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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. Zearalenone exposure affects epigenetic modifications of mouse eggs.

    PubMed

    Zhu, Cheng-Cheng; Hou, Yan-Jun; Han, Jun; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2014-11-01

    Zearalenone (ZEA) is a mycotoxin produced by various Fusarium fungi, which has been shown to cause several cases of mycotoxicosis in farm animals and humans. However, there is no evidence regarding the effect of ZEA on mouse egg developmental competence. In this study, we found that the activation rate of maturated oocytes was affected in mice by ZEA treatment, indicating that ZEA affects egg developmental competence. And we explored possible mechanisms of low mouse maturated oocyte developmental competence after ZEA treatment from an epigenetic modification perspective. The fluorescence intensity analysis showed that 5-methyl cytosine level increased after ZEA treatment, indicating that the general DNA methylation level increased in the treated eggs. Moreover, histone methylations were also altered: H3K4me2 as well as H3K9me3 and H4K20me1, me2, me3 levels decreased in eggs that were cultured in high-dose ZEA medium. Thus, our results indicated that ZEA decreased egg developmental competence by affecting the epigenetic modifications. PMID:25155023

  3. 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)

  4. Particle statistics affects quantum decay and Fano interference.

    PubMed

    Crespi, Andrea; Sansoni, Linda; Della Valle, Giuseppe; Ciamei, Alessio; Ramponi, Roberta; Sciarrino, Fabio; Mataloni, Paolo; Longhi, Stefano; Osellame, Roberto

    2015-03-01

    Quantum mechanical decay, Fano interference, and bound states with energy in the continuum are ubiquitous phenomena in different areas of physics. Here we experimentally demonstrate that particle statistics strongly affects quantum mechanical decay in a multiparticle system. By considering propagation of two-photon states in engineered photonic lattices, we simulate quantum decay of two noninteracting particles in a multilevel Fano-Anderson model. Remarkably, when the system sustains a bound state in the continuum, fractional decay is observed for bosonic particles, but not for fermionic ones. Complete decay in the fermionic case arises because of the Pauli exclusion principle, which forbids the bound state to be occupied by the two fermions. Our experiment indicates that particle statistics can tune many-body quantum decay from fractional to complete.

  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.

  6. 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. PMID:26675372

  7. 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

  8. 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 ...

  9. Vanadium inhalation in a mouse model for the understanding of air-suspended particle systemic repercussion.

    PubMed

    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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Proteomic and metabolomic profiling of a trait anxiety mouse model implicate affected pathways.

    PubMed

    Zhang, Yaoyang; Filiou, Michaela D; Reckow, Stefan; Gormanns, Philipp; Maccarrone, Giuseppina; Kessler, Melanie S; Frank, Elisabeth; Hambsch, Boris; Holsboer, Florian; Landgraf, Rainer; Turck, Christoph W

    2011-12-01

    Depression and anxiety disorders affect a great number of people worldwide. Whereas singular factors have been associated with the pathogenesis of psychiatric disorders, growing evidence emphasizes the significance of dysfunctional neural circuits and signaling pathways. Hence, a systems biology approach is required to get a better understanding of psychiatric phenotypes such as depression and anxiety. Furthermore, the availability of biomarkers for these disorders is critical for improved diagnosis and monitoring treatment response. In the present study, a mouse model presenting with robust high versus low anxiety phenotypes was subjected to thorough molecular biomarker and pathway discovery analyses. Reference animals were metabolically labeled with the stable (15)N isotope allowing an accurate comparison of protein expression levels between the high anxiety-related behavior versus low anxiety-related behavior mouse lines using quantitative mass spectrometry. Plasma metabolomic analyses identified a number of small molecule biomarkers characteristic for the anxiety phenotype with particular focus on myo-inositol and glutamate as well as the intermediates involved in the tricarboxylic acid cycle. In silico analyses suggested pathways and subnetworks as relevant for the anxiety phenotype. Our data demonstrate that the high anxiety-related behavior and low anxiety-related behavior mouse model is a valuable tool for anxiety disorder drug discovery efforts. PMID:21862759

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

    PubMed Central

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

    2014-01-01

    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. PMID:25360441

  16. 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.

  17. 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. PMID:25360441

  18. 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.

  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. 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

  1. Effects of Low Dose Particle Radiation to Mouse Neonatal Neurons in Culture

    NASA Astrophysics Data System (ADS)

    Nojima, K.; Vazquez, M. E.; Okayasu, R.; Nagaoka, S.

    To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions by HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05Gy up to 2.0Gy. The subsequent biological effectswere evaluated by an induction of apoptosis and neuron survival focusing on the dependencies of the animal strains, SCID, B6, B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to particle radiation as evaluated by 10% apoptotic criterion. The LET dependency was compared with using SCID and B6 cells exposing to different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency was observed in the high LET (55 -200 keV/μ m) and low dose (<0.5 Gy) regions. The survivability profiles of the neurons were different in the mouse strains and ions. In this repot, a result of memory and learning function to adult mice after whole-body and brainlocal irradiation at carbon ion and iron ion.

  2. Exits in order: How crowding affects particle lifetimes

    NASA Astrophysics Data System (ADS)

    Penington, Catherine J.; Baker, Ruth E.; Simpson, Matthew J.

    2016-06-01

    Diffusive processes are often represented using stochastic random walk frameworks. The amount of time taken for an individual in a random walk to intersect with an absorbing boundary is a fundamental property that is often referred to as the particle lifetime, or the first passage time. The mean lifetime of particles in a random walk model of diffusion is related to the amount of time required for the diffusive process to reach a steady state. Mathematical analysis describing the mean lifetime of particles in a standard model of diffusion without crowding is well known. However, the lifetime of agents in a random walk with crowding has received much less attention. Since many applications of diffusion in biology and biophysics include crowding effects, here we study a discrete model of diffusion that incorporates crowding. Using simulations, we show that crowding has a dramatic effect on agent lifetimes, and we derive an approximate expression for the mean agent lifetime that includes crowding effects. Our expression matches simulation results very well, and highlights the importance of crowding effects that are sometimes overlooked.

  3. Exits in order: How crowding affects particle lifetimes.

    PubMed

    Penington, Catherine J; Baker, Ruth E; Simpson, Matthew J

    2016-06-28

    Diffusive processes are often represented using stochastic random walk frameworks. The amount of time taken for an individual in a random walk to intersect with an absorbing boundary is a fundamental property that is often referred to as the particle lifetime, or the first passage time. The mean lifetime of particles in a random walk model of diffusion is related to the amount of time required for the diffusive process to reach a steady state. Mathematical analysis describing the mean lifetime of particles in a standard model of diffusion without crowding is well known. However, the lifetime of agents in a random walk with crowding has received much less attention. Since many applications of diffusion in biology and biophysics include crowding effects, here we study a discrete model of diffusion that incorporates crowding. Using simulations, we show that crowding has a dramatic effect on agent lifetimes, and we derive an approximate expression for the mean agent lifetime that includes crowding effects. Our expression matches simulation results very well, and highlights the importance of crowding effects that are sometimes overlooked. PMID:27369497

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

    PubMed Central

    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. PMID:24198486

  5. Genetic loci that affect aristolochic acid-induced nephrotoxicity in the mouse

    PubMed Central

    2011-01-01

    Aristolochic acids (AA) are plant-derived nephrotoxins and carcinogens found in traditional medicines and herbal remedies. AA causes aristolochic acid nephropathy (AAN) and is a suspected environmental agent in Balkan endemic nephropathy (BEN) and its associated upper urothelial cancer. Approximately 5–10% of individuals exposed to AA develop renal insufficiency and/or cancer; thus a genetic predisposition to AA sensitivity has been proposed. The mouse is an established animal model of AAN, and inbred murine strains vary in AA sensitivity, confirming the genetic predisposition. We mapped quantitative trait loci (QTL) correlated with proximal tubule dysfunction after exposure to AA in an F2 population of mice, derived from breeding an AA-resistant strain (C57BL/6J) and an AA-sensitive strain (DBA/2J). A single main QTL was identified on chromosome 4 (Aanq1); three other interacting QTLs, (Aanq2–4) also were detected. The Aanq1 region was also detected in untreated mice, raising the possibility that preexisting differences in proximal tubule function may affect the severity of AA-elicited toxicity. This study lays the groundwork for identifying the genetic pathways contributing to AA sensitivity in the mouse and will further our understanding of human susceptibility to AA found widely in traditional medicines. PMID:21429970

  6. Soil Particle Heterogeneity Affects the Growth of a Rhizomatous Wetland Plant

    PubMed Central

    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. PMID:23936110

  7. Solar Sources of Earth-affecting Energetic Particles

    NASA Technical Reports Server (NTRS)

    Gopalswamy, Nat

    2012-01-01

    Particle radiation from the Sun is one of the most important sources of hazardous space weather in the vicinity of Earth. Detailed studies of the origin of the so-called large solar energetic particle (SEP) events became possible only during the solar cycle 23, thanks to the availability of nearly continuous observation of the solar sources ofthese events. In particular, coronal mass ejections (CMEs), which are found to be a key requirement for the occurrence of an SEP event, have been recorded continuously only starting in the 1990s. The physical connection between CMEs and SEPs is that the CMEs drive a fast-mode MHD shock, which accelerates SEPs in the corona and interplanetary medium. The earliest indication of a shock is the occurrence of a type II radio burst at frequencies anywhere from more than a hundred MHz to a few MHz. Recent investigations using STEREO observations have revealed that the shock forms very close to the Sun - a mere 100,000 km above the surface. The shock formation depends not only on the CME properties, but also on the physical conditions in the ambient medium that supports shock propagation. This paper considers extreme cases of SEP events and the associated CMEs and type II radio bursts to illustrate the variability observed in SEP event properties. Comparison will be made between the events of solar cycles 23 and 24.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. Factors Affecting the Occurrence of Large Solar Energetic Particle Events

    NASA Astrophysics Data System (ADS)

    Gopalswamy, N.; Yashiro, S.; Akiyama, S.; Xie, H.; Makela, P. A.; Thakur, N.

    2014-12-01

    In order to understand the paucity of high-energy solar energetic particle (SEP) events in solar cycle 24, we examined all major eruptions (soft X-ray flare size ≥M5.0) on the front side of the Sun during the period from December 1, 2008 to January 31, 2014. There were 59 such eruptions that were associated with CMEs. When a flux rope was fitted to the white-light CMEs observed by SOHO and STEREO it was found that the CME sources were on the disk only for 55 eruptions. There were 16 large SEP events (proton intensity ≥10 pfu in the >10 MeV channel) detected by GOES and 4 by STEREO-B in association with these eruptions. When the CMEs were grouped according to their speeds (<1500 km/s and ≥ 1500 km/s) it was found that only three of the <1500 km/s CMEs (or 11%) were associated with large SEP events compared to 17 or (61%) of the ≥ 1500 km/s CMEs. This result confirms the importance of CME speed for SEP association. In fact there were ten other large SEP events with flare size

  14. 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.

  15. Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain.

    PubMed

    Shah, Disha; Blockx, Ines; Keliris, Georgios A; Kara, Firat; Jonckers, Elisabeth; Verhoye, Marleen; Van der Linden, Annemie

    2016-07-01

    Resting-state functional MRI (rsfMRI) is a widely implemented technique used to investigate large-scale topology in the human brain during health and disease. Studies in mice provide additional advantages, including the possibility to flexibly modulate the brain by pharmacological or genetic manipulations in combination with high-throughput functional connectivity (FC) investigations. Pharmacological modulations that target specific neurotransmitter systems, partly mimicking the effect of pathological events, could allow discriminating the effect of specific systems on functional network disruptions. The current study investigated the effect of cholinergic and serotonergic antagonists on large-scale brain networks in mice. The cholinergic system is involved in cognitive functions and is impaired in, e.g., Alzheimer's disease, while the serotonergic system is involved in emotional and introspective functions and is impaired in, e.g., Alzheimer's disease, depression and autism. Specific interest goes to the default-mode-network (DMN), which is studied extensively in humans and is affected in many neurological disorders. The results show that both cholinergic and serotonergic antagonists impaired the mouse DMN-like network similarly, except that cholinergic modulation additionally affected the retrosplenial cortex. This suggests that both neurotransmitter systems are involved in maintaining integrity of FC within the DMN-like network in mice. Cholinergic and serotonergic modulations also affected other functional networks, however, serotonergic modulation impaired the frontal and thalamus networks more extensively. In conclusion, this study demonstrates the utility of pharmacological rsfMRI in animal models to provide insights into the role of specific neurotransmitter systems on functional networks in neurological disorders. PMID:26195064

  16. LRRK2 is expressed in areas affected by Parkinson's disease in the adult mouse brain.

    PubMed

    Simón-Sánchez, Javier; Herranz-Pérez, Vicente; Olucha-Bordonau, Francisco; Pérez-Tur, Jordi

    2006-02-01

    The leucine-rich repeat kinase 2 (LRRK2) gene was recently found to have multiple mutations that are causative for autosomal dominant inherited Parkinson's disease (PD). Previously, we used Northern blot analysis to show that this gene was expressed in the cerebellum, cerebral cortex, medulla, spinal cord, occipital pole, frontal lobe, temporal lobe and caudate putamen. However, a more comprehensive map of LRRK2 mRNA localization in the central nervous system is still lacking. In this study we have mapped the distribution of the mRNA encoding for LRRK2 using nonradioactive in situ hybridization. We detected a moderate expression of this PD-related gene throughout the adult B2B6 mouse brain. A stronger hybridization signal was observed in deep cerebral cortex layers, superficial cingulate cortex layers, the piriform cortex, hippocampal formation, caudate putamen, substantia nigra, the basolateral and basomedial anterior amygdala nuclei, reticular thalamic nucleus and also in the cerebellar granular cell layer. Given that LRRK2 mRNA is highly enriched in motor systems and also is expressed in other systems, we may conclude that mutations in LRRK2 may affect several motor and nonmotor structures that may play an important role in the development of PD.

  17. The mouse brown (b/Tyrp1(b) ) allele does not affect pheomelanin synthesis in mice.

    PubMed

    Hirobe, Tomohisa; Ito, Shosuke; Wakamatsu, Kazumasa; Kawa, Yoko; Abe, Hiroyuki

    2014-02-01

    B (Tyrp1 (+)), the wild type allele at the mouse brown locus, produces black eumelanin, while b (Tyrp1(b) ), the recessive allele, produces brown eumelanin and exhibits lower tyrosinase (Tyr)-related protein 1 (Tyrp1) activity. However, it is unknown whether melanocyte proliferation and differentiation are affected by the Tyrp1(b) mutation. The proliferation rate of brown (C57BL/10JHir (B10)-Tyrp1(b) / Tyrp1(b) ) melanocytes cultured in a serum-free melanocyte proliferation medium (MDMD) was similar to that of black (B10-Tyrp1(+)/Tyrp1(+) ) melanocytes. Although brown melanocytes exhibited normal morphology, their pigmentation was lower than that of black melanocytes. However, Tyr activity in brown melanocytes was increased both in vivo and in vitro. Melanosomes of cultured brown melanocytes were mostly spherical stage III melanosomes with granular depositions of pigments, whereas those of cultured black melanocytes were mostly stage IV ellipsoidal melanosomes with pigment depositions in intraluminal fibrils. Chemical analysis of melanin present in dorsal hairs of 5-week-old mice from the F2 generation between brown and recessive yellow (B10-Mc1r(e)/Mc1r(e) ) or agouti (B10-A/A) mice showed that eumelanin content was greatly decreased in brown and brown agouti (cinnamon) mice, whereas pheomelanin contents in brown recessive yellow and cinnamon mice did not differ from the corresponding Tyrp1(+)/- mice. These results suggest that the brown allele greatly inhibits eumelanin, but not pheomelanin synthesis.

  18. 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.

  19. 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.

  20. 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.

  1. Interface deformations affect the orientation transition of magnetic ellipsoidal particles adsorbed at fluid-fluid interfaces.

    PubMed

    Davies, Gary B; Krüger, Timm; Coveney, Peter V; Harting, Jens; Bresme, Fernando

    2014-09-21

    Manufacturing new soft materials with specific optical, mechanical and magnetic properties is a significant challenge. Assembling and manipulating colloidal particles at fluid interfaces is a promising way to make such materials. We use lattice-Boltzmann simulations to investigate the response of magnetic ellipsoidal particles adsorbed at liquid-liquid interfaces to external magnetic fields. We provide further evidence for the first-order orientation phase transition predicted by Bresme and Faraudo [Journal of Physics: Condensed Matter, 2007, 19, 375110]. We show that capillary interface deformations around the ellipsoidal particle significantly affect the tilt-angle of the particle for a given dipole-field strength, altering the properties of the orientation transition. We propose scaling laws governing this transition, and suggest how to use these deformations to facilitate particle assembly at fluid-fluid interfaces. PMID:25069609

  2. Interface deformations affect the orientation transition of magnetic ellipsoidal particles adsorbed at fluid-fluid interfaces.

    PubMed

    Davies, Gary B; Krüger, Timm; Coveney, Peter V; Harting, Jens; Bresme, Fernando

    2014-09-21

    Manufacturing new soft materials with specific optical, mechanical and magnetic properties is a significant challenge. Assembling and manipulating colloidal particles at fluid interfaces is a promising way to make such materials. We use lattice-Boltzmann simulations to investigate the response of magnetic ellipsoidal particles adsorbed at liquid-liquid interfaces to external magnetic fields. We provide further evidence for the first-order orientation phase transition predicted by Bresme and Faraudo [Journal of Physics: Condensed Matter, 2007, 19, 375110]. We show that capillary interface deformations around the ellipsoidal particle significantly affect the tilt-angle of the particle for a given dipole-field strength, altering the properties of the orientation transition. We propose scaling laws governing this transition, and suggest how to use these deformations to facilitate particle assembly at fluid-fluid interfaces.

  3. 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

  4. Inhibition does not affect the timing code for vocalizations in the mouse auditory midbrain

    PubMed Central

    Dimitrov, Alexander G.; Cummins, Graham I.; Mayko, Zachary M.; Portfors, Christine V.

    2014-01-01

    Many animals use a diverse repertoire of complex acoustic signals to convey different types of information to other animals. The information in each vocalization therefore must be coded by neurons in the auditory system. One way in which the auditory system may discriminate among different vocalizations is by having highly selective neurons, where only one or two different vocalizations evoke a strong response from a single neuron. Another strategy is to have specific spike timing patterns for particular vocalizations such that each neural response can be matched to a specific vocalization. Both of these strategies seem to occur in the auditory midbrain of mice. The neural mechanisms underlying rate and time coding are unclear, however, it is likely that inhibition plays a role. Here, we examined whether inhibition is involved in shaping neural selectivity to vocalizations via rate and/or time coding in the mouse inferior colliculus (IC). We examined extracellular single unit responses to vocalizations before and after iontophoretically blocking GABAA and glycine receptors in the IC of awake mice. We then applied a number of neurometrics to examine the rate and timing information of individual neurons. We initially evaluated the neuronal responses using inspection of the raster plots, spike-counting measures of response rate and stimulus preference, and a measure of maximum available stimulus-response mutual information. Subsequently, we used two different event sequence distance measures, one based on vector space embedding, and one derived from the Victor/Purpura Dq metric, to direct hierarchical clustering of responses. In general, we found that the most salient feature of pharmacologically blocking inhibitory receptors in the IC was the lack of major effects on the functional properties of IC neurons. Blocking inhibition did increase response rate to vocalizations, as expected. However, it did not significantly affect spike timing, or stimulus selectivity of

  5. Polysaccharide from seeds of Plantago asiatica L. affects lipid metabolism and colon microbiota of mouse.

    PubMed

    Hu, Jie-Lun; Nie, Shao-Ping; Wu, Qi-Meng; Li, Chang; Fu, Zhi-Hong; Gong, Joshua; Cui, Steve W; Xie, Ming-Yong

    2014-01-01

    Polysaccharide from the seeds of Plantago asiatica L. was given via oral administration to mice (0.4 g/kg body weight, 30 days) to observe its effects on mouse nutrient metabolism and colon microbiota. It was found the polysaccharide intake could lower the apparent absorption of lipid. Total triglyceride, cholesterol, and atherogenic index in blood serum with total lipid and cholesterol levels in liver of polysaccharide group mice were all significantly lower than those of the control group (p < 0.05). Furthermore, the effect of the polysaccharide intake on mouse colon bacterial communities was investigated. Mice from the polysaccharide group showed a higher colon bacterial diversity than the control group. Bacteroides sp., Eubacterium sp., butyrate-producing bacteria Butyrivibrio sp., and probiotics Bifidobacterium bifidum , Lactobacillus fermentum , and Lactobacillus reuteri in mouse colon were all increased after polysaccharide intake. These indicated that the intake of polysaccharide from P. asiatica L. could be beneficial for lipid metabolism and colon microbiota. PMID:24341731

  6. 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

  7. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. 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

  10. 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.

  11. 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

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

    PubMed

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

    2015-10-01

    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

  13. 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.

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

    PubMed Central

    Tremblay, Michel G.; Moss, Tom

    2016-01-01

    ABSTRACT 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. PMID:27399837

  15. Laser Fusion of Mouse Embryonic Cells and Intra-Embryonic Fusion of Blastomeres without Affecting the Embryo Integrity

    PubMed Central

    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. PMID:23227157

  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. 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. Mice move smoothly: irrelevant object variation affects perception, but not computer mouse actions.

    PubMed

    Janczyk, Markus; Pfister, Roland; Kunde, Wilfried

    2013-11-01

    Human-Computer Interactions pose special demands on the motor system, especially regarding the virtual tool transformations underlying typical mouse movements. We investigated whether such virtual tool-transformed movements are similarly resistant to irrelevant variation of a target object as skilled natural movements are. Results show that such irrelevant information deteriorates performance in perceptual tasks, whereas movement parameters remain unaffected, suggesting that the control of virtual tools draws on the same mechanisms as natural actions do. The results are discussed in terms of their practical utility and recent findings investigating unskilled and transformed movements in the framework of the action/perception model and the integration of tools into the body schema.

  19. 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.

  20. 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. PMID:27136179

  1. 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.

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

    PubMed

    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

  3. 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

  4. 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

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

    PubMed

    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.

  6. MiR-16 regulates mouse peritoneal macrophage polarization and affects T-cell activation.

    PubMed

    Jia, Xiaoqin; Li, Xiaomin; Shen, Yating; Miao, Junjun; Liu, Hao; Li, Guoli; Wang, Zhengbing

    2016-10-01

    MiR-16 is a tumour suppressor that is down-regulated in certain human cancers. However, little is known on its activity in other cell types. In this study, we examined the biological significance and underlying mechanisms of miR-16 on macrophage polarization and subsequent T-cell activation. Mouse peritoneal macrophages were isolated and induced to undergo either M1 polarization with 100 ng/ml of interferon-γ and 20 ng/ml of lipopolysaccharide, or M2 polarization with 20 ng/ml of interleukin (IL)-4. The identity of polarized macrophages was determined by profiling cell-surface markers by flow cytometry and cytokine production by ELISA. Macrophages were infected with lentivirus-expressing miR-16 to assess the effects of miR-16. Effects on macrophage-T cell interactions were analysed by co-culturing purified CD4(+) T cells with miR-16-expressing peritoneal macrophages, and measuring activation marker CD69 by flow cytometry and cytokine secretion by ELISA. Bioinformatics analysis was applied to search for potential miR-16 targets and understand its underlying mechanisms. MiR-16-induced M1 differentiation of mouse peritoneal macrophages from either the basal M0- or M2-polarized state is indicated by the significant up-regulation of M1 marker CD16/32, repression of M2 marker CD206 and Dectin-1, and increased secretion of M1 cytokine IL-12 and nitric oxide. Consistently, miR-16-expressing macrophages stimulate the activation of purified CD4(+) T cells. Mechanistically, miR-16 significantly down-regulates the expression of PD-L1, a critical immune suppressor that controls macrophage-T cell interaction and T-cell activation. MiR-16 plays an important role in shifting macrophage polarization from M2 to M1 status, and functionally activating CD4(+) T cells. This effect is potentially mediated through the down-regulation of immune suppressor PD-L1.

  7. 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.

  8. 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

  9. 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.

  10. 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. PMID:17516662

  11. 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.

  12. 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

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

    PubMed

    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.

  14. 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.

  15. 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.

  16. 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. PMID:27237783

  17. Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate

    PubMed Central

    INOUE, MASASHI; LI, XIA; McCAUGHEY, STUART A.; BEAUCHAMP, GARY K.; BACHMANOV, ALEXANDER A.

    2013-01-01

    In mice, behavioral acceptance of the bitter compound sucrose octaacetate (SOA) depends on allelic variation of a single gene, Soa. The SW.B6-Soab congenic mouse strain has the genetic background of an “SOA taster” SWR/J strain and an Soa-containing donor chromosome fragment from an “SOA nontaster” C57BL/6J strain. Using microsatellite markers polymorphic between the two parental strains, we determined that the donor fragment spans 5–10 cM of distal chromosome 6. The SWR/J mice avoided SOA in two-bottle tests with water and had strong responses to SOA in two gustatory nerves, the chorda tympani (CT) and glossopharyngeal (GL). In contrast, the SW.B6-Soab mice were indifferent to SOA in two-bottle tests and had very weak responses to SOA in both of these nerves. The SWR/J and SW.B6-Soab mice did not differ in responses of either nerve to sucrose, NaCl, HCl, or the bitter-tasting stimuli quinine, denatonium, strychnine, 6-n-propylthiouracil, phenylthiocarbamide, and MgSO4. Thus the effect of the Soa genotype on SOA avoidance is mediated by peripheral taste responsiveness to SOA, involving taste receptor cells innervated by both the CT and GL nerves. PMID:11328963

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

    PubMed Central

    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.

    2016-01-01

    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. PMID:26980613

  19. 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.

  20. Maternal stress affects postnatal growth and the pituitary expression of prolactin in mouse offspring.

    PubMed

    Gao, Pengfei; Ishige, Atsushi; Murakami, Yu; Nakata, Hideyuki; Oka, Jun-Ichiro; Munakata, Kaori; Yamamoto, Masahiro; Nishimura, Ko; Watanabe, Kenji

    2011-03-01

    Maternal stress exerts long-lasting psychiatric and somatic on offspring, which persist into adulthood. However, the effect of maternal stress on the postnatal growth of pups has not been widely reported. In this study, we found that maternal immobilization stress (IS) during lactation resulted in low body weight of male mouse offspring, which persisted after weaning. Despite free access to chow, IS induced maternal malnutrition and decreased the serum insulin-like growth factor-1 (IGF-1) levels in the mothers and in the pups. mRNA expression analysis of anterior pituitary hormones in the pups revealed that growth hormone (GH) and prolactin (PRL), but no other hormones, were decreased by IS. Expression of the pituitary transcription factor PIT1 and isoforms of PITX2, which are essential for the development and function of GH-producing somatotropes and PRL-producing lactotropes, was decreased, whereas that of PROP1, which is critical for the earlier stages of pituitary development, was unchanged. Immunohistochemistry also showed a decrease in pituitary PRL protein expression. These results suggest that stress in a postpartum mother has persistent effects on the body weight of the offspring. Reduced PRL expression in the offspring's pituitary gland may play a role in these effects.

  1. Factors affecting meiotic and developmental competence of primary spermatocyte nuclei injected into mouse oocytes.

    PubMed

    Kimura, Y; Tateno, H; Handel, M A; Yanagimachi, R

    1998-10-01

    Mature mouse oocytes that have received the nuclei of pachytene primary spermatocytes (or metaphase I chromosomes of primary spermatocytes) can develop into fertile offspring. However, success rate in this study was low. No more than 3.8% of transferred 2-cell embryos arising from spermatocyte-injected oocytes developed to full term. Nevertheless, the birth of normal offspring seems to suggest that at least in some primary spermatocytes the functional genomic imprinting is complete before transfer and/or consolidated after the transfer. Although injected spermatocyte nuclei could undergo two successive meiotic divisions within oocytes, abnormalities of both divisions were commonly observed, and sister chromatids often separated prematurely during the second meiotic division. Chromosome breakage/rearrangements were also frequently seen before the first cleavage. Such abnormalities of chromosome behavior are probably the major causes of the poor preimplantation development of zygotes arising from primary spermatocyte-injected oocytes. Thus, clinical use of primary spermatocytes as substitutes for spermatozoa in assisted fertilization is not advisable until the causes of chromosomal abnormalities are better understood through extensive animal studies. PMID:9746737

  2. 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. PMID:26980613

  3. Hotfoot mouse mutations affect the delta 2 glutamate receptor gene and are allelic to lurcher.

    PubMed

    Lalouette, A; Guénet, J L; Vriz, S

    1998-05-15

    Hotfoot (ho) is a recessive mouse mutation characterized by cerebellar ataxia associated with relatively mild abnormalities of the cerebellum. It has been previously mapped to Chromosome 6, and at least eight independent alleles have been reported. Here we show that the hotfoot phenotype is associated with mutations in the glutamate receptor ionotropic delta2 gene (Grid2). We have identified a 510-bp deletion in the Grid2 coding sequence in the ho4J allele, resulting in a deletion of 170 amino acids of the extracellular domain of the receptor. Analysis of a second allele, hoTgN37INRA, revealed a 4-kb deletion in the Grid2 transcript. The GRID2 protein in these hotfoot mutants probably has a reduced (or null) activity since the phenotype of hotfoot bears similarities with the previously described phenotype of Grid2 knockout mice. The exceptionally high number of independent alleles at the ho locus is an invaluable tool for investigating the function of the glutamate receptor ionotropic delta2 protein, which so far remains largely unknown.

  4. Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

    PubMed Central

    2013-01-01

    Background Vaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature. Results Nineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value < 0.05) to Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability

  5. 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%. PMID:26153914

  6. [Changes in prostaglandin systhetase activity in mouse tissues as affected by S-[N-(3-aminopropyl)-2-aminoethyl] thiophosphoric acid].

    PubMed

    Prianishnikova, E N; Zhulanova, Z I; Romantsev, E F

    1980-01-01

    Effect of various concentrations of a radioprotector S-[N-(3 aminopropyl)-2-aminoethyl] thiophosphoric acid on the activity of prostaglandine synthetase was studied in mouse liver microsomes as well as in the soluble fractions of testicules and brain in vitro. The activity of prostaglandine synthetase was estimated by monitoring the formation of labelled PGF2 alpha and PGE2 from I-14C-arachidonic acid. The radioprotector at concentration 1.66 mg/ml stimulated formation of PGF2 alpha in all the tissues studied. At the lower concentrations of the radioprotector only slight stimulation of the biosynthesis of prostaglandines in testicules was noted. No effect on their synthesis in the brain soluble fraction could be observed while in the liver microsomes it was inhibited. The radioprotective substance studied apparently affected the cyclooxygenase activity, which is a key enzyme in the prostaglandine-synthesizing system.

  7. 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.

  8. Diethylhexyl phthalate exposure impairs follicular development and affects oocyte maturation in the mouse.

    PubMed

    Zhang, Xi-Feng; Zhang, Lian-Jun; Li, Lan; Feng, Yan-Ni; Chen, Bo; Ma, Jin-Mei; Huynh, Evanna; Shi, Qing-Hua; De Felici, Massimo; Shen, Wei

    2013-06-01

    Diethylhexyl phthalate (DEHP) is an estrogen-like compound widely used as a commercial plasticizer and present in medical devices, tubing, food containers and packaging. It is considered an endocrine disruptor and studies on experimental animals showed that exposure to DEHP can alter the function of several organs including liver, kidneys, lungs and reproductive system, particularly the developing testes of prenatal and neonatal males. Exposure to DEHP has been proposed as a potential human health hazard. This study assessed the effects of DEHP on folliculogenesis and oocyte maturation using the mouse as the experimental model. Newborn female mice were hypodermically injected with DEHP at doses of 20 and 40 μg/kg per body weight following different exposure regimens during the weaning period. We found that DEHP altered both folliculogenesis and oocyte development. In particular, DEHP exposure significantly decreased the number of the primordial follicles at pubertal and adult age by possibly accelerating the rate of follicle recruitment dynamics, reduced and/or delayed the level of imprinted gene methylation in the oocytes and increased metaphase II spindle abnormalities in oocytes matured in vitro. Furthermore, the weight of pups and litter size of mothers exposed to DEHP were significantly lower than controls. Finally, the number of primordial follicles appeared significantly reduced also in the F1 offspring at the adult age. These results show that DEHP may have a number of adverse effects on oogenesis, especially when exposure occurs during early postnatal age, arising concerns about the exposure of human female infants and children to this compound.

  9. 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. PMID:27492329

  10. 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.

  11. 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

  12. CDK2 Activation in Mouse Epidermis Induces Keratinocyte Proliferation but Does Not Affect Skin Tumor Development

    PubMed Central

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

    2008-01-01

    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 p21Cip1 and p27Kip1. 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 K5Cdk4D158N mice. The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. CDK2 activation via overexpression of CDK4D158N, but not of CDK2, resulted in epidermal hyperplasia. We observed elevated levels of p21Cip1 in K5Cdk2, but not in K5Cdk4D158N, epidermis, suggesting that CDK2 overexpression elicits a p21Cip1 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. PMID:18599613

  13. 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.

  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. Dietary nucleotides affect hepatic growth and composition in the weanling mouse.

    PubMed

    Novak, D A; Carver, J D; Barness, L A

    1994-01-01

    The effect of dietary nucleotides upon hepatic growth and composition was examined in weanling mice. For 5 weeks, mice were fed either Purina Rat Chow, a nucleotide-free diet (NT-), a nucleotide-free diet supplemented with a mixture of five nucleotides (0.21% w/w), (NT+) or a nucleotide-free diet supplemented with adenosine 5'-monophosphate (0.0425% w/w) (NTA). Hepatic cholesterol and lipid phosphorous were significantly higher, whereas liver weight (expressed as a percentage of body weight), and glycogen were lower in animals fed NT- vs all other groups. NTA-fed animals presented a greater contrast to the NT- group than did animals fed the mixture of nucleotides. Liver fatty acid composition and distribution of phospholipid subclasses were not affected by dietary nucleotide supplementation. Dietary nucleotide supplementation in weanling mice affects hepatic growth and composition; adenosine 5'-monophosphate may play a unique role in these effects.

  16. Factors affecting the survival, fertilization, and embryonic development of mouse oocytes after vitrification using glass capillaries.

    PubMed

    Tan, Xiuwen; Song, Enliang; Liu, Xiaomu; You, Wei; Wan, Fachun

    2009-09-01

    Cryopreservation of mammalian oocytes is an important way to provide a steady source of materials for research and practice of parthenogenetic activation, in vitro fertilization, and nuclear transfer. However, oocytes cryopreservation has not been common used, as there still are some problems waiting to be solved on the repeatability, safety, and validity. Then, it is necessary to investigate the damage occurred from vitrification and find a way to avoid or repair it. In this study, mouse mature oocytes were firstly pretreated in different equilibrium media, such as 5% ethylene glycol (EG) + 5% dimethyl sulfoxide (DMSO), 10% EG + 10% DMSO, and 15% EG + 15% DMSO in TCM199 supplemented with 20% fetal calf serum (FCS), for 1, 3, and 5 min, respectively, and then oocytes were transferred into vitrification solution (20% EG, 20% DMSO, 0.3 M sucrose, and 20% FCS in TCM199, M2, Dulbecco's phosphate buffered saline, and 0.9% saline medium, respectively) and immediately loaded into glass capillaries to be plunged into liquid nitrogen. After storage from 1 h to 1 wk, they were diluted in stepwise sucrose solutions. The surviving oocytes were stained for cortical granule, meiotic spindles, and chromosomes. Oocytes without treatments were used as controls. The results showed that oocytes pretreated in 5% EG +5% DMSO group for 3-5 min or in 10% EG + 10% DMSO group for 1-3 min were better than other treatments. Oocytes vitrified in TCM199 as basic medium showed higher survival and better subsequent embryonic development than other groups. When the concentration of FCS in vitrification solution reduced below 15%, the rates of survival, fertilization, and developing to blastocyst declined dramatically. The inner diameter (0.6 mm) of glass capillaries and amount of vitrification solution (1-3 microl) achieved more rapid cooling and warming and so reduce the injury to oocytes. Cropreservation led to the exocytosis of cortical granule of oocytes (about 10%) and serious disturbance of

  17. Factors affecting the survival, fertilization, and embryonic development of mouse oocytes after vitrification using glass capillaries.

    PubMed

    Tan, Xiuwen; Song, Enliang; Liu, Xiaomu; You, Wei; Wan, Fachun

    2009-09-01

    Cryopreservation of mammalian oocytes is an important way to provide a steady source of materials for research and practice of parthenogenetic activation, in vitro fertilization, and nuclear transfer. However, oocytes cryopreservation has not been common used, as there still are some problems waiting to be solved on the repeatability, safety, and validity. Then, it is necessary to investigate the damage occurred from vitrification and find a way to avoid or repair it. In this study, mouse mature oocytes were firstly pretreated in different equilibrium media, such as 5% ethylene glycol (EG) + 5% dimethyl sulfoxide (DMSO), 10% EG + 10% DMSO, and 15% EG + 15% DMSO in TCM199 supplemented with 20% fetal calf serum (FCS), for 1, 3, and 5 min, respectively, and then oocytes were transferred into vitrification solution (20% EG, 20% DMSO, 0.3 M sucrose, and 20% FCS in TCM199, M2, Dulbecco's phosphate buffered saline, and 0.9% saline medium, respectively) and immediately loaded into glass capillaries to be plunged into liquid nitrogen. After storage from 1 h to 1 wk, they were diluted in stepwise sucrose solutions. The surviving oocytes were stained for cortical granule, meiotic spindles, and chromosomes. Oocytes without treatments were used as controls. The results showed that oocytes pretreated in 5% EG +5% DMSO group for 3-5 min or in 10% EG + 10% DMSO group for 1-3 min were better than other treatments. Oocytes vitrified in TCM199 as basic medium showed higher survival and better subsequent embryonic development than other groups. When the concentration of FCS in vitrification solution reduced below 15%, the rates of survival, fertilization, and developing to blastocyst declined dramatically. The inner diameter (0.6 mm) of glass capillaries and amount of vitrification solution (1-3 microl) achieved more rapid cooling and warming and so reduce the injury to oocytes. Cropreservation led to the exocytosis of cortical granule of oocytes (about 10%) and serious disturbance of

  18. 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.

  19. 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.

  20. 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

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

    PubMed

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

    2014-05-01

    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-CTL antigen-4 (CTLA-4) or agonist anti-glucocorticoid-induced TNF family-related gene (GITR) immunomodulatory monoclonal antibodies (mAb). In the challenging therapeutic setting, VRP-TRP2 plus anti-GITR or anti-CTLA-4 mAb induced complete tumor regression in 90% and 50% of mice, respectively. These mAbs had similar adjuvant effects in priming an adaptive immune response against the vaccine-encoded antigen, augmenting, respectively, approximately 4- and 2-fold the TRP2-specific CD8(+) T-cell response and circulating Abs, compared with 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 intratumor CD4(+)Foxp3(-) T cells expressing the negative costimulatory 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 anticancer vaccines can provide therapeutic antitumor 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.

  2. 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

  3. Reduced Expression of the Vesicular Acetylcholine Transporter and Neurotransmitter Content Affects Synaptic Vesicle Distribution and Shape in Mouse Neuromuscular Junction

    PubMed Central

    Rodrigues, Hermann A.; Fonseca, Matheus de C.; Camargo, Wallace L.; Lima, Patrícia M. A.; Martinelli, Patrícia M.; Naves, Lígia A.; Prado, Vânia F.; Prado, Marco A. M.; Guatimosim, Cristina

    2013-01-01

    In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KDHOM) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KDHOM mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1–43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or no stimulation, VAChT KDHOM neuromuscular junctions did not differ from WT on total number of vesicles but showed altered distribution. Additionally, motor nerve terminals in VAChT KDHOM exhibited small and flattened synaptic vesicles similar to that observed in WT mice treated with vesamicol that blocks acetylcholine uptake. Based on these results, we propose that decreased VAChT levels affect synaptic vesicle biogenesis and distribution whereas a lower ACh content affects vesicles shape. PMID:24260111

  4. Reduced expression of the vesicular acetylcholine transporter and neurotransmitter content affects synaptic vesicle distribution and shape in mouse neuromuscular junction.

    PubMed

    Rodrigues, Hermann A; Fonseca, Matheus de C; Camargo, Wallace L; Lima, Patrícia M A; Martinelli, Patrícia M; Naves, Lígia A; Prado, Vânia F; Prado, Marco A M; Guatimosim, Cristina

    2013-01-01

    In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KD(HOM)) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KD(HOM) mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1-43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or no stimulation, VAChT KD(HOM) neuromuscular junctions did not differ from WT on total number of vesicles but showed altered distribution. Additionally, motor nerve terminals in VAChT KD(HOM) exhibited small and flattened synaptic vesicles similar to that observed in WT mice treated with vesamicol that blocks acetylcholine uptake. Based on these results, we propose that decreased VAChT levels affect synaptic vesicle biogenesis and distribution whereas a lower ACh content affects vesicles shape. PMID:24260111

  5. A Trouble Shared Is a Trouble Halved: Social Context and Status Affect Pain in Mouse Dyads

    PubMed Central

    Gioiosa, Laura; Chiarotti, Flavia; Alleva, Enrico; Laviola, Giovanni

    2009-01-01

    In mice behavioral response to pain is modulated by social status. Recently, social context also has been shown to affect pain sensitivity. In our study, we aimed to investigate the effects of interaction between status and social context in dyads of outbred CD-1 male mice in which the dominance/submission relationship was stable. Mice were assessed for pain response in a formalin (1% concentration) test either alone (individually tested-IT), or in pairs of dominant and subordinate mice. In the latter condition, they could be either both injected (BI) or only one injected (OI) with formalin. We observed a remarkable influence of social context on behavioral response to painful stimuli regardless of the social status of the mice. In the absence of differences between OI and IT conditions, BI mice exhibited half as much Paw-licking behavior than OI group. As expected, subordinates were hypoalgesic in response to the early phase of the formalin effects compared to dominants. Clear cut-differences in coping strategies of dominants and subordinates appeared. The former were more active, whereas the latter were more passive. Finally, analysis of behavior of the non-injected subjects (the observers) in the OI dyads revealed that dominant observers were more often involved in Self-grooming behavior upon observation of their subordinate partner in pain. This was not the case for subordinate mice observing the pain response of their dominant partner. In contrast, subordinate observers Stared at the dominant significantly more frequently compared to observer dominants in other dyads. The observation of a cagemate in pain significantly affected the observer's behavior. Additionally, the quality of observer's response was also modulated by the dominance/submission relationship. PMID:19129917

  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. 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

  8. Effects of lipopolysaccharide on 56Fe-particle radiation-induced impairment of synaptic plasticity in the mouse hippocampus.

    PubMed

    Vlkolinský, Roman; Krucker, Thomas; Smith, Anna L; Lamp, Tyra C; Nelson, Gregory A; Obenaus, Andre

    2007-10-01

    Space radiation, including high-mass, high-Z, high-energy particles (HZE; e.g. (56)Fe), represents a significant health risk for astronauts, and the central nervous system (CNS) may be a vulnerable target. HZE-particle radiation may directly affect neuronal function, or during immunological challenge, it may alter immune system-to-CNS communication. To test these hypotheses, we exposed mice to accelerated iron particles ((56)Fe; 600 MeV/nucleon; 1, 2, 4 Gy; brain only) and 1 month later prepared hippocampal slices to measure the effects of radiation on neurotransmission and synaptic plasticity in CA1 neurons. In a model of immune system-to-CNS communication, these electrophysiological parameters were measured in irradiated mice additionally challenged with the peripheral immunological stressor lipopolysaccharide (LPS) injected intraperitoneally 4 h before the slice preparation. Exposure to (56)Fe particles alone increased dendritic excitability and inhibited plasticity. In control mice (0 Gy), LPS treatment also inhibited synaptic plasticity. Paradoxically, in mice exposed to 2 Gy, the LPS treatment restored synaptic plasticity to levels similar to those found in controls (0 Gy, no LPS). Our results indicate that HZE-particle radiation alters normal electrophysiological properties of the CNS and the hippocampal response to LPS. PMID:17903042

  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.

  10. Aging does not affect soluble guanylate cyclase redox state in mouse aortas.

    PubMed

    Shimosato, Takashi; Tawa, Masashi; Iwasaki, Hirotaka; Imamura, Takeshi; Okamura, Tomio

    2016-05-01

    Aging is associated with endothelial dysfunction, defined as a reduction in nitric oxide (NO) bioavailability. Although the redox state of the NO acceptor soluble guanylate cyclase (sGC) is another determinant factor for its bioavailability and is disturbed by reactive oxygen species (ROS) known to be increased with age, it is unclear whether aging actually has an impact on vascular sGC redox equilibrium. Therefore, this study investigated this issue using two different types of compounds, the sGC stimulator BAY 41-2272 and the sGC activator BAY 60-2770. Plasma thiobarbituric acid-reactive substances (TBARS) levels were markedly higher in aged (19-20 months old) mice than in young (2-3 months old) mice, whereas superoxide levels in endothelium-denuded aortas were not different between the groups. The relaxant response of endothelium-denuded aortas to either BAY 41-2272 or BAY 60-2770 was identical in aged and young mice. In addition, the vascular cGMP production stimulated with BAY 41-2272 or BAY 60-2770 in aged mice was the same level as that in young mice. These findings suggest that aging accompanied by an increase in systemic oxidative stress does not affect vascular smooth muscle ROS generation and sGC redox equilibrium. Unless ROS are increased in vascular smooth muscle, the sGC redox equilibrium might remain unchanged.

  11. Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model.

    PubMed

    de Haar, Colin; Hassing, Ine; Bol, Marianne; Bleumink, Rob; Pieters, Raymond

    2005-10-01

    To gain more insight into the mechanisms of particulate matter (PM)-induced adjuvant activity, we studied the kinetics of airway toxicity/inflammation and allergic sensitization to ovalbumin (OVA) in response to ultrafine carbon black particles (CBP). Mice were exposed intranasally to OVA alone or in combination with different concentrations of CBP. Airway toxicity and inflammation were assessed at days 4 and 8. Immune adjuvant effects were studied in the lung draining peribronchial lymph nodes (PBLN) at day 8. Antigen-specific IgE was measured at days 21 and 28, whereas allergic airway inflammation was studied after OVA challenges (day 28). Results show that a total dose of 200 microg CBP per mouse, but not 20 microg or 2 microg, induced immediate airway inflammation. This 200 microg CBP was the only dose that had immune adjuvant activity, by inducing enlargement of the PBLN and increasing OVA-specific production of Th2 cytokines (IL-4, IL-5, and IL-10). The immune adjuvant activity of 200 microg CBP dosing was further examined. Whereas increased OVA-specific IgE levels in serum on day 21 confirms systemic sensitization, this was further supported by allergic airway inflammation after challenges with OVA. Our data show a link between early airway toxicity and adjuvant effects of CBP. In addition, results indicate that local cytokine production early after exposure to CBP is predictive of allergic airway inflammation. In addition this model appears suitable for studying the role of airway toxicity, inflammation and other mechanisms of particle adjuvant activity, and predicting the adjuvant potential of different particles.

  12. Establishment of a method to determine the magnetic particles in mouse tissues

    NASA Astrophysics Data System (ADS)

    Wu, Yifan; Zhang, Wuxu; Wang, Yuxia; Li, Qian; Gao, Guo; Dong, Na; Hu, Hengyao; Wang, Kan; Wu, Junhua; Gao, Zhongcai; Cui, Daxiang

    2012-12-01

    This work is aimed to evaluate a method to detect the residual magnetic nanoparticles (MNPs) in animal tissues. Ferric ions released from MNPs through acidification with hydrochloric acid can be measured by complexation with potassium thiocyanate. MNPs in saline could be well detected by this chemical colorimetric method, whereas the detected sensitivity decreased significantly when MNPs were mixed with mouse tissue homogenates. In order to check the MNPs in animal tissues accurately, three improvements have been made. Firstly, proteinase K was used to digest the proteins that might bind with iron, and secondly, ferrosoferric oxide (Fe3O4) was collected by a magnetic field which could capture MNPs and leave the bio-iron in the supernatant. Finally, the collected MNPs were carbonized in the muffle furnace at 420°C before acidification to ruin the groups that might bind with ferric ions such as porphyrin. Using this method, MNPs in animal tissues could be well measured while avoiding the disturbance of endogenous iron and iron-binding groups.

  13. Establishment of a method to determine the magnetic particles in mouse tissues.

    PubMed

    Wu, Yifan; Zhang, Wuxu; Wang, Yuxia; Li, Qian; Gao, Guo; Dong, Na; Hu, Hengyao; Wang, Kan; Wu, Junhua; Gao, Zhongcai; Cui, Daxiang

    2012-01-01

    This work is aimed to evaluate a method to detect the residual magnetic nanoparticles (MNPs) in animal tissues. Ferric ions released from MNPs through acidification with hydrochloric acid can be measured by complexation with potassium thiocyanate. MNPs in saline could be well detected by this chemical colorimetric method, whereas the detected sensitivity decreased significantly when MNPs were mixed with mouse tissue homogenates. In order to check the MNPs in animal tissues accurately, three improvements have been made. Firstly, proteinase K was used to digest the proteins that might bind with iron, and secondly, ferrosoferric oxide (Fe3O4) was collected by a magnetic field which could capture MNPs and leave the bio-iron in the supernatant. Finally, the collected MNPs were carbonized in the muffle furnace at 420°C before acidification to ruin the groups that might bind with ferric ions such as porphyrin. Using this method, MNPs in animal tissues could be well measured while avoiding the disturbance of endogenous iron and iron-binding groups. PMID:23216680

  14. Perineuronal nets affect parvalbumin expression in GABAergic neurons of the mouse hippocampus.

    PubMed

    Yamada, J; Ohgomori, T; Jinno, S

    2015-02-01

    Recent studies have suggested that the perineuronal net (PNN), a specialised extracellular matrix structure, and parvalbumin (PV), an EF-hand calcium-binding protein, are involved in the regulation of plasticity of neural circuits. Here, we aimed to quantitatively estimate the relationship between the two plasticity regulators, PV and PNNs, in the hippocampus of young adult mice. Dual fluorescence staining for PV and Wisteria floribunda agglutinin (a broad PNN marker) showed that a substantial population of PV-expressing (PV(+) ) GABAergic neurons lacked PNNs. Optical disector analysis demonstrated that there were fewer PNN(+) neurons than PV(+) neurons. The ratio of PNN expression in PV(+) neurons was generally lower in the dendritic layers than in the principal cell layers, whereas the ratio of PV expression in PNN(+) neurons was effectively 100%. The mean PV fluorescence was significantly higher in PNN(+) /PV(+) neurons than in PNN(-) /PV(+) neurons. Cumulative frequencies for single-cell PV fluorescence indicated that intensely stained PV(+) neurons tend to be enwrapped by PNNs, whereas weakly stained PV(+) neurons are likely to lack PNNs. We digested the PNNs by a unilateral injection of chondroitinase ABC (chABC) into the dorsal CA1 region. Although the densities of PV(+) neurons remained unchanged, the PV fluorescence declined 7 days after chABC injection. Quantitative real-time polymerase chain reaction analysis demonstrated a reduction in PV mRNA expression following chABC injection. These findings indicate that the presence or absence of PNNs affects the relative PV expression in GABAergic neurons in the hippocampus.

  15. Residual radiation damage in the mouse foot after exposure to heavy particles

    SciTech Connect

    Carpenter, S.G.; Raju, M.R.

    1981-02-01

    Mice receiving a first treatment with graded doses of various heavy charged particles to one of their hind legs were re-exposed to a fixed dose of x rays eight months later to study the memory of residual damage from the first treatment. No significant memory of the first radiation exposure was observed for acute skin reaction. However, there is an indication of memory for foot deformity. The results do not seem to indicate any significant differences in memory after exposure to /sup 60/Co gamma rays compared with protons or heavy ions, if biological effectiveness of the doses is taken into consideration.

  16. Residual radiation damage in the mouse foot after exposure to heavy particles

    SciTech Connect

    Carpenter, S.G.; Raju, M.R.

    1981-02-01

    Mice receiving a first treatment with graded doses of various heavy charged particles (protons and heavy ions) to one of their hind legs were re-exposed to a fixed dose of x rays eight months later to study the memory of residual damage from the first treatment. No significant memory of the first radiation exposure was observed for acute skin reaction. However, there is an indication of memory for foot deformity. The results do not seem to indicate any significant differences in memory after exposure to 60Co gamma rays compared with protons or heavy ions, if biological effectiveness of the doses is taken into consideration.

  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. Conditional Knockout of Tumor Overexpressed Gene in Mouse Neurons Affects RNA Granule Assembly, Granule Translation, LTP and Short Term Habituation

    PubMed Central

    Barbarese, Elisa; Ifrim, Marius F.; Hsieh, Lawrence; Guo, Caiying; Tatavarty, Vedakumar; Maggipinto, Michael J.; Korza, George; Tutolo, Jessica W.; Giampetruzzi, Anthony; Le, Hien; Ma, Xin-Ming; Levine, Eric; Bishop, Brian; Kim, Duck O.; Kuwada, Shigeyuki; Carson, John H.

    2013-01-01

    In neurons, specific RNAs are assembled into granules, which are translated in dendrites, however the functional consequences of granule assembly are not known. Tumor overexpressed gene (TOG) is a granule-associated protein containing multiple binding sites for heterogeneous nuclear ribonucleoprotein (hnRNP) A2, another granule component that recognizes cis-acting sequences called hnRNP A2 response elements (A2REs) present in several granule RNAs. Translation in granules is sporadic, which is believed to reflect monosomal translation, with occasional bursts, which are believed to reflect polysomal translation. In this study, TOG expression was conditionally knocked out (TOG cKO) in mouse hippocampal neurons using cre/lox technology. In TOG cKO cultured neurons granule assembly and bursty translation of activity-regulated cytoskeletal associated (ARC) mRNA, an A2RE RNA, are disrupted. In TOG cKO brain slices synaptic sensitivity and long term potentiation (LTP) are reduced. TOG cKO mice exhibit hyperactivity, perseveration and impaired short term habituation. These results suggest that in hippocampal neurons TOG is required for granule assembly, granule translation and synaptic plasticity, and affects behavior. PMID:23936366

  19. 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.

  20. Targeted disruption of the mouse testis-enriched gene Znf230 does not affect spermatogenesis or fertility

    PubMed Central

    Liu, Yunqiang; Tao, Dachang; Lu, Yongjie; Yang, Yuan; Ma, Yongxin; Zhang, Sizhong

    2014-01-01

    The mouse testis-enriched Znf230 gene, which encodes a type of RING finger protein, is present primarily in the nuclei of spermatogonia, the acrosome and the tail of spermatozoa. To investigate the role of Znf230 in spermatogenesis, we generated Znf230-deficient mice by disrupting Znf230 exon-5 and exon-6 using homologous recombination. The homozygous Znf230-knockout (KO) mice did not exhibit Znf230 mRNA expression and Znf230 protein production. Znf230 KO mice exhibited no obvious impairment in body growth or fertility. Male Znf230 KO mice had integral reproductive systems and mature sperm that were regular in number and shape. The developmental stages of male germ cells of Znf230 KO mice were also normal. We further examined variations in the transcriptomes of testicular tissue between Znf230 KO and wild-type mice through microarray analysis. The results showed that the mRNA level of one unclassified transcript 4921513I08Rik was increased and that the mRNA levels of three other transcripts, i.e., 4930448A20Rik, 4931431B13Rik and potassium channel tetramerisation domain containing 14(Kctd14), were reduced more than two-fold in Znf230 KO mice compared with wild-type mice. Using our current examination techniques, these findings suggested that Znf230 deficiency in mice may not affect growth, fertility or spermatogenesis. PMID:25505846

  1. 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.

  2. 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.

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

    PubMed

    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

  4. 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

  5. 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

  6. A mouse model of non-motor symptoms in Parkinson's disease: focus on pharmacological interventions targeting affective dysfunctions

    PubMed Central

    Bonito-Oliva, Alessandra; Masini, Débora; Fisone, Gilberto

    2014-01-01

    Non-motor symptoms, including psychiatric disorders, are increasingly recognized as a major challenge in the treatment of Parkinson's disease (PD). These ailments, which often appear in the early stage of the disease, affect a large number of patients and are only partly resolved by conventional antiparkinsonian medications, such as L-DOPA. Here, we investigated non-motor symptoms of PD in a mouse model based on bilateral injection of the toxin 6-hydroxydopamine (6-OHDA) in the dorsal striatum. This model presented only subtle gait modifications, which did not affect horizontal motor activity in the open-field test. Bilateral 6-OHDA lesion also impaired olfactory discrimination, in line with the anosmia typically observed in early stage parkinsonism. The effect of 6-OHDA was then examined for mood-related dysfunctions. Lesioned mice showed increased immobility in the forced swim test and tail suspension test, two behavioral paradigms of depression. Moreover, the lesion exerted anxiogenic effects, as shown by reduced time spent in the open arms, in the elevated plus maze test, and by increased thigmotaxis in the open-field test. L-DOPA did not modify depressive- and anxiety-like behaviors, which were instead counteracted by the dopamine D2/D3 receptor agonist, pramipexole. Reboxetine, a noradrenaline reuptake inhibitor, was also able to revert the depressive and anxiogenic effects produced by the lesion with 6-OHDA. Interestingly, pre-treatment with desipramine prior to injection of 6-OHDA, which is commonly used to preserve noradrenaline neurons, did not modify the effect of the lesion on depressive- and anxiety-like behaviors. Thus, in the present model, mood-related conditions are independent of the reduction of noradrenaline caused by 6-OHDA. Based on these findings we propose that the anti-depressive and anxiolytic action of reboxetine is mediated by promoting dopamine transmission through blockade of dopamine uptake from residual noradrenergic terminals. PMID

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

    PubMed

    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

  8. 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

  9. 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

  10. Particles from wood smoke and road traffic differently affect the innate immune system of the lung.

    PubMed

    Samuelsen, Mari; Cecilie Nygaard, Unni; Løvik, Martinus

    2009-09-01

    The effect of particles from road traffic and wood smoke on the innate immune response in the lung was studied in a lung challenge model with the intracellular bacterium Listeria monocytogenes. Female Balb/cA mice were instilled intratracheally with wood smoke particles, particles from road traffic collected during winter (studded tires used; St+), and during autumn (no studded tires; St-), or diesel exhaust particles (DEP). Simultaneously with, and 1 or 7 days after particle instillation, 10(5) bacteria were inoculated intratracheally. Bacterial numbers in the lungs and spleen 1 day after Listeria challenge were determined, as an indicator of cellular activation. In separate experiments, bronchoalveolar lavage (BAL) fluid was collected 4 h and 24 h after particle instillation. All particles tested reduced the numbers of bacteria in the lung 24 h after bacterial inoculation. When particles were given simultaneously with Listeria, the reduction was greatest for DEP, followed by St+ and St-, and least for wood smoke particles. Particle effects were no longer apparent after 7 days. Neutrophil numbers in BAL fluid were increased for all particle exposed groups. St+ and St- induced the highest levels of IL-1beta, MIP-2, MCP-1, and TNF-alpha, followed by DEP, which induced no TNF-alpha. In contrast, wood smoke particles only increased lactate dehydrogenase (LDH) activity, indicating a cytotoxic effect of these particles. In conclusion, all particles tested activated the innate immune system as determined with Listeria. However, differences in kinetics of anti-Listeria activity and levels of proinflammatory mediators point to cellular activation by different mechanisms. PMID:19552530

  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. Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain.

    PubMed

    Smith, Craig M; Shen, Pei-Juan; Banerjee, Avantika; Bonaventure, Pascal; Ma, Sherie; Bathgate, Ross A D; Sutton, Steven W; Gundlach, Andrew L

    2010-10-01

    Relaxin-3 (RLN3) and its native receptor, relaxin family peptide 3 receptor (RXFP3), constitute a newly identified neuropeptide system enriched in mammalian brain. The distribution of RLN3/RXFP3 networks in rat brain and recent experimental studies suggest a role for this system in modulation of arousal, stress, metabolism, and cognition. In order to facilitate exploration of the biology of RLN3/RXFP3 in complementary murine models, this study mapped the neuroanatomical distribution of the RLN3/RXFP3 system in mouse brain. Adult, male wildtype and RLN3 knock-out (KO)/LacZ knock-in (KI) mice were used to map the central distribution of RLN3 gene expression and RLN3-like immunoreactivity (-LI). The distribution of RXFP3 mRNA and protein was determined using [(35)S]-oligonucleotide probes and a radiolabeled RXFP3-selective agonist ([(125)I]-R3/I5), respectively. High densities of neurons expressing RLN3 mRNA, RLN3-associated beta-galactosidase activity and RLN3-LI were detected in the nucleus incertus (or nucleus O), while smaller populations of positive neurons were observed in the pontine raphé, the periaqueductal gray and a region adjacent to the lateral substantia nigra. RLN3-LI was observed in nerve fibers/terminals in nucleus incertus and broadly throughout the pons, midbrain, hypothalamus, thalamus, septum, hippocampus, and neocortex, but was absent in RLN3 KO/LacZ KI mice. This RLN3 neural network overlapped the regional distribution of RXFP3 mRNA and [(125)I]-R3/I5 binding sites in wildtype and RLN3 KO/LacZ KI mice. These findings provide further evidence for the conserved nature of RLN3/RXFP3 systems in mammalian brain and the ability of RLN3/RXFP3 signaling to modulate "behavioral state" and an array of circuits involved in arousal, stress responses, affective state, and cognition.

  13. 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

  14. 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.

  15. 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.

  16. The weight of computer mouse affects the wrist motion and forearm muscle activity during fast operation speed task.

    PubMed

    Chen, Han-Ming; Lee, Chang-Sian; Cheng, Chih-Hsiu

    2012-06-01

    The frequent use of the computer mouse was reported to be associated with the development of the musculoskeletal disorders in the wrist, forearm, and shoulder regions. This study was to examine the effect of the mouse weights and operation speeds on the wrist motion and muscle activity. 25 subjects (20 males and 5 females) were instructed to repetitively point-and-click the mouse between two targets displaced in the monitor with five different weighted mice (weights around 70, 100, 130, 160, and 190 g) at the fast (50 repetition/min) and slow (25 repetition/min) operation speeds. Surface electromyographic activity of the extensor carpi radialis, extensor carpi ulnaris, extensor digitorum, and upper trapezius muscles were recorded, and the electrogoniometer was used to register the wrist motions. The results showed that the maximal ulnar deviation was not significantly different among the examined conditions. The wrist movement range and the forearm muscle activities showed a V-shape tendency with the lowest value in the mouse weight of 130 g. This tendency was diminished during the slow speed tasks. The results suggested that the proper mouse weight could benefit the users in terms of increasing the movement efficiency and decreasing the muscular costs.

  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. Onion peel tea ameliorates obesity and affects blood parameters in a mouse model of high-fat-diet-induced obesity.

    PubMed

    Matsunaga, Shogo; Azuma, Kazuo; Watanabe, Mayumi; Tsuka, Takeshi; Imagawa, Tomohiro; Osaki, Tomohiro; Okamoto, Yoshiharu

    2014-02-01

    The present study examined the effects of onion peel tea (OPT) in a mouse model of high-fat-diet-induced obesity. BALB/c mice were fed a high-fat diet for three weeks, followed by a normal diet with or without OPT for 28 days. OPT suppressed the increases in body weight and level of epididymal fat tissue; it also significantly reduced the serum concentrations of total cholesterol on day 14 and those of glucose and leptin on day 28. The results indicate that OPT has anti-obesity effects in an experimental mouse model of high-fat-diet-induced obesity. PMID:24396409

  19. 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.

  20. 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

  1. 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.

  2. The effect of local IL-4 delivery or CCL2 blockade on implant fixation and bone structural properties in a mouse model of wear particle induced osteolysis.

    PubMed

    Sato, Taishi; Pajarinen, Jukka; Behn, Anthony; Jiang, Xinyi; Lin, Tzu-Hua; Loi, Florence; Yao, Zhenyu; Egashira, Kensuke; Yang, Fan; Goodman, Stuart B

    2016-09-01

    Modulation of macrophage polarization and prevention of CCL2-induced macrophage chemotaxis are emerging strategies to reduce wear particle induced osteolysis and aseptic total joint replacement loosening. In this study, the effect of continuous IL-4 delivery or bioactive implant coating that constitutively releases a protein inhibitor of CCL2 signaling (7ND) on particle induced osteolysis were studied in the murine continuous femoral intramedullary particle infusion model. Polyethylene particles with or without IL-4 were infused into mouse distal femurs implanted with hollow titanium rods using subcutaneous infusion pumps. In another experimental group, particles were infused into the femur through a 7ND coated rod. After 4 weeks, fixation of the implant was assessed using a pullout test. The volume of trabecular bone and the geometry of the local cortical bone were assessed by µCT and the corresponding structural properties of the cortical bone determined by torsional testing. Continuous IL-4 delivery led to increased trabecular bone volume as well as enhanced local bone geometry and structural properties, while 7ND implant coating did not have effect on these parameters. The results suggest that local IL-4 treatment is a promising strategy to mitigate wear particle induced osteolysis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2255-2262, 2016.

  3. 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.

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

    PubMed

    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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. 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.

  8. 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...

  9. 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

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

    PubMed

    Moskovitz, Jackob; Du, Fang; Bowman, Connor F; Yan, Shirley S

    2016-03-15

    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.

  11. Diet calcium level but not calcium supplement particle size affects bone density and mechanical properties in ovariectomized rats.

    PubMed

    Shahnazari, Mohammad; Martin, Berdine R; Legette, Leecole L; Lachcik, Pamela J; Welch, Jo; Weaver, Connie M

    2009-07-01

    Calcium (Ca) supplements, especially Ca carbonate (CaCO3), are the main alternative sources of dietary Ca and an important part of a treatment regimen for osteoporosis, the most common metabolic bone disorder of aging and menopause. In a female ovariectomized (OVX) rat model for studying postmenopausal osteoporosis, we tested the hypothesis that a small compared with a large particle size of CaCO3 (13.0- vs. 18.5-mum geometric diameter) would result in increased Ca balance and subsequently bone mass and that this would be affected by dietary Ca level. We used 6-mo-old rats that were OVX either at 6 or 3 mo of age as models of early or stable menopausal status, respectively. The rats received semipurified diets that contained either 0.4 or 0.2% dietary Ca provided from CaCO3 of 2 particle sizes. A group of Sham-operated rats with intact ovaries served as control and were fed 0.4% dietary Ca from large particles. Estrogen deficiency as a result of ovariectomy had an adverse effect on bone density, mineral content, and bone mechanical properties (P < 0.001). Reducing dietary Ca from 0.4 to 0.2% resulted in significant adverse effects on bone density and mechanical properties (P < 0.001). The particle size of CaCO3 did not affect total Ca balance, bone dual energy X-ray absorptiometry and peripheral quantitative computed tomography indices, bone ash and Ca content, or the mechanical determinants of bone strength. We conclude that a decrease in particle size of CaCO3 to 70% of that typically found in Ca supplements does not provide a benefit to overall Ca metabolism or bone characteristics and that the amount of Ca consumed is of greater influence in enhancing Ca nutrition and skeletal strength.

  12. Gum tragacanth dispersions: Particle size and rheological properties affected by high-shear homogenization.

    PubMed

    Farzi, Mina; Yarmand, Mohammad Saeed; Safari, Mohammad; Emam-Djomeh, Zahra; Mohammadifar, Mohammad Amin

    2015-08-01

    The effect of high-shear homogenization on the rheological and particle size characteristics of three species of gum tragacanth (GT) was detected. Dispersions were subjected to 0-20 min treatment. Static light scattering techniques and rheological tests were used to study the effect of treatment. The results showed that the process caused a decrease in particle size parameters for all three species, but interestingly, the apparent viscosities increased. The highest increase of apparent viscosity was found for solutions containing Astragalus gossypinus, which possessed the highest insoluble fraction. The viscoelastic behaviors of dispersions were also significantly influenced by the process. Homogenization caused an increase in both G' and G″, in all three species. The alterations seem to be highly dependent on GT species and structure. The results could be of high importance in the industry, since the process will lead to textural modifications of food products containing GT.

  13. Do particle size and surface functionality affect uptake and depuration of gold nanoparticles by aquatic invertebrates?

    PubMed

    Park, Sujung; Woodhall, James; Ma, Guibin; Veinot, Jonathan G C; Boxall, Alistair B A

    2015-04-01

    Because of the widespread use of engineered nanoparticles (ENPs) in consumer and industrial products, it is inevitable that these materials will enter the environment. It is often stated that the uptake of ENPs into organisms in the environment is related to the particle size and surface functionality. To test this assumption, the present study investigated the uptake and depuration of gold nanoparticle (Au NPs) coated with either citrate (Au-citrate NPs), mercaptoundecanoic acid (Au-MUDA NPs), amino polyethylene glycol (PEG) thiol (Au-NH2 NPs), or PEG (Au-PEG NP) by the aquatic invertebrate Gammarus pulex. The studies were performed using a range of standard ecotoxicity media and natural waters, resulting in varying degrees of aggregation of the different NPs. Uptake of gold by G. pulex varied depending on the surface coatings, with Au-MUDA and Au-citrate NPs being taken up to a greater extent than Au-NH2 and Au-PEG NPs in all test media and natural waters. In all test media evaluated, higher amounts of amino and PEG-coated ENPs were eliminated compared with MUDA- and citrate-coated ENPs. No obvious relationships were seen between the aggregation state of the different Au NPs in treatment and uptake, suggesting that the widely accepted assumption that Au NP uptake is related to particle size does not hold for the range of aggregation states studied (67.1-178.8 nm). Positive correlations between particle number concentration in the media and uptake were observed, indicating that this factor might partly explain the differences in uptake of a particle from different media types.

  14. 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

  15. 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

  16. 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

  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. 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.

  19. How does particle shape affect the near jamming properties of granular materials? Pentagons vs. disks

    NASA Astrophysics Data System (ADS)

    Zhao, Yiqiu; Bares, Jonathan; Behringer, Bob

    Understanding the role of particle shape in system-scale properties is a fundamental challenge in granular physics. We investigated the difference between the response of systems made of pentagons vs. more traditional disks. We performed isotropic compression experiments on 2D photoelastic pentagons and disks near the jamming transition. These experiments show qualitative and quantitative differences in the macroscopic responses of the two systems, such as shifts in the packing fraction at jamming onset and differences in the contact number evolution. Some of these differences are due to a reduction of packing order and the appearance of side-side contacts for the pentatons. We also examined the stress relaxation and dynamical heterogeneity of pentagon particles by performing cyclic compression to allow the system explore phase diagram. We contrast disk and pentagon evolution using four-point-susceptibility and G2 techniques. Work supported by NSF-DMR1206351, DMS1248071, NASA NNX15AD38G, and the W.M. Keck Foundation.

  20. 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.

  1. The forkhead transcription factor Foxl2 is sumoylated in both human and mouse: sumoylation affects its stability, localization, and activity.

    PubMed

    Marongiu, Mara; Deiana, Manila; Meloni, Alessandra; Marcia, Loredana; Puddu, Alessandro; Cao, Antonio; Schlessinger, David; Crisponi, Laura

    2010-01-01

    The FOXL2 forkhead transcription factor is expressed in ovarian granulosa cells, and mutated FOXL2 causes the blepharophimosis, ptosis and epicanthus inversus syndrome (BPES) and predisposes to premature ovarian failure. Inactivation of Foxl2 in mice demonstrated its indispensability for female gonadal sex determination and ovary development and revealed its antagonism of Sox9, the effector of male testis development. To help to define the regulatory activities of FOXL2, we looked for interacting proteins. Based on yeast two-hybrid screening, we found that FOXL2 interacts with PIAS1 and UBC9, both parts of the sumoylation machinery. We showed that human FOXL2 is sumoylated in transfected cell lines, and that endogenous mouse Foxl2 is comparably sumoylated. This modification changes its cellular localization, stability and transcriptional activity. It is intriguing that similar sumoylation and regulatory consequences have also been reported for SOX9, the male counterpart of FOXL2 in somatic gonadal tissues. PMID:20209145

  2. 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.

  3. 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. PMID:25922214

  4. 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.

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

    PubMed

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

    2000-05-01

    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. Environment-, drug- and stress-induced alterations in body temperature affect the neurotoxicity of substituted amphetamines in the C57BL/6J mouse.

    PubMed

    Miller, D B; O'Callaghan, J P

    1994-08-01

    In the companion paper we demonstrated that d-methamphetamine (d-METH), d-methylenedioxyamphetamine (d-MDA) and d-methylenedioxymethamephetamine (d-MDMA), but not d-fenfluramine (d-FEN), appear to damage dopaminergic projections to the striatum of the mouse. An elevation in core temperature also was associated with exposure to d-METH, d-MDA and d-MDMA, whereas exposure to d-FEN lowered core temperature. Given these findings, we examined the effects of temperature on substituted amphetamine (AMP)-induced neurotoxicity in the C57BL/6J mouse. Levels of striatal dopamine (DA) and glial fibrillary acidic protein (GFAP) were taken as indicators of neurotoxicity. Alterations in ambient temperature, pretreatment with drugs reported to cause hypothermia in the mouse and hypothermia induced by restraint stress were used to affect AMP-induced neurotoxicity. Mice received d-METH (10 mg/kg), d-MDA (20 mg/kg) or d-MDMA (20 mg/kg) every 2 hr for a total of four s.c. injections. All three AMPs increased core temperature and caused large (> 75%) decreases in striatal dopamine and large (> 300%) increases in striatal glial fibrillary acidic protein 72 hr after the last injection. Lowering ambient temperature from 22 degrees C to 15 degrees C blocked (d-MDA and d-MDMA) or severely attenuated (d-METH) these effects. Pretreatment with MK-801 lowered core temperature and blocked AMP-induced neurotoxicity; elevation of ambient temperature during this regimen elevated core temperature and markedly attenuated the neuroprotective effects of MK-801. Pretreatment with MK-801 also lowered core temperature in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice but did not block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. 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.

  9. 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.

  10. Glucocorticoids specifically enhance L-type calcium current amplitude and affect calcium channel subunit expression in the mouse hippocampus.

    PubMed

    Chameau, Pascal; Qin, Yongjun; Spijker, Sabine; Smit, August Benjamin; Smit, Guus; Joëls, Marian

    2007-01-01

    Previous studies have shown that corticosterone enhances whole cell calcium currents in CA1 pyramidal neurons, through a pathway involving binding of glucocorticoid receptor homodimers to the DNA. We examined whether glucocorticoids show selectivity for L- over N-type of calcium currents. Moreover, we addressed the putative gene targets that eventually lead to the enhanced calcium currents. Electrophysiological recordings were performed in nucleated patches that allow excellent voltage control. Calcium currents in these patches almost exclusively involve N- and L-type channels. We found that L- but not N-type calcium currents were largely enhanced after treatment with a high dose of corticosterone sufficient to activate glucocorticoid receptors. Voltage dependency and kinetic properties of the currents were unaffected by the hormone. Nonstationary noise analysis suggests that the increased current is not caused by a larger unitary conductance, but rather to a doubling of the number of functional channels. Quantitative real-time PCR revealed that transcripts of the Ca(v)1 subunits encoding for the N- or L-type calcium channels are not upregulated in the mouse CA1 area; instead, a strong, direct, and consistent upregulation of the beta4 subunit was observed. This indicates that the corticosteroid-induced increase in number of L-type calcium channels is not caused by a simple transcriptional regulation of the pore-forming subunit of the channels.

  11. Failure of human and mouse leptin to affect insulin, glucagon and somatostatin secretion by the perfused rat pancreas at physiological glucose concentration.

    PubMed

    Leclercq-Meyer, V; Malaisse, W J

    1998-06-25

    In isolated perfused pancreas from normal rats, a rise in d-glucose concentration from 3.3 to 8.3 mM provoked a rapid phasic stimulation of both insulin and somatostatin secretion and rapid fall in glucagon output, these changes being reversed when the concentration of the hexose was brought back to its initial low level. In the presence of 8.3 mM d-glucose, the administration of either human or mouse leptin (10 nM in both cases) for 15 min failed to affect significantly the perfusion pressure and release of the three hormones. It is concluded that leptin does not exert any major immediate and direct effect upon pancreatic insulin, glucagon and somatostatin secretion, at least at the physiological concentration of d-glucose normally found in the plasma of fed rats. PMID:9723892

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

    PubMed

    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.

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

    SciTech Connect

    Howell, R.W.; Goddu, S.M.; Narra, V.R.

    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 {sup 148}Gd 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 {sup 210}Po and {sup 212}Pb 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{sub {alpha}} = 9.14 - 0.510 E{sub {alpha}}, where 3 < E{sub {alpha}} < 9 MeV. The validity of this empirical relationship is tested by determining the RBE of the prolific {alpha}-particle emitter {sup 223}Ra (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{sub {alpha}} relationship to predict the biological effects of {alpha}-particle emitters in vivo. 42 refs., 5 figs., 1 tab.

  14. 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

  15. Particle size of hydroxyapatite granules calcified from red algae affects the osteogenic potential of human mesenchymal stem cells in vitro.

    PubMed

    Weissenboeck, Martina; Stein, Elisabeth; Undt, Gerhard; Ewers, Rolf; Lauer, Gunter; Turhani, Dritan

    2006-01-01

    Hydroxyapatite (HA) microparticles as a carrier in an injectable tissue-engineered bone filler are considered promising candidates for the treatment of small bone defects in the craniomaxillofacial region. HA granules calcified from red algae, varying in size, were evaluated in vitro for their suitability to be used as a carrier for human mesenchymal stem cells (hMSCs). Three groups of granules were produced in grain sizes of 10-100, 200-500 and 600-1,000 mum. After seeding and culturing hMSCs under osteogenic differentiation conditions onto HA particles for 3, 6 and 9 days, cellular proliferation (tetrazolium salt, XTT), alkaline phosphatase (ALP)-specific activity and total protein synthesis were investigated. The osteoblastic phenotype of the cells was evaluated by assaying the bone-specific genes osteocalcin, osteopontin and collagen type I. XTT assay revealed significantly higher (p < 0.01) proliferation of cells grown on the smallest grain size after 9 days of culture. Regarding ALP-specific activity, significantly higher levels of activity were detected in cells grown on the smallest grain size. Different grain sizes had no significant effects on the secretion of osteocalcin and osteopontin. Collagen type I production was significantly higher (p < 0.05) in cells grown on the biggest grain size in comparison with the two other grain sizes. These results show that the particle size of HA microparticles affects the osteogenic potential of cultured hMSCs and lead to the conclusion that particle size has differential effects on ALP-specific activity and collagen type I production.

  16. Stimulation of sugar uptake and thymidine incorporation in mouse 3T3 cells by calcium phosphate and other extracellular particles.

    PubMed Central

    Barnes, D W; Colowick, S P

    1977-01-01

    Evidence is presented that the marked stimulation of sugar uptake and thymidine incorporation by addition of extra Ca2+ to stationary phase mouse 3T3 cells in culture is phosphate dependent and due to the action of the calcium phosphate precipitate formed in the medium. The cells are similarly stimulated by a variety of particulate materials, including calcium pyrophosphate, barium sulfate, kaolin, and polystrene beads. The precipitate effects on sugar uptake are of the same magnitude as those seen with certain hormones (insulin, epidermal growth factor) or with fresh 10% calf serum. The effect of barium sulfate on thymidine incorporation is also of the same magnitude as seen with these hormones, but much less than half that found with fresh calf serum. The stimulation by barium sulfate or hormones of thymidine incorporation is not phosphate dependent. PMID:202958

  17. Stimulation of sugar uptake and thymidine incorporation in mouse 3T3 cells by calcium phosphate and other extracellular particles.

    PubMed

    Barnes, D W; Colowick, S P

    1977-12-01

    Evidence is presented that the marked stimulation of sugar uptake and thymidine incorporation by addition of extra Ca2+ to stationary phase mouse 3T3 cells in culture is phosphate dependent and due to the action of the calcium phosphate precipitate formed in the medium. The cells are similarly stimulated by a variety of particulate materials, including calcium pyrophosphate, barium sulfate, kaolin, and polystrene beads. The precipitate effects on sugar uptake are of the same magnitude as those seen with certain hormones (insulin, epidermal growth factor) or with fresh 10% calf serum. The effect of barium sulfate on thymidine incorporation is also of the same magnitude as seen with these hormones, but much less than half that found with fresh calf serum. The stimulation by barium sulfate or hormones of thymidine incorporation is not phosphate dependent. PMID:202958

  18. A preliminary evaluation of immune stimulation following exposure to metal particles and ions using the mouse popliteal lymph node assay.

    PubMed

    Tvermoes, Brooke E; Unice, Kenneth M; Winans, Bethany; Kovochich, Michael; Christian, Whitney V; Donovan, Ellen; Fung, Ernest S; Finley, Brent L; Kimber, Ian; Paustenbach, Dennis J

    2016-10-01

    The objective of this preliminary study was to evaluate the threshold for immune stimulation in mice following local exposure to metal particles and ions representative of normal-functioning cobalt-chromium (CoCr) metal-on-metal (MoM) hip implants. The popliteal lymph node assay (PLNA) was used in this study to assess immune responses in BALB/c mice following treatment with chromium-oxide (Cr2O3) particles, metal salts (CoCl2, CrCl3 and NiCl2), or Cr2O3 particles together with metal salts using single-dose exposures representing approximately 10days (0.000114mg), 19years (0.0800mg), and 40years (0.171mg) of normal implant wear. The immune response elicited following treatment with Cr2O3 particles together with metal salts was also assessed at four additional doses equivalent to approximately 1.5months (0.0005mg), 0.6years (0.0025mg), 2.3years (0.01mg), and 9.3years (0.04mg) of normal implant wear. Mice were injected subcutaneously (50μL) into the right hind foot with the test article, or with the relevant vehicle control. The proliferative response of the draining lymph node cells (LNC) was measured four days after treatment, and stimulation indices (SI) were derived relative to vehicle controls. The PLNA was negative (SI<3) for all Cr2O3 particle doses, and was also negative at the lowest dose of the metal salt mixture, and the lowest four doses of the Cr2O3 particles with metal salt mixture. The PLNA was positive (SI>3) at the highest two doses of the metal salt mixture and the highest three doses of the Cr2O3 particles with the metal salt mixture. The provisional NOAEL and LOAEL values identified in this study for immune activation corresponds to Co and Cr concentrations in the synovial fluid approximately 500 and 2000 times higher than that reported for normal-functioning MoM hip implants, respectively. Overall, these results indicate that normal wear conditions are unlikely to result in immune stimulation in individuals not previously sensitized to metals.

  19. 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.

  20. The incidence of Streptococcus pneumoniae otitis media is affected by the polymicrobial environment particularly Moraxella catarrhalis in a mouse nasal colonisation model.

    PubMed

    Krishnamurthy, Ajay; McGrath, John; Cripps, Allan W; Kyd, Jennelle M

    2009-04-01

    Otitis media (OM) is a highly prevalent paediatric disease with both bacterial and viral triggers of infection. This study has investigated how combinations of bacteria associated with nasal colonisation and the occurrence and absence of viral infection (Sendai virus) induce OM in a mouse nasal colonisation model. The respiratory virus significantly contributed to bacterial OM for all bacterial combinations (p<0.001). Streptococcus pneumoniae consistently dominated as the causative bacterium of OM and when co-infected with S. pneumoniae, Moraxella catarrhalis more significantly affected pneumococcal OM than did non-typeable Haemophilus influenzae (p<0.001) by increasing the incidence rate, infection bacterial load and duration of infection. Nitric oxide levels in the middle ear, an indicator of inflammation, peaked at day 3 in single bacterium groups, but at day 1 in mixed bacterial groups and was produced in all bacteria inoculated groups even in the absence of viable bacterial recovery. Phagocytic cells were recruited rapidly to the ear following nasal inoculation but over time their numbers did not correlate with persistence of bacterial infection. The study has shown that the composition of bacteria in the nasal cavity and respiratory viral infection significantly affected the OM incidence rate, duration of infection and bacterial load (severity).

  1. Radiation-induced mouse chimeras: a cellular analysis of the major lymphoid compartments, factors affecting lethal graft versus host disease and host-tumor interactions

    SciTech Connect

    Almaraz, R.

    1981-01-01

    The major lymphoid compartments of allogeneic bone marrow chimeras were evaluated for the extent of cell chimerism and distribution of Thy 1 and la bearing cells. These chimeras contained lymphoid cell primarily of donor origin. The bone marrow compartment was a mixture of host and donor origin cells. The distribution of Thy 1 and la bearing cells was similar as in normal mice. The effect of adult thymectomy alone or followed by whole-body irradiation and bone marrow reconstitution on the distribution of the Thy 1 positive cells was also investigated. Thymectomy with or without WBI and bone marrow reconstitution significantly lowered the number of Thy 1 bearing cells in the blood and spleen. The number of la bearing cells did not appear to be affected by thymectomy. The role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation induced fully allogeneic mouse chimeras was studied. Mice reconstituted with allogeneic bone marrow from bled donors had a statistically lower incidence of GVHD than those reconstituted with bone marrow from unbled donors. Addition of mature peripheral lymphocytes from blood to the reconstituting bone marrow cells from bled donors reduplicated the high incidence of lethal GVHD. It was demonstrated that the bone marrow of mice not exsanguinated prior to harvesting of bone marrow contained significant numbers of peripheral contaminating cells in the harvested bone marrow. The role of suppressor cell elimination in resisting tumor growth was investigated using radiation induced mouse chimeras. Local effects of irradiation alone at the site of tumor inoculation could account for this lack of growth.

  2. Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts.

    PubMed

    Beck, Michaël; Moreels, Marjan; Quintens, Roel; Abou-El-Ardat, Khalil; El-Saghire, Hussein; Tabury, Kevin; Michaux, Arlette; Janssen, Ann; Neefs, Mieke; Van Oostveldt, Patrick; De Vos, Winnok H; Baatout, Sarah

    2014-08-01

    Microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist to simulate space flight experiments. In the present study, an experimental model was utilized to monitor gene expression changes in fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation (IR), comprising a mixture of high‑linear energy transfer (LET) neutrons and low-LET gamma-rays, and/or simulated microgravity using the random positioning machine (RPM), after which microarrays were performed. The data were analyzed both by gene set enrichment analysis (GSEA) and single gene analysis (SGA). Simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes. Three of these genes are targets of the nuclear factor‑erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell response to simulated microgravity. In addition, simulated gravity decreased the expression of genes involved in cytoskeleton remodeling, which may have been caused by the downregulation of the serum response factor (SRF), possibly through the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the downregulation of genes involved in cytoskeleton remodeling, as well as in cell cycle regulation and DNA damage response pathways. Many of the genes or gene sets that were altered in the individual treatments (RPM or IR) were not altered in the combined treatment (RPM and IR), indicating a complex interaction between RPM and IR.

  3. 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

  4. 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.

  5. The lonely mouse - single housing affects serotonergic signaling integrity measured by 8-OH-DPAT-induced hypothermia in male mice.

    PubMed

    Kalliokoski, Otto; Teilmann, A Charlotte; Jacobsen, Kirsten R; Abelson, Klas S P; Hau, Jann

    2014-01-01

    Male BALB/c mice single-housed for a period of three weeks were found to respond with a more marked hypothermia to a challenge with a selective serotonergic agonist (8-OH-DPAT) than their group-housed counterparts. This effect of single housing was verified by screening a genetically heterogeneous population of male mice on a C57BL/6 background from a breeding colony. Enhanced activity of the implicated receptor (5-HT1A) leading to an amplified hypothermic effect is strongly associated with depressive states. We therefore suggest that the 8-OH-DPAT challenge can be used to demonstrate a negative emotional state brought on by e.g. long-term single housing in male laboratory mice. The study emphasizes the importance of social housing, and demonstrates that male mice deprived of social contact respond with altered serotonergic signaling activity. Male mice not only choose social contact when given the option, as has previously been shown, but will also, when it is deprived, be negatively affected by its absence. We propose that the 8-OH-DPAT challenge constitutes a simple, but powerful, tool capable of manifesting the effect of social deprivation in laboratory mice. It potentially allows not only for an unbiased, biochemical evaluation of psychological stressors, but may also allow for determining whether the effect of these can be counteracted.

  6. 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.

  7. "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.

  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. Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts.

    PubMed

    Beck, Michaël; Moreels, Marjan; Quintens, Roel; Abou-El-Ardat, Khalil; El-Saghire, Hussein; Tabury, Kevin; Michaux, Arlette; Janssen, Ann; Neefs, Mieke; Van Oostveldt, Patrick; De Vos, Winnok H; Baatout, Sarah

    2014-08-01

    Microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist to simulate space flight experiments. In the present study, an experimental model was utilized to monitor gene expression changes in fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation (IR), comprising a mixture of high‑linear energy transfer (LET) neutrons and low-LET gamma-rays, and/or simulated microgravity using the random positioning machine (RPM), after which microarrays were performed. The data were analyzed both by gene set enrichment analysis (GSEA) and single gene analysis (SGA). Simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes. Three of these genes are targets of the nuclear factor‑erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell response to simulated microgravity. In addition, simulated gravity decreased the expression of genes involved in cytoskeleton remodeling, which may have been caused by the downregulation of the serum response factor (SRF), possibly through the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the downregulation of genes involved in cytoskeleton remodeling, as well as in cell cycle regulation and DNA damage response pathways. Many of the genes or gene sets that were altered in the individual treatments (RPM or IR) were not altered in the combined treatment (RPM and IR), indicating a complex interaction between RPM and IR. PMID:24859186

  10. Despite strong behavioral disruption, Delta9-tetrahydrocannabinol does not affect cell proliferation in the adult mouse dentate gyrus.

    PubMed

    Kochman, Linda J; dos Santos, Angela Amancio; Fornal, Casimir A; Jacobs, Barry L

    2006-10-01

    Marijuana is a widely abused illicit drug known to cause significant cognitive impairments. Marijuana has been hypothesized to target neurons in the hippocampus because of the abundance of cannabinoid receptors present in this structure. While there is no clear evidence of neuropathology in vivo, suppression of brain mitogenesis, and ultimately neurogenesis, may provide a sensitive index of marijuana's more subtle effects on neural mechanisms subserving cognitive functions. We examined the effects of different doses and treatment regimens of Delta(9)-tetrahydrocannabinol (THC), the main active ingredient in marijuana, on cell proliferation in the dentate gyrus of adult male mice. Following drug treatment, the thymidine analog 5-bromo-2'-deoxyuridine (BrdU; 200 mg/kg, i.p.) was administered two hours prior to sacrifice to assess cell proliferation, the first step in neurogenesis. Administration of THC produced dose-dependent catalepsy and suppression of motor activity. The number of BrdU-labeled cells was not significantly changed from vehicle control levels following either acute (1, 3, 10, 30 mg/kg, i.p.), sequential (two injections of 10 or 30 mg/kg, i.p., separated by 5 h), or chronic escalating (20 to 80 mg/kg, p.o.; for 3 weeks) drug administration. Furthermore, acute administration of the potent synthetic cannabinoid receptor agonist R-(+)-WIN 55,212-2 (WIN; 5 mg/kg, i.p.) also had no significant effect on cell proliferation. These findings provide no evidence for an effect of THC on hippocampal cell proliferation, even at doses producing gross behavioral intoxication. Whether marijuana or THC affects neurogenesis remains to be explored.

  11. 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.

  12. 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.

  13. Herpes simplex type 1 defective interfering particles do not affect the antiviral activity of acyclovir, foscarnet and adenine arabinoside.

    PubMed

    Harmenberg, J G; Svensson, L T

    1988-03-01

    The concentration of defective interfering particles (DI-particles) of herpes simplex type 1 virus was analysed by electron microscopy and plaque titration. Fifteen consecutive passages of undiluted virus in green monkey kidney cells were followed. No relationship was found between the concentration of DI-particles and the activity of antiviral substances such as acyclovir, foscarnet and adenine arabinoside.

  14. 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.

  15. 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

    2015-12-01

    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.

  16. 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. PMID:27338842

  17. 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. PMID:26305411

  18. Chronic alcohol exposure affects pancreatic acinar mitochondrial thiamin pyrophosphate uptake: studies with mouse 266-6 cell line and primary cells.

    PubMed

    Srinivasan, Padmanabhan; Nabokina, Svetlana; Said, Hamid M

    2015-11-01

    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).

  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. Particle geometry affects differentially substrate composition and enzyme profiles by Pleurotus ostreatus growing on sugar cane bagasse.

    PubMed

    Membrillo, Isabel; Sánchez, Carmen; Meneses, Marcos; Favela, Ernesto; Loera, Octavio

    2011-01-01

    The growth of Pleurotus ostreatus was analyzed on three particle sizes of sugar cane bagasse: 0.92 mm and 1.68 mm in diameter, in addition to heterogeneous fibers (average 2.9 mm in diameter). Specific growth rate on heterogeneous particles was lower (μ=0.043 h(-1)), although soluble protein production was maximal (809 μg/g dry wt). Higher μ values were reached on the other two particles sizes (0.049-0.05 h(-1)) with less soluble protein (500 μg/g dry wt). Xylanases and laccases were favored in heterogeneous particles; while the highest selectivity for xylanases over cellulases was observed in 1.68 mm particles, corresponding with the maximal hemicellulose breakdown. Lignin and cellulose were preferentially degraded in smallest particles. This study shows that the geometrical ratio, shape and size of sugar cane bagasse fibers strongly influence packing density for SSF substrate, with an impact in the production of extracellular enzymes, growth rates and composition changes in substrate.

  1. 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

  2. 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.

  3. How do changes in bulk soil organic carbon content affect carbon concentrations in individual soil particle fractions?

    NASA Astrophysics Data System (ADS)

    Yang, X. M.; Drury, C. F.; Reynolds, W. D.; Yang, J. Y.

    2016-06-01

    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.

  4. 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

    2016-01-01

    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.

  5. 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

  6. 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

    2016-01-01

    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

  7. 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.

  8. 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. PMID:24521067

  9. 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.

  10. 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

  11. Mouse ECG findings in aging, with conduction system affecting drugs and in cardiac pathologies: Development and validation of ECG analysis algorithm in mice.

    PubMed

    Merentie, Mari; Lipponen, Jukka A; Hedman, Marja; Hedman, Antti; Hartikainen, Juha; Huusko, Jenni; Lottonen-Raikaslehto, Line; Parviainen, Viktor; Laidinen, Svetlana; Karjalainen, Pasi A; Ylä-Herttuala, Seppo

    2015-12-01

    Mouse models are extremely important in studying cardiac pathologies and related electrophysiology, but very few mouse ECG analysis programs are readily available. Therefore, a mouse ECG analysis algorithm was developed and validated. Surface ECG (lead II) was acquired during transthoracic echocardiography from C57Bl/6J mice under isoflurane anesthesia. The effect of aging was studied in young (2-3 months), middle-aged (14 months) and old (20-24 months) mice. The ECG changes associated with pharmacological interventions and common cardiac pathologies, that is, acute myocardial infarction (AMI) and progressive left ventricular hypertrophy (LVH), were studied. The ECG raw data were analyzed with an in-house ECG analysis program, modified specially for mouse ECG. Aging led to increases in P-wave duration, atrioventricular conduction time (PQ interval), and intraventricular conduction time (QRS complex width), while the R-wave amplitude decreased. In addition, the prevalence of arrhythmias increased during aging. Anticholinergic atropine shortened PQ time, and beta blocker metoprolol and calcium-channel blocker verapamil increased PQ interval and decreased heart rate. The ECG changes after AMI included early JT elevation, development of Q waves, decreased R-wave amplitude, and later changes in JT/T segment. In progressive LVH model, QRS complex width was increased at 2 and especially 4 weeks timepoint, and also repolarization abnormalities were seen. Aging, drugs, AMI, and LVH led to similar ECG changes in mice as seen in humans, which could be reliably detected with this new algorithm. The developed method will be very useful for studies on cardiovascular diseases in mice.

  12. 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

  13. Kidney adysplasia and variable hydronephrosis, a new mutation affecting the odd-skipped related 1 gene in the mouse, causes variable defects in kidney development and hydronephrosis

    PubMed Central

    Davisson, Muriel T.; Cook, Susan A.; Akeson, Ellen C.; Liu, Don; Heffner, Caleb; Gudis, Polyxeni; Fairfield, Heather

    2015-01-01

    Many genes, including odd-skipped related 1 (Osr1), are involved in regulation of mammalian kidney development. We describe here a new recessive mutation (kidney adysplasia and variable hydronephrosis, kavh) in the mouse that leads to downregulation of Osr1 transcript, causing several kidney defects: agenesis, hypoplasia, and hydronephrosis with variable age of onset. The mutation is closely associated with a reciprocal translocation, T(12;17)4Rk, whose Chromosome 12 breakpoint is upstream from Osr1. The kavh/kavh mutant provides a model to study kidney development and test therapies for hydronephrosis. PMID:25834070

  14. A nonsense mutation in mouse Tardbp affects TDP43 alternative splicing activity and causes limb-clasping and body tone defects.

    PubMed

    Ricketts, Thomas; McGoldrick, Philip; 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 Tardbp(Q101X) mice to investigate this mutation in perturbing TDP43 biology at endogenous expression levels. We found the Tardbp(Q101X) 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 SOD1(G93Adl) 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 Tardbp(Q101X) mutant mice are a useful tool for the dissection of TDP43 protein regulation, effects on splicing, embryonic development and neuromuscular phenotypes

  15. Kidney adysplasia and variable hydronephrosis, a new mutation affecting the odd-skipped related 1 gene in the mouse, causes variable defects in kidney development and hydronephrosis.

    PubMed

    Davisson, Muriel T; Cook, Susan A; Akeson, Ellen C; Liu, Don; Heffner, Caleb; Gudis, Polyxeni; Fairfield, Heather; Murray, Stephen A

    2015-06-15

    Many genes, including odd-skipped related 1 (Osr1), are involved in regulation of mammalian kidney development. We describe here a new recessive mutation (kidney adysplasia and variable hydronephrosis, kavh) in the mouse that leads to downregulation of Osr1 transcript, causing several kidney defects: agenesis, hypoplasia, and hydronephrosis with variable age of onset. The mutation is closely associated with a reciprocal translocation, T(12;17)4Rk, whose Chromosome 12 breakpoint is upstream from Osr1. The kavh/kavh mutant provides a model to study kidney development and test therapies for hydronephrosis.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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...

  3. 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

  4. Long-term, six-dimensional live-cell imaging for the mouse preimplantation embryo that does not affect full-term development.

    PubMed

    Yamagata, Kazuo; Suetsugu, Rinako; Wakayama, Teruhiko

    2009-06-01

    Mammalian preimplantation embryonic development is achieved by tightly coordinated regulation of a great variety of temporal and spatial changes. Therefore, it would be valuable to analyze these events three-dimensionally and dynamically. We have previously developed a live-cell imaging method based on the expression of fluorescent proteins, using mRNA injection and time-lapse florescence microscopy. However, with conventional fluorescent microscopy, three-dimensional images could not be obtained due to the thickness of the embryos and the optical problem in which ;out-of focus blur' cannot be eliminated. Moreover, as the repeated exposure of intense excitation light to the cell yields phototoxicity, long-term observation was detrimental to embryonic development. Here, we improved our imaging system to enable six-dimensional live-cell imaging of mouse preimplantation embryos (x, y and z axes, time-lapse, multicolor and multisample). Importantly, by improving the imaging devices and optimizing the conditions for imaging, such as intensity of excitation and time intervals for image acquisition, the procedure itself was not detrimental to full-term development, although it is a prolonged imaging process. For example, live pups were obtained from embryos to which two different wavelengths of excitation (488 and 561 nm) were applied at 7.5-min intervals for about 70 h, and 51 images were acquired in the z axis at each time point; thus, a total of 56,814 fluorescent images were taken. All the pups were healthy, reproductively normal and not transgenic. Thus, this live-cell imaging technology is safe for full-term mouse development. This offers a novel approach for developmental and reproductive research in that it enables both retrospective and prospective analyses of development. It might also be applicable to assessment of embryo quality in fields such as human reproductive technology and production animal research.

  5. Immune Status, Strain Background, and Anatomic Site of Inoculation Affect Mouse Papillomavirus (MmuPV1) Induction of Exophytic Papillomas or Endophytic Trichoblastomas

    PubMed Central

    Sundberg, John P.; Proctor, Mary; Ingle, Arvind; Silva, Kathleen A.; Dadras, Soheil S.; Jenson, A. Bennett; Ghim, Shin-je

    2014-01-01

    Papillomaviruses (PVs) induce papillomas, premalignant lesions, and carcinomas in a wide variety of species. PVs are classified first based on their host and tissue tropism and then their genomic diversities. A laboratory mouse papillomavirus, MmuPV1 (formerly MusPV), was horizontally transmitted within an inbred colony of NMRI-Foxn1nu/Foxn1nu (nude; T cell deficient) mice of an unknown period of time. A ground-up, filtered papilloma inoculum was not capable of infecting C57BL/6J wild-type mice; however, immunocompetent, alopecic, S/RV/Cri-ba/ba (bare) mice developed small papillomas at injection sites that regressed. NMRI-Foxn1nu and B6.Cg-Foxn1nu, but not NU/J-Foxn1nu, mice were susceptible to MmuPV1 infection. B6 congenic strains, but not other congenic strains carrying the same allelic mutations, lacking B- and T-cells, but not B-cells alone, were susceptible to infection, indicating that mouse strain and T-cell deficiency are critical to tumor formation. Lesions initially observed were exophytic papillomas around the muzzle, exophytic papillomas on the tail, and condylomas of the vaginal lining which could be induced by separate scarification or simultaneous scarification of MmuPV1 at all four sites. On the dorsal skin, locally invasive, poorly differentiated tumors developed with features similar to human trichoblastomas. Transcriptome analysis revealed significant differences between the normal skin in these anatomic sites and in papillomas versus trichoblastomas. The primarily dysregulated genes involved molecular pathways associated with cancer, cellular development, cellular growth and proliferation, cell morphology, and connective tissue development and function. Although trichoepitheliomas are benign, aggressive tumors, few of the genes commonly associated with basal cell carcinoma or squamous cells carcinoma were highly dysregulated. PMID:25474466

  6. Investigations of the relationship between use of in vitro cell culture-quantitative PCR and a mouse-based bioassay for evaluating critical factors affecting the disinfection performance of pulsed UV light for treating Cryptosporidium parvum oocysts in saline.

    PubMed

    Garvey, Mary; Farrell, Hugh; Cormican, Martin; Rowan, Neil

    2010-03-01

    Cryptosporidium parvum is an enteric coccidian parasite that is recognised as a frequent cause of water-borne disease in humans. We report for the first time on use of the in vitro HCT-8 cell culture-quantitative PCR (qPCR) assay and the in vivo SCID-mouse bioassay for evaluating critical factors that reduce or eliminate infectivity of C. parvum after irradiating oocysts in saline solution under varying operational conditions with pulsed UV light. Infections post UV treatments were detected by immunofluorescence (IF) microscopy and by quantitative PCR in cell culture, and by IF staining of faeces and by hematoxylin and eosin staining of intestinal villi in mice. There was a good agreement between using cell culture-qPCR and the mouse assay for determining reduction or elimination of C. parvum infectivity as a consequence of varying UV operating conditions. Reduction in infectivity depended on the intensity of lamp discharge energy applied, amount of pulsing and population size of oocysts (P < or = 0.05). Conventional radiometer was unable to measure fluence or UV dose in saline samples due to the ultra-short non-continuous nature of the high-energy light pulses. Incorporation of humic acid at a concentration above that found in surface water (i.e., < or =10 ppm) did not significantly affect PUV disinfection capability irrespective of parameters tested (P < or = 0.05). These observations show that use of this HCT-8 cell culture assay is equivalent to using the 'gold standard' mouse-based infectivity assay for determining disinfection performances of PUV for treating C. parvum in saline solution. PMID:20096310

  7. 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...

  8. 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 Central

    Riabov, V.; Tretyakova, I.; Alexander, R. B.; Pushko, P.; Klyushnenkova, E. N.

    2015-01-01

    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 PSA65–73. In the blood of vaccinated mice, 18.4±4.1% of CD8+ T cells were PSA-specific as determined by the staining with H-2Db/PSA65–73 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. PMID:26319744

  9. 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.

  10. 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. PMID:25839898

  11. High-resolution genetic localization of a modifying locus affecting disease severity in the juvenile cystic kidneys (jck) mouse model of polycystic kidney disease

    PubMed Central

    Beier, David R.

    2016-01-01

    We have previously demonstrated that a locus on proximal Chr 4 modifies disease severity in the juvenile cystic kidney (jck) mouse, a model of polycystic kidney disease (PKD) that carries a mutation of the Nek8 serine-threonine kinase. In this study we used QTL analysis of independently constructed B6.D2 congenic lines to confirm this and showed that this locus has a highly significant effect. We constructed sub-congenic lines to more specifically localize the modifier and have determined it resides in a 3.2 Mb interval containing 28 genes. These include Invs and Anks6, which are both excellent candidates for the modifier as mutations in these genes result in PKD and both genes are known to genetically and physically interact with Nek8. However, examination of strain-specific DNA sequence and kidney expression did not reveal clear differences that might implicate either gene as a modifier of PKD severity. The fact that our high-resolution analysis did not yield an unambiguous result highlights the challenge of establishing the causality of strain-specific variants as genetic modifiers, and suggests that alternative strategies be considered. PMID:27114383

  12. Early-life lead exposure affects the activity of TNF-alpha and expression of SNARE complex in hippocampus of mouse pups.

    PubMed

    Li, N; Yu, Z L; Wang, L; Zheng, Y T; Jia, J X; Wang, Q; Zhu, M J; Liu, X H; Xia, X; Li, W J

    2009-12-01

    This study aims to investigate the effects of maternal lead exposure on learning and memory ability and the protein expression of TNF-alpha and SNARE complex (SNAP-25, VAMP-2, and Syntaxin 1A) in hippocampus of mice offspring. Pb exposure was initiated from beginning of gestation to weaning. Pb acetate administered in drinking solutions was dissolved in distilled deionized water at 0.1%, 0.5%, and 1% groups, respectively. On the PND21, the learning and memory ability of mouse pups was tested by water maze test, and the Pb levels in their blood and hippocampus were also determined. The protein expression of TNF-alpha and SNARE complex in hippocampus was measured by immunohistochemistry and Western blotting. The Pb levels in blood and hippocampus of all exposure groups were significantly higher than control group (P < 0.05). In the water maze test, the performances of 0.5% and 1% groups were worse than that of control group (P < 0.05). The expression of TNF-alpha, Syntaxin 1A, and VAMP-2 was increased in Pb-exposed groups comparing control group (P < 0.05), but the expression of SNAP-25 was decreased (P < 0.05). Up-regulation of TNF-alpha and disturbance of SNARE expression in the hippocampus of pups may contribute to impairment of learning and memory ability associated with maternal Pb exposure.

  13. 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.

  14. 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.

  15. Novel mutations in Lrp6 orthologs in mouse and human neural tube defects affect a highly dosage-sensitive Wnt non-canonical planar cell polarity pathway

    PubMed Central

    Allache, Redouane; Lachance, Stéphanie; Guyot, Marie Claude; De Marco, Patrizia; Merello, Elisa; Justice, Monica J.; Capra, Valeria; Kibar, Zoha

    2014-01-01

    Wnt signaling has been classified as canonical Wnt/β-catenin-dependent or non-canonical planar cell polarity (PCP) pathway. Misregulation of either pathway is linked mainly to cancer or neural tube defects (NTDs), respectively. Both pathways seem to antagonize each other, and recent studies have implicated a number of molecular switches that activate one pathway while simultaneously inhibiting the other thereby partially mediating this antagonism. The lipoprotein receptor–related protein Lrp6 is crucial for the activation of the Wnt/β-catenin pathway, but its function in Wnt/PCP signaling remains largely unknown. In this study, we investigate the role of Lrp6 as a molecular switch between both Wnt pathways in a novel ENU mouse mutant of Lrp6 (Skax26m1Jus) and in human NTDs. We demonstrate that Skax26m1Jus represents a hypermorphic allele of Lrp6 with increased Wnt canonical and abolished PCP-induced JNK activities. We also show that Lrp6Skax26-Jus genetically interacts with a PCP mutant (Vangl2Lp) where double heterozygotes showed an increased frequency of NTDs and defects in cochlear hair cells’ polarity. Importantly, our study also demonstrates the association of rare and novel missense mutations in LRP6 that is an inhibitor rather than an activator of the PCP pathway with human NTDs. We show that three LRP6 mutations in NTDs led to a reduced Wnt canonical activity and enhanced PCP signaling. Our data confirm an inhibitory role of Lrp6 in PCP signaling in neurulation and indicate the importance of a tightly regulated and highly dosage-sensitive antagonism between both Wnt pathways in this process. PMID:24203697

  16. 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

  17. 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.

  18. Inhalable Particles for "Pincer Therapeutics" Targeting Nitazoxanide as Bactericidal and Host-Directed Agent to Macrophages in a Mouse Model of Tuberculosis.

    PubMed

    Gupta, Anuradha; Meena, Jairam; Sharma, Deepak; Gupta, Pushpa; Gupta, Umesh Dutta; Kumar, Sadan; Sharma, Sharad; Panda, Amulya K; Misra, Amit

    2016-09-01

    Nitazoxanide (NTZ) has moderate mycobactericidal activity and is also an inducer of autophagy in mammalian cells. High-payload (40-50% w/w) inhalable particles containing NTZ alone or in combination with antituberculosis (TB) agents isoniazid (INH) and rifabutin (RFB) were prepared with high incorporation efficiency of 92%. In vitro drug release was corrected for drug degradation during the course of study and revealed first-order controlled release. Particles were efficiently taken up in vitro by macrophages and maintained intracellular drug concentrations at one order of magnitude higher than NTZ in solution for 6 h. Dose-dependent killing of Mtb and restoration of lung and spleen architecture were observed in experimentally infected mice treated with inhalations containing NTZ. Adjunct NTZ with INH and RFB cleared culturable bacteria from the lung and spleen and markedly healed tissue architecture. NTZ can be used in combination with INH-RFB to kill the pathogen and heal the host. PMID:27463245

  19. 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

    2015-01-01

    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. PMID:26102067

  20. Disruption of the ErbB signaling in adolescence increases striatal dopamine levels and affects learning and hedonic-like behavior in the adult mouse.

    PubMed

    Golani, Idit; Tadmor, Hagar; Buonanno, Andres; Kremer, Ilana; Shamir, Alon

    2014-11-01

    The ErbB signaling pathway has been genetically and functionally implicated in schizophrenia. Numerous findings support the dysregulation of Neuregulin (NRG) and epidermal growth factor (EGF) signaling in schizophrenia. However, it is unclear whether alterations of these pathways in the adult brain or during development are involved in the pathophysiology of schizophrenia. Herein we characterized the behavioral profile and molecular changes resulting from pharmacologically blocking the ErbB signaling pathway during a critical period in the development of decision making, planning, judgments, emotions, social cognition and cognitive skills, namely adolescence. We demonstrate that chronic administration of the pan-ErbB kinase inhibitor JNJ-28871063 (JNJ) to adolescent mice elevated striatal dopamine levels and reduced preference for sucrose without affecting locomotor activity and exploratory behavior. In adulthood, adolescent JNJ-treated mice continue to consume less sucrose and needed significantly more correct-response trials to reach the learning criterion during the discrimination phase of the T-maze reversal learning task than their saline-injected controls. In addition, JNJ mice exhibited deficit in reference memory but not in working memory as measured in the radial arm maze. Inhibition of the pathway during adolescence did not affect exploratory behavior and locomotor activity in the open field, social interaction, social memory, and reversal learning in adult mice. Our data suggest that alteration of ErbB signaling during adolescence resulted in changes in the dopaminergic systems that emerge in pathological learning and hedonic behavior in adulthood, and pinpoints the possible role of the pathway in the development of cognitive skills and motivated behavior. PMID:25451700

  1. 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

  2. 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.

  3. 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.

  4. 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. PMID:26700248

  5. Ca2+-Mg2+ ATPase of mouse cardiac sarcoplasmic reticulum is affected by membrane n-6 and n-3 polyunsaturated fatty acid content.

    PubMed

    Swanson, J E; Lokesh, B R; Kinsella, J E

    1989-03-01

    White mice, 18-20 g, were fed purified diets containing two weight percent safflower oil plus ten weight percent menhaden, corn, or olive oil for 2 wk. Menhaden oil ingestion resulted in significantly higher levels of 22:6(n-3) and 20:5(n-3), particularly 22:6(n-3), and lower levels of 20:4(n-6) and 18:2(n-6) in cardiac sarcoplasmic reticulum (SR) phospholipids than did corn or olive oil ingestion. These changes in fatty acid composition resulted in a significant decrease in the value of the n-6/n-3 fatty acid ratio of cardiac SR phospholipids. The ratio was 2.8 versus 0.2 in choline phospholipids and 1.9 versus 0.2 in ethanolamine phospholipids in SR of mice fed corn or menhaden oil, respectively. This reduction in the n-6/n-3 fatty acid ratio was associated with a lower relative activity of Ca2+-Mg2+ ATPase, and a lower initial rate of calcium transport and maximum calcium uptake in SR vesicles from mice fed menhaden oil rather than olive or corn oils. The specific activity of NADPH cytochrome C reductase (EC 1.6.2.3) of cardiac SR was not affected by dietary lipids. These data indicate that modification of SR by 22:6(n-3) may change the SR bilayer structure resulting in alteration of the calcium transport properties of SR vesicles. In addition, our results suggest that reduction of calcium flux across cardiac SR following fish oil consumption may also reduce the susceptibility of myocytes to rapid changes in calcium concentrations which may occur during ischemia and reperfusion.

  6. 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.

  7. Disruption of the arsenic (+3 oxidation state) methyltransferase gene in the mouse alters the phenotype for methylation of arsenic and affects distribution and retention of orally administered arsenate.

    PubMed

    Drobna, Zuzana; Naranmandura, Hua; Kubachka, Kevin M; Edwards, Brenda C; Herbin-Davis, Karen; Styblo, Miroslav; Le, X Chris; Creed, John T; Maeda, Noboyu; Hughes, Michael F; Thomas, David J

    2009-10-01

    The arsenic (+3 oxidation state) methyltransferase (As3mt) gene encodes a 43 kDa protein that catalyzes methylation of inorganic arsenic. Altered expression of AS3MT in cultured human cells controls arsenic methylation phenotypes, suggesting a critical role in arsenic metabolism. Because methylated arsenicals mediate some toxic or carcinogenic effects linked to inorganic arsenic exposure, studies of the fate and effects of arsenicals in mice which cannot methylate arsenic could be instructive. This study compared retention and distribution of arsenic in As3mt knockout mice and in wild-type C57BL/6 mice in which expression of the As3mt gene is normal. Male and female mice of either genotype received an oral dose of 0.5 mg of arsenic as arsenate per kg containing [(73)As]-arsenate. Mice were radioassayed for up to 96 h after dosing; tissues were collected at 2 and 24 h after dosing. At 2 and 24 h after dosing, livers of As3mt knockouts contained a greater proportion of inorganic and monomethylated arsenic than did livers of C57BL/6 mice. A similar predominance of inorganic and monomethylated arsenic was found in the urine of As3mt knockouts. At 24 h after dosing, As3mt knockouts retained significantly higher percentages of arsenic dose in liver, kidneys, urinary bladder, lungs, heart, and carcass than did C57BL/6 mice. Whole body clearance of [(73)As] in As3mt knockouts was substantially slower than in C57BL/6 mice. At 24 h after dosing, As3mt knockouts retained about 50% and C57BL/6 mice about 6% of the dose. After 96 h, As3mt knockouts retained about 20% and C57BL/6 mice retained less than 2% of the dose. These data confirm a central role for As3mt in the metabolism of inorganic arsenic and indicate that phenotypes for arsenic retention and distribution are markedly affected by the null genotype for arsenic methylation, indicating a close linkage between the metabolism and retention of arsenicals.

  8. Oxidative DNA damage and defence gene expression in the mouse lung after short-term exposure to diesel exhaust particles by inhalation.

    PubMed

    Risom, Lotte; Dybdahl, Marianne; Bornholdt, Jette; Vogel, Ulla; Wallin, Håkan; Møller, Peter; Loft, Steffen

    2003-11-01

    Exposure to diesel exhaust particles (DEP) is suspected to contribute to lung cancer and cardiopulmonary diseases. In recent years generation of reactive oxygen species capable of inducing cellular oxidative stress has been in focus as one of the underlying mechanisms behind the genotoxic effects of particles. However, the role of the antioxidative defence system still needs to be clarified, especially in relation to low-dose DEP exposures. The aim of this study was to characterize the effects of short-term exposure to DEP in terms of DNA damage and expression of key response genes towards oxidative stress in lungs of mice. Mice were exposed by inhalation to 20 or 80 mg/m3 DEP inhaled as either a single dose, or four lower doses (5 and 20 mg/m3) inhaled on four consecutive days. Our results indicate that HO-1 mRNA expression in lung tissue was up-regulated after both types of DEP exposures, whereas OGG1 expression was only up-regulated after repeated exposures. The level of oxidative DNA damage in terms of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) was increased in the lung tissue after a single exposure, whereas increased levels of DNA strand breaks was observed in bronchoalveolar lavage cells after repeated DEP exposures. The levels of 8-oxodG and OGG1 mRNA in lung tissue were mirror images. This suggests that after repeated exposures, up-regulation of DNA repair counteracts an increased rate of 8-oxodG formation leaving the steady state level of 8-oxodG in DNA unchanged. In conclusion, this study indicates that a single high dose of DEP generates 8-oxodG in lung tissue, whereas the same dose inhaled as four low-exposures may up-regulate the antioxidative defence system and protect against generation of 8-oxodG. PMID:12919962

  9. 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.

  10. 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. PMID:26498840

  11. 8-Cl-Adenosine enhances 1,25-dihydroxyvitamin D3-induced growth inhibition without affecting 1,25-dihydroxyvitamin D3-stimulated differentiation of primary mouse epidermal keratinocytes

    PubMed Central

    Bollag, Wendy B; Zhong, Xiaofeng; Josephson, Sarah

    2004-01-01

    Background Epidermal keratinocytes continuously proliferate and differentiate to form the mechanical and water permeability barrier that makes terrestrial life possible. In certain skin diseases, these processes become dysregulated, resulting in abnormal barrier formation. In particular, skin diseases such as psoriasis, actinic keratosis and basal and squamous cell carcinomas are characterized by hyperproliferation and aberrant or absent differentiation of epidermal keratinocytes. We previously demonstrated that 8-Cl-adenosine (8-Cl-Ado) can induce keratinocyte growth arrest without inducing differentiation. Results To determine if this agent might be useful in treating hyperproliferative skin disorders, we investigated whether 8-Cl-Ado could enhance the ability of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], a known keratinocyte differentiating agent and a clinical treatment for psoriasis, to inhibit keratinocyte growth. We found that low concentrations of 8-Cl-Ado and 1,25(OH)2D3 appeared to act additively to reduce proliferation of primary mouse epidermal keratinocytes. However, another agent (transforming growth factor-beta) that triggers growth arrest without inducing differentiation also coincidentally inhibits differentiation elicited by other agents; inhibition of differentiation is suboptimal for treating skin disorders, as differentiation is often already reduced. Thus, we determined whether 8-Cl-Ado also decreased keratinocyte differentiation induced by 1,25(OH)2D3, as measured using the early and late differentiation markers, keratin 1 protein levels and transglutaminase activity, respectively. 8-Cl-Ado did not affect 1,25(OH)2D3-stimulated keratin 1 protein expression or transglutaminase activity. Conclusions Our results suggest that 8-Cl-Ado might be useful in combination with differentiating agents for the treatment of hyperproliferative disorders of the skin. PMID:15279680

  12. 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

  13. Laboratory Studies of the Role of Organic Coatings in Affecting the Reactivity of Gas-Phase Ozone with Particle-Borne PAHs

    NASA Astrophysics Data System (ADS)

    Zhou, S.; Lee, A.; McWhinney, R. D.; Abbatt, J.

    2010-12-01

    Atmospheric aerosols have a variety of important impacts, including visibility reduction, climate change and adverse health effects. A dominant fraction of atmospheric aerosol is now known to be composed of organic substances, which can be of primary or secondary origin. Organic aerosols can change their physical and chemical properties e.g. hygroscopicity, density, toxicity and composition via atmospheric oxidative ‘aging’. Even though much progress in our understanding of aerosol aging has been made in recent years, the aerosol oxidation rate and mechanism remain poorly understood. Both field and laboratory studies show evidence that heterogeneous surface reactions contribute to aerosol aging, however, bulk reactions in the particle following heterogeneous uptake of reactive species (such as OH, NO3 and O3) may also contribute to the aerosol aging process owing to the moderately long life time (1 to 2 weeks) that organic aerosol may experience. In the present study, we are expanding upon recent studies of the reactions between O3 and particle-borne PAHs conducted by both our group and others. In particular, it is now well recognized that surface-bound PAHs react rapidly under atmospheric oxidant conditions. However, it is not known the degree to which this reactivity is suppressed by organic coatings that (initially) bury the PAH. Studies will be presented where PAHs are coated with a range of different organic coatings (e.g. liquid vs solid) and then exposed to ozone within both a flow-tube and a newly built atmospheric simulation chamber. The PAH and ozone concentrations are analyzed by an Aerodyne Mass Spectrometer (AMS) and Thermo ozone analyzer (Type C49), respectively. The particle size distributions are measured with a scanning mobility particle sizer (SMPS) system. A detailed particle coating procedure, experimental results, effect of relative humidity, and light intensity on the kinetics will be presented.

  14. 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.

  15. 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.

  16. 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

  17. Replacement of tyrosine D with phenylalanine affects the normal proton transfer pathways for the reduction of P680+ in oxygen-evolving photosystem II particles from Chlamydomonas.

    PubMed

    Jeans, C; Schilstra, M J; Ray, N; Husain, S; Minagawa, J; Nugent, J H A; Klug, D R

    2002-12-31

    We have probed the electrostatics of P680(+) reduction in oxygenic photosynthesis using histidine-tagged and histidine-tagged Y(D)-less Photosystem II cores. We make two main observations: (i) that His-tagged Chlamydomonas cores show kinetics which are essentially identical to those of Photosystem II enriched thylakoid membranes from spinach; (ii) that the microsecond kinetics, previously shown to be proton/hydrogen transfer limited [Schilstra et al. (1998) Biochemistry 37, 3974-3981], are significantly different in Y(D)-less Chlamydomonas particles when compared with both the His-tagged Chlamydomonas particles and the spinach membranes. The oscillatory nature of the kinetics in both Chlamydomonas samples is normal, indicating that S-state cycling is unaffected by either the histidine-tagging or the replacement of tyrosine D with phenylalanine. We propose that the effects on the proton-coupled electron transfers of P680(+) reduction in the absence of Y(D) are likely to be due to pK shifts of residues in a hydrogen-bonded network of amino acids in the vicinity of Y(Z). Tyrosine D is 35 A from Y(Z) and yet has a significant influence on proton-coupled electron transfer events in the vicinity of Y(Z). This finding emphasizes the delicacy of the proton balance that Photosystem II has to achieve during the water splitting process. PMID:12501204

  18. Factors affecting the microstructure and mechanical properties of Ti-Al3Ti core-shell-structured particle-reinforced Al matrix composites

    NASA Astrophysics Data System (ADS)

    Guo, Baisong; Yi, Jianhong; Ni, Song; Shen, Rujuan; Song, Min

    2016-04-01

    This work studied the effects of matrix powder and sintering temperature on the microstructure and mechanical properties of in situ formed Ti-Al3Ti core-shell-structured particle-reinforced pure Al-based composites. It has been shown that both factors have significant effects on the morphology of the reinforcements and densification behaviour of the composites. Due to the strong interfacial bonding and the limitation of the crack propagation in the intermetallic shell during deformation by soft Al matrix and Ti core, the composite fabricated using fine spherical-shaped Al powder and sintered at 570 °C for 5 h has the optimal combination of the overall mechanical properties. The study provides a direction for the optimum combination of high strength and ductility of the composites by adjusting the fabrication parameters.

  19. The phagocytosis of crystalline silica particles by macrophages.

    PubMed

    Gilberti, Renée M; Joshi, Gaurav N; Knecht, David A

    2008-11-01

    Silicosis is a chronic lung disease induced by the inhalation of crystalline silica. Exposure of cultured macrophages to crystalline silica leads to cell death; however, the mechanism of cell-particle interaction, the fate of particles, and the cause of death are unknown. Time-lapse imaging shows that mouse macrophages avidly bind particles that settle onto the cell surface and that cells also extend protrusions to capture distant particles. Using confocal optical sectioning, silica particles were shown to be present within the cytoplasmic volume of live cells. In addition, electron microscopy and elemental analysis showed silica in internal cellular sections. To further examine the phagocytosis process, the kinetics of particle uptake was quantified using an assay in which cells were exposed to ovalbumin (OVA)-coated particles, and an anti-OVA antibody was used to distinguish surface-bound from internalized particles. Fc receptor-mediated uptake of antibody-coated silica particles was nearly complete within 5 minutes. In contrast, no OVA-coated particles were internalized at this time. After 30 minutes, 30% of bound silica was internalized and uptake continued slowly thereafter. OVA-coated latex beads, regardless of surface charge, were internalized at a similarly slow rate. These results demonstrate that macrophages internalize silica and that nonopsonized phagocytosis occurs by a temporally, and possibly mechanistically, distinct pathway from Fc receptor-mediated phagocytosis. Eighty percent of macrophages die within 12 hours of silica exposure. Neither OVA coating nor tetramethylrhodamine isothiocyanate labeling has any effect on cell death. Interestingly, antibody coating dramatically reduces silica toxicity. We hypothesize that the route of particle entry and subsequent phagosome trafficking affects the toxicity of internalized particles.

  20. The Phagocytosis of Crystalline Silica Particles by Macrophages

    PubMed Central

    Gilberti, Renée M.; Joshi, Gaurav N.; Knecht, David A.

    2008-01-01

    Silicosis is a chronic lung disease induced by the inhalation of crystalline silica. Exposure of cultured macrophages to crystalline silica leads to cell death; however, the mechanism of cell–particle interaction, the fate of particles, and the cause of death are unknown. Time-lapse imaging shows that mouse macrophages avidly bind particles that settle onto the cell surface and that cells also extend protrusions to capture distant particles. Using confocal optical sectioning, silica particles were shown to be present within the cytoplasmic volume of live cells. In addition, electron microscopy and elemental analysis showed silica in internal cellular sections. To further examine the phagocytosis process, the kinetics of particle uptake was quantified using an assay in which cells were exposed to ovalbumin (OVA)-coated particles, and an anti-OVA antibody was used to distinguish surface-bound from internalized particles. Fc receptor–mediated uptake of antibody-coated silica particles was nearly complete within 5 minutes. In contrast, no OVA-coated particles were internalized at this time. After 30 minutes, 30% of bound silica was internalized and uptake continued slowly thereafter. OVA-coated latex beads, regardless of surface charge, were internalized at a similarly slow rate. These results demonstrate that macrophages internalize silica and that nonopsonized phagocytosis occurs by a temporally, and possibly mechanistically, distinct pathway from Fc receptor–mediated phagocytosis. Eighty percent of macrophages die within 12 hours of silica exposure. Neither OVA coating nor tetramethylrhodamine isothiocyanate labeling has any effect on cell death. Interestingly, antibody coating dramatically reduces silica toxicity. We hypothesize that the route of particle entry and subsequent phagosome trafficking affects the toxicity of internalized particles. PMID:18556590

  1. Wnt signaling and gastrointestinal tumorigenesis in mouse models.

    PubMed

    Taketo, M M

    2006-12-01

    The canonical Wnt signaling plays important roles in embryonic development and tumorigenesis. For the latter, induced mutations in mice have greatly contributed to our understanding of the molecular mechanisms of cancer initiation and progression. Here, I will review recent reports on gastrointestinal cancer model mice, with an emphasis on the roles of the Wnt signal pathway. They include: mouse models for familial adenomatous polyposis; modifying factors that affect mouse intestinal polyposis, including the genes that help cancer progression; Wnt target genes that affect mouse intestinal polyposis; and a mouse model of gastric cancer that mimics Helicobacter pyroli infection. PMID:17143296

  2. 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.

  3. 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)

  4. 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.

  5. 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.

  6. 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.

  7. Ca(2+)-independent F-actin assembly and disassembly during Fc receptor- mediated phagocytosis in mouse macrophages

    PubMed Central

    1991-01-01

    Phagocytosis of IgG-coated particles by macrophages is presumed to involve the actin-based cytoskeleton since F-actin accumulates beneath forming phagosomes, and particle engulfment is blocked by cytochalasins, drugs that inhibit actin filament assembly. However, it is unknown whether Fc receptor ligation affects the rate or extent of F- actin assembly during phagocytosis of IgG-coated particles. To examine this question we have used a quantitative spectrofluorometric method to examine F-actin dynamics during a synchronous wave of phagocytosis of IgG-coated red blood cells by inflammatory mouse macrophages. We observed a biphasic rise in macrophage F-actin content during particle engulfment, with maxima at 1 and 5 min after the initiation of phagocytosis. F-actin declined to resting levels by 30 min, by which time particle engulfment was completed. These quantitative increases in macrophage F-actin were reflected in localized changes in F-actin distribution. Previous work showed that the number of IgG-coated particles engulfed by macrophages is unaffected by buffering extracellular calcium or by clamping cytosolic free calcium concentration ([Ca2+]i) to very low levels (Di Virgilio, F., B. C. Meyer, S. Greenberg, and S. C. Silverstein. 1988. J. Cell Biol. 106: 657-666). To determine whether clamping [Ca2+]i in macrophages affects the rate of particle engulfment, or the assembly or disassembly of F- actin during phagocytosis, we examined these parameters in macrophages whose [Ca2+]i had been clamped to approximately less than 3 nM with fura 2/AM and acetoxymethyl ester of EGTA. We found that the initial rate of phagocytosis, and the quantities of F-actin assembled and disassembled were similar in Ca(2+)-replete and Ca(2+)-depleted macrophages. We conclude that Fc receptor-mediated phagocytosis in mouse macrophages is accompanied by an ordered sequence of assembly and disassembly of F-actin that is insensitive to [Ca2+]i. PMID:2026648

  8. 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.

  9. 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.

  10. 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…

  11. Mouse genome database 2016.

    PubMed

    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.

  12. 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

  13. Mouse genome database 2016.

    PubMed

    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. M2698 is a potent dual-inhibitor of p70S6K and Akt that affects tumor growth in mouse models of cancer and crosses the blood-brain barrier

    PubMed Central

    Machl, Andreas; Wilker, Erik W; Tian, Hui; Liu, Xiaohong; Schroeder, Patricia; Clark, Anderson; Huck, Bayard R

    2016-01-01

    Dysregulated PI3K/Akt/mTOR (PAM) pathway signaling occurs in ~30% of human cancers, making it a rational target for new therapies; however, the effectiveness of some PAM pathway inhibitors, such as mTORC rapalogs, may be compromised by a compensatory feedback loop leading to Akt activation. In this study, the p70S6K/Akt dual inhibitor, M2698 (previously MSC2363318A), was characterized as a potential anti-cancer agent through examination of its pharmacokinetic, pharmacodynamic and metabolic properties, and anti-tumor activity. M2698 was highly potent in vitro (IC50 1 nM for p70S6K, Akt1 and Akt3 inhibition; IC50 17 nM for pGSK3β indirect inhibition) and in vivo (IC50 15 nM for pS6 indirect inhibition), and relatively selective (only 6/264 kinases had an IC50 within 10-fold of p70S6K). Orally administered M2698 crossed the blood-brain barrier in rats and mice, with brain tumor exposure 4-fold higher than non-disease brain. Dose-dependent inhibition of target substrate phosphorylation was observed in vitro and in vivo, indicating that M2698 blocked p70S6K to provide potent PAM pathway inhibition while simultaneously targeting Akt to overcome the compensatory feedback loop. M2698 demonstrated dose-dependent tumor growth inhibition in mouse xenograft models derived from PAM pathway-dysregulated human triple-negative (MDA-MB-468) and Her2-expressing breast cancer cell lines (MDA-MB-453 and JIMT-1), and reduced brain tumor burden and prolonged survival in mice with orthotopically implanted U251 glioblastoma. These findings highlight M2698 as a promising PAM pathway inhibitor whose unique mechanism of action and capacity to pass the blood-brain barrier warrant clinical investigation in cancers with PAM pathway dysregulation, and those with central nervous system involvement. PMID:27186432

  15. Translating Mouse Vocalizations: Prosody and Frequency Modulation

    PubMed Central

    Lahvis, Garet P.; Alleva, Enrico; Scattoni, Maria Luisa

    2010-01-01

    Mental illness can include impaired abilities to express emotions or respond to the emotions of others. Speech provides a mechanism for expressing emotions, by both what words are spoken and by the melody or intonation of speech (prosody). Through the perception of variations in prosody, an individual can detect changes in another's emotional state. Prosodic features of mouse ultrasonic vocalizations (USVs), indicated by changes in frequency and amplitude, also convey information. Dams retrieve pups that emit separation calls, females approach males emitting solicitous calls, and mice can become fearful of a cue associated with the vocalizations of a distressed conspecific. Since acoustic features of mouse USVs respond to drugs and genetic manipulations that influence reward circuits, USV analysis can be employed to examine how genes influence social motivation, affect regulation, and communication. The purpose of this review is to discuss how genetic and developmental factors influence aspects of the mouse vocal repertoire and how mice respond to the vocalizations of their conspecifics. To generate falsifiable hypotheses about the emotional content of particular calls, this review addresses USV analysis within the framework of affective neuroscience (e.g. measures of motivated behavior such as conditioned place preference tests, brain activity, and systemic physiology). Suggested future studies include employment of an expanded array of physiological and statistical approaches to identify the salient acoustic features of mouse vocalizations. We are particularly interested in rearing environments that incorporate sufficient spatial and temporal complexity to familiarize developing mice with a broader array of affective states. PMID:20497235

  16. 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

    Kong, Lingbo; Yang, Chongfei; Yu, Lifeng; 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.

  17. Rare particles

    SciTech Connect

    Kutschera, W.

    1984-01-01

    The use of Accelerator Mass Spectrometry (AMS) to search for hypothetical particles and known particles of rare processes is discussed. The hypothetical particles considered include fractionally charged particles, anomalously heavy isotopes, and superheavy elements. The known particles produced in rare processes discussed include doubly-charged negative ions, counting neutrino-produced atoms in detectors for solar neutrino detection, and the spontaneous emission of /sup 14/C from /sup 223/Ra. 35 references. (WHK)

  18. Magnetic Particle Imaging

    SciTech Connect

    Minard, Kevin R.

    2010-02-01

    Rapid advances in the synthesis of superparamagnetic nanoparticles has stimulated widespread interest in their use as contrast agents for visualizing biological processes with Magnetic Resonance Imaging (MRI). With this approach, strong particle magnetism alters the MRI signal from nearby water protons and this, in turn, affects observed image contrast. Magnetic particle detection with MRI is therefore indirect and suffers from several associated problems, including poor quantification and tissuedependent performance. Magnetic Particle Imaging (MPI) overcomes these by directly measuring the amount of superparamagnetic material at each location. Mass sensitivity, spatial resolution, and imaging time is also comparable to or better than that achieved with MRI. Moreover, MPI is relatively inexpensive, meets all current safety guidelines, is quantitative, provides unambiguous contrast with tissue-independent performance, and can detect lower particle concentrations. Here, the basic principles behind MPI are described, factors affecting sensitivity and resolution are discussed, and potential utility for biomedical use is examined.

  19. 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.

  20. Particle separation

    DOEpatents

    Moosmuller, Hans; Chakrabarty, Rajan K.; Arnott, W. Patrick

    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.

  1. 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.

  2. Children computer mouse use and anthropometry.

    PubMed

    Hughes, Erin E; Johnson, Peter W

    2012-01-01

    Studies have shown that increased computer use among adults in occupational settings is associated with the development of cumulative trauma disorders; however, the need to address how adult-sized mice and keyboards are affecting children is becoming increasingly important as both access to and use of computers is increasing among today's youth. To address the potential mismatch that exists between child stature and computer input device size and activation force, we have applied existing, age-specific, anthropometric data to elements of device design, including mouse size (length, width, height, switch location), and mouse-button activation forces. Trends supported the development of smaller computer input devices with lower activation forces for smaller statured individuals including children. Distinct and consistent trends in size delineations were seen across gender and age groups-trends that correlate well with grades and schooling in the United States education system . Three to four mouse sizes would be recommended: a mouse sized for adult and high school males; one for adult and high school females and junior high males; one for elementary school children, aged 6 to 10 years; and possibly a mouse for the smallest users who are less than six years old. PMID:22316827

  3. Removing the cloak of invisibility: phenotyping the mouse

    PubMed Central

    Justice, Monica J.

    2008-01-01

    If you study a human disease, it is likely that you have tried to generate a mouse model. Sometimes, these models are excellent; others are disappointing. Or, so we think. How often does our mouse mutant not model the human disease because of limitations in how we may look at it? In any living organism, many factors work together to produce the phenotype. Here, new phenotyping paradigms for assessing mouse biology and physiology are described and proposed. Advances in mouse phenotype assessments have paralleled human clinical diagnostics. The future brings a multitude of mouse strains that might be exposed to a variety of conditions. To assess health will require the ability to perform a broad-based phenotype assessment of every animal until we can understand how the perturbation of one system affects others. PMID:19048073

  4. 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.

  5. Spectral imaging of mouse calvaria undergoing craniosynstosis

    NASA Astrophysics Data System (ADS)

    Crane, Nicole J.; Wang, Wei; Ignelzi, Michael A., Jr.; Morris, Michael D.

    2003-07-01

    Craniosynostosis, the premature fusion of the skull bones at the sutures, is the second most common human birth defect that affects the face and skull. The top most flat bones that comprise the skull, or calvaria, are most often affected. We previously showed that treatment of mouse calvaria with FGF2-soaked beads leads to craniosynostosis. In this study we treated mouse calvaria with FGF2-soaked beads and then used Raman imaging to demonstrate the spatial distribution of apatitic mineral and matrix in the sutures. There was no difference between FGF2 treated and control calvaria in the type of mineral produced (a lightly carbonated apatite), however we did observe increased mineral deposition in FGF2 treated calvaria. Raman imaging has great promise to detect the earliest mineral and matrix changes that occur in craniosynostosis.

  6. Chimeric HBcAg virus-like particles presenting a HPV 16 E7 epitope significantly suppressed tumor progression through preventive or therapeutic immunization in a TC-1-grafted mouse model

    PubMed Central

    Chu, Xiaojie; Li, Yang; Long, Qiong; Xia, Ye; Yao, Yufeng; Sun, Wenjia; Huang, Weiwei; Yang, Xu; Liu, Cunbao; Ma, Yanbing

    2016-01-01

    Background Therapeutic human papillomavirus (HPV) vaccines are currently being developed. However, no therapeutic efficacy has been achieved in clinical trials for the treatment of cervical intraepithelial neoplasia or cancer. One of the important issues in increasing vaccine efficacy is determining the best way to enhance tumor antigen-specific cellular immune responses. This study aimed to explore the virus-like particles (VLPs) of hepatitis B core antigen (HBcAg) as potential therapeutic vaccine carriers and to assess its immunological characteristics. Methods Chimeric VLPs presenting a HPV 16 cytotoxic T lymphocytes epitope E749–57 (amino acid 49–57 of the E7 protein) were prepared using recombinant genes. C57BL/6 mice were immunized with VLPs and grafted with tumor cells TC-1 which is an E7-expressing tumorigenic cell line. The dynamic tumor growth was monitored and anti-tumor immune responses were investigated. Results Using a preventive strategy, immunization with VLPs resulted in nearly complete suppression of tumor growth. In treatment studies, VLP immunization significantly suppressed the tumor progression in mice carrying 2–3 mm tumors and in those bearing even larger tumors with diameters up to 8–9 mm. The VLP structure was shown to be important to induce vigorous antitumor immunity and effects. In immunized mice, enhanced E749–57-specific cellular immune responses were evidenced by increased interferon (IFN)-γ expression and decreased interleukin (IL)-4 expression in splenic lymphocytes, as well as an elevated number of effector cells expressing IFN-γ in response to the in vitro stimulation of the specific peptide E749–57. In addition, effective immune memory after VLP immunization was maintained for at least 16 weeks, preventing significant tumor growth after subsequent TC-1 challenge. Conclusion While VLPs were highly immunogenic in stimulating humoral immunity, our results strongly indicated that VLPs, such as HBcAg particles, might

  7. 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.

  8. The comparison of the effect of LTR72 and MF59 adjuvants on mouse humoral response to intranasal immunisation with human papillomavirus type 6b (HPV-6b) virus-like particles.

    PubMed

    Greer, C E; Petracca, R; Buonamassa, D T; Di Tommaso, A; Gervase, B; Reeve, R L; Ugozzoli, M; Van Nest, G; De Magistris, M T; Bensi, G

    2000-12-01

    Infections with genital human papillomaviruses (HPV) are likely to be neutralised more efficiently if a mucosal immune response can be elicited at the viral entry site. Local IgA antibodies are highly induced when antigens are co-administered with mucosal adjuvants, such as cholera toxin (CT) and Escherichia coli heat labile enterotoxin (LT) which, however, are not expected to have wide application because of their pronounced toxicity. We have immunised mice intranasally with HPV-6b virus-like particles (VLPs) and a genetically modified LT-derived molecule with only residual toxicity, LTR72, and compared the humoral responses with those obtained following systemic immunisation with VLPs and the MF59 adjuvant. Titration of anti-HPV antibodies in sera and vaginal secretions established that LTR72 was able to elicit higher serum and mucosal IgA titers, in addition to IgG serum levels, comparable to those obtained by parenteral immunisation. These results confirm the potential of toxin-derived adjuvants and extend their use in combination with HPV antigens.

  9. 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.

  10. 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.

  11. CD36 and Proteoglycan-Mediated Pathways for (n-3) Fatty Acid–Enriched Triglyceride-Rich Particle Blood Clearance in Mouse Models In Vivo and in Peritoneal Macrophages In Vitro1,2

    PubMed Central

    Densupsoontorn, Narumon; Carpentier, Yvon A.; Racine, Radjini; Murray, Faith M.; Seo, Toru; Ramakrishnan, Rajasekhar; Deckelbaum, Richard J.

    2008-01-01

    Because the mechanisms of (n-3) fatty acid–enriched triglyceride-rich particle [(n-3)-TGRP] uptake are not well characterized, we questioned whether (n-3)-TGRP are removed via “nonclassical” pathways, e.g., pathways other than an LDL receptor and/or involving apolipoprotein E (apoE). Chylomicron-sized model (n-3)-TGRP labeled with [3H]cholesteryl ether were injected into wild-type (WT) and CD36 knockout (CD36−/−) mice at low, nonsaturating and high, saturating doses. Blood clearance of (n-3)-TGRP was determined by calculating fractional catabolic rates. At saturating doses, blood clearance of (n-3)-TGRP was slower in CD36−/− mice relative to WT mice, suggesting that in part CD36 contributes to (n-3)-TGRP uptake. To further examine the potential nonclassical clearance pathways, peritoneal-elicited macrophages from WT and CD36−/− mice were incubated with (n-3)-TGRP in the presence of apoE, lactoferrin, and/or sodium chlorate. Cellular (n-3)-TGRP uptake was measured to test the roles of apoE-mediated pathways and/or proteoglycans. ApoE-mediated pathways compensated in part for defective (n-3)-TGRP uptake in CD36−/− cells. Lactoferrin decreased (n-3)-TGRP uptake in the presence of apoE. Inhibition of cell proteoglycan synthesis by chlorate reduced (n-3)-TGRP uptake in both groups of macrophages, and chlorate effects were independent of apoE. We conclude that although CD36 is involved, it is not the primary contributor to the blood clearance of (n-3)-TGRP. The removal of (n-3)-TGRP likely relies more on nonclassical pathways, such as proteoglycan-mediated pathways. PMID:18203888

  12. 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.

  13. Particle-Charge Spectrometer

    NASA Technical Reports Server (NTRS)

    Fuerstenau, Stephen; Wilson, Gregory R.

    2008-01-01

    An instrument for rapidly measuring the electric charges and sizes (from approximately 1 to approximately 100 micrometers) of airborne particles is undergoing development. Conceived for monitoring atmospheric dust particles on Mars, instruments like this one could also be used on Earth to monitor natural and artificial aerosols in diverse indoor and outdoor settings for example, volcanic regions, clean rooms, powder-processing machinery, and spray-coating facilities. The instrument incorporates a commercially available, low-noise, ultrasensitive charge-sensing preamplifier circuit. The input terminal of this circuit--the gate of a field-effect transistor--is connected to a Faraday-cage cylindrical electrode. The charged particles of interest are suspended in air or other suitable gas that is made to flow along the axis of the cylindrical electrode without touching the electrode. The flow can be channeled and generated by any of several alternative means; in the prototype of this instrument, the gas is drawn along a glass capillary tube (see upper part of figure) coaxial with the electrode. The size of a particle affects its rate of acceleration in the flow and thus affects the timing and shape of the corresponding signal peak generated by the charge-sensing amplifier. The charge affects the magnitude (and thus also the shape) of the signal peak. Thus, the signal peak (see figure) conveys information on both the size and electric charge of a sensed particle. In experiments thus far, the instrument has been found to be capable of measuring individual aerosol particle charges of magnitude greater than 350 e (where e is the fundamental unit of electric charge) with a precision of +/- 150 e. The instrument can sample particles at a rate as high as several thousand per second.

  14. 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.

  15. The Mouse SAGE Site: database of public mouse SAGE libraries.

    PubMed

    Divina, Petr; Forejt, Jirí

    2004-01-01

    The Mouse SAGE Site is a web-based database of all available public libraries generated by the Serial Analysis of Gene Expression (SAGE) from various mouse tissues and cell lines. The database contains mouse SAGE libraries organized in a uniform way and provides web-based tools for browsing, comparing and searching SAGE data with reliable tag-to-gene identification. A modified approach based on the SAGEmap database is used for reliable tag identification. The Mouse SAGE Site is maintained on an ongoing basis at the Institute of Molecular Genetics, Academy of Sciences of the Czech Republic and is accessible at the internet address http://mouse.biomed.cas.cz/sage/.

  16. 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.

  17. 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.

  18. 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.

  19. Particle preconcentrator

    DOEpatents

    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.

  20. 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.

  1. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus.

    PubMed

    Zhang, Dali; Xiong, Wei; Jackson, Michael F; Parkinson, Fiona E

    2016-07-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5'-nucleotidase activity. Wild-type (CD73(+/+)) and ecto-5'-nucleotidase-deficient (CD73(-/-)) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73(+/+) mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73(+/+) mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg(2+) conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5'-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73(-/-) mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5'-nucleotidase activity. PMID:27189965

  2. How Morphological Constraints Affect Axonal Polarity in Mouse Neurons

    PubMed Central

    Bugnicourt, Ghislain; Saoudi, Yasmina; Andrieux, Annie; Gory-Fauré, Sylvie; Villard, Catherine

    2012-01-01

    Neuronal differentiation is under the tight control of both biochemical and physical information arising from neighboring cells and micro-environment. Here we wished to assay how external geometrical constraints applied to the cell body and/or the neurites of hippocampal neurons may modulate axonal polarization in vitro. Through the use of a panel of non-specific poly-L-lysine micropatterns, we manipulated the neuronal shape. By applying geometrical constraints on the cell body we provided evidence that centrosome location was not predictive of axonal polarization but rather follows axonal fate. When the geometrical constraints were applied to the neurites trajectories we demonstrated that axonal specification was inhibited by curved lines. Altogether these results indicated that intrinsic mechanical tensions occur during neuritic growth and that maximal tension was developed by the axon and expressed on straight trajectories. The strong inhibitory effect of curved lines on axon specification was further demonstrated by their ability to prevent formation of multiple axons normally induced by cytochalasin or taxol treatments. Finally we provided evidence that microtubules were involved in the tension-mediated axonal polarization, acting as curvature sensors during neuronal differentiation. Thus, biomechanics coupled to physical constraints might be the first level of regulation during neuronal development, primary to biochemical and guidance regulations. PMID:22457779

  3. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus

    PubMed Central

    Zhang, Dali; Xiong, Wei; Jackson, Michael F.

    2016-01-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5′-nucleotidase activity. Wild-type (CD73+/+) and ecto-5′-nucleotidase-deficient (CD73−/−) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73+/+ mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73+/+ mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg2+ conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5′-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73−/− mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5′-nucleotidase activity. PMID:27189965

  4. 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. PMID:26472183

  5. 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.

  6. 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.

  7. Operant responding following exposure to HZE particles and its relationship to particle energy and LET

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. Affective Learning.

    ERIC Educational Resources Information Center

    Brown, Charles T.

    This paper addresses itself to the question, "What does feeling have to do with knowing?" Two movements in affective education are discussed which have come into focus in recent years and which attempt to define the relationship between knowing and feeling. The first, a conscious application of the role of arousal in learning, emphasizes arousal…

  9. 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.

  10. 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.

  11. ISOLATION OF MOUSE NEUTROPHILS

    PubMed Central

    Swamydas, Muthulekha; Luo, Yi; Dorf, Martin E.; Lionakis, Michail S.

    2015-01-01

    Neutrophils represent the first line of defense against bacterial and fungal pathogens. Indeed, patients with inherited and acquired qualitative and quantitative neutrophil defects are at high risk for developing bacterial and fungal infections and suffering adverse outcomes from these infections. Therefore, research aiming at defining the molecular factors that modulate neutrophil effector function under homeostatic conditions and during infection is essential for devising strategies to augment neutrophil function and improve the outcome of infected individuals. This unit describes a reproducible density gradient centrifugation-based protocol that can be applied in any laboratory to harvest large numbers of highly enriched and highly viable neutrophils from the bone marrow of mice both at the steady state and following infection with Candida albicans as described in UNIT 19.6. In another protocol, we also present a method that combines gentle enzymatic tissue digestion with a positive immunomagnetic selection technique or Fluorescence-activated cell sorting (FACS) to harvest highly pure and highly viable preparations of neutrophils directly from mouse tissues such as the kidney, the liver or the spleen. Finally, methods for isolating neutrophils from mouse peritoneal fluid and peripheral blood are included. Mouse neutrophils isolated by these protocols can be used for examining several aspects of cellular function ex vivo including pathogen binding, phagocytosis and killing, neutrophil chemotaxis, oxidative burst, degranulation and cytokine production, and for performing neutrophil adoptive transfer experiments. PMID:26237011

  12. RIKEN mouse genome encyclopedia.

    PubMed

    Hayashizaki, Yoshihide

    2003-01-01

    We have been working to establish the comprehensive mouse full-length cDNA collection and sequence database to cover as many genes as we can, named Riken mouse genome encyclopedia. Recently we are constructing higher-level annotation (Functional ANnoTation Of Mouse cDNA; FANTOM) not only with homology search based annotation but also with expression data profile, mapping information and protein-protein database. More than 1,000,000 clones prepared from 163 tissues were end-sequenced to classify into 159,789 clusters and 60,770 representative clones were fully sequenced. As a conclusion, the 60,770 sequences contained 33,409 unique. The next generation of life science is clearly based on all of the genome information and resources. Based on our cDNA clones we developed the additional system to explore gene function. We developed cDNA microarray system to print all of these cDNA clones, protein-protein interaction screening system, protein-DNA interaction screening system and so on. The integrated database of all the information is very useful not only for analysis of gene transcriptional network and for the connection of gene to phenotype to facilitate positional candidate approach. In this talk, the prospect of the application of these genome resourced should be discussed. More information is available at the web page: http://genome.gsc.riken.go.jp/.

  13. Sequence, molecular properties, and chromosomal mapping of mouse lumican

    NASA Technical Reports Server (NTRS)

    Funderburgh, J. L.; Funderburgh, M. L.; Hevelone, N. D.; Stech, M. E.; Justice, M. J.; Liu, C. Y.; Kao, W. W.; Conrad, G. W.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    PURPOSE. Lumican is a major proteoglycan of vertebrate cornea. This study characterizes mouse lumican, its molecular form, cDNA sequence, and chromosomal localization. METHODS. Lumican sequence was determined from cDNA clones selected from a mouse corneal cDNA expression library using a bovine lumican cDNA probe. Tissue expression and size of lumican mRNA were determined using Northern hybridization. Glycosidase digestion followed by Western blot analysis provided characterization of molecular properties of purified mouse corneal lumican. Chromosomal mapping of the lumican gene (Lcn) used Southern hybridization of a panel of genomic DNAs from an interspecific murine backcross. RESULTS. Mouse lumican is a 338-amino acid protein with high-sequence identity to bovine and chicken lumican proteins. The N-terminus of the lumican protein contains consensus sequences for tyrosine sulfation. A 1.9-kb lumican mRNA is present in cornea and several other tissues. Antibody against bovine lumican reacted with recombinant mouse lumican expressed in Escherichia coli and also detected high molecular weight proteoglycans in extracts of mouse cornea. Keratanase digestion of corneal proteoglycans released lumican protein, demonstrating the presence of sulfated keratan sulfate chains on mouse corneal lumican in vivo. The lumican gene (Lcn) was mapped to the distal region of mouse chromosome 10. The Lcn map site is in the region of a previously identified developmental mutant, eye blebs, affecting corneal morphology. CONCLUSIONS. This study demonstrates sulfated keratan sulfate proteoglycan in mouse cornea and describes the tools (antibodies and cDNA) necessary to investigate the functional role of this important corneal molecule using naturally occurring and induced mutants of the murine lumican gene.

  14. The effects of nanoparticles on mouse testis Leydig cells in vitro.

    PubMed

    Komatsu, Tomoko; Tabata, Masako; Kubo-Irie, Miyoko; Shimizu, Takahisa; Suzuki, Ken-Ichiro; Nihei, Yoshimasa; Takeda, Ken

    2008-12-01

    We have indicated the possibility that nanoparticles such as diesel exhaust particles (DEP) and titanium dioxide (TiO(2)) may impair the male mouse reproductive system. In this study, to evaluate the direct effect of nanoparticles on testis-constituent cells, we examined the effect of DEP, TiO(2) and carbon black (CB) on mouse Leydig TM3 cells, the testosterone-producing cells of the testis. The uptake of three nanoparticles into Leydig cells was detected using transmission electron microscopy (TEM) or field emission type scanning electron microscopy/energy-dispersive X-ray spectroscopy (FE-SEM/EDS). We examined the cytotoxicity and the effect on gene expression by treatment with nanoparticles. TiO(2) was more cytotoxic to Leydig cells than other nanoparticles. The proliferation of Leydig cells was suppressed transiently by treatment with TiO(2) or DEP. The expression of heme oxygenase-1 (HO-1), a sensitive marker for oxidative stress, was induced remarkably by treatment with DEP. Furthermore, CB and DEP slightly increased the gene expression of the steroidogenic acute regulatory (StAR) protein, the factor that controls mitochondrial cholesterol transfer. In this study, we found that DEPs, TiO(2) and CB nanoparticles were taken up by Leydig cells, and affected the viability, proliferation and gene expression. The patterns were unique for each nanoparticle. PMID:18805477

  15. Functional genomics in the mouse.

    PubMed

    Perkins, Archibald S

    2002-08-01

    The mouse is the premier genetic model organism for the study of human disease and development. With the recent advances in sequencing of the human and mouse genomes, there is strong interest now in large-scale approaches to decipher the function of mouse genes using various mutagenesis technologies. This review discusses what tools are currently available for manipulating and mutagenizing the mouse genome, such as ethylnitrosourea and gene trap mutagenesis, engineered inversions and deletions using the cre-lox system, and proviral insertional mutagenesis in somatic cells, and how these are being used to uncover gene function.

  16. 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

  17. 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.

  18. Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges.

    PubMed

    Jiskoot, Wim; Kijanka, Grzegorz; Randolph, Theodore W; Carpenter, John F; Koulov, Atanas V; Mahler, Hanns-Christian; Joubert, Marisa K; Jawa, Vibha; Narhi, Linda O

    2016-05-01

    The success of clinical and commercial therapeutic proteins is rapidly increasing, but their potential immunogenicity is an ongoing concern. Most of the studies that have been conducted over the past few years to examine the importance of various product-related attributes (in particular several types of aggregates and particles) and treatment regimen (such as dose, dosing schedule, and route of administration) in the development of unwanted immune responses have utilized one of a variety of mouse models. In this review, we discuss the utility and drawbacks of different mouse models that have been used for this purpose. Moreover, we summarize the lessons these models have taught us and some of the challenges they present. Finally, we provide recommendations for future research utilizing mouse models to improve our understanding of critical factors that may contribute to protein immunogenicity. PMID:27044944

  19. Immune Activity of BCG Infected Mouse Macrophages Treated with a Novel Recombinant Mouse Lactoferrin.

    PubMed

    O'Shea, Kelly M; Hwang, Shen-An; Actor, Jeffrey K

    2015-01-01

    Lactoferrin has been investigated for its adjuvant action to boost the BCG vaccine. Previous studies demonstrated that lactoferrin (LF) enhanced efficacy of the Bacillus Calmette-Guérin (BCG) vaccine to protect mice against the virulent Erdman Mycobacterium tuberculosis challenge. The studies here investigate the hypothesis that a novel CHO-derived recombinant mouse LF can modify cytokine production and antigen presentation molecules on macrophages. The mouse LF (rmLF) was examined for effects on bone marrow derived macrophage (BMM) activities when cultured with BCG. Comparisons were made to CHO-derived recombinant human LF (rhLF). Inflammatory cytokine responses were investigated, as were antigen presentation and associated co-stimulatory molecules. Cytokine responses were subsequently measured when these cells were co-cultured with naïve or BCG sensitized CD4+ lymphocytes. While overall responses were similar between mouse, human, and bovine forms, the homologous rmLF treated infected BMMs showed unique activation patterns of cytokine production. These results indicate that species-specific LF can have different effects on mouse macrophages exposed to BCG, thus potentially affecting adjuvant activity when used in models of vaccination in mice.

  20. 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

  1. [Affective dependency].

    PubMed

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy.

  2. [Affective dependency].

    PubMed

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy. PMID:23888587

  3. Characterization of Bcor expression in mouse development.

    PubMed

    Wamstad, Joseph A; Bardwell, Vivian J

    2007-04-01

    Mutation of the gene encoding the transcriptional corepressor BCOR results in the X-linked disorder Oculofaciocardiodental syndrome (OFCD or MCOPS2). Female OFCD patients suffer from severe ocular, craniofacial, cardiac, and digital developmental defects and males do not survive through gestation. BCOR can mediate transcriptional repression by the oncoprotein BCL6 and has the ability to reduce transcriptional activation by AF9, a known mixed-lineage leukemia (MLL) fusion partner. The essential role of BCOR in development and its ability to modulate activity of known oncogenic proteins prompted us to determine the expression profile of Bcor during mouse development. Identification of independently transcribed exons in the 5' untranslated region of Bcor suggests that three independent promoters control the expression of Bcor in mice. Although Bcor is widely expressed in adult mouse tissues, analysis of known spliced isoforms in the coding region of Bcor reveals differential isoform usage. Whole mount in situ hybridization of mouse embryos shows that Bcor is strongly expressed in the extraembryonic tissue during gastrulation and expression significantly increases throughout the embryo after embryonic turning. During organogenesis and fetal stages Bcor is differentially expressed in multiple tissue lineages, with a notable presence in the developing nervous system. Strikingly, we observed that Bcor expression in the eye, brain, neural tube, and branchial arches correlates with tissues affected in OFCD patients. PMID:17344103

  4. 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.

  5. c-Rel Regulates Inscuteable Gene Expression during Mouse Embryonic Stem Cell Differentiation.

    PubMed

    Ishibashi, Riki; Kozuki, Satoshi; Kamakura, Sachiko; Sumimoto, Hideki; Toyoshima, Fumiko

    2016-02-12

    Inscuteable (Insc) regulates cell fate decisions in several types of stem cells. Although it is recognized that the expression levels of mouse INSC govern the balance between symmetric and asymmetric stem cell division, regulation of mouse Insc gene expression remains poorly understood. Here, we showed that mouse Insc expression transiently increases at an early stage of differentiation, when mouse embryonic stem (mES) cells differentiate into bipotent mesendoderm capable of producing both endoderm and mesoderm in defined culture conditions. We identified the minimum transcriptional regulatory element (354 bases) that drives mouse Insc transcription in mES cells within a region >5 kb upstream of the mouse Insc transcription start site. We found that the transcription factor reticuloendotheliosis oncogene (c-Rel) bound to the minimum element and promoted mouse Insc expression in mES cells. In addition, short interfering RNA-mediated knockdown of either mouse INSC or c-Rel protein decreased mesodermal cell populations without affecting differentiation into the mesendoderm or endoderm. Furthermore, overexpression of mouse INSC rescued the mesoderm-reduced phenotype induced by knockdown of c-Rel. We propose that regulation of mouse Insc expression by c-Rel modulates cell fate decisions during mES cell differentiation.

  6. Trajectory dependent particle response for anisotropic mono domain particles in magnetic particle imaging

    NASA Astrophysics Data System (ADS)

    Graeser, M.; Bente, K.; Neumann, A.; Buzug, T. M.

    2016-02-01

    In magnetic particle imaging, scanners use different spatial sampling techniques to cover the field of view (FOV). As spatial encoding is realized by a selective low field region (a field-free-point, or field-free-line), this region has to be moved through the FOV on specific sampling trajectories. To achieve these trajectories complex time dependent magnetic fields are necessary. Due to the superposition of the selection field and the homogeneous time dependent fields, particles at different spatial positions experience different field sequences. As a result, the dynamic behaviour of those particles can be strongly spatially dependent. So far, simulation studies that determined the trajectory quality have used the Langevin function to model the particle response. This however, neglects the dynamic relaxation of the particles, which is highly affected by magnetic anisotropy. More sophisticated models based on stochastic differential equations that include these effects were only used for one dimensional excitation. In this work, a model based on stochastic differential equations is applied to two-dimensional trajectory field sequences, and the effects of these field sequences on the particle response are investigated. The results show that the signal of anisotropic particles is not based on particle parameters such as size and shape alone, but is also determined by the field sequence that a particle ensemble experiences at its spatial position. It is concluded, that the particle parameters can be optimized in terms of the used trajectory.

  7. 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.

  8. 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.

  9. Exercise increases mitochondrial glutamate oxidation in the mouse cerebral cortex.

    PubMed

    Herbst, Eric A F; Holloway, Graham P

    2016-07-01

    The present study investigated the impact of acute exercise on stimulating mitochondrial respiratory function in mouse cerebral cortex. Where pyruvate-stimulated respiration was not affected by acute exercise, glutamate respiration was enhanced following the exercise bout. Additional assessment revealed that this affect was dependent on the presence of malate and did not occur when substituting glutamine for glutamate. As such, our results suggest that glutamate oxidation is enhanced with acute exercise through activation of the malate-aspartate shuttle. PMID:27184881

  10. Functional colloidal particles for immunoresearch

    NASA Technical Reports Server (NTRS)

    Yen, S. P. S.; Rembaum, A.; Molday, R. W.; Dreyer, W.

    1976-01-01

    The paper deals with the development of a new class of immunological reagents consisting of antibodies covalently bonded to polymeric microspheres to serve as convenient markers for detection of cell surface antigens by scanning electron and light microscopy. Attention is focused on the design and synthesis of spherical particles containing hydroxyl and carboxyl groups on their surface in a wide range of sizes (30-340 nm diam) by emulsion copolymerization, the preparation of spherical particles ranging from 300 nm to 3 microns and containing a variety of functional groups by means of ionizing radiation, and the experimental conditions for the covalent bonding of fluorescent molecules and antibodies to the spheres by means of the cyanogen bromide, carbodiimide and glutaraldehyde methods. These reagents are used to locate antigens on red blood cells, on mouse and human lymphocytes, and on the surface of photoreceptors. They offer a number of advantages and applications for the study of cell surfaces for immunodiagnosis.

  11. Involvement of mouse and porcine PLCζ-induced calcium oscillations in preimplantation development of mouse embryos

    SciTech Connect

    Yoneda, Akihiro; Watanabe, Tomomasa

    2015-05-01

    In mammals, phospholipase Cζ (PLCζ) has the ability to trigger calcium (Ca{sup 2+}) oscillations in oocytes, leading to oocyte activation. Although there is a species-specific difference in the PLCζ-induced Ca{sup 2+} oscillatory pattern, whether PLCζ-induced Ca{sup 2+} oscillations affect preimplantation embryonic development remains unclear. Here, we show that Ca{sup 2+} oscillations in mouse PLCζ cRNA-injected oocytes stopped just before pronuclear formation, while that in porcine PLCζ cRNA-injected oocytes continued for several hours after pronuclei had been formed. This difference of Ca{sup 2+} oscillations in oocytes after pronuclear formation was dependent on the difference in the nuclear localization signal (NLS) sequence of PLCζ between the mouse and pig. However, mouse and porcine PLCζ cRNA-injected oocytes parthenogenetically developed to blastocysts regardless of the absence or presence of Ca{sup 2+} oscillations after pronuclear formation. Furthermore, the developmental rate of mouse or porcine PLCζ-activated oocytes injected with round spermatids to the blastocyst stage was not significantly different from that of strontium-activated oocytes injected with round spermatids. These results suggest that the PLCζ-induced Ca{sup 2+} oscillatory pattern in mouse oocytes is dependent on the NLS sequence of PLCζ and injection of PLCζ may be a useful method for activation of round spermatid-injected and somatic nuclear transferred oocytes. - Highlights: • Porcine PLCζ-induced Ca{sup 2+} oscillations continued after pronuclear formation. • The Ca{sup 2+} oscillatory pattern was dependent on the difference in the NLS sequence of PLCζ. • PLCζ-activated oocytes parthenogenetically developed to blastocysts. • PLCζ-activated oocytes injected with round spermatids developed to blastocysts.

  12. The mouse genome informatics and the mouse genome database

    SciTech Connect

    Maltais, L.J.; Blackburn, R.E.; Bradt, D.W.

    1994-09-01

    The Mouse Genome Database (MGD) is a centralized, comprehensive database of the mouse genome that includes genetic mapping data, comparative mapping data, gene descriptions, mutant phenotype descriptions, strains and allelic polymorphism data, inbred strain characteristics, physical mapping data, and molecular probes and clones data. Data in MGD are obtained from the published literature and by electronic transfer from laboratories working on large backcross panels of mice. MGD provides tools that enable the user to search the database, retrieve data, generate reports, analyze data, annotate records, and build genetic maps. The Encyclopedia of the Mouse Genome provides a graphic user interface to mouse genome data. It consists of software tools including: LinkMap, a graphic display of genetic linkage maps with the ability to magnify regions of high locus density: CytoMap, a graphic display of cytogenetic maps showing banded chromosomes with cytogenetic locations of genes and chromosomal aberrations; CATS, a catalog searching tool for text retrieval of mouse locus descriptions. These software tools provide access to the following data sets: Chromosome Committee Reports, MIT Genome Center data, GBASE reports, Mouse Locus Catalog (MLC), and Mouse Cytogenetic Mapping Data. The MGD is available to the scientific community through the World Wide Web (WWW) and Gopher. In addition GBASE can be accessed via the Internet.

  13. 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.

  14. 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.

  15. Cloning the laboratory mouse.

    PubMed

    Wakayama, T; Yanagimachi, R

    1999-06-01

    A brief account is given of early attempts to clone mammals (mice) by transferring cells (nuclei) of preimplantation embryos into enucleated oocytes, zygotes or blastomeres of two-cell embryos. This is followed by a brief review of recent successes using adult somatic cells: mammary gland cells for sheep, muscle cells for cattle and cumulus cells for mice. We have developed a technique for cloning the laboratory mouse by transferring cumulus cell nuclei into enucleated oocytes. With this technique, we have produced a population of over 80 cloned animals, and have carried the process over four generations. Development and fertility of these appear normal. However, the yield is very low; only approximately 1% of injected oocytes are carried to term. The challenge is now to understand the reason for this high loss. Is it a problem of technique, genomic reprogramming, somatic mutation, imprinting or incompatible cell cycle phases?

  16. 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.

  17. 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.

  18. Unstressing intemperate models: how cold stress undermines mouse modeling.

    PubMed

    Karp, Christopher L

    2012-06-01

    Mus musculus enjoys pride of place at the center of contemporary biomedical research. Despite being the current model system of choice for in vivo mechanistic analysis, mice have clear limitations. The literature is littered with examples of therapeutic approaches that showed promise in mouse models but failed in clinical trials. More generally, mice often provide poor mimics of the human diseases being modeled. Available data suggest that the cold stress to which laboratory mice are ubiquitously subjected profoundly affects mouse physiology in ways that impair the modeling of human homeostasis and disease. Experimental attention to this key, albeit largely ignored, environmental variable is likely to have a broad transformative effect on biomedical research.

  19. Ultrastructural study of Rift Valley fever virus in the mouse model

    SciTech Connect

    Reed, Christopher; Steele, Keith E.; Honko, Anna; Shamblin, Joshua; Hensley, Lisa E.; Smith, Darci R.

    2012-09-15

    Detailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed in the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV-host interactions and further characterize the mouse model of RVF.

  20. Particles causing lung disease

    SciTech Connect

    Kilburn, K.H.

    1984-04-01

    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. 164 references, 1 figure, 2 tables.

  1. Whole mouse cryo-imaging

    NASA Astrophysics Data System (ADS)

    Wilson, David; Roy, Debashish; Steyer, Grant; Gargesha, Madhusudhana; Stone, Meredith; McKinley, Eliot

    2008-03-01

    The Case cryo-imaging system is a section and image system which allows one to acquire micron-scale, information rich, whole mouse color bright field and molecular fluorescence images of an entire mouse. Cryo-imaging is used in a variety of applications, including mouse and embryo anatomical phenotyping, drug delivery, imaging agents, metastastic cancer, stem cells, and very high resolution vascular imaging, among many. Cryo-imaging fills the gap between whole animal in vivo imaging and histology, allowing one to image a mouse along the continuum from the mouse -> organ -> tissue structure -> cell -> sub-cellular domains. In this overview, we describe the technology and a variety of exciting applications. Enhancements to the system now enable tiled acquisition of high resolution images to cover an entire mouse. High resolution fluorescence imaging, aided by a novel subtraction processing algorithm to remove sub-surface fluorescence, makes it possible to detect fluorescently-labeled single cells. Multi-modality experiments in Magnetic Resonance Imaging and Cryo-imaging of a whole mouse demonstrate superior resolution of cryo-images and efficiency of registration techniques. The 3D results demonstrate the novel true-color volume visualization tools we have developed and the inherent advantage of cryo-imaging in providing unlimited depth of field and spatial resolution. The recent results continue to demonstrate the value cryo-imaging provides in the field of small animal imaging research.

  2. Mouse Models of Neurofibromatosis 1 and 21

    PubMed Central

    Gutmann, David H; Giovannini, Marco

    2002-01-01

    Abstract The neurofibromatoses represent two of the most common inherited tumor predisposition syndromes affecting the nervous system. Individuals with neurofibromatosis 1 (NF1) are prone to the development of astrocytomas and peripheral nerve sheath tumors whereas those affected with neurofibromatosis 2 (NF2) develop schwannomas and meningiomas. The development of traditional homozygous knockout mice has provided insights into the roles of the NF1 and NF2 genes during development and in differentiation, but has been less instructive regarding the contribution of NF1 and NF2 dysfunction to the pathogenesis of specific benign and malignant tumors. Recent progress employing novel mouse targeting strategies has begun to illuminate the roles of the NF1 and NF2 gene products in the molecular pathogenesis of NF-associated tumors. PMID:12082543

  3. Harnessing a Physiologic Mechanism for siRNA Delivery With Mimetic Lipoprotein Particles

    PubMed Central

    Nakayama, Tomoko; Butler, James S; Sehgal, Alfica; Severgnini, Mariano; Racie, Tim; Sharman, Jennifer; Ding, Feng; Morskaya, Svetlana Shulga; Brodsky, Joshua; Tchangov, Lubomir; Kosovrasti, Verbena; Meys, Mike; Nechev, Lubomir; Wang, Gang; Peng, Chang Geng; Fang, Yupang; Maier, Martin; Rajeev, Kallanthottathil G; Li, Robert; Hettinger, Julia; Barros, Scott; Clausen, Valerie; Zhang, Xuemei; Wang, Qianfan; Hutabarat, Renta; Dokholyan, Nikolay V; Wolfrum, Christian; Manoharan, Muthiah; Kotelianski, Victor; Stoffel, Markus; Sah, Dinah WY

    2012-01-01

    Therapeutics based on RNA interference (RNAi) have emerged as a potential new class of drugs for treating human disease by silencing the target messenger RNA (mRNA), thereby reducing levels of the corresponding pathogenic protein. The major challenge for RNAi therapeutics is the development of safe delivery vehicles for small interfering RNAs (siRNAs). We previously showed that cholesterol-conjugated siRNAs (chol-siRNA) associate with plasma lipoprotein particles and distribute primarily to the liver after systemic administration to mice. We further demonstrated enhancement of silencing by administration of chol-siRNA pre-associated with isolated high-density lipoprotein (HDL) or low-density lipoprotein (LDL). In this study, we investigated mimetic lipoprotein particle prepared from recombinant apolipoprotein A1 (apoA) and apolipoprotein E3 (apoE) as a delivery vehicle for chol-siRNAs. We show that apoE-containing particle (E-lip) is highly effective in functional delivery of chol-siRNA to mouse liver. E-lip delivery was found to be considerably more potent than apoA-containing particle (A-lip). Furthermore, E-lip–mediated delivery was not significantly affected by high endogenous levels of plasma LDL. These results demonstrate that E-lip has substantial potential as delivery vehicles for lipophilic conjugates of siRNAs. PMID:22850721

  4. Computer Workstation: Pointer/Mouse

    MedlinePlus

    ... and long term use. Potential Hazards: When the sensitivity for the input device is not appropriately set, ... provide adequate control. A mouse that has insufficient sensitivity may require large deviation of the wrist to ...

  5. Mouse models for cancer research

    PubMed Central

    Zhang, Wei; Moore, Lynette; Ji, Ping

    2011-01-01

    Mouse models of cancer enable researchers to learn about tumor biology in complicated and dynamic physiological systems. Since the development of gene targeting in mice, cancer biologists have been among the most frequent users of transgenic mouse models, which have dramatically increased knowledge about how cancers form and grow. The Chinese Journal of Cancer will publish a series of papers reporting the use of mouse models in studying genetic events in cancer cases. This editorial is an overview of the development and applications of mouse models of cancer and directs the reader to upcoming papers describing the use of these models to be published in coming issues, beginning with three articles in the current issue. PMID:21352691

  6. Mouse Models of Gastric Carcinogenesis

    PubMed Central

    Yu, Sungsook; Yang, Mijeong

    2014-01-01

    Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field. PMID:25061535

  7. Reactivity of mouse antibodies against bromelain-treated mouse erythrocytes with thrombin-treated mouse platelets.

    PubMed Central

    Kawaguchi, S

    1989-01-01

    The reactivity of mouse antibodies against bromelain-treated mouse erythrocytes (BrMRBC) with mouse platelets before and after thrombin treatment was assessed by flow cytometry. Anti-BrMRBC antibodies could bind to thrombin-treated platelets, although normal platelets were also weakly reactive with the antibodies. The binding of anti-BrMRBC antibodies to platelets was confirmed by complement-dependent lysis. It is suggested that thrombin-activated platelets may be a real target for anti-BrMRBC antibodies. PMID:2467876

  8. Construction of mouse adenovirus type 1 mutants.

    PubMed

    Cauthen, Angela N; Welton, Amanda R; Spindler, Katherine R

    2007-01-01

    Mouse adenovirus provides a model for studying adenovirus pathogenesis in the natural host. The ability to make viral mutants allows the investigation of specific mouse adenoviral gene contributions to virus-host interactions. Methods for propagation and titration of wild-type mouse adenovirus, production of viral DNA and viral DNA-protein complex, and transfection of mouse cells to obtain mouse adenovirus mutants are described in this chapter. Plaque purification, propagation, and titration of the mutant viruses are also presented.

  9. Mink-mouse interspecific hybridomas.

    PubMed

    Ufimtseva, E G; Galakhar, N L; Matjakhina, L D; Khlebodarova, T M; Djatchenko, S N

    1991-08-01

    Mink-mouse interspecific hybridomas were produced by fusion of the american mink spleen cells with the NSO cells. Seven cloned lines of the mink-mouse hybridoma were isolated, and their functional mink Ig secretion and karyological characteristics are given. During cytogenetic analysis of mink-mouse hybridoma cell lines, we observed the elimination of mink chromosomes, and inter- and intralineral variability of the numbers of the cells with particular quantities of mink DNA. We did not find that the characteristic peculiarities of mink DNA distribution in the hybridoma cell lines had any bearing upon the secretion or non-secretion of mink Ig. There was no synthesis of lambda-L-chains of mink Ig in line 7 cells because the line lost the lambda-gene. With the aid of in situ hybridization with 3H-labeled total mink DNA, a considerable transformation of hybridoma cell karyotype was observed. Multiple integration of the mink DNA into mouse chromosomes and the appearance of chromosomes not characteristic for either the mink or mouse parent cells were noted. Increasing numbers of cells with translocations of mink chromosomes fragments into mouse chromosomes were found in the hybridoma lines cultivated for lengthy periods. PMID:1937502

  10. Mouse genetics: Catalogue and scissors

    PubMed Central

    Sung, Young Hoon; Baek, In-Jeoung; Seong, Je Kyung; Kim, Jin-Soo; Lee, Han-Woong

    2012-01-01

    Phenotypic analysis of gene-specific knockout (KO) mice has revolutionized our understanding of in vivo gene functions. As the use of mouse embryonic stem (ES) cells is inevitable for conventional gene targeting, the generation of knockout mice remains a very time-consuming and expensive process. To accelerate the large-scale production and phenotype analyses of KO mice, international efforts have organized global consortia such as the International Knockout Mouse Consortium (IKMC) and International Mouse Phenotype Consortium (IMPC), and they are persistently expanding the KO mouse catalogue that is publicly available for the researches studying specific genes of interests in vivo. However, new technologies, adopting zinc-finger nucleases (ZFNs) or Transcription Activator-Like Effector (TALE) Nucleases (TALENs) to edit the mouse genome, are now emerging as valuable and effective shortcuts alternative for the conventional gene targeting using ES cells. Here, we introduce the recent achievement of IKMC, and evaluate the significance of ZFN/TALEN technology in mouse genetics. [BMB Reports 2012; 45(12): 686-692] PMID:23261053

  11. A Reverse Stroop Task with Mouse Tracking.

    PubMed

    Yamamoto, Naohide; Incera, Sara; McLennan, Conor T

    2016-01-01

    In a reverse Stroop task, observers respond to the meaning of a color word irrespective of the color in which the word is printed-for example, the word red may be printed in the congruent color (red), an incongruent color (e.g., blue), or a neutral color (e.g., white). Although reading of color words in this task is often thought to be neither facilitated by congruent print colors nor interfered with incongruent print colors, this interference has been detected by using a response method that does not give any bias in favor of processing of word meanings or processing of print colors. On the other hand, evidence for the presence of facilitation in this task has been scarce, even though this facilitation is theoretically possible. By modifying the task such that participants respond to a stimulus color word by pointing to a corresponding response word on a computer screen with a mouse, the present study investigated the possibility that not only interference but also facilitation would take place in a reverse Stroop task. Importantly, in this study, participants' responses were dynamically tracked by recording the entire trajectories of the mouse. Arguably, this method provided richer information about participants' performance than traditional measures such as reaction time and accuracy, allowing for more detailed (and thus potentially more sensitive) investigation of facilitation and interference in the reverse Stroop task. These trajectories showed that the mouse's approach toward correct response words was significantly delayed by incongruent print colors but not affected by congruent print colors, demonstrating that only interference, not facilitation, was present in the current task. Implications of these findings are discussed within a theoretical framework in which the strength of association between a task and its response method plays a critical role in determining how word meanings and print colors interact in reverse Stroop tasks. PMID:27199881

  12. A Reverse Stroop Task with Mouse Tracking.

    PubMed

    Yamamoto, Naohide; Incera, Sara; McLennan, Conor T

    2016-01-01

    In a reverse Stroop task, observers respond to the meaning of a color word irrespective of the color in which the word is printed-for example, the word red may be printed in the congruent color (red), an incongruent color (e.g., blue), or a neutral color (e.g., white). Although reading of color words in this task is often thought to be neither facilitated by congruent print colors nor interfered with incongruent print colors, this interference has been detected by using a response method that does not give any bias in favor of processing of word meanings or processing of print colors. On the other hand, evidence for the presence of facilitation in this task has been scarce, even though this facilitation is theoretically possible. By modifying the task such that participants respond to a stimulus color word by pointing to a corresponding response word on a computer screen with a mouse, the present study investigated the possibility that not only interference but also facilitation would take place in a reverse Stroop task. Importantly, in this study, participants' responses were dynamically tracked by recording the entire trajectories of the mouse. Arguably, this method provided richer information about participants' performance than traditional measures such as reaction time and accuracy, allowing for more detailed (and thus potentially more sensitive) investigation of facilitation and interference in the reverse Stroop task. These trajectories showed that the mouse's approach toward correct response words was significantly delayed by incongruent print colors but not affected by congruent print colors, demonstrating that only interference, not facilitation, was present in the current task. Implications of these findings are discussed within a theoretical framework in which the strength of association between a task and its response method plays a critical role in determining how word meanings and print colors interact in reverse Stroop tasks.

  13. Discharge Property of Resin Particles Refined by Silica Particles

    NASA Astrophysics Data System (ADS)

    Makabe, Akira; Narita, Miyuki; Makino, Kazutaka; Hamada, Fumio

    2001-12-01

    The discharge property in the solid state has been utilized for ceramics processing and printer technology. The charge of particles has to be controlled in these fields because it affects the particle filling process in ceramics processing and the print quality of a printer. Fine silica particles are used to refine ceramics or resin particles for optimization of flowability, the discharge ability and the wettability. However, it is difficult to understand these properties, because critical factors “affecting” for these properties have not been elucidated yet. For example, the discharge property has not been examined in connection with the surface chemical structure of particles. In this study, we report the electron accepting or electron donating ability of chemicals and find that the discharge property is significantly influenced by that ability. Work function values are measured for polystyrene resin particles covered by different kinds of silica particles. In addition, we suggest a simple evaluation method for solid discharge through the measuring of pH in solution form. The relationships among the discharge, pH and work function values are examined. As a result, we arrive at some results to elucidate these phenomena.

  14. The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009

    SciTech Connect

    Russell, Liane B

    2013-01-01

    The large mouse genetics program at the Oak Ridge National Lab is often re-membered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-Chromosome s importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a valuable

  15. Microfabricated particle focusing device

    DOEpatents

    Ravula, Surendra K.; Arrington, Christian L.; Sigman, Jennifer K.; Branch, Darren W.; Brener, Igal; Clem, Paul G.; James, Conrad D.; Hill, Martyn; Boltryk, Rosemary June

    2013-04-23

    A microfabricated particle focusing device comprises an acoustic portion to preconcentrate particles over large spatial dimensions into particle streams and a dielectrophoretic portion for finer particle focusing into single-file columns. The device can be used for high throughput assays for which it is necessary to isolate and investigate small bundles of particles and single particles.

  16. Tricellulin deficiency affects tight junction architecture and cochlear hair cells

    PubMed Central

    Nayak, Gowri; Lee, Sue I.; Yousaf, Rizwan; Edelmann, Stephanie E.; Trincot, Claire; Van Itallie, Christina M.; Sinha, Ghanshyam P.; Rafeeq, Maria; Jones, Sherri M.; Belyantseva, Inna A.; Anderson, James M.; Forge, Andrew; Frolenkov, Gregory I.; Riazuddin, Saima

    2013-01-01

    The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media and reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a tricellular tight junction protein known as tricellulin, lead to nonsyndromic hearing loss (DFNB49). We generated a knockin mouse that carries a mutation orthologous to the TRIC coding mutation linked to DFNB49 hearing loss in humans. Tricellulin was absent from the tricellular junctions in the inner ear epithelia of the mutant animals, which developed rapidly progressing hearing loss accompanied by loss of mechanosensory cochlear hair cells, while the endocochlear potential and paracellular permeability of a biotin-based tracer in the stria vascularis were unaltered. Freeze-fracture electron microscopy revealed disruption of the strands of intramembrane particles connecting bicellular and tricellular junctions in the inner ear epithelia of tricellulin-deficient mice. These ultrastructural changes may selectively affect the paracellular permeability of ions or small molecules, resulting in a toxic microenvironment for cochlear hair cells. Consistent with this hypothesis, hair cell loss was rescued in tricellulin-deficient mice when generation of normal endolymph was inhibited by a concomitant deletion of the transcription factor, Pou3f4. Finally, comprehensive phenotypic screening showed a broader pathological phenotype in the mutant mice, which highlights the non-redundant roles played by tricellulin. PMID:23979167

  17. Tau phosphorylation affects its axonal transport and degradation

    PubMed Central

    Rodríguez-Martín, Teresa; Cuchillo-Ibáñez, Inmaculada; Noble, Wendy; Nyenya, Fanon; Anderton, Brian H.; Hanger, Diane P.

    2013-01-01

    Phosphorylated forms of microtubule-associated protein tau accumulate in neurofibrillary tangles in Alzheimer's disease. To investigate the effects of specific phosphorylated tau residues on its function, wild type or phosphomutant tau was expressed in cells. Elevated tau phosphorylation decreased its microtubule binding and bundling, and increased the number of motile tau particles, without affecting axonal transport kinetics. In contrast, reducing tau phosphorylation enhanced the amount of tau bound to microtubules and inhibited axonal transport of tau. To determine whether differential tau clearance is responsible for the increase in phosphomimic tau, we inhibited autophagy in neurons which resulted in a 3-fold accumulation of phosphomimic tau compared with wild type tau, and endogenous tau was unaffected. In autophagy-deficient mouse embryonic fibroblasts, but not in neurons, proteasomal degradation of phosphomutant tau was also reduced compared with wild type tau. Therefore, autophagic and proteasomal pathways are involved in tau degradation, with autophagy appearing to be the primary route for clearing phosphorylated tau in neurons. Defective autophagy might contribute to the accumulaton of tau in neurodegenerative diseases. PMID:23601672

  18. Interplay of particle shape and suspension properties: a study of cube-like particles.

    PubMed

    Audus, Debra J; Hassan, Ahmed M; Garboczi, Edward J; Douglas, Jack F

    2015-05-01

    With advances in anisotropic particle synthesis, particle shape is now a feasible parameter for tuning suspension properties. However, there is a need to determine how these newly synthesized particles affect suspension properties and a need to solve the inverse problem of inferring the particle shape from property measurements. Either way, accurate suspension property predictions are required. Towards this end, we calculated a set of dilute suspension properties for a family of cube-like particles that smoothly interpolate between spheres and cubes. Using three conceptually different methods, we numerically computed the electrical properties of particle suspensions, including the intrinsic conductivity of perfect conductors and insulators. We also considered hydrodynamic properties relevant to particle solutions including the hydrodynamic radius, the intrinsic viscosity and the intrinsic solvent diffusivity. Additionally, we determined the second osmotic virial coefficient using analytic expressions along with numerical integration. As the particles became more cube-like, we found that all of the properties investigated become more sensitive to particle shape.

  19. Toxicity of astatine-211 in the mouse.

    PubMed

    Cobb, L M; Harrison, A; Butler, S A

    1988-11-01

    The toxicity of the alpha particle emitting halogen astatine-211 was examined in male and female mice. Pathological changes were seen in mice killed at 14 days and/or at 56 days following a single injection of 61 kBq211 At per g body weight. The tissues affected, in order of severity were: spleen, lymph nodes, bone marrow, gonads, thyroid, salivary glands and stomach.

  20. Mapping mouse hemangioblast maturation from headfold stages

    PubMed Central

    Rhee, Jerry M.; Iannaccone, Philip M.

    2012-01-01

    The mouse posterior primitive streak at neural plate/headfold stages (NP/HF, ~7.5dpc–8dpc) represents an optimal window from which hemangioblasts can be isolated. We performed immunohistochemistry on this domain using established monoclonal antibodies for proteins that affect blood and endothelial fates. We demonstrate that HoxB4 and GATA1 are the first set of markers that segregate independently to endothelial or blood populations during NP/HF stages of mouse embryonic development. In a subset of cells, both proteins are co-expressed and immunoreactivities appear mutually excluded within nuclear spaces. We searched for this particular state at later sites of hematopoietic stem cell emergence, viz., the aorta-gonadmesonephros (AGM) and the fetal liver at 10.5–11.5dpc, and found that only a rare number of cells displayed this character. Based on this spatial-temporal argument, we propose that the earliest blood progenitors emerge either directly from the epiblast or through segregation within the allantoic core domain (ACD) through reduction of cell adhesion and pSmad1/5 nuclear signaling, followed by a stochastic decision toward a blood or endothelial fate that involves GATA1 and HoxB4, respectively. A third form in which binding distributions are balanced may represent a common condition shared by hemangioblasts and HSCs. We developed a heuristic model of hemangioblast maturation, in part, to be explicit about our assumptions. PMID:22426104

  1. Mouse Models of Frailty: an Emerging Field.

    PubMed

    Seldeen, K L; Pang, M; Troen, B R

    2015-10-01

    Frailty is highly prevalent in the elderly, increasing the risk of poor outcomes that include falls, incident disability, hospitalization, and mortality. Thus, a great need exists to characterize the underlying mechanisms and ultimately identify strategies that prevent, delay, and even reverse frailty. Mouse models can provide insight into molecular mechanisms of frailty by reducing variability in lifestyle and genetic factors that can complicate interpretation of human clinical data. Frailty, generally recognized as a syndrome involving reduced homeostatic reserve in response to physiologic challenges and increasing susceptibility to poor health outcomes, is predominantly assessed using two independent strategies, integrated phenotype and deficit accumulation. The integrated phenotype defines frailty by the presentation of factors affecting functional capacity such as weight loss, exhaustion, low activity levels, slow gait, and grip strength. The deficit accumulation paradigm draws parameters from a greater range of physiological systems, such as the ability to perform daily activities, coordination and gait, mental components, physiological problems, and history and presence of medical morbidities. This strategic division also applies within the emerging field of mouse frailty models, with both methodologies showing usefulness in providing insight into physiologic mechanisms and testing interventions. Our review will explore the strategies used, caveats in methodology, and future directions in the application of animal models for the study of the frailty syndrome.

  2. Modeling cytomegalovirus infection in mouse tumor models.

    PubMed

    Price, Richard Lee; Chiocca, Ennio Antonio

    2015-01-01

    The hypothesis that cytomegalovirus (CMV) modulates cancer is evolving. Originally discovered in glioblastoma in 2002, the number of cancers, where intratumoral CMV antigen is detected, has increased in recent years suggesting that CMV actively affects the pathobiology of certain tumors. These findings are controversial as several groups have also reported inability to replicate these results. Regardless, several clinical trials for glioblastoma are underway or have been completed that target intratumoral CMV with anti-viral drugs or immunotherapy. Therefore, a better understanding of the possible pathobiology of CMV in cancer needs to be ascertained. We have developed genetic, syngeneic, and orthotopic malignant glioma mouse models to study the role of CMV in cancer development and progression. These models recapitulate for the most part intratumoral CMV expression as seen in human tumors. Additionally, we discovered that CMV infection in Trp53(-/+) mice promotes pleomorphic rhabdomyosarcomas. These mouse models are not only a vehicle for studying pathobiology of the viral-tumor interaction but also a platform for developing and testing cancer therapeutics. PMID:25853089

  3. Calcineurin/NFAT pathway mediates wear particle-induced TNF-α release and osteoclastogenesis from mice bone marrow macrophages in vitro

    PubMed Central

    Liu, Feng-xiang; Wu, Chuan-long; Zhu, Zhen-an; Li, Mao-qiang; Mao, Yuan-qing; Liu, Ming; Wang, Xiao-qing; Yu, De-gang; Tang, Ting-ting

    2013-01-01

    Aim: To investigate the roles of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in regulation of wear particles-induced cytokine release and osteoclastogenesis from mouse bone marrow macrophages in vitro. Methods: Osteoclasts were induced from mouse bone marrow macrophages (BMMs) in the presence of 100 ng/mL receptor activator of NF-κB ligand (RANKL). Acridine orange staining and MTT assay were used to detect the cell viability. Osteoclastogenesis was determined using TRAP staining and RT-PCR. Bone pit resorption assay was used to examine osteoclast phenotype. The expression and cellular localization of NFATc1 were examined using RT-PCR and immunofluorescent staining. The production of TNFα was analyzed with ELISA. Results: Titanium (Ti) or polymethylmethacrylate (PMMA) particles (0.1 mg/mL) did not significantly change the viability of BMMs, but twice increased the differentiation of BMMs into mature osteoclasts, and markedly increased TNF-α production. The TNF-α level in the PMMA group was significantly higher than in the Ti group (96 h). The expression of NFATc1 was found in BMMs in the presence of the wear particles and RANKL. In bone pit resorption assay, the wear particles significantly increased the resorption area and total number of resorption pits in BMMs-seeded ivory slices. Addition of 11R-VIVIT peptide (a specific inhibitor of calcineurin-mediated NFAT activation, 2.0 μmol/L) did not significantly affect the viability of BMMs, but abolished almost all the wear particle-induced alterations in BMMs. Furthermore, VIVIT reduced TNF-α production much more efficiently in the PMMA group than in the Ti group (96 h). Conclusion: Calcineurin/NFAT pathway mediates wear particles-induced TNF-α release and osteoclastogenesis from BMMs. Blockade of this signaling pathway with VIVIT may provide a promising therapeutic modality for the treatment of periprosthetic osteolysis. PMID:24056707

  4. Functionally charged nanosize particles differentially activate BV2 microglia.

    EPA Science Inventory

    The effect of particle surface charge on the biological activation of immortalized mouse microglia (BV2) was examined. Nanosize (860-950 nm) spherical polystyrene microparticles (SPM) were coated with carboxyl (COOH-) or dimethyl amino (CH3)2-N- groups to give a net negative or p...

  5. An approach to evaluating and correcting aerodynamic particle sizer measurements for phantom particle count creation.

    PubMed

    Heitbrink, W A; Baron, P A

    1992-07-01

    An aerodynamic particle sizer (APS) can be used to make real-time measurements of the aerodynamic particle size distribution over the range of 0.5 to 32 microns. This instrument is very useful in conducting health-related aerosol measurements involving aerosol generation, respirator efficiency, and particulate sampling efficiency. One of the two signal processors within the APS can create spurious or phantom particle counts that can significantly affect relative measurements and calculated mass distributions. In the APS, particle size measurement is based upon a particle's transit time between two laser beams that are perpendicular to an accelerating airflow. The signal processors measure each particle's transit from the time between the two pulses of scattered light that are generated as the particle passes through the two laser beams. When only a single pulse from a particle is detected, another pulse can cause the recording of a randomly sized phantom particle. The small particle processor (SPP), which measures particle transit from the times in digital increments of 4 nanoseconds, can create phantom particles; the large particle processor (LPP), which measures particle transit times in digital increments of 66.67 nanoseconds, is designed to prevent the creation of phantom particles. These two processors overlap in the range of 5.2 to 15.4 microns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1496933

  6. Interpretation of the Moessbauer Spectra of the Magnetic Nanoparticles in Mouse Spleen

    SciTech Connect

    Chuev, Mikhail A.; Cherepanov, Valery M.; Polikarpov, Mikhail A.; Panchenko, Vladislav Y.; Deyev, Sergey M.; Mischenko, Iliya N.; Nikitin, Maxim P.

    2010-12-02

    We have developed a stochastic model for description of relaxation effects in the system of homogeneously magnetized single-domain particles and applied the model to the analysis of Moessbauer spectra of magnetic nanoparticles (Chemicell ARA) and mouse spleen after i.v. injection into animals. We estimate that the fraction of exogenous iron in nanoparticles in the mouse spleen 3 months after injection was 0.27{+-}0.03. The spectra of the residual nanoparticles in the spleen had almost the same isomer shift but smaller mean hyperfine magnetic field values indicating decrease in the magnetic anisotropy energy (size) of the particles compared to the initial ones in the course of biodegradation. Concentration of ferritin-like iron was about three-fold higher than that in the spleen of untreated animals showing ferritin-like forms in the mouse spleen.

  7. Mouse models of primary Sjögren’s syndrome

    PubMed Central

    Park, Young-Seok; Gauna, Adrienne E.; Cha, Seunghee

    2015-01-01

    Sjögren’s syndrome (SjS) is a chronic autoimmune disorder characterized by immune cell infiltration and progressive injury to the salivary and lacrimal glands. As a consequence, patients with SjS develop xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). SjS is the third most common rheumatic autoimmune disorder, affecting 4 million Americans with over 90% of patients being female. Current diagnostic criteria for SjS frequently utilize histological examinations of minor salivary glands for immune cell foci, serology for autoantibodies, and dry eye evaluation by corneal or conjunctival staining. SjS can be classified as primary or secondary SjS, depending on whether it occurs alone or in association with other systemic rheumatic conditions, respectively. Clinical manifestations typically become apparent when the disease is relatively advanced in SjS patients, which poses a challenge for early diagnosis and treatment of SjS. Therefore, SjS mouse models, because of their close resemblance to the human SjS, have been extremely valuable to identify early disease markers and to investigate underlying biological and immunological dysregulations. However, it is important to bear in mind that no single mouse model has duplicated all aspects of SjS pathogenesis and clinical features, mainly due to the multifactorial etiology of SjS that includes numerous susceptibility genes and environmental factors. As such, various mouse models have been developed in the field to try to recapitulate SjS. In this review, we focus on recent mouse models of primary SjS and describe them under three categories of spontaneous, genetically engineered, and experimentally induced development of SjS-like disease. In addition, we discuss future perspectives of SjS mouse models highlighting pros and cons of utilizing mouse models and demands for improved models. PMID:25777752

  8. 10. international mouse genome conference

    SciTech Connect

    Meisler, M.H.

    1996-12-31

    Ten years after hosting the First International Mammalian Genome Conference in Paris in 1986, Dr. Jean-Louis Guenet presided over the Tenth Conference at the Pasteur Institute, October 7--10, 1996. The 1986 conference was a satellite to the Human Gene Mapping Workshop and had approximately 50 attendees. The 1996 meeting was attended by 300 scientists from around the world. In the interim, the number of mapped loci in the mouse increased from 1,000 to over 20,000. This report contains a listing of the program and its participants, and two articles that review the meeting and the role of the laboratory mouse in the Human Genome project. More than 200 papers were presented at the conference covering the following topics: International mouse chromosome committee meetings; Mutant generation and identification; Physical and genetic maps; New technology and resources; Chromatin structure and gene regulation; Rate and hamster genetic maps; Informatics and databases; and Quantitative trait analysis.

  9. Teratology studies in the mouse.

    PubMed

    Marsden, Edward; Leroy, Mariline

    2013-01-01

    The rat is the routine species of choice as the rodent model for regulatory safety testing of xenobiotics such as medicinal products, food additives, and other chemicals. However, the rat is not always suitable for pharmacological, toxicological, immunogenic, pharmacokinetic, or even practical reasons. Under such circumstances, the mouse offers an alternative for finding a suitable rodent model acceptable to the regulatory authorities. Since all essential routes of administration are possible, the short reproductive cycle and large litter size of the mouse make it a species well adapted for use in teratology studies. Given that good quality animals, including virgin mated females, can be acquired relatively easily and inexpensively, the mouse has been used in reproductive toxicity studies for decades and study protocols are well established.

  10. Modeling metastasis in the mouse

    PubMed Central

    Bos, Paula D.; Nguyen, Don X.; Massagué, Joan

    2010-01-01

    Metastasis is a complex clinical and biological problem presently under intense study, and several model systems are in use to experimentally recapitulate and dissect the various steps of the metastatic process. Genetically engineered mouse models provide faithful renditions of events in tumor progression, angiogenesis, and local invasion that set the stage for metastasis, whereas engrafting of human or mouse tumor tissues into mouse hosts has been successfully exploited to investigate metastatic dissemination and colonization of distant organs. Real-time, high-resolution microscopy in live animals, and comprehensive genetic and molecular profiling are effective tools to interrogate diverse metastatic cancer cell phenotypes as well as the metastatic tumor microenvironment in different organs. By integrating the information obtained with these complementary approaches the field is currently obtaining an unprecedented level of understanding of the biology, molecular basis, and therapeutic vulnerabilities of metastasis. PMID:20598638

  11. Automation of particle accelerator control

    SciTech Connect

    Silbar, R.R.; Schultz, D.E.

    1988-01-01

    We have begun a program aiming toward automatic control of charged-particle beam optics using artificial intelligence programming techniques. In developing our prototype, we are working with LISP machines and the KEE expert system shell. Our first goal was to develop a 'mouseable' representation of a typical beamline. This responds actively to changes input from the mouse or keyboard, giving an updated display of the beamline itself, its optical properties, and the instrumentation and control devices as seen by the operator. We have incorporated the Fortran beam optics code TRANSPORT for simulation of the beam. The paper describes the experience gained in this process and discusses plans to extend the work so that it is usable, in real-time, on an operating beamline. 11 refs., 2 figs.

  12. Morphological analysis of mouse lungs after treatment with magnetite-based magnetic fluid stabilized with DMSA

    NASA Astrophysics Data System (ADS)

    Garcia, Mônica Pereira; Miranda Parca, Renata; Braun Chaves, Sacha; Paulino Silva, Luciano; Djalma Santos, Antonio; Guerrero Marques Lacava, Zulmira; César Morais, Paulo; Azevedo, Ricardo Bentes

    2005-05-01

    Mouse lungs injected with magnetic fluids based on magnetite nanoparticles stabilized by 2,3-dimercaptosuccinic acid were studied. We observed clusters of magnetic nanoparticles inside blood vessels, within the organ parenchyma and cells, as well as increased numbers of leukocytes in the organ. Both the particle concentration and organ inflammation diminished in a time-dependent manner.

  13. Sampling of respirable isocyanate particles.

    PubMed

    Gylestam, Daniel; Gustavsson, Marcus; Karlsson, Daniel; Dalene, Marianne; Skarping, Gunnar

    2014-04-01

    An advanced design of a denuder impactor (DI) sampler has been developed for characterization of possible airborne isocyanate exposure in different particle size fractions. The sampler is equipped with 12 different parallel denuder tubes, 4 impaction stages with the cut-off values (d50) of: 9.5, 4, 2.5 and 1 µm, and an end filter that collects particles < 1 µm. All collecting parts were impregnated with di-n-butylamine DBA as the reagent in a mixture with acetic acid. The performance of the DI sampler was studied on a standard atmosphere containing gas and particulate isocyanates. The isocyanate atmosphere was generated by liquid permeation of 2,4-, 2,6-Toluene Diisocyanate (TDI), 1,6-Hexamethylene Diisocyanate (HDI) and Isophorone Diisocyanate (IPDI). 4,4'-Methylene Diphenyl Diisocyanate (MDI) particles were generated by heating of technical MDI and condensing the mixture of gas and particle-borne MDI in an atmosphere containing mixed salt particles. The study was performed in a 0.85 m3 environmental chamber with stainless steel walls. With the advancement of the DI sampler it is now possible to collect isocyanate particle samples for up to 320 min. The performance of the DI sampler is essentially unaffected by the humidity. The DI sampler and the ASSET EZ4-NCO sampler (Sigma-Aldrich/Supelco, Bellefonte, PA, USA) gave similar results. Sample losses within the DI sampler are low. In the environmental chamber it was observed that the particle distribution may be affected by the humidity and ageing. A scanning mobility particle sizer (SMPS) was used to separate a flow of selected fractions containing MDI particles from mixed MDI and salt particles. The particle-size distribution had a maximum at about 300 nm, but later in the environmental chamber 1 µm dominated. The distribution was very different as compared to with only NaCl or MDI present. The biological relevance for studying isocyanate nano particles is significant as these have the possibility to reach the

  14. Interallelic complementation at the mouse Mitf locus.

    PubMed Central

    Steingrímsson, Eiríkur; Arnheiter, Heinz; Hallsson, Jón Hallsteinn; Lamoreux, M Lynn; Copeland, Neal G; Jenkins, Nancy A

    2003-01-01

    Mutations at the mouse microphthalmia locus (Mitf) affect the development of different cell types, including melanocytes, retinal pigment epithelial cells of the eye, and osteoclasts. The MITF protein is a member of the MYC supergene family of basic-helix-loop-helix-leucine-zipper (bHLHZip) transcription factors and is known to regulate the expression of cell-specific target genes by binding DNA as homodimer or as heterodimer with related proteins. The many mutations isolated at the locus have different effects on the phenotype and can be arranged in an allelic series in which the phenotypes range from near normal to white microphthalmic animals with osteopetrosis. Previous investigations have shown that certain combinations of Mitf alleles complement each other, resulting in a phenotype more normal than that of each homozygote alone. Here we analyze this interallelic complementation in detail and show that it is limited to one particular allele, Mitf(Mi-white) (Mitf(Mi-wh)), a mutation affecting the DNA-binding domain. Both loss- and gain-of-function mutations are complemented, as are other Mitf mutations affecting the DNA-binding domain. Furthermore, this behavior is not restricted to particular cell types: Both eye development and coat color phenotypes are complemented. Our analysis suggests that Mitf(Mi-wh)-associated interallelic complementation is due to the unique biochemical nature of this mutation. PMID:12586714

  15. The Mouse Genome Database (MGD): mouse biology and model systems.

    PubMed

    Bult, Carol J; Eppig, Janan T; Kadin, James A; Richardson, Joel E; Blake, Judith A

    2008-01-01

    The Mouse Genome Database, (MGD, http://www.informatics.jax.org/), integrates genetic, genomic and phenotypic information about the laboratory mouse, a primary animal model for studying human biology and disease. MGD data content includes comprehensive characterization of genes and their functions, standardized descriptions of mouse phenotypes, extensive integration of DNA and protein sequence data, normalized representation of genome and genome variant information including comparative data on mammalian genes. Data within MGD are obtained from diverse sources including manual curation of the biomedical literature, direct contributions from individual investigator's laboratories and major informatics resource centers such as Ensembl, UniProt and NCBI. MGD collaborates with the bioinformatics community on the development of data and semantic standards such as the Gene Ontology (GO) and the Mammalian Phenotype (MP) Ontology. MGD provides a data-mining platform that enables the development of translational research hypotheses based on comparative genotype, phenotype and functional analyses. Both web-based querying and computational access to data are provided. Recent improvements in MGD described here include the association of gene trap data with mouse genes and a new batch query capability for customized data access and retrieval.

  16. Evaluation of in vivo low-dose mouse irradiation system

    NASA Astrophysics Data System (ADS)

    Noh, S. J.; Kim, H. J.; Kim, H.; Kye, Y.-U.; Kim, J. K.; Son, T. G.; Lee, M. W.; Jeong, D. H.; Yang, K. M.; Nam, S.-H.; Kang, Y.-R.

    2016-03-01

    This study aims to develop a facility that can irradiate subjects with a desired low dose, which can be used to assess the biological effects of low-dose radiation. We develop a single-occupancy mouse-cage and shelf system with adjustable geometric parameters, such as the distances and angles of the cages relative to the collimator. We assess the irradiation-level accuracy using two measurement methods. First, we calculate the angle and distance of each mouse cage relative to the irradiator. We employ a Monte Carlo n-particle simulation for all of the cages at a given distance from the radiation source to calculate the air kerma and the relative absorbed dose in the in-house designed shelving system; these are found to be approximately 0.108 and 0.109 Gy, respectively. Second, we measure the relative absorbed dose using glass dosimeters inserted directly into the heads and bodies of the mice. For a conventional irradiation system, the irradiation measurements show a maximum discrepancy of 42% between the absorbed and desired doses, whereas a discrepancy of only 6% from the desired dose is found for the designed mouse apartment system. In addition, multi-mouse cages are shown to yield to significantly greater differences in the mouse head and body relative absorbed doses, compared to the discrepancies found for single-occupancy cages in the conventional irradiation system. Our findings suggest that the in-house shelving system has greater reliability for the biological analysis of the effects of low-dose radiation.

  17. International Mouse Phenotyping Consortium (IMPC) —

    Cancer.gov

    The International Mouse Phenotyping Consortium (IMPC) comprises a group of major mouse genetics research institutions along with national funding organisations formed to address the challenge of developing an encyclopedia of mammalian gene function.

  18. The particles in town air

    PubMed Central

    Ellison, J. McK.

    1965-01-01

    Particles constitute an important part of air pollution, and their behaviour when suspended in air is very different from that of gas molecules: in particular, the mechanisms by which they become deposited on surfaces are different, and consequently the methods normally used for removing particles from the air, either for sampling or for cleaning it, rely mainly on mechanisms that do not enter into the behaviour of gas molecules. These mechanisms are described, and the ways in which they affect the problems of air pollution and its measurement are discussed. ImagesFIG. 8 PMID:14315713

  19. Enhanced stopping of macro-particles in particle-in-cell simulations

    SciTech Connect

    May, J.; Tonge, J.; Ellis, I.; Mori, W. B.; Fiuza, F.; Fonseca, R. A.; Silva, L. O.

    2014-05-15

    We derive an equation for energy transfer from relativistic charged particles to a cold background plasma appropriate for finite-size particles that are used in particle-in-cell simulation codes. Expressions for one-, two-, and three-dimensional particles are presented, with special attention given to the two-dimensional case. This energy transfer is due to the electric field of the wake set up in the background plasma by the relativistic particle. The enhanced stopping is dependent on the q{sup 2}/m, where q is the charge and m is the mass of the relativistic particle, and therefore simulation macro-particles with large charge but identical q/m will stop more rapidly. The stopping power also depends on the effective particle shape of the macro-particle. These conclusions are verified in particle-in-cell simulations. We present 2D simulations of test particles, relaxation of high-energy tails, and integrated fast ignition simulations showing that the enhanced drag on macro-particles may adversely affect the results of these simulations in a wide range of high-energy density plasma scenarios. We also describe a particle splitting algorithm which can potentially overcome this problem and show its effect in controlling the stopping of macro-particles.

  20. Adenovirus-mediated siRNA targeting CXCR2 attenuates titanium particle-induced osteolysis by suppressing osteoclast formation.

    PubMed

    Wang, Chen; Liu, Yang; Wang, Yang; Li, Hao; Zhang, Ran-Xi; He, Mi-Si; Chen, Liang; Wu, Ning-Ning; Liao, Yong; Deng, Zhong-Liang

    2016-01-01

    BACKGROUND Wear particle-induced peri-implant loosening is the most common complication affecting long-term outcomes in patients who undergo total joint arthroplasty. Wear particles and by-products from joint replacements may cause chronic local inflammation and foreign body reactions, which can in turn lead to osteolysis. Thus, inhibiting the formation and activity of osteoclasts may improve the functionality and long-term success of total joint arthroplasty. The aim of this study was to interfere with CXC chemokine receptor type 2 (CXCR2) to explore its role in wear particle-induced osteolysis. MATERIAL AND METHODS Morphological and biochemical assays were used to assess osteoclastogenesis in vivo and in vitro. CXCR2 was upregulated in osteoclast formation. RESULTS Local injection with adenovirus-mediated siRNA targeting CXCR2 inhibited titanium-induced osteolysis in a mouse calvarial model in vivo. Furthermore, siCXCR2 suppressed osteoclast formation both directly by acting on osteoclasts themselves and indirectly by altering RANKL and OPG expression in osteoblasts in vitro. CONCLUSIONS CXCR2 plays a critical role in particle-induced osteolysis, and siCXCR2 may be a novel treatment for aseptic loosening. PMID:26939934

  1. Adenovirus-Mediated siRNA Targeting CXCR2 Attenuates Titanium Particle-Induced Osteolysis by Suppressing Osteoclast Formation

    PubMed Central

    Wang, Chen; Liu, Yang; Wang, Yang; Li, Hao; Zhang, Ran-Xi; He, Mi-Si; Chen, Liang; Wu, Ning-Ning; Liao, Yong; Deng, Zhong-Liang

    2016-01-01

    Background Wear particle-induced peri-implant loosening is the most common complication affecting long-term outcomes in patients who undergo total joint arthroplasty. Wear particles and by-products from joint replacements may cause chronic local inflammation and foreign body reactions, which can in turn lead to osteolysis. Thus, inhibiting the formation and activity of osteoclasts may improve the functionality and long-term success of total joint arthroplasty. The aim of this study was to interfere with CXC chemokine receptor type 2 (CXCR2) to explore its role in wear particle-induced osteolysis. Material/Methods Morphological and biochemical assays were used to assess osteoclastogenesis in vivo and in vitro. CXCR2 was upregulated in osteoclast formation. Results Local injection with adenovirus-mediated siRNA targeting CXCR2 inhibited titanium-induced osteolysis in a mouse calvarial model in vivo. Furthermore, siCXCR2 suppressed osteoclast formation both directly by acting on osteoclasts themselves and indirectly by altering RANKL and OPG expression in osteoblasts in vitro. Conclusions CXCR2 plays a critical role in particle-induced osteolysis, and siCXCR2 may be a novel treatment for aseptic loosening. PMID:26939934

  2. Microphysical Processes Affecting the Pinatubo Volcanic Plume

    NASA Technical Reports Server (NTRS)

    Hamill, Patrick; Houben, Howard; Young, Richard; Turco, Richard; Zhao, Jingxia

    1996-01-01

    In this paper we consider microphysical processes which affect the formation of sulfate particles and their size distribution in a dispersing cloud. A model for the dispersion of the Mt. Pinatubo volcanic cloud is described. We then consider a single point in the dispersing cloud and study the effects of nucleation, condensation and coagulation on the time evolution of the particle size distribution at that point.

  3. Lipid Extraction from Mouse Feces

    PubMed Central

    Kraus, Daniel; Yang, Qin; Kahn, Barbara B.

    2016-01-01

    The analysis of feces composition is important for the study of energy metabolism, which comprises various measurements of energy intake, energy expenditure, and energy wasting. The current protocol describes how to measure energy-dense lipids in mouse feces using a modification of the method proposed by Folch et al. (1957). PMID:27110587

  4. Mouse Models of Rheumatoid Arthritis.

    PubMed

    Caplazi, P; Baca, M; Barck, K; Carano, R A D; DeVoss, J; Lee, W P; Bolon, B; Diehl, L

    2015-09-01

    Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients.

  5. APOPTOSIS IN WHOLE MOUSE OVARIES

    EPA Science Inventory

    Apoptosis in Whole Mouse Ovaries
    Robert M. Zucker Susan C. Jeffay and Sally D. Perreault
    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711.

  6. Mouse Models of Diabetic Neuropathy

    PubMed Central

    O'Brien, Phillipe D.; Sakowski, Stacey A.; Feldman, Eva L.

    2014-01-01

    Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and is associated with significant morbidity and mortality. DPN is characterized by progressive, distal-to-proximal degeneration of peripheral nerves that leads to pain, weakness, and eventual loss of sensation. The mechanisms underlying DPN pathogenesis are uncertain, and other than tight glycemic control in type 1 patients, there is no effective treatment. Mouse models of type 1 (T1DM) and type 2 diabetes (T2DM) are critical to improving our understanding of DPN pathophysiology and developing novel treatment strategies. In this review, we discuss the most widely used T1DM and T2DM mouse models for DPN research, with emphasis on the main neurologic phenotype of each model. We also discuss important considerations for selecting appropriate models for T1DM and T2DM DPN studies and describe the promise of novel emerging diabetic mouse models for DPN research. The development, characterization, and comprehensive neurologic phenotyping of clinically relevant mouse models for T1DM and T2DM will provide valuable resources for future studies examining DPN pathogenesis and novel therapeutic strategies. PMID:24615439

  7. Mouse models of myelodysplastic syndromes

    PubMed Central

    Beachy, Sarah H.; Aplan, Peter D.

    2010-01-01

    Synopsis Three general approaches have been used in an attempt to model myelodysplastic syndrome (MDS) in mice, including treatment with mutagens or carcinogens, xenotransplantation of human MDS cells, and genetic engineering of mouse hematopoietic cells. Xenotransplantation of cells from MDS patients has proved difficult, possibly due to the innate characteristics of the MDS clone and microenvironmental influences, including adverse effects of a host immune response. Genetic engineering of hematopoietic cells or mice has been accomplished by in vitro transfer of genes to mouse hematopoietic cells with subsequent transplantation into an irradiated host, or by modification of the mouse germline to generate mice with altered expression of genes of interest. A number of genes have been studied using these approaches, including RUNX1, Evi1, Npm1, SALL4B, NUP98-HOXD13, BCL2/NRAS, Arid4a, Polg and Dido. This review discusses the phenotypes observed in available mouse models for MDS with a concentration on a model that leads to aberrant expression of conserved homeobox (HOX) genes that are important regulators of normal hematopoiesis. Utilizing these models of MDS should allow a more complete understanding of the disease process and provide a platform for pre-clinical testing of therapeutic approaches. PMID:20359631

  8. Mouse Cochlear Whole Mount Immunofluorescence

    PubMed Central

    Akil, Omar; Lustig, Lawrence R.

    2016-01-01

    This protocol comprises the entire process of immunofluorescence staining on mouse cochlea whole mount, starting from tissue preparation to the mounting of the tissue. This technique provides “three-dimensional” views of the stained components in order to determine the localization of a protein of interest in the tissue in its natural state and environment. PMID:27547786

  9. Component(s) of Sendai virus that can induce interferon in mouse spleen cells.

    PubMed Central

    Ito, Y; Hosaka, Y

    1983-01-01

    To identify the active component of Sendai virus that induces interferon in mouse spleen cells, infectious and noninfectious viruses, envelope particles derived from them, and isolated hemagglutinin-neuraminidase (HN) glycoproteins were examined for interferon induction. The interaction between membranous structures containing Sendai virus HN glycoprotein and the receptors on the cell surface was shown to be sufficient for interferon induction in mouse spleen cells, suggesting that the actual inducer of interferon in mouse spleen cells is the HN glycoprotein of Sendai virus. When mouse spleen cells were stimulated in vitro with Sendai virus grown in eggs or LLC-MK2 cells or with membranous structures containing glycoproteins obtained from these viruses, interferon could be detected in the culture fluid. Furthermore, isolated HN glycoprotein per se could induce interferon in the cells. A linear correlation was found between the titer of interferon induced and the hemagglutinating activity of the membranous structure containing the HN glycoprotein. It was concluded from these findings that HN glycoprotein was the active component of Sendai virus responsible for interferon induction in mouse spleen cells and that viral RNA and F glycoprotein were not required. The results also showed that the interaction between HN glycoprotein and receptors on the cell surface triggered production of type I interferon (IFN-alpha and IFN-beta). Although when Sendai virus was incubated at 56 degrees C for 5 min it lost its hemolytic and hemagglutinating activities, it induced a considerable amount of interferon in the culture fluid of mouse spleen cells. The interferon-inducing ability of heat-inactivated virus could be absorbed with mouse spleen cells but not with sheep erythrocytes or mouse erythrocytes, indicating that the inactivated virus retained ability to bind to mouse lymphoid cells. PMID:6301988

  10. Solar Energetic Particle Variations

    NASA Technical Reports Server (NTRS)

    Reames, D. V.

    2003-01-01

    In the largest solar energetic-particle (SEP) events, acceleration occurs at shock waves driven out from the Sun by coronal mass ejections (CMEs). In fact, the highest proton intensities directly measured near Earth at energies up to approximately 1 GeV occur at the time of passage of shocks, which arrive about a day after the CMEs leave the Sun. CME-driven shocks expanding across magnetic fields can fill over half of the heliosphere with SEPs. Proton-generated Alfven waves trap particles near the shock for efficient acceleration but also throttle the intensities at Earth to the streaming limit early in the events. At high energies, particles begin to leak from the shock and the spectrum rolls downward to form an energy-spectral 'knee' that can vary in energy from approximately 1 MeV to approximately 1 GeV in different events. All of these factors affect the radiation dose as a function of depth and latitude in the Earth's atmosphere and the risk to astronauts and equipment in space. SEP ionization of the polar atmosphere produces nitrates that precipitate to become trapped in the polar ice. Observations of nitrate deposits in ice cores reveal individual large SEP events and extend back approximately 400 years. Unlike sunspots, SEP events follow the approximately 80-100-year Gleissberg cycle rather faithfully and are now at a minimum in that cycle. The largest SEP event in the last 400 years appears to be related to the flare observed by Carrington in 1859, but the probability of SEP events with such large fluences falls off sharply because of the streaming limit.

  11. EFFECTS OF LEAKAGE NEUTRAL PARTICLES ON SHOCKS

    SciTech Connect

    Ohira, Yutaka

    2012-10-20

    In this paper, we investigate effects of neutral particles on shocks propagating into the partially ionized medium. We find that for 120 km s{sup -1} < u {sub sh} < 3000 km s{sup -1} (u {sub sh} is the shock velocity), about 10% of upstream neutral particles leak into the upstream region from the downstream region. Moreover, we investigate how the leakage neutral particles affect the upstream structure of the shock and particle accelerations. Using four-fluid approximations (upstream ions, upstream neutral particles, leakage neutral particles, and pickup ions), we provide analytical solutions of the precursor structure due to leakage neutral particles. It is shown that the upstream flow is decelerated in the precursor region and the shock compression ratio becomes smaller than without leakage neutral particles, but the total compression ratio does not change. Even if leakage of neutral particles is small (a few percent of total upstream particles), this smaller compression ratio of the shock can explain steep gamma-ray spectra from young supernova remnants. Furthermore, leakage neutral particles could amplify the magnetic field and heat the upstream region.

  12. Role of serotonin in seasonal affective disorder.

    PubMed

    Gupta, A; Sharma, P K; Garg, V K; Singh, A K; Mondal, S C

    2013-01-01

    This review was prepared with an aim to show role of serotonin in seasonal affective disorder. Seasonal affective disorder, which is also called as winter depression or winter blues, is mood disorder in which persons with normal mental health throughout most of the year will show depressive symptoms in the winter or, less commonly, in the summer. Serotonin is an important endogenous neurotransmitter which also acts as neuromodulator. The least invasive, natural, and researched treatment of seasonal affective disorder is natural or otherwise is light therapy. Negative air ionization, which acts by liberating charged particles on the sleep environment, has also become effective in treatment of seasonal affective disorder.  

  13. Particle interactions in microemulsion systems

    SciTech Connect

    Brouwer, W.M.; Nieuwenhuis, E.A.; Kops-Werkhoven, M.M.

    1983-03-01

    This study obtains information about the type of interactions between microemulsion particles as a function of their composition using time averaged and dynamic light scattering and sedimentation measurements and checks the consistency of the experimental data with respect to the generalized Einstein relation. Interactions between microemulsion particles are affected by the flexibility of the soap chains. The more flexible the soap chains, the lesser the attraction forces between the particles. The lack of consistency in the interaction behavior as obtained from different experimental techniques is an important observation, which leads to the conclusion that care should be taken in the determination of the interaction behavior in microemulsion systems from one or 2 experimental techniques. 24 referernces.

  14. Prevention of Wear Particle-Induced Osteolysis by a Novel V-ATPase Inhibitor Saliphenylhalamide through Inhibition of Osteoclast Bone Resorption

    PubMed Central

    Lin, Zhen; Cao, Lei; Chim, Shek M.; Pavlos, Nathan J.; Xu, Jiake; Zheng, Ming Hao; Dai, Ke Rong

    2012-01-01

    Wear particle-induced peri-implant loosening (Aseptic prosthetic loosening) is one of the most common causes of total joint arthroplasty. It is well established that extensive bone destruction (osteolysis) by osteoclasts is responsible for wear particle-induced peri-implant loosening. Thus, inhibition of osteoclastic bone resorption should prevent wear particle induced osteolysis and may serve as a potential therapeutic avenue for prosthetic loosening. Here, we demonstrate for the first time that saliphenylhalamide, a new V-ATPase inhibitor attenuates wear particle-induced osteolysis in a mouse calvarial model. In vitro biochemical and morphological assays revealed that the inhibition of osteolysis is partially attributed to a disruption in osteoclast acidification and polarization, both a prerequisite for osteoclast bone resorption. Interestingly, the V-ATPase inhibitor also impaired osteoclast differentiation via the inhibition of RANKL-induced NF-κB and ERK signaling pathways. In conclusion, we showed that saliphenylhalamide affected multiple physiological processes including osteoclast differentiation, acidification and polarization, leading to inhibition of osteoclast bone resorption in vitro and wear particle-induced osteolysis in vivo. The results of the study provide proof that the new generation V-ATPase inhibitors, such as saliphenylhalamide, are potential anti-resorptive agents for treatment of peri-implant osteolysis. PMID:22509274

  15. Hippocampal Damage in Mouse and Human Forms of Systemic Autoimmune Disease

    PubMed Central

    Ballok, David A.; Woulfe, John; Sur, Monalisa; Cyr, Michael; Sakic, Boris

    2006-01-01

    Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) and cognitive deficits of unknown etiology. By using autoimmune MRL-lpr mice as an animal model of NP-SLE, we examine the relationship between autoimmunity, hippocampal damage, and behavioral dysfunction. Fluoro Jade B (FJB) staining and anti-ubiquitin (anti-Ub) immunocytochemistry were used to assess neuronal damage in young (asymptomatic) and aged (diseased) mice, while spontaneous alternation behavior (SAB) was used to estimate the severity of hippocampal dysfunction. The causal relationship between autoimmunity and neuropathology was tested by prolonged administration of the immunosuppressive drug cyclophosphamide (CY). In comparison to congenic MRL +/+ controls, SAB acquisition rates and performance in the “reversal” trial were impaired in diseased MRL-lpr mice, suggesting limited use of the spatial learning strategy. FJB-positive neurons and anti-Ub particles were frequent in the CA3 region. Conversely, CY treatment attenuated the SAB deficit and overall FJB staining. Similarly to mouse brain, the hippocampus from a patient who died from NP-SLE showed reduced neuronal density in the CA3 region and dentate gyrus, as well as increased FJB positivity in these regions. Gliosis and neuronal loss were observed in the gray matter, and T lymphocytes and stromal calcifications were common in the choroid plexus. Taken together, these results suggest that systemic autoimmunity induces significant hippocampal damage, which may underlie affective and cognitive deficits in NP-SLE. PMID:15301441

  16. Ingestion of yeast forms of Sporothrix schenckii by mouse peritoneal macrophages.

    PubMed Central

    Oda, L M; Kubelka, C F; Alviano, C S; Travassos, L R

    1983-01-01

    The ingestion by thioglycolate-elicited mouse peritoneal macrophages of yeast forms of two strains of Sporothrix schenckii was studied. Yeast forms opsonized with concanavalin A (ConA) were extensively phagocytized, and the phagocytic indexes depended on the concentration of ConA and apparently on the number of lectin receptors at the yeast surface as well. Neuraminidase treatment of S. schenckii increased the ingestion of unopsonized yeasts 7.7-fold. The addition of monosaccharides and derivatives partially inhibited phagocytosis. Mannose, rhamnose, and galactose, which are major constituents of S. schenckii surface antigens, reduced the phagocytic indexes by 40 to 50%. Glucosamine, N-acetylglucosamine, and N-acetylneuraminic acid were equally effective as inhibitors of phagocytosis. A mixture of five neutral sugars and glucosamine inhibited phagocytosis by 73%. The inhibitory effect of simple sugars could be amplified by using neuraminidase-treated yeast cells. Pentoses and glucose were inactive or slightly inhibitory. A purified rhamnomannan inhibited phagocytosis of the homologous strain, whereas partially purified peptidopolysaccharides were toxic to peritoneal macrophages. A partially purified galactomannan from S. schenckii was inhibitory (62% inhibition), and a peptidopolysaccharide fraction in which the O-linked carbohydrate chains had been removed neither was toxic to macrophages nor inhibited phagocytosis. Pretreatment of macrophages with simple sugars under conditions inhibiting ingestion or binding of S. schenckii did not affect phagocytosis of latex particles or sensitized sheep erythrocytes. The presence of receptors at the peritoneal macrophages which bind S. schenckii cell surface components is suggested. PMID:6832808

  17. Hippocampal damage in mouse and human forms of systemic autoimmune disease.

    PubMed

    Ballok, David A; Woulfe, John; Sur, Monalisa; Cyr, Michael; Sakic, Boris

    2004-01-01

    Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) and cognitive deficits of unknown etiology. By using autoimmune MRL-lpr mice as an animal model of NP-SLE, we examine the relationship between autoimmunity, hippocampal damage, and behavioral dysfunction. Fluoro Jade B (FJB) staining and anti-ubiquitin (anti-Ub) immunocytochemistry were used to assess neuronal damage in young (asymptomatic) and aged (diseased) mice, while spontaneous alternation behavior (SAB) was used to estimate the severity of hippocampal dysfunction. The causal relationship between autoimmunity and neuropathology was tested by prolonged administration of the immunosuppressive drug cyclophosphamide (CY). In comparison to congenic MRL +/+ controls, SAB acquisition rates and performance in the "reversal" trial were impaired in diseased MRL-lpr mice, suggesting limited use of the spatial learning strategy. FJB-positive neurons and anti-Ub particles were frequent in the CA3 region. Conversely, CY treatment attenuated the SAB deficit and overall FJB staining. Similarly to mouse brain, the hippocampus from a patient who died from NP-SLE showed reduced neuronal density in the CA3 region and dentate gyrus, as well as increased FJB positivity in these regions. Gliosis and neuronal loss were observed in the gray matter, and T lymphocytes and stromal calcifications were common in the choroid plexus. Taken together, these results suggest that systemic autoimmunity induces significant hippocampal damage, which may underlie affective and cognitive deficits in NP-SLE. PMID:15301441

  18. Soft particles at a fluid interface

    NASA Astrophysics Data System (ADS)

    Mehrabian, Hadi; Harting, Jens; Snoeijer, Jacco H.

    2015-11-01

    Particles added to a fluid interface can be used as a surface stabilizer in the food, oil and cosmetic industries. As an alternative to rigid particles, it is promising to consider highly deformable particles that can adapt their conformation at the interface. In this study, we compute the shapes of soft elastic particles using molecular dynamics simulations of a cross-linked polymer gel, complemented by continuum calculations based on the linear elasticity. It is shown that the particle shape is not only affected by the Young's modulus of the particle, but also strongly depends on whether the gel is partially or completely wetting the fluid interface. We find that the molecular simulations for the partially wetting case are very accurately described by the continuum theory. By contrast, when the gel is completely wetting the fluid interface the linear theory breaks down and we reveal that molecular details have a strong influence on the equilibrium shape.

  19. Manipulation of particles by weak forces

    NASA Technical Reports Server (NTRS)

    Adler, M. S.; Savkar, S. D.; Summerhayes, H. R.

    1972-01-01

    Quantitative relations between various force fields and their effects on the motion of particles of various sizes and physical characteristics were studied. The forces considered were those derived from light, heat, microwaves, electric interactions, magnetic interactions, particulate interactions, and sound. A physical understanding is given of the forces considered as well as formulae which express how the size of the force depends on the physical and electrical properties of the particle. The drift velocity in a viscous fluid is evaluated as a function of initial acceleration and the effects of thermal random motion are considered. A means of selectively sorting or moving particles by choosing a force system and/or environment such that the particle of interest reacts uniquely was developed. The forces considered and a demonstration of how the initial acceleration, drift velocity, and ultimate particle density distribution is affected by particle, input, and environmental parameters are tabulated.

  20. Retinoic acid has different effects on UCP1 expression in mouse and human adipocytes

    PubMed Central

    2013-01-01

    Background Increased adipose thermogenesis is being considered as a strategy aimed at preventing or reversing obesity. Thus, regulation of the uncoupling protein 1 (UCP1) gene in human adipocytes is of significant interest. Retinoic acid (RA), the carboxylic acid form of vitamin A, displays agonist activity toward several nuclear hormone receptors, including RA receptors (RARs) and peroxisome proliferator-activated receptor δ (PPARδ). Moreover, RA is a potent positive regulator of UCP1 expression in mouse adipocytes. Results The effects of all-trans RA (ATRA) on UCP1 gene expression in models of mouse and human adipocyte differentiation were investigated. ATRA induced UCP1 expression in all mouse white and brown adipocytes, but inhibited or had no effect on UCP1 expression in human adipocyte cell lines and primary human white adipocytes. Experiments with various RAR agonists and a RAR antagonist in mouse cells demonstrated that the stimulatory effect of ATRA on UCP1 gene expression was indeed mediated by RARs. Consistently, a PPARδ agonist was without effect. Moreover, the ATRA-mediated induction of UCP1 expression in mouse adipocytes was independent of PPARγ coactivator-1α. Conclusions UCP1 expression is differently affected by ATRA in mouse and human adipocytes. ATRA induces UCP1 expression in mouse adipocytes through activation of RARs, whereas expression of UCP1 in human adipocytes is not increased by exposure to ATRA. PMID:24059847

  1. EFFECTS OF TUMORS ON INHALED PHARMACOLOGIC DRUGS: II. PARTICLE MOTION

    EPA Science Inventory

    ABSTRACT

    Computer simulations were conducted to describe drug particle motion in human lung bifurcations with tumors. The computations used FIDAP with a Cray T90 supercomputer. The objective was to better understand particle behavior as affected by particle characteristics...

  2. Mouse Models of Rare Craniofacial Disorders.

    PubMed

    Achilleos, Annita; Trainor, Paul A

    2015-01-01

    A rare disease is defined as a condition that affects less than 1 in 2000 individuals. Currently more than 7000 rare diseases have been documented, and most are thought to be of genetic origin. Rare diseases primarily affect children, and congenital craniofacial syndromes and disorders constitute a significant proportion of rare diseases, with over 700 having been described to date. Modeling craniofacial disorders in animal models has been instrumental in uncovering the etiology and pathogenesis of numerous conditions and in some cases has even led to potential therapeutic avenues for their prevention. In this chapter, we focus primarily on two general classes of rare disorders, ribosomopathies and ciliopathies, and the surprising finding that the disruption of fundamental, global processes can result in tissue-specific craniofacial defects. In addition, we discuss recent advances in understanding the pathogenesis of an extremely rare and specific craniofacial condition known as syngnathia, based on the first mouse models for this condition. Approximately 1% of all babies are born with a minor or major developmental anomaly, and individuals suffering from rare diseases deserve the same quality of treatment and care and attention to their disease as other patients. PMID:26589934

  3. A Reverse Stroop Task with Mouse Tracking

    PubMed Central

    Yamamoto, Naohide; Incera, Sara; McLennan, Conor T.

    2016-01-01

    In a reverse Stroop task, observers respond to the meaning of a color word irrespective of the color in which the word is printed—for example, the word red may be printed in the congruent color (red), an incongruent color (e.g., blue), or a neutral color (e.g., white). Although reading of color words in this task is often thought to be neither facilitated by congruent print colors nor interfered with incongruent print colors, this interference has been detected by using a response method that does not give any bias in favor of processing of word meanings or processing of print colors. On the other hand, evidence for the presence of facilitation in this task has been scarce, even though this facilitation is theoretically possible. By modifying the task such that participants respond to a stimulus color word by pointing to a corresponding response word on a computer screen with a mouse, the present study investigated the possibility that not only interference but also facilitation would take place in a reverse Stroop task. Importantly, in this study, participants’ responses were dynamically tracked by recording the entire trajectories of the mouse. Arguably, this method provided richer information about participants’ performance than traditional measures such as reaction time and accuracy, allowing for more detailed (and thus potentially more sensitive) investigation of facilitation and interference in the reverse Stroop task. These trajectories showed that the mouse’s approach toward correct response words was significantly delayed by incongruent print colors but not affected by congruent print colors, demonstrating that only interference, not facilitation, was present in the current task. Implications of these findings are discussed within a theoretical framework in which the strength of association between a task and its response method plays a critical role in determining how word meanings and print colors interact in reverse Stroop tasks. PMID:27199881

  4. Mouse models of intestinal inflammation and cancer.

    PubMed

    Westbrook, Aya M; Szakmary, Akos; Schiestl, Robert H

    2016-09-01

    Chronic inflammation is strongly associated with approximately one-fifth of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here, we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With

  5. Mousepox outbreak in a laboratory mouse colony.

    PubMed

    Dick, E J; Kittell, C L; Meyer, H; Farrar, P L; Ropp, S L; Esposito, J J; Buller, R M; Neubauer, H; Kang, Y H; McKee, A E

    1996-12-01

    Mousepox was diagnosed in and eradicated from a laboratory mouse colony at the Naval Medical Research Institute. The outbreak began with increased mortality in a single room; subsequently, small numbers of animals in separate cages in other rooms were involved. Signs of disease were often mild, and overall mortality was low; BALB/cByJ mice were more severely affected, and many of them died spontaneously. Conjunctivitis was the most common clinical sign of disease in addition to occasional small, crusty scabs on sparsely haired or hairless areas of skin. Necropsy findings included conjunctivitis, enlarged spleen, and pale liver. Hemorrhage into the pyloric region of the stomach and proximal portion of the small intestine was observed in experimentally infected animals. In immune competent and immune deficient mice, the most common histologic finding was multifocal to coalescing splenic necrosis; necrosis was seen less frequently in liver, lymph nodes, and Peyer's patches. Necrosis was rarely observed in ovary, vagina, uterus, colon, or lung. Splenic necrosis often involved over 50% of the examined tissue, including white and red pulp. Hepatic necrosis was evident as either large, well-demarcated areas of coagulative necrosis or as multiple, random, interlacing bands of necrosis. Intracytoplasmic eosinophilic inclusion bodies were seen in conjunctival mucosae and haired palpebra. Ectromelia virus was confirmed as the causative agent of the epizootic by electron microscopy, immunohistochemistry, animal inoculations, serologic testing, virus isolation, and polymerase chain reaction. Serologic testing was of little value in the initial stages of the outbreak, although 6 weeks later, orthopoxvirus-specific antibody was detected in colony mice by indirect fluorescent antibody and enzyme-linked immunosorbent assay procedures. The outbreak originated from injection of mice with a contaminated, commercially produced, pooled mouse serum. The most relevant concern may be the

  6. Live dynamic imaging and analysis of developmental cardiac defects in mouse models with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Lopez, Andrew L.; Wang, Shang; Garcia, Monica; Valladolid, Christian; Larin, Kirill V.; Larina, Irina V.

    2015-03-01

    Understanding mouse embryonic development is an invaluable resource for our interpretation of normal human embryology and congenital defects. Our research focuses on developing methods for live imaging and dynamic characterization of early embryonic development in mouse models of human diseases. Using multidisciplinary methods: optical coherence tomography (OCT), live mouse embryo manipulations and static embryo culture, molecular biology, advanced image processing and computational modeling we aim to understand developmental processes. We have developed an OCT based approach to image live early mouse embryos (E8.5 - E9.5) cultured on an imaging stage and visualize developmental events with a spatial resolution of a few micrometers (less than the size of an individual cell) and a frame rate of up to hundreds of frames per second and reconstruct cardiodynamics in 4D (3D+time). We are now using these methods to study how specific embryonic lethal mutations affect cardiac morphology and function during early development.

  7. Generation of mouse mutants as tools in dissecting the molecular clock.

    PubMed

    Anand, Sneha N; Edwards, Jessica K; Nolan, Patrick M

    2012-01-01

    Elucidation of the molecular basis of mammalian circadian rhythms has progressed dramatically in recent years through the characterization of mouse mutants. With the implementation of numerous mouse genetics programs, comprehensive sets of mutations in genes affecting circadian output measures have been generated. Although incomplete, existing arrays of mutants have been instrumental in our understanding of how the internal SCN clock interacts with the environment and how it conveys its rhythm to remote oscillators. The use of ENU mutagenesis has proven to be a significant contributor, generating mutations leading to subtle and distinct alterations in circadian protein function. In parallel, progress with mouse gene targeting allows one to study gene function in depth by ablating it entirely, in specific tissues at specific times, or by targeting specific functional domains. This has culminated in worldwide efforts to target every gene in the mouse genome allowing researchers to study multiple gene targeting effects systematically.

  8. Particle shape variations within a Luvisol profile

    NASA Astrophysics Data System (ADS)

    Jakab, Gergely; Kiss, Klaudia; Szalai, Zoltán; Ringer, Marianna; Zacháry, Dóra; Szabó, Judit; Varga, György

    2016-04-01

    Particle size distribution has crucial importance in soil physics. On the other hand particle shape properties were only taken into account in case of transport process investigations. Eolic or fluvial translocations have an effective impact on particle shape changes of loose sediment grains. Pedogenic processes also affect soil particle shape, however, this type of degradation and reformation based on chemical interactions. Moreover soil particles are strongly associated with each other and organic components hence the preparation of individual grains is difficult. Present study aims to compare particle size and shape data among several horizons of a Luvisol. The theoretically uniform initial sediment profile was differentiated due to pedogenesis and particle migration within the solum. Shape properties was estimated using two dimensional static image analysis. The applied device was Morphologi G3 by Malvern Instruments. Sample dispersion was made by high pressured air injection that scatters the particles onto a glass plate. The images are taken via a set of optics with various magnifications. Low (10 times) magnification was used for particles > 10 μ and high (50 times) magnification for particles < 10 μ. Particle size distribution was measured using the Fritch Analysette 22 MicroTec Plus laser diffraction device. Preliminary results suggest that the clay size particles are more rounded compared to the bigger grains in each horizon. Most angular particles are in the parent material and on the surface, while the most rounded are in the "B" horizons. This result could be the effect of particle size distribution differences among the horizons, however size distribution results seems to be a function of the applied method, eg. image analysis or laser diffraction. Present study was supported by National Hungarian Research Found K100180, G. Jakab was supported by the János Bolyai fellowship of the HAS.

  9. Monodisperse Block Copolymer Particles with Controllable Size, Shape, and Nanostructure

    NASA Astrophysics Data System (ADS)

    Shin, Jae Man; Kim, Yongjoo; Kim, Bumjoon; PNEL Team

    Shape-anisotropic particles are important class of novel colloidal building block for their functionality is more strongly governed by their shape, size and nanostructure compared to conventional spherical particles. Recently, facile strategy for producing non-spherical polymeric particles by interfacial engineering received significant attention. However, achieving uniform size distribution of particles together with controlled shape and nanostructure has not been achieved. Here, we introduce versatile system for producing monodisperse BCP particles with controlled size, shape and morphology. Polystyrene-b-polybutadiene (PS-b-PB) self-assembled to either onion-like or striped ellipsoid particle, where final structure is governed by amount of adsorbed sodium dodecyl sulfate (SDS) surfactant at the particle/surrounding interface. Further control of molecular weight and particle size enabled fine-tuning of aspect ratio of ellipsoid particle. Underlying physics of free energy for morphology formation and entropic penalty associated with bending BCP chains strongly affects particle structure and specification.

  10. Mouse Models of Human Phenylketonuria

    PubMed Central

    Shedlovsky, A.; McDonald, J. D.; Symula, D.; Dove, W. F.

    1993-01-01

    Phenylketonuria (PKU) results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine (PHE) to tyrosine. Although this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known of the mechanism(s) involved in the pathology of PKU. We have combined mouse germline mutagenesis with screens for hyperphenylalaninemia to isolate three mutants deficient in phenylalanine hydroxylase (PAH) activity and cross-reactive protein. Two of these have reduced PAH mRNA and display characteristics of untreated human PKU patients. A low PHE diet partially reverses these abnormalities. Our success in using high frequency random germline point mutagenesis to obtain appropriate disease models illustrates how such mutagenesis can complement the emergent power of targeted mutagenesis in the mouse. The mutants now can be used as models in studying both maternal PKU and somatic gene therapy. PMID:8375656

  11. Aging Research Using Mouse Models

    PubMed Central

    Ackert-Bicknell, Cheryl L.; Anderson, Laura; Sheehan, Susan; Hill, Warren G.; Chang, Bo; Churchill, Gary A.; Chesler, Elissa J.; Korstanje, Ron; Peters, Luanne L.

    2015-01-01

    Despite the dramatic increase in human lifespan over the past century, there remains pronounced variability in “health-span”, or the period of time in which one is generally healthy and free of disease. Much of the variability in health-span and lifespan is thought to be genetic in origin. Understanding the genetic mechanisms of aging and identifying ways to boost longevity is a primary goal in aging research. Here, we describe a pipeline of phenotypic assays for assessing mouse models of aging. This pipeline includes behavior/cognition testing, body composition analysis, and tests of kidney function, hematopoiesis, immune function and physical parameters. We also describe study design methods for assessing lifespan and health-span, and other important considerations when conducting aging research in the laboratory mouse. The tools and assays provided can assist researchers with understanding the correlative relationships between age-associated phenotypes and, ultimately, the role of specific genes in the aging process. PMID:26069080

  12. Genealogies of mouse inbred strains.

    PubMed

    Beck, J A; Lloyd, S; Hafezparast, M; Lennon-Pierce, M; Eppig, J T; Festing, M F; Fisher, E M

    2000-01-01

    The mouse is a prime organism of choice for modelling human disease. Over 450 inbred strains of mice have been described, providing a wealth of different genotypes and phenotypes for genetic and other studies. As new strains are generated and others become extinct, it is useful to review periodically what strains are available and how they are related to each other, particularly in the light of available DNA polymorphism data from microsatellite and other markers. We describe the origins and relationships of inbred mouse strains, 90 years after the generation of the first inbred strain. Given the large collection of inbred strains available, and that published information on these strains is incomplete, we propose that all genealogical and genetic data on inbred strains be submitted to a common electronic database to ensure this valuable information resource is preserved and used efficiently.

  13. Particle Tracks in Aerogel

    NASA Technical Reports Server (NTRS)

    2005-01-01

    In an experiment using a special air gun, particles are shot into aerogel at high velocities. Closeup of particles that have been captured in aerogel are shown here. The particles leave a carrot-shaped trail in the aerogel. Aerogel was used on the Stardust spacecraft to capture comet particles from Comet Wild 2.

  14. Development and testing of a mouse simulated space flight model

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, G.

    1985-01-01

    The development and testing of a mouse model for simulating some aspects of weightlessness that occur during space flight, and the carrying out of immunological flight experiments on animals was discussed. The mouse model is an antiorthostatic, hypokinetic, hypodynamic suspension model similar to the one used with rats. It is shown that this murine model yield similar results to the rat model of antiorthostatic suspension for simulating some aspects of weightlessness. It is also shown that mice suspended in this model have decreased interferon-alpha/beta production as compared to control, nonsuspended mice or to orthostatically suspended mice. It is suggested that the conditions occuring during space flight could possibly affect interferon production. The regulatory role of interferon in nonviral diseases is demonstrated including several bacterial and protozoan infections indicating the great significance of interferon in resistance to many types of infectious diseases.

  15. Gain and frequency tuning within the mouse cochlear apex

    SciTech Connect

    Oghalai, John S.; Raphael, Patrick D.; Gao, Simon; Lee, Hee Yoon; Groves, Andrew K.; Zuo, Jian; Applegate, Brian E.

    2015-12-31

    Normal mammalian hearing requires cochlear outer hair cell active processes that amplify the traveling wave with high gain and sharp tuning, termed cochlear amplification. We have used optical coherence tomography to study cochlear amplification within the apical turn of the mouse cochlea. We measured not only classical basilar membrane vibratory tuning curves but also vibratory responses from the rest of the tissues that compose the organ of Corti. Basilar membrane tuning was sharp in live mice and broad in dead mice, whereas other regions of the organ of Corti demonstrated phase shifts consistent with additional filtering beyond that provided by basilar membrane mechanics. We use these experimental data to support a conceptual framework of how cochlear amplification is tuned within the mouse cochlear apex. We will also study transgenic mice with targeted mutations that affect different biomechanical aspects of the organ of Corti in an effort to localize the underlying processes that produce this additional filtering.

  16. Gain and frequency tuning within the mouse cochlear apex

    NASA Astrophysics Data System (ADS)

    Oghalai, John S.; Gao, Simon; Lee, Hee Yoon; Raphael, Patrick D.; Groves, Andrew K.; Zuo, Jian; Applegate, Brian E.

    2015-12-01

    Normal mammalian hearing requires cochlear outer hair cell active processes that amplify the traveling wave with high gain and sharp tuning, termed cochlear amplification. We have used optical coherence tomography to study cochlear amplification within the apical turn of the mouse cochlea. We measured not only classical basilar membrane vibratory tuning curves but also vibratory responses from the rest of the tissues that compose the organ of Corti. Basilar membrane tuning was sharp in live mice and broad in dead mice, whereas other regions of the organ of Corti demonstrated phase shifts consistent with additional filtering beyond that provided by basilar membrane mechanics. We use these experimental data to support a conceptual framework of how cochlear amplification is tuned within the mouse cochlear apex. We will also study transgenic mice with targeted mutations that affect different biomechanical aspects of the organ of Corti in an effort to localize the underlying processes that produce this additional filtering.

  17. Genetically modified mouse models for premature ovarian failure (POF).

    PubMed

    Jagarlamudi, Krishna; Reddy, Pradeep; Adhikari, Deepak; Liu, Kui

    2010-02-01

    Premature ovarian failure (POF) is a complex disorder that affects approximately 1% of women. POF is characterized by the depletion of functional ovarian follicles before the age of 40 years, and clinically, patients may present with primary amenorrhea or secondary amenorrhea. Although some genes have been hypothesized to be candidates responsible for POF, the etiology of most of the cases is idiopathic, with the underlying causes still unidentified because of the heterogeneity of the disease. In this review, we consider some mutant mouse models that exhibit phenotypes which are comparable to human POF, and we suggest that the use of these mouse models may help us to gain a better understanding of the molecular mechanisms underlying POF in humans.

  18. Comprehensive Neurocognitive Endophenotyping Strategies for Mouse Models of Genetic Disorders

    PubMed Central

    Hunsaker, Michael R.

    2012-01-01

    There is a need for refinement of the current behavioral phenotyping methods for mouse models of genetic disorders. The current approach is to perform a behavioral screen using standardized tasks to define a broad phenotype of the model. This phenotype is then compared to what is known concerning the disorder being modeled. The weakness inherent in this approach is twofold: First, the tasks that make up these standard behavioral screens do not model specific behaviors associated with a given genetic mutation but rather phenotypes affected in various genetic disorders; secondly, these behavioral tasks are insufficiently sensitive to identify subtle phenotypes. An alternate phenotyping strategy is to determine the core behavioral phenotypes of the genetic disorder being studied and develop behavioral tasks to evaluate specific hypotheses concerning the behavioral consequences of the genetic mutation. This approach emphasizes direct comparisons between the mouse and human that facilitate the development of neurobehavioral biomarkers or quantitative outcome measures for studies of genetic disorders across species. PMID:22266125

  19. Development of the mouse vestibular system in the absence of gravity perception

    NASA Technical Reports Server (NTRS)

    Smith, Michael; Yuan Wang, Xiang; Wolgemuth, Debra J.; Murashov, Alexander K.

    2003-01-01

    The tilted mutant mouse, which lacks otoconia in the inner ear, was used to study development of the mouse vestibular system in the absence of gravity perception. Otoconia are dense particles composed of proteins and calcium carbonate crystals suspended in the gelatinous macular membrane. They enhance, and are largely responsible for, sensitivity to gravity. Morphometric analysis of the vestibular ganglion showed that the mutant developed more slowly than the normal controls, both in rate of development and cell number, particularly during the first week of post-natal development. The mutant ganglia also exhibited a reduction of cells during the first 6 days of post-natal development.

  20. Retinofugal Projections in the Mouse

    PubMed Central

    Morin, Lawrence P.; Studholme, Keith M.

    2014-01-01

    The laboratory mouse is increasingly a subject for visual system investigation, but there has been no comprehensive evaluation of this species’ visual projections. Here, projections were visualized and mapped following intraocular injection of cholera toxin B subunit. Tissue was processed using standard procedures applied to 30 Am free floating sections with diaminobenzidine as the chromogen. The mouse retina projects to approximately 46 brain regions, including 14 not previously described in this species. These include two amygdaloid nuclei, the horizontal limb of the diagonal band, the paraventricular hypothalamic nucleus, several visual thalamic nuclei, the paranigral nucleus, several pretectal nuclei, and the dorsal cortex of the inferior colliculus. Dense retinal patches were also observed in a narrow portion of the ipsilateral intermediate layer of the superior colliculus. The superior fasciculus of the accessory optic tract, which innervates the medial terminal nucleus, was also determined to be a terminal zone throughout its length. The results are compared with previous descriptions of projections from mouse intrinsically photoreceptive retinal ganglion cells, and with data from the hamster, Nile grass rat and laboratory rat. The retinal projection patterns are similar in all four species, although there are many differences with respect to the details. The specific visual functions of most retinorecipient areas are unknown, but there is substantial convergence of retinal projections onto regions concerned with olfaction and audition. PMID:24889098

  1. Mouse Models of Gastric Cancer

    PubMed Central

    Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

    2013-01-01

    Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

  2. Theoretical and experimental examination of particle-particle interaction effects on induced dipole moments and dielectrophoretic responses of multiple particle chains.

    PubMed

    Moncada-Hernandez, Hector; Nagler, Eliot; Minerick, Adrienne R

    2014-07-01

    Dielectrophoresis (DEP), an electrokinetic phenomenon based on particle polarizations in nonuniform electric fields, is increasingly employed for particle and cell characterizations and manipulations in microdevices. However, particle number densities are rarely varied and particle-particle interactions are largely overlooked, but both affect particle's effective polarizations by changing the local electric field, which directly impacts particle assembly into chains. This work examines theoretical and experimental particle-particle interactions and dielectrophoretic responses in nonuniform electric fields, then presents individual and chain velocities of spherical polystyrene microparticles and red blood cells (RBCs) under DEP forces in a modified quadruple electrode microdevice. Velocities are independently compared between 1, 2, 3, and 4 polystyrene beads and RBCs assembled into chains aligned with the electric field. Simulations compared induced dipole moments for particles experiencing the same (single point) and changing (multiple points) electric fields. Experiments and simulations are compared by plotting DEP velocities versus applied signal frequency from 1 kHz to 80 MHz. Simulations indicate differences in the DEP force exerted on each particle according to chain position. Simulations and experiments show excellent qualitative agreement; chains with more particles experienced a decrease in the DEP response for both polystyrene beads and RBCs. These results advance understanding of the extent that induced dipole polarizations with multiple particle chains affect observed behaviors in electrokinetic cellular diagnostic systems.

  3. Particle capture by aquatic vegetation modeled in flume experiments: the effects of particle size, stem density, biofilm, and flow velocity

    NASA Astrophysics Data System (ADS)

    Kerwin, R.; Fauria, K.; Nover, D.; Schladow, G.

    2014-12-01

    Vegetated floodplains and wetlands can trap and remove particles from suspension thereby affecting water quality, land accretion, and wetland functioning. However, the rate of particle removal by vegetation remains poorly characterized, especially for fine particles. In this study, we monitored particle concentration and size distribution (1.25 - 250 µm diameter suspended road dust) in a laboratory flume as flow velocity, plant stem density, initial particle concentration, and the presence of biofilm on vegetation were varied. We characterized change in particle concentration through time by calculating decay constants, termed capture rates. Based on our experiments, we found that suspended particle concentration decayed more rapidly in the presence, rather than in the absence, of vegetation. Additionally, particle capture rates increased with stem density, particle size, and the presence of biofilm, while decreasing with flow velocity. These results demonstrate that low flow velocities and the presence of biofilm optimize particle capture by vegetation. Our results are relevant to floodplain and wetland restoration efforts.

  4. The microlesion concept in HZE particle dosimetry

    NASA Astrophysics Data System (ADS)

    Todd, Paul; Walker, James T.

    High energy, high-Z (HZE) particles are present in high-altitude and high-inclination satellite orbits. Most of the HZE dose above LET = 200 keV/μm is due to Fe nuclei. Individual HZE particles can damage several cells adjacent to one another along the particle track in tissue. The outcome has been described as a ``microlesion'' by D. Grahn. The present study attempts to define conditions for microlesions in specific tissues, to seek biological evidence that microlesions are produced, and to evaluate the microlesion as a potentially useful unit of dose in assessing hazards to spaceworkers. Microlesions in individual cells and hair follicles have been described. Microbial studies have provided some evidence for independent secondary electron action. Whether or not a few hundred microlesions would be damaging to the whole organism depends upon the nature of damage to critical tissues. For example, cancer may occur if microlesions kill several cells in a straight line and mutate other cells alongside the particle track. Fe particle irradiation of the mouse Harderian gland (Fry et al., this issue) produces tumors efficiently. Microlesions in the lens, cornea, and retina need to be considered. Further dialogue is required before a final decision can be made concerning the most appropriate way to assess the HZE hazard.

  5. D-Cycloserine enhances social exploration in the Balb/c mouse.

    PubMed

    Jacome, Luis F; Burket, Jessica A; Herndon, Amy L; Deutsch, Stephen I

    2011-05-30

    Inbred Balb/c mice show deficits of sociability. The endogenous tone of NMDA receptor-mediated neurotransmission is altered in Balb/c mice, which may explain the beneficial effect of D-cycloserine on impaired sociability. In the current study, Balb/c mice spent more time than the Swiss Webster comparator strain in the open arms of an elevated plus maze (EPM), suggesting that they are not more anxious or fearful in the absence of a social stimulus mouse. Moreover, Balb/c and Swiss Webster mice did not differ in the amount of time they spent exploring an inanimate object in an open field. Differences in exploratory activity between strains emerged only when a salient social stimulus mouse was enclosed in the open field. D-Cycloserine increased the amount of time Balb/c mice spent exploring the enclosed stimulus mouse to levels observed in vehicle-treated Swiss Webster mice. Finally, irrespective of strain, D-cycloserine increased exploratory activity as measured in open arm entries in the EPM, when no enclosed stimulus mouse was present. The data show that mouse strain influences D-cycloserine's effect on exploration in the presence of a salient social stimulus mouse. In the absence of an enclosed stimulus mouse, D-cycloserine increased open arm entries significantly in both the sociability-impaired Balb/c and comparator Swiss Webster strains. Thus, D-cycloserine positively affects exploratory activity in general, but strain differences emerge when the stimulus eliciting exploration is a salient social stimulus mouse versus an inanimate object. Further, the sociability deficit of the Balb/c mouse is not an epiphenomenon of increased generalized anxiety.

  6. Mouse DNA contamination in human tissue tested for XMRV

    PubMed Central

    2010-01-01

    Background We used a PCR-based approach to study the prevalence of genetic sequences related to a gammaretrovirus, xenotropic murine leukemia virus-related virus, XMRV, in human prostate cancer. This virus has been identified in the US in prostate cancer patients and in those with chronic fatigue syndrome. However, with the exception of two patients in Germany, XMRV has not been identified in prostate cancer tissue in Europe. Most putative associations of new or old human retroviruses with diseases have turned out to be due to contamination. We have looked for XMRV sequences in DNA extracted from formalin-fixed paraffin- embedded prostate tissues. To control for contamination, PCR assays to detect either mouse mitochondrial DNA (mtDNA) or intracisternal A particle (IAP) long terminal repeat DNA were run on all samples, owing to their very high copy number in mouse cells. Results In general agreement with the US prevalence, XMRV-like sequences were found in 4.8% of prostate cancers. However, these were also positive, as were 21.5% of XMRV-negative cases, for IAP sequences, and many, but not all were positive for mtDNA sequences. Conclusions These results show that contamination with mouse DNA is widespread and detectable by the highly sensitive IAP assay, but not always with less sensitive assays, such as murine mtDNA PCR. This study highlights the ubiquitous presence of mouse DNA in laboratory specimens and offers a means of rigorous validation for future studies of murine retroviruses in human disease. PMID:21171966

  7. TOXICITY OF AMORPHOUS SILICA NANOPARTICLES IN MOUSE KERATINOCYTES

    SciTech Connect

    Yu, Kyung; Wang, Wei; Gu, Baohua; Hussain, Saber

    2009-01-01

    The present study was designed to examine the uptake, localization and the cytotoxic effects of well-dispersed amorphous silica nanoparticles in mouse keratinocytes (HEL-30). Mouse keratinocytes were exposed for 24h to various concentrations of amorphous silica nanoparticles in homogeneous suspensions of average size distribution (30, 48, 118 and 535 nm SiO2) then assessed for uptake and biochemical changes. Results of transmission electron microscopy revealed all sizes of silica were taken up into the cells and localized into the cytoplasm. The lactate dehydrogenase (LDH) assay shows LDH leakage was dose- and size-dependent with exposure to 30 and 48 nm nanoparticles. However, no LDH leakage was observed for either 118 or 535 nm nanoparticles. The mitochondrial viability assay (MTT) showed significant toxicity for 30 and 48 nm at high concentrations (100 g/mL) compare to the 118 and 535 nm particles. Further studies were carried out to investigate if cellular reduced GSH and mitochondria membrane potential are involved in the mechanism of SiO2 toxicity. The redox potential of cells (GSH) was reduced significantly at concentrations of 50, 100 and 200 g/mL at 30 nm nanoparticle exposures. However, silica nanoparticles larger than 30 nm showed no changes in GSH levels. Reactive oxygen species (ROS) formation did not show any significant change between controls and the exposed cells. In summary, amorphous silica nanoparticles below 100 nm induced cytotoxicity suggest size-of the particles is critical to produce biological effects.

  8. Study of Ice Particle Formation and Lifetime in Space Environment

    NASA Technical Reports Server (NTRS)

    Jeng, D.

    1972-01-01

    The ice particles are formed when liquid and/or humid gases vent to the space. These submicroscopic ice particles are potential contamination sources of the environments during Skylab operations. The critical size of ice particle and its nucleation rate based on the theory of homogeneous and heterogeneous nucleation by sublimation are analyzed. The equations which are pertinent for studying the growth and evaporation of the ice particles are formulated. The mechanisms affecting the lifetime of ice particle are discussed. The gas dynamic techniques for experimental study of ice particle formation are proposed.

  9. Mouse embryonic stem cells with a multi-integrase mouse artificial chromosome for transchromosomic mouse generation.

    PubMed

    Yoshimura, Yuki; Nakamura, Kazuomi; Endo, Takeshi; Kajitani, Naoyo; Kazuki, Kanako; Kazuki, Yasuhiro; Kugoh, Hiroyuki; Oshimura, Mitsuo; Ohbayashi, Tetsuya

    2015-08-01

    The mouse artificial chromosome (MAC) has several advantages as a gene delivery vector, including stable episomal maintenance of the exogenous genetic material and the ability to carry large and/or multiple gene inserts including their regulatory elements. Previously, a MAC containing multi-integration site (MI-MAC) was generated to facilitate transfer of multiple genes into desired cells. To generate transchromosomic (Tc) mice containing a MI-MAC with genes of interest, the desired genes were inserted into MI-MAC in CHO cells, and then the MI-MAC was transferred to mouse embryonic stem (mES) cells via microcell-mediated chromosome transfer (MMCT). However, the efficiency of MMCT from CHO to mES cells is very low (<10(-6)). In this study, we constructed mES cell lines containing a MI-MAC vector to directly insert a gene of interest into the MI-MAC in mES cells via a simple transfection method for Tc mouse generation. The recombination rate of the GFP gene at each attachment site (FRT, PhiC31attP, R4attP, TP901-1attP and Bxb1attP) on MI-MAC was greater than 50% in MI-MAC mES cells. Chimeric mice with high coat colour chimerism were generated from the MI-MAC mES cell lines and germline transmission from the chimera was observed. As an example for the generation of Tc mice with a desired gene by the MI-MAC mES approach, a Tc mouse strain ubiquitously expressing Emerald luciferase was efficiently established. Thus, the findings suggest that this new Tc strategy employing mES cells and a MI-MAC vector is efficient and useful for animal transgenesis.

  10. Mouse embryonic stem cells with a multi-integrase mouse artificial chromosome for transchromosomic mouse generation.

    PubMed

    Yoshimura, Yuki; Nakamura, Kazuomi; Endo, Takeshi; Kajitani, Naoyo; Kazuki, Kanako; Kazuki, Yasuhiro; Kugoh, Hiroyuki; Oshimura, Mitsuo; Ohbayashi, Tetsuya

    2015-08-01

    The mouse artificial chromosome (MAC) has several advantages as a gene delivery vector, including stable episomal maintenance of the exogenous genetic material and the ability to carry large and/or multiple gene inserts including their regulatory elements. Previously, a MAC containing multi-integration site (MI-MAC) was generated to facilitate transfer of multiple genes into desired cells. To generate transchromosomic (Tc) mice containing a MI-MAC with genes of interest, the desired genes were inserted into MI-MAC in CHO cells, and then the MI-MAC was transferred to mouse embryonic stem (mES) cells via microcell-mediated chromosome transfer (MMCT). However, the efficiency of MMCT from CHO to mES cells is very low (<10(-6)). In this study, we constructed mES cell lines containing a MI-MAC vector to directly insert a gene of interest into the MI-MAC in mES cells via a simple transfection method for Tc mouse generation. The recombination rate of the GFP gene at each attachment site (FRT, PhiC31attP, R4attP, TP901-1attP and Bxb1attP) on MI-MAC was greater than 50% in MI-MAC mES cells. Chimeric mice with high coat colour chimerism were generated from the MI-MAC mES cell lines and germline transmission from the chimera was observed. As an example for the generation of Tc mice with a desired gene by the MI-MAC mES approach, a Tc mouse strain ubiquitously expressing Emerald luciferase was efficiently established. Thus, the findings suggest that this new Tc strategy employing mES cells and a MI-MAC vector is efficient and useful for animal transgenesis. PMID:26055730

  11. Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may affect their sensitizing properties.

    PubMed

    Madsen, Jakob Torp; Vogel, Stefan; Johansen, Jeanne Duus; Andersen, Klaus Ejner

    2011-06-01

    Attempts to improve formulation of topical products are a continuing process and the development of micro- and nanovesicular systems as well as polymeric microparticles has led to marketing of topical drugs and cosmetics using these technologies. Encapsulation of some well-known contact allergens in ethanolic liposomes have been reported to enhance allergenicity compared with the allergens in similar vehicles without liposomes. The present report includes data on more sensitization studies using the mouse local lymph node assay with three contact allergens encapsulated in different dermal drug-delivery systems: liposomes, ethosomes, and polycaprolactone particles. The results show that the drug-delivery systems are not sensitizers in themselves. Encapsulating the hydrophilic contact allergen potassium dichromate in all three drug-delivery systems did not affect the sensitizing capacity of potassium dichromate compared with control solutions. However, encapsulating the lipophilic contact allergen dinitrochlorobenzene (DNCB) in polycaprolactone reduced the sensitizing capacity to 1211 ± 449 compared with liposomes (7602 ± 2658) and in acetone:olive oil (4:1) (5633 ± 666). The same trend was observed for encapsulating isoeugenol in polycaprolactone (1100 ± 406) compared with a formulation in acetone:olive oil (4491 ± 819) and in liposomes (3668 ± 950). Further, the size of DNCB-loaded liposomes did not affect the sensitizing properties. These results suggest that modern dermal drug-delivery systems may in some cases magnify or decrease the sensitizing capacity of the encapsulated contact allergen.

  12. Particle capture device

    DOEpatents

    Jayne, John T.; Worsnop, Douglas R.

    2016-02-23

    In example embodiments, particle collection efficiency in aerosol analyzers and other particle measuring instruments is improved by a particle capture device that employs multiple collisions to decrease momentum of particles until the particles are collected (e.g., vaporized or come to rest). The particle collection device includes an aperture through which a focused particle beam enters. A collection enclosure is coupled to the aperture and has one or more internal surfaces against which particles of the focused beam collide. One or more features are employed in the collection enclosure to promote particles to collide multiple times within the enclosure, and thereby be vaporized or come to rest, rather than escape through the aperture.

  13. Laser particle sorter

    DOEpatents

    Martin, J.C.; Buican, T.N.

    1987-11-30

    Method and apparatus are provided for sorting particles, such as biological particles. A first laser is used to define an optical path having an intensity gradient which is effective to propel the particles along the path but which is sufficiently weak that the particles are not trapped in an axial direction. A probe laser beam is provided for interrogating the particles to identify predetermined phenotypical characteristics of the particles. A second laser beam is provided to intersect the driving first laser beam, wherein the second laser beam is activated by an output signal indicative of a predetermined characteristic. The second laser beam is switchable between a first intensity and a second intensity, where the first intensity is effective to displace selected particles from the driving laser beam and the second intensity is effective to propel selected particles along the deflection laser beam. The selected particles may then be propelled by the deflection beam to a location effective for further analysis. 2 figs.

  14. Laser particle sorter

    DOEpatents

    Martin, John C.; Buican, Tudor N.

    1989-01-01

    Method and apparatus for sorting particles, such as biological particles. A first laser defines an optical path having an intensity gradient which is effective to propel the particles along the path but which is sufficiently weak that the particles are not trapped in an axial direction. A probe laser beam interrogates the particles to identify predetermined phenotypical characteristics of the particles. A second laser beam intersects the driving first laser beam, wherein the second laser beam is activated by an output signal indicative of a predetermined characteristic. The second laser beam is switchable between a first intensity and a second intensity, where the first intensity is effective to displace selected particles from the driving laser beam and the second intensity is effective to propel selected particles along the deflection laser beam. The selected particles may then be propelled by the deflection beam to a location effective for further analysis.

  15. Investigation of particles size effects in Dissipative Particle Dynamics (DPD) modelling of colloidal suspensions

    NASA Astrophysics Data System (ADS)

    Mai-Duy, N.; Phan-Thien, N.; Khoo, B. C.

    2015-04-01

    In the Dissipative Particle Dynamics (DPD) simulation of suspension, the fluid (solvent) and colloidal particles are replaced by a set of DPD particles and therefore their relative sizes (as measured by their exclusion zones) can affect the maximal packing fraction of the colloidal particles. In this study, we investigate roles of the conservative, dissipative and random forces in this relative size ratio (colloidal/solvent). We propose a mechanism of adjusting the DPD parameters to properly model the solvent phase (the solvent here is supposed to have the same isothermal compressibility to that of water).

  16. Virtual Energetic Particle Observatory (VEPO)

    NASA Astrophysics Data System (ADS)

    Cooper, J. F.; Lal, N.; McGuire, R. E.; Szabo, A.; Narock, T. W.; Armstrong, T. P.; Manweiler, J. W.; Patterson, J. D.; Hill, M. E.; Vandergriff, J. D.; McKibben, R. B.; Lopate, C.; Tranquille, C.

    2008-12-01

    The Virtual Energetic Particle Observatory (VEPO) focuses on improved discovery, access, and usability of heliospheric energetic particle and ancillary data products from selected spacecraft and sub-orbital instruments of the heliophysics data environment. The energy range of interest extends over the full range of particle acceleration from keV energies of suprathermal seed particles to GeV energies of galactic cosmic ray particles. Present spatial coverage is for operational and legacy spacecraft operating from the inner to the outer heliosphere, e.g. from measurements by the two Helios spacecraft to 0.3 AU to the inner heliosheath region now being traversed by the two Voyager spacecraft. This coverage will eventually be extended inward to ten solar radii by the planned NASA solar probe mission and at the same time beyond the heliopause into the outer heliosheath by continued Voyager operations. The geospace fleet of spacecraft providing near-Earth interplanetary measurements, selected magnetospheric spacecraft providing direct measurements of penetrating interplanetary energetic particles, and interplanetary cruise measurements from planetary spacecraft missions further extend VEPO resources to the domain of geospace and planetary interactions. Ground-based (e.g., neutron monitor) and high-altitude suborbital measurements can expand coverage to the highest energies of galactic cosmic rays affected by heliospheric interaction and of solar energetic particles. Science applications include investigation of solar flare and coronal mass ejection events, acceleration and transport of interplanetary particles within the inner heliosphere, cosmic ray interactions with planetary surfaces and atmospheres, sources of suprathermal and anomalous cosmic ray ions in the outer heliosphere, and solar cycle modulation of galactic cosmic rays. Robotic and human exploration, and eventual habitation, of planetary and space environments beyond the Earth require knowledge of radiation

  17. Virtual Energetic Particle Observatory (VEPO)

    NASA Technical Reports Server (NTRS)

    Cooper, John F.; Lal, Nand; McGuire, Robert E.; Szabo, Adam; Narock, Thomas W.; Armstrong, Thomas P.; Manweiler, Jerry W.; Patterson, J. Douglas; Hill, Matthew E.; Vandergriff, Jon D.; McKibben, Robert B.; Lopate, Clifford; Tranquille, Cecil

    2008-01-01

    The Virtual Energetic Particle Observatory (VEPO) focuses on improved discovery, access, and usability of heliospheric energetic particle and ancillary data products from selected spacecraft and sub-orbital instruments of the heliophysics data environment. The energy range of interest extends over the full range of particle acceleration from keV energies of suprathermal seed particles to GeV energies of galactic cosmic ray particles. Present spatial coverage is for operational and legacy spacecraft operating from the inner to the outer heliosphere, e.g. from measurements by the two Helios spacecraft to 0.3 AU to the inner heliosheath region now being traversed by the two Voyager spacecraft. This coverage will eventually be extended inward to ten solar radii by the planned NASA solar probe mission and at the same time beyond the heliopause into the outer heliosheath by continued Voyager operations. The geospace fleet of spacecraft providing near-Earth interplanetary measurements, selected magnetospheric spacecraft providing direct measurements of penetrating interplanetary energetic particles, and interplanetary cruise measurements from planetary spacecraft missions further extend VEPO resources to the domain of geospace and planetary interactions. Ground-based (e.g., neutron monitor) and high-altitude suborbital measurements can expand coverage to the highest energies of galactic cosmic rays affected by heliospheric interaction and of solar energetic particles. Science applications include investigation of solar flare and coronal mass ejection events. acceleration and transport of interplanetary particles within the inner heliosphere, cosmic ray interactions with planetary surfaces and atmospheres, sources of suprathermal and anomalous cosmic ray ions in the outer heliosphere, and solar cycle modulation of galactic cosmic rays. Robotic and human exploration, and eventual habitation, of planetary and space environments beyond the Earth require knowledge of radiation

  18. Mouse mammary tumor biology: a short history.

    PubMed

    Cardiff, Robert D; Kenney, Nicholas

    2007-01-01

    For over a century, mouse mammary tumor biology and the associated Mouse mammary tumor virus (MMTV) have served as the foundation for experimental cancer research, in general, and, in particular, experimental breast cancer research. Spontaneous mouse mammary tumors were the basis for studies of the natural history of neoplasia, oncogenic viruses, host responses, endocrinology, and neoplastic progression. However, lacking formal proof of a human mammary tumor virus, the preeminence of the mouse model faded in the 1980s. Since the late 1980s, genetically engineered mice (GEM) have proven extremely useful for studying breast cancer and have become the animal model for human breast cancer. Hundreds of mouse models of human breast cancer have been developed since the first demonstration, in 1984, that the mouse mammary gland could be molecularly targeted and used to test the oncogenicity of candidate human genes. Now, very few scientists can avoid using a mouse model to test the biology of their favorite gene. The GEM have attracted a new generation of molecular and cellular biologists eager to apply their skills to these surrogates of the human disease. Newcomers often enter the field without an appreciation of the origins of mouse mammary tumor biology and the basis for many of the prevailing concepts. Our purpose in writing this short history of mouse mammary tumor biology is to provide a historical perspective for the benefit of the newcomers. If Einstein was correct in that "we stand on the shoulders of giants," the neophytes should meet their giants.

  19. Granular dampers: does particle shape matter?

    NASA Astrophysics Data System (ADS)

    Pourtavakoli, Hamzeh; Parteli, Eric J. R.; Pöschel, Thorsten

    2016-07-01

    By means of particle-based numerical simulations using the discrete element method, we address the question of how the performance of granular dampers is affected by the shape of the granular particles. In consistence with previous experiments performed with nearly spherical particles we find that independently of the particles’ shape, the granular system is characterized by a gas-like regime for small amplitudes of the container’s oscillation and by a collect-and-collide regime for large amplitude forcing. Both regimes are separated by an optimal operation mode—the critical amplitude of the damping oscillation for which the energy dissipation is maximal—which is independent of the particle shape for given conditions of particle mass, material properties and number of particles. However, in the gas-like regime, we find that spherical particles lead to more efficient energy dissipation compared to complex shaped particles of the same mass. In this regime, a dependence on the damper’s efficiency on the particle shape is found.

  20. Controlling particle orientation during forming

    NASA Astrophysics Data System (ADS)

    Nycz, Shawn Michael

    Particle orientation is a microstructural feature that can significantly impact the properties of a fired ceramic. For example, Patwardhan and Cannon showed that particle orientation occurring during tape casting affects dimensional control due to the influence that particle shape has on sintering kinetics. The particle orientation was caused by the complex shear state that occurs during tape casting. This dissertation examined the relationship between shear state and the resulting particle orientation and its influence on selected properties of the body. The first step towards this was the determination of the shear state during tape casting. Based on measured geometries and rheologies, computational fluid dynamics (CFD) simulations were performed which predicted shear rates throughout the geometry. The simulations predicted that for slurries exhibiting power-law shear thinning behavior, shear rate is higher near the doctor blade and the slurry is not only sheared between the doctor blade and substrate but also into the slurry reservoir and behind the doctor blade. Tape casting was performed on the compositions that were characterized for the determination of shear state. Casting parameters such as doctor blade gap and casting velocity were varied to alter the shear profile in the system. These samples were then analyzed to determine the particle orientation and texture in various regions throughout the tapes. An optical texture measurement technique based on the birefringence of green bodies was developed to address the need for highly sensitive measurements capable of detecting small variations in green texture. Results given by this technique were found to be consistent with measurements performed by XRD. Experimental samples were analyzed and localized texture measurements were found to follow shear profiles predicted by the CFD simulations. Elastic moduli of fired samples exhibiting a range of textures were measured to reveal effects of particle orientation

  1. Therapeutic cloning in the mouse.

    PubMed

    Mombaerts, Peter

    2003-09-30

    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice.

  2. Composite powder particles

    NASA Technical Reports Server (NTRS)

    Parker, Donald S. (Inventor); MacDowell, Louis G. (Inventor)

    2009-01-01

    A liquid coating composition including a coating vehicle and composite powder particles disposed within the coating vehicle. Each composite powder particle may include a magnesium component, a zinc component, and an indium component.

  3. Solar Neutral Particles

    NASA Video Gallery

    This animation shows a neutral solar particle's path leaving the sun, following the magnetic field lines out to the heliosheath. The solar particle hits a hydrogen atom, stealing its electron, and ...

  4. Acoustic particle separation

    NASA Technical Reports Server (NTRS)

    Barmatz, M. B.; Stoneburner, J. D.; Jacobi, N.; Wang, T. (Inventor)

    1985-01-01

    A method is described which uses acoustic energy to separate particles of different sizes, densities, or the like. The method includes applying acoustic energy resonant to a chamber containing a liquid of gaseous medium to set up a standing wave pattern that includes a force potential well wherein particles within the well are urged towards the center, or position of minimum force potential. A group of particles to be separated is placed in the chamber, while a non-acoustic force such as gravity is applied, so that the particles separate with the larger or denser particles moving away from the center of the well to a position near its edge and progressively smaller lighter particles moving progressively closer to the center of the well. Particles are removed from different positions within the well, so that particles are separated according to the positions they occupy in the well.

  5. Particle exposures and infections

    EPA Science Inventory

    Particle exposures increase the risk for human infections. Particles can deposit in the nose, pharynx, larynx, trachea, bronchi, and distal lung and, accordingly, the respiratory tract is the system most frequently infected after such exposure; however, meningitis also occurs. Ci...

  6. Expression of Superparamagnetic Particles on FORC Diagrams

    NASA Astrophysics Data System (ADS)

    Hirt, A. M.; Kumari, M.; Crippa, F.; Petri-Fink, A.

    2015-12-01

    Identification of superparamagnetic (SP) particles in natural materials provides information on processes that lead to the new formation or dissolution of iron oxides. SP particles express themselves on first-order reversal curve (FORC) diagrams as a distribution centered near the origin of the diagram. Pike et al. (2001, GJI, 145, 721) demonstrated that thermal relaxation produces an upward shift in the FORC distribution, and attributed this to a pause encountered at each reversal field. In this study we examine the relationship between this upward shift and particles size on two sets of synthetic iron oxide nanoparticles. One set of coated magnetite particles have well-constrained particles size with 9, 16 and 20 nm as their diameter. A second set from the FeraSpin™ Series, consisting of FeraSpinXS, M and XL, were evaluated. Rock magnetic experiments indicate that the first set of samples is exclusively magnetite, whereas the FeraSpin samples contain predominantly magnetite with some degree of oxidation. Samples from both sets show that the upward shift of the FORC distribution at the origin increases with decreasing particle size. The amount of shift in the FeraSpin series is less when compared to the samples from the first set. This is attributed to the effect of interaction that counteracts the effect of thermal relaxation behavior of the SP particles. The FeraSpin series also shows a broader FORC distribution on the vertical axis that appears to be related to non-saturation of the hysteresis curve at maximum applied field. This non-saturation behavior can be due to spins of very fine particles or oxidation to hematite. AC susceptibility at low temperature indicates that particle interaction may affect the effective magnetic particle size. Our results suggest that the FORC distribution in pure SP particle systems provides information on the particle size distribution or oxidation, which can be further evaluated with low temperature techniques.

  7. The effect of particle size, location and season on the toxicity of urban and rural particulate matter

    PubMed Central

    Mirowsky, Jaime; Hickey, Christina; Horton, Lori; Blaustein, Martin; Galdanes, Karen; Peltier, Richard E.; Chillrud, Steven; Chen, Lung Chi; Ross, James; Nadas, Arthur; Lippmann, Morton; Gordon, Terry

    2014-01-01

    Particulate matter (PM) varies in chemical composition and mass concentration based on a number of factors including location, season, source and particle size. The aim of this study was to evaluate the in vitro and in vivo toxicity of coarse and fine PM simultaneously collected at three rural and two urban sites within the metropolitan New York City (NYC) region during two seasons, and to assess how particle size and elemental composition affect toxicity. Human pulmonary microvascular endothelial (HPMEC-ST1.6R) and bronchial epithelial (BEAS-2B) cell lines were exposed to PM (50 μg/mL) and analyzed for reactive oxygen species (ROS). Mice (FVB/N) were exposed by oropharyngeal aspiration to 50 μg PM, and lavage fluid was analyzed for total protein and PMN influx. The ROS response was greater in the HPMEC-ST1.6R cell line compared to BEAS-2B cells, but the responses were significantly correlated (p<0.01). The ROS response was affected by location, locale and the location:size interaction in both cell lines, and an additional association for size was observed from HPMEC-ST1.6R cells. Urban fine PM generated the highest ROS response. In the mouse model, inflammation was associated with particle size and by a season:size interaction, with coarse PM producing greater PMN inflammation. This study showed that the aerodynamic size, locale (i.e. urban versus rural), and site of PM samples affected the ROS response in pulmonary endothelial and epithelial cells and the inflammatory response in mice. Importantly, these responses were dependent upon the chemical composition of the PM samples. PMID:24255952

  8. Neuroanatomical changes in a mouse model of early life neglect.

    PubMed

    Duque, Alvaro; Coman, Daniel; Carlyle, Becky C; Bordner, Kelly A; George, Elizabeth D; Papademetris, Xenophon; Hyder, Fahmeed; Simen, Arthur A

    2012-04-01

    Using a novel mouse model of early life neglect and abuse (ENA) based on maternal separation with early weaning, George et al. (BMC Neurosci 11:123, 2010) demonstrated behavioral abnormalities in adult mice, and Bordner et al. (Front Psychiatry 2(18):1-18, 2011) described concomitant changes in mRNA and protein expression. Using the same model, here we report neuroanatomical changes that include smaller brain size and abnormal inter-hemispheric asymmetry, decreases in cortical thickness, abnormalities in subcortical structures, and white matter disorganization and atrophy most severely affecting the left hemisphere. Because of the similarities between the neuroanatomical changes observed in our mouse model and those described in human survivors of ENA, this novel animal model is potentially useful for studies of human ENA too costly or cumbersome to be carried out in primates. Moreover, our current knowledge of the mouse genome makes this model particularly suited for targeted anatomical, molecular, and pharmacological experimentation not yet possible in other species. PMID:21984312

  9. Influence of age, irradiation and humanization on NSG mouse phenotypes

    PubMed Central

    Knibbe-Hollinger, Jaclyn S.; Fields, Natasha R.; Chaudoin, Tammy R; Epstein, Adrian A.; Makarov, Edward; Akhter, Sidra P.; Gorantla, Santhi; Bonasera, Stephen J.; Gendelman, Howard E.; Poluektova, Larisa Y.

    2015-01-01

    ABSTRACT Humanized mice are frequently utilized in bench to bedside therapeutic tests to combat human infectious, cancerous and degenerative diseases. For the fields of hematology-oncology, regenerative medicine, and infectious diseases, the immune deficient mice have been used commonly in basic research efforts. Obstacles in true translational efforts abound, as the relationship between mouse and human cells in disease pathogenesis and therapeutic studies requires lengthy investigations. The interplay between human immunity and mouse biology proves ever more complicated when aging, irradiation, and human immune reconstitution are considered. All can affect a range of biochemical and behavioral functions. To such ends, we show age- and irradiation-dependent influences for the development of macrocytic hyper chromic anemia, myelodysplasia, blood protein reductions and body composition changes. Humanization contributes to hematologic abnormalities. Home cage behavior revealed day and dark cycle locomotion also influenced by human cell reconstitutions. Significant age-related day-to-day variability in movement, feeding and drinking behaviors were observed. We posit that this data serves to enable researchers to better design translational studies in this rapidly emerging field of mouse humanization. PMID:26353862

  10. Particle Segregation at Contact Lines of Evaporating Colloidal Drops: Influence of the Substrate Wettability and Particle Charge-Mass Ratio.

    PubMed

    Noguera-Marín, Diego; Moraila-Martínez, Carmen L; Cabrerizo-Vílchez, Miguel A; Rodríguez-Valverde, Miguel A

    2015-06-23

    Segregation of particles during capillary/convective self-assembly is interesting for self-stratification in colloidal deposits. In evaporating drops containing colloidal particles, the wettability properties of substrate and the sedimentation of particles can affect their accumulation at contact lines. In this work we studied the size segregation and discrimination of charged particles with different densities. We performed in-plane particle counting at evaporating triple lines by using fluorescence confocal microscopy. We studied separately substrates with very different wettability properties and particles with different charge-mass ratios at low ionic strength. We used binary colloidal suspensions to compare simultaneously the deposition of two different particles. The particle deposition rate strongly depends on the receding contact angle of the substrate. We further observed a singular behavior of charged polystyrene particles in binary mixtures under "salt-free" conditions explained by the "colloidal Brazil nut" effect.

  11. Particle Segregation at Contact Lines of Evaporating Colloidal Drops: Influence of the Substrate Wettability and Particle Charge-Mass Ratio.

    PubMed

    Noguera-Marín, Diego; Moraila-Martínez, Carmen L; Cabrerizo-Vílchez, Miguel A; Rodríguez-Valverde, Miguel A

    2015-06-23

    Segregation of particles during capillary/convective self-assembly is interesting for self-stratification in colloidal deposits. In evaporating drops containing colloidal particles, the wettability properties of substrate and the sedimentation of particles can affect their accumulation at contact lines. In this work we studied the size segregation and discrimination of charged particles with different densities. We performed in-plane particle counting at evaporating triple lines by using fluorescence confocal microscopy. We studied separately substrates with very different wettability properties and particles with different charge-mass ratios at low ionic strength. We used binary colloidal suspensions to compare simultaneously the deposition of two different particles. The particle deposition rate strongly depends on the receding contact angle of the substrate. We further observed a singular behavior of charged polystyrene particles in binary mixtures under "salt-free" conditions explained by the "colloidal Brazil nut" effect. PMID:26000909

  12. Stabilization of Pickering Emulsions with Oppositely Charged Latex Particles: Influence of Various Parameters and Particle Arrangement around Droplets.

    PubMed

    Nallamilli, Trivikram; Binks, Bernard P; Mani, Ethayaraja; Basavaraj, Madivala G

    2015-10-20

    In this study we explore the fundamental aspects of Pickering emulsions stabilized by oppositely charged particles. Using oppositely charged latex particles as a model system, Pickering emulsions with good long-term stability can be obtained without the need for any electrolyte. The effects of parameters like oil to water ratio, mixed particle composition, and pH on emulsion type and stability are explored and linked to the behavior of the aqueous particle dispersion prior to emulsification. The particle composition is found to affect the formation of emulsions, viz., stable emulsions were obtained close to a particle number ratio of 1:1, and no emulsion was formed with either positively or negatively charged particles alone. The emulsions in particle mixtures exhibited phase inversion from oil-in-water to water-in-oil beyond an oil volume fraction of 0.8. Morphological features of emulsion droplets in terms of particle arrangement on the droplets are discussed.

  13. Classical confined particles

    NASA Technical Reports Server (NTRS)

    Horzela, Andrzej; Kapuscik, Edward

    1993-01-01

    An alternative picture of classical many body mechanics is proposed. In this picture particles possess individual kinematics but are deprived from individual dynamics. Dynamics exists only for the many particle system as a whole. The theory is complete and allows to determine the trajectories of each particle. It is proposed to use our picture as a classical prototype for a realistic theory of confined particles.

  14. Ultrasonic vocalizations: a tool for behavioural phenotyping of mouse models of neurodevelopmental disorders.

    PubMed

    Scattoni, Maria Luisa; Crawley, Jacqueline; Ricceri, Laura

    2009-04-01

    In neonatal mice ultrasonic vocalizations have been studied both as an early communicative behaviour of the pup-mother dyad and as a sign of an aversive affective state. Adult mice of both sexes produce complex ultrasonic vocalization patterns in different experimental/social contexts. Vocalizations are becoming an increasingly valuable assay for behavioural phenotyping throughout the mouse life-span and alterations of the ultrasound patterns have been reported in several mouse models of neurodevelopmental disorders. Here we also show that the modulation of vocalizations by maternal cues (maternal potentiation paradigm) - originally identified and investigated in rats - can be measured in C57BL/6 mouse pups with appropriate modifications of the rat protocol and can likely be applied to mouse behavioural phenotyping. In addition we suggest that a detailed qualitative evaluation of neonatal calls together with analysis of adult mouse vocalization patterns in both sexes in social settings, may lead to a greater understanding of the communication value of vocalizations in mice. Importantly, both neonatal and adult USV altered patterns can be determined during the behavioural phenotyping of mouse models of human neurodevelopmental and neuropsychiatric disorders, starting from those in which deficits in communication are a primary symptom.

  15. Mouse infection models for space flight immunology

    NASA Technical Reports Server (NTRS)

    Chapes, Stephen Keith; Ganta, Roman Reddy; Chapers, S. K. (Principal Investigator)

    2005-01-01

    Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.

  16. When is a Particle?

    ERIC Educational Resources Information Center

    Drell, Sidney D.

    1978-01-01

    Gives a new definition for the concept of the elementary particle in nuclear physics. Explains why the existance of the quark as an elementary particle could be an accepted fact even though it lacks what traditionally identifies a particle. Compares this with the development which took place during the discovery of the neutrino in the early…

  17. Particle charge spectrometer

    NASA Technical Reports Server (NTRS)

    Fuerstenau, Stephen D. (Inventor)

    2004-01-01

    An airflow through a tube is used to guide a charged particle through the tube. A detector may be used to detect charge passing through the tube on the particle. The movement of the particle through the tube may be used to both detect its charge and size.

  18. Review of particle properties

    SciTech Connect

    Wohl; Cahn, R.N.; Rittenberg, A.; Trippe, T.G.; Yost, G.P.; Porter, F.; Hernandez, J.J.; Montanet, L.; Hendrick, R.E.; Crawford, R.L.

    1984-04-01

    This review of the properties of leptons, mesons, and baryons is an updating of the Review of Particle Properties, Particle Data Group (Phys. Lett. 111B (1982)). Data are evaluated, listed, averaged, and summarized in tables. Numerous tables, figures, and formulae of interest to particle physicists are also included. A data booklet is available.

  19. High energy particle astronomy.

    NASA Technical Reports Server (NTRS)

    Buffington, A.; Muller, R. A.; Smith, L. H.; Smoot, G. F.

    1972-01-01

    Discussion of techniques currently used in high energy particle astronomy for measuring charged and neutral cosmic rays and their isotope and momentum distribution. Derived from methods developed for accelerator experiments in particle physics, these techniques help perform important particle astronomy experiments pertaining to nuclear cosmic ray and gamma ray research, electron and position probes, and antimatter searches.

  20. Anatomy of Particle Diffusion

    ERIC Educational Resources Information Center

    Bringuier, E.

    2009-01-01

    The paper analyses particle diffusion from a thermodynamic standpoint. The main goal of the paper is to highlight the conceptual connection between particle diffusion, which belongs to non-equilibrium statistical physics, and mechanics, which deals with particle motion, at the level of third-year university courses. We start out from the fact…

  1. Wind reduction by aerosol particles

    NASA Astrophysics Data System (ADS)

    Jacobson, Mark Z.; Kaufman, Yoram J.

    2006-12-01

    Aerosol particles are known to affect radiation, temperatures, stability, clouds, and precipitation, but their effects on spatially-distributed wind speed have not been examined to date. Here, it is found that aerosol particles, directly and through their enhancement of clouds, may reduce near-surface wind speeds below them by up to 8% locally. This reduction may explain a portion of observed ``disappearing winds'' in China, and it decreases the energy available for wind-turbine electricity. In California, slower winds reduce emissions of wind-driven soil dust and sea spray. Slower winds and cooler surface temperatures also reduce moisture advection and evaporation. These factors, along with the second indirect aerosol effect, may reduce California precipitation by 2-5%, contributing to a strain on water supply.

  2. Clementine RRELAX SRAM Particle Spectrometer

    NASA Technical Reports Server (NTRS)

    Buehler, M.; Soli, G.; Blaes, B.; Ratliff, J.; Garrett, H.

    1994-01-01

    The Clementine RRELAX radiation monitor chip consists of a p-FET total dose monitor and a 4-kbit SRAM particle spectrometer. Eight of these chips were included in the RRELAX and used to detect the passage of the Clementine (S/C) and the innerstage adapter (ISA) through the earth's radiation belts and the 21-Feb 1994 solar flare. This is the first space flight for this 1.2 micron rad-soft custom CMOS radiation monitor. This paper emphasizes results from the SRAM particle detector which showed that it a) has a detection range of five orders of magnitude relative to the 21-Feb solar flare, b) is not affected by electrons, and c) detected microflares occurring with a 26.5 day period.

  3. Inferring transient particle transport dynamics in live cells.

    PubMed

    Monnier, Nilah; Barry, Zachary; Park, Hye Yoon; Su, Kuan-Chung; Katz, Zachary; English, Brian P; Dey, Arkajit; Pan, Keyao; Cheeseman, Iain M; Singer, Robert H; Bathe, Mark

    2015-09-01

    Live-cell imaging and particle tracking provide rich information on mechanisms of intracellular transport. However, trajectory analysis procedures to infer complex transport dynamics involving stochastic switching between active transport and diffusive motion are lacking. We applied Bayesian model selection to hidden Markov modeling to infer transient transport states from trajectories of mRNA-protein complexes in live mouse hippocampal neurons and metaphase kinetochores in dividing human cells. The software is available at http://hmm-bayes.org/.

  4. Mouse Models of Tumor Immunotherapy.

    PubMed

    Ngiow, Shin Foong; Loi, Sherene; Thomas, David; Smyth, Mark J

    2016-01-01

    Immunotherapy is now evolving into a major therapeutic option for cancer patients. Such clinical advances also promote massive interest in the search for novel immunotherapy targets, and to understand the mechanism of action of current drugs. It is projected that a series of novel immunotherapy agents will be developed and assessed for their therapeutic activity. In light of this, in vivo experimental mouse models that recapitulate human malignancies serve as valuable tools to validate the efficacy and safety profile of immunotherapy agents, before their transition into clinical trials. In this review, we will discuss the major classes of experimental mouse models of cancer commonly used for immunotherapy assessment and provide examples to guide the selection of appropriate models. We present some new data concerning the utility of a carcinogen-induced tumor model for comparing immunotherapies and combining immunotherapy with chemotherapy. We will also highlight some recent advances in experimental modeling of human malignancies in mice that are leading towards personalized therapy in patients.

  5. Mouse models for liver cancer.

    PubMed

    Bakiri, Latifa; Wagner, Erwin F

    2013-04-01

    Hepatocellular carcinoma (HCC), the most common form of primary liver cancer is the third leading cause of cancer-related cell death in human and the fifth in women worldwide. The incidence of HCC is increasing despite progress in identifying risk factors, understanding disease etiology and developing anti-viral strategies. Therapeutic options are limited and survival after diagnosis is poor. Therefore, better preventive, diagnostic and therapeutic tools are urgently needed, in particular given the increased contribution from systemic metabolic disease to HCC incidence worldwide. In the last three decades, technological advances have facilitated the generation of genetically engineered mouse models (GEMMs) to mimic the alterations frequently observed in human cancers or to conduct intervention studies and assess the relevance of candidate gene networks in tumor establishment, progression and maintenance. Because these studies allow molecular and cellular manipulations impossible to perform in patients, GEMMs have improved our understanding of this complex disease and represent a source of great potential for mechanism-based therapy development. In this review, we provide an overview of the current state of HCC modeling in the mouse, highlighting successes, current challenges and future opportunities.

  6. Adrenomedullin increases the short-circuit current in the mouse seminal vesicle: actions on chloride secretion.

    PubMed

    Liao, S B; Cheung, K H; O, W S; Tang, Fai

    2014-08-01

    Adrenomedullin (ADM) may regulate seminal vesicle fluid secretion, and this may affect sperm quality. In this study, we investigated the effect of ADM on chloride secretion in the mouse seminal vesicle. The presence of ADM in mouse seminal vesicle was confirmed using immunostaining, and the molecular species was determined using gel filtration chromatography coupled with enzyme-linked assay for ADM. The effects of ADM on chloride secretion were studied by short-circuit current technique in a whole-mount preparation of mouse seminal vesicle in an Ussing chamber. The effects of specific ADM and calcitonin gene-related peptide (CGRP) receptor antagonists were investigated. Whether the ADM effect depended on the cAMP- and/or calcium-activated chloride channel was also studied using specific chloride channel blockers. The results showed that ADM was present in seminal vesicle epithelial cells. The major molecular species was precursor in the mouse seminal vesicle. ADM increased short-circuit current through the calcium-activated chloride channel in mouse seminal vesicle, and CGRP receptor was involved. We conclude that ADM may regulate chloride and fluid secretion from the seminal vesicle, which may affect the composition of the seminal plasma bathing the sperm and, hence, fertility.

  7. Investigation of refractory black carbon-containing particle morphologies using the single-particle soot photometer (SP2)

    DOE PAGESBeta

    Sedlacek, III, Arthur J.; Lewis, Ernie R.; Onasch, Timothy B.; Lambe, Andrew T.; Davidovits, Paul

    2015-07-24

    An important source of uncertainty in radiative forcing by absorbing aerosol particles is the uncertainty in their morphologies (i.e., the location of the absorbing substance on/in the particles). To examine the effects of particle morphology on the response of an individual black carbon-containing particle in a Single-Particle Soot Photometer (SP2), a series of experiments was conducted to investigate black carbon-containing particles of known morphology using Regal black (RB), a proxy for collapsed soot, as the light-absorbing substance. Particles were formed by coagulation of RB with either a solid substance (sodium chloride or ammonium sulfate) or a liquid substance (dioctyl sebacate),more » and by condensation with dioctyl sebacate, the latter experiment forming particles in a core-shell configuration. Each particle type experienced fragmentation (observed as negative lagtimes), and each yielded similar lagtime responses in some instances, confounding attempts to differentiate particle morphology using current SP2 lagtime analysis. SP2 operating conditions, specifically laser power and sample flow rate, which in turn affect the particle heating and dissipation rates, play an important role in the behavior of particles in the SP2, including probability of fragmentation. This behavior also depended on the morphology of the particles and on the thermo-chemical properties of the non-RB substance. Although these influences cannot currently be unambiguously separated, the SP2 analysis may still provide useful information on particle mixing states and black carbon particle sources.« less

  8. Investigation of refractory black carbon-containing particle morphologies using the single-particle soot photometer (SP2)

    SciTech Connect

    Sedlacek, III, Arthur J.; Lewis, Ernie R.; Onasch, Timothy B.; Lambe, Andrew T.; Davidovits, Paul

    2015-07-24

    An important source of uncertainty in radiative forcing by absorbing aerosol particles is the uncertainty in their morphologies (i.e., the location of the absorbing substance on/in the particles). To examine the effects of particle morphology on the response of an individual black carbon-containing particle in a Single-Particle Soot Photometer (SP2), a series of experiments was conducted to investigate black carbon-containing particles of known morphology using Regal black (RB), a proxy for collapsed soot, as the light-absorbing substance. Particles were formed by coagulation of RB with either a solid substance (sodium chloride or ammonium sulfate) or a liquid substance (dioctyl sebacate), and by condensation with dioctyl sebacate, the latter experiment forming particles in a core-shell configuration. Each particle type experienced fragmentation (observed as negative lagtimes), and each yielded similar lagtime responses in some instances, confounding attempts to differentiate particle morphology using current SP2 lagtime analysis. SP2 operating conditions, specifically laser power and sample flow rate, which in turn affect the particle heating and dissipation rates, play an important role in the behavior of particles in the SP2, including probability of fragmentation. This behavior also depended on the morphology of the particles and on the thermo-chemical properties of the non-RB substance. Although these influences cannot currently be unambiguously separated, the SP2 analysis may still provide useful information on particle mixing states and black carbon particle sources.

  9. Detection of coding microsatellite frameshift mutations in DNA mismatch repair-deficient mouse intestinal tumors.

    PubMed

    Woerner, Stefan M; Tosti, Elena; Yuan, Yan P; Kloor, Matthias; Bork, Peer; Edelmann, Winfried; Gebert, Johannes

    2015-11-01

    Different DNA mismatch repair (MMR)-deficient mouse strains have been developed as models for the inherited cancer predisposing Lynch syndrome. It is completely unresolved, whether coding mononucleotide repeat (cMNR) gene mutations in these mice can contribute to intestinal tumorigenesis and whether MMR-deficient mice are a suitable molecular model of human microsatellite instability (MSI)-associated intestinal tumorigenesis. A proof-of-principle study was performed to identify mouse cMNR-harboring genes affected by insertion/deletion mutations in MSI murine intestinal tumors. Bioinformatic algorithms were developed to establish a database of mouse cMNR-harboring genes. A panel of five mouse noncoding mononucleotide markers was used for MSI classification of intestinal matched normal/tumor tissues from MMR-deficient (Mlh1(-/-) , Msh2(-/-) , Msh2(LoxP/LoxP) ) mice. cMNR frameshift mutations of candidate genes were determined by DNA fragment analysis. Murine MSI intestinal tumors but not normal tissues from MMR-deficient mice showed cMNR frameshift mutations in six candidate genes (Elavl3, Tmem107, Glis2, Sdccag1, Senp6, Rfc3). cMNRs of mouse Rfc3 and Elavl3 are conserved in type and length in their human orthologs that are known to be mutated in human MSI colorectal, endometrial and gastric cancer. We provide evidence for the utility of a mononucleotide marker panel for detection of MSI in murine tumors, the existence of cMNR instability in MSI murine tumors, the utility of mouse subspecies DNA for identification of polymorphic repeats, and repeat conservation among some orthologous human/mouse genes, two of them showing instability in human and mouse MSI intestinal tumors. MMR-deficient mice hence are a useful molecular model system for analyzing MSI intestinal carcinogenesis.

  10. Auditory development in progressive motor neuronopathy mouse mutants.

    PubMed

    Volkenstein, Stefan; Brors, Dominik; Hansen, Stefan; Berend, Achim; Mlynski, Robert; Aletsee, Christoph; Dazert, Stefan

    2009-11-01

    The present study was performed to elucidate the hearing development in the progressive motor neuronopathy (pmn) mouse mutant. This mouse has been used as a model for human motoneuron disease. A missense mutation in the tubulin-specific chaperon E (Tbce) gene on mouse chromosome 13 was localized as the underlying genetic defect. The protein encoded by the Tbce gene is essential for the formation of primary tubulin complexes. Studies on motoneurons show disorganization in microtubules and disturbed axonal transport, followed by retrograde degeneration of the motoneurons. A similar pathomechanism is also possible for hearing disorders where disrupted microtubules could cause functional deficits in spiral ganglion neurons or in cochlear hair cells. Click auditory brainstem response (ABR) audiometry in homozygous pmn mutants showed a normal onset of hearing, but an increasing hearing threshold from postnatal day 26 (P26) on to death, compared to heterozygous mutants and wild-type mice. Histological sections of the cochlea at different ages showed a regular morphology. Additionally, spiral ganglion explants from mutant and wild-type mice were cultured. The neurite length from pmn mutants was shorter than in wild-type mice, and the neurite number/explant was significantly decreased in pmn mutants. We show that the pmn mouse mutant is a model for a progressive rapid hearing loss from P26 on, after initially normal hearing development. Heterozygous mice are not affected by this defect. With the knowledge of the well-known pathomechanism of this defect in motoneurons, a dysfunction of cellular mechanisms regulating tubulin assembling suggests that tubulin assembling plays an essential role in hearing function and maintenance.

  11. Auditory development in progressive motor neuronopathy mouse mutants.

    PubMed

    Volkenstein, Stefan; Brors, Dominik; Hansen, Stefan; Berend, Achim; Mlynski, Robert; Aletsee, Christoph; Dazert, Stefan

    2009-11-01

    The present study was performed to elucidate the hearing development in the progressive motor neuronopathy (pmn) mouse mutant. This mouse has been used as a model for human motoneuron disease. A missense mutation in the tubulin-specific chaperon E (Tbce) gene on mouse chromosome 13 was localized as the underlying genetic defect. The protein encoded by the Tbce gene is essential for the formation of primary tubulin complexes. Studies on motoneurons show disorganization in microtubules and disturbed axonal transport, followed by retrograde degeneration of the motoneurons. A similar pathomechanism is also possible for hearing disorders where disrupted microtubules could cause functional deficits in spiral ganglion neurons or in cochlear hair cells. Click auditory brainstem response (ABR) audiometry in homozygous pmn mutants showed a normal onset of hearing, but an increasing hearing threshold from postnatal day 26 (P26) on to death, compared to heterozygous mutants and wild-type mice. Histological sections of the cochlea at different ages showed a regular morphology. Additionally, spiral ganglion explants from mutant and wild-type mice were cultured. The neurite length from pmn mutants was shorter than in wild-type mice, and the neurite number/explant was significantly decreased in pmn mutants. We show that the pmn mouse mutant is a model for a progressive rapid hearing loss from P26 on, after initially normal hearing development. Heterozygous mice are not affected by this defect. With the knowledge of the well-known pathomechanism of this defect in motoneurons, a dysfunction of cellular mechanisms regulating tubulin assembling suggests that tubulin assembling plays an essential role in hearing function and maintenance. PMID:19735697

  12. Expression of DMP1 in the developing mouse tongue embryo.

    PubMed

    Murata, Hidetaka; Sunohara, Msataka; Sato, Iwao

    2015-07-01

    Dentin matrix protein 1 (DMP-1) is an important factor in the mineralization of hard tissues. However, it has many other functions in addition to the regulation of mineralized tissues. We analyzed the expression and localization of DMP-1 by immunohistochemical staining and in situ hybridization in the developing mouse tongue during embryonic days 12.5 (E12.5), E14.5, E17.5, and E18.5. We also detected the mRNA abundance of tongue morphogenesis markers such as FGF6, TGF-β1, Collagen I, osteocalcin, chondromodulin 1, tenomodulin, Vascular endothelial growth factor (VEGF), caspase-3, and Aifm from embryonic stages by real-time RT-PCR. The antisense probe for DMP-1 was detected in a few mesenchymal cells surrounding blood vessels at E12.5, and faint localization was seen at E18.5 in the embryonic mouse tongue by in situ hybridization. The DMP-1 and osteocalcin abundance levels gradually increased compared with the other tongue markers from E12.5 to E18.5 (p<0.001). Cluster analyses identified the following distinct clusters for mRNA abundance in the tongue: cluster 1, E12.5; cluster 2, E14.5 and E17.5; and cluster 3, E18.5. The positive correlation between DMP-1 and osteocalcin (Pearson's r=0.685; p<0.05) and negative correlation between DMP-1 and Caspase-3 (Pearson's r=-0.632; p<0.05) were analyzed. These data suggested that DMP-1 potentially influences osteocalcin and Caspase-3 during mouse tongue development and morphogenesis. DMP-1 also affects the angiogenic marker VEGF in specific stages and areas, terminating the differentiation of the tongue from other developing tissues. We conclude that DMP-1 may be involved in regulating the temporal expression at embryonic stages in the mouse tongue.

  13. Mouse Behavior: Conjectures about Adaptations for Survival.

    ERIC Educational Resources Information Center

    Rop, Charles

    2001-01-01

    Presents an experiment on mouse behavior in which students learn to observe, pay attention to details, record field notes, and ask questions about their observations. Uses a white mouse to eliminate the risk of disease that a wild rodent might carry. Lists materials, set up, and procedure. (YDS)

  14. Measuring Viscoelastic Deformation with an Optical Mouse

    ERIC Educational Resources Information Center

    Ng, T. W.

    2004-01-01

    The feasibility of using an optical mouse to track the viscoelastic deformation of low-density polyethylene films that have a fixed attached load is presented. It is seen that using an optical mouse and with rudimentary experiment paraphernalia and arrangement, it is possible to get good measurements of viscoelastic deformation.

  15. Silver Nanoparticles: A study of dissolution, kinetics, and factors affecting pulmonary inflammation

    NASA Astrophysics Data System (ADS)

    Saunders, Eric L.

    The growing use of silver (Ag) nanoparticles (NP) in consumer and industrial goods has led to an increase in interest in the health effects associated with exposure, both occupationally and environmentally. The aim of this research is to examine the contribution of size, shape, and dissolution of AgNP, with its corresponding effect on pulmonary inflammation and clearance. In addition this study looks at metallothionein (MT) and the role it plays as an inflammatory modulator. A nose only exposure method was used to expose three strains of mouse (two inbred, one knockout) to two different sizes of AgNP (˜25 nm and ˜100 nm). This research demonstrates that size, chemistry, and dissolution play key roles in NP deposition and inflammatory response, while no conclusions could be drawn about shape. Additionally, this study found that the main factors affecting the deposition of NP in mice both acutely and sub-chronically are particle size and mouse strain. The results of this study also indicate a relationship between MT2 and inflammation. It was found that the mRNA levels of MT2 were greatly up-regulated in the livers and lungs of mice exposed to AgNP, while MT protein levels were not significantly altered to correlate with the altered regulation of mRNA. Finally, this study showed that, for AgNP, the mechanisms of pulmonary clearance and dissolution happened rapidly and that they, combined, likely represent a major pathway of AgNP transport out of the lung. Taken as a whole, the data in this study show that dissolution, coupled with protein interaction, is a significant mediator of pulmonary inflammation and translocation of AgNP.

  16. Primordial Particles; Collisions of Inelastic Particles

    NASA Astrophysics Data System (ADS)

    Sagi, George

    2011-03-01

    Three-dimensional matter is not defined by Euclidian or Cartesian geometries. Newton's and Einstein's laws are related to the motions of elastic masses. The study of collisions of inelastic particles opens up new vistas in physics. The present article reveals how such particles create clusters composed of various numbers of particles. The Probability of each formation, duplets, triplets, etc. can be calculated. The particles are held together by a binding force, and depending upon the angles of collisions they may also rotate around their center of geometry. Because of these unique properties such inelastic particles are referred to as primordial particles, Pp. When a given density of Pp per cubic space is given, then random collisions create a field. The calculation of the properties of such primordial field is very complex and beyond the present study. However, the angles of collisions are infinite in principle, but the probabilities of various cluster sizes are quantum dependent. Consequently, field calculations will require new complex mathematical methods to be discovered yet.

  17. Affective Dynamics in Psychopathology

    PubMed Central

    Trull, Timothy J.; Lane, Sean P.; Koval, Peter; Ebner-Priemer, Ulrich W.

    2016-01-01

    We discuss three varieties of affective dynamics (affective instability, emotional inertia, and emotional differentiation). In each case, we suggest how these affective dynamics should be operationalized and measured in daily life using time-intensive methods, like ecological momentary assessment or ambulatory assessment, and recommend time-sensitive analyses that take into account not only the variability but also the temporal dependency of reports. Studies that explore how these affective dynamics are associated with psychological disorders and symptoms are reviewed, and we emphasize that these affective processes are within a nexus of other components of emotion regulation.

  18. Highly Charged Particles Cause a Larger Current Blockage in Micropores Compared to Neutral Particles.

    PubMed

    Qiu, Yinghua; Lin, Chih-Yuan; Hinkle, Preston; Plett, Timothy S; Yang, Crystal; Chacko, Jenu Varghese; Digman, Michelle A; Yeh, Li-Hsien; Hsu, Jyh-Ping; Siwy, Zuzanna S

    2016-09-27

    Single pores in the resistive-pulse technique are used as an analytics tool to detect, size, and characterize physical as well as chemical properties of individual objects such as molecules and particles. Each object passing through a pore causes a transient change of the transmembrane current called a resistive pulse. In high salt concentrations when the pore diameter is significantly larger than the screening Debye length, it is assumed that the particle size and surface charge can be determined independently from the same experiment. In this article we challenge this assumption and show that highly charged hard spheres can cause a significant increase of the resistive-pulse amplitude compared to neutral particles of a similar diameter. As a result, resistive pulses overestimate the size of charged particles by even 20%. The observation is explained by the effect of concentration polarization created across particles in a pore, revealed by numerical modeling of ionic concentrations, ion current, and local electric fields. It is notable that in resistive-pulse experiments with cylindrical pores, concentration polarization was previously shown to influence ionic concentrations only at pore entrances; consequently, additional and transient modulation of resistive pulses was observed when a particle entered or left the pore. Here we postulate that concentration polarization can occur across transported particles at any particle position along the pore axis and affect the magnitude of the entire resistive pulse. Consequently, the recorded resistive pulses of highly charged particles reflect not only the particles' volume but also the size of the depletion zone created in front of the moving particle. Moreover, the modeling identified that the effective surface charge density of particles depended not only on the density of functional groups on the particle but also on the capacitance of the Stern layer. The findings are of crucial importance for sizing particles and

  19. The Mouse Genome Database (MGD): from genes to mice--a community resource for mouse biology.

    PubMed

    Eppig, Janan T; Bult, Carol J; Kadin, James A; Richardson, Joel E; Blake, Judith A; Anagnostopoulos, A; Baldarelli, R M; Baya, M; Beal, J S; Bello, S M; Boddy, W J; Bradt, D W; Burkart, D L; Butler, N E; Campbell, J; Cassell, M A; Corbani, L E; Cousins, S L; Dahmen, D J; Dene, H; Diehl, A D; Drabkin, H J; Frazer, K S; Frost, P; Glass, L H; Goldsmith, C W; Grant, P L; Lennon-Pierce, M; Lewis, J; Lu, I; Maltais, L J; McAndrews-Hill, M; McClellan, L; Miers, D B; Miller, L A; Ni, L; Ormsby, J E; Qi, D; Reddy, T B K; Reed, D J; Richards-Smith, B; Shaw, D R; Sinclair, R; Smith, C L; Szauter, P; Walker, M B; Walton, D O; Washburn, L L; Witham, I T; Zhu, Y

    2005-01-01

    The Mouse Genome Database (MGD) forms the core of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a model organism database resource for the laboratory mouse. MGD provides essential integration of experimental knowledge for the mouse system with information annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genotype (sequence) through phenotype information, including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships among genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent improvements in MGD discussed here include the enhancement of phenotype resources, the re-development of the International Mouse Strain Resource, IMSR, the update of mammalian orthology datasets and the electronic publication of classic books in mouse genetics.

  20. Adhesive particle shielding

    DOEpatents

    Klebanoff, Leonard Elliott; Rader, Daniel John; Walton, Christopher; Folta, James

    2009-01-06

    An efficient device for capturing fast moving particles has an adhesive particle shield that includes (i) a mounting panel and (ii) a film that is attached to the mounting panel wherein the outer surface of the film has an adhesive coating disposed thereon to capture particles contacting the outer surface. The shield can be employed to maintain a substantially particle free environment such as in photolithographic systems having critical surfaces, such as wafers, masks, and optics and in the tools used to make these components, that are sensitive to particle contamination. The shield can be portable to be positioned in hard-to-reach areas of a photolithography machine. The adhesive particle shield can incorporate cooling means to attract particles via the thermophoresis effect.

  1. Synthesis and cleavage processing of oncornavirus proteins during interferon inhibition of virus particle release.

    PubMed Central

    Shapiro, S Z; Strand, M; Billiau, A

    1977-01-01

    The effect of interferon on the rate of synthesis and the cleavage processing of viral proteins in mouse cells, chronically infected with Rauscher murine leukemia virus, has been studied by immunoprecipitation of newly synthesized viral proteins from virus-infected cells pulse-labeled with [35S]methionine. Immuno-precipitated, labeled polypeptides were resolved by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and then examined by autoradiography. Cleavage processing was studied in the same manner with cells that had been pulse-labeled and then incubated with non-radioactive media for a sufficient time to allow normal cleavage processing to occur. At a concentration that strongly inhibited the release of virus particles, interferon had no effect on the synthesis of proteins carrying antigenic determinants of the major core protein p30 or of the envelope glycoprotein gp69/71. Nor did it affect the post-translational cleavage processing of the precursors to these proteins. Similarly, interferon did not affect labeling or chasing of precursor protein carrying the p15 determinants; labeling of p15 itself could not be studied because it does not contain methionine. PMID:70406

  2. Quantitative image analysis of laminin immunoreactivity in skin basement membrane irradiated with 1 GeV/nucleon iron particles

    NASA Technical Reports Server (NTRS)

    Costes, S.; Streuli, C. H.; Barcellos-Hoff, M. H.

    2000-01-01

    We previously reported that laminin immunoreactivity in mouse mammary epithelium is altered shortly after whole-body irradiation with 0.8 Gy from 600 MeV/nucleon iron ions but is unaffected after exposure to sparsely ionizing radiation. This observation led us to propose that the effect could be due to protein damage from the high ionization density of the ion tracks. If so, we predicted that it would be evident soon after radiation exposure in basement membranes of other tissues and would depend on ion fluence. To test this hypothesis, we used immunofluorescence, confocal laser scanning microscopy, and image segmentation techniques to quantify changes in the basement membrane of mouse skin epidermis. At 1 h after exposure to 1 GeV/nucleon iron ions with doses from 0.03 to 1.6 Gy, neither the visual appearance nor the mean pixel intensity of laminin in the basement membrane of mouse dorsal skin epidermis was altered compared to sham-irradiated tissue. This result does not support the hypothesis that particle traversal directly affects laminin protein integrity. However, the mean pixel intensity of laminin immunoreactivity was significantly decreased in epidermal basement membrane at 48 and 96 h after exposure to 0.8 Gy 1 GeV/nucleon iron ions. We confirmed this effect with two additional antibodies raised against affinity-purified laminin 1 and the E3 fragment of the long-arm of laminin 1. In contrast, collagen type IV, another component of the basement membrane, was unaffected. Our studies demonstrate quantitatively that densely ionizing radiation elicits changes in skin microenvironments distinct from those induced by sparsely ionizing radiation. Such effects may might contribute to the carcinogenic potential of densely ionizing radiation by altering cellular signaling cascades mediated by cell-extracellular matrix interactions.

  3. Constituent Particle Clustering and Pitting Corrosion

    NASA Astrophysics Data System (ADS)

    Harlow, D. Gary

    2012-08-01

    Corrosion is a primary degradation mechanism that affects the durability and integrity of structures made of aluminum alloys, and it is a concern for commercial transport and military aircraft. In aluminum alloys, corrosion results from local galvanic coupling between constituent particles and the metal matrix. Due to variability in particle sizes, spatial location, and chemical composition, to name a few critical variables, corrosion is a complex stochastic process. Severe pitting is caused by particle clusters that are located near the material surface, which, in turn, serve as nucleation sites for subsequent corrosion fatigue crack growth. These evolution processes are highly dependent on the spatial statistics of particles. The localized corrosion growth rate is primarily dependent on the galvanic process perpetuated by particle-to-particle interactions and electrochemical potentials. Frequently, severe pits are millimeters in length, and these pits have a dominant impact on the structural prognosis. To accommodate large sizes, a model for three-dimensional (3-D) constituent particle microstructure is proposed. To describe the constituent particle microstructure in three dimensions, the model employs a fusion of classic stereological techniques, spatial point pattern analyses, and qualitative observations. The methodology can be carried out using standard optical microscopy and image analysis techniques.

  4. Clay particle retention in small constructed wetlands.

    PubMed

    Braskerud, B C

    2003-09-01

    Constructed wetlands (CWs) can be used to mitigate non-point source pollution from arable fields. Previous investigations have shown that the relative soil particle retention in small CWs increases when hydraulic load increases. This paper investigates why this phenomenon occurs, even though common retention models predict the opposite, by studying clay and silt particle retention in two Norwegian CWs. Retention was measured with water flow proportional sampling systems in the inlet and outlet of the wetlands, and the texture of the suspended solids was analyzed. The surface area of the CWs was small compared to the watershed area (approximately 0.07%), giving high average hydraulic loads (1.1 and 2.0 md(-1)). One of the watersheds included only old arable land, whereas the other included areas with disturbed topsoil after artificial land leveling. Clay particle retention was 57% for the CW in the first watershed, and 22% for the CW in the disturbed watershed. The different behavior of the wetlands could be due to differences in aggregate size and stability of the particles entering the wetlands. Results showed that increased hydraulic loads did affect CW retention negatively. However, as runoff increased, soil particles/aggregates with higher sedimentation velocities entered the CWs (e.g., the clay particles behaved as silt particles). Hence, clay particle settling velocity is not constant as assumed in many prediction models. The net result was increased retention.

  5. Simulations of intracavity laser heating of particles

    NASA Astrophysics Data System (ADS)

    Linford, Gary J.

    1991-05-01

    The interaction physics of intracavity laser heated particles has been analyzed for the case of a moderate power (20 kW), high repetition rate (OM 12 kHz) Nd:YAG laser oscillator producing low energy (OM 10-5 J) optical pulses at (lambda) = 1.06 (mu) . The particles considered in this work are contaminants that inadvertently become attached to intracavity optical surfaces lying within the beam line of the laser during the course of assembly and test. Computer simulations were written to describe the behavior of a variety of dielectric, refractory, and metallic particles when irradiated with small diameter (OM 10-2 cm), high intensity (108 W/cm2) intracavity laser radiation. The simulations have shown that owing to the small laser beam diameters, contaminating intracavity particles larger than 5 (mu) can affect the dynamics of Nd:YAG laser oscillation, causing mode changes, delaying the achievement of peak laser power, and reducing performance. Significant heating of the particles may occur during the relatively short (OM 40 ns) oscillation build-up time applicable to these laser cavities. Ablation of material, melting, and vaporization of small diameter (< 10-4 cm) particles under these intracavity laser conditions is predicted. Steady-state conditions are calculated for high repetition rate operation with the result that asymptotic particle and substrate temperatures depend upon the thermal properties of the optical substrates. Operating regimes for which laser heated particle damage does not occur were determined.

  6. Chemical Composition of Laboratory Generated Seafoam Particles

    NASA Astrophysics Data System (ADS)

    Tyree, C. A.; Alexandrova, O. A.; Allen, J. O.

    2005-12-01

    Remote marine aerosols include a significant number of sea-salt particles that may be effective cloud condensation nuclei. For example, O`Dowd and Smith (1993) found that remote marine aerosols in the particle size range 0.1-3.0 μm were dominated by sea-salt particles in the case of moderate-to-high wind speeds. Measurements of the flux of sub-micron sea-salt particles for the same wind speed vary by orders of magnitude, which indicate that other parameters, for example, may have a role in their production (Reid et al., 2001). Previous laboratory experiments using artificial seawater have shown that organic content (Garrett, 1968) and salinity (Mortensson et al., 2003) affect sea-salt particle production. We present laboratory measurements of sea-salt particles generated from seawater foams and compare them to measurements of remote marine particles. Foam droplets were generated by bubbling air through a fine pore diffuser into aqueous media in a precleaned glass column. The effect of salinity was studied by varying the salinity of artificial seawater over the range 0-3.5%. The effect of organic content was also studied by diluting filtered seawater with artificial seawater. Size distributions of dried seafoam droplets were measured using a scanning mobility particle sizer. Seafoam particles were also size segregated and collected using a Micro-Orifice Uniform Deposit Impactor. Collected material was analyzed for sodium, chloride, sulfate, and dissolved organic carbon (DOC). Sub-micron particle size distributions were unimodal with a mean diameter of ~100 nm in agreement with recent seafoam laboratory experiments (Martensson et al., 2003). This mode is comparable to the "accumulation" mode particles typical of the remote marine environment and known to contain significant amounts of sea-salt (Bates et al., 1998). The size and number of seafoam particles were dependent on salinity; mean droplet size and total number concentration increased with salinity

  7. Interplanetary Disturbances Affecting Space Weather

    NASA Astrophysics Data System (ADS)

    Wimmer-Schweingruber, Robert F.

    2014-01-01

    The Sun somehow accelerates the solar wind, an incessant stream of plasma originating in coronal holes and some, as yet unidentified, regions. Occasionally, coronal, and possibly sub-photospheric structures, conspire to energize a spectacular eruption from the Sun which we call a coronal mass ejection (CME). These can leave the Sun at very high speeds and travel through the interplanetary medium, resulting in a large-scale disturbance of the ambient background plasma. These interplanetary CMEs (ICMEs) can drive shocks which in turn accelerate particles, but also have a distinct intrinsic magnetic structure which is capable of disturbing the Earth's magnetic field and causing significant geomagnetic effects. They also affect other planets, so they can and do contribute to space weather throughout the heliosphere. This paper presents a historical review of early space weather studies, a modern-day example, and discusses space weather throughout the heliosphere.

  8. Size Effects on the Magnetic Properties of Nanoscale Particles

    NASA Astrophysics Data System (ADS)

    Chen, Jianping

    %, and 10% by quinuclidine, pyridine and carbon