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Sample records for particles affects mouse

  1. A glycoside of Nicotina tabacum affects mouse dopaminergic behavior.

    PubMed

    Masuda, Y; Ohnuma, S; Kawagoe, M; Sugiyama, T

    2003-01-01

    Climbing in the forced swimming test is considered a dopaminergic-specific behavior. A substance of Nicotina tabacum affecting dopamine neuronal activity was investigated using the mouse behavioral system. The substance was found to be a glycoside with the peripheral sugar chain structures Fuc alpha 1-2Gal, Gal beta 1-4GlcNAc and GalNAc alpha 1-3GalNAc and with basic polymannoses. The glycoside dose-dependently increased behavior via D2 neuronal activity, but not D1 activity. This suggests that smoking can affect human brain function not only via the nicotinic cholinergic neuron, but also via the D2 neuron.

  2. Factors affecting the cryosurvival of mouse two-cell embryos.

    PubMed

    Critser, J K; Arneson, B W; Aaker, D V; Huse-Benda, A R; Ball, G D

    1988-01-01

    A series of 4 experiments was conducted to examine factors affecting the survival of frozen-thawed 2-cell mouse embryos. Rapid addition of 1.5 M-DMSO (20 min equilibration at 25 degrees C) and immediate, rapid removal using 0.5 M-sucrose did not alter the frequency (mean +/- s.e.m.) of blastocyst development in vitro when compared to untreated controls (90.5 +/- 2.7% vs 95.3 +/- 2.8%). There was an interaction between the temperature at which slow cooling was terminated and thawing rate. Termination of slow cooling (-0.3 degrees C/min) at -40 degrees C with subsequent rapid thawing (approximately 1500 degrees C/min) resulted in a lower frequency of blastocyst development than did termination of slow cooling at -80 degrees C with subsequent slow thawing (+8 degrees C/min) (36.8 +/- 5.6% vs 63.9 +/- 5.7%). When slow cooling was terminated between -40 and -60 degrees C, higher survival rates were achieved with rapid thawing. When slow cooling was terminated below -60 degrees C, higher survival rates were obtained with slow thawing rates. In these comparisons absolute survival rates were highest among embryos cooled below -60 degrees C and thawed slowly. However, when slow cooling was terminated at -32 degrees C, with subsequent rapid warming, survival rates were not different from those obtained when embryos were cooled to -80 degrees C and thawed slowly (52.4 +/- 9.5%, 59.5 +/- 8.6%). These results suggest that optimal cryosurvival rates may be obtained from 2-cell mouse embryos by a rapid or slow thawing procedure, as has been found for mouse preimplantation embryos at later stages.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. How particle shape affects the flow through granular materials.

    PubMed

    Nemati Hayati, Ali; Ahmadi, Mohammad Mehdi; Mohammadi, Soheil

    2012-03-01

    Flow through the pores of granular materials has many instances in practice. Therefore, it is interesting to realize how some parameters, such as the shape of the particles affect the passing flow. Following the recent mathematical theory proposed by the authors, this paper deals with the issue of how tortuosity and permeability are influenced by the particle shape. Comparison of the results with the experimental data reveals the competency of the theory in predicting the impact of particle geometry.

  4. Traumatic Brain Injury Severity Affects Neurogenesis in Adult Mouse Hippocampus.

    PubMed

    Wang, Xiaoting; Gao, Xiang; Michalski, Stephanie; Zhao, Shu; Chen, Jinhui

    2016-04-15

    Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC) proliferation in the hippocampal dentate gyrus. However, various groups have reported contradictory results on whether TBI increases neurogenesis, partially due to a wide range in the severities of injuries seen with different TBI models. To address whether the severity of TBI affects neurogenesis in the injured brain, we assessed neurogenesis in mouse brains receiving different severities of controlled cortical impact (CCI) with the same injury device. The mice were subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI severity on neurogenesis were evaluated at three stages: NSC proliferation, immature neurons, and newly-generated mature neurons. The results showed that mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI promoted NSC proliferation without increasing neurogenesis. Severe TBI increased neurogenesis at all three stages. Our data suggest that the severity of injury affects adult neurogenesis in the hippocampus, and thus it may partially explain the inconsistent results of different groups regarding neurogenesis following TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide a potential approach for using endogenous NSCs to protect against neuronal loss after trauma.

  5. Do plastic particles affect microalgal photosynthesis and growth?

    PubMed

    Sjollema, Sascha B; Redondo-Hasselerharm, Paula; Leslie, Heather A; Kraak, Michiel H S; Vethaak, A Dick

    2016-01-01

    The unbridled increase in plastic pollution of the world's oceans raises concerns about potential effects these materials may have on microalgae, which are primary producers at the basis of the food chain and a major global source of oxygen. Our current understanding about the potential modes and mechanisms of toxic action that plastic particles exert on microalgae is extremely limited. How effects might vary with particle size and the physico-chemical properties of the specific plastic material in question are equally unelucidated, but may hold clues to how toxicity, if observed, is exerted. In this study we selected polystyrene particles, both negatively charged and uncharged, and three different sizes (0.05, 0.5 and 6μm) for testing the effects of size and material properties. Microalgae were exposed to different polystyrene particle sizes and surface charges for 72h. Effects on microalgal photosynthesis and growth were determined by pulse amplitude modulation fluorometry and flow cytometry, respectively. None of the treatments tested in these experiments had an effect on microalgal photosynthesis. Microalgal growth was negatively affected (up to 45%) by uncharged polystyrene particles, but only at high concentrations (250mg/L). Additionally, these adverse effects were demonstrated to increase with decreasing particle size. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Cadmium stimulates mouse skin fibroblast apoptosis by affecting intracellular homeostasis.

    PubMed

    Wang, Hui; Yu, Yang; Li, Jingshuang; Wu, Handong; Sun, Jing; Zhang, Zhen; Geng, Lijing; Yu, Xiaolei; Liu, Zheng

    2017-01-01

    Cadmium (Cd(2+)) is an important industrial and environmental pollutant and has been shown to induce apoptosis in a variety of cell types and tissues. To assess the specific effects of low-dose Cd(2+ )on the skin. This organ is easily exposed to Cd(2+), but how it damages cells is not fully understood. Mouse skin fibroblasts were treated with low doses of Cd(2+ )(0.4, 0.8 or 1.6 μM) for 12-48 h, and we observed cell morphological alterations, measured DNA damage and quantified cell viability changes. Cd(2+)-treated fibroblasts exhibited morphological changes and evidence of DNA damage, as well as higher numbers of apoptotic and necrotic cells. There were increased caspase -3, -8 and -9 activities when fibroblasts were treated with 0.4, 0.8 and 1.6 μM CdCl2 for 24 h. Higher intracellular calcium (Ca(2+)) and reactive oxygen species (ROS) levels, and enhanced efflux of extracellular Ca(2+ )and potassium (K(+)). The mitochondrial membrane potential was lowered in treated cells, and the cell cycle arrested in the G0/G1 phase. Bax and Fas gene expression increased and Bcl-2 gene expression decreased. The results demonstrate that Cd(2+ )exerts typical apoptotic effects in mouse skin fibroblasts. It strongly inhibited proliferation and induced apoptosis in a dose- and duration-dependent manner. Ca(2+ )homeostasis was disturbed by oxidative stress, mitochondrial dysfunction and caspase-mediated apoptosis. K(+ )efflux and Bax, Bcl-2 and Fas gene expression regulation play important roles in Cd(2+)-induced dysfunction by disrupting intracellular homeostasis in mouse skin fibroblasts.

  7. How particle properties affect the assembly and characteristics of colloidal particle bands

    NASA Astrophysics Data System (ADS)

    Yoda, Minami; Yee, Andrew

    2016-11-01

    The interaction of suspended particles with a planar wall is a classic problem of colloid science. Particle-wall interactions in a flowing suspension are a newer area of interest, motivated by applications in microfluidics. Recent studies show that radius a = 245 nm particles in a dilute (volume fraction φ = 0.17%) suspension are attracted to the wall, form 1D "pearl chains," then assemble into concentrated streamwise bands with a roughly constant cross-stream spacing in combined Poiseuille and electroosmotic flow through fused-silica microchannels. The bands only exist within a few μm of the wall, and occur above a minimum shear rate γ˙ and electric field magnitude | E | . Attracting (i.e., concentrating) the particles to (near) the wall is a prerequisite for band formation; however, bands are not observed in all cases when particles are attracted to the wall. Particle properties appear to have a significant effect on these phenomena: decreasing φ, for example, appears to increase both the minimum γ˙ and | E | for band formation. Results are presented on how the assembly and characteristics of the bands are affected by properties such as φ, a (where a < 1 μ m), and zeta-potential ζp. Supported by ARO.

  8. Functionally Charged Polystyrene Particles Activate Immortalized Mouse Microglia (BV2): Cellular and Genomic Response

    EPA Science Inventory

    The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Same size (~850-950 nm) spherical polystyrene microparticles (SPM) with net negative (carboxyl, COOH-) or positive (dimethyl amino, CH3)2

  9. Functionally Charged Polystyrene Particles Activate Immortalized Mouse Microglia (BV2): Cellular and Genomic Response

    EPA Science Inventory

    The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Same size (~850-950 nm) spherical polystyrene microparticles (SPM) with net negative (carboxyl, COOH-) or positive (dimethyl amino, CH3)2

  10. FACTORS AFFECTING THE DEPOSITION OF INHALED POROUS DRUG PARTICLES

    EPA Science Inventory

    Abstract
    Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol ...

  11. FACTORS AFFECTING THE DEPOSITION OF INHALED POROUS DRUG PARTICLES

    EPA Science Inventory

    Abstract
    Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol ...

  12. Efficacy of a technique for exposing the mouse lung to particles aspirated from the pharynx.

    PubMed

    Rao, G V S; Tinkle, Sally; Weissman, David N; Antonini, James M; Kashon, Michael L; Salmen, Rebecca; Battelli, Lori A; Willard, Patsy A; Hoover, Mark D; Hubbs, Ann F

    2003-08-08

    Recent studies have demonstrated that the mouse lung can be exposed to soluble antigens by aspiration of these antigens from the pharynx. This simple technique avoids the trauma associated with intratracheal instillation. In this study, the pharyngeal aspiration technique was validated for exposing the mouse lung to respirable particles. Using respirable fluorescent amine-modified polystyrene latex beads and beryllium oxide particles, we investigated the localization of aspirated particles within the lung and the relationship between the amount of material placed in the pharynx and the amount deposited in the lung. For exposure, mice were anesthetized with isoflurane in a bell jar, placed on a slant board, and the tongue was gently held in full extension while a 50-microl suspension of particles was pipetted onto the base of the tongue. Tongue restraint was maintained until at least two breaths were completed. Less than a minute after exposure, all mice awoke from anesthesia without visible sequela. There were no significant differences in particle distribution between the left and right side of the lung (p=.16). Particles were widely disseminated in a peribronchiolar pattern within the alveolar region. There was a linear and significant correlation (r2=.99) between the amount administered and the amount deposited in the lung. In beryllium-exposed mice, measurable lung beryllium was 77.5 to 88.2% of the administered beryllium. These findings demonstrate that following aspiration of pharyngeal deposited particles, exposures to the deep lung are repeatable, technically simple, and highly correlated to the administered dose.

  13. Vanadium Inhalation in a Mouse Model for the Understanding of Air-Suspended Particle Systemic Repercussion

    PubMed Central

    Fortoul, T. I.; Rodriguez-Lara, V.; Gonzalez-Villalva, A.; Rojas-Lemus, M.; Cano-Gutierrez, G.; Ustarroz-Cano, M.; Colin-Barenque, L.; Montaño, L. F.; García-Pelez, I.; Bizarro-Nevares, P.; Lopez-Valdez, N.; Falcon-Rodriguez, C. I.; Jimenez-Martínez, R. S.; Ruiz-Guerrero, M. L.; López-Zepeda, L. S.; Morales-Rivero, A.; Muñiz-Rivera-Cambas, A.

    2011-01-01

    There is an increased concern about the health effects that air-suspended particles have on human health which have been dissected in animal models. Using CD-1 mouse, we explore the effects that vanadium inhalation produce in different tissues and organs. Our findings support the systemic effects of air pollution. In this paper, we describe our findings in different organs in our conditions and contrast our results with the literature. PMID:21716674

  14. Diesel exhaust particle toxicity on spermatogenesis in the mouse is aryl hydrocarbon receptor dependent.

    PubMed

    Izawa, Hiromi; Kohara, Machiko; Watanabe, Gen; Taya, Kazuyoshi; Sagai, Masaru

    2007-10-01

    Diesel exhaust particles (DEPs) are particulate matter from diesel exhaust containing many toxic compounds, such as polyaromatic hydrocarbons (PAHs). Some toxicities of PAH are considered to express via aryl hydrocarbon receptor (AhR). We hypothesized that the male reproductive toxicity of DEPs may depend on PAHs. BALB/c male mice received 24.7, 74.0 or 220 microg/mouse DEP suspension or vehicle injected into the dorsal subcutaneous layer 10 times during 5 weeks. The mice were euthanized, and blood and organs were collected 2 weeks after the last treatment. The epididymis weights, relative epididymis weights per body weight and daily sperm productions and viabilities of the 74.0 and 220 microg/mouse DEP-treated groups decreased significantly compared with those of the vehicle group. The total incidence of sperm abnormalities in the 74.0 and 220 microg/mouse DEP-treated groups increased significantly compared with the vehicle group. The seminiferous epithelium area ratios of the 74.0 and 220 microg/mouse DEP-treated groups were significantly higher compared with the vehicle and 24.6 microg/mouse DEP-treated groups. The ratios of seminiferous tubules with elongated-type spermatids in the 74.0 and 220 microg/mouse DEP-treated groups were significantly decreased compared with the vehicle group. The testosterone level and hepatic ethoxyresorufin-O-deethylase (EROD) activity as an indirect index of AhR activity in the 74.0 microg/mouse DEP-treated group were significantly increased compared with those of the vehicle group. These results clearly demonstrated that DEPs suppress testicular function, especially spermatogenesis and sperm motility. These effects may be AhR dependent.

  15. Anti-PrP antibodies detected at terminal stage of prion-affected mouse.

    PubMed

    Sassa, Yukiko; Kataoka, Natsumi; Inoshima, Yasuo; Ishiguro, Naotaka

    2010-01-01

    The causative agent of prion diseases is the pathological isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). PrPSc has an identical amino acid sequence to PrPC; thus, it has been assumed that an immune response against PrPSc could not be found in prion-affected animals. In this study, we found the anti-prion protein (PrP) antibody at the terminal stage of mouse scrapie. Several sera from mice in the terminal stage of scrapie reacted to the recombinant mouse PrP (rMPrP) molecules and brain homogenates of mouse prion diseases. These results indicate that mouse could recognize PrPC or PrPSc as antigens by the host immune system. Furthermore, immunization with rMPrP generates high titers of anti-PrP antibodies in wild-type mice. Some anti-PrP antibodies immunized with rMPrP prevent PrPSc replication in vitro. The mouse sera from terminal prion disease have several wide epitopes, although mouse sera immunized with rMPrP possess narrow epitopes.

  16. Computational Modeling of Nanoscale and Microscale Particle Deposition, Retention and Dosimetry in the Mouse Respiratory Tract

    PubMed Central

    Asgharian, B.; Price, O.T.; Oldham, M.; Chen, L.C.; Saunders, E.L.; Gordon, T.; Mikheev, V.B.; Minard, K.R.; Teeguarden, J. G.

    2015-01-01

    Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat, human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles. PMID:25373829

  17. Exposure to heavy charged particles affects thermoregulation in rats

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A.; Dalton, T.K.; Joseph, J.A.; Harris, A.H.; Rabin, B.M. |

    1994-09-01

    Rats exposed to 0.1-5 Gy of heavy particles ({sup 56}Fe, {sup 40}Ar, {sup 20}Ne or {sup 4}He) showed dose-dependent changes in body temperature. Lower doses of all particles produced hyperthermia, and higher doses of {sup 20}Ne and {sup 56}Fe produced hypothermia. Of the four HZE particles, {sup 56}Fe particles were the most potent and {sup 4}He particles were the least potent in producing changes in thermoregulation. The {sup 20}Ne and {sup 40}Ar particles produced an intermediate level of change in body temperature. Significantly greater hyperthermia was produced by exposure to 1 Gy of {sup 20}Ne, {sup 40}Ar and {sup 56}Fe particles than by exposure to 1 Gy of {sup 60}Co {gamma} rays. Pretreating rats with the cyclo-oxygenase inhibitor indomethacin attenuated the hyperthermia produced by exposure to 1 Gy of {sup 56}Fe particles, indicating that prostaglandins mediate {sup 56}Fe-particle-induced hyperthermia. The hypothermia produced by exposure to 5 Gy of {sup 56}Fe particles is mediated by histamine and can be attenuated by treatment with the antihistamines mepyramine and cimetidine. 15 refs., 4 figs.

  18. Mechanisms of particle-induced pulmonary inflammation in a mouse model: exposure to wood dust.

    PubMed

    Määttä, Juha; Lehto, Maili; Leino, Marina; Tillander, Sari; Haapakoski, Rita; Majuri, Marja-Leena; Wolff, Henrik; Rautio, Sari; Welling, Irma; Husgafvel-Pursiainen, Kirsti; Savolainen, Kai; Alenius, Harri

    2006-09-01

    Repeated airway exposure to wood dust has long been known to cause adverse respiratory effects such as asthma and chronic bronchitis and impairment of lung function. However, the mechanisms underlying the inflammatory responses of the airways after wood dust exposure are poorly known. We used a mouse model to elucidate the mechanisms of particle-induced inflammatory responses to fine wood dust particles. BALB/c mice were exposed to intranasally administered fine (more than 99% of the particles had a particle size of < or = 5 microm, with virtually identical size distribution) birch or oak dusts twice a week for 3 weeks. PBS, LPS, and titanium dioxide were used as controls. Intranasal instillation of birch or oak dusts elicited influx of inflammatory cells to the lungs in mice. Enhancement of lymphocytes and neutrophils was seen after oak dust exposure, whereas eosinophil infiltration was higher after birch dust exposure. Infiltration of inflammatory cells was associated with an increase in the mRNA levels of several cytokines, chemokines, and chemokine receptors in lung tissue. Oak dust appeared to be a more potent inducer of these inflammatory mediators than birch dust. The results from our in vivo mouse model show that repeated airway exposure to wood dust can elicit lung inflammation, which is accompanied by induction of several proinflammatory cytokines and chemokines. Oak and birch dusts exhibited quantitative and qualitative differences in the elicitation of pulmonary inflammation, suggesting that the inflammatory responses induced by the wood species may rise via different cellular mechanisms.

  19. Dimethylsulfoxide-soluble smoking particles and nicotine affect vascular contractibility.

    PubMed

    Zhang, Jin-Yan; Cao, Lei; Zheng, Xiao-Hui; Xu, Cang-Bao; Cao, Yong-Xiao

    2009-10-01

    The aim is to study the effect of dimethylsulfoxide-soluble smoking particles (DSP) and nicotine on the contractility of rat mesenteric artery. The superior mesenteric artery segments were cultured with DSP or nicotine for 24 h. The vascular contractibility was recorded with myograph system. DSP 0.4 mL/L and nicotine 0.48 and 0.96 mg/L shifted the concentration-contractile curves induced by sarafotoxin 6c, a selective agonist for ET(B) receptor toward the left with increased E(max). DSP 0.4 mL/L and nicotine 0.96 mg/L shifted ET(A) receptor-mediated the concentration-contractile curves toward the left with increased E(max). However, nicotine 0.06 mg/L which is the equivalent concentration of nicotine in DSP 0.4 mL/L did not affect the curves and the E(max) mediated with ET(A) receptor and ET(B) receptor. DSP 0.2 and 0.4 mL/L shifted the concentration-contractile curves induced by noradrenaline toward the right with decreased E(max). Neither did nicotine 0.06 and 0.96 mg/L. Both DSP and nicotine shifted the concentration-contractile curves induced by 5-hydroxytryptamine (5-HT) toward the right parallely. DSP changed the phenotypes towards an increased efficacy of ET(A) receptor and ET(B) receptor, and a reduced efficacy of 5-HT receptor and alpha-adrenocceptor. The effects of DSP on ET(B) receptor, ET(A) receptor and alpha-adrenocceptor were independent of nicotine. The effect on 5-HT receptor was responsible to nicotine.

  20. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    SciTech Connect

    Manley, N.B.; Fabrikant, J.I.; Alpen, E.L.

    1988-12-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. This study concerns the cell population and cell cycle kinetics of the subependymal layer in the mouse brain, and the effects of charged particle irradiations on this cell population. Quantitative high resolution autoradiography was used to study the kinetic parameters in this cell layer. This study should help in understanding the effects of these high-energy heavy ions on normal mammalian brain tissue. The response of the mammalian brain exposure to charged particle ionizing radiation may be extremely variable. It varies from minimal physiological changes to overt tissue necrosis depending on a number of factors such as: the administered dose, dose-rate, the volume of the irradiated tissue, and the biological end-point being examined.

  1. Particle film affects black pecan aphid (Homoptera: Aphididae) on pecan.

    PubMed

    Cottrell, Ted E; Wood, Bruce W; Reilly, Charles C

    2002-08-01

    Three species of aphids attack pecan foliage, Carya illinoensis (Wang.) K. Koch, and cause economic damage. We tested a kaolin-based particle film against one of these aphid species, black pecan aphid, Melanocallis caryaefoliae (Davis). Effect of particle film on host selection, adult mortality, and production of nymphs by M. caryaefoliae was tested on seedling pecans in the laboratory. Fewer M. caryaefoliae adults selected treated foliage compared with untreated foliage. A higher percentage of adults that did select treated foliage were recovered from upper leaf surfaces compared with the percentage of adults recovered from upper leaf surfaces of untreated leaves. Observations with a microscope revealed an accumulation of particle film on aphid body parts, especially on tarsi, and strongly suggests that aphid mobility was restricted. Adult mortality was higher on treated foliage and led to an overall decrease in production of nymphs on those seedlings. In addition, we measured spectral properties of treated seedling pecan foliage. Light reflectance by treated foliage was increased and absorptance decreased compared with control foliage whereas transmittance of light through control and particle film-treated leaves was similar. We did not detect any phytotoxic effect on pecan due to application of particle film.

  2. Effects of Solar Particle Event-Like Proton Radiation and/or Simulated Microgravity on Circulating Mouse Blood Cells.

    PubMed

    Romero-Weaver, Ana L; Lin, Liyong; Carabe-Fernandez, Alejandro; Kennedy, Ann R

    2014-08-01

    Astronauts traveling in space missions outside of low Earth orbit will be exposed for longer times to a microgravity environment. In addition, the increased travel time involved in exploration class missions will result in an increased risk of exposure to significant doses of solar particle event (SPE) radiation. Both conditions could significantly affect the number of circulating blood cells. Therefore, it is critical to determine the combined effects of exposure to both microgravity and SPE radiation. The purpose of the present study was to assess these risks by evaluating the effects of SPE-like proton radiation and/or microgravity, as simulated with the hindlimb unloading (HU) system, on circulating blood cells using mouse as a model system. The results indicate that exposure to HU alone caused minimal or no significant changes in mouse circulating blood cell numbers. The exposure of mice to SPE-like proton radiation with or without HU treatment caused a significant decrease in the number of circulating lymphocytes, granulocytes and platelets. The reduced numbers of circulating lymphocytes, granulocytes, and platelets, resulting from the SPE-like proton radiation exposure, with or without HU treatment, in mice suggest that astronauts participating in exploration class missions may be at greater risk of developing infections and thrombotic diseases; thus, countermeasures may be necessary for these biological endpoints.

  3. First in vivo traveling wave magnetic particle imaging of a beating mouse heart

    NASA Astrophysics Data System (ADS)

    Vogel, P.; Rückert, M. A.; Klauer, P.; Kullmann, W. H.; Jakob, P. M.; Behr, V. C.

    2016-09-01

    Magnetic particle imaging (MPI) is a non-invasive imaging modality for direct detection of superparamagnetic iron-oxide nanoparticles based on the nonlinear magnetization response of magnetic materials to alternating magnetic fields. This highly sensitive and rapid method allows both a quantitative and a qualitative analysis of the measured signal. Since the first publication of MPI in 2005 several different scanner concepts have been presented and in 2009 the first in vivo imaging results of a beating mouse heart were shown. However, since the field of view (FOV) of the first MPI-scanner only covers a small region several approaches and hardware enhancements were presented to overcome this issue and could increase the FOV on cost of acquisition speed. In 2014 an alternative scanner concept, the traveling wave MPI (TWMPI), was presented, which allows scanning an entire mouse-sized volume at once. In this paper the first in vivo imaging results using the TWMPI system are presented. By optimizing the trajectory the temporal resolution is sufficiently high to resolve the dynamic of a beating mouse heart.

  4. Fullerene fine particles adhere to pollen grains and affect their autofluorescence and germination.

    PubMed

    Aoyagi, Hideki; Ugwu, Charles U

    2011-01-01

    Adhesion of commercially produced fullerene fine particles to Cryptomeria japonica, Chamaecyparis obtusa and Camellia japonica pollen grains was investigated. The autofluorescence of pollen grains was affected by the adhesion of fullerene fine particles to the pollen grains. The degree of adhesion of fullerene fine particles to the pollen grains varied depending on the type of fullerene. Furthermore, germination of Camellia japonica pollen grains was inhibited by the adhesion of fullerene fine particles.

  5. Novel Endogenous Type D Retroviral Particles Expressed at High Levels in a SCID Mouse Thymic Lymphoma

    PubMed Central

    Ristevski, Sika; Purcell, Damian F. J.; Marshall, John; Campagna, Daniella; Nouri, Sara; Fenton, Simon P.; McPhee, Dale A.; Kannourakis, George

    1999-01-01

    A xenograft model of the human disease Langerhans cell histiocytosis (LCH) was investigated with severe combined immunodeficiency (SCID) mice. Transplantation of human LCH biopsy material into SCID mice resulted in the generation of mouse tumors resembling lymphomas. A thymoma cell line (ThyE1M6) was generated from one of these mice and found to display significant levels of Mg2+-dependent reverse transcriptase activity. Electron microscopy revealed particles with type D retroviral morphology budding from ThyE1M6 cells at a high frequency, whereas control cultures were negative. Reverse transcription-PCR of virion RNA with degenerate primers for conserved regions of various mouse, human, and primate retroviruses amplified novel sequences related to primate type D retroviruses, murine intracisternal A particles, Jaagsiekte sheep retrovirus, and murine long interspersed nuclear elements but not other retroviral classes. We demonstrate that these sequences represent a novel group of endogenous retroviruses expressed at low levels in mice but expressed at high levels in the ThyE1M6 cell line. Furthermore, we propose that the activation of endogenous retroviral elements may be associated with a high incidence of thymomas in SCID mice. PMID:10233925

  6. Soil particle heterogeneity affects the growth of a rhizomatous wetland plant.

    PubMed

    Huang, Lin; Dong, Bi-Cheng; Xue, Wei; Peng, Yi-Ke; Zhang, Ming-Xiang; Yu, Fei-Hai

    2013-01-01

    Soil is commonly composed of particles of different sizes, and soil particle size may greatly affect the growth of plants because it affects soil physical and chemical properties. However, no study has tested the effects of soil particle heterogeneity on the growth of clonal plants. We conducted a greenhouse experiment in which individual ramets of the wetland plant Bolboschoenus planiculmis were grown in three homogeneous soil treatments with uniformly sized quartz particles (small: 0.75 mm, medium: 1.5 mm, or large: 3 mm), one homogeneous treatment with an even mixture of large and medium particles, and two heterogeneous treatments consisting of 16 or 4 patches of large and medium particles. Biomass, ramet number, rhizome length and spacer length were significantly greater in the treatment with only medium particles than in the one with only large particles. Biomass, ramet number, rhizome length and tuber number in the patchy treatments were greater in patches of medium than of large particles; this difference was more pronounced when patches were small than when they were large. Soil particle size and soil particle heterogeneity can greatly affect the growth of clonal plants. Thus, studies to test the effects of soil heterogeneity on clonal plants should distinguish the effects of nutrient heterogeneity from those of particle heterogeneity.

  7. Genetic deletion of the EGFR ligand epigen does not affect mouse embryonic development and tissue homeostasis.

    PubMed

    Dahlhoff, Maik; Schäfer, Matthias; Wolf, Eckhard; Schneider, Marlon R

    2013-02-15

    The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor with manifold functions during development, tissue homeostasis and disease. EGFR activation, the formation of homodimers or heterodimers (with the related ERBB2-4 receptors) and downstream signaling is initiated by the binding of a family of structurally related growth factors, the EGFR ligands. Genetic deletion experiments clarified the biological function of all family members except for the last characterized ligand, epigen. We employed gene targeting in mouse embryonic stem cells to generate mice lacking epigen expression. Loss of epigen did not affect mouse development, fertility, or organ physiology. Quantitative RT-PCR analysis revealed increased expression of betacellulin and EGF in a few organs of epigen-deficient mice, suggesting a functional compensation by these ligands. In conclusion, we completed the genetic analysis of EGFR ligands and show that epigen has non-essential functions or functions that can be compensated by other EGFR ligands during growth and tissue homeostasis.

  8. Effect of aerosol particles generated by ultrasonic humidifiers on the lung in mouse

    PubMed Central

    2013-01-01

    Background Ultrasonic humidifiers silently generate water droplets as a cool fog and produce most of the dissolved minerals in the fog in the form of an aerosolized “white dust.” However, the health effect of these airborne particles is largely unknown. This study aimed to characterize the aerosol particles generated by ultrasonic humidifiers and to investigate their effect on the lung tissue of mice. Methods An ultrasonic humidifier was operated with tap water, high-silica water, ultrapure water, or other water types. In a chamber (0.765 m3, ventilation ratio 11.5 m3/hr), male ICR mice (10-week-old) were exposed by inhalation to an aerosol-containing vapor generated by the humidifier. After exposure for 7 or 14 days, lung tissues and bronchoalveolar lavage fluid (BALF) were collected from each mouse and examined by microarray, quantitative reverse transcription-polymerase chain reaction, and light and electron microscopy. Results Particles generated from the humidifier operated with tap water had a mass concentration of 0.46 ± 0.03 mg/m3, number concentration of (5.0 ± 1.1) × 104/cm3, and peak size distribution of 183 nm. The particles were phagocytosed by alveolar macrophages in the lung of mice. Inhalation of particles caused dysregulation of genes related to mitosis, cell adhesion molecules, MHC molecules and endocytosis, but did not induce any signs of inflammation or tissue injury in the lung. Conclusion These results indicate that aerosol particles released from ultrasonic humidifiers operated with tap water initiated a cellular response but did not cause severe acute inflammation in pulmonary tissue. Additionally, high mineral content tap water is not recommended and de-mineralized water should be recommended in order to exclude any adverse effects. PMID:24359587

  9. High-resolution identification of mercury in particles in mouse kidney after acute lethal exposure.

    PubMed

    Cunha, Elisabete M; Silva, Daniela P; Aguas, Artur P

    2003-12-01

    Contamination of the food chain by mercury is a major concern of Public Health of our day. Kidney and nervous system are the major targets of mercury toxicity in mammals. We show here that the detailed subcellular in vivo topography of microparticles of mercury in tissues can be achieved by scanning electron microscopy (SEM) coupled with X-ray elemental microanalysis (XRM). SEM-XRM offered the fine topography of mercury in the kidney of BALB/c mice that were submitted to an intraperitoneal lethal injection of mercuric chloride (HgCl2). All of the renal mercury was seen inside blood vessels located in both cortex and medulla of the mouse kidney. This blood-born mercury was organised in spheroid particles of less than 50 nm in diameter (31.4 +/- 14.1 nm). They were seen attached either to aggregates of plasma proteins or to the surface of blood cells. No evidence of internalisation of mercury by blood, endothelial or kidney cells was found. The average kidney density of mercury microspheres was 1920 +/- 1320 particles per mm2. We propose SEM-XRM as an elective approach to further investigations, at the subcellular level, on the quantitative dynamics of mercury particles in the tissues.

  10. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    SciTech Connect

    Manley, N.B.

    1988-01-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. The decrease in the values of the labeling indices 1 week after charged particle irradiation was dose- and ion-dependent. Mitotic indices 1 week after 10 and 25 Gy helium and after 10 Gy neon were the same as those seen in the control mice. Analysis of cell kinetics 1 week after 10 Gy helium and 10 Gy neon irradiation suggests the presence of a progenitor subpopulation that is proliferating with a shorter cell cycle. Comparison of the responses to the different charged particle beams indicates that neon ions are more effective in producing direct cellular damage than the helium ions, but the surviving proliferating cells several divisions later continue to maintain active cell renewal. Based on the 1 week post-irradiation H{sup 3}-TdR labeling indices, a rough estimate of the RBE for neon ions is at least 2.5 when compared to helium ions.

  11. Down-regulation of small rubber particle protein expression affects integrity of rubber particles and rubber content in Taraxacum brevicorniculatum.

    PubMed

    Hillebrand, Andrea; Post, Janina J; Wurbs, David; Wahler, Daniela; Lenders, Malte; Krzyzanek, Vladislav; Prüfer, Dirk; Gronover, Christian Schulze

    2012-01-01

    The biosynthesis of rubber is thought to take place on the surface of rubber particles in laticifers, highly specialized cells that are present in more than 40 plant families. The small rubber particle protein (SRPP) has been supposed to be involved in rubber biosynthesis, and recently five SRPPs (TbSRPP1-5) were identified in the rubber-producing dandelion species Taraxacum brevicorniculatum. Here, we demonstrate by immunogold labeling that TbSRPPs are localized to rubber particles, and that rubber particles mainly consist of TbSRPP3, 4 and 5 as shown by high-resolution two-dimensional gel electrophoresis and mass spectrometric analysis. We also carried out an RNA-interference approach in transgenic plants to address the function of TbSRPPs in rubber biosynthesis as well as rubber particle morphology and stability. TbSRPP-RNAi transgenic T. brevicorniculatum plants showed a 40-50% reduction in the dry rubber content, but neither the rubber weight average molecular mass nor the polydispersity of the rubber were affected. Although no phenotypical differences to wild-type particles could be observed in vivo, rubber particles from the TbSRPP-RNAi transgenic lines were less stable and tend to rapidly aggregate in expelling latex after wounding of laticifers. Our results prove that TbSRPPs are very crucial for rubber production in T. brevicorniculatum, probably by contributing to a most favourable and stable rubber particle architecture for efficient rubber biosynthesis and eventually storage.

  12. Down-Regulation of Small Rubber Particle Protein Expression Affects Integrity of Rubber Particles and Rubber Content in Taraxacum brevicorniculatum

    PubMed Central

    Hillebrand, Andrea; Post, Janina J.; Wurbs, David; Wahler, Daniela; Lenders, Malte; Krzyzanek, Vladislav; Prüfer, Dirk; Gronover, Christian Schulze

    2012-01-01

    The biosynthesis of rubber is thought to take place on the surface of rubber particles in laticifers, highly specialized cells that are present in more than 40 plant families. The small rubber particle protein (SRPP) has been supposed to be involved in rubber biosynthesis, and recently five SRPPs (TbSRPP1–5) were identified in the rubber-producing dandelion species Taraxacum brevicorniculatum. Here, we demonstrate by immunogold labeling that TbSRPPs are localized to rubber particles, and that rubber particles mainly consist of TbSRPP3, 4 and 5 as shown by high-resolution two-dimensional gel electrophoresis and mass spectrometric analysis. We also carried out an RNA-interference approach in transgenic plants to address the function of TbSRPPs in rubber biosynthesis as well as rubber particle morphology and stability. TbSRPP-RNAi transgenic T. brevicorniculatum plants showed a 40–50% reduction in the dry rubber content, but neither the rubber weight average molecular mass nor the polydispersity of the rubber were affected. Although no phenotypical differences to wild-type particles could be observed in vivo, rubber particles from the TbSRPP-RNAi transgenic lines were less stable and tend to rapidly aggregate in expelling latex after wounding of laticifers. Our results prove that TbSRPPs are very crucial for rubber production in T. brevicorniculatum, probably by contributing to a most favourable and stable rubber particle architecture for efficient rubber biosynthesis and eventually storage. PMID:22911861

  13. Aging rather than aneuploidy affects monoamine neurotransmitters in brain regions of Down syndrome mouse models.

    PubMed

    Dekker, Alain D; Vermeiren, Yannick; Albac, Christelle; Lana-Elola, Eva; Watson-Scales, Sheona; Gibbins, Dorota; Aerts, Tony; Van Dam, Debby; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Potier, Marie-Claude; De Deyn, Peter P

    2017-09-01

    Altered concentrations of monoamine neurotransmitters and metabolites have been repeatedly found in people with Down syndrome (DS, trisomy 21). Because of the limited availability of human post-mortem tissue, DS mouse models are of great interest to study these changes and the underlying neurobiological mechanisms. Although previous studies have shown the potential of Ts65Dn mice - the most widely used mouse model of DS - to model noradrenergic changes, a comprehensive monoaminergic characterization in multiple brain regions has not been performed so far. Here, we used RP-HPLC with electrochemical detection to quantify (nor)adrenergic (NA, adrenaline and MHPG), dopaminergic (DA, HVA and DOPAC), and serotonergic compounds (tryptophan, 5-HT and 5-HIAA) in ten regionally dissected brain regions of Ts65Dn mice, as well as in Dp1Tyb mice - a novel DS mouse model. Comparing young adult aneuploid mice (2.5-5.5months) with their euploid WT littermates did not reveal generalized monoaminergic dysregulation, indicating that the genetic overload in these mice barely affected the absolute concentrations at this age. Moreover, we studied the effect of aging in Ts65Dn mice: comparing aged animals (12-13months) with their younger counterparts revealed a large number of significant changes. In general, the (nor)adrenergic system appeared to be reduced, while serotonergic compounds were increased with aging. Dopaminergic alterations were less consistent. These overall patterns appeared to be relatively similar for Ts65Dn and WT mice, though more observed changes were regarded significant for WT mice. Similar human post-mortem studies are necessary to validate the monoaminergic construct validity of the Ts65Dn and Dp1Typ mouse models. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Factors Affecting the Intensity of Solar Energetic Particle Events

    NASA Technical Reports Server (NTRS)

    Gopalswamy, Natchimuthuk

    2011-01-01

    This paper updates the influence of environmental and source factors of shocks driven by coronal mass ejections (CMEs) that are likely to influence the solar energetic particle (SEP) events. The intensity variation due to CME interaction reported that is confirmed by expanding the investigation to all the large SEP events of solar cycle 23. The large SEP events are separated into two groups, one associated with CMEs running into other CMEs, and the other with CMEs running into the ambient solar wind. SEP events with CME interaction generally have a higher intensity. New possibilities such as the influence of coronal holes on the SEP intensity are also discussed. For example, the presence of a large coronal hole between a well-connected eruption and the solar disk center may render the shock poorly connected because of the interaction between the CME and the coronal hole. This point is illustrated using the 2004 December 3 SEP event delayed by about 12 hours from the onset of the associated CME. There is no other event at the Sun that can be associated with the SEP onset. This event is consistent with the possibility that the coronal hole interaction influences the connectivity of the CMEs that produce SEPs, and hence the intensity of the SEP event.

  15. Inherited somatic mosaicism caused by an intracisternal A particle insertion in the mouse tyrosinase gene.

    PubMed

    Wu, M; Rinchik, E M; Wilkinson, E; Johnson, D K

    1997-02-04

    A recessive, fully penetrant mutation (c(m1OR)) at the mouse albino locus that results in coat-color mottling has been characterized at the molecular level. Restriction mapping and DNA sequencing analyses provide evidence that mutants carry a 5.4-kb intracisternal A particle (IAP) element insertion upstream of the tyrosinase (Tyr) promoter. Northern blot analysis and reverse transcription-PCR results show that the tyrosinase gene is expressed at much lower levels in mutant than in wild-type mice. The mutant Tyr gene still retains the tissue-specific expression pattern, and the Tyr transcript is not initiated from the IAP long terminal repeat promoter. We propose that the IAP insertion isolates the promoter of the tyrosinase gene from upstream cis-acting regulatory elements, leading to a substantially decreased level of Tyr gene expression in mutants.

  16. Intracerebral Inoculation of Mouse-Passaged Saffold Virus Type 3 Affects Cerebellar Development in Neonatal Mice

    PubMed Central

    Kotani, Osamu; Suzuki, Tadaki; Yokoyama, Masaru; Iwata-Yoshikawa, Naoko; Nakajima, Noriko; Sato, Hironori; Hasegawa, Hideki; Taguchi, Fumihiro; Shimizu, Hiroyuki

    2016-01-01

    ABSTRACT Saffold virus (SAFV), a human cardiovirus, is occasionally detected in infants with neurological disorders, including meningitis and cerebellitis. We recently reported that SAFV type 3 isolates infect cerebellar glial cells, but not large neurons, in mice. However, the impact of this infection remained unclear. Here, we determined the neuropathogenesis of SAFV type 3 in the cerebella of neonatal ddY mice by using SAFV passaged in the cerebella of neonatal BALB/c mice. The virus titer in the cerebellum increased following the inoculation of each of five passaged strains. The fifth passaged strain harbored amino acid substitutions in the VP2 (H160R and Q239R) and VP3 (K62M) capsid proteins. Molecular modeling of the capsid proteins suggested that the VP2-H160R and VP3-K62M mutations alter the structural dynamics of the receptor binding surface via the formation of a novel hydrophobic interaction between the VP2 puff B and VP3 knob regions. Compared with the original strain, the passaged strain showed altered growth characteristics in human-derived astroglial cell lines and greater replication in the brains of neonatal mice. In addition, the passaged strain was more neurovirulent than the original strain, while both strains infected astroglial and neural progenitor cells in the mouse brain. Intracerebral inoculation of either the original or the passaged strain affected brain Purkinje cell dendrites, and a high titer of the passaged strain induced cerebellar hypoplasia in neonatal mice. Thus, infection by mouse-passaged SAFV affected cerebellar development in neonatal mice. This animal model contributes to the understanding of the neuropathogenicity of SAFV infections in infants. IMPORTANCE Saffold virus (SAFV) is a candidate neuropathogenic agent in infants and children, but the neuropathogenicity of the virus has not been fully elucidated. Recently, we evaluated the pathogenicity of two clinical SAFV isolates in mice. Similar to other neurotropic

  17. Altered Sleep and Affect in the Neurotensin Receptor 1 Knockout Mouse

    PubMed Central

    Fitzpatrick, Karrie; Winrow, Christopher J.; Gotter, Anthony L.; Millstein, Joshua; Arbuzova, Janna; Brunner, Joseph; Kasarskis, Andrew; Vitaterna, Martha H.; Renger, John J.; Turek, Fred W.

    2012-01-01

    Study Objective: Sleep and mood disorders have long been understood to have strong genetic components, and there is considerable comorbidity of sleep abnormalities and mood disorders, suggesting the involvement of common genetic pathways. Here, we examine a candidate gene implicated in the regulation of both sleep and affective behavior using a knockout mouse model. Design: Previously, we identified a quantitative trait locus (QTL) for REM sleep amount, REM sleep bout number, and wake amount in a genetically segregating population of mice. Here, we show that traits mapping to this QTL correlated with an expression QTL for neurotensin receptor 1 (Ntsr1), a receptor for neurotensin, a ligand known to be involved in several psychiatric disorders. We examined sleep as well as behaviors indicative of anxiety and depression in the NTSR1 knockout mouse. Measurements and Results: NTSR1 knockouts had a lower percentage of sleep time spent in REM sleep in the dark phase and a larger diurnal variation in REM sleep duration than wild types under baseline conditions. Following sleep deprivation, NTSR1 knockouts exhibited more wake and less NREM rebound sleep. NTSR1 knockouts also showed increased anxious and despair behaviors. Conclusions: Here we illustrate a link between expression of the Ntsr1 gene and sleep traits previously associated with a particular QTL. We also demonstrate a relationship between Ntsr1 and anxiety and despair behaviors. Given the considerable evidence that anxiety and depression are closely linked with abnormalities in sleep, the data presented here provide further evidence that neurotensin and Ntsr1 may be a component of a pathway involved in both sleep and mood disorders. Citation: Fitzpatrick K; Winrow CJ; Gotter AL; Millstein J; Arbuzova J; Brunner J; Kasarskis A; Vitaterna MH; Renger JJ; Turek FW. Altered sleep and affect in the neurotensin receptor 1 knockout mouse. SLEEP 2012;35(7):949-956. PMID:22754041

  18. Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour

    PubMed Central

    Hernández-Hernández, Oscar; Guiraud-Dogan, Céline; Sicot, Géraldine; Huguet, Aline; Luilier, Sabrina; Steidl, Esther; Saenger, Stefanie; Marciniak, Elodie; Obriot, Hélène; Chevarin, Caroline; Nicole, Annie; Revillod, Lucile; Charizanis, Konstantinos; Lee, Kuang-Yung; Suzuki, Yasuhiro; Kimura, Takashi; Matsuura, Tohru; Cisneros, Bulmaro; Swanson, Maurice S.; Trovero, Fabrice; Buisson, Bruno; Bizot, Jean-Charles; Hamon, Michel; Humez, Sandrine; Bassez, Guillaume; Metzger, Friedrich; Buée, Luc; Munnich, Arnold; Sergeant, Nicolas; Gourdon, Geneviève

    2013-01-01

    Myotonic dystrophy type 1 is a complex multisystemic inherited disorder, which displays multiple debilitating neurological manifestations. Despite recent progress in the understanding of the molecular pathogenesis of myotonic dystrophy type 1 in skeletal muscle and heart, the pathways affected in the central nervous system are largely unknown. To address this question, we studied the only transgenic mouse line expressing CTG trinucleotide repeats in the central nervous system. These mice recreate molecular features of RNA toxicity, such as RNA foci accumulation and missplicing. They exhibit relevant behavioural and cognitive phenotypes, deficits in short-term synaptic plasticity, as well as changes in neurochemical levels. In the search for disease intermediates affected by disease mutation, a global proteomics approach revealed RAB3A upregulation and synapsin I hyperphosphorylation in the central nervous system of transgenic mice, transfected cells and post-mortem brains of patients with myotonic dystrophy type 1. These protein defects were associated with electrophysiological and behavioural deficits in mice and altered spontaneous neurosecretion in cell culture. Taking advantage of a relevant transgenic mouse of a complex human disease, we found a novel connection between physiological phenotypes and synaptic protein dysregulation, indicative of synaptic dysfunction in myotonic dystrophy type 1 brain pathology. PMID:23404338

  19. Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour.

    PubMed

    Hernández-Hernández, Oscar; Guiraud-Dogan, Céline; Sicot, Géraldine; Huguet, Aline; Luilier, Sabrina; Steidl, Esther; Saenger, Stefanie; Marciniak, Elodie; Obriot, Hélène; Chevarin, Caroline; Nicole, Annie; Revillod, Lucile; Charizanis, Konstantinos; Lee, Kuang-Yung; Suzuki, Yasuhiro; Kimura, Takashi; Matsuura, Tohru; Cisneros, Bulmaro; Swanson, Maurice S; Trovero, Fabrice; Buisson, Bruno; Bizot, Jean-Charles; Hamon, Michel; Humez, Sandrine; Bassez, Guillaume; Metzger, Friedrich; Buée, Luc; Munnich, Arnold; Sergeant, Nicolas; Gourdon, Geneviève; Gomes-Pereira, Mário

    2013-03-01

    Myotonic dystrophy type 1 is a complex multisystemic inherited disorder, which displays multiple debilitating neurological manifestations. Despite recent progress in the understanding of the molecular pathogenesis of myotonic dystrophy type 1 in skeletal muscle and heart, the pathways affected in the central nervous system are largely unknown. To address this question, we studied the only transgenic mouse line expressing CTG trinucleotide repeats in the central nervous system. These mice recreate molecular features of RNA toxicity, such as RNA foci accumulation and missplicing. They exhibit relevant behavioural and cognitive phenotypes, deficits in short-term synaptic plasticity, as well as changes in neurochemical levels. In the search for disease intermediates affected by disease mutation, a global proteomics approach revealed RAB3A upregulation and synapsin I hyperphosphorylation in the central nervous system of transgenic mice, transfected cells and post-mortem brains of patients with myotonic dystrophy type 1. These protein defects were associated with electrophysiological and behavioural deficits in mice and altered spontaneous neurosecretion in cell culture. Taking advantage of a relevant transgenic mouse of a complex human disease, we found a novel connection between physiological phenotypes and synaptic protein dysregulation, indicative of synaptic dysfunction in myotonic dystrophy type 1 brain pathology.

  20. The interaction of cobalt metal with different carbides and other mineral particles on mouse peritoneal macrophages.

    PubMed

    Lison, D; Lauwerys, R

    1995-06-01

    Chronic inhalation of hard metal particles can produce an interstitial lung disease (hard metal disease). Recent studies on rats and on isolated alveolar and peritoneal macrophages have demonstrated that this disorder can be explained by an interaction between cobalt metal (Co) and tungsten carbide (WC) particles, which represent the main constituents of hard metal. The exact mechanism of this interaction is still undefined. The present study was undertaken to assess in vitro whether a similar interaction also occurs between cobalt and other metallic carbide particles which may also be incorporated in hard metals depending on the desired applications. When tested separately, Co and metallic carbide particles did not affect the cell integrity. In contrast, TiC, NbC and Cr(3)C(2) exerted a synergistic effect with Co (interactive carbides) while TaC, Mo(2)C and SiC did not (non-interactive carbides). The interaction did not simply result from an increased cobalt bioavailability since cobalt uptake by the macrophages was increased 4-7-fold in the presence of interactive as well as non-interactive carbides. The interactive effect appeared dependent on the size of the carbide particles, which suggests that a physicochemical reaction taking place at the interface between certain carbides and cobalt particles may be responsible for the toxicity of the Co-carbide mixture. Other non-carbide particles (Fe, diamond, crystalline silica) did not produce a similar interaction with cobalt. This observation may contribute to the better delineation of the pathogenesis of hard metal disease.

  1. Factors affecting the concentration of outdoor particles indoors (COPI): Identification of data needs and existing data

    SciTech Connect

    Thatcher, Tracy L.; McKone, Thomas E.; Fisk, William J.; Sohn, Michael D.; Delp, Woody W.; Riley, William J.; Sextro, Richard G.

    2001-12-01

    The process of characterizing human exposure to particulate matter requires information on both particle concentrations in microenvironments and the time-specific activity budgets of individuals among these microenvironments. Because the average amount of time spent indoors by individuals in the US is estimated to be greater than 75%, accurate characterization of particle concentrations indoors is critical to exposure assessments for the US population. In addition, it is estimated that indoor particle concentrations depend strongly on outdoor concentrations. The spatial and temporal variations of indoor particle concentrations as well as the factors that affect these variations are important to health scientists. For them, knowledge of the factors that control the relationship of indoor particle concentrations to outdoor levels is particularly important. In this report, we identify and evaluate sources of data for those factors that affect the transport to and concentration of outdoor particles in the indoor environment. Concentrations of particles indoors depend upon the fraction of outdoor particles that penetrate through the building shell or are transported via the air handling (HVAC) system, the generation of particles by indoor sources, and the loss mechanisms that occur indoors, such as deposition. To address these issues, we (i) identify and assemble relevant information including the behavior of particles during air leakage, HVAC operations, and particle filtration; (ii) review and evaluate the assembled information to distinguish data that are directly relevant to specific estimates of particle transport from those that are only indirectly useful and (iii) provide a synthesis of the currently available information on building air-leakage parameters and their effect on indoor particle matter concentrations.

  2. Factors affecting computer mouse use for young children: implications for AAC.

    PubMed

    Costigan, F Aileen; Light, Janice C; Newell, Karl M

    2012-06-01

    More than 12% of preschoolers receiving special education services have complex communication needs, including increasing numbers of children who do not have significant motor impairments (e.g., children with autism spectrum disorders, Down syndrome, etc.). In order to meet their diverse communication needs (e.g., face-to-face, written, Internet, telecommunication), these children may use mainstream technologies accessed via the mouse, yet little is known about factors that affect the mouse performance of young children. This study used a mixed factorial design to investigate the effects of age, target size, and angle of approach on accuracy and time required for accurate target selection with a mouse for 20 3-year-old and 20 4-year-old children. The 4-year-olds were generally more accurate and faster than the 3-year-olds. Target size and angle mediated differences in performance within age groups. The 3-year-olds were more accurate and faster in selecting the medium and large targets relative to the small target, were faster in selecting the large relative to the medium target, and were faster in selecting targets along the vertical relative to the diagonal angle. The 4-year-olds were faster in selecting the medium and large targets relative to the small target. Implications for improving access to AAC include the preliminary suggestion of age-related threshold target sizes that support sufficient accuracy, the possibility of efficiency benefits when target size is increased up to an age-related threshold, and identification of the potential utility of the vertical angle as a context for training navigational input device use.

  3. Mancozeb adversely affects meiotic spindle organization and fertilization in mouse oocytes.

    PubMed

    Rossi, Gianna; Palmerini, Maria Grazia; Macchiarelli, Guido; Buccione, Roberto; Cecconi, Sandra

    2006-07-01

    In this study the effects of mancozeb, a widely used ethylenebisdithiocarbamate fungicide, on mouse oocyte meiotic maturation and fertilization were analyzed. Oocyte cumulus cell-complexes were matured in vitro with or without increasing concentrations of the fungicide (from 0.001 to 1 microg/ml) that, due to its different stability in organic solvents and in water, was resuspended either in dimethyl sulfoxide or in culture medium. Although, about 95% of oocytes reached the metaphase II stage; mancozeb-exposed oocytes showed a dose-dependent increase of alterations in spindle morphology, and this negative effect was more evident when the fungicide was resuspended in culture medium. Under the latter culture condition, oocytes matured in the presence of 0.1 and 1 microg/ml mancozeb showed a significant reduction also in the formation of male and female pronuclei. These results indicate that mancozeb can adversely affect mammalian reproductive performance, likely by perturbing microtubular organization during meiotic maturation.

  4. Intracerebral inoculation of mouse-passaged Saffold virus type 3 affects cerebellar development in neonatal mice.

    PubMed

    Kotani, Osamu; Suzuki, Tadaki; Yokoyama, Masaru; Iwata-Yoshikawa, Naoko; Nakajima, Noriko; Sato, Hironori; Hasegawa, Hideki; Taguchi, Fumihiro; Shimizu, Hiroyuki; Nagata, Noriyo

    2016-08-31

    Saffold virus (SAFV), a human cardiovirus, is occasionally detected in infants with neurological disorders, including meningitis and cerebellitis. We recently reported that SAFV type 3 isolates infect cerebellar glial cells, but not large neurons, in mice. However, the impact of this infection remained unclear. Here, we determined the neuropathogenesis of SAFV type 3 in the cerebella of neonatal ddY mice using SAFV passaged in the cerebellum of neonatal BALB/c mice. The virus titer in the cerebellum increased following inoculation of each of five passaged strains. The fifth passaged strain harbored amino acid substitutions in the VP2 (H160R and Q239R) and VP3 (K62M) capsid proteins. Molecular modeling of the capsid proteins suggested that the VP2-H160R and VP3-K62M mutations alter the structural dynamics of the receptor binding surface via formation of a novel hydrophobic interaction between the VP2 puff B and VP3 knob regions. When compared with the original strain, the passaged strain showed altered growth characteristics in human-derived astroglial cell lines and higher replication in the brains of neonatal mice. In addition, the passaged strain was more neurovirulent than the original strain, while both strains infected astroglial and neural progenitor cells in the mouse brain. Intracerebral inoculation of either the original or passaged strain affected brain Purkinje cell dendrites, and a high titer of the passaged strain induced cerebellar hypoplasia in neonatal mice. Thus, infection by mouse-passaged SAFV affected cerebellar development in neonatal mice. This animal model contributes to the understanding of the neuropathogenicity of SAFV infections in infants.

  5. Cadmium affects mitotically inherited histone modification pathways in mouse embryonic stem cells.

    PubMed

    Gadhia, S R; O'Brien, D; Barile, F A

    2015-12-25

    The fetal basis of adult disease (FeBAD) theorizes that embryonic challenges initiate pathologies in adult life through epigenetic modification of gene expression. In addition, inheritance of H3K27 methylation marks, especially in vitro, is still controversial. Metals, such as Cd, are known to affect differentiation, DNA repair and epigenetic status in mES cells. We tested the premise that Cd exerts differential toxicity in mouse embryonic stem (mES) cells by targeting total histone protein (THP) production early in stem cell development, while affecting H3K27-mono-methylation (H3K27me(1)) in latter stages of differentiation. The inability of mES cells to recover from Cd insult at concentrations greater than IC50 indicates that maximum cytotoxicity occurs during initial hours of exposure. Moreover, as a measure of chromatin stability, low dose acute Cd exposure lowers THP production. The heritable effects of Cd exposure on cell proliferation, chromatin stability and transcription observed through several cell population doublings were detected only during alternate passages on days 3, 7, and 11, presumably due to slower maturation of histone methylation marks. These findings demonstrate a selective disruption of chromatin structure following acute Cd exposure, an effect not seen in developmentally mature cells. Hence, we present that acute Cd toxicity is cumulative and disrupts DNA repair, while concurrently affecting cell cycle progression, chromatin stability and transcriptional state in mES cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Physical and environmental factors affecting the persistence of explosives particles (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Papantonakis, Michael R.; Nguyen, Viet K.; Furstenberg, Robert; White, Caitlyn; Shuey, Melissa; Kendziora, Christopher A.; McGill, R. Andrew

    2017-05-01

    Knowledge of the persistence of trace explosives materials is critical to aid the security community in designing detection methods and equipment. The physical and environmental factors affecting the lifetimes of particles include temperature, airflow, interparticle distance, adlayers, humidity, particle field size and vapor pressure. We are working towards a complete particle persistence model that captures the relative importance of these effects to allow the user, with known environmental conditions, to predict particle lifetimes for explosives or other chemicals. In this work, particles of explosives are sieved onto smooth glass substrates using particle sizes and loadings relevant to those deposited by fingerprint deposition. The coupon is introduced into a custom flow cell and monitored under controlled airflow, humidity and temperature. Photomicroscopy images of the sample taken at fixed time intervals are analyzed to monitor particle sublimation and characterized as a size-independent radial sublimation velocity for each particle in the ensemble. In this paper we build on previous work by comparing the relationship between sublimation of different materials and their vapor pressures. We also describe the influence of a sebum adlayer on particle sublimation, allowing us to better model `real world' samples.

  7. Response of mouse epidermal cells to single doses of heavy-particles

    NASA Technical Reports Server (NTRS)

    Leith, J. T.; Schilling, W. A.; Welch, G. P.

    1972-01-01

    The survival of mouse epidermal cells to heavy-particles has been studied In Vivo by the Withers clone technique. Experiments with accelerated helium, lithium and carbon ions were performed. The survival curve for the helium ion irradiations used a modified Bragg curve method with a maximum tissue penetration of 465 microns, and indicated that the dose needed to reduce the original cell number to 1 surviving cell/square centimeters was 1525 rads with a D sub o of 95 rads. The LET at the basal cell layer was 28.6 keV per micron. Preliminary experiments with lithium and carbon used treatment doses of 1250 rads with LET's at the surface of the skin of 56 and 193 keV per micron respectively. Penetration depths in skin were 350 and 530 microns for the carbon and lithium ions whose Bragg curves were unmodified. Results indicate a maximum RBE for skin of about 2 using the skin cloning technique. An attempt has been made to relate the epidermal cell survival curve to mortality of the whole animal for helium ions.

  8. Loss of Sleep Affects the Ultrastructure of Pyramidal Neurons in the Adolescent Mouse Frontal Cortex

    PubMed Central

    de Vivo, Luisa; Nelson, Aaron B.; Bellesi, Michele; Noguti, Juliana; Tononi, Giulio; Cirelli, Chiara

    2016-01-01

    Study Objective: The adolescent brain may be uniquely affected by acute sleep deprivation (ASD) and chronic sleep restriction (CSR), but direct evidence is lacking. We used electron microscopy to examine how ASD and CSR affect pyramidal neurons in the frontal cortex of adolescent mice, focusing on mitochondria, endosomes, and lysosomes that together perform most basic cellular functions, from nutrient intake to prevention of cellular stress. Methods: Adolescent (1-mo-old) mice slept (S) or were sleep deprived (ASD, with novel objects and running wheels) during the first 6–8 h of the light period, chronically sleep restricted (CSR) for > 4 days (using novel objects, running wheels, social interaction, forced locomotion, caffeinated water), or allowed to recover sleep (RS) for ∼32 h after CSR. Ultrastructural analysis of 350 pyramidal neurons was performed (S = 82; ASD = 86; CSR = 103; RS = 79; 4 to 5 mice/group). Results: Several ultrastructural parameters differed in S versus ASD, S versus CSR, CSR versus RS, and S versus RS, although the different methods used to enforce wake may have contributed to some of the differences between short and long sleep loss. Differences included larger cytoplasmic area occupied by mitochondria in CSR versus S, and higher number of secondary lysosomes in CSR versus S and RS. We also found that sleep loss may unmask interindividual differences not obvious during baseline sleep. Moreover, using a combination of 11 ultrastructural parameters, we could predict in up to 80% of cases whether sleep or wake occurred at the single cell level. Conclusions: Ultrastructural analysis may be a powerful tool to identify which cellular organelles, and thus which cellular functions, are most affected by sleep and sleep loss. Citation: de Vivo L, Nelson AB, Bellesi M, Noguti J, Tononi G, Cirelli C. Loss of sleep affects the ultrastructure of pyramidal neurons in the adolescent mouse frontal cortex. SLEEP 2016;39(4):861–874. PMID:26715225

  9. Characterization of Cement Particles Found in Peri-implantitis-Affected Human Biopsy Specimens.

    PubMed

    Burbano, Maria; Wilson, Thomas G; Valderrama, Pilar; Blansett, Jonathan; Wadhwani, Chandur P K; Choudhary, Pankaj K; Rodriguez, Lucas C; Rodrigues, Danieli C

    2015-01-01

    Peri-implantitis is a disease characterized by soft tissue inflammation and continued loss of supporting bone, which can result in implant failure. Peri-implantitis is a multifactorial disease, and one of its triggering factors may be the presence of excess cement in the soft tissues surrounding an implant. This descriptive study evaluated the composition of foreign particles from 36 human biopsy specimens with 19 specimens selected for analysis. The biopsy specimens were obtained from soft tissues affected by peri-implantitis around cement-retained implant crowns and compared with the elemental composition of commercial luting cement. Nineteen biopsy specimens were chosen for the comparison, and five test cements (TempBond, Telio, Premier Implant Cement, Intermediate Restorative Material, and Relyx) were analyzed using scanning electron microscopy equipped with energy dispersive x-ray spectroscopy. This enabled the identification of the chemical composition of foreign particles embedded in the tissue specimens and the composition of the five cements. Statistical analysis was conducted using classification trees to pair the particles present in each specimen with the known cements. The particles in each biopsy specimen could be associated with one of the commercial cements with a level of probability ranging between .79 and 1. TempBond particles were found in one biopsy specimen, Telio particles in seven, Premier Implant Cement particles in four, Relyx particles in four, and Intermediate Restorative Material particles in three. Particles found in human soft tissue biopsy specimens around implants affected by peri-implant disease were associated with five commercially available dental cements.

  10. The Autism Diagnosis in Translation: Shared Affect in Children and Mouse Models of ASD

    PubMed Central

    Bishop, Somer L.; Lahvis, Garet P.

    2013-01-01

    on dynamic social processes and clinical skill, scores from these measures do not necessarily lend themselves directly to experimental investigations into the causes of ASD. Studies of the neurobiology of autism require experimental animal models. Mice are particularly useful, in this regard, for elucidating genetic and toxicologjcal contributions to impairments in social function (Halladay et al., 2009). Behavioral tests have been developed that are relevant to autism (Crawley, 2004, 2007), including measures of repetitive behaviors (Lewis, Tanimura, Lee, & Bodfish, 2007; Moy et al., 2008), social behavior (Brodkin, 2007; Lijam et al., 1997; Moretti, Bouwknecht, Teague, Paylor, & Zoghbi, 2005), and vocal communication (Panksepp et al., 2007). Advances also include development of high-throughput measures of mouse sociability that can be used to reliably compare inbred mouse strains (Moy, et al., 2008; Nadler et al., 2004), as well as measures of social reward (Panksepp & Lahvis, 2007) and empathy (Chen, Panksepp, & Lahvis, 2009; Langford et al., 2006). With continued generation of mouse gene-targeted mice that are directly relevant to genetic linkages in ASD, there remains an urgent need to utilize a full suite of mouse behavioral tests that allows for a comprehensive assessment of the spectrum of social difficulties relevant to ASD. Using impairments in shared affect as an example, this paper explores potential avenues for collaboration between clinical and basic scientists, within an amply considered translational framework. PMID:21882361

  11. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver.

    PubMed

    Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

    2015-11-24

    Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5'-Terminal Oligo Pyrimidine tract (5'-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5'-UTR (TISU) motif. The increased translation efficiency of 5'-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.

  12. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

    PubMed Central

    Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

    2015-01-01

    Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light–dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5′-Terminal Oligo Pyrimidine tract (5′-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5′-UTR (TISU) motif. The increased translation efficiency of 5′-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. PMID:26554015

  13. Amino acid carryover in the subzonal space of mouse fertilized ova affects subsequent transport kinetics.

    PubMed

    Rudraraju, Nirmala; Baltz, Jay M

    2009-11-01

    SummaryWe have investigated whether culture in glycine-containing medium affects subsequent glycine transport by the specific transport system, GLYT1, which is the sole glycine transporter in fertilized mouse ova. When fertilized ova were maintained for 6 h in culture with a physiological level of glycine (1 mM), subsequent transport of radiolabelled glycine was decreased by 40% compared with fertilized ova that had been maintained in glycine-free medium. Kinetic measurements showed that the apparent glycine affinity was decreased after culture with glycine (Km increased from 0.20 to 0.41 mM), but maximal transport rate was unchanged (similar Vmax of 20 and 23 fmol/fertilized ovum/min). These findings could have reflected activation of GLYT1 by prolonged substrate starvation, similar to some other amino acid transport systems. However, our findings were instead consistent with the alteration in glycine transport being due to trapping of glycine within the zona pellucida resulting in competitive transport inhibition even after ova were removed from glycine-containing media. First, even very brief exposures to glycine resulted in decreased subsequent glycine transport rates, with a maximal effect apparent within ~6 min. Second, extensive washing (at least six) reversed the effect. Third, the effect was absent when zona-free fertilized ova were used. Thus, it appears that components of the external environment of preimplantation embryos may continue to affect transport kinetics for a period even after embryos are removed from environments that contain them.

  14. Verifying of endocrine disruptor chemical affect to the mouse testes: can raman spectroscopy support histology study?

    NASA Astrophysics Data System (ADS)

    Andriana, Bibin B.; Oshima, Yusuke; Takanezawa, Sota; Tay, Tat W.; Rosawati Soeratman, Catherine Linda; Alam, Mohammad S.; Mitsuoka, Hiroki; Zhu, Xiao B.; Suzuki, Toshiaki; Yamamoto, Yuko S.; Tsunekawa, Naoki; Kanai, Yoshiakira; Kurohmaru, Masamichi; Sato, Hidetoshi

    2009-02-01

    One of suspect environmental endocrine disruptors that affect mouse male reproduction by altering the morphology of Sertoli cells and spermatogenic cells is phthalate. The effects of mono(2-ethylhexyl)phthalate (MEHP), one of metabolites of di(2-ethylhexyl)phthalate , on immature mouse testes in vivo were examined. We have recently shown that MEHP induced Sertoli cells necrosis and spermatogenic cells apoptosis in mice by TUNEL method, F-actin staining, and ultrastructural study, but there is no data for biochemical changing of testes due to those methods could not explore. To verify in detail of it, we conducted Raman spectroscopy study with 785 nm wavelength laser line, 50mW of laser power and 3 minutes of exposure time to analysis the MEHP-treated testicular tissue, which has been fixatived by 4% paraformaldehyde (PFA). Five weeks old (5 w.o) male mice were used in this experiment. As the results, the alterations were observed by Raman spectroscopy that there are significantly differences of DNA, actin filament, type IV collagen and amide I between control group (0 μM MEHP) and treatment group (100 μM MEHP). These results significantly support histology staining observation (such as the apoptotic spermatogenic cells which is associated with DNA fragmentation and F-actin disruption) and ultrastructural observation (such as mitochondria rupture and disintegration of nucleus membrane). Raman spectroscopy can be used for 4% PFA-fixatived tissue observation. However, we recommend that Raman spectroscopy may be able to be expanded as an armamentarium not just for the clarification of histology staining and ultrastructural study, but furthermore, it may be as a non-invasion assessment for screening animal tissue toxicity of chemical in future.

  15. Age affects gene expression in mouse spermatogonial stem/progenitor cells.

    PubMed

    Kokkinaki, Maria; Lee, Tin-Lap; He, Zuping; Jiang, Jiji; Golestaneh, Nady; Hofmann, Marie-Claude; Chan, Wai-Yee; Dym, Martin

    2010-06-01

    Spermatogenesis in man starts with spermatogonial stem cells (SSCs), and leads to the production of sperm in approximately 64 days, common to old and young men. Sperm from elderly men are functional and able to fertilize eggs and produce offspring, even though daily sperm production is more than 50% lower and damage to sperm DNA is significantly higher in older men than in those who are younger. Our hypothesis is that the SSC/spermatogonial progenitors themselves age. To test this hypothesis, we studied the gene expression profile of mouse SSC/progenitor cells at several ages using microarrays. After sequential enzyme dispersion, we purified the SSC/progenitors with immunomagnetic cell sorting using an antibody to GFRA1, a known SSC/progenitor cell marker. RNA was isolated and used for the in vitro synthesis of amplified and labeled cRNAs that were hybridized to the Affymetrix mouse genome microarrays. The experiments were repeated twice with different cell preparations, and statistically significant results are presented. Quantitative RT-PCR analysis was used to confirm the microarray results. Comparison of four age groups (6 days, 21 days, 60 days, and 8 months old) showed a number of genes that were expressed specifically in the older mice. Two of them (i.e. Icam1 and Selp) have also been shown to mark aging hematopoietic stem cells. On the other hand, the expression levels of the genes encoding the SSC markers Gfra1 and Plzf did not seem to be significantly altered by age, indicating that age affects only certain SSC/progenitor properties.

  16. CD24 expression does not affect dopamine neuronal survival in a mouse model of Parkinson's disease

    PubMed Central

    Hayat, Shaista; Carnwath, Tom; Garas, Shaady; Sleeman, Jonathan P.; Barker, Roger A.

    2017-01-01

    Parkinson’s disease (PD) is a progressive neurodegenerative condition that is characterised by the loss of specific populations of neurons in the brain. The mechanisms underlying this selective cell death are unknown but by using laser capture microdissection, the glycoprotein, CD24 has been identified as a potential marker of the populations of cells that are affected in PD. Using in situ hybridization and immunohistochemistry on sections of mouse brain, we confirmed that CD24 is robustly expressed by many of these subsets of cells. To determine if CD24 may have a functional role in PD, we modelled the dopamine cell loss of PD in Cd24 mutant mice using striatal delivery of the neurotoxin 6-OHDA. We found that Cd24 mutant mice have an anatomically normal dopamine system and that this glycoprotein does not modulate the lesion effects of 6-OHDA delivered into the striatum. We then undertook in situ hybridization studies on sections of human brain and found—as in the mouse brain—that CD24 is expressed by many of the subsets of the cells that are vulnerable in PD, but not those of the midbrain dopamine system. Finally, we sought to determine if CD24 is required for the neuroprotective effect of Glial cell-derived neurotrophic factor (GDNF) on the dopaminergic nigrostriatal pathway. Our results indicate that in the absence of CD24, there is a reduction in the protective effects of GDNF on the dopaminergic fibres in the striatum, but no difference in the survival of the cell bodies in the midbrain. While we found no obvious role for CD24 in the normal development and maintenance of the dopaminergic nigrostriatal system in mice, it may have a role in mediating the neuroprotective aspects of GDNF in this system. PMID:28182766

  17. Efficiency of log wood combustion affects the toxicological and chemical properties of emission particles.

    PubMed

    Tapanainen, Maija; Jalava, Pasi I; Mäki-Paakkanen, Jorma; Hakulinen, Pasi; Lamberg, Heikki; Ruusunen, Jarno; Tissari, Jarkko; Jokiniemi, Jorma; Hirvonen, Maija-Riitta

    2012-05-01

    Particulate matter (PM) has been identified as a major environmental pollutant causing severe health problems. Large amounts of the harmful particulate matter (PM) are emitted from residential wood combustion, but the toxicological properties of wood combustion particles are poorly known. To investigate chemical and consequent toxicological characteristics of PM(1) emitted from different phases of batch combustion in four heating appliances. Mouse RAW264.7 macrophages and human BEAS-2B bronchial epithelial cells were exposed for 24 h to different doses (15-300 µg/mL) of wood combustion particles. After the exposure, cytotoxicity, genotoxicity, production of the inflammatory mediators (TNF-α and MIP-2) and effects on the cell cycle were assessed. Furthermore, the detected toxicological responses were compared with the chemical composition of PM(1) samples including PAHs, metals and ions. All the wood combustion samples exerted high cytotoxicity, but only moderate inflammatory activity. The particles emitted from the inefficient phase of batch combustion in the sauna stove (SS) induced the most extensive cytotoxic and genotoxic responses in mammalian cells. Polycyclic aromatic hydrocarbons (PAHs) and other organic compounds in PM(1) samples might have contributed to these effects. Instead, water-soluble metals seemed to participate in the cytotoxic responses triggered by the particles from more efficient batch combustion in the masonry heaters. Overall, the toxicological responses were decreased when the combustion phase was more efficient. Efficiency of batch combustion plays a significant role in the harmfulness of PM even under incomplete wood combustion processes.

  18. Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells.

    PubMed

    Omar Zaki, Siti Sarah; Katas, Haliza; Hamid, Zariyantey Abd

    2015-11-01

    Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1(+)), myeloid-committed progenitors (CD11b(+), Gr-1(+)), and lymphoid-committed progenitors (CD45(+), CD3e(+)). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1(+) cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b(+) and Gr-1(+) cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45(+) and CD3e(+) cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Histochemical and biochemical analysis of the size-dependent nanoimmunoresponse in mouse Peyer’s patches using fluorescent organosilica particles

    PubMed Central

    Awaad, Aziz; Nakamura, Michihiro; Ishimura, Kazunori

    2012-01-01

    Background/objective The size-dependent mucosal immunoresponse against nanomaterials (nanoimmunoresponse) is an important approach for mucosal vaccination. In the present work, the size-dependent nanoimmunoresponse of mouse Peyer’s patches (PPs) and immunoglobulin A (IgA) level was investigated using fluorescent thiol-organosilica particles. Methods Various sizes of fluorescent thiol-organosilica particles (100, 180, 365, 745, and 925 nm in diameter) were administered orally. PPs were analyzed histochemically, and IgA levels in PP homogenates, intestinal secretions around PPs, and bile were analyzed biochemically. Results When compared with the larger particles (745 and 925 nm), oral administration of smaller thiol-organosilica particles (100, 180, and 365 nm) increased the number of CD11b+ macrophages and IgA+ cells in the subepithelial domes of the PPs. Additionally, administration of larger particles induced the expression of alpha-L-fucose and mucosal IgA on the surface of M cells in the follicle-associated epithelia of PPs and increased the number of 33D1+ dendritic cells in the subepithelial domes of the PPs. IgA contents in the bile and PP homogenates were high after the administration of the 100 nm particles, but IgA levels in the intestinal secretions were high after the administration of the 925 nm particles. Two size-dependent routes of IgA secretions into the intestinal lumen, the enterohepatic route for smaller particles and the mucosal route for larger particles were proposed. Conclusion Thiol-organosilica particles demonstrated size-dependent nanoimmunoresponse after oral administration. The size of the particles may control the mucosal immunity in PPs and were useful in mucosal vaccination approaches. PMID:22619503

  20. Zebra pattern in rocks as a function of grain growth affected by second-phase particles

    NASA Astrophysics Data System (ADS)

    Kelka, Ulrich; Koehn, Daniel; Beaudoin, Nicolas

    2015-09-01

    In this communication we present a simple microdynamic model which can explain the beginning of the zebra pattern formation in rocks. The two dimensional model consists of two main processes, mineral replacement along a reaction front, and grain boundary migration affected by impurities. In the numerical model we assume that an initial distribution of second-phase particles is present due to sedimentary layering. The reaction front percolates the model and redistributes second-phase particles by shifting them until the front is saturated and drops the particles again. This produces and enhances initial layering. Grain growth is hindered in layers with high second-phase particle concentrations whereas layers with low concentrations coarsen. Due to the grain growth activity in layers with low second-phase particle concentrations these impurities are collected at grain boundaries and the crystals become very clean. Therefore the white layers in the pattern contain large grains with low concentration of second-phase particles, whereas the dark layers contain small grains with a large second-phase particle concentration.

  1. Concordance in Genomic Changes Between Mouse Lungs and Human Airway Epithelial Cells Exposed to Diesel Exhaust Particles

    EPA Science Inventory

    Human and animal toxicity studies have shown that exposure to diesel exhaust particles (DEP) or their constituents affect multiple biological processes including immune and inflammatory pathways, mutagenesis and in some cases carcinogenesis. This study compared genomic changes by...

  2. Concordance in Genomic Changes Between Mouse Lungs and Human Airway Epithelial Cells Exposed to Diesel Exhaust Particles

    EPA Science Inventory

    Human and animal toxicity studies have shown that exposure to diesel exhaust particles (DEP) or their constituents affect multiple biological processes including immune and inflammatory pathways, mutagenesis and in some cases carcinogenesis. This study compared genomic changes by...

  3. Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis

    PubMed Central

    Chen, Lin; Adar, Rivka; Yang, Xiao; Monsonego, Efrat O.; Li, Cuiling; Hauschka, Peter V.; Yayon, Avner; Deng, Chu-Xia

    1999-01-01

    Missense mutations in fibroblast growth factor receptor 3 (FGFR3) result in several human skeletal dysplasias, including the most common form of dwarfism, achondroplasia. Here we show that a glycine-to-cysteine substitution at position 375 (Gly375Cys) in human FGFR3 causes ligand-independent dimerization and phosphorylation of FGFR3 and that the equivalent substitution at position 369 (Gly369Cys) in mouse FGFR3 causes dwarfism with features mimicking human achondroplasia. Accordingly, homozygous mice were more severely affected than heterozygotes. The resulting mutant mice exhibited macrocephaly and shortened limbs due to retarded endochondral bone growth and premature closure of cranial base synchondroses. Compared with their wild-type littermates, mutant mice growth plates shared an expanded resting zone and narrowed proliferating and hypertrophic zones, which is correlated with the activation of Stat proteins and upregulation of cell-cycle inhibitors. Reduced bone density is accompanied by increased activity of osteoclasts and upregulation of genes that are related to osteoblast differentiation, including osteopontin, osteonectin, and osteocalcin. These data reveal an essential role for FGF/FGFR3 signals in both chondrogenesis and osteogenesis during endochondral ossification. J. Clin. Invest. 104:1517–1525 (1999). PMID:10587515

  4. Effects of drugs affecting the noradrenergic system on convulsions in the quaking mouse.

    PubMed

    Chermat, R; Doaré, L; Lachapelle, F; Simon, P

    1981-12-01

    Handling-induced convulsions in the quaking mouse can be blocked by: phenobarbital, pentobarbital or phenytoin; postsynaptic alpha-adrenoceptor agonists (noradrenaline, phenylephrine, CRL 40028); presynaptic alpha-adrenoceptor blockers (yohimbine, mianserine); catecholamine liberating agent (amphetamine); noradrenaline reuptake inhibitors (cocaine, imipramine, desipramine). Moreover, the protective effect of yohimbine was antagonized by clonidine, prazosin or alpha-methylparatyrosine, and the protective effect of CRL 40028 was antagonized by prazosin but not by alpha-methyltyrosine. Drugs acting by other mechanisms (pilocarpine, atropine, trihexyphenidyl, (--)-5-HTP, methysergide, pimozide, clonidine, alpha-methyl DOPA, prazosin, isoprenaline, salbutamol) did not protect against convulsions. A slight protection was obtained with high doses of apomorphine and also with (+/-)-propranolol. This effect is probably not related to blockade of beta-adrenoceptors because the same effect was obtained with (+)propranolol. In young quaking mice, where susceptibility to convulsions is low, both postsynaptic alpha-adrenoceptor blockers and presynaptic alpha-adrenoceptor antagonist lowered the convulsive threshold. Thus, this seems to constitute an interesting model for the in vivo study of substances which affect the central alpha-adrenoceptors either pre- or postsynaptically.

  5. Social defeat interacts with Disc1 mutations in the mouse to affect behavior.

    PubMed

    Haque, F Nipa; Lipina, Tatiana V; Roder, John C; Wong, Albert H C

    2012-08-01

    DISC1 (Disrupted-in-schizophrenia 1) is a strong candidate susceptibility gene for psychiatric disease that was originally discovered in a family with a chromosomal translocation severing this gene. Although the family members with the translocation had an identical genetic mutation, their clinical diagnosis and presentation varied significantly. Gene-environment interactions have been proposed as a mechanism underlying the complex heritability and variable phenotype of psychiatric disorders such as major depressive disorder and schizophrenia. We hypothesized that gene-environment interactions would affect behavior in a mutant Disc1 mouse model. We examined the effect of chronic social defeat (CSD) as an environmental stressor in two lines of mice carrying different Disc1 point mutations, on behaviors relevant to psychiatric illness: locomotion in a novel open field (OF), pre-pulse inhibition (PPI) of the acoustic startle response, latent inhibition (LI), elevated plus maze (EPM), forced swim test (FST), sucrose consumption (SC), and the social interaction task for sociability and social novelty (SSN). We found that Disc1-L100P +/- and wild-type mice have similar anxiety responses to CSD, while Q31L +/- mice had a very different response. We also found evidence of significant gene-environment interactions in the OF, EPM and SSN.

  6. Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth.

    PubMed

    Madeja, Zofia; Yadi, Hakim; Apps, Richard; Boulenouar, Selma; Roper, Stephen J; Gardner, Lucy; Moffett, Ashley; Colucci, Francesco; Hemberger, Myriam

    2011-03-08

    The mammalian fetus represents a semiallograft within the maternal uterus yet is not rejected. This situation is particularly pronounced in species with a hemochorial type of placentation, such as humans and rodents, where maternal tissues and blood are in direct contact with fetal trophoblast and thus potentially with paternal antigens. The main polymorphic antigens responsible for graft rejection are MHC antigens. In humans the trophoblast cells invading into the decidua have a unique pattern of MHC class I expression characterized by both classical (HLA-C) and nonclassical (HLA-G and HLA-E) molecules. Whether such an unusual MHC repertoire on the surface of trophoblast is a conserved feature between species with hemochorial placentation has not been resolved. Here we demonstrate, using a range of methods, that C57BL/6 mouse trophoblast predominantly expresses only one MHC class I antigen, H2-K, at the cell surface of giant cells but lacks expression of nonclassical MHC molecules. Antigenic disparity between parental MHCs affects trophoblast-induced transformation of the uterine vasculature and, consequently, placental and fetal gowth. Maternal uterine blood vessels were more dilated, allowing for increased blood supply, in certain combinations of maternal and paternal MHC haplotypes, and these allogeneic fetuses and placentas were heavier at term compared with syngeneic controls. Thus, maternal-fetal immune interactions are instrumental to optimize reproductive success. This cross-talk has important implications for human disorders of pregnancy, such as preeclampsia and fetal growth restriction.

  7. Paternal benzo[a]pyrene exposure affects gene expression in the early developing mouse embryo.

    PubMed

    Brevik, Asgeir; Lindeman, Birgitte; Rusnakova, Vendula; Olsen, Ann-Karin; Brunborg, Gunnar; Duale, Nur

    2012-09-01

    The health of the offspring depends on the genetic constitution of the parental germ cells. The paternal genome appears to be important; e.g., de novo mutations in some genes seem to arise mostly from the father, whereas epigenetic modifications of DNA and histones are frequent in the paternal gonads. Environmental contaminants which may affect the integrity of the germ cells comprise the polycyclic aromatic hydrocarbon, benzo[a]pyrene (B[a]P). B[a]P has received much attention due to its ubiquitous distribution, its carcinogenic and mutagenic potential, and also effects on reproduction. We conducted an in vitro fertilization (IVF) experiment using sperm cells from B[a]P-exposed male mice to study effects of paternal B[a]P exposure on early gene expression in the developing mouse embryo. Male mice were exposed to a single acute dose of B[a]P (150 mg/kg, ip) 4 days prior to isolation of cauda sperm, followed by IVF of oocytes from unexposed superovulated mice. Gene expression in fertilized zygotes/embryos was determined using reverse transcription-qPCR at the 1-, 2-, 4-, 8-, and blastocyst cell stages of embryo development. We found that paternal B[a]P exposure altered the expression of numerous genes in the developing embryo especially at the blastocyst stage. Some genes were also affected at earlier developmental stages. Embryonic gene expression studies seem useful to identify perturbations of signaling pathways resulting from exposure to contaminants, and can be used to address mechanisms of paternal effects on embryo development.

  8. Exacerbation of thrombotic events by diesel exhaust particle in mouse model of hypertension.

    PubMed

    Nemmar, Abderrahim; Zia, Shaheen; Subramaniyan, Deepa; Fahim, Mohamed A; Ali, Badreldin H

    2011-07-11

    Several epidemiological studies have shown that acute exposure to particulate air pollution is associated with increases in cardiovascular morbidity and mortality, and that these effects are especially exacerbated among individuals with pre-existing compromised cardiovascular function such as hypertension. This study was undertaken to determine the cardiovascular effect of diesel exhaust on TO mice made hypertensive by implanting osmotic minipump infusing angiotensin II or vehicle (control). On day 13, the animals were intratracheally instilled with either DEP (15 μg/mouse) or saline. 24 h later, pulmonary exposure to DEP had significantly decreased the systolic blood pressure (SBP) in hypertensive (HT) mice (P<0.01), but not in normotensive (NT) mice. The number of leukocytes and red blood cells, and the plasma interleukin 6 concentration in plasma, however, were not affected in any of the animals. The PaO₂ was decreased, and PaCO₂ increased in DEP-treated HT mice compared to NT mice treated with DEP (P<0.05). The number of circulating platelets was significantly increased in DEP-treated HT versus saline-treated HT and DEP-treated NT mice. Moreover, in NT mice, DEP exposure induced a prothrombotic effect in pial arterioles compared with saline-treated NT mice (P<0.05). Interestingly, in DEP-treated HT mice, the prothrombotic events were significantly aggravated compared with saline-treated HT and DEP-treated NT mice. The direct addition of DEP (0.1-1 μg/ml) to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced in blood of HT mice. In vitro exposure to DEP (0.25-1 μg/ml) led to activated intravascular coagulation, an effect that was confirmed by a shortening of both the activated partial thromboplastin time (aPTT) and the prothrombin time (PT). The effect of DEP on aPTT was potentiated in the plasma of HT mice. It can be concluded that the thrombotic events caused by

  9. Nanomorphology of Itokawa regolith particles: Application to space-weathering processes affecting the Itokawa asteroid

    NASA Astrophysics Data System (ADS)

    Matsumoto, Toru; Tsuchiyama, Akira; Uesugi, Kentaro; Nakano, Tsukasa; Uesugi, Masayuki; Matsuno, Junya; Nagano, Takashi; Shimada, Akira; Takeuchi, Akihisa; Suzuki, Yoshio; Nakamura, Tomoki; Nakamura, Michihiko; Gucsik, Arnold; Nagaki, Keita; Sakaiya, Tatsuhiro; Kondo, Tadashi

    2016-08-01

    The morphological properties of 26 regolith particles from asteroid Itokawa were observed using scanning electron microscopes in combination with an investigation of their three-dimensional shapes obtained through X-ray microtomography. Surface observations of a cross section of the LL5 chondrite, and of crystals of olivine and pyroxene, were also performed for comparison. Some Itokawa particles have surfaces corresponding to walls of microdruses in the LL chondrite, where concentric polygonal steps develop and euhedral or subhedral grains exist. These formed through vapor growth owing to thermal annealing, which might have been caused by thermal metamorphism or shock-induced heating in Itokawa's parent body. Most of the Itokawa particles have more or less fractured surfaces, indicating that they were formed by disaggregation, probably caused by impacts. Itokawa particles with angular and rounded edges observed in computed tomography images are associated with surfaces exhibiting clear and faint structures, respectively. These surfaces can be interpreted by invoking different degrees of abrasion after regolith formation. A possible mechanism for the abrasion process is grain migration caused by impact-driven seismic waves. Space-weathered rims with blisters are distributed heterogeneously across the Itokawa regolith particles. This heterogeneous distribution can be explained by particle motion and fracturing, combined with solar-wind irradiation of the particle surfaces. The regolith activity-including grain motion, fracturing, and abrasion-might effectively act as refreshing process of Itokawa particles against space-weathered rim formation. The space-weathering processes affecting Itokawa would have developed simultaneously with space-weathered rim formation and regolith particle refreshment.

  10. How salt lakes affect atmospheric new particle formation: A case study in Western Australia.

    PubMed

    Kamilli, K A; Ofner, J; Krause, T; Sattler, T; Schmitt-Kopplin, P; Eitenberger, E; Friedbacher, G; Lendl, B; Lohninger, H; Schöler, H F; Held, A

    2016-12-15

    New particle formation was studied above salt lakes in-situ using a mobile aerosol chamber set up above the salt crust and organic-enriched layers of seven different salt lakes in Western Australia. This unique setup made it possible to explore the influence of salt lake emissions on atmospheric new particle formation, and to identify interactions of aqueous-phase and gas-phase chemistry. New particle formation was typically observed at enhanced air temperatures and enhanced solar irradiance. Volatile organic compounds were released from the salt lake surfaces, probably from a soil layer enriched in organic compounds from decomposed leaf litter, and accumulated in the chamber air. After oxidation of these organic precursor gases, the reaction products contributed to new particle formation with observed growth rates from 2.7 to 25.4nmh(-1). The presence of ferrous and ferric iron and a drop of pH values in the salt lake water just before new particle formation events indicated that organic compounds were also oxidized in the aqueous phase, affecting the new particle formation process in the atmosphere. The contribution of aqueous-phase chemistry to new particle formation is assumed, as a mixture of hundreds of oxidized organic compounds was characterized with several analytical techniques. This chemically diverse composition of the organic aerosol fraction contained sulfur- and nitrogen-containing organic compounds, and halogenated organic compounds. Coarse mode particles were analyzed using electron microscopy, energy dispersive X-ray spectroscopy and Raman spectroscopy. Ultra-high resolution mass spectrometry was applied to analyze filter samples. A targeted mass spectral analysis revealed the formation of organosulfates from monoterpene precursors and two known tracers for secondary organic aerosol formation from atmospheric oxidation of 1,8-cineole, which indicates that a complex interplay of aqueous-phase and gas-phase oxidation of monoterpenes contributes to

  11. Intracisternal A particle genes: Distribution in the mouse genome, active subtypes, and potential roles as species-specific mediators of susceptibility to cancer.

    PubMed

    Qin, Chunhua; Wang, Zhibin; Shang, Jin; Bekkari, Kavitha; Liu, Rong; Pacchione, Stephen; McNulty, Kathleen A; Ng, Alan; Barnum, John E; Storer, Richard D

    2010-01-01

    Rodents, mice and rats in particular, are the species of choice for evaluating chemical carcinogenesis. However, different species and strains often respond very differently, undermining the logic of extrapolation of animal results to humans and complicating risk assessment. Intracisternal A particles (IAPs), endogenous retroviral sequences, are an important class of transposable elements that induce genomic mutations and cell transformation by disrupting gene expression. Several lines of evidence support a role of IAPs as mouse-specific genetic factors in responses to toxicity and expression of disease phenotypes. Since multiple subtypes and copies of IAPs are present in the mouse genome, their activity and locations relative to functional genes are of critical importance. This study identified the major "active" subtypes of IAPs (subtype 1/1a) that are responsible for newly transposed IAP insertions described in the literature, and confirmed that (1) polymorphisms for IAP insertions exist among different mouse strains and (2) promoter activity of the LTRs can be modulated by chemicals. This study further identified all the genes in the C57BL/6 mouse genome with IAP subtype 1 and 1a sequences inserted in their proximity, and the major biofunctional categories and cellular signaling networks of those genes. Since many "IAP-associated genes" play important roles in the regulation of cell proliferation, cell cycle, and cell death, the associated IAPs, upon activation, can affect cellular responses to xenobiotics and disease processes, especially carcinogenesis. This systemic analysis provides a solid foundation for further investigations of the role of IAPs as species- and strain-specific disease susceptibility factors.

  12. Combining Video, Audio and Lexical Indicators of Affect in Spontaneous Conversation via Particle Filtering

    PubMed Central

    Savran, Arman; Cao, Houwei; Shah, Miraj; Nenkova, Ani; Verma, Ragini

    2013-01-01

    We present experiments on fusing facial video, audio and lexical indicators for affect estimation during dyadic conversations. We use temporal statistics of texture descriptors extracted from facial video, a combination of various acoustic features, and lexical features to create regression based affect estimators for each modality. The single modality regressors are then combined using particle filtering, by treating these independent regression outputs as measurements of the affect states in a Bayesian filtering framework, where previous observations provide prediction about the current state by means of learned affect dynamics. Tested on the Audio-visual Emotion Recognition Challenge dataset, our single modality estimators achieve substantially higher scores than the official baseline method for every dimension of affect. Our filtering-based multi-modality fusion achieves correlation performance of 0.344 (baseline: 0.136) and 0.280 (baseline: 0.096) for the fully continuous and word level sub challenges, respectively. PMID:25300451

  13. Changes in end-to-end interactions of tropomyosin affect mouse cardiac muscle dynamics.

    PubMed

    Gaffin, Robert D; Gokulan, Kuppan; Sacchettini, James C; Hewett, Timothy E; Klevitsky, Raisa; Robbins, Jeffrey; Sarin, Vandana; Zawieja, David C; Meininger, Gerald A; Muthuchamy, Mariappan

    2006-08-01

    The ends of striated muscle tropomyosin (TM) are integral for thin filament cooperativity, determining the cooperative unit size and regulating the affinity of TM for actin. We hypothesized that altering the alpha-TM carboxy terminal overlap end to the beta-TM counterpart would affect the amino-terminal association, which would alter the end-to-end interactions of TM molecules in the thin filament regulatory strand and affect the mechanisms of cardiac muscle contraction. To test this hypothesis, we generated transgenic (TG) mouse lines that express a mutant form of alpha-TM in which the first 275 residues are from alpha-TM and the last nine amino acids are from beta-TM (alpha-TM9aaDeltabeta). Molecular analyses show that endogenous alpha-TM mRNA and protein are nearly completely replaced with alpha-TM9aaDeltabeta. Working heart preparations data show that the rates of contraction and relaxation are reduced in alpha-TM9aaDeltabeta hearts. Left ventricular pressure and time to peak pressure are also reduced (-12% and -13%, respectively). The ratio of maximum to minimum first derivatives of change in left ventricular systolic pressure with respect to time (ratio of +dP/dt to -dP/dt, respectively) is increased, but tau is not changed significantly. Force-intracellular calcium concentration ([Ca2+]i) measurements from intact papillary fibers demonstrate that alpha-TM9aaDeltabeta TG fibers produce less force per given [Ca2+]i compared with nontransgenic fibers. Taken together, the data demonstrate that the rate of contraction is primarily affected in TM TG hearts. Protein docking studies show that in the mutant molecule, the overall carbon backbone is perturbed about 1.5 A, indicating that end-to-end interactions are altered. These results demonstrate that the localized flexibility present in the coiled-coil structures of TM isoforms is different, and that plays an important role in interacting with neighboring thin filament regulatory proteins and with differentially

  14. Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue

    PubMed Central

    Mirsch, Johanna; Tommasino, Francesco; Frohns, Antonia; Conrad, Sandro; Durante, Marco; Scholz, Michael; Friedrich, Thomas; Löbrich, Markus

    2015-01-01

    Charged particles are increasingly used in cancer radiotherapy and contribute significantly to the natural radiation risk. The difference in the biological effects of high-energy charged particles compared with X-rays or γ-rays is determined largely by the spatial distribution of their energy deposition events. Part of the energy is deposited in a densely ionizing manner in the inner part of the track, with the remainder spread out more sparsely over the outer track region. Our knowledge about the dose distribution is derived solely from modeling approaches and physical measurements in inorganic material. Here we exploited the exceptional sensitivity of γH2AX foci technology and quantified the spatial distribution of DNA lesions induced by charged particles in a mouse model tissue. We observed that charged particles damage tissue nonhomogenously, with single cells receiving high doses and many other cells exposed to isolated damage resulting from high-energy secondary electrons. Using calibration experiments, we transformed the 3D lesion distribution into a dose distribution and compared it with predictions from modeling approaches. We obtained a radial dose distribution with sub-micrometer resolution that decreased with increasing distance to the particle path following a 1/r2 dependency. The analysis further revealed the existence of a background dose at larger distances from the particle path arising from overlapping dose deposition events from independent particles. Our study provides, to our knowledge, the first quantification of the spatial dose distribution of charged particles in biologically relevant material, and will serve as a benchmark for biophysical models that predict the biological effects of these particles. PMID:26392532

  15. Repeated acute exposures to hypergravity during early development subtly affect CD-1 mouse neurobehavioural profile.

    PubMed

    Francia, Nadia; Simeoni, Michelle; Petruzzi, Simona; Santucci, Daniela; Aloe, Luigi; Alleva, Enrico

    2006-05-15

    Exposure to altered gravitational environment, especially during critical ontogenetic phases, may induce persistent nervous system modifications and behavioural anomalies. This study evaluated the effects of hypergravity exposure on the development of the nervous system and assessed the relevance of parity in the mother's responses to altered gravitational stimuli. CD-1 mouse pups of both sexes delivered by primiparous and biparous dams were exposed to 1h of 2 G rotationally induced hypergravity from PND2 to PND9. Sensorimotor responses and somatic growth were daily measured (PND2-PND15), ultrasonic vocalisations recorded on PNDs 2, 5 and 9, and homing behaviour evaluated on PND12. In addition, spatial orientation ability was assessed in a T-maze on PND18, while mice exploratory behaviour and locomotor activity were evaluated in an open-field test (PND21). Long-term effects of hypergravity exposure on both spatial learning (Morris water-maze test) and brain levels of NGF and BDNF were also investigated at adulthood. Rotation per se induced a delay in somatic growth, sensorimotor responses and ultrasonic vocalisation profile, while hypergravity highlighted sex differences in open-field behaviour. Strategies to solve a spatial learning task, rather than learning per se, were affected by early exposure to rotation, while hypergravity selectively altered behavioural profile in the reversal phase of the test. Early exposure to rotation per se also decreased hypothalamic BDNF levels, while hypergravity reduced NGF levels in the frontal cortex. Previous maternal experience did not interact with hypergravity exposure, while differences between offspring of primiparous and biparous dams were observed in sensorimotor development and exploratory behaviour.

  16. Timing of mTOR activation affects tuberous sclerosis complex neuropathology in mouse models.

    PubMed

    Magri, Laura; Cominelli, Manuela; Cambiaghi, Marco; Cursi, Marco; Leocani, Letizia; Minicucci, Fabio; Poliani, Pietro Luigi; Galli, Rossella

    2013-09-01

    Tuberous sclerosis complex (TSC) is a dominantly inherited disease with high penetrance and morbidity, and is caused by mutations in either of two genes, TSC1 or TSC2. Most affected individuals display severe neurological manifestations - such as intractable epilepsy, mental retardation and autism - that are intimately associated with peculiar CNS lesions known as cortical tubers (CTs). The existence of a significant genotype-phenotype correlation in individuals bearing mutations in either TSC1 or TSC2 is highly controversial. Similar to observations in humans, mouse modeling has suggested that a more severe phenotype is associated with mutation in Tsc2 rather than in Tsc1. However, in these mutant mice, deletion of either gene was achieved in differentiated astrocytes. Here, we report that loss of Tsc1 expression in undifferentiated radial glia cells (RGCs) early during development yields the same phenotype detected upon deletion of Tsc2 in the same cells. Indeed, the same aberrations in cortical cytoarchitecture, hippocampal disturbances and spontaneous epilepsy that have been detected in RGC-targeted Tsc2 mutants were observed in RGC-targeted Tsc1 mutant mice. Remarkably, thorough characterization of RGC-targeted Tsc1 mutants also highlighted subventricular zone (SVZ) disturbances as well as STAT3-dependent and -independent developmental-stage-specific defects in the differentiation potential of ex-vivo-derived embryonic and postnatal neural stem cells (NSCs). As such, deletion of either Tsc1 or Tsc2 induces mostly overlapping phenotypic neuropathological features when performed early during neurogenesis, thus suggesting that the timing of mTOR activation is a key event in proper neural development.

  17. Particle size distribution of rice flour affecting the starch enzymatic hydrolysis and hydration properties.

    PubMed

    de la Hera, Esther; Gomez, Manuel; Rosell, Cristina M

    2013-10-15

    Rice flour is becoming very attractive as raw material, but there is lack of information about the influence of particle size on its functional properties and starch digestibility. This study evaluates the degree of dependence of the rice flour functional properties, mainly derived from starch behavior, with the particle size distribution. Hydration properties of flours and gels and starch enzymatic hydrolysis of individual fractions were assessed. Particle size heterogeneity on rice flour significantly affected functional properties and starch features, at room temperature and also after gelatinization; and the extent of that effect was grain type dependent. Particle size heterogeneity on rice flour induces different pattern in starch enzymatic hydrolysis, with the long grain having slower hydrolysis as indicated the rate constant (k). No correlation between starch digestibility and hydration properties or the protein content was observed. It seems that in intact granules interactions with other grain components must be taken into account. Overall, particle size fractionation of rice flour might be advisable for selecting specific physico-chemical properties.

  18. Animal Slurry Acidification Affects Particle Size Distribution and Improves Separation Efficiency.

    PubMed

    Regueiro, I; Pociask, M; Coutinho, J; Fangueiro, D

    2016-05-01

    Solid-liquid separation is performed to improve slurry management, and acidification of the slurry is used to reduce ammonia emissions. Acidification is known to affect slurry characteristics, and we hypothesized that it may affect mechanical separation. Our objective in this study was to assess the effects of slurry acidification on particle size distribution and separation efficiency. Two types of slurry, aged pig and fresh dairy, and two different acidification additives, sulfuric acid and aluminum sulfate (alum), were studied. We found that acidification with sulfuric acid promoted phosphorus (P) solubilization for both slurries, but no change was observed with alum. More ammonium was found in the acidified dairy slurry compared with raw dairy slurry, but no difference was found in aged pig slurry. Acidification before separation increased the proportion of the solid fraction in the slurries, and the effect was significantly higher with alum. When alum was used to acidify the slurries, the proportion of particles larger than 100 μm increased significantly, as did the P concentration in this particle size range. The efficiency of P separation increased markedly in both slurries when alum was used, with the removal to the solid fraction of the dairy slurry being almost complete (90%). Because the priority in mechanical separation is to increase the P content in the solid fraction, the use of alum before centrifugation may be the most suitable option for enhancing its nutrient content. We conclude that separation efficiency and particle size distribution are significantly affected by acidification, but the extent of the effects depends on slurry type and on the type of additive used for acidification. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  19. Modeling of mouse eye and errors in ocular parameters affecting refractive state

    NASA Astrophysics Data System (ADS)

    Bawa, Gurinder

    Rodents eye are particularly used to study refractive error state of an eye and development of refractive eye. Genetic organization of rodents is similar to that of humans, which makes them interesting candidates to be researched upon. From rodents family mice models are encouraged over rats because of availability of genetically engineered models. Despite of extensive work that has been performed on mice and rat models, still no one is able to quantify an optical model, due to variability in the reported ocular parameters. In this Dissertation, we have extracted ocular parameters and generated schematics of eye from the raw data from School of Medicine, Detroit. In order to see how the rays would travel through an eye and the defects associated with an eye; ray tracing has been performed using ocular parameters. Finally we have systematically evaluated the contribution of various ocular parameters, such as radii of curvature of ocular surfaces, thicknesses of ocular components, and refractive indices of ocular refractive media, using variational analysis and a computational model of the rodent eye. Variational analysis revealed that variation in all the ocular parameters does affect the refractive status of the eye, but depending upon the magnitude of the impact those parameters are listed as critical or non critical. Variation in the depth of the vitreous chamber, thickness of the lens, radius of the anterior surface of the cornea, radius of the anterior surface of the lens, as well as refractive indices for the lens and vitreous, appears to have the largest impact on the refractive error and thus are categorized as critical ocular parameters. The radii of the posterior surfaces of the cornea and lens have much smaller contributions to the refractive state, while the radii of the anterior and posterior surfaces of the retina have no effect on the refractive error. These data provide the framework for further refinement of the optical models of the rat and mouse

  20. Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model

    SciTech Connect

    Xiao, Fei; Zhai, Zanjing; Jiang, Chuan; Liu, Xuqiang; Li, Haowei; Qu, Xinhua; Ouyang, Zhengxiao; Fan, Qiming; Tang, Tingting; Qin, An; Gu, Dongyun

    2015-01-01

    Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-κB and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure. - Highlights: • Geraniin suppresses osteoclasts formation and function in vitro. • Geraniin impairs RANKL-induced nuclear factor-κB and ERK signaling pathway. • Geraniin suppresses osteolysis in vivo. • Geraniin may be used for treating osteoclast related diseases.

  1. Genes affected by mouse mammary tumor virus (MMTV) proviral insertions in mouse mammary tumors are deregulated or mutated in primary human mammary tumors

    PubMed Central

    Callahan, Robert; Mudunuri, Uma; Bargo, Sharon; Raafat, Ahmed; McCurdy, David; Boulanger, Corinne; Lowther, William; Stephens, Robert; Luke, Brian T.; Stewart, Claudia; Wu, Xiaolin; Munroe, David; Smith, Gilbert H.

    2012-01-01

    The accumulation of mutations is a contributing factor in the initiation of premalignant mammary lesions and their progression to malignancy and metastasis. We have used a mouse model in which the carcinogen is the mouse mammary tumor virus (MMTV) which induces clonal premalignant mammary lesions and malignant mammary tumors by insertional mutagenesis. Identification of the genes and signaling pathways affected in MMTV-induced mouse mammary lesions provides a rationale for determining whether genetic alteration of the human orthologues of these genes/pathways may contribute to human breast carcinogenesis. A high-throughput platform for inverse PCR to identify MMTV-host junction fragments and their nucleotide sequences in a large panel of MMTV-induced lesions was developed. Validation of the genes affected by MMTV-insertion was carried out by microarray analysis. Common integration site (CIS) means that the gene was altered by an MMTV proviral insertion in at least two independent lesions arising in different hosts. Three of the new genes identified as CIS for MMTV were assayed for their capability to confer on HC11 mouse mammary epithelial cells the ability for invasion, anchorage independent growth and tumor development in nude mice. Analysis of MMTV induced mammary premalignant hyperplastic outgrowth (HOG) lines and mammary tumors led to the identification of CIS restricted to 35 loci. Within these loci members of the Wnt, Fgf and Rspo gene families plus two linked genes (Npm3 and Ddn) were frequently activated in tumors induced by MMTV. A second group of 15 CIS occur at a low frequency (2-5 observations) in mammary HOGs or tumors. In this latter group the expression of either Phf19 or Sdc2 was shown to increase HC11 cells invasion capability. Foxl1 expression conferred on HC11 cells the capability for anchorage-independent colony formation in soft agar and tumor development in nude mice. The published transcriptome and nucleotide sequence analysis of gene

  2. Folate supplementation differently affects uracil content in DNA in the mouse colon and liver

    USDA-ARS?s Scientific Manuscript database

    High folate intake may increase the risk of cancer, especially in the elderly. The present study examined the effects of ageing and dietary folate on uracil misincorporation into DNA, which has a mutagenic effect, in the mouse colon and liver. Old (18 months; n 42) and young (4 months; n 42) male C5...

  3. Initial gut microbiota structure affects sensitivity to DSS-induced colitis in a mouse model.

    PubMed

    Li, Min; Wu, Yanqiu; Hu, Yingxin; Zhao, Liping; Zhang, Chenhong

    2017-08-15

    The dextran sulfate sodium (DSS)-induced colitis model is a widely applied mouse model, but controversial results have been obtained from experiments using the same mouse strain under the same conditions. Because the gut microbiota play an important role in DSS-induced colitis, it is essential to evaluate the influence of the initial gut microbiota in this model. Here, we identified significant variations in the initial gut microbiota of different batches of mice and found that the initial intestinal microbiota had a profound influence on DSS-induced colitis. We performed three independent trials using the same C57BL/6J mouse model with DSS treatment and used high-throughput 16S rRNA gene sequencing to analyze the gut microbiota. We found that the structure and composition of the gut microbiota in mice with severe colitis, as compared with mice with milder colon damage, had unique features, such as an increase in Akkermansia bacteria and a decrease in Barnesiella spp. Moreover, these varied gut bacteria in the different trials also showed different responses to DSS treatment. Our work suggests that, in studies using mouse models, the gut microbiota must be considered when examining mechanisms of diseases, to ensure that comparable results are obtained.

  4. [Knockdown of Larp4b in Lin(-) cells does not affect the colony forming ability of mouse hematopoietic cells].

    PubMed

    Wang, Xiao-Juan; Pang, Ya-Kun; Cheng, Hui; Dong, Fang; Liang, Hao-Yue; Zhang, Ying-Chi; Wang, Xiao-Min; Xu, Jing; Cheng, Tao; Yuan, Wei-Ping

    2013-06-01

    Larp4b is a member of the LARP family, which can interact with RNA and generally stimulate the translation of mRNA. Abnormal expression of Larp4b can be found in leukemia patients in our previous study. This study was purposed to detect the relative expression of Larp4b mRNA in different subpopulations of mouse hematopoietic cells, to construct lentivirus vector containing shLarp4b targeting mouse gene Larp4b and to explore its effects on mouse Lin(-) cells infected with shLarp4b by lentivirus. SF-LV-shLarP4b-EGFP and control vectors were constructed and two-plasmid lentivirus packing system was used to transfect 293T cells. After 48 h and 72 h, lentivirus SF-LV-shLarp4b-EGFP was harvested and was used to infect Lin(-) cells. After 48 h, EGFP(+) cells was sorted by flow cytometry (FCM). Meanwhile, semi-quantitative real time-PCR, AnnexinV-PE/7-AAD staining, PI staining and colony forming cell assay (CFC) were performed to determine the expression of Larp4b and its effect on the proliferation of hematopoietic progenitor cells. The results showed that Larp4b was highly expressed in myeloid cells. SF-LV-shLarp4b-EGFP was successfully constructed according to the restriction endonuclease digestion assay. RT-PCR confirmed that Larp4b was efficiently knockdown in mouse Lin(-) cells. The low expression of Larp4b did not affect the colony forming number, the apoptosis and cell cycle of Lin(-) cells. It is concluded that knockdown of Larp4b in mouse Lin(-) cells do not contribute to the colony forming ability and the growth of Lin(-) cells in vitro. This useful knockdown system will be used to study in vivo Larp4b in future.

  5. Rotational diffusion affects the dynamical self-assembly pathways of patchy particles.

    PubMed

    Newton, Arthur C; Groenewold, Jan; Kegel, Willem K; Bolhuis, Peter G

    2015-12-15

    Predicting the self-assembly kinetics of particles with anisotropic interactions, such as colloidal patchy particles or proteins with multiple binding sites, is important for the design of novel high-tech materials, as well as for understanding biological systems, e.g., viruses or regulatory networks. Often stochastic in nature, such self-assembly processes are fundamentally governed by rotational and translational diffusion. Whereas the rotational diffusion constant of particles is usually considered to be coupled to the translational diffusion via the Stokes-Einstein relation, in the past decade it has become clear that they can be independently altered by molecular crowding agents or via external fields. Because virus capsids naturally assemble in crowded environments such as the cell cytoplasm but also in aqueous solution in vitro, it is important to investigate how varying the rotational diffusion with respect to transitional diffusion alters the kinetic pathways of self-assembly. Kinetic trapping in malformed or intermediate structures often impedes a direct simulation approach of a kinetic network by dramatically slowing down the relaxation to the designed ground state. However, using recently developed path-sampling techniques, we can sample and analyze the entire self-assembly kinetic network of simple patchy particle systems. For assembly of a designed cluster of patchy particles we find that changing the rotational diffusion does not change the equilibrium constants, but significantly affects the dynamical pathways, and enhances (suppresses) the overall relaxation process and the yield of the target structure, by avoiding (encountering) frustrated states. Besides insight, this finding provides a design principle for improved control of nanoparticle self-assembly.

  6. Rotational diffusion affects the dynamical self-assembly pathways of patchy particles

    PubMed Central

    Newton, Arthur C.; Groenewold, Jan; Kegel, Willem K.; Bolhuis, Peter G.

    2015-01-01

    Predicting the self-assembly kinetics of particles with anisotropic interactions, such as colloidal patchy particles or proteins with multiple binding sites, is important for the design of novel high-tech materials, as well as for understanding biological systems, e.g., viruses or regulatory networks. Often stochastic in nature, such self-assembly processes are fundamentally governed by rotational and translational diffusion. Whereas the rotational diffusion constant of particles is usually considered to be coupled to the translational diffusion via the Stokes–Einstein relation, in the past decade it has become clear that they can be independently altered by molecular crowding agents or via external fields. Because virus capsids naturally assemble in crowded environments such as the cell cytoplasm but also in aqueous solution in vitro, it is important to investigate how varying the rotational diffusion with respect to transitional diffusion alters the kinetic pathways of self-assembly. Kinetic trapping in malformed or intermediate structures often impedes a direct simulation approach of a kinetic network by dramatically slowing down the relaxation to the designed ground state. However, using recently developed path-sampling techniques, we can sample and analyze the entire self-assembly kinetic network of simple patchy particle systems. For assembly of a designed cluster of patchy particles we find that changing the rotational diffusion does not change the equilibrium constants, but significantly affects the dynamical pathways, and enhances (suppresses) the overall relaxation process and the yield of the target structure, by avoiding (encountering) frustrated states. Besides insight, this finding provides a design principle for improved control of nanoparticle self-assembly. PMID:26621742

  7. Variables Affecting Smooth Particle Hydrodynamics Simulation of High-Velocity Flyer Plate Impact Experiments

    SciTech Connect

    Somasundaram, Deepak S; Trabia, Mohamed; O'Toole, Brendan; Hixson, Robert S

    2014-01-23

    This paper describes our work to characterize the variables affecting the smoothed particle hydrodynamics (SPH) method in the LS-DYNA package for simulating high-velocity flyer plate impact experiments. LS-DYNA simulations are compared with one-dimensional experimental data of an oxygen-free high-conductivity (OFHC) copper flyer plate impacting another plate of the same material. The comparison is made by measuring the velocity of a point on the back surface of the impact plate using the velocity interferometer system for any reflector (VISAR) technique.

  8. Myelin basic protein is affected by reduced synthesis of myelin proteolipid protein in the jimpy mouse.

    PubMed Central

    Fannon, A M; Moscarello, M A

    1990-01-01

    Myelin basic proteins (MBPs) from 6-day-old, 10-day-old, 20-day-old and adult normal mouse brain were compared with those from 20-day-old jimpy (dysmyelinating mutant) mouse brain to determine the effect of reduced levels of proteolipid protein (PLP) on MBPs. Alkaline-urea-gel electrophoresis showed that 6-day-old and 10-day-old normal and jimpy MBPs lacked charge microheterogeneity, since C8 (the least cationic of the components; not be confused with complement component C8) was the only charge isomer present. In contrast, MBPs from 20-day-old and adult normal mouse brain displayed extensive charge microheterogeneity, having at least eight components. A 32 kDa MBP was the major isoform observed on immunoblots of acid-soluble protein from 6-day-old and 10-day-old normal and 20-day-old jimpy mouse brain. There were eight bands present in 20-day-old and adult normal mouse brain. Purified human MBP charge heteromers C1, C2, C3 and C4 reacted strongly with rat 14 kDa MBP antiserum, whereas the reaction with human C8 was weak. This suggested that MBPs from early-myelinating and jimpy mice did not react to MBP antisera because C8 was the major charge isomer in these animals. Purification of MBPs from normal and jimpy brain by alkaline-gel electrophoresis showed that both normal and jimpy MBPs have size heterogeneity when subjected to SDS/PAGE. However, the size isoforms in normal mouse brain (32, 21, 18.5, 17 and 14 kDa) differed from those in jimpy brain (32, 21, 20, 17, 15 and 14 kDa) in both size and relative amounts. Amino acid analyses of MBPs from jimpy brain showed an increase in glutamic acid, alanine and ornithine, and a decrease in histidine, arginine and proline. The changes in glutamic acid, ornithine and arginine are characteristic of the differences observed in human C8 when compared with C1. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:1693071

  9. Factors Affecting Pathogen Survival in Finished Dairy Compost with Different Particle Sizes Under Greenhouse Conditions.

    PubMed

    Diao, Junshu; Chen, Zhao; Gong, Chao; Jiang, Xiuping

    2015-09-01

    This study investigated the survival of Escherichia coli O157:H7 and Salmonella Typhimurium in finished dairy compost with different particle sizes during storage as affected by moisture content and temperature under greenhouse conditions. The mixture of E. coli O157:H7 and S. Typhimurium strains was inoculated into the finished composts with moisture contents of 20, 30, and 40%, separately. The finished compost samples were then sieved into 3 different particle sizes (>1000, 500-1000, and <500 μm) and stored under greenhouse conditions. For compost samples with moisture contents of 20 and 30%, the average Salmonella reductions in compost samples with particle sizes of >1000, 500-1000, and <500 μm were 2.15, 2.27, and 2.47 log colony-forming units (CFU) g(-1) within 5 days of storage in summer, respectively, as compared with 1.60, 2.03, and 2.26 log CFU g(-1) in late fall, respectively, and 2.61, 3.33, and 3.67 log CFU g(-1) in winter, respectively. The average E. coli O157:H7 reductions in compost samples with particle sizes of >1000, 500-1000, and <500 μm were 1.98, 2.30, and 2.54 log CFU g(-1) within 5 days of storage in summer, respectively, as compared with 1.70, 2.56, and 2.90 log CFU g(-1) in winter, respectively. Our results revealed that both Salmonella and E. coli O157:H7 in compost samples with larger particle size survived better than those with smaller particle sizes, and the initial rapid moisture loss in compost may contribute to the fast inactivation of pathogens in the finished compost. For the same season, the pathogens in the compost samples with the same particle size survived much better at the initial moisture content of 20% compared to 40%.

  10. Naphthenic Acid Mixtures from Oil Sands Process-Affected Water Enhance Differentiation of Mouse Embryonic Stem Cells and Affect Development of the Heart.

    PubMed

    Mohseni, Paria; Hahn, Noah A; Frank, Richard A; Hewitt, L Mark; Hajibabaei, Mehrdad; Van Der Kraak, Glen

    2015-08-18

    Extraction of petrochemicals from the surface mining of oil sand deposits results in generation of large volumes of oil sands process-affected water (OSPW). Naphthenic acids (NA) are generally considered to be among the most toxic components of OSPW. Previous studies have shown that NAs are toxic to aquatic organisms, however knowledge of their effects on mammalian health and development is limited. In the present study, we evaluated the developmental effects of an NA extract prepared from fresh OSPW on differentiating mouse embryonic stem cells (ESC). We found that treatment of differentiating cells with the NA extract at noncytotoxic concentrations alters expression of various lineage specification markers and development of the heart. Notably, expression of cardiac specific markers such as Nkx2.5, Gata4, and Mef2c were significantly up-regulated. Moreover, exposure to the NA extract enhanced differentiation of embryoid bodies and resulted in the early appearance of spontaneously beating clusters. Interestingly, exposure of undifferentiated mouse ESCs to the NA extract did not change the expression level of pluripotency markers (i.e., Oct4, Nanog, and Sox2). Altogether, these data identify some of the molecular pathways affected by components within this NA extract during differentiation of mammalian cells.

  11. Wear particles generated from studded tires and pavement induces inflammatory reactions in mouse macrophage cells.

    PubMed

    Lindbom, John; Gustafsson, Mats; Blomqvist, Göran; Dahl, Andreas; Gudmundsson, Anders; Swietlicki, Erik; Ljungman, Anders G

    2007-06-01

    Health risks associated with exposure to airborne particulate matter (PM) have been shown epidemiologically as well as experimentally, pointing to both respiratory and cardiovascular effects. These health risks are of increasing concern in society, and to protect public health, a clarification of the toxic properties of particles from different sources is of importance. Lately, wear particles generated from traffic have been recognized as a major contributing source to the overall particle load, especially in the Nordic countries where studded tires are used. The aim of this study was to further investigate and compare the ability to induce inflammatory mediators of different traffic-related wear particles collected from an urban street, a subway station, and studded tire-pavement wear. Inflammatory effects were measured as induction of nitric oxide (NO), IL-6, TNF-alpha, arachidonic acid (AA), and lipid peroxidation after exposure of the murine macrophage like cell line RAW 264.7. In addition, the redox potential of the particles was measured in a cell-free system. The results show that all particles tested induce IL-6, TNF-alpha, and NO, and those from the urban street were the most potent ones. In contrast, particles collected from a subway station were most potent to induce lipid peroxidation, AA release, and formation of ROS. Particles from studded tire-pavement wear, generated using a road simulator, were able to induce inflammatory cytokines, NO, lipid peroxidation, and ROS formation. Interestingly, particles generated from pavement containing granite as the main stone material were more potent than those generated from pavement containing quartzite as the main stone material.

  12. Loss of all 3 Extended Synaptotagmins does not affect normal mouse development, viability or fertility.

    PubMed

    Tremblay, Michel G; Moss, Tom

    2016-09-01

    The extended synaptotagmins, E-Syt1, 2 and 3, are multiple C2 domain membrane proteins that are tethered to the endoplasmic reticulum and interact in a calcium dependent manner with plasma membrane phospholipids to form endoplasmic reticulum - plasma membrane junctions. These junctions have been implicated in the exchange of phospholipids between the 2 organelles. The E-Syts have further been implicated in receptor signaling and endocytosis and can interact directly with fibroblast growth factor and other cell surface receptors. Despite these multiple functions, the search for a requirement in vivo has been elusive. Most recently, we found that the genes for E-Syt2 and 3 could be inactivated without effect on mouse development, viability, fertility or morphology. We have now created insertion and deletion mutations in the last of the mouse E-Syt genes. We show that E-Syt1 is specifically expressed throughout the embryonic skeleton during the early stages of chrondrogenesis in a pattern quite distinct from that of E-Syt2 or 3. Despite this, E-Syt1 is also not required for mouse development and propagation. We further show that even the combined inactivation of all 3 E-Syt genes has no effect on mouse viability or fertility in the laboratory. However, this inactivation induces an enhancement in the expression of the genes encoding Orp5/8, Orai1, STIM1 and TMEM110, endoplasmic reticulum - plasma membrane junction proteins that potentially could compensate for E-Syt loss. Given the multiple functions suggested for the E-Syts and their evolutionary conservation, our unexpected findings suggest that they may only provide a survival advantage under specific conditions that have as yet to be identified.

  13. Alterations in welding process voltage affect the generation of ultrafine particles, fume composition, and pulmonary toxicity.

    PubMed

    Antonini, James M; Keane, Michael; Chen, Bean T; Stone, Samuel; Roberts, Jenny R; Schwegler-Berry, Diane; Andrews, Ronnee N; Frazer, David G; Sriram, Krishnan

    2011-12-01

    The goal was to determine if increasing welding voltage changes the physico-chemical properties of the fume and influences lung responses. Rats inhaled 40 mg/m³ (3 h/day × 3 days) of stainless steel (SS) welding fume generated at a standard voltage setting of 25 V (regular SS) or at a higher voltage (high voltage SS) of 30 V. Particle morphology, size and composition were characterized. Bronchoalveolar lavage was performed at different times after exposures to assess lung injury. Fumes collected from either of the welding conditions appeared as chain-like agglomerates of nanometer-sized primary particles. High voltage SS welding produced a greater number of ultrafine-sized particles. Fume generated by high voltage SS welding was higher in manganese. Pulmonary toxicity was more substantial and persisted longer after exposure to the regular SS fume. In summary, a modest raise in welding voltage affected fume size and elemental composition and altered the temporal lung toxicity profile.

  14. Visualization of nasal airflow patterns in a patient affected with atrophic rhinitis using particle image velocimetry

    NASA Astrophysics Data System (ADS)

    Garcia, G. J. M.; Mitchell, G.; Bailie, N.; Thornhill, D.; Watterson, J.; Kimbell, J. S.

    2007-10-01

    The relationship between airflow patterns in the nasal cavity and nasal function is poorly understood. This paper reports an experimental study of the interplay between symptoms and airflow patterns in a patient affected with atrophic rhinitis. This pathology is characterized by mucosal dryness, fetor, progressive atrophy of anatomical structures, a spacious nasal cavity, and a paradoxical sensation of nasal congestion. A physical replica of the patient's nasal geometry was made and particle image velocimetry (PIV) was used to visualize and measure the flow field. The nasal replica was based on computed tomography (CT) scans of the patient and was built in three steps: three-dimensional reconstruction of the CT scans; rapid prototyping of a cast; and sacrificial use of the cast to form a model of the nasal passage in clear silicone. Flow patterns were measured by running a water-glycerol mixture through the replica and evaluating the displacement of particles dispersed in the liquid using PIV. The water-glycerol flow rate used corresponded to an air flow rate representative of a human breathing at rest. The trajectory of the flow observed in the left passage of the nose (more affected by atrophic rhinitis) differed markedly from what is considered normal, and was consistent with patterns of epithelial damage observed in cases of the condition. The data are also useful for validation of computational fluid dynamics predictions.

  15. Sorting it out: bedding particle size and nesting material processing method affect nest complexity.

    PubMed

    Robinson-Junker, Amy; Morin, Amelia; Pritchett-Corning, Kathleen; Gaskill, Brianna N

    2017-04-01

    As part of routine husbandry, an increasing number of laboratory mice receive nesting material in addition to standard bedding material in their cages. Nesting material improves health outcomes and physiological performance in mice that receive it. Providing usable nesting material uniformly and efficiently to various strains of mice remains a challenge. The aim of this study was to determine how bedding particle size, method of nesting material delivery, and processing of the nesting material before delivery affected nest building in mice of strong (BALB/cAnNCrl) and weak (C3H/HeNCrl) gathering abilities. Our data suggest that processing nesting material through a grinder in conjunction with bedding material, although convenient for provision of bedding with nesting material 'built-in', negatively affects the integrity of the nesting material and subsequent nest-building outcomes. We also found that C3H mice, previously thought to be poor nest builders, built similarly scored nests to those of BALB/c mice when provided with unprocessed nesting material. This was true even when nesting material was mixed into the bedding substrate. We also observed that when nesting material was mixed into the bedding substrate, mice of both strains would sort their bedding by particle size more often than if it were not mixed in. Our findings support the utility of the practice of distributing nesting material mixed in with bedding substrate, but not that of processing the nesting material with the bedding in order to mix them.

  16. Laser fusion of mouse embryonic cells and intra-embryonic fusion of blastomeres without affecting the embryo integrity.

    PubMed

    Krivokharchenko, Alexander; Karmenyan, Artashes; Sarkisov, Oleg; Bader, Michael; Chiou, Arthur; Shakhbazyan, Avetik

    2012-01-01

    Manipulation with early mammalian embryos is the one of the most important approach to study preimplantation development. Artificial cell fusion is a research tool for various biotechnological experiments. However, the existing methods have various disadvantages, first of them impossibility to fuse selected cells within multicellular structures like mammalian preimplantation embryos. In our experiments we have successfully used high repetition rate picosecond near infrared laser beam for fusion of pairs of oocytes and oocytes with blastomeres. Fused cells looked morphologically normal and keep their ability for further divisions in vitro. We also fused two or three blastomeres inside four-cell mouse embryos. The presence of one, two or three nuclei in different blastomeres of the same early preimplantation mouse embryo was confirmed under UV-light after staining of DNA with the vital dye Hoechst-33342. The most of established embryos demonstrated high viability and developed in vitro to the blastocyst stage. We demonstrated for the first time the use of laser beam for the fusion of various embryonic cells of different size and of two or three blastomeres inside of four-cell mouse embryos without affecting the embryo's integrity and viability. These embryos with blastomeres of various ploidy maybe unique model for numerous purposes. Thus, we propose laser optical manipulation as a new tool for investigation of fundamental mechanisms of mammalian development.

  17. Stochastic simulation of alveolar particle deposition in lungs affected by different types of emphysema.

    PubMed

    Sturm, R; Hofmann, W

    2004-01-01

    In the present study, disease-specific stochastic models were developed for the computation of particle deposition in lungs affected by COPD, emphysema, or both, distinguishing between four types of pulmonary emphysema-centriacinar, paraseptal, panacinar, and bullous. To simulate COPD, airway calibers of the tracheobronchial tree were randomly reduced between 20% and 50% in each airway. For the study of pure COPD ("blue bloaters"), alveolated airway dimensions of the healthy lung were used, while for the simulation of emphysema without COPD ("pink puffers"), normal conductive airway diameters were assumed. Deposition calculations in diseased lungs were carried out by assuming (a) identical inspiration and expiration times (no breath-hold time) and (b) a continuous increase of the functional residual capacity (from 3,300 to 5,000 mL), accompanied by a simultaneous drop of the tidal volume (from 1,000 to 500 mL). Independent of particle size, total alveolar deposition in emphysematous lungs was significantly decreased relative to normal lungs. In particular, the deposition maximum at large particle sizes, which is a characteristic for healthy subjects, completely disappeared. Among the various emphysema models, deposition was smallest in lungs with bullous emphysema due to strongly enhanced settling and diffusion distances within the alveolar structures. A change of the lung volume caused a further decrease in particle deposition. Alveolar deposition in "blue bloaters" and "pink puffers" was very similar to the deposition in patients suffering from COPD and emphysema. Alveolar deposition per acinar airway generation was also strongly reduced in diseased lungs compared to normal lungs. Besides this reduction, deposition patterns became more uniform throughout the alveolar region.

  18. Novel approach for formation of platelet-like particles from mouse embryonic stem cells without using feeder cells.

    PubMed

    Tsuji, Kayoko; Ohnuma, Masaaki; Jung, Stephanie M; Moroi, Masaaki

    2009-01-01

    Megakaryocytes (MKs) and platelet-like particles (PLPs) have generally been obtained by culturing embryonic stem (ES) cells over feeder cells. However, using feeder cells need many labor-consuming processes and the MK and PLP fractions obtained are often contaminated by such cells and their fragments. Here we describe our new culture system for differentiating mouse ES cells to MKs and PLPs without using feeder cells. ES cells are differentiated to cells with MK-like morphology and properties, including proplatelet formation, high ploidy (>8N), and CD41 expression. The culture medium contained PLPs expressing platelet glycoproteins, CD41 and GPIb. Integrin alpha(IIb)beta(3) of PLPs can be activated by thrombin. Addition of the metalloproteinase inhibitor TAPI-2 to the culture increased the surface expression of GPIbalpha and augmented the adhesion of PLPs to immobilized von Willebrand factor through decreasing the shedding of GPIbalpha. Thus our mouse ES cells culture system is a suitable and efficient method for obtaining MKs and functional PLPs that obviates the need for feeder cells.

  19. Preclinical safety assessment of a DNA vaccine using particle-mediated epidermal delivery in domestic pig, minipig and mouse.

    PubMed

    Dincer, Zuhal; Jones, Stewart; Haworth, Richard

    2006-07-01

    DNA vaccination involves the direct injection of genes coding for specific antigenic proteins. One technique known as particle-mediated epidermal delivery (PMED) is a practical approach for epidermal delivery and provides a strong immune response. An important aspect of the preclinical safety assessment of DNA vaccines is the selection of a pharmacologically relevant animal model for the assessment of antigen expression, optimization of delivery and formulation of the plasmid. This paper describes a comparative study of domestic pig, minipig and mouse in regard to local tolerance and antigen expression of HIV immunotherapeutic using PMED. Pig/minipig is considered a good model for the safety assessment of DNA vaccines due to the similarity to human skin. Local reactions were evaluated at 10 min, 4, 24 and 48 h. Histology of administration sites revealed epidermal necrosis with associated dermal inflammation at 10 min and 4h, and subsequent regeneration with repair at 24 and 48 h. The degree and extent of these changes varied according to species. Domestic pig and minipig showed superficial epidermal necrosis and complete repair, while the mouse showed full-thickness epidermal necrosis and partial repair. Expression of HIV antigen was confirmed using immunohistochemistry in all three species at 4, 24 and 48 h. The results showed that PMED is an effective system for DNA vaccine delivery as demonstrated by the antigen expression seen as early as 4 h.

  20. Understanding how hydrodynamics affects particle transport in saturated fractures using modelling and experimental results

    NASA Astrophysics Data System (ADS)

    Cianflone, S.; Lakhian, V.; Dickson, S. E.

    2013-12-01

    Approximately 35% of Canadians and Americans utilize groundwater for drinking water and as such, it is essential to understand the mechanisms which may jeopardize this resource. Porous media aquifers typically provide significant removal of particulate contaminants (eg. viruses, bacteria); however, fractures in fractured rock aquifers and aquitards often provide pathways for particles to move in greater numbers and speed than in porous media. Thus, understanding flow and transport in fractures is important for the preservation and use of groundwater sources. Models based on coupling flow and transport equations can be used in understanding transport in fractures. Both experiments and simulations have shown that there are inconsistencies in current transport, attachment and detachment theory, particularly when particle size is varied. The assumption that hydrodynamic effects do not significantly affect transport of particles is likely untrue. As well, it has been shown that preferential flow paths occur in fractures, but the effects of path specific properties such as fracture geometry have yet to be thoroughly explored. It has been observed that eddies caused by local changes in geometry exist in fractures in the environment and models have demonstrated that such eddies will retard the flow of particles. In this work, two 2D fractures were randomly generated with a mean aperture of approximately 2mm. Finite element software, COMSOL Multiphysics, generated flow fields through the fractures by numerically solving the steady-state Navier-Stokes equation for varied flow rates. Eddies were observed in one of the fractures at both low (~1 m/day) and high (>100 m/day) velocities. A program was written using random walk particle tracking to simulate transport. Theories of attachment, detachment and matrix flow are not included in this model in order to isolate hydrodynamic forces. In combination with the modelling procedure, the two fractures were inscribed into pieces of

  1. IL-6 signaling blockade increases inflammation but does not affect muscle function in the mdx mouse

    PubMed Central

    2012-01-01

    Background IL-6 is a pleiotropic cytokine that modulates inflammatory responses and plays critical roles in muscle maintenance and remodeling. In the mouse model (mdx) of Duchenne Muscular Dystrophy, IL-6 and muscle inflammation are elevated, which is believed to contribute to the chronic inflammation and failure of muscle regeneration in DMD. The purpose of the current study was to examine the effect of blocking IL-6 signaling on the muscle phenotype including muscle weakness and pathology in the mdx mouse. Methods A monoclonal antibody against the IL-6 receptor (IL-6r mAb) that blocks local and systemic IL-6 signaling was administered to mdx and BL-10 mice for 5 weeks and muscle function, histology, and inflammation were examined. Results IL-6r mAb treatment increased mdx muscle inflammation including total inflammation score and ICAM-1 positive lumens in muscles. There was no significant improvement in muscle strength nor muscle pathology due to IL-6r mAb treatment in mdx mice. Conclusions These results showed that instead of reducing inflammation, IL-6 signaling blockade for 5 weeks caused an increase in muscle inflammation, with no significant change in indices related to muscle regeneration and muscle function. The results suggest a potential anti-inflammatory instead of the original hypothesized pro-inflammatory role of IL-6 signaling in the mdx mice. PMID:22716658

  2. Nuclear DNA fragmentation negatively affects zona binding competence of Y bearing mouse spermatozoa.

    PubMed

    Kumar, Dayanidhi; Upadhya, Dinesh; Uppangala, Shubhashree; Salian, Sujit Raj; Kalthur, Guruprasad; Adiga, Satish Kumar

    2013-12-01

    To investigate the influence of sperm DNA integrity on the zona binding ability of mouse spermatozoa in relation to their sex chromosomal constitution. In this prospective experimental study, the sperm DNA fragmentation was induced by exposing testicular area of Swiss Albino mice (Mus musculus) to different doses of γ-radiation (0, 2.5, 5.0 and 10.0 Gy). Sperm DNA fragmentation was quantified by single cell gel electrophoresis (comet assay). In vitro sperm zona binding assay was performed and the numbers of zona bound X and Y bearing spermatozoa were determined using fluorescence in situ hybridization (FISH). The assessment of zona pellucida bound X and Y-bearing spermatozoa using fluorescence in situ hybridization has revealed a unique binding pattern. The number of zona bound Y-spermatozoa declined significantly (P < 0.01 to 0.0001) with increase in the DNA damage. The skewed binding pattern of X and Y-bearing sperm was strongly correlated with the extent of sperm DNA damage. The zona pellucida may have a role in preventing DNA damaged mouse sperm binding especially towards Y-bearing sperm. However, the exact mechanism behind this observation needs to be elucidated further.

  3. Serotonin Increases Cilia-Driven Particle Transport via an Acetylcholine-Independent Pathway in the Mouse Trachea

    PubMed Central

    Krasteva, Gabriela; Kummer, Wolfgang

    2009-01-01

    Background Mucociliary clearance in the airways is driven by the coordinated beating of ciliated cells. Classical neuromediators such as noradrenalin and acetylcholine increase ciliary beat frequency and thus cilia-driven transport. Despite the fact that the neuromediator serotonin is ciliostimulatory in invertebrates and has been implied in releasing acetylcholine from the airway epithelium, its role in regulating cilia function in vertebrate airways is not established. Methodology/Principal Findings We examined the effects of serotonin on ciliary beat frequency and cilia-driven particle transport in the acutely excised submerged mouse trachea and determined the sources of serotonin in this tissue by immunohistochemistry. Serotonin (100 µM) increased cilary beat frequency (8.9±1.2 Hz to 17.0±2.7 Hz) and particle transport speed (38.9±4.6 µm/s to 83.4±8.3 µm/s) to an extent that was comparable to a supramaximal dose of ATP. The increase in particle transport speed was totally prevented by methysergide (100 µM). Blockade of muscarinic receptors by atropine (1 µM) did not reduce the effect of serotonin, although it was effective in preventing the increase in particle transport speed mediated by muscarine (100 µM). Immunohistochemistry demonstrated serotonin in mast cells pointing towards mast cells and platelets as possible endogenous sources of serotonin. Conclusions/Significance These results indicate that serotonin is a likely endogenous mediator that can increase cilia-driven transport independent from acetylcholine during activation of mast cells and platelets. PMID:19290057

  4. Accumulative difference image protocol for particle tracking in fluorescence microscopy tested in mouse lymphonodes.

    PubMed

    Villa, Carlo E; Caccia, Michele; Sironi, Laura; D'Alfonso, Laura; Collini, Maddalena; Rivolta, Ilaria; Miserocchi, Giuseppe; Gorletta, Tatiana; Zanoni, Ivan; Granucci, Francesca; Chirico, Giuseppe

    2010-08-17

    The basic research in cell biology and in medical sciences makes large use of imaging tools mainly based on confocal fluorescence and, more recently, on non-linear excitation microscopy. Substantially the aim is the recognition of selected targets in the image and their tracking in time. We have developed a particle tracking algorithm optimized for low signal/noise images with a minimum set of requirements on the target size and with no a priori knowledge of the type of motion. The image segmentation, based on a combination of size sensitive filters, does not rely on edge detection and is tailored for targets acquired at low resolution as in most of the in-vivo studies. The particle tracking is performed by building, from a stack of Accumulative Difference Images, a single 2D image in which the motion of the whole set of the particles is coded in time by a color level. This algorithm, tested here on solid-lipid nanoparticles diffusing within cells and on lymphocytes diffusing in lymphonodes, appears to be particularly useful for the cellular and the in-vivo microscopy image processing in which few a priori assumption on the type, the extent and the variability of particle motions, can be done.

  5. Winds of winter: How solar wind driven particle precipitation can affect northern winters

    NASA Astrophysics Data System (ADS)

    Asikainen, Timo; Maliniemi, Ville; Mursula, Kalevi

    2017-04-01

    Solar wind drives the variability in the near Earth space. Coupling of solar wind and the magnetosphere feeds energetic particles into the inner magnetosphere through reconnection in the magnetotail. During the declining phase of the solar cycle long-lived high-speed solar wind streams are more commonly observed at Earth's orbit. These accelerate particles to higher energies and in the process lead to enhanced particle precipitation into the atmosphere. Electrons from tens to hundreds of keV precipitate down to the mesosphere and upper stratosphere, where they can create nitrogen and hydrogen oxides. During winter, nitrogen oxides have enhanced lifetime in the polar night. They can descend down to the mid-stratosphere and destroy ozone, which leads to cooling of the high-latitude stratosphere. This enhances the meridional temperature gradient and westerly winds under the thermal-wind balance, thus accelerating the polar vortex. This mechanism is successfully modeled by chemistry-climate models. Dynamical changes in the stratosphere can descend down to the troposphere. During strong polar vortex, the northern annular mode (NAM) is anomalously positive. Positive NAM encloses the cold arctic air into the polar region and enhances the westerly winds at mid-latitudes. Enhancement of westerlies bring warm and moist air from Atlantic to the Northern Eurasia causing positive temperature anomalies. At the same time negative temperature anomalies are observed in the Northern Canada and Greenland. Our recent observations show that the positive relation between precipitating electron fluxes/geomagnetic activity and NAM exists during winter. Positive NAM pattern is observed during the declining phase of the solar cycle at least since the late 19th century. We also find that the quasi-biennial oscillation (QBO) of equatorial winds strongly modulate this relation at high latitudes. These results give additional evidence that not only solar electromagnetic radiation but also the

  6. Affective dysfunction in a mouse model of Rett syndrome: Therapeutic effects of environmental stimulation and physical activity.

    PubMed

    Kondo, Mari A; Gray, Laura J; Pelka, Gregory J; Leang, Sook-Kwan; Christodoulou, John; Tam, Patrick P L; Hannan, Anthony J

    2016-02-01

    Rett syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) and consequent dysregulation of brain maturation. Patients suffer from a range of debilitating physical symptoms, however, behavioral and emotional symptoms also severely affect their quality of life. Here, we present previously unreported and clinically relevant affective dysfunction in the female heterozygous Mecp2(tm1Tam) mouse model of RTT (129sv and C57BL6 mixed background). The affective dysfunction and aberrant anxiety-related behavior of the Mecp2(+/-) mice were found to be reversible with environmental enrichment (EE) from 4 weeks of age. The effect of exercise alone (via wheel running) was also explored, providing the first evidence that increased voluntary physical activity in an animal model of RTT is beneficial for some phenotypes. Mecp2(+/-) mutants displayed elevated corticosterone despite decreased Crh expression, demonstrating hypothalamic-pituitary-adrenal axis dysregulation. EE of Mecp2(+/-) mice normalized basal serum corticosterone and hippocampal BDNF protein levels. The enrichment-induced rescue appears independent of the transcriptional regulation of the MeCP2 targets Bdnf exon 4 and Crh. These findings provide new insight into the neurodevelopmental role of MeCP2 and pathogenesis of RTT, in particular the affective dysfunction. The positive outcomes of environmental stimulation and physical exercise have implications for the development of therapies targeting the affective symptoms, as well as behavioral and cognitive dimensions, of this devastating neurodevelopmental disorder.

  7. In vivo verification of particle therapy: how Compton camera configurations affect 3D image quality

    NASA Astrophysics Data System (ADS)

    Mackin, D.; Draeger, E.; Peterson, S.; Polf, J.; Beddar, S.

    2017-05-01

    The steep dose gradients enabled by the Bragg peaks of particle therapy beams are a double edged sword. They enable highly conformal dose distributions, but even small deviations from the planned beam range can cause overdosing of healthy tissue or under-dosing of the tumour. To reduce this risk, particle therapy treatment plans include margins large enough to account for all the sources of range uncertainty, which include patient setup errors, patient anatomy changes, and CT number to stopping power ratios. Any system that could verify the beam range in vivo, would allow reduced margins and more conformal dose distributions. Toward our goal developing such a system based on Compton camera (CC) imaging, we studied how three configurations (single camera, parallel opposed, and orthogonal) affect the quality of the 3D images. We found that single CC and parallel opposed configurations produced superior images in 2D. The increase in parallax produced by an orthogonal CC configuration was shown to be beneficial in producing artefact free 3D images.

  8. The Dynamin 2 inhibitor Dynasore affects the actin filament distribution during mouse early embryo development.

    PubMed

    Wang, Qiao-Chu; Liu, Jun; Duan, Xing; Cui, Xiang-Shun; Kim, Nam-Hyung; Xiong, Bo; Sun, Shao-Chen

    2015-01-01

    Dynamin 2 is a large GTPase notably involved in clathrin-mediated endocytosis, cell migration and cytokinesis in mitosis. Our previous study identified that Dynamin 2 regulated polar body extrusion in mammalian oocytes, but its roles in early embryo development, remain elusive. Here, we report the critical roles of Dynamin 2 in mouse early embryo development. Dynamin 2 accumulated at the periphery of the blastomere during embryonic development. When Dynamin 2 activity was inhibited by Dynasore, embryos failed to cleave to the 2-cell or 4-cell stage. Moreover, the actin filament distribution and relative amount were aberrant in the treatment group. Similar results were observed when embryos were cultured with Dynasore at the 8-cell stage; the embryos failed to undergo compaction and develop to the morula stage, indicating a role of Dynamin 2 in embryo cytokinesis. Therefore, our data indicate that Dynamin 2 might participate in the early embryonic development through an actin-based cytokinesis.

  9. Early development in the mouse: Would it be affected by microgravity?

    NASA Astrophysics Data System (ADS)

    Lehtonen, E.; Snow, M. H. L.

    Gravity has been identified as a morphogenetic signal in Amphibian and bird embryonic development so it is plausible that it might be such in mammals as well. Since early mammalian development shows some apparently significant differences to these other groups, a brief summary of mouse embryogenesis will be given identifying events in which polarity is an important feature and consequently, in which gravity may be a causative factor. These include compaction and polarization during cleavage, establishment of the radial axis, the embryonic-abembryonic axis, the dorso-ventral axis, and the anterior-posterior axis, implantation, and the later rotation of the embryo. The experimental data on these morphogenetic steps will be discussed and an assessment of the possible involvement of gravity will be made.

  10. Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1 Function

    PubMed Central

    Shi, Xiao; Walter, Nicole A. R.; Harkness, John H.; Neve, Kim A.; Williams, Robert W.; Lu, Lu; Belknap, John K.; Eshleman, Amy J.; Phillips, Tamara J.; Janowsky, Aaron

    2016-01-01

    Methamphetamine (MA) and neurotransmitter precursors and metabolites such as tyramine, octopamine, and β-phenethylamine stimulate the G protein-coupled trace amine-associated receptor 1 (TAAR1). TAAR1 has been implicated in human conditions including obesity, schizophrenia, depression, fibromyalgia, migraine, and addiction. Additionally TAAR1 is expressed on lymphocytes and astrocytes involved in inflammation and response to infection. In brain, TAAR1 stimulation reduces synaptic dopamine availability and alters glutamatergic function. TAAR1 is also expressed at low levels in heart, and may regulate cardiovascular tone. Taar1 knockout mice orally self-administer more MA than wild type and are insensitive to its aversive effects. DBA/2J (D2) mice express a non-synonymous single nucleotide polymorphism (SNP) in Taar1 that does not respond to MA, and D2 mice are predisposed to high MA intake, compared to C57BL/6 (B6) mice. Here we demonstrate that endogenous agonists stimulate the recombinant B6 mouse TAAR1, but do not activate the D2 mouse receptor. Progeny of the B6XD2 (BxD) family of recombinant inbred (RI) strains have been used to characterize the genetic etiology of diseases, but contrary to expectations, BXDs derived 30–40 years ago express only the functional B6 Taar1 allele whereas some more recently derived BXD RI strains express the D2 allele. Data indicate that the D2 mutation arose subsequent to derivation of the original RIs. Finally, we demonstrate that SNPs in human TAAR1 alter its function, resulting in expressed, but functional, sub-functional and non-functional receptors. Our findings are important for identifying a predisposition to human diseases, as well as for developing personalized treatment options. PMID:27031617

  11. Cerebral endothelial expression of Robo1 affects brain infiltration of polymorphonuclear neutrophils during mouse stroke recovery.

    PubMed

    Gangaraju, Sandhya; Sultan, Khadeejah; Whitehead, Shawn N; Nilchi, Ladan; Slinn, Jacqueline; Li, Xuesheng; Hou, Sheng T

    2013-06-01

    Increased brain infiltration of polymorphonuclear neutrophils (PMNs) occurs early after stroke and is important in eliciting brain inflammatory response during stroke recovery. In order to understand the molecular mechanism of PMN entry, we investigated the expression and requirement for Slit1, a chemorepulsive guidance cue, and its cognate receptor, Robo1, in a long-term recovery mouse model of cerebral ischemia. The expression levels of Robo1 were significantly decreased bilaterally at 24h following reperfusion. Robo1 expression levels remained suppressed in the ipsilateral cortex until 28d post MCAO-reperfusion, while the levels of Robo1 in the contralateral cortex recovered to the level of sham-operated mouse by 7d reperfusion. Circulating PMNs express high levels of Slit1, but not Robo1. Influx of PMNs into the ischemic core area occurred early (24h) after cerebral ischemia, when endothelial Robo1 expression was significantly reduced in the ischemic brain, indicating that Robo1 may form a repulsive barrier to PMN entry into the brain parenchyma. Indeed, blocking Slit1 on PMNs in a transwell migration assay in combination with an antibody blocking of Robo1 on human umbilical vein endothelial cells (HUVEC) significantly increased PMN transmigration during oxygen glucose deprivation, an in vitro model of ischemia. Collectively, in the normal brain, the presence of Slit1 on PMNs, and Robo1 on cerebral endothelial cells, generated a repulsive force to prevent the infiltration of PMNs into the brain. During stroke recovery, a transient reduction in Robo1 expression on the cerebral endothelial cells allowed the uncontrolled infiltration of Slit1-expressing PMNs into the brain causing inflammatory reactions.

  12. Pulmonary Responses to Stachybotrys chartarum and Its Toxins: Mouse Strain Affects Clearance and Macrophage Cytotoxicity

    PubMed Central

    Lichtenstein, Jamie H. Rosenblum; Molina, Ramon M.; Donaghey, Thomas C.; Amuzie, Chidozie J.; Pestka, James J.; Coull, Brent A.; Brain, Joseph D.

    2010-01-01

    We investigated differences in the pulmonary and systemic clearance of Stachybotrys chartarum spores in two strains of mice, BALB/c and C57BL/6J. To evaluate clearance, mice were intratracheally instilled with a suspension of radiolabeled S. chartarum spores or with unlabeled spores. The lungs of C57BL/6J mice showed more rapid spore clearance than the lungs of BALB/c mice, which correlated with increased levels of spore-associated radioactivity in the GI tracts of C57BL/6J as compared with BALB/c mice. To identify mechanisms responsible for mouse strain differences in spore clearance and previously described lung inflammatory responses, we exposed alveolar macrophages (AMs) lavaged from BALB/c and C57BL/6J mice to S. chartarum spores, S. chartarum spore toxin (SST), and satratoxin G (SG) in vitro. The S. chartarum spores were found to be highly toxic with most cells from either mouse strain being killed within 24 h when exposed to a spore:cell ratio of 1:75. The spores were more lethal to AMs from C57BL/6J than those from BALB/c mice. In mice, the SST elicited many of the same inflammatory responses as the spores in vivo, including AM recruitment, pulmonary hemorrhage, and cytokine production. Our data suggest that differences in pulmonary spore clearance may contribute to the differences in pulmonary responses to S. chartarum between BALB/c and C57BL/6J mice. Enhanced AM survival and subsequent macrophage-mediated inflammation may also contribute to the higher susceptibility of BALB/c mice to S. chartarum pulmonary effects. Analogous genetic differences among humans may contribute to reported variable sensitivity to S. chartarum. PMID:20385656

  13. Pulmonary responses to Stachybotrys chartarum and its toxins: mouse strain affects clearance and macrophage cytotoxicity.

    PubMed

    Lichtenstein, Jamie H Rosenblum; Molina, Ramon M; Donaghey, Thomas C; Amuzie, Chidozie J; Pestka, James J; Coull, Brent A; Brain, Joseph D

    2010-07-01

    We investigated differences in the pulmonary and systemic clearance of Stachybotrys chartarum spores in two strains of mice, BALB/c and C57BL/6J. To evaluate clearance, mice were intratracheally instilled with a suspension of radiolabeled S. chartarum spores or with unlabeled spores. The lungs of C57BL/6J mice showed more rapid spore clearance than the lungs of BALB/c mice, which correlated with increased levels of spore-associated radioactivity in the GI tracts of C57BL/6J as compared with BALB/c mice. To identify mechanisms responsible for mouse strain differences in spore clearance and previously described lung inflammatory responses, we exposed alveolar macrophages (AMs) lavaged from BALB/c and C57BL/6J mice to S. chartarum spores, S. chartarum spore toxin (SST), and satratoxin G (SG) in vitro. The S. chartarum spores were found to be highly toxic with most cells from either mouse strain being killed within 24 h when exposed to a spore:cell ratio of 1:75. The spores were more lethal to AMs from C57BL/6J than those from BALB/c mice. In mice, the SST elicited many of the same inflammatory responses as the spores in vivo, including AM recruitment, pulmonary hemorrhage, and cytokine production. Our data suggest that differences in pulmonary spore clearance may contribute to the differences in pulmonary responses to S. chartarum between BALB/c and C57BL/6J mice. Enhanced AM survival and subsequent macrophage-mediated inflammation may also contribute to the higher susceptibility of BALB/c mice to S. chartarum pulmonary effects. Analogous genetic differences among humans may contribute to reported variable sensitivity to S. chartarum.

  14. Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model.

    PubMed

    Friedrichs, Patrick; Schlotterer, Andrea; Sticht, Carsten; Kolibabka, Matthias; Wohlfart, Paulus; Dietrich, Axel; Linn, Thomas; Molema, Grietje; Hammes, Hans-Peter

    2017-07-01

    The aim of this study was to evaluate damage to the neurovascular unit in a mouse model of hyperglycaemic memory. A streptozotocin-induced mouse model of diabetes (C57BL/6J background) received insulin-releasing pellets and pancreatic islet-cell transplantation. Damage to the neurovascular unit was studied by quantitative retinal morphometry for microvascular changes and microarray analysis, with subsequent functional annotation clustering, for changes of the retinal genome. Sustained microvascular damage was confirmed by persistent loss of pericytes in the retinal vasculature (PC/mm(2)): compared with healthy controls (1981 ± 404 PC/mm(2)), the pericyte coverage of the retinal vasculature was significantly reduced in diabetic mice (1571 ± 383 PC/mm(2), p < 0.001) and transplanted mice (1606 ± 268 PC/mm(2), p < 0.001). Genes meeting the criteria for hyperglycaemic memory were attributed to the cytoskeletal and nuclear cell compartments of the neurovascular unit. The most prominent regulated genes in the cytoskeletal compartment were Ddx51, Fgd4, Pdlim7, Utp23, Cep57, Csrp3, Eml5, Fhl3, Map1a, Mapk1ip1, Mnda, Neil2, Parp2, Myl12b, Dynll1, Stag3 and Sntg2, and in the nuclear compartment were Ddx51, Utp23, Mnda, Kmt2e, Nr6a1, Parp2, Cdk8, Srsf1 and Zfp326. We demonstrated that changes in gene expression and microvascular damage persist after euglycaemic re-entry, indicating memory. The datasets generated during and/or analysed during the current study are available in the GEO repository, GSE87433, www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=idmbysgctluxviv&acc=GSE87433 .

  15. G6pd Deficiency Does Not Affect the Cytosolic Glutathione or Thioredoxin Antioxidant Defense in Mouse Cochlea.

    PubMed

    White, Karessa; Kim, Mi-Jung; Ding, Dalian; Han, Chul; Park, Hyo-Jin; Meneses, Zaimary; Tanokura, Masaru; Linser, Paul; Salvi, Richard; Someya, Shinichi

    2017-06-07

    Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP(+) to NADPH and is thought to be the principal source of NADPH for the cytosolic glutathione and thioredoxin antioxidant defense systems. We investigated the roles of G6PD in the cytosolic antioxidant defense in the cochlea of G6pd hypomorphic mice that were backcrossed onto normal-hearing CBA/CaJ mice. Young G6pd-deficient mice displayed a significant decrease in cytosolic G6PD protein levels and activities in the inner ears. However, G6pd deficiency did not affect the cytosolic NADPH redox state, or glutathione or thioredoxin antioxidant defense in the inner ears. No histological abnormalities or oxidative damage was observed in the cochlea of G6pd hemizygous males or homozygous females. Furthermore, G6pd deficiency did not affect auditory brainstem response hearing thresholds, wave I amplitudes or wave I latencies in young males or females. In contrast, G6pd deficiency resulted in increased activities and protein levels of cytosolic isocitrate dehydrogenase 1, an enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate and NADP(+) to NADPH, in the inner ear. In a mouse inner ear cell line, knockdown of Idh1, but not G6pd, decreased cell growth rates, cytosolic NADPH levels, and thioredoxin reductase activities. Therefore, under normal physiological conditions, G6pd deficiency does not affect the cytosolic glutathione or thioredoxin antioxidant defense in mouse cochlea. Under G6pd deficiency conditions, isocitrate dehydrogenase 1 likely functions as the principal source of NADPH for cytosolic antioxidant defense in the cochlea.SIGNIFICANCE STATEMENT Glucose-6-phosphate dehydrogenase (G6PD) is the first and rate-limiting enzyme of the pentose phosphate pathway; it catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconate and NADP(+) to NADPH and

  16. Combination of Alphavirus replicon particle-based vaccination with immunomodulatory antibodies: therapeutic activity in the B16 melanoma mouse model and immune correlates

    PubMed Central

    Avogadri, Francesca; Zappasodi, Roberta; Yang, Arvin; Budhu, Sadna; Malandro, Nicole; Hirshhorn-Cymerman, Daniel; Tiwari, Shakuntala; Maughan, Maureen F.; Olmsted, Robert; Wolchok, Jedd D; Merghoub, Taha

    2015-01-01

    Induction of potent immune responses to self-antigens remains a major challenge in tumor immunology. We have shown that a vaccine based on alphavirus replicon particles (VRP) activates strong cellular and humoral immunity to tyrosinase related protein-2 (TRP2) melanoma antigen, providing prophylactic and therapeutic effects in stringent mouse models. Here we report that the immunogenicity and efficacy of this vaccine is increased in combination with either antagonist anti-CTLA-4 or agonist anti-GITR immunomodulatory monoclonal antibodies (mAbs). In the challenging therapeutic setting, VRP-TRP2 plus anti-GITR or anti-CTLA-4 mAb induced complete tumor regression respectively in 90% and 50% of mice. These mAbs had similar adjuvant effects in priming an adaptive immune response against the vaccine-encoded antigen, augmenting respectively ~4- and 2-fold the TRP2-specific CD8+ T-cell response and circulating Abs, compared to the vaccine alone. Furthermore, while both mAbs increased the frequency of tumor-infiltrating CD8+ T cells, anti-CTLA-4 mAb also increased the quantity of intra-tumor CD4+Foxp3− T cells expressing the negative co-stimulatory molecule programmed death-1 (PD-1). Concurrent GITR expression on these cells suggests that they might be controlled by anti-GITR mAbs, thus potentially explaining their differential accumulation under the two treatment conditions. These findings indicate that combining immunomodulatory mAbs with alphavirus-based anti-cancer vaccines can provide therapeutic anti-tumor immune responses in a stringent mouse model, suggesting potential utility in clinical trials. They also indicate that tumor-infiltrating CD4+Foxp3−PD-1+ T cells may affect the outcome of immunomodulatory treatments. PMID:24795357

  17. Single particle tracking of internalized metallic nanoparticles reveals heterogeneous directed motion after clathrin dependent endocytosis in mouse chromaffin cells.

    PubMed

    Gabriel, Manuela; Moya, Jose; Gallo, Luciana; Marengo, Fernando; Estrada, Laura

    2017-09-13

    Most accepted single particle tracking methods are able to obtain high-resolution trajectories for relatively short periods of time. In this work we apply a straightforward combination of single-particle tracking microscopy and metallic nanoparticles internalization on mouse chromaffin cells to unveil the intracellular trafficking mechanism of metallic-nanoparticle-loaded vesicle (MNP-V) complexes after clathrin dependent endocytosis. We found that directed transport is the major route of MNP-Vs intracellular trafficking after stimulation (92.6% of the trajectories measured). We then studied the MNP-V speed at each point along the trajectory, and found that the application of a second depolarization stimulus during the tracking provokes an increase in the percentage of low-speed trajectory points in parallel with a decrease in the number of high-speed trajectory points. This result suggests that stimulation may facilitate the compartmentalization of internalized MNPs in a more restricted location such as was already demonstrated in neuronal and neuroendocrine cells (Bronfman et al 2003). Although further experiments will be required to address the mechanisms underlying this transport dynamics, our studies provide quantitative evidence of the heterogeneous behavior of vesicles mobility after endocytosis in chromaffin cells highlighting the potential of MNPs as alternative labels in optical microscopy to provide new insights into the vesicles dynamics in a wide variety of cellular environments. © 2017 IOP Publishing Ltd.

  18. Quantification of particles of lethal mercury in mouse viscera: high-resolution study of mercury in cells and tissues.

    PubMed

    Cunha, Elisabete M; Cherdwongcharoensuk, D; Aguas, Artur P

    2003-07-01

    To investigate the early visceral distribution of mercury (Hg), we have intraperitoneally injected a lethal dose of HgCl2 that killed BALB/c mice within 2-4 min. Scanning electron microscopy coupled with X-ray microanalysis (SEM-XRM) was used to detect and quantify Hg in situ in different organs. The highest density of Hg was seen in the liver (60.9+/-24.9 Hg particles per mm2 of tissue); this density was three and six times higher than those of renal or splenic Hg, respectively. Hg was scarce in the lungs and absent in the brain. Considering the relative weights of mouse viscera, our quantitative data show that the liver captured 89% of the visceral Hg; the kidneys captured 8.5% and the spleen just 1.7%. SEM-XRM revealed that most of the visceral Hg was associated with resident macrophages, a few Hg dots being detected on the surface of erythrocytes. We conclude that: (i) most intraperitoneally injected Hg was captured by liver Kupffer cells within minutes of injection; (ii) a 10-fold lower density of Hg particles was observed in the kidneys, and a 50-fold lower deposition of Hg was found in the spleen; (iii) SEM-XRM is an adequate method to quantify microparticles of Hg in tissues and cells.

  19. Mouse ovarian follicles secrete factors affecting the growth and development of like-sized ovarian follicles in vitro.

    PubMed

    Spears, Norah; Baker, Stuart; Srsen, Vlastimil; Lapping, Rebecca; Mullan, Julie; Nelson, Robert; Allison, Vivian

    2002-12-01

    A series of experiments have been carried out to determine whether follicles secrete factors able to affect the growth and development of other, like-sized follicles. Late preantral mouse ovarian follicles were either cocultured or cultured in media conditioned by previously cultured follicles. In particular, the experiments examined whether follicles do secrete such factors, whether the level of FSH in the culture media can affect that process, and what the nature of such secretory factor(s) might be. First, pairs of follicles were cocultured across a polycarbonate membrane containing pores. This showed that communication between the follicles resulted in the stimulation of growth and that the stimulation was due, at least in part, to the production of secretory factor(s). In subsequent experiments, follicles were cultured in media that had been preconditioned by previously cultured follicles. The concentration of FSH in the cultures determined the effect of the conditioned media: conditioned media was stimulatory to follicle growth when levels of FSH remained high throughout the culture, but inhibitory when FSH levels were dropped midway through the cultures. Heat inactivation removed this inhibitory effect, showing that the factor was likely to be a protein; addition of follistatin to the conditioned media did not alter its effect, indicating that the factor was unlikely to be activin. We have shown through a series of culture experiments that mouse follicles secrete factor(s) that can affect the development of other like-sized follicles when cultured from the late preantral to Graafian stages. Furthermore, we have shown that the effect (or production) of such factors is dependent on the FSH environment of the follicles.

  20. Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes.

    PubMed

    Lu, Yin; Wang, Jianshe; Guo, Xuejiang; Yan, Shengmin; Dai, Jiayin

    2017-03-01

    Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (>1.5-fold and P<0.05 compared with the control). Eight of these miRNAs were further selected for TaqMan qPCR analysis. Proteomic profile analysis indicated that many changed proteins after PFOA treatment, including intersectin 1 (ITSN1), serine protease inhibitor A3K (Serpina3k), and apolipoprotein a1 (APOA1), were involved in endocytosis and blood-testis barrier (BTB) processes. These changes were further verified by immunohistochemical and Western blot analyses. Endocytosis-related genes were selected for qPCR analysis, with many found to be significantly changed after PFOA treatment, including epidermal growth factor receptor pathway substrate 8 (Eps8), Eps15, cortactin, cofilin, espin, vinculin, and zyxin. We further predicted the potential interaction between changed miRNAs and proteins, which indicated that miRNAs might play a role in the post-translational regulation of gene expression after PFOA treatment in mouse testes. Among them, miR-133b-3p/clathrin light chain A (CLTA) was selected and verified in vitro by transfection and luciferase activity assay. Results showed that PFOA exposure affects endocytosis in mouse testes and that CLTA is a potential target of miR-133b-3p. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Late structural changes in mouse coronary arteries after iron-particle irradiation of the orbital region.

    PubMed

    Yang, V C

    1993-06-01

    A single dose of 0.1 or 0.2 Gy iron particles was given to B6CF1 female mice at 4 months of age. Degenerative changes in the coronary arteries due to orbital irradiation were observed 15 months after irradiation. The major changes included smooth muscle degeneration with fibrosis and accumulation of debris and extracellular matrix in the medial layer of the vessels. Quantitative analysis indicates that the average fractional volume of degenerated area is 12% in the unirradiated group. The corresponding percentages are 28% (P < 0.01) and 24% (P < 0.01) after 0.1 and 0.2 Gy irradiation, respectively.

  2. Gradient Index Microlens Implanted in Prefrontal Cortex of Mouse Does Not Affect Behavioral Test Performance over Time

    PubMed Central

    Lee, Seon A.; Holly, Kevin S.; Voziyanov, Vladislav; Villalba, Stephanie L.; Tong, Rudi; Grigsby, Holly E.; Glasscock, Edward; Szele, Francis G.; Vlachos, Ioannis; Murray, Teresa A.

    2016-01-01

    Implanted gradient index lenses have extended the reach of standard multiphoton microscopy from the upper layers of the mouse cortex to the lower cortical layers and even subcortical regions. These lenses have the clarity to visualize dynamic activities, such as calcium transients, with subcellular and millisecond resolution and the stability to facilitate repeated imaging over weeks and months. In addition, behavioral tests can be used to correlate performance with observed changes in network function and structure that occur over time. Yet, this raises the questions, does an implanted microlens have an effect on behavioral tests, and if so, what is the extent of the effect? To answer these questions, we compared the performance of three groups of mice in three common behavioral tests. A gradient index lens was implanted in the prefrontal cortex of experimental mice. We compared their performance with mice that had either a cranial window or a sham surgery. Three presurgical and five postsurgical sets of behavioral tests were performed over seven weeks. Behavioral tests included rotarod, foot fault, and Morris water maze. No significant differences were found between the three groups, suggesting that microlens implantation did not affect performance. The results for the current study clear the way for combining behavioral studies with gradient index lens imaging in the prefrontal cortex, and potentially other regions of the mouse brain, to study structural, functional, and behavioral relationships in the brain. PMID:26799938

  3. Proliferation of mouse embryonic stem cell progeny and the spontaneous contractile activity of cardiomyocytes are affected by microtopography.

    PubMed

    Biehl, Jesse K; Yamanaka, Satoshi; Desai, Tejal A; Boheler, Kenneth R; Russell, Brenda

    2009-08-01

    The niche in which stem cells reside and differentiate is a complex physicochemical microenvironment that regulates cell function. The role played by three-dimensional physical contours was studied on cell progeny derived from mouse embryonic stem cells using microtopographies created on PDMS (poly-dimethyl-siloxane) membranes. While markers of differentiation were not affected, the proliferation of heterogeneous mouse embryonic stem cell-derived progeny was attenuated by 15 microm-, but not 5 microm-high microprojections. This reduction was reversed by Rho kinase and myosin light chain kinase inhibition, which diminishes the tension generating ability of stress fibers. Purified cardiomyocytes derived from embryonic stem cells also showed significant blunting of proliferation and increased beating rates compared with cells grown on flat substrates. Thus, proliferation of stem cell-derived progeny appears to be regulated by microtopography through tension-generation of contractility in the third-dimension. These results emphasize the importance of topographic cues in the modulation of stem cell progeny behavior.

  4. Androgens affect muscle, motor neuron, and survival in a mouse model of SOD1-related amyotrophic lateral sclerosis.

    PubMed

    Aggarwal, Tanya; Polanco, Maria J; Scaramuzzino, Chiara; Rocchi, Anna; Milioto, Carmelo; Emionite, Laura; Ognio, Emanuela; Sambataro, Fabio; Galbiati, Mariarita; Poletti, Angelo; Pennuto, Maria

    2014-08-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of upper and lower motor neurons and skeletal muscle atrophy. Epidemiologic and experimental evidence suggest the involvement of androgens in ALS pathogenesis, but the mechanism through which androgens modify the ALS phenotype is unknown. Here, we show that androgen ablation by surgical castration extends survival and disease duration of a transgenic mouse model of ALS expressing mutant human SOD1 (hSOD1-G93A). Furthermore, long-term treatment of orchiectomized hSOD1-G93A mice with nandrolone decanoate (ND), an anabolic androgenic steroid, worsened disease manifestations. ND treatment induced muscle fiber hypertrophy but caused motor neuron death. ND negatively affected survival, thereby dissociating skeletal muscle pathology from life span in this ALS mouse model. Interestingly, orchiectomy decreased androgen receptor levels in the spinal cord and muscle, whereas ND treatment had the opposite effect. Notably, stimulation with ND promoted the recruitment of endogenous androgen receptor into biochemical complexes that were insoluble in sodium dodecyl sulfate, a finding consistent with protein aggregation. Overall, our results shed light on the role of androgens as modifiers of ALS pathogenesis via dysregulation of androgen receptor homeostasis.

  5. An n-3 Fatty Acid Deficient Diet Affects Mouse Spatial Learning in the Barnes Circular Maze

    PubMed Central

    Fedorova, Irina; Hussein, Nahed; Di Martino, Carmine; Moriguchi, Toru; Hoshiba, Junji; Majchrzak, Sharon; Salem, Norman

    2008-01-01

    Deficiency in n-3 fatty acids has been accomplished through the use of an artificial rearing method in which ICR mouse pups were hand fed a deficient diet starting from the second day of life. There was a 51% loss of total brain DHA in mice with an n-3 fatty acid deficient diet relative to those with a diet sufficient in n-3 fatty acids. N-3 fatty acid adequate and deficient mice did not differ in terms of locomotor activity in the open field test or in anxiety-related behavior in the elevated plus maze. The n-3 fatty acid deficient mice demonstrated impaired learning in the reference-memory version of the Barnes circular maze as they spent more time and made more errors in search of an escape tunnel. No difference in performance between all dietary groups in the cued and working memory version of the Barnes maze was observed. This indicated that motivational, motor and sensory factors did not contribute to the reference memory impairment. PMID:18037280

  6. Removal of mouse ovary fat pad affects sex hormones, folliculogenesis and fertility.

    PubMed

    Wang, Hong-Hui; Cui, Qian; Zhang, Teng; Guo, Lei; Dong, Ming-Zhe; Hou, Yi; Wang, Zhen-Bo; Shen, Wei; Ma, Jun-Yu; Sun, Qing-Yuan

    2017-02-01

    As a fat storage organ, adipose tissue is distributed widely all over the body and is important for energy supply, body temperature maintenance, organ protection, immune regulation and so on. In humans, both underweight and overweight women find it hard to become pregnant, which suggests that appropriate fat storage can guarantee the female reproductive capacity. In fact, a large mass of adipose tissue distributes around the reproductive system both in the male and female. However, the functions of ovary fat pad (the nearest adipose tissue to ovary) are not known. In our study, we found that the ovary fat pad-removed female mice showed decreased fertility and less ovulated mature eggs. We further identified that only a small proportion of follicles developed to antral follicle, and many follicles were blocked at the secondary follicle stage. The overall secretion levels of estrogen and FSH were lower in the whole estrus cycle (especially at proestrus); however, the LH level was higher in ovary fat pad-removed mice than that in control groups. Moreover, the estrus cycle of ovary fat pad-removed mice showed significant disorder. Besides, the expression of FSH receptor decreased, but the LH receptor increased in ovary fat pad-removed mice. These results suggest that ovary fat pad is important for mouse reproduction.

  7. Mainstream smoke and sidestream smoke affect the cardiac differentiation of mouse embryonic stem cells discriminately.

    PubMed

    Cheng, Wei; Zhou, Ren; Feng, Yan; Wang, Yan

    2016-05-16

    Epidemiology studies suggest that maternal smoking and passive smoking have strongly resulted in the occurrence of congenital heart defects (CHD) in offspring. Cigarette smoke (CS) can be divided into mainstream smoke (MS) and sidestream smoke (SS); CS chemistry study indicates that significant differences exist in the composition of MS and SS. Therefore, MS and SS were suspected to process toxicity dissimilarly. However, much less was known about the difference in the developmental effects induced by MS and SS. In the current study, heart development was mimicked by mouse embryonic stem cells (ESCs) differentiation. After MS and SS exposure, by tracing the bone morphogenetic protein (BMP)-Smad4 signalling pathway, interruption of downstream gene expression was observed, including Gata4, Mef2c and Nkx2.5, as well as myosin heavy chain and myosin light chain. Specifically, SS caused inhibition of Gata4 expression, even at non-cytotoxic concentration. Further, SS-induced hypoacetylation in promoter regions of Gata4 reflected the orchestration of CS-gene modulation-epigenetic regulation. Even though SS induced apoptosis in ESC-derived cardiomyocytes, the partial clearance in cells with down-regulated Gata4 caused these cells to survive and undergo further differentiation, which laid potential risk for abnormal heart development. These data uncovered the difference between MS and SS on heart development preliminarily. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Mouse Stbd1 is N-myristoylated and affects ER–mitochondria association and mitochondrial morphology

    PubMed Central

    Demetriadou, Anthi; Morales-Sanfrutos, Julia; Nearchou, Marianna; Baba, Otto; Kyriacou, Kyriacos; Tate, Edward W.; Drousiotou, Anthi

    2017-01-01

    ABSTRACT Starch binding domain-containing protein 1 (Stbd1) is a carbohydrate-binding protein that has been proposed to be a selective autophagy receptor for glycogen. Here, we show that mouse Stbd1 is a transmembrane endoplasmic reticulum (ER)-resident protein with the capacity to induce the formation of organized ER structures in HeLa cells. In addition to bulk ER, Stbd1 was found to localize to mitochondria-associated membranes (MAMs), which represent regions of close apposition between the ER and mitochondria. We demonstrate that N-myristoylation and binding of Stbd1 to glycogen act as major determinants of its subcellular targeting. Moreover, overexpression of non-myristoylated Stbd1 enhanced the association between ER and mitochondria, and further induced prominent mitochondrial fragmentation and clustering. Conversely, shRNA-mediated Stbd1 silencing resulted in an increase in the spacing between ER and mitochondria, and an altered morphology of the mitochondrial network, suggesting elevated fusion and interconnectivity of mitochondria. Our data unravel the molecular mechanism underlying Stbd1 subcellular targeting, support and expand its proposed function as a selective autophagy receptor for glycogen and uncover a new role for the protein in the physical association between ER and mitochondria. PMID:28137759

  9. Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission.

    PubMed

    Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J

    2016-07-01

    Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood.

  10. Abca7 deletion does not affect adult neurogenesis in the mouse.

    PubMed

    Li, Hongyun; Karl, Tim; Garner, Brett

    2016-01-20

    ATP-binding cassette transporter A7 (ABCA7) is highly expressed in the brain. Recent genome-wide association studies (GWAS) have identified ABCA7 single nucleotide polymorphisms (SNPs) that increase Alzheimer's disease (AD) risk, however, the mechanisms by which ABCA7 may control AD risk remain to be fully elucidated. Based on previous research suggesting that certain ABC transporters may play a role in the regulation of neurogenesis, we conducted a study of cell proliferation and neurogenic potential using cellular bromodeoxyuridine (BrdU) incorporation and doublecortin (DCX) immunostaining in adult Abca7 deficient mice and wild-type-like (WT) littermates. In the present study counting of BrdU-positive and DCX-positive cells in an established adult neurogenesis site in the dentate gyrus (DG) indicated there were no significant differences when WT and Abca7 deficient mice were compared. We also measured the area occupied by immunohistochemical staining for BrdU and DCX in the DG and the subventricular zone (SVZ) of the same mice and this confirmed that ABCA7 does not play a significant role in the regulation of cell proliferation or neurogenesis in the adult mouse.

  11. A Pex7 hypomorphic mouse model for plasmalogen deficiency affecting the lens and skeleton

    PubMed Central

    Braverman, Nancy; Zhang, Rui; Chen, Li; Nimmo, Graeme; Scheper, Sarah; Tran, Tammy; Chaudhury, Rupsa; Moser, Ann; Steinberg, Steven

    2010-01-01

    Rhizomelic chondrodysplasia punctata type 1 is a peroxisome biogenesis disorder with the clinical features of rhizomelia, abnormal epiphyseal calcifications, congenital cataracts, and profound growth and developmental delays. It is a rare autosomal recessive disorder, caused by defects in the peroxisome receptor, Pex7. The pathology results from a deficiency of plasmalogens, a critical class of ether phospholipids whose functions are largely unknown. To study plasmalogens in an animal model, avoid early mortality and facilitate therapeutic investigations in this disease, we engineered a hypomorphic mouse model in which Pex7 transcript levels are reduced to less than 5% of wild type. These mice are born in expected ratios, are fertile and have a normal life span. However, they are petite and develop early cataracts. Further investigations showed delayed endochondral ossification and abnormalities in lens fibers. The biochemical features of reduced Pex7 function were reproduced in this model, including tissue plasmalogen deficiency, phytanic acid accumulation, reduced import of Pex7 ligands and consequent defects in plasmalogen biosynthesis and phytanic acid oxidation. Dietary supplementation with batyl alcohol, a plasmalogen precursor, recovered ether phospholipids in blood, but did not alter the clinical phenotype. The relatively mild phenotype of these mice mimics patients with milder pex7 defects, and highlights the skeleton and lens as sensitive markers of plasmalogen deficiency. The role of plasmalogens in the normal function of these tissues at various ages can now be studied and additional therapeutic interventions tested in this model. PMID:20060764

  12. Mouse Stbd1 is N-myristoylated and affects ER-mitochondria association and mitochondrial morphology.

    PubMed

    Demetriadou, Anthi; Morales-Sanfrutos, Julia; Nearchou, Marianna; Baba, Otto; Kyriacou, Kyriacos; Tate, Edward W; Drousiotou, Anthi; Petrou, Petros P

    2017-03-01

    Starch binding domain-containing protein 1 (Stbd1) is a carbohydrate-binding protein that has been proposed to be a selective autophagy receptor for glycogen. Here, we show that mouse Stbd1 is a transmembrane endoplasmic reticulum (ER)-resident protein with the capacity to induce the formation of organized ER structures in HeLa cells. In addition to bulk ER, Stbd1 was found to localize to mitochondria-associated membranes (MAMs), which represent regions of close apposition between the ER and mitochondria. We demonstrate that N-myristoylation and binding of Stbd1 to glycogen act as major determinants of its subcellular targeting. Moreover, overexpression of non-myristoylated Stbd1 enhanced the association between ER and mitochondria, and further induced prominent mitochondrial fragmentation and clustering. Conversely, shRNA-mediated Stbd1 silencing resulted in an increase in the spacing between ER and mitochondria, and an altered morphology of the mitochondrial network, suggesting elevated fusion and interconnectivity of mitochondria. Our data unravel the molecular mechanism underlying Stbd1 subcellular targeting, support and expand its proposed function as a selective autophagy receptor for glycogen and uncover a new role for the protein in the physical association between ER and mitochondria. © 2017. Published by The Company of Biologists Ltd.

  13. Diazinon oxon affects the differentiation of mouse N2a neuroblastoma cells.

    PubMed

    Sidiropoulou, Erasmia; Sachana, Magdalini; Flaskos, John; Harris, Wayne; Hargreaves, Alan J; Woldehiwet, Zerai

    2009-04-01

    The aim of this study was to assess the neurotoxicity of diazinon oxon (DZO), a major in vivo metabolite of the phosphorothionate insecticide diazinon (DZ), on differentiating mouse N2a neuroblastoma cells. When used at concentrations of 1, 5 and 10 microM, DZO did not cause cell death but it impaired the outgrowth of axon-like processes after 24 h. Densitometric scanning of Western blots of lysates of N2a cells revealed that exposure to 5 or 10 microM DZO for 24 h increased the expression of phosphorylated neurofilament heavy chain (NFH) compared to controls, while there was no significant change in total NFH. By contrast, treatment of N2a cells with 1-10 microM DZO resulted in marked reductions in the expression of the axon growth-associated protein GAP-43. DZO-treated cells also showed an increased expression of the heat shock protein HSP-70 compared to controls. The above biochemical changes were not temporally related to inhibition of acetylcholinesterase (AChE). These data suggest that biologically relevant, subcytotoxic levels of DZO may exert neurotoxic effects on differentiating cells and that the mechanisms involved are different from those attributed to its parent compound.

  14. Shortening amplitude affects the incomplete force recovery after active shortening in mouse soleus muscle.

    PubMed

    Van Noten, Pieter; Van Leemputte, Marc

    2009-12-11

    Compared to isometric contraction, the force producing capacity of muscle is reduced (force depression, FD) after a work producing shortening phase. It has been suggested that FD results from an inhibition of cross-bridge binding. Because the rate constants of the exponential force (re)development are thought to be primarily determined by cross-bridge attachment/detachment rate, we aimed to investigate the components of force redevelopment (REDEV) after 0.6, 1.2 and 2.4mm shortening, resulting in varying amounts of FD (from about 5% to about 16%), in mouse soleus muscle (n=11). Compared to isometric force development (DEV), the time to reach steady-state during REDEV was about 3 times longer (370 versus 1261ms) increasing with increasing amplitude. Contrary to a single, a double exponential function with one component set equal to the rate constant of DEV (14.3s(-1)), accurately described REDEV (RMS<0.8%). The rate constant of the additional slow component decreased with increasing shortening amplitude and was associated with work delivered during shortening (R(2)=0.75) and FD (R(2)=0.77). We concluded that a work related slow exponential component is induced to the trajectory of incomplete force recovery after shortening, causing FD. These results suggest that after shortening, aside from cross-bridges with normal attachment/detachment rate, cross-bridges with reduced cycling rate are active.

  15. Effect of Exposure to Atmospheric Ultrafine Particles on Production of Free Fatty Acids and Lipid Metabolites in the Mouse Small Intestine

    PubMed Central

    Li, Rongsong; Navab, Kaveh; Hough, Greg; Daher, Nancy; Zhang, Min; Mittelstein, David; Lee, Katherine; Pakbin, Payam; Saffari, Arian; Bhetraratana, May; Sulaiman, Dawoud; Beebe, Tyler; Wu, Lan; Jen, Nelson; Wine, Eytan; Tseng, Chi-Hong; Araujo, Jesus A.; Fogelman, Alan; Sioutas, Constantinos; Navab, Mohamed

    2014-01-01

    Background: Exposure to ambient ultrafine particulate matter (UFP) is a well-recognized risk factor for cardiovascular and respiratory diseases. However, little is known about the effects of air pollution on gastrointestinal disorders. Objective: We sought to assess whether exposure to ambient UFP (diameter < 180 nm) increased free fatty acids and lipid metabolites in the mouse small intestine. Methods: Ldlr-null mice were exposed to filtered air (FA) or UFP collected at an urban Los Angeles, California, site that was heavily affected by vehicular emissions; the exposure was carried out for 10 weeks in the presence or absence of D-4F, an apolipoprotein A-I mimetic peptide with antioxidant and anti-inflammation properties on a high-fat or normal chow diet. Results: Compared with FA, exposure to UFP significantly increased intestinal hydroxyeicosatetraenoic acids (HETEs), including 15-HETE, 12-HETE, 5-HETE, as well as hydroxyoctadecadienoic acids (HODEs), including 13-HODE and 9-HODE. Arachidonic acid (AA) and prostaglandin D2 (PGD2) as well as some of the lysophosphatidic acids (LPA) in the small intestine were also increased in response to UFP exposure. Administration of D-4F significantly reduced UFP-mediated increase in HETEs, HODEs, AA, PGD2, and LPA. Although exposure to UFP further led to shortened villus length accompanied by prominent macrophage and neutrophil infiltration into the intestinal villi, administration of D-4F mitigated macrophage infiltration. Conclusions: Exposure to UFP promotes lipid metabolism, villus shortening, and inflammatory responses in mouse small intestine, whereas administration of D-4F attenuated these effects. Our findings provide a basis to further assess the mechanisms underlying UFP-mediated lipid metabolism in the digestive system with clinical relevance to gut homeostasis and diseases. Citation: Li R, Navab K, Hough G, Daher N, Zhang M, Mittelstein D, Lee K, Pakbin P, Saffari A, Bhetraratana M, Sulaiman D, Beebe T, Wu L, Jen

  16. Oral administration of nano-titanium dioxide particle disrupts hepatic metabolic functions in a mouse model.

    PubMed

    Yang, Julin; Luo, Min; Tan, Zhen; Dai, Manyun; Xie, Minzhu; Lin, Jiao; Hua, Huiying; Ma, Qing; Zhao, Jinshun; Liu, Aiming

    2017-01-01

    TiO2 nano-particle (TiO2 NP) is widely used in industrial, household necessities, as well as medicinal products. However, the effect of TiO2 NP on liver metabolic function has not been reported. In this study, after mice were orally administered TiO2 NP (21nm) for 14days, the serum and liver tissues were assayed by biochemical analysis, real time quantitative polymerase chain reaction, western blot and transmission electron microscopy. The serum bilirubin was increased in a dose dependent manner. Deposition of TiO2 NP in hepatocytes and the abnormality of microstructures was observed. Expression of metabolic genes involved in the endogenous and exogenous metabolism was modified, supporting the toxic phenotype. Collectively, oral administration of TiO2 NP (21nm) led to deposition of particles in hepatocytes, mitochondrial edema, and the disturbance of liver metabolism function. These data suggested oral administration disrupts liver metabolic functions, which was more sensitive than regular approaches to detect material hepatotoxicity. This study provided useful information for risk analysis and regulation of TiO2 NPs by administration agencies. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Fluence-based relative biological effectiveness for charged particle carcinogenesis in mouse Harderian gland

    NASA Technical Reports Server (NTRS)

    Alpen, E. L.; Power-Risius, P.; Curtis, S. B.; Deguzman, R.; Fry, R. J. M.

    1994-01-01

    Neoplasia in the rodent Harderian gland has been used to determine the carcinogenic potential of irradiation by HZE particles. Ions from protons to lanthanum at energies up to 670 MeV/a have been used to irradiate mice, and prevalence of Harderian gland tumors has been measured 16 months after irradiation. The Relative Biological Effectiveness (RBE) for tumor induction has been expressed as the RBE(sub max), which is the ratio of the initial slopes of the dose vs prevalence curve. The RBE(sub max) has been found to be approximately 30 for ions with Linear Energy Transfer (LET) values in excess of 100 keV/micrometer. Analysis on the basis of fluence as a substitute for dose has shown that on a per particle basis all of the ions with LET values in excess of 100 keV/micrometer have equal effectiveness. An analysis of the probabilities of ion traversals of the nucleus has shown that for these high stopping powers that a single hit is effective in producing neoplastic transformation.

  18. Fluence-based relative biological effectiveness for charged particle carcinogenesis in mouse Harderian gland

    NASA Technical Reports Server (NTRS)

    Alpen, E. L.; Power-Risius, P.; Curtis, S. B.; Deguzman, R.; Fry, R. J. M.

    1994-01-01

    Neoplasia in the rodent Harderian gland has been used to determine the carcinogenic potential of irradiation by HZE particles. Ions from protons to lanthanum at energies up to 670 MeV/a have been used to irradiate mice, and prevalence of Harderian gland tumors has been measured 16 months after irradiation. The Relative Biological Effectiveness (RBE) for tumor induction has been expressed as the RBE(sub max), which is the ratio of the initial slopes of the dose vs prevalence curve. The RBE(sub max) has been found to be approximately 30 for ions with Linear Energy Transfer (LET) values in excess of 100 keV/micrometer. Analysis on the basis of fluence as a substitute for dose has shown that on a per particle basis all of the ions with LET values in excess of 100 keV/micrometer have equal effectiveness. An analysis of the probabilities of ion traversals of the nucleus has shown that for these high stopping powers that a single hit is effective in producing neoplastic transformation.

  19. Fluence-based relative biological effectiveness for charged particle carcinogenesis in mouse Harderian gland

    NASA Astrophysics Data System (ADS)

    Alpen, E. L.; Powers-Risius, P.; Curtis, S. B.; Deguzman, R.; Fry, R. J. M.

    1994-10-01

    Neoplasia in the rodent Harderian gland has been used to determine the carcinogenic potential of irradiation by HZE particles. Ions from protons to lanthanum at energies up to 670 MeV/a have been used to irradiate mice, and prevalence of Harderian gland tumors has been measured 16 months after irradiation. The RBE for tumor induction has been expressed as the RBEmax, which is the ratio of the initial slopes of the dose vs prevalence curve. The RBEmax has been found to be approximately 30 for ions with LET values in excess of 100 keV/μm. Analysis on the basis of fluence as a substitute for dose has shown that on a per particle basis all of the ions with LET values in excess of 100 keV/μm have equal effectiveness. An analysis of the probabilities of ion traversals of the nucleus has shown that for these high stopping powers that a single hit is effective in producing neoplastic transformation.

  20. Exposure to Concentrated Ambient Particles Does Not Affect Vascular Function in Patients with Coronary Heart Disease

    PubMed Central

    Mills, Nicholas L.; Robinson, Simon D.; Fokkens, Paul H. B.; Leseman, Daan L. A. C.; Miller, Mark R.; Anderson, David; Freney, Evelyn J.; Heal, Mathew R.; Donovan, Robert J.; Blomberg, Anders; Sandström, Thomas; MacNee, William; Boon, Nicholas A.; Donaldson, Ken; Newby, David E.; Cassee, Flemming R.

    2008-01-01

    Background Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans. Objectives We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction. Methods Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables—including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine—6–8 hr after both exposures. Results Particulate concentrations (mean ± SE) in the exposure chamber (190 ± 37 μg/m3) were higher than ambient levels (31 ± 8 μg/m3) and levels in filtered air (0.5 ± 0.4 μg/m3; p < 0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9 ± 8.5 vs. 4.9 ± 1.2 pg/mL, p < 0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p < 0.001 for all), CAPs exposure had no effect on vascular function in either group. Conclusions Despite achieving marked increases in particulate matter, exposure to CAPs—low in combustion-derived particles—did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans. PMID:18560524

  1. Factors affecting the stability of the performance of ambient fine-particle concentrators.

    PubMed

    Kim, S; Sioutas, C; Chang, M C; Gong, H

    2000-01-01

    This article describes a systematic evaluation of factors affecting the stability of the performance of Harvard ambient fine-particle concentrators, an essential requirement for controlled animal and human exposure studies that utilize these technologies. Phenomenological problems during the operation of the concentrator, including pressure drop increase and decrease in concentration enrichment, were statistically correlated with ambient air parameters such as temperature, relative humidity, PM2.5 mass concentration, and mass median diameter. The normalized hourly pressure drop across the concentrator was strongly associated (R2 = .81) with the product of ambient PM2.5 mass concentration and the difference between the vapor pressure downstream of the impactor nozzle and the saturation vapor pressure at the adiabatic expansion temperature (i.e., the temperature of the aerosol immediately downstream of the virtual impactors). From multiple regression analysis, the average enrichment factor was predicted reasonably well (R2 = .67) by aerosol mass median diameter and the normalized hourly pressure drop. Based on these results, we can anticipate in any given day whether an exposure study can be conducted without a considerable increase in the concentrator pressure drop, which might lead to an abrupt or premature termination of the exposure. As particle mass concentration and ambient dewpoint are the two main parameters responsible for raising the pressure drop across the concentrator, efforts should be made to either desiccate the ambient aerosol at days of high dewpoints, or to dilute the ambient PM at days of high concentrations, prior to drawing the aerosol through the virtual impactors. The latter approach is recommended on days of severe ambient pollution conditions because it is simpler and also makes it possible to maintain the appropriate concentration level delivered to the exposure chamber.

  2. A gene affecting Wallerian nerve degeneration maps distally on mouse chromosome 4.

    PubMed Central

    Lyon, M F; Ogunkolade, B W; Brown, M C; Atherton, D J; Perry, V H

    1993-01-01

    When a nerve axon is cut or crushed, the nerve fibers in the distal part of the axon, separated from the cell body, undergo a form of spontaneous degeneration, known as Wallerian degeneration. A substrain of the mouse inbred strain C57BL, known as C57BL/Ola, carries a mutant form of a gene involved in Wallerian degeneration in the peripheral and central nervous systems, and in retrograde degeneration of retinal ganglion cells. Wallerian degeneration in this substrain is abnormally slow. Previously the defect had been shown to be due to an autosomal dominant gene. The locus has been given the name and symbol Wallerian degeneration Wld, with the mutant allele Wlds (Wallerian degeneration-slow). The Wld locus has now been mapped, by using conventional and molecular markers, to the distal end of chromosome 4, near the locus of pronatriodilatin (Pnd). The order of loci (with recombination distances in centimorgans, cM) is cen-D4Mit11-8.9 +/- 1.7 cM-Fuca-2.5 +/- 0.93 cM-Akp-2-3.2 +/- 1.1 cM-D4Mit48-3.5 +/- 1.1 cM-(Wld, Pnd, D4Mit49)-0.71 +/- 0.50 cM-(Eno-1, D4Mit33)-1.4 +/- 0.70 cM-D4Mit42-2.5 +/- 0.93 cM-D4Smh6b. The information on the position of the Wld locus should be valuable in further characterization of this gene involved in nerve degeneration and regeneration. PMID:8415768

  3. CDK2 activation in mouse epidermis induces keratinocyte proliferation but does not affect skin tumor development.

    PubMed

    Macias, Everardo; Miliani de Marval, Paula L; De Siervi, Adriana; Conti, Claudio J; Senderowicz, Adrian M; Rodriguez-Puebla, Marcelo L

    2008-08-01

    It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. We have previously shown that mice overexpressing CDK4 under control of the keratin 5 promoter (K5CDK4 mice) develop epidermal hyperplasia and increased susceptibility to squamous cell carcinomas. In this model, CDK4 overexpression results in increased CDK2 activity associated with the noncatalytic function of CDK4, sequestration of p21(Cip1) and p27(Kip1). Furthermore, we have shown that ablation of Cdk2 reduces Ras-Cdk4 tumorigenesis, suggesting that increased CDK2 activity plays an important role in Ras-mediated tumorigenesis. To investigate this hypothesis, we generated two transgenic mouse models of elevated CDK2 kinase activity, K5Cdk2 and K5Cdk4(D158N) mice. The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. CDK2 activation via overexpression of CDK4(D158N), but not of CDK2, resulted in epidermal hyperplasia. We observed elevated levels of p21(Cip1) in K5Cdk2, but not in K5Cdk4(D158N), epidermis, suggesting that CDK2 overexpression elicits a p21(Cip1) response to maintain keratinocyte homeostasis. Surprisingly, we found that neither CDK2 overexpression nor the indirect activation of CDK2 enhanced skin tumor development. Thus, although the indirect activation of CDK2 is sufficient to induce keratinocyte hyperproliferation, activation of CDK2 alone does not induce malignant progression in Ras-mediated tumorigenesis.

  4. Absence of Neuroplastin-65 Affects Synaptogenesis in Mouse Inner Hair Cells and Causes Profound Hearing Loss

    PubMed Central

    Carrott, Leanne; Aguilar, Carlos; Johnson, Stuart L.; Chessum, Lauren; West, Melissa; Morse, Susan; Dorning, Joanne; Smart, Elizabeth; Hardisty-Hughes, Rachel; Ball, Greg; Parker, Andrew; Barnard, Alun R.; MacLaren, Robert E.; Wells, Sara; Marcotti, Walter

    2016-01-01

    The Neuroplastin gene encodes two synapse-enriched protein isoforms, Np55 and Np65, which are transmembrane glycoproteins that regulate several cellular processes, including the genesis, maintenance, and plasticity of synapses. We found that an absence of Np65 causes early-onset sensorineural hearing loss and prevented the normal synaptogenesis in inner hair cells (IHCs) in the newly identified mouse mutant pitch. In wild-type mice, Np65 is strongly upregulated in the cochlea from around postnatal day 12 (P12), which corresponds to the onset of hearing. Np65 was specifically localized at the presynaptic region of IHCs. We found that the colocalization of presynaptic IHC ribbons and postsynaptic afferent terminals is greatly reduced in pitch mutants. Moreover, IHC exocytosis is also reduced with mutant mice showing lower rates of vesicle release. Np65 appears to have a nonessential role in vision. We propose that Np65, by regulating IHC synaptogenesis, is critical for auditory function in mammals. SIGNIFICANCE STATEMENT In the mammalian cochlea, the sensory inner hair cells (IHCs) encode auditory information. They do this by converting sound wave-induced mechanical motion of their hair bundles into an electrical current. This current generates a receptor potential that controls release of glutamate neurotransmitter from their ribbon synapses onto the auditory afferent fiber. We show that the synapse-enriched protein Np65, encoded by the Neuroplastin gene, is localized at the IHC presynaptic region. In mutant mice, absence of Np65 causes early-onset sensorineural hearing loss and prevents normal neurotransmitter release in IHCs and colocalization of presynaptic ribbons with postsynaptic afferents. We identified Neuroplastin as a novel deafness gene required for ribbon synapse formation and function, which is critical for sound perception in mammals. PMID:26740663

  5. Absence of Neuroplastin-65 Affects Synaptogenesis in Mouse Inner Hair Cells and Causes Profound Hearing Loss.

    PubMed

    Carrott, Leanne; Bowl, Michael R; Aguilar, Carlos; Johnson, Stuart L; Chessum, Lauren; West, Melissa; Morse, Susan; Dorning, Joanne; Smart, Elizabeth; Hardisty-Hughes, Rachel; Ball, Greg; Parker, Andrew; Barnard, Alun R; MacLaren, Robert E; Wells, Sara; Marcotti, Walter; Brown, Steve D M

    2016-01-06

    The Neuroplastin gene encodes two synapse-enriched protein isoforms, Np55 and Np65, which are transmembrane glycoproteins that regulate several cellular processes, including the genesis, maintenance, and plasticity of synapses. We found that an absence of Np65 causes early-onset sensorineural hearing loss and prevented the normal synaptogenesis in inner hair cells (IHCs) in the newly identified mouse mutant pitch. In wild-type mice, Np65 is strongly upregulated in the cochlea from around postnatal day 12 (P12), which corresponds to the onset of hearing. Np65 was specifically localized at the presynaptic region of IHCs. We found that the colocalization of presynaptic IHC ribbons and postsynaptic afferent terminals is greatly reduced in pitch mutants. Moreover, IHC exocytosis is also reduced with mutant mice showing lower rates of vesicle release. Np65 appears to have a nonessential role in vision. We propose that Np65, by regulating IHC synaptogenesis, is critical for auditory function in mammals. In the mammalian cochlea, the sensory inner hair cells (IHCs) encode auditory information. They do this by converting sound wave-induced mechanical motion of their hair bundles into an electrical current. This current generates a receptor potential that controls release of glutamate neurotransmitter from their ribbon synapses onto the auditory afferent fiber. We show that the synapse-enriched protein Np65, encoded by the Neuroplastin gene, is localized at the IHC presynaptic region. In mutant mice, absence of Np65 causes early-onset sensorineural hearing loss and prevents normal neurotransmitter release in IHCs and colocalization of presynaptic ribbons with postsynaptic afferents. We identified Neuroplastin as a novel deafness gene required for ribbon synapse formation and function, which is critical for sound perception in mammals. Copyright © 2016 Carrott, Bowl et al.

  6. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model.

    PubMed

    Yu, Yueyue; Lu, Lei; Sun, Jun; Petrof, Elaine O; Claud, Erika C

    2016-09-01

    Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics.

  7. Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland

    NASA Technical Reports Server (NTRS)

    Ehrhart, E. J.; Gillette, E. L.; Barcellos-Hoff, M. H.; Chaterjee, A. (Principal Investigator)

    1996-01-01

    High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by gamma irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin immunoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid-remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation.

  8. Neuropathological Consequences of Gestational Exposure to Concentrated Ambient Fine and Ultrafine Particles in the Mouse.

    PubMed

    Klocke, Carolyn; Allen, Joshua L; Sobolewski, Marissa; Mayer-Pröschel, Margot; Blum, Jason L; Lauterstein, Dana; Zelikoff, Judith T; Cory-Slechta, Deborah A

    2017-04-01

    Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution. We previously reported that postnatal exposure of mice to concentrated ambient ultrafine particles (UFP; ≤100 nm) via the University of Rochester HUCAPS system during a critical developmental window of CNS development, equivalent to human 3rd trimester, produced male-predominant neuropathological and behavioral characteristics common to multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), in humans. The current study sought to determine whether vulnerability to fine (≤2.5 μm) and UFP air pollution exposure extends to embryonic periods of brain development in mice, equivalent to human 1st and 2nd trimesters. Pregnant mice were exposed 6 h/day from gestational days (GDs) 0.5-16.5 using the New York University VACES system to concentrated ambient fine/ultrafine particles at an average concentration of 92.69 μg/m3 over the course of the exposure period. At postnatal days (PNDs) 11-15, neuropathological consequences were characterized. Gestational air pollution exposures produced ventriculomegaly, increased corpus callosum (CC) area and reduced hippocampal area in both sexes. Both sexes demonstrated CC hypermyelination and increased microglial activation and reduced total CC microglia number. Analyses of iron deposition as a critical component of myelination revealed increased iron deposition in the CC of exposed female offspring, but not in males. These findings demonstrate that vulnerability of the brain to air pollution extends to gestation and produces features of several neurodevelopmental disorders in both sexes. Further, they highlight the importance of the commonalities of components of particulate matter exposures as a source of neurotoxicity and common CNS alterations. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e

  9. Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland

    SciTech Connect

    Ehrhart, E.J.; Gillette, E.L.; Barcellos-Hoff, M.H.

    1996-02-01

    High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by {gamma} irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin inummoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation. 40 refs., 3 figs.

  10. Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland

    NASA Technical Reports Server (NTRS)

    Ehrhart, E. J.; Gillette, E. L.; Barcellos-Hoff, M. H.; Chaterjee, A. (Principal Investigator)

    1996-01-01

    High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by gamma irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin immunoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid-remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation.

  11. Passage number affects the pluripotency of mouse embryonic stem cells as judged by tetraploid embryo aggregation.

    PubMed

    Li, Xiang-Yun; Jia, Qing; Di, Ke-Qian; Gao, Shu-Min; Wen, Xiao-Hui; Zhou, Rong-Yan; Wei, Wei; Wang, Li-Ze

    2007-03-01

    The aim of this study was to determine whether the number of passages affected the developmental pluripotency of embryonic stem (ES) cells as measured by the attainment of adult fertile mice derived from embryonic stem (ES) cell/tetraploid embryo complementation. Thirty-six newborns were produced by the aggregation of tetraploid embryos and hybrid ES cells after various numbers of passages. These newborns were entirely derived from ES cells as judged by microsatellite DNA, coat-color phenotype, and germline transmission. Although 15 survived to adulthood, 17 died of respiratory failure, and four were eaten by their foster mother. From the 15 mice that reached adulthood and that could reproduce, none arose from ES cells at passage level 15 or more. All 15 arose from cells at passages 3-11. Our results demonstrate that the number of passages affects the developmental pluripotency of ES cells.

  12. Effects of paclitaxel on the development of neuropathy and affective behaviors in the mouse.

    PubMed

    Toma, Wisam; Kyte, S Lauren; Bagdas, Deniz; Alkhlaif, Yasmin; Alsharari, Shakir D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Bigbee, John W; Gewirtz, David A; Damaj, M Imad

    2017-05-01

    Paclitaxel, one of the most commonly used cancer chemotherapeutic drugs, effectively extends the progression-free survival of breast, lung, and ovarian cancer patients. However, paclitaxel and other chemotherapy drugs elicit peripheral nerve fiber dysfunction or degeneration that leads to peripheral neuropathy in a large proportion of cancer patients. Patients receiving chemotherapy also often experience changes in mood, including anxiety and depression. These somatic and affective disorders represent major dose-limiting side effects of chemotherapy. Consequently, the present study was designed to develop a preclinical model of paclitaxel-induced negative affective symptoms in order to identify treatment strategies and their underlying mechanisms of action. Intraperitoneal injections of paclitaxel (8 mg/kg) resulted in the development and maintenance of mechanical and cold allodynia. Carboplatin, another cancer chemotherapeutic drug that is often used in combination with paclitaxel, sensitized mice to the nociceptive effects of paclitaxel. Paclitaxel also induced anxiety-like behavior, as assessed in the novelty suppressed feeding and light/dark box tests. In addition, paclitaxel-treated mice displayed depression-like behavior during the forced swim test and an anhedonia-like state in the sucrose preference test. In summary, paclitaxel produced altered behaviors in assays modeling affective states in C57BL/6J male mice, while increases in nociceptive responses were longer in duration. The characterization of this preclinical model of chemotherapy-induced allodynia and affective symptoms, possibly related to neuropathic pain, provides the basis for determining the mechanism(s) underlying severe side effects elicited by paclitaxel, as well as for predicting the efficacy of potential therapeutic interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Fractal Scaling of Particle Size Distribution and Relationships with Topsoil Properties Affected by Biological Soil Crusts

    PubMed Central

    Gao, Guang-Lei; Ding, Guo-Dong; Wu, Bin; Zhang, Yu-Qing; Qin, Shu-Gao; Zhao, Yuan-Yuan; Bao, Yan-Feng; Liu, Yun-Dong; Wan, Li; Deng, Ji-Feng

    2014-01-01

    Background Biological soil crusts are common components of desert ecosystem; they cover ground surface and interact with topsoil that contribute to desertification control and degraded land restoration in arid and semiarid regions. Methodology/Principal Findings To distinguish the changes in topsoil affected by biological soil crusts, we compared topsoil properties across three types of successional biological soil crusts (algae, lichens, and mosses crust), as well as the referenced sandland in the Mu Us Desert, Northern China. Relationships between fractal dimensions of soil particle size distribution and selected soil properties were discussed as well. The results indicated that biological soil crusts had significant positive effects on soil physical structure (P<0.05); and soil organic carbon and nutrients showed an upward trend across the successional stages of biological soil crusts. Fractal dimensions ranged from 2.1477 to 2.3032, and significantly linear correlated with selected soil properties (R2 = 0.494∼0.955, P<0.01). Conclusions/Significance Biological soil crusts cause an important increase in soil fertility, and are beneficial to sand fixation, although the process is rather slow. Fractal dimension proves to be a sensitive and useful index for quantifying changes in soil properties that additionally implies desertification. This study will be essential to provide a firm basis for future policy-making on optimal solutions regarding desertification control and assessment, as well as degraded ecosystem restoration in arid and semiarid regions. PMID:24516668

  14. Uptake by mouse peritoneal macrophages of large cholesteryl ester-rich particles isolated from human atherosclerotic lesions.

    PubMed

    Hoff, H F; Clevidence, B A

    1987-06-01

    We have previously shown that a lipoprotein fraction consisting of large cholesteryl ester-rich particles can be isolated from homogenates of human aortic plaques by gel exclusion chromatography. This fraction was recognized by a high-affinity binding site on mouse peritoneal macrophages (MPM) resulting in unregulated uptake, stimulation of cholesterol esterification, and massive accumulation of cholesteryl esters. In this report we have further characterized such a fraction, designated lipid-protein complex (LP), which can be isolated from the void volume fraction of a Bio-Gel A-150m column following chromatography of plaque extracts. LP possessed a mean cholesterol-to-protein ratio of 2.3; it was heterogeneous in size and structure as observed by electron microscopy after negative staining, and it stimulated cholesterol esterification in MPM in a linear fashion over a 48-hr time interval, suggesting that the binding site on MPM recognizing LP was not down-regulated by intracellular cholesterol content. This uptake resulted in the presence of oil red O-positive intracellular droplets and numerous vacuoles containing electron-dense structures, whereas MPM incubated without lipoprotein showed few vacuoles or lipid droplets. Using SDS-PAGE and immunoblot and dot-blot techniques, we found that the major proteins associated with LP were albumin and fibronectin, whereas apoB and apoE were present in lower amounts. These proteins may be responsible for opsonization of LP, making it recognizable to receptors on MPM and facilitating LP uptake by MPM. LP isolated from tissue extracts without homogenization had the same structural and functional characteristics, suggesting that homogenization per se was not responsible for creating a particle that was recognized by MPM. However, homogenization yielded two to three times more LP. MPM uptake of LP derived from lysed foam cells may represent one of the mechanisms by which fatty streak lesions may grow to larger atherosclerotic

  15. Perinatal exposure to diesel exhaust affects gene expression in mouse cerebrum.

    PubMed

    Tsukue, Naomi; Watanabe, Manabu; Kumamoto, Takayuki; Takano, Hirohisa; Takeda, Ken

    2009-11-01

    Many environmental toxins alter reproductive function and affect the central nervous system (CNS). Gonadal steroid hormones cause differentiation of neurons and affect brain function and behavior during the perinatal period, and the CNS is thought to be particularly susceptible to toxic insult during this period. It was, therefore, hypothesized that inhalation of diesel exhaust (DE) during the fetal or suckling period would disrupt the sexual differentiation of brain function in mice, and the effects of exposure to DE during the perinatal period on sexual differentiation related gene expression of the brain were investigated. In the fetal period exposure group, pregnant ICR mice were exposed to DE from 1.5 days post-coitum (dpc) until 16 dpc. In the neonatal period exposure group, dams and their offspring were exposed to DE from the day of birth [postnatal day (PND)-0] until PND-16. Then, the cerebrums of males and females at PND-2, -5, and -16 from both groups were analyzed for expression level of mRNA encoding stress-related proteins [cytochrome P450 1A1 (CYP1A1), heme oxygenase-1 (HO-1)] and steroid hormone receptors [estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), androgen receptor (AR)]. Expression levels of ER alpha and ER beta mRNA were increased in the cerebrum of newborns in the DE exposure groups as well as mRNA for CYP1A1 and HO-1. Results indicate that perinatal exposure to DE during the critical period of sexual differentiation of the brain may affect endocrine function.

  16. Cardiac metabolic pathways affected in the mouse model of barth syndrome.

    PubMed

    Huang, Yan; Powers, Corey; Madala, Satish K; Greis, Kenneth D; Haffey, Wendy D; Towbin, Jeffrey A; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W; Khuchua, Zaza

    2015-01-01

    Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS.

  17. Cardiac Metabolic Pathways Affected in the Mouse Model of Barth Syndrome

    PubMed Central

    Huang, Yan; Powers, Corey; Madala, Satish K.; Greis, Kenneth D.; Haffey, Wendy D.; Towbin, Jeffrey A.; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W.; Khuchua, Zaza

    2015-01-01

    Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS. PMID:26030409

  18. Loss of Sleep Affects the Ultrastructure of Pyramidal Neurons in the Adolescent Mouse Frontal Cortex.

    PubMed

    de Vivo, Luisa; Nelson, Aaron B; Bellesi, Michele; Noguti, Juliana; Tononi, Giulio; Cirelli, Chiara

    2016-04-01

    The adolescent brain may be uniquely affected by acute sleep deprivation (ASD) and chronic sleep restriction (CSR), but direct evidence is lacking. We used electron microscopy to examine how ASD and CSR affect pyramidal neurons in the frontal cortex of adolescent mice, focusing on mitochondria, endosomes, and lysosomes that together perform most basic cellular functions, from nutrient intake to prevention of cellular stress. Adolescent (1-mo-old) mice slept (S) or were sleep deprived (ASD, with novel objects and running wheels) during the first 6-8 h of the light period, chronically sleep restricted (CSR) for > 4 days (using novel objects, running wheels, social interaction, forced locomotion, caffeinated water), or allowed to recover sleep (RS) for ∼32 h after CSR. Ultrastructural analysis of 350 pyramidal neurons was performed (S = 82; ASD = 86; CSR = 103; RS = 79; 4 to 5 mice/group). Several ultrastructural parameters differed in S versus ASD, S versus CSR, CSR versus RS, and S versus RS, although the different methods used to enforce wake may have contributed to some of the differences between short and long sleep loss. Differences included larger cytoplasmic area occupied by mitochondria in CSR versus S, and higher number of secondary lysosomes in CSR versus S and RS. We also found that sleep loss may unmask interindividual differences not obvious during baseline sleep. Moreover, using a combination of 11 ultrastructural parameters, we could predict in up to 80% of cases whether sleep or wake occurred at the single cell level. Ultrastructural analysis may be a powerful tool to identify which cellular organelles, and thus which cellular functions, are most affected by sleep and sleep loss. © 2016 Associated Professional Sleep Societies, LLC.

  19. When size matters: differences in demineralized bone matrix particles affect collagen structure, mesenchymal stem cell behavior, and osteogenic potential.

    PubMed

    Dozza, B; Lesci, I G; Duchi, S; Della Bella, E; Martini, L; Salamanna, F; Falconi, M; Cinotti, S; Fini, M; Lucarelli, E; Donati, D

    2017-04-01

    Demineralized bone matrix (DBM) is a natural, collagen-based, osteoinductive biomaterial. Nevertheless, there are conflicting reports on the efficacy of this product. The purpose of this study was to evaluate whether DBM collagen structure is affected by particle size and can influence DBM cytocompatibility and osteoinductivity. Sheep cortical bone was ground and particles were divided in three fractions with different sizes, defined as large (L, 1-2 mm), medium (M, 0.5-1 mm), and small (S, <0.5 mm). After demineralization, the chemical-physical analysis clearly showed a particle size-dependent alteration in collagen structure, with DBM-M being altered but not as much as DBM-S. DBM-M displayed a preferable trend in almost all biological characteristics tested, although all DBM particles revealed an optimal cytocompatibility. Subcutaneous implantation of DBM particles into immunocompromised mice resulted in bone induction only for DBM-M. When sheep MSC were seeded onto particles before implantation, all DBM particles were able to induce new bone formation with the best incidence for DBM-M and DBM-S. In conclusion, the collagen alteration in DBM-M is likely the best condition to promote bone induction in vivo. Furthermore, the choice of 0.5-1 mm particles may enable to obtain more efficient and consistent results among different research groups in bone tissue-engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1019-1033, 2017.

  20. Nutrient demand interacts with grass particle length to affect digestion responses and chewing activity in dairy cows.

    PubMed

    Kammes, K L; Allen, M S

    2012-02-01

    Effects of grass particle length on dry matter intake (DMI), milk production, ruminal fermentation and pool sizes, digestion and passage kinetics, and chewing activity and the relationship of these effects with preliminary DMI (pDMI) were evaluated using 15 ruminally and duodenally cannulated Holstein cows in a crossover design with a 14-d preliminary period and two 18-d treatment periods. During the preliminary period, pDMI of individual cows ranged from 22.6 to 29.8 kg/d (mean=25.8 kg/d) and 3.5% fat-corrected milk yield ranged from 29.2 to 56.9 kg/d (mean=41.9 kg/d). Experimental treatments were diets containing orchardgrass silage chopped to either (a) 19-mm (long) or (b) 10-mm (short) theoretical length of cut as the sole forage. Grass silages contained approximately 46% neutral detergent fiber (NDF); diets contained 50% forage, 23% forage NDF, and 28% total NDF. Preliminary DMI, an index of nutrient demand, was determined during the last 4 d of the preliminary period when cows were fed a common diet and used as a covariate. Main effects of grass particle length and their interaction with pDMI were tested by ANOVA. Grass particle length and its interaction with pDMI did not affect milk yield, milk composition, or rumen pH. Long particle length tended to decrease DMI compared with short particle length, which might have been limited by rumen fill or chewing time, or both. Passage rates of feed fractions did not differ between long and short particle lengths and were not related to level of intake. As pDMI increased, long particles decreased ruminal digestion rate of potentially digestible NDF at a faster rate than short particles. As a result, long particles decreased or tended to decrease rates of ruminal turnover for NDF, organic matter, and dry matter and increased their rumen pools compared with short particles for cows with high pDMI. Long particles increased eating time, which affected cows with high intake to the greatest extent, and total chewing time

  1. Programming of mouse obesity by maternal exposure to concentrated ambient fine particles.

    PubMed

    Chen, Minjie; Wang, Xiaoke; Hu, Ziying; Zhou, Huifen; Xu, Yanyi; Qiu, Lianglin; Qin, Xiaobo; Zhang, Yuhao; Ying, Zhekang

    2017-06-23

    Many diseases including obesity may originate through alterations in the early-life environment that interrupts fetal development. Increasing evidence has shown that exposure to ambient fine particles (PM2.5) is associated with abnormal fetal development. However, its long-term metabolic effects on offspring have not been systematically investigated. To determine if maternal exposure to PM2.5 programs offspring obesity, female C57Bl/6j mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pre-conception, pregnancy, and lactation, and the developmental and metabolic responses of offspring were assessed. The growth trajectory of offspring revealed that maternal exposure to CAP significantly decreased offspring birth weight but increased body weight of adult male but not female offspring, and the latter was expressed as increased adiposity. These adult male offspring had increased food intake, but were sensitive to exogenous leptin. Their hypothalamic expression of Socs3 and Pomc, two target genes of leptin, was not changed, and the hypothalamic expression of NPY, an orexigenic peptide that is inhibited by leptin, was significantly increased. These decreases in central anorexigenic signaling were accompanied by reduced plasma leptin and its expression in adipose tissues, the primary source of circulating leptin. In contrast, maternal exposure did not significantly change any of these indexes in adult female offspring. Pyrosequencing demonstrated that the leptin promoter methylation of adipocytes was significantly increased in CAP-exposed male but not female offspring. Our data indicate that maternal exposure to ambient PM2.5 programs obesity in male offspring probably through alterations in the methylation of the promoter region of the leptin gene.

  2. Nano-sized and micro-sized polystyrene particles affect phagocyte function

    PubMed Central

    Prietl, B.; Meindl, C.; Roblegg, E.; Pieber, T. R.; Lanzer, G.; Fröhlich, E.

    2015-01-01

    Adverse effect of nanoparticles may include impairment of phagocyte function. To identify the effect of nanoparticle size on uptake, cytotoxicity, chemotaxis, cytokine secretion, phagocytosis, oxidative burst, nitric oxide production and myeloperoxidase release, leukocytes isolated from human peripheral blood, monocytes and macrophages were studied. Carboxyl polystyrene (CPS) particles in sizes between 20 and 1,000 nm served as model particles. Twenty nanometers CPS particles were taken up passively, while larger CPS particles entered cells actively and passively. Twenty nanometers CPS were cytotoxic to all phagocytes, ≥500 nm CPS particles only to macrophages. Twenty nanometers CPS particles stimulated IL-8 secretion in human monocytes and induced oxidative burst in monocytes. Five hundred nanometers and 1,000 nm CPS particles stimulated IL-6 and IL-8 secretion in monocytes and macrophages, chemotaxis towards a chemotactic stimulus of monocytes and phagocytosis of bacteria by macrophages and provoked an oxidative burst of granulocytes. At very high concentrations, CPS particles of 20 and 500 nm stimulated myeloperoxidase release of granulocytes and nitric oxide generation in macrophages. Cytotoxic effect could contribute to some of the observed effects. In the absence of cytotoxicity, 500 and 1,000 nm CPS particles appear to influence phagocyte function to a greater extent than particles in other sizes. PMID:24292270

  3. Multiple Nicotinic Acetylcholine Receptor Subtypes in the Mouse Amygdala Regulate Affective Behaviors and Response to Social Stress.

    PubMed

    Mineur, Yann S; Fote, Gianna M; Blakeman, Sam; Cahuzac, Emma L M; Newbold, Sylvia A; Picciotto, Marina R

    2016-05-01

    Electrophysiological and neurochemical studies implicate cholinergic signaling in the basolateral amygdala (BLA) in behaviors related to stress. Both animal studies and human clinical trials suggest that drugs that alter nicotinic acetylcholine receptor (nAChR) activity can affect behaviors related to mood and anxiety. Clinical studies also suggest that abnormalities in cholinergic signaling are associated with major depressive disorder, whereas pre-clinical studies have implicated both β2 subunit-containing (β2*) and α7 nAChRs in the effects of nicotine in models of anxiety- and depression-like behaviors. We therefore investigated whether nAChR signaling in the amygdala contributes to stress-mediated behaviors in mice. Local infusion of the non-competitive non-selective nAChR antagonist mecamylamine or viral-mediated downregulation of the β2 or α7 nAChR subunit in the amygdala all induced robust anxiolytic- and antidepressant-like effects in several mouse behavioral models. Further, whereas α7 nAChR subunit knockdown was somewhat more effective at decreasing anxiety-like behavior, only β2 subunit knockdown decreased resilience to social defeat stress and c-fos immunoreactivity in the BLA. In contrast, α7, but not β2, subunit knockdown effectively reversed the effect of increased ACh signaling in a mouse model of depression. These results suggest that signaling through β2* nAChRs is essential for baseline excitability of the BLA, and a decrease in signaling through β2 nAChRs alters anxiety- and depression-like behaviors even in unstressed animals. In contrast, stimulation of α7 nAChRs by acetylcholine may mediate the increased depression-like behaviors observed during the hypercholinergic state observed in depressed individuals.

  4. How do amines affect the growth of recently formed aerosol particles

    NASA Astrophysics Data System (ADS)

    Lehtipalo, Katrianne; Schobesberger, Siegfried; Sipilä, Mikko; Jokinen, Tuija; Sarnela, Nina; Franchin, Alessandro; Nieminen, Tuomo; Riccobono, Francesco; Duplissy, Jonathan; Riipinen, Ilona; Kulmala, Markku; Worsnop, Douglas; Cloud Collaboration

    2013-05-01

    Growth rates of recently born nanometer-scale particles were measured during the CLOUD experiments at CERN. Combining the data from several recently developed measurement techniques allowed us to follow the growth of the particles starting from molecules to molecular clusters and finally to climatically relevant particles. We studied the binary system with sulphuric acid and water, and the ternary systems with ammonia or dimethylamine added to the chamber, both in purely neutral situation, and with ionization from cosmic rays or the CERN particle beam.

  5. How illumination and contrast affect the area measurement of small particles by digital imaging

    NASA Astrophysics Data System (ADS)

    Taylor, Robert A.; Godbey, Luther C.

    1992-02-01

    Images from conventional video systems are being digitized in computers for the analysis of small particles. The method was developed to automate particle counting and area measurements of dark trash particles in cotton. However, it can be applied to many similar area measurement problems. Because video output is linearly proportional to the amount of light reflected, the best spectral band for optimum particle discrimination should be centered at the wavelength of maximum difference in reflectance between particles and their surroundings. However, due to the distribution of the illumination energy and the distribution of the detector sensitivity, peak performance bands are shifted. Reflectance from cleaned cotton samples and trash particles were measured to define spectral contrast. Pixel intensity histograms form the video system are reported for simulated area reference samples (painted dots on panels) and for actual cotton samples to demonstrate the particle discrimination mechanism. particles from different parts of the cotton plant were used to demonstrate the importance of considering a particle's contrast in the area measurement.

  6. Chronic Social Stress Affects Synaptic Maturation of Newly Generated Neurons in the Adult Mouse Dentate Gyrus

    PubMed Central

    Chen, Chien-Chung; Huang, Chiung-Chun

    2016-01-01

    Background: Chronic stress has been found to suppress adult neurogenesis, but it remains unclear whether it may affect the maturation process of adult-born neurons. Here, we examined the influence of chronic social defeat stress on the morphological and electrophysiological properties of adult-born dentate granule cells at different developmental stages. Methods: Adult C57BL/6 mice were subjected to 10 days of chronic social defeat stress followed by a social interaction test 24 hours after the last defeat. Defeated mice were segregated into susceptible and unsusceptible subpopulations based on a measure of social interaction test. Combining electrophysiology with retrovirus-mediated birth-dating and labeling, we examined the impact of chronic social defeat stress on temporal regulation of synaptic plasticity of adult-born dentate granule cells along their maturation. Results: Chronic social defeat stress decreases the survival and dendritic complexity of adult-born dentate granule cells. While chronic social defeat stress doesn’t alter the intrinsic electrophysiological properties and synaptic transmission of surviving adult-born dentate granule cells, it promotes the developmental switch in synaptic N-methyl-D-aspartate receptors from predominant GluN2B- to GluN2A-containing receptors, which transform the immature synapse of adult-born dentate granule cells from one that exhibits enhanced long-term potentiation to one that has normal levels of long-term potentiation. Furthermore, chronic social defeat stress increases the level of endogenous repressor element-1 silencing transcription factor mRNA in adult-born dentate granule cells, and knockdown of the repressor element-1 silencing transcription factor in adult-born dentate granule cells rescues chronic social defeat stress-induced morphological deficits and accelerated developmental switch in synaptic N-methyl-D-aspartate receptor subunit composition. Conclusions: These results uncover a previously

  7. Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease.

    PubMed

    Hofmann, Lukas; Karl, Franziska; Sommer, Claudia; Üçeyler, Nurcan

    2017-01-01

    Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3) due to α-galactosidase A (α-Gal A) deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO) and compared results with those of age-matched male wildtype (WT) littermates. Young (3 months) and old (≥ 18 months) mice were tested in the naïve state and after i.pl. injection of complete Freund`s adjuvant (CFA) as an inflammatory pain model. We used the elevated plus maze (EPM), the light-dark box (LDB) and the open field test (OF) to investigate anxiety-like behavior. The forced swim test (FST) and Morris water maze (MWM) were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in naïve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05). After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05) and naïve young Fabry KO mice (p<0.05) in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05). Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors.

  8. Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease

    PubMed Central

    Karl, Franziska; Sommer, Claudia; Üçeyler, Nurcan

    2017-01-01

    Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3) due to α-galactosidase A (α-Gal A) deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO) and compared results with those of age-matched male wildtype (WT) littermates. Young (3 months) and old (≥ 18 months) mice were tested in the naïve state and after i.pl. injection of complete Freund`s adjuvant (CFA) as an inflammatory pain model. We used the elevated plus maze (EPM), the light-dark box (LDB) and the open field test (OF) to investigate anxiety-like behavior. The forced swim test (FST) and Morris water maze (MWM) were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in naïve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05). After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05) and naïve young Fabry KO mice (p<0.05) in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05). Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors. PMID:28662189

  9. Methyl-donor deficiency in adolescence affects memory and epigenetic status in the mouse hippocampus.

    PubMed

    Tomizawa, H; Matsuzawa, D; Ishii, D; Matsuda, S; Kawai, K; Mashimo, Y; Sutoh, C; Shimizu, E

    2015-03-01

    DNA methylation is one of the essential factors in the control of gene expression. Alteration of the DNA methylation pattern has been linked to various neurological, behavioral and neurocognitive dysfunctions. Recent studies have pointed out the importance of epigenetics in brain development and functions including learning and memory. Nutrients related to one-carbon metabolism are known to play important roles in the maintenance of genomic DNA methylation. Previous studies have shown that the long-term administration of a diet lacking essential one-carbon nutrients such as methionine, choline and folic acid (methyl donors) caused global DNA hypermethylation in the brain. Therefore, the long-term feeding of a methyl-donor-deficient diet may cause abnormal brain development including learning and memory. To confirm this hypothesis, 3-week-old mice were maintained on a folate-, methionine- and choline-deficient (FMCD) or control (CON) diet for 3 weeks. We found that the methyl-donor deficiency impaired both novel object recognition and fear extinction after 3 weeks of treatment. The FMCD group showed spontaneous recovery of fear that differed from that in CON. In addition, we found decreased Gria1 gene expression and specific CpG hypermethylation of the Gria1 promoter region in the FMCD hippocampus. Our data suggest that a chronic dietary lack of methyl donors in the developmental period affects learning, memory and gene expressions in the hippocampus. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  10. Interface evolution of a particle in a supersaturated solution affected by a far-field uniform flow

    NASA Astrophysics Data System (ADS)

    Chen, Ming-Wen; Wang, Zi-Dong

    2013-09-01

    The effect of far-field uniform flow on the morphological evolution of a spherical particle in a supersaturated solution affected by a far-field uniform flow is studied by using the matched asymptotic expansion method. The analytical solution for the interface shape, concentration field, and interface velocity of the particle growth shows that the convection induced by the far-field uniform flow facilitates the growth of the spherical particle, the upstream flow imposed on the particle enhances the growth velocity of the interface when the flow comes in, the downstream flow lowers the growth velocity of the surface when the flow goes out, and the interface morphology evolves into a peach-like shape.

  11. Long-Term Effects of Diesel Exhaust Particles on Airway Inflammation and Remodeling in a Mouse Model

    PubMed Central

    Kim, Byeong-Gon; Lee, Pureun-Haneul; Lee, Shin-Hwa; Kim, Young-En; Shin, Mee-Yong; Kang, Yena; Bae, Seong-Hwan; Kim, Min-Jung; Rhim, TaiYoun; Park, Choon-Sik

    2016-01-01

    Purpose Diesel exhaust particles (DEPs) can induce and trigger airway hyperresponsiveness (AHR) and inflammation. The aim of this study was to investigate the effect of long-term DEP exposure on AHR, inflammation, lung fibrosis, and goblet cell hyperplasia in a mouse model. Methods BALB/c mice were exposed to DEPs 1 hour a day for 5 days a week for 3 months in a closed-system chamber attached to a ultrasonic nebulizer (low dose: 100 µg/m3 DEPs, high dose: 3 mg/m3 DEPs). The control group was exposed to saline. Enhanced pause was measured as an indicator of AHR. Animals were subjected to whole-body plethysmography and then sacrificed to determine the performance of bronchoalveolar lavage and histology. Results AHR was higher in the DEP group than in the control group, and higher in the high-dose DEP than in the low-dose DEP groups at 4, 8, and 12 weeks. The numbers of neutrophils and lymphocytes were higher in the high-dose DEP group than in the low-dose DEP group and control group at 4, 8, and 12 weeks. The levels of interleukin (IL)-5, IL-13, and interferon-γ were higher in the low-dose DEP group than in the control group at 12 weeks. The level of IL-10 was higher in the high-dose DEP group than in the control group at 12 weeks. The level of vascular endothelial growth factor was higher in the low-dose and high-dose DEP groups than in the control group at 12 weeks. The level of IL-6 was higher in the low-dose DEP group than in the control group at 12 weeks. The level of transforming growth factor-β was higher in the high-dose DEP group than in the control group at 4, 8, and 12 weeks. The collagen content and lung fibrosis in lung tissue was higher in the high-dose DEP group at 8 and 12 weeks. Conclusions These results suggest that long-term DEP exposure may increase AHR, inflammation, lung fibrosis, and goblet cell hyperplasia in a mouse model. PMID:26922935

  12. Cellular Intrinsic Mechanism Affecting the Outcome of AML Treated with Ara-C in a Syngeneic Mouse Model

    PubMed Central

    Tan, Dongming; Su, Guangsong; Zheng, Yanwen; He, Chao; Mao, Zhengwei J.; Singleton, Timothy P.; Yin, Bin

    2014-01-01

    The mechanisms underlying acute myeloid leukemia (AML) treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. PMID:25314317

  13. Differential effect of chronic stress on mouse hippocampal memory and affective behavior: Role of major ovarian hormones.

    PubMed

    Karisetty, Bhanu Chandra; Maitra, Swati; Wahul, Abhipradnya Bipin; Musalamadugu, Anusha; Khandelwal, Nitin; Guntupalli, Sumasri; Garikapati, Ramya; Jhansyrani, Thatiparthi; Kumar, Arvind; Chakravarty, Sumana

    2017-02-01

    Molecular mechanisms of depression-like pathophysiology in female rodent models are less reported compared to males, despite its higher prevalence in human females. Moreover, the stress-response in brain circuitries including reward and cognition circuitries varies with age or hormonal status of the females. So, to understand the stress-induced mood and cognitive disorders in intact females (with ovaries) and ovariectomized (OVX) females, we studied changes in mouse hippocampus, a functionally heterogeneous neural structure involved in both affective and cognitive behaviors. Here, we used a 6-day Chronic Unpredictable Stress (CUS) paradigm in mice to induce depression and related mood disorders. Interestingly, intact females and OVX females showed difference in mood disorder sub-phenotypes to CUS. Similar to an earlier report of CUS affecting the critical reward circuitry structure the nucleus accumbens differently in females with and without ovaries, cognitive behavior in intact females and OVX females also responded differentially to CUS, as evident from Morris Water Maze (MWM) test results. We report that the presence or absence of ovarian hormones, particularly the estrogen, has a significant impact in altering the hippocampus related spatial memory and affective behavior, in females. Our results also illustrate that estrogen administration improves both reward and cognitive behavior, and plays a significant role in alleviating stress-induced despair behavior and enhancing spatial reference memory following a brief 6-day stressful paradigm. Further, it also indicates that the NMDA receptor subunits, GRIN2A and GRIN2B, might mediate the effects of estrogen in the hippocampal functions, thus suggestive of a translational significance of the finding.

  14. Relaxin Affects Smooth Muscle Biophysical Properties and Mechanical Activity of the Female Mouse Colon.

    PubMed

    Squecco, Roberta; Garella, Rachele; Idrizaj, Eglantina; Nistri, Silvia; Francini, Fabio; Baccari, Maria Caterina

    2015-12-01

    The hormone relaxin (RLX) has been reported to influence gastrointestinal motility in mice. However, at present, nothing is known about the effects of RLX on the biophysical properties of the gastrointestinal smooth muscle cells (SMCs). Other than extending previous knowledge of RLX on colonic motility, the purpose of this study was to investigate the ability of the hormone to induce changes in resting membrane potential (RMP) and on sarcolemmal ion channels of colonic SMCs of mice that are related to its mechanical activity. To this aim, we used a combined mechanical and electrophysiological approach. In the mechanical experiments, we observed that RLX caused a decay of the basal tone coupled to an increase of the spontaneous contractions, completely abolished by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (ODQ). The electrophysiological results indicate for the first time that RLX directly affects the SMC biophysical properties inducing hyperpolarization of RMP and cycles of slow hyperpolarization/depolarization oscillations. The effects of RLX on RMP were abolished by ODQ as well as by a specific inhibitor of the cGMP-dependent protein kinase, KT5823. RLX reduced Ca(2+) entry through the voltage-dependent L-type channels and modulated either voltage- or ATP-dependent K(+) channels. These effects were abolished by ODQ, suggesting the involvement of the nitric oxide/guanylate cyclase pathway in the effects of RLX on RMP and ion channel modulation. These actions of RLX on membrane properties may contribute to the regulation of the proximal colon motility by the nitric oxide/cGMP/cGMP-dependent protein kinase pathway.

  15. Ultrafine particles affect the balance of endogenous pro- and anti-inflammatory lipid mediators in the lung: in-vitro and in-vivo studies

    PubMed Central

    2012-01-01

    Background Exposure to ultrafine particles exerts diverse harmful effects including aggravation of pulmonary diseases like asthma. Recently we demonstrated in a mouse model for allergic airway inflammation that particle-derived oxidative stress plays a crucial role during augmentation of allergen-induced lung inflammation by ultrafine carbon particle (UfCP) inhalation. The mechanisms how particle inhalation might change the inflammatory balance in the lungs, leading to accelerated inflammatory reactions, remain unclear. Lipid mediators, known to be immediately generated in response to tissue injury, might be strong candidates for priming this particle-triggered change of the inflammatory balance. Methods We hypothesize that inhalation of UfCP may disturb the balance of pro- and anti-inflammatory lipid mediators in: i) a model for acute allergic pulmonary inflammation, exposing mice for 24 h before allergen challenge to UfCP inhalation (51.7 nm, 507 μg/m3), and ii) an in-vitro model with primary rat alveolar macrophages (AM) incubated with UfCP (10 μg/1 x 106 cells/ml) for 1 h. Lungs and AM were analysed for pro- and anti-inflammatory lipid mediators, namely leukotriene B4 (LTB4), prostaglandin E2 (PGE2), 15(S)-hydroxy-eicosatetraenoic acid (15(S)-HETE), lipoxin A4 (LXA4) and oxidative stress marker 8-isoprostane by enzyme immunoassays and immunohistochemistry. Results In non-sensitized mice UfCP exposure induced a light non-significant increase of all lipid mediators. Similarly but significantly in rat AM all lipid mediators were induced already within 1 h of UfCP stimulation. Also sensitized and challenge mice exposed to filtered air showed a partially significant increase in all lipid mediators. In sensitized and challenged mice UfCP exposure induced highest significant levels of all lipid mediators in the lungs together with the peak of allergic airway inflammation on day 7 after UfCP inhalation. The levels of LTB4, 8-isoprostane and PGE2 were significantly

  16. Humidity affects the morphology of particles emitted from beclomethasone dipropionate pressurized metered dose inhalers.

    PubMed

    Ivey, James W; Bhambri, Pallavi; Church, Tanya K; Lewis, David A; McDermott, Mark T; Elbayomy, Shereen; Finlay, Warren H; Vehring, Reinhard

    2017-03-30

    The effects of propellant type, cosolvent content, and air humidity on the morphology and solid phase of the particles produced from solution pressurized metered dose inhalers containing the corticosteroid beclomethasone dipropionate were investigated. The active ingredient was dissolved in the HFA propellants 134a and 227ea with varying levels of the cosolvent ethanol and filled into pressurized metered dose inhalers. Inhalers were actuated into an evaporation chamber under controlled temperature and humidity conditions and sampled using a single nozzle, single stage inertial impactor. Particle morphology was assessed qualitatively using field emission scanning electron microscopy and focused ion beam-helium ion microscopy. Drug solid phase was assessed using Raman microscopy. The relative humidity of the air during inhaler actuation was found to have a strong effect on the particle morphology, with solid spheroidal particles produced in dry air and highly porous particles produced at higher humidity levels. Air humidification was found to have no effect on the solid phase of the drug particles, which was predominantly amorphous for all tested formulations. A critical level of air relative humidity was required to generate porous particles for each tested formulation. This critical relative humidity was found to depend on the amount of ethanol used in the inhaler, but not on the type of propellant utilized. The results indicate that under the right circumstances water vapor saturation followed by nucleated water condensation or ice deposition occurs during particle formation from evaporating propellant-cosolvent-BDP droplets. This finding reveals the importance of condensed water or ice as a templating agent for porosity when particle formation occurs at saturated conditions, with possible implications on the pharmacokinetics of solution pMDIs and potential applications in particle engineering for drug delivery.

  17. Particle Acceleration Affected by the Evolving Velocity Structures in the Solar Wind

    NASA Astrophysics Data System (ADS)

    Tsubouchi, K.

    2015-12-01

    It is accepted that high-energy particles are efficiently generated during their crossing of shocks in space, where the diffusive shock acceleration is the most standard process to explain the observed energy spectrum beyond the order of a gigaelectronvolt. In contrast, recent spacecraft observations have shown different characteristics in a lower energy range (a kilo- to megaelectronvolt): particles in the heliosphere have a power-law spectrum in particle speed with a spectral index of -5, which is commonly found in any solar wind conditions. This is a puzzling result that the shocks are not a necessary element responsible for accelerating particles. The alternative mechanism, a pump acceleration, is proposed where particles are accelerated in a region containing large-scale compressions and expansions (e.g., Fisk and Gloeckler, JGR 2014). In the present study, we elucidate the validity of this mechanism by performing hybrid simulations to investigate the particle, particularly pickup ions, dynamics in various situations of non-uniform velocity field, such as a simple fast/slow flow interaction, sinusoidal structures, or random profiles, and to compare the velocity spectrum of suprathermal particles in each case. We also study the scale dependence of acceleration processes by comparing the spectrum of the energetic H+, He+, and O+.

  18. Factors affecting the association between ambient concentrations and personal exposures to particles and gases.

    PubMed

    Sarnat, Stefanie Ebelt; Coull, Brent A; Schwartz, Joel; Gold, Diane R; Suh, Helen H

    2006-05-01

    Results from air pollution exposure assessment studies suggest that ambient fine particles [particulate matter with aerodynamic diameterparticles, the strength of the personal-ambient association can differ by particle component and level of home ventilation. For gases, however, such as ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2), the impact of home ventilation on personal-ambient associations is untested. We measured 24-hr personal exposures and corresponding ambient concentrations to PM2.5, sulfate (SO2-(4)), elemental carbon, O3, NO2, and SO2 for 10 nonsmoking older adults in Steubenville, Ohio. We found strong associations between ambient particle concentrations and corresponding personal exposures. In contrast, although significant, most associations between ambient gases and their corresponding exposures had low slopes and R2 values; the personal-ambient NO2 association in the fall season was moderate. For both particles and gases, personal-ambient associations were highest for individuals spending most of their time in high- compared with low-ventilated environments. Cross-pollutant models indicated that ambient particle concentrations were much better surrogates for exposure to particles than to gases. With the exception of ambient NO2 in the fall, which showed moderate associations with personal exposures, ambient gases were poor proxies for both gas and particle exposures. In combination, our results suggest that a) ventilation may be an important modifier of the magnitude of effect in time-series health studies, and b) results from time-series health studies based on 24-hr ambient concentrations are more readily interpretable for particles than for gases.

  19. Factors Affecting the Association between Ambient Concentrations and Personal Exposures to Particles and Gases

    PubMed Central

    Sarnat, Stefanie Ebelt; Coull, Brent A.; Schwartz, Joel; Gold, Diane R.; Suh, Helen H.

    2006-01-01

    Results from air pollution exposure assessment studies suggest that ambient fine particles [particulate matter with aerodynamic diameter ≤ 2.5 μg (PM2.5)], but not ambient gases, are strong proxies of corresponding personal exposures. For particles, the strength of the personal–ambient association can differ by particle component and level of home ventilation. For gases, however, such as ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2), the impact of home ventilation on personal–ambient associations is untested. We measured 24-hr personal exposures and corresponding ambient concentrations to PM2.5, sulfate (SO42−), elemental carbon, O3, NO2, and SO2 for 10 nonsmoking older adults in Steubenville, Ohio. We found strong associations between ambient particle concentrations and corresponding personal exposures. In contrast, although significant, most associations between ambient gases and their corresponding exposures had low slopes and R2 values; the personal–ambient NO2 association in the fall season was moderate. For both particles and gases, personal–ambient associations were highest for individuals spending most of their time in high- compared with low-ventilated environments. Cross-pollutant models indicated that ambient particle concentrations were much better surrogates for exposure to particles than to gases. With the exception of ambient NO2 in the fall, which showed moderate associations with personal exposures, ambient gases were poor proxies for both gas and particle exposures. In combination, our results suggest that a) ventilation may be an important modifier of the magnitude of effect in time-series health studies, and b) results from time-series health studies based on 24-hr ambient concentrations are more readily interpretable for particles than for gases. PMID:16675415

  20. Mechanism of activation of the mouse c-mos oncogene by the LTR of an intracisternal A-particle gene.

    PubMed Central

    Horowitz, M; Luria, S; Rechavi, G; Givol, D

    1984-01-01

    In the mouse myeloma XRPC-24 the DNA of an intracisternal A-particle (IAP) is inserted within the coding region of c-mos. This insertion splits the c-mos into a 3' rc-mos and a 5' rc-mos separated by approximately 4.7 kb of IAP DNA. The insertion is in a head-to-head orientation and brings the 5' LTR of the IAP in juxtaposition to the 3' rc-mos such that the IAP and the 3' rc-mos are transcribed in opposite directions. The intact c-mos gene is usually dormant, whereas the 3' rc-mos is actively transcribed and is capable of transforming NIH3T3 cells. In an effort to understand the nature of this activation we mapped the 5' ends of the 3' rc-mos mRNA present in XPRC-24. We found two main mRNA start sites, one mapping to the junction of the 3' rc-mos and the 5' LTR, and the other located 10 nucleotides upstream to this junction, within the 5' LTR. This result indicates that the 3' rc-mos in XRPC-24 was activated by insertion of a promoter provided by the LTR of an IAP genome. Furthermore, the 5' LTR appears to possess promoter activities in two directions. This conclusion was confirmed by the fact that this 5' LTR, in both orientations, was able to activate the bacterial gene coding for chloramphenicol acetyltransferase (CAT) in the modular vector pSVOCAT. Images Fig. 2. Fig. 5. PMID:6098457

  1. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) deficiencies affect expression of lipolytic activities in mouse adipose tissues.

    PubMed

    Morak, Maria; Schmidinger, Hannes; Riesenhuber, Gernot; Rechberger, Gerald N; Kollroser, Manfred; Haemmerle, Guenter; Zechner, Rudolf; Kronenberg, Florian; Hermetter, Albin

    2012-12-01

    Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patterns of brown and white adipose tissue from ATGL (-/-) and HSL (-/-) mice using differential activity-based gel electrophoresis. This method is based on activity-recognition probes possessing the same substrate analogous structure but carrying different fluorophores for specific detection of the enzyme patterns of two different tissues in one electrophoresis gel. We found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose tissue. Enzyme activities of mouse tissues on acylglycerol substrates were analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for at least in part by other enzymes. The proteins that responded to ATGL-deficiency in brown adipose tissue were overexpressed and their activities on acylglycerols were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase candidates as they catalyze the hydrolysis of long-chain acylglycerols.

  2. Adipose Triglyceride Lipase (ATGL) and Hormone-Sensitive Lipase (HSL) Deficiencies Affect Expression of Lipolytic Activities in Mouse Adipose Tissues*

    PubMed Central

    Morak, Maria; Schmidinger, Hannes; Riesenhuber, Gernot; Rechberger, Gerald N.; Kollroser, Manfred; Haemmerle, Guenter; Zechner, Rudolf; Kronenberg, Florian; Hermetter, Albin

    2012-01-01

    Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patters of brown and white adipose tissue from ATGL (−/−) and HSL (−/−) mice using differential activity-based gel electrophoresis. This method is based on activity-recognition probes possessing the same substrate analogous structure but carrying different fluorophores for specific detection of the enzyme patterns of two different tissues in one electrophoresis gel. We found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose tissue. Enzyme activities of mouse tissues on acylglycerol substrates were analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for at least in part by other enzymes. The proteins that responded to ATGL-deficiency in brown adipose tissue were overexpressed and their activities on acylglycerols were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase candidates as they catalyze the hydrolysis of long-chain acylglycerols. PMID:22984285

  3. Severity of Demyelinating and Axonal Neuropathy Mouse Models Is Modified by Genes Affecting Structure and Function of Peripheral Nodes.

    PubMed

    Morelli, Kathryn H; Seburn, Kevin L; Schroeder, David G; Spaulding, Emily L; Dionne, Loiuse A; Cox, Gregory A; Burgess, Robert W

    2017-03-28

    Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of inherited polyneuropathies. Mutations in 80 genetic loci can cause forms of CMT, resulting in demyelination and axonal dysfunction. The clinical presentation, including sensory deficits, distal muscle weakness, and atrophy, can vary greatly in severity and progression. Here, we used mouse models of CMT to demonstrate genetic interactions that result in a more severe neuropathy phenotype. The cell adhesion molecule Nrcam and the Na(+) channel Scn8a (NaV1.6) are important components of nodes. Homozygous Nrcam and heterozygous Scn8a mutations synergized with both an Sh3tc2 mutation, modeling recessive demyelinating Charcot-Marie-Tooth type 4C, and mutations in Gars, modeling dominant axonal Charcot-Marie-Tooth type 2D. We conclude that genetic variants perturbing the structure and function of nodes interact with mutations affecting the cable properties of axons by thinning myelin or reducing axon diameter. Therefore, genes integral to peripheral nodes are candidate modifiers of peripheral neuropathy.

  4. A conserved sequence in the mouse variable T cell receptor alpha recombination signal sequence 23-bp spacer can affect recombination.

    PubMed

    Probst, Jochen; Blumenthal, Sibylle G; Tenzer, Stefan; Weinschenk, Toni; Dittmer, Jürgen; Schoor, Oliver; Six, Adrien; Rammensee, Hans-Georg; Pascolo, Steve

    2004-08-01

    Although the V-gene segments coding for the TCR alpha and delta chains are mixed together in the alpha delta locus and are recombined by the same processes, some gene segments (TRAV) are rearranged only with TCR Jalpha gene segments, some (TRDV) only with TCR Ddelta gene segments and some (TRADV) with both. To date, no molecular signal is known that can characterize these three different types of gene segments. Studying the recombination signal sequences (RSS) of all mouse TCR V-gene segments we observed that 80% of the TRAV contain a palindrome sequence (CTGCAG) or its related variant CTGTAG in their 23-bp spacer. Using gel-shift assays we show that these sequences are specifically recognized by some nuclear proteins that are expressed by fresh thymocytes, fresh lymphocytes and tumor cells. Recombination assays on plasmid substrates in a pre-B cell line showed that RSS containing the CTGCAG sequence can impair recombination. From the protein fractions containing the CTGCAG-binding activity, three proteins were identified: G3BP1 (a nucleic-acid-binding protein with a proposed helicase activity) and two proteins from the high-mobility group (HMG) family--HMGB2 and HMGB3. We hypothesize that these proteins can affect recombination at the TCR alpha delta locus.

  5. Final Report: "Collaborative Project. Understanding the Chemical Processes That Affect Growth Rates of Freshly Nucleated Particles"

    SciTech Connect

    Smith, James N.; McMurry, Peter H.

    2015-11-12

    This final technical report describes our research activities that have, as the ultimate goal, the development of a model that explains growth rates of freshly nucleated particles. The research activities, which combine field observations with laboratory experiments, explore the relationship between concentrations of gas-phase species that contribute to growth and the rates at which those species are taken up. We also describe measurements of the chemical composition of freshly nucleated particles in a variety of locales, as well as properties (especially hygroscopicity) that influence their effects on climate. Our measurements include a self-organized, DOE-ARM funded project at the Southern Great Plains site, the New Particle Formation Study (NPFS), which took place during spring 2013. NPFS data are available to the research community on the ARM data archive, providing a unique suite observations of trace gas and aerosols that are associated with the formation and growth of atmospheric aerosol particles.

  6. Colon cancer metastasis in mouse liver is not affected by hypercoagulability due to Factor V Leiden mutation

    PubMed Central

    Klerk, CPW; Smorenburg, SM; Spek, CA; Van Noorden, CJF

    2007-01-01

    Abstract Clinical trials have shown life-prolonging effects of antithrombotics in cancer patients, but the molecular mechanisms remain unknown due to the multitude of their effects. We investigated in a mouse model whether one of the targets of antithrombotic therapy, fibrin deposition, stimulates tumour development. Fibrin may provide either protection of cancer cells in the circulation against mechanical stress and the immune system, or form a matrix for tumours and/or angiogenesis in tumours to develop. Mice homozygous for Factor V Leiden (FVL), a mutation in one of the coagulation factors that facilitates fibrin formation, were used to investigate whether hypercoagulability affects tumour development in an experimental metastasis model. Liver metastases of colon cancer were induced in mice with the FVL mutation and wild-type littermates. At day 21, number and size of tumours at the liver surface, fibrin/fibrinogen distribution, vessel density and the presence of newly formed vessels in tumours were analysed. Number and size of tumours did not differ between mice with and without the FVL mutation. Fibrin/fibrinogen was found in the cytoplasm of hepatocytes and cancer cells, in blood vessels in liver and tumour tissue and diffusely distributed outside vessels in tumours, indicating leaky vessels. Vessel density and angiogenesis varied widely between tumours, but a pre-dominance for vessel-rich or vessel-poor tumours or vessel formation could not be found in either genotype. In conclusion, the FVL mutation has no effect on the development of secondary tumours of colon cancer in livers of mice. Fibrin deposition and thus inhibition of fibrin formation by anticoagulants do not seem to affect tumour development in this model. PMID:17635646

  7. Inhibition of Protease-Activated Receptor 1 Does not Affect Dendritic Homeostasis of Cultured Mouse Dentate Granule Cells

    PubMed Central

    Schuldt, Gerlind; Galanis, Christos; Strehl, Andreas; Hick, Meike; Schiener, Sabine; Lenz, Maximilian; Deller, Thomas; Maggio, Nicola; Vlachos, Andreas

    2016-01-01

    Protease-activated receptors (PARs) are widely expressed in the central nervous system (CNS). While a firm link between PAR1-activation and functional synaptic and intrinsic neuronal properties exists, studies on the role of PAR1 in neural structural plasticity are scarce. The physiological function of PAR1 in the brain remains not well understood. We here sought to determine whether prolonged pharmacologic PAR1-inhibition affects dendritic morphologies of hippocampal neurons. To address this question we employed live-cell microscopy of mouse dentate granule cell dendrites in 3-week old entorhino-hippocampal slice cultures prepared from Thy1-GFP mice. A subset of cultures were treated with the PAR1-inhibitor SCH79797 (1 μM; up to 3 weeks). No major effects of PAR1-inhibition on static and dynamic parameters of dentate granule cell dendrites were detected under control conditions. Granule cells of PAR1-deficient slice cultures showed unaltered dendritic morphologies, dendritic spine densities and excitatory synaptic strength. Furthermore, we report that PAR1-inhibition does not prevent dendritic retraction following partial deafferentation in vitro. Consistent with this finding, no major changes in PAR1-mRNA levels were detected in the denervated dentate gyrus (DG). We conclude that neural PAR1 is not involved in regulating the steady-state dynamics or deafferentation-induced adaptive changes of cultured dentate granule cell dendrites. These results indicate that drugs targeting neural PAR1-signals may not affect the stability and structural integrity of neuronal networks in healthy brain regions. PMID:27378862

  8. Biopsy of embryos produced by in vitro fertilization affects development in C57BL/6 mouse strain

    PubMed Central

    Sugawara, Atsushi; Ward, Monika A.

    2012-01-01

    Preimplantation genetic diagnosis (PGD) is considered highly successful in respect to its accuracy in detecting genetic anomalies but the effects of embryo biopsy on embryonic/fetal growth and development are less known, particularly in conjunction with in vitro fertilization (IVF). Here, we compared biopsied (B) and non-biopsied (NB) mouse embryos for their developmental competence. Embryos C57BL/6 (B6) and B6D2F2 (F2) generated by IVF were subjected to single blastomere biopsy at the 4-cell stage, and were either cultured for 120 h and subjected to differential inner cell mass (ICM) and trophoblast (T) staining, or were transferred into the uterine tubes of surrogate mothers after 72 h of culture, to examine their pre- and post-implantation development, respectively. Non-biopsied embryos from the same IVF cohorts served as controls. Embryo biopsy negatively affected preimplantation development to blastocyst in C57BL/6 (69 vs 79%, P<0.01) but not in B6D2F1 mice (89 vs 91%, P=NS). Although B6 embryos had lower total cell number than F2 (B6: 47 and 61 vs. F1: 53 and 70; B and NB, respectively, P<0.05) there were no differences between B and NB blastocysts in %ICM (B6: 19.8 vs 19.8; F2: 20.9 vs 20.4, P=NS) and ICM:T ratio (B6: 4.7 vs 4.7; F2: 4.4 vs. 4.7) in both mouse strains. Post-implantation development to live fetuses of B embryos as compared to NB counterparts was impaired in C57BL/6 (6 vs 18%, P<0.001) but not in B6D2F1 mice (26 vs 35%, P=NS). We conclude that blastomere biopsy impairs embryonic/fetal development in mice known to be sensitive to in vitro culture and manipulations. Such mice model infertile couples with poor quality gametes seeking help in assisted reproduction technologies (ART) clinics. PMID:23174776

  9. Stanniocalcin-1 Protects a Mouse Model from Renal Ischemia-Reperfusion Injury by Affecting ROS-Mediated Multiple Signaling Pathways

    PubMed Central

    Liu, Dajun; Shang, Huiping; Liu, Ying

    2016-01-01

    Stanniocalcin-1 (STC-1) protects against renal ischemia-reperfusion injury (RIRI). However, the molecular mechanisms remain widely unknown. STC-1 inhibits reactive oxygen species (ROS), whereas most ROS-mediated pathways are associated with ischemic injury. Therefore, to explore the mechanism, the effects of STC-1 on ROS-medicated pathways were studied. Non-traumatic vascular clamps were used to establish RIRI mouse models. The serum levels of STC-1, interleukin-6 (IL-6), interferon (IFN) γ, P53, and capase-3 were measured by ELISA kits. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by fluorescence spectrofluorometer. All these molecules changed significantly in a RIRI model mouse when compared with those in a sham control. Kidney cells were isolated from sham and model mice. STC-1 was overexpressed or knockout in these kidney cells. The molecules in ROS-medicated pathways were measured by real-time quantitative PCR and Western blot. The results showed that STC-1 is an effective ROS scavenger. The serum levels of STC-1, MDA and SOD activity were increased while the serum levels of IL-6, iIFN-γ, P53, and capase-3 were decreased in a model group when compared with a sham control (p < 0.05). Furthermore, the levels of STC-1,p53, phosphorylated mitogen-activated protein kinase kinase (p-MEKK-1), c-Jun N-terminal kinase (p-JNK), extracellular signal-regulated kinase (p-ERK), IkB kinase (p-IKK), nuclear factor (NF) κB, apoptosis signal-regulating kinase 1 (ASK-1) and caspase-3 changed significantly in kidney cells isolated from a RIRI model when compared to those isolated from a sham control (p < 0.05). Meanwhile, STC-1 overexpression or silence caused significant changes of the levels of these ROS-mediated molecules. Therefore, STC-1 maybe improve anti-inflammation, anti-oxidant and anti-apoptosis activities by affecting ROS-mediated pathways, especially the phospho-modifications of the respective proteins, resulting in the increase of SOD and

  10. Durum wheat particle size affects starch and protein digestion in vitro.

    PubMed

    Mandalari, Giuseppina; Merali, Zara; Ryden, Peter; Chessa, Simona; Bisignano, Carlo; Barreca, Davide; Bellocco, Ersilia; Laganà, Giuseppina; Faulks, Richard M; Waldron, Keith W

    2016-10-26

    The term bioaccessibility refers to the proportion of a nutrient released from a complex food matrix during digestion and, therefore, becoming potentially available for absorption in the gastrointestinal tract. In the present study, we assessed the starch and protein bioaccessibility from a range of wheat endosperm products differing in particle size. Five porridge meals (size A, flour, mean particle size 0.11 mm, size B, small, mean particle size 0.38 mm, size C, semolina, mean particle size 1.01 mm, size D, medium, mean particle size 1.44 mm, size E, large, mean particle size 1.95 mm) with theoretically different postprandial glycaemic responses were subjected to oral processing in vitro, followed by simulated gastric and duodenal digestion. A significant increase (P < 0.001) in starch degradation was observed in size A (52%) compared with size E (25%). Both sizes C and D gave less, although not significantly, digestible starch (32 and 28%, respectively). The glucose release significantly decreased as the particle size of the meal increased (92.16% detected for size A vs 47.39% for size E). In agreement with starch degradation and glucose release, size A gave the most digestible protein. This data provide further evidence that, by decreasing the size of wheat endosperm, starch release and glycaemic response are enhanced. We also showed that protein bioaccessibility followed a similar trend as for starch digestion. Finally, these results support the hypothesis that different degrees of starch encapsulation elicit different blood glucose responses.

  11. Detailed predictions of particle aspiration affected by respiratory inhalation and airflow

    NASA Astrophysics Data System (ADS)

    Inthavong, Kiao; Ge, Qin Jiang; Li, Xiang Dong; Tu, Ji Yuan

    2012-12-01

    The effects of air pollution found in the atmosphere and exposure to airborne particles are an important problem in the interest of public health. Exposure to contaminated air under different flow conditions is studied using the latest computational fluid dynamics models. For the first time the upper respiratory airway is integrated into a human body and placed inside a room, facing different airflow speeds (0.05-0.35 m s-1). It was found that the airflow streamlines diverged as it approached the human body, at the torso and accelerated upwards past the face and head before separating at the rear of the head, forming recirculating regions in the wake behind the body. Inhaled particles were tracked backwards to determine its origins. At a plane upstream from the face the locations of particles inhaled form a region known as the critical area, which is presented. This study establishes a better understanding of particle inhalability and provides a step towards a more holistic approach in determining inhalation toxicology effects of exposure to atmospheric particles.

  12. Collaborative Project: Understanding the Chemical Processes tat Affect Growth rates of Freshly Nucleated Particles

    SciTech Connect

    McMurry, Peter; Smuth, James

    2015-11-12

    This final technical report describes our research activities that have, as the ultimate goal, the development of a model that explains growth rates of freshly nucleated particles. The research activities, which combine field observations with laboratory experiments, explore the relationship between concentrations of gas-phase species that contribute to growth and the rates at which those species are taken up. We also describe measurements of the chemical composition of freshly nucleated particles in a variety of locales, as well as properties (especially hygroscopicity) that influence their effects on climate.

  13. A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells.

    PubMed Central

    Partanen, Sanna; Storch, Stephan; Löffler, Hans-Gerhard; Hasilik, Andrej; Tyynelä, Jaana; Braulke, Thomas

    2003-01-01

    The substitution of an active-site aspartic acid residue by asparagine in the lysosomal protease cathepsin D (CTSD) results in a loss of enzyme activity and severe cerebrocortical atrophy in a novel form of neuronal ceroid lipofuscinosis in sheep [Tyynelä, Sohar, Sleat, Gin, Donnelly, Baumann, Haltia and Lobel (2000) EMBO J. 19, 2786-2792]. In the present study we have introduced the corresponding mutation by replacing aspartic acid residue 293 with asparagine (D293N) into the mouse CTSD cDNA to analyse its effect on synthesis, transport and stability in transfected HEK-293 cells. The complete inactivation of mutant D293N mouse CTSD was confirmed by a newly developed fluorimetric quantification system. Moreover, in the heterologous overexpression systems used, mutant D293N mouse CTSD was apparently unstable and proteolytically modified during early steps of the secretory pathway, resulting in a loss of mass by about 1 kDa. In the affected sheep, the endogenous mutant enzyme was stable but also showed the shift in its molecular mass. In HEK-293 cells, the transport of the mutant D293N mouse CTSD to the lysosome was delayed and associated with a low secretion rate compared with wild-type CTSD. These data suggest that the mutation may result in a conformational change which affects stability, processing and transport of the enzyme. PMID:12350228

  14. Age-related BMAL1 change affects mouse bone marrow stromal cell proliferation and osteo-differentiation potential

    PubMed Central

    Chen, Yijia; Xu, Xiaomei; Tan, Zhen; Ye, Cui; Chen, Yangxi

    2012-01-01

    Introduction Aging people's bone regeneration potential is always impaired. Bone marrow stromal cells (MSCs) contain progenitors of osteoblasts. Donor age may affect MSCs’ proliferation and differentiation potential, but the genomic base is still unknown. Due to recent research's indication that a core circadian component, brain and muscle ARNT-like 1 protein (BMAL1), has a role in premature aging, we investigated the normal aging mechanism in mice with their MSCs and Bmal1 gene/protein level. Material and methods 1, 6 and 16 month old C57BL/6 mice were used and the bone marrow stromal cells were gained and cultured at early passage. Bmal1 gene and protein level were detected in these cells. Marrow stromal cells were also induced to differentiate to osteoblasts or adipocytes. Three groups of mice MSCs were compared on proliferation by flow cytometry, on cell senescence by SA-β-gal expression and after osteo-induction on osteogenic potential by the expression of osterix (Osx), alkaline phosphatase (ALP) and osteocalcin (OCN). Results Bmal1 gene and protein level as well as S-phase fraction of the cell cycle decreased in MSCs along with the aging process. At the same time, SA-β-gal+ levels increased, especially in the aged mice MSCs. When induced to be osteogenic, Osx gene expression and ALP activity declined in the mid-age and aged mice MSCs, while OCN protein secretion deteriorated in the aged mice MSCs. Conclusions These findings demonstrate that mouse MSCs changed with their proliferation and osteo-differentiation abilities at different aging stages, and that Bmal1 is related to the normal aging process in MSCs. PMID:22457671

  15. Primary particle size distribution of eroded material affected by degree of aggregate slaking and seal development

    USDA-ARS?s Scientific Manuscript database

    Primary particle size distribution (PSD) of eroded sediments can be used to estimate potential nutrient losses from soil and pollution hazards to the environment. We studied eroded sediment PSDs from three saturated soils, packed in trays (20 x 40 x 4 cm), that had undergone either minimal aggregate...

  16. Black Carbon Absorption at the Global Scale Is Affected by Particle-Scale Diversity in Composition

    NASA Technical Reports Server (NTRS)

    Fierce, Laura; Bond, Tami C.; Bauer, Susanne E.; Mena, Francisco; Riemer, Nicole

    2016-01-01

    Atmospheric black carbon (BC) exerts a strong, but uncertain, warming effect on the climate. BC that is coated with non-absorbing material absorbs more strongly than the same amount of BC in an uncoated particle, but the magnitude of this absorption enhancement (E(sub abs)) is not well constrained. Modelling studies and laboratory measurements have found stronger absorption enhancement than has been observed in the atmosphere. Here, using a particle-resolved aerosol model to simulate diverse BC populations, we show that absorption is overestimated by as much as a factor of two if diversity is neglected and population-averaged composition is assumed across all BC-containing particles. If, instead, composition diversity is resolved, we find E(sub abs) = 1 - 1.5 at low relative humidity, consistent with ambient observations. This study offers not only an explanation for the discrepancy between modelled and observed absorption enhancement, but also demonstrates how particle-scale simulations can be used to develop relationships for global-scale models.

  17. Black Carbon Absorption at the Global Scale Is Affected by Particle-Scale Diversity in Composition

    NASA Technical Reports Server (NTRS)

    Fierce, Laura; Bond, Tami C.; Bauer, Susanne E.; Mena, Francisco; Riemer, Nicole

    2016-01-01

    Atmospheric black carbon (BC) exerts a strong, but uncertain, warming effect on the climate. BC that is coated with non-absorbing material absorbs more strongly than the same amount of BC in an uncoated particle, but the magnitude of this absorption enhancement (E(sub abs)) is not well constrained. Modelling studies and laboratory measurements have found stronger absorption enhancement than has been observed in the atmosphere. Here, using a particle-resolved aerosol model to simulate diverse BC populations, we show that absorption is overestimated by as much as a factor of two if diversity is neglected and population-averaged composition is assumed across all BC-containing particles. If, instead, composition diversity is resolved, we find E(sub abs) = 1 - 1.5 at low relative humidity, consistent with ambient observations. This study offers not only an explanation for the discrepancy between modelled and observed absorption enhancement, but also demonstrates how particle-scale simulations can be used to develop relationships for global-scale models.

  18. High hydrostatic pressure specifically affects molecular dynamics and shape of low-density lipoprotein particles

    PubMed Central

    Golub, M.; Lehofer, B.; Martinez, N.; Ollivier, J.; Kohlbrecher, J.; Prassl, R.; Peters, J.

    2017-01-01

    Lipid composition of human low-density lipoprotein (LDL) and its physicochemical characteristics are relevant for proper functioning of lipid transport in the blood circulation. To explore dynamical and structural features of LDL particles with either a normal or a triglyceride-rich lipid composition we combined coherent and incoherent neutron scattering methods. The investigations were carried out under high hydrostatic pressure (HHP), which is a versatile tool to study the physicochemical behavior of biomolecules in solution at a molecular level. Within both neutron techniques we applied HHP to probe the shape and degree of freedom of the possible motions (within the time windows of 15 and 100 ps) and consequently the flexibility of LDL particles. We found that HHP does not change the types of motion in LDL, but influences the portion of motions participating. Contrary to our assumption that lipoprotein particles, like membranes, are highly sensitive to pressure we determined that LDL copes surprisingly well with high pressure conditions, although the lipid composition, particularly the triglyceride content of the particles, impacts the molecular dynamics and shape arrangement of LDL under pressure. PMID:28382948

  19. Black carbon absorption at the global scale is affected by particle-scale diversity in composition

    PubMed Central

    Fierce, Laura; Bond, Tami C.; Bauer, Susanne E.; Mena, Francisco; Riemer, Nicole

    2016-01-01

    Atmospheric black carbon (BC) exerts a strong, but uncertain, warming effect on the climate. BC that is coated with non-absorbing material absorbs more strongly than the same amount of BC in an uncoated particle, but the magnitude of this absorption enhancement (Eabs) is not well constrained. Modelling studies and laboratory measurements have found stronger absorption enhancement than has been observed in the atmosphere. Here, using a particle-resolved aerosol model to simulate diverse BC populations, we show that absorption is overestimated by as much as a factor of two if diversity is neglected and population-averaged composition is assumed across all BC-containing particles. If, instead, composition diversity is resolved, we find Eabs=1−1.5 at low relative humidity, consistent with ambient observations. This study offers not only an explanation for the discrepancy between modelled and observed absorption enhancement, but also demonstrates how particle-scale simulations can be used to develop relationships for global-scale models. PMID:27580627

  20. Navy bean flour particle size and protein content affect cake baking and batter quality

    USDA-ARS?s Scientific Manuscript database

    Whole navy bean flour and its fine and coarse particle size fractions were used to completely replace wheat flour in cakes. Replacement of wheat flour with whole bean flour significantly increased the protein content. The protein content was adjusted to three levels with navy bean starch. The effect...

  1. CULTURE CONDITIONS AFFECT HUMAN AIRWAY EPITHELIAL CELL RESPONSE TO DIESEL PARTICLE EXPOSURE IN VITRO

    EPA Science Inventory

    Diesel exhaust particles (DEP) are a ubiquitous ambient air contaminant that may contribute to the health effects of particulate matter inhalation. In vitro studies have shown that DEP exposure induces pro-inflammatory proteins in human airway epithelial cells (HAEC) with varying...

  2. High hydrostatic pressure specifically affects molecular dynamics and shape of low-density lipoprotein particles

    NASA Astrophysics Data System (ADS)

    Golub, M.; Lehofer, B.; Martinez, N.; Ollivier, J.; Kohlbrecher, J.; Prassl, R.; Peters, J.

    2017-04-01

    Lipid composition of human low-density lipoprotein (LDL) and its physicochemical characteristics are relevant for proper functioning of lipid transport in the blood circulation. To explore dynamical and structural features of LDL particles with either a normal or a triglyceride-rich lipid composition we combined coherent and incoherent neutron scattering methods. The investigations were carried out under high hydrostatic pressure (HHP), which is a versatile tool to study the physicochemical behavior of biomolecules in solution at a molecular level. Within both neutron techniques we applied HHP to probe the shape and degree of freedom of the possible motions (within the time windows of 15 and 100 ps) and consequently the flexibility of LDL particles. We found that HHP does not change the types of motion in LDL, but influences the portion of motions participating. Contrary to our assumption that lipoprotein particles, like membranes, are highly sensitive to pressure we determined that LDL copes surprisingly well with high pressure conditions, although the lipid composition, particularly the triglyceride content of the particles, impacts the molecular dynamics and shape arrangement of LDL under pressure.

  3. CULTURE CONDITIONS AFFECT HUMAN AIRWAY EPITHELIAL CELL RESPONSE TO DIESEL PARTICLE EXPOSURE IN VITRO

    EPA Science Inventory

    Diesel exhaust particles (DEP) are a ubiquitous ambient air contaminant that may contribute to the health effects of particulate matter inhalation. In vitro studies have shown that DEP exposure induces pro-inflammatory proteins in human airway epithelial cells (HAEC) with varying...

  4. High hydrostatic pressure specifically affects molecular dynamics and shape of low-density lipoprotein particles.

    PubMed

    Golub, M; Lehofer, B; Martinez, N; Ollivier, J; Kohlbrecher, J; Prassl, R; Peters, J

    2017-04-06

    Lipid composition of human low-density lipoprotein (LDL) and its physicochemical characteristics are relevant for proper functioning of lipid transport in the blood circulation. To explore dynamical and structural features of LDL particles with either a normal or a triglyceride-rich lipid composition we combined coherent and incoherent neutron scattering methods. The investigations were carried out under high hydrostatic pressure (HHP), which is a versatile tool to study the physicochemical behavior of biomolecules in solution at a molecular level. Within both neutron techniques we applied HHP to probe the shape and degree of freedom of the possible motions (within the time windows of 15 and 100 ps) and consequently the flexibility of LDL particles. We found that HHP does not change the types of motion in LDL, but influences the portion of motions participating. Contrary to our assumption that lipoprotein particles, like membranes, are highly sensitive to pressure we determined that LDL copes surprisingly well with high pressure conditions, although the lipid composition, particularly the triglyceride content of the particles, impacts the molecular dynamics and shape arrangement of LDL under pressure.

  5. Black carbon absorption at the global scale is affected by particle-scale diversity in composition

    NASA Astrophysics Data System (ADS)

    Fierce, Laura; Bond, Tami C.; Bauer, Susanne E.; Mena, Francisco; Riemer, Nicole

    2016-09-01

    Atmospheric black carbon (BC) exerts a strong, but uncertain, warming effect on the climate. BC that is coated with non-absorbing material absorbs more strongly than the same amount of BC in an uncoated particle, but the magnitude of this absorption enhancement (Eabs) is not well constrained. Modelling studies and laboratory measurements have found stronger absorption enhancement than has been observed in the atmosphere. Here, using a particle-resolved aerosol model to simulate diverse BC populations, we show that absorption is overestimated by as much as a factor of two if diversity is neglected and population-averaged composition is assumed across all BC-containing particles. If, instead, composition diversity is resolved, we find Eabs=1-1.5 at low relative humidity, consistent with ambient observations. This study offers not only an explanation for the discrepancy between modelled and observed absorption enhancement, but also demonstrates how particle-scale simulations can be used to develop relationships for global-scale models.

  6. Isolation and characterization of mouse-human microcell hybrid cell clones permissive for infectious HIV particle release

    PubMed Central

    Coskun, Ayse K.; van Maanen, Marc; Janka, David; Stockton, David; Stankiewicz, Pawel; Yatsenko, Svetlana; Sutton, Richard E.

    2007-01-01

    Mouse cells are non-permissive to human immunodeficiency virus type 1 (HIV) in that there is a pronounced post-integration block to viral replication. We have recently demonstrated that mouse-human somatic cell hybrids that contain human chromosome 2 increase both HIV Capsid (CA) production and infectious virus release. Here we report on the isolation of three mouse-human microcell hybrids (MCHs) that behave similarly, starting from a pool of 500 MCH clones. Release of virus was specific to HIV and cell revertants that no longer contained any human chromosome fragments did not release CA or infectious virus. Two of the three cell clones were identical as judged by PCR STS content and fluorescence in situ hybridization (FISH) and contained a single 2-12 human chromosome chimera. The third cell clone only contained human chromosome 12, as determined by PCR, FISH, and microarray analyses. There were no consistent differences in Gag protein and spliced/unspliced viral RNA levels between mouse cell lines. CMV promoter-driven, codon-optimized gag-pol had no effect on infectious HIV release from these mouse cells, despite allowing Gag targeting and increasing CA production. These permissive mouse-human MCHs and their corresponding non-permissive revertants may prove useful for mechanistic studies and also for identifying the responsible gene(s) or factor(s) involved in the production of HIV. PMID:17270231

  7. Human Metapneumovirus Virus-Like Particles Induce Protective B and T Cell Responses in a Mouse Model

    PubMed Central

    Cox, Reagan G.; Erickson, John J.; Hastings, Andrew K.; Becker, Jennifer C.; Johnson, Monika; Craven, Ryan E.; Tollefson, Sharon J.; Boyd, Kelli L.

    2014-01-01

    ABSTRACT Human metapneumovirus (HMPV) is a leading cause of respiratory disease in infants, children, and the elderly worldwide, yet no licensed vaccines exist. Live-attenuated vaccines present safety challenges, and protein subunit vaccines induce primarily antibody responses. Virus-like particles (VLPs) are an attractive alternative vaccine approach because of reduced safety concerns compared with live vaccines. We generated HMPV VLPs by expressing viral proteins in suspension-adapted human embryonic kidney epithelial (293-F) cells and found that the viral matrix (M) and fusion (F) proteins were sufficient to form VLPs. We previously reported that the VLPs resemble virus morphology and incorporate fusion-competent F protein (R. G. Cox, S. B. Livesay, M. Johnson, M. D. Ohi, and J. V. Williams, J. Virol. 86:12148–12160, 2012), which we hypothesized would elicit F-specific antibody and T cell responses. In this study, we tested whether VLP immunization could induce protective immunity to HMPV by using a mouse model. C57BL/6 mice were injected twice intraperitoneally with VLPs alone or with adjuvant and subsequently challenged with HMPV. Mice were euthanized 5 days postinfection, and virus titers, levels of neutralizing antibodies, and numbers of CD3+ T cells were quantified. Mice immunized with VLPs mounted an F-specific antibody response and generated CD8+ T cells recognizing an F protein-derived epitope. VLP immunization induced a neutralizing-antibody response that was enhanced by the addition of either TiterMax Gold or α-galactosylceramide adjuvant, though adjuvant reduced cellular immune responses. Two doses of VLPs conferred complete protection from HMPV replication in the lungs of mice and were not associated with a Th2-skewed cytokine response. These results suggest that nonreplicating VLPs are a promising vaccine candidate for HMPV. IMPORTANCE Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection in infants, children, and the

  8. Coarsening Behavior of the (Ti, Nb)(C, N) Complex Particle in a Microalloyed Steel Weld Heat-Affected Zone Considering the Critical Particle Size

    NASA Astrophysics Data System (ADS)

    Moon, Joonoh; Kim, Sanghoon; Lee, Jongbong; Lee, Changhee

    2007-11-01

    Our recent report revealed the effect of critical particle size on the particle coarsening behavior of the TiN particle. In the present work, the equation for critical particle size is extended by considering the change of particle volume fraction during the continuous thermal cycle. By considering the concept of modified critical particle size, coarsening of the (Ti, Nb)(C, N) complex particle is calculated, and the calculated results are in good agreement with experimental data.

  9. Fabrication of vitamin E-enriched nanoemulsions: factors affecting particle size using spontaneous emulsification.

    PubMed

    Saberi, Amir Hossein; Fang, Yuan; McClements, David Julian

    2013-02-01

    Oil-in-water nanoemulsions are finding increasing use as delivery systems to encapsulate lipophilic bioactive components in functional food, personal care, and pharmaceutical products. We have investigated the influence of system composition and preparation conditions on the particle size of vitamin E acetate (VE)-loaded nanoemulsions prepared by spontaneous emulsification. This method relies on the formation of very fine oil droplets when an oil/surfactant mixture is added to water. The oil-to-emulsion ratio content was kept constant (10 wt.%) while the surfactant-to-emulsion ratio (%SER) was varied (from 2.5 to 10 wt.%). Oil phase composition (vitamin E to medium chain triglyceride ratio) had a major effect on particle size, with the smallest droplets being formed at 8 wt.% VE and 2 wt.% MCT. Surfactant type also had an appreciable impact on particle size, with TWEEN® 80 giving the smallest droplets from a group of food-grade non-ionic surfactants (TWEEN® 20, 40, 60, 80, and 85). Surfactant-to-emulsion ratio also had to be optimized to produce fine droplets, with the smallest droplets being formed at SER=10 wt.%. Particle size could also be reduced by increasing the temperature and stirring speed used when the oil/surfactant mixture was added to water. By optimizing system composition and homogenization conditions we were able to form VE-loaded nanoemulsions with small mean droplet diameters (d<50 nm) and low polydispersity indexes (PDI<0.13). The spontaneous emulsification method therefore has great potential for forming nanoemulsion-based delivery systems for food, personal care, and pharmaceutical applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Empirical search for factors affecting mean particle size of PLGA microspheres containing macromolecular drugs.

    PubMed

    Szlęk, Jakub; Pacławski, Adam; Lau, Raymond; Jachowicz, Renata; Kazemi, Pezhman; Mendyk, Aleksander

    2016-10-01

    Poly(lactic-co-glycolic acid) (PLGA) has become one of the most promising in design, development, and optimization for medical applications polymers. PLGA-based multiparticulate dosage forms are usually prepared as microspheres where the size is from 5 to 100 µm, depending on the route of administration. The main objectives of the study were to develop a predictive model of mean volumetric particle size and on its basis extract knowledge of PLGA containing proteins forming behaviour. In the present study, a model for the prediction of mean volumetric particle size developed by an rgp package of R environment is presented. Other tools like fscaret, monmlp, fugeR, MARS, SVM, kNNreg, Cubist, randomForest and piecewise linear regression are also applied during the data mining procedure. The feature selection provided by the fscaret package reduced the original input vector from a total of 295 input variables to 10, 16 and 19. The developed models had good predictive ability, which was confirmed by a normalized root-mean-square error (NRMSE) of 6.8 to 11.1% in 10-fold cross validation training procedure. Moreover, the best models were validated using external experimental data. The superior predictiveness had a model obtained by rgp in the form of a classical equation with a normalized root-mean-squared error (NRMSE) of 6.1%. A new approach is proposed for computational modelling of the mean particle size of PLGA microspheres and rules extraction from tree-based models. The feature selection leads to revealing chemical descriptor variables which are important in predicting the size of PLGA microspheres. In order to achieve better understanding in the relationships between particle size and formulation characteristics, the surface analysis method and rules extraction procedures were applied. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Morbillivirus and henipavirus attachment protein cytoplasmic domains differently affect protein expression, fusion support and particle assembly.

    PubMed

    Sawatsky, Bevan; Bente, Dennis A; Czub, Markus; von Messling, Veronika

    2016-05-01

    The amino-terminal cytoplasmic domains of paramyxovirus attachment glycoproteins include trafficking signals that influence protein processing and cell surface expression. To characterize the role of the cytoplasmic domain in protein expression, fusion support and particle assembly in more detail, we constructed chimeric Nipah virus (NiV) glycoprotein (G) and canine distemper virus (CDV) haemagglutinin (H) proteins carrying the respective heterologous cytoplasmic domain, as well as a series of mutants with progressive deletions in this domain. CDV H retained fusion function and was normally expressed on the cell surface with a heterologous cytoplasmic domain, while the expression and fusion support of NiV G was dramatically decreased when its cytoplasmic domain was replaced with that of CDV H. The cell surface expression and fusion support functions of CDV H were relatively insensitive to cytoplasmic domain deletions, while short deletions in the corresponding region of NiV G dramatically decreased both. In addition, the first 10 residues of the CDV H cytoplasmic domain strongly influence its incorporation into virus-like particles formed by the CDV matrix (M) protein, while the co-expression of NiV M with NiV G had no significant effect on incorporation of G into particles. The cytoplasmic domains of both the CDV H and NiV G proteins thus contribute differently to the virus life cycle.

  12. Particle length of silages affects apparent ruminal synthesis of B vitamins in lactating dairy cows.

    PubMed

    Castagnino, D S; Kammes, K L; Allen, M S; Gervais, R; Chouinard, P Y; Girard, C L

    2016-08-01

    Effects of particle length of silages on apparent ruminal synthesis (ARS) and postruminal supply of B vitamins were evaluated in 2 feeding trials. Diets containing alfalfa (trial 1) or orchardgrass (trial 2) silages, chopped to either 19mm (long cut, LC) or 10mm (short cut, SC) theoretical particle length, as the sole forage were offered to ruminally and duodenally cannulated lactating Holstein cows in crossover design experiments. Forages chopped to a theoretical particle length of 19 and 10mm had mean particles sizes of 14.1 and 8.1mm, respectively, in trial 1, and 15.3 and 11.3mm, respectively, in trial 2. Trial 1 was conducted with 13 multiparous cows in two 19-d treatment periods; both diets contained approximately 20% forage neutral detergent fiber (NDF), 25% total NDF, and forage-to-concentrate ratios were approximately 47:53. Trial 2 was conducted with 15 cows in two 18-d treatment periods; both diets contained approximately 23% forage NDF, 28% total NDF, and had a forage-to-concentrate ratio of 50:50. Thiamine, riboflavin, niacin, vitamin B6, folates, and vitamin B12 were measured in feed and duodenal content. Daily ARS was calculated as the duodenal flow minus the intake. In trial 1, daily intake of individual B vitamins was increased with the LC diet, but ARS of thiamine, riboflavin, vitamin B6, and folates was reduced. In trial 2, except for folates, intakes of the other B vitamins were decreased with the LC diets, whereas ARS of riboflavin, niacin, and vitamin B6 was increased. Daily ARS of thiamine, riboflavin, niacin, and vitamin B6 were correlated negatively with their intake, suggesting that ruminal bacteria reduced their synthesis when dietary supply increased. Microbial activity could have also reduced degradation of thiamine, riboflavin, and niacin, which is supported by (1) the negative correlation between ARS of these vitamins and ruminal pH or microbial N duodenal flow; and (2) the positive correlation between ARS and ruminal concentrations

  13. Mouse dyskerin mutations affect accumulation of telomerase RNA and small nucleolar RNA, telomerase activity, and ribosomal RNA processing.

    PubMed

    Mochizuki, Yuko; He, Jun; Kulkarni, Shashikant; Bessler, Monica; Mason, Philip J

    2004-07-20

    Dyskerin is a nucleolar protein present in small nucleolar ribonucleoprotein particles that modify specific uridine residues of rRNA by converting them to pseudouridine. Dyskerin is also a component of the telomerase complex. Point mutations in the human gene encoding dyskerin cause the skin and bone marrow failure syndrome dyskeratosis congenita (DC). To test the extent to which disruption of pseudouridylation or telomerase activity may contribute to the pathogenesis of DC, we introduced two dyskerin mutations into murine embryonic stem cells. The A353V mutation is the most frequent mutation in patients with X-linked DC, whereas the G402E mutation was identified in a single family. The A353V, but not the G402E, mutation led to severe destabilization of telomerase RNA, a reduction in telomerase activity, and a significant continuous loss of telomere length with increasing numbers of cell divisions during in vitro culture. Both mutations caused a defect in overall pseudouridylation and a small but detectable decrease in the rate of pre-rRNA processing. In addition, both mutant embryonic stem cell lines showed a decrease in the accumulation of a subset of H/ACA small nucleolar RNAs, correlating with a significant decrease in site-specific pseudouridylation efficiency. Interestingly, the H/ACA snoRNAs decreased in the G402E mutant cell line differed from those affected in A353V mutant cells. Hence, our findings show that point mutations in dyskerin may affect both the telomerase and pseudouridylation pathways and the extent to which these functions are altered can vary for different mutations.

  14. particles

    NASA Astrophysics Data System (ADS)

    Xia, Yu; Chen, Zhihong; Zhang, Zhengguo; Fang, Xiaoming; Liang, Guozheng

    2014-05-01

    We explore a facile and nontoxic hydrothermal route for synthesis of a Cu2ZnSnS4 nanocrystalline material by using l-cysteine as the sulfur source and ethylenediaminetetraacetic acid (EDTA) as the complexing agent. The effects of the amount of EDTA, the mole ratio of the three metal ions, and the hydrothermal temperature and time on the phase composition of the obtained product have been systematically investigated. The addition of EDTA and an excessive dose of ZnCl2 in the hydrothermal reaction system favor the generation of kesterite Cu2ZnSnS4. Pure kesterite Cu2ZnSnS4 has been synthesized at 180°C for 12 h from the reaction system containing 2 mmol of EDTA at 2:2:1 of Cu/Zn/Sn. It is confirmed by Raman spectroscopy that those binary and ternary phases are absent in the kesterite Cu2ZnSnS4 product. The kesterite Cu2ZnSnS4 material synthesized by the hydrothermal process consists of flower-like particles with 250 to 400 nm in size. It is revealed that the flower-like particles are assembled from single-crystal Cu2ZnSnS4 nanoflakes with ca. 20 nm in size. The band gap of the Cu2ZnSnS4 nanocrystalline material is estimated to be 1.55 eV. The films fabricated from the hierarchical Cu2ZnSnS4 particles exhibit fast photocurrent responses under intermittent visible-light irradiation, implying that they show potentials for use in solar cells and photocatalysis.

  15. Temperature and burning history affect emissions of greenhouse gases and aerosol particles from tropical peatland fire

    NASA Astrophysics Data System (ADS)

    Kuwata, Mikinori; Kai, Fuu Ming; Yang, Liudongqing; Itoh, Masayuki; Gunawan, Haris; Harvey, Charles F.

    2017-01-01

    Tropical peatland burning in Asia has been intensifying over the last decades, emitting huge amounts of gas species and aerosol particles. Both laboratory and field studies have been conducted to investigate emission from peat burning, yet a significant variability in data still exists. We conducted a series of experiments to characterize the gas and particulate matter emitted during burning of a peat sample from Sumatra in Indonesia. Heating temperature of peat was found to regulate the ratio of CH4 to CO2 in emissions (ΔCH4/ΔCO2) as well as the chemical composition of particulate matter. The ΔCH4/ΔCO2 ratio was larger for higher temperatures, meaning that CH4 emission is more pronounced at these conditions. Mass spectrometric analysis of organic components indicated that aerosol particles emitted at higher temperatures had more unsaturated bonds and ring structures than that emitted from cooler fires. The result was consistently confirmed by nuclear magnetic resonance analysis. In addition, CH4 emitted by burning charcoal, which is derived from previously burned peat, was lower by at least an order of magnitude than that from fresh peat. These results highlight the importance of both fire history and heating temperature for the composition of tropical peat-fire emissions. They suggest that remote sensing technologies that map fire histories and temperatures could provide improved estimates of emissions.

  16. ULTRAFINE CARBON PARTICLE (UFCP) INHALATION AFFECTS CARDIOVASCULAR PERFORMANCE IN HYPERTENSIVE RATS (SHR)

    EPA Science Inventory

    Inhaled UfCP affect cardiovascular performance in healthy rats (Harder et al. Inhal Toxicol 2005; 17:29-42) without apparent pulmonary damage. To assess whether geriatric cardiovascular compromised rats are more susceptible to UfCP effects, male adult (6months) and geriatric (13m...

  17. ULTRAFINE CARBON PARTICLE (UFCP) INHALATION AFFECTS CARDIOVASCULAR PERFORMANCE IN HYPERTENSIVE RATS (SHR)

    EPA Science Inventory

    Inhaled UfCP affect cardiovascular performance in healthy rats (Harder et al. Inhal Toxicol 2005; 17:29-42) without apparent pulmonary damage. To assess whether geriatric cardiovascular compromised rats are more susceptible to UfCP effects, male adult (6months) and geriatric (13m...

  18. Hazardous or not - Are adult and juvenile individuals of Potamopyrgus antipodarum affected by non-buoyant microplastic particles?

    PubMed

    Imhof, Hannes K; Laforsch, Christian

    2016-11-01

    Microplastic has been ubiquitously detected in freshwater ecosystems. A variety of freshwater organisms were shown to ingest microplastic particles, while a high potential for adverse effects are expected. However, studies addressing the effect of microplastic in freshwater species are still scarce compared to studies on marine organisms. In order to gain further insights into possible adverse effects of microplastic particles on freshwater invertebrates and to set the base for further experiments we exposed the mud snail (Potampoyrgus antipodarum) to a large range of common and environmentally relevant non-buoyant polymers (polyamide, polyethylene terephthalate, polycarbonate, polystyrene, polyvinylchloride). The impact of these polymers was tested by performing two exposure experiments with irregular shaped microplastic particles with a broad size distribution in a low (30%) and a high microplastic dose (70%) in the food. First, possible effects on adult P. antipodarum were assessed by morphological and life-history parameters. Second, the effect of the same mixture on the development of juvenile P. antipodarum until maturity was analyzed. Adult P. antipodarum showed no morphological changes after the exposure to the microplastic particles, even if supplied in a high dose. Moreover, although P. antipodarum is an established model organism and reacts especially sensitive to endocrine active substances no effects on embryogenesis were detected. Similarly, the juvenile development until maturity was not affected. Considering, that most studies showing effects on marine and freshwater invertebrates mostly exposed their experimental organisms to very small (≤20 μm) polystyrene microbeads, we anticipate that these effects may be highly dependent on the chemical composition of the polymer itself and the size and shape of the particles. Therefore, more studies are necessary to enable the identification of harmful synthetic polymers as some of them may be

  19. Quantification of virus-like particles suggests viral infection in corals affected by Porites tissue loss

    NASA Astrophysics Data System (ADS)

    Lawrence, Scott A.; Davy, Joanne E.; Aeby, Greta S.; Wilson, William H.; Davy, Simon K.

    2014-09-01

    Porites tissue loss is a common disease of Porites compressa on Hawaiian reefs. Despite its prevalence, to date, the aetiological agent of the disease has not been found. The apparent lack of a microbial causative agent in the similar disease Porites bleaching with tissue loss, as well as increasing evidence of viral infections in scleractinian corals and Symbiodinium, led us to hypothesise that a virus may be responsible. Electron microscopy revealed the presence of numerous and varied virus-like particles (VLPs) in healthy and diseased P. compressa colonies. While overall virus numbers were similar in all samples, the abundance of a group of icosahedral VLPs differed significantly between healthy and diseased colonies. While not conclusive, these results suggest that viruses may play a role in this disease, and provide a basis for further studies.

  20. Changes in particle size distribution of suspended sediment affected by gravity erosion on the Loess Plateau, China

    NASA Astrophysics Data System (ADS)

    Guo, Wen-Zhao; Xu, Xiang-Zhou; Liu, Ya-Kun; Zhang, Hong-Wu; Zhu, Ming-Dong

    2017-04-01

    Gravity erosion generates an enormous volume of sediment on the steep hillslopes throughout the world, yet the response from particle size distribution (PSD) of suspended sediment to mass failure remains poorly understood. Here rainfall simulation experiments were conducted on the natural loess slopes to induce a series of mass failures under rainfall intensity of 48 mm h-1, and then an index of enrichment/dilution ratio was used to quantitatively explore the change trend of suspended sediment PSD affected by gravity erosion. To determine suspended sediment, water samples were collected in a polyethylene bottle directly from the gully runoff and channel flow in the pre and during- slope failures events. Then, the particle fractions of samples were done by combining sieving method and photoelectric sedimentometer technique. The results are shown as follows: (1) Gravity erosion has a significant influence on the particle size distribution of suspended sediment. As the mass erosion occurred, the proportion of sand-sized particles was decreased from 71.2 to 50.8%, whereas the proportions of clay and silt were increased remarkably from 1.3 to 7.3% and 27.5 to 41.9%, respectively. Hence the sediment can be more easily transported into channel flow while the suspended sediment load becomes finer as gravitational erosion occurs. (2) The median particle size (d50), sediment heterogeneity (H) and fractal dimensions (D) were significantly correlated with gravity erosion. As a result, d50 was decreased from 0.084 to 0.051 mm, H was increase from 5.6 to 26.8, and D was magnified from 2.60 to 2.78. This implies that mass failure makes the particle size distribution of suspended sediment more nonuniform and irregular. (3) Suspended sediment tended to enrich in the silt and clay fractions, while it diluted in the sand fractions during landslide erosion. Meanwhile, the enrichment/dilution ratios were 13.9 for the clay fractions, 1.4 for clay, and 0.7 for sand. This reflects the

  1. Reciprocal mouse and human limb phenotypes caused by gain- and loss-of-function mutations affecting Lmbr1.

    PubMed Central

    Clark, R M; Marker, P C; Roessler, E; Dutra, A; Schimenti, J C; Muenke, M; Kingsley, D M

    2001-01-01

    The major locus for dominant preaxial polydactyly in humans has been mapped to 7q36. In mice the dominant Hemimelic extra toes (Hx) and Hammertoe (Hm) mutations map to a homologous chromosomal region and cause similar limb defects. The Lmbr1 gene is entirely within the small critical intervals recently defined for both the mouse and human mutations and is misexpressed at the exact time that the mouse Hx phenotype becomes apparent during limb development. This result suggests that Lmbr1 may underlie preaxial polydactyly in both mice and humans. We have used deletion chromosomes to demonstrate that the dominant mouse and human limb defects arise from gain-of-function mutations and not from haploinsufficiency. Furthermore, we created a loss-of-function mutation in the mouse Lmbr1 gene that causes digit number reduction (oligodactyly) on its own and in trans to a deletion chromosome. The loss of digits that we observed in mice with reduced Lmbr1 activity is in contrast to the gain of digits observed in Hx mice and human polydactyly patients. Our results suggest that the Lmbr1 gene is required for limb formation and that reciprocal changes in levels of Lmbr1 activity can lead to either increases or decreases in the number of digits in the vertebrate limb. PMID:11606546

  2. Anthocyanin suppresses CoCrMo particle-induced osteolysis by inhibiting IKKα/β mediated NF-κB signaling in a mouse calvarial model.

    PubMed

    Li, Yamin; Li, Juehong; Li, Bin; Qin, Hui; Peng, Xiaochun; Zhao, Yaochao; Chen, Yunsu

    2017-05-01

    Wear particle-induced osteolysis and bone resorption have been identified as critical factors of implant failure and total joint revision, in which nuclear factor kappa B (NF-κB) signaling and chronic inflammation have been shown to play key roles. Although anthocyanin is known to have anti-inflammatory function via blocking NF-κB pathway, it is still unclear whether anthocyanin has a protective effect on particle-induced osteolysis. In the present study, we aimed to investigate the detailed effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model. One hundred and twelve male BALB/c mice were divided randomly into four groups: sham group (sham operation and injection with PBS), vehicle group (CoCrMo particle treatment and injection with PBS), low-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.1mg/g/day), and high-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.4mg/g/day). Mice were sacrificed after two weeks, harvesting the calvariae tissue for in depth analysis by micro-CT, histomorphometry, immunohistochemical and molecular biology analysis. As expected, anthocyanin markedly inhibited CoCrMo particle-induced inflammatory infiltration and decreased bone loss in vivo. Anthocyanin also reversed the increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL)/osteoproteger (OPG) and suppressed osteoclast formation in CoCrMo particle-stimulated calvaria. Additionally, anthocyanin significantly reduced the expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the calvaria of CoCrMo-stimulated mice. Furthermore, we confirmed that anthocyanin attenuated osteolysis by blocking NF-κB pathway via inhibiting inhibitor of nuclear factor kappa-B kinase α/β (IKKα/β) phosphorylation. In conclusion, our study demonstrated that anthocyanin can protect against

  3. RBE and genetic susceptibility of mouse and rat spermatogonial stem cells to protons, heavy charged particles and 1.5 MeV neutrons

    NASA Astrophysics Data System (ADS)

    Vaglenov, A.; Fedorenko, B.; Kaltenboeck, B.

    The main purpose of the present study is to provide data on RBE and genetic susceptibility in the mouse and the rat when exposed to protons, HZE particles and neutrons. Genetic damage from exposure to 50 MeV and 9 GeV protons, 4 GeV/nucleon helium ions, 4 GeV/nucleon carbon ions and 1.5 MeV neutrons was studied in adult (CBA × C57Bl/6J) F1 mice. Damage from 9 GeV protons and 4 GeV helium ions was studied in adult Wistar rats. The incidence of reciprocal translocations (RT) induced in the spermatogonial stem cells of each species was recorded. RBE values were derived by comparing linear regression coefficients from dose-responses within the same dose-range for each of the radiation types tested and 60Co γ-rays or by means of a direct nonparametric method. RT yields measured after mouse and rat spermatogonial irradiation with protons, heavy charged particles and neutrons fit the linear model of the dose-response relationship. Relative to 60Co γ-rays, RBE values are as follows for mouse spermatogonia: 0.9 for 50 MeV protons; 1.3 for 9 GeV protons; 0.7 for 4 GeV helium ions; and 1.3 for 4 GeV carbon ions. For rat spermatogonia, values were: 1.7 for 9 GeV protons and 1.3 for helium ions. Compared to mice irradiated using the same experimental design, rats were more susceptible to high-LET radiations, with susceptibility assessed by genetic damage to their spermatogonial stem cells. The RBE of 1.5 MeV neutron is about 6.6.

  4. Navy Bean Flour Particle Size and Protein Content Affect Cake Baking and Batter Quality(1).

    PubMed

    Singh, Mukti; Byars, Jeffrey A; Liu, Sean X

    2015-06-01

    Whole navy bean flour and its fine and coarse particle size fractions were used to completely replace wheat flour in cakes. Replacement of wheat flour with whole bean flour significantly increased the protein content. The protein content was adjusted to 3 levels with navy bean starch. The effect of navy bean flour and its fractions at 3 levels of protein on cake batter rheology and cake quality was studied and compared with wheat flour samples. Batters prepared from navy bean flour and its fractions had higher viscosity than the cake flour. Reducing the protein content by addition of starch significantly lowered the viscosity of cake batters. The whole navy bean flour and coarse bean fraction cakes were softer than cakes made with wheat flour but had reduced springiness. Principal component analysis showed a clear discrimination of cakes according to protein. It also showed that low protein navy bean flour cakes were similar to wheat flour cakes. Navy bean flour with protein content adjusted to the level of cake (wheat) flour has potential as a healthy alternative in gluten-free cakes.

  5. Meteorological phenomena affecting the presence of solid particles suspended in the air during winter

    NASA Astrophysics Data System (ADS)

    Cariñanos, P.; Galán, C.; Alcázar, P.; Dominguez, E.

    Winter is not traditionally considered to be a risky season for people who suffer from pollen allergies. However, increasing numbers of people are showing symptoms in winter. This prompted our investigation into the levels of solid material in the air, and some of the meteorological phenomena that allow their accumulation. This study showed a possible relationship between the phenomenon of thermal inversion, which occurs when very low temperatures, cloudless skies and atmospheric calms coincide, and an increase in the concentration of solid material in the atmosphere. Frequently, this situation is associated with other predictable phenomena such as fog, dew and frost. This may allow a warning system to be derived for urban pollution episodes. The effect caused by parameters such as wind and rainfall was also analysed. Solid material was differentiated into non-biological material from natural and non-natural sources (e.g. soot, dust, sand, diesel exhaust particles, partially burnt residues) and biological material. The latter mainly comprises pollen grains and fungal spores. Owing to its abundance and importance as a causal agent of winter allergies, Cupressaceae pollen was considered separately.

  6. Enhancement of Heat-Affected Zone Toughness of a Low Carbon Steel by TiN Particle

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Li, Xiaobao; Ma, Han

    2016-08-01

    Enhancement of heat-affected zone toughness of a weight percentage of 0.014 pct Ti-bearing low carbon steel by TiN particle was investigated. An increase in nitrogen weight percentage from 0.0031 to 0.0083 pct results in increasing of number density of TiN precipitates from 4 × 103 to 3 × 105/mm2, and reduces prior austenite grain size from 850 to 350 μm with a soaking of 1673 K (1400 °C) for 2000 seconds. Effective refinement of austenite grain prohibits formation of ferrite side plate and/or upper bainite, and densely distributed TiN particles promote intra-granular ferrite formation, which is accompanied by an increase of 40 K to 60 K (40 °C to 60 °C) in austenite decomposition temperature during continuous cooling process. The changes in transformed products improved impact toughness of heat-affected zone efficiently, ex., increase absorbed energy of less than 42 J to more than 320 J with a simulated t 8/5 of 550 seconds.

  7. Do Solar Coronal Holes Affect the Properties of Solar Energetic Particle Events?

    NASA Technical Reports Server (NTRS)

    Kahler, S. W.; Arge, C. N.; Akiyama, S.; Gopalswamy, N.

    2013-01-01

    The intensities and timescales of gradual solar energetic particle (SEP) events at 1 AU may depend not only on the characteristics of shocks driven by coronal mass ejections (CMEs), but also on large-scale coronal and interplanetary structures. It has long been suspected that the presence of coronal holes (CHs) near the CMEs or near the 1-AU magnetic footpoints may be an important factor in SEP events. We used a group of 41 E (is) approx. 20 MeV SEP events with origins near the solar central meridian to search for such effects. First we investigated whether the presence of a CH directly between the sources of the CME and of the magnetic connection at 1 AU is an important factor. Then we searched for variations of the SEP events among different solar wind (SW) stream types: slow, fast, and transient. Finally, we considered the separations between CME sources and CH footpoint connections from 1 AU determined from four-day forecast maps based on Mount Wilson Observatory and the National Solar Observatory synoptic magnetic-field maps and the Wang-Sheeley-Arge model of SW propagation. The observed in-situ magnetic-field polarities and SW speeds at SEP event onsets tested the forecast accuracies employed to select the best SEP/CH connection events for that analysis. Within our limited sample and the three analytical treatments, we found no statistical evidence for an effect of CHs on SEP event peak intensities, onset times, or rise times. The only exception is a possible enhancement of SEP peak intensities in magnetic clouds.

  8. Do Solar Coronal Holes Affect the Properties of Solar Energetic Particle Events?

    NASA Astrophysics Data System (ADS)

    Kahler, S. W.; Arge, C. N.; Akiyama, S.; Gopalswamy, N.

    2014-02-01

    The intensities and timescales of gradual solar energetic particle (SEP) events at 1 AU may depend not only on the characteristics of shocks driven by coronal mass ejections (CMEs), but also on large-scale coronal and interplanetary structures. It has long been suspected that the presence of coronal holes (CHs) near the CMEs or near the 1-AU magnetic footpoints may be an important factor in SEP events. We used a group of 41 E≈ 20 MeV SEP events with origins near the solar central meridian to search for such effects. First we investigated whether the presence of a CH directly between the sources of the CME and of the magnetic connection at 1 AU is an important factor. Then we searched for variations of the SEP events among different solar wind (SW) stream types: slow, fast, and transient. Finally, we considered the separations between CME sources and CH footpoint connections from 1 AU determined from four-day forecast maps based on Mount Wilson Observatory and the National Solar Observatory synoptic magnetic-field maps and the Wang-Sheeley-Arge model of SW propagation. The observed in-situ magnetic-field polarities and SW speeds at SEP event onsets tested the forecast accuracies employed to select the best SEP/CH connection events for that analysis. Within our limited sample and the three analytical treatments, we found no statistical evidence for an effect of CHs on SEP event peak intensities, onset times, or rise times. The only exception is a possible enhancement of SEP peak intensities in magnetic clouds.

  9. Methionine sulfoxide reductase A affects β-amyloid solubility and mitochondrial function in a mouse model of Alzheimer's disease

    PubMed Central

    Du, Fang; Bowman, Connor F.; Yan, Shirley S.

    2016-01-01

    Accumulation of oxidized proteins, and especially β-amyloid (Aβ), is thought to be one of the common causes of Alzheimer's disease (AD). The current studies determine the effect of an in vivo methionine sulfoxidation of Aβ through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and Aβ in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins, and thus its ablation in the AD-mouse model will increase the formation of methionine sulfoxide in Aβ. Indeed, the novel MsrA-deficient APP mice (APP+/MsrAKO) exhibited higher levels of soluble Aβ in brain compared with APP+ mice. Furthermore, mitochondrial respiration and the activity of cytochrome c oxidase were compromised in the APP+/MsrAKO compared with control mice. These results suggest that lower MsrA activity modifies Aβ solubility properties and causes mitochondrial dysfunction, and augmenting its activity may be beneficial in delaying AD progression. PMID:26786779

  10. Mutations in the hormone regulatory element of mouse mammary tumor virus differentially affect the response to progestins, androgens, and glucocorticoids.

    PubMed Central

    Gowland, P L; Buetti, E

    1989-01-01

    Transcription of the mouse mammary tumor virus DNA is known to be induced by several steroid hormones. Using chimeric MMTV plasmids containing mutations within the hormone regulatory element, we have previously studied the regions required for the glucocorticoid response in mouse fibroblasts. Here we report the characterization of elements essential for the stimulation by progestins and androgens as compared with glucocorticoids. The same set of mutant plasmids was transfected into the human mammary tumor cell line T47D, and the specific transcripts were analyzed by an S1 nuclease protection assay. Androgen-mediated stimulation, although weak, showed an extended sensitivity to mutations, with a slight preference for the proximal region. The results with progestin suggest that sequences within all the described sites protected by the receptor in vitro are required and that the promoter-proximal region (-128 to -78 from the RNA start site) is more important than the distal one (-190 to -160). Moreover, a binding site for nuclear factor I was not required for the progestin response, whereas it was required for glucocorticoids. Thus, the various steroid receptors play a role in the differential regulation of mouse mammary tumor virus transcription by recognizing distinct sequence differences in the hormone regulatory element and interacting with different factors bound to the promoter. Images PMID:2550809

  11. Optimization of route of administration for coexposure to ovalbumin and particle matter to induce adjuvant activity in respiratory allergy in the mouse.

    PubMed

    Steerenberg, P A; van Dalen, W J; Withagen, C E T; Dormans, J A M A; van Loveren, H

    2003-11-01

    Epidemiological and experimental studies have not only shown that air pollution induces increased pulmonary morbidity, and mortality, but also that air pollution components may potentiate allergic responses. The respiratory allergy model to ovalbumin in the mouse has been shown a useful tool to characterize the adjuvant potency of air pollution components. However, the choice for the most effective route of administration for testing small amounts of air pollution component is hampered by the diversity of routes of administration used. To test the adjuvant activity of airborne particles (Ottawa dust EHC-93), we studied the optimal route of respiratory administration: intranasally (in) and aerosol (aero) in comparison with responses observed by intraperitoneal (ip) with diesel exhaust particles (DEP) as a positive control. Our results show that the combination of in/aero with ovalbumin caused almost similar immunoglobulin (Ig)E and inflammatory responses compared to the ip/aero. In/in application induced less responses for IgE, less inflammation in the lung, and less increased numbers of eosinophils in the bronchoalveolar lavage (BAL). This response increased dramatically when ovalbumin was coadministered with DEP. Subsequently, EHC-93, which is made up of airborne particles, was tested via the in/in route of administration. EHC-93 induced similar IgE responses, inflammation, and eosinophilic response in BAL compared to DEP. In addition, EHC-93 increased the airway responsiveness of the ovalbumin-sensitized mice measured in unrestrained condition and not in nonsensitized control mice. It is concluded that intranasal sensitization with intranasal challenge with airborne particles (EHC-93) is an effective route of administration to show potency of adjuvant activity of airborne particles.

  12. MiRNA-320 in the human follicular fluid is associated with embryo quality in vivo and affects mouse embryonic development in vitro.

    PubMed

    Feng, Ruizhi; Sang, Qing; Zhu, Yan; Fu, Wei; Liu, Miao; Xu, Yan; Shi, Huijuan; Xu, Yao; Qu, Ronggui; Chai, Renjie; Shao, Ruijin; Jin, Li; He, Lin; Sun, Xiaoxi; Wang, Lei

    2015-03-03

    Previous work from our laboratory demonstrated the existence of miRNAs in human follicular fluid. In the current study, we have sought to identify miRNAs that might affect oocyte/embryo quality in patients undergoing intracytoplasmic sperm injection and to investigate their roles in in vitro fertilization outcomes in mouse oocytes. 53 samples were classified as Group 1 (high quality) if the day-3 embryos had seven and more cells or as Group 2 (low quality) if the embryos had six and fewer cells. TaqMan Human microRNAs cards and qRT-PCR were performed to verify differently expressed miRNAs. The function of the corresponding miRNA was investigated in mouse oocytes by injecting them with miRNA-inhibitor oligonucleotides. We found that hsa-miR-320a and hsa-miR-197 had significantly higher expression levels in the Group 1 follicular fluids than in Group 2 (p = 0.0073 and p = 0.008, respectively). Knockdown of mmu-miR-320 in mouse oocytes strongly decreased the proportions of MII oocytes that developed into two-cell and blastocyst stage embryos (p = 0.0048 and p = 0.0069, respectively). Wnt signaling pathway components had abnormal expression level in miR-320 inhibitor-injected oocytes. This study provides the first evidence that miRNAs in human follicular fluid are indicative of and can influence embryo quality.

  13. Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model*

    PubMed Central

    Calattini, Sara; Fusil, Floriane; Mancip, Jimmy; Dao Thi, Viet Loan; Granier, Christelle; Gadot, Nicolas; Scoazec, Jean-Yves; Zeisel, Mirjam B.; Baumert, Thomas F.; Lavillette, Dimitri; Dreux, Marlène; Cosset, François-Loïc

    2015-01-01

    Lipoprotein components are crucial factors for hepatitis C virus (HCV) assembly and entry. As hepatoma cells producing cell culture-derived HCV (HCVcc) particles are impaired in some aspects of lipoprotein metabolism, it is of upmost interest to biochemically and functionally characterize the in vivo produced viral particles, particularly regarding how lipoprotein components modulate HCV entry by lipid transfer receptors such as scavenger receptor BI (SR-BI). Sera from HCVcc-infected liver humanized FRG mice were separated by density gradients. Viral subpopulations, termed HCVfrg particles, were characterized for their physical properties, apolipoprotein association, and infectivity. We demonstrate that, in contrast to the widely spread distribution of apolipoproteins across the different HCVcc subpopulations, the most infectious HCVfrg particles are highly enriched in apoE, suggesting that such apolipoprotein enrichment plays a role for entry of in vivo derived infectious particles likely via usage of apolipoprotein receptors. Consistent with this salient feature, we further reveal previously undefined functionalities of SR-BI in promoting entry of in vivo produced HCV. First, unlike HCVcc, SR-BI is a particularly limiting factor for entry of HCVfrg subpopulations of very low density. Second, HCVfrg entry involves SR-BI lipid transfer activity but not its capacity to bind to the viral glycoprotein E2. In conclusion, we demonstrate that composition and biophysical properties of the different subpopulations of in vivo produced HCVfrg particles modulate their levels of infectivity and receptor usage, hereby featuring divergences with in vitro produced HCVcc particles and highlighting the powerfulness of this in vivo model for the functional study of the interplay between HCV and liver components. PMID:26224633

  14. Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model.

    PubMed

    Calattini, Sara; Fusil, Floriane; Mancip, Jimmy; Dao Thi, Viet Loan; Granier, Christelle; Gadot, Nicolas; Scoazec, Jean-Yves; Zeisel, Mirjam B; Baumert, Thomas F; Lavillette, Dimitri; Dreux, Marlène; Cosset, François-Loïc

    2015-09-18

    Lipoprotein components are crucial factors for hepatitis C virus (HCV) assembly and entry. As hepatoma cells producing cell culture-derived HCV (HCVcc) particles are impaired in some aspects of lipoprotein metabolism, it is of upmost interest to biochemically and functionally characterize the in vivo produced viral particles, particularly regarding how lipoprotein components modulate HCV entry by lipid transfer receptors such as scavenger receptor BI (SR-BI). Sera from HCVcc-infected liver humanized FRG mice were separated by density gradients. Viral subpopulations, termed HCVfrg particles, were characterized for their physical properties, apolipoprotein association, and infectivity. We demonstrate that, in contrast to the widely spread distribution of apolipoproteins across the different HCVcc subpopulations, the most infectious HCVfrg particles are highly enriched in apoE, suggesting that such apolipoprotein enrichment plays a role for entry of in vivo derived infectious particles likely via usage of apolipoprotein receptors. Consistent with this salient feature, we further reveal previously undefined functionalities of SR-BI in promoting entry of in vivo produced HCV. First, unlike HCVcc, SR-BI is a particularly limiting factor for entry of HCVfrg subpopulations of very low density. Second, HCVfrg entry involves SR-BI lipid transfer activity but not its capacity to bind to the viral glycoprotein E2. In conclusion, we demonstrate that composition and biophysical properties of the different subpopulations of in vivo produced HCVfrg particles modulate their levels of infectivity and receptor usage, hereby featuring divergences with in vitro produced HCVcc particles and highlighting the powerfulness of this in vivo model for the functional study of the interplay between HCV and liver components. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Radiotoxicity of gadolinium-148 and radium-223 in mouse testes: relative biological effectiveness of alpha-particle emitters in vivo.

    PubMed

    Howell, R W; Goddu, S M; Narra, V R; Fisher, D R; Schenter, R E; Rao, D V

    1997-03-01

    The biological effects of radionuclides that emit alpha particles are of considerable interest in view of their potential for therapy and their presence in the environment. The present work is a continuation of our ongoing effort to study the radiotoxicity of alpha-particle emitters in vivo using the survival of murine testicular sperm heads as the biological end point. Specifically, the relative biological effectiveness (RBE) of very low-energy alpha particles (3.2 MeV) emitted by 148Gd is investigated and determined to be 7.4 +/- 2.4 when compared to the effects of acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210Po and 212Pb in equilibrium with its daughters, is used to revise and extend the range of validity of our previous RBE-energy relationship for alpha particles emitted by tissue-incorporated radionuclides. The new empirical relationship is given by RBE alpha = 9.14 - 0.510 E alpha where 3 < E alpha < 9 MeV. The validity of this empirical relationship is tested by determining the RBE of the prolific alpha-particle emitter 223Ra (in equilibrium with its daughters) experimentally in the same biological model and comparing the value obtained experimentally with the predicted value. The resulting RBE values are 5.4 +/- 0.9 and 5.6, respectively. This close agreement strongly supports the adequacy of the empirical RBE-E alpha relationship to predict the biological effects of alpha-particle emitters in vivo.

  16. Radiotoxicity of Gadolinium-148 and Radium-223 in Mouse Testes: Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo

    PubMed Central

    Howell, Roger W.; Goddu, S. Murty; Narra, Venkat R.; Fisher, Darrell R.; Schenter, Robert E.; Rao, Dandamudi V.

    2012-01-01

    The biological effects of radionuclides that emit α particles are of considerable interest in view of their potential for therapy and their presence in the environment. The present work is a continuation of our ongoing effort to study the radiotoxicity of α-particle emitters in vivo using the survival of murine testicular sperm heads as the biological end point. Specifically, the relative biological effectiveness (RBE) of very low-energy α particles (3.2 MeV) emitted by 148Gd is investigated and determined to be 7.4 ± 2.4 when compared to the effects of acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210Po and 212Pb in equilibrium with its daughters, is used to revise and extend the range of validity of our previous RBE–energy relationship for α particles emitted by tissue-incorporated radionuclides. The new empirical relationship is given by RBEα = 9.14 − 0.510 Eα, where 3 < Eα < 9 MeV. The validity of this empirical relationship is tested by determining the RBE of the prolific α-particle emitter 223Ra (in equilibrium with its daughters) experimentally in the same biological model and comparing the value obtained experimentally with the predicted value. The resulting RBE values are 5.4 ± 0.9 and 5.6, respectively. This close agreement strongly supports the adequacy of the empirical RBE-Eα relationship to predict the biological effects of α-particle emitters in Vivo. PMID:9052681

  17. Avertin®, but Not Volatile Anesthetics Addressing the Two-Pore Domain K+ Channel, TASK-1, Slows Down Cilia-Driven Particle Transport in the Mouse Trachea

    PubMed Central

    Murtaza, Ghulam; Mermer, Petra; Pfeil, Uwe; Kummer, Wolfgang

    2016-01-01

    Rationale Volatile anesthetics inhibit mucociliary clearance in the airways. The two-pore domain K+ channel, TASK-1, represents one of their molecular targets in that they increase its open probability. Here, we determine whether particle transport speed (PTS) at the mucosal surface of the mouse trachea, an important factor of the cilia-driven mechanism in mucociliary clearance, is regulated by TASK-1. Methodology/Results RT-PCR analysis revealed expression of TASK-1 mRNA in the manually dissected and laser-assisted microdissected tracheal epithelium of the mouse. Effects of anesthetics (isoflurane and Avertin®) and TASK-1 inhibitors (anandamide and A293) on ciliary activity were investigated by assessment of PTS at the mucosal surface of the explanted and opened murine trachea. Neither TASK-1 inhibitors nor isoflurane had any impact on basal and ATP-stimulated PTS. Avertin® reduced basal PTS, and ATP-stimulated PTS decreased in its presence in wild-type (WT) mice. Avertin®-induced decrease in basal PTS persisted in WT mice in the presence of TASK-1 inhibitors, and in two different strains of TASK-1 knockout mice. Conclusions/Significance Our findings indicate that TASK-1 is expressed by the tracheal epithelium but is not critically involved in the regulation of tracheal PTS in mice. Avertin® reduces PTS independent of TASK-1. PMID:27930725

  18. A mouse model for ulcerative colitis based on NOD-scid IL2R γnull mice reconstituted with peripheral blood mononuclear cells from affected individuals

    PubMed Central

    Palamides, Pia; Jodeleit, Henrika; Föhlinger, Michael; Beigel, Florian; Herbach, Nadja; Mueller, Thomas; Wolf, Eckhard; Siebeck, Matthias

    2016-01-01

    ABSTRACT Animal models reflective of ulcerative colitis (UC) remain a major challenge, and yet are crucial to understand mechanisms underlying the onset of disease and inflammatory characteristics of relapses and remission. Mouse models in which colitis-like symptoms are induced through challenge with toxins such as oxazolone, dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) have been instrumental in understanding the inflammatory processes of UC. However, these neither reflect the heterogeneous symptoms observed in the UC-affected population nor can they be used to test the efficacy of inhibitors developed against human targets where high sequence and structural similarity of the respective ligands is lacking. In an attempt to overcome these problems, we have developed a mouse model that relies on NOD-scid IL2R γnull mice reconstituted with peripheral blood mononuclear cells derived from UC-affected individuals. Upon challenge with ethanol, mice developed colitis-like symptoms and changes in the colon architecture, characterized by influx of inflammatory cells, edema, crypt loss, crypt abscesses and epithelial hyperplasia, as previously observed in immune-competent mice. TARC, TGFβ1 and HGF expression increased in distal parts of the colon. Analysis of human leucocytes isolated from mouse spleen revealed an increase in frequencies of CD1a+, CD64+, CD163+ and TSLPR+ CD14+ monocytes, and antigen-experienced CD44+ CD4+ and CD8+ T-cells in response to ethanol. Analysis of human leucocytes from the colon of challenged mice identified CD14+ monocytes and CD11b+ monocytes as the predominant populations. Quantitative real-time PCR (RT-PCR) analysis from distal parts of the colon indicated that IFNγ might be one of the cytokines driving inflammation. Treatment with infliximab ameliorated symptoms and pathological manifestations, whereas pitrakinra had no therapeutic benefit. Thus, this model is partially reflective of the human disease and might

  19. A single genetic element in H-2K affects mouse T-cell antiviral function in poxvirus infection

    PubMed Central

    1976-01-01

    Cell transfer experiments using mice with recombinant H-2 haplotypes were used to map the H-2 regions which must be shared by ectromelia- immune T-cell donors and virus-infected recipients for transfer of virus clearance mechanisms in the spleen. K- or D-region genes were necessary and sufficient; I-region genes were not involved. The remainder of the mouse genome could be varied widely without impairing the efficacy of T-cell antiviral function, provided either a K or a D region was shared in the donor-receipient combination. A mutation in a single genetic element of the K region of the H-2 complex abolished the antiviral effect of immune T-cell transfer in a donor-recipient combination which shared the K end. PMID:55454

  20. Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia.

    PubMed

    Vaillant, Fanny; Lauzier, Benjamin; Ruiz, Matthieu; Shi, Yanfen; Lachance, Dominic; Rivard, Marie-Eve; Bolduc, Virginie; Thorin, Eric; Tardif, Jean-Claude; Des Rosiers, Christine

    2016-10-01

    While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker If current, vs. β-blockers like metoprolol. This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB(+/+);LDLR(-/-)). Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with (13)C-labeled substrates to assess substrate fluxes through energy metabolic pathways. Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression. Copyright © 2016 the American Physiological Society.

  1. Radioprotection of mouse colony forming units-spleen against heavy-charged particle damage by WR 2721.

    PubMed

    Afzal, S M; Ainsworth, E J

    1987-01-01

    The effectiveness of S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR 2721) to protect against the heavy-charged particle beams with dose-averaged LET infinity's ranging from 26 to 260 keV/micron was studied using the marrow colony forming units-spleen as a model system. WR 2721 (400 mg/kg) was injected ip 30 min before whole-body irradiation in the plateau ionization region of the Bragg curve. Significant protection was observed at 26, 51, and 135 keV/micron LET values where the data were collected with 20Ne, 28Si, and 40Ar ions, respectively. The largest component of protection was the slope change, where at LET values of 26 and 51 keV/micron the DMFs (slope) were 2.1 and 2.3, respectively, which are very close to the gamma-ray value of 2.4 (gamma LET approximately equal to 0.2 keV/micron). Protection, however, decreased with increase in LET from 51 to 135 keV/micron to the DMF value of 1.2 and no significant protection was observed against 56Fe ions at 260 keV/micron. Significant increases in extrapolation number occurred with gamma rays and neon particles. The results are discussed in terms of charged particle track structure, radiation chemistry, and potential clinical applications.

  2. Modeling of conductive particle motion in viscous medium affected by an electric field considering particle-electrode interactions and microdischarge phenomenon

    NASA Astrophysics Data System (ADS)

    Eslami, Ghiyam; Esmaeilzadeh, Esmaeil; Pérez, Alberto T.

    2016-10-01

    Up and down motion of a spherical conductive particle in dielectric viscous fluid driven by a DC electric field between two parallel electrodes was investigated. A nonlinear differential equation, governing the particle dynamics, was derived, based on Newton's second law of mechanics, and solved numerically. All the pertaining dimensionless groups were extracted. In contrast to similar previous works, hydrodynamic interaction between the particle and the electrodes, as well as image electric forces, has been taken into account. Furthermore, the influence of the microdischarge produced between the electrodes and the approaching particle on the particle dynamics has been included in the model. The model results were compared with experimental data available in the literature, as well as with some additional experimental data obtained through the present study showing very good agreement. The results indicate that the wall hydrodynamic effect and the dielectric liquid ionic conductivity are very dominant factors determining the particle trajectory. A lower bound is derived for the charge transferred to the particle while rebounding from an electrode. It is found that the time and length scales of the post-microdischarge motion of the particle can be as small as microsecond and micrometer, respectively. The model is able to predict the so called settling/dwelling time phenomenon for the first time.

  3. "Flashes in eyes" at Space Flight are the Signals that Retina is under "Hard" Affecting of Cosmic Charged Particles

    NASA Astrophysics Data System (ADS)

    Trukhanov, Kirill

    "Flashes in eyes" at Space Flight are the Signals that Retina is under "Hard" Affecting of Cosmic Charged Particles K.A. Trukhanov SSC RF - Institute of bio-medical problems RAS, Moscow The report is dedicated to the further development of the hypothesis that seeming streak images are caused by a "hard" action of cosmic ions passing through the multilayer structure of retinal ganglion cell axons. It is suggested that the axons are exсited or are blocked by a passage of charged particles through the retina. The simplified mathematical model has been developed to establish a relation of an exposure conditions and visual images of streaks. The hypothesis explains many peculiarities of streaks remaining without any explanations in the literature. For example, it explains the horizontal orientation of streaks, the sensation (feeling) of fast moving ("spreading") of streaks, etc. The total cross-section of the axon manyfold exceeds cross-section of a photoreceptor. The damage of the multilayer axon structure is equivalent to the damage of the tens of thousands of photoreceptors. The offered mechanism is not linked to photobiological processes and does not demand complete dark adaptation for flash sensations. Taking into account composite processes of visual perception, the necessity of some adaptation time, naturally, remains. Thus, the developed hypothesis requires a specification of retinal damage estimations at long-term flight (for example, to Mars). It is interesting to note that there is the surprising similarity of a loss in the visual field (the scotomata) at traumata of retinal nerve fibers to visual images of some streaks. It is not inconceivable that the retina will turn out to be one of critical structures at long interplanetary flight. Thus, there is return to an idea which belongs to Prof. C.A. Tobias that the visual tract can be one of critical structures in relation to the space radiation. The cataractogenesis must be taken into account too.

  4. NF-kappaB inhibitor dehydroxymethylepoxyquinomicin suppresses osteoclastogenesis and expression of NFATc1 in mouse arthritis without affecting expression of RANKL, osteoprotegerin or macrophage colony-stimulating factor.

    PubMed

    Kubota, Tetsuo; Hoshino, Machiko; Aoki, Kazuhiro; Ohya, Keiichi; Komano, Yukiko; Nanki, Toshihiro; Miyasaka, Nobuyuki; Umezawa, Kazuo

    2007-01-01

    Inhibition of NF-kappaB is known to be effective in reducing both inflammation and bone destruction in animal models of arthritis. Our previous study demonstrated that a small cell-permeable NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), suppresses expression of proinflammatory cytokines and ameliorates mouse arthritis. It remained unclear, however, whether DHMEQ directly affects osteoclast precursor cells to suppress their differentiation to mature osteoclasts in vivo. The effect of DHMEQ on human osteoclastogenesis also remained elusive. In the present study, we therefore examined the effect of DHMEQ on osteoclastogenesis using a mouse collagen-induced arthritis model, and using culture systems of fibroblast-like synovial cells obtained from patients with rheumatoid arthritis, and of osteoclast precursor cells from peripheral blood of healthy volunteers. DHMEQ significantly suppressed formation of osteoclasts in arthritic joints, and also suppressed expression of NFATc1 along the inner surfaces of bone lacunae and the eroded bone surface, while serum levels of soluble receptor activator of NF-kappaB ligand (RANKL), osteoprotegerin and macrophage colony-stimulating factor were not affected by the treatment. DHMEQ also did not suppress spontaneous expression of RANKL nor of macrophage colony-stimulating factor in culture of fibroblast-like synovial cells obtained from patients with rheumatoid arthritis. These results suggest that DHMEQ suppresses osteoclastogenesis in vivo, through downregulation of NFATc1 expression, without significantly affecting expression of upstream molecules of the RANKL/receptor activator of NF-kappaB/osteoprotegerin cascade, at least in our experimental condition. Furthermore, in the presence of RANKL and macrophage colony-stimulating factor, differentiation and activation of human osteoclasts were also suppressed by DHMEQ, suggesting the possibility of future application of NF-kappaB inhibitors to rheumatoid arthritis

  5. Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE−/− Alzheimer's mouse model

    PubMed Central

    Kempf, Stefan J.; Janik, Dirk; Barjaktarovic, Zarko; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Neff, Frauke; Saran, Anna; Larsen, Martin R.; Tapio, Soile

    2016-01-01

    Accruing data indicate that radiation-induced consequences resemble pathologies of neurodegenerative diseases such as Alzheimer's. The aim of this study was to elucidate the effect on hippocampus of chronic low-dose-rate radiation exposure (1 mGy/day or 20 mGy/day) given over 300 days with cumulative doses of 0.3 Gy and 6.0 Gy, respectively. ApoE deficient mutant C57Bl/6 mouse was used as an Alzheimer's model. Using mass spectrometry, a marked alteration in the phosphoproteome was found at both dose rates. The radiation-induced changes in the phosphoproteome were associated with the control of synaptic plasticity, calcium-dependent signalling and brain metabolism. An inhibition of CREB signalling was found at both dose rates whereas Rac1-Cofilin signalling was found activated only at the lower dose rate. Similarly, the reduction in the number of activated microglia in the molecular layer of hippocampus that paralleled with reduced levels of TNFα expression and lipid peroxidation was significant only at the lower dose rate. Adult neurogenesis, investigated by Ki67, GFAP and NeuN staining, and cell death (activated caspase-3) were not influenced at any dose or dose rate. This study shows that several molecular targets induced by chronic low-dose-rate radiation overlap with those of Alzheimer's pathology. It may suggest that ionising radiation functions as a contributing risk factor to this neurodegenerative disease. PMID:27708245

  6. Next-Generation Sequencing Identifies the Danforth's Short Tail Mouse Mutation as a Retrotransposon Insertion Affecting Ptf1a Expression

    PubMed Central

    Vlangos, Christopher N.; Siuniak, Amanda N.; Robinson, Dan; Chinnaiyan, Arul M.; Lyons, Robert H.; Cavalcoli, James D.; Keegan, Catherine E.

    2013-01-01

    The semidominant Danforth's short tail (Sd) mutation arose spontaneously in the 1920s. The homozygous Sd phenotype includes severe malformations of the axial skeleton with an absent tail, kidney agenesis, anal atresia, and persistent cloaca. The Sd mutant phenotype mirrors features seen in human caudal malformation syndromes including urorectal septum malformation, caudal regression, VACTERL association, and persistent cloaca. The Sd mutation was previously mapped to a 0.9 cM region on mouse chromosome 2qA3. We performed Sanger sequencing of exons and intron/exon boundaries mapping to the Sd critical region and did not identify any mutations. We then performed DNA enrichment/capture followed by next-generation sequencing (NGS) of the critical genomic region. Standard bioinformatic analysis of paired-end sequence data did not reveal any causative mutations. Interrogation of reads that had been discarded because only a single end mapped correctly to the Sd locus identified an early transposon (ETn) retroviral insertion at the Sd locus, located 12.5 kb upstream of the Ptf1a gene. We show that Ptf1a expression is significantly upregulated in Sd mutant embryos at E9.5. The identification of the Sd mutation will lead to improved understanding of the developmental pathways that are misregulated in human caudal malformation syndromes. PMID:23437000

  7. Protective effect of enterovirus-71 (EV71) virus-like particle vaccine against lethal EV71 infection in a neonatal mouse model

    PubMed Central

    CAO, LEI; MAO, FENGFENG; PANG, ZHENG; YI, YAO; QIU, FENG; TIAN, RUIGUANG; MENG, QINGLING; JIA, ZHIYUAN; BI, SHENGLI

    2015-01-01

    Enterovirus-71 (EV71) is a viral pathogen that causes severe cases of hand, foot and mouth disease (HFMD) among young children, with significant mortality. Effective vaccines against HFMD are urgently required. Several EV71 virus-like particle (VLP) vaccine candidates were found to be protective in the neonatal mouse EV71 challenge model. However, to what extent the VLP vaccine protects susceptible organs against EV71 infection in vivo has remained elusive. In the present study, the comprehensive immunogenicity of a potential EV71 vaccine candidate based on VLPs was evaluated in a neonatal mouse model. Despite lower levels of neutralizing antibodies to EV71 in the sera of VLP-immunized mice compared with those in mice vaccinated with inactivated EV71, the VLP-based vaccine was shown to be able to induce immunoglobulin (Ig)G and IgA memory-associated cellular immune responses to EV71. Of note, the EV71 VLP vaccine candidate was capable of inhibiting viral proliferation in cardiac muscle, skeletal muscle, lung and intestine of immunized mice and provided effective protection against the pathological damage caused by viral attack. In particular, the VLP vaccine was able to inhibit the transportation of EV71 from the central nervous system to the muscle tissue and greatly protected muscle tissue from infection, along with recovery from the viral infection. This led to nearly 100% immunoprotective efficacy, enabling neonatal mice delivered by VLP-immunized female adult mice to survive and grow with good health. The present study provided valuable additional knowledge of the specific protective efficacy of the EV71 VLP vaccine in vivo, which also indicated that it is a promising potential candidate for being developed into an EV71 vaccine. PMID:25936344

  8. Protective effect of enterovirus‑71 (EV71) virus‑like particle vaccine against lethal EV71 infection in a neonatal mouse model.

    PubMed

    Cao, Lei; Mao, Fengfeng; Pang, Zheng; Yi, Yao; Qiu, Feng; Tian, Ruiguang; Meng, Qingling; Jia, Zhiyuan; Bi, Shengli

    2015-08-01

    Enterovirus-71 (EV71) is a viral pathogen that causes severe cases of hand, foot and mouth disease (HFMD) among young children, with significant mortality. Effective vaccines against HFMD are urgently required. Several EV71 virus-like particle (VLP) vaccine candidates were found to be protective in the neonatal mouse EV71 challenge model. However, to what extent the VLP vaccine protects susceptible organs against EV71 infection in vivo has remained elusive. In the present study, the comprehensive immunogenicity of a potential EV71 vaccine candidate based on VLPs was evaluated in a neonatal mouse model. Despite lower levels of neutralizing antibodies to EV71 in the sera of VLP-immunized mice compared with those in mice vaccinated with inactivated EV71, the VLP-based vaccine was shown to be able to induce immunoglobulin (Ig)G and IgA memory-associated cellular immune responses to EV71. Of note, the EV71 VLP vaccine candidate was capable of inhibiting viral proliferation in cardiac muscle, skeletal muscle, lung and intestine of immunized mice and provided effective protection against the pathological damage caused by viral attack. In particular, the VLP vaccine was able to inhibit the transportation of EV71 from the central nervous system to the muscle tissue and greatly protected muscle tissue from infection, along with recovery from the viral infection. This led to nearly 100% immunoprotective efficacy, enabling neonatal mice delivered by VLP-immunized female adult mice to survive and grow with good health. The present study provided valuable additional knowledge of the specific protective efficacy of the EV71 VLP vaccine in vivo, which also indicated that it is a promising potential candidate for being developed into an EV71 vaccine.

  9. Nano-size scaling of alloy intra-particle vs. inter-particle separation transitions: prediction of distinctly interface-affected critical behaviour.

    PubMed

    Polak, M; Rubinovich, L

    2016-07-21

    Phase-separation second-order transitions in binary alloy particles consisting of ∼1000 up to ∼70 000 atoms (∼1-10 nm) are modeled focusing on the unexplored issue of finite-size scaling in such systems, particularly on evaluation of correlation-length critical exponents. Our statistical-thermodynamic approach is based on mean-field analytical expression for the Ising model free energy that facilitates highly efficient computations furnishing comprehensive data for fcc rectangular nanoparticles (NPs). These are summed up in intra- and inter-particle scaling plots as well as in nanophase separation diagrams. Temperature-induced variations in the interface thickness in Janus-type intra-particle configurations and NP size-dependent shifts in the critical temperature of their transition to solid-solution reflect power-law behavior with the same critical exponent, ν = 0.83. It is attributed to dominant interfacial effects that are absent in inter-particle transitions. Variations in ν with nano-size, as revealed by a refined analysis, are linearly extrapolated in order to bridge the gap to larger particles within and well beyond the nanoscale, ultimately yielding ν = 1.0. Besides these findings, the study indicates the key role of the surface-area to volume ratio as an effective linear size, revealing a universal, particle-shape independent, nanoscaling of the critical-temperature shifts.

  10. Nutrient demand interacts with legume particle length to affect digestion responses and rumen pool sizes in dairy cows.

    PubMed

    Kammes, K L; Ying, Y; Allen, M S

    2012-05-01

    Effects of legume particle length on dry matter intake (DMI), milk production, ruminal fermentation and pool sizes, and digestion and passage kinetics, and the relationship of these effects with preliminary DMI (pDMI) were evaluated using 13 ruminally and duodenally cannulated Holstein cows in a crossover design with a 14-d preliminary period and two 19-d treatment periods. During the preliminary period, pDMI of individual cows ranged from 22.8 to 32.4 kg/d (mean=26.5 kg/d) and 3.5% fat-corrected milk yield ranged from 22.9 to 62.4 kg/d (mean=35.1 kg/d). Experimental treatments were diets containing alfalfa silage chopped to (1) 19 mm (long cut, LC) or (2) 10 mm (short cut, SC) theoretical length of cut as the sole forage. Alfalfa silages contained approximately 43% neutral detergent fiber (NDF); diets contained approximately 47% forage and 20% forage NDF. Preliminary DMI, an index of nutrient demand, was determined during the last 4 d of the preliminary period, when cows were fed a common diet, and used as a covariate. Main effects of legume particle length and their interaction with pDMI were tested by ANOVA. Alfalfa particle length and its interaction with pDMI did not affect milk yield or rumen pH. The LC diet decreased milk fat concentration more per kilogram of pDMI increase than the SC diet and increased yields of milk fat and fat-corrected milk less per kilogram of pDMI increase than the SC diet, resulting in a greater benefit for LC at low pDMI and for SC at high pDMI. The LC diet tended to decrease DMI compared with the SC diet. Ruminal digestion and passage rates of feed fractions did not differ between LC and SC and were not related to level of intake. The LC diet tended to decrease the rate of ruminal turnover for NDF but increased NDF rumen pools at a slower rate than the SC diet as pDMI increased. This indicated that the faster NDF turnover rate did not counterbalance the higher DMI for SC, resulting in larger NDF rumen pools for SC than LC. As p

  11. Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome.

    PubMed

    Remeseiro, Silvia; Cuadrado, Ana; Kawauchi, Shimako; Calof, Anne L; Lander, Arthur D; Losada, Ana

    2013-12-01

    Cornelia de Lange Syndrome (CdLS) is a genetic disorder linked to mutations in cohesin and its regulators. To date, it is unclear which function of cohesin is more relevant to the pathology of the syndrome. A mouse heterozygous for the gene encoding the cohesin loader Nipbl recapitulates many features of CdLS. We have carefully examined Nipbl deficient cells and here report that they have robust cohesion all along the chromosome. DNA replication, DNA repair and chromosome segregation are carried out efficiently in these cells. While bulk cohesin loading is unperturbed, binding to certain promoters such as the Protocadherin genes in brain is notably affected and alters gene expression. These results provide further support for the idea that developmental defects in CdLS are caused by deregulated transcription and not by malfunction of cohesion-related processes. © 2013 Elsevier B.V. All rights reserved.

  12. The Cys18-Cys137 Disulfide Bond in Mouse Angiotensinogen Does Not Affect AngII-dependent Functions In Vivo

    PubMed Central

    Wu, Congqing; Xu, Yinchuan; Lu, Hong; Howatt, Deborah A.; Balakrishnan, Anju; Moorleghen, Jessica J.; Vander Kooi, Craig W.; Cassis, Lisa A.; Wang, Jian-an; Daugherty, Alan

    2015-01-01

    Renin cleavage of angiotensinogen (AGT) releases angiotensin I (AngI) in the initial step of producing all angiotensin peptides. It has been suggested recently that redox regulation of a disulfide bond in AGT involving Cys18-Cys137 may be important to its renin cleavage efficiency in vivo. The purpose of this study was to test this prediction in a mouse model by comparing AngII production and AngII-dependent functions in mice expressing wild-type AGT versus a mutated form of AGT lacking the disulfide bond. Wild-type (hepAGT+/+) and hepatocyte-specific AGT deficient (hepAGT−/−) littermates were developed in an LDL receptor −/− background. hepAGT+/+ mice were injected intraperitoneally with adeno-associated viral (AAV) vector containing a null insert. hepAGT−/− mice were injected with AAV containing a null insert, wild-type AGT, or Cys18Ser and Cys137Ser mutated AGT. Two weeks after AAV injection, mice were fed a Western diet for 12 weeks. Administration of AAV containing either form of AGT led to similar plasma AGT concentrations in hepAGT−/− mice. High plasma renin concentrations in hepAGT−/− mice were suppressed equally by both forms of AGT, which were accompanied by comparable increases of plasma AngII concentrations similar to hepAGT+/+ mice. AAV-driven expression of both forms of AGT led to equivalent increases of systolic blood pressure and augmentation of atherosclerotic lesion size in hepAGT−/− mice. These measurements were comparable to systolic blood pressure and atherosclerotic lesions in hepAGT+/+ mice. These data indicate that the Cys18-Cys137 disulfide bond in AGT is dispensable for AngII production and AngII-dependent functions in mice. PMID:25691624

  13. High milk consumption does not affect prostate tumor progression in two mouse models of benign and neoplastic lesions.

    PubMed

    Bernichtein, Sophie; Pigat, Natascha; Capiod, Thierry; Boutillon, Florence; Verkarre, Virginie; Camparo, Philippe; Viltard, Mélanie; Méjean, Arnaud; Oudard, Stéphane; Souberbielle, Jean-Claude; Friedlander, Gérard; Goffin, Vincent

    2015-01-01

    Epidemiological studies that have investigated whether dairy (mainly milk) diets are associated with prostate cancer risk have led to controversial conclusions. In addition, no existing study clearly evaluated the effects of dairy/milk diets on prostate tumor progression, which is clinically highly relevant in view of the millions of men presenting with prostate pathologies worldwide, including benign prostate hyperplasia (BPH) or high-grade prostatic intraepithelial neoplasia (HGPIN). We report here a unique interventional animal study to address this issue. We used two mouse models of fully penetrant genetically-induced prostate tumorigenesis that were investigated at the stages of benign hyperplasia (probasin-Prl mice, Pb-Prl) or pre-cancerous PIN lesions (KIMAP mice). Mice were fed high milk diets (skim or whole) for 15 to 27 weeks of time depending on the kinetics of prostate tumor development in each model. Prostate tumor progression was assessed by tissue histopathology examination, epithelial proliferation, stromal inflammation and fibrosis, tumor invasiveness potency and expression of various tumor markers relevant for each model (c-Fes, Gprc6a, activated Stat5 and p63). Our results show that high milk consumption (either skim or whole) did not promote progression of existing prostate tumors when assessed at early stages of tumorigenesis (hyperplasia and neoplasia). For some parameters, and depending on milk type, milk regimen could even exhibit slight protective effects towards prostate tumor progression by decreasing the expression of tumor-related markers like Ki-67 and Gprc6a. In conclusion, our study suggests that regular milk consumption should not be considered detrimental for patients presenting with early-stage prostate tumors.

  14. High Milk Consumption Does Not Affect Prostate Tumor Progression in Two Mouse Models of Benign and Neoplastic Lesions

    PubMed Central

    Boutillon, Florence; Verkarre, Virginie; Camparo, Philippe; Viltard, Mélanie; Méjean, Arnaud; Oudard, Stéphane; Souberbielle, Jean-Claude; Friedlander, Gérard; Goffin, Vincent

    2015-01-01

    Epidemiological studies that have investigated whether dairy (mainly milk) diets are associated with prostate cancer risk have led to controversial conclusions. In addition, no existing study clearly evaluated the effects of dairy/milk diets on prostate tumor progression, which is clinically highly relevant in view of the millions of men presenting with prostate pathologies worldwide, including benign prostate hyperplasia (BPH) or high-grade prostatic intraepithelial neoplasia (HGPIN). We report here a unique interventional animal study to address this issue. We used two mouse models of fully penetrant genetically-induced prostate tumorigenesis that were investigated at the stages of benign hyperplasia (probasin-Prl mice, Pb-Prl) or pre-cancerous PIN lesions (KIMAP mice). Mice were fed high milk diets (skim or whole) for 15 to 27 weeks of time depending on the kinetics of prostate tumor development in each model. Prostate tumor progression was assessed by tissue histopathology examination, epithelial proliferation, stromal inflammation and fibrosis, tumor invasiveness potency and expression of various tumor markers relevant for each model (c-Fes, Gprc6a, activated Stat5 and p63). Our results show that high milk consumption (either skim or whole) did not promote progression of existing prostate tumors when assessed at early stages of tumorigenesis (hyperplasia and neoplasia). For some parameters, and depending on milk type, milk regimen could even exhibit slight protective effects towards prostate tumor progression by decreasing the expression of tumor-related markers like Ki-67 and Gprc6a. In conclusion, our study suggests that regular milk consumption should not be considered detrimental for patients presenting with early-stage prostate tumors. PMID:25938513

  15. Heat-induced structural changes affect OVA-antigen processing and reduce allergic response in mouse model of food allergy.

    PubMed

    Golias, Jaroslav; Schwarzer, Martin; Wallner, Michael; Kverka, Miloslav; Kozakova, Hana; Srutkova, Dagmar; Klimesova, Klara; Sotkovsky, Petr; Palova-Jelinkova, Lenka; Ferreira, Fatima; Tuckova, Ludmila

    2012-01-01

    The egg protein ovalbumin (OVA) belongs to six most frequent food allergens. We investigated how thermal processing influences its ability to induce allergic symptoms and immune responses in mouse model of food allergy. Effect of increased temperature (70°C and 95°C) on OVA secondary structure was characterized by circular dichroism and by the kinetics of pepsin digestion with subsequent HPLC. BALB/c mice were sensitized intraperitoneally and challenged with repeated gavages of OVA or OVA heated to 70°C (h-OVA). Levels of allergen-specific serum antibodies were determined by ELISA (IgA and IgGs) or by β-hexosaminidase release test (IgE). Specific activities of digestive enzymes were determined in brush border membrane vesicles of jejunal enterocytes. Cytokine production and changes in regulatory T cells in mesenteric lymph nodes and spleen were assessed by ELISA and FACS. Heating of OVA to 70°C caused mild irreversible changes in secondary structure compared to boiling to 95°C (b-OVA), but both OVA treatments led to markedly different digestion kinetics and Tregs induction ability in vitro, compared to native OVA. Heating of OVA significantly decreased clinical symptoms (allergic diarrhea) and immune allergic response on the level of IgE, IL-4, IL-5, IL-13. Furthermore, h-OVA induced lower activities of serum mast cell protease-1 and enterocyte brush border membrane alkaline phosphatase as compared to native OVA. On the other hand h-OVA stimulated higher IgG2a in sera and IFN-γ secretion by splenocytes. Minor irreversible changes in OVA secondary structure caused by thermal processing changes both its digestion and antigenic epitopes formation, which leads to activation of different T cell subpopulations, induces shift towards Th1 response and ultimately reduces its allergenicity.

  16. High fat feeding affects the number of GPR120 cells and enteroendocrine cells in the mouse stomach

    PubMed Central

    Widmayer, Patricia; Goldschmid, Hannah; Henkel, Helena; Küper, Markus; Königsrainer, Alfred; Breer, Heinz

    2015-01-01

    Long-term intake of dietary fat is supposed to be associated with adaptive reactions of the organism and it is assumptive that this is particularly true for fat responsive epithelial cells in the mucosa of the gastrointestinal tract. Recent studies suggest that epithelial cells expressing the receptor for medium and long chain fatty acids, GPR120 (FFAR4), may operate as fat sensors. Changes in expression level and/or cell density are supposed to be accompanied with a consumption of high fat (HF) diet. To assess whether feeding a HF diet might impact on the expression of fatty acid receptors or the number of lipid sensing cells as well as enteroendocrine cell populations, gastric tissue samples of non-obese and obese mice were compared using a real time PCR and immunohistochemical approach. In this study, we have identified GPR120 cells in the corpus region of the mouse stomach which appeared to be brush cells. Monitoring the effect of HF diet on the expression of GPR120 revealed that after 3 weeks and 6 months the level of mRNA for GPR120 in the tissue was significantly increased which coincided with and probably reflected a significant increase in the number of GPR120 positive cells in the corpus region; in contrast, within the antrum region, the number of GPR120 cells decreased. Furthermore, dietary fat intake also led to changes in the number of enteroendocrine cells producing either ghrelin or gastrin. After 3 weeks and even more pronounced after 6 months the number of ghrelin cells and gastrin cells was significantly increased. These results imply that a HF diet leads to significant changes in the cellular repertoire of the stomach mucosa. Whether these changes are a consequence of the direct exposure to HF in the luminal content or a physiological response to the high level of fat in the body remains elusive. PMID:25774135

  17. The effect of high energy (HZE) particle radiation (Ar-40) on aging parameters of mouse hippocampus and retina

    NASA Technical Reports Server (NTRS)

    Philpott, D. E.; Kato, K.; Corbett, R.; Stevenson, J.; Black, S.; Sapp, W.; Miquel, J.; Lindseth, K. A.; Benton, E. V.

    1985-01-01

    Eight month old C57BL6 mice were exposed (head only) to 0.5 rad or 50 rads of Argon particles at the Lawrence Berkeley Radiation Facility, CA. Neuromotor performance was assessed monthly for six months beginning twelve weeks post-irradiation using a 'string test'. The decline in motor performance was dose-related and none of the animals was able to complete the task after four months of testing. Morphological changes were monitored six and twelve months post-irradiation by light and electron microscopy. The synaptic density in the CA-1 area of the hippocampus decreased six and twelve months after irradiation. The decrease after twelve months was less than after six months. The width of the outer nuclear layer (ONL) of the retina increased with increasing dose. The number of blood vessels between the ONL and the ganglion layer decreased twelve months after irradiation and this area did not show significant accumulation of age pigment.

  18. The effect of high energy (HZE) particle radiation (Ar-40) on aging parameters of mouse hippocampus and retina

    NASA Technical Reports Server (NTRS)

    Philpott, D. E.; Kato, K.; Corbett, R.; Stevenson, J.; Black, S.; Sapp, W.; Miquel, J.; Lindseth, K. A.; Benton, E. V.

    1985-01-01

    Eight month old C57BL6 mice were exposed (head only) to 0.5 rad or 50 rads of Argon particles at the Lawrence Berkeley Radiation Facility, CA. Neuromotor performance was assessed monthly for six months beginning twelve weeks post-irradiation using a 'string test'. The decline in motor performance was dose-related and none of the animals was able to complete the task after four months of testing. Morphological changes were monitored six and twelve months post-irradiation by light and electron microscopy. The synaptic density in the CA-1 area of the hippocampus decreased six and twelve months after irradiation. The decrease after twelve months was less than after six months. The width of the outer nuclear layer (ONL) of the retina increased with increasing dose. The number of blood vessels between the ONL and the ganglion layer decreased twelve months after irradiation and this area did not show significant accumulation of age pigment.

  19. A mouse model for ulcerative colitis based on NOD-scid IL2R γnull mice reconstituted with peripheral blood mononuclear cells from affected individuals.

    PubMed

    Palamides, Pia; Jodeleit, Henrika; Föhlinger, Michael; Beigel, Florian; Herbach, Nadja; Mueller, Thomas; Wolf, Eckhard; Siebeck, Matthias; Gropp, Roswitha

    2016-09-01

    Animal models reflective of ulcerative colitis (UC) remain a major challenge, and yet are crucial to understand mechanisms underlying the onset of disease and inflammatory characteristics of relapses and remission. Mouse models in which colitis-like symptoms are induced through challenge with toxins such as oxazolone, dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) have been instrumental in understanding the inflammatory processes of UC. However, these neither reflect the heterogeneous symptoms observed in the UC-affected population nor can they be used to test the efficacy of inhibitors developed against human targets where high sequence and structural similarity of the respective ligands is lacking. In an attempt to overcome these problems, we have developed a mouse model that relies on NOD-scid IL2R γ(null) mice reconstituted with peripheral blood mononuclear cells derived from UC-affected individuals. Upon challenge with ethanol, mice developed colitis-like symptoms and changes in the colon architecture, characterized by influx of inflammatory cells, edema, crypt loss, crypt abscesses and epithelial hyperplasia, as previously observed in immune-competent mice. TARC, TGFβ1 and HGF expression increased in distal parts of the colon. Analysis of human leucocytes isolated from mouse spleen revealed an increase in frequencies of CD1a+, CD64+, CD163+ and TSLPR+ CD14+ monocytes, and antigen-experienced CD44+ CD4+ and CD8+ T-cells in response to ethanol. Analysis of human leucocytes from the colon of challenged mice identified CD14+ monocytes and CD11b+ monocytes as the predominant populations. Quantitative real-time PCR (RT-PCR) analysis from distal parts of the colon indicated that IFNγ might be one of the cytokines driving inflammation. Treatment with infliximab ameliorated symptoms and pathological manifestations, whereas pitrakinra had no therapeutic benefit. Thus, this model is partially reflective of the human disease and might help

  20. Factors affecting magnetic retention of particles in the upper airways: an in vitro and ex vivo study.

    PubMed

    Ally, J; Amirfazli, A; Roa, W

    2006-01-01

    This paper presents the results of experiments using an in vitro model and an ex vivo animal model (Rana catesbeiana) to study magnetic particle retention in the conducting airways, specifically the trachea and bronchi. The purpose of these experiments was to determine the significant factors for retention of magnetic particles deposited from an aerosol at the airway surface using a magnetic field. The results indicate that the apparent viscosity of the mucus layer at low shear rates is the most significant obstacle to particle retention. The results also show that particle size and aggregation play major roles in particle retention. The mucus transport rate, unlike the effect of fluid velocity in intravenous applications, did not appear to be a determining factor for particle retention. It was also found that a suitably designed magnetic system, aside from having a high intensity, needs to exert a strong radial field to promote particle aggregation. The findings suggest that one possible approach to magnetic particle retention could be delivery of a mucolytic agent along with the drug particles. This study provides the fundamentals needed for development of a targeted magnetic drug delivery system for inhaled therapeutic aerosol particles.

  1. Inhibition of the malate-aspartate shuttle in mouse pancreatic islets abolishes glucagon secretion without affecting insulin secretion.

    PubMed

    Stamenkovic, Jelena A; Andersson, Lotta E; Adriaenssens, Alice E; Bagge, Annika; Sharoyko, Vladimir V; Gribble, Fiona; Reimann, Frank; Wollheim, Claes B; Mulder, Hindrik; Spégel, Peter

    2015-05-15

    Altered secretion of insulin as well as glucagon has been implicated in the pathogenesis of Type 2 diabetes (T2D), but the mechanisms controlling glucagon secretion from α-cells largely remain unresolved. Therefore, we studied the regulation of glucagon secretion from αTC1-6 (αTC1 clone 6) cells and compared it with insulin release from INS-1 832/13 cells. We found that INS-1 832/13 and αTC1-6 cells respectively secreted insulin and glucagon concentration-dependently in response to glucose. In contrast, tight coupling of glycolytic and mitochondrial metabolism was observed only in INS-1 832/13 cells. Although glycolytic metabolism was similar in the two cell lines, TCA (tricarboxylic acid) cycle metabolism, respiration and ATP levels were less glucose-responsive in αTC1-6 cells. Inhibition of the malate-aspartate shuttle, using phenyl succinate (PhS), abolished glucose-provoked ATP production and hormone secretion from αTC1-6 but not INS-1 832/13 cells. Blocking the malate-aspartate shuttle increased levels of glycerol 3-phosphate only in INS-1 832/13 cells. Accordingly, relative expression of constituents in the glycerol phosphate shuttle compared with malate-aspartate shuttle was lower in αTC1-6 cells. Our data suggest that the glycerol phosphate shuttle augments the malate-aspartate shuttle in INS-1 832/13 but not αTC1-6 cells. These results were confirmed in mouse islets, where PhS abrogated secretion of glucagon but not insulin. Furthermore, expression of the rate-limiting enzyme of the glycerol phosphate shuttle was higher in sorted primary β- than in α-cells. Thus, suppressed glycerol phosphate shuttle activity in the α-cell may prevent a high rate of glycolysis and consequently glucagon secretion in response to glucose. Accordingly, pyruvate- and lactate-elicited glucagon secretion remains unaffected since their signalling is independent of mitochondrial shuttles.

  2. Response of extracellular matrix regulators in mouse lung after exposure to photons, protons and simulated solar particle event protons.

    PubMed

    Tian, Jian; Pecaut, Michael J; Coutrakon, George B; Slater, James M; Gridley, Daila S

    2009-07-01

    This study compared the effects of photons (gamma rays), protons and simulated solar particle event protons (sSPE) on the expression of profibrotic factors/extracellular matrix (ECM) regulators in lung tissue after whole-body irradiation. TGF-beta1, matrix metalloproteinase 2 and 9 (MMP-2, -9), and tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1, -2) were assessed on days 4 and 21 in lungs from C57BL/6 mice exposed to 0 Gy or 2 Gy photons (0.7 Gy/min), protons (0.9 Gy/min) and sSPE (0.056 Gy/h). RT-PCR, histological and immunohistochemical techniques were used. The most striking changes included (1) up-regulation of TGF-beta1 by photons and sSPE, but not protons, at both times, (2) MMP-2 enhancement by photons and sSPEs, (3) TIMP-1 up-regulation by photons at both times, and (4) more collagen accumulation after exposure to either photons or sSPE than after exposure to protons. The findings demonstrate that expression of important ECM regulators was highly dependent upon the radiation regimen as well as the time after exposure. The data further suggest that irradiation during an SPE may increase an astronaut's risk for pulmonary complications. The greater perturbations after photon exposure compared to proton exposure have clinical implications and warrant further investigation.

  3. Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water.

    PubMed

    Chen, Baowei; Arnold, Lora L; Cohen, Samuel M; Thomas, David J; Le, X Chris

    2011-12-01

    Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic (iAs) producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated arsenicals may contribute to toxicity associated with exposure to inorganic arsenic. Here, adult female wild-type (WT) C57BL/6 mice and female As3mt knockout (KO) mice received drinking water that contained 1, 10, or 25 ppm (mg/l) of arsenite for 33 days and blood, liver, kidney, and lung were taken for arsenic speciation. Genotype markedly affected concentrations of arsenicals in tissues. Summed concentrations of arsenicals in plasma were higher in WT than in KO mice; in red blood cells, summed concentrations of arsenicals were higher in KO than in WT mice. In liver, kidney, and lung, summed concentrations of arsenicals were greater in KO than in WT mice. Although capacity for arsenic methylation is much reduced in KO mice, some mono-, di-, and tri-methylated arsenicals were found in tissues of KO mice, likely reflecting the activity of other tissue methyltransferases or preabsorptive metabolism by the microbiota of the gastrointestinal tract. These results show that the genotype for arsenic methylation determines the phenotypes of arsenic retention and distribution and affects the dose- and organ-dependent toxicity associated with exposure to inorganic arsenic.

  4. [Coupled Cytotoxicity of C60 Nano-Crystal Particle with Cu2+ to the Mouse Peritoneal Macrophage RAW 264.7].

    PubMed

    Yu, Ye; Bian, Wei-lin; Zhang, Hui-min; Zhang, Bo; He, Yi-liang

    2015-07-01

    This work evaluated the cytotoxicity effect of nC60 nano-crystal particle associated with Cu2+ by using mouse peritoneal microphage RAW264. 7 as the test cell line. The results showed that when exposed to nC60 of 6. 6 mg . L-1 and 9. 9 mg . L-1 for 24h, the cell viability decreased 45% and 70% , respectively, and had obvious time-response and dose-response. It was found that Cu2, could reduce the toxicity of nC60 on RAW 264. 7. The cell viability reduced to 25% when exposed to 6. 6 mg . L-1 nC60 with 2 mg . L-1 Cu2+, and reduced to 15% when exposed to 9. 9 mg . L-1 nC60 with 5 mg . L-1 Cu2+. The nC60 could adsorb Cu2+ and the adsorption isotherm was fitted to the Langmuir adsorptiqn isotherm. The adsprption of Cu2+ on the surface of nC60 may decrease the cytotoxicity nC60 on RAW 264.7.

  5. Seasonal variation in chemical composition of size-segregated urban air particles and the inflammatory activity in the mouse lung.

    PubMed

    Happo, M S; Hirvonen, M-R; Hälinen, A I; Jalava, P I; Pennanen, A S; Sillanpää, M; Hillamo, R; Salonen, R O

    2010-01-01

    We investigated the seasonal variations in the chemical composition and in vivo inflammatory activity of urban air particulate samples in four size ranges (PM(10-2.5), PM(2.5-1), PM(1-0.2), and PM(0.2)). The samples were collected in Helsinki using a high-volume cascade impactor (HVCI). Healthy C57BL/6J mice were intratracheally instilled with a single dose (10 mg/kg) of the particulate samples. The lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and keratinocyte-derived chemokine [KC]) at 4 h, and total cell number and total protein concentration at 12 h. The PM(10-2.5) and PM(2.5-1) samples had much higher inflammatory potency than the PM(1-0.2) and PM(0.2) samples. The relative inflammatory activities of the autumn samples were the highest on an equal mass basis, but when estimated for the particulate mass per cubic meter of air, the springtime samples had the highest inflammatory potential. Resuspended soil material and other non-exhaust particulate material from traffic were associated with a high inflammatory activity of the PM(10-2.5) and PM(2.5-1) samples. Secondary inorganic ions in the PM(1-0.2) and PM(0.2) samples had inconsistent negative or positive correlations with the inflammatory activity. There were no systematic seasonal variations in the tracers of incomplete combustion and atmospherically oxidized organics in the PM(1-0.2) and PM(0.2) samples, which probably explains their low correlations with the inflammatory activity. In conclusion, in a relatively clean Nordic city, the resuspension of road dust and other non-exhaust particulate material from traffic were the major sources of inflammatory activity of urban air inhalable particles.

  6. Factors affecting the validity of the 13C-urea breath test for in vivo determination of Helicobacter pylori infection status in a mouse model.

    PubMed

    Hammond, P D; Stutzenberger, F J; Butler, R N; Read, L C; Davidson, G P

    1999-12-01

    The mouse model using a human isolate of Helicobacter pylori is being widely accepted as an economical means of studying gastric infection. A noninvasive monitoring method would be useful for repeated testing to establish the time course of infection and the efficacy of treatments. In this study, we describe factors that affected interpretation of 13C urea breath test results for the assessment of H. pylori infection status in this model. Female C57B1/6 mice that underwent gavage with H. pylori or saline were breath-tested using 50 micrograms of 13C urea at intervals up to 2 months after inoculation. The generation of 13CO2 (excess delta 13CO2) by infected mice was compared to that of uninfected controls. The effects of diet, fasting, and coprophagy on the reliability of the 13C urea breath test were quantitated. Both commercial and synthetic mouse diets exhibited marked in vitro urease activity. A minimum fasting time of 13 hours prior to breath testing significantly reduced this dietary contribution to excess delta 13CO2 values. The coprophagic tendency of the mice caused spuriously high excess delta 13CO2 counts in the breath of both control and H. pylori-infected mice. Although the dietary contribution to spuriously high values of excess delta 13CO2 in mice breath-tested for H. pylori infection was reduced by fasting, the high nonspecific urease activity generated by coprophagy severely limited the reliability of the urea breath test in the assessment of H. pylori infection status.

  7. Effects of particle size and coating on toxicologic parameters, fecal elimination kinetics and tissue distribution of acutely ingested silver nanoparticles in a mouse model.

    PubMed

    Bergin, Ingrid L; Wilding, Laura A; Morishita, Masako; Walacavage, Kim; Ault, Andrew P; Axson, Jessica L; Stark, Diana I; Hashway, Sara A; Capracotta, Sonja S; Leroueil, Pascale R; Maynard, Andrew D; Philbert, Martin A

    2016-01-01

    Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity.

  8. Effects of particle size and coating on toxicologic parameters, fecal elimination kinetics and tissue distribution of acutely ingested silver nanoparticles in a mouse model

    PubMed Central

    Bergin, Ingrid L.; Wilding, Laura A.; Morishita, Masako; Walacavage, Kim; Ault, Andrew P.; Axson, Jessica L.; Stark, Diana I.; Hashway, Sara A.; Capracotta, Sonja S.; Leroueil, Pascale R.; Maynard, Andrew D.; Philbert, Martin A.

    2015-01-01

    Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity. PMID:26305411

  9. Fat mass- and obesity-associated gene Fto affects the dietary response in mouse white adipose tissue.

    PubMed

    Ronkainen, Justiina; Huusko, Tuija J; Soininen, Raija; Mondini, Eleonora; Cinti, Francesca; Mäkelä, Kari A; Kovalainen, Miia; Herzig, Karl-Heinz; Järvelin, Marjo-Riitta; Sebert, Sylvain; Savolainen, Markku J; Salonurmi, Tuire

    2015-03-18

    Common variants of human fat mass- and obesity-associated gene Fto have been linked with higher body mass index, but the biological explanation for the link has remained obscure. Recent findings suggest that these variants affect the homeobox protein IRX3. Here we report that FTO has a role in white adipose tissue which modifies its response to high-fat feeding. Wild type and Fto-deficient mice were exposed to standard or high-fat diet for 16 weeks after which metabolism, behavior and white adipose tissue morphology were analyzed together with adipokine levels and relative expression of genes regulating white adipose tissue adipogenesis and Irx3. Our results indicate that Fto deficiency increases the expression of genes related to adipogenesis preventing adipocytes from becoming hypertrophic after high-fat diet. In addition, we report a novel finding of increased Irx3 expression in Fto-deficient mice after high-fat feeding indicating a complex link between FTO, IRX3 and fat metabolism.

  10. Developmental Exposure to Ethinylestradiol Affects Reproductive Physiology, the GnRH Neuroendocrine Network and Behaviors in Female Mouse

    PubMed Central

    Derouiche, Lyes; Keller, Matthieu; Martini, Mariangela; Duittoz, Anne H.; Pillon, Delphine

    2015-01-01

    During development, environmental estrogens are able to induce an estrogen mimetic action that may interfere with endocrine and neuroendocrine systems. The present study investigated the effects on the reproductive function in female mice following developmental exposure to pharmaceutical ethinylestradiol (EE2), the most widespread and potent synthetic steroid present in aquatic environments. EE2 was administrated in drinking water at environmentally relevant (ENVIR) or pharmacological (PHARMACO) doses [0.1 and 1 μg/kg (body weight)/day respectively], from embryonic day 10 until postnatal day 40. Our results show that both groups of EE2-exposed females had advanced vaginal opening and shorter estrus cycles, but a normal fertility rate compared to CONTROL females. The hypothalamic population of GnRH neurons was affected by EE2 exposure with a significant increase in the number of perikarya in the preoptic area of the PHARMACO group and a modification in their distribution in the ENVIR group, both associated with a marked decrease in GnRH fibers immunoreactivity in the median eminence. In EE2-exposed females, behavioral tests highlighted a disturbed maternal behavior, a higher lordosis response, a lack of discrimination between gonad-intact and castrated males in sexually experienced females, and an increased anxiety-related behavior. Altogether, these results put emphasis on the high sensitivity of sexually dimorphic behaviors and neuroendocrine circuits to disruptive effects of EDCs. PMID:26696819

  11. Anabolic androgens affect the competitive interactions in cell migration and adhesion between normal mouse urothelial cells and urothelial carcinoma cells.

    PubMed

    Huang, Chi-Ping; Hsieh, Teng-Fu; Chen, Chi-Cheng; Hung, Xiao-Fan; Yu, Ai-Lin; Chang, Chawnshang; Shyr, Chih-Rong

    2014-09-26

    The urothelium is constantly rebuilt by normal urothelial cells to regenerate damaged tissues caused by stimuli in urine. However, the urothelial carcinoma cells expand the territory by aberrant growth of tumor cells, which migrate and occupy the damaged tissues to spread outside and disrupt the normal cells and organized tissues and form a tumor. Therefore, the interaction between normal urothelial cells and urothelial carcinoma cells affect the initiation and progression of urothelial tumors if normal urothelial cells fail to migrate and adhere to the damages sites to regenerate the tissues. Here, comparing normal murine urothelial cells with murine urothelial carcinoma cells (MBT-2), we found that normal cells had less migration ability than carcinoma cells. And in our co-culture system we found that carcinoma cells had propensity migrating toward normal urothelial cells and carcinoma cells had more advantages to adhere than normal cells. To reverse this condition, we used anabolic androgen, dihyrotestosterone (DHT) to treat normal cells and found that DHT treatment increased the migration ability of normal urothelial cells toward carcinoma cells and the adhesion capacity in competition with carcinoma cells. This study provides the base of a novel therapeutic approach by using anabolic hormone-enforced normal urothelial cells to regenerate the damage urothelium and defend against the occupancy of carcinoma cells to thwart cancer development and recurrence.

  12. Chronic hypoxia in pregnancy affects thymus development in Balb/c mouse offspring via IL2 Signaling.

    PubMed

    Zhang, Xiaopeng; Zhou, Xiuwen; Li, Lingjun; Sun, Miao; Gao, Qingqing; Zhang, Pengjie; Tang, Jiaqi; He, Yu; Zhu, Di; Xu, Zhice

    2016-04-01

    Hypoxia during pregnancy can adversely affect development. This study, addressed the impact of prenatal hypoxia on thymus development in the rodent offspring. Pregnant Balb/c mice were exposed to hypoxia or normoxia during pregnancy, and the thymuses of their offspring were tested. Chronic hypoxia during pregnancy resulted in significantly decreased fetal body weight, with an increased thymus-to-body weight ratio. Histological analysis revealed a smaller cortical zone in the thymus of the offspring exposed to hypoxia. A reduction in the cortical T lymphocyte population corresponded to increased mRNA abundance of caspase 3 (Casp3) and decreased expression of the proliferation marker Ki-67 (Mki67). Differences in T lymphocyte sub-populations in the thymus further indicate that thymus development in offspring was retarded or stagnated by prenatal hypoxia. The abundance of IL2 and its receptor was reduced in the thymus following prenatal hypoxia. This was accompanied by an increase in thymus HIF1A and IKKβ and a decrease in phosphorylated NFKB, MAP2K1, and MAPK1/3 compared to control pregnancies. Together, these results implicate deficiencies in IL2-mediated signaling as one source of prenatal-hypoxia-impaired thymus development. © 2016 Wiley Periodicals, Inc.

  13. Quinolinic acid injection in mouse medial prefrontal cortex affects reversal learning abilities, cortical connectivity and hippocampal synaptic plasticity

    PubMed Central

    Latif-Hernandez, Amira; Shah, Disha; Ahmed, Tariq; Lo, Adrian C.; Callaerts-Vegh, Zsuzsanna; Van der Linden, Annemie; Balschun, Detlef; D’Hooge, Rudi

    2016-01-01

    Intracerebral injection of the excitotoxic, endogenous tryptophan metabolite, quinolinic acid (QA), constitutes a chemical model of neurodegenerative brain disease. Complementary techniques were combined to examine the consequences of QA injection into medial prefrontal cortex (mPFC) of C57BL6 mice. In accordance with the NMDAR-mediated synapto- and neurotoxic action of QA, we found an initial increase in excitability and an augmentation of hippocampal long-term potentiation, converting within two weeks into a reduction and impairment, respectively, of these processes. QA-induced mPFC excitotoxicity impaired behavioral flexibility in a reversal variant of the hidden-platform Morris water maze (MWM), whereas regular, extended MWM training was unaffected. QA-induced mPFC damage specifically affected the spatial-cognitive strategies that mice use to locate the platform during reversal learning. These behavioral and cognitive defects coincided with changes in cortical functional connectivity (FC) and hippocampal neuroplasticity. FC between various cortical regions was assessed by resting-state fMRI (rsfMRI) methodology, and mice that had received QA injection into mPFC showed increased FC between various cortical regions. mPFC and hippocampus (HC) are anatomically as well as functionally linked as part of a cortical network that controls higher-order cognitive functions. Together, these observations demonstrate the central functional importance of rodent mPFC as well as the validity of QA-induced mPFC damage as a preclinical rodent model of the early stages of neurodegeneration. PMID:27819338

  14. Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain.

    PubMed

    Schnydrig, Sabine; Korner, Lukas; Landweer, Svenja; Ernst, Beat; Walker, Gaby; Otten, Uwe; Kunz, Dieter

    2007-12-11

    Peripheral inflammation induced by intraperitoneal (i.p.) injection of Lipopolysaccharide (LPS) is known to cause functional impairments in the brain affecting memory and learning. One of mechanisms may be the interference with neurotrophin (NT) expression and function. In the current study we administered a single, high dose of LPS (3mg/kg, i.p.) into mice and investigated changes in brain-derived neurotrophic factor (BDNF) gene expression within 1-6 days after LPS injection. Crude synaptosomes were isolated from brain tissue and subjected to Western-blot analyses. We found transient reductions in synaptosomal proBDNF- and BDNF protein expression, with a maximal decrease at day 3 as compared to saline injected controls. The time course of reduction of BDNF mRNA in whole brain extracts parallels the decrease in protein levels in synaptosomes. LPS effects in the central nervous system (CNS) are known to crucially involve the activation of the hypothalamic-pituitary-adrenal (HPA) axis. We analysed the time course of corticotropin releasing hormone (CRH)- and proopiomelanocortin (POMC) mRNA expression. As observed for BDNF-, CRH- and POMC mRNA levels are also significantly reduced on day 3 indicating a comparable time course. These results suggest that peripheral inflammation causes a reduction of trophic supply in the brain, including BDNF at synaptic sites. The mechanisms involved could be a negative feedback of the activated HPA axis.

  15. The spectral karyotype of L5178Y TK⁺/⁻ mouse lymphoma cells clone 3.7.2C and factors affecting mutant frequency at the thymidine kinase (tk) locus in the microtitre mouse lymphoma assay.

    PubMed

    Fellows, Mick D; McDermott, Angela; Clare, Katie R; Doherty, Ann; Aardema, Marilyn J

    2014-01-01

    There has been much discussion on acceptable spontaneous mutant frequencies in the mouse lymphoma assay (MLA). This culminated in the International Workshop on Genotoxicity Testing (IWGT) recommended control limits for the microtitre version of 50-170 mutants/10(6) viable cells, which has now been included in the draft Organization for Economic Co-Operation and Development guideline for assays investigating mammalian cell gene mutation at the tk locus. Some of the factors affecting mutant frequency have been investigated. It was shown that when culturing methotrexate cleansed TK⁺/⁻ cells, a spontaneous mutant frequency of ∼100 mutants/10⁶ viable cells was achieved after only 26 doublings. However, after further culturing for ∼6 months the spontaneous mutant frequency only gradually increased. Culturing for this time did not affect the karyotype of the cell in so much as the modal chromosome number remained stable. The spontaneous mutant frequency could effectively be manipulated by cleansing with various concentrations of methotrexate. The necessity for using appropriately heat-inactivated horse serum was confirmed. Finally, following treatment with 4-nitroquinoline-N-oxide, cells did not preferentially survive when plated at high cell densities (1.6 cells plus 2,000 feeder cells/well) versus cells at low density (1.6 cells/well). It was considered that these findings confirm that the dynamics of spontaneous mutant formation in the MLA are complex. However, the karyotype of L5178Y cells is remarkably stable and assuming investigators are using cells with appropriate provenance and good culturing technique, it is clear that the IWGT recommendations are achievable.

  16. Atrial natriuretic peptide affects cardiac remodeling, function, heart failure, and survival in a mouse model of dilated cardiomyopathy.

    PubMed

    Wang, Dong; Gladysheva, Inna P; Fan, Tai-Hwang M; Sullivan, Ryan; Houng, Aiilyan K; Reed, Guy L

    2014-03-01

    Dilated cardiomyopathy is a frequent cause of heart failure and death. Atrial natriuretic peptide (ANP) is a biomarker of dilated cardiomyopathy, but there is controversy whether ANP modulates the development of heart failure. Therefore, we examined whether ANP affects heart failure, cardiac remodeling, function, and survival in a well-characterized, transgenic model of dilated cardiomyopathy. Mice with dilated cardiomyopathy with normal ANP levels survived longer than mice with partial ANP (P<0.01) or full ANP deficiency (P<0.001). In dilated cardiomyopathy mice, ANP protected against the development of heart failure as indicated by reduced lung water, alveolar congestion, pleural effusions, etc. ANP improved systolic function and reduced cardiomegaly. Pathological cardiac remodeling was diminished in mice with normal ANP as indicated by decreased ventricular interstitial and perivascular fibrosis. Mice with dilated cardiomyopathy and normal ANP levels had better systolic function (P<0.001) than mice with dilated cardiomyopathy and ANP deficiency. Dilated cardiomyopathy was associated with diminished cardiac transcripts for NP receptors A and B in mice with normal ANP and ANP deficiency, but transcripts for NP receptor C and C-type natriuretic peptide were selectively altered in mice with dilated cardiomyopathy and ANP deficiency. Taken together, these data indicate that ANP has potent effects in experimental dilated cardiomyopathy that reduce the development of heart failure, prevent pathological remodeling, preserve systolic function, and reduce mortality. Despite the apparent overlap in physiological function between the NPs, these data suggest that the role of ANP in dilated cardiomyopathy and heart failure is not compensated physiologically by other NPs.

  17. Mono-(2-ethylhexyl)-phthalate (MEHP) affects ERK-dependent GDNF signalling in mouse stem-progenitor spermatogonia.

    PubMed

    Lucas, Benjamin E G; Fields, Christopher; Joshi, Neeraj; Hofmann, Marie-Claude

    2012-09-04

    Many commercial and household products such as lubricants, cosmetics, plastics, and paint contain phthalates, in particular bis-(2-ethyhexyl)-phthalate (DEHP). As a consequence, phthalates have been found in a number of locations and foods (streambeds, household dust, bottled water and dairy products). Epidemiological and animal studies analysing phthalate exposure in males provide evidence of degradation in sperm quality, associated to an increase in the incidence of genital birth defects and testicular cancers. In the testis, spermatogenesis is maintained throughout life by a small number of spermatogonial stem cells (SSCs) that self-renew or differentiate to produce adequate numbers of spermatozoa. Disruption or alteration of SSC self-renewal induce decreased sperm count and sperm quality, or may potentially lead to testicular cancer. GDNF, or glial cell-line-derived neurotrophic factor, is a growth factor that is essential for the self-renewal of SSCs and continuous spermatogenesis. In the present study, the SSC-derived cell line C18-4 was used as a model for preliminary assessment of the effects of mono-(2-ethylhexyl)-phthalate (MEHP, main metabolite of DEHP) on spermatogonial stem cells. Our data demonstrate that MEHP disrupts one of the known GDNF signalling pathways in these cells. MEHP induced a decrease of C18-4 cell viability in a time- and dose-dependent manner, as well as a disruption of ERK1/2 activation but not of SRC signalling. As a result, we observed a decrease of expression of the transcription factor FOS, which is downstream of the GDNF/ERK1/2 axis in these cells. Taken together, our data suggest that MEHP exposure affects SSC proliferation through inhibition of specific signalling molecules. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Exposure for ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats*

    EPA Science Inventory

    Rationale: Exposure to particulate matter is a risk factor for cardiopulmonary disease but the related molecular mechanisms are poorly understood. Previously we studied cardiovascular responses in healthy WKY rats following inhalation exposure to ultrafine carbon particles (UfCPs...

  19. Exposure for ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats*

    EPA Science Inventory

    Rationale: Exposure to particulate matter is a risk factor for cardiopulmonary disease but the related molecular mechanisms are poorly understood. Previously we studied cardiovascular responses in healthy WKY rats following inhalation exposure to ultrafine carbon particles (UfCPs...

  20. Gas-particle partitioning of persistent organic pollutants in the Western Balkan countries affected by war conflicts.

    PubMed

    Radonic, Jelena; Sekulic, Maja Turk; Miloradov, Mirjana Vojinovic; Cupr, Pavel; Klánová, Jana

    2009-01-01

    Bombing and destruction of the industrial and military targets accompanied by complete or incomplete combustion during the war conflict and NATO operation in former Yugoslavia caused the emission of persistent organic pollutants into the atmosphere, water, and soil. A total of 129 ambient air samples from 24 background, urban, and industrial sites, including hot spots, were collected to assess a gas-particle partitioning behavior of various persistent organic pollutants. High volume sampling technique was applied with quartz filters that collect the atmospheric particles and polyurethane foam filters (PUF) that retain the gaseous compounds. Three to ten samples were taken at each site. GFs and PUFs were analyzed separately for their content of polychlorinated biphenyls, organochlorine pesticides, and polyaromatic hydrocarbons. Gas phase and particle phase concentrations of selected persistent organic pollutants (POPs) in all samples were converted into the particle-bound fractions Phi. These fractions were found to be highly variable, but generally highest in Bosnia and Herzegovina due to the elevated levels of total suspended material in ambient air. Experimental values of particle-associated fraction were compared to the Junge-Pankow model. Interestingly, a model for urban/industrial environments provided a better prediction of partitioning behavior than a model for background and rural background sites. That is probably because the total amount of atmospheric particles is higher in the Balkan region than found in the previously published studies. Even though it has been stated in previous studies that less than 5% of polychlorinated biphenyls (PCBs) are bound to the particles, up to 67% of PCBs were particle associated at several sampling sites in this study. PCB-contaminated soils are probably still one of the strong sources of particles to the atmosphere. Information on the particle-bound fractions of POPs is important not only for prediction of their fate but

  1. Particle size distribution, concentration, and magnetic attraction affect transport of polymer-modified Fe(0) nanoparticles in sand columns.

    PubMed

    Phenrat, Tanapon; Kim, Hye-Jin; Fagerlund, Fritjof; Illangasekare, Tissa; Tilton, Robert D; Lowry, Gregory V

    2009-07-01

    The effect of particle concentration, size distribution (polydispersity) and magnetic attractive forces (Fe(0) content) on agglomeration and transport of poly(styrene sulfonate) (PSS) modified NZVI was studied in water-saturated sand (d(p) = 300 microm) columns. Particle concentrations ranged from 0.03 to 6 g/L in 5 mM NaCl/5 mM NaHCO3 at a pore water velocity of 3.2 x 10(-4) m/s. Three NZVI dispersions with different intrinsic particle size distributions obtained from sequential sedimentation are compared. The influence of magnetic attraction (Fe(0) content) on NZVI agglomeration and deposition in porous media is assessed by comparing the deposition behavior of PSS-modified NZVI (magnetic) having different Fe(0) contents with PSS-modified hematite (nonmagnetic) with the same surface modifier. At low particle concentration (30 mg/L) all particles were mobile in sand columns regardless of size or magnetic attractive forces. At high concentration (1 to 6 g/L), deposition of the relatively monodisperse dispersion containing PSS-modified NZVI (hydrodynamic radius (R(H)) = 24 nm) with the lowest Fe(0) content (4 wt%) is low (attachment efficiency (alpha) = 2.5 x 10(-3)), insensitive to particle concentration, and similar to PSS-modified hematite. At 1 to 6 g/L, the attachment efficiency of polydisperse dispersions containing both primary particles and sintered aggregates (R(H) from 15 to 260 nm) of PSS-modified NZVI with a range of Fe(0) content (10-60%) is greater (alpha = 1.2 x 10(-2) to 7.2 x 10(-2) and is sensitive to particle size distribution. The greater attachment for larger, more polydisperse Fe(0) nanoparticles with higher Fe(0) content is a result of their agglomeration during transport in porous media because the magnetic attractive force between particles increases with the sixth power of particle/agglomerate radius. A filtration model that considers agglomeration in porous media and subsequent deposition explains the observed transport of polydisperse PSS

  2. Metabolic depression during warm torpor in the Golden spiny mouse (Acomys russatus) does not affect mitochondrial respiration and hydrogen peroxide release.

    PubMed

    Grimpo, Kirsten; Kutschke, Maria; Kastl, Anja; Meyer, Carola W; Heldmaier, Gerhard; Exner, Cornelia; Jastroch, Martin

    2014-01-01

    Small mammals actively decrease metabolism during daily torpor and hibernation to save energy. Recently, depression of mitochondrial substrate oxidation in isolated liver mitochondria was observed and associated to hypothermic/hypometabolic states in Djungarian hamsters, mice and hibernators. We aimed to clarify whether hypothermia or hypometabolism causes mitochondrial depression during torpor by studying the Golden spiny mouse (Acomys russatus), a desert rodent which performs daily torpor at high ambient temperatures of 32°C. Notably, metabolic rate but not body temperature is significantly decreased under these conditions. In isolated liver, heart, skeletal muscle or kidney mitochondria we found no depression of respiration. Moderate cold exposure lowered torpor body temperature but had minor effects on minimal metabolic rate in torpor. Neither decreased body temperature nor metabolic rate impacted mitochondrial respiration. Measurements of mitochondrial proton leak kinetics and determination of P/O ratio revealed no differences in mitochondrial efficiency. Hydrogen peroxide release from mitochondria was not affected. We conclude that interspecies differences of mitochondrial depression during torpor do not support a general relationship between mitochondrial respiration, body temperature and metabolic rate. In Golden spiny mice, reduction of metabolic rate at mild temperatures is not triggered by depression of substrate oxidation as found in liver mitochondria from other cold-exposed rodents.

  3. Mouse model of rare TOR1A variant found in sporadic focal dystonia impairs domains affected in DYT1 dystonia patients and animal models.

    PubMed

    Bhagat, Srishti L; Qiu, Sunny; Caffall, Zachary F; Wan, Yehong; Pan, Yuanji; Rodriguiz, Ramona M; Wetsel, William C; Badea, Alexandra; Hochgeschwender, Ute; Calakos, Nicole

    2016-09-01

    Rare de novo mutations in genes associated with inherited Mendelian disorders are potential contributors to sporadic disease. DYT1 dystonia is an autosomal dominant, early-onset, generalized dystonia associated with an in-frame, trinucleotide deletion (n. delGAG, p. ΔE 302/303) in the Tor1a gene. Here we examine the significance of a rare missense variant in the Tor1a gene (c. 613T>A, p. F205I), previously identified in a patient with sporadic late-onset focal dystonia, by modeling it in mice. Homozygous F205I mice have motor impairment, reduced steady-state levels of TorsinA, altered corticostriatal synaptic plasticity, and prominent brain imaging abnormalities in areas associated with motor function. Thus, the F205I variant causes abnormalities in domains affected in people and/or mouse models with the DYT1 Tor1a mutation (ΔE). Our findings establish the pathological significance of the F205I Tor1a variant and provide a model with both etiological and phenotypic relevance to further investigate dystonia mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Ketogenic diet delays the phase of circadian rhythms and does not affect AMP-activated protein kinase (AMPK) in mouse liver.

    PubMed

    Genzer, Yoni; Dadon, Maayan; Burg, Chen; Chapnik, Nava; Froy, Oren

    2015-12-05

    Ketogenic diet (KD) is used for weight loss or to treat epilepsy. KD leads to liver AMP-activated protein kinase (AMPK) activation, which would be expected to inhibit gluconeogenesis. However, KD leads to increased hepatic glucose output. As AMPK and its active phosphorylated form (pAMPK) show circadian oscillation, this discrepancy could stem from wrong-time-of-day sampling. The effect of KD was tested on mouse clock gene expression, AMPK, mTOR, SIRT1 and locomotor activity for 2 months and compared to low-fat diet (LFD). KD led to 1.5-fold increased levels of blood glucose and insulin. Brain pAMPK/AMPK ratio was 40% higher under KD, whereas that in liver was not affected. KD led to 40% and 20% down-regulation of the ratio of pP70S6K/P70S6K, the downstream target of mTOR, in the brain and liver, respectively. SIRT1 levels were 40% higher in the brain, but 40% lower in the liver of KD-fed mice. Clock genes showed delayed rhythms under KD. In the brain of KD-fed mice, amplitudes of clock genes were down-regulated, whereas 6-fold up-regulation was found in the liver. The metabolic state under KD indicates reduced satiety in the brain and reduced anabolism alongside increased gluconeogenesis in the liver.

  5. Treatment with the MAO-A inhibitor clorgyline elevates monoamine neurotransmitter levels and improves affective phenotypes in a mouse model of Huntington disease.

    PubMed

    Garcia-Miralles, Marta; Ooi, Jolene; Ferrari Bardile, Costanza; Tan, Liang Juin; George, Maya; Drum, Chester L; Lin, Rachel Yanping; Hayden, Michael R; Pouladi, Mahmoud A

    2016-04-01

    Abnormal monoamine oxidase A and B (MAO-A/B) activity and an imbalance in monoamine neurotransmitters have been suggested to underlie the pathobiology of depression, a major psychiatric symptom observed in patients with neurodegenerative diseases, such as Huntington disease (HD). Increased MAO-A/B activity has been observed in brain tissue from patients with HD and in human and rodent HD neural cells. Using the YAC128 mouse model of HD, we studied the effect of an irreversible MAO-A inhibitor, clorgyline, on the levels of select monoamine neurotransmitters associated with affective function. We observed a decrease in striatal levels of the MAO-A/B substrates, dopamine and norepinephrine, in YAC128 HD mice compared with wild-type mice, which was accompanied by increased anxiety- and depressive-like behaviour at five months of age. Treatment for 26 days with clorgyline restored dopamine, serotonin, and norepinephrine neurotransmitter levels in the striatum and reduced anxiety- and depressive-like behaviour in YAC128 HD mice. This study supports a potential therapeutic use for MAO-A inhibitors in the treatment of depression and anxiety in patients with HD.

  6. Constitutive activation of ectodermal β-catenin induces ectopic outgrowths at various positions in mouse embryo and affects abdominal ventral body wall closure.

    PubMed

    Zhu, Xuming; Huang, Sixia; Zhang, Lingling; Wu, Yumei; Chen, Yingwei; Tao, Yixin; Wang, Yushu; He, Shigang; Shen, Sanbing; Wu, Ji; Li, Baojie; Guo, Xizhi; He, Lin; Ma, Gang

    2014-01-01

    Vertebrate limbs originate from the lateral plate mesoderm (LPM) and the overlying ectoderm. While normal limb formation in defined regions has been well studied, the question of whether other positions retain limb-forming potential has not been fully investigated in mice. By ectopically activating β-catenin in the ectoderm with Msx2-cre, we observed that local tissue outgrowths were induced, which either progressed into limb-like structure within the inter-limb flank or formed extra tissues in other parts of the mouse embryo. In the presumptive abdominal region of severely affected embryos, ectopic limb formation was coupled with impaired abdominal ventral body wall (AVBW) closure, which indicates the existence of a potential counterbalance of limb formation and AVBW closure. At the molecular level, constitutive β-catenin activation was sufficient to trigger, but insufficient to maintain the ectopic expression of a putative limb-inducing factor, Fgf8, in the ectoderm. These findings provide new insight into the mechanism of limb formation and AVBW closure, and the crosstalk between the Wnt/β-catenin pathway and Fgf signal.

  7. Moisture content and particle size of dehydrated egg yolk affect lipid and cholesterol extraction using supercritical carbon dioxide.

    PubMed

    Froning, G W; Wehling, R L; Cuppett, S; Niemann, L

    1998-11-01

    Egg yolk was spray-dried under conditions to produce a small particle size powder and a large particle size powder. Particle size was determined using a Nikon Optiophot microscope. Spray-dried egg yolk was also adjusted to various moisture levels as follows: control (2 to 4% moisture), 7% moisture, and 12% moisture. Supercritical carbon dioxide extraction (SCE) of each of these moisture treatments at 45 C/306 atm using 30 g CO2/g of sample was completed. For the particle size study, 45 g CO2/g of sample at 45 C/306 atm was utilized. Particle size exhibited a significant effect on cholesterol and lipids extracted using SCE. As moisture content of dried egg yolk increased to 7%, there was a significant increase in lipids extracted using supercritical carbon dioxide. Moisture content had no significant effect on cholesterol extraction. After extracting SCE higher moisture spray-dried egg yolk, sponge cake volume was significantly reduced compared to that of the control. The reduced sponge cake volume may be due to protein denaturation.

  8. Rearing Light Intensity Affects Inner Retinal Pathology in a Mouse Model of X-Linked Retinoschisis but Does Not Alter Gene Therapy Outcome.

    PubMed

    Marangoni, Dario; Yong, Zeng; Kjellström, Sten; Vijayasarathy, Camasamudram; A Sieving, Paul; Bush, Ronald A

    2017-03-01

    To test the effects of rearing light intensity on retinal function and morphology in the retinoschisis knockout (Rs1-KO) mouse model of X-linked retinoschisis, and whether it affects functional outcome of RS1 gene replacement. Seventy-six Rs1-KO mice were reared in either cyclic low light (LL, 20 lux) or moderate light (ML, 300 lux) and analyzed at 1 and 4 months. Retinal function was assessed by electroretinogram and cavity size by optical coherence tomography. Expression of inward-rectifier K+ channel (Kir4.1), water channel aquaporin-4 (AQP4), and glial fibrillary acidic protein (GFAP) were analyzed by Western blotting. In a separate study, Rs1-KO mice reared in LL (n = 29) or ML (n = 27) received a unilateral intravitreal injection of scAAV8-hRs-IRBP at 21 days, and functional outcome was evaluated at 4 months by electroretinogram. At 1 month, no functional or structural differences were found between LL- or ML-reared Rs1-KO mice. At 4 months, ML-reared Rs1-KO mice showed significant reduction of b-wave amplitude and b-/a-wave ratio with no changes in a-wave, and a significant increase in cavity size, compared to LL-reared animals. Moderate light rearing increased Kir4.1 expression in Rs1-KO mice by 4 months, but not AQP4 and GFAP levels. Administration of scAAV8-hRS1-IRBP to Rs1-KO mice showed similar improvement of inner retinal ERG function independent of LL or ML rearing. Rearing light conditions affect the development of retinal cavities and post-photoreceptor function in Rs1-KO mice. However, the effect of rearing light intensity does not interact with the efficacy of RS1 gene replacement in Rs1-KO mice.

  9. Rearing Light Intensity Affects Inner Retinal Pathology in a Mouse Model of X-Linked Retinoschisis but Does Not Alter Gene Therapy Outcome

    PubMed Central

    Marangoni, Dario; Yong, Zeng; Kjellström, Sten; Vijayasarathy, Camasamudram; A. Sieving, Paul; Bush, Ronald A.

    2017-01-01

    Purpose To test the effects of rearing light intensity on retinal function and morphology in the retinoschisis knockout (Rs1-KO) mouse model of X-linked retinoschisis, and whether it affects functional outcome of RS1 gene replacement. Methods Seventy-six Rs1-KO mice were reared in either cyclic low light (LL, 20 lux) or moderate light (ML, 300 lux) and analyzed at 1 and 4 months. Retinal function was assessed by electroretinogram and cavity size by optical coherence tomography. Expression of inward-rectifier K+ channel (Kir4.1), water channel aquaporin-4 (AQP4), and glial fibrillary acidic protein (GFAP) were analyzed by Western blotting. In a separate study, Rs1-KO mice reared in LL (n = 29) or ML (n = 27) received a unilateral intravitreal injection of scAAV8-hRs-IRBP at 21 days, and functional outcome was evaluated at 4 months by electroretinogram. Results At 1 month, no functional or structural differences were found between LL- or ML-reared Rs1-KO mice. At 4 months, ML-reared Rs1-KO mice showed significant reduction of b-wave amplitude and b-/a-wave ratio with no changes in a-wave, and a significant increase in cavity size, compared to LL-reared animals. Moderate light rearing increased Kir4.1 expression in Rs1-KO mice by 4 months, but not AQP4 and GFAP levels. Administration of scAAV8-hRS1-IRBP to Rs1-KO mice showed similar improvement of inner retinal ERG function independent of LL or ML rearing. Conclusions Rearing light conditions affect the development of retinal cavities and post-photoreceptor function in Rs1-KO mice. However, the effect of rearing light intensity does not interact with the efficacy of RS1 gene replacement in Rs1-KO mice. PMID:28297725

  10. Radial pressure in the solar nebula as affecting the motions of planetesimals. [toroidal particle concentration in planetary evolution

    NASA Technical Reports Server (NTRS)

    Whipple, F. L.

    1973-01-01

    Growing planetesimals and a range of drag laws depending on the Reynolds number and on the ratio of particle size to mean free path are considered. Particles spiral in the direction of positive gradient, thus being concentrated toward toroidal concentrations of gas. The effect increases with decreasing rates of particle growth, i.e., with increasing time scales of planet formation by accretion. In the outer regions, where evidence suggests that comets were formed and Uranus and Neptune were so accumulated, the effect of the pressure gradient is to clear the forming comets from those regions. The large mass of Neptune may have developed because of this effect, perhaps Neptune's solar distance was reduced from Bode's law, and perhaps no comet belt exists beyond Neptune. In the asteroid belt, on a slow time scale, the effect may have spiraled planetesimals toward Mars and Jupiter, thus contributing to the lack of planet formation in this region.

  11. How do changes in bulk soil organic carbon content affect carbon concentrations in individual soil particle fractions?

    PubMed Central

    Yang, X. M.; Drury, C. F.; Reynolds, W. D.; Yang, J. Y.

    2016-01-01

    We test the common assumption that organic carbon (OC) storage occurs on sand-sized soil particles only after the OC storage capacity on silt- and clay-sized particles is saturated. Soil samples from a Brookston clay loam in Southwestern Ontario were analysed for the OC concentrations in bulk soil, and on the clay (<2 μm), silt (2–53 μm) and sand (53–2000 μm) particle size fractions. The OC concentrations in bulk soil ranged from 4.7 to 70.8 g C kg−1 soil. The OC concentrations on all three particle size fractions were significantly related to the OC concentration of bulk soil. However, OC concentration increased slowly toward an apparent maximum on silt and clay, but this maximum was far greater than the maximum predicted by established C sequestration models. In addition, significant increases in OC associated with sand occurred when the bulk soil OC concentration exceeded 30 g C kg−1, but this increase occurred when the OC concentration on silt + clay was still far below the predicted storage capacity for silt and clay fractions. Since the OC concentrations in all fractions of Brookston clay loam soil continued to increase with increasing C (bulk soil OC content) input, we concluded that the concept of OC storage capacity requires further investigation. PMID:27251365

  12. How does vegetation affect sedimentation on tidal marshes? Investigating particle capture and hydrodynamic controls on biologically mediated sedimentation

    NASA Astrophysics Data System (ADS)

    Mudd, Simon M.; D'Alpaos, Andrea; Morris, James T.

    2010-09-01

    Plants are known to enhance sedimentation on intertidal marshes. It is unclear, however, if the dominant mechanism of enhanced sedimentation is direct organic sedimentation, particle capture by plant stems, or enhanced settling due to a reduction in turbulent kinetic energy within flows through the plant canopy. Here we combine several previously reported laboratory studies with an 18 year record of salt marsh macrophyte characteristics to quantify these mechanisms. In dense stands of Spartina alterniflora (with projected plant areas per unit volume of >10 m-1) and rapid flows (>0.4 m s-1), we find that the fraction of sedimentation from particle capture can instantaneously exceed 70%. In most marshes dominated by Spartina alterniflora, however, we find particle settling, rather than capture, will account for the majority of inorganic sedimentation. We examine a previously reported 2 mm yr-1 increase in accretion rate following a fertilization experiment in South Carolina. Prior studies at the site have ruled out organic sedimentation as the cause of this increased accretion. We apply our newly developed models of particle capture and effective settling velocity to the fertilized and control sites and find that virtually all (>99%) of the increase in accretion rates can be attributed to enhanced settling brought about by reduced turbulent kinetic energy in the fertilized canopy. Our newly developed models of biologically mediated sedimentation are broadly applicable and can be applied to marshes where data relating biomass to stem diameter and projected plant area are available.

  13. How do changes in bulk soil organic carbon content affect carbon concentrations in individual soil particle fractions?

    PubMed

    Yang, X M; Drury, C F; Reynolds, W D; Yang, J Y

    2016-06-02

    We test the common assumption that organic carbon (OC) storage occurs on sand-sized soil particles only after the OC storage capacity on silt- and clay-sized particles is saturated. Soil samples from a Brookston clay loam in Southwestern Ontario were analysed for the OC concentrations in bulk soil, and on the clay (<2 μm), silt (2-53 μm) and sand (53-2000 μm) particle size fractions. The OC concentrations in bulk soil ranged from 4.7 to 70.8 g C kg(-1) soil. The OC concentrations on all three particle size fractions were significantly related to the OC concentration of bulk soil. However, OC concentration increased slowly toward an apparent maximum on silt and clay, but this maximum was far greater than the maximum predicted by established C sequestration models. In addition, significant increases in OC associated with sand occurred when the bulk soil OC concentration exceeded 30 g C kg(-1), but this increase occurred when the OC concentration on silt + clay was still far below the predicted storage capacity for silt and clay fractions. Since the OC concentrations in all fractions of Brookston clay loam soil continued to increase with increasing C (bulk soil OC content) input, we concluded that the concept of OC storage capacity requires further investigation.

  14. How does breathing frequency affect the performance of an N95 filtering facepiece respirator and a surgical mask against surrogates of viral particles?

    PubMed

    He, Xinjian; Reponen, Tiina; McKay, Roy; Grinshpun, Sergey A

    2014-01-01

    Breathing frequency (breaths/min) differs among individuals and levels of physical activity. Particles enter respirators through two principle penetration pathways: faceseal leakage and filter penetration. However, it is unknown how breathing frequency affects the overall performance of N95 filtering facepiece respirators (FFRs) and surgical masks (SMs) against viral particles, as well as other health-relevant submicrometer particles. A FFR and SM were tested on a breathing manikin at four mean inspiratory flows (MIFs) (15, 30, 55, and 85 L/min) and five breathing frequencies (10, 15, 20, 25, and 30 breaths/min). Filter penetration (Pfilter) and total inward leakage (TIL) were determined for the tested respiratory protection devices against sodium chloride (NaCl) aerosol particles in the size range of 20 to 500 nm. "Faceseal leakage-to-filter" (FLTF) penetration ratios were calculated. Both MIF and breathing frequency showed significant effects (p < 0.05) on Pfilter and TIL. Increasing breathing frequency increased TIL for the N95 FFR whereas no clear trends were observed for the SM. Increasing MIF increased Pfilter and decreased TIL resulting in decreasing FLTF ratio. Most of FLTF ratios were >1, suggesting that the faceseal leakage was the primary particle penetration pathway at various breathing frequencies. Breathing frequency is another factor (besides MIF) that can significantly affect the performance of N95 FFRs, with higher breathing frequencies increasing TIL. No consistent trend of increase or decrease of TIL with either MIF or breathing frequency was observed for the tested SM. To potentially extend these findings beyond the manikin/breathing system used, future studies are needed to fully understand the mechanism causing the breathing frequency effect on the performance of respiratory protection devices on human subjects.

  15. Identification of the Bile Acid Transporter Slco1a6 as a Candidate Gene That Broadly Affects Gene Expression in Mouse Pancreatic Islets

    PubMed Central

    Tian, Jianan; Keller, Mark P.; Oler, Angie T.; Rabaglia, Mary E.; Schueler, Kathryn L.; Stapleton, Donald S.; Broman, Aimee Teo; Zhao, Wen; Kendziorski, Christina; Yandell, Brian S.; Hagenbuch, Bruno; Broman, Karl W.; Attie, Alan D.

    2015-01-01

    We surveyed gene expression in six tissues in an F2 intercross between mouse strains C57BL/6J (abbreviated B6) and BTBR T+ tf/J (abbreviated BTBR) made genetically obese with the Leptinob mutation. We identified a number of expression quantitative trait loci (eQTL) affecting the expression of numerous genes distal to the locus, called trans-eQTL hotspots. Some of these trans-eQTL hotspots showed effects in multiple tissues, whereas some were specific to a single tissue. An unusually large number of transcripts (∼8% of genes) mapped in trans to a hotspot on chromosome 6, specifically in pancreatic islets. By considering the first two principal components of the expression of genes mapping to this region, we were able to convert the multivariate phenotype into a simple Mendelian trait. Fine mapping the locus by traditional methods reduced the QTL interval to a 298-kb region containing only three genes, including Slco1a6, one member of a large family of organic anion transporters. Direct genomic sequencing of all Slco1a6 exons identified a nonsynonymous coding SNP that converts a highly conserved proline residue at amino acid position 564 to serine. Molecular modeling suggests that Pro564 faces an aqueous pore within this 12-transmembrane domain-spanning protein. When transiently overexpressed in HEK293 cells, BTBR organic anion transporting polypeptide (OATP)1A6-mediated cellular uptake of the bile acid taurocholic acid (TCA) was enhanced compared to B6 OATP1A6. Our results suggest that genetic variation in Slco1a6 leads to altered transport of TCA (and potentially other bile acids) by pancreatic islets, resulting in broad gene regulation. PMID:26385979

  16. Chronic alcohol exposure affects pancreatic acinar mitochondrial thiamin pyrophosphate uptake: studies with mouse 266-6 cell line and primary cells

    PubMed Central

    Srinivasan, Padmanabhan; Nabokina, Svetlana

    2015-01-01

    Thiamin is essential for normal metabolic activity of all mammalian cells, including those of the pancreas. Cells obtain thiamin from their surroundings and enzymatically convert it into thiamin pyrophosphate (TPP) in the cytoplasm; TPP is then taken up by mitochondria via a specific carrier the mitochondrial TPP transporter (MTPPT; product of the SLC25A19 gene). Chronic alcohol exposure negatively impacts the health of pancreatic acinar cells (PAC), but its effect on physiological/molecular parameters of MTPPT is not known. We addressed this issue using mouse pancreatic acinar tumor cell line 266-6 and primary PAC of wild-type and transgenic mice carrying the SLC25A19 promoter that were fed alcohol chronically. Chronic alcohol exposure of 266-6 cells (but not to its nonoxidative metabolites ethyl palmitate and ethyl oleate) led to a significant inhibition in mitochondrial TPP uptake, which was associated with a decreased expression of MTPPT protein, mRNA, and activity of the SLC25A19 promoter. Similarly, chronic alcohol feeding of mice led to a significant inhibition in expression of MTPPT protein, mRNA, heterogeneous nuclear RNA, as well as in activity of SLC25A19 promoter in PAC. While chronic alcohol exposure did not affect DNA methylation of the Slc25a19 promoter, a significant decrease in histone H3 euchromatin markers and an increase in H3 heterochromatin marker were observed. These findings show, for the first time, that chronic alcohol exposure negatively impacts pancreatic MTPPT, and that this effect is exerted, at least in part, at the level of Slc25a19 transcription and appears to involve epigenetic mechanism(s). PMID:26316591

  17. Identification of the Bile Acid Transporter Slco1a6 as a Candidate Gene That Broadly Affects Gene Expression in Mouse Pancreatic Islets.

    PubMed

    Tian, Jianan; Keller, Mark P; Oler, Angie T; Rabaglia, Mary E; Schueler, Kathryn L; Stapleton, Donald S; Broman, Aimee Teo; Zhao, Wen; Kendziorski, Christina; Yandell, Brian S; Hagenbuch, Bruno; Broman, Karl W; Attie, Alan D

    2015-11-01

    We surveyed gene expression in six tissues in an F2 intercross between mouse strains C57BL/6J (abbreviated B6) and BTBR T(+) tf/J (abbreviated BTBR) made genetically obese with the Leptin(ob) mutation. We identified a number of expression quantitative trait loci (eQTL) affecting the expression of numerous genes distal to the locus, called trans-eQTL hotspots. Some of these trans-eQTL hotspots showed effects in multiple tissues, whereas some were specific to a single tissue. An unusually large number of transcripts (∼8% of genes) mapped in trans to a hotspot on chromosome 6, specifically in pancreatic islets. By considering the first two principal components of the expression of genes mapping to this region, we were able to convert the multivariate phenotype into a simple Mendelian trait. Fine mapping the locus by traditional methods reduced the QTL interval to a 298-kb region containing only three genes, including Slco1a6, one member of a large family of organic anion transporters. Direct genomic sequencing of all Slco1a6 exons identified a nonsynonymous coding SNP that converts a highly conserved proline residue at amino acid position 564 to serine. Molecular modeling suggests that Pro564 faces an aqueous pore within this 12-transmembrane domain-spanning protein. When transiently overexpressed in HEK293 cells, BTBR organic anion transporting polypeptide (OATP)1A6-mediated cellular uptake of the bile acid taurocholic acid (TCA) was enhanced compared to B6 OATP1A6. Our results suggest that genetic variation in Slco1a6 leads to altered transport of TCA (and potentially other bile acids) by pancreatic islets, resulting in broad gene regulation.

  18. The NK Cell Response to Mouse Cytomegalovirus Infection Affects the Level and Kinetics of the Early CD8+ T-Cell Response

    PubMed Central

    Mitrović, Maja; Arapović, Jurica; Jordan, Stefan; Fodil-Cornu, Nassima; Ebert, Stefan; Vidal, Silvia M.; Krmpotić, Astrid; Reddehase, Matthias J.

    2012-01-01

    Natural killer (NK) cells and CD8+ T cells play a prominent role in the clearance of mouse cytomegalovirus (MCMV) infection. The role of NK cells in modulating the CD8+ T-cell response to MCMV infection is still the subject of intensive research. For analyzing the impact of NK cells on mounting of a CD8+ T-cell response and the contribution of these cells to virus control during the first days postinfection (p.i.), we used C57BL/6 mice in which NK cells are specifically activated through the Ly49H receptor engaged by the MCMV-encoded ligand m157. Our results indicate that the requirement for CD8+ T cells in early MCMV control inversely correlates with the engagement of Ly49H. While depletion of CD8+ T cells has only a minor effect on the early control of wild-type MCMV, CD8+ T cells are essential in the control of Δm157 virus. The frequencies of virus epitope-specific CD8+ T cells and their activation status were higher in mice infected with Δm157 virus. In addition, these mice showed elevated levels of alpha interferon (IFN-α) and several other proinflammatory cytokines as early as 1.5 days p.i. Although the numbers of conventional dendritic cells (cDCs) were reduced later during infection, particularly in Δm157-infected mice, they were not significantly affected at the peak of the cytokine response. Altogether, we concluded that increased antigen load, preservation of early cDCs' function, and higher levels of innate cytokines collectively account for an enhanced CD8+ T-cell response in C57BL/6 mice infected with a virus unable to activate NK cells via the Ly49H–m157 interaction. PMID:22156533

  19. Dietary forage concentration and particle size affect sorting, feeding behaviour, intake and growth of Chinese Holstein male calves.

    PubMed

    Muhammad, A U R; Xia, C Q; Cao, B H

    2016-04-01

    The objective of study was to evaluate the effect of forage concentration (F:C) and forage particle length (FPL) on sorting, feeding behaviour, intake, growth and body measurements of growing calves. Twenty-eight weaned calves of body weight 156.79 ± 33.44 (mean ± SD) were used in 2 × 2 factorial arrangements with the factors FPL of hay grass (full and short) and hay grass concentrations (low, 50% and high, 65%). The treatments were as follows: full length (FL) with low F:C (50:50), FL with high F:C(65:35), short length (SL) with low F:C (50:50) and SL with high F:C (65:35). Increasing F:C and decreasing FPL enhanced sorting for short and fine particle and sorting against long particle (p < 0.05). Dry matter intake (DMI) was decreased by decreasing the FPL (p < 0.05). Increasing F:C (65:35) increased the DMI (p < 0.05). A positive interaction between FPL and F:C was found for (daily weight gain) DWG, weight gain (WG) and feed conversation ratio (FCR) (p < 0.05). In case of feeding behaviour, interaction for eating time and eating time per kilogram DM was present. Increasing the F:C increased the eating time in both FL and SL (p < 0.05). Chopping of hay had decreased the chewing time (p < 0.05). Increasing F:C increased chewing time per kilogram DMI. High F:C decreased the lying time (p < 0.05) in FL and SL treatments (p < 0.05). Increasing F:C reduced the overall abnormal behaviour (p < 0.05). These results suggested that animals performed better at higher F:C at SL diet. Intensity of sorting for short and fine particle and against long particle increased at higher F:C and SL diets. Eating time and eating time per kilogram DMI increased by increasing F:C level in both FL and SL treatments. Chewing time increased by increasing the FPL, while increasing the F:C enhanced the chewing time per kilogram DMI and reduced animal's abnormal behaviour. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  20. Factors affecting non-tailpipe aerosol particle emissions from paved roads: On-road measurements in Stockholm, Sweden

    NASA Astrophysics Data System (ADS)

    Hussein, Tareq; Johansson, Christer; Karlsson, Hans; Hansson, Hans-Christen

    A large fraction of urban PM 10 concentrations is due to non-exhaust traffic emissions. In this paper, a mobile measurement system has been used to quantify the relative importance of road particle emission and suspension of accumulated dust versus direct pavement wear, tire type (studded, friction, and summer), pavement type, and vehicle speed. Measurements were performed during May-September on selected roads with different pavements and traffic conditions in the Stockholm region. The highest particle mass concentrations were always observed behind the studded tire and the lowest were behind the summer tire; studded-to-summer ratios were 4.4-17.3 and studded-to-friction ratios were 2.0-6.4. This indicates that studded tires lead to higher emissions than friction and summer tires regardless to the asphalt type. By comparing with measurements in a road simulator, it could be estimated that the pavement wear due to the friction tires was 0.018-0.068 of the suspension of accumulated road dust. Likewise for studded tires road-wear was estimated to be 1.2-4.8 the suspension of accumulated dust. This indicates that wear due to friction tires is very small compared to the suspension of accumulated dust and that suspension due to studded tires may sometimes be as large as the wear of the road. But this will vary depending on, e.g. the amount of dust accumulated on the roads. An important dependence on vehicle speed was also observed. During May, the particle mass concentrations behind the studded tire at vehicle speed 100 km h -1 were about 10 times higher than that at 20 km h -1. The speed dependence was not so pronounced in September, which could be due to less accumulated dust on the roads. The particle number size distribution of the emissions due to road wear by studded tire was characterized by a clear increase in number concentrations of the coarse fraction of aerosol particles, with a geometric mean diameter between 3 and 5 μm. The size distribution of the

  1. Particle Size of Milk Protein Concentrate Powder Affects the Texture of High-Protein Nutrition Bars During Storage.

    PubMed

    Banach, J C; Clark, S; Lamsal, B P

    2017-03-07

    Milk protein concentrate powder with 85% protein (MPC85) was jet-milled to give 2 particle size distributions (that is, JM-Coarse and JM-Fine) or freeze-dried (FD), in order to improve the functional properties of MPC85 for use in high-protein nutrition (HPN) bars. Volume-weighted mean diameter decreased from 86 μm to 49, 22, and 8 μm in FD, JM-Coarse, and JM-Fine, respectively (P < 0.05). The MPC85 powders modified by jet-milling and freeze-drying were significantly denser than the control MPC85 (P < 0.05). Volume of occluded air in the modified powders decreased (P < 0.05) by an order of magnitude, yet only FD possessed a lower volume of interstitial air (P < 0.05). Particle size reduction and freeze-drying MPC85 decreased its water holding capacity and improved its dispersibility by at least 20%. Contact angle measurements showed that these modifications increased initial hydrophobicity and did not improve wettability. HPN bars made from JM-Fine or FD were firmer by 40 or 17 N, respectively, than the control on day 0 (P < 0.05). HPN bar maximum compressive force increased by 38%, 33%, and 242% after 42 d at 32 °C when formulated with JM-Fine, FD, or control MPC85, respectively. HPN bars prepared with JM-Fine were less crumbly than those formulated with control or FD MPC85. Physically altering the particle structure of MPC85 improved its ability to plasticize within HPN bars and this improved their cohesiveness and textural stability.

  2. Erosion study in turbomachinery affected by coal and ash particles. Annual progress report, November 1, 1978-December 31, 1979

    SciTech Connect

    Tabakoff, W.; Hamed, A.; Ramachandran, J.; Kotwal, R.; Beacher, B.

    1980-02-01

    Three alloys were tested in the test facility which has been designed to simulate the aerodynamic and thermodynamic conditions in the turbine. The effects on erosion due to the high tempeature coal ash gas stream was determined at several gas temperatures, particle velocities and angles of attack. The test results for 304 stainless steel, Rene 41 and A286, and the corresponding conclusions are presented. In addition, a series of experiments were conducted to determine the effects of fly ash constituents on the erosion of iron and nickel base alloys. A new semi-empirical equation has been obtained for the prediction of metal erosion due to the fly ash.

  3. Formation of vitamin D nanoemulsion-based delivery systems by spontaneous emulsification: factors affecting particle size and stability.

    PubMed

    Guttoff, Marrisa; Saberi, Amir Hossein; McClements, David Julian

    2015-03-15

    Oil-in-water nanoemulsions are particularly suitable for encapsulation of lipophilic nutraceuticals because of their ability to form stable and transparent delivery systems with high oral bioavailability. In this study, the influence of system composition and preparation conditions on the particle size and stability of vitamin D nanoemulsions prepared by spontaneous emulsification (SE) was investigated. SE relies on the formation of small oil droplets when an oil/surfactant mixture is titrated into an aqueous solution. The influence of oil phase composition (vitamin D and MCT), surfactant-to-oil ratio (SOR), surfactant type (Tween 20, 40, 60, 80 and 85), and stirring conditions on the initial particle size of vitamin D nanoemulsions was studied. Nanoemulsions with small droplet diameters (d<200 nm) could be formed using Tween 80 at SOR⩾1 at high stirring speeds (800 rpm). These systems were relatively stable to droplet growth at ambient temperatures (<10% in diameter after 1 month storage), but unstable to heating (T>80°C). The thermal stability of the nanoemulsions could be improved by adding a cosurfactant (sodium dodecyl sulphate (SDS)). The spontaneous emulsification method is simple and inexpensive to carry out and therefore has great potential for forming nanoemulsion-based delivery systems for food, personal care, and pharmaceutical applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Differential proteomic analysis of mouse macrophages exposed to adsorbate-loaded heavy fuel oil derived combustion particles using an automated sample-preparation workflow.

    PubMed

    Kanashova, Tamara; Popp, Oliver; Orasche, Jürgen; Karg, Erwin; Harndorf, Horst; Stengel, Benjamin; Sklorz, Martin; Streibel, Thorsten; Zimmermann, Ralf; Dittmar, Gunnar

    2015-08-01

    Ship diesel combustion particles are known to cause broad cytotoxic effects and thereby strongly impact human health. Particles from heavy fuel oil (HFO) operated ships are considered as particularly dangerous. However, little is known about the relevant components of the ship emission particles. In particular, it is interesting to know if the particle cores, consisting of soot and metal oxides, or the adsorbate layers, consisting of semi- and low-volatile organic compounds and salts, are more relevant. We therefore sought to relate the adsorbates and the core composition of HFO combustion particles to the early cellular responses, allowing for the development of measures that counteract their detrimental effects. Hence, the semi-volatile coating of HFO-operated ship diesel engine particles was removed by stepwise thermal stripping using different temperatures. RAW 264.7 macrophages were exposed to native and thermally stripped particles in submersed culture. Proteomic changes were monitored by two different quantitative mass spectrometry approaches, stable isotope labeling by amino acids in cell culture (SILAC) and dimethyl labeling. Our data revealed that cells reacted differently to native or stripped HFO combustion particles. Cells exposed to thermally stripped particles showed a very differential reaction with respect to the composition of the individual chemical load of the particle. The cellular reactions of the HFO particles included reaction to oxidative stress, reorganization of the cytoskeleton and changes in endocytosis. Cells exposed to the 280 °C treated particles showed an induction of RNA-related processes, a number of mitochondria-associated processes as well as DNA damage response, while the exposure to 580 °C treated HFO particles mainly induced the regulation of intracellular transport. In summary, our analysis based on a highly reproducible automated proteomic sample-preparation procedure shows a diverse cellular response, depending on the

  5. The CELF1 RNA-Binding Protein Regulates Decay of Signal Recognition Particle mRNAs and Limits Secretion in Mouse Myoblasts

    PubMed Central

    Russo, Joseph; Lee, Jerome E.; López, Carolina M.; Anderson, John; Nguyen, Thuy-mi P.; Heck, Adam M.; Wilusz, Jeffrey

    2017-01-01

    We previously identified several mRNAs encoding components of the secretory pathway, including signal recognition particle (SRP) subunit mRNAs, among transcripts associated with the RNA-binding protein CELF1. Through immunoprecipitation of RNAs crosslinked to CELF1 in myoblasts and in vitro binding assays using recombinant CELF1, we now provide evidence that CELF1 directly binds the mRNAs encoding each of the subunits of the SRP. Furthermore, we determined the half-lives of the Srp transcripts in control and CELF1 knockdown myoblasts. Our results indicate CELF1 is a destabilizer of at least five of the six Srp transcripts and that the relative abundance of the SRP proteins is out of balance when CELF1 is depleted. CELF1 knockdown myoblasts exhibit altered secretion of a luciferase reporter protein and are impaired in their ability to migrate and close a wound, consistent with a defect in the secreted extracellular matrix. Importantly, similar defects in wound healing are observed when SRP subunit imbalance is induced by over-expression of SRP68. Our studies support the existence of an RNA regulon containing Srp mRNAs that is controlled by CELF1. One implication is that altered function of CELF1 in myotonic dystrophy may contribute to changes in the extracellular matrix of affected muscle through defects in secretion. PMID:28129347

  6. Addition of pectin and soy soluble polysaccharide affects the particle size distribution of casein suspensions prepared from acidified skim milk.

    PubMed

    Liu, JinRu; Nakamura, Akihiro; Corredig, Milena

    2006-08-23

    Pectins are negatively charged polysaccharides employed as stabilizers in acidified milk dispersions, where caseins aggregate because of the low pH and serum separation needs to be prevented. The objective of this research was to study the effect of charge on the stabilizing functionality of the polysaccharide in acid milk drinks. Unstandardized pectins with various charges (as degree of esterification, DE) as well as soybean soluble polysaccharide (SSPS) were tested for their stabilizing behavior as a function of pH and concentration. Skim milk was acidified by glucono-delta-lactone and then homogenized in the presence of polysaccharide at different pH values (in the range from 4.2 to 3.0). Measurements of particle size distribution demonstrated that pectins with a DE of 71.4, 68.6, and 67.4 stabilized milk at pH > 4.0. Pectins with a lower DE (63.9%) needed a higher concentration (0.4%) at the same pH to show a monomodal distribution of particle sizes. Pectins with lower DE (<50%) did not stabilize the dispersions. Although this difference in behavior was attributed mainly to the pectin charge, the efficiency in stabilizing the casein dispersion decreased with decreasing pectin size. For example, the high methoxyl pectin (HMP) with 63.9 DE was smaller in size than the HMPs with a higher charge. Pectins showed a pH-dependent stabilization effect, as at pH < 4.0 the dispersions contained aggregates. When SSPS was used to stabilize acid milk, at pH < 4.0, it showed a better stabilization behavior than HMP. When SSPS and pectin were used in combination, the particle size distribution of the acid milk dispersion was pH-dependent, and results were similar to those for samples containing pectin alone. This suggested that in the mixture, pectin dominated the behavior over SSPS, even when an excess of SSPS was added to the dispersions before homogenization.

  7. Particle size of calcium carbonate does not affect apparent and standardized total tract digestibility of calcium, retention of calcium, or growth performance of growing pigs.

    PubMed

    Merriman, L A; Stein, H H

    2016-09-01

    Two experiments were conducted to evaluate particle size of calcium carbonate used in diets fed to growing pigs. Experiment 1 was conducted to determine apparent total tract digestibility (ATTD), standardized total tract digestibility (STTD), and retention of Ca among diets containing calcium carbonate produced to different particle sizes, and Exp. 2 was conducted to determine if growth performance of weanling pigs is affected by particle size of calcium carbonate. In Exp. 1, 4 diets based on corn and potato protein isolate were formulated to contain 0.70% Ca and 0.33% standardized total tract digestible P, but the calcium carbonate used in the diets was ground to 4 different particle sizes (200, 500, 700, or 1,125 μm). A Ca-free diet was formulated to determine basal endogenous losses of Ca. In Exp. 2, 4 diets were based on corn and soybean meal and the only difference among diets was that each diet contained calcium carbonate ground to the 4 particle sizes used in Exp. 1. In Exp. 1, 40 barrows (15.42 ± 0.70 kg initial BW) were allotted to the 5 diets with 8 replicate pigs per diet using a randomized complete block design, and in Exp. 2, 128 pigs with an initial BW of 9.61 ± 0.09 kg were randomly allotted to 4 experimental diets. Results of Exp. 1 indicated that basal endogenous losses of Ca were 0.329 g/kg DMI. The ATTD of Ca was 70.0 ± 3.2, 74.3 ± 2.7, 70.0 ± 2.9, and 72.1 ± 2.7 and the STTD of Ca was 74.2 ± 3.2, 78.5 ± 2.7, 74.1 ± 2.9, and 76.2 ± 2.7 for calcium carbonate ground to 200, 500, 700, or 1,125 μm, respectively. Retention of Ca was 67.4 ± 3.1, 70.4 ± 2.6, 63.9 ± 2.8, and 67.2 ± 2.2 for diets containing calcium carbonate ground to 200, 500, 700, or 1,125 μm, respectively. There were no differences among diets for ATTD of Ca, STTD of Ca, or retention of Ca. The ATTD of P was 64.5 ± 1.7, 66.8 ± 2.6, 64.2 ± 3.0, and 63.2 ± 1.7% and retention of P was 61.4 ± 1.4, 63.8 ± 2.8, 61.9 ± 2.8, and 60.9 ± 1.5 for diets containing calcium

  8. Tmc1 Point Mutation Affects Ca2+ Sensitivity and Block by Dihydrostreptomycin of the Mechanoelectrical Transducer Current of Mouse Outer Hair Cells

    PubMed Central

    Corns, Laura F.; Johnson, Stuart L.; Kros, Corné J.

    2016-01-01

    transmembrane channel-like protein isoform 1 (TMC1) channels in the mammalian cochlea. Using a mutant mouse model (Beethoven) for progressive hearing loss in humans (DFNA36), which harbors a point mutation in the Tmc1 gene, we show that this mutation affects the MET channel pore, reducing its Ca2+ permeability and its affinity for the permeant blocker dihydrostreptomycin. A number of phenomena that we ascribe to Ca2+-dependent adaptation appear stronger, in compensation for the reduced Ca2+ entry. PMID:26758827

  9. Small deletions in the potato leafroll virus readthrough protein affect particle morphology, aphid transmission, virus movement and accumulation.

    PubMed

    Peter, Kari A; Liang, Delin; Palukaitis, Peter; Gray, Stewart M

    2008-08-01

    Potato leafroll virus (PLRV) capsid comprises 180 coat protein (CP) subunits, with some percentage containing a readthrough domain (RTD) extension located on the particle's surface. The RTD N terminus is highly conserved in luteovirids and this study sought to identify biologically active sites within this region of the PLRV RTD. Fourteen three-amino-acid-deletion mutants were generated from a cloned infectious PLRV cDNA and delivered to plants by Agrobacterium inoculations. All mutant viruses accumulated locally in infiltrated tissues and expressed the readthrough protein (RTP) containing the CP and RTD sequences in plant tissues; however, when purified, only three mutant viruses incorporated the RTP into the virion. None of the mutant viruses were aphid transmissible, but the viruses persisted in aphids for a period sufficient to allow for virus transmission. Several mutant viruses were examined further for systemic infection in four host species. All mutant viruses, regardless of RTP incorporation, moved systemically in each host, although they accumulated at different rates in systemically infected tissues. The biological properties of the RTP are sensitive to modifications in both the RTD conserved and variable regions.

  10. Gamma ray sterilization of delta inulin adjuvant particles (Advax™) makes minor, partly reversible structural changes without affecting adjuvant activity.

    PubMed

    Cooper, P D; Barclay, T G; Ginic-Markovic, M; Petrovsky, N

    2014-01-23

    We earlier identified a developmental series of seven isoforms/polymorphs of microparticulate inulin by comparing non-covalent bonding strengths. Their pharmaceutical utility lies in the modulation of cellular immunity, exploited as vaccine adjuvants (Advax™) especially for delta inulin (DI). As such particles cannot be sterilized by filtration we explore the effect of (60)Co gamma radiation (GR) on inulin isoforms, particularly DI. Its adjuvant activity and overt physical properties were unaffected by normal GR sterilizing doses (up to 25kGy). Heating irradiated isoform suspensions near their critical dissolution temperature revealed increased solubility deduced to reflect a single lethal event in one component of a multi-component structure. Local oxidative effects of GR on DI were not found. The observed DI loss was almost halved by re-annealing at the critical temperature: surviving inulin chains apparently reassemble into smaller amounts of the original type of structure. Colorimetric tetrazolium assay revealed increases in reducing activity after GR of raw inulin powder, which yielded DI with normal physical properties but only 25% normal recovery yet 4× normal reducing ability, implying final retention of some GR-changed inulin chains. These findings suggest minimal inulin chain cleavage and confirm that GR may be a viable strategy for terminal sterilization of microparticulate inulin adjuvants. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Gamma ray sterilization of delta inulin adjuvant particles (Advax™) makes minor, partly reversible structural changes without affecting adjuvant activity

    PubMed Central

    Cooper, P. D.; Barclay, T. G.; Ginic-Markovic, M.; Petrovsky, N.

    2014-01-01

    We earlier identified a developmental series of seven isoforms/polymorphs of microparticulate inulin by comparing non-covalent bonding strengths. Their pharmaceutical utility lies in modulation of cellular immunity, exploited as vaccine adjuvants (Advax™) especially for delta inulin (DI). As such particles cannot be sterilized by filtration we explore the effect of 60Co gamma radiation (GR) on inulin isoforms, particularly DI. Its adjuvant activity and overt physical properties were unaffected by normal GR sterilizing doses (up to 25 kGy). Heating irradiated isoform suspensions near their critical dissolution temperature revealed increased solubility deduced to reflect a single lethal event in one component of a multi-component structure. Local oxidative effects of GR on DI were not found. The observed DI loss was almost halved by re-annealing at the critical temperature: surviving inulin chains apparently reassemble into smaller amounts of the original type of structure. Colorimetric tetrazolium assay revealed increases in reducing activity after GR of raw inulin powder, which yielded DI with normal physical properties but only 25% normal recovery yet 4× normal reducing ability, implying final retention of some GR-changed inulin chains. These findings suggest minimal inulin chain cleavage and confirm that GR may be a viable strategy for terminal sterilization of microparticulate inulin adjuvants. PMID:24342245

  12. Chondrocyte gene expression is affected by very small iron oxide particles-labeling in long-term in vitro MRI tracking.

    PubMed

    Foldager, Casper Bindzus; Pedersen, Michael; Ringgaard, Steffen; Bünger, Cody; Lind, Martin

    2011-03-01

    To investigate the effect and dose response of very small iron oxide particles (VSOP) labeling of human chondrocytes for long-term in vitro MRI tracking. Chondrocytes were isolated from cartilage biopsies from four patients. The cells for the dose-response study were labeled with 25, 50, or 100 μg/mL VSOP. Quantitative gene expression and cellular proliferation were compared with unlabeled controls at day 1, 3, and 7. The cells suited for MRI tracking were labeled with 50 μg/mL VSOP and embedded in alginate beads, followed by MRI (using T2-weighted sequences) at day 0, 1, 3, 7, 14, 21, 28, and histology was performed at each time-point. Histology revealed that VSOP particles were intracellularly confined at all time-points, whereas no extracellular VSOPs were observed. A mean reduction in T2-value of 25.1 ms (±SD 3.5 ms) was found on T2-maps. The chondrocyte-specific genes aggrecan, collagen type 2, and sox9 were all affected by labeling, the two latter in a dose-dependent manner. VSOPs had no effect on proliferation. VSOP labeling of chondrocytes affected gene expression but not proliferation. The labeled chondrocytes could be recognized by MRI for 4 weeks without significant changes in the T2 relaxation time. Copyright © 2011 Wiley-Liss, Inc.

  13. Mouse Liver Sinusoidal Endothelium Eliminates HIV-Like Particles from Blood at a Rate of 100 Million per Minute by a Second-Order Kinetic Process

    PubMed Central

    Mates, Jessica M.; Yao, Zhili; Cheplowitz, Alana M.; Suer, Ozan; Phillips, Gary S.; Kwiek, Jesse J.; Rajaram, Murugesan V. S.; Kim, Jonghan; Robinson, John M.; Ganesan, Latha P.; Anderson, Clark L.

    2017-01-01

    We crafted human immunodeficiency virus (HIV)-like particles of diameter about 140 nm, which expressed two major HIV-1 proteins, namely, env and gag gene products, and used this reagent to simulate the rate of decay of HIV from the blood stream of BALB/c male mice. We found that most (~90%) of the particles were eliminated (cleared) from the blood by the liver sinusoidal endothelial cells (LSECs), the remainder from Kupffer cells; suggesting that LSECs are the major liver scavengers for HIV clearance from blood. Decay was rapid with kinetics suggesting second order with respect to particles, which infers dimerization of a putative receptor on LSEC. The number of HIV-like particles required for saturating the clearance mechanism was approximated. The capacity for elimination of blood-borne HIV-like particles by the sinusoid was 112 million particles per minute. Assuming that the sinusoid endothelial cells were about the size of glass-adherent macrophages, then elimination capacity was more than 540 particles per hour per endothelial cell. PMID:28167948

  14. The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: II. Characteristics and tolerances of the pocket mouse and incidence of disease.

    PubMed

    Linberg, R G; Kraft, L M; Simmonds, R C; Bailey, O T; Dunlap, W A; Haymaker, W

    1975-04-01

    Pocket mice are facultative homoiotherms with the ability to drop their metabolic rate dramatically while at rest or in response to environmental stresses. Under these conditions, they characteristically enter a state of prolonged torpor. These animals require no drinking water and they can live in darkness for many months without apparent ill effect. They tolerate a wide range of ambient temperature, ralative humidity, and oxygen pressure and have survied without food for a mean of 14 d at an ambient temperature of 20 degrees C (68 degrees F). Studies carried out on the pocket mouse colony used for the Apollo XVII flight revealed, in the animals tested, no serological evidence of viral disease, no pathogenic enterobacteria or respiratory Mycoplasma on culture, a 25% incidence of sarcosporidiosis, and a 2% incidence of chronic meningitis or meningoencephalitis. The conclusion reached is that the pocket mouse is a highly adaptive animal and very well suited for space flight.

  15. Drugs affecting the cholinergic system in the intact mammalian eye. I. Evaluation of the miotic activity of acetylcholine-like drugs in the mouse eye.

    PubMed

    Maayani, S; Treister, G; Sokolovsky, M

    1975-03-01

    The effect of concentration and pH on the miotic activity of five acetylcholine-like drugs were studied in the intact mouse eye. The data suggests that it is mainly the nonionized form of the drug which contributes to its miotic activity. Acetylcholine-like drugs, degradable by cholinesterases, exert their miotic activity at higher concentrations than do those which are resistant to enzymatic hydrolysis. More active acetylcholine-like drugs appear to be less sensitive to concentration changes.

  16. SUPPRESSION OF BASAL AND CYTOKINE INDUCED EXPRESSION OF ANTIGEN PRESENTATION MARKERS ON MOUSE LUNG EPITHELIAL CELLS EXPOSED TO DIESEL EXHAUST PARTICLES.

    EPA Science Inventory

    Diesel exhaust particles (DEP) constitute a significant component of airborne particulates in urban environment. Exposure to DEP is known to enhance susceptibility to viral and bacterial infections. We hypothesized that DEP could partially exert its effect on disease susceptibili...

  17. SUPPRESSION OF BASAL AND CYTOKINE INDUCED EXPRESSION OF ANTIGEN PRESENTATION MARKERS ON MOUSE LUNG EPITHELIAL CELLS EXPOSED TO DIESEL EXHAUST PARTICLES.

    EPA Science Inventory

    Diesel exhaust particles (DEP) constitute a significant component of airborne particulates in urban environment. Exposure to DEP is known to enhance susceptibility to viral and bacterial infections. We hypothesized that DEP could partially exert its effect on disease susceptibili...

  18. Nonuniform distribution of carbonitride particles and its effect on prior austenite grain size in the simulated coarse-grained heat-affected zone of thermomechanical control-processed steels

    NASA Astrophysics Data System (ADS)

    Tian, D. W.; Karjalainen, L. P.; Qian, Bainian; Chen, Xiaofeng

    1996-12-01

    The spatial distribution of carbonitride particles in the simulated coarse-grained heat-affected zone (HAZ) of Nb-Ti microalloyed thermomechanical control-processed (TMCP) steels was investigated using a scanning transmission electron microscope (STEM). It was found that the particles in quenched coarse-grained HAZ were frequently distributed in a nonuniform way, forming clusters and arrays of particles. This nonhomogeneity is defined by the grouping tendency of particles and described by the closeness of the average number density (the mean particle number per unit area) to the average local number density (the mean particle number per unit area, excluding the examined areas without particles). A high concentration of Nb (0.04 mass pct in this article) promoted the formation of carbonitride particle arrays and clusters because of its high segregation tendency at grain and subgrain boundaries during the cooling of a slab. Some of these particles remain undissolved at the peak temperature of a welding thermocycle and may result in sympathetic nucleation of new particles on them. The effectiveness of the particle groups to restrict grain growth is discussed.

  19. Co-precipitation of DEAE-dextran coated SPIONs: how synthesis conditions affect particle properties, stem cell labelling and MR contrast.

    PubMed

    Barrow, Michael; Taylor, Arthur; García Carrión, Jaime; Mandal, Pranab; Park, B Kevin; Poptani, Harish; Murray, Patricia; Rosseinsky, Matthew J; Adams, Dave J

    2016-09-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as contrast agents for stem cell tracking using magnetic resonance imaging (MRI). The total mass of iron oxide that can be internalised into cells without altering their viability or phenotype is an important criterion for the generation of contrast, with SPIONs designed for efficient labelling of stem cells allowing for an increased sensitivity of detection. Although changes in the ratio of polymer and iron salts in co-precipitation reactions are known to affect the physicochemical properties of SPIONs, particularly core size, the effects of these synthesis conditions on stem cell labelling and magnetic resonance (MR) contrast have not been established. Here, we synthesised a series of cationic SPIONs with very similar hydrodynamic diameters and surface charges, but different polymer content. We have investigated how the amount of polymer in the co-precipitation reaction affects core size and modulates not only the magnetic properties of the SPIONs but also their uptake into stem cells. SPIONs with the largest core size and lowest polymer content presented the highest magnetisation and relaxivity. These particles also had the greatest uptake efficiency without any deleterious effect on either the viability or function of the stem cells. However, for all particles internalised in cells, the T2 and T2(*) relaxivity was independent of the SPION's core size. Our results indicate that the relative mass of iron taken up by cells is the major determinant of MR contrast generation and suggest that the extent of SPION uptake can be regulated by the amount of polymer used in co-precipitation reactions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. ENDOTOXIN PRIMING, OZONE EXPOSURE, AND AGE AFFECT ULTRAFINE PARTICLE-INDUCED INFLAMMATION AND ANTIOXIDANT GENE EXPRESSION IN MOUSE LUNG AND HEART. (R827354C005)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  1. ENDOTOXIN PRIMING, OZONE EXPOSURE, AND AGE AFFECT ULTRAFINE PARTICLE-INDUCED INFLAMMATION AND ANTIOXIDANT GENE EXPRESSION IN MOUSE LUNG AND HEART. (R827354C005)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. Evidence for regulatory genes on mouse chromosome 7 that affect the quantitative expression of proteins in the fetal and newborn liver.

    PubMed Central

    Giometti, C S; Gemmell, M A; Taylor, J; Tollaksen, S L; Angeletti, R; Gluecksohn-Waelsch, S

    1992-01-01

    A series of deletions around the albino locus on mouse chromosome 7 is believed to include one or more regulatory genes that control the activities of a cluster of liver enzymes. To further characterize the functions of this region of the mouse genome, we have used quantitative two-dimensional electrophoresis to analyze the effects of two of these deletions, c3H and c14CoS, on the expression of liver proteins. More than 400 distinct protein gene products were quantitated in livers from fetal and newborn wild-type homozygous (cch/cch), heterozygous (cch/c3H or cch/c14CoS), and deletion homozygous (c3H/c3H or c14CoS/c14CoS) mice. Livers of fetal and newborn c3H heterozygotes and homozygous wild-type littermates produced qualitatively identical protein patterns after two-dimensional electrophoresis. In livers of c3H homozygous fetuses, however, abnormal amounts (either increased or decreased relative to homozygous wild-type and heterozygous littermates) of 29 proteins were found. Twenty-eight of these 29 protein anomalies were also found in livers of newborn c3H homozygotes. Livers of fetal and newborn mice homozygous for the c14CoS deletion, which overlaps the c3H deletion and produces a similar phenotype, expressed normal amounts of these proteins. One of the 29 proteins (MSN807) has an amino-terminal sequence similar to a 23-kDa translationally controlled protein abundant in mouse erythroleukemia and sarcoma-180 cells. These results suggest that normal chromosome 7 contains genes, located within the region of the c3H but not the c14CoS deletion, that regulate the abundance of specific proteins in the liver. These proteins cannot be related to the phenotypic alterations shared by the c3H and c14CoS deletions. Images PMID:1549608

  3. Knockdown of the intraflagellar transport protein IFT46 stimulates selective gene expression in mouse chondrocytes and affects early development in zebrafish.

    PubMed

    Gouttenoire, Jérôme; Valcourt, Ulrich; Bougault, Carole; Aubert-Foucher, Elisabeth; Arnaud, Estelle; Giraud, Lionel; Mallein-Gerin, Frédéric

    2007-10-19

    Bone morphogenetic proteins (BMPs) act as multifunctional regulators in morphogenesis during development. In particular they play a determinant role in the formation of cartilage molds and their replacement by bone during endochondral ossification. In cell culture, BMP-2 favors chondrogenic expression and promotes hypertrophic maturation of chondrocytes. In mouse chondrocytes we have identified a BMP-2-sensitive gene encoding a protein of 301 amino acids. This protein, named mIFT46, is the mouse ortholog of recently identified Caenorhabditis elegans and Chlamydomonas reinhardtii intraflagellar transport (IFT) proteins. After generation of a polyclonal antibody against mIFT46, we showed for the first time that the endogenous protein is located in the primary cilium of chondrocytes. We also found that mIFT46 is preferentially expressed in early hypertrophic chondrocytes located in the growth plate. Additionally, mIFT46 knockdown by small interfering RNA oligonucleotides in cultured chondrocytes specifically stimulated the expression of several genes related to skeletogenesis. Furthermore, Northern blotting analysis indicated that mIFT46 is also expressed before chondrogenesis in embryonic mouse development, suggesting that the role of mIFT46 might not be restricted to cartilage. To explore the role of IFT46 during early development, we injected antisense morpholino oligonucleotides in Danio rerio embryos to reduce zebrafish IFT46 protein (zIFT46) synthesis. Dramatic defects in embryonic development such as a dorsalization and a tail duplication were observed. Thus our results taken together indicate that the ciliary protein IFT46 has a specific function in chondrocytes and is also essential for normal development of vertebrates.

  4. A Nonsense Mutation in Mouse Tardbp Affects TDP43 Alternative Splicing Activity and Causes Limb-Clasping and Body Tone Defects

    PubMed Central

    Fratta, Pietro; de Oliveira, Hugo M.; Kent, Rosie; Phatak, Vinaya; Brandner, Sebastian; Blanco, Gonzalo; Greensmith, Linda; Acevedo-Arozena, Abraham; Fisher, Elizabeth M. C.

    2014-01-01

    Mutations in TARDBP, encoding Tar DNA binding protein-43 (TDP43), cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Attempts to model TDP43 dysfunction in mice have used knockouts or transgenic overexpressors, which have revealed the difficulties of manipulating TDP43, whose level is tightly controlled by auto-regulation. In a complementary approach, to create useful mouse models for the dissection of TDP43 function and pathology, we have identified a nonsense mutation in the endogenous mouse Tardbp gene through screening an N-ethyl-N-nitrosourea (ENU) mutant mouse archive. The mutation is predicted to cause a Q101X truncation in TDP43. We have characterised TardbpQ101X mice to investigate this mutation in perturbing TDP43 biology at endogenous expression levels. We found the TardbpQ101X mutation is homozygous embryonic lethal, highlighting the importance of TDP43 in early development. Heterozygotes (Tardbp+/Q101X) have abnormal levels of mutant transcript, but we find no evidence of the truncated protein and mice have similar full-length TDP43 protein levels as wildtype littermates. Nevertheless, Tardbp+/Q101X mice have abnormal alternative splicing of downstream gene targets, and limb-clasp and body tone phenotypes. Thus the nonsense mutation in Tardbp causes a mild loss-of-function phenotype and behavioural assessment suggests underlying neurological abnormalities. Due to the role of TDP43 in ALS, we investigated potential interactions with another known causative gene, mutant superoxide dismutase 1 (SOD1). Tardbp+/Q101X mice were crossed with the SOD1G93Adl transgenic mouse model of ALS. Behavioural and physiological assessment did not reveal modifying effects on the progression of ALS-like symptoms in the double mutant progeny from this cross. In summary, the TardbpQ101X mutant mice are a useful tool for the dissection of TDP43 protein regulation, effects on splicing, embryonic development and neuromuscular phenotypes. These mice are

  5. Anti-tumor effect of the alphavirus-based virus-like particle vector expressing prostate-specific antigen in a HLA-DR transgenic mouse model of prostate cancer.

    PubMed

    Riabov, V; Tretyakova, I; Alexander, R B; Pushko, P; Klyushnenkova, E N

    2015-10-05

    The goal of this study was to determine if an alphavirus-based vaccine encoding human Prostate-Specific Antigen (PSA) could generate an effective anti-tumor immune response in a stringent mouse model of prostate cancer. DR2bxPSA F1 male mice expressing human PSA and HLA-DRB1(*)1501 transgenes were vaccinated with virus-like particle vector encoding PSA (VLPV-PSA) followed by the challenge with Transgenic Adenocarcinoma of Mouse Prostate cells engineered to express PSA (TRAMP-PSA). PSA-specific cellular and humoral immune responses were measured before and after tumor challenge. PSA and CD8 reactivity in the tumors was detected by immunohistochemistry. Tumor growth was compared in vaccinated and control groups. We found that VLPV-PSA could infect mouse dendritic cells in vitro and induce a robust PSA-specific immune response in vivo. A substantial proportion of splenic CD8 T cells (19.6 ± 7.4%) produced IFNγ in response to the immunodominant peptide PSA(65-73). In the blood of vaccinated mice, 18.4 ± 4.1% of CD8 T cells were PSA-specific as determined by the staining with H-2D(b)/PSA(65-73) dextramers. VLPV-PSA vaccination also strongly stimulated production of IgG2a/b anti-PSA antibodies. Tumors in vaccinated mice showed low levels of PSA expression and significant CD8+ T cell infiltration. Tumor growth in VLPV-PSA vaccinated mice was significantly delayed at early time points (p=0.002, Gehan-Breslow test). Our data suggest that TC-83-based VLPV-PSA vaccine can efficiently overcome immune tolerance to PSA, mediate rapid clearance of PSA-expressing tumor cells and delay tumor growth. The VLPV-PSA vaccine will undergo further testing for the immunotherapy of prostate cancer.

  6. The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model

    PubMed Central

    Woolf, Eric C.; Curley, Kara L.; Liu, Qingwei; Turner, Gregory H.; Charlton, Julie A.; Preul, Mark C.; Scheck, Adrienne C.

    2015-01-01

    Background The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood. Methods To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma. Results Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4. Conclusions The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas. PMID:26083629

  7. ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells

    PubMed Central

    Riso, Vincenzo; Cammisa, Marco; Kukreja, Harpreet; Anvar, Zahra; Verde, Gaetano; Sparago, Angela; Acurzio, Basilia; Lad, Shraddha; Lonardo, Enza; Sankar, Aditya; Helin, Kristian; Feil, Robert; Fico, Annalisa; Angelini, Claudia; Grimaldi, Giovanna; Riccio, Andrea

    2016-01-01

    ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS and non-ICRBS suggesting that different cis-acting regulatory functions are repressed by ZFP57 at these two classes of target loci. Overall, these data demonstrate that ZFP57 is pivotal to maintain the allele-specific epigenetic modifications of ICRs that in turn are necessary for maintaining the imprinted expression over long distances. At non-ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet required. PMID:27257070

  8. The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model.

    PubMed

    Woolf, Eric C; Curley, Kara L; Liu, Qingwei; Turner, Gregory H; Charlton, Julie A; Preul, Mark C; Scheck, Adrienne C

    2015-01-01

    The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood. To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma. Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4. The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas.

  9. Loss of epidermal hypoxia-inducible factor-1α accelerates epidermal aging and affects re-epithelialization in human and mouse.

    PubMed

    Rezvani, Hamid Reza; Ali, Nsrein; Serrano-Sanchez, Martin; Dubus, Pierre; Varon, Christine; Ged, Cécile; Pain, Catherine; Cario-André, Muriel; Seneschal, Julien; Taïeb, Alain; de Verneuil, Hubert; Mazurier, Frédéric

    2011-12-15

    In mouse and human skin, HIF-1α is constitutively expressed in the epidermis, mainly in the basal layer. HIF-1α has been shown to have crucial systemic functions: regulation of kidney erythropoietin production in mice with constitutive HIF-1α epidermal deletion, and hypervascularity following epidermal HIF-1α overexpression. However, its local role in keratinocyte physiology has not been clearly defined. To address the function of HIF-1α in the epidermis, we used the mouse model of HIF-1α knockout targeted to keratinocytes (K14-Cre/Hif1a(flox/flox)). These mice had a delayed skin phenotype characterized by skin atrophy and pruritic inflammation, partly mediated by basement membrane disturbances involving laminin-332 (Ln-332) and integrins. We also investigated the relevance of results of studies in mice to human skin using reconstructed epidermis and showed that HIF-1α knockdown in human keratinocytes impairs the formation of a viable reconstructed epidermis. A diminution of keratinocyte growth potential, following HIF-1α silencing, was associated with a decreased expression of Ln-322 and α6 integrin and β1 integrin. Overall, these results indicate a role of HIF-1α in skin homeostasis especially during epidermal aging.

  10. Differential Radiosensitivity Phenotypes of DNA-PKcs Mutations Affecting NHEJ and HRR Systems following Irradiation with Gamma-Rays or Very Low Fluences of Alpha Particles

    PubMed Central

    Little, John B.; Kato, Takamitsu A.; Shih, Hung-Ying; Xie, Xian-Jin; Wilson Jr., Paul F.; Brogan, John R.; Kurimasa, Akihiro; Chen, David J.; Bedford, Joel S.; Chen, Benjamin P. C.

    2014-01-01

    We have examined cell-cycle dependence of chromosomal aberration induction and cell killing after high or low dose-rate γ irradiation in cells bearing DNA-PKcs mutations in the S2056 cluster, the T2609 cluster, or the kinase domain. We also compared sister chromatid exchanges (SCE) production by very low fluences of α-particles in DNA-PKcs mutant cells, and in homologous recombination repair (HRR) mutant cells including Rad51C, Rad51D, and Fancg/xrcc9. Generally, chromosomal aberrations and cell killing by γ-rays were similarly affected by mutations in DNA-PKcs, and these mutant cells were more sensitive in G1 than in S/G2 phase. In G1-irradiated DNA-PKcs mutant cells, both chromosome- and chromatid-type breaks and exchanges were in excess than wild-type cells. For cells irradiated in late S/G2 phase, mutant cells showed very high yields of chromatid breaks compared to wild-type cells. Few exchanges were seen in DNA-PKcs-null, Ku80-null, or DNA-PKcs kinase dead mutants, but exchanges in excess were detected in the S2506 or T2609 cluster mutants. SCE induction by very low doses of α-particles is resulted from bystander effects in cells not traversed by α-particles. SCE seen in wild-type cells was completely abolished in Rad51C- or Rad51D-deficient cells, but near normal in Fancg/xrcc9 cells. In marked contrast, very high levels of SCEs were observed in DNA-PKcs-null, DNA-PKcs kinase-dead and Ku80-null mutants. SCE induction was also abolished in T2609 cluster mutant cells, but was only slightly reduced in the S2056 cluster mutant cells. Since both non-homologous end-joining (NHEJ) and HRR systems utilize initial DNA lesions as a substrate, these results suggest the possibility of a competitive interference phenomenon operating between NHEJ and at least the Rad51C/D components of HRR; the level of interaction between damaged DNA and a particular DNA-PK component may determine the level of interaction of such DNA with a relevant HRR component. PMID:24714417

  11. Differential radiosensitivity phenotypes of DNA-PKcs mutations affecting NHEJ and HRR systems following irradiation with gamma-rays or very low fluences of alpha particles.

    PubMed

    Lin, Yu-Fen; Nagasawa, Hatsumi; Little, John B; Kato, Takamitsu A; Shih, Hung-Ying; Xie, Xian-Jin; Wilson, Paul F; Brogan, John R; Kurimasa, Akihiro; Chen, David J; Bedford, Joel S; Chen, Benjamin P C

    2014-01-01

    We have examined cell-cycle dependence of chromosomal aberration induction and cell killing after high or low dose-rate γ irradiation in cells bearing DNA-PKcs mutations in the S2056 cluster, the T2609 cluster, or the kinase domain. We also compared sister chromatid exchanges (SCE) production by very low fluences of α-particles in DNA-PKcs mutant cells, and in homologous recombination repair (HRR) mutant cells including Rad51C, Rad51D, and Fancg/xrcc9. Generally, chromosomal aberrations and cell killing by γ-rays were similarly affected by mutations in DNA-PKcs, and these mutant cells were more sensitive in G1 than in S/G2 phase. In G1-irradiated DNA-PKcs mutant cells, both chromosome- and chromatid-type breaks and exchanges were in excess than wild-type cells. For cells irradiated in late S/G2 phase, mutant cells showed very high yields of chromatid breaks compared to wild-type cells. Few exchanges were seen in DNA-PKcs-null, Ku80-null, or DNA-PKcs kinase dead mutants, but exchanges in excess were detected in the S2506 or T2609 cluster mutants. SCE induction by very low doses of α-particles is resulted from bystander effects in cells not traversed by α-particles. SCE seen in wild-type cells was completely abolished in Rad51C- or Rad51D-deficient cells, but near normal in Fancg/xrcc9 cells. In marked contrast, very high levels of SCEs were observed in DNA-PKcs-null, DNA-PKcs kinase-dead and Ku80-null mutants. SCE induction was also abolished in T2609 cluster mutant cells, but was only slightly reduced in the S2056 cluster mutant cells. Since both non-homologous end-joining (NHEJ) and HRR systems utilize initial DNA lesions as a substrate, these results suggest the possibility of a competitive interference phenomenon operating between NHEJ and at least the Rad51C/D components of HRR; the level of interaction between damaged DNA and a particular DNA-PK component may determine the level of interaction of such DNA with a relevant HRR component.

  12. Exercise differentially affects metabolic functions and white adipose tissue in female letrozole- and dihydrotestosterone-induced mouse models of polycystic ovary syndrome.

    PubMed

    Marcondes, Rodrigo R; Maliqueo, Manuel; Fornes, Romina; Benrick, Anna; Hu, Min; Ivarsson, Niklas; Carlström, Mattias; Cushman, Samuel W; Stenkula, Karin G; Maciel, Gustavo A R; Stener-Victorin, Elisabet

    2017-03-24

    Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue.

  13. Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse.

    PubMed

    Sluyter, Frans; Jamot, Laure; Bertholet, Jean-Yves; Crusio, Wim E

    2005-04-22

    BACKGROUND: The aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF) terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J). RESULTS: Although we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype) at adult age. CONCLUSION: Prenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures) or involve different animal models.

  14. Tumor growth affects the metabonomic phenotypes of multiple mouse non-involved organs in an A549 lung cancer xenograft model

    PubMed Central

    Xu, Shan; Tian, Yuan; Hu, Yili; Zhang, Nijia; Hu, Sheng; Song, Dandan; Wu, Zhengshun; Wang, Yulan; Cui, Yanfang; Tang, Huiru

    2016-01-01

    The effects of tumorigenesis and tumor growth on the non-involved organs remain poorly understood although many research efforts have already been made for understanding the metabolic phenotypes of various tumors. To better the situation, we systematically analyzed the metabolic phenotypes of multiple non-involved mouse organ tissues (heart, liver, spleen, lung and kidney) in an A549 lung cancer xenograft model at two different tumor-growth stages using the NMR-based metabonomics approaches. We found that tumor growth caused significant metabonomic changes in multiple non-involved organ tissues involving numerous metabolic pathways, including glycolysis, TCA cycle and metabolisms of amino acids, fatty acids, choline and nucleic acids. Amongst these, the common effects are enhanced glycolysis and nucleoside/nucleotide metabolisms. These findings provided essential biochemistry information about the effects of tumor growth on the non-involved organs. PMID:27329570

  15. Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse

    PubMed Central

    Sluyter, Frans; Jamot, Laure; Bertholet, Jean-Yves; Crusio, Wim E

    2005-01-01

    Background The aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF) terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J). Results Although we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype) at adult age. Conclusion Prenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures) or involve different animal models. PMID:15916699

  16. Components of Diesel Exhaust Particles Diversely Enhance a Variety of Respiratory Diseases Related to Infection or Allergy: Extracted Organic Chemicals and the Residual Particles after Extraction Differently Affect Respiratory Diseases

    PubMed Central

    Takano, Hirohisa; Yanagisawa, Rie; Inoue, Ken-ichiro

    2007-01-01

    Experimental and epidemiological studies have reported that diesel exhaust particles (DEP) can aggravate a variety of respiratory diseases including infection or allergy. However, the responsible components in DEP for the enhancement have not been identified. The present review demonstrates the different effects of the components of DEP on the respiratory diseases related to infection or allergy. We exposed mice to the organic chemicals (DEP-OC) and the residual carbonaceous nuclei (washed DEP) derived from DEP in the presence or absence of bacterial endotoxin (lipopolysaccharide: LPS) or allergen. In our first series of experiments, washed DEP combined with LPS synergistically exacerbated lung injury, which was concomitant with the enhanced lung expression of proinflammatory cytokines and chemokines, whereas DEP-OC combined with LPS did not. In contrast, our second series of experiments showed that DEP-OC, rather than washed DEP, enhanced allergen-related eosinophilic inflammation and proliferation of goblet cells in the airway epithelium, which was paralleled by the enhanced lung expression of eotaxin and interleukin-5. However, washed DEP with ovalbmin showed less change and increased the lung expression of interferon-γ. It is suggested that DEP components diversely affect various types of respiratory diseases, while the combination of organic chemicals and carbonaceous nuclei (whole DEP) mostly aggravate respiratory diseases. PMID:18188411

  17. Slc7a11 (xCT) protein expression is not altered in the depressed brain and system xc- deficiency does not affect depression-associated behaviour in the corticosterone mouse model.

    PubMed

    Demuyser, Thomas; Deneyer, Lauren; Bentea, Eduard; Albertini, Giulia; Femenia, Teresa; Walrave, Laura; Sato, Hideyo; Danbolt, Niels C; De Bundel, Dimitri; Michotte, Alex; Lindskog, Maria; Massie, Ann; Smolders, Ilse

    2017-09-08

    The cystine/glutamate antiporter (system xc-) is believed to contribute to nonvesicular glutamate release from glial cells in various brain areas. Although recent investigations implicate system xc- in mood disorders, unambiguous evidence has not yet been established. Therefore, we evaluated the possible role of system xc- in the depressive state. We conducted a protein expression analysis of the specific subunit of system xc- (xCT) in brain regions of the corticosterone mouse model, Flinders Sensitive Line rat model and post-mortem tissue of depressed patients. We next subjected system xc- deficient mice to the corticosterone model and analysed their behaviour in several tests. Lastly, we subjected additional cohorts of xCT deficient and wildtype mice to N-acetylcysteine treatment to unveil whether the previously reported antidepressant-like effects are dependent upon system xc-. We did not detect any changes in xCT expression levels in the animal models or patients compared to proper controls. Furthermore, loss of system xc- had no effect on depression- and anxiety-like behaviour. Finally, the antidepressant-like effects of N-acetylcysteine are not mediated via system xc-. xCT protein expression is not altered in the depressed brain and system xc- deficiency does not affect depression-associated behaviour in the corticosterone mouse model.

  18. Long-term treatment with L-DOPA or pramipexole affects adult neurogenesis and corresponding non-motor behavior in a mouse model of Parkinson's disease.

    PubMed

    Chiu, W-H; Depboylu, C; Hermanns, G; Maurer, L; Windolph, A; Oertel, W H; Ries, V; Höglinger, G U

    2015-08-01

    Non-motor symptoms such as hyposmia and depression are often observed in Parkinson's disease (PD) and can precede the onset of motor symptoms for years. The underlying pathological alterations in the brain are not fully understood so far. Dysregulation of adult neurogenesis in the dentate gyrus of the hippocampus and the olfactory bulb has been recently suggested to be implicated in non-motor symptoms of PD. However, there is so far no direct evidence to support the relationship of non-motor symptoms and the modulation of adult neurogenesis following dopamine depletion and/or dopamine replacement. In this study, we investigated the long-term effects of l-DOPA and pramipexole, a dopamine agonist, in a mouse model of bilateral intranigral 6-OHDA lesion, in order to assess the impact of adult neurogenesis on non-motor behavior. We found that l-DOPA and pramipexole can normalize decreased neurogenesis in the hippocampal dentate gyrus and the periglomerular layer of the olfactory bulb caused by a 6-OHDA lesion. Interestingly, pramipexole showed an antidepressant and anxiolytic effect in the forced swim test and social interaction test. However, there was no significant change in learning and memory function after dopamine depletion and dopamine replacement, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Renal Failure Affects the Enzymatic Activities of the Three First Steps in Hepatic Heme Biosynthesis in the Acute Intermittent Porphyria Mouse

    PubMed Central

    Unzu, Carmen; Sampedro, Ana; Sardh, Eliane; Mauleón, Itsaso; Enríquez de Salamanca, Rafael; Prieto, Jesús

    2012-01-01

    Chronic kidney disease is a long-term complication in acute intermittent porphyria (AIP). The pathophysiological significance of hepatic overproduction of the porphyrin precursors aminolevulinate acid (ALA) and porphobilinogen (PBG) in chronic kidney disease is unclear. We have investigated the effect of repetitive acute attacks on renal function and the effect of total or five-sixth nephrectomy causing renal insufficiency on hepatic heme synthesis in the porphobilinogen deaminase (PBGD)-deficient (AIP) mouse. Phenobarbital challenge in the AIP-mice increased urinary porphyrin precursor excretion. Successive attacks throughout 14 weeks led to minor renal lesions with no impact on renal function. In the liver of wild type and AIP mice, 5/6 nephrectomy enhanced transcription of the first and rate-limiting ALA synthase. As a consequence, urinary PBG excretion increased in AIP mice. The PBG/ALA ratio increased from 1 in sham operated AIP animals to over 5 (males) and over 13 (females) in the 5/6 nephrectomized mice. Total nephrectomy caused a rapid decrease in PBGD activity without changes in enzyme protein level in the AIP mice but not in the wild type animals. In conclusion, high concentration of porphyrin precursors had little impact on renal function. However, progressive renal insufficiency aggravates porphyria attacks and increases the PBG/ALA ratio, which should be considered a warning sign for potentially life-threatening impairment in AIP patients with signs of renal failure. PMID:22412963

  20. Absence of Nrf2 or Its Selective Overexpression in Neurons and Muscle Does Not Affect Survival in ALS-Linked Mutant hSOD1 Mouse Models

    PubMed Central

    Vargas, Marcelo R.; Burton, Neal C.; Gan, Li; Johnson, Delinda A.; Schäfer, Matthias; Werner, Sabine; Johnson, Jeffrey A.

    2013-01-01

    The nuclear factor erythroid 2-related factor 2 (Nrf2) governs the expression of antioxidant and phase II detoxifying enzymes. Nrf2 activation can prevent or reduce cellular damage associated with several types of injury in many different tissues and organs. Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons and subsequent muscular atrophy. We have previously shown that Nrf2 activation in astrocytes delays neurodegeneration in ALS mouse models. To further investigate the role of Nrf2 in ALS we determined the effect of absence of Nrf2 or its restricted overexpression in neurons or type II skeletal muscle fibers on symptoms onset and survival in mutant hSOD1 expressing mice. We did not observe any detrimental effect associated with the lack of Nrf2 in two different mutant hSOD1 animal models of ALS. However, restricted Nrf2 overexpression in neurons or type II skeletal muscle fibers delayed disease onset but failed to extend survival in hSOD1G93A mice. These results highlight the concept that not only the pharmacological target but also the cell type targeted may be relevant when considering a Nrf2-mediated therapeutic approach for ALS. PMID:23418589

  1. Molecular analyses and identification of promising candidate genes for loci on mouse chromosome 1 affecting alcohol physical dependence and associated withdrawal.

    PubMed

    Denmark, D L; Buck, K J

    2008-07-01

    We recently mapped quantitative trait loci (QTLs) with large effects on predisposition to physical dependence and associated withdrawal severity following chronic and acute alcohol exposure (Alcdp1/Alcw1) to a 1.1-Mb interval of mouse chromosome 1 syntenic with human chromosome 1q23.2-23.3. Here, we provide a detailed analysis of the genes within this interval and show that it contains 40 coding genes, 17 of which show validated genotype-dependent transcript expression and/or non-synonymous coding sequence variation that may underlie the influence of Alcdp1/Alcw1 on ethanol dependence and associated withdrawal. These high priority candidates are involved in diverse cellular functions including intracellular trafficking, oxidative homeostasis, mitochondrial respiration, and extracellular matrix dynamics, and indicate both established and novel aspects of the neurobiological response to ethanol. This work represents a substantial advancement toward identification of the gene(s) that underlies the phenotypic effects of Alcdp1/Alcw1. Additionally, a multitude of QTLs for a variety of complex traits, including diverse behavioral responses to ethanol, have been mapped in the vicinity of Alcdp1/Alcw1, and as many as four QTLs on human chromosome 1q have been implicated in human mapping studies for alcoholism and associated endophenotypes. Thus, our results will be primary to further efforts to identify genes involved in a wide variety of behavioral responses to alcohol and may directly facilitate progress in human alcoholism genetics.

  2. Pulsed or continuous electromagnetic field induce p53/p21-mediated apoptotic signaling pathway in mouse spermatogenic cells in vitro and thus may affect male fertility.

    PubMed

    Solek, Przemyslaw; Majchrowicz, Lena; Bloniarz, Dominika; Krotoszynska, Ewelina; Koziorowski, Marek

    2017-05-01

    The impact of electromagnetic field (EMF) on the human health and surrounding environment is a common topic investigated over the years. A significant increase in the electromagnetic field concentration arouses public concern about the long-term effects of EMF on living organisms associated with many aspects. In the present study, we investigated the effects of pulsed and continuous electromagnetic field (PEMF/CEMF) on mouse spermatogenic cell lines (GC-1 spg and GC-2 spd) in terms of cellular and biochemical features in vitro. We evaluated the effect of EMF on mitochondrial metabolism, morphology, proliferation rate, viability, cell cycle progression, oxidative stress balance and regulatory proteins. Our results strongly suggest that EMF induces oxidative and nitrosative stress-mediated DNA damage, resulting in p53/p21-dependent cell cycle arrest and apoptosis. Therefore, spermatogenic cells due to the lack of antioxidant enzymes undergo oxidative and nitrosative stress-mediated cytotoxic and genotoxic events, which contribute to infertility by reduction in healthy sperm cells pool. In conclusion, electromagnetic field present in surrounding environment impairs male fertility by inducing p53/p21-mediated cell cycle arrest and apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Homer Protein–Metabotropic Glutamate Receptor Binding Regulates Endocannabinoid Signaling and Affects Hyperexcitability in a Mouse Model of Fragile X Syndrome

    PubMed Central

    Alger, Bradley E.

    2015-01-01

    The Fmr1 knock-out mouse model of fragile X syndrome (Fmr1−/y) has an epileptogenic phenotype that is triggered by group I metabotropic glutamate receptor (mGluR) activation. We found that a membrane-permeable peptide that disrupts mGluR5 interactions with long-form Homers enhanced mGluR-induced epileptiform burst firing in wild-type (WT) animals, replicating the early stages of hyperexcitability in Fmr1−/y. The peptide enhanced mGluR-evoked endocannabinoid (eCB)-mediated suppression of inhibitory synapses, decreased it at excitatory synapses in WTs, but had no effect on eCB actions in Fmr1−/y. At a low concentration, the mGluR agonist did not generate eCBs at excitatory synapses but nevertheless induced burst firing in both Fmr1−/y and peptide-treated WT slices. This burst firing was suppressed by a cannabinoid receptor antagonist. We suggest that integrity of Homer scaffolds is essential for normal mGluR–eCB functioning and that aberrant eCB signaling resulting from disturbances of this molecular structure contributes to the epileptic phenotype of Fmr1−/y. PMID:25740522

  4. Specific deletion of Cdc42 does not affect meiotic spindle organization/migration and homologous chromosome segregation but disrupts polarity establishment and cytokinesis in mouse oocytes.

    PubMed

    Wang, Zhen-Bo; Jiang, Zong-Zhe; Zhang, Qing-Hua; Hu, Meng-Wen; Huang, Lin; Ou, Xiang-Hong; Guo, Lei; Ouyang, Ying-Chun; Hou, Yi; Brakebusch, Cord; Schatten, Heide; Sun, Qing-Yuan

    2013-12-01

    Mammalian oocyte maturation is distinguished by highly asymmetric meiotic divisions during which a haploid female gamete is produced and almost all the cytoplasm is maintained in the egg for embryo development. Actin-dependent meiosis I spindle positioning to the cortex induces the formation of a polarized actin cap and oocyte polarity, and it determines asymmetric divisions resulting in two polar bodies. Here we investigate the functions of Cdc42 in oocyte meiotic maturation by oocyte-specific deletion of Cdc42 through Cre-loxP conditional knockout technology. We find that Cdc42 deletion causes female infertility in mice. Cdc42 deletion has little effect on meiotic spindle organization and migration to the cortex but inhibits polar body emission, although homologous chromosome segregation occurs. The failure of cytokinesis is due to the loss of polarized Arp2/3 accumulation and actin cap formation; thus the defective contract ring. In addition, we correlate active Cdc42 dynamics with its function during polar body emission and find a relationship between Cdc42 and polarity, as well as polar body emission, in mouse oocytes.

  5. Ammonia affects the glycosylation patterns of recombinant mouse placental lactogen-I by chinese hamster ovary cells in a pH-dependent manner

    SciTech Connect

    Borys, M.C.; Linzer, D.I.H.; Papoutsakis, E.T. )

    1994-03-15

    The N-linked glycosylation of the recombinant protein mouse placental lactogen-I (mPL-I) expressed by Chinese hamster ovary (CHO) cells under nongrowth conditions was inhibited by increasing levels of ammonium chloride in a serum-free, protein expression medium. The effect of ammonia on glycosylation was dependent on the extracellular pH (pH[sub e]). In media containing 0 and 9 mM ammonium chloride, the percentage of the most heavily glycosylated forms of secreted mPL-I decreased from ca. 90% to ca. 25% at pH[sub e] 8.0, and from ca. 90% to ca. 65% at pH[sub e] 7.6, respectively. However, at pH[sub e] 7.2, the most heavily glycosylated forms of secreted mPL-I decreased from ca. 90% to ca. 80% in media containing 0 and 9 mM ammonium chloride, respectively. Inhibition of mPL-I glycosylation was found to correlate with the calculated concentration of the ammonia species. Control experiments showed that the ammonia species. Control experiments showed that the ammonia effect on mPL-I glycosylation could not be attributed to increased chloride concentration or osmolarity, or to extracellular events after secretion of the recombinant protein into the supernatant. Ammonium chloride, inhibited the expression rate of mPL-I by CHO cells at low pH[sub e].

  6. Triclosan activates aryl hydrocarbon receptor (AhR)-dependent apoptosis and affects Cyp1a1 and Cyp1b1 expression in mouse neocortical neurons.

    PubMed

    Szychowski, Konrad A; Wnuk, Agnieszka; Kajta, Małgorzata; Wójtowicz, Anna K

    2016-11-01

    Triclosan (TCS) is an antimicrobial agent that is used extensively in personal care and in sanitizing products, such as soaps, toothpastes, and hair products. A number of studies have revealed the presence of TCS in human tissues, such as fat, liver and brain, in addition to blood and breast milk. The aim of the present study was to investigate the impact of TCS on AhR and Cyp1a1/Cyp1b1 signaling in mouse neocortical neurons in primary cultures. In addition to the use of selective ligands and siRNAs, expression levels of mRNA and proteins as well as caspase-3 activity, reactive oxygen species (ROS) formation, and lactate dehydrogenase (LDH) release have been measured. We also studied the involvement of the AhR in TCS-induced LDH release and caspase-3 activation as well as the effect of TCS on ROS generation. Cultures of neocortical neurons were prepared from Swiss mouse embryos on day 15/16 of gestation. The cells were cultured in phenol red-free Neurobasal medium with B27 and glutamine, and the neurons were exposed to 1 and 10µM TCS. Our experiments showed that the expression of AhR and Cyp1a1 mRNA decreased in cells exposed to 10µM TCS for 3 or 6h. In the case of Cyp1b1, mRNA expression remained unchanged compared with the control group following 3h of exposure to TCS, but after 6h, the mRNA expression of Cyp1b1 was decreased. Our results confirmed that the AhR is involved in the TCS mechanism of action, and our data demonstrated that after the cells were transfected with AhR siRNA, the cytotoxic and pro-apoptotic properties of TCS were decreased. The decrease in Cyp1a1 mRNA and protein expression levels accompanied by a decrease in its activity. The stimulation of Cyp1a1 activity produced by the application of an AhR agonist (βNF) was attenuated by TCS, whereas the addition of AhR antagonist (αNF) reversed the inhibitory effects of TCS. In our experiments, TCS diminished Cyp1b1 mRNA and enhanced its protein expression. In case of Cyp1a1 we observed

  7. Functional expression of P2X family receptors in macrophages is affected by microenvironment in mouse T cell acute lymphoblastic leukemia

    SciTech Connect

    Chen, Shayan; Feng, Wenli; Yang, Xiao; Yang, Wanzhu; Ru, Yongxin; Liao, Jinfeng; Wang, Lina; Lin, Yongmin; Ren, Qian; Zheng, Guoguang

    2014-04-18

    Highlights: • We study the impact of leukemic microenvironment on P2X family receptors in Mφs. • Bone marrow and spleen Mφs are studied in Notch1-induced mouse leukemia model. • Increased expression of P2X7R is found in Mφs during the development of leukemia. • Elevated P2X7R-mediated calcium response is found in Mφs at late stage of leukemia. • More apoptotic Mφs are found in bone marrow and spleen at late stage of leukemia. - Abstract: Nucleotides are important players in intercellular signaling communication network. P2X family receptors (P2XRs) are ATP-gated plasma membrane ion channels with diverse biological functions. Macrophages are important components in the microenvironment of hematopoiesis participating in both physiological and pathological processes. However, the role of P2XRs in macrophages in leukemia has not been established. Here we investigated expression pattern and functions of P2XRs in macrophages from bone marrow (BM) and spleen of Notch1-induced T-ALL mice. Real-time PCR showed that P2XRs except P2X5R were expressed in BM and spleen macrophages. Furthermore, with the development of leukemia, the expression of P2X7R increased in both BM and spleen macrophages whereas expression of P2X1R increased in spleen macrophages. Live cell imaging recoding the Ca{sup 2+} response demonstrated that P2X7R expressed in macrophages was functional. TUNEL and electron microscopy analysis found that apoptotic macrophages were frequently observed in BM and spleen at late stage of leukemia, which was partly contributed by the activation of overexpressed P2X7R. Our results suggested that the intercellular communication mediated by nucleotides might orchestrate in the pathological process of leukemia and could be a potential target for the treatment of leukemia.

  8. Endostar enhances the antitumor effects of radiation by affecting energy metabolism and alleviating the tumor microenvironment in a Lewis lung carcinoma mouse model

    PubMed Central

    ZHENG, YONG-FA; GE, WEI; XU, HUI-LIN; CAO, DE-DONG; LIU, LIANG; MING, PING-PO; LI, CHANG-HU; XU, XI-MING; TAO, WEI-PING; TAO, ZE-ZHANG

    2015-01-01

    Lung cancer is a leading cause of morbidity and mortality. Previous studies have identified that an improvement in treatment efficacy was achieved using Endostar; however, the role of Endostar in lung cancer remains poorly understood. The present study investigated whether the enhanced antitumor effects of Endostar in combination with radiation involved changes in the metabolism and microenvironment in non-small cell lung cancer. A Lewis lung carcinoma mouse model was used, including the control, Endostar (ES), radiotherapy (RT) and Endostar plus radiotherapy (ES + RT) groups. The tumor inhibition rates and growth were described based on changes in tumor volume. In addition, ultraviolet enzymatic analysis was performed to determine the lactate level and reverse transcription-polymerase chain reaction was used to measure the mRNA expression of lactate dehydrogenase (LDH). A Meph-3 pH meter was used to detect the ranges of tumor interstitial tissue pH, and immunohistochemical analysis was adopted to examine hypoxia within the tumor microenvironment. The tumor inhibition rate of the ES + RT group was significantly higher compared with the other three groups (P<0.05). Following treatment, the lactate levels decreased in all three treatment groups compared with the control, particularly in the ES + RT group (P<0.05). Reduced LDH expression and hypoxic fraction in the tumor microenvironment were also observed in the ES + RT group (P<0.05). Furthermore, changes from acidic to alkaline pH in the tumor microenvironment were detected in the ES + RT group. The present study suggested that Endostar is involved in the regulation of metabolism and tumor microenvironment hypoxia, which may be responsible for the enhanced antitumor effect of Endostar in combination with radiotherapy. PMID:26722291

  9. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    SciTech Connect

    Karman, Bethany N. Basavarajappa, Mallikarjuna S. Craig, Zelieann R. Flaws, Jodi A.

    2012-05-15

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ►TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ►Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ►TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  10. In Vivo Murine Model of Continuous Intramedullary Infusion of Particles – A Preliminary Study

    PubMed Central

    Ma, Ting; Ortiz, Steven G.; Huang, Zhinong; Ren, Peigen; Smith, R. Lane; Goodman, Stuart B.

    2008-01-01

    Continued production of wear debris affects both initial osseointegration and subsequent bone remodeling of total joint replacements (TJRs). However, continuous delivery of clinically relevant particles using a viable, cost effective, quantitative animal model to simulate the scenario in humans has been a challenge for orthopaedic researchers. In this study, we successfully infused blue-dyed polystyrene particles, similar in size to wear debris in humans, to the intramedullary space of the mouse femur for four weeks using an osmotic pump. Approximately 40% of the original particle load (85 ul) was delivered into the intramedullary space, an estimate of 3 × 10 9 particles. The visible blue dye carried by the particles confirmed the delivery. This model demonstrated that continuous infusion of particles to the murine bone-implant interface is possible. In vivo biological processes associated using wear debris particles can be studied using this new animal model. PMID:18777575

  11. Norovirus P particle-based active Aβ immunotherapy elicits sufficient immunogenicity and improves cognitive capacity in a mouse model of Alzheimer’s disease

    PubMed Central

    Fu, Lu; Li, Yingnan; Hu, Yue; Zheng, Yayuan; Yu, Bin; Zhang, Haihong; Wu, Jiaxin; Wu, Hui; Yu, Xianghui; Kong, Wei

    2017-01-01

    Disease-modifying immunotherapies focusing on reducing amyloid-beta (Aβ) deposition are the main treatment for Alzheimer’s disease (AD). However, none of the Aβ immunotherapies has produced clinically meaningful results to date. The main reason for this lack of efficacy is that the vaccine induces insufficiently high antibody titers, as it contains small B-cell epitope of Aβ to avoid Aβ42-specific T-cell activation. With the aim of generating a potent AD vaccine, we designed the protein PP-3copy-Aβ1-6-loop123, comprising three copies of Aβ1-6 inserted into three loops of a novel vaccine platform, the norovirus P particle, which could present Aβ at its surface and remarkably enhance the immunogenicity of the vaccine. We demonstrated that PP-3copy-Aβ1-6-loop123 was able to elicit high antibody titers against Aβ42, without causing T-cell activation, in AD mice regardless of their age. Importantly, PP-3copy-Aβ1-6-loop123 treatment successfully reduced amyloid deposition, rescued memory loss, and repaired hippocampus damage in AD mice. The Aβ antibodies induced by this active immunotherapy reacted with and disrupted aggregated Aβ, reducing its cellular toxicity. In addition, our results suggested PP-3copy-Aβ1-6-loop123 immunization could restore Aβ42 homeostasis in both the serum and brain. Thus, the P particle-based Aβ epitope vaccine is a sufficiently immunogenic and safe immunotherapeutic intervention for Alzheimer’s disease. PMID:28106117

  12. Hepatic expression of the GH/JAK/STAT/IGF pathway, acute-phase response signalling and complement system are affected in mouse offspring by prenatal and early postnatal exposure to maternal high-protein diet.

    PubMed

    Vanselow, Jens; Kucia, Marzena; Langhammer, Martina; Koczan, Dirk; Rehfeldt, Charlotte; Metges, Cornelia C

    2011-12-01

    Effects of pre- and early postnatal exposure to maternal high-protein diets are not well understood. Transcription profiling was performed in male mouse offspring exposed to maternal high-protein diet during pregnancy and/or lactation to identify affected hepatic molecular pathways. Dams were fed isoenergetic diets with control (20% w/w) or high protein levels (40%). The hepatic expression profiles were evaluated by differential microarray analysis 3 days (d3) and 3 weeks (d21) after birth. Offspring from three different high-protein dietary groups, HP (d3, high-protein diet during pregnancy), HPHP (d21, high-protein diet during pregnancy and lactation) and CHP (d21, control diet during pregnancy and high-protein diet during lactation), were compared with age-matched offspring from dams fed control diet. Offspring body and liver mass of all high-protein groups were decreased. Prenatal high-protein diet affected hepatic expression of genes mapping to the acute response/complement system and the GH/JAK/STAT/IGF signalling pathways. Maternal exposure to high-protein diet during lactation affected hepatic gene expression of the same pathways but additionally affected genes mapping to protein, fatty acid, hexose and pyruvate metabolism. (1) Genes of the acute response/complement system and GH/JAK/STAT/IGF pathways were down-regulated in offspring of dams exposed to high-protein diets during pregnancy and/or lactation. (2) Genes related to nutrient and energy metabolism, however, were only affected when high-protein diet was administered during lactation. (3) Modulation of the GH/JAK/STAT/IGF pathway might be responsible for reduced body and liver masses by maternal high-protein diet.

  13. Ovarian Sex Hormones Modulate Compulsive, Affective and Cognitive Functions in A Non-Induced Mouse Model of Obsessive-Compulsive Disorder

    PubMed Central

    Mitra, Swarup; Bastos, Cristiane P.; Bates, Katherine; Pereira, Grace S.; Bult-Ito, Abel

    2016-01-01

    There is currently a lack of understanding of how surgical menopause can influence obsessions, compulsions and associated affective and cognitive functions in female obsessive-compulsive disorder (OCD) patients. Early menopause in women due to surgical removal of ovaries not only causes dramatic hormonal changes, but also may induce affective and cognitive disorders. Here, we tested if surgical removal of ovaries (ovariectomy, OVX), which mimics surgical menopause in humans, would result in exacerbation of compulsive, affective and cognitive behaviors in mice strains that exhibit a spontaneous compulsive-like phenotype. Female mice from compulsive-like BIG, non-compulsive SMALL and randomly-bred Control strains were subjected to OVX or sham-surgery. After 7 days animals were tested for nest building and marble burying to measure compulsive-like behavior. The elevated plus maze and open field tests measured anxiety-like behaviors, while memory was assessed by the novel object recognition. Acute OVX resulted in exacerbation of compulsive-like and anxiety-like behaviors in compulsive-like BIG mice. No significant effects of OVX were observed for the non-compulsive SMALL and Control strains. Object recognition memory was impaired in compulsive-like BIG female mice compared to the Control mice, without an effect of OVX on the BIG mice. We also tested whether 17 β-estradiol (E2) or progesterone (P4) could reverse the effects of OVX. E2, but not P4, attenuated the compulsive-like behaviors in compulsive-like BIG OVX female mice. The actions of the sex steroids on anxiety-like behaviors in OVX females were strain and behavioral test dependent. Altogether, our results indicate that already existing compulsions can be worsened during acute ovarian deprivation concomitant with exacerbation of affective behaviors and responses to hormonal intervention in OVX female mice can be influenced by genetic background. PMID:27881956

  14. Liquid marbles stabilized by charged polymer latexes: how does the drying of the latex particles affect the properties of liquid marbles?

    PubMed

    Sun, Guanqing; Sheng, Yifeng; Wu, Jie; Ma, Guanghui; Ngai, To

    2014-10-28

    The coating of solid particles on the surface of liquid in air makes liquid marbles a promising approach in the transportation of a small amount of liquid. The stabilization of liquid marbles by polymeric latex particles imparts extra triggers such as pH and temperature, leading to the remote manipulation of droplets for many potential applications. Because the functionalized polymeric latexes can exist either as colloidally stable latex or as flocculated latex in a dispersion, the drying of latex dispersions under different conditions may play a significant role in the stabilization of subsequent liquid marbles. This article presents the investigation of liquid marbles stabilized by poly(styrene-co-methacrylic acid) (PS-co-MAA) particles drying under varied conditions. Protonation of the particles before freeze drying makes the particles excellent liquid marble stabilizers, but it is hard to stabilize liquid marbles for particles dried in their deprotonated states. The static properties of liquid marbles with increasing concentrations of protonating reagent revealed that the liquid marbles are gradually undermined by protonating the stabilizers. Furthermore, the liquid marbles stabilized by different particles showed distinct behaviors in separation and merging manipulated by tweezers. This study shows that the initial state of the particles should be carefully taken into account in formulating liquid marbles.

  15. Inoculation with enterococci does not affect colon inflammation in the multi-drug resistance 1a-deficient mouse model of IBD.

    PubMed

    Barnett, Matthew P G; Dommels, Yvonne E M; Butts, Christine A; Zhu, Shuotun; McNabb, Warren C; Roy, Nicole C

    2016-03-03

    Intestinal bacteria are thought to play a role in the pathogenesis of human inflammatory bowel disease (IBD). We investigated whether oral inoculation with specific intestinal bacteria increased colon inflammation in the multi-drug resistance 1a-deficient (Mdr1a (-/-) ) mouse model of IBD. Five-week-old Mdr1a (-/-) mice (FVB background) and FVB mice were randomly assigned to one of two treatment groups (Control or Inoculation, n = 12 per group). All mice were fed AIN-76A rodent diet, and mice in the Inoculation groups also received a single oral bacterial inoculation consisting of twelve cultured Enterococcus species combined with conventional intestinal flora obtained from the gastrointestinal tract of healthy mice (EF.CIF). Body weight, food intake, and disease activity index (DAI) were assessed throughout the study, and at 21 or 24 weeks of age, inflammation was assessed post-mortem by determining colon length and histological injury score (HIS), and plasma serum amyloid A (SAA). Mdr1a (-/-) mice consumed more food than FVB mice at 13 weeks of age (P < 0.05). There was also a significant effect of genotype on body weight, with Mdr1a (-/-) mice weighing less than FVB mice throughout the study (P < 0.05) regardless of treatment, but there was no effect of inoculation on body weight (P > 0.25). Colon HIS of Mdr1a (-/-) mice was significantly higher than that of FVB mice in the Control (9.3 ± 4.7 (mean ± SD) vs. 0.58 ± 0.51; P < 0.001) and Inoculation (6.7 ± 5.1 vs. 0.92 ± 0.39; P < 0.001) groups. There was no difference in colon HIS of Mdr1a (-/-) mice in the Control group compared with Mdr1a (-/-) mice in the Inoculation group (P = 0.25), nor was there any difference in within-group variation of colon HIS in these two Mdr1a (-/-) groups. DAI was higher in Mdr1a (-/-) mice than in FVB mice, but there was no effect of treatment in either strain, nor were there any differences in colon length or plasma SAA. Inoculation of Mdr1a (-/-) mice with the EF

  16. Effective cancer therapy with the alpha-particle emitter [211At]astatine in a mouse model of genetically modified sodium/iodide symporter-expressing tumors.

    PubMed

    Petrich, Thorsten; Quintanilla-Martinez, Leticia; Korkmaz, Zekiye; Samson, Elenore; Helmeke, Hans Jürgen; Meyer, Geerd Jürgen; Knapp, Wolfram H; Pötter, Eyck

    2006-02-15

    The sodium/iodide symporter (NIS) gene is currently explored in several trials to eradicate experimental cancer with radiodine ((131)I) by its beta-emission. We recently characterized NIS-specific cellular uptake of an alternative halide, radioastatine ((211)At), which emits high-energy alpha-particles. The aim of this study was to investigate in vivo effects of the high linear energy transfer (LET) emitter (211)At on tumor growth and outcome in nude mice. We administered radioastatide in a fractionated therapy scheme to NMRI nude mice harboring rapidly growing solid tumors established from a papillary thyroid carcinoma cell line genetically modified to express NIS (K1-NIS). Animals were observed over 1 year. Tumor growth, body weight, blood counts, survival, and side effects were measured compared with control groups without therapy and/or lack of NIS expression. Within 3 months, radioastatide caused complete primary tumor eradication in all cases of K1-NIS tumor-bearing nude mice (n = 25) with no tumor recurrence during 1 year follow-up. Survival rates of the K1-NIS/(211)At group were 96% after 6 months and 60% after 1 year, in contrast to those of control groups (maximum survival 40 days). Our study indicates that (211)At represents a promising substrate for NIS-mediated therapy of various cancers either with endogenous or gene transfer-mediated NIS expression.

  17. Comparative Label-Free Mass Spectrometric Analysis of Mildly versus Severely Affected mdx Mouse Skeletal Muscles Identifies Annexin, Lamin, and Vimentin as Universal Dystrophic Markers.

    PubMed

    Holland, Ashling; Henry, Michael; Meleady, Paula; Winkler, Claudia K; Krautwald, Mirjam; Brinkmeier, Heinrich; Ohlendieck, Kay

    2015-06-19

    The primary deficiency in the membrane cytoskeletal protein dystrophin results in complex changes in dystrophic muscles. In order to compare the degree of secondary alterations in differently affected subtypes of skeletal muscles, we have conducted a global analysis of proteome-wide changes in various dystrophin-deficient muscles. In contrast to the highly degenerative mdx diaphragm muscle, which showed considerable alterations in 35 distinct proteins, the spectrum of mildly to moderately dystrophic skeletal muscles, including interosseus, flexor digitorum brevis, soleus, and extensor digitorum longus muscle, exhibited a smaller number of changed proteins. Compensatory mechanisms and/or cellular variances may be responsible for differing secondary changes in individual mdx muscles. Label-free mass spectrometry established altered expression levels for diaphragm proteins associated with contraction, energy metabolism, the cytoskeleton, the extracellular matrix and the cellular stress response. Comparative immunoblotting verified the differences in the degree of secondary changes in dystrophin-deficient muscles and showed that the up-regulation of molecular chaperones, the compensatory increase in proteins of the intermediate filaments, the fibrosis-related increase in collagen levels and the pathophysiological decrease in calcium binding proteins is more pronounced in mdx diaphragm as compared to the less severely affected mdx leg muscles. Annexin, lamin, and vimentin were identified as universal dystrophic markers.

  18. Development of Mouse Lung Deposition Models

    DTIC Science & Technology

    2015-07-01

    Particle inhalability in mice was lower than that in rats . In contrast, deposition of the same size particle was higher in mice nasal passages than...that in rats . Thus, fewer particles entered the mouse lung in comparison with rat particle inhalation. The penetration was severely limited for...geometry that was previously developed for humans, rats , and rhesus monkeys [6], [7]. Inputs to the model included lung geometry and volumes, and

  19. The Mouse That Soared

    NASA Astrophysics Data System (ADS)

    2004-09-01

    Astronomers have used an X-ray image to make the first detailed study of the behavior of high-energy particles around a fast moving pulsar. The image, from NASA's Chandra X-ray Observatory, shows the shock wave created as a pulsar plows supersonically through interstellar space. These results will provide insight into theories for the production of powerful winds of matter and antimatter by pulsars. Chandra's image of the glowing cloud, known as the Mouse, shows a stubby bright column of high-energy particles, about four light years in length, swept back by the pulsar's interaction with interstellar gas. The intense source at the head of the X-ray column is the pulsar, estimated to be moving through space at about 1.3 million miles per hour. VLA Radio Image of the Mouse, Full Field VLA Radio Image of the Mouse, Full Field A cone-shaped cloud of radio-wave-emitting particles envelopes the X-ray column. The Mouse, a.k.a. G359.23-0.82, was discovered in 1987 by radio astronomers using the National Science Foundation's Very Large Array in New Mexico. It gets its name from its appearance in radio images that show a compact snout, a bulbous body, and a remarkable long, narrow, tail that extends for about 55 light years. "A few dozen pulsar wind nebulae are known, including the spectacular Crab Nebula, but none have the Mouse's combination of relatively young age and incredibly rapid motion through interstellar space," said Bryan Gaensler of the Harvard-Smithsonian Center for Astrophysics and lead author of a paper on the Mouse that will appear in an upcoming issue of The Astrophysical Journal. "We effectively are seeing a supersonic cosmic wind tunnel, in which we can study the effects of a pulsar's motion on its pulsar wind nebula, and test current theories." Illustration of the Mouse System Illustration of the Mouse System Pulsars are known to be rapidly spinning, highly magnetized neutron stars -- objects so dense that a mass equal to that of the Sun is packed into a

  20. Auroral particles

    NASA Astrophysics Data System (ADS)

    Evans, David S.

    1987-06-01

    The problems concerning the aurora posed prior to the war are now either solved in principle or were restated in a more fundamental form. The pre-war hypothesis concerning the nature of the auroral particles and their energies was fully confirmed, with the exception that helium and oxygen ions were identified as participating in the auroral particle precipitation in addition to the protons. The nature of the near-Earth energization processes affecting auroral particles was clarified. Charged particle trajectories in various electric field geometries were modeled. The physical problems have now moved from determining the nature and geometry of the electric fields, which accelerate charged particles near the Earth, to accounting for the existence of these electric fields as a natural consequence of the solar wind's interaction with Earth. Ultimately the reward in continuing the work in auroral and magnetospheric particle dynamics will be a deeper understanding of the subtleties of classical electricity and magnetism as applied to situations not blessed with well-defined and invariant geometries.

  1. Auroral particles

    NASA Technical Reports Server (NTRS)

    Evans, David S.

    1987-01-01

    The problems concerning the aurora posed prior to the war are now either solved in principle or were restated in a more fundamental form. The pre-war hypothesis concerning the nature of the auroral particles and their energies was fully confirmed, with the exception that helium and oxygen ions were identified as participating in the auroral particle precipitation in addition to the protons. The nature of the near-Earth energization processes affecting auroral particles was clarified. Charged particle trajectories in various electric field geometries were modeled. The physical problems have now moved from determining the nature and geometry of the electric fields, which accelerate charged particles near the Earth, to accounting for the existence of these electric fields as a natural consequence of the solar wind's interaction with Earth. Ultimately the reward in continuing the work in auroral and magnetospheric particle dynamics will be a deeper understanding of the subtleties of classical electricity and magnetism as applied to situations not blessed with well-defined and invariant geometries.

  2. The method used to culture host cells (Sf9 cells) can affect the qualities of baculovirus budding particles expressing recombinant proteins.

    PubMed

    Hattori, Tomomi; Nakanishi, Kohei; Mori, Takaaki; Tomita, Masahiro; Tsumoto, Kanta

    2016-01-01

    Budded virus (BV) particles of baculovirus (Autographa californica nucleopolyhedrovirus, AcNPV) are harvested from the supernatant of liquid culture of Sf9 host cells by ultracentrifugation. Using polyacrylamide gel electrophoresis, Western blot and transmission electron microscopy (TEM) of BV samples fractionated closely by sucrose density gradient centrifugation, we observed that BVs exhibited different qualities depending on whether they had been harvested from the supernatant from a standing (static), shaking (suspension), or standing/shaking (pre-/post-infection) culture of Sf9 cells. The amount of BV protein apparently increased in the order of standing, standing/shaking, and shaking procedure, and the yield of intact particles showed an opposite trend. TEM observation clearly showed that appropriate fractions of the standing and standing/shaking cultures contained more intact BV particles than those from the shaking culture. These results suggest that the qualities of recombinant BV particles may be related to the culture conditions of the host cells.

  3. Low-dose γ-rays modify CD4(+) T cell signalling response to simulated solar particle event protons in a mouse model.

    PubMed

    Rizvi, Asma; Pecaut, Michael J; Slater, James M; Subramaniam, Shruti; Gridley, Daila S

    2011-01-01

    Astronauts on missions are exposed to low-dose/low-dose-rate (LDR) radiation and could receive high doses during solar particle events (SPE). This study investigated T cell function in response to LDR radiation and simulated SPE (sSPE) protons, alone and in combination. C57BL/6 mice received LDR γ-radiation (⁵⁷Co) to a total dose of 0.01 Gray (Gy) at 0.179 mGy/h, either with or without subsequent exposure to 1.7 Gy sSPE protons delivered over 36 h. Mice were euthanised on days 4 and 21 post-exposure. T cells with cluster of differentiation 4 (CD4(+)) were negatively isolated from spleens and activated with anti-CD3 antibody. Cells and supernatants were evaluated for survival/signalling proteins and cytokines. The most striking effects were noted on day 21. In the survival pathway, nuclear factor-kappaB (NF-κB; total and active forms) and p38 mitogen activated protein kinase (p38MAPK; total) were significantly increased and cJun N-terminal kinase (JNK; total and active) was decreased when mice were primed with LDR γ-rays prior to sSPE exposure (P < 0.001). Evaluation of the T cell antigen receptor (TCR) signalling pathway revealed that LDR γ-ray exposure normalised the high sSPE proton-induced level of lymphocyte specific protein tyrosine kinase (Lck; total and active) on day 21 (P < 0.001 for sSPE vs. LDR + sSPE), while radiation had no effect on active zeta-chain-associated protein kinase 70 (Zap-70). There was increased production of interleukin-2 (IL-2) and IL-4 and decreased transforming growth factor-β1 in the LDR + sSPE group compared to the sSPE group. The data demonstrate, for the first time, that protracted exposure to LDR γ-rays can significantly modify the effects of sSPE protons on critical survival/signalling proteins and immunomodulatory cytokines produced by CD4(+) T cells.

  4. Chandra Catches the `Mouse'

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Astronomers have used an x-ray image to make the first detailed study of the behavior of high-energy particles around a fast moving pulsar. This image, from NASA's Chandra X-Ray Observatory (CXO), shows the shock wave created as a pulsar plows supersonically through interstellar space. These results will provide insight into theories for the production of powerful winds of matter and antimatter by pulsars. Chandra's image of the glowing cloud, known as the Mouse, shows a stubby bright column of high-energy particles, about four light years in length, swept back by the pulsar's interaction with interstellar gas. The intense source at the head of the X-ray column is the pulsar, estimated to be moving through space at about 1.3 million miles per hour. A cone-shaped cloud of radio-wave-emitting particles envelopes the x-ray column. The Mouse, a.k.a. G359.23-0.82, was discovered in 1987 by radio astronomers using the National Science Foundation's Very Large Array in New Mexico. G359.23-0.82 gets its name from its appearance in radio images that show a compact snout, a bulbous body, and a remarkable long, narrow, tail that extends for about 55 light years. NASA's Marshall Space Flight Center in Huntsville, Alabama manages the Chandler program.

  5. Mouse phenotyping.

    PubMed

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  6. The RetC620R Mutation Affects Renal and Enteric Development in a Mouse Model of Hirschsprung’s Disease

    PubMed Central

    Carniti, Cristiana; Belluco, Sara; Riccardi, Elena; Cranston, Aaron N.; Mondellini, Piera; Ponder, Bruce A.J.; Scanziani, Eugenio; Pierotti, Marco A.; Bongarzone, Italia

    2006-01-01

    In rare families RET tyrosine kinase receptor substitutions located in exon 10 (especially at positions 609, 618, and 620) can concomitantly cause the MEN 2A (multiple endocrine neoplasia type 2A) or FMTC (familial medullary thyroid carcinoma) cancer syndromes, and Hirschsprung’s disease (HSCR). No animal model mimicking the co-existence of the MEN 2 pathology and HSCR is available, and the association of these activating mutations with a developmental defect still represents an unresolved problem. The aim of this work was to investigate the significance of the RETC620R substitution in the pathogenesis of both gain- and loss-of-function RET-associated diseases. We report the generation of a line of mice carrying the C620R mutation in the Ret gene. Although RetC620R homozygotes display severe defects in kidney organogenesis and enteric nervous system development leading to perinatal lethality. RetC620R heterozygotes recapitulate features characteristic of HSCR including hypoganglionosis of the gastrointestinal tract. Surprisingly, heterozygotes do not show any defects in the thyroid that might be attributable to a gain-of-function mutation. The RetC620R allele is responsible for HSCR and affects the development of kidneys and the enteric nervous system (ENS). These mice represent an interesting model for studying new therapeutic approaches for the treatment of HSCR disease. PMID:16565500

  7. Toll-like receptor 7 suppresses virus replication in neurons but does not affect viral pathogenesis in a mouse model of Langat virus infection

    PubMed Central

    Baker, David G.; Woods, Tyson A.; Butchi, Niranjan B.; Morgan, Timothy M.; Taylor, R. Travis; Sunyakumthorn, Piyanate; Mukherjee, Piyali; Lubick, Kirk J.; Best, Sonja M.

    2013-01-01

    Toll-like receptor 7 (TLR7) recognizes guanidine-rich viral ssRNA and is an important mediator of peripheral immune responses to several ssRNA viruses. However, the role that TLR7 plays in regulating the innate immune response to ssRNA virus infections in specific organs such as the central nervous system (CNS) is not as clear. This study examined the influence of TLR7 on the neurovirulence of Langat virus (LGTV), a ssRNA tick-borne flavivirus. TLR7 deficiency did not substantially alter the onset or incidence of LGTV-induced clinical disease; however, it did significantly affect virus levels in the CNS with a log10 increase in virus titres in brain tissue from TLR7-deficient mice. This difference in virus load was also observed following intracranial inoculation, indicating a direct effect of TLR7 deficiency on regulating virus replication in the brain. LGTV-induced type I interferon responses in the CNS were not dependent on TLR7, being higher in TLR7-deficient mice compared with wild-type controls. In contrast, induction of pro-inflammatory cytokines including tumour necrosis factor, CCL3, CCL4 and CXCL13 were dependent on TLR7. Thus, although TLR7 is not essential in controlling LGTV pathogenesis, it is important in controlling virus infection in neurons in the CNS, possibly by regulating neuroinflammatory responses. PMID:23136362

  8. Toll-like receptor 7 suppresses virus replication in neurons but does not affect viral pathogenesis in a mouse model of Langat virus infection.

    PubMed

    Baker, David G; Woods, Tyson A; Butchi, Niranjan B; Morgan, Timothy M; Taylor, R Travis; Sunyakumthorn, Piyanate; Mukherjee, Piyali; Lubick, Kirk J; Best, Sonja M; Peterson, Karin E

    2013-02-01

    Toll-like receptor 7 (TLR7) recognizes guanidine-rich viral ssRNA and is an important mediator of peripheral immune responses to several ssRNA viruses. However, the role that TLR7 plays in regulating the innate immune response to ssRNA virus infections in specific organs such as the central nervous system (CNS) is not as clear. This study examined the influence of TLR7 on the neurovirulence of Langat virus (LGTV), a ssRNA tick-borne flavivirus. TLR7 deficiency did not substantially alter the onset or incidence of LGTV-induced clinical disease; however, it did significantly affect virus levels in the CNS with a log(10) increase in virus titres in brain tissue from TLR7-deficient mice. This difference in virus load was also observed following intracranial inoculation, indicating a direct effect of TLR7 deficiency on regulating virus replication in the brain. LGTV-induced type I interferon responses in the CNS were not dependent on TLR7, being higher in TLR7-deficient mice compared with wild-type controls. In contrast, induction of pro-inflammatory cytokines including tumour necrosis factor, CCL3, CCL4 and CXCL13 were dependent on TLR7. Thus, although TLR7 is not essential in controlling LGTV pathogenesis, it is important in controlling virus infection in neurons in the CNS, possibly by regulating neuroinflammatory responses.

  9. Melatonin adjusts the expression pattern of clock genes in the suprachiasmatic nucleus and induces antidepressant-like effect in a mouse model of seasonal affective disorder.

    PubMed

    Nagy, Andras David; Iwamoto, Ayaka; Kawai, Misato; Goda, Ryosei; Matsuo, Haruka; Otsuka, Tsuyoshi; Nagasawa, Mao; Furuse, Mitsuhiro; Yasuo, Shinobu

    2015-05-01

    Recently, we have shown that C57BL/6J mice exhibit depression-like behavior under short photoperiod and suggested them as an animal model for investigating seasonal affective disorder (SAD). In this study, we tested if manipulations of the circadian clock with melatonin treatment could effectively modify depression-like and anxiety-like behaviors and brain serotonergic system in C57BL/6J mice. Under short photoperiods (8-h light/16-h dark), daily melatonin treatments 2 h before light offset have significantly altered the 24-h patterns of mRNA expression of circadian clock genes (per1, per2, bmal1 and clock) within the suprachiasmatic nuclei (SCN) mostly by increasing amplitude in their expressional rhythms without inducing robust phase shifts in them. Melatonin treatments altered the expression of genes of serotonergic neurotransmission in the dorsal raphe (tph2, sert, vmat2 and 5ht1a) and serotonin contents in the amygdala. Importantly, melatonin treatment reduced the immobility in forced swim test, a depression-like behavior. As a key mechanism of melatonin-induced antidepressant-like effect, the previously proposed phase-advance hypothesis of the circadian clock could not be confirmed under conditions of our experiment. However, our findings of modest adjustments in both the amplitude and phase of the transcriptional oscillators in the SCN as a result of melatonin treatments may be sufficient to associate with the effects seen in the brain serotonergic system and with the improvement in depression-like behavior. Our study confirmed a predictive validity of C57BL/6J mice as a useful model for the molecular analysis of links between the clock and brain serotonergic system, which could greatly accelerate our understanding of the pathogenesis of SAD, as well as the search for new treatments.

  10. P-glycoprotein differentially affects escitalopram, levomilnacipran, vilazodone and vortioxetine transport at the mouse blood-brain barrier in vivo.

    PubMed

    Bundgaard, Christoffer; Eneberg, Elin; Sánchez, Connie

    2016-04-01

    P-glycoprotein (P-gp)-mediated brain efflux of xenobiotics is a well-known process, which may result in suboptimal target engagement and consequently reduced efficacy of drugs exerting their therapeutic effects in the central nervous system. In the present study the role of P-gp in transport across the blood-brain barrier (BBB) was investigated with a series of newer antidepressants (levomilnacipran, vilazodone and vortioxetine) and a control substrate (escitalopram) using P-gp knock-out (KO) and P-gp competent wild-type (WT) mice. Brain and plasma exposure time-courses were measured after an acute subcutaneous dose and at steady-state obtained after subcutaneous drug infusion by osmotic minipumps. Following acute dosing, the brain-to-plasma KO/WT exposure enhancement ratios ((AUCbrain ko/AUCplasma ko)/(AUCbrain WT/AUCplasma WT)) were 5.8 (levomilnacipran), 5.4 (vilazodone), 3.1 (escitalopram) and 0.9 (vortioxetine), respectively. At steady-state, assessment of Kp,uu (unbound brain concentrations/unbound plasma concentrations) revealed a restriction in the brain distribution in WT mice for all compounds except vortioxetine. Levomilnacipran exhibited the most pronounced efflux with a Kp,uu-value of 0.038 in WT mice which was increased to 0.37 in KO mice. Based on both the acute and steady-state distribution data, the results suggest that levomilnacipran, vilazodone and escitalopram are susceptible to P-gp mediated efflux at the BBB in vivo in mice, whereas vortioxetine was practically devoid of being affected by P-gp in vivo. The functional impact of the drug transport-controlling role of P-gp at the BBB was demonstrated by in vivo cortical serotonin transporter occupancy of vilazodone, which exhibited a 20-fold higher plasma EC50 in WT mice compared to KOs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Antidepressant-like effect of bright light is potentiated by L-serine administration in a mouse model of seasonal affective disorder.

    PubMed

    Kawai, Misato; Goda, Ryosei; Otsuka, Tsuyoshi; Iwamoto, Ayaka; Uotsu, Nobuo; Furuse, Mitsuhiro; Yasuo, Shinobu

    2015-09-01

    Bright light therapy is used as the primary treatment for seasonal affective disorder; however, the mechanisms underlying its antidepressant effect are not fully understood. Previously, we found that C57BL/6J mice exhibit increased depression-like behavior during a short-day condition (SD) and have lowered brain serotonin (5-HT) content. This study analyzed the effect of bright light on depression-like behaviors and the brain serotonergic system using the C57BL/6J mice. In the mice maintained under SD, bright light treatment (1000 lx, daily 1 h exposure) for 1 week reduced immobility time in the forced swimming test and increased intake of saccharin solution in a saccharin intake test. However, the light treatment did not modify 5-HT content and selective 5-HT uptake in the amygdala, or temporal patterns of core body temperature and wheel-running activity throughout a day. In the next experiment, we attempted to enhance the effect of bright light by using L-serine, a precursor of D-serine that acts as an N-methyl-D-aspartic acid receptor coagonist. Daily subcutaneous injection of L-serine for 2 weeks prior to the bright light strongly reduced the immobility time in the forced swimming test, suggesting a synergistic effect of light and L-serine. Furthermore, bright light increased the total number of 5-HT-immunoreactive cells and cells that had colocalized 5-HT and c-Fos immunosignals in several subregions of the raphe nuclei. These effects were potentiated by prior injection of L-serine. These data suggest that the bright light may elicit an antidepressant-like effect via enhanced 5-HT signals in the brain and L-serine can enhance these effects.

  12. Ethylene oxide inhalation at different exposure-rates affects binding levels in mouse germ cells and hemoglobin. Possible explanation for the effect.

    PubMed

    Sega, G A; Brimer, P A; Generoso, E E

    1991-08-01

    Male mice were exposed to [3H]EtO by inhalation at different exposure rates (300 parts per million (ppm) of EtO for 1 h: 150 ppm for 2 h: 75 ppm for 4 h). The total exposure was fixed at 300 ppm-h. The amount of EtO binding to developing spermatogenic stages, to sperm DNA, to testis DNA and to hemoglobin was then measured as a function of the EtO exposure rate. Generally, as the exposure rate increased there was an increase in the amount of EtO binding to the targets. For example, alkylation of sperm from the caudal epididymides 6 d posttreatment, of DNA from the vas sperm (averaged over 4 time points), of testis DNA (90 min posttreatment), and of hemoglobin (averaged over 4 time points), was 2.0 +/- 0.2 (SD), 1.8 +/- 0.4, 2.9 +/- 0.3, and 1.5 +/- 0.1 times greater, respectively, after an exposure to 300 ppm for 1 h than after an exposure to 75 ppm for 4 h. The testicular DNA from animals exposed to 300 ppm of [3H]EtO for 1 h was also analyzed for the presence of N7-hydroxyethylguanine (N7HEG) and O6-hydroxyethylguanine (O6HEG). The half-life (T1 2) of the N7HEG in the testis DNA was calculated to be 2.8 d. This lesion was removed relatively rapidly from the testis DNA and was probably excised by enzymatic repair. No formation of O6HEG was detected in any of the testis DNA samples analyzed. Additional experiments showed that the exposure rate effect was the result of less total EtO being taken in by the mice over long exposure times compared to that taken in during shorter exposure times at higher concentrations. This result argues against the idea that the exposure rate effect is the result of physiological/enzymological changes affecting transport or metabolism of the chemical within the animals under different exposure rate conditions.

  13. Short communication: Forage particle size and fat intake affect rumen passage, the fatty acid profile of milk, and milk fat production in dairy cows consuming dried distillers grains with solubles.

    PubMed

    Ramirez Ramirez, H A; Harvatine, K J; Kononoff, P J

    2016-01-01

    Four ruminally cannulated Holstein cows averaging (± SD) 116 ± 18 d in milk and 686 ± 52 kg of body weight were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments to test the effects of forage particle size and concentration of corn oil on milk fat depression. Cows were housed in individual stalls, milked daily at 0700 and 1800 h, and individually fed daily at 0900 h for ad libitum consumption allowing approximately 10% orts. Four 28-d periods, in which each cow was offered 1 of 4 total mixed rations, included reduced-fat dried distillers grains with solubles at 30% of dietary dry matter and differed in forage particle size by inclusion of chopped grass hay (LONGP) or grass hay pellets (SHORTP) and 0 or 2% corn oil (CO). Dietary treatments were 0% corn oil + short particle size (CO0+SHORTP), 0% corn oil + long particle size (CO0+LONGP), 2% corn oil + short particle size (CO2 + SHORTP), and 2% corn oil + long particle size (CO2 + LONGP). Dry matter intake and milk yield were not affected by treatment averaging 26.5 ± 1.19 kg/d and 32.8 ± 3.34 kg/d, respectively. A decrease was found in 3.5% fat-corrected milk with the inclusion of oil resulting in 34.6 and 26.6 ± 2.6 kg/d for 0 and 2% oil diets, respectively. An oil × size interaction was found for milk fat concentration resulting in 2.27, 3.02, 3.62, and 3.62 ± 0.23% for CO2+SHORTP, CO2 + LONGP, CO0 + SHORTP, and CO0 + LONGP, respectively. Fat yield was reduced from 1.22 to 0.81 ± 0.09 kg/d with 2% oil diets. Cows consuming diets with long particle size spent 29 more minutes eating compared with the cows consuming short particle size (198 and 169 ± 15 min/d). Rumination time decreased from 504 to 400 ± 35 min/d for cows consuming short particle size compared with long particle size. Total chewing was reduced from 702 to 570 ± 4 min/d when cows consumed short particle size. Feeding long particle size decreased rate of passage of dry matter from 3.38 to 2.89 ± 0.42%/h

  14. Intracisternal A-particle element transposition into the murine beta-glucuronidase gene correlates with loss of enzyme activity: a new model for beta-glucuronidase deficiency in the C3H mouse.

    PubMed

    Gwynn, B; Lueders, K; Sands, M S; Birkenmeier, E H

    1998-11-01

    The severity of human mucopolysaccharidosis type VII (MPS VII), or Sly syndrome, depends on the relative activity of the enzyme beta-glucuronidase. Loss of beta-glucuronidase activity can cause hydrops fetalis, with in utero or postnatal death of the patient. In this report, we show that beta-glucuronidase activity is not detectable by a standard fluorometric assay in C3H/HeOuJ (C3H) mice homozygous for a new mutation, gusmps2J. These gusmps2J/gusmps2J mice are born and survive much longer than the previously characterized beta-glucuronidase-null B6.C-H-2(bm1)/ByBir-gusmps (gusmps/gusmps) mice. Northern blot analysis of liver from gusmps2J/gusmps2J mice demonstrates a 750-bp reduction in size of beta-glucuronidase mRNA. A 5.4-kb insertion in the Gus-sh nucleotide sequence from these mice was localized by Southern blot analysis to intron 8. The ends of the inserted sequences were cloned by inverse PCR and revealed an intracisternal A-particle (IAP) element inserted near the 3' end of the intron. The sequence of the long terminal repeat (LTR) regions of the IAP most closely matches that of a composite LTR found in transposed IAPs previously identified in the C3H strain. The inserted IAP may contribute to diminished beta-glucuronidase activity either by interfering with transcription or by destabilizing the message. The resulting phenotype is much less severe than that previously described in the gusmps/gusmps mouse and provides an opportunity to study MPS VII on a genetic background that clearly modulates disease severity.

  15. Structural properties affecting the settling of coarse crushed coal in gasifiers. [With upward flow of gas through bed; effect of particle size and distribution

    SciTech Connect

    Hauserman, W.B.

    1984-01-01

    Coarsely crushed coals show wide variation in their ease and uniformity of settling through a fixed-bed gasifier. Their relative rate of thermal and mechanical attrition determine the limits of stable settling rates against upward flowing gases. Laboratory measurements of permeability and bulk shear strength of crushed lignite over a wide particle size range indicate gas/solid flow ratios over which stable settling rates are possible. The key factors in comparing coals as potential gasifier feeds are their thermal and mechanical friabilities and their caking tendency. For noncaking lignites, measurements of mechanical friabilities show a sharp increase with degree of pre-drying. While permeability decreases with decreasing particle size, bulk shear strength also decreases, though less sharply. For broad ranges of particle size, both parameters are dominated by the smaller particles present. Test procedures have been established to predict the shifts in size distribution during drying, pyrolysis, and settling, which in turn determine whether semi-stable bridges, bubbles, or channelling will occur. The slug flow assumption traditionally used in mathematical modelling of gasifier fuel bed behavior is not realistic. Laboratory data on friability, permeability, and shear strengt support failure scenarios for gasifier malfunctions near upper limits of throughput capacity and indicate a need for improved control over the fuel bed settling mechanisms.

  16. The absence of Ser389 phosphorylation in p53 affects the basal gene expression level of many p53-dependent genes and alters the biphasic response to UV exposure in mouse embryonic fibroblasts.

    PubMed

    Bruins, Wendy; Bruning, Oskar; Jonker, Martijs J; Zwart, Edwin; van der Hoeven, Tessa V; Pennings, Jeroen L A; Rauwerda, Han; de Vries, Annemieke; Breit, Timo M

    2008-03-01

    Phosphorylation is important in p53-mediated DNA damage responses. After UV irradiation, p53 is phosphorylated specifically at murine residue Ser389. Phosphorylation mutant p53.S389A cells and mice show reduced apoptosis and compromised tumor suppression after UV irradiation. We investigated the underlying cellular processes by time-series analysis of UV-induced gene expression responses in wild-type, p53.S389A, and p53(-/-) mouse embryonic fibroblasts. The absence of p53.S389 phosphorylation already causes small endogenous gene expression changes for 2,253, mostly p53-dependent, genes. These genes showed basal gene expression levels intermediate to the wild type and p53(-/-), possibly to readjust the p53 network. Overall, the p53.S389A mutation lifts p53-dependent gene repression to a level similar to that of p53(-/-) but has lesser effect on p53-dependently induced genes. In the wild type, the response of 6,058 genes to UV irradiation was strictly biphasic. The early stress response, from 0 to 3 h, results in the activation of processes to prevent the accumulation of DNA damage in cells, whereas the late response, from 12 to 24 h, relates more to reentering the cell cycle. Although the p53.S389A UV gene response was only subtly changed, many cellular processes were significantly affected. The early response was affected the most, and many cellular processes were phase-specifically lost, gained, or altered, e.g., induction of apoptosis, cell division, and DNA repair, respectively. Altogether, p53.S389 phosphorylation seems essential for many p53 target genes and p53-dependent processes.

  17. Mouse brain responses to charged particle radiation

    NASA Astrophysics Data System (ADS)

    Nelson, Gregory; Nelson, Gregory; Chang, Polly; Favre, Cecile; Fike, John; Mao, Xiao-Wen; Obenaus, Andre; Pecaut, Michael; Vlkolinsky, Roman; Song, Sheng-Kwei; Spigelman, Igor; Stampanoni, Marco

    CHANGES IN DISEASE LATENCY AND HOMEOSTASIS: 1) APP23 transgenic mice exhibit many of the pathological features of Alzheimer's Disease, and the disease progression is continuous over several months. Electrophysiological measurements have shown that disease-related decreases in synaptic efficacy occur earlier in irradiated APP23 animals. 2) Using vascular polymer cast technology combined with micro-tomographic imaging, microvasculature changes following irradiation have been detected and are consistent with loss of vessels and an increased spacing between them. The time course of vessel changes to control and irradiated animals is being constructed. 3) In order to assess the ability of the brain to respond to external environmental shocks and restore orderly normal function (homeostasis), we apply a controlled septic shock by treating animals with lipopolysaccharide (LPS). We find that in irradiated animals, the patterns of electrophysiological changes associated with reactions to lipopolysaccharide (LPS) are complex and unlike those of either LPS or irradiation alone. They further suggest that the brain continues to remodel for up to 6 months following radiation. This is consistent with the idea that irradiation may potentiate the risks from late secondary insults.

  18. Whole and particle-free diesel exhausts differentially affect cardiac electrophysiology, blood pressure, and autonomic balance in heart failure-prone rats.

    PubMed

    Carll, Alex P; Hazari, Mehdi S; Perez, Christina M; Krantz, Quentin Todd; King, Charly J; Winsett, Darrell W; Costa, Daniel L; Farraj, Aimen K

    2012-08-01

    Epidemiological studies strongly link short-term exposures to vehicular traffic and particulate matter (PM) air pollution with adverse cardiovascular (CV) events, especially in those with preexisting CV disease. Diesel engine exhaust is a key contributor to urban ambient PM and gaseous pollutants. To determine the role of gaseous and particulate components in diesel exhaust (DE) cardiotoxicity, we examined the effects of a 4-h inhalation of whole DE (wDE) (target PM concentration: 500 µg/m(3)) or particle-free filtered DE (fDE) on CV physiology and a range of markers of cardiopulmonary injury in hypertensive heart failure-prone rats. Arterial blood pressure (BP), electrocardiography, and heart rate variability (HRV), an index of autonomic balance, were monitored. Both fDE and wDE decreased BP and prolonged PR interval during exposure, with more effects from fDE, which additionally increased HRV triangular index and decreased T-wave amplitude. fDE increased QTc interval immediately after exposure, increased atrioventricular (AV) block Mobitz II arrhythmias shortly thereafter, and increased serum high-density lipoprotein 1 day later. wDE increased BP and decreased HRV root mean square of successive differences immediately postexposure. fDE and wDE decreased heart rate during the 4th hour of postexposure. Thus, DE gases slowed AV conduction and ventricular repolarization, decreased BP, increased HRV, and subsequently provoked arrhythmias, collectively suggesting parasympathetic activation; conversely, brief BP and HRV changes after exposure to particle-containing DE indicated a transient sympathetic excitation. Our findings suggest that whole- and particle-free DE differentially alter CV and autonomic physiology and may potentially increase risk through divergent pathways.

  19. Whole and Particle-Free Diesel Exhausts Differentially Affect Cardiac Electrophysiology, Blood Pressure, and Autonomic Balance in Heart Failure–Prone Rats

    PubMed Central

    Farraj, Aimen K.

    2012-01-01

    Epidemiological studies strongly link short-term exposures to vehicular traffic and particulate matter (PM) air pollution with adverse cardiovascular (CV) events, especially in those with preexisting CV disease. Diesel engine exhaust is a key contributor to urban ambient PM and gaseous pollutants. To determine the role of gaseous and particulate components in diesel exhaust (DE) cardiotoxicity, we examined the effects of a 4-h inhalation of whole DE (wDE) (target PM concentration: 500 µg/m3) or particle-free filtered DE (fDE) on CV physiology and a range of markers of cardiopulmonary injury in hypertensive heart failure–prone rats. Arterial blood pressure (BP), electrocardiography, and heart rate variability (HRV), an index of autonomic balance, were monitored. Both fDE and wDE decreased BP and prolonged PR interval during exposure, with more effects from fDE, which additionally increased HRV triangular index and decreased T-wave amplitude. fDE increased QTc interval immediately after exposure, increased atrioventricular (AV) block Mobitz II arrhythmias shortly thereafter, and increased serum high-density lipoprotein 1 day later. wDE increased BP and decreased HRV root mean square of successive differences immediately postexposure. fDE and wDE decreased heart rate during the 4th hour of postexposure. Thus, DE gases slowed AV conduction and ventricular repolarization, decreased BP, increased HRV, and subsequently provoked arrhythmias, collectively suggesting parasympathetic activation; conversely, brief BP and HRV changes after exposure to particle-containing DE indicated a transient sympathetic excitation. Our findings suggest that whole- and particle-free DE differentially alter CV and autonomic physiology and may potentially increase risk through divergent pathways. PMID:22543275

  20. On the presence of enriched amounts of 235U in hot particles from the terrestrial area affected by the Palomares accident (Spain).

    PubMed

    Jiménez-Ramos, M C; Barros, H; García-Tenorio, R; García-León, M; Vioque, I; Manjón, G

    2007-01-01

    The characterisation by ICP-MS of an isolated Pu-U hot particle originating from the nuclear weapons accident in Palomares (Spain) shows, for the first time, that its uranium content is highly enriched in (235)U. The enrichment has been confirmed by independent analyses of two surface soil samples collected in a heavily contaminated area close to the impact point of one of the bombs. This finding clarifies better the composition of the weapons involved in the accident and is of importance when the inventory of U and Pu in the contaminated area are to be calculated.

  1. Noninvasive magnetic resonance imaging detection of cerebral amyloid angiopathy-related microvascular alterations using superparamagnetic iron oxide particles in APP transgenic mouse models of Alzheimer's disease: application to passive Abeta immunotherapy.

    PubMed

    Beckmann, Nicolau; Gérard, Christelle; Abramowski, Dorothée; Cannet, Catherine; Staufenbiel, Matthias

    2011-01-19

    Cerebral amyloid angiopathy (CAA) is a common feature of Alzheimer's disease (AD). More advanced stages are accompanied by microhemorrhages and vasculitis. Peripheral blood-borne macrophages are intimately linked to cerebrovascular pathology coincident with AD. Magnetic resonance imaging (MRI) was used to noninvasively study microvascular lesions in amyloid precursor protein transgenic mouse AD models. Foci of signal attenuation were detected in cortical and thalamic brain regions of aged APP23 mice. Their strength and number was considerably enhanced by intravenous administration of iron oxide nanoparticles, which are taken up by macrophages through absorptive endocytosis, 24 h before image acquisition. The number of cortical sites displaying signal attenuation increased with age. Histology at these sites demonstrated the presence of iron-containing macrophages in the vicinity of CAA-affected blood vessels. A fraction of the sites additionally showed thickened vessel walls and vasculitis. Consistent with the visualization of CAA-associated lesions, MRI detected a much smaller number of attenuated signal sites in APP23xPS45 mice, for which a strong presenilin mutation caused a shift toward amyloid β(42), thus reducing vascular amyloid. Similar results were obtained with APP24 and APP51 mice, which develop significantly less CAA and microvascular pathology than APP23. In a longitudinal study, we noninvasively demonstrated the reinforced formation of microvascular pathology during passive amyloid β immunotherapy of APP23 mice. Histology confirmed that foci of signal attenuation reflected an increase in CAA-related lesions. Our data demonstrate that MRI has the sensitivity to noninvasively monitor the development of vascular pathology and its possible enhancement by amyloid β immunotherapy in transgenic mice modeling AD.

  2. Is the Ergogenicity of Caffeine Affected by Increasing Age? The Direct Effect of a Physiological Concentration of Caffeine on the Power Output of Maximally Stimulated EDL and Diaphragm Muscle Isolated from the Mouse.

    PubMed

    Tallis, J; James, R S; Cox, V M; Duncan, M J

    2017-01-01

    Caffeine is a well-established performance enhancing nutritional supplement in a young healthy population, however far less is known about how its ergogenicity is affected by increasing age. A recent review has highlighted the value of studies examining the direct effect of caffeine on isolated skeletal muscle contractility, but the present work is the first to assess the direct effect of 70µM caffeine (physiological maximum) on the maximal power output of isolated mammalian muscle from an age range representing developmental to early ageing. Female CD1 mice were aged to 3, 10, 30 and 50 weeks (n = 20 in each case) and either whole EDL or a section of the diaphragm was isolated and maximal power output determined using the work loop technique. Once contractile performance was maximised, each muscle preparation was treated with 70µM caffeine and its contractile performance was measured for a further 60 minutes. In both mouse EDL and diaphragm 70µM caffeine treatment resulted in a significant increase in maximal muscle power output that was greatest at 10 or 30 weeks (up to 5% and 6% improvement respectively). This potentiation of maximal muscle power output was significantly lower at the early ageing time point, 50 weeks (up to 3% and 2% improvement respectively), and in mice in the developmental stage, at 3 weeks of age (up to 1% and 2% improvement respectively). Uniquely, the present findings indicate a reduced age specific sensitivity to the performance enhancing effect of caffeine in developmental and aged mice which is likely to be attributed to age related muscle growth and degradation, respectively. Importantly, the findings indicate that caffeine may still provide a substantial ergogenic aid in older populations which could prove important for improving functional capacity in tasks of daily living.

  3. In utero exposure of mice to diesel exhaust particles affects spatial learning and memory with reduced N-methyl-D-aspartate receptor expression in the hippocampus of male offspring.

    PubMed

    Yokota, Satoshi; Sato, Akira; Umezawa, Masakazu; Oshio, Shigeru; Takeda, Ken

    2015-09-01

    Diesel exhaust consists of diesel exhaust particles (DEPs) and gaseous compounds. Previous studies reported that in utero exposure to diesel exhaust affects the central nervous system. However, there was no clear evidence that these effects were caused by diesel exhaust particles themselves, gaseous compounds, or both. Here, we explored the effects of in utero exposure to DEPs on learning and memory in male ICR mice. DEP solutions were administered subcutaneously to pregnant ICR mice at a dose of 0 or 200 μg/kg body weight on gestation days 6, 9, 12, 15, and 18. We examined learning and memory in 9-to-10-week-old male offspring using the Morris water maze test and passive avoidance test. Immediately after the behavioral tests, hippocampi were isolated. Hippocampal N-methyl-D-aspartate receptor (NR) expression was also measured by quantitative RT-PCR analysis. Mice exposed to DEPs in utero showed deficits in the Morris water maze test, but their performance was not significantly different from that of control mice in the passive avoidance test. In addition, DEP-exposed mice exhibited decreased hippocampal NR2A expression. The present results indicate that maternal DEP exposure disrupts learning and memory in male offspring, which is associated with reduced hippocampal NR2A expression.

  4. Agglutination of Mouse Erythrocytes by Eperythrozoon coccoides

    PubMed Central

    Iralu, Vichazelhu; Ganong, Kevin D.

    1983-01-01

    Erythrocytes from blood of mice infected with Eperythrozoon coccoides for 3 or 4 days agglutinated spontaneously. Washed E. coccoides particles agglutinated washed erythrocytes of uninfected mice. E. coccoides-mediated agglutination of normal mouse erythrocytes would be an excellent system for studies of bacterial adhesion. Images PMID:6832825

  5. Particle separation

    DOEpatents

    Moosmuller, Hans [Reno, NV; Chakrabarty, Rajan K [Reno, NV; Arnott, W Patrick [Reno, NV

    2011-04-26

    Embodiments of a method for selecting particles, such as based on their morphology, is disclosed. In a particular example, the particles are charged and acquire different amounts of charge, or have different charge distributions, based on their morphology. The particles are then sorted based on their flow properties. In a specific example, the particles are sorted using a differential mobility analyzer, which sorts particles, at least in part, based on their electrical mobility. Given a population of particles with similar electrical mobilities, the disclosed process can be used to sort particles based on the net charge carried by the particle, and thus, given the relationship between charge and morphology, separate the particles based on their morphology.

  6. Particle separation

    NASA Technical Reports Server (NTRS)

    Moosmuller, Hans (Inventor); Chakrabarty, Rajan K. (Inventor); Arnott, W. Patrick (Inventor)

    2011-01-01

    Embodiments of a method for selecting particles, such as based on their morphology, is disclosed. In a particular example, the particles are charged and acquire different amounts of charge, or have different charge distributions, based on their morphology. The particles are then sorted based on their flow properties. In a specific example, the particles are sorted using a differential mobility analyzer, which sorts particles, at least in part, based on their electrical mobility. Given a population of particles with similar electrical mobilities, the disclosed process can be used to sort particles based on the net charge carried by the particle, and thus, given the relationship between charge and morphology, separate the particles based on their morphology.

  7. Mouse Curve Biometrics

    SciTech Connect

    Schulz, Douglas A.

    2007-10-08

    A biometric system suitable for validating user identity using only mouse movements and no specialized equipment is presented. Mouse curves (mouse movements with little or no pause between them) are individually classied and used to develop classication histograms, which are representative of an individual's typical mouse use. These classication histograms can then be compared to validate identity. This classication approach is suitable for providing continuous identity validation during an entire user session.

  8. Real-time non-invasive detection of inhalable particulates delivered into live mouse airways.

    PubMed

    Donnelley, Martin; Morgan, Kaye S; Fouras, Andreas; Skinner, William; Uesugi, Kentaro; Yagi, Naoto; Siu, Karen K W; Parsons, David W

    2009-07-01

    Fine non-biological particles small enough to be suspended in the air are continually inhaled as we breathe. These particles deposit on airway surfaces where they are either cleared by airway defences or can remain and affect lung health. Pollutant particles from vehicles, building processes and mineral and industrial dusts have the potential to cause both immediate and delayed health problems. Because of their small size, it has not been possible to non-invasively examine how individual particles deposit on live airways, or to consider how they behave on the airway surface after deposition. In this study, synchrotron phase-contrast X-ray imaging (PCXI) has been utilized to detect and monitor individual particle deposition. The in vitro detectability of a range of potentially respirable particulates was first determined. Of the particulates tested, only asbestos, quarry dust, fibreglass and galena (lead sulfate) were visible in vitro. These particulates were then examined after delivery into the nasal airway of live anaesthetized mice; all were detectable in vivo but each exhibited different surface appearances and behaviour along the airway surface. The two fibrous particulates appeared as agglomerations enveloped by fluid, while the non-fibrous particulates were present as individual particles. Synchrotron PCXI provides the unique ability to non-invasively detect and track deposition of individual particulates in live mouse airways. With further refinement of particulate sizing and delivery techniques, PCXI should provide a novel approach for live animal monitoring of airway particulates relevant to lung health.

  9. Building a Brainier Mouse.

    ERIC Educational Resources Information Center

    Tsien, Joe Z.

    2000-01-01

    Describes a genetic engineering project to build an intelligent mouse. Cites understanding the molecular basis of learning and memory as a very important step. Concludes that while science will never create a genius mouse that plays the stock market, it can turn a mouse into a quick learner with a better memory. (YDS)

  10. Building a Brainier Mouse.

    ERIC Educational Resources Information Center

    Tsien, Joe Z.

    2000-01-01

    Describes a genetic engineering project to build an intelligent mouse. Cites understanding the molecular basis of learning and memory as a very important step. Concludes that while science will never create a genius mouse that plays the stock market, it can turn a mouse into a quick learner with a better memory. (YDS)

  11. Mouse models of myasthenia gravis.

    PubMed

    Ban, Joanne; Phillips, William D

    2015-01-01

    Myasthenia gravis is a muscle weakness disease characterized by autoantibodies that target components of the neuromuscular junction, impairing synaptic transmission. The most common form of myasthenia gravis involves antibodies that bind the nicotinic acetylcholine receptors in the postsynaptic membrane. Many of the remaining cases are due to antibodies against muscle specific tyrosine kinase (MuSK). Recently, autoantibodies against LRP4 (another component of the MuSK signaling complex in the postsynaptic membrane) were identified as the likely cause of myasthenia gravis in some patients. Fatiguing weakness is the common symptom in all forms of myasthenia gravis, but muscles of the body are differentially affected, for reasons that are not fully understood. Much of what we have learnt about the immunological and neurobiological aspects of the pathogenesis derives from mouse models. The most widely used mouse models involve either passive transfer of autoantibodies, or active immunization of the mouse with acetylcholine receptors or MuSK protein. These models can provide a robust replication of many of the features of the human disease. Depending upon the protocol, acute fatiguing weakness develops 2 - 14 days after the start of autoantibody injections (passive transfer) or might require repeated immunizations over several weeks (active models). Here we review mouse models of myasthenia gravis, including what they have contributed to current understanding of the pathogenic mechanisms and their current application to the testing of therapeutics.

  12. In-vivo administration of clozapine affects behaviour but does not reverse dendritic spine deficits in the 14-3-3ζ KO mouse model of schizophrenia-like disorders.

    PubMed

    Jaehne, Emily J; Ramshaw, Hayley; Xu, Xiangjun; Saleh, Eiman; Clark, Scott R; Schubert, Klaus Oliver; Lopez, Angel; Schwarz, Quenten; Baune, Bernhard T

    2015-11-01

    Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has been shown to reverse behavioural and dendritic spine deficits in mice. It has recently been shown that deficiency of 14-3-3ζ has an association with schizophrenia, and that a mouse model lacking this protein displays several schizophrenia-like behavioural deficits. To test the effect of clozapine in this mouse model, 14-3-3ζ KO mice were administered clozapine (5mg/kg) for two weeks prior to being analysed in a test battery of cognition, anxiety, and despair (depression-like) behaviours. Following behavioural testing brain samples were collected for analysis of specific anatomical defects and dendritic spine formation. We found that clozapine reduced despair behaviour of 14-3-3ζ KO mice in the forced swim test (FST) and altered the behaviour of wild types and 14-3-3ζ KO mice in the Y-maze task. In contrast, clozapine had no effects on hippocampal laminar defects or decreased dendritic spine density observed in 14-3-3ζ KO mice. Our results suggest that clozapine may have beneficial effects on clinical behaviours associated with deficiencies in the 14-3-3ζ molecular pathway, despite having no effects on morphological defects. These findings may provide mechanistic insight to the action of this drug.

  13. Mouse models of otitis media: strengths and limitations.

    PubMed

    Bhutta, Mahmood Fazal

    2012-10-01

    There has been a rapid rise in the use of the mouse to investigate pathobiology of otitis media. This is for good reason, including easy husbandry, but also capacity for genetic manipulation of the mouse. Insights into human disease have been gleaned from mouse models, but there are limitations of the mouse-to-man approach. First, important differences exist between mouse and man, particularly in immune function. Second, functional equivalence of genes in the 2 species is not ensured. Third, laboratory mice of a uniform genetic background and environment are an inadequate model of the plethora of factors affecting complex disease in humans. Finally, gene function in mouse models is often obliterated using gene knockout technology, but this is a poor mimic of normal gene variation in man. These drawbacks of the mouse may in the future limit its usefulness in otitis media research.

  14. Particle generator

    DOEpatents

    Hess, Wayne P.; Joly, Alan G.; Gerrity, Daniel P.; Beck, Kenneth M.; Sushko, Peter V.; Shlyuger, Alexander L.

    2005-06-28

    Energy tunable solid state sources of neutral particles are described. In a disclosed embodiment, a halogen particle source includes a solid halide sample, a photon source positioned to deliver photons to a surface of the halide, and a collimating means positioned to accept a spatially defined plume of hyperthermal halogen particles emitted from the sample surface.

  15. Pyrroloquinoline Quinine Inhibits RANKL-Mediated Expression of NFATc1 in Part via Suppression of c-Fos in Mouse Bone Marrow Cells and Inhibits Wear Particle-Induced Osteolysis in Mice

    PubMed Central

    Smith, Wanli; Zhu, Shu; Zhu, Jinyu; Zhu, Qingsheng

    2013-01-01

    The effects of pyrroloquinoline quinine (PQQ) on RANKL-induced osteoclast differentiation and on wear particle-induced osteolysis were examined in this study. PQQ inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages (BMMs) in a dose-dependent manner without any evidence of cytotoxicity. The mRNA expression of c-Fos, NFATc1, and TRAP in RANKL-treated BMMs was inhibited by PQQ treatment. Moreover, RANKL-induced c-Fos and NFATc1 protein expression was suppressed by PQQ. PQQ additionally inhibited the bone resorptive activity of differentiated osteoclasts. Further a UHMWPE-induced murine calvaria erosion model study was performed to assess the effects of PQQ on wear particle-induced osteolysis in vivo. Mice treated with PQQ demonstrated marked attenuation of bone erosion based on Micro-CT and histologic analysis of calvaria. These results collectively suggested that PQQ demonstrated inhibitory effects on osteoclast differentiation in vitro and may suppress wear particle-induced osteolysis in vivo, indicating that PQQ may therefore serve as a useful drug in the prevention of bone loss. PMID:23613773

  16. Particle therapy

    SciTech Connect

    Raju, M.R.

    1993-09-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics.

  17. Particle separator

    DOEpatents

    Hendricks, Charles D.

    1990-01-01

    Method and apparatus (10) are provided for separating and classifying particles (48,50,56) by dispersing the particles within a fluid (52) that is upwardly flowing within a cone-shaped pipe (12) that has its large end (20) above its small end (18). Particles of similar size and shape (48,50) migrate to individual levels (A,B) within the flowing fluid. As the fluid is deflected by a plate (42) at the top end of the pipe (12), the smallest particles are collected on a shelf-like flange (40). Ever larger particles are collected as the flow rate of the fluid is increased. To prevent particle sticking on the walls (14) of the pipe (12), additional fluid is caused to flow into the pipe (12) through holes (68) that are specifically provided for that purpose. Sticking is further prevented by high frequency vibrators (70) that are positioned on the apparatus (10).

  18. Particle astrophysics

    NASA Technical Reports Server (NTRS)

    Sadoulet, Bernard; Cronin, James; Aprile, Elena; Barish, Barry C.; Beier, Eugene W.; Brandenberger, Robert; Cabrera, Blas; Caldwell, David; Cassiday, George; Cline, David B.

    1991-01-01

    The following scientific areas are reviewed: (1) cosmology and particle physics (particle physics and the early universe, dark matter, and other relics); (2) stellar physics and particles (solar neutrinos, supernovae, and unconventional particle physics); (3) high energy gamma ray and neutrino astronomy; (4) cosmic rays (space and ground observations). Highest scientific priorities for the next decade include implementation of the current program, new initiatives, and longer-term programs. Essential technological developments, such as cryogenic detectors of particles, new solar neutrino techniques, and new extensive air shower detectors, are discussed. Also a certain number of institutional issues (the funding of particle astrophysics, recommended funding mechanisms, recommended facilities, international collaborations, and education and technology) which will become critical in the coming decade are presented.

  19. Particle astrophysics

    NASA Astrophysics Data System (ADS)

    Sadoulet, Bernard; Cronin, James; Aprile, Elena; Barish, Barry C.; Beier, Eugene W.; Brandenberger, Robert; Cabrera, Blas; Caldwell, David; Cassiday, George; Cline, David B.

    The following scientific areas are reviewed: (1) cosmology and particle physics (particle physics and the early universe, dark matter, and other relics); (2) stellar physics and particles (solar neutrinos, supernovae, and unconventional particle physics); (3) high energy gamma ray and neutrino astronomy; (4) cosmic rays (space and ground observations). Highest scientific priorities for the next decade include implementation of the current program, new initiatives, and longer-term programs. Essential technological developments, such as cryogenic detectors of particles, new solar neutrino techniques, and new extensive air shower detectors, are discussed. Also a certain number of institutional issues (the funding of particle astrophysics, recommended funding mechanisms, recommended facilities, international collaborations, and education and technology) which will become critical in the coming decade are presented.

  20. Magnetic particles

    NASA Technical Reports Server (NTRS)

    Chang, Manchium (Inventor); Colvin, Michael S. (Inventor)

    1989-01-01

    Magnetic polymer particles are formed by swelling porous, polymer particles and impregnating the particles with an aqueous solution of precursor magnetic metal salt such as an equimolar mixture of ferrous chloride and ferric chloride. On addition of a basic reagent such as dilute sodium hydroxide, the metal salts are converted to crystals of magnetite which are uniformly contained througout the pores of the polymer particle. The magnetite content can be increased and neutral buoyancy achieved by repetition of the impregnaton and neutralization steps to adjust the magnetite content to a desired level.

  1. The Knockout Mouse Project

    PubMed Central

    Austin, Christopher P; Battey, James F; Bradley, Allan; Bucan, Maja; Capecchi, Mario; Collins, Francis S; Dove, William F; Duyk, Geoffrey; Dymecki, Susan; Eppig, Janan T; Grieder, Franziska B; Heintz, Nathaniel; Hicks, Geoff; Insel, Thomas R; Joyner, Alexandra; Koller, Beverly H; Lloyd, K C Kent; Magnuson, Terry; Moore, Mark W; Nagy, Andras; Pollock, Jonathan D; Roses, Allen D; Sands, Arthur T; Seed, Brian; Skarnes, William C; Snoddy, Jay; Soriano, Philippe; Stewart, David J; Stewart, Francis; Stillman, Bruce; Varmus, Harold; Varticovski, Lyuba; Verma, Inder M; Vogt, Thomas F; von Melchner, Harald; Witkowski, Jan; Woychik, Richard P; Wurst, Wolfgang; Yancopoulos, George D; Young, Stephen G; Zambrowicz, Brian

    2009-01-01

    Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. PMID:15340423

  2. An encyclopedia of mouse DNA elements (Mouse ENCODE).

    PubMed

    Stamatoyannopoulos, John A; Snyder, Michael; Hardison, Ross; Ren, Bing; Gingeras, Thomas; Gilbert, David M; Groudine, Mark; Bender, Michael; Kaul, Rajinder; Canfield, Theresa; Giste, Erica; Johnson, Audra; Zhang, Mia; Balasundaram, Gayathri; Byron, Rachel; Roach, Vaughan; Sabo, Peter J; Sandstrom, Richard; Stehling, A Sandra; Thurman, Robert E; Weissman, Sherman M; Cayting, Philip; Hariharan, Manoj; Lian, Jin; Cheng, Yong; Landt, Stephen G; Ma, Zhihai; Wold, Barbara J; Dekker, Job; Crawford, Gregory E; Keller, Cheryl A; Wu, Weisheng; Morrissey, Christopher; Kumar, Swathi A; Mishra, Tejaswini; Jain, Deepti; Byrska-Bishop, Marta; Blankenberg, Daniel; Lajoie, Bryan R; Jain, Gaurav; Sanyal, Amartya; Chen, Kaun-Bei; Denas, Olgert; Taylor, James; Blobel, Gerd A; Weiss, Mitchell J; Pimkin, Max; Deng, Wulan; Marinov, Georgi K; Williams, Brian A; Fisher-Aylor, Katherine I; Desalvo, Gilberto; Kiralusha, Anthony; Trout, Diane; Amrhein, Henry; Mortazavi, Ali; Edsall, Lee; McCleary, David; Kuan, Samantha; Shen, Yin; Yue, Feng; Ye, Zhen; Davis, Carrie A; Zaleski, Chris; Jha, Sonali; Xue, Chenghai; Dobin, Alex; Lin, Wei; Fastuca, Meagan; Wang, Huaien; Guigo, Roderic; Djebali, Sarah; Lagarde, Julien; Ryba, Tyrone; Sasaki, Takayo; Malladi, Venkat S; Cline, Melissa S; Kirkup, Vanessa M; Learned, Katrina; Rosenbloom, Kate R; Kent, W James; Feingold, Elise A; Good, Peter J; Pazin, Michael; Lowdon, Rebecca F; Adams, Leslie B

    2012-08-13

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  3. Axonal localization of Ca2+-dependent activator protein for secretion 2 is critical for subcellular locality of brain-derived neurotrophic factor and neurotrophin-3 release affecting proper development of postnatal mouse cerebellum.

    PubMed

    Sadakata, Tetsushi; Kakegawa, Wataru; Shinoda, Yo; Hosono, Mayu; Katoh-Semba, Ritsuko; Sekine, Yukiko; Sato, Yumi; Saruta, Chihiro; Ishizaki, Yasuki; Yuzaki, Michisuke; Kojima, Masami; Furuichi, Teiichi

    2014-01-01

    Ca2+-dependent activator protein for secretion 2 (CAPS2) is a protein that is essential for enhanced release of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) from cerebellar granule cells. We previously identified dex3, a rare alternative splice variant of CAPS2, which is overrepresented in patients with autism and is missing an exon 3 critical for axonal localization. We recently reported that a mouse model CAPS2Δex3/Δex3 expressing dex3 showed autistic-like behavioral phenotypes including impaired social interaction and cognition and increased anxiety in an unfamiliar environment. Here, we verified impairment in axonal, but not somato-dendritic, localization of dex3 protein in cerebellar granule cells and demonstrated cellular and physiological phenotypes in postnatal cerebellum of CAPS2Δex3/Δex3 mice. Interestingly, both BDNF and NT-3 were markedly reduced in axons of cerebellar granule cells, resulting in a significant decrease in their release. As a result, dex3 mice showed developmental deficits in dendritic arborization of Purkinje cells, vermian lobulation and fissurization, and granule cell precursor proliferation. Paired-pulse facilitation at parallel fiber-Purkinje cell synapses was also impaired. Together, our results indicate that CAPS2 plays an important role in subcellular locality (axonal vs. somato-dendritic) of enhanced BDNF and NT-3 release, which is indispensable for proper development of postnatal cerebellum.

  4. Mouse models of the laminopathies

    SciTech Connect

    Stewart, Colin L. . E-mail: stewartc@ncifcrf.gov; Kozlov, Serguei; Fong, Loren G.; Young, Stephen G. . E-mail: sgyoung@mednet.ucla.edu

    2007-06-10

    The A and B type lamins are nuclear intermediate filament proteins that comprise the bulk of the nuclear lamina, a thin proteinaceous structure underlying the inner nuclear membrane. The A type lamins are encoded by the lamin A gene (LMNA). Mutations in this gene have been linked to at least nine diseases, including the progeroid diseases Hutchinson-Gilford progeria and atypical Werner's syndromes, striated muscle diseases including muscular dystrophies and dilated cardiomyopathies, lipodystrophies affecting adipose tissue deposition, diseases affecting skeletal development, and a peripheral neuropathy. To understand how different diseases arise from different mutations in the same gene, mouse lines carrying some of the same mutations found in the human diseases have been established. We, and others have generated mice with different mutations that result in progeria, muscular dystrophy, and dilated cardiomyopathy. To further our understanding of the functions of the lamins, we also created mice lacking lamin B1, as well as mice expressing only one of the A type lamins. These mouse lines are providing insights into the functions of the lamina and how changes to the lamina affect the mechanical integrity of the nucleus as well as signaling pathways that, when disrupted, may contribute to the disease.

  5. Particle preconcentrator

    SciTech Connect

    Linker, K.L.; Conrad, F.J.; Custer, C.A.; Rhykerd, C.L. Jr

    2000-07-11

    An apparatus and method are disclosed for preconcentrating particles and vapors. The preconcentrator apparatus permits detection of highly diluted amounts of particles in a main gas stream, such as a stream of ambient air. A main gas stream having airborne particles entrained therein is passed through a previous screen. The particles accumulate upon the screen, as the screen acts as a sort of selective particle filter. The flow of the main gas stream is then interrupted by diaphragm shutter valves, whereupon a cross-flow of carrier gas stream is blown parallel past the faces of the screen to dislodge the accumulated particles and carry them to a particle or vapor detector, such as an ion mobility spectrometer. The screen may be heated, such as by passing an electrical current there through, to promote desorption of particles therefrom during the flow of the carrier gas. Various types of screens are disclosed. The apparatus and method of the invention may find particular utility in the fields of narcotics, explosives detection and chemical agents.

  6. Particle preconcentrator

    DOEpatents

    Linker, K.L.; Conrad, F.J.; Custer, C.A.; Rhykerd, C.L. Jr.

    1998-12-29

    An apparatus and method are disclosed for preconcentrating particles and vapors. The preconcentrator apparatus permits detection of highly diluted amounts of particles in a main gas stream, such as a stream of ambient air. A main gas stream having airborne particles entrained therein is passed through a pervious screen. The particles accumulate upon the screen, as the screen acts as a sort of selective particle filter. The flow of the main gas stream is then interrupted by diaphragm shutter valves, whereupon a cross-flow of carrier gas stream is blown parallel past the faces of the screen to dislodge the accumulated particles and carry them to a particle or vapor detector, such as an ion mobility spectrometer. The screen may be heated, such as by passing an electrical current there through, to promote desorption of particles therefrom during the flow of the carrier gas. Various types of screens are disclosed. The apparatus and method of the invention may find particular utility in the fields of narcotics, explosives detection and chemical agents. 3 figs.

  7. Particle preconcentrator

    DOEpatents

    Linker, Kevin L.; Conrad, Frank J.; Custer, Chad A.; Rhykerd, Jr., Charles L.

    1998-01-01

    An apparatus and method for preconcentrating particles and vapors. The preconcentrator apparatus permits detection of highly diluted amounts of particles in a main gas stream, such as a stream of ambient air. A main gas stream having airborne particles entrained therein is passed through a pervious screen. The particles accumulate upon the screen, as the screen acts as a sort of selective particle filter. The flow of the main gas stream is then interrupted by diaphragm shutter valves, whereupon a cross-flow of carrier gas stream is blown parallel past the faces of the screen to dislodge the accumulated particles and carry them to a particle or vapor detector, such as an ion mobility spectrometer. The screen may be heated, such as by passing an electrical current there through, to promote desorption of particles therefrom during the flow of the carrier gas. Various types of screens are disclosed. The apparatus and method of the invention may find particular utility in the fields of narcotics, explosives detection and chemical agents.

  8. Particle preconcentrator

    DOEpatents

    Linker, Kevin L.; Conrad, Frank J.; Custer, Chad A.; Rhykerd, Jr., Charles L.

    2000-01-01

    An apparatus and method for preconcentrating particles and vapors. The preconcentrator apparatus permits detection of highly diluted amounts of particles in a main gas stream, such as a stream of ambient air. A main gas stream having airborne particles entrained therein is passed through a pervious screen. The particles accumulate upon the screen, as the screen acts as a sort of selective particle filter. The flow of the main gas stream is then interrupted by diaphragm shutter valves, whereupon a cross-flow of carrier gas stream is blown parallel past the faces of the screen to dislodge the accumulated particles and carry them to a particle or vapor detector, such as an ion mobility spectrometer. The screen may be heated, such as by passing an electrical current there through, to promote desorption of particles therefrom during the flow of the carrier gas. Various types of screens are disclosed. The apparatus and method of the invention may find particular utility in the fields of narcotics, explosives detection and chemical agents.

  9. Particle preconcentrator

    SciTech Connect

    Linker, Kevin L.; Conrad, Frank J.; Custer, Chad A.; Rhykerd, Jr., Charles L.

    2005-09-20

    An apparatus and method for preconcentrating particles and vapors. The preconcentrator apparatus permits detection of highly diluted amounts of particles in a main gas stream, such as a stream of ambient air. A main gas stream having airborne particles entrained therein is passed through a pervious screen. The particles accumulate upon the screen, as the screen acts as a sort of selective particle filter. The flow of the main gas stream is then interrupted by diaphragm shutter valves, whereupon a cross-flow of carrier gas stream is blown parallel past the faces of the screen to dislodge the accumulated particles and carry them to a particle or vapor detector, such as an ion mobility spectrometer. The screen may be heated, such as by passing an electrical current there through, to promote desorption of particles therefrom during the flow of the carrier gas. Various types of screens are disclosed. The apparatus and method of the invention may find particular utility in the fields of narcotics, explosives detection and chemical agents.

  10. Mouse models of human thalassemia

    SciTech Connect

    Anderson, W.F.; Martinell, J.; Whitney, J.B. III; Popp, R.A.

    1981-01-01

    The group of diseases called the thalassemias is the largest single-gene health problem in the world according the World Health Organization. The thalassemias are lethal hereditary anemias in which the infants cannot make their own blood. Three mouse mutants are shown to be models of the human disease ..cap alpha..-thalassemia. However, since an additional gene is affected, these mutants represent a particularly severe condition in which death occurs in the homozygous embryo even before globin genes are activated. Phenotypic and genotypic characteristics are described. (ACR)

  11. Particle Deposition onto Enclosure Surfaces

    DTIC Science & Technology

    2009-08-20

    8217, respectively. 27 Thatcher and Nazaroff47 studied the influence of different surface roughness on particle deposition under natural convection in...21 6.2 Airflow Characteristics Affecting Particle Deposition 22 6.2.1 Forced Convection 22 6.2.2 Natural Convection 24 6.3 Surface...particle size under natural convection conditions 24 6. Comparison of experimentally measured deposition velocity for surfaces of various

  12. The MOUSE Squad

    ERIC Educational Resources Information Center

    Borja, Rhea R.

    2004-01-01

    This article presents a New York city after-school program started by MOUSE (Making Opportunities for Upgrading Schools and Education), a national nonprofit group that teaches students how to fix computers, and equips them with the communication and problem-solving skills to help them in the working world. The MOUSE program is part of a trend…

  13. Mouse genome database 2016

    PubMed Central

    Bult, Carol J.; Eppig, Janan T.; Blake, Judith A.; Kadin, James A.; Richardson, Joel E.

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data. PMID:26578600

  14. Operant responding following exposure to HZE particles and its relationship to particle energy and LET

    USDA-ARS?s Scientific Manuscript database

    On exploratory class missions astronauts will be exposed to range of heavy particles which differ in terms of particle energy and particle linear energy transfer. The present experiments were designed to evaluate how these physical characteristics of different particles affect cognitive performance...

  15. Elementary particles

    NASA Astrophysics Data System (ADS)

    Fritzsch, Harald; Heusch, Karin

    Introduction -- Electrons and atomic nuclei -- Quantum properties of atoms and particles -- The knives of Democritus -- Quarks inside atomic nuclei -- Quantum electrodynamics -- Quantum chromodynamics -- Mesons, baryons, and quarks -- Electroweak interactions -- Grand unification -- Conclusion.

  16. Magnetic particles

    NASA Technical Reports Server (NTRS)

    Chang, Manchium (Inventor); Colvin, Michael S. (Inventor); Rembaum, Alan (Inventor); Richards, Gil F. (Inventor)

    1987-01-01

    Metal oxide containing polymers and particularly styrene, acrylic or protein polymers containing fine, magnetic iron oxide particles are formed by combining a NO.sub.2 -substituted polymer with an acid such as hydrochloric acid in the presence of metal, particularly iron particles. The iron is oxidized to fine, black Fe.sub.3 O.sub.4 particles which deposit selectively on the polymer particles. Nitrated polymers are formed by reacting functionally substituted, nitrated organic compounds such as trinitrobenzene sulfonate or dinitrofluoro benzene with a functionally coreactive polymer such as an amine modified acrylic polymer or a protein. Other transition metals such as cobalt can also be incorporated into polymers using this method.

  17. On Characterizing Particle Shape

    NASA Technical Reports Server (NTRS)

    Ennis, Bryan J.; Rickman, Douglas; Rollins, A. Brent; Ennis, Brandon

    2014-01-01

    It is well known that particle shape affects flow characteristics of granular materials, as well as a variety of other solids processing issues such as compaction, rheology, filtration and other two-phase flow problems. The impact of shape crosses many diverse and commercially important applications, including pharmaceuticals, civil engineering, metallurgy, health, and food processing. Two applications studied here include the dry solids flow of lunar simulants (e.g. JSC-1, NU-LHT-2M, OB-1), and the flow properties of wet concrete, including final compressive strength. A multi-dimensional generalized, engineering method to quantitatively characterize particle shapes has been developed, applicable to both single particle orientation and multi-particle assemblies. The two-dimension, three dimension inversion problem is also treated, and the application of these methods to DEM model particles will be discussed. In the case of lunar simulants, flow properties of six lunar simulants have been measured, and the impact of particle shape on flowability - as characterized by the shape method developed here -- is discussed, especially in the context of three simulants of similar size range. In the context of concrete processing, concrete construction is a major contributor to greenhouse gas production, of which the major contributor is cement binding loading. Any optimization in concrete rheology and packing that can reduce cement loading and improve strength loading can also reduce currently required construction safety factors. The characterization approach here is also demonstrated for the impact of rock aggregate shape on concrete slump rheology and dry compressive strength.

  18. Rapid Measurements of Aerosol Ionic Composition and 3-10 nm Particle Size Distributions On The NASA P3 To Better Quantify Processes Affecting Aerosols Advected From East Asia

    NASA Technical Reports Server (NTRS)

    Weber, Rodney J.

    2004-01-01

    The Particle Into Liquid Sample (PILS) was deployed on the NASA P3 for airborne measurements of fine particle ionic chemical composition. The data have been quality assured and reside in the NASA data archive. We have analyzed our data to characterize the sources and atmospheric processing of fine aerosol particles advected from the region during the experiments. Fine particle water-soluble potassium was found to serve as a useful aerosol tracer for biomass smoke. Ratios of PILS potassium to sulfate are used as a means of estimating the percent contribution of biomass burning to fine particle mass in mixed plumes advecting from Asia. The high correlations between K+ and NO3(sup -) and NH4(sup +)' indicated that biomass burning was a significant source of these aerosol compounds in the region. It is noteworthy that the air mass containing the highest concentrations of fine particles recorded in all of ACE-Asia and TRACE-P appeared to be advecting from the Bejing/Tientsin urban region and also had the highest K(+), NO3(sup -) and NH4(sup +) concentrations of both studies. Based on K+/SO4(sup 2-) ratio's, we estimated that the plume was composed of approx. 60% biomass burning emissions, possibly from the use of bio-fuels in the urban regions.

  19. Rapid Measurements of Aerosol Ionic Composition and 3-10 nm Particle Size Distributions On The NASA P3 To Better Quantify Processes Affecting Aerosols Advected From East Asia

    NASA Technical Reports Server (NTRS)

    Weber, Rodney J.

    2004-01-01

    The Particle Into Liquid Sample (PILS) was deployed on the NASA P3 for airborne measurements of fine particle ionic chemical composition. The data have been quality assured and reside in the NASA data archive. We have analyzed our data to characterize the sources and atmospheric processing of fine aerosol particles advected from the region during the experiments. Fine particle water-soluble potassium was found to serve as a useful aerosol tracer for biomass smoke. Ratios of PILS potassium to sulfate are used as a means of estimating the percent contribution of biomass burning to fine particle mass in mixed plumes advecting from Asia. The high correlations between K+ and NO3(sup -) and NH4(sup +)' indicated that biomass burning was a significant source of these aerosol compounds in the region. It is noteworthy that the air mass containing the highest concentrations of fine particles recorded in all of ACE-Asia and TRACE-P appeared to be advecting from the Bejing/Tientsin urban region and also had the highest K(+), NO3(sup -) and NH4(sup +) concentrations of both studies. Based on K+/SO4(sup 2-) ratio's, we estimated that the plume was composed of approx. 60% biomass burning emissions, possibly from the use of bio-fuels in the urban regions.

  20. Lagrangian Trajectory of Small Particles in Superfluid He II

    NASA Astrophysics Data System (ADS)

    Kubo, Wataru; Tsuji, Yoshiyuki

    2017-06-01

    Small tracer particles in He II are visualized, and their motions are analyzed. Lagrangian velocity distribution is computed by analyzing the visualized particle images through particle tracking velocimetry technique. We studied how the particle sizes affect the statistics of particle motions.

  1. Nanoparticles can cross mouse placenta and induce trophoblast apoptosis.

    PubMed

    Huang, Jian-Pei; Hsieh, Patrick C H; Chen, Chen-Yu; Wang, Tao-Yeuan; Chen, Pei-Chun; Liu, Chang-Ching; Chen, Chen-Chun; Chen, Chie-Pein

    2015-12-01

    The effects of nanoparticles on pregnancy remain unclear. In this study, we investigate whether nanoparticles of a specific size can cross the placenta and affect trophoblast function. Fluorescently labelled carboxylate-modified polystyrene beads with diameters of 20, 40, 100, 200, and 500 nm were chosen as model particles. In vitro, trophoblast cell line (3A-Sub-E) or primary culture of term trophoblasts was used for nanoparticle uptake analysis using flow cytometry, confocal microscopy, BrdU proliferation assay and analysis of cell apoptosis using Western blot. Intravenous injection of nanoparticles into pregnant mice at embryonic day 17 was used to study whether nanoparticles can cross the placenta. The mouse placentas were collected and quantitatively analyzed using high-performance liquid chromatography for nanoparticle uptake. Fluorescent polystyrene particles with diameters of up to 500 nm were taken up by the placenta and were able to cross the placental barrier. The fluorescent polystyrene particles were observed in various organs of fetuses after 4 h of administration to pregnant mice. The nanoparticle uptake by placental tissue was significantly increased in nanoparticles with a diameter of 40 nm. No linear association was evident between nanoparticle size and uptake. Nanoparticles with diameters of 20 nm (200 μg/ml) and 40 nm (500 μg/ml) could induce trophoblast cell apoptosis with increased cleaved caspase 3 and reduced cell proliferation. Our findings suggest that nanoparticles can cross the placenta and be taken up by fetal organs. Certain concentrations of carboxylate-modified polystyrene nanoparticles may be cytotoxic to trophoblasts, which could alter placental function. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. [Echocardiography in mouse].

    PubMed

    Fayssoil, A

    2008-06-01

    Assessing cardiac phenotype requires invasive or noninvasive techniques in mouse. Echocardiography is a noninvasive technique for evaluating cardiac function. The purpose of this paper is to underline echocardiography modalities and new tools Doppler applications like tissue Doppler imaging.

  3. Mouse Cleaning Apparatus and Method

    NASA Technical Reports Server (NTRS)

    Williams, Glenn L. (Inventor)

    2005-01-01

    The method of using the mouse pad cleaning apparatus is disclosed and claimed. The method comprises the steps of uncovering the mouse cleaning surface, applying the mouse and ball of the mouse to the cleaning surface, moving the mouse in a rotational pattern on the mouse cleaning surface, removing the mouse form the mouse cleaning surface, washing the cleaning surface, and covering the mouse cleaning surface. A mouse pad cleaning apparatus comprising a plurality of substrates, each said substrate having adhesive thereon, said plurality of substrates residing in and affixed to a receptacle. A single substrate having adhesive, which may be washable or non-washable, thereon may be employed. The washable adhesive may be an organopolysiloxane or gelatinous elastomer.

  4. Carbon particles

    DOEpatents

    Hunt, Arlon J.

    1984-01-01

    A method and apparatus whereby small carbon particles are made by pyrolysis of a mixture of acetylene carried in argon. The mixture is injected through a nozzle into a heated tube. A small amount of air is added to the mixture. In order to prevent carbon build-up at the nozzle, the nozzle tip is externally cooled. The tube is also elongated sufficiently to assure efficient pyrolysis at the desired flow rates. A key feature of the method is that the acetylene and argon, for example, are premixed in a dilute ratio, and such mixture is injected while cool to minimize the agglomeration of the particles, which produces carbon particles with desired optical properties for use as a solar radiant heat absorber.

  5. Stable particles

    SciTech Connect

    Samios, N.P.

    1993-12-31

    I have been asked to review the subject of stable particles, essentially the particles that eventually comprised the meson and baryon octets. with a few more additions -- with an emphasis on the contributions made by experiments utilizing the bubble chamber technique. In this activity, much work had been done by the photographic emulsion technique and cloud chambers-exposed to cosmic rays as well as accelerator based beams. In fact, many if not most of the stable particles were found by these latter two techniques, however, the forte of the bubble chamber (coupled with the newer and more powerful accelerators) was to verify, and reinforce with large statistics, the existence of these states, to find some of the more difficult ones, mainly neutrals and further to elucidate their properties, i.e., spin, parity, lifetimes, decay parameters, etc.

  6. Particle Sizer

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Microspheres are tiny plastic beads that represent the first commercial products manufactured in orbit. An example of how they are used is a new aerodynamic particle sizer designated APS 33B produced by TSI Incorporated. TSI purchased the microspheres from the National Bureau of Standards which certified their exact size and the company uses them in calibration of the APS 33B* instrument, latest in a line of TSI systems for generating counting and weighing minute particles of submicron size. Instruments are used for evaluating air pollution control devices, quantifying environments, meteorological research, testing filters, inhalation, toxicology and other areas where generation or analysis of small airborne particles is required. * The APS 33B is no longer being manufactured. An improved version, APS 3320, is now being manufactured. 2/28/97

  7. Particle Geophysics

    NASA Astrophysics Data System (ADS)

    Tanaka, Hiroyuki K. M.

    2014-05-01

    Geophysics research has long been dominated by classical mechanics, largely disregarding the potential of particle physics to augment existing techniques. The purpose of this article is to review recent progress in probing Earth's interior with muons and neutrinos. Existing results for various volcanological targets are reviewed. Geoneutrinos are also highlighted as examples in which the neutrino probes elucidate the composition of Earth's deep interior. Particle geophysics has the potential to serve as a useful paradigm to transform our understanding of Earth as dramatically as the X-ray transformed our understanding of medicine and the body.

  8. Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

    PubMed

    Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

    2015-12-01

    Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice.

  9. Particles causing lung disease.

    PubMed Central

    Kilburn, K H

    1984-01-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and

  10. Particle blender

    DOEpatents

    Willey, Melvin G.

    1981-01-01

    An infinite blender that achieves a homogeneous mixture of fuel microspheres is provided. Blending is accomplished by directing respective groups of desired particles onto the apex of a stationary coaxial cone. The particles progress downward over the cone surface and deposit in a space at the base of the cone that is described by a flexible band provided with a wide portion traversing and in continuous contact with the circumference of the cone base and extending upwardly therefrom. The band, being attached to the cone at a narrow inner end thereof, causes the cone to rotate on its arbor when the band is subsequently pulled onto a take-up spool. As a point at the end of the wide portion of the band passes the point where it is tangent to the cone, the blended particles are released into a delivery tube leading directly into a mold, and a plate mounted on the lower portion of the cone and positioned between the end of the wide portion of the band and the cone assures release of the particles only at the tangent point.

  11. Airborne Particles.

    ERIC Educational Resources Information Center

    Ojala, Carl F.; Ojala, Eric J.

    1987-01-01

    Describes an activity in which students collect airborne particles using a common vacuum cleaner. Suggests ways for the students to convert their data into information related to air pollution and human health. Urges consideration of weather patterns when analyzing the results of the investigation. (TW)

  12. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  13. Particle Growth Processes in Screening Smokes.

    DTIC Science & Technology

    1981-03-26

    These are axial and radial convection, Brownian coagulation, Brownian diffusion, and thermophoresis . Evolution of the aerosol in the heated jet... thermophoresis . As in the isothermal process affecting the particle size distribution, coagulation is the dominant rate process affecting the particle size

  14. The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: IX Results of examination of the nasal mucosa.

    PubMed

    Kraft, L M; Vogel, F S; Lloyd, B; Benton, E V; Cruty, M R; Haymaker, W; Leon, A; Billingham, J; Turnbill, C E; Teas, V; Look, B C; Suri, K; Miquel, J; Ashley, W W; Behnke, A R; Samorajski, T; Bailey, O T; Zeman, W

    1975-04-01

    The olfactory epithelium, but not the nasal respiratory epithelium, of the four pocket mice (Perognathus longimembris) that survived their flight on Apollo XVII showed both diffuse alterations and numerous disseminated focal lesions. The olfactory mucosa of the mouse that died during flight was also affected, but to a minor degree insofar as could be determined. All this was in contrast to the normal appearance of the olfactory mucosa of the numerous control animals. A number of possible causes were considered: systemic or regional infection; inhaled particulate material (seed dust); by-products from the KO2 bed in aerosol or particulate form; gas contaminants originating in the flight package; volatile substances from the dead mouse; weightlessness; and cosmic ray particle radiation. Where feasible, studies were conducted in an effort to rule in or rule out some of these potentially causative factors. No definitive conclusions were reached as to the cause of the lesions in the flight mice.

  15. Mouse Models of Alzheimer's Disease.

    PubMed

    Esquerda-Canals, Gisela; Montoliu-Gaya, Laia; Güell-Bosch, Jofre; Villegas, Sandra

    2017-03-10

    Alzheimer's disease (AD) is a neurodegenerative disorder that nowadays affects more than 40 million people worldwide and it is predicted to exponentially increase in the coming decades. Because no curative treatment exists, research on the pathophysiology of the disease, as well as the testing of new drugs, are mandatory. For these purposes, animal models constitute a valuable, although perfectible tool. This review takes a tour through several aspects of mouse models of AD, such as the generation of transgenic models, the relevance of the promoter driving the expression of the transgenes, and the concrete transgenes used to simulate AD pathophysiology. Then, transgenic mouse lines harboring mutated human genes at several loci such as APP, PSEN1, APOEɛ4, and ob (leptin) are reviewed. Therefore, not only the accumulation of the Aβ peptide is emulated but also cholesterol and insulin metabolism. Further novel information about the disease will allow for the development of more accurate animal models, which in turn will undoubtedly be helpful for bringing preclinical research closer to clinical trials in humans.

  16. Selective particle capture by asynchronously beating cilia

    NASA Astrophysics Data System (ADS)

    Ding, Yang; Kanso, Eva

    2015-12-01

    Selective particle filtration is fundamental in many engineering and biological systems. For example, many aquatic microorganisms use filter feeding to capture food particles from the surrounding fluid, using motile cilia. One of the capture strategies is to use the same cilia to generate feeding currents and to intercept particles when the particles are on the downstream side of the cilia. Here, we develop a 3D computational model of ciliary bands interacting with flow suspended particles and calculate particle trajectories for a range of particle sizes. Consistent with experimental observations, we find optimal particle sizes that maximize capture rate. The optimal size depends nonlinearly on cilia spacing and cilia coordination, synchronous vs. asynchronous. These parameters affect the cilia-generated flow field, which in turn affects particle trajectories. The low capture rate of smaller particles is due to the particles' inability to cross the flow streamlines of neighboring cilia. Meanwhile, large particles have difficulty entering the sub-ciliary region once advected downstream, also resulting in low capture rates. The optimal range of particle sizes is enhanced when cilia beat asynchronously. These findings have potentially important implications on the design and use of biomimetic cilia in processes such as particle sorting in microfluidic devices.

  17. Correlation studies on surface particle detection methods

    NASA Technical Reports Server (NTRS)

    Peterson, Ronald V.; White, James C.

    1988-01-01

    The accurate determination of dust levels on optical surfaces is necessary to assess sensor system performance. A comparison study was made on several particle measurement methods including those based on direct imaging and light scattering. The effectiveness of removing the particles from the surface prior to determining particle size distributions was also assessed. These studies revealed that some methods, especially those requiring particle removal before analysis, are subject to large systematic errors affecting particle size distributions. Thus, an understanding of the particle measurement methods employed is necessary before any surface cleanliness or obstruction value assignments are accepted as true representations of an optical surface contamination condition.

  18. Investigation of plasma particle interactions with variable particle sizes

    NASA Astrophysics Data System (ADS)

    Dropmann, Michael; Laufer, Rene; Herdrich, Georg; Matthews, Lorin; Hyde, Truell

    2015-11-01

    In dusty plasmas, the dust particles are subjected to many forces of different origins. Both the gas and plasma directly affect the dust particles through electric fields, neutral drag, ion drag and thermophoretic forces, while the particles themselves interact with one another through a screened coulomb potential, which can be influenced by flowing ions. Recently, micron sized particles have been used as probes to analyze the electric fields in the plasma directly. A proper analysis of the resulting data requires a full understanding of the manner in which these forces couple to the dust particles. In most cases each of the forces exhibit unique characteristics, many of which are partially dependent on the particle size. In this study, five different particle sizes are used to investigate the forces resident in the sheath above the lower electrode of a GEC RF reference cell. The particles are tracked using a high-speed camera, yielding two-dimensional force maps allowing the force on the particles to be described as a polynomial series. It will be shown that the data collected can be analyzed to reveal information about the origins of the various forces. Support from the NSF and the DOE (award numbers PHY-1262031 and PHY-1414523) is gratefully acknowledged.

  19. Antibodies to mouse lung capillary endothelium.

    PubMed

    Rorvik, M C; Allison, D P; Hotchkiss, J A; Witschi, H P; Kennel, S J

    1988-07-01

    We are interested in developing monoclonal antibodies (MoAbs) that recognize specific cell types in the lung of BALB/c mice. Normal mouse lung homogenate was used to immunize F344 rats and hybridomas were produced by fusion of rat spleen cells with mouse myeloma SP 2/0. Two hybridomas were selected which produced MoAbs active in immunohistochemistry of lung cells. MoAb 273-34A and 411-201B both show extensive peroxidase staining of capillary endothelial cells within alveolar walls of lungs at the light microscopic level. To demonstrate cell specificity, immunoelectron microscopy with gold-labeled antibody was performed. Lightly fixed lungs were frozen and thin-sectioned before staining with MoAb and 5-nm gold particles coupled to secondary antibody. Quantitative analyses of these cryosections show that both antibodies, used at optimal concentrations, are specific for binding to capillary endothelial cells. More than 95% of the gold particles are associated with capillary endothelial cells on the thin side of the alveolar wall. When capillaries adjoined thick septa containing interstitial cells, about two thirds of the gold particles were associated with endothelial cells and about one quarter with interstitial cells. These MoAbs should be useful in studying the role of endothelial cells in toxic lung injury.

  20. On the modification of particle dispersion in isotropic turbulence by free rotation of particle

    NASA Astrophysics Data System (ADS)

    Park, Yongnam; Lee, Changhoon

    2008-11-01

    Effect of a particle's spin is investigated numerically by considering the effect of lift occurring due to difference of rotations of a particle and of fluid such as the Saffman lift and Magnus force. These lift forces have been neglected in many previous works on particle-laden turbulence. The trajectory of particles can be changed by the lift forces, resulting in significant modification of the stochastic characteristics of heavy particles. Probability density functions and autocorrelations are examined of velocity, acceleration of solid particle and acceleration of fluid at the position of solid particle. Changes in velocity statistics are negligible but statistics related with acceleration are a little bit changed by particle's rotation. When a laden particle encounters with coherent structures during the motion, the particle's rotation might significantly affects the motion due to intermittently large fluid acceleration near coherent structures. The result can be used for development of stochastic model for particle dispersion. Detailed physical interpretation will be presented in the meeting.

  1. Particle acceleration

    NASA Technical Reports Server (NTRS)

    Vlahos, L.; Machado, M. E.; Ramaty, R.; Murphy, R. J.; Alissandrakis, C.; Bai, T.; Batchelor, D.; Benz, A. O.; Chupp, E.; Ellison, D.

    1986-01-01

    Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV.

  2. Particle classifier

    SciTech Connect

    Etkin, B.

    1987-04-14

    This patent describes a classifier for particulate material comprising a housing having an inlet to receive a classifying air flow flowing in a given direction, collection means downstream of the inlet to receive material classified by the air flow, and material introduction means intermediate the inlet and the collection means to introduce particles entrained in a secondary air stream into the housing in a direction other than the given direction. The material introduction means includes a material outlet aperture in a wall of the housing extending generally perpendicular to the given direction, conveying means to convey material and the secondary air stream to the material outlet and diverting means to divert the secondary air stream to a direction generally parallel to the classifying air flow flowing in the given direction. The diverting means includes a surface extending downstream from the outlet and adjacent thereto and being dimensioned to divert the secondary airstream by a Coanda effect generally parallel to the given direction and thereby segregate the secondary air/stream from the particles and permit continued movement of the particles along predictable trajectories.

  3. Mouse bladder wall injection.

    PubMed

    Fu, Chi-Ling; Apelo, Charity A; Torres, Baldemar; Thai, Kim H; Hsieh, Michael H

    2011-07-12

    Mouse bladder wall injection is a useful technique to orthotopically study bladder phenomena, including stem cell, smooth muscle, and cancer biology. Before starting injections, the surgical area must be cleaned with soap and water and antiseptic solution. Surgical equipment must be sterilized before use and between each animal. Each mouse is placed under inhaled isoflurane anesthesia (2-5% for induction, 1-3% for maintenance) and its bladder exposed by making a midline abdominal incision with scissors. If the bladder is full, it is partially decompressed by gentle squeezing between two fingers. The cell suspension of interest is intramurally injected into the wall of the bladder dome using a 29 or 30 gauge needle and 1 cc or smaller syringe. The wound is then closed using wound clips and the mouse allowed to recover on a warming pad. Bladder wall injection is a delicate microsurgical technique that can be mastered with practice.

  4. Aging fingerprints in combustion particles

    NASA Astrophysics Data System (ADS)

    Zelenay, V.; Mooser, R.; Tritscher, T.; Křepelová, A.; Heringa, M. F.; Chirico, R.; Prévôt, A. S. H.; Weingartner, E.; Baltensperger, U.; Dommen, J.; Watts, B.; Raabe, J.; Huthwelker, T.; Ammann, M.

    2011-05-01

    Soot particles can significantly influence the Earth's climate by absorbing and scattering solar radiation as well as by acting as cloud condensation nuclei. However, despite their environmental (as well as economic and political) importance, the way these properties are affected by atmospheric processing is still a subject of discussion. In this work, soot particles emitted from two different cars, a EURO 2 transporter, a EURO 3 passenger vehicle, and a wood stove were investigated on a single-particle basis. The emitted exhaust, including the particulate and the gas phase, was processed in a smog chamber with artificial solar radiation. Single particle specimens of both unprocessed and aged soot were characterized using x-ray absorption spectroscopy and scanning electron microscopy. Comparison of the spectra from the unprocessed and aged soot particles revealed changes in the carbon functional group content, such as that of carboxylic carbon, which can be ascribed to both the condensation of secondary organic compounds on the soot particles and oxidation of primary soot particles upon photochemical aging. Changes in the morphology and size of the single soot particles were also observed upon aging. Furthermore, we show that the soot particles take up water in humid environments and that their water uptake capacity increases with photochemical aging.

  5. Particle image velocimetry in viscoelastic fluids and particle interaction effects

    NASA Astrophysics Data System (ADS)

    Mirsepassi, Alireza; Rankin, Derek Dunn

    2014-01-01

    Two main assumptions in laser doppler velocimetry and particle image velocimetry (PIV) are that tracer particles are following the flow faithfully and that they are not interacting hydrodynamically or affecting the flow field. It has been shown, however, that particles in polymeric fluids even in low volumetric concentrations ( ϕ < 1 % v/v) can interact profoundly because of the viscoelastic nature of the background fluid, leading even to particle chain or string formation. The objective of this study is to determine how these interactions can affect the flow conclusions drawn from PIV measurements. We chose a highly viscoelastic and shear thinning fluid and confirmed that particle string formation does occur rapidly in a simple shear flow of this fluid. Then, we measured via PIV, the fully developed velocity profile in the mid-plane of a square channel over a wide range of particle loadings 0.005-0.2 % v/v. The measurements confirm that despite the chaining process, there is no discernible effect of particle interaction on PIV velocity measurements.

  6. Circular, confined distribution for charged particle beams

    DOEpatents

    Garnett, R.W.; Dobelbower, M.C.

    1995-11-21

    A charged particle beam line is formed with magnetic optics that manipulate the charged particle beam to form the beam having a generally rectangular configuration to a circular beam cross-section having a uniform particle distribution at a predetermined location. First magnetic optics form a charged particle beam to a generally uniform particle distribution over a square planar area at a known first location. Second magnetic optics receive the charged particle beam with the generally square configuration and affect the charged particle beam to output the charged particle beam with a phase-space distribution effective to fold corner portions of the beam toward the core region of the beam. The beam forms a circular configuration having a generally uniform spatial particle distribution over a target area at a predetermined second location. 26 figs.

  7. Circular, confined distribution for charged particle beams

    DOEpatents

    Garnett, Robert W.; Dobelbower, M. Christian

    1995-01-01

    A charged particle beam line is formed with magnetic optics that manipulate the charged particle beam to form the beam having a generally rectangular configuration to a circular beam cross-section having a uniform particle distribution at a predetermined location. First magnetic optics form a charged particle beam to a generally uniform particle distribution over a square planar area at a known first location. Second magnetic optics receive the charged particle beam with the generally square configuration and affect the charged particle beam to output the charged particle beam with a phase-space distribution effective to fold corner portions of the beam toward the core region of the beam. The beam forms a circular configuration having a generally uniform spatial particle distribution over a target area at a predetermined second location.

  8. An encyclopedia of mouse DNA elements (Mouse ENCODE)

    PubMed Central

    2012-01-01

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics eff