aerospace vehicles by ground-based pilots to maintain safe flights.

  7. Estrogen receptor KO mice study on rapid modulation of spines and long-term depression in the hippocampus.

    PubMed

    Murakami, Gen; Hojo, Yasushi; Ogiue-Ikeda, Mari; Mukai, Hideo; Chambon, Pierre; Nakajima, Kohei; Ooishi, Yuuki; Kimoto, Tetsuya; Kawato, Suguru

    2015-09-24

    Rapid modulation of hippocampal synaptic plasticity through synaptic estrogen receptors is an essential topic. We analyzed estradiol-induced modulation of CA1 dendritic spines using adult male ERαKO and ERβKO mice. A 2h treatment of estradiol particularly increased the density of middle-head spines (diameter 0.3-0.4 µm) in wild type mouse hippocampal slices. The enhancement of spinogenesis was completely suppressed by MAP kinase inhibitor. Estradiol-induced increase in middle-head spines was observed in ERβKO mice (which express ERα), but not in ERαKO, indicating that ERα is necessary for the spinogenesis. Direct observation of the dynamic estradiol-induced enhancing effect on rapid spinogenesis was performed using time-lapse imaging of spines in hippocampal live slices from yellow fluorescent protein expressed mice. Both appearance and disappearance of spines occurred, and the number of newly appeared spines was significantly greater than that of disappeared spines, resulting in the net increase of the spine density within 2h. As another type of synaptic modulation, we observed that estradiol rapidly enhanced N-methyl-D-aspartate (NMDA)-induced long-term depression (LTD) in CA1 of the wild type mouse hippocampus. In contrast, estradiol did not enhance NMDA-LTD in ERαKO mice, indicating the involvement of ERα in the estrogen signaling. This article is part of a Special Issue entitled SI: Brain and Memory. PMID:25498865

  8. [KoMPASS--design, implementation and experiences concerning a structured communication skills training for physicians dealing with oncology].

    PubMed

    Vitinius, Frank; Sonntag, Bernd; Barthel, Yvette; Brennfleck, Barbara; Kuhnt, Susanne; Werner, Andreas; Schönefuß, Götz; Petermann-Meyer, Andrea; Gutberlet, Susanne; Stein, Barbara; Söllner, Wolfgang; Kruse, Johannes; Keller, Monika

    2013-12-01

    Goal of the KoMPASS project is to develop and test a training program that effectively improves oncologists' communication skills. The training draws with regard to concept, content and didactic methods to the specific challenges arising in interactions with cancer patients. Concept and didactical methods for an intensive training (KoMPASS Training) are being presented and complemented with experiences gathered during 39 trainings with 335 physicians, as well as findings from the training evaluation by participants. The participants' feedback after 4 months indicates successful transfer into clinical practice along with personal relief, improved self-efficacy, and communicative competencies. Even experienced practitioners ascribe high practical usefulness, and personal learning achievements to the KoMPASS training. The results of the concomitant study concerning self-efficacy, empathy, work-related stress and communicative competence will be published later. PMID:23677627

  9. Switching of the rotational direction of rhizoidal colonies in a newly isolated Bacillus mycoides strain Ko01.

    PubMed

    Cochran, Courtney; Masuda, Hisako

    2016-01-01

    Bacillus mycoides are known to form rhizoidal colonies on solid medium. In this study, a new strain of B. mycoides, strain Ko01, was isolated from soil. Genetic and growth patterns indicated that this strain belongs to subgroup II of the B. cereus group. Strain Ko01 forms extensive rhizoidal colonies with predictable directions of rotation. The concentration of the agar, and not the chemical composition, altered the direction of the colony rotation, switching from counterclockwise to clockwise. Agar concentration-dependent switching of rotation direction was unique to strain Ko01 and was not seen in colonies of other B. mycoides strains that were tested. Factors affecting colony chirality patterns appeared to be variable among B. mycoides strains. This feature can be used for the classification of B. mycoides strains. PMID:27118071

  10. Failure of T cell homing, reduced CD4/CD8alphaalpha intraepithelial lymphocytes, and inflammation in the gut of vitamin D receptor KO mice.

    PubMed

    Yu, Sanhong; Bruce, Danny; Froicu, Monica; Weaver, Veronika; Cantorna, Margherita T

    2008-12-30

    Specific pathogen-free IL-10 KO mice failed to develop inflammatory bowel disease (IBD), whereas IL-10/vitamin D receptor (VDR) double KO mice developed fulminating IBD. WT CD4 T cells inhibited experimental IBD, while VDR KO CD4 T cells failed to suppress IBD. VDR KO mice had normal numbers and functions of regulatory T cells. The percentages of IL-17- and IFN-gamma-secreting T cells in the gut of mice reconstituted with WT and VDR KO CD4 T cells were also not different. Instead, there were twice as many CD8alphaalpha intraepithelial lymphocytes (IEL) in mice that were reconstituted with WT CD4 T cells than in mice reconstituted with VDR KO CD4 T cells. Furthermore, VDR KO mice had reduced numbers of CD8alphaalpha IEL, absent CD4/CD8alphaalpha populations, and as a result low IL-10 production in the IEL. The lack of CD8alphaalpha IEL was due in part to decreased CCR9 expression on T cells that resulted in the failure of the VDR KO T cells to home to the small intestine. We conclude that the VDR mediates T cell homing to the gut and as a result the VDR KO mouse has reduced numbers of CD8alphaalpha IEL with low levels of IL-10 leading to increased inflammatory response to the normally harmless commensal flora. PMID:19095793

  11. Fermentation of sugars in orange peel hydrolysates to ethanol by recombinant Escherichia coli KO11

    SciTech Connect

    Grohmann, K.; Cameron, R.G.; Buslig, B.S.

    1995-12-31

    The conversion of monosaccharides in orange peel hydrolysates to ethanol by recombinant Escherichia coli KO11 has been investigated in pH-controlled batch fermentations at 32 and 37{degrees}C. pH values and concentration of peel hydrolysate were varied to determine approximate optimal conditions and limitations of these fermentations. Very high yields of ethanol were achieved by this microorganism at reasonable ethanol concentrations (28-48 g/L). The pH range between 5.8 and 6.2 appears to be optimal. The microorganism can convert all major monosaccharides in orange peel hydrolysates to ethanol and to smaller amounts of acetic and lactic acids. Acetic acid is coproduced in equimolar amounts with ethanol by catabolism of salts of galacturonic acid.

  12. Echium Oil Reduces Atherosclerosis in apoB100-only LDLrKO Mice

    PubMed Central

    Forrest, Lolita M.; Boudyguina, Elena; Wilson, Martha D.; Parks, John S.

    2012-01-01

    Introduction The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides. Objective We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis. Methods Mice were fed palm, echium, or fish oil-containing diets for 16 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. Results Compared to palm oil, echium oil feeding resulted in significantly less plasma triglyceride and cholesterol levels, and atherosclerosis, comparable to that of fish oil. Conclusion This is the first report that echium oil is anti-atherogenic, suggesting that it may be a botanical alternative to fish oil for atheroprotection. PMID:22100249

  13. CaV3.2 KO mice have altered retinal waves but normal direction selectivity.

    PubMed

    Hamby, Aaron M; Rosa, Juliana M; Hsu, Ching-Hsiu; Feller, Marla B

    2015-01-01

    Early in development, before the onset of vision, the retina establishes direction-selective responses. During this time period, the retina spontaneously generates bursts of action potentials that propagate across its extent. The precise spatial and temporal properties of these "retinal waves" have been implicated in the formation of retinal projections to the brain. However, their role in the development of direction selective circuits within the retina has not yet been determined. We addressed this issue by combining multielectrode array and cell-attached recordings to examine mice that lack the CaV3.2 subunit of T-type Ca2+ channels (CaV3.2 KO) because these mice exhibit disrupted waves during the period that direction selective circuits are established. We found that the spontaneous activity of these mice displays wave-associated bursts of action potentials that are altered from that of control mice: the frequency of these bursts is significantly decreased and the firing rate within each burst is reduced. Moreover, the projection patterns of the retina demonstrate decreased eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN). However, after eye-opening, the direction selective responses of CaV3.2 KO direction selective ganglion cells (DSGCs) are indistinguishable from those of wild-type DSGCs. Our data indicate that although the temporal properties of the action potential bursts associated with retinal waves are important for activity-dependent refining of retinal projections to central targets, they are not critical for establishing direction selectivity in the retina. PMID:25873107

  14. Calcium sensitivity and myofilament lattice structure in titin N2B KO mice

    PubMed Central

    Lee, Eun-Jeong; Nedrud, Joshua; Schemmel, Peter; Gotthardt, Michael; Irving, Thomas C.; Granzier, Henk L

    2012-01-01

    The cellular basis of the Frank-Starling “Law of the Heart” is the length-dependence of activation, but the mechanisms by which the sarcomere detects length changes and converts this information to altered calcium sensitivity has remained elusive. Here the effect of titin-based passive tension on the length-dependence of activation (LDA) was studied by measuring the tension-pCa relation in skinned mouse LV muscle at two sarcomere lengths (SLs). N2B KO myocardium, where the N2B spring element in titin is deleted and passive tension is elevated, was compared to WT myocardium. Myofilament lattice structure was studied with low-angle X-ray diffraction; the myofilament lattice spacing (d10) was measured as well as the ratio of the intensities of the 1,1 and 1,0 diffraction peaks (I11/I10) as an estimate of the degree of association of myosin heads with the thin filaments. Experiments were carried out in skinned muscle in which the lattice spacing was reduced with Dextran-T500. Experiments with and without lattice compression were also carried out following PKA phosphorylation of the skinned muscle. Under all conditions that were tested, LDA was significantly larger in N2B KO myocardium compared to WT myocardium, with the largest differences following PKA phosphorylation. A positive correlation between passive tension and LDA was found that persisted when the myofilament lattice was compressed with Dextran and that was enhanced following PKA phosphorylation. Low-angle X-ray diffraction revealed a shift in mass from thin filaments to thick filaments as sarcomere length was increased. Furthermore, a positive correlation was obtained between myofilament lattice spacing and passive tension and the change in I11/I10 and passive tension and these provide possible explanations for how titin-based passive tension might regulate calcium sensitivity. PMID:23246787

  15. The Košice meteorite fall: Atmospheric trajectory, fragmentation, and orbit

    NASA Astrophysics Data System (ADS)

    BorovičKa, Jiří; Tóth, Juraj; Igaz, Antal; Spurný, Pavel; Kalenda, Pavel; Haloda, Jakub; Svoreå, Ján; Kornoš, Leonard; Silber, Elizabeth; Brown, Peter; HusáRik, Marek

    2013-10-01

    The Košice meteorite fall occurred in eastern Slovakia on February 28, 2010, 22:25 UT. The very bright bolide was imaged by three security video cameras from Hungary. Detailed bolide light curves were obtained through clouds by radiometers on seven cameras of the European Fireball Network. Records of sonic waves were found on six seismic and four infrasonic stations. An atmospheric dust cloud was observed the next morning before sunrise. After careful calibration, the video records were used to compute the bolide trajectory and velocity. The meteoroid, of estimated mass of 3500 kg, entered the atmosphere with a velocity of 15 km s-1 on a trajectory with a slope of 60° to the horizontal. The largest fragment ceased to be visible at a height of 17 km, where it was decelerated to 4.5 km s-1. A maximum brightness of absolute stellar magnitude about -18 was reached at a height of 36 km. We developed a detailed model of meteoroid atmospheric fragmentation to fit the observed light curve and deceleration. We found that Košice was a weak meteoroid, which started to fragment under the dynamic pressure of only 0.1 MPa and fragmented heavily under 1 MPa. In total, 78 meteorites were recovered in the predicted fall area during official searches. Other meteorites were found by private collectors. Known meteorite masses ranged from 0.56 g to 2.37 kg. The meteorites were classified as ordinary chondrites of type H5 and shock stage S3. The heliocentric orbit had a relatively large semimajor axis of 2.7 AU and aphelion distance of 4.5 ± 0.5 AU. Backward numerical integration of the preimpact orbit indicates possible large variations of the orbital elements in the past due to resonances with Jupiter.

  16. Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1-Ko mice.

    PubMed

    Pietropaolo, Susanna; Goubran, Mina G; Joffre, Corinne; Aubert, Agnes; Lemaire-Mayo, Valerie; Crusio, Wim E; Layé, Sophie

    2014-11-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to critically influence brain development and functions. Dietary supplementation with n-3 PUFAs has been suggested as a non-pharmacological therapy for a number of developmental disorders, e.g., autistic spectrum disorders (ASD), but human studies so far have led to conflicting results. Furthermore, it has been hypothesized that the therapeutic impact of n-3 PUFAs on these disorders might be explained by their anti-inflammatory properties and their promoting effects on synaptic function and plasticity, but no clear evidence has been produced in this direction. We evaluated the impact of n-3 PUFA dietary supplementation in a mouse model of fragile X syndrome (FXS), i.e., a major developmental disease and the most frequent monogenic cause of ASD. Fmr1-KO and wild-type mice were provided with a diet enriched or not with n-3 PUFAs from weaning until adulthood when they were tested for multiple FXS-like behaviors. The brain expression of several cytokines and of brain-derived neurotrophic factor (BDNF) was concomitantly assessed as inflammatory and synaptic markers. n-3 PUFA supplementation rescued most of the behavioral abnormalities displayed by Fmr1-KO mice, including alterations in emotionality, social interaction and non-spatial memory, although not their deficits in social recognition and spatial memory. n-3 PUFAs also rescued most of the neuroinflammatory imbalances of KOs, but had a limited impact on their BDNF deficits. These results demonstrate that n-3 PUFAs dietary supplementation, although not a panacea, has a considerable therapeutic value for FXS and potentially for ASD, suggesting a major mediating role of neuroinflammatory mechanisms. PMID:25080404

  17. Methods for In-Flight Wing Shape Predictions of Highly Flexible Unmanned Aerial Vehicles: Formulation of Ko Displacement Theory

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Fleischer, Van Tran

    2010-01-01

    The Ko displacement theory is formulated for a cantilever tubular wing spar under bending, torsion, and combined bending and torsion loading. The Ko displacement equations are expressed in terms of strains measured at multiple sensing stations equally spaced on the surface of the wing spar. The bending and distortion strain data can then be input to the displacement equations to calculate slopes, deflections, and cross-sectional twist angles of the wing spar at the strain-sensing stations for generating the deformed shapes of flexible aircraft wing spars. The displacement equations have been successfully validated for accuracy by finite-element analysis. The Ko displacement theory that has been formulated could also be applied to calculate the deformed shape of simple and tapered beams, plates, and tapered cantilever wing boxes. The Ko displacement theory and associated strain-sensing system (such as fiber optic sensors) form a powerful tool for in-flight deformation monitoring of flexible wings and tails, such as those often employed on unmanned aerial vehicles. Ultimately, the calculated displacement data can be visually displayed in real time to the ground-based pilot for monitoring the deformed shape of unmanned aerial vehicles during flight.

  18. Acquisition of the Korean Imperfective Aspect Markers "-ko iss-" and "-a iss-" by Japanese Learners: A Multiple-Factor Account

    ERIC Educational Resources Information Center

    Ryu, Ju-Yeon; Horie, Kaoru; Shirai, Yasuhiro

    2015-01-01

    Although cross-linguistic research on second language tense-aspect acquisition has uncovered universal tendencies concerning the association between verbal semantics and tense-aspect markers, it is still unclear what mechanisms underlie this link. This study investigates the acquisition of two imperfective aspect markers ("-ko iss-" and…

  19. Incorporation of Half-Cycle Theory Into Ko Aging Theory for Aerostructural Flight-Life Predictions

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Tran, Van T.; Chen, Tony

    2007-01-01

    The half-cycle crack growth theory was incorporated into the Ko closed-form aging theory to improve accuracy in the predictions of operational flight life of failure-critical aerostructural components. A new crack growth computer program was written for reading the maximum and minimum loads of each half-cycle from the random loading spectra for crack growth calculations and generation of in-flight crack growth curves. The unified theories were then applied to calculate the number of flights (operational life) permitted for B-52B pylon hooks and Pegasus adapter pylon hooks to carry the Hyper-X launching vehicle that air launches the X-43 Hyper-X research vehicle. A crack growth curve for each hook was generated for visual observation of the crack growth behavior during the entire air-launching or captive flight. It was found that taxiing and the takeoff run induced a major portion of the total crack growth per flight. The operational life theory presented can be applied to estimate the service life of any failure-critical structural components.

  20. The conditional KO approach: Cre/Lox technology in human neurons

    PubMed Central

    Patzke, Christopher; Südhof, Thomas C.

    2016-01-01

    ABSTRACT The use of human pluripotent stem cells to model human diseases has become a new standard in biomedical sciences. To this end, patient-derived somatic cells are studied in vitro to mimic human pathological conditions. Here, we describe an alternative experimental strategy, the ‘conditional KO approach’, which allows engineering disease-relevant mutations in pluripotent stem cells from healthy donors. In combination with the Cre/Lox technology, this strategy enables us to study the molecular causes of human diseases independent of the genetic background or of genetic alterations induced by clonal selection. As a proof-of-principle, we generated pluripotent stem cells with conditional loss-of-function mutations in the human STXBP1 gene that encodes Munc18-1. Using neurons derived from these cells, we show that heterozygous disruption of STXBP1 produces a specific and selective impairment in synaptic transmission that may account for the severe neurological disease caused by such mutations in human patients. PMID:27141410

  1. Understanding side reactions in K-O2 batteries for improved cycle life.

    PubMed

    Ren, Xiaodi; Lau, Kah Chun; Yu, Mingzhe; Bi, Xuanxuan; Kreidler, Eric; Curtiss, Larry A; Wu, Yiying

    2014-11-12

    Superoxide based metal-air (or metal-oxygen) batteries, including potassium and sodium-oxygen batteries, have emerged as promising alternative chemistries in the metal-air battery family because of much improved round-trip efficiencies (>90%). In order to improve the cycle life of these batteries, it is crucial to understand and control the side reactions between the electrodes and the electrolyte. For potassium-oxygen batteries using ether-based electrolytes, the side reactions on the potassium anode have been identified as the main cause of battery failure. The composition of the side products formed on the anode, including some reaction intermediates, have been identified and quantified. Combined experimental studies and density functional theory (DFT) calculations show the side reactions are likely driven by the interaction of potassium with ether molecules and the crossover of oxygen from the cathode. To inhibit these side reactions, the incorporation of a polymeric potassium ion selective membrane (Nafion-K(+)) as a battery separator is demonstrated that significantly improves the battery cycle life. The K-O2 battery with the Nafion-K(+) separator can be discharged and charged for more than 40 cycles without increases in charging overpotential. PMID:25295518

  2. Extension of Ko Straight-Beam Displacement Theory to Deformed Shape Predictions of Slender Curved Structures

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Fleischer, Van Tran

    2011-01-01

    The Ko displacement theory originally developed for shape predictions of straight beams is extended to shape predictions of curved beams. The surface strains needed for shape predictions were analytically generated from finite-element nodal stress outputs. With the aid of finite-element displacement outputs, mathematical functional forms for curvature-effect correction terms are established and incorporated into straight-beam deflection equations for shape predictions of both cantilever and two-point supported curved beams. The newly established deflection equations for cantilever curved beams could provide quite accurate shape predictions for different cantilever curved beams, including the quarter-circle cantilever beam. Furthermore, the newly formulated deflection equations for two-point supported curved beams could provide accurate shape predictions for a range of two-point supported curved beams, including the full-circular ring. Accuracy of the newly developed curved-beam deflection equations is validated through shape prediction analysis of curved beams embedded in the windward shallow spherical shell of a generic crew exploration vehicle. A single-point collocation method for optimization of shape predictions is discussed in detail

  3. One-step bulk synthesis of stable, near unit-cell sized oxide nanoparticles and nanoparticle blends using KO2.

    PubMed

    Sutto, Thomas E

    2014-05-01

    Presented here is a novel one-step synthesis of oxide or hydroxide nanoparticles using, for the first time, potassium superoxide (KO2). This work demonstrates that the reaction of KO2 with different salt solutions produces grams of stable, near unit-cell sized nanoparticles. This new synthetic technique is applied to representative elements from across the periodic table to rapidly produce nanometer sized oxides or hydroxides of Mg, Al, Y, Ti, Mn, Fe, Co, Ni, Cu, Zn, Sn, Tl, Pb, and Ce. This technique is also used to produce blends of nanoparticles, demonstrating the ability to prepare complex materials such as nanoparticulate blends of a lithium cathode material (LiCoO2), the multiferroic compound (BiMnO(3+δ)), and the superconducting YBa2Cu3O(7-γ). PMID:24724979

  4. Different effects of raised [K+]o on membrane potential and contraction in mouse fast- and slow-twitch muscle.

    PubMed

    Cairns, S P; Hing, W A; Slack, J R; Mills, R G; Loiselle, D S

    1997-08-01

    Increasing extracellular K+ concentration ([K+]o) from 4 to 7-14 mM reduced both tetanic force and resting membrane potential (Em) in isolated slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles of the mouse. The tetanic force-[K+]o relationships showed a greater force loss over 8-11 mM [K+]o in soleus than EDL, mainly because the Em was 2-3 mV less negative at each [K+]o in soleus. The tetanic force-resting Em relationships show that force was reduced in two phases: phase 1 (Em < -60 mV), a 20% force decline in which the relationships superimposed in soleus and EDL, and phase 2 (Em -60 to -55 mV), a marked force decline that was steeper in EDL than soleus. Additionally in phase 2, longer stimulation pulses restored tetanic force; the twitch force-stimulation strength relationship was shifted toward higher voltages; caffeine, a myoplasmic Ca2+ concentration elevator, increased maximum force; and twitch force fell abruptly. We suggest that 1) the K(+)-depressed force is due to reduced Ca2+ release resulting from an altered action potential profile (phase 1) and inexcitable fibers due to an increased action potential threshold (phase 2), and 2) K+ contributes to fatigue in both fast- and slow-twitch muscle when it causes depolarization to about -60 mV. PMID:9277357

  5. Distinct calcium signals in developing cortical interneurons persist despite disorganization of cortex by Tbr1 KO.

    PubMed

    Easton, C R; Dickey, C W; Moen, S P; Neuzil, K E; Barger, Z; Anderson, T M; Moody, W J; Hevner, R F

    2016-07-01

    Cortical development involves the structuring of network features by genetically programmed molecular signaling pathways. Additionally, spontaneous ion channel activity refines neuronal connections. We examine Ca(2+) fluctuations in the first postnatal week of normal mouse neocortex and that expressing knockout of the transcription factor T-brain-1 (Tbr1): a signaling molecule in cortical patterning and differentiation of excitatory neurons. In cortex, glutamatergic neurons express Tbr1 just before the onset of population electrical activity that is accompanied by intracellular Ca(2+) increases. It is known that glutamatergic cells are disordered with Tbr1 KO such that normal laying of the cortex, with newer born cells residing in superficial layers, does not occur. However, the fate of cortical interneurons is not well studied, nor is the ability of Tbr1 deficient cortex to express normal physiological activity. Using fluorescent proteins targeted to interneurons, we find that cortical interneurons are also disordered in the Tbr1 knockout. Using Ca(2+) imaging we find that population activity in mutant cortex occurs at normal frequencies with similar sensitivity to GABAA receptor blockade as in nonmutant cortex. Finally, using multichannel fluorescence imaging of Ca(2+) indicator dye and interneurons labeled with red fluorescent protein, we identify an additional Ca(2+) signal in interneurons distinct from population activity and with different pharmacological sensitivities. Our results show the population activity described here is a robust property of the developing network that continues in the absence of an important signaling molecule, Tbr1, and that cortical interneurons generate distinct forms of activity that may serve different developmental functions. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 705-720, 2016. PMID:26473411

  6. The antagonistic effect of K+o and dihydro-ouabain on the Na+ pump current of single rat and guinea-pig cardiac cells.

    PubMed Central

    Hermans, A N; Glitsch, H G; Verdonck, F

    1995-01-01

    1. The antagonistic effect of extracellular potassium ions (K+o) and dihydro-ouabain (DHO) on the Na(+)-K+ pump current (Ip) was studied in isolated ventricular cells. 2. The myocytes were isolated from rats and guinea-pigs, two species with different sensitivity towards cardiac glycosides. Ip measurements were performed at 32-34 degrees C by means of whole-cell recording. The membrane potential was held at -20 mV throughout. 3. The DHO concentration ([DHO]) required for half-maximal Ip inhibition (apparent KD value, KD') amounted to 2.4 x 10(-3) and 1.4 x 10(-5) M for rat and guinea-pig myocytes, respectively, at 5.4 mM K+o. 4. The data suggest one-to-one binding of DHO to the Na(+)-K+ pump and a smaller association rate constant, as well as a larger dissociation rate constant, for binding of DHO in the rat cells. 5. Ip activation by K+o was nearly identical in myocytes of both species and was measured to be half-maximal at approximately 1 mM K+o. Half-maximal Ip activation by K+o remained essentially unchanged, but Ip decreased in media containing [DHO] near the respective KD' at 5.4 mM K+o. 6. The concentration-response curve of Ip inhibition by DHO was shifted to higher [DHO] at higher [K+]o. KD' increased correspondingly. The slope of the curve was unaffected. 7. Ip and KD' displayed a similar dependence on [K+]o. 8. KD' was larger in Na(+)-free than in Na(+)-containing media under conditions in which the activation of Ip by K+o was nearly the same. 9. It is concluded that the antagonism between K+o and DHO, with regard to the activation of Ip, is non-competitive. A possible mechanism of the antagonism is discussed. The mechanism implies binding of K+o and DHO to different conformational states of the Na(+)-K+ pump which are temporarily exposed to the external face of the sarcolemma in the pump cycle. The DHO-bound states do not participate in the generation of Ip. PMID:7623280

  7. Studies of N ~ 40 Ni isotopes via neutron-knockout (nKO) and deep-inelastic (DI) reactions

    NASA Astrophysics Data System (ADS)

    Chiara, C. J.; Recchia, F.; Gade, A.; Janssens, R. V. F.; Walters, W. B.

    2013-10-01

    V. BADER, T. BAUGHER, D. BAZIN, J.S. BERRYMAN, B.A. BROWN, C. LANGER, N. LARSON, S.N. LIDDICK, E. LUNDERBERG, S. NOJI, C. PROKOP, S.R. STROBERG, S. SUCHYTA, D. WEISSHAAR, S. WILLIAMS, NSCL/MSU, M. ALBERS, M. ALCORTA, P.F. BERTONE, M.P. CARPENTER, J. CHEN, C.R. HOFFMAN, F.G. KONDEV, T. LAURITSEN, A.M. ROGERS, D. SEWERYNIAK, S. ZHU, ANL, C.M. CAMPBELL, LBNL, H.M. DAVID, D.T. DOHERTY, U. of Edinburgh/ANL, A. KORICHI, CSNSM-IN2P3/ANL, C.J. LISTER, U. of Mass.-Lowell, K. WIMMER, Central Mich. U. -- Excited states in 68Ni were populated in 2nKO reactions at NSCL. Prompt γ rays were detected with the GRETINA array located in front of the S800 separator. A hodoscope at the S800 focal plane captured the 68Ni ions, where isomeric decays could be correlated with prompt γ rays. Decay of the first excited state, a 0+ isomer, was observed, confirming that its energy substantially differs from the literature value. Comparing the decay patterns of excited states with shell-model calculations provides insight into their underlying structure. Data from 70Zn + 208Pb DI reactions studied with Gammasphere provide results consistent with the 2nKO. Single-particle strengths are also under investigation in the odd- A Ni isotopes via 1nKO reactions. Supported in part by the DoE (DE-FG02-94ER40834, DE-AC02-06CH11357), NSF (PHY-1102511), and NNSA (DE-NA0000979).

  8. Both chronic treatments by epothilone D and fluoxetine increase the short-term memory and differentially alter the mood status of STOP/MAP6 KO mice.

    PubMed

    Fournet, Vincent; de Lavilléon, Gaetan; Schweitzer, Annie; Giros, Bruno; Andrieux, Annie; Martres, Marie-Pascale

    2012-12-01

    Recent evidence underlines the crucial role of neuronal cytoskeleton in the pathophysiology of psychiatric diseases. In this line, the deletion of STOP/MAP6 (Stable Tubule Only Polypeptide), a microtubule-stabilizing protein, triggers various neurotransmission and behavioral defects, suggesting that STOP knockout (KO) mice could be a relevant experimental model for schizoaffective symptoms. To establish the predictive validity of such a mouse line, in which the brain serotonergic tone is dramatically imbalanced, the effects of a chronic fluoxetine treatment on the mood status of STOP KO mice were characterized. Moreover, we determined the impact, on mood, of a chronic treatment by epothilone D, a taxol-like microtubule-stabilizing compound that has previously been shown to improve the synaptic plasticity deficits of STOP KO mice. We demonstrated that chronic fluoxetine was either antidepressive and anxiolytic, or pro-depressive and anxiogenic, depending on the paradigm used to test treated mutant mice. Furthermore, control-treated STOP KO mice exhibited paradoxical behaviors, compared with their clear-cut basal mood status. Paradoxical fluoxetine effects and control-treated STOP KO behaviors could be because of their hyper-reactivity to acute and chronic stress. Interestingly, both epothilone D and fluoxetine chronic treatments improved the short-term memory of STOP KO mice. Such treatments did not affect the serotonin and norepinephrine transporter densities in cerebral areas of mice. Altogether, these data demonstrated that STOP KO mice could represent a useful model to study the relationship between cytoskeleton, mood, and stress, and to test innovative mood treatments, such as microtubule-stabilizing compounds. PMID:23013328

  9. Age-related T-cell cytokine profile parallels corneal disease severity in Sjögren’s syndrome-like keratoconjunctivitis sicca in CD25KO mice*

    PubMed Central

    Hwang, Cindy S.; Pitcher, John D.; Pangelinan, Solherny B.; Rahimy, Ehsan; Chen, Wei; Yoon, Kyung-Chul; Farley, William J.; Niederkorn, Jerry Y.; Stern, Michael E.; Li, De-Quan; Pflugfelder, Stephen C.

    2010-01-01

    Objectives. IL-2rα (CD25)−/− mice develop autoimmunity and lymphoproliferative disorders, including SS-like disease. The objective of this study was to evaluate the severity of corneal epithelial disease and T-cell cytokine profile in the ocular surface tissues of CD25KO mice. Methods. CD25KO mice were evaluated at 8, 12 and 16 weeks of age. Corneal epithelial smoothness and corneal permeability were measured. Phenotype of infiltrating lymphocytes was evaluated by immunohistochemistry. Th-1, -2 and -17 associated factors were measured by real-time PCR in cornea and conjunctiva and by Luminex immunobead assay in tears. Results. Compared with 8-week-old wild-type (WT) mice, CD25KO mice of the same age had significantly greater corneal irregularity and a significant increase in the number of CD4+ and CD8+ T cells infiltrating the conjunctiva. CD25KO mice had significantly higher levels of IL-6, TGF-β1, IL-23R, IL-17A, IL-17F, IL-21, CCL20, IL-10, GATA-3 and IFN-γ mRNA transcripts in their cornea and conjunctiva than WT mice at 8 weeks. IL-17A and IL-17F mRNA transcripts peaked at 12 weeks, whereas IFN-γ spiked at 16 weeks in CD25KO mice. Increased expression of IL-17A and IL-17F at 12 weeks in CD25KO mice was accompanied by a worsening of corneal surface parameters and an increase of CD4+ T cell infiltrating the cornea. Conclusions. Disruption of IL-2 signalling in CD25KO mice results in age-dependent SS-like autoimmune lacrimal-keratoconjunctivitis. A mix of Th-1 and Th-17 cytokines was detected. The peak severity of corneal epithelial disease corresponded to the peak of IL-17 expression. PMID:20007286

  10. Microstructure and texture of zinc deformed by extrusion with forward-backward rotating die (KoBo)

    NASA Astrophysics Data System (ADS)

    Sztwiertnia, K.; Kawalko, J.; Bieda, M.; Jaskowski, M.; Pieła, K.; Bochniak, W.

    2015-04-01

    The KoBo device is a press with a cyclically rotating die enabling extrusion of ingots with the permanent destabilization of their substructure. The method involves a cyclic change of deformation path that increases the plasticity of the material and inhibits formation and propagation of cracks. The possibility of using KoBo for obtaining zinc wires with high mechanical properties was explored. A polycrystalline zinc ingot of purity of 99.995% was subjected to extrusion at room temperature. The microstructure of the material was investigated primarily via high-resolution electron backscatter diffraction using a scanning electron microscope. The microstructure is heterogeneous and consists of grains elongated slightly in the extrusion direction (ED). The material has a relatively sharp nearly axial texture with the ED scattered between the <1 0 -1 0> and <2 -1 -1 0> directions. More than 95% of high-angle grain boundaries do not correspond to any twin or low Σ CSL boundaries. The dimensions of the grains range from 10 - 20 micrometers down to the sub-micron scale. Despite the relatively large grains, the final product exhibits very good mechanical properties, which could not be explained by the Hall - Petch relation. It was found that besides grain refinement two other effects could affect the material mechanical properties. These effects are formation of nanograins inside the large, micrometer-sized grains and formation of broad areas of high-density crystal lattice defects extended along the HAGBs.

  11. Applications of Ko Displacement Theory to the Deformed Shape Predictions of the Doubly-Tapered Ikhana Wing

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Richards, W. Lance; Fleischer, Van Tran

    2009-01-01

    The Ko displacement theory, formulated for weak nonuniform (slowly changing cross sections) cantilever beams, was applied to the deformed shape analysis of the doubly-tapered wings of the Ikhana unmanned aircraft. The two-line strain-sensing system (along the wingspan) was used for sensing the bending strains needed for the wing-deformed shapes (deflections and cross-sectional twist) analysis. The deflection equation for each strain-sensing line was expressed in terms of the bending strains evaluated at multiple numbers of strain-sensing stations equally spaced along the strain-sensing line. For the preflight shape analysis of the Ikhana wing, the strain data needed for input to the displacement equations for the shape analysis were obtained from the nodal-stress output of the finite-element analysis. The wing deflections and cross-sectional twist angles calculated from the displacement equations were then compared with those computed from the finite-element computer program. The Ko displacement theory formulated for weak nonlinear cantilever beams was found to be highly accurate in the deformed shape predictions of the doubly-tapered Ikhana wing.

  12. Comparative study of dermal components and plasma TGF-β1 levels in Slc39a13/Zip13-KO mice.

    PubMed

    Hirose, Takuya; Ogura, Takayuki; Tanaka, Keisuke; Minaguchi, Jun; Yamauchi, Takeshi; Fukada, Toshiyuki; Koyama, Yoh-ichi; Takehana, Kazushige

    2015-11-01

    Ehlers-Danlos syndrome (EDS) is a group of disorders caused by abnormalities that are identified in the extracellular matrix. Transforming growth factor-β1 (TGF-β1) plays a crucial role in formation of the extracellular matrix. It has been reported that the loss of function of zinc transporter ZRT/IRT-like protein 13 (ZIP13) causes the spondylocheiro dysplastic form of EDS (SCD-EDS: OMIM 612350), in which dysregulation of the TGF-β1 signaling pathway is observed, although the relationship between the dermis abnormalities and peripheral TGF-β1 level has been unclear. We investigated the characteristics of the dermis of the Zip13-knockout (KO) mouse, an animal model for SCD-EDS. Both the ratio of dermatan sulfate (DS) in glycosaminoglycan (GAG) components and the amount of collagen were decreased, and there were very few collagen fibrils with diameters of more than 150 nm in Zip13-KO mice dermis. We also found that the TGF-β1 level was significantly higher in Zip13-KO mice serum. These results suggest that collagen synthesis and collagen fibril fusion might be impaired in Zip13-KO mice and that the possible decrease of decorin level by reduction of the DS ratio probably caused an increase of free TGF-β1 in Zip13-KO mice. In conclusion, skin fragility due to defective ZIP13 protein may be attributable to impaired extracellular matrix synthesis accompanied by abnormal peripheral TGF-β homeostasis. PMID:26050750

  13. Bortezomib, C1-inhibitor and plasma exchange do not prolong the survival of multi-transgenic GalT-KO pig kidney xenografts in baboons.

    PubMed

    Le Bas-Bernardet, S; Tillou, X; Branchereau, J; Dilek, N; Poirier, N; Châtelais, M; Charreau, B; Minault, D; Hervouet, J; Renaudin, K; Crossan, C; Scobie, L; Takeuchi, Y; Diswall, M; Breimer, M E; Klar, N; Daha, M R; Simioni, P; Robson, S C; Nottle, M B; Salvaris, E J; Cowan, P J; d'Apice, A J F; Sachs, D H; Yamada, K; Lagutina, I; Duchi, R; Perota, A; Lazzari, G; Galli, C; Cozzi, E; Soulillou, J-P; Vanhove, B; Blancho, G

    2015-02-01

    Galactosyl-transferase KO (GalT-KO) pigs represent a potential solution to xenograft rejection, particularly in the context of additional genetic modifications. We have performed life supporting kidney xenotransplantation into baboons utilizing GalT-KO pigs transgenic for human CD55/CD59/CD39/HT. Baboons received tacrolimus, mycophenolate mofetil, corticosteroids and recombinant human C1 inhibitor combined with cyclophosphamide or bortezomib with or without 2-3 plasma exchanges. One baboon received a control GalT-KO xenograft with the latter immunosuppression. All immunosuppressed baboons rejected the xenografts between days 9 and 15 with signs of acute humoral rejection, in contrast to untreated controls (n = 2) that lost their grafts on days 3 and 4. Immunofluorescence analyses showed deposition of IgM, C3, C5b-9 in rejected grafts, without C4d staining, indicating classical complement pathway blockade but alternate pathway activation. Moreover, rejected organs exhibited predominantly monocyte/macrophage infiltration with minimal lymphocyte representation. None of the recipients showed any signs of porcine endogenous retrovirus transmission but some showed evidence of porcine cytomegalovirus (PCMV) replication within the xenografts. Our work indicates that the addition of bortezomib and plasma exchange to the immunosuppressive regimen did not significantly prolong the survival of multi-transgenic GalT-KO renal xenografts. Non-Gal antibodies, the alternative complement pathway, innate mechanisms with monocyte activation and PCMV replication may have contributed to rejection. PMID:25612490

  14. Comparative study of dermal components and plasma TGF-β1 levels in Slc39a13/Zip13-KO mice

    PubMed Central

    HIROSE, Takuya; OGURA, Takayuki; TANAKA, Keisuke; MINAGUCHI, Jun; YAMAUCHI, Takeshi; FUKADA, Toshiyuki; KOYAMA, Yoh-ichi; TAKEHANA, Kazushige

    2015-01-01

    Ehlers-Danlos syndrome (EDS) is a group of disorders caused by abnormalities that are identified in the extracellular matrix. Transforming growth factor-β1 (TGF-β1) plays a crucial role in formation of the extracellular matrix. It has been reported that the loss of function of zinc transporter ZRT/IRT-like protein 13 (ZIP13) causes the spondylocheiro dysplastic form of EDS (SCD-EDS: OMIM 612350), in which dysregulation of the TGF-β1 signaling pathway is observed, although the relationship between the dermis abnormalities and peripheral TGF-β1 level has been unclear. We investigated the characteristics of the dermis of the Zip13-knockout (KO) mouse, an animal model for SCD-EDS. Both the ratio of dermatan sulfate (DS) in glycosaminoglycan (GAG) components and the amount of collagen were decreased, and there were very few collagen fibrils with diameters of more than 150 nm in Zip13-KO mice dermis. We also found that the TGF-β1 level was significantly higher in Zip13-KO mice serum. These results suggest that collagen synthesis and collagen fibril fusion might be impaired in Zip13-KO mice and that the possible decrease of decorin level by reduction of the DS ratio probably caused an increase of free TGF-β1 in Zip13-KO mice. In conclusion, skin fragility due to defective ZIP13 protein may be attributable to impaired extracellular matrix synthesis accompanied by abnormal peripheral TGF-β homeostasis. PMID:26050750

  15. Entomological evaluation of PermaNet 2.0® and K-O Tab 1-2-3® treated nets in comparison to nets conventionally treated with deltamethrin, after repeated washing.

    PubMed

    Kayedi, Mohammad Hassan; Khamisabadi, Kiumars; Dehghani, Nader; Haghdoost, Ali Akbar

    2015-06-01

    The residual insecticidal power of two types of ITNs (PermaNet 2.0® (PN2) and K-O Tab 1-2-3® (KO 123)), compared to K-O Tab® (KO) treated nets, was assessed. The nets were tested unwashed, and after being washed, by hand 5, 15 and 21 times, respectively. After each wash, the nets were dried vertically on a line, in the shade. Two types of bioassays (mean median knock down times (MMKDT) and mortality 24 hours after a 3-minute exposure (%mortality)) were used, along with reared female Anopheles stephensi. The number of washes had a great impact on MMKDT and %mortality of all types of nets. This impact was greater for conventionally treated nets, indicating that PN2 and KO 123 nets are significantly more wash resistant than KO nets after 21 washes. There was no significant difference between PN2 and KO 123 with respect to %mortality 24 hours after a 3-minute exposure at 0, 15 and 21 washes. Similarly, the same results were obtained for MMKDT, and the differences between PN2 and KO 123 were not statistically significant. This study demonstrates that the efficacy of KO 123 nets is as beneficial as the efficacy of PN2 nets up to 21 washes. PMID:25978624

  16. Entomological evaluation of PermaNet 2.0® and K-O Tab 1-2-3® treated nets in comparison to nets conventionally treated with deltamethrin, after repeated washing

    PubMed Central

    Kayedi, Mohammad Hassan; Khamisabadi, Kiumars; Dehghani, Nader; Haghdoost, Ali Akbar

    2015-01-01

    The residual insecticidal power of two types of ITNs (PermaNet 2.0® (PN2) and K-O Tab 1-2-3® (KO 123)), compared to K-O Tab® (KO) treated nets, was assessed. The nets were tested unwashed, and after being washed, by hand 5, 15 and 21 times, respectively. After each wash, the nets were dried vertically on a line, in the shade. Two types of bioassays (mean median knock down times (MMKDT) and mortality 24 hours after a 3-minute exposure (%mortality)) were used, along with reared female Anopheles stephensi. The number of washes had a great impact on MMKDT and %mortality of all types of nets. This impact was greater for conventionally treated nets, indicating that PN2 and KO 123 nets are significantly more wash resistant than KO nets after 21 washes. There was no significant difference between PN2 and KO 123 with respect to %mortality 24 hours after a 3-minute exposure at 0, 15 and 21 washes. Similarly, the same results were obtained for MMKDT, and the differences between PN2 and KO 123 were not statistically significant. This study demonstrates that the efficacy of KO 123 nets is as beneficial as the efficacy of PN2 nets up to 21 washes. PMID:25978624

  17. Lipidomics profile of a NAPE-PLD KO mouse provides evidence of a broader role of this enzyme in lipid metabolism in the brain.

    PubMed

    Leishman, Emma; Mackie, Ken; Luquet, Serge; Bradshaw, Heather B

    2016-06-01

    A leading hypothesis of N-acyl ethanolamine (NAE) biosynthesis, including the endogenous cannabinoid anandamide (AEA), is that it depends on hydrolysis of N-acyl-phosphatidylethanolamines (NAPE) by a NAPE-specific phospholipase D (NAPE-PLD). Thus, deletion of NAPE-PLD should attenuate NAE levels. Previous analyses of two different NAPE-PLD knockout (KO) strains produced contradictory data on the importance of NAPE-PLD to AEA biosynthesis. Here, we examine this hypothesis with a strain of NAPE-PLD KO mice whose lipidome is uncharacterized. Using HPLC/MS/MS, over 70 lipids, including the AEA metabolite, N-arachidonoyl glycine (NAGly), the endocannabinoid 2-arachidonyl glycerol (2-AG) and prostaglandins (PGE(2) and PGF(2α)), and over 60 lipoamines were analyzed in 8 brain regions of KO and wild-type (WT) mice. Lipidomics analysis of this third NAPE-PLD KO strain shows a broad range of lipids that were differentially affected by lipid species and brain region. Importantly, all 6 NAEs measured were significantly reduced, though the magnitude of the effect varied by fatty acid saturation length and brain region. 2-AG levels were only impacted in the brainstem, where levels were significantly increased in KO mice. Correspondingly, levels of arachidonic acid were significantly decreased exclusively in brainstem. NAGly levels were significantly increased in 4 brain regions and levels of PGE(2) increased in 6 of 8 brain regions in KO mice. These data indicate that deletion of NAPE-PLD has far broader effects on the lipidome than previously recognized. Therefore, behavioral characteristics of suppressing NAPE-PLD activity may be due to a myriad of effects on lipids and not simply due to reduced AEA biosynthesis. PMID:26956082

  18. NEXAFS experiment and multiple scattering calculations on KO2: Effects on the π resonance in the solid phase

    NASA Astrophysics Data System (ADS)

    Pedio, M.; Wu, Z. Y.; Benfatto, M.; Mascaraque, A.; Michel, E.; Ottaviani, C.; Crotti, C.; Peloi, M.; Zacchigna, M.; Comicioli, C.

    2002-10-01

    The high-energy resolution O K-edge absorption near-edge x-ray absorption fine structure spectrum has been measured for in situ prepared potassium superoxide. The experimental data have been analyzed in detail by multiple scattering calculations using self-consistent field potentials. In particular, the so-called π resonance at the rising edge, which presents a double-peak structure, has been totally resolved and reproduced by the calculations. This analysis indicates that the grown material is arranged in a KO2 structure with an O-O distance between 1.31 and 1.34 Å. Moreover, the calculation demonstrates both a complete ionic character of the bound between the O2- anion and K atoms and a strong interaction between the anion and solid-state matrices.

  19. Vibrational spectra and structure of the KO 2 complex in solid argon. A far-infrared study

    NASA Astrophysics Data System (ADS)

    Tremblay, Benoît; Manceron, Laurent; Roy, Pascale; Le, Anne-Marie; Quéré; Roy, Denis

    1994-10-01

    The observation of new fundamental frequencies for the potassium superoxide KO 2 is reported for different isotopic species: ν 3 of 39K 16O 2, 39K 18O 2 and 39K 16O 18O, and ν 2 of 41K 16O 2, 41K 18O 2, 41K 16O 18O and 39K 17O 18O. Using these values and a fixed OO internuclear distance, we calculated the geometry and force constants from a harmonic force field. We estimated an OKO angle of 37° ± 2°, and a KO internuclear distance of the order of 2.10±0.14 Å. These values disagree with previous theoretical determinations.

  20. Coastal vulnerability to typhoon inundation in the Bay of Bangkok, Thailand? Evidence from carbonate boulder deposits on Ko Larn island

    NASA Astrophysics Data System (ADS)

    Terry, James P.; Jankaew, Kruawun; Dunne, Kieran

    2015-11-01

    At the head of the Gulf of Thailand, the subsiding Chao Phraya delta and adjacent low-lying coastlines surrounding the Bay of Bangkok are at risk of coastal flooding. Although a significant marine inundation event has not been experienced in historical times, this work identifies coastal depositional evidence for high-energy waves in the past. On Ko Larn island in eastern Bay of Bangkok, numerous coastal carbonate boulders (CCBs) were discovered at elevations up to 4+ m above sea level, the largest weighing over 1.3 tonnes. For the majority of CCBs, their karstified appearance bears testimony to long periods of immobility since original deposition, whilst their geomorphic settings on coastal slopes of coarse blocky talus is helpful in recognising lifting (saltation) as the probable mode of wave transport. In the absence of local tsunamigenic potential, these CCBs are considered to be prehistoric typhoon deposits, presumably sourced from fringing coral reefs by high-energy wave action. Application of existing hydrodynamic flow transport equations reveals that 4.7 m/s and 7.1 m/s are the minimum flow velocities required to transport 50% and 100% of the measured CCBs, respectively. Such values are consistent with cyclone-impacted coastlines studied elsewhere in the tropical Asia-Pacific region. Overall, the evidence of elevated carbonate boulder deposits on Ko Larn implies that typhoons before the modern record may have entered the Bay of Bangkok. The recurrence of a similar event in future would have the potential to cause damaging marine inundation on surrounding low-lying coastlines.

  1. Vasoactive Intestinal Peptide Knockout (VIP KO) mouse model of sulfite-sensitive asthma: up-regulation of novel lung carbonyl reductase

    PubMed Central

    2011-01-01

    Background We earlier reported spontaneous features of asthma in Vasoactive Intestinal Peptide knockout mice (VIP KO): 1) peribronchiolar airway inflammation, with accumulation of lymphocytes and eosinophils, 2) pro-inflammatory cytokine production of IL-5, IL-6, with IFN-γ, and 3) airway hyper-responsiveness to inhaled methacholine. In human asthma, a phenotype with sulfite sensitivity leads to airway inflammation and hyper-responsiveness to inhaled sulfites, and is associated with upregulation of anti-oxidant protein lung carbonyl reductase. For the present experiments, we examined the role of VIP in modulating anti-oxidant genes and their proteins, including lung carbonyl reductase. Results Four male VIP KO mice and four wild-type age- and gender matched mice had lungs examined for whole genome microarray and a proteomics approach using mass spectrometry. The proteomics analysis revealed that a novel variant of anti-oxidant protein lung carbonyl reductase (car3) was uniquely and markedly elevated in the VIP KO mice. RT-PCR indicated that carbonic anhydrase 3, which is an anti-oxidant protein, was elevated in the VIP KO mice. Conclusions These data support the concept that VIP influences the endogenous oxidant/antioxidant balance. One potential implication is that VIP and its analogues may be used to treat inflammatory diseases, including asthma. PMID:22103391

  2. Genome Sequence of Halomonas sp. Strain KO116, an Ionic Liquid-Tolerant Marine Bacterium Isolated from a Lignin-Enriched Seawater Microcosm.

    PubMed

    O'Dell, Kaela B; Woo, Hannah L; Utturkar, Sagar; Klingeman, Dawn; Brown, Steven D; Hazen, Terry C

    2015-01-01

    Halomonas sp. strain KO116 was isolated from Nile Delta Mediterranean Sea surface water enriched with insoluble organosolv lignin. It was further screened for growth on alkali lignin minimal salts medium agar. The strain tolerates the ionic liquid 1-ethyl-3-methylimidazolium acetate. Its complete genome sequence is presented in this report. PMID:25953187

  3. Genome Sequence of Halomonas sp. Strain KO116, an Ionic Liquid-Tolerant Marine Bacterium Isolated from a Lignin-Enriched Seawater Microcosm

    PubMed Central

    O’Dell, Kaela B.; Woo, Hannah L.; Utturkar, Sagar; Klingeman, Dawn; Brown, Steven D.

    2015-01-01

    Halomonas sp. strain KO116 was isolated from Nile Delta Mediterranean Sea surface water enriched with insoluble organosolv lignin. It was further screened for growth on alkali lignin minimal salts medium agar. The strain tolerates the ionic liquid 1-ethyl-3-methylimidazolium acetate. Its complete genome sequence is presented in this report. PMID:25953187

  4. Bortezomib, C1-inhibitor and Plasma Exchange Do Not Prolong the Survival of Multi-transgenic GalT-KO Pig Kidney Xenografts in Baboons

    PubMed Central

    Le, Bas-Bernardet S.; Tillou, X.; Branchereau, J.; Dilek, N.; Poirier, N.; Châtelais, M.; Charreau, B.; Minault, D.; Hervouet, J.; Renaudin, K.; Crossan, C.; Scobie, L.; Takeuchi, Y.; Diswall, M.; Breimer, M.E.; Klar, N.; Daha, M.R.; Simioni, P.; Robson, S.C.; Nottle, M.B.; Salvaris, E.J.; Cowan, P.J.; d’Apice, A.J.F.; Sachs, D.H.; Yamada, K.; Lagutina, I.; Duchi, R.; Perota, A.; Lazzari, G.; Galli, C.; Cozzi, E.; Soulillou, J.-P.; B., Vanhove; Blancho, G.

    2014-01-01

    Galactosyl-transferase knock-out (GalT-KO) pigs represent a potential solution to xenograft rejection, particularly in the context of additional genetic modifications. We have performed life supporting kidney xenotransplantation into baboons utilizing GalT-KO pigs transgenic for human CD55/CD59/CD39/HT. Baboons received tacrolimus, mycophenolate mofetil, corticosteroids and recombinant human C1 Inhibitor combined with cyclophosphamide or bortezomib with or without 2–3 plasma exchanges. One baboon received a control GalT-KO xenograft with the latter immunosuppression. All immunosuppressed baboons rejected the xenografts between days 9 to 15 with signs of acute humoral rejection, in contrast to untreated controls (n=2) which lost their grafts on day 3 and 4. Immunofluorescence analyses showed deposition of IgM, C3, C5b-9 in rejected grafts, without C4d staining, indicating classical complement pathway blockade but alternate pathway activation. Moreover, rejected organs exhibited predominantly monocyte/macrophage infiltration with minimal lymphocyte representation. None of the recipients showed any signs of PERV transmission but some showed evidence of PCMV replication within the xenografts. Our work indicates that the addition of bortezomib and plasma exchange to the immunosuppressive regimen did not significantly prolong the survival of multi-transgenic GalT-KO renal xenografts. Non-Gal antibodies, the alternative complement pathway, innate mechanisms with monocyte activation and PCMV replication may have contributed to rejection. PMID:25612490

  5. 75 FR 35513 - Application of Schuman Aviation Company Ltd. D/B/A Makani Kai Helicopters D/B/A Ko Olina...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-22

    ... Office of the Secretary Application of Schuman Aviation Company Ltd. D/B/A Makani Kai Helicopters D/B/A Ko Olina Helicopters D/B/A Pacific Air Express D/B/A Makani Kai Air Charters; For Commuter Authority... cause why it should not issue an order finding Schuman Aviation Company Ltd. d/b/a Makani...

  6. Genome Sequence of Halomonas sp. Strain KO116, an Ionic Liquid- Tolerant Marine Bacterium Isolated from a Lignin-Enriched Seawater Microcosm

    DOE PAGESBeta

    O'Dell, Kaela; Woo, Hannah L.; Utturkar, Sagar M.; Klingeman, Dawn Marie; Brown, Steven D.; Hazen, Terry C.

    2015-05-07

    Halomonas sp. strain KO116 was isolated from Nile Delta Mediterranean Sea surface water enriched with insoluble organosolv lignin. It was further screened for growth on alkali lignin minimal salts medium agar. The strain tolerates the ionic liquid 1-ethyl-3-methylimidazolium acetate. Its complete genome sequence is presented in this report.

  7. Gambogic acid induces mitochondria-dependent apoptosis by modulation of Bcl-2 and Bax in mantle cell lymphoma JeKo-1 cells

    PubMed Central

    Xu, Jingyan; Zhou, Min; Wang, Jing; Zhang, Qiguo; Xu, Yong; Xu, Yueyi; Zhang, Qian; Xu, Xihui; Zeng, Hui

    2013-01-01

    Objective To study the mechanisms in gambogic acid (GA) -induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro. Methods The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki-67 immunocytochemical detection. Apoptosis, cell cycle and mitochondrial membrane potential were measured by flow cytometric analysis. Caspase-3, -8 and -9 were detected by colorimetric assay. Bcl-2 and Bax were analyzed by Western blotting. Results GA inhibited cell growth in a time- and dose- dependent manner. GA induces apoptosis in JeKo-1 cells but not in normal bone marrow cells, which was involved in reducing the membrane potential of mitochondria, activating caspases-3, -8 and -9 and decreasing the ratio of Bcl-2 and Bax without cell cycle arresting. Conclusions GA induced apoptosis in human MCL JeKo-1 cells by regulating Bcl-2/Bax and activating caspase-3, -8 and -9 via mitochondrial pathway without affecting cell cycle. PMID:23592899

  8. EXPRESSION OF EGFR AND ITS LIGANDS IN RESPONSE TO TCDD OR RETINOIC ACID IN EGF AND TGFALPHA KO FETAL MOUSE PALATE

    EPA Science Inventory

    EXPRESSION OF EGFR AND ITS LIGANDS IN RESPONSE TO TCDD OR RETINOIC ACID IN EGF AND TGF" KO FETAL MOUSE PALATE. Abbott, Barbara D.1; Boyd, Hadiya2; Wood, Carmen1; Held, Gary1. 1.EPA, ORD, NHEERL, RTD, US EPA, Research Triangle Park, NC, USA. 2MARC Program, NCCU, Durham, NC, USA. <...

  9. [Dr Srećko Marac (1921-1985): a physician, sychiatrist/phychotherapist, and a poet].

    PubMed

    Radovancević, Ljubomir; Pavlović, Eduard

    2009-01-01

    Srećko Marac was born in Susak in 1921 and died in Zagreb in 1990. Having completed the Susak grammar school, he moved to Padua and later to Zagreb to study medicine. During WW2 he dropped the studies and joined the antifascist resistance known as the People's Liberation War. After the war, he completed medical studies in Zagreb. He worked as army physician in Bjelovar and in the Military Hospital in Zagreb. He specialised in psychiatry and practiced psychotherapy in the former Zagreb Mental Health Centre. In 1973, he published his first selection of poems wrought over a long time, with a simple title Pjesme (Poems). The aim of this article was to take a better look at this 1973 collection, see its structure and composition, its content, moods, and ways it communicates to the reader. The collection consists of five parts: Ad tyrannos, Iz partizana (from Resistance), Lutanja/ traZenja/snovi...(Roamings, Quests, Dreams...), Satire i kusanja humora (Satire and Attempts at Humour), and More/brda i domovina (Sea, Hills, and Homeland). Instead of a conclusion, this article proposes to save this wonderful and compassionate poetphysician from oblivion. PMID:20500012

  10. Quantitative phosphoproteomics of murine Fmr1-KO cell lines provides new insights into FMRP-dependent signal transduction mechanisms.

    PubMed

    Matic, Katarina; Eninger, Timo; Bardoni, Barbara; Davidovic, Laetitia; Macek, Boris

    2014-10-01

    Fragile X mental retardation protein (FMRP) is an RNA-binding protein that has a major effect on neuronal protein synthesis. Transcriptional silencing of the FMR1 gene leads to loss of FMRP and development of Fragile X syndrome (FXS), the most common known hereditary cause of intellectual impairment and autism. Here we utilize SILAC-based quantitative phosphoproteomics to analyze murine FMR1(-) and FMR1(+) fibroblastic cell lines derived from FMR1-KO embryos to identify proteins and phosphorylation sites dysregulated as a consequence of FMRP loss. We quantify FMRP-related changes in the levels of 5,023 proteins and 6,133 phosphorylation events and map them onto major signal transduction pathways. Our study confirms global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 in the absence of FMRP, which is connected to attenuation of long-term potentiation. We detect differential expression of several key proteins from the p53 pathway, pointing to the involvement of p53 signaling in dysregulated cell cycle control in FXS. Finally, we detect differential expression and phosphorylation of proteins involved in pre-mRNA processing and nuclear transport, as well as Wnt and calcium signaling, such as PLC, PKC, NFAT, and cPLA2. We postulate that calcium homeostasis is likely affected in molecular pathogenesis of FXS. PMID:25168779

  11. Structure elucidation of a pungent compound in black cardamom: Amomum tsao-ko Crevost et Lemarié (Zingiberaceae).

    PubMed

    Starkenmann, Christian; Mayenzet, Fabienne; Brauchli, Robert; Wunsche, Laurent; Vial, Christian

    2007-12-26

    Natural plant extracts containing taste modifier compounds will gain more commercial interest in the future. Black cardamom, Amomum tsao-ko Crevost et Lemarié, used as a spice in Asia, produces a nice refreshing effect in the mouth. Therefore, an ethyl acetate extract was prepared, and constituents were separated by liquid chromatography. Guided by the tasting of each fraction (LC tasting), a new pungent compound was discovered, (+/-)-trans-2,3,3a,7a-tetrahydro-1H-indene-4-carbaldehyde. To confirm this new structure, a synthesis was performed starting from cyclopentene-1-carbaldehyde. The Wittig conditions were determined to control the stereochemistry of the ring fusion to prepare (+/-)-trans-(2,3,3a,7a-tetrahydro-1 H-inden-4-yl) methanol and (+/-)-cis-(2,3,3a,7a-tetrahydro-1H-inden-4-yl) methanol. After oxidation, (+/-)-trans-2,3,3a,7a-tetrahydro-1H-indene-4-carbaldehyde and (+/-)-cis-2,3,3a,7a-tetrahydro-1H-indene-4-carbaldehyde were tasted in water and only the trans-2,3,3a,7a-tetrahydro-1H-indene-4-carbaldehyde, present in black cardamom, produced a trigeminal effect in the mouth. PMID:18020415

  12. Traditional Medicine in the Pristine Village of Prokoško Lake on Vranica Mountain, Bosnia and Herzegovina

    PubMed Central

    Šarić-Kundalić, Broza; Fritz, Elisabeth; Dobeš, Christoph; Saukel, Johannes

    2010-01-01

    The results of an ethnobotanical study conducted in the pristine village of Prokoško Lake (Vranica Mountain, Bosnia and Herzegovina) in summer 2007 is presented. Informal interviews involving 12 informants known as “traditional healers” provided data from 43 plants used in 82 prescriptions. The applied plants were used for a broad spectrum of indications. The most frequent were gastro-intestinal tract ailments, blood system disorders, skin ailments, respiratory tract ailments and urinary-genital tract ailments. The most frequent preparation was an infusion. Other often used preparations were ointments or balms and decocts. The special Bosnian balms known as “mehlems” were prepared from freshly chopped or freshly pressed herbal parts of various plant species. Warmed resins from Abies or Picea species, raw cow or pig lard, olive oil and honey served as basis. The traditional doctors, who usually worked as a team, enjoyed such a good reputation that people from all over the country were visiting in search of alternative ways to cure their ailments and diseases. The practical techniques applied by the healers and some of their attitudes and values are reported. PMID:21179347

  13. Adaptation Of Forgotten Buildings The Example Of The Ruins Of The Kościelec Protestant Church In Piaski

    NASA Astrophysics Data System (ADS)

    Gleń, Piotr; Jarocka-Mikrut, Aleksandra

    2015-12-01

    Small towns in the Lublin Province are abundant with buildings possessed of outstanding historical and architectural values, representing the culture of past generations. Piaski, about 30 km east of Lublin, also boasts some of the remarkable characteristic of small towns. Not only does it feature post-Jewish tenements, but also a palace and complexes of religious buildings situated on its outskirts. This article focuses on the Kościelec - an unused, dilapidated former Protestant church. Now, works are being carried out that have inspired the Piaski town authorities to try to find a best-use scenario for the former church, in order to preserve its architectural values for future generations. The authors of this article aim to prove the necessity of research and analysis in finding the best new functions for properties whose function has already been imposed. The example of successfully completed revitalisation works at the palace and park complex in Gardzienice, located not far from the baroque Protestant church in Piaski, illustrates the advantages of some of the adaptation processes that can be employed in such buildings.

  14. The effect of high [K+]o on spontaneous Ca2+ waves in freshly isolated interstitial cells of Cajal from the rabbit urethra

    PubMed Central

    Drumm, Bernard T.; Sergeant, Gerard P.; Hollywood, Mark A.; Thornbury, Keith T.; Matsuda, Toshio T.; Baba, Akemichi; Harvey, Brian J.; McHale, Noel G.

    2014-01-01

    Abstract Interstitial cells of Cajal (ICC) act as putative pacemaker cells in the rabbit urethra. Pacemaker activity in ICC results from spontaneous global Ca2+ waves that can be increased in frequency by raising external [K+]. The purpose of this study was to elucidate the mechanism of this response. Intracellular [Ca2+] was measured in fluo‐4‐loaded smooth muscle cells (SMCs) and ICC using a Nipkow spinning disk confocal microscope. Increasing [K+]o to 60 mmol/L caused an increase in [Ca2+]i accompanied by contraction in SMCs. Raising [K+]o did not cause contraction in ICC, but the frequency of firing of spontaneous calcium waves increased. Reducing [Ca2+]o to 0 mmol/L abolished the response in both cell types. Nifedipine of 1 μmol/L blocked the response of SMC to high [K+]o, but did not affect the increase in firing in ICC. This latter effect was blocked by 30 μmol/L NiCl2 but not by the T‐type Ca2+ channel blocker mibefradil (300 nmol/L). However, inhibition of Ca2+ influx via reverse‐mode sodium/calcium exchange (NCX) using either 1 μmol/L SEA0400 or 5 μmol/L KB‐R7943 did block the effect of high [K+]o on ICC. These data suggest that high K+ solution increases the frequency of calcium waves in ICC by increasing Ca2+ influx through reverse‐mode NCX. PMID:24744882

  15. Rejection of Cardiac Xenografts Transplanted from α 1,3-Galactosyltransferase Gene-Knockout (GalT-KO) Pigs to Baboons

    PubMed Central

    Hisashi, Y.; Yamada, K.; Kuwaki, K.; Tseng, Y.-L; Dor, F. J. M. F.; Houser, S. L; Robson, S. C.; Schuurman, H.-J.; Cooper, D. K. C.; Sachs, D. H.; Colvin, R. B.; Shimizu, A.

    2010-01-01

    The use of α 1,3-galactosyltransferase gene-knockout (GalT-KO) swine donors in discordant xenotransplantation has extended the survival of cardiac xenografts in baboons following transplantation. Eight baboons received heterotopic cardiac xenografts from GalT-KO swine and were treated with a chronic immunosuppressive regimen. The pathologic features of acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR) and chronic rejection were assessed in the grafts. No hyperacute rejection developed and one graft survived up to 6 months after transplantation. However, all GalT-KO heart grafts underwent graft failure with AHXR, ACXR and/or chronic rejection. AHXR was characterized by interstitial hemorrhage and multiple thrombi in vessels of various sizes. ACXR was characterized by TUNEL+ graft cell injury with the infiltration of T cells (including CD3 and TIA-1+ cytotoxic T cells), CD4+ cells, CD8+ cells, macrophages and a small number of B and NK cells. Chronic xenograft vasculopathy, a manifestation of chronic rejection, was characterized by arterial intimal thickening with TUNEL+ dead cells, antibody and complement deposition, and/or cytotoxic T-cell infiltration. In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens. PMID:19032222

  16. [Mercury in edible mushrooms from the area of Kościersk forests and from the Vistula peninsula].

    PubMed

    Falandysz, J; Marcinowicz, A; Chwir, A

    1996-01-01

    The total mercury concentrations were determined in caps and stalks or a whole fruiting bodies of 13 species of edible mushrooms collected at the area of Kościerzyna forests (District of Gdańsk) and the Vistula Peninsula (District of Elblag) in 1993/94. The method of measurement was cold-vapour atomic absorption spectrometry (CV-AAS) after wet digestion of the samples with concentrated nitric acid. Macrolepiota procera showed highest mercury concentration among species investigated and contained, respectively, 1100 micrograms/kg dry wt in caps and 580 micrograms/kg in stalks, while Lycoperdon perlatum showed 1100 micrograms/kg in a whole fruiting body. Suillus granulatus, Xerocomus subtomentosus, Leccinum scabrum, Oudemansiella platyphylla and Lactarius delicious contained mercury in concentration from 150 to 370 micrograms/kg dry wt in caps and from 70 to 180 micrograms/kg in stalks. Suillus bovinus, Chroogomphus rutilus and Armillariella mellea showed smallest concentrations of mercury between species examined, i.e. in caps from 29 to 65 micrograms/kg and in stalks from 23 to 49 micrograms/kg, on a average. Leccinum scabrum and Xerocomus badius were collected from the both distant in space sampling sites. In the case of L. scabrum the concentrations of mercury were very similar for the both sites investigated, i.e. between 290 +/- 100 and 370 +/- 330 in caps, and 180 +/- 60 and 220 +/- 160 micrograms/kg dry wt in stalks, while for X. badius differed and were between 73 +/- 20 and 220 +/- 60 in caps, and 49 +/- 13 and 130 +/- 40 in stalks (p < 0.001). PMID:9064742

  17. Oriental Medicine Kyung-Ok-Ko Prevents and Alleviates Dehydroepiandrosterone-Induced Polycystic Ovarian Syndrome in Rats

    PubMed Central

    Lee, Jin Moo; Bae, Chun-Sik; Kim, Sung-Hoon; Ryu, Jong Hoon; Cho, Ik-Hyun

    2014-01-01

    Kyung-Ok-Ko (KOK), a traditional herbal prescription composed of Rehmannia glutinosa Liboschitz var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey, has been widely used in traditional Oriental medicine as a vitalizing medicine or as the prescription for patients with age-associated disorders such as amnesia and stroke. However, the potential protective value of KOK for the treatment of polycystic ovarian syndrome (PCOS) is largely unknown. We investigated whether pre-administration (daily from 2 hours before PCOS induction) and post-administration (daily after induction of PCOS) of KOK (0.5, 1.0, and 2.0 g/kg/day, p.o.) could have a protective effect in a dehydroepiandrosterone (DHEA, s.c.)-induced PCOS rat model. Pre-administration of KOK significantly decreased the elevated body weight and ovary weight, elevated size and number of follicular cysts, elevated level of serum glucose, and estradiol after DHEA injection. KOK reduced the elevated percentage of CD8 (+) T lymphocytes in lymph nodes, the elevated mRNA expression of CD11b and CD3 in ovaries, and infiltration of macrophages in ovarian tissue with PCOS. KOK diminished the increased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), chemokines (IL-8, MCP-1), and iNOS in the ovaries, and increased the reduced mRNA expression of growth factors (EGF, TGF-β) by DHEA injection. Post-administration of KOK also improved the DHEA-induced PCOS-like symptoms, generally similar to those evident from pre-administration of KOK. KOK may effectively prevent and improve DHEA-induced PCOS via anti-inflammatory action, indicating its preventive and therapeutic potential for suppressing PCOS. PMID:24520334

  18. Content of metals and metabolites in honey originated from the vicinity of industrial town Košice (eastern Slovakia).

    PubMed

    Kováčik, Jozef; Grúz, Jiří; Biba, Ondřej; Hedbavny, Josef

    2016-03-01

    Composition of three types of honey (mixed forest honey and monofloral-black locust and rapeseed honeys) originated from the vicinity of an industrial town (Košice, Slovak Republic) was compared. Higher content of minerals including toxic metals in forest honey (1358.6 ng Ni/g, 85.6 ng Pb/g, and 52.4 ng Cd/g) than in rapeseed and black locust honeys confirmed that botanical origin rather than the distance for eventual source of pollution (steel factory) affects metal deposition. Benzoic acid derivatives were typically more accumulated in forest but cinnamic acid derivatives and some flavonoids in rapeseed honey (in free and/or glycoside-bound fraction). In terms of quantity, p-hydroxybenzoic and p-coumaric acids were mainly abundant. Total phenols, thiols, and proteins were abundant in forest honey. Some metals and phenols contributed to separation of honeys based on principal component analysis (PCA). Native amount of 5-(hydroxymethyl)furfural was not related to honey type (~11 μg/g) and was elevated after strong acid hydrolysis (200-350 μg/g) but it did not interfere with the assay of phenols by Folin-Ciocalteu reagent. This is the first report of metals and metabolites in the same study, and data are discussed with available literature. We conclude that black locust (acacia) honey is the most suitable for daily use and that central European monofloral honeys contain lower amounts of toxic metals in comparison with other geographical regions. PMID:26517990

  19. The effect of dietary antioxidant on the COPD risk: the community-based KoGES (Ansan–Anseong) cohort

    PubMed Central

    Joshi, Pankaj; Kim, Woo Jin; Lee, Sang-Ah

    2015-01-01

    Background Dietary antioxidants have been suggested to have protective role against chronic obstructive pulmonary disease (COPD), but few prospective studies examined this relationship. The prospective study was conducted to evaluate the effect of dietary antioxidants on COPD risk and lung function in the Korean population. Methods The data were collected from the community-based Korean Genome Epidemiology Study (KoGES) cohort. To diagnose COPD, forced expiratory volume (FEV1) and forced vital capacity (FVC) were measured by spirometry. The dietary intake of antioxidant vitamins was estimated from validated Food-Frequency Questionnaire. For the analysis, 325 COPD patients and 6,781 at risk subjects were selected from the cohort of 10,038 subjects. Multiple logistic regression models were used to examine the odds ratio (OR) after adjusting for age, sex, marital status, income, history of asthma, history of tuberculosis, and smoking. Results The risk of COPD was positively associated with aging, low education, low household income, lower body mass index, and cigarette smoking. The risk of COPD decreased with increase in the dietary vitamin C (ORQ1 vs Q5=0.66, Ptrend=0.03) and vitamin E (ORQ1 vs Q5=0.56, Ptrend=0.05) intake, predominantly, in men (Ptrend=0.01 and 0.05 for vitamins C and E, respectively). In addition, the lung function was significantly improved with increase in vitamins C (FEV1, P=0.04; FVC, P=0.03) and E (FEV1, P=0.03; FVC, P=0.04) intake. No statistically significant interactions were observed between smoking and vitamin C or E intake in relation to COPD risk among men. Conclusion Our results suggest the independent beneficial effect of antioxidants, particularly vitamins C and E, on COPD risk and lung function in men. PMID:26504380

  20. Keanakākoʻi Tephra produced by 300 years of explosive eruptions following collapse of Kīlauea's caldera in about 1500 CE

    USGS Publications Warehouse

    Swanson, Donald A.; Rose, Timothy R.; Fiske, Richard S.; McGeehin, John P.

