Sample records for mice demonstrate features

  1. Software for Demonstration of Features of Chain Polymerization Processes

    ERIC Educational Resources Information Center

    Sosnowski, Stanislaw

    2013-01-01

    Free software for the demonstration of the features of homo- and copolymerization processes (free radical, controlled radical, and living) is described. The software is based on the Monte Carlo algorithms and offers insight into the kinetics, molecular weight distribution, and microstructure of the macromolecules formed in those processes. It also…

  2. Intermittent cold stress enhances features of atherosclerotic plaque instability in apolipoprotein E?deficient mice.

    PubMed

    Zheng, Xi; Wang, Qiang; Zhang, Yan; Yang, Dachun; Li, De; Tang, Bing; Li, Xiuchuan; Yang, Yongjian; Ma, Shuangtao

    2014-10-01

    The cold weather is associated with an increased occurrence of acute coronary events. However, the mechanisms underlying cold?induced myocardial infarctions have not yet been fully elucidated. In the present study, 20 male, eight week?old, apolipoprotein E (ApoE)?deficient mice were subjected to either control conditions or intermittent cold exposure for eight weeks. Mice in the cold group were placed in a cold room at 4?C for 4 h per day, while the mice in the control group were kept in a room at 24?C. Cold?exposed mice did not significantly differ from control mice in body weight, fasting glucose concentration and plasma lipid levels, including triglyceride, total cholesterol, low?density lipoprotein and high?density lipoprotein. The hematoxylin and eosin?stained sections of the aortic root demonstrated increased plaque size in the cold group compared with the control group (P<0.01). Furthermore, cold?treated mice exhibited significantly decreased plaque collagen and vascular smooth muscle cell deposition and increased macrophage and lymphocyte content (P<0.05 or P<0.01), which are typical features of atherosclerotic plaque instability. Additionally, the protein expression of matrix metalloproteinase (MMP)?2, MMP?9 and MMP?14 were significantly increased (P<0.05 or P<0.01), whereas tissue inhibitor of matrix metalloproteinase (TIMP)?1 expression was decreased (P<0.05) following exposure to a cold environment. The present study demonstrated that chronic intermittent cold stress may increase atherosclerotic plaque size and promote plaque instability in ApoE?deficient mice by altering the balance of MMPs and TIMPs. These findings may provide mechanistic insights into sudden cardiac death in cold environments. PMID:25109747

  3. Demonstration of Spectrum Sensing with Blindly Learned Feature

    E-print Network

    Zhang, Peng; Guo, Nan

    2011-01-01

    Spectrum sensing is essential in cognitive radio. By defining leading \\textit{eigenvector} as feature, we introduce a blind feature learning algorithm (FLA) and a feature template matching (FTM) algorithm using learned feature for spectrum sensing. We implement both algorithms on Lyrtech software defined radio platform. Hardware experiment is performed to verify that feature can be learned blindly. We compare FTM with a blind detector in hardware and the results show that the detection performance for FTM is about 3 dB better.

  4. ATF4 activity: a common feature shared by many kinds of slow-aging mice

    PubMed Central

    Li, Weiquan; Li, Xinna; Miller, Richard A

    2014-01-01

    ATF4, a DNA-binding factor that modulates responses to amino acid availability and ribosomal function, has been shown to be altered in both liver and fibroblasts from two strains of long-lived mice, i.e. Snell dwarf and PAPP-A knockout mice. New data now show elevated ATF4 levels, and elevation of ATF4-dependent proteins and mRNAs, in liver of mice treated with acarbose or rapamycin, calorically restricted mice, methionine-restricted mice, and mice subjected to litter crowding. Elevation of ATF4, at least in liver, thus seems to be a shared feature of diets, drugs, genes, and developmental alterations that extend maximum lifespan in mice. PMID:25156122

  5. ATF4 activity: a common feature shared by many kinds of slow-aging mice.

    PubMed

    Li, Weiquan; Li, Xinna; Miller, Richard A

    2014-12-01

    ATF4, a DNA-binding factor that modulates responses to amino acid availability and ribosomal function, has been shown to be altered in both liver and fibroblasts from two strains of long-lived mice, i.e. Snell dwarf and PAPP-A knockout mice. New data now show elevated ATF4 levels, and elevation of ATF4-dependent proteins and mRNAs, in liver of mice treated with acarbose or rapamycin, calorically restricted mice, methionine-restricted mice, and mice subjected to litter crowding. Elevation of ATF4, at least in liver, thus seems to be a shared feature of diets, drugs, genes, and developmental alterations that extend maximum lifespan in mice. PMID:25156122

  6. Autism-associated gene Dlgap2 mutant mice demonstrate exacerbated aggressive behaviors and orbitofrontal cortex deficits

    PubMed Central

    2014-01-01

    Background As elegant structures designed for neural communication, synapses are the building bricks of our mental functions. Recently, many studies have pointed out that synaptic protein-associated mutations may lead to dysfunctions of social cognition. Dlgap2, which encodes one of the main components of scaffold proteins in postsynaptic density (PSD), has been addressed as a candidate gene in autism spectrum disorders. To elucidate the disturbance of synaptic balance arising from Dlgap2 loss-of-function in vivo, we thus generated Dlgap2 ?/? mice to investigate their phenotypes of synaptic function and social behaviors. Methods The creation of Dlgap2 ?/? mice was facilitated by the recombineering-based method, Cre-loxP system and serial backcross. Reversal learning in a water T-maze was used to determine repetitive behaviors. The three-chamber approach task, resident–intruder test and tube task were performed to characterize the social behaviors of mutant mice. Cortical synaptosomal fraction, Golgi-Cox staining, whole-cell patch electrophysiology and transmission electron microscopy were all applied to investigate the function and structure of synapses in the orbitofrontal cortex (OFC) of Dlgap2 ?/? mice. Results Dlgap2 ?/? mice displayed exacerbated aggressive behaviors in the resident–intruder task, and elevated social dominance in the tube test. In addition, Dlgap2 ?/? mice exhibited a clear reduction of receptors and scaffold proteins in cortical synapses. Dlgap2 ?/? mice also demonstrated lower spine density, decreased peak amplitude of miniature excitatory postsynaptic current and ultra-structural deficits of PSD in the OFC. Conclusions Our findings clearly demonstrate that Dlgap2 plays a vital role in social behaviors and proper synaptic functions of the OFC. Moreover, these results may provide valuable insights into the neuropathology of autism. PMID:25071926

  7. In vitro and in vivo demonstration of risperidone implants in mice

    PubMed Central

    Rabin, C.; Liang, Y.; Ehrlichman, R.S.; Budhian, A.; Metzger, K. L.; Majewski-Tiedeken, C.; Winey, K. I.; Siegel, S.J.