    2012-01-01

    The Keanakākoʻi Tephra at Kīlauea Volcano has previously been interpreted by some as the product of a caldera-forming eruption in 1790 CE. Our study, however, finds stratigraphic and 14C evidence that the tephra instead results from numerous eruptions throughout a 300-year period between about 1500 and 1800. The stratigraphic evidence includes: (1) as many as six pure lithic ash beds interleaved in sand dunes made of earlier Keanakākoʻi vitric ash, (2) three lava flows from Kīlauea and Mauna Loa interbedded with the tephra, (3) buried syneruptive cultural structures, (4) numerous intraformational water-cut gullies, and (5) abundant organic layers rich in charcoal within the tephra section. Interpretation of 97 new accelerator mass spectrometry (AMS) 14C ages and 4 previous conventional ages suggests that explosive eruptions began in 1470–1510 CE, and that explosive activity continued episodically until the early 1800s, probably with two periods of quiescence lasting several decades. Kīlauea's caldera, rather than forming in 1790, predates the first eruption of the Keanakākoʻi and collapsed in 1470–1510, immediately following, and perhaps causing, the end of the 60-year-long, 4–6 km3 ʻAilāʻau eruption from the east side of Kīlauea's summit area. The caldera was several hundred meters deep when the Keanakākoʻi began erupting, consistent with oral tradition, and probably had a volume of 4–6 km3. The caldera formed by collapse, but no eruption of lava coincided with its formation. A large volume of magma may have quickly drained from the summit reservoir and intruded into the east rift zone, perhaps in response to a major south-flank slip event, leading to summit collapse. Alternatively, magma may have slowly drained from the reservoir during the prolonged ʻAilāʻau eruption, causing episodic collapses before the final, largest downdrop took place. Two prolonged periods of episodic explosive eruptions are known at Kīlauea, the Keanakāko

  1. Keanakākoʻi Tephra produced by 300 years of explosive eruptions following collapse of Kīlauea's caldera in about 1500 CE

    USGS Publications Warehouse

    Swanson, Donald A.; Rose, Timothy R.; Fiske, Richard S.; McGeehin, John P.

    2012-01-01

    The Keanakākoʻi Tephra at Kīlauea Volcano has previously been interpreted by some as the product of a caldera-forming eruption in 1790 CE. Our study, however, finds stratigraphic and 14C evidence that the tephra instead results from numerous eruptions throughout a 300-year period between about 1500 and 1800. The stratigraphic evidence includes: (1) as many as six pure lithic ash beds interleaved in sand dunes made of earlier Keanakākoʻi vitric ash, (2) three lava flows from Kīlauea and Mauna Loa interbedded with the tephra, (3) buried syneruptive cultural structures, (4) numerous intraformational water-cut gullies, and (5) abundant organic layers rich in charcoal within the tephra section. Interpretation of 97 new accelerator mass spectrometry (AMS) 14C ages and 4 previous conventional ages suggests that explosive eruptions began in 1470–1510 CE, and that explosive activity continued episodically until the early 1800s, probably with two periods of quiescence lasting several decades. Kīlauea's caldera, rather than forming in 1790, predates the first eruption of the Keanakākoʻi and collapsed in 1470–1510, immediately following, and perhaps causing, the end of the 60-year-long, 4–6 km3 ʻAilāʻau eruption from the east side of Kīlauea's summit area. The caldera was several hundred meters deep when the Keanakākoʻi began erupting, consistent with oral tradition, and probably had a volume of 4–6 km3. The caldera formed by collapse, but no eruption of lava coincided with its formation. A large volume of magma may have quickly drained from the summit reservoir and intruded into the east rift zone, perhaps in response to a major south-flank slip event, leading to summit collapse. Alternatively, magma may have slowly drained from the reservoir during the prolonged ʻAilāʻau eruption, causing episodic collapses before the final, largest downdrop took place. Two prolonged periods of episodic explosive eruptions are known at Kīlauea, the Keanakāko

  2. Abnormal Type I Collagen Post-translational Modification and Crosslinking in a Cyclophilin B KO Mouse Model of Recessive Osteogenesis Imperfecta

    PubMed Central

    Cabral, Wayne A.; Perdivara, Irina; Weis, MaryAnn; Terajima, Masahiko; Blissett, Angela R.; Chang, Weizhong; Perosky, Joseph E.; Makareeva, Elena N.; Mertz, Edward L.; Leikin, Sergey; Tomer, Kenneth B.; Kozloff, Kenneth M.; Eyre, David R.; Yamauchi, Mitsuo; Marini, Joan C.

    2014-01-01

    Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause recessively inherited osteogenesis imperfecta type IX, a moderately severe to lethal bone dysplasia. To investigate the role of CyPB in collagen folding and post-translational modifications, we generated Ppib−/− mice that recapitulate the OI phenotype. Knock-out (KO) mice are small, with reduced femoral areal bone mineral density (aBMD), bone volume per total volume (BV/TV) and mechanical properties, as well as increased femoral brittleness. Ppib transcripts are absent in skin, fibroblasts, femora and calvarial osteoblasts, and CyPB is absent from KO osteoblasts and fibroblasts on western blots. Only residual (2–11%) collagen prolyl 3-hydroxylation is detectable in KO cells and tissues. Collagen folds more slowly in the absence of CyPB, supporting its rate-limiting role in folding. However, treatment of KO cells with cyclosporine A causes further delay in folding, indicating the potential existence of another collagen PPIase. We confirmed and extended the reported role of CyPB in supporting collagen lysyl hydroxylase (LH1) activity. Ppib−/− fibroblast and osteoblast collagen has normal total lysyl hydroxylation, while increased collagen diglycosylation is observed. Liquid chromatography/mass spectrometry (LC/MS) analysis of bone and osteoblast type I collagen revealed site-specific alterations of helical lysine hydroxylation, in particular, significantly reduced hydroxylation of helical crosslinking residue K87. Consequently, underhydroxylated forms of di- and trivalent crosslinks are strikingly increased in KO bone, leading to increased total crosslinks and decreased helical hydroxylysine- to lysine-derived crosslink ratios. The altered

  3. Histone acetylation rescues contextual fear conditioning in nNOS KO mice and accelerates extinction of cued fear conditioning in wild type mice.

    PubMed

    Itzhak, Yossef; Anderson, Karen L; Kelley, Jonathan B; Petkov, Martin

    2012-05-01

    Epigenetic regulation of chromatin structure is an essential molecular mechanism that contributes to the formation of synaptic plasticity and long-term memory (LTM). An important regulatory process of chromatin structure is acetylation and deacetylation of histone proteins. Inhibition of histone deacetylase (HDAC) increases acetylation of histone proteins and facilitate learning and memory. Nitric oxide (NO) signaling pathway has a role in synaptic plasticity, LTM and regulation of histone acetylation. We have previously shown that NO signaling pathway is required for contextual fear conditioning. The present study investigated the effects of systemic administration of the HDAC inhibitor sodium butyrate (NaB) on fear conditioning in neuronal nitric oxide synthase (nNOS) knockout (KO) and wild type (WT) mice. The effect of single administration of NaB on total H3 and H4 histone acetylation in hippocampus and amygdala was also investigated. A single administration of NaB prior to fear conditioning (a) rescued contextual fear conditioning of nNOS KO mice and (b) had long-term (weeks) facilitatory effect on the extinction of cued fear memory of WT mice. The facilitatory effect of NaB on extinction of cued fear memory of WT mice was confirmed in a study whereupon NaB was administered during extinction. Results suggest that (a) the rescue of contextual fear conditioning in nNOS KO mice is associated with NaB-induced increase in H3 histone acetylation and (b) the accelerated extinction of cued fear memory in WT mice is associated with NaB-induced increase in H4 histone acetylation. Hence, a single administration of HDAC inhibitor may rescue NO-dependent cognitive deficits and afford a long-term accelerating effect on extinction of fear memory of WT mice. PMID:22452925

  4. In Vivo Quantification of 5-HT2A Brain Receptors in Mdr1a KO Rats with 123I-R91150 Single-Photon Emission Computed Tomography.

    PubMed

    Dumas, Noé; Moulin-Sallanon, Marcelle; Fender, Pascal; Tournier, Benjamin B; Ginovart, Nathalie; Charnay, Yves; Millet, Philippe

    2015-01-01

    Our goal was to identify suitable image quantification methods to image 5-hydroxytryptamine2A (5-HT2A) receptors in vivo in Mdr1a knockout (KO) rats (i.e., P-glycoprotein KO) using 123I-R91150 single-photon emission computed tomography (SPECT). The 123I-R91150 binding parameters estimated with different reference tissue models (simplified reference tissue model [SRTM], Logan reference tissue model, and tissue ratio [TR] method) were compared to the estimates obtained with a comprehensive three-tissue/seven-parameter (3T/7k)-based model. The SRTM and Logan reference tissue model estimates of 5-HT2A receptor (5-HT2AR) nondisplaceable binding potential (BPND) correlated well with the absolute receptor density measured with the 3T/7k gold standard (r > .89). Quantification of 5-HT2AR using the Logan reference tissue model required at least 90 minutes of scanning, whereas the SRTM required at least 110 minutes. The TR method estimates were also highly correlated to the 5-HT2AR density (r > .91) and only required a single 20-minute scan between 100 and 120 minutes postinjection. However, a systematic overestimation of the BPND values was observed. The Logan reference tissue method is more convenient than the SRTM for the quantification of 5-HT2AR in Mdr1a KO rats using 123I-R91150 SPECT. The TR method is an interesting and simple alternative, despite its bias, as it still provides a valid index of 5-HT2AR density. PMID:26105563

  5. Decreasing the Level of Ethyl Acetate in Ethanolic Fermentation Broths of Escherichia coli KO11 by Expression of Pseudomonas putida estZ Esterase†

    PubMed Central

    Hasona, Adnan; York, S. W.; Yomano, L. P.; Ingram, L. O.; Shanmugam, K. T.

    2002-01-01

    During the fermentation of sugars to ethanol relatively high levels of an undesirable coproduct, ethyl acetate, are also produced. With ethanologenic Escherichia coli strain KO11 as the biocatalyst, the level of ethyl acetate in beer containing 4.8% ethanol was 192 mg liter−1. Although the E. coli genome encodes several proteins with esterase activity, neither wild-type strains nor KO11 contained significant ethyl acetate esterase activity. A simple method was developed to rapidly screen bacterial colonies for the presence of esterases which hydrolyze ethyl acetate based on pH change. This method allowed identification of Pseudomonas putida NRRL B-18435 as a source of this activity and the cloning of a new esterase gene, estZ. Recombinant EstZ esterase was purified to near homogeneity and characterized. It belongs to family IV of lipolytic enzymes and contains the conserved catalytic triad of serine, aspartic acid, and histidine. As expected, this serine esterase was inhibited by phenylmethylsulfonyl fluoride and the histidine reagent diethylpyrocarbonate. The native and subunit molecular weights of the recombinant protein were 36,000, indicating that the enzyme exists as a monomer. By using α-naphthyl acetate as a model substrate, optimal activity was observed at pH 7.5 and 40°C. The Km and Vmax for α-naphthyl acetate were 18 μM and 48.1 μmol · min−1 · mg of protein−1, respectively. Among the aliphatic esters tested, the highest activity was obtained with propyl acetate (96 μmol · min−1 · mg of protein−1), followed by ethyl acetate (66 μmol · min−1 · mg of protein−1). Expression of estZ in E. coli KO11 reduced the concentration of ethyl acetate in fermentation broth (4.8% ethanol) to less than 20 mg liter−1. PMID:12039716

  6. Rhenium and chalcophile elements in basaltic glasses from Ko'olau and Moloka'i volcanoes: Magmatic outgassing and composition of the Hawaiian plume

    NASA Astrophysics Data System (ADS)

    Norman, Marc D.; Garcia, Michael O.; Bennett, Victoria C.

    2004-09-01

    The behavior of chalcophile metals in volcanic environments is important for a variety of economic and environmental applications, and for understanding large-scale processes such as crustal recycling into the mantle. In order to better define the behavior of chalcophile metals in ocean island volcanoes, we measured the concentrations of Re, Cd, Bi, Cu, Pb, Zn, Pt, S, and a suite of major elements and lithophile trace elements in moderately evolved (6-7% MgO) tholeiitic glasses from Ko'olau and Moloka'i volcanoes. Correlated variations in the Re, Cd, and S contents of these glasses are consistent with loss of these elements as volatile species during magmatic outgassing. Bismuth also shows a good correlation with S in the Ko'olau glasses, but undegassed glasses from Moloka'i have unexpectedly low Bi contents. Rhenium appears to have been more volatile than either Cd or Bi in these magmas. Undegassed glasses with 880-1400 ppm S have 1.2-1.5 ppb Re and 130-145 ppb Cd. In contrast, outgassed melts with low S (<200 ppm) are depleted in these elements by factors of 2-5. Key ratios such as Re/Yb and Cu/Re are fractionated significantly from mantle values. Copper, Pb, and Pt contents of these glasses show no correlation with S, ruling out segregation of an immiscible magmatic sulfide phase as the cause of these variations. Undegassed Hawaiian tholeiites have Re/Yb ratios significantly higher than those of MORB, and extend to values greater than that of the primitive mantle. Loss of Re during outgassing of ocean island volcanoes, may help resolve the apparent paradox of low Re/Os ratios in ocean island basalts with radiogenic Os isotopic compositions. Plume source regions with Re/Yb ratios greater than that of the primitive mantle may provide at least a partial solution to the "missing Re" problem in which one or more reservoirs with high Re/Yb are required to balance the low Re/Yb of MORB. Lithophile trace element compositions of most Ko'olau and Moloka'i tholeiites are

  7. Abundance, composition and growth rate of coral recruits on dead corals following the 2010 bleaching event at Mu Ko Surin, the Andaman Sea

    NASA Astrophysics Data System (ADS)

    Yucharoen, Mathinee; Yeemin, Thamasak; Casareto, Beatriz E.; Suzuki, Yoshimi; Samsuvan, Watchara; Sangmanee, Kanwara; Klinthong, Wanlaya; Pengsakun, Sittiporn; Sutthacheep, Makamas

    2015-06-01

    Elevated seawater temperatures in the summer months of 2010 were associated with widespread coral mortality in Thailand. A large number of corals at Mu Ko Surin died following the bleaching event. Understanding of the recruitment of corals would improve our ability to predict the potential for coral recovery from the impacts of bleaching events, as well as the interpretation of spatio-temporal variability in coral community structure. This study aims to examine the composition, abundance and growth rate of juvenile corals and the potential of reef recovery at Mu Ko Surin in order to help to understand how reefs react to major disturbances. We found that the densities of coral recruits varied among years and study sites. In the year 2011, coral recruitments ranged between 0.18 ± 0.02 to 1.67 ± 0.07 recruits per m2 for 10 study sites. While in 2012, the monitoring revealed a range between 0.96 ± 0.16 and 2.19 ± 0.21 recruits per m2 from 5 study sites. Fungia, Acropora, Porites and Favites were the dominant groups of coral recruits. In terms substrate forms, they were significant differences between sampling years but the preferential dominant substrate forms did not differ. The Acropora recruits at Ko Torinla showed normal distributions of size class during the two periods. Their ranges in 2011 and 2012 were 4-30 and 13-54 mm, respectively. Six species of Acropora recruits, i.e. Acropora intermedia, A. nasuta, A. cerealis, A. subulata, A. muricata and A. latistella were found. They showed diverse growth rates due to the spatial distribution of 2.11 ± 0.59 to 7.47 ± 1.37 cm per year. This study provides useful data in terms of coral recruitment and recovery from degradation and disturbance, especially from temperature changes induced by coral bleaching. The findings suggest that there is the possibility for coral recovery around Mu Ko Surin following the 2010 bleaching event.

  8. Excited states of fluorescent proteins, mKO and DsRed: chromophore-protein electrostatic interaction behind the color variations.

    PubMed

    Hasegawa, Jun-ya; Ise, Takehiko; Fujimoto, Kazuhiro J; Kikuchi, Akihiro; Fukumura, Eiko; Miyawaki, Atsushi; Shiro, Yoshitsugu

    2010-03-01

    The emitting states of green fluorescent protein (GFP), monomeric Kusabira orange (mKO), and Discosoma red (DsRed) were studied using QM/MM and SAC-CI methods. By comparing the electronic structures among the green-, orange-, and red-emitting states as well as their electrostatic and quantum mechanical interactions within the protein cavity, the basic mechanisms for determining emission colors have been clarified. We found that the orange and red emissions of mKO and DsRed, respectively, result from cancellation between two effects, the pi skeleton extension (red shift) and protein electrostatic potential (blue shift). The extension of the pi skeleton enhances the intramolecular charge-transfer character of the transition, which makes the fluorescence energy more sensitive to the protein's electrostatic potential. On the basis of this mechanism, we predicted amino acid mutations that could red shift the emission energy of DsRed. A novel single amino acid mutation, which was examined computationally, reduced the DsRed emission energy from 2.14 (579 nm) to 1.95 eV (636 nm), which is approaching near-infrared fluorescence. PMID:20131896

  9. Als2 mRNA splicing variants detected in KO mice rescue severe motor dysfunction phenotype in Als2 knock-down zebrafish.

    PubMed

    Gros-Louis, Francois; Kriz, Jasna; Kabashi, Edor; McDearmid, Jonathan; Millecamps, Stéphanie; Urushitani, Makoto; Lin, Li; Dion, Patrick; Zhu, Qinzhang; Drapeau, Pierre; Julien, Jean-Pierre; Rouleau, Guy A

    2008-09-01

    Recessive ALS2 mutations are linked to three related but slightly different neurodegenerative disorders: amyotrophic lateral sclerosis, hereditary spastic paraplegia and primary lateral sclerosis. To investigate the function of the ALS2 encoded protein, we generated Als2 knock-out (KO) mice and zAls2 knock-down zebrafish. The Als2(-/-) mice lacking exon 2 and part of exon 3 developed mild signs of neurodegeneration compatible with axonal transport deficiency. In contrast, zAls2 knock-down zebrafish had severe developmental abnormalities, swimming deficits and motor neuron perturbation. We identified, by RT-PCR, northern and western blotting novel Als2 transcripts in mouse central nervous system. These Als2 transcripts were present in Als2 null mice as well as in wild-type littermates and some rescued the zebrafish phenotype. Thus, we speculate that the newly identified Als2 mRNA species prevent the Als2 KO mice from developing severe neurodegenerative disease and might also regulate the severity of the motor neurons phenotype observed in ALS2 patients. PMID:18558633

  10. Transport of marine fish larvae to Saroma-ko Lagoon (Hokkaido, Japan) in relation to the availability of zooplankton prey under the winter ice cover

    NASA Astrophysics Data System (ADS)

    Fortier, Martin; Fortier, Louis

    1997-02-01

    To assess the importance of ice-covered Saroma-ko Lagoon as a winter nursery area for young fish spawned offshore, we monitored the recruitment of marine fish larvae from the Sea of Okhotsk to the lagoon as well as the availability of larval fish prey under the ice cover from 24 February to 23 March 1992. Sand lance ( Ammodytes sp.) and walleye pollock ( Theragra chalcogramma) larvae recruited to the lagoon on flood tide whereas snake prickleback ( Lumpenus sagitta) larvae were exported to the Sea of Okhotsk on ebb. Before the ice breakup, ice microalgae made up the bulk of the microalgal biomass in the lagoon. The production and release of ice algae did not trigger the maturation of the late copepodite stages of copepods, and the proportion of adult females in the copepod assemblage remained low. The production of copepod nauplii (the main prey of fish larvae) under the ice was probably insufficient to insure suitable feeding and growth of fish larvae entering the lagoon in winter. Sand lance larvae, the most abundant species to colonize the lagoon in February-March, had to survive for nearly two months at low food abundance. Based on our results, the importance of Saroma-ko Lagoon as a winter nursery area for fish larvae appears negligible.

  11. PREVALENCE OF TREMATODE LARVAE IN INTERMEDIATE HOSTS: SNAILS AND FISH IN KO AE SUB-DISTRICT OF KHUEANG NAI, UBON RATCHATHANI PROVINCE, THAILAND.

    PubMed

    Sripa, Jittiyawadee; Kiatsopit, Nadda; Piratae, Supawadee

    2016-05-01

    Ko Ae Sub-district of Khueang Nai, Ubon Ratchathani Province, Thailand is located in an endemic area for Opisthorchis viverrini and other fish-borne zoonotic trematodes (FZT) infection. This study shows the status in Ko Ae Sub-district of FZT infection based on availability of intermediate hosts and necessary requirements for the transmission of FZT. A cross-sectional survey of intermediate hosts of FZT, including Bithynia siamensis goniomphalos and cyprinoid fish, was conducted from April 2013 to December 2014. Examination of 1,000 snails revealed 3.4% were infected with trematode cercariae, with a density of infection greater than 100 cercariae per infected snail. Six groups of morphologically-distinguishable trematode cercariae were identified, namely, cystophorous, echinostome, furcocercous, mutabile, parapleurolophocercous, and xiphidio, the latter being the most predominant type. Among 250 cyprinoid fish samples with metacercariae present at their caudal fins and examined for FZT by pepsin digestion, metacer- cariae of Haplorchis taichui, H. pumilio, and Centrocestus formosanus were found. Unidentified metacercariae collected from fish caudal fins were subsequently shown using a PCR-based assay to be C. formosanus. No infection by O. viverrini in the intermediate hosts, Bithynia siamensis goniomphalos and cyprinoid fish was evident. The study provides new information regarding trematode larvae infection in the primary and secondary intermediate hosts of FZT in this area of Thailand. PMID:27405122

  12. Study on the biodegradation of alternatives (four species including C8H8F9KO3S) for perfluorooctane sulfonate

    PubMed Central

    Choi, Bong-In; Na, Suk-Hyun; Kwak, Yeong-Don; Ryu, Byung-Taek; Chung, Seon-Yong

    2015-01-01

    Objectives The objective of this study was to evaluate the biodegradation potential of four perfluorooctane sulfonic acid (PFOS) alternatives that were developed at Changwon National University. While PFOS has been used widely in industrial and consumer products, it is known to be a persistent organic pollutant. Therefore, greener alternatives are highly desirable. Methods Biodegradation tests were run for 28 days using standard test protocols. The biochemical oxygen demand was measured daily throughout the experimental period, and the data were used to calculate the biodegradation rates. Microorganisms were isolated from the some of the tests that showed evidence of biodegradation. Results C8H8F9KO3S, which has the same number of carbons as the parent compound PFOS but a reduced number of fluorines, showed the highest biodegradation rate followed by C10H8F13KO3S. Chemical alternatives with lower number of carbons did not biodegrade readily in the experiments. Conclusions Together, these results suggest that it may be advantageous to develop PFOS alternatives with 8 carbons, the same as PFOS, but a reduced number of fluorines; as such, chemicals are more susceptible to biodegradation than the parent compound. PMID:26206369

  13. Proceedings of the 11th International Conference on Magnetic Fluids (ICMF 11) (Košice, Slovakia, 23-27 July 2007).

    PubMed

    Kopčanský, Peter; Timko, Milan; Kováč, Josef; Václavíková, Miroslava; Odenbach, Stefan

    2008-05-21

    The 11th International Conference on Magnetic Fluids (ICMF 11) was held in Košice, Slovakia between 23-27 July 2007. Attendance at the conference was high and its motivation was in line with the ten previous ICMF conferences organized in Udine, Orlando, Bangor, Sendai-Tokyo, Riga, Paris, Bhavnagar, Timisoara, Bremen and Guarujá. The conference in Slovakia reflected the scientific community's enthusiasm and worldwide support, with 256 participants, from 30 countries attending.The main objective of ICMF 11 was to promote progress and knowledge in the field of magnetic fluids regarding their chemistry, physical and magnetic properties, heat and mass transfer, surface phenomena, as well as their technological and biomedical applications. As research on magnetic fluids is essentially interdisciplinary, experts from related areas were invited to present their contributions with a view to increasing knowledge in the field and highlighting new trends. Submitted communications were refereed by members of the Scientific Organizing Committee and abstracts were assembled in a book of abstracts. Participants presented 180 posters in two poster sessions and 56 oral presentations. All presentations contributed to a greater understanding of the area, and helped to bridge the gap between physics, chemistry, technology, biology and medical sciences. Contributions to this conference are presented in 115 scientific papers, with some published in Journal of Physics: Condensed Matter and the rest in Magnetohydrodynamics. The organization of the conference was made possible by generous support from the Institute of Experimental Physics and Institute of Geotechnics of the Slovak Academy of Sciences, the University of Pavol Jozef Šafárik and the Slovak Physical Society. Financial support from Ferrotec, Cryosoft Ltd, Mikrochem, Liquids Research Ltd, Askony and US Steel Košice, is also gratefully acknowledged. PMID:21694229

  14. Ocular and systemic safety of a recombinant AAV8 vector for X-linked retinoschisis gene therapy: GLP studies in rabbits and Rs1-KO mice.

    PubMed

    Marangoni, Dario; Bush, Ronald A; Zeng, Yong; Wei, Lisa L; Ziccardi, Lucia; Vijayasarathy, Camasamudram; Bartoe, Joshua T; Palyada, Kiran; Santos, Maria; Hiriyanna, Suja; Wu, Zhijian; Colosi, Peter; Sieving, Paul A

    2016-01-01

    X-linked retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding the protein retinoschisin (RS1) and is one of the most common causes of macular degeneration in young men. Our therapeutic approach for XLRS is based on the administration of AAV8-scRS/IRBPhRS, an adeno-associated viral vector coding the human RS1 protein, via the intravitreal (IVT) route. Two Good Laboratory Practice studies, a 9-month study in New Zealand White rabbits (n = 124) injected with AAV8-scRS/IRBPhRS at doses of 2E9, 2E10, 2E11, and 1.5E12 vector genomes/eye (vg/eye), and a 6-month study in Rs1-KO mice (n = 162) dosed with 2E9 and 2E10 vg/eye of the same vector were conducted to assess ocular and systemic safety. A self-resolving, dose-dependent vitreal inflammation was the main ocular finding, and except for a single rabbit dosed with 1.5E12 vg/eye, which showed a retinal detachment, no other ocular adverse event was reported. Systemic toxicity was not identified in either species. Biodistribution analysis in Rs1-KO mice detected spread of vector genome in extraocular tissues, but no evidence of organ or tissues damage was found. These studies indicate that IVT administration of AAV8-scRS/IRBPhRS is safe and well tolerated and support its advancement into a phase 1/2a clinical trial for XLRS. PMID:27626041

  15. Ocular and systemic safety of a recombinant AAV8 vector for X-linked retinoschisis gene therapy: GLP studies in rabbits and Rs1-KO mice

    PubMed Central

    Marangoni, Dario; Bush, Ronald A; Zeng, Yong; Wei, Lisa L; Ziccardi, Lucia; Vijayasarathy, Camasamudram; Bartoe, Joshua T; Palyada, Kiran; Santos, Maria; Hiriyanna, Suja; Wu, Zhijian; Colosi, Peter; Sieving, Paul A

    2016-01-01

    X-linked retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding the protein retinoschisin (RS1) and is one of the most common causes of macular degeneration in young men. Our therapeutic approach for XLRS is based on the administration of AAV8-scRS/IRBPhRS, an adeno-associated viral vector coding the human RS1 protein, via the intravitreal (IVT) route. Two Good Laboratory Practice studies, a 9-month study in New Zealand White rabbits (n = 124) injected with AAV8-scRS/IRBPhRS at doses of 2E9, 2E10, 2E11, and 1.5E12 vector genomes/eye (vg/eye), and a 6-month study in Rs1-KO mice (n = 162) dosed with 2E9 and 2E10 vg/eye of the same vector were conducted to assess ocular and systemic safety. A self-resolving, dose-dependent vitreal inflammation was the main ocular finding, and except for a single rabbit dosed with 1.5E12 vg/eye, which showed a retinal detachment, no other ocular adverse event was reported. Systemic toxicity was not identified in either species. Biodistribution analysis in Rs1-KO mice detected spread of vector genome in extraocular tissues, but no evidence of organ or tissues damage was found. These studies indicate that IVT administration of AAV8-scRS/IRBPhRS is safe and well tolerated and support its advancement into a phase 1/2a clinical trial for XLRS. PMID:27626041

  16. Preface: Proceedings of the 11th International Conference on Magnetic Fluids (ICMF 11) (Košice, Slovakia, 23 27 July 2007)

    NASA Astrophysics Data System (ADS)

    Kopčanský, Peter; Timko, Milan; Kováč, Josef; Václavíková, Miroslava; Odenbach, Stefan

    2008-05-01

    The 11th International Conference on Magnetic Fluids (ICMF 11) was held in Košice, Slovakia between 23-27 July 2007. Attendance at the conference was high and its motivation was in line with the ten previous ICMF conferences organized in Udine, Orlando, Bangor, Sendai-Tokyo, Riga, Paris, Bhavnagar, Timisoara, Bremen and Guarujá. The conference in Slovakia reflected the scientific community's enthusiasm and worldwide support, with 256 participants, from 30 countries attending.The main objective of ICMF 11 was to promote progress and knowledge in the field of magnetic fluids regarding their chemistry, physical and magnetic properties, heat and mass transfer, surface phenomena, as well as their technological and biomedical applications. As research on magnetic fluids is essentially interdisciplinary, experts from related areas were invited to present their contributions with a view to increasing knowledge in the field and highlighting new trends. Submitted communications were refereed by members of the Scientific Organizing Committee and abstracts were assembled in a book of abstracts. Participants presented 180 posters in two poster sessions and 56 oral presentations. All presentations contributed to a greater understanding of the area, and helped to bridge the gap between physics, chemistry, technology, biology and medical sciences. Contributions to this conference are presented in 115 scientific papers, with some published in Journal of Physics: Condensed Matter and the rest in Magnetohydrodynamics. The organization of the conference was made possible by generous support from the Institute of Experimental Physics and Institute of Geotechnics of the Slovak Academy of Sciences, the University of Pavol Jozef Šafárik and the Slovak Physical Society. Financial support from Ferrotec, Cryosoft Ltd, Mikrochem, Liquids Research Ltd, Askony and US Steel Košice, is also gratefully acknowledged.

  17. Geochemistry, Petrology, and Provenance of Magnetite-Rich Ortaklar Cu Deposit Hosting Basalts from Koçali Complex, Gaziantep, Turkey

    NASA Astrophysics Data System (ADS)

    Yun, E.; Lee, I.; Kang, J.; Dönmez, C.; Yildirim, N.

    2015-12-01

    Magnetite-rich Cyprus type VMS deposit has been recently discovered from the Ortaklar-Gaziantep region within Koçali complex, SE Turkey. Magnetite rich sulfide ore bodies are in close contact with underlying footwall spilitic basalts. These basalts are part of Koçali mélange, which represents an accreted oceanic complex during closing of southern Neotethys. These extrusives are low-K, low alkali tholeiites with Ca rich, partially sericitized plagioclase subophitically enclosed by augite with disseminated Fe-Ti oxides and pyrite. Mineral crystallization sequence of plagioclase followed by augite and opaque is typical of MORB. Major and trace element analyses for least altered basalts based on LOI (1.5~3.6 wt%), Ce/Ce* (0.9~1.1) exhibit limited range of element abundances. Low Mg# (59~60) suggests that basalts were derived from moderately evolved magma with fractional crystallization. HFSE (Th, Nb, Hf, Zr) were used for tectonic discrimination and basalts were plotted within MORB end spectrum, near MORB-IAT boundary. N-MORB normalized La to Lu ranges from 0.4 to 0.9 times N-MORB with LREE depletion [(La/Sm)N = 0.58~0.67] and flat HREE [(Tb/Lu)N = 0.95~1.05]. Chondrite normalized REE patterns resemble those of N-MORB but characterized by severe LREE depletion [(La/Sm)CN = 0.35~0.45]. LREE depletion coupled with high Sm/Nd (0.36~0.43), high CaO/Na2O (5.0~6.2) and low Nb/Yb (0.23~0.39) suggest depleted N-MORB composition derived from the refractory mantle source. Analyzed basalts are similar to those found from other rift (Costa Rica Rift Hole 504b) and intra-transform fault (Siqueiros transform). Magnetite emplacement occurring close to the ore-host boundary and lack of pyrrhotite from hosting basalts imply an involvement of oxidized hydrothermal fluids. Basalts probably have formed by late stage, partial melting of the refractory mantle at low pressure, shallow depth, and H2O rich environment. Possible source of mantle heterogeneity can be identified by isotope

  18. High heat flux test with HIP-bonded Ferritic Martensitic Steel mock-up for the first wall of the KO HCML TBM

    NASA Astrophysics Data System (ADS)

    Won Lee, Dong; Dug Bae, Young; Kwon Kim, Suk; Yun Shin, Hee; Guen Hong, Bong; Cheol Bang, In

    2011-10-01

    In order for a Korean Helium Cooled Molten Lithium (HCML) Test Blanket Module (TBM) to be tested in the International Thermonuclear Experimental Reactor (ITER), fabrication method for the TBM FW such as Hot Isostatic Pressing (HIP, 1050 °C, 100 MPa, 2 h) has been developed including post HIP heat treatment (PHHT, normalizing at 950 °C for 2 h and tempering at 750 °C for 2 h) with Ferritic Martensitic Steel (FMS). Several mock-ups were fabricated using the developed methods and one of them, three-channel mock-up, was used for performing a High Heat Flux (HHF) test to verify the joint integrity. Test conditions were determined using the commercial code, ANSYS-11, and the test was performed in the Korea Heat Load Test (KoHLT) facility, which was used a radiation heating with a graphite heater. The mock-up survived up to 1000 cycles under 1.0 MW/m 2 heat flux and there is no delamination or failure during the test.

  19. NAMPT knockdown attenuates atherosclerosis and promotes reverse cholesterol transport in ApoE KO mice with high-fat-induced insulin resistance

    PubMed Central

    Li, Shengbing; Wang, Cong; Li, Ke; Li, Ling; Tian, Mingyuan; Xie, Jing; Yang, Mengliu; Jia, Yanjun; He, Junying; Gao, Lin; Boden, Guenther; Liu, Hua; Yang, Gangyi

    2016-01-01

    NAMPT has been suggested association with atherosclerosis and insulin resistance. However, the impact of NAMPT on atherosclerosis remained unknown. Therefore, the objective of this study was to use a NAMPT loss-of-function approach to investigate the effect of NAMPT on atherosclerosis in hypercholesterolemic mice. We demonstrated that a specific NAMPT knockdown increased plasma HDL-C levels, reduced the plaque area of the total aorta en face and the cross-sectional aortic sinus, decreased macrophage number and apoptosis, and promoted RCT in HFD-fed ApoE KO mice. These changes were accompanied by increased PPARα, LXRα, ABCA1 and ABCG1 expressions in the liver. NAMPT knockdown also facilitated cholesterol efflux in RAW264.7 cells. We further investigated the effect of NAMPT knockdown on the PPARα-LXRα pathway of cholesterol metabolism with MK886 (a selective inhibitor of PPARα) in RAW264.7 macrophages. MK886 abolished the ability of NAMPT knockdown to decrease intracellular cholesterol levels to enhance the rate of 3H-cholesterol efflux and to increase ABCA1/G1 and LXRα expressions in RAW264.7 macrophages. Our observations demonstrate that NAMPT knockdown exerted antiatherogenic effects by promoting cholesterol efflux and macrophage RCT through the PPARα- LXRα- ABCA1/G1pathway in vitro and in vivo. PMID:27229177

  20. Neurocognitive endophenotypes in CGG KI and Fmr1 KO mouse models of Fragile X-Associated disorders: an analysis of the state of the field

    PubMed Central

    Hunsaker, Michael R.

    2013-01-01

    It has become increasingly important that the field of behavioral genetics identifies not only the gross behavioral phenotypes associated with a given mutation, but also the behavioral endophenotypes that scale with the dosage of the particular mutation being studied. Over the past few years, studies evaluating the effects of the polymorphic CGG trinucleotide repeat on the FMR1 gene underlying Fragile X-Associated Disorders have reported preliminary evidence for a behavioral endophenotype in human Fragile X Premutation carrier populations as well as the CGG knock-in (KI) mouse model. More recently, the behavioral experiments used to test the CGG KI mouse model have been extended to the Fmr1 knock-out (KO) mouse model. When combined, these data provide compelling evidence for a clear neurocognitive endophenotype in the mouse models of Fragile X-Associated Disorders such that behavioral deficits scale predictably with genetic dosage. Similarly, it appears that the CGG KI mouse effectively models the histopathology in Fragile X-Associated Disorders across CGG repeats well into the full mutation range, resulting in a reliable histopathological endophenotype. These endophenotypes may influence future research directions into treatment strategies for not only Fragile X Syndrome, but also the Fragile X Premutation and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). PMID:24627796

  1. NAMPT knockdown attenuates atherosclerosis and promotes reverse cholesterol transport in ApoE KO mice with high-fat-induced insulin resistance.

    PubMed

    Li, Shengbing; Wang, Cong; Li, Ke; Li, Ling; Tian, Mingyuan; Xie, Jing; Yang, Mengliu; Jia, Yanjun; He, Junying; Gao, Lin; Boden, Guenther; Liu, Hua; Yang, Gangyi

    2016-01-01

    NAMPT has been suggested association with atherosclerosis and insulin resistance. However, the impact of NAMPT on atherosclerosis remained unknown. Therefore, the objective of this study was to use a NAMPT loss-of-function approach to investigate the effect of NAMPT on atherosclerosis in hypercholesterolemic mice. We demonstrated that a specific NAMPT knockdown increased plasma HDL-C levels, reduced the plaque area of the total aorta en face and the cross-sectional aortic sinus, decreased macrophage number and apoptosis, and promoted RCT in HFD-fed ApoE KO mice. These changes were accompanied by increased PPARα, LXRα, ABCA1 and ABCG1 expressions in the liver. NAMPT knockdown also facilitated cholesterol efflux in RAW264.7 cells. We further investigated the effect of NAMPT knockdown on the PPARα-LXRα pathway of cholesterol metabolism with MK886 (a selective inhibitor of PPARα) in RAW264.7 macrophages. MK886 abolished the ability of NAMPT knockdown to decrease intracellular cholesterol levels to enhance the rate of (3)H-cholesterol efflux and to increase ABCA1/G1 and LXRα expressions in RAW264.7 macrophages. Our observations demonstrate that NAMPT knockdown exerted antiatherogenic effects by promoting cholesterol efflux and macrophage RCT through the PPARα- LXRα- ABCA1/G1pathway in vitro and in vivo. PMID:27229177

  2. What makes hydromagmatic eruptions violent? Some insights from the Keanakāko'i Ash, Kı̄lauea Volcano, Hawai'i

    USGS Publications Warehouse

    Mastin, Larry G.; Christiansen, Robert L.; Thornber, Carl R.; Lowenstern, Jacob B.; Beeson, Melvin H.

    2004-01-01

    Volcanic eruptions at the summit of Ki??ilauea volcano, Hawai'i, are of two dramatically contrasting types: (1) benign lava flows and lava fountains; and (2) violent, mostly prehistoric eruptions that dispersed tephra over hundreds of square kilometers. The violence of the latter eruptions has been attributed to mixing of water and magma within a wet summit caldera; however, magma injection into water at other volcanoes does not consistently produce widespread tephras. To identify other factors that may have contributed to the violence of these eruptions, we sampled tephra from the Keanaka??ko'i Ash, the most recent large hydromagmatic deposit, and measured vesicularity, bubble-number density and dissolved volatile content of juvenile matrix glass to constrain magma ascent rate and degree of degassing at the time of quenching. Bubble-number densities (9 ?? 104- 1 ?? 107 cm-3) of tephra fragments exceed those of most historically erupted Ki??lauean tephras (3 ?? 103-1.8 ?? 105 cm-3), and suggest exceptionally high magma effusion rates. Dissolved sulfur (average = 330 ppm) and water (0.15-0.45 wt.%) concentrations exceed equilibrium-saturation values at 1 atm pressure (100-150 ppm and ???0.09%, respectively), suggesting that clasts quenched before equilibrating to atmospheric pressure. We interpret these results to suggest rapid magma injection into a wet crater, perhaps similar to continuous-uprush jets at Surtsey. Estimates of Reynolds number suggest that the erupting magma was turbulent and would have mixed with surrounding water in vortices ranging downward in size to centimeters. Such fine-scale mixing would have ensured rapid heat exchange and extensive magma fragmentation, maximizing the violence of these eruptions.

  3. Lytic Myophage Abp53 Encodes Several Proteins Similar to Those Encoded by Host Acinetobacter baumannii and Phage phiKO2 ▿ †

    PubMed Central

    Lee, Chia-Ni; Tseng, Tsai-Tien; Lin, Juey-Wen; Fu, Yung-Chieh; Weng, Shu-Fen; Tseng, Yi-Hsiung

    2011-01-01

    Acinetobacter baumannii is an important Gram-negative opportunistic pathogen causing nosocomial infections. The emergence of multiple-drug-resistant A. baumannii isolates has increased in recent years. Directed toward phage therapy, a lytic phage of A. baumannii, designated Abp53, was isolated from a sputum sample in this study. Abp53 has an isometric head and a contractile tail with tail fibers (belonging to Myoviridae), a latent period of about 10 min, and a burst size of approximately 150 PFU per infected cell. Abp53 could completely lyse 27% of the A. baumannii isolates tested, which were all multiple drug resistant, but not other bacteria. Mg2+ enhanced the adsorption and productivity of, and host lysis by, Abp53. Twenty Abp53 virion proteins were visualized in SDS-polyacrylamide gel electrophoresis, with a 47-kDa protein being the predicted major capsid protein. Abp53 has a double-stranded DNA genome of 95 kb. Sequence analyses of a 10-kb region revealed 8 open reading frames. Five of the encoded proteins, including 3 tail components and 2 hypothetical proteins, were similar to proteins encoded by A. baumannii strain ACICU. ORF1176 (one of the tail components, 1,176 amino acids [aa]), which is also similar to tail protein gp21 of Klebsiella phage phiKO2, contained repeated domains similar to those within the ACICU_02717 protein of A. baumannii ACICU and gp21. These findings suggest a common ancestry and horizontal gene transfer during evolution. As phages can expand the host range by domain duplication in tail fiber proteins, repeated domains in ORF1176 might have a similar significance in Abp53. PMID:21821767

  4. Analysis of storage possibility of raw and smoked breast meat of oat-fattened White Kołuda® goose based on their quality characteristics.

    PubMed

    Damaziak, K; Stelmasiak, A; Michalczuk, M; Wyrwisz, J; Moczkowska, M; Marcinkowska-Lesiak, M M; Niemiec, J; Wierzbicka, A

    2016-09-01

    Raw and smoked (spickgans) fillets of oat-fattened White Kołuda® goose were packed in: PET - ethylene terephthalate bags; VSP - 99% vacuum; MAP1 - 80% O2, 20% CO2; MAP2 - 70% N2, 30% O2; MAP3 - 30% O2, 40% N2, 30% CO2, and stored at a temperature of 2°C. On the day of packaging (0 d) and during storage of raw (5, 7, 10 d) and smoked fillets (5, 10, 15 d), the samples were analyzed for weight losses, physicochemical traits, and chemical composition. The study demonstrated the effect of storage time and packaging method on storage yield of raw and smoked fillets. In VSP, the raw fillets were characterized by the lowest amount of leakage, whereas spickgans were characterized by the highest storage yield and weight loss. The analysis of the effect of the modified atmosphere demonstrated the lowest weight loss of raw fillets at, simultaneously, the smallest amount of leakage in MAP1. The spickgans stored in MAP2 showed higher weight, higher yield after storage, and lower storage loss in all terms of analyses compared to MAP1 and MAP3. The greatest cooking loss at simultaneously the lowest pH values was determined for the samples stored in VSP. The WBSF values of raw fillets were decreasing along with storage time, in contrast to WBSF values of spickgans, in which case the value of this parameter increased compared to 0 d. Raw fillets stored in MAP1 and MAP3 were characterized by the most significant increase in the value of L*, by a decrease in the value of a* and an increase in that of b* parameter. Visual assessment of spickgans on 15 d of storage revealed the presence of white sediment on the surface of products, except for the samples stored in VSP. The study demonstrated the effect of storage time on the contents of protein and fat in raw fillets and on the contents of salt and fat in spickgans. PMID:27143769

  5. Compensatory T-type Ca2+ channel activity alters D2-autoreceptor responses of Substantia nigra dopamine neurons from Cav1.3 L-type Ca2+ channel KO mice

    PubMed Central

    Poetschke, Christina; Dragicevic, Elena; Duda, Johanna; Benkert, Julia; Dougalis, Antonios; DeZio, Roberta; Snutch, Terrance P.; Striessnig, Joerg; Liss, Birgit

    2015-01-01

    The preferential degeneration of Substantia nigra dopamine midbrain neurons (SN DA) causes the motor-symptoms of Parkinson’s disease (PD). Voltage-gated L-type calcium channels (LTCCs), especially the Cav1.3-subtype, generate an activity-related oscillatory Ca2+ burden in SN DA neurons, contributing to their degeneration and PD. While LTCC-blockers are already in clinical trials as PD-therapy, age-dependent functional roles of Cav1.3 LTCCs in SN DA neurons remain unclear. Thus, we analysed juvenile and adult Cav1.3-deficient mice with electrophysiological and molecular techniques. To unmask compensatory effects, we compared Cav1.3 KO mice with pharmacological LTCC-inhibition. LTCC-function was not necessary for SN DA pacemaker-activity at either age, but rather contributed to their pacemaker-precision. Moreover, juvenile Cav1.3 KO but not WT mice displayed adult wildtype-like, sensitised inhibitory dopamine-D2-autoreceptor (D2-AR) responses that depended upon both, interaction of the neuronal calcium sensor NCS-1 with D2-ARs, and on voltage-gated T-type calcium channel (TTCC) activity. This functional KO-phenotype was accompanied by cell-specific up-regulation of NCS-1 and Cav3.1-TTCC mRNA. Furthermore, in wildtype we identified an age-dependent switch of TTCC-function from contributing to SN DA pacemaker-precision in juveniles to pacemaker-frequency in adults. This novel interplay of Cav1.3 L-type and Cav3.1 T-type channels, and their modulation of SN DA activity-pattern and D2-AR-sensitisation, provide new insights into flexible age- and calcium-dependent activity-control of SN DA neurons and its pharmacological modulation. PMID:26381090

  6. Nitrilotris(methylenephosphonato)potassium K[μ6-NH(CH2PO3)3H4]: Synthesis, structure, and the nature of the K-O chemical bond

    NASA Astrophysics Data System (ADS)

    Somov, N. V.; Chausov, F. F.; Zakirova, R. M.

    2016-07-01

    The crystal structure of nitrilotris(methylenephosphonato)potassium K[μ6-NH(CH2PO3)3H4]—a three-dimensional coordination polymer—was determined. The potassium atom is coordinated by seven oxygen atoms belonging to the six nearest ligand molecules, resulting in distorted monocapped octahedral coordination geometry. The complex contains the four-membered chelate ring K-O-P-O. The K-O chemical bond is predominantly ionic. Meanwhile, the bonds of the potassium atom with some oxygen atoms have a noticeable covalent component. In addition to coordination bonds, the molecules in the crystal packing are linked by hydrogen bonds.

  7. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome.

    PubMed

    Costa, Lara; Sardone, Lara M; Lacivita, Enza; Leopoldo, Marcello; Ciranna, Lucia

    2015-01-01

    Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome

  8. Generation of a Double KO Mouse by Simultaneous Targeting of the Neighboring Genes Tmem176a and Tmem176b Using CRISPR/Cas9: Key Steps from Design to Genotyping.

    PubMed

    Lemoine, Aurélie; Chauveau-Le Friec, Gaëlle; Langa, Francina; Louvet, Cédric

    2016-05-20

    The CRISPR/Cas9 system has been tailored to a revolutionary genetic tool because of its remarkable simplicity and efficacy. While complex genome editing in the mouse since the 1990s has been dominated by the use of embryonic stem (ES) cells, CRISPR/Cas9 now offers a versatile and fast approach to precisely modify virtually any DNA regions directly in mouse zygotes. Yet, this relative simplicity does not preclude a conscientious preparatory work that is often neglected when initiating a project. Here, we describe the key steps leading to successful generation of a double knockout (KO) mouse by simultaneously targeting two homolog genes, Tmem176a and Tmem176b, which are located in the same genomic locus. Additionally, we show that similar efficiency can be obtained in a mixed genetic background or directly in the C57BL/6 inbred strain. Thus, presented as a detailed case study that should be helpful to the non-specialists, we focus on the genotyping strategy to anticipate the various possibilities. PMID:27234594

  9. Identification of a Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitor, BIP-135, That Prolongs the Median Survival Time of Δ7 SMA KO Mouse Model of Spinal Muscular Atrophy

    PubMed Central

    2011-01-01

    The discovery of upregulated glycogen synthase kinase-3 (GSK-3) in various pathological conditions has led to the development of a host of chemically diverse small molecule GSK-3 inhibitors, such as BIP-135. GSK-3 inhibition emerged as an alternative therapeutic target for treating spinal muscular atrophy (SMA) when a number of GSK-3 inhibitors were shown to elevate survival motor neuron (SMN) levels in vitro and to rescue motor neurons when their intrinsic SMN level was diminished by SMN-specific short hairpin RNA (shRNA). Despite their cellular potency, the in vivo efficacy of GSK-3 inhibitors has yet to be evaluated in an animal model of SMA. Herein, we disclose that a potent and reasonably selective GSK-3 inhibitor, namely BIP-135, was tested in a transgenic Δ7 SMA KO mouse model of SMA and found to prolong the median survival of these animals. In addition, this compound was shown to elevate the SMN protein level in SMA patient-derived fibroblast cells as determined by Western blot, and was neuroprotective in a cell-based, SMA-related model of oxidative stress-induced neurodegeneration. PMID:22348181

  10. Comments on "Determination and Analysis of the Theoretical Production of a Bucket Wheel Excavator" / Uwagi I Komentarze Do Pracy: "Określanie I Analiza Teoretycznej Wydajności Pracy Koparki Wielonaczyniowej Kołowej"

    NASA Astrophysics Data System (ADS)

    Bošnjak, Srđan M.

    2015-03-01

    This paper comments on the recently published work dealing with the problem in the determination of the theoretical output of the bucket wheel excavator. It also includes remarks on the inadequacy in the problem approach and highlights the mistakes in the mathematical model. This work emphasizes the demand for a much wider and deeper approach to the problem of determining the output of the bucket wheel excavator. Opublikowany niedawno artykuł autorstwa Che i Chena (2014) poświecony jest ważnej kwestii jaką jest określenie teoretycznej wydajności koparki kołowej wielonaczyniowej. W załączonym przeglądzie literatury Che i Chen (2014) nie umieścili pozycji odnoszących się do metod urabiania, parametrów pracy koparki oraz teoretycznej wydajności wydobycia i być może to właśnie jest przyczyną pewnych niedokładności powstałych w trakcie rozwiązywania problemu. Intencją autora obecnej publikacji było: • Odniesienie się do krytycyzmu wyrażonego przez Che i Chena (2014) dotyczącego procedury obliczania prędkości w ruchu łukowym podanej w cytowanej literaturze przedmiotu (Pajer i in., 1971; Vetrov, 1971; Rasper, 1975; Durst i Vogt, 1988); • Zbadanie różnic pomiędzy procedurą określania teoretycznej wydajności zaproponowaną w pracy Che i Chena (2014) a odpowiednimi rozwiązaniami podanymi w literaturze; • Określenie prawidłowości i stosowalności teorii zaprezentowanej w pracy Che i Chena (2014) poprzez porównanie wyników uzyskanych z wykorzystaniem ich teorii oraz teorii podanych w wymienionych pozycjach literatury. W rozdziale 2 pracy (Che i Chen 2014) zatytułowanym " Uprzednio stosowane metody określania teoretycznej wydajności pracy koparki kołowej wielonaczyniowej" autorzy nie podali głównych odniesień literaturowych z których zaczerpnięte zostały równania (1)-(6)**. Ponadto, nie podali charakterystyki modelu działania koparki, na podstawie którego wyprowadzone zostały rzeczone r

  11. Influence of organics and silica on Fe(II) oxidation rates and cell-mineral aggregate formation by the green-sulfur Fe(II)-oxidizing bacterium Chlorobium ferrooxidans KoFox - Implications for Fe(II) oxidation in ancient oceans

    NASA Astrophysics Data System (ADS)

    Gauger, Tina; Byrne, James M.; Konhauser, Kurt O.; Obst, Martin; Crowe, Sean; Kappler, Andreas

    2016-06-01

    Most studies on microbial phototrophic Fe(II) oxidation (photoferrotrophy) have focused on purple bacteria, but recent evidence points to the importance of green-sulfur bacteria (GSB). Their recovery from modern ferruginous environments suggests that these photoferrotrophs can offer insights into how their ancient counterparts grew in Archean oceans at the time of banded iron formation (BIF) deposition. It is unknown, however, how Fe(II) oxidation rates, cell-mineral aggregate formation, and Fe-mineralogy vary under environmental conditions reminiscent of the geological past. To address this, we studied the Fe(II)-oxidizer Chlorobium ferrooxidans KoFox, a GSB living in co-culture with the heterotrophic Geospirillum strain KoFum. We investigated the mineralogy of Fe(III) metabolic products at low/high light intensity, and in the presence of dissolved silica and/or fumarate. Silica and fumarate influenced the crystallinity and particle size of the produced Fe(III) minerals. The presence of silica also enhanced Fe(II) oxidation rates, especially at high light intensities, potentially by lowering Fe(II)-toxicity to the cells. Electron microscopic imaging showed no encrustation of either KoFox or KoFum cells with Fe(III)-minerals, though weak associations were observed suggesting co-sedimentation of Fe(III) with at least some biomass via these aggregates, which could support diagenetic Fe(III)-reduction. Given that GSB are presumably one of the most ancient photosynthetic organisms, and pre-date cyanobacteria, our findings, on the one hand, strengthen arguments for photoferrotrophic activity as a likely mechanism for BIF deposition on a predominantly anoxic early Earth, but, on the other hand, also suggest that preservation of remnants of Fe(II)-oxidizing GSB as microfossils in the rock record is unlikely.

  12. Distribution and age-related bioaccumulation of lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As) in tissues of common carp (Cyprinus carpio) and European catfish (Sylurus glanis) from the Buško Blato reservoir (Bosnia and Herzegovina).

    PubMed

    Has-Schön, Elizabeta; Bogut, Ivan; Vuković, Rosemary; Galović, Dalida; Bogut, Ante; Horvatić, Janja

    2015-09-01

    The purpose of this study was to quantify the bioaccumulation of Pb, Hg, Cd, and As in tissues of carp (Cyprinus carpio) and catfish (Silurus glanis) from Buško Blato in Bosnia and Herzegovina. Arsenic concentrations were below the Maximal Admissible Concentration (MAC) for Croatia and other countries. Mercury concentrations were below 1 mg kg(-1), but in most muscle samples of both species and all catfish liver samples, the values were higher than 0.5 mg kg(-1) (higher than the MAC for many countries including Croatia). Lead concentrations were higher than 1 mg kg(-1) (the MAC for Croatia) in most muscle samples; all kidney and most catfish liver samples also exceeded 1 mg kg(-1). Cadmium concentrations in all tissues, other than the gonads, were higher than 0.1 mg kg(-1) (MAC for Croatia), with the highest concentrations found in the kidneys. The only gender difference was found in carp, where a 68.4% higher concentration of As was found in the fry compared to the milt (P<0.05). Concentrations of all of the elements were higher in catfish compared to carp for most tissues. Significant correlations were found between all of the elements in the muscles and the liver of carp. In catfish, the muscles were the only tissue in which multiple correlations were found. Linear positive correlations with age and body mass were demonstrated for the concentrations of all heavy metals for all tissues except the gonads in both fish species. We concluded that significant heavy metal accumulation in carp and a catfish tissues correlates with age and body mass; bioaccumulation is species- and tissue-specific and is different for each element. PMID:25966047

  13. The temporal association of excessive health expenditure with suicidal ideation among primary income earners: a cross-sectional design using the Korean Welfare Panel Survey (KoWePS)

    PubMed Central

    Shin, Jaeyong; Choi, Jae Woo; Jang, Sung-in; Choi, Young; Lee, Sang Gyu; Ihm, Tae Hwan; Park, Eun-Cheol

    2015-01-01

    Objective Excessive health expenditure (EHE) is a global issue for households suffering from high-cost medical conditions, low incomes and limited insurance coverage. After the international financial crisis of 2008, EHE became a social problem in developed countries. Such economic crisis might induce severe mental stress, resulting in suicidal ideation. Methods We used the Korean Welfare Panel Study (KoWePS) from 2011 to 2013 and selected primary income earners, who were defined as practical and economic representatives of households; the total number of analysed samples was 4247 of 5717 households in the database. We only included households that had never experienced EHE before 2011. To examine the temporal relationship between EHE and suicidal ideation, we conducted a logistic regression analysis. Results Among 4247 participants, 146 (3.4%) experienced suicidal ideation, whereas 4101 (96.6%) did not. One scale of depression score (OR=1.28, CI 1.23 to 1.34, p<0.001) was associated with increased suicidal ideation. Such ideation was influenced to a greater extent by a recent EHE above 10% of disposable income (OR=1.91, CI 1.16 to 3.15, p=0.012) than by either a remote EHE (OR=1.29, CI 0.71 to 2.32) or one in 2011 and 2012 (OR=1.67, CI 1.01 to 2.78, p=0.048). Conclusions In this study, more recent EHE resulted in more suicidal ideation. In conclusion, we suggest that recent household EHE might be considered as an important factor to prevent suicidal ideation and to improve the mental health of individuals. PMID:26082463

  14. NH2-terminal globular domain of human platelet glycoprotein Ib alpha has a methionine 145/threonine145 amino acid polymorphism, which is associated with the HPA-2 (Ko) alloantigens.

    PubMed Central

    Kuijpers, R W; Faber, N M; Cuypers, H T; Ouwehand, W H; von dem Borne, A E

    1992-01-01

    The glycoprotein (GP) Ib/IX complex, a prominent platelet GP complex, is the primary receptor for vWF. Previously, we have established that an antigenic polymorphism of platelets, the HPA-2 or Ko alloantigen system, is located on the 45-kD amino-terminal globular domain of GPIb alpha. With the polymerase chain reaction, we have amplified two segments of the GPIb alpha gene coding for the first 382 amino acids of two HPA-2a and two HPA-2b homozygous individuals. Nucleotide sequence analysis revealed as the only difference a C-T polymorphism at position 434 of the coding region for the mature protein. This base change results in a substitution of threonine (ACG) in HPA-2a (Kob) to methionine (ATG) in HPA-2b (Koa) at amino acid position 145. The C-T polymorphism is reflected in a difference in restriction enzyme recognition, resulting in an Aha 2-site in the HPA-2b allele and a SfaN1 site in the HPA-2a allele. Restriction fragment length polymorphism analysis of the amplified DNA of 3 HPA-2(a-,b+), 2 HPA-2(a+,b+), and 11 HPA-2(a+,b-) donors showed that these restriction sites were associated with the HPA-2 alleles. DNA-typing for the HPA-2 alloantigen system on genomic DNA obtained from a small number of cells may be applied for determining the genotype of a fetus from an immunized mother or of severely thrombocytopenic patients. Images PMID:1346615

  15. No Interaction with Alcohol Consumption, but Independent Effect of C12orf51 (HECTD4) on Type 2 Diabetes Mellitus in Korean Adults Aged 40-69 Years: The KoGES_Ansan and Ansung Study

    PubMed Central

    Kim, Jihye; Oh, Bermseok; Lim, Ji Eun; Kim, Mi Kyung

    2016-01-01

    Previously, genetic polymorphisms of C12orf51 (HECTD4) (rs2074356 and/or rs11066280) have been shown to be related to alcohol consumption and type 2 diabetes (T2D). This study aimed to prospectively examine whether C12orf51 had an interaction with or independent effect on alcohol consumption and the risk of T2D. The present study included 3,244 men and 3,629 women aged 40 to 69 years who participated in the Korean Genome and Epidemiology Study (KoGES)_Ansan and Ansung Study. Cox proportional hazards models were used to estimate HRs and 95% CIs for T2D. rs2074356 and rs11066280 were associated with the risk of T2D after adjusting for alcohol consumption (rs2074356 for AA: HR = 0.39 and 95% CI = 0.17–0.87 in men, and HR = 0.36 and 95% CI = 0.13–0.96 in women; rs11066280 for AA: HR = 0.44 and 95% CI = 0.23–0.86 in men, and HR = 0.39 and 95% CI = 0.16–0.94 in women). We identified that the association of each variant (rs2074356 and rs11065756) in C12orf51 was nearly unchanged after adjusted for alcohol consumption. Therefore, the association of 2 SNPs in C12orf51 with diabetes may not be mediated by alcohol use. There was no interaction effect between alcohol consumption and the SNPs with T2D. However, even in never-drinkers, minor allele homozygote strongly influenced T2D risk reduction (rs2074356 for AA: HR = 0.35, 95% CI = 0.14–0.90, and p-trend = 0.0035 in men and HR = 0.34, 95% CI = 0.13–0.93, and p-trend = 0.2348 in women; rs11066280 for AA: HR = 0.36, 95% CI = 0.16–0.82, and p-trend = 0.0014 in men and HR = 0.39, 95% CI = 0.16–0.95, and p-trend = 0.3790 in women), while alcohol consumption did not influence the risk of T2D within each genotype. rs2074356 and rs11066280 in or near C12orf51, which is related to alcohol drinking behavior, may longitudinally decrease the risk of T2D, but not through regulation of alcohol consumption. PMID:26891264

  16. Cross-Sectional and Longitudinal Associations between Egg Consumption and Metabolic Syndrome in Adults ≥ 40 Years Old: The Yangpyeong Cohort of the Korean Genome and Epidemiology Study (KoGES_Yangpyeong)

    PubMed Central

    Woo, Hye Won; Choi, Bo Youl; Kim, Mi Kyung

    2016-01-01

    Since the 1970s, the public has been advised to limit egg consumption even though there is little evidence of any harmful effect of eggs on blood cholesterol. The purpose of this cross-sectional and prospective study was to evaluate the potential association between egg consumption and metabolic syndrome (MetS) and MetS components in adults ≥ 40 years in KoGES_Yangpyeong. Yangpyeong is a rural area in South Korea. A total of 2,887 subjects (men 1,115, women 1,772) were recruited from 2005 to 2009, based on a physical examination and questionnaires administered using standardized protocol. After excluding subjects who had MetS at baseline, 1,663 subjects (675 men, 958 women) were followed for 3.20 years (range: 0.34–8.70). During the follow-up period, MetS occurred in 289 subjects. More than 3 eggs per week was significantly associated with decreased risk of MetS in both men (RR = 0.46, 95% CI, 0.26–0.82, P for trend = 0.1093) and women (RR = 0.54, 95% CI, 0.31–0.93, P for trend 0.0325) compared to non-users. There was a cross-sectional inverse relationship between egg consumption and abdominal obesity in men and women. Also, prospectively, higher egg consumption in men was associated with a decreased risk of high fasting blood glucose (RR = 0.39, 95% CI, 0.22–0.67, P for trend = 0.0042) and high triglycerides (RR = 0.42, 95% CI, 0.22–0.80, P for trend = 0.1080). In conclusion, our findings suggest that higher egg consumption may reduce the risk of MetS both in men and women, and the risk of high fasting blood glucose and high triglycerides in men. Current guidelines regarding egg consumption may need to be re-visited for healthy middle-aged and elderly people. PMID:26808174

  17. Cross-Sectional and Longitudinal Associations between Egg Consumption and Metabolic Syndrome in Adults ≥ 40 Years Old: The Yangpyeong Cohort of the Korean Genome and Epidemiology Study (KoGES_Yangpyeong).

    PubMed

    Woo, Hye Won; Choi, Bo Youl; Kim, Mi Kyung

    2016-01-01

    Since the 1970s, the public has been advised to limit egg consumption even though there is little evidence of any harmful effect of eggs on blood cholesterol. The purpose of this cross-sectional and prospective study was to evaluate the potential association between egg consumption and metabolic syndrome (MetS) and MetS components in adults ≥ 40 years in KoGES_Yangpyeong. Yangpyeong is a rural area in South Korea. A total of 2,887 subjects (men 1,115, women 1,772) were recruited from 2005 to 2009, based on a physical examination and questionnaires administered using standardized protocol. After excluding subjects who had MetS at baseline, 1,663 subjects (675 men, 958 women) were followed for 3.20 years (range: 0.34-8.70). During the follow-up period, MetS occurred in 289 subjects. More than 3 eggs per week was significantly associated with decreased risk of MetS in both men (RR = 0.46, 95% CI, 0.26-0.82, P for trend = 0.1093) and women (RR = 0.54, 95% CI, 0.31-0.93, P for trend 0.0325) compared to non-users. There was a cross-sectional inverse relationship between egg consumption and abdominal obesity in men and women. Also, prospectively, higher egg consumption in men was associated with a decreased risk of high fasting blood glucose (RR = 0.39, 95% CI, 0.22-0.67, P for trend = 0.0042) and high triglycerides (RR = 0.42, 95% CI, 0.22-0.80, P for trend = 0.1080). In conclusion, our findings suggest that higher egg consumption may reduce the risk of MetS both in men and women, and the risk of high fasting blood glucose and high triglycerides in men. Current guidelines regarding egg consumption may need to be re-visited for healthy middle-aged and elderly people. PMID:26808174

  18. Ko te Maoopopo ko te Lima Malohi: Collaboration Is Our Strength

    ERIC Educational Resources Information Center

    Meredith, Kathryn; Andersen, Tim; Neale, Louella; Taylor, Colleen; Schuster, Ezra

    2008-01-01

    A delegation from the Ministry of Education, Special Education (GSE) went to Tokelau in 2007 in response to a request from the Tokelauan government to help establish services for children with special education needs. The team was led by Ezra Schuster and made up of a special education advisor, a speech-language therapist, an advisor on deaf…

  19. Chapter 8. An indigenous narrative of resilience: Malama ko Aloha.

    PubMed

    Johnson, Jeannette L; Beamer, Keola

    2013-11-01

    Many indigenous cultures use storytelling as the foundation for the transmission of important cultural information. Stories passed down from generation to generation sometimes teach, record history, provide examples, or inform. One important function of storytelling is the transmission of stories about cultural resilience illustrating how a cultural group has kept strong in the face of adversity. This article shows how storytelling in the Hawaiian culture has been used for this purpose and how the Beamer family has served as the master storytellers of their culture, keeping the culture and traditions alive through their music, dance, and stories. PMID:24087870

  20. Materials Data on KO2 (SG:139) by Materials Project

    DOE Data Explorer

    Kristin Persson

    2016-05-20

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  1. Materials Data on KO2 (SG:15) by Materials Project

    DOE Data Explorer

    Kristin Persson

    2016-02-05

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  2. Materials Data on KO3 (SG:140) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-11-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  3. Maori Parents and Education: Ko Nga Matua Maori me te Matauranga.

    ERIC Educational Resources Information Center

    McKinley, Sheridan

    In New Zealand, Maori children attend English-medium schools, schools with a bilingual unit, or kura kaupapa Maori. This study identified aspirations and concerns of Maori parents regarding their children's education, identified issues related to parents' participation in their child's education, and developed strategies to address concerns and…

  4. Ultraviolet and X-ray detection of the 56 Peg system (KO 2p + WD)

    NASA Technical Reports Server (NTRS)

    Schindler, M.; Stencel, R. E.; Linsky, J. L.; Basri, G.; Helfand, D.

    1982-01-01

    Both IUE short and long wavelength exposures of the 56 Peg system are discussed. This mild barium star has an X-ray luminosity of 3 x 10 to the 31st power ergs/1, comparable to the rapidly rotating RS CVn binary systems, yet lies in a region of the HR diagram where stellar X-rays are generally not observed. This cool, bright giant is not a rapid rotator and the key to understanding its emission lies in the recent discovery of its white dwarf companion. Accretion onto the white dwarf of approximately 0.1% of the stellar wind of the primary is sufficient to power an X-ray source of the observed luminosity. Reprocessing of the X-rays in the cool dense stellar wind explains the origin of the UV emission line spectrum, and may explain the time varying asymmetry of the Mg 2 kappa line profile that is observed. Graphs which show observed fluxes and wavelengths are discussed.

  5. Fmr1 KO and Fenobam Treatment Differentially Impact Distinct Synapse Populations of Mouse Neocortex

    PubMed Central

    Wang, Gordon X.; Smith, Stephen J; Mourrain, Philippe

    2015-01-01

    SUMMARY Cognitive deficits in fragile X syndrome (FXS) are attributed to molecular abnormalities of the brain’s vast and heterogeneous synapse populations. Unfortunately, the density of synapses coupled with their molecular heterogeneity presents formidable challenges in understanding the specific contribution of synapse changes in FXS. We demonstrate powerful new methods for the large-scale molecular analysis of individual synapses that allow quantification of numerous specific changes in synapse populations present in the cortex of a mouse model of FXS. Analysis of nearly a million individual synapses reveals distinct, quantitative changes in synaptic proteins distributed across over 6,000 pairwise metrics. Some, but not all, of these synaptic alterations are reversed by treatment with the candidate therapeutic fenobam, an mGluR5 antagonist. These patterns of widespread, but diverse synaptic protein changes in response to global perturbation suggest that FXS and its treatment must be understood as a networked system at the synapse level. PMID:25521380

  6. "He Kuleana Ko Kakou": Hawaiian-Language Learners and the Construction of (Alter)Native Identities

    ERIC Educational Resources Information Center

    Snyder-Frey, Alicia

    2013-01-01

    This article examines the various language ideologies and cultural models that inform Hawaiian-language learners' experiences, language practices, and socio-ethnic identity as they attempt to become speakers of their heritage language. While Hawaiian-language education is often noted as a revitalization success story, and certainly is in…

  7. Two-Thirds Majority Vote Rule KO'd in California

    ERIC Educational Resources Information Center

    Garber, Lee O.

    1970-01-01

    The California Supreme Court rule on June 30th that local bond issues requiring two-thirds voter approval for passage violated the equal protection clause of the Fourteenth Amendment. (Westbrook v. Mihaly). (MF)

  8. High resolution EUV spectroscopy of 56 Pegasi (KO 2p + wd)

    NASA Technical Reports Server (NTRS)

    Jordan, C.; Brown, A.; Ayres, T. R.; Linsky, J. L.; Stencel, R. E.

    1982-01-01

    The hypothesis that X-ray and UV emission by 56 Pegasi (K0II p + wd) originates in a conventional chromosphere, transition region and corona, as opposed to Schindler's hypothesis of accretion of the cool stellar wind onto the white dwarf companion, is discussed. Analysis of IUE data indicates that within the uncertainties associated with determining the stellar radius and abundances, the chromosphere, transition region, and corona of 56 Peg are similar to that of Beta Draconis both in structure and energy balance. The accretion hypothesis is not a unique explanation of the observed spectral properties and the white dwarf companion may not play a direct role. Furthermore, 56 Peg, according to current values of V-R and luminosity class, is on the nonsolar side of the Linsky-Haisch dividing line whereas Beta Draconis is on the solar side.

  9. Ko Wai Au? Who Am I? Examining the Multiple Identities of Maori Youth

    ERIC Educational Resources Information Center

    Faircloth, Susan C.; Hynds, Anne; Jacob, Helen; Green, Clint; Thompson, Patrick

    2016-01-01

    In this paper, we present preliminary findings from a unique collaborative research project involving six Deaf Maori rangatahi (youth) in Tamaki Makaurau (Auckland), Aotearoa New Zealand. This study utilized kaupapa whanau (research family) protocols, established in consultation with two cultural advisory groups within New Zealand and the young…

  10. Multi-element analysis of emeralds and associated rocks by k(o) neutron activation analysis

    PubMed

    Acharya; Mondal; Burte; Nair; Reddy; Reddy; Reddy; Manohar

    2000-12-01

    Multi-element analysis was carried out in natural emeralds, their associated rocks and one sample of beryl obtained from Rajasthan, India. The concentrations of 21 elements were assayed by Instrumental Neutron Activation Analysis using the k0 method (k0 INAA method) and high-resolution gamma ray spectrometry. The data reveal the segregation of some elements from associated (trapped and host) rocks to the mineral beryl forming the gemstones. A reference rock standard of the US Geological Survey (USGS BCR-1) was also analysed as a control of the method. PMID:11077961

  11. Dietary changes in Vietnamese marriage immigrant women: The KoGES follow-up study

    PubMed Central

    Hwang, Ji-Yun; Lee, Hakim; Ko, Ahra; Han, Chan-Jung; Chung, Hye Won

    2014-01-01

    BACKGROUND/OBJECTIVES The immigrant population has grown considerably in South Korea since the early 1990s due to international marriages. Dietary changes in immigrants are an important issue, because they are related to health and disease patterns. This study was conducted to compare changes in dietary intake between baseline and follow-up periods. SUBJECTS/METHODS Two hundreds thirty three Vietnamese female married immigrants. Baseline data were collected during 2006-2009, and the follow-up data were collected during 2008 and 2010. Food consumption was assessed using a 1-day 24-hour recall. RESULTS The amount of the total food consumed (P < 0.001) including that of cereals (P = 0.004), vegetables (P = 0.003), and fruits (P = 0.002) decreased at follow-up compared to that at baseline, whereas consumption of milk and dairy products increased (P = 0.004). Accordingly, the overall energy and nutrient intake decreased at follow-up, including carbohydrates (P = 0.012), protein (P = 0.021), fiber (P = 0.008), iron (P = 0.009), zinc (P = 0.006), and folate (P = 0.002). Among various anthropometric and biochemical variables, mean skeletal muscle mass decreased (P = 0.012), plasma high density lipoprotein-cholesterol increased, (P = 0.020) and high sensitivity C-reactive protein decreased at follow-up (P < 0.001). CONCLUSIONS A long-term follow-up study is needed to investigate the association between changes in food and nutrient intake and anthropometric and biochemical variables in these Vietnamese female marriage immigrants. PMID:24944778

  12. 5-HT1B receptor modulation of the serotonin transporter in vivo: studies using KO mice.

    PubMed

    Montañez, Sylvia; Munn, Jaclyn L; Owens, W Anthony; Horton, Rebecca E; Daws, Lynette C

    2014-07-01

    The serotonin transporter (SERT) controls the strength and duration of serotonergic neurotransmission by the high-affinity uptake of serotonin (5-HT) from extracellular fluid. SERT is a key target for many psychotherapeutic and abused drugs, therefore understanding how SERT activity and expression are regulated is of fundamental importance. A growing literature suggests that SERT activity is under regulatory control of the 5-HT1B autoreceptor. The present studies made use of mice with a constitutive reduction (5-HT1B+/-) or knockout of 5-HT1B receptors (5-HT1B-/-), as well as mice with a constitutive knockout of SERT (SERT-/-) to further explore the relationship between SERT activity and 5-HT1B receptor expression. High-speed chronoamperometry was used to measure clearance of 5-HT from CA3 region of hippocampus in vivo. Serotonin clearance rate, over a range of 5-HT concentrations, did not differ among 5-HT1B receptor genotypes, nor did [(3)H]cyanoimipramine binding to SERT in this brain region, suggesting that SERT activity is not affected by constitutive reduction or loss of 5-HT1B receptors; alternatively, it might be that other transport mechanisms for 5-HT compensate for loss of 5-HT1B receptors. Consistent with previous reports, we found that the 5-HT1B receptor antagonist, cyanopindolol, inhibited 5-HT clearance in wild-type mice. However, this effect of cyanopindolol was lost in 5-HT1B-/- mice and diminished in 5-HT1B+/- mice, indicating that the 5-HT1B receptor is necessary for cyanopindolol to inhibit 5-HT clearance. Likewise, cyanopindolol was without effect on 5-HT clearance in SERT-/- mice, demonstrating a requirement for the presence of both SERT and 5-HT1B receptors in order for cyanopindolol to inhibit 5-HT clearance in CA3 region of hippocampus. Our findings are consistent with SERT being under the regulatory control of 5-HT1B autoreceptors. Future studies to identify signaling pathways involved may help elucidate novel therapeutic targets for the treatment of psychiatric disorders, particularly those linked to gene variants of the 5-HT1B receptor. PMID:24246466

  13. Modifying Behavioral Phenotypes in Fmr1 KO Mice: Genetic Background Differences Reveal Autistic-Like Responses

    PubMed Central

    Spencer, Corinne M.; Alekseyenko, Olga; Hamilton, Shannon M.; Thomas, Alexia M.; Serysheva, Ekaterina; Yuva-Paylor, Lisa A.; Paylor, Richard

    2010-01-01

    Scientific Abstract Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in humans. In addition to cognitive impairment, patients may exhibit hyperactivity, attention deficits, social difficulties and anxiety, and autistic-like behaviors. The degree to which patients display these behaviors varies considerably and is influenced by family history, suggesting that genetic modifiers play a role in the expression of behaviors in FXS. Several studies have examined behavior in a mouse model of FXS in which the Fmr1 gene has been ablated. Most of those studies were done in Fmr1 knockout mice on a pure C57BL/6 or FVB strain background. To gain a better understanding of the effects of genetic background on behaviors resulting from the loss of Fmr1 gene expression, we generated F1 hybrid lines from female Fmr1 heterozygous mice on a pure C57BL/6J background bred with male Fmr1 wild-type mice of various background strains (A/J, DBA/2J, FVB/NJ, 129S1/SvImJ and CD-1). Male Fmr1 knockout and wild-type littermates from each line were examined in an extensive behavioral test battery. Results clearly indicate that multiple behavioral responses are dependent on genetic background, including autistic-like traits that are present on limited genetic backgrounds. This approach has allowed us to identify improved models for different behavioral symptoms present in FXS including autistic-like traits. PMID:21268289

  14. Fireball Kościerzyna - 2009.05.31 20:49:38 UT

    NASA Astrophysics Data System (ADS)

    Wisniewski, M.; Fietkiewicz, K.; Zolcadek, P.; Dygos, P.; Krasnowski, M.; Polakowski, K.

    2010-01-01

    On the night of May 31, 2009, at 20:49:38 UT an extremely bright fireball occurred over northern Poland. Three cameras of Polish Fireball Network recorded this event. Images from PFN24 Gniewowo was completely saturated by meteor flash. We use data from PFN05 Poznan and PFN22 Czernice Borowe for calculations. We develop Meteor Identification Software (MIS) to detect meteor in series of images, estimate position and luminosity of the event. Our software is capable to analyse each sub-frame of interlaced images. Positions determined by MIS software have much smaller dispersion than estimated by MetRec. Koscierzyna Fireball have no chance to produce meteorite due to high entry speed and composition.

  15. Calibration of the reactor neutron spectrum for the ko-NAA standardization using several approaches

    NASA Astrophysics Data System (ADS)

    Kučera, J.; Frána, J.; Horák, Z.; Marek, M.; Tomášek, F.; Viereibl, L.

    1999-01-01

    The parameters f and α ( f-thermal/epithermal neutron fluence rate, α—a parameter accounting for the non-ideality of the 1/E epithermal neutron fluence rate distribution) were determined using the following approaches: “Cd-covered multi-monitor” and “Cd-ratio for multimonitor” methods, two versions of the “bare multi-monitor” method, and two neutron dosimetry approaches, namely two-group formalism and reactor spectrum unfolding using the SAND II computer code. It has been found that the determination of α values close to zero is associated with a relatively high uncertainty. On the other hand, it has been demonstrated that under these circumstances the uncertainty of α has only a little effect on the accuracy of results obtained by k0-NAA, especially for elements whose nuclides have a low resonance integral to thermal neutron cross section ratio.

  16. [GeKo KidS--Health Literacy in School Children].

    PubMed

    Splieth, C H; Franze, M; Plachta-Danielzik, S; Thyrian, J R; Schmidt, C O; John, U; Kohlmann, T; Müller, M J; Hoffmann, W

    2015-09-01

    The main goal of this study was the evaluation of an intervention programme for the promotion of health literacy in school-aged children (grade 5-6). The project and the programme were highly accepted, the extension of the annual dental health examination was suitable to collect data within evaluation projects in schools. In spite of positive outcomes, a longer supervision phase would be necessary in order to optimise and to implement other programme components fully. PMID:24671890

  17. Basilar Membrane Measurements from Wild Type, Prestin 499, and Prestin KO mice

    NASA Astrophysics Data System (ADS)

    Weddell, Thomas; Mellado-Lagarde, Marcia; Lukashkina, Victoria; Lukashkin, Andrei; Zuo, Jian; Russell, Ian

    2011-11-01

    It has been predicted that a nonfunctional prestin in the mammalian cochlea would produce a basilar membrane response at lower characteristic frequency, as we see in the prestin knock-out mouse, but with a reduced sensitivity that would reflect an enhanced coupling between basilar membrane and reticular lamina and inner hair cell stereocilia. We demonstrate here that this is the case in measurements from the 499 mouse where prestin in the lateral membrane of the outer hair cells is present but effectively silenced.

  18. Revisiting the deflection dilemma

    NASA Astrophysics Data System (ADS)

    Drmola, Jakub; Mareš, Miroslav

    2015-10-01

    As space becomes more commercial, argue Jakub Drmola and Miroslav Mare', developments such as asteroid mining will bring new risks. How can we maintain planetary security without restricting new industries?

  19. Tapawha, Key Competencies and Strength and Difficulties Questionnaire. From Idea to Application. "No te Whakaro ka mahia, He Tumomo Aromatawai Ko te Arotahi, Ko Nga Ahua Tapawha me nga Pukenga Matua"

    ERIC Educational Resources Information Center

    Gilmore, Gwen; Waru, Hohepa

    2012-01-01

    This paper discusses the use of a Strengths and Difficulties Questionnaire (SDQ) in the context of a Youth Justice Residential school setting in New Zealand (NZ). The school does not currently have a method of screening for educational purposes and, more specifically, key competencies. The use of the SDQ as a tool to support the educational…

  20. Outdoor artificial light at night, obesity, and sleep health: Cross-sectional analysis in the KoGES study.

    PubMed

    Koo, Yong Seo; Song, Jin-Young; Joo, Eun-Yeon; Lee, Heon-Jeong; Lee, Eunil; Lee, Sang-kun; Jung, Ki-Young

    2016-01-01

    Obesity is a common disorder with many complications. Although chronodisruption plays a role in obesity, few epidemiological studies have investigated the association between artificial light at night (ALAN) and obesity. Since sleep health is related to both obesity and ALAN, we investigated the association between outdoor ALAN and obesity after adjusting for sleep health. We also investigated the association between outdoor ALAN and sleep health. This cross-sectional survey included 8526 adults, 39-70 years of age, who participated in the Korean Genome and Epidemiology Study. Outdoor ALAN data were obtained from satellite images provided by the US Defense Meteorological Satellite Program. We obtained individual data regarding outdoor ALAN; body mass index; depression; and sleep health including sleep duration, mid-sleep time, and insomnia; and other demographic data including age, sex, educational level, type of residential building, monthly household income, alcohol consumption, smoking status and consumption of caffeine or alcohol before sleep. A logistic regression model was used to investigate the association between outdoor ALAN and obesity. The prevalence of obesity differed significantly according to sex (women 47% versus men 39%, p < 0.001) and outdoor ALAN (high 55% versus low 40%, p < 0.001). Univariate logistic regression analysis revealed a significant association between high outdoor ALAN and obesity (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.14-1.35, p < 0.001). Furthermore, multivariate logistic regression analyses showed that high outdoor ALAN was significantly associated with obesity after adjusting for age and sex (OR 1.25, 95% CI 1.14-1.37, p < 0.001) and even after controlling for various other confounding factors including age, sex, educational level, type of residential building, monthly household income, alcohol consumption, smoking, consumption of caffeine or alcohol before sleep, delayed sleep pattern, short sleep duration and habitual snoring (OR 1.20, 95% CI 1.06-1.36, p = 0.003). The findings of our study provide epidemiological evidence that outdoor ALAN is significantly related to obesity. PMID:26950542

  1. Neck Circumference and Incidence of Diabetes Mellitus over 10 Years in the Korean Genome and Epidemiology Study (KoGES)

    PubMed Central

    Cho, Nam H.; Oh, Tae Jung; Kim, Kyoung Min; Choi, Sung Hee; Lee, Jae Ho; Park, Kyong Soo; Jang, Hak Chul; Kim, Jong Yeol; Lee, Hong Kyu; Lim, Soo

    2015-01-01

    Neck circumference, a proxy for upper-body fat, may be a unique fat depot that indicates metabolic risk beyond whole body fat. We investigated whether neck circumference is associated with development of diabetes mellitus (DM) in a subset of data with Korean Genome and Epidemiology Study (n = 3521, age range = 42–71 years). Nondiabetic subjects at the baseline were categorized into 4 groups (Q1–Q4) according to their neck circumference. Parameters related with β-cell function and insulin resistance including Epworth sleepiness scale and snoring habit were examined. The development of DM was confirmed biannually based on a 75-g oral glucose tolerance test. Over the 10 years, 2623 (74.5%) among 3521 subjects were followed-up. Among them, 632 (24.1%) developed DM. The incidence of DM increased from 17.6% in Q1 to 18.2% in Q2, to 25.4% in Q3, and to 36.0% in Q4 (P < 0.001). After adjusting for most risk factors related with DM, the relative risks of DM development were 0.989 (95% confidence interval, 0.638–1.578), 1.660 (1.025–2.687), and 1.746 (1.037–2.942) in men and 0.939 (0.540–1.769), 1.518 (0.808–2.853), and 2.077 (1.068–4.038) in women in Q2, Q3, and Q4, respectively when compared to Q1. This finding indicates negative impact from large neck circumference in the development of DM. PMID:26681338

  2. Ko te reo te mauri o te mana Maori: The Language Is the Life Essence of Maori Existence.

    ERIC Educational Resources Information Center

    Robust, Te Tuhi

    This paper discusses the impact that recent educational reforms by the New Zealand government had on Maori individuals involved in community decision-making processes, focusing on one predominantly Maori rural community. Three strands of recent educational change in New Zealand are the move to self-managing institutions; ongoing debate over…

  3. Metal levels associated with tin dredging and smelting and their effect upon intertidal reef flats at ko phuket, Thailand

    NASA Astrophysics Data System (ADS)

    Brown, B. E.; Holley, M. C.

    1982-10-01

    Reef flats in the vicinity of tin dredging and smelting activities around the Laem Pan Wah peninsula, Phuket, and been quantitatively surveyed. the diversity of corals on all intertidal reefs was low (≏10 genera), the dominant genera being Porites, Montipora, Acropora and Platygyra. Two basic types of reef can be discerned, one dominated by Porites lutea and faviid species and the other by Montipora ramosa and Acropora aspera, reef type apparently being governed by the degree of exposure to water movement. Other natural factors affecting coral cover included freshwater run off, considerable sedimentation, and aerial exposure for 2 3 h each day. Heavy metal concentrations in invertebrate species such as the oyster Saccostrea, the bivalve Isognomon, and in the alga Padina reflected elevated metal levels at all sites when compared with controls (Figs. 8 and 9). In particular, levels of metals were considerably elevated in molluscs taken from the reef below the tin smelter. Interestingly, dead coral cover on this reef, although high, was not significantly different from values observed on reefs several kilometres away from the smelter, which were not apparently under the influence of such increased metal loads (Fig. 2). No elevation in metal concentrations in coral tissue or skeleton was evident at any site. It would appear, then, that these intertidal coral species are not obviously affected by the levels of metals discharged at the smelter site.

  4. Variable temperature EPR studies of Cu2+ and VO2+ doped potassium dihydrogen citrate (C6H7KO7)

    NASA Astrophysics Data System (ADS)

    Aygun, Zeynep

    2013-03-01

    Electron paramagnetic resonance (EPR) studies of single crystals and powder samples of Cu2+ and VO2+ doped potassium dihydrogen citrate (PDHC) have been carried out at different temperatures. The temperature-dependant g and A values have been obtained for powder spectra of both Cu2+ and VO2+ ions in PDHC and the ground state of Cu2+ ion has been determined. The powder spectra recorded for Cu2+ ion in the temperature range 70-298 K are discussed with Jahn-Teller distortion. It is concluded that the g and A values of Cu2+: PDHC show the static property at low temperatures. For all temperatures, the result g// < g⊥ < ge of VO2+: PDHC indicates that the unpaired electron exists in the dxy orbital.

  5. EPR and optical studies of vanadium doped potassium dihydrogen citrate (C 6H 7KO 7) single crystal

    NASA Astrophysics Data System (ADS)

    Yarbaşi, Zeynep; Karabulut, Abdulhalik; Karabulut, Bünyamin

    2011-09-01

    An EPR and optical studies of VO 2+ doped potassium dihydrogen citrate (PDHC) single crystals have been carried out at room temperature. It crystallizes in triclinic symmetry with the unit cell dimensions: a = 11.343 Å, b = 13.078 Å, c = 6.272 Å, α = 89.79°, β = 94.36°, γ = 104.2°. The angular variation of EPR spectra have shown that two different VO 2+ complexes are located in different chemical environments and each environment contains one magnetically VO 2+ site occupying substitutional position in the lattice and show very high angular dependence.

  6. Seismotectonic characteristics of the Krško Basin with relation to seismic safety of existing and planned nuclear infrastructure

    NASA Astrophysics Data System (ADS)

    Bavec, Miloš; Atanackov, Jure; Jamšek Rupnik, Petra

    2015-04-01

    The Kr\\vsko Basin hosts complex infrastructure and is being investigated as a potential site for several future projects including a new NPP and a low and intermediate level radioactive waste repository. A large database of geological, geophysical and geotechnical data has been accumulated, producing increasingly detailed tectonic and seismotectonic models of the Kr\\vsko Basin. The first tectonic and seismotectonic investigation campaign was undertaken in the 1970s for the first Kr\\vsko NPP (Arsovski et al., 1973). The next study (Fajfar et al., 1994) was followed by an extensive geophysical survey in in which basin axis-trending syncline was reevaluated (Persoglia, ed., 2000). In 2004 the geological, tectonic and seismotectonic characteristics of the Kr\\vsko Basin were readdressed by performing a periodic seismic hazard assessment for the NPP (Swan et al., 2004). After which, a series of field investigations were conducted for the potential radwaste repository site evaluation (Brenčič, ed., 2006; Petkovšek, ed., 2009). In 2008-2013 a set of geological, geotechnical and seismological investigations were performed for the proposed new NPP unit (Bazargan-Sabet et al., 2010). As part of this project the seismotectonic model and the seismic source model were updated (Bavec et al., 2010a,b). Particular attention was given to the Libna fault (Bavec et al., 2013), which was also the subject of a follow up study to further evaluate the age of deformed sediments in the basin (Cline et al., 2013). A new phase of geological, geophysical and geomorphic investigations is being undertaken in the Kr\\vsko basin by the team of Rizzo Associates and Geological Survey of Slovenia to refine on the geological and seismological inputs to the planned PSHA. The Basin has experienced moderate and dispersed seismic activity. The catalogue of known earthquakes in the region (ARSO, 2011) extends back to the early 17th century. The strongest earthquake in the Kr\\vsko basin was the January 29th 1917 Mw=5.7 Brežice (IMSK=VIII) (Živčič et al., 2010). In 2002 a seismic network was built that now consists of five stations within 15 km of the NPP (Vidrih, ed., 2006). The Kr\\vsko Basin generally coincides with the Kr\\vsko syncline stretching from the Novo Mesto district to the Hrvatsko Zagorje in Croatia. The stratigraphic succession consists of Mesozoic basement sedimentary rocks, overlain by mostly clastic Neogene sediments and covered by Plio-Quaternary and Quaternary terrestrial sediments, and very young fluvial deposits. There are indications for faulting in the Plio-Quaternary deposits while the Mid-Pleistocene terrace remnants are tilted towards the pre-Quaternary Kr\\vsko syncline axis in both limbs of the syncline, indicating post-Mid-Pleistocene folding (Swan et al., 2004). Late Pleistocene and Holocene surfaces are not tilted. The Kr\\vsko syncline is placed in the extension of the Mid-Hungarian zone. This zone borders with the Sava compressive wedge to the N (Placer, 1998) and the Dinaric tectonic zone to the W. The position of the syncline near the intersection of the three structural domains is resembled in its seismotectonic characteristics.

  7. Fatty liver index as a simple predictor of incident diabetes from the KoGES-ARIRANG study.

    PubMed

    Yadav, Dhananjay; Choi, Eunhee; Ahn, Song Vogue; Koh, Sang Baek; Sung, Ki-Chul; Kim, Jang-Young; Huh, Ji Hye

    2016-08-01

    The fatty liver index (FLI), calculated from serum triglyceride, body mass index, waist circumference, and gamma-glutamyltransferase, is considered a surrogate marker of nonalcoholic fatty liver disease (NAFLD). We investigated whether FLI predicts the development of diabetes mellitus (DM) and assessed the predictive ability of FLI for new onset of DM in a prospective population-based cohort study.We analyzed a total of 2784 adults (944 men and 1840 women) aged 40 to 70 years without DM at baseline. Participants were classified according to FLI values into 3 groups: FLI < 30, no NAFLD; 30 ≤ FLI ≤ 59, intermediate NAFLD; and FLI ≥ 60, participants with NAFLD. The area under the receiver-operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to determine whether FLI improved DM risk prediction.During a mean of 2.6 years follow-up, 88 (3.16%) participants developed DM. The odds ratio analyzed from multivariable-adjusted models (95% confidence interval [CI]) for new onset of DM increased in a continuous manner with increased FLI (<30 vs 30-59 vs ≥60 = 1 vs 1.87 [95% CI 1.05-3.33] vs 2.84 [95% CI 1.4-5.75], respectively). The AUC significantly increased when FLI was added to the conventional DM prediction model (0.835, 95% CI: 0.789-0.881, P = 0.0289 vs traditional DM prediction model). The category-free NRI was 0.417 (95% CI: 0.199-0.635) and the IDI was 0.015 (95% CI: 0.003-0.026) for overall study participants.We found that FLI, a surrogate marker of hepatic steatosis, resulted in significant improvement in DM risk prediction. Our finding suggests that FLI may have clinical and prognostic information for incident DM among the Korean adult population. PMID:27495073

  8. Fatty liver index as a simple predictor of incident diabetes from the KoGES-ARIRANG study

    PubMed Central

    Yadav, Dhananjay; Choi, Eunhee; Ahn, Song Vogue; Koh, Sang Baek; Sung, Ki-Chul; Kim, Jang-Young; Huh, Ji Hye

    2016-01-01

    Abstract The fatty liver index (FLI), calculated from serum triglyceride, body mass index, waist circumference, and gamma-glutamyltransferase, is considered a surrogate marker of nonalcoholic fatty liver disease (NAFLD). We investigated whether FLI predicts the development of diabetes mellitus (DM) and assessed the predictive ability of FLI for new onset of DM in a prospective population-based cohort study. We analyzed a total of 2784 adults (944 men and 1840 women) aged 40 to 70 years without DM at baseline. Participants were classified according to FLI values into 3 groups: FLI < 30, no NAFLD; 30 ≤ FLI ≤ 59, intermediate NAFLD; and FLI ≥ 60, participants with NAFLD. The area under the receiver-operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to determine whether FLI improved DM risk prediction. During a mean of 2.6 years follow-up, 88 (3.16%) participants developed DM. The odds ratio analyzed from multivariable-adjusted models (95% confidence interval [CI]) for new onset of DM increased in a continuous manner with increased FLI (<30 vs 30–59 vs ≥60 = 1 vs 1.87 [95% CI 1.05–3.33] vs 2.84 [95% CI 1.4–5.75], respectively). The AUC significantly increased when FLI was added to the conventional DM prediction model (0.835, 95% CI: 0.789–0.881, P = 0.0289 vs traditional DM prediction model). The category-free NRI was 0.417 (95% CI: 0.199–0.635) and the IDI was 0.015 (95% CI: 0.003–0.026) for overall study participants. We found that FLI, a surrogate marker of hepatic steatosis, resulted in significant improvement in DM risk prediction. Our finding suggests that FLI may have clinical and prognostic information for incident DM among the Korean adult population. PMID:27495073

  9. No-migration variance petition. Appendices K--O, Response to notice of deficiencies: Volume 6, Revision 1

    SciTech Connect

    Fischer, N.T.

    1990-03-01

    This document reports data collected as part of the Ecological Monitoring Program (EMP) at the Waste Isolation Pilot Plant near Carlsbad, New Mexico, for Calendar Year 1987. Also included are data from the last quarter (October through December) of 1986. This report divides data collection activities into two parts. Part A covers general environmental monitoring which includes meteorology, aerial photography, air quality monitoring, water quality monitoring, and wildlife population surveillance. Part B focuses on the special studies being performed to evaluate the impacts of salt dispersal from the site on the surrounding ecosystem. The fourth year of salt impact monitoring was completed in 1987. These studies involve the monitoring of soil chemistry, soil microbiota, and vegetation in permanent study plots. None of the findings indicate that the WIPP project is adversely impacting environmental quality at the site. As in 1986, breeding bird censuses completed this year indicate changes in the local bird fauna associated with the WIPP site. The decline in small mammal populations noted in the 1986 census is still evident in the 1987 data; however, populations are showing signs of recovery. There is no indication that this decline is related to WIPP activities. Rather, the evidence indicates that natural population fluctuations may be common in this ecosystem. The salt impact studies continue to reveal some short-range transport of salt dust from the saltpiles. This material accumulates at or near the soil surface during the dry seasons in areas near the saltpiles, but is flushed deeper into the soil during the rainy season. Microbial activity does not appear to be affected by this salt importation. Vegetation coverage and density data from 1987 also do not show any detrimental effect associated with aerial dispersal of salt.

  10. Stress and its Expression According to Contemporary Science and Ancient Indian Wisdom: Perseverative Cognition and the Pañca kośas

    PubMed Central

    Rajesh, Sasidharan K.; Ilavarasu, Judu V.; Srinivasan, T. M.; Nagendra, H. R.

    2014-01-01

    Stress is recognised as the most challenging issue of modern times. Contemporary science has understood this phenomenon from one aspect and Indian philosophy gives its traditional reasons based on classical texts. Modern science has recently proposed a concept of perseverative cognition (PC) as an important reason for chronic stress. This has shown how constant rumination on an unpalatable event, object or person leads to various lifestyle disorders. Similarly classical yoga texts like the Taittiriya Upanishad, the Bhagavad Gita, and the Yoga Vashistha describe stress in their unique ways. We have here attempted a detailed classification, description, manifestation, and development of a disease and its management through these models. This paper in a nutshell projects these two models of stress and shows how they could be used in future for harmonious management of lifestyle disorders. PMID:24891803

  11. Associations of dietary intake and metabolic syndrome risk parameters in Vietnamese female marriage immigrants in South Korea: The KoGES follow-up study

    PubMed Central

    Yang, Hyesu; Kim, Hyesook; Kim, Ji-Myung; Chung, Hye Won

    2016-01-01

    BACKGROUND/OBJECTIVES This study was conducted to compare the overall changes in dietary intake and metabolic syndrome risk parameters in Vietnamese marriage-based female immigrants over time. SUBJECTS/METHODS The subjects of this study were 581 Vietnamese marriage-based female immigrants, who were recruited from local clinical centers in Korea. Baseline data were collected from 2006-2011 and the follow-up data were collected from 2012-2014. Dietary food intake was assessed by a 1-day 24-hour recall method. RESULTS Compared to the baseline, the mean body weight, body mass index, waist circumference, high density lipoprotein (HDL)-cholesterol, systolic blood pressure and diastolic blood pressure increased while the fasting blood sugar, triglycerides and low density lipoprotein-cholesterol decreased at follow-up. The total consumption of foods such as vegetables/fruits/seaweeds/mushrooms, oil and fat, and eggs decreased during the follow-up period, whereas the consumption of sugars, beverages and meats increased. Partial correlation between the rate of change [(Follow-up - Baseline) / Baseline × 100] in metabolic syndrome risk parameters and food intake after controlling for confounding factors showed that the waist circumference was positively correlated with either the total plant food intake (r = 0.1042, P = 0.0129) or the total food intake (r = 0.0880, P = 0.0359). The plasma levels of total cholesterol (r = -0.1918, P = 0.0289) and HDL-cholesterol (r = -0.1424, P = 0.0007) were negatively correlated with the percentage of total intake from plant food, and HDL-cholesterol levels were positively correlated with the intake of total animal food (r = 0.0980, P = 0.0217). The serum C-reactive protein levels were positively correlated with the total intake of animal food (r = 0.2374, P < 0.0001) or the percentage of total intake from animal food (r = 0.1346, P = 0.0016). CONCLUSIONS These results suggest that the change rate of dietary intake such as total plant food or animal food is associated with the change rates of metabolic syndrome risk parameters. PMID:27247728

  12. Editorial for Issue 1, Jan 2016 title of the editorial 2016 : A year for JCCS Editorial changes and CCN3 KO mice at ICCNS.

    PubMed

    Perbal, Bernard

    2016-03-01

    The year 2016 will see significant improvements for the Journal of Cell Communication and Signaling with the earning of an official Impact Factor and the merger of Springer Science + Business Media and part of Macmillan Sciences and Education. It will also be an important year for the International CCN Society (ICCNS) with the nomination of a new Scientific Board and reinforcement of interactions with other major scientific societies interested in various aspects of Cell Signaling. Starting this year the ICCNS will become an official provider of CCN3 knock out mice to ICCNS members. This first step in opening up access to certified reagents as a service for our CCN scientific community is part of our intention and efforts to attain the highest degree of assistance and enabler of scientific cooperation and communication in Science Communication. PMID:26907872

  13. Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice

    PubMed Central

    Bortolussi, G; Codarin, E; Antoniali, G; Vascotto, C; Vodret, S; Arena, S; Cesaratto, L; Scaloni, A; Tell, G; Muro, A F

    2015-01-01

    Severe hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced encephalopathy and eventually death by kernicterus. Despite extensive studies, the molecular and cellular mechanisms of bilirubin toxicity are still poorly defined. To fill this gap, we investigated the molecular processes underlying neuronal injury in a mouse model of severe neonatal jaundice, which develops hyperbilirubinemia as a consequence of a null mutation in the Ugt1 gene. These mutant mice show cerebellar abnormalities and hypoplasia, neuronal cell death and die shortly after birth because of bilirubin neurotoxicity. To identify protein changes associated with bilirubin-induced cell death, we performed proteomic analysis of cerebella from Ugt1 mutant and wild-type mice. Proteomic data pointed-out to oxidoreductase activities or antioxidant processes as important intracellular mechanisms altered during bilirubin-induced neurotoxicity. In particular, they revealed that down-representation of DJ-1, superoxide dismutase, peroxiredoxins 2 and 6 was associated with hyperbilirubinemia in the cerebellum of mutant mice. Interestingly, the reduction in protein levels seems to result from post-translational mechanisms because we did not detect significant quantitative differences in the corresponding mRNAs. We also observed an increase in neuro-specific enolase 2 both in the cerebellum and in the serum of mutant mice, supporting its potential use as a biomarker of bilirubin-induced neurological damage. In conclusion, our data show that different protective mechanisms fail to contrast oxidative burst in bilirubin-affected brain regions, ultimately leading to neurodegeneration. PMID:25950469

  14. Fontinalis antipyretica as a bioindicator of environmental conditions in freshwater ecosystem from Sava River watershed and Cerknişko Lake, Slovenia

    NASA Astrophysics Data System (ADS)

    Kanduč, Tjaša; Mechora, Špela; Stibilj, Vekoslava

    2014-05-01

    Polluted waters recharging from agriculture water systems into watersheds have influence on water quality and living habitat. Stable isotopes of carbon and nitrogen in combination with other minor and trace elements are often used to trace biogeochemical processes and contamination of water systems. The aim of the study was to assess state of environment with minor and trace elements and stable isotopes of C and N in selected Slovenian streams. Ten locations in Notranjska region, Slovenia, with different land use in the catchment (town, village, agricultural areas, farms, dairy farms), including reference point considered as non-polluted site, were sampled. Samples of water and aquatic moss F. antipyretica in Slovenian fresh waters were taken in all four seasons during years 2010 and 2012, but for stable isotope analyses of C and N only in three seasons during years 2010 and 2011. The water chemistry of investigated locations is dominated by hydrogen carbonate - calcium - magnesium, concentrations of nitrate seasonally range from 2.07 mg/l to 6.4 mg/l and at reference site does not exceed 1.3 mg/l. Total alkalinity of water at investigated locations ranges from 2.9 to 6.02 mM. The pH of investigated water range from 7.2 to 8.5, waters are saturated with oxygen (up to 134%) and conductivity ranges from 295 to 525 mikroS/cm, while at reference site conductivity is up to 180 mikroS/cm. The content of minor and trace elements in F. antipyretica ranged for Ni 4-38 mikrog/g, Zn 17-105 mikrog/g, Pb 2-28 mikrog/g, Cd 220-1953 ng/g, Cu 4-27 mikrog/g, Cr 4-49 mikrog/g, As 1-6 mikrog/g and Se 0.33-3.24 mikrog/g. The most polluted watershed was Pšata stream (agricultural areas, cattle farm) with highest values for Ni, Cr, Pb, Zn and As. The highest content of Se, was found in village (dairy farms) in Žerovniščica stream. The highest values were measured in February and October. Isotopic composition of dissolved inorganic carbon seasonally range from -13.3 to -8.1‰, and indicate waters dominated by degradation of organic matter and dissolution of carbonates. At the reference point average measured isotopic composition of dissolved inorganic carbon value is -2.7‰ which confirmed that this is a non-polluted site. Isotopic composition of carbon of F. antipyretica seasonally ranges from -45 to -32.9‰ and isotopic composition of nitrogen from -0.2‰ to 6.5‰, respectively. In comparison to C3 terrestrial plants F. antipyretica has more negative isotopic composition of carbon value, which is probably related with the difference in CO2 plant fixation and depends on isotopic composition of dissolved inorganic carbon in water, which is primarily controlled by geological composition and soil thickness in the watershed. Higher isotopic composition of nitrogen value found in F. antipyretica is related to agricultural activity in watershed, while at the reference site measured isotopic composition of nitrogen value is -4.1 ‰. From our study it is evident that isotopic composition of carbon and nitrogen is useful tracer of natural and anthropogenic inputs from terrestrial (fertilizing, sewage sludge) to water system.

  15. Development and evaluation of a food frequency questionnaire for Vietnamese female immigrants in Korea: the Korean Genome and Epidemiology Study (KoGES)

    PubMed Central

    Kim, Sun Hye; Choi, Ha Ney; Hwang, Ji-Yun; Chang, Namsoo; Kim, Wha Young; Chung, Hye Won

    2011-01-01

    The objectives of this study were to develop a food-frequency questionnaire (FFQ) for Vietnamese female immigrants in Korea and to evaluate the validity of the FFQ. A total of 80 food items were selected in developing the FFQ according to consumption frequency, the contribution of energy and other nutrients, and the cooking methods based on one-day 24 hour recall (24HR) from 918 Vietnamese female immigrants between November 2006 and November 2007. The FFQ was validated by comparison with 24HR of 425 Vietnamese female immigrants between November 2008 and August 2009. The absolute nutrient intake calculated from the FFQ was higher than that estimated by 24HR for most nutrients. The correlation coefficients between 24HR and FFQ ranged from 0.10 (vitamin C) - 0.36 (energy) for crude intake, 0.05 (vitamin E) - 0.32 (calcium) for per 1000 kcal, and 0.08 (zinc) - 0.34 (calcium) for energy-adjusted, respectively. More than 70% of subjects were classified into the same or adjacent agreement groups for nutrients other than fiber, sodium, vitamin A, vitamin C, and vitamin E, while less than 10% of subjects were classified into complete disagreement groups. We conclude that the FFQ appears to be an acceptable tool for estimating nutrient intake and dietary patterns of Vietnamese female immigrants in Korea. Future studies to validate the FFQ using various biomarkers or other dietary assessment methods are needed. PMID:21779531

  16. Rice-eating pattern and the risk of metabolic syndrome especially waist circumference in Korean Genome and Epidemiology Study (KoGES)

    PubMed Central

    2013-01-01

    Background Metabolic syndrome poses a serious health threat in Asian countries. Rice is a staple food in Korea, and carbohydrate intake is associated with the risk of MetS. We hypothesized that various rice-eating patterns in a carbohydrate-based diet would have different effects on the risk of MetS. Methods Participants were 26,006 subjects enrolled in the Korean Genome and Epidemiology Study between 2004 and 2006. They were classified into four dietary patterns - white rice, rice with beans, rice with multi-grains, and mixed based on their food frequency questionnaire responses. We compared metabolic risk traits according to the rice-eating patterns. Results Nutrients consumption and the presence of MetS risk factors differed according to rice-eating patterns. In men odds ratio(OR) for central obesity was slightly elevated in mixed group(1.18). In women, the risk for central obesity and abnormal fasting glucose were lower in the rice with beans group (adjusted OR =0.79, 0.83 respectively) and central obesity in rice with multi-grains(adjusted OR=0.91) than the white rice group. In postmenopausal women, ORs for central obesity (0.78) and abnormal fasting glucose (0.75) in the rice with beans group and ORs for central obesity (0.83), abnormal HDL-cholesterol (0.87) and MetS(0.85) in the rice with multi-grains group was lower than those in white rice group. In premenopausal women, the risk for central obesity (OR=0.77) was reduced in the rice with beans group. Conclusion The risk for MetS was lower in the rice with beans and rice with multi-grains groups compared with the white rice group, particularly in postmenopausal women. PMID:23339671

  17. Modernization Of Public Space Floor And Its Impact On Area - The Example Of The Kościuszko Square In Białystok

    NASA Astrophysics Data System (ADS)

    Tofiluk, Anna

    2015-12-01

    The last 25 years have been in many Polish cities a period of intensive modernization and renewals of the existing public spaces. Most of all the resurfacing of the pavement and changing of street furniture have been held. In many cases, the transformations in the urban areas were integrated with exclusion from traffic. The question arises what criteria architects or landscape architects follow and what design solutions apply. It is also interesting how the new shape of the floor in public spaces (understood here as a pavement and street furniture together) can help to create integrating and activating space for residents. And how it can affect the quality of life in a wider area. This article attempts to answer these questions based on new solutions on Kosciuszko Square in Białystok, executed in 2005-2009.

  18. Behavior of the Hawaiian Hawaiian Hoary Bat (Lasiurus cinereus semotus ) at wind turbines and its distribution across the North Ko`olau Mountains , O`ahu

    USGS Publications Warehouse

    Bonaccorso, Frank; Gorresen, P.M.; Cryan, Paul M.; Huso, Manuela M.P.; Hein, Cris D.; Schirmacher, Michael; Johnson, Jessica H.; Montoya-Aiona, Kristina; Brinck, Kevin W.

    2015-01-01

    We studied the landscape distribution of endemic Hawaiian hoary bats (Lasiurus cinereus semotus) on the north Ko‘olau Mountains of O‘ahu, Hawai‘i, from May 2013 to May 2014, while simultaneously studying their behavior at wind turbines within the broader landscape. This research aimed to assess the risk that wind turbines pose to bats on the island and integrated a variety of methods, including acoustic monitoring, thermal videography, and fatality searches. Our findings indicate that hoary bats were acoustically cryptic and occurred sparsely in the region. Overall site occupancy rate was 55% during the 1-year period of acoustic monitoring at 23 sites, and there was only an 8% chance of acoustically detecting a bat on a given night if it was present. We detected bats less frequently in windward northern parts of the study area and at windy, lower-elevation sites with rough terrain. Bats were detected more frequently in leeward southern parts of the study area and at wind-sheltered, higher-elevation sites with flat ridgetops. Acoustic detections were consistently low from October through February and increased at most sites to peak in April through August. However, meteorological conditions were not found to be associated with the acoustic prevalence of bats on a night-to-night basis.We observed more than three thousand events involving bats during six months of nightly video surveillance at four wind turbines. Video monitoring revealed several links to weather at the local scale, despite acoustic detections not clearly relating to weather in our broader landscape analysis. Video demonstrated bats occurring near turbines more often on nights with little rain, warmer temperatures, moderate wind speeds, low humidity, and the low but rising barometric pressures indicative of fair weather and improved foraging conditions. Video monitoring also demonstrated that the presence of bats near turbines strongly correlates with insect presence. We detected bats on video rather infrequently, averaging only one to two passes per hour. Most detections were brief (median = 4.0 sec) and involved single bats (97%), with the amount of time during which bats were observed totaling to only 0.10% of the video analyzed (about 3.8 hours of 3,847 total hours). Bats frequently foraged in the airspace near turbines. These results differ from a recent similar study on the mainland (continental North America) and may indicate that Hawaiian hoary bats spend less time closely approaching wind turbines and show less interest in them than their more-migratory mainland conspecifics. We speculate that the Hawaiian hoary bats we observed were locally resident and frequenting high-quality habitat near familiar structures. In contrast, hoary bats observed at wind facilities on the mainland appear to approach and investigate unfamiliar landscape structures that they mistake for trees as they migrate long distances. Consequently, Hawaiian hoary bats may be less susceptible to fatality at wind turbines on a per-encounter basis than hoary bats in North America. Only one bat carcass was found at the four turbines searched daily for six months. The relatively high probability of finding carcasses provided strong assurance that few carcasses were likely missed — there was less than a 10% chance that total fatality at the four turbines monitored for half a year exceeded three bats.

  19. Methyl-Arginine Profile of Brain from Aged PINK1-KO+A53T-SNCA Mice Suggests Altered Mitochondrial Biogenesis

    PubMed Central

    Auburger, Georg; Gispert, Suzana

    2016-01-01

    Hereditary Parkinson's disease can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) or the autosomal recessive deficiency of PINK1. We recently showed that the combination of PINK1-knockout with overexpression of A53T-SNCA in double mutant (DM) mice potentiates phenotypes and reduces survival. Now we studied brain hemispheres of DM mice at age of 18 months in a hypothesis-free approach, employing a quantitative label-free global proteomic mass spectrometry scan of posttranslational modifications focusing on methyl-arginine. The strongest effects were documented for the adhesion modulator CMAS, the mRNA decapping/deadenylation factor PATL1, and the synaptic plasticity mediator CRTC1/TORC1. In addition, an intriguing effect was observed for the splicing factor PSF/SFPQ, known to interact with the dopaminergic differentiation factor NURR1 as well as with DJ-1, the protein responsible for the autosomal recessive PARK7 variant of PD. CRTC1, PSF, and DJ-1 are modulators of PGC1alpha and of mitochondrial biogenesis. This pathway was further stressed by dysregulations of oxygen sensor EGLN3 and of nuclear TMPO. PSF and TMPO cooperate with dopaminergic differentiation factors LMX1B and NURR1. Further dysregulations concerned PRR18, TRIO, HNRNPA1, DMWD, WAVE1, ILDR2, DBNDD1, and NFM. Thus, we report selective novel endogenous stress responses in brain, which highlight early dysregulations of mitochondrial homeostasis and midbrain vulnerability. PMID:27034888

  20. CD36/SR-B2-TLR2 Dependent Pathways Enhance Porphyromonas gingivalis Mediated Atherosclerosis in the Ldlr KO Mouse Model

    PubMed Central

    Brown, Paul M.; Kennedy, David J.; Morton, Richard E.; Febbraio, Maria

    2015-01-01

    There is strong epidemiological association between periodontal disease and cardiovascular disease but underlying mechanisms remain ill-defined. Because the human periodontal disease pathogen, Porphyromonas gingivalis (Pg), interacts with innate immune receptors Toll-like Receptor (TLR) 2 and CD36/scavenger receptor-B2 (SR-B2), we studied how CD36/SR-B2 and TLR pathways promote Pg-mediated atherosclerosis. Western diet fed low density lipoprotein receptor knockout (Ldlr°) mice infected orally with Pg had a significant increase in lesion burden compared with uninfected controls. This increase was entirely CD36/SR-B2-dependent, as there was no significant change in lesion burden between infected and uninfected Ldlr° mice. Western diet feeding promoted enhanced CD36/SR-B2-dependent IL1β generation and foam cell formation as a result of Pg lipopolysaccharide (PgLPS) exposure. CD36/SR-B2 and TLR2 were necessary for inflammasome activation and optimal IL1ß generation, but also resulted in LPS induced lethality (pyroptosis). Modified forms of LDL inhibited Pg-mediated IL1ß generation in a CD36/SR-B2-dependent manner and prevented pyroptosis, but promoted foam cell formation. Our data show that Pg infection in the oral cavity can lead to significant TLR2-CD36/SR-B2 dependent IL1ß release. In the vessel wall, macrophages encountering systemic release of IL1ß, PgLPS and modified LDL have increased lipid uptake, foam cell formation, and release of IL1ß, but because pyroptosis is inhibited, this enables macrophage survival and promotes increased plaque development. These studies may explain increased lesion burden as a result of periodontal disease, and suggest strategies for development of therapeutics. PMID:25938460

  1. Adeno-associated virus serotype 8 ApoA-I gene transfer reduces progression of atherosclerosis in ApoE-KO mice: comparison of intramuscular and intravenous administration.

    PubMed

    Cimmino, Giovanni; Giannarelli, Chiara; Chen, Wei; Alique, Matilde; Santos-Gallego, Carlos G; Fuster, Valentin; Hajjar, Roger J; Walsh, Christopher E; Badimon, Juan J

    2011-03-01

    Apolipoprotein A-I (ApoA-I)/high-density lipoprotein (HDL)-raising treatments are effective antiatherosclerotic strategies. We have compared the antiatherogenic effects of human ApoA-I (hApoA-I) overexpression by intraportal and intramuscular gene transfer in atherosclerotic ApoE-knockout mice. Atherosclerotic lesions were induced by atherogenic diet. After atherosclerosis induction, a group of animals was killed and served as atherosclerosis baseline-control group. The remaining animals were randomized into the following groups: (1) atherosclerosis-progression-control, (2) intraportal/vector administration, and (3) intramuscular/vector administration. Aortas and hearts were processed for atherosclerotic quantification by en face Sudan IV and Oil Red-O, respectively. Liver and muscle specimens were processed for protein/gene expression analysis. A sustained increase in hApoA-I/HDL plasma levels was observed in both transduced groups. hApoA-I overexpression abolished plaque progression versus progression-control group. hApoA-I overexpression significantly reduced lesion macrophage, feature indicative of plaque stabilization. Scavenger receptor class-B type I (SR-BI), but not ATP-binding cassette, sub-family A (ABCA), member 1 (ABCA-1), was significantly upregulated in treated groups versus progression-controls. The results of this study show a similar effect of hApoA-I/HDL overexpression on plaque progression/stabilization by 2 different routes of administration. Our results showing similar effects using either intramuscular administration and intraportal route of administration may have significant clinical implications, given the reduced medical risk to patient and cost of intramuscular injections. PMID:21164355

  2. Dietary factors related to body weight in adult Vietnamese in the rural area of Haiphong, Vietnam: the Korean Genome and Epidemiology Study (KoGES)

    PubMed Central

    Kim, Sun Hye; Hwang, Ji-Yun; Kim, Mi Kyung; Chung, Hye Won; Nguyet, Tran Thi Phuc

    2010-01-01

    The objectives of this study were to examine the association between dietary factors and underweight and overweight adult Vietnamese living in the rural areas of Vietnam. A cross-sectional study of 497 Vietnamese aged 19 to 60 years (204 males, 293 females) was conducted in rural areas of Haiphong, Vietnam. The subjects were classified as underweight, normal weight, and overweight based on BMI. General characteristics, anthropometric parameters, blood profiles, and eating habits were obtained and dietary intake was assessed using 24-hour recalls for 2 consecutive days. A high prevalence of both underweight (BMI < 18.5 kg/m2) and overweight (BMI ≥ 23 kg/m2) individuals was observed (14.2% and 21.6% for males and 18.9% and 20.6% for females, respectively). For both genders, the overweight group were older than the under- and normal weight groups (P = 0.0118 for males and P = 0.0002 for females). In female subjects, the overweight group consumed significantly less cereals (P = 0.0033), energy (P = 0.0046), protein (P = 0.0222), and carbohydrate (P = 0.0017) and more fruits (P = 0.0026) than the underweight group; however, no such differences existed in males. The overweight subjects overate more frequently (P = 0.0295) and consumed fish (P = 0.0096) and fruits (P = 0.0083) more often. The prevalence of both underweight and overweight individuals pose serious public health problems in the rural areas of Vietnamese and the overweight group was related to overeating and high fish and fruit consumption. These findings may provide basic data for policymakers and dieticians in order to develop future nutrition and health programs for rural populations in Vietnam. PMID:20607070

  3. CD36/SR-B2-TLR2 Dependent Pathways Enhance Porphyromonas gingivalis Mediated Atherosclerosis in the Ldlr KO Mouse Model.

    PubMed

    Brown, Paul M; Kennedy, David J; Morton, Richard E; Febbraio, Maria

    2015-01-01

    There is strong epidemiological association between periodontal disease and cardiovascular disease but underlying mechanisms remain ill-defined. Because the human periodontal disease pathogen, Porphyromonas gingivalis (Pg), interacts with innate immune receptors Toll-like Receptor (TLR) 2 and CD36/scavenger receptor-B2 (SR-B2), we studied how CD36/SR-B2 and TLR pathways promote Pg-mediated atherosclerosis. Western diet fed low density lipoprotein receptor knockout (Ldlr°) mice infected orally with Pg had a significant increase in lesion burden compared with uninfected controls.This increase was entirely CD36/SR-B2-dependent, as there was no significant change in lesion burden between infected and uninfected Cd36o/Ldlro mice [corrected]. Western diet feeding promoted enhanced CD36/SR-B2-dependent IL1β generation and foam cell formation as a result of Pg lipopolysaccharide (PgLPS) exposure. CD36/SR-B2 and TLR2 were necessary for inflammasome activation and optimal IL1ß generation, but also resulted in LPS induced lethality (pyroptosis). Modified forms of LDL inhibited Pg-mediated IL1ß generation in a CD36/SR-B2-dependent manner and prevented pyroptosis, but promoted foam cell formation. Our data show that Pg infection in the oral cavity can lead to significant TLR2-CD36/SR-B2 dependent IL1ß release. In the vessel wall, macrophages encountering systemic release of IL1ß, PgLPS and modified LDL have increased lipid uptake, foam cell formation, and release of IL1ß, but because pyroptosis is inhibited, this enables macrophage survival and promotes increased plaque development. These studies may explain increased lesion burden as a result of periodontal disease, and suggest strategies for development of therapeutics. PMID:25938460

  4. Evaluation of Wheel Loaders in Open Pit Marble Quarrying by Using the AHP and Topsis Approaches / Ocena pracy ładowarki na podwoziu kołowym w odkrywkowej kopalni marmuru w oparciu o metody AHP i topsis

    NASA Astrophysics Data System (ADS)

    Kun, Mete; Topaloǧlu, Şeyda; Malli, Tahir

    2013-03-01

    The marble mining in Turkey has been rising since the early 80's. In relation to that, the marble income has become noticeably bigger than those of other mining sectors. In recent years, marble and natural stone export composes half of the total mine export with a value of two billion dollars. This rapid development observed in marble operation has increased the importance of mining economics, income-expenditure balance and cost analysis. The most important cost elements observed in marble quarrying are machinery and equipment, labor costs and geological structures of the field. The aim of this study is to is to propose a multi-criteria decision making (MCDM) approach to evaluate the wheel loader alternatives and select the best loader under multiple criteria. A two-step methodology based on two MCDM methods, which are namely the Analytic Hierarchy Process (AHP) and the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS), are used in the evaluation procedure. More precisely, AHP is applied to determine the relative weights of evaluation criteria and TOPSIS is applied to rank the wheel loader alternatives. The proposed approach also provides a relatively simple and very well suited decision making tool for this type of decision making problems.

  5. COMPARISON OF OVERALL METABOLISM OF 1,2,3,7,8-PENTACHLORODIBENZO-P-DIOXIN (PECDD) IN CYP1A2(-L-)KNOCKOUT (KO) AND C57BL/6N PARENTAL STRAINS OF MICE

    EPA Science Inventory

    Assessment of immune responses to Penicillium chrysogenum and characterization of its allergens

    Yongjoo Chung1, Michael E Viana2, Lisa B Copeland3, and MaryJane K Selgrade3, Marsha D W Ward3. 1 UNC, SPH, Chapel Hill, NC, 2NCSU, CVM, Raleigh, NC, 3US EPA, ORD, NHEERL, RTP,...

  6. Electronic structure investigation of the room temperature coadsorption of oxygen and potassium on Ni(100): from oxygen submonolayer coverage to saturated NiO/Ni(100) via an Ni(100)-(3×3)-(K+O) structure.

    NASA Astrophysics Data System (ADS)

    Finetti, P.; Scantlebury, M. J.; McGrath, R.; Borgatti, F.; Sambi, M.; Zaratin, L.; Granozzi, G.

    2000-08-01

    We have investigated the room temperature potassium-promoted oxidation of Ni(100) by means of O 1s and K 2p X-ray photoemission spectroscopy (XPS), relative work function and O 1s X-ray absorption spectroscopy (XAS) measurements. Within the potassium coverage range we examine in this study ( θK=0.10-0.25 ML), coadsorption of about 0.5 ML of oxygen results in the formation of a (3×3) pattern which is peculiar to the coadsorption of alkalis and oxygen on Ni(100). This structure is stable against further oxygen uptake or against adsorption of other species such as CO. However, by means of O 1s XPS and XAS observations we determine an overall potassium-enhanced oxidation rate of about two orders of magnitude. The O 1s XPS data show that oxygen coadsorbed with K on Ni(100) is still bonded primarily to Ni and thus rule out the formation of potassium oxide or other K xO y compounds such as peroxide or superoxide. The line-shape analysis of the K 2p XPS data show that upon oxygen coadsorption the alkali metal layer undergoes a metal-insulator type of transition. The O 1s XPS data rule out the possibility that this transition is due to a large charge transfer between coadsorbed species so other mechanisms are discussed. The work function changes induced by O on the K-precovered surface are consistent with the formation of a bilayered structure in which oxygen is adsorbed underneath the alkali metal layer at K coverages above the work function minimum. However, we find that the alkali-induced minimum of the work function is not related to the occurrence of structural properties, in particular the formation of the (3×3) structure, or electronic properties such as the metal-insulator transition of the K layer. Therefore a coplanar alkali-oxygen coadsorption model cannot be ruled out. The O 1s XAS data show that the presence of potassium on Ni(100) lowers the O coverage for the onset of the formation of cubic NiO.

  7. Environmental assessment of freshwater ecosystems of the Sava River watershed and Cerkniško Lake, Slovenia, using the bioindicator species Fontinalis antipyretica: insights from stable isotopes and selected elements.

    PubMed

    Mechora, Špela; Kanduč, Tjaša

    2016-06-01

    Ten locations in the Notranjska region, Slovenia, with different land use in the catchment (town, village and agricultural areas), including reference points with different geological composition considered as unpolluted sites, were sampled for water and aquatic moss to evaluate environmental assessment in fresh water systems of the Sava River watershed. Samples of fresh water and Fontinalis antipyretica were taken in all four seasons during the years 2010 and 2012. The water chemistry of the investigated locations was dominated by [Formula: see text], while concentrations of [Formula: see text] seasonally ranged from 2.1 to 6.4 mg L(-1) and at one of the reference sites did not exceed 1.3 mg L(-1). δ(13)CDIC values seasonally ranged from -13.3 to -8.1 ‰ and indicated waters dominated by degradation of organic matter and dissolution of carbonates. δ(13)Cplant values of F. antipyretica seasonally ranged from -45 to -32.9 ‰ and of δ(15)Nplant from -0.2 to 6.5 ‰. The higher δ(15)N value of 6.5 ‰ found in F. antipyretica was related to agricultural activity in the watershed. The content of minor and trace elements in F. antipyretica ranged from 4-38 µg g(-1) for Ni, 17-105 µg g(-1) for Zn, 2-28 µg g(-1) for Pb, 0.26-1.95 µg g(-1) for Cd, 4-27 µg g(-1) for Cu, 4-49 µg g(-1) for Cr, 1-6 µg g(-1) for As and 0.33-3.24 µg g(-1) for Se. The most polluted watershed was the Pšata stream (agricultural area, cattle farm with the highest concentration of nitrate in water) also with highest values for Ni, Cr, Pb, Zn and As. PMID:26758230

  8. Genetic diversity of koala retroviral envelopes.

    PubMed

    Xu, Wenqin; Gorman, Kristen; Santiago, Jan Clement; Kluska, Kristen; Eiden, Maribeth V

    2015-03-01

    Genetic diversity, attributable to the low fidelity of reverse transcription, recombination and mutation, is an important feature of infectious retroviruses. Under selective pressure, such as that imposed by superinfection interference, gammaretroviruses commonly adapt their envelope proteins to use alternative receptors to overcome this entry block. The first characterized koala retroviruses KoRV subgroup A (KoRV-A) were remarkable in their absence of envelope genetic variability. Once it was determined that KoRV-A was present in all koalas in US zoos, regardless of their disease status, we sought to isolate a KoRV variant whose presence correlated with neoplastic malignancies. More than a decade after the identification of KoRV-A, we isolated a second subgroup of KoRV, KoRV-B from koalas with lymphomas. The envelope proteins of KoRV-A and KoRV-B are sufficiently divergent to confer the ability to bind and employ distinct receptors for infection. We have now obtained a number of additional KoRV envelope variants. In the present studies we report these variants, and show that they differ from KoRV-A and KoRV-B envelopes in their host range and superinfection interference properties. Thus, there appears to be considerable variation among KoRVs envelope genes suggesting genetic diversity is a factor following the KoRV-A infection process. PMID:25789509

  9. Construction and Characterization of an Infectious Molecular Clone of Koala Retrovirus

    PubMed Central

    Shojima, Takayuki; Hoshino, Shigeki; Abe, Masumi; Yasuda, Jiro; Shogen, Hiroko; Kobayashi, Takeshi

    2013-01-01

    Koala retrovirus (KoRV) is a gammaretrovirus that is currently endogenizing into koalas. Studies on KoRV infection have been hampered by the lack of a replication-competent molecular clone. In this study, we constructed an infectious molecular clone, termed plasmid pKoRV522, of a KoRV isolate (strain Aki) from a koala reared in a Japanese zoo. The virus KoRV522, derived from pKoRV522, grew efficiently in human embryonic kidney (HEK293T) cells, attaining 106 focus-forming units/ml. Several mutations in the Gag (L domain) and Env regions reported to be involved in reduction in viral infection/production in vitro are found in pKoRV522, yet KoRV522 replicated well, suggesting that any effects of these mutations are limited. Indeed, a reporter virus pseudotyped with pKoRV522 Env was found to infect human, feline, and mink cell lines efficiently. Analyses of KoRV L-domain mutants showed that an additional PPXY sequence, PPPY, in Gag plays a critical role in KoRV budding. Altogether, our results demonstrate the construction and characterization of the first infectious molecular clone of KoRV. The infectious clone reported here will be useful for elucidating the mechanism of endogenization of the virus in koalas and screening for antiretroviral drugs for KoRV-infected koalas. PMID:23427161

  10. 77 FR 76491 - Findings of Research Misconduct

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-28

    ... histomorphometric and microCT results by using the values of HS1 knockout (KO) mice and their controls to represent the CathepsinK cre- Cortactin KO mice and their controls; Dr. Biosse-Duplan also switched two sets of numbers between the HS1 KO mice and their controls to ] falsely demonstrate a difference in bone...

  11. Narp knockout mice show normal reactivity to novelty but attenuated recovery from neophobia.

    PubMed

    Blouin, Ashley M; Lee, Jongah J; Tao, Bo; Smith, Dani R; Johnson, Alexander W; Baraban, Jay M; Reti, Irving M

    2013-11-15

    Narp knockout (KO) mice demonstrate cognitive inflexibility and addictive behavior, which are associated with abnormal reactivity to a novel stimulus. To assess reactivity to novelty, we tested Narp KO and wild-type (WT) mice on a neophobia procedure. Both Narp KO and WT mice showed a similar decrease in consumption upon initial exposure to a novel flavor, but Narp KO mice did not increase consumption with subsequent exposures to the novel flavor like the WT mice. Therefore, Narp KO mice do not have abnormal reactivity to novelty but show deficits in adapting behavior to reflect the updated value of a stimulus. PMID:24120400

  12. Phosphatase Wip1 Masters IL-17-producing Neutrophil-mediated Colitis in Mice.

    PubMed

    Hu, Xuelian; Wang, Peng; Du, Junfeng; Yang, Fan; Tian, Yuan; Shen, Xiaofei; Yang, Tao; Zhang, Lianfeng; Zhao, Yong

    2016-06-01

    Wild-type p53-induced phosphatase 1 (Wip1) is currently believed to be a promising drug target for cancer therapy. Our recent studies showed that deletion of Wip1 remarkably promoted neutrophil inflammatory response. Whether Wip1 is involved in the regulation of inflammatory bowel disease is unknown. In the present study, we found that Wip1 knockout (KO) mice were more susceptible to colitis induced by dextran sulphate sodium (DSS) than wild-type mice as substantiated by the lower mouse survival ratio, rapid bodyweight loss, increased disease activity index, shorter colon length, and more severe pathology of colons in Wip1KO mice. Using full bone marrow chimera mouse models, we demonstrated that Wip1 intrinsically controls inflammatory response of immune cells. Deletion of IL-17 (Wip1/IL-17 double KO mice) significantly rescued the pathology in Wip1KO mice. Neutrophils of DSS-treated wild-type and Wip1KO mice expressed significantly higher IL-17. After adoptive transfer of sorted Wip1KO or double KO neutrophils into IL-17KO mice, mice receiving double KO neutrophils were more resistant to DSS-induced colitis than mice receiving Wip1KO neutrophils. These data collectively indicate that Wip1 modulates host sensitivity to colitis by intrinsically regulating immune cells. The enhanced IL-17 expression in neutrophils contributed to the increased sensitivity and severity of colitis in Wip1KO mice. Thus, Wip1 may be used as a drug target to treat colitis. PMID:26950306

  13. Basal Bone Phenotype and Increased Anabolic Responses to Intermittent Parathyroid Hormone in Healthy Male COX-2 Knockout Mice

    PubMed Central

    Xu, Manshan; Choudhary, Shilpa; Voznesensky, Olga; Gao, Qi; Adams, Douglas; Diaz-Doran, Vilmaris; Wu, Qian; Goltzman, David; Raisz, Lawrence G.; Pilbeam, Carol C.

    2011-01-01

    Cyclooxygenase-2 (COX-2) knockout (KO) mice in inbred strains can have renal dysfunction with secondary hyperparathyroidism (HPTH), making direct effects of COX-2 KO on bone difficult to assess. COX-2 KO mice in an outbred CD-1 background did not have renal dysfunction but still had two-fold elevated PTH compared to wild type (WT) mice. Compared to WT mice, KO mice had increased serum markers of bone turnover, decreased femoral bone mineral density (BMD) and cortical bone thickness, but no differences in trabecular bone volume by μCT or dynamic histomorphometry. Because PTH is a potent inducer of COX-2 and prostaglandin (PG) production, we examined effects of COX-2 KO on bone responses after three weeks of intermittent PTH. Intermittent PTH increased femoral BMD and cortical bone area more in KO mice than in WT mice and increased trabecular bone volume in the distal femur in both WT and KO mice. Although not statistically significant, PTH-stimulated increases in trabecular bone tended to be greater in KO mice than in WT mice. PTH increased serum markers of bone formation and resorption more in KO than in WT mice but increased the ratio of osteoblastic surface to osteoclastic surface only in KO mice. PTH also increased femoral mineral apposition rates and bone formation rates in KO mice more than in WT mice. Acute mRNA responses to PTH of genes that might mediate some anabolic and catabolic effects of PTH tended to be greater in KO than WT mice. We conclude that (1) the basal bone phenotype in male COX-2 KO mice might reflect HPTH, COX-2 deficiency or both, and (2) increased responses to intermittent PTH in COX-2 KO mice, despite the presence of chronic HPTH, suggest that absence of COX-2 increased sensitivity to PTH. It is possible that manipulation of endogenous PGs could have important clinical implications for anabolic therapy with PTH. PMID:20471507

  14. Distinct function of estrogen receptor α in smooth muscle and fibroblast cells in prostate development.

    PubMed

    Vitkus, Spencer; Yeh, Chiuan-Ren; Lin, Hsiu-Hsia; Hsu, Iawen; Yu, Jiangzhou; Chen, Ming; Yeh, Shuyuan

    2013-01-01

    Estrogen signaling, through estrogen receptor (ER)α, has been shown to cause hypertrophy in the prostate. Our recent report has shown that epithelial ERα knockout (KO) will not affect the normal prostate development or homeostasis. However, it remains unclear whether ERα in different types of stromal cells has distinct roles in prostate development. This study proposed to elucidate how KO of ERα in the stromal smooth muscle or fibroblast cells may interrupt cross talk between prostate stromal and epithelial cells. Smooth muscle ERαKO (smERαKO) mice showed decreased glandular infolding with the proximal area exhibiting a significant decrease. Fibroblast ERαKO mouse prostates did not exhibit this phenotype but showed a decrease in the number of ductal tips. Additionally, the amount of collagen observed in the basement membrane was reduced in smERαKO prostates. Interestingly, these phenotypes were found to be mutually exclusive among smERαKO or fibroblast ERαKO mice. Compound KO of ERα in both fibroblast and smooth muscle showed combined phenotypes from each of the single KO. Further mechanistic studies showed that IGF-I and epidermal growth factor were down-regulated in prostate smooth muscle PS-1 cells lacking ERα. Together, our results indicate the distinct functions of fibroblast vs. smERα in prostate development. PMID:23204329

  15. Establishment of Immortalized BMP2/4 Double Knock‐Out Osteoblastic Cells Is Essential for Study of Osteoblast Growth, Differentiation, and Osteogenesis

    PubMed Central

    Wu, Li‐An; Wang, Feng; Donly, Kevin J.; Baker, Andrew; Wan, Chunyan; Luo, Daoshu; MacDougall, Mary

    2015-01-01

    Bone morphogenetic proteins 2 and 4 (BMP2/4) are essential for osteoblast differentiation and osteogenesis. Generation of a BMP2/4 dual knock‐out (ko/ko) osteoblastic cell line is a valuable asset for studying effects of BMP2/4 on skeletal development. In this study, our goal was to create immortalized mouse deleted BMP2/4 osteoblasts by infecting adenoviruses with Cre recombinase and green fluorescent protein genes into immortalized murine floxed BMP2/4 osteoblasts. Transduced BMP2/4ko/ko cells were verified by green immunofluorescence and PCR. BMP2/4ko/ko osteoblasts exhibited small size, slow cell proliferation rate and cell growth was arrested in G1 and G2 phases. Expression of bone‐relate genes was reduced in the BMP2/4ko/ko cells, resulting in delay of cell differentiation and mineralization. Importantly, extracellular matrix remodeling was impaired in the BMP2/4ko/ko osteoblasts as reflected by decreased Mmp‐2 and Mmp‐9 expressions. Cell differentiation and mineralization were rescued by exogenous BMP2 and/or BMP4. Therefore, we for the first time described establishment of an immortalized deleted BMP2/4 osteoblast line useful for study of mechanisms in regulating osteoblast lineages. J. Cell. Physiol. 231: 1189–1198, 2016. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:26595646

  16. KOALA RETROVIRUS: A REVIEW.

    PubMed

    Kinney, Matthew E; Pye, Geoffrey W

    2016-06-01

    Koala retrovirus (KoRV) is a gammaretrovirus that has been identified in both captive and free-ranging koalas ( Phascolarctos cinereus ) with variable geographic distribution in Australia. KoRV is capable of both exogenous and endogenous transmission, which provides an interesting research platform for scientists to study active retrovirus endogenization into a host genome and offers veterinary scientists an opportunity to examine the clinical consequences of KoRV infection in koalas. Causation between KoRV and frequently recognized clinical conditions associated with immune suppression and neoplasia in koalas has not been definitively established, however research continues to evaluate a potential association. Three KoRV variants, KoRV-A, KoRV-B, and KoRV-J, have been the most thoroughly described and preliminary evidence suggests KoRV variability may be fundamental in host pathogenicity. In addition to reviewing what is currently known about KoRV, this article discusses treatment, management, and future research directions. PMID:27468008

  17. Establishment of Immortalized BMP2/4 Double Knock-Out Osteoblastic Cells Is Essential for Study of Osteoblast Growth, Differentiation, and Osteogenesis.

    PubMed

    Wu, Li-An; Wang, Feng; Donly, Kevin J; Baker, Andrew; Wan, Chunyan; Luo, Daoshu; MacDougall, Mary; Chen, Shuo

    2016-06-01

    Bone morphogenetic proteins 2 and 4 (BMP2/4) are essential for osteoblast differentiation and osteogenesis. Generation of a BMP2/4 dual knock-out ((ko/ko)) osteoblastic cell line is a valuable asset for studying effects of BMP2/4 on skeletal development. In this study, our goal was to create immortalized mouse deleted BMP2/4 osteoblasts by infecting adenoviruses with Cre recombinase and green fluorescent protein genes into immortalized murine floxed BMP2/4 osteoblasts. Transduced BMP2/4(ko/ko) cells were verified by green immunofluorescence and PCR. BMP2/4(ko/ko) osteoblasts exhibited small size, slow cell proliferation rate and cell growth was arrested in G1 and G2 phases. Expression of bone-relate genes was reduced in the BMP2/4(ko/ko) cells, resulting in delay of cell differentiation and mineralization. Importantly, extracellular matrix remodeling was impaired in the BMP2/4(ko/ko) osteoblasts as reflected by decreased Mmp-2 and Mmp-9 expressions. Cell differentiation and mineralization were rescued by exogenous BMP2 and/or BMP4. Therefore, we for the first time described establishment of an immortalized deleted BMP2/4 osteoblast line useful for study of mechanisms in regulating osteoblast lineages. PMID:26595646

  18. Retention of bacterial lipopolysaccharide at the site of subcutaneous injection.

    PubMed Central

    Yokochi, T.; Inoue, Y.; Yokoo, J.; Kimura, Y.; Kato, N.

    1989-01-01

    The tissue distribution of Klebsiella pneumoniae O3 lipopolysaccharide (KO3 LPS) was studied in mice injected subcutaneously (s.c.) or intraperitoneally (i.p.) with 125I-labeled KO3 LPS. Marked retention of KO3 LPS radioactivity could be found at the site of s.c. injection for several weeks. On the other hand, about 85% of the radioactivity rapidly disappeared from the peritoneal cavity within 6 h after i.p. injection. The long-term presence of KO3 LPS at the injection site was also supported by experiments with 51Cr-labeled KO3 LPS and immunoblotting and immunofluorescence staining methods. The R-form LPS lacking the O-specific polysaccharide chain of KO3 LPS and the lipid A fraction of KO3 LPS seemed to remain at the site in larger amounts and for longer times than KO3 LPS. There were no marked differences in the retention pattern at the injection site among KO3 LPS, Escherichia coli LPS, Salmonella typhosa LPS, and Salmonella enteritidis LPS. However, much less radioactivity accumulated in the livers and spleens of mice injected with either KO3 LPS or S. typhosa LPS compared with the other LPS preparations. It was suggested that retention of LPS at the site of s.c. injection may play an important role in the development of various biological actions of s.c. injected LPS. Images PMID:2722239

  19. Tumor Necrosis Factor (TNF) Receptor Superfamily Member 1b on CD8+ T Cells and TNF Receptor Superfamily Member 1a on Non-CD8+ T Cells Contribute Significantly to Upper Genital Tract Pathology Following Chlamydial Infection

    PubMed Central

    Manam, Srikanth; Thomas, Joshua D.; Li, Weidang; Maladore, Allison; Schripsema, Justin H.; Ramsey, Kyle H.; Murthy, Ashlesh K.

    2015-01-01

    Background. We demonstrated previously that tumor necrosis factor α (TNF-α)–producing Chlamydia-specific CD8+ T cells cause oviduct pathological sequelae. Methods. In the current study, we used wild-type C57BL/6J (WT) mice with a deficiency in genes encoding TNF receptor superfamily member 1a (TNFR1; TNFR1 knockout [KO] mice), TNF receptor superfamily member 1b (TNFR2; TNFR2 KO mice), and both TNFR1 and TNFR2 (TNFR1/2 double KO [DKO] mice) and mix-match adoptive transfers of CD8+ T cells to study chlamydial pathogenesis. Results. TNFR1 KO, TNFR2 KO, and TNFR1/2 DKO mice displayed comparable clearance of primary or secondary genital Chlamydia muridarum infection but significantly reduced oviduct pathology, compared with WT animals. The Chlamydia-specific total cellular cytokine response in splenic and draining lymph nodes and the antibody response in serum were comparable between the WT and KO animals. However, CD8+ T cells from TNFR2 KO mice displayed significantly reduced activation (CD11a expression and cytokine production), compared with TNFR1 KO or WT animals. Repletion of TNFR2 KO mice with WT CD8+ T cells but not with TNFR2 KO CD8+ T cells and repletion of TNFR1 KO mice with either WT or TNFR1 KO CD8+ T cells restored oviduct pathology to WT levels in both KO groups. Conclusions. Collectively, these results demonstrate that TNFR2-bearing CD8+ T cells and TNFR1-bearing non-CD8+ T cells contribute significantly to oviduct pathology following genital chlamydial infection. PMID:25552370

  20. Reversal of an Unconditioned Behavioral Preference for Specific Food Pellets by Intervention of Whisker Sensory Inputs

    PubMed Central

    Kim, Hannah; Lee, Yunjin; Kim, Ji-Eun

    2016-01-01

    Adenylyl cyclase type-5 (AC5) is preferentially expressed in the dorsal striatum. Recently, we reported that AC5 knockout (KO) mice preferred food pellets carrying an olfactory cue produced by AC5 KO mice during food consumption (AC5 KO pellets) over food pellets that had been taken by wildtype (WT) mice. In the present study, we demonstrated that whisker trimming on the right side of the face but not the left in AC5 KO mice blocked the behavioral preference for AC5 KO pellets. Conversely, whisker trimming on the right but not the left in WT mice induced a behavioral preference for AC5 KO pellets. Mice lacking D2 dopamine receptor (D2 KO mice) also showed a behavioral preference for AC5 KO pellets. In D2 mice, whisker trimming on the right side of the face but not the left blocked a behavioral preference for AC5 KO food pellets. AC5 KO mice had increased level of phospho-CaMKIIα in the dorsal striatum, and WT mice with whiskers cut on either side also showed increased p-CaMKIIα level in the dorsal striatum. The siRNA-mediated inhibition of CaMKIIα in the dorsal striatum in either the right or the left hemisphere in AC5 KO mice and D2 KO mice blocked the behavioral preference for AC5 KO pellets. However, behavioral changes induced by this inhibition on each side showed asymmetrical time courses. These results suggest that an unconditioned behavioral preference for specific food pellets can be switched on or off based on the balance of states of neural activity in the dorsal striatum regulated by a signaling pathway centered on AC5 and D2 and the sensory inputs of whiskers from the right side of the face. PMID:27122994

  1. Extracellular potassium and chemosensitivity in the rat carotid body, in vitro.

    PubMed Central

    Pepper, D R; Landauer, R C; Kumar, P

    1996-01-01

    1. The effects of raising extracellular potassium concentration ([K+]o) from 3.0 to 5.3, 9.5 or 16.8 mM on chemoreceptor responses to hypoxia, hypercapnia and asphyxia were examined in a superfused in vitro rat carotid body preparation. 2. Single-exponential functions with offset were fitted to the chemoreceptor discharge responses to ramp decreases in Po2. Increasing [K+]o was without effect upon the rate constants of the fitted exponential functions (P > 0.20). Increasing [K+]o, significantly increased the horizontal asymptote (chemoreceptor discharge in hyperoxia) in a non-linear fashion when all levels of [K+]o were included in the analysis (P < 0.001) but not when a comparison was made only between 3.0 and 5.3 mM Ko+ (P > 0.40). The rightward position of the response curves, as quantified by the Po2 at 50% maximum discharge, was linearly related to [K+]o but only when all levels of [K+]o were included in the analysis (P < 0.03). Chemoreceptor sensitivity to [K+]o increased non-linearly as [K+]o was increased but this effect was not dependent upon the Po2 (P > 0.90). 4. Increasing PCO2 in hyperoxia increased chemoreceptor discharge linearly at all levels of [K+]o. Whilst discharge at any level of PCO2 was elevated by increased levels of [K+]o, raising [K+]o did not increase CO2 sensitivity (P > 0.20). Similarly, increasing PCO2 did not increase chemosensitivity to [K+]o. The lack of effect of [K+]o upon CO2 chemosensitivity was also observed as Po2 was decreased to hypoxic levels (P > 0.10). 5. Our data demonstrate that an elevation of [K+]o can increase chemoreceptor discharge in the in vitro carotid body in a PO2- and PCO2-independent manner, suggesting that the PO2-dependent effects of [K+]o, previously reported in vivo may be due to other indirect effects of [K+]o or hypoxia. PMID:8799903

  2. The Rpe65rd12 Allele Exerts a Semidominant Negative Effect on Vision in Mice

    PubMed Central

    Wright, Charles B.; Chrenek, Micah A.; Feng, Wei; Getz, Shannon E.; Duncan, Todd; Pardue, Machelle T.; Feng, Yue; Redmond, T. Michael; Boatright, Jeffrey H.; Nickerson, John M.

    2014-01-01

    Purpose. The rd12 mouse was reported as a recessively inherited Rpe65 mutation. We asked if the rd12 mutation resides in Rpe65 and how the mutation manifests itself. Methods. A complementation test was performed by mating Rpe65KO (KO/KO) and rd12 mice together to determine if the rd12 mutation is in the Rpe65 gene. Visual function of wild-type (+/+), KO/+, rd12/+, KO/KO, rd12/rd12, and KO/rd12 mice was measured by optokinetic tracking (OKT) and ERG. Morphology was assessed by retinal cross section. qRT-PCR quantified Rpe65 mRNA levels. Immunoblotting measured the size and level of RPE65 protein. Rpe65 mRNA localization was visualized with RNA fluorescence in situ hybridization (FISH). Fractions of Rpe65 mRNA-bound proteins were separated by linear sucrose gradient fractionation. Results. The KO and rd12 alleles did not complement. The rd12 allele induced a negative semidominant effect on visual function; OKT responses became undetectable 120 days earlier in rd12/rd12 mice compared with KO/KO mice. rd12/+ mice lost approximately 21% visual acuity by P210. rd12/rd12 mice had fewer cone photoreceptor nuclei than KO/KO mice at P60. rd12/rd12 mice expressed 71% +/+ levels of Rpe65 mRNA, but protein was undetectable. Mutant mRNA was appropriately spliced, exported to the cytoplasm, trafficked, and contained no other coding mutation aside from the known nonsense mutation. Mutant mRNA was enriched on ribosome-free messenger ribonucleoproteins (mRNPs), whereas wild-type mRNA was enriched on actively translating polyribosomes. Conclusions. The rd12 lesion is in Rpe65. The rd12 mutant phenotype inherits in a semidominant manner. The effects of the mutant mRNA on visual function may result from inefficient binding to ribosomes for translation. PMID:24644049

  3. The role of insulin receptor substrate 2 in hypothalamic and β cell function

    PubMed Central

    Choudhury, Agharul I.; Heffron, Helen; Smith, Mark A.; Al-Qassab, Hind; Xu, Allison W.; Selman, Colin; Simmgen, Marcus; Clements, Melanie; Claret, Marc; MacColl, Gavin; Bedford, David C.; Hisadome, Kazunari; Diakonov, Ivan; Moosajee, Vazira; Bell, Jimmy D.; Speakman, John R.; Batterham, Rachel L.; Barsh, Gregory S.; Ashford, Michael L.J.; Withers, Dominic J.

    2005-01-01

    Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 in β cells and a population of hypothalamic neurons (RIPCreIrs2KO), in all neurons (NesCreIrs2KO), and in proopiomelanocortin neurons (POMCCreIrs2KO) to determine the role of Irs2 in the CNS and β cell. RIPCreIrs2KO mice displayed impaired glucose tolerance and reduced β cell mass. Overt diabetes did not ensue, because β cells escaping Cre-mediated recombination progressively populated islets. RIPCreIrs2KO and NesCreIrs2KO mice displayed hyperphagia, obesity, and increased body length, which suggests altered melanocortin action. POMCCreIrs2KO mice did not display this phenotype. RIPCreIrs2KO and NesCreIrs2KO mice retained leptin sensitivity, which suggests that CNS Irs2 pathways are not required for leptin action. NesCreIrs2KO and POMCCreIrs2KO mice did not display reduced β cell mass, but NesCreIrs2KO mice displayed mild abnormalities of glucose homeostasis. RIPCre neurons did not express POMC or neuropeptide Y. Insulin and a melanocortin agonist depolarized RIPCre neurons, whereas leptin was ineffective. Insulin hyperpolarized and leptin depolarized POMC neurons. Our findings demonstrate a critical role for IRS2 in β cell and hypothalamic function and provide insights into the role of RIPCre neurons, a distinct hypothalamic neuronal population, in growth and energy homeostasis. PMID:15841180

  4. Vitamin D Regulates the Gut Microbiome and Protects Mice from Dextran Sodium Sulfate–Induced Colitis123

    PubMed Central

    Ooi, Jot Hui; Li, Yunfei; Rogers, Connie J.; Cantorna, Margherita T.

    2013-01-01

    The active form of vitamin D [1,25-dihydroxycholecalciferol, 1,25(OH)2D3] and the vitamin D receptor (VDR) regulate susceptibility to experimental colitis. The effect of the bacterial microflora on the susceptibility of C57BL/6 mice to dextran sodium sulfate–induced colitis was determined. Mice that cannot produce 1,25(OH)2D3 [Cyp27b1 (Cyp) knockout (KO)], VDR KO as well as their wild-type littermates were used. Cyp KO and VDR KO mice had more bacteria from the Bacteroidetes and Proteobacteria phyla and fewer bacteria from the Firmicutes and Deferribacteres phyla in the feces compared with wild-type. In particular, there were more beneficial bacteria, including the Lactobacillaceae and Lachnospiraceae families, in feces from Cyp KO and VDR KO mice than in feces from wild-type. Helicobacteraceae family member numbers were elevated in Cyp KO compared with wild-type mice. Depletion of the gut bacterial flora using antibiotics protected mice from colitis. 1,25(OH)2D3 treatment (1.25 μg/100 g diet) of Cyp KO mice decreased colitis severity and reduced the numbers of Helicobacteraceae in the feces compared with the numbers in the feces of untreated Cyp KO mice. The mechanisms by which the dysbiosis occurs in VDR KO and Cyp KO mice included lower expression of E-cadherin on gut epithelial and immune cells and fewer tolerogenic dendritic cells that resulted in more gut inflammation in VDR and Cyp KO mice compared with wild-type mice. Increased host inflammation has been shown to provide pathogens with substrates to out-compete more beneficial bacterial species. Our data demonstrate that vitamin D regulates the gut microbiome and that 1,25(OH)2D3 or VDR deficiency results in dysbiosis, leading to greater susceptibility to injury in the gut. PMID:23966330

  5. Koala Retroviruses: Evolution and Disease Dynamics.

    PubMed

    Xu, Wenqin; Eiden, Maribeth V

    2015-11-01

    A retroviral etiology for malignant neoplasias in koalas has long been suspected. Evidence for retroviral involvement was bolstered in 2000 by the isolation of a koala retrovirus (KoRV), now termed KoRV-A. KoRV-A is an endogenous retrovirus-a retrovirus that infects germ cells-a feature that makes it a permanent resident of the koala genome. KoRV-A lacks the genetic diversity of an exogenous retrovirus, a quality associated with the ability of a retrovirus to cause neoplasias. In 2013, a second KoRV isolate, KoRV-B, was obtained from koalas with lymphomas in the Los Angeles Zoo. Unlike KoRV-A, which is present in the genomes of all koalas in the United States, KoRV-B is restricted in its distribution and is associated with host pathology (neoplastic disease). Here, our current understanding of the evolution of endogenous and exogenous KoRVs, and the relationship between them, is reviewed to build a perspective on the future impact of these viruses on koala sustainability. PMID:26958909

  6. Generation of α1,3-galactosyltransferase and cytidine monophospho-N-acetylneuraminic acid hydroxylase gene double-knockout pigs

    PubMed Central

    MIYAGAWA, Shuji; MATSUNARI, Hitomi; WATANABE, Masahito; NAKANO, Kazuaki; UMEYAMA, Kazuhiro; SAKAI, Rieko; TAKAYANAGI, Shuko; TAKEISHI, Toki; FUKUDA, Tooru; YASHIMA, Sayaka; MAEDA, Akira; EGUCHI, Hiroshi; OKUYAMA, Hiroomi; NAGAYA, Masaki; NAGASHIMA, Hiroshi

    2015-01-01

    Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) are new tools for producing gene knockout (KO) animals. The current study reports produced genetically modified pigs, in which two endogenous genes were knocked out. Porcine fibroblast cell lines were derived from homozygous α1,3-galactosyltransferase (GalT) KO pigs. These cells were subjected to an additional KO for the cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) gene. A pair of ZFN-encoding mRNAs targeting exon 8 of the CMAH gene was used to generate the heterozygous CMAH KO cells, from which cloned pigs were produced by somatic cell nuclear transfer (SCNT). One of the cloned pigs obtained was re-cloned after additional KO of the remaining CMAH allele using the same ZFN-encoding mRNAs to generate GalT/CMAH-double homozygous KO pigs. On the other hand, the use of TALEN-encoding mRNAs targeting exon 7 of the CMAH gene resulted in efficient generation of homozygous CMAH KO cells. These cells were used for SCNT to produce cloned pigs homozygous for a double GalT/CMAH KO. These results demonstrate that the combination of TALEN-encoding mRNA, in vitro selection of the nuclear donor cells and SCNT provides a robust method for generating KO pigs. PMID:26227017

  7. Generation of α1,3-galactosyltransferase and cytidine monophospho-N-acetylneuraminic acid hydroxylase gene double-knockout pigs.

    PubMed

    Miyagawa, Shuji; Matsunari, Hitomi; Watanabe, Masahito; Nakano, Kazuaki; Umeyama, Kazuhiro; Sakai, Rieko; Takayanagi, Shuko; Takeishi, Toki; Fukuda, Tooru; Yashima, Sayaka; Maeda, Akira; Eguchi, Hiroshi; Okuyama, Hiroomi; Nagaya, Masaki; Nagashima, Hiroshi

    2015-01-01

    Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) are new tools for producing gene knockout (KO) animals. The current study reports produced genetically modified pigs, in which two endogenous genes were knocked out. Porcine fibroblast cell lines were derived from homozygous α1,3-galactosyltransferase (GalT) KO pigs. These cells were subjected to an additional KO for the cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) gene. A pair of ZFN-encoding mRNAs targeting exon 8 of the CMAH gene was used to generate the heterozygous CMAH KO cells, from which cloned pigs were produced by somatic cell nuclear transfer (SCNT). One of the cloned pigs obtained was re-cloned after additional KO of the remaining CMAH allele using the same ZFN-encoding mRNAs to generate GalT/CMAH-double homozygous KO pigs. On the other hand, the use of TALEN-encoding mRNAs targeting exon 7 of the CMAH gene resulted in efficient generation of homozygous CMAH KO cells. These cells were used for SCNT to produce cloned pigs homozygous for a double GalT/CMAH KO. These results demonstrate that the combination of TALEN-encoding mRNA, in vitro selection of the nuclear donor cells and SCNT provides a robust method for generating KO pigs. PMID:26227017

  8. Biomass Burning

    NASA Video Gallery

    As part of NASA's 2013 Reel Science Communications program, student Michelle Ko from Pasadena California worked with NASA scientists and communications specialists to produce this impressive video ...

  9. Up-regulation of Thrombospondin-2 in Akt1-null Mice Contributes to Compromised Tissue Repair Due to Abnormalities in Fibroblast Function*

    PubMed Central

    Bancroft, Tara; Bouaouina, Mohamed; Roberts, Sophia; Lee, Monica; Calderwood, David A.; Schwartz, Martin; Simons, Michael; Sessa, William C.; Kyriakides, Themis R.

    2015-01-01

    Vascular remodeling is essential for tissue repair and is regulated by multiple factors, including thrombospondin-2 (TSP2) and hypoxia/VEGF-induced activation of Akt. In contrast to TSP2 knock-out (KO) mice, Akt1 KO mice have elevated TSP2 expression and delayed tissue repair. To investigate the contribution of increased TSP2 to Akt1 KO mice phenotypes, we generated Akt1/TSP2 double KO (DKO) mice. Full-thickness excisional wounds in DKO mice healed at an accelerated rate when compared with Akt1 KO mice. Isolated dermal Akt1 KO fibroblasts expressed increased TSP2 and displayed altered morphology and defects in migration and adhesion. These defects were rescued in DKO fibroblasts or after TSP2 knockdown. Conversely, the addition of exogenous TSP2 to WT cells induced cell morphology and migration rates that were similar to those of Akt1 KO cells. Akt1 KO fibroblasts displayed reduced adhesion to fibronectin with manganese stimulation when compared with WT and DKO cells, revealing an Akt1-dependent role for TSP2 in regulating integrin-mediated adhesions; however, this effect was not due to changes in β1 integrin surface expression or activation. Consistent with these results, Akt1 KO fibroblasts displayed reduced Rac1 activation that was dependent upon expression of TSP2 and could be rescued by a constitutively active Rac mutant. Our observations show that repression of TSP2 expression is a critical aspect of Akt1 function in tissue repair. PMID:25389299

  10. Tissue-Specific Effects of the Nuclear Factor κB Subunit p50 on Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Frantz, Stefan; Tillmanns, Jochen; Kuhlencordt, Peter J.; Schmidt, Isabel; Adamek, Anna; Dienesch, Charlotte; Thum, Thomas; Gerondakis, Steve; Ertl, Georg; Bauersachs, Johann

    2007-01-01

    Nuclear factor κB (NF-κB) is a ubiquitous transcription factor activated by various stimuli implicated in ischemia-reperfusion injury. However, the role of NF-κB in cardiac ischemia-reperfusion injury has not yet been well defined. Therefore, we investigated reperfusion damage in mice with targeted deletion of the NF-κB subunit p50. Electrophoretic mobility shift assays validated NF-κB activation in wild-type (WT) but not p50 knockout (KO) mice. KO and WT animals underwent 30 minutes of coronary artery ligation and 24 hours of reperfusion in vivo. Ischemia-reperfusion damage was significantly reduced in the p50 KO when compared with matching WT mice. Although adhesion molecules such as intercellular adhesion molecule were up-regulated in left ventricles of p50 KO animals, fewer neutrophils infiltrated the infarct area, suggesting leukocytes as a potential mediator of the protection observed in the p50 KO. This was confirmed in adoptive transfer experiments: whereas transplantation of KO bone marrow in KO animals sustained the protective effect on ischemia-reperfusion injury, transplantation of WT bone marrow in KO animals abolished it. Thus, deletion of the NF-κB subunit p50 reduces ischemia-reperfusion injury in vivo, associated with less neutrophil infiltration. Bone marrow transplantation experiments indicate that impaired NF-κB activation in p50 KO leukocytes attenuates cardiac damage. PMID:17556593

  11. Diacylglycerol Lipase α Knockout Mice Demonstrate Metabolic and Behavioral Phenotypes Similar to Those of Cannabinoid Receptor 1 Knockout Mice.

    PubMed

    Powell, David R; Gay, Jason P; Wilganowski, Nathaniel; Doree, Deon; Savelieva, Katerina V; Lanthorn, Thomas H; Read, Robert; Vogel, Peter; Hansen, Gwenn M; Brommage, Robert; Ding, Zhi-Ming; Desai, Urvi; Zambrowicz, Brian

    2015-01-01

    After creating >4,650 knockouts (KOs) of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1) KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase α or β (Dagla or Daglb), which catalyze biosynthesis of the endocannabinoid (EC) 2-arachidonoylglycerol (2-AG), or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild-type (WT) littermates; when data from multiple cohorts of adult mice were combined, body fat was 47 and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. By contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight (BW) similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride, and total cholesterol levels, and after glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: (1) the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; (2) in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and (3) small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower BW and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric side

  12. Diacylglycerol Lipase α Knockout Mice Demonstrate Metabolic and Behavioral Phenotypes Similar to Those of Cannabinoid Receptor 1 Knockout Mice

    PubMed Central

    Powell, David R.; Gay, Jason P.; Wilganowski, Nathaniel; Doree, Deon; Savelieva, Katerina V.; Lanthorn, Thomas H.; Read, Robert; Vogel, Peter; Hansen, Gwenn M.; Brommage, Robert; Ding, Zhi-Ming; Desai, Urvi; Zambrowicz, Brian

    2015-01-01

    After creating >4,650 knockouts (KOs) of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1) KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase α or β (Dagla or Daglb), which catalyze biosynthesis of the endocannabinoid (EC) 2-arachidonoylglycerol (2-AG), or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild-type (WT) littermates; when data from multiple cohorts of adult mice were combined, body fat was 47 and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. By contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight (BW) similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride, and total cholesterol levels, and after glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: (1) the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; (2) in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and (3) small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower BW and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric side

  13. Targeted overexpression of the human urotensin receptor transgene in smooth muscle cells: effect of UT antagonism in ApoE knockout mice fed with Western diet.

    PubMed

    Papadopoulos, Panayiota; Bousette, Nicolas; Al-Ramli, Wisam; You, Zhipeng; Behm, David J; Ohlstein, Eliot H; Harrison, Stephen M; Douglas, Stephen A; Giaid, Adel

    2009-06-01

    Urotensin II (UII) and its receptor UT are upregulated in the pathological setting of various cardiovascular diseases including atherosclerosis. However, their exact role in atherosclerosis remains to be determined. In the present study we used four strains of mice; wild-type (WT), UT(+) (a transgenic strain expressing human UT driven by the alpha-smooth muscle-specific, SM22, promoter), ApoE knockout (ko), and UT(+)/ApoE ko. All animals were fed high fat diet for 12 weeks. Western blot analysis revealed a significant increase in aortic UT expression in UT(+) relative to WT mice (P<0.05). Aortas of ApoE ko mice expressed comparable UT protein level to that of UT(+). Immunohistochemistry revealed the presence of strong expression of UT and UII proteins in the atheroma of UT(+), ApoE ko and UT(+)/ApoE ko mice, particularly in foam cells. Serum cholesterol and triglyceride levels were significantly increased in ApoE ko and in UT(+)/ApoE ko but not in UT(+) mice when compared to WT mice (P<0.0001). Analysis of aortas showed a significant increase in atherosclerotic lesion in the UT(+), ApoE ko and UT(+)/ApoE ko compared to WT mice (P<0.05). Oral administration of the UT receptor antagonist SB-657510A (30 microg/Kg/day gavage) for 10 weeks in a group of ApoE ko mice fed on high fat diet resulted in a significant reduction of lesion (P<0.001). SB-657510A also significantly reduced ACAT-1 protein expression in the atherosclerotic lesion of ApoE ko mice (P<0.05). The present findings demonstrate an important role for UT in the pathogenesis of atherosclerosis. The use of UT receptor antagonists may provide a beneficial tool in the management of this debilitating disease process. PMID:19111831

  14. A greater role for the norepinephrine transporter than the serotonin transporter in murine nociception

    PubMed Central

    Hall, F. Scott; Schwarzbaum, Joshua M.; Perona, Maria T.G.; Templin, J. Scott; Caron, Marc G.; Lesch, Klaus-Peter; Murphy, Dennis L.; Uhl, George R.

    2010-01-01

    Norepinephrine and serotonin involvement in nociceptive functions is supported by observations of analgesic effects of norepinephrine transporter (NET) and serotonin transporter (SERT) inhibitors such as amitriptyline. However, the relative contribution of NET and SERT to baseline nociception, as well as amitriptyline analgesia, is unclear. Amitriptyline and morphine analgesia in wild-type (WT) mice and littermates with gene knockout (KO) of SERT, NET or both transporters was conducted using the hotplate and tail-flick tests. Hypoalgesia was observed in NET KO mice, and to a lesser extent in SERT KO mice. The magnitude of this hypoalgesia in NET KO mice was so profound that it limited the assessment of drug-induced analgesia. Nonetheless, the necessary exclusion of these subjects because of profound baseline hypoalgesia strongly supports the role of norepinephrine and NET in basal nociceptive behavior while indicating a much smaller role for serotonin and SERT. To further clarify the role of NET and SERT in basal nociceptive sensitivity further experiments were conducted in SERT KO and NET KO mice across a range of temperatures. NET KO mice were again found to have pronounced thermal hypoalgesia compared to WT mice in both the hotplate and tail-flick tests, and only limited effects were observed in SERT KO mice. Furthermore, in the acetic acid writhing test of visceral nociception pronounced hypoalgesia was again found in NET KO mice, but no effect in SERT KO mice. As some of these effects may have resulted from developmental consequences of NET KO, the effects of the selective NET blocker nisoxetine and the selective SERT blocker fluoxetine were also examined in WT mice: only nisoxetine produced analgesia in these mice. Collectively these data suggest that NET has a far greater role in determining baseline analgesia, and perhaps other analgesic effects, than SERT. PMID:21129446

  15. Etomidate Impairs Long-Term Potentiation In Vitro by Targeting α5-Subunit Containing GABAA Receptors on Nonpyramidal Cells

    PubMed Central

    Rodgers, F. Clifford; Zarnowska, Ewa D.; Laha, Kurt T.; Engin, Elif; Zeller, Anja; Keist, Ruth; Rudolph, Uwe

    2015-01-01

    Previous experiments using genetic and pharmacological manipulations have provided strong evidence that etomidate impairs synaptic plasticity and memory by modulating α5-subunit containing GABAA receptors (α5-GABAARs). Because α5-GABAARs mediate tonic inhibition (TI) in hippocampal CA1 pyramidal cells and etomidate enhances TI, etomidate enhancement of TI in pyramidal cells has been proposed as the underlying mechanism (Martin et al., 2009). Here we tested this hypothesis by selectively removing α5-GABAARs from pyramidal neurons (CA1–pyr–α5–KO) and comparing the ability of etomidate to enhance TI and block LTP in fl–α5 (WT), global–α5–KO (gl–α5–KO), and CA1–pyr–α5–KO mice. Etomidate suppressed LTP in slices from WT and CA1–pyr–α5–KO but not gl–α5–KO mice. There was a trend toward reduced TI in both gl–α5–KO and CA1–pyr–α5–KO mice, but etomidate enhanced TI to similar levels in all genotypes. The dissociation between effects of etomidate on TI and LTP in gl–α5–KO mice indicates that increased TI in pyramidal neurons is not the mechanism by which etomidate impairs LTP and memory. Rather, the ability of etomidate to block LTP in WT and CA1–pyr–α5–KO mice, but not in gl–α5–KO mice, points toward α5-GABAARs on nonpyramidal cells as the essential effectors controlling plasticity in this in vitro model of learning and memory. PMID:26134653

  16. Priming Effects Associated with the Hierarchical Levels of Classification Systems

    ERIC Educational Resources Information Center

    Loehrlein, Aaron J.

    2012-01-01

    The act of categorization produces conceptual representations in memory while knowledge organization (KO) systems provide conceptual representations that are used in information storage and retrieval systems. Previous research has explored how KO systems can be designed to resemble the user's internal conceptual structures. However, the more…

  17. Lack of stress responses to long-term effects of corticosterone in Caps2 knockout mice.

    PubMed

    Mishima, Yuriko; Shinoda, Yo; Sadakata, Tetsushi; Kojima, Masami; Wakana, Shigeharu; Furuichi, Teiichi

    2015-01-01

    Chronic stress is associated with anxiety and depressive disorders, and can cause weight gain. Ca(2+)-dependent activator protein for secretion 2 (CAPS2) is involved in insulin release. Caps2 knockout (KO) mice exhibit decreased body weight, reduced glucose-induced insulin release, and abnormal psychiatric behaviors. We chronically administered the stress hormone corticosterone (CORT), which induces anxiety/depressive-like behavior and normally increases plasma insulin levels, via the drinking water for 10 weeks, and we examined the stress response in KO mice. Chronic CORT exposure inhibited stress-induced serum CORT elevation in wild-type (WT) mice, but not in KO mice. Poor weight gain in CORT-treated animals was observed until week 6 in WT mice, but persisted for the entire duration of the experiment in KO mice, although there is no difference in drug*genotype interaction. Among KO mice, food consumption was unchanged, while water consumption was higher, over the duration of the experiment in CORT-treated animals, compared with untreated animals. Moreover, serum insulin and leptin levels were increased in CORT-treated WT mice, but not in KO mice. Lastly, both WT and KO mice displayed anxiety/depressive-like behavior after CORT administration. These results suggest that Caps2 KO mice have altered endocrine responses to CORT administration, while maintaining CORT-induced anxiety/depressive-like behavior. PMID:25754523

  18. Serum Antibody Response to Koala Retrovirus Antigens Varies in Free-Ranging Koalas ( Phascolarctos cinereus ) in Australia: Implications for Vaccine Design.

    PubMed

    Waugh, Courtney; Gillett, Amber; Polkinghorne, Adam; Timms, Peter

    2016-04-28

    Little is known about the immune response in the koala ( Phascolarctos cinereus ) to its retroviruses. Koala retroviruses (KoRVs) have been linked to neoplasia in wild and captive koalas, but there is no treatment available. We tested the KoRV-specific serum immunoglobulin G antibody response in nonimmunized and immunized koalas. PMID:27054470

  19. aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose tissue is one of the major sites for fatty acid synthesis and lipid storage. We generated adipose (fat)-specific ACC1 knockout (FACC1KO) mice using the aP2-Cre/loxP system. FACC1KO mice showed prenatal growth retardation; after weaning, however, their weight gain was comparable to that of wi...

  20. On Crosslinguistic Variations in Imperfective Aspect: The Case of L2 Korean

    ERIC Educational Resources Information Center

    Lee, EunHee; Kim, Hae-Young

    2007-01-01

    This article examines the acquisition of Korean imperfective markers, the progressive "-ko iss-" and the resultative "-a iss-," with a view to understanding how tense/aspect morphology expands beyond prototype associations with inherent aspects of the verbs. We hypothesized that "-a iss-" will develop later than "-ko iss-," but that the…

  1. Involvement of endogenous neuromedin U and neuromedin S in thermoregulation.

    PubMed

    Nakahara, Keiko; Akagi, Ai; Shimizu, Seiya; Tateno, Satoshi; Qattali, Abdul Wahid; Mori, Kenji; Miyazato, Mikiya; Kangawa, Kenji; Murakami, Noboru

    2016-02-19

    We investigated the possible involvement of neuromedin U (NMU) and neuromedin S (NMS) in thermoregulation in rats. Intracerebroventricular (icv) injection of NMU or NMS increased the back surface temperature (BS-T) in a dose-dependent manner during both the light and dark periods. Pre-treatment with the β3 blocker SR59230A, and the cyclooxygenase blocker indomethacin, inhibited the increase in BS-T induced by NMS. Icv injection of NMS and NMU increased the expression of mRNAs for prostaglandin E synthase and cyclooxygenase 2 (COX2) in the hypothalamus, and that of mRNA for uncoupling protein 1 (UCP1) in the brown adipose tissue. Comparison of thermogenesis in terms of body temperature under normal and cold conditions revealed that NMS-KO and double-KO mice had a significantly low BS-T during the active phase, whereas NMU-KO mice did not. Exposure to low temperature decreased the BS temperature in all KO mice, but BS-T was lower in NMS-KO and double-KO mouse than in NMU-KO mice. Calorie and oxygen consumption was also significantly lower in all KO mice than in wild-type mice during the dark period. These results suggest that NMU and NMS are involved in thermoregulation via the prostaglandin E2 and β3 adrenergic receptors, but that endogenous NMS might play a more predominant role than NMU. PMID:26826380

  2. XB130 promotes bronchioalveolar stem cell and Club cell proliferation in airway epithelial repair and regeneration

    PubMed Central

    Toba, Hiroaki; Wang, Yingchun; Bai, Xiaohui; Zamel, Ricardo; Cho, Hae-Ra; Liu, Hongmei; Lira, Alonso; Keshavjee, Shaf; Liu, Mingyao

    2015-01-01

    Proliferation of bronchioalveolar stem cells (BASCs) is essential for epithelial repair. XB130 is a novel adaptor protein involved in the regulation of epithelial cell survival, proliferation and migration through the PI3K/Akt pathway. To determine the role of XB130 in airway epithelial injury repair and regeneration, a naphthalene-induced airway epithelial injury model was used with XB130 knockout (KO) mice and their wild type (WT) littermates. In XB130 KO mice, at days 7 and 14, small airway epithelium repair was significantly delayed with fewer number of Club cells (previously called Clara cells). CCSP (Club cell secreted protein) mRNA expression was also significantly lower in KO mice at day 7. At day 5, there were significantly fewer proliferative epithelial cells in the KO group, and the number of BASCs significantly increased in WT mice but not in KO mice. At day 7, phosphorylation of Akt, GSK-3β, and the p85α subunit of PI3K was observed in airway epithelial cells in WT mice, but to a much lesser extent in KO mice. Microarray data also suggest that PI3K/Akt-related signals were regulated differently in KO and WT mice. An inhibitory mechanism for cell proliferation and cell cycle progression was suggested in KO mice. XB130 is involved in bronchioalveolar stem cell and Club cell proliferation, likely through the PI3K/Akt/GSK-3β pathway. PMID:26360608

  3. Similar phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage.

    PubMed

    Asai, Masato; Asai, Naoya; Murata, Ayana; Yokota, Hirofumi; Ohmori, Kenji; Mii, Shinji; Enomoto, Atsushi; Murakumo, Yoshiki; Takahashi, Masahide

    2012-10-01

    Girdin is an Akt substrate and actin-binding protein. Mice with germ-line deletions of Girdin (a non-conditional knockout, (ncKO)) exhibit complete postnatal lethality accompanied by growth retardation and neuronal cell migration defects, which results in hypoplasia of the olfactory bulb and granule cell dispersion in the dentate gyrus. However, the physiological and molecular abnormalities in Girdin ncKO mice are not fully understood. In this study, we first defined the distribution of Girdin in neonates (P1) and adults (6months or older) using β-galactosidase activity in tissues from ncKO mice. The results indicate that Girdin is expressed throughout the nervous system (brain, spinal cord, enteric and autonomic nervous systems). In addition, β-galactosidase activity was detected in non-neural tissues, particularly in tissues with high tensile force, such as tendons, heart valves, and skeletal muscle. In order to identify the cellular population where the Girdin ncKO phenotype originates, newly generated Girdin flox mice were crossed with nestin promoter-driven Cre transgenic mice to obtain Girdin conditional knockout (cKO) mice. The phenotype of Girdin cKO mice was almost identical to ncKO mice, including postnatal lethality, growth retardation and decreased neuronal migration. Our findings indicate that loss of Girdin in the nestin cell lineage underlies the phenotype of Girdin ncKO mice. PMID:22974978

  4. Analysis of metabolic effects of menthol on WFS1-deficient mice.

    PubMed

    Ehrlich, Marite; Ivask, Marilin; Raasmaja, Atso; Kõks, Sulev

    2016-01-01

    In this study, we investigated the physiological regulation of energy metabolism in wild-type (WT) and WFS1-deficient (Wfs1KO) mice by measuring the effects of menthol treatment on the O2 consumption, CO2 production, rectal body temperature, and heat production. The basal metabolism and behavior was different between these genotypes as well as TRP family gene expressions. Wfs1KO mice had a shorter life span and weighed less than WT mice. The food and water intake of Wfs1KO mice was lower as well as the body temperature when compared to their WT littermates. Furthermore, Wfs1KO mice had higher basal O2 consumption, and CO2 and heat production than WT mice. In addition, Wfs1KO mice showed a higher response to menthol administration in comparison to WT mice. The strongest menthol effect was seen on different physiological measures 12 h after oral administration. The highest metabolic response of Wfs1KO mice was seen at the menthol dose of 10 mg/kg. Menthol increased O2 consumption, and CO2 and heat production in Wfs1KO mice when compared to their WT littermates. In addition, the expression of Trpm8 gene was increased. In conclusion, our results show that the Wfs1KO mice develop a metabolic phenotype characterized with several physiological dysfunctions. PMID:26733243

  5. Opposing Roles of Tyrosine Kinase Receptors Mer and Axl Determine Clinical Outcomes in Experimental Immune-Mediated Nephritis.

    PubMed

    Zhen, Yuxuan; Priest, Stephen O; Shao, Wen-Hai

    2016-09-15

    Glomerulonephritis is one of the most severe manifestations of systemic lupus erythematosus, with considerable morbidity and mortality. There remains a major unmet need for successful management of lupus nephritis. TAM family receptor tyrosine kinases (Mer and Axl) play an important role in the maintenance of immune homeostasis in the kidney. Mer is constitutively expressed in the glomeruli; Axl expression is inducible in glomeruli under inflammatory conditions. To investigate the distinct functions of Axl and Mer in lupus nephritis, we compared the severity of nephrotoxic serum glomerulonephritis in wild-type (WT), Axl-knockout (KO), Mer-KO, and Axl/Mer-KO mice. Mer-KO mice developed severe glomerulonephritis, with significantly decreased survival and increased blood urea nitrogen levels compared with WT mice given the same treatment. However, nephrotoxic serum-treated Axl-KO mice had significantly increased survival rates and improved renal function compared with similarly treated WT, Mer-KO, and Axl/Mer-KO mice. Interestingly, mice lacking both Axl and Mer developed kidney inflammation comparable to WT mice. Western blot analysis revealed significantly increased Stat3 phosphorylation and caspase-1 activation in the kidneys of nephritic Mer-KO mice. In contrast, Axl-deficient nephrotoxic serum-injected mice showed decreased Akt phosphorylation and Bcl-xL upregulation. Thus, the reciprocal activation of Axl and Mer receptor tyrosine kinases has a major impact on the outcome of renal inflammation. PMID:27527599

  6. Attenuated Response to Methamphetamine Sensitization and Deficits in Motor Learning and Memory after Selective Deletion of [beta]-Catenin in Dopamine Neurons

    ERIC Educational Resources Information Center

    Diaz-Ruiz, Oscar; Zhang, YaJun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F.; Ladenheim, Bruce; Cadet, Jean Lud; Lupica, Carl R.; Tagliaferro, Adriana; Brusco, Alicia; Backman, Cristina M.

    2012-01-01

    In the present study, we analyzed mice with a targeted deletion of [beta]-catenin in DA neurons (DA-[beta]cat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-[beta]cat KO mice showed significant…

  7. Contribution of Invariant Natural Killer T Cells to Skin Wound Healing.

    PubMed

    Tanno, Hiromasa; Kawakami, Kazuyoshi; Ritsu, Masae; Kanno, Emi; Suzuki, Aiko; Kamimatsuno, Rina; Takagi, Naoyuki; Miyasaka, Tomomitsu; Ishii, Keiko; Imai, Yoshimichi; Maruyama, Ryoko; Tachi, Masahiro

    2015-12-01

    In the present study, we determined the contribution of invariant natural killer T (iNKT) cells to the skin wound healing process. In iNKT cell-deficient (Jα18KO) mice lacking iNKT cells, wound closure was significantly delayed compared with wild-type mice. Collagen deposition, expression of α-smooth muscle actin and CD31, and wound breaking strength were significantly attenuated in Jα18KO mice. The adoptive transfer of liver mononuclear cells from wild-type but not from Jα18KO or interferon (IFN)-γ gene-disrupted (IFN-γKO) mice resulted in the reversal of this impaired wound healing in Jα18KO mice. IFN-γ expression was induced in the wounded tissues, which was significantly decreased at 6, 12, and 24 hours, but increased on day 3 after wounding in Jα18KO mice. The main source of the late-phase IFN-γ production in Jα18KO mice were neutrophils rather than NK cells and T cells. Administration of α-galactosylceramide, an activator of iNKT cells, resulted in the acceleration of wound healing on day 3 in wild-type mice. This effect was not observed in IFN-γKO mice. These results indicate that iNKT cells play important roles in wound healing. The iNKT cell-induced IFN-γ production may regulate the wound healing process in the early phase. PMID:26468976

  8. Impaired Discrimination Learning in Mice Lacking the NMDA Receptor NR2A Subunit

    ERIC Educational Resources Information Center

    Brigman, Jonathan L.; Feyder, Michael; Saksida, Lisa M.; Bussey, Timothy J.; Mishina, Masayoshi; Holmes, Andrew

    2008-01-01

    N-Methyl-D-aspartate receptors (NMDARs) mediate certain forms of synaptic plasticity and learning. We used a touchscreen system to assess NR2A subunit knockout mice (KO) for (1) pairwise visual discrimination and reversal learning and (2) acquisition and extinction of an instrumental response requiring no pairwise discrimination. NR2A KO mice…

  9. Leishmania (Viannia) braziliensis amastigotes from patients with mucosal leishmaniasis have increased ability to disseminate and are controlled by nitric oxide at the early stage of murine infection.

    PubMed

    Gomes, Clayson M; Ávila, Lucilla R; Santos, Jéssica C; Oliveira, Pollyana G; Tomé, Fernanda D; Pereira, Ledice I A; Dorta, Miriam L; Lino, Ruy S; Ribeiro-Dias, Fátima; Oliveira, Milton A P

    2016-06-01

    Mucosal leishmaniasis (ML) caused by Leishmania (Vianna) braziliensis usually appears after the healing of the primary lesion when amastigotes disseminate from the infection site to the mucosal area. Here, we investigated murine infection with amastigotes obtained from patients with ML or localized cutaneous leishmaniasis (LCL). Amastigotes were used to infect wild type, IFN-γ KO and inducible nitric oxide synthase (iNOS) KO mice. Amastigotes from patients with LCL induced lesions that appeared earlier in IFN-γ KO than parasites from ML. The lesion after infection with ML appeared early in iNOS KO than in IFN-γ KO mice and in iNOS KO mice parasites from ML and LCL cause similar lesions at the initial phase of infection, while parasites from ML induced greater lesions than the ones from LCL at the late phase. A greater number of parasites were observed in spleen of IFN-γ KO and iNOS KO mice infected with amastigotes from patients with ML than those with LCL. Parasites from ML infect a lower percentage of macrophages and are killed independent on IFN-γ and dependent on NO. The data suggest that amastigotes responsible for mucosal lesion in humans develop slowly on the initial phase of infection due to high susceptibility to NO and they have an increased ability to disseminate. PMID:27073255

  10. Thyroid follicle development requires Smad1/5- and endothelial cell-dependent basement membrane assembly.

    PubMed

    Villacorte, Mylah; Delmarcelle, Anne-Sophie; Lernoux, Manon; Bouquet, Mahé; Lemoine, Pascale; Bolsée, Jennifer; Umans, Lieve; de Sousa Lopes, Susana Chuva; Van Der Smissen, Patrick; Sasaki, Takako; Bommer, Guido; Henriet, Patrick; Refetoff, Samuel; Lemaigre, Frédéric P; Zwijsen, An; Courtoy, Pierre J; Pierreux, Christophe E

    2016-06-01

    Thyroid follicles, the functional units of the thyroid gland, are delineated by a monolayer of thyrocytes resting on a continuous basement membrane. The developmental mechanisms of folliculogenesis, whereby follicles are formed by the reorganization of a non-structured mass of non-polarized epithelial cells, are largely unknown. Here we show that assembly of the epithelial basement membrane is crucial for folliculogenesis and is controlled by endothelial cell invasion and by BMP-Smad signaling in thyrocytes. Thyroid-specific Smad1 and Smad5 double-knockout (Smad1/5(dKO)) mice displayed growth retardation, hypothyroidism and defective follicular architecture. In Smad1/5(dKO) embryonic thyroids, epithelial cells remained associated in large clusters and formed small follicles. Although similar follicular defects are found in Vegfa knockout (Vegfa(KO)) thyroids, Smad1/5(dKO) thyroids had normal endothelial cell density yet impaired endothelial differentiation. Interestingly, both Vegfa(KO) and Smad1/5(dKO) thyroids displayed impaired basement membrane assembly. Furthermore, conditioned medium (CM) from embryonic endothelial progenitor cells (eEPCs) rescued the folliculogenesis defects of both Smad1/5(dKO) and Vegfa(KO) thyroids. Laminin α1, β1 and γ1, abundantly released by eEPCs into CM, were crucial for folliculogenesis. Thus, epithelial Smad signaling and endothelial cell invasion promote folliculogenesis via assembly of the basement membrane. PMID:27068110

  11. DBI/ACBP loss-of-function does not affect anxiety-like behaviour but reduces anxiolytic responses to diazepam in mice.

    PubMed

    Budry, Lionel; Bouyakdan, Khalil; Tobin, Stephanie; Rodaros, Demetra; Marcher, Ann-Britt; Mandrup, Susanne; Fulton, Stephanie; Alquier, Thierry

    2016-10-15

    Diazepam is well known for its anxiolytic properties, which are mediated via activation of the GABAA receptor. Diazepam Binding Inhibitor (DBI), also called acyl-CoA binding protein (ACBP), is a ubiquitously expressed protein originally identified based on its ability to displace diazepam from its binding site on the GABAA receptor. Central administration of ACBP or its cleaved fragment, commonly referred to as endozepines, induces proconflict and anxiety-like behaviour in rodents. For this reason, ACBP is known as an anxiogenic peptide. However, the role of endogenous ACBP in anxiety-like behaviour and anxiolytic responses to diazepam has not been investigated. To address this question, we assessed anxiety behaviour and anxiolytic responses to diazepam in two complementary loss-of-function mouse models including astrocyte-specific ACBP KO (ACBP(GFAP) KO) and whole-body KO (ACBP KO) mice. Male and female ACBP(GFAP) KO and ACBP KO mice do not show significant changes in anxiety-like behaviour compared to control littermates during elevated plus maze (EPM) and open field (OF) tests. Surprisingly, ACBP(GFAP) KO and ACBP KO mice were unresponsive to the anxiolytic effect of a low dose of diazepam during EPM tests. In conclusion, our experiments using genetic ACBP loss-of-function models suggest that endozepines deficiency does not affect anxiety-like behaviour in mice and impairs the anxiolytic action of diazepam. PMID:27363924

  12. Imbalance between Glutamate and GABA in Fmr1 Knockout Astrocytes Influences Neuronal Development

    PubMed Central

    Wang, Lu; Wang, Yan; Zhou, Shimeng; Yang, Liukun; Shi, Qixin; Li, Yujiao; Zhang, Kun; Yang, Le; Zhao, Minggao; Yang, Qi

    2016-01-01

    Fragile X syndrome (FXS) is a form of inherited mental retardation that results from the absence of the fragile X mental retardation protein (FMRP), the product of the Fmr1 gene. Numerous studies have shown that FMRP expression in astrocytes is important in the development of FXS. Although astrocytes affect neuronal dendrite development in Fmr1 knockout (KO) mice, the factors released by astrocytes are still unclear. We cultured wild type (WT) cortical neurons in astrocyte-conditioned medium (ACM) from WT or Fmr1 KO mice. Immunocytochemistry and Western blotting were performed to detect the dendritic growth of both WT and KO neurons. We determined glutamate and γ-aminobutyric acid (GABA) levels using high-performance liquid chromatography (HPLC). The total neuronal dendritic length was reduced when cultured in the Fmr1 KO ACM. This neurotoxicity was triggered by an imbalanced release of glutamate and GABA from Fmr1 KO astrocytes. We found increased glutaminase and GABA transaminase (GABA-T) expression and decreased monoamine oxidase B expression in Fmr1 KO astrocytes. The elevated levels of glutamate contributed to oxidative stress in the cultured neurons. Vigabatrin (VGB), a GABA-T inhibitor, reversed the changes caused by glutamate and GABA release in Fmr1 KO astrocytes and the abnormal behaviors in Fmr1 KO mice. Our results indicate that the imbalance in the astrocytic glutamate and GABA release may be involved in the neuropathology and the underlying symptoms of FXS, and provides a therapeutic target for treatment. PMID:27517961

  13. New insight into the role of MMP14 in metabolic balance

    PubMed Central

    Bhat, Ramray; Bruni-Cardoso, Alexandre; Chen, Emily I.; Jorgens, Danielle M.; Coutinho, Kester; Louie, Katherine; Bowen, Benjamin Ben; Inman, Jamie L.; Tecca, Victoria; Lee, Sarah J.; Becker-Weimann, Sabine; Northen, Trent; Seiki, Motoharu; Borowsky, Alexander D.; Auer, Manfred

    2016-01-01

    Membrane-anchored matrix metalloproteinase 14 (MMP14) is involved broadly in organ development through both its proteolytic and signal-transducing functions. Knockout of Mmp14 (KO) in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is poorly understood. Since the mammary gland develops after birth and is thus dependent for its functional progression on systemic and local cues, we chose it as an organ model for understanding why KO mice fail to thrive. A global analysis of the mammary glands’ proteome in the wild type (WT) and KO mice provided insight into an unexpected role of MMP14 in maintaining metabolism and homeostasis. We performed mass spectrometry and quantitative proteomics to determine the protein signatures of mammary glands from 7 to 11 days old WT and KO mice and found that KO rudiments had a significantly higher level of rate-limiting enzymes involved in catabolic pathways. Glycogen and lipid levels in KO rudiments were reduced, and the circulating levels of triglycerides and glucose were lower. Analysis of the ultrastructure of mammary glands imaged by electron microscopy revealed a significant increase in autophagy signatures in KO mice. Finally, Mmp14 silenced mammary epithelial cells displayed enhanced autophagy. Applied to a systemic level, these findings indicate that MMP14 is a crucial regulator of tissue homeostasis. If operative on a systemic level, these findings could explain how Mmp14KO litter fail to thrive due to disorder in metabolism. PMID:27478693

  14. A cell-death-defying factor, anamorsin mediates cell growth through inactivation of PKC and p38MAPK

    SciTech Connect

    Saito, Yuri; Shibayama, Hirohiko; Tanaka, Hirokazu; Tanimura, Akira; Kanakura, Yuzuru

    2011-02-11

    Research highlights: {yields} Anamorsin (AM) (also called CIAPIN-1) is a cell-death-defying factor. {yields} Biological mechanisms of AM functions have not been elucidated yet. {yields} PKC{theta} , PKC{delta} and p38MAPK were more phosphorylated in AM deficient MEF cells. {yields} AM may negatively regulates PKCs and p38MAPK in MEF cells. -- Abstract: Anamorsin (AM) plays crucial roles in hematopoiesis and embryogenesis. AM deficient (AM KO) mice die during late gestation; AM KO embryos are anemic and very small compared to wild type (WT) embryos. To determine which signaling pathways AM utilizes for these functions, we used murine embryonic fibroblast (MEF) cells generated from E-14.5 AM KO or WT embryos. Proliferation of AM KO MEF cells was markedly retarded, and PKC{theta}, PKC{delta}, and p38MAPK were more highly phosphorylated in AM KO MEF cells. Expression of cyclinD1, the target molecule of p38MAPK, was down-regulated in AM KO MEF cells. p38MAPK inhibitor as well as PKC inhibitor restored expression of cyclinD1 and cell growth in AM KO MEF cells. These data suggest that PKC{theta}, PKC{delta}, and p38MAPK activation lead to cell cycle retardation in AM KO MEF cells, and that AM may negatively regulate novel PKCs and p38MAPK in MEF cells.

  15. Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging.

    PubMed

    Arum, Oge; Saleh, Jamal; Boparai, Ravneet; Turner, Jeremy; Kopchick, John; Khardori, Romesh; Bartke, Andrzej

    2014-01-01

    The correlation of physiological sensitivity to insulin ( vis-à-vis glycemic regulation) and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity). The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR) by altering their insulin sensitivity. We hypothesized that maximized insulin responsiveness is what causes GHR-KO mice to exhibit a suppressed survivorship response to dietary (including caloric) restriction; and attempted to refute this hypothesis by assessing the effects of CR on GHR-KO mice for varied slow-aging-associated phenotypes. In contrast to previous reports, we found GHR-KO mice on CR to be less responsive than their ad libitum (A.L.) counterparts to the hypoglycemia-inducing effects of insulin. Further, CR had negligible effects on the metabolism or cognition of GHR-KO mice. Therefore, our data suggest that the effects of CR on the insulin sensitivity of GHR-KO mice do not concur with the effects of CR on the aging of GHR-KO mice. PMID:25789159

  16. MyD88 and TRIF mediate divergent inflammatory and regenerative responses to skeletal muscle ischemia

    PubMed Central

    Sachdev, Ulka; Cui, Xiangdong; Xu, Jia; Xu, Jun; Tzeng, Edith

    2014-01-01

    Abstract We have previously shown that MyD88 KO mice appear protected from ischemic muscle injury while TRIF KO mice exhibit sustained necrosis after femoral artery ligation (FAL). However, our previous data did not differentiate whether the protective effect of absent MyD88 signaling was secondary to attenuated injury after FAL or quicker recovery from the insult. The purpose of this study was to delineate these different possibilities. On the basis of previous findings, we hypothesized that MyD88 signaling promotes enhanced inflammation while TRIF mediates regeneration after skeletal muscle ischemia. Our results show that after FAL, both MyD88 KO mice and TRIF KO mice have evidence of ischemia, as do their control counterparts. However, MyD88 KO mice had lower levels of serum IL‐6 24 h after FAL, while TRIF KO mice demonstrated sustained serum IL‐6 up to 1 week after injury. Additionally, MyD88 KO mice had higher nuclear content and larger myofibers than control animals 1 week after injury. IL‐6 is known to have differential effects in myoblast function, and can inhibit proliferation and differentiation. In tibialis anterior muscle harvested from injured animals, IL‐6 levels were higher and the proliferative marker MyoD was lower in TRIF KO mice by PCR. Furthermore, expression of MyD88 appeared to be higher in skeletal muscle of TRIF KO mice. In vitro, we showed that myoblast differentiation and proliferation were attenuated in response to IL‐6 treatment giving credence to the finding that low IL‐6 in MyD88 KO mice may be responsible for larger myocyte sizes 1 week after FAL. We conclude that MyD88 and TRIF work in concert to mediate a balanced response to ischemic injury. PMID:24844636

  17. Proliferation of Endogenous Retroviruses in the Early Stages of a Host Germ Line Invasion

    PubMed Central

    Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D.; Roca, Alfred L.

    2015-01-01

    Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire–dam–progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5′- and 3′-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5′-LTR sequence was identical to the 3′-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200–49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. PMID:25261407

  18. Nonlinear behaviour of conduction and block in cardiac tissue with heterogeneous expression of connexin 43.

    PubMed

    Prudat, Yann; Kucera, Jan P

    2014-11-01

    Altered gap junctional coupling potentiates slow conduction and arrhythmias. To better understand how heterogeneous connexin expression affects conduction at the cellular scale, we investigated conduction in tissue consisting of two cardiomyocyte populations expressing different connexin levels. Conduction was mapped using microelectrode arrays in cultured strands of foetal murine ventricular myocytes with predefined contents of connexin 43 knockout (Cx43KO) cells. Corresponding computer simulations were run in randomly generated two-dimensional tissues mimicking the cellular architecture of the strands. In the cultures, the relationship between conduction velocity (CV) and Cx43KO cell content was nonlinear. CV first decreased significantly when Cx43KO content was increased from 0 to 50%. When the Cx43KO content was ≥60%, CV became comparable to that in 100% Cx43KO strands. Co-culturing Cx43KO and wild-type cells also resulted in significantly more heterogeneous conduction patterns and in frequent conduction blocks. The simulations replicated this behaviour of conduction. For Cx43KO contents of 10-50%, conduction was slowed due to wavefront meandering between Cx43KO cells. For Cx43KO contents ≥60%, clusters of remaining wild-type cells acted as electrical loads that impaired conduction. For Cx43KO contents of 40-60%, conduction exhibited fractal characteristics, was prone to block, and was more sensitive to changes in ion currents compared to homogeneous tissue. In conclusion, conduction velocity and stability behave in a nonlinear manner when cardiomyocytes expressing different connexin amounts are combined. This behaviour results from heterogeneous current-to-load relationships at the cellular level. Such behaviour is likely to be arrhythmogenic in various clinical contexts in which gap junctional coupling is heterogeneous. PMID:25128085

  19. Nax signaling evoked by an increase in [Na+] in CSF induces water intake via EET-mediated TRPV4 activation.

    PubMed

    Sakuta, Hiraki; Nishihara, Eri; Hiyama, Takeshi Y; Lin, Chia-Hao; Noda, Masaharu

    2016-08-01

    Water-intake behavior is under the control of brain systems that sense body fluid conditions at sensory circumventricular organs (sCVOs); however, the underlying mechanisms have not yet been elucidated in detail. Nax is a sodium (Na(+)) level sensor in the brain, and the transient receptor potential vanilloid (TRPV) channels TRPV1 and TRPV4 have been proposed to function as osmosensors. We herein investigated voluntary water intake immediately induced after an intracerebroventricular administration of a hypertonic NaCl solution in TRPV1-, TRPV4-, Nax-, and their double-gene knockout (KO) mice. The induction of water intake by TRPV1-KO mice was normal, whereas intake by TRPV4-KO and Nax-KO mice was significantly less than that by WT mice. Water intake by Nax/TRPV4-double KO mice was similar to that by the respective single KO mice. When TRPV4 activity was blocked with a specific antagonist HC-067047, water intake by WT mice was significantly reduced, whereas intake by TRPV4-KO and Nax-KO mice was not. Similar results were obtained with the administration of miconazole, which inhibits the biosynthesis of epoxyeicosatrienoic acids (EETs), endogenous agonists for TRPV4, from arachidonic acid (AA). Intracerebroventricular injection of hypertonic NaCl with AA or 5,6-EET restored water intake by Nax-KO mice to the wild-type level but not that by TRPV4-KO mice. These results suggest that the Na(+) signal generated in Nax-positive glial cells leads to the activation of TRPV4-positive neurons in sCVOs to stimulate water intake by using EETs as gliotransmitters. Intracerebroventricular injection of equiosmolar hypertonic sorbitol solution induced small but significant water intake equally in all the genotypes, suggesting the presence of an unknown osmosensor in the brain. PMID:27252474

  20. Proliferation of endogenous retroviruses in the early stages of a host germ line invasion.

    PubMed

    Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D; Roca, Alfred L

    2015-01-01

    Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire-dam-progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5'- and 3'-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5'-LTR sequence was identical to the 3'-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200-49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. PMID:25261407

  1. Effects of gender on locomotor sensitivity to amphetamine, body weight, and fat mass in regulator of G protein signaling 9 (RGS9) knockout mice.

    PubMed

    Walker, Paul D; Jarosz, Patricia A; Bouhamdan, Mohamad; MacKenzie, Robert G

    2015-01-01

    Regulator of G-protein signaling (RGS) protein 9-2 is enriched in the striatum where it modulates dopamine and opioid receptor-mediated signaling. RGS9 knockout (KO) mice show increased psychostimulant-induced behavioral sensitization, as well as exhibit higher body weights and greater fat accumulation compared to wild-type (WT) littermates. In the present study, we found gender influences on each of these phenotypic characteristics. Female RGS9 KO mice exhibited greater locomotor sensitization to amphetamine (1.0mg/kg) treatment as compared to male RGS9 KO mice. Male RGS9 KO mice showed increased body weights as compared to male WT littermates, while no such differences were detected in female mice. Quantitative magnetic resonance showed that male RGS9 KO mice accumulated greater fat mass vs. WT littermates at 5months of age. Such observations could not be explained by increased caloric consumption since male and female RGS9 KO mice demonstrated equivalent daily food intake as compared to their respective WT littermates. Although indirect calorimetry methods found decreased oxygen consumption and carbon dioxide production during the 12-hour dark phase in male RGS9 KO vs. WT mice which are indicative of less energy expenditure, male RGS9 KO mice exhibited lower levels of locomotor activity during this period. Genotype had no effect on metabolic activities when KO and WT groups were compared under fasting vs. feeding treatments. In summary, these results highlight the importance of factoring gender into the experimental design since many studies conducted in RGS9 KO mice utilize locomotor activity as a measured outcome. PMID:25455864

  2. PPARγ deficiency results in severe, accelerated osteoarthritis associated with aberrant mTOR signalling in the articular cartilage

    PubMed Central

    Vasheghani, Faezeh; Zhang, Yue; Li, Ying-Hua; Blati, Meryem; Fahmi, Hassan; Lussier, Bertrand; Roughley, Peter; Lagares, David; Endisha, Helal; Saffar, Bahareh; Lajeunesse, Daniel; Marshall, Wayne K; Rampersaud, Y Raja; Mahomed, Nizar N; Gandhi, Rajiv; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Kapoor, Mohit

    2015-01-01

    Objectives We have previously shown that peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor, is essential for the normal growth and development of cartilage. In the present study, we created inducible cartilage-specific PPARγ knockout (KO) mice and subjected these mice to the destabilisation of medial meniscus (DMM) model of osteoarthritis (OA) to elucidate the specific in vivo role of PPARγ in OA pathophysiology. We further investigated the downstream PPARγ signalling pathway responsible for maintaining cartilage homeostasis. Methods Inducible cartilage-specific PPARγ KO mice were generated and subjected to DMM model of OA. We also created inducible cartilage-specific PPARγ/mammalian target for rapamycin (mTOR) double KO mice to dissect the PPARγ signalling pathway in OA. Results Compared with control mice, PPARγ KO mice exhibit accelerated OA phenotype with increased cartilage degradation, chondrocyte apoptosis, and the overproduction of OA inflammatory/catabolic factors associated with the increased expression of mTOR and the suppression of key autophagy markers. In vitro rescue experiments using PPARγ expression vector reduced mTOR expression, increased expression of autophagy markers and reduced the expression of OA inflammatory/catabolic factors, thus reversing the phenotype of PPARγ KO mice chondrocytes. To dissect the in vivo role of mTOR pathway in PPARγ signalling, we created and subjected PPARγ-mTOR double KO mice to the OA model to see if the genetic deletion of mTOR in PPARγ KO mice (double KO) can rescue the accelerated OA phenotype observed in PPARγ KO mice. Indeed, PPARγ-mTOR double KO mice exhibit significant protection/reversal from OA phenotype. Significance PPARγ maintains articular cartilage homeostasis, in part, by regulating mTOR pathway. PMID:25573665

  3. K+ homeostasis and central pattern generation in the metathoracic ganglion of the locust.

    PubMed

    Rodgers, Corinne I; Labrie, John D; Robertson, R Meldrum

    2009-07-01

    Stress-induced arrest of ventilatory motor pattern generation is tightly correlated with an abrupt increase in extracellular potassium concentration ([K+]o) within the metathoracic neuropil of the locust, Locusta migratoria. Na+/K+-ATPase inhibition with ouabain elicits repetitive surges of [K+]o that coincide with arrest and recovery of motor activity. Here we show that ouabain induces repetitive [K+]o events in a concentration-dependent manner. 10(-5)M, 10(-4)M, and 10(-3)M ouabain was bath-applied in semi-intact locust preparations. 10(-4)M and 10(-3)M ouabain reliably induced repetitive [K+]o events whereas 10(-5)M ouabain had no significant effect. In comparison to 10(-4)M ouabain, 10(-3)M ouabain increased the number and hastened the time to onset of repetitive [K+]o waves, prolonged [K+]o event duration, increased resting [K+]o, and diminished the absolute value of [K+]o waves. Recovery of motor patterning following [K+]o events was less likely in 10(-3)M ouabain. In addition, we show that K+ channel inhibition using TEA suppressed the onset and decreased the amplitude of ouabain-induced repetitive [K+]o waves. Our results demonstrate that ventilatory circuit function in the locust CNS is dependent on the balance between mechanisms of [K+] accumulation and [K+] clearance. We suggest that with an imbalance in favour of accumulation the system tends towards a bistable state with transitions mediated by positive feedback involving voltage-dependent K+ channels. PMID:19482133

  4. Enhanced cognitive function and antidepressant-like effects after krill oil supplementation in rats

    PubMed Central

    2013-01-01

    Background The purpose of the study was to evaluate the effects of krill oil (KO) on cognition and depression-like behaviour in rats. Methods Cognition was assessed using the Aversive Light Stimulus Avoidance Test (ALSAT). The Unavoidable Aversive Light Stimulus (UALST) and the Forced Swimming Test (FST) were used to evaluate the antidepressant-like effects of KO. Imipramine (IMIP) was used as the antidepressant reference substance. Results After 7 weeks of KO intake, both males and females treated with KO were significantly better in discriminating between the active and the inactive levers in the ALSAT from day 1 of training (p<0.01). Both KO and IMIP prevented resignation/depression on the third day in the UALST. Similarly, a shorter immobility time was observed for the KO and IMIP groups compared to the control in the FST (p<0.001). These data support a robust antidepressant-like potential and beneficial cognitive effect of KO. Changes in expression of synaptic plasticity-related genes in the prefrontal cortex and hippocampus were also investigated. mRNA for brain-derived neurotrophic factor (Bdnf) was specifically upregulated in the hippocampus of female rats receiving 7 weeks of KO supplementation (p=0.04) and a similar trend was observed in males (p=0.08). Males also exhibited an increase in prefrontal cortex expression of Arc mRNA, a key protein in long-term synaptic plasticity (p=0.05). IMIP induced clear effects on several plasticity related genes including Bdnf and Arc. Conclusions These results indicate that active components (eicosapentaenoic acid, docosahexaenoic acid and astaxanthin) in KO facilitate learning processes and provide antidepressant-like effects. Our findings also suggest that KO might work through different physiological mechanisms than IMIP. PMID:23351783

  5. Vascular reactivity, 5-HT uptake, and blood pressure in the serotonin transporter knockout rat.

    PubMed

    Linder, A Elizabeth; Diaz, Jessica; Ni, Wei; Szasz, Theo; Burnett, Robert; Watts, Stephanie W

    2008-04-01

    The handling of serotonin [5-hydroxytryptamine (5-HT)] depends on the serotonin transporter (SERT). A SERT knockout (KO) rat is a useful model to test the hypothesis that SERT is the primary mechanism for arterial 5-HT uptake and to investigate the impact of SERT removal on blood pressure. Wild-type (WT) and KO rats were used to measure 5-HT content (plasma, raphe, aorta, carotid, and mesenteric artery), aortic isometric contraction, and blood pressure. HPLC supported the lack of circulating 5-HT in plasma (ng/ml plasma, WT, 310 +/- 96; and KO, 1.0 +/- 0.5; P < 0.05). Immunohistochemistry and Western blot analyses validated the presence of the SERT protein in the WT rats and a lesser expression in the KO rat. The aorta isolated from KO rats had a normal contraction to phenylephrine and norepinephrine and a normal relaxation to the endothelium-dependent agonist acetylcholine compared with the aorta from WT. In contrast, the potency of 5-HT was increased in the aorta from KO rats compared with WT rats [-log EC(50) (M); WT, 5.71 +/- 0.08; and KO, 6.7 +/- 0.18] and maximum contraction was reduced [%phenylephrine (10 muM) contraction, WT, 113 +/- 6%; and KO, 52 +/- 12%]. 5-HT uptake was reduced but not abolished in arteries of the KO compared with the WT rats. Diurnal mean arterial blood pressure, heart rate, and locomotor activity level of the KO rats were similar to the WT rats. These data suggest that there are other mechanisms of 5-HT uptake in the arteries of the rat and that although the absence of circulating 5-HT and/or SERT function sensitizes arteries to 5-HT, SERT dysfunction does not impair normal blood pressure. PMID:18263707

  6. Comparison of bioavailability of krill oil versus fish oil and health effect

    PubMed Central

    Ulven, Stine M; Holven, Kirsten B

    2015-01-01

    Background The aim of this review is to summarize the effects of krill oil (KO) or fish oil (FO) on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) incorporation in plasma phospholipids or membrane of red blood cells (RBCs) as shown in human and animal studies. Furthermore, we discuss the findings in relation to the possible different health effects, focusing on lipids, inflammatory markers, cardiovascular disease risk, and biological functions of these two sources of long-chain n-3 polyunsaturated fatty acids (PUFAs). Methods A literature search was conducted in PubMed in January 2015. In total, 113 articles were identified, but based on selection criteria, 14 original papers were included in the review. Results Studies on bioavailability of EPA and DHA from KO and FO in humans and animals are limited and the interpretation is difficult, as different amounts of EPA and DHA have been used, duration of intervention differs, and different study groups have been included. Two human studies – one postprandial study and one intervention study – used the same amount of EPA and DHA from KO or FO, and they both showed that the bioavailability of EPA and DHA from KO seems to be higher than that from FO. Limited effects of KO and FO on lipids and inflammatory markers in human and animal studies were reported. Gene expression data from animal studies showed that FO upregulated the cholesterol synthesis pathway, which was the opposite of the effect mediated by KO. KO also regulated far more metabolic pathways than FO, which may indicate different biological effects of KO and FO. Conclusion There seems to be a difference in bioavailability of EPA and DHA after intake of KO and FO, but more studies are needed before a firm conclusion can be made. It is also necessary to document the beneficial health effects of KO with more human studies and to elucidate if these effects differ from those after regular fish and FO intake. PMID:26357480

  7. Impact of Notch1 Deletion in Macrophages on Proinflammatory Cytokine Production and the Outcome of Experimental Autoimmune Encephalomyelitis.

    PubMed

    Wongchana, Wipawee; Lawlor, Rebecca G; Osborne, Barbara A; Palaga, Tanapat

    2015-12-01

    Notch signaling is involved in regulating TLR-mediated responses in activated macrophages. In this study, we investigated the impact of Notch signaling in macrophages in an experimental autoimmune encephalomyelitis (EAE) model. To examine the impact of deficiency in Notch signaling in activated macrophages in EAE, an adoptive transfer of activated macrophages derived from Notch1(fl/fl) × Mx1cre(+/-) (Notch1 knockout [N1KO]) or CSL/Rbp-jκ(fl/fl) × Mx1cre(+/-) (CSL/RBP-Jκ KO) mice was performed prior to induction of EAE. Mice receiving activated N1KO macrophages showed decreased severity of EAE compared with mice receiving wild-type or CSL/RBP-Jκ KO macrophages. In vitro restimulation of splenocytes by myelin oligodendrocyte glycoprotein 35-55 peptide from these mice revealed that cells from mice receiving N1KO macrophages produced significantly less IL-17 compared with the control mice, whereas IFN-γ production was similar in both groups. We found that activated N1KO, but not CSL/RBP-Jκ KO, macrophages produced less IL-6 and had lower CD80 expression compared with wild-type and did not exhibit any defect in IL-12p40/70 production, whereas activated macrophages from CSL/RBP-Jκ KO mice phenocopied γ-secretase inhibitor treatment for reduced IL-12p40/70 production. Furthermore, the nuclear translocation of the NF-κB subunit c-Rel was compromised in γ-secretase inhibitor-treated and CSL/RBP-Jκ KO but not N1KO macrophages. These results suggest that Notch1 and CSL/RBP-Jκ in macrophages may affect the severity of EAE differently, possibly through modulating IL-6 and CD80 expression, which is involved in the Th17 but not Th1 response. PMID:26503951

  8. Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis.

    PubMed

    Wu, Lian; Wang, Feng; Donly, Kevin J; Wan, Chunyan; Luo, Daoshu; Harris, Stephen E; MacDougall, Mary; Chen, Shuo

    2015-11-01

    Bmp2 is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta, showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain lot of primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis. In this study, our goal was to generate an immortalized deleted Bmp2 dental papilla mesenchymal (iBmp2(ko/ko)dp) cell line by introducing Cre recombinase and green fluorescent protein (GFP) into the immortalized mouse floxed Bmp2 dental papilla mesenchymal (iBmp2(fx/fx)dp) cells. iBmp2(ko/ko)dp cells were confirmed by GFP and PCR. The deleted Bmp2 cells exhibited slow cell proliferation rate and cell growth was arrested in G2 phase. Expression of tooth-related marker genes and cell differentiation were decreased in the deleted cells. Importantly, extracellular matrix remodeling was impaired in the iBmp2(ko/ko)dp cells as reflected by the decreased Mmp-9 expression. In addition, with exogenous Bmp2 induction, these cell differentiation and mineralization were rescued as well as extracellular matrix remodeling was enhanced. Therefore, we for the first time described establishment of iBmp(ko/ko) cells that are useful for study of mechanisms in regulating dental papilla mesenchymal cell lineages. PMID:26037045

  9. NG2 proteoglycan-dependent recruitment of tumor macrophages promotes pericyte-endothelial cell interactions required for brain tumor vascularization

    PubMed Central

    Yotsumoto, Fusanori; You, Weon-Kyoo; Cejudo-Martin, Pilar; Kucharova, Karolina; Sakimura, Kenji; Stallcup, William B

    2015-01-01

    Early stage growth of intracranial B16F10 tumors is reduced by 87% in myeloid-specific NG2 null (Mac-NG2ko) mice and by 77% in pericyte-specific NG2 null (PC-NG2ko) mice, demonstrating the importance of the NG2 proteoglycan in each of these stromal compartments. In both genotypes, loss of pericyte-endothelial cell interaction results in numerous structural defects in tumor blood vessels, including decreased formation of endothelial cell junctions and decreased assembly of the vascular basal lamina. All vascular deficits are larger in Mac-NG2ko mice than in PC-NG2ko mice, correlating with the greater decrease in pericyte-endothelial cell interaction in Mac-NG2ko animals. Accordingly, tumor vessels in Mac-NG2ko mice have a smaller diameter, lower degree of patency, and higher degree of leakiness than tumor vessels in PC-NG2ko mice, leading to less efficient tumor blood flow and to increased intratumoral hypoxia. While reduced pericyte interaction with endothelial cells in PC-NG2ko mice is caused by loss of NG2-dependent pericyte activation of β1 integrin signaling in endothelial cells, reduced pericyte-endothelial cell interaction in Mac-NG2ko mice is due to a 90% reduction in NG2-dependent macrophage recruitment to tumors. The absence of a macrophage-derived signal(s) in Mac-NG2ko mice results in the loss of pericyte ability to associate with endothelial cells, possibly due to reduced expression of N-cadherin by both pericytes and endothelial cells. PMID:26137396

  10. Trps1 deficiency inhibits the morphogenesis of secondary hair follicles via decreased Noggin expression

    SciTech Connect

    Sun, Yujing; Nakanishi, Masako; Sato, Fuyuki; Oikawa, Kosuke; Muragaki, Yasuteru; Zhou, Gengyin

    2015-01-16

    Highlights: • The number of secondary hair follicles is reduced by half in Trps1 KO embryonic skin compared to wild-type skin. • Noggin expression is significantly decreased and BMP signaling is promoted in Trps1 KO embryonic skin. • Treatment with a Noggin or BMP inhibitor rescued the decreased number of hair follicles in Trps1 KO skin graft cultures. • Cell proliferation and apoptosis of the epidermis were normalized by Noggin treatment. - Abstract: A representative phenotype of patients with tricho-rhino-phalangeal syndrome (TRPS) is sparse hair. To understand the developmental defects of these patient’s hair follicles, we analyzed the development of hair follicles histologically and biochemically using Trps1 deficient (KO) mice. First, we compared the numbers of primary hair follicles in wild-type (WT) and KO embryos at different developmental stages. No differences were observed in the E14.5 skins of WT and KO mice. However, at later time points, KO fetal skin failed to properly develop secondary hair follicles, and the number of secondary hair follicles present in E18.5 KO skin was approximately half compared to that of WT skin. Sonic hedgehog expression was significantly decreased in E17.5 KO skin, whereas no changes were observed in Eda/Edar expression in E14.5 or E17.5 skins. In addition, Noggin expression was significantly decreased in E14.5 and E17.5 KO skin compared to WT skin. In parallel with the suppression of Noggin expression, BMP signaling was promoted in the epidermal cells of KO skins compared to WT skins as determined by immunohistochemistry for phosphorylated Smad1/5/8. The reduced number of secondary hair follicles was restored in skin graft cultures treated with a Noggin and BMP inhibitor. Furthermore, decreased cell proliferation, and increased apoptosis in KO skin was rescued by Noggin treatment. Taken together, we conclude that hair follicle development in Trps1 KO embryos is impaired directly or indirectly by decreased Noggin