    2008-01-01

    Background Nonadherence with medication is a critical limitation in current long-term treatment of schizophrenia and a primary factor in poor quality-of-life outcomes. However, few treatments have addressed this shortcoming using an implantable drug delivery approach. The goal of this study was to provide in vitro and in vivo proof of concept for a long-term implantable risperidone delivery system in mice. Methods Implantable formulations of risperidone were created using the biodegradable polymer Poly Lactic co Glycolic Acid (PLGA) combined with various drug loads. Implant bioactivity was tested using in vitro release and stability studies, as well as in vivo pharmacokinetic and behavioral studies in mice. Results The pattern of risperidone release is influenced by various parameters, including polymer composition and drug load. In vitro measures demonstrate that risperidone is stable in implants under physiological conditions. Behavioral measures demonstrate the bioactivity of risperidone implants delivering 3mg/kg/day in mice, while pharmacokinetic analyses indicate that reversibility is maintained throughout the delivery interval. Conclusions The current report suggests that implantable formulations are a viable approach to providing long-term delivery of antipsychotic medications based on in vivo animal studies and pharmacokinetics. Implantable medications demonstrated here can last two months or longer while maintaining coherence and removability past full release, suggesting a potential paradigm shift in the long-term treatment of schizophrenia. PMID:17765477

  8. Unique features of retrovirus expression in F/St mice.

    PubMed Central

    Morse, H C; Kozak, C A; Yetter, R A; Hartley, J W

    1982-01-01

    F/St mice are unique in producing high levels of both ecotropic and xenotropic murine leukemia virus. The high ecotropic virus phenotype is determined by three or more V (virus-inducing) loci. A single locus for inducibility of xenotropic murine leukemia virus was mapped to chromosome 1 close to, but possibly not allelic to, Bxv-1. Although the high ecotropic virus phenotype is phenotypically dominant, the high xenotropic virus phenotype was recessive in all crosses tested. Suppression of xenotropic murine leukemia virus is governed by a single gene which is not linked to the xenotropic V locus. PMID:6286989

  9. Demonstration of Nondeclarative Sequence Learning in Mice: Development of an Animal Analog of the Human Serial Reaction Time Task

    ERIC Educational Resources Information Center

    Christie, Michael A.; Hersch, Steven M.

    2004-01-01

    In this paper, we demonstrate nondeclarative sequence learning in mice using an animal analog of the human serial reaction time task (SRT) that uses a within-group comparison of behavior in response to a repeating sequence versus a random sequence. Ten female B6CBA mice performed eleven 96-trial sessions containing 24 repetitions of a 4-trial…

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

    PubMed

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

    2015-01-01

    After creating >4,650 knockouts (KOs) of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1) KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase ? or ? (Dagla or Daglb), which catalyze biosynthesis of the endocannabinoid (EC) 2-arachidonoylglycerol (2-AG), or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild-type (WT) littermates; when data from multiple cohorts of adult mice were combined, body fat was 47 and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. By contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight (BW) similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride, and total cholesterol levels, and after glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: (1) the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; (2) in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and (3) small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower BW and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric side-effects. PMID:26082754

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

    PubMed Central

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

    2015-01-01

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

  12. Premature skin aging features rescued by inhibition of NADPH oxidase activity in XPC-deficient mice.

    PubMed

    Hosseini, Mohsen; Mahfouf, Walid; Serrano-Sanchez, Martin; Raad, Houssam; Harfouche, Ghida; Bonneu, Marc; Claverol, Stephane; Mazurier, Frederic; Rossignol, Rodrigue; Taieb, Alain; Rezvani, Hamid Reza

    2015-04-01

    Xeroderma pigmentosum type C (XP-C) is characterized mostly by a predisposition to skin cancers and accelerated photoaging, but little is known about premature skin aging in this disease. By comparing young and old mice, we found that the level of progerin and p16(INK4a) expression, ?-galactosidase activity, and reactive oxygen species, which increase with age, were higher in young Xpc(-/-) mice than in young Xpc(+/+) ones. The expression level of mitochondrial complexes and mitochondrial functions in the skin of young Xpc(-/-) was as low as in control aged Xpc(+/+)animals. Furthermore, the metabolic profile in young Xpc(-/-) mice resembled that found in aged Xpc(+/+) mice. Furthermore, premature skin aging features in young Xpc(-/-) mice were mostly rescued by inhibition of nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) activity by using a NOX1 peptide inhibitor, suggesting that the continuous oxidative stress due to overactivation of NOX1 has a causative role in the underlying pathophysiology. PMID:25437426

  13. Conceptual damage-sensitive features for structural health monitoring: Laboratory and field demonstrations

    NASA Astrophysics Data System (ADS)

    Catbas, F. Necati; Gul, Mustafa; Burkett, Jason L.

    2008-10-01

    The use of damage-sensitive features to evaluate structural condition or health is a very critical aspect of structural health monitoring. The purpose of this paper is to investigate the potential of two different damage-sensitive features for detecting damage. Different damage scenarios are simulated on a large-scale laboratory structure and a three-span highway bridge for demonstration. The features presented in this paper are the modal flexibility-based deflection and curvature both of which are obtained directly from dynamic properties. In the literature, flexibility associated with mode shapes and mode shapes curvatures have been mostly explored. In this study, multi-input-multi-output dynamic data are used to obtain modal flexibility, which is a close approximation to the actual flexibility. A main novelty is that the curvature is calculated from the deflected shapes using the modal flexibility as opposed to using modal vectors. In this paper, the theory of the methodology is explained and then experimental studies and results are presented. For the experimental studies, the laboratory specimen and the three-span bridge were gradually damaged. It is shown that both deflection and curvature are conceptual and physically meaningful features for damage detection and localization. The issues and the requirements for these features to perform successfully are also presented.

  14. Compared with DBA/2J mice, C57BL/6J mice demonstrate greater preference for saccharin and less avoidance of a cocaine-paired saccharin cue

    PubMed Central

    Freet, Christopher S.; Arndt, Amanda; Grigson, Patricia S.

    2014-01-01

    Rats avoid intake of a saccharin cue when paired with a drug of abuse. While this is true for most subjects, the degree of avoidance of the drug-paired cue depends upon many factors including an individual rat’s preference for rewards. That said, the direction of this effect is complex. For example, reward-preferring Lewis rats exhibit greater cocaine-induced avoidance of a saccharin cue relative to Fischer 344 rats; while reward-preferring mice that over express ?FosB (NSE-tTA x TetOp-?FosB) exhibit less avoidance of the drug-paired taste cue compared to controls. The aim here was to use two strains of commonly used mice, C57BL/6J and DBA/2J, to determine whether known differences in sensitivity to rewards will facilitate or attenuate drug-induced suppression of intake of a drug-paired taste cue. The results of Experiment 1 demonstrate that C57BL/6J mice, compared with DBA/2J mice, exhibit attenuated suppression of saccharin intake when it is paired with cocaine. The results of Experiment 2 demonstrate that strain differences in impulsivity are not likely to account for these differences. It is proposed that, while the C57BL/6J mice typically are more responsive to drug, they also are more responsive to natural rewards (in this case saccharin), and the stronger preference for saccharin serves to militate against drug. PMID:23544599

  15. Alzheimer's disease-like pathological features in transgenic mice expressing the APP intracellular domain

    PubMed Central

    Ghosal, Kaushik; Vogt, Daniel L.; Liang, Man; Shen, Yong; Lamb, Bruce T.; Pimplikar, Sanjay W.

    2009-01-01

    The hypothesis that amyloid-? (A?) peptides are the primary cause of Alzheimer's disease (AD) remains the best supported theory of AD pathogenesis. Yet, many observations are inconsistent with the hypothesis. A? peptides are generated when amyloid precursor protein (APP) is cleaved by presenilins, a process that also produces APP intracellular domain (AICD). We previously generated AICD-overexpressing transgenic mice that showed abnormal activation of GSK-3?, a pathological feature of AD. We now report that these mice exhibit additional AD-like characteristics, including hyperphosphorylation and aggregation of tau, neurodegeneration and working memory deficits that are prevented by treatment with lithium, a GSK-3? inhibitor. Consistent with its potential role in AD pathogenesis, we find AICD levels to be elevated in brains from AD patients. The in vivo findings that AICD can contribute to AD pathology independently of A? have important therapeutic implications and may explain some observations that are discordant with the amyloid hypothesis. PMID:19837693

  16. Behavioral phenotyping of Parkin-deficient mice: looking for early preclinical features of Parkinson's disease.

    PubMed

    Rial, Daniel; Castro, Adalberto A; Machado, Nuno; Garção, Pedro; Gonçalves, Francisco Q; Silva, Henrique B; Tomé, Angelo R; Köfalvi, Attila; Corti, Olga; Raisman-Vozari, Rita; Cunha, Rodrigo A; Prediger, Rui D

    2014-01-01

    There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson's disease (PD) begin many years before the appearance of the characteristic motor symptoms. Neuropsychiatric, sensorial and cognitive deficits are recognized as early non-motor manifestations of PD, and are not attenuated by the current anti-parkinsonian therapy. Although loss-of-function mutations in the parkin gene cause early-onset familial PD, Parkin-deficient mice do not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to dopaminergic neurotoxins such as 6-OHDA and MPTP. Here, we employed adult homozygous C57BL/6 mice with parkin gene deletion on exon 3 (parkin-/-) to further investigate the relevance of Parkin in the regulation of non-motor features, namely olfactory, emotional, cognitive and hippocampal synaptic plasticity. Parkin-/- mice displayed normal performance on behavioral tests evaluating olfaction (olfactory discrimination), anxiety (elevated plus-maze), depressive-like behavior (forced swimming and tail suspension) and motor function (rotarod, grasping strength and pole). However, parkin-/- mice displayed a poor performance in the open field habituation, object location and modified Y-maze tasks suggestive of procedural and short-term spatial memory deficits. These behavioral impairments were accompanied by impaired hippocampal long-term potentiation (LTP). These findings indicate that the genetic deletion of parkin causes deficiencies in hippocampal synaptic plasticity, resulting in memory deficits with no major olfactory, emotional or motor impairments. Therefore, parkin-/- mice may represent a promising animal model to study the early stages of PD and for testing new therapeutic strategies to restore learning and memory and synaptic plasticity impairments in PD. PMID:25486126

  17. Elovl2 ablation demonstrates that systemic DHA is endogenously produced and is essential for lipid homeostasis in mice[S

    PubMed Central

    Pauter, Anna M.; Olsson, Petter; Asadi, Abolfazl; Herslöf, Bengt; Csikasz, Robert I.; Zadravec, Damir; Jacobsson, Anders

    2014-01-01

    The potential role of endogenously synthesized PUFAs is a highly overlooked area. Elongation of very long-chain fatty acids (ELOVLs) in mammals is catalyzed by the ELOVL enzymes to which the PUFA elongase ELOVL2 belongs. To determine its in vivo function, we have investigated how ablation of ELOVL2, which is highly expressed in liver, affects hepatic lipid composition and function in mice. The Elovl2?/? mice displayed substantially decreased levels of 22:6(n-3), DHA, and 22:5(n-6), docosapentaenoic acid (DPA) n-6, and an accumulation of 22:5(n-3) and 22:4(n-6) in both liver and serum, showing that ELOVL2 primarily controls the elongation process of PUFAs with 22 carbons to produce 24-carbon precursors for DHA and DPAn-6 formation in vivo. The impaired PUFA levels positively influenced hepatic levels of the key lipogenic transcriptional regulator sterol-regulatory element binding protein 1c (SREBP-1c), as well as its downstream target genes. Surprisingly, the Elovl2?/? mice were resistant to hepatic steatosis and diet-induced weight gain, implying that hepatic DHA synthesis via ELOVL2, in addition to controlling de novo lipogenesis, also regulates lipid storage and fat mass expansion in an SREBP-1c-independent fashion. The changes in fatty acid metabolism were reversed by dietary supplementation with DHA. PMID:24489111

  18. Segmental and Generalized Vitiligo: Both Forms Demonstrate Inflammatory Histopathological Features and Clinical Mosaicism

    PubMed Central

    Attili, Venkat Ratnam; Attili, Sasi Kiran

    2013-01-01

    Background: Segmental vitiligo (SV) and generalized vitiligo (GV) are perceived to evolve by different mechanisms, the former with unspecified neural mechanisms and the latter by melanocyte specific autoimmune mechanisms. However, the two diverse mechanisms are difficult to reconcile in cases of “mixed vitiligo”. To test the possibility of a common pathogenesis, we reviewed clinical and histopathological features of SV and GV. Materials and Methods: As part of an ongoing histopathological study on vitiligo and vitiligo like lesions, over a 10 year period from 2002 to 2011, biopsies were taken routinely from evolving or recently evolved lesions. 50 cases of SV with quasi-dermatomal distribution and 154 cases of GV were identified and the clinical and histopathological features were compared. Results: Mild clinical inflammation was recorded in 33 of 154 GV cases but, none among 50 SV had such features. In addition to bilateral symmetrical involvement, mirror image lesions with unusual segmentation were observed in nine cases of GV. SV with a few bilateral lesions (4) and GV with quasi-dermatomal lesions (3), i.e., mixed vitiligo, were included in their corresponding groups for analytical purposes. Focal lichenoid inflammation of varying degrees around epidermal/adnexal melanocytes was identified as a common feature in evolving lesions of both SV (78%) and GV (70%). Conclusions: SV and GV demonstrated a similar inflammatory histopathological spectrum. “Segmentation/mosaicism”, identified for the first time in GV is another unifying factor. Cutaneous mosaicism harboring fragile melanocyte populations, which are susceptible to external as well as auto-inflammatory mechanisms, is an attractive hypothesis to pursue in the causation of vitiligo. PMID:24249893

  19. Monoamine oxidase A and A/B knockout mice display autistic-like features

    PubMed Central

    Bortolato, Marco; Godar, Sean C.; Alzghoul, Loai; Zhang, Junlin; Darling, Ryan D.; Simpson, Kimberly L.; Bini, Valentina; Chen, Kevin; Wellman, Cara L.; Lin, Rick C. S.; Shih, Jean C.

    2012-01-01

    Converging lines of evidence show that a sizable subset of autism-spectrum disorders (ASDs) is characterized by increased blood levels of serotonin (5-hydroxytryptamine, 5-HT), yet the mechanistic link between these two phenomena remains unclear. The enzymatic degradation of brain 5-HT is mainly mediated by monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels, particularly during early developmental stages. Here we show that both mutant lines exhibit numerous behavioural hallmarks of ASDs, such as social and communication impairments, perseverative and stereotypical responses, behavioural inflexibility, as well as subtle tactile and motor deficits. Furthermore, both MAOA and A/B KO mice displayed neuropathological alterations reminiscent of typical ASD features, including reduced thickness of the corpus callosum, increased dendritic arborization of pyramidal neurons in the prefrontal cortex and disrupted microarchitecture of the cerebellum. The severity of repetitive responses and neuropathological aberrances was generally greater in MAOA/B KO animals. These findings suggest that the neurochemical imbalances induced by MAOAdeficiency (either by itself or in conjunction with lack of MAOB) may result in an array of abnormalities similar to those observed in ASDs. Thus, MAOA and A/B KO mice may afford valuable models to help elucidate the neurobiological bases of these disorders and related neurodevelopmental problems. PMID:22850464

  20. Monoamine oxidase A and A/B knockout mice display autistic-like features.

    PubMed

    Bortolato, Marco; Godar, Sean C; Alzghoul, Loai; Zhang, Junlin; Darling, Ryan D; Simpson, Kimberly L; Bini, Valentina; Chen, Kevin; Wellman, Cara L; Lin, Rick C S; Shih, Jean C

    2013-05-01

    Converging lines of evidence show that a sizable subset of autism-spectrum disorders (ASDs) is characterized by increased blood levels of serotonin (5-hydroxytryptamine, 5-HT), yet the mechanistic link between these two phenomena remains unclear. The enzymatic degradation of brain 5-HT is mainly mediated by monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels, particularly during early developmental stages. Here we show that both mutant lines exhibit numerous behavioural hallmarks of ASDs, such as social and communication impairments, perseverative and stereotypical responses, behavioural inflexibility, as well as subtle tactile and motor deficits. Furthermore, both MAOA and A/B KO mice displayed neuropathological alterations reminiscent of typical ASD features, including reduced thickness of the corpus callosum, increased dendritic arborization of pyramidal neurons in the prefrontal cortex and disrupted microarchitecture of the cerebellum. The severity of repetitive responses and neuropathological aberrances was generally greater in MAOA/B KO animals. These findings suggest that the neurochemical imbalances induced by MAOA deficiency (either by itself or in conjunction with lack of MAOB) may result in an array of abnormalities similar to those observed in ASDs. Thus, MAOA and A/B KO mice may afford valuable models to help elucidate the neurobiological bases of these disorders and related neurodevelopmental problems. PMID:22850464

  1. Pathophysiological Features of Asthma Develop in Parallel in House Dust Mite–Exposed Neonatal Mice

    PubMed Central

    Saglani, Sejal; Mathie, Sara A.; Gregory, Lisa G.; Bell, Matthew J.; Bush, Andrew; Lloyd, Clare M.

    2012-01-01

    Asthma frequently commences in early life during airway and immune development and exposure to new environmental challenges. Endobronchial biopsies from children with asthma are abnormal, and lung function is maximally reduced by 6 years of age. As longitudinal biopsy studies are unethical in children, the relationship between development of pathology and reduced lung function is unknown. We aimed to establish a novel neonatal mouse model of allergic airways disease to investigate the developmental sequence of the pathophysiologic features of asthma. Neonatal Balb/c mice were challenged three times weekly from Day 3 of life using intranasal house dust mite (HDM) or saline for up to 12 weeks. Weekly assessments of airway inflammation and remodeling were made. Airway hyperresponsiveness (AHR) to methacholine was assessed from Week 2 onward. Total and eosinophilic inflammation was significantly increased in the lungs of HDM-exposed neonates from Week 2 onwards, and a peak was seen at 3 weeks. Goblet cells and peribronchiolar reticulin deposition were significantly increased in HDM-exposed neonates from Week 3, and peribronchiolar collagen was significantly greater from Week 4. HDM-exposed neonates had increased AHR from Week 2 onward. Although inflammation and AHR had subsided after 4 weeks without allergen challenge, the increased reticulin and collagen deposition persisted in HDM-exposed mice. Neonatal mice exposed to intranasal HDM developed eosinophilic inflammation, airway remodeling, and AHR as reported in pediatric asthma. Importantly, all abnormalities developed in parallel, not sequentially, between 2 and 3 weeks of age. PMID:19151316

  2. An endocrinology laboratory exercise demonstrating the effect of confinement stress on the immune system of mice

    NSDL National Science Digital Library

    Jacqueline Brehe (Carroll College Biology)

    2008-03-04

    This article describes a simple laboratory exercise for examining the effect of stress on the immune system in mice. Mice are subjected to confinement stress for 1 h, after which a sample of blood is collected via the caudal vein. Blood samples are smeared onto microscope slides, air dried, and stained with Wright's Giemsa stain. When differential white blood cell counts are performed, there are noticeable differences between the neutrophil and lymphocyte counts of stressed versus control mice. The protocol is simple enough for students to perform, and the entire experiment can be completed within 3 h. Examples of ways in which the basic protocol can be modified to accommodate a shorter laboratory class are provided. This hands-on laboratory experiment provides students with experience using the scientific method to investigate the interaction between the endocrine and immune systems in response to stress.

  3. Prion Protein Amino Acid Determinants of Differential Susceptibility and Molecular Feature of Prion Strains in Mice and Voles

    PubMed Central

    Agrimi, Umberto; Nonno, Romolo; Dell'Omo, Giacomo; Di Bari, Michele Angelo; Conte, Michela; Chiappini, Barbara; Esposito, Elena; Di Guardo, Giovanni; Windl, Otto; Vaccari, Gabriele; Lipp, Hans-Peter

    2008-01-01

    The bank vole is a rodent susceptible to different prion strains from humans and various animal species. We analyzed the transmission features of different prions in a panel of seven rodent species which showed various degrees of phylogenetic affinity and specific prion protein (PrP) sequence divergences in order to investigate the basis of vole susceptibility in comparison to other rodent models. At first, we found a differential susceptibility of bank and field voles compared to C57Bl/6 and wood mice. Voles showed high susceptibility to sheep scrapie but were resistant to bovine spongiform encephalopathy, whereas C57Bl/6 and wood mice displayed opposite features. Infection with mouse-adapted scrapie 139A was faster in voles than in C57Bl/6 and wood mice. Moreover, a glycoprofile change was observed in voles, which was reverted upon back passage to mice. All strains replicated much faster in voles than in mice after adapting to the new species. PrP sequence comparison indicated a correlation between the transmission patterns and amino acids at positions 154 and 169 (Y and S in mice, N and N in voles). This correlation was confirmed when inoculating three additional rodent species: gerbils, spiny mice and oldfield mice with sheep scrapie and 139A. These rodents were chosen because oldfield mice do have the 154N and 169N substitutions, whereas gerbil and spiny mice do not have them. Our results suggest that PrP residues 154 and 169 drive the susceptibility, molecular phenotype and replication rate of prion strains in rodents. This might have implications for the assessment of host range and molecular traceability of prion strains, as well as for the development of improved animal models for prion diseases. PMID:18654630

  4. Clinical Features: CDKL5 mutations have been demonstrated in a broad spectrum of phenotypes [1-5], including

    E-print Network

    Das, Soma

    3/10 Clinical Features: CDKL5 mutations have been demonstrated in a broad spectrum of phenotypes [1 feature found in patients reported to date with CDKL5 mutations is the early onset of seizures. 13/14 patients studied had seizures before 3 months of age [1]. Inheritance: CDKL5 mutations are X

  5. Clinical Features: CDKL5 mutations have been demonstrated in a broad spectrum of phenotypes [1-5], including

    E-print Network

    Gilad, Yoav

    6/11 Clinical Features: CDKL5 mutations have been demonstrated in a broad spectrum of phenotypes [1 feature found in patients reported to date with CDKL5 mutations is the early onset of seizures. 13/14 patients studied had seizures before 3 months of age [1]. Inheritance: CDKL5 mutations are X

  6. Clinical Features: CDKL5 mutations have been demonstrated in a broad spectrum of phenotypes [1-5], including

    E-print Network

    Ober, Carole

    1/13 Clinical Features: CDKL5 mutations have been demonstrated in a broad spectrum of phenotypes [1 feature found in patients reported to date with CDKL5 mutations is the early onset of seizures. 13/14 patients studied had seizures before 3 months of age [1]. Inheritance: CDKL5 mutations are X

  7. Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice

    PubMed Central

    Pai, Yun Jin; Leung, Kit-Yi; Savery, Dawn; Hutchin, Tim; Prunty, Helen; Heales, Simon; Brosnan, Margaret E.; Brosnan, John T.; Copp, Andrew J.; Greene, Nicholas D.E.

    2015-01-01

    Glycine decarboxylase (GLDC) acts in the glycine cleavage system to decarboxylate glycine and transfer a one-carbon unit into folate one-carbon metabolism. GLDC mutations cause a rare recessive disease non-ketotic hyperglycinemia (NKH). Mutations have also been identified in patients with neural tube defects (NTDs); however, the relationship between NKH and NTDs is unclear. We show that reduced expression of Gldc in mice suppresses glycine cleavage system activity and causes two distinct disease phenotypes. Mutant embryos develop partially penetrant NTDs while surviving mice exhibit post-natal features of NKH including glycine accumulation, early lethality and hydrocephalus. In addition to elevated glycine, Gldc disruption also results in abnormal tissue folate profiles, with depletion of one-carbon-carrying folates, as well as growth retardation and reduced cellular proliferation. Formate treatment normalizes the folate profile, restores embryonic growth and prevents NTDs, suggesting that Gldc deficiency causes NTDs through limiting supply of one-carbon units from mitochondrial folate metabolism. PMID:25736695

  8. Knock-In Reporter Mice Demonstrate that DNA Repair by Non-homologous End Joining Declines with Age

    PubMed Central

    Vaidya, Amita; Mao, Zhiyong; Tian, Xiao; Spencer, Brianna; Seluanov, Andrei; Gorbunova, Vera

    2014-01-01

    Accumulation of genome rearrangements is a characteristic of aged tissues. Since genome rearrangements result from faulty repair of DNA double strand breaks (DSBs), we hypothesized that DNA DSB repair becomes less efficient with age. The Non-Homologous End Joining (NHEJ) pathway repairs a majority of DSBs in vertebrates. To examine age-associated changes in NHEJ, we have generated an R26NHEJ mouse model in which a GFP-based NHEJ reporter cassette is knocked-in to the ROSA26 locus. In this model, NHEJ repair of DSBs generated by the site-specific endonuclease, I-SceI, reconstitutes a functional GFP gene. In this system NHEJ efficiency can be compared across tissues of the same mouse and in mice of different age. Using R26NHEJ mice, we found that NHEJ efficiency was higher in the skin, lung, and kidney fibroblasts, and lower in the heart fibroblasts and brain astrocytes. Furthermore, we observed that NHEJ efficiency declined with age. In the 24-month old animals compared to the 5-month old animals, NHEJ efficiency declined 1.8 to 3.8-fold, depending on the tissue, with the strongest decline observed in the skin fibroblasts. The sequence analysis of 300 independent NHEJ repair events showed that, regardless of age, mice utilize microhomology sequences at a significantly higher frequency than expected by chance. Furthermore, the frequency of microhomology-mediated end joining (MMEJ) events increased in the heart and lung fibroblasts of old mice, suggesting that NHEJ becomes more mutagenic with age. In summary, our study provides a versatile mouse model for the analysis of NHEJ in a wide range of tissues and demonstrates that DNA repair by NHEJ declines with age in mice, which could provide a mechanism for age-related genomic instability and increased cancer incidence with age. PMID:25033455

  9. Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age.

    PubMed

    Vaidya, Amita; Mao, Zhiyong; Tian, Xiao; Spencer, Brianna; Seluanov, Andrei; Gorbunova, Vera

    2014-07-01

    Accumulation of genome rearrangements is a characteristic of aged tissues. Since genome rearrangements result from faulty repair of DNA double strand breaks (DSBs), we hypothesized that DNA DSB repair becomes less efficient with age. The Non-Homologous End Joining (NHEJ) pathway repairs a majority of DSBs in vertebrates. To examine age-associated changes in NHEJ, we have generated an R26NHEJ mouse model in which a GFP-based NHEJ reporter cassette is knocked-in to the ROSA26 locus. In this model, NHEJ repair of DSBs generated by the site-specific endonuclease, I-SceI, reconstitutes a functional GFP gene. In this system NHEJ efficiency can be compared across tissues of the same mouse and in mice of different age. Using R26NHEJ mice, we found that NHEJ efficiency was higher in the skin, lung, and kidney fibroblasts, and lower in the heart fibroblasts and brain astrocytes. Furthermore, we observed that NHEJ efficiency declined with age. In the 24-month old animals compared to the 5-month old animals, NHEJ efficiency declined 1.8 to 3.8-fold, depending on the tissue, with the strongest decline observed in the skin fibroblasts. The sequence analysis of 300 independent NHEJ repair events showed that, regardless of age, mice utilize microhomology sequences at a significantly higher frequency than expected by chance. Furthermore, the frequency of microhomology-mediated end joining (MMEJ) events increased in the heart and lung fibroblasts of old mice, suggesting that NHEJ becomes more mutagenic with age. In summary, our study provides a versatile mouse model for the analysis of NHEJ in a wide range of tissues and demonstrates that DNA repair by NHEJ declines with age in mice, which could provide a mechanism for age-related genomic instability and increased cancer incidence with age. PMID:25033455

  10. CEP290 alleles in mice disrupt tissue-specific cilia biogenesis and recapitulate features of syndromic ciliopathies.

    PubMed

    Rachel, Rivka A; Yamamoto, Erin A; Dewanjee, Mrinal K; May-Simera, Helen L; Sergeev, Yuri V; Hackett, Alice N; Pohida, Katherine; Munasinghe, Jeeva; Gotoh, Norimoto; Wickstead, Bill; Fariss, Robert N; Dong, Lijin; Li, Tiansen; Swaroop, Anand

    2015-07-01

    Distinct mutations in the centrosomal-cilia protein CEP290 lead to diverse clinical findings in syndromic ciliopathies. We show that CEP290 localizes to the transition zone in ciliated cells, precisely to the region of Y-linkers between central microtubules and plasma membrane. To create models of CEP290-associated ciliopathy syndromes, we generated Cep290(ko/ko) and Cep290(gt/gt) mice that produce no or a truncated CEP290 protein, respectively. Cep290(ko/ko) mice exhibit early vision loss and die from hydrocephalus. Retinal photoreceptors in Cep290(ko/ko) mice lack connecting cilia, and ciliated ventricular ependyma fails to mature. The minority of Cep290(ko/ko) mice that escape hydrocephalus demonstrate progressive kidney pathology. Cep290(gt/gt) mice die at mid-gestation, and the occasional Cep290(gt/gt) mouse that survives shows hydrocephalus and severely cystic kidneys. Partial loss of CEP290-interacting ciliopathy protein MKKS mitigates lethality and renal pathology in Cep290(gt/gt) mice. Our studies demonstrate domain-specific functions of CEP290 and provide novel therapeutic paradigms for ciliopathies. PMID:25859007

  11. Chitin assay used to demonstrate renal localization and cortisone-enhanced growth of Aspergillus fumigatus mycelium in mice.

    PubMed Central

    Lehmann, P F; White, L O

    1975-01-01

    Aspergillus fumigatus mycelium in untreated mice (N-mice) and cortisone acetate-treated mice (C-mice) has been quantified by chemical assay of fungal chitin. Cortisone pretreatment rendered mice more susceptible to infection by A. fumigatus (mean lethal dose at 20 days, congruent to 10(6) for N-mice; less than 10(4) for C-mice). In both N- and C-mice there was renal localization of mycelial infection at conidial doses less than the mean lethal dose. At a conidial dose greater than the mean lethal dose, mycelial infection was found in the kidneys and brain of N-mice and in the kidneys, liver, and heart of C-mice. Chitin assay results showed that A. fumigatus mycelium grew more rapidly in C-mice. It is suggested that the resistance of N-mice to mycelial development may be an important mechanism whereby natural resistance to A. fumigatus is conferred. PMID:1104488

  12. Development of Smallpox Vaccine Candidates with Integrated Interleukin-15 That Demonstrate Superior Immunogenicity, Efficacy, and Safety in Mice?

    PubMed Central

    Perera, Liyanage P.; Waldmann, Thomas A.; Mosca, Joseph D.; Baldwin, Nicole; Berzofsky, Jay A.; Oh, Sang-Kon

    2007-01-01

    The potential use of variola virus, the etiological agent of smallpox, as a bioterror agent has heightened the interest in the reinitiation of smallpox vaccination. However, the currently licensed Dryvax vaccine, despite its documented efficacy in eradicating smallpox, is not optimal for the vaccination of contemporary populations with large numbers of individuals with immunodeficiencies because of severe adverse effects that can occur in such individuals. Therefore, the development of safer smallpox vaccines that can match the immunogenicity and efficacy of Dryvax for the vaccination of contemporary populations remains a priority. Using the Wyeth strain of vaccinia virus derived from the Dryvax vaccine, we generated a recombinant Wyeth interleukin-15 (IL-15) with integrated IL-15, a cytokine with potent immunostimulatory functions. The integration of IL-15 into the Wyeth strain resulted in a >1,000-fold reduction in lethality of vaccinated athymic nude mice and induced severalfold-higher cellular and humoral immune responses in wild-type mice that persisted longer than those induced by the parental Wyeth strain. The superior efficacy of Wyeth IL-15 was further demonstrated by the ability of vaccinated mice to fully survive a lethal intranasal challenge of virulent vaccinia virus even 10 months after vaccination, whereas all mice vaccinated with parental Wyeth strain succumbed. By integrating IL-15 into modified vaccinia virus Ankara (MVA), a virus currently under consideration as a substitute for the Dryvax vaccine, we developed a second vaccine candidate (MVA IL-15) with greater immunogenicity and efficacy than Dryvax. Thus, Wyeth IL-15 and MVA IL-15 viruses hold promise as more-efficacious and safe alternatives to the Dryvax vaccine. PMID:17553867

  13. Reduced TET2 function leads to T-cell lymphoma with follicular helper T-cell-like features in mice

    PubMed Central

    Muto, H; Sakata-Yanagimoto, M; Nagae, G; Shiozawa, Y; Miyake, Y; Yoshida, K; Enami, T; Kamada, Y; Kato, T; Uchida, K; Nanmoku, T; Obara, N; Suzukawa, K; Sanada, M; Nakamura, N; Aburatani, H; Ogawa, S; Chiba, S

    2014-01-01

    TET2 (Ten Eleven Translocation 2) is a dioxygenase that converts methylcytosine (mC) to hydroxymethylcytosine (hmC). TET2 loss-of-function mutations are highly frequent in subtypes of T-cell lymphoma that harbor follicular helper T (Tfh)-cell-like features, such as angioimmunoblastic T-cell lymphoma (30–83%) or peripheral T-cell lymphoma, not otherwise specified (10–49%), as well as myeloid malignancies. Here, we show that middle-aged Tet2 knockdown (Tet2gt/gt) mice exhibit Tfh-like cell overproduction in the spleen compared with control mice. The Tet2 knockdown mice eventually develop T-cell lymphoma with Tfh-like features after a long latency (median 67 weeks). Transcriptome analysis revealed that these lymphoma cells had Tfh-like gene expression patterns when compared with splenic CD4-positive cells of wild-type mice. The lymphoma cells showed lower hmC densities around the transcription start site (TSS) and higher mC densities at the regions of the TSS, gene body and CpG islands. These epigenetic changes, seen in Tet2 insufficiency-triggered lymphoma, possibly contributed to predated outgrowth of Tfh-like cells and subsequent lymphomagenesis. The mouse model described here suggests that TET2 mutations play a major role in the development of T-cell lymphoma with Tfh-like features in humans. PMID:25501021

  14. Clinical Features: CDKL5 mutations have been demonstrated in a broad spectrum of phenotypes [1-5], including

    E-print Network

    Gilad, Yoav

    3/10 Clinical Features: CDKL5 mutations have been demonstrated in a broad spectrum of phenotypes [1 in patients reported to date with CDKL5 mutations is the early onset of seizures. 13/14 patients studied had seizures before 3 months of age [1]. Inheritance: CDKL5 mutations are X-linked and appear to be less common

  15. Treatment with CB2 Agonist JWH-133 Reduces Histological Features Associated with Erectile Dysfunction in Hypercholesterolemic Mice

    PubMed Central

    Fraga-Silva, Rodrigo Araujo; Costa-Fraga, Fabiana Pereira; Faye, Younouss; Savergnini, Silvia Quintao; Lenglet, Sébastien; Mach, François; Steffens, Sabine; Stergiopulos, Nikolaos; Souza dos Santos, Robson Augusto; da Silva, Rafaela Fernandes

    2013-01-01

    Hypercholesterolemia is one of the most important risk factors for erectile dysfunction, mostly due to the impairment of oxidative stress and endothelial function in the penis. The cannabinoid system might regulate peripheral mechanisms of sexual function; however, its role is still poorly understood. We investigated the effects of CB2 activation on oxidative stress and fibrosis within the corpus cavernosum of hypercholesterolemic mice. Apolipoprotein-E-knockout mice were fed with a western-type diet for 11 weeks and treated with JWH-133 (selective CB2 agonist) or vehicle during the last 3 weeks. CB2 receptor expression, total collagen content, and reactive oxygen species (ROS) production within the penis were assessed. In vitro corpus cavernosum strips preparation was performed to evaluate the nitric oxide (NO) bioavailability. CB2 protein expression was shown in cavernosal endothelial and smooth muscle cells of wild type and hypercholesterolemic mice. Treatment with JWH-133 reduced ROS production and NADPH-oxidase expression in hypercholesterolemic mice penis. Furthermore, JWH-133 increased endothelial NO synthase expression in the corpus cavernosum and augmented NO bioavailability. The decrease in oxidative stress levels was accompanied with a reduction in corpus cavernosum collagen content. In summary, CB2 activation decreased histological features, which were associated with erectile dysfunction in hypercholesterolemic mice. PMID:24302957

  16. Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease.

    PubMed Central

    Yamanaka, S; Johnson, M D; Grinberg, A; Westphal, H; Crawley, J N; Taniike, M; Suzuki, K; Proia, R L

    1994-01-01

    Tay-Sachs disease, the prototype of the GM2 gangliosidoses, is a catastrophic neurodegenerative disorder of infancy. The disease is caused by mutations in the HEXA gene resulting in an absence of the lysosomal enzyme, beta-hexosaminidase A. As a consequence of the enzyme deficiency, GM2 ganglioside accumulates progressively, beginning early in fetal life, to excessive amounts in the central nervous system. Rapid mental and motor deterioration starting in the first year of life leads to death by 2-4 years of age. Through the targeted disruption of the mouse Hexa gene in embryonic stem cells, we have produced mice with biochemical and neuropathologic features of Tay-Sachs disease. The mutant mice displayed < 1% of normal beta-hexosaminidase A activity and accumulated GM2 ganglioside in their central nervous system in an age-dependent manner. The accumulated ganglioside was stored in neurons as membranous cytoplasmic bodies characteristically found in the neurons of Tay-Sachs disease patients. At 3-5 months of age, the mutant mice showed no apparent defects in motor or memory function. These beta-hexosaminidase A-deficient mice should be useful for devising strategies to introduce functional enzyme and genes into the central nervous system. This model may also be valuable for studying the biochemical and pathologic changes occurring during the course of the disease. Images PMID:7937929

  17. G protein-coupled receptor kinase-3-deficient mice exhibit WHIM syndrome features and attenuated inflammatory responses

    PubMed Central

    Tarrant, Teresa K.; Billard, Matthew J.; Timoshchenko, Roman G.; McGinnis, Marcus W.; Serafin, D. Stephen; Foreman, Oded; Esserman, Denise A.; Chao, Nelson J.; Lento, William E.; Lee, David M.; Patel, Dhavalkumar; Siderovski, David P.

    2013-01-01

    Chemokine receptor interactions coordinate leukocyte migration in inflammation. Chemokine receptors are GPCRs that when activated, are phosphorylated by GRKs to turn off G protein-mediated signaling yet recruit additional signaling machinery. Recently, GRK3 was identified as a negative regulator of CXCL12/CXCR4 signaling that is defective in human WHIM syndrome. Here, we report that GRK3?/? mice exhibit numerous features of human WHIM, such as impaired CXCL12-mediated desensitization, enhanced CXCR4 signaling to ERK activation, altered granulocyte migration, and a mild myelokathexis. Moreover, GRK3?/? protects mice from two acute models of inflammatory arthritis (K/BxN serum transfer and CAIA). In these granulocyte-dependent disease models, protection of GRK3?/? mice is mediated by retention of cells in the marrow, fewer circulating granulocytes in the peripheral blood, and reduced granulocytes in the joints during active inflammation. In contrast to WHIM, GRK3?/? mice have minimal hypogammaglobulinemia and a peripheral leukocytosis with increased lymphocytes and absent neutropenia. Thus, we conclude that the loss of GRK3-mediated regulation of CXCL12/CXCR4 signaling contributes to some, but not all, of the complete WHIM phenotype and that GRK3 inhibition may be beneficial in the treatment of inflammatory arthritis. PMID:23935208

  18. Anatomic, Hematologic, and Biochemical Features of C57BL/6NCrl Mice Maintained on Chronic Oral Corticosterone

    PubMed Central

    Cassano, Amy E; White, Julie R; Penraat, Kelley A; Wilson, Christopher D; Rasmussen, Skye; Karatsoreos, Ilia N

    2012-01-01

    Metabolic syndrome is a condition that typically includes central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension. Disruption of the hypothalamic–pituitary–adrenal axis, a regulator of corticosterone secretion, occurs in some cases of metabolic syndrome and obesity, and Cushing hypercortisolemia is associated with obesity and metabolic disorders. We therefore assessed anatomic and clinical pathology in C57BL/6NCrl mice to evaluate the effects of chronic corticosterone in the drinking water at doses of 25, 50, and 100 ?g/mL for 25 d. Treated mice developed obesity, glucose intolerance, electrolyte aberrations, and dyslipidemia that were dose-dependent and most severe in the 100-?g/mL treatment group. To evaluate return to normal function, additional C57BL/6NCrl mice received corticosterone-free water for 2 wk after the 25-d treatment period. According to results of gross examination, mice appeared to recover within days of exogenous corticosterone withdrawal; however, adrenal gland vacuolation and protein, lipid, and electrolyte abnormalities persisted. Together, these findings support chronic corticosterone exposure through the drinking water as a potentially useful, noninvasive method to induce some features of metabolic syndrome. PMID:23114038

  19. Triple monoamine uptake inhibitors demonstrate a pharmacologic association between excessive drinking and impulsivity in high-alcohol-preferring (HAP) mice.

    PubMed

    O'Tousa, David S; Warnock, Kaitlin T; Matson, Liana M; Namjoshi, Ojas A; Linn, Michael Van; Tiruveedhula, Veera Venkata; Halcomb, Meredith E; Cook, James; Grahame, Nicholas J; June, Harry L

    2015-03-01

    Approximately 30% of current drinkers in the United States drink excessively, and are referred to as problem/hazardous drinkers. These individuals, who may not meet criteria for alcohol abuse or dependence, comprise binge, heavy drinkers, or both. Given their high prevalence, interventions that reduce the risk of binge and heavy drinking have important public health implications. Impulsivity has been repeatedly associated with excessive drinking in the clinical literature. As impulsivity is correlated with, and may play a critical role in, the initiation and maintenance of excessive drinking, this behavior may be an important target for therapeutic intervention. Hence, a better understanding of pharmacological treatments capable of attenuating excessive drinking and impulsivity may markedly improve clinical outcomes. The high-alcohol-preferring (HAP) mice represent a strong rodent model to study the relationship between impulsivity and excessive alcohol drinking, as recent evidence indicates they consume high levels of alcohol throughout their active cycle and are innately impulsive. Using this model, the present study demonstrates that the triple monoamine uptake inhibitors (TUIs) amitifadine and DOV 102, 677 effectively attenuate binge drinking, heavy drinking assessed via a 24-hour free-choice assay, and impulsivity measured by the delay discounting procedure. In contrast, 3-PBC, a GABA-A ?1 preferring ligand with mixed agonist-antagonist properties, attenuates excessive drinking without affecting impulsivity. These findings suggest that in HAP mice, monoamine pathways may predominate as a common mechanism underlying impulsivity and excessive drinking, while the GABAergic system may be more salient in regulating excessive drinking. We further propose that TUIs such as amitifadine and DOV 102, 677 may be used to treat the co-occurrence of impulsivity and excessive drinking. PMID:24118509

  20. JNK-interacting protein 1 mediates Alzheimer's-like pathological features in AICD-transgenic mice.

    PubMed

    Margevicius, Daniel R; Bastian, Chinthasagar; Fan, Qingyuan; Davis, Roger J; Pimplikar, Sanjay W

    2015-08-01

    Amyloid precursor protein, which generates amyloid beta peptides, is intimately associated with Alzheimer's disease (AD) pathogenesis. We previously showed that transgenic mice overexpressing amyloid precursor protein intracellular domain (AICD), a peptide generated simultaneously with amyloid beta, develop AD-like pathologies, including hyperphosphorylated tau, loss of synapses, and memory impairments. AICD is known to bind c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP1), a scaffold protein that associates with and activates JNK. The aim of this study was to examine the role of JIP1 in AICD-induced AD-like pathologies in vivo, since the JNK pathway is aberrantly activated in AD brains and contributes to AD pathologies. We generated AICD-Tg mice lacking the JIP1 gene (AICD; JIP1(-/-)) and found that although AICD; JIP1(-/-) mice exhibit increased AICD, the absence of JIP1 results in decreased levels of hyperphosphorylated tau and activated JNK. AICD; JIP1(-/-) mice are also protected from synaptic loss and show improved performance in behavioral tests. These results suggest that JIP1 mediates AD-like pathologies in AICD-Tg mice and that JNK signaling may contribute to amyloid-independent mechanisms of AD pathogenesis. PMID:26022769

  1. Ectopic clustering of Cajal-Retzius and subplate cells is an initial pathological feature in Pomgnt2-knockout mice, a model of dystroglycanopathy.

    PubMed

    Nakagawa, Naoki; Yagi, Hirokazu; Kato, Koichi; Takematsu, Hiromu; Oka, Shogo

    2015-01-01

    Aberrant glycosylation of dystroglycan causes congenital muscular dystrophies associated with cobblestone lissencephaly, classified as dystroglycanopathy. However, pathological features in the onset of brain malformations, including the precise timing and primary cause of the pial basement membrane disruption and abnormalities in the migration of pyramidal neurons, remain unexplored. Using the Pomgnt2-knockout (KO) mouse as a dystroglycanopathy model, we show that breaches of the pial basement membrane appeared at embryonic day 11.5, coinciding with the ectopic clustering of Cajal-Retzius cells and subplate neurons and prior to the migration onset of pyramidal neurons. Furthermore, in the Pomgnt2-KO cerebral cortex, preplate splitting failure likely occurred due to the aggregation of Cajal-Retzius and subplate cells, and migrating pyramidal neurons lost polarity and radial orientation. Our findings demonstrate the initial pathological events in dystroglycanopathy mice and contribute to our understanding of how dystroglycan dysfunction affects brain development and progresses to cobblestone lissencephaly. PMID:26060116

  2. Ectopic clustering of Cajal–Retzius and subplate cells is an initial pathological feature in Pomgnt2-knockout mice, a model of dystroglycanopathy

    PubMed Central

    Nakagawa, Naoki; Yagi, Hirokazu; Kato, Koichi; Takematsu, Hiromu; Oka, Shogo

    2015-01-01

    Aberrant glycosylation of dystroglycan causes congenital muscular dystrophies associated with cobblestone lissencephaly, classified as dystroglycanopathy. However, pathological features in the onset of brain malformations, including the precise timing and primary cause of the pial basement membrane disruption and abnormalities in the migration of pyramidal neurons, remain unexplored. Using the Pomgnt2-knockout (KO) mouse as a dystroglycanopathy model, we show that breaches of the pial basement membrane appeared at embryonic day 11.5, coinciding with the ectopic clustering of Cajal–Retzius cells and subplate neurons and prior to the migration onset of pyramidal neurons. Furthermore, in the Pomgnt2-KO cerebral cortex, preplate splitting failure likely occurred due to the aggregation of Cajal–Retzius and subplate cells, and migrating pyramidal neurons lost polarity and radial orientation. Our findings demonstrate the initial pathological events in dystroglycanopathy mice and contribute to our understanding of how dystroglycan dysfunction affects brain development and progresses to cobblestone lissencephaly. PMID:26060116

  3. Recombinant Vascular Endothelial Growth Factor 121 Attenuates Autoantibody-Induced Features of Pre-eclampsia in Pregnant Mice

    PubMed Central

    Siddiqui, Athar H.; Irani, Roxanna A.; Zhang, Yujin; Dai, Yingbo; Blackwell, Sean C.; Ramin, Susan M.; Kellems, Rodney E.; Xia, Yang

    2012-01-01

    BACKGROUND Pre-eclampsia (PE) is a serious hypertensive disorder of pregnancy characterized by excessive production of a soluble form of the vascular endothelial growth factor (VEGF) receptor-1, termed soluble fms-like tyrosine kinase-1 (sFlt-1). This placental-derived factor is believed to be a key contributor to the clinical features of PE. Women with PE are also characterized by the presence of autoantibodies, termed angiotensin type 1 receptor activating autoantibody (AT1-AA), that activate the major angiotensin receptor, AT1. These autoantibodies cause clinical features of PE and elevated sFlt-1 when injected into pregnant mice. The research reported here used this autoantibody-injection model of PE to assess the therapeutic potential of recombinant VEGF121, a relatively stable form of the natural ligand. METHODS Immunoglobulin G (IgG) from women with PE was injected into pregnant mice with or without continuous infusion of recombinant VEGF121. Injected mice were monitored for symptoms of PE. RESULTS As a result of infusion of recombinant VEGF121 autoantibody-induced hypertension (systolic blood pressure) was reduced from 159 ± 5 to 124 ± 5 mm Hg, proteinuria from 111 ± 16 to 40 ± 5 mg protein/mg creatinine and blood urea nitrogen levels from 31 ± 1 mg/ dl to 18 ± 2 mg/dl, P < 0.05. Histological analysis revealed that autoantibody-induced glomerular damage including the narrowing of Bowman’s space and occlusion of capillary loop spaces was largely prevented by VEGF121 infusion. Finally, impaired placental angiogenesis resulting from AT1-AA injection was significantly improved by VEGF121 infusion. CONCLUSIONS The infusion of recombinant VEGF121 significantly attenuated autoantibody-induced features of PE. PMID:21183928

  4. Microarray Analyses Demonstrate the Involvement of Type I Interferons in Psoriasiform Pathology Development in D6-deficient Mice*

    PubMed Central

    Baldwin, Helen M.; Pallas, Kenneth; King, Vicky; Jamieson, Thomas; McKimmie, Clive S.; Nibbs, Robert J. B.; Carballido, José M.; Jaritz, Marcus; Rot, Antal; Graham, Gerard J.

    2013-01-01

    The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes. PMID:24194523

  5. Temporal vocal features suggest different call-pattern generating mechanisms in mice and bats

    PubMed Central

    2013-01-01

    Background Mice produce ultrasonic vocalizations in various inter-individual encounters and with high call rates. However, it is so far virtually unknown how these vocal patterns are generated. On the one hand, these vocal patterns could be embedded into the normal respiratory cycle, as happens in bats and other mammals that produce similar call rates and frequencies. On the other, mice could possess distinct vocal pattern generating systems that are capable of modulating the respiratory cycle, which is what happens in non-human and human primates. In the present study, we investigated the temporal call patterns of two different mammalian species, bats and mice, in order to differentiate between these two possibilities for mouse vocalizations. Our primary focus was on comparing the mechanisms for the production of rapid, successive ultrasound calls of comparable frequency ranges in the two species. Results We analyzed the temporal call pattern characteristics of mice, and we compared these characteristics to those of ultrasonic echolocation calls produced by horseshoe bats. We measured the distributions of call durations, call intervals, and inter-call intervals in the two species. In the bat, and consistent with previous studies, we found that call duration was independent of corresponding call intervals, and that it was negatively correlated with the corresponding inter-call interval. This indicates that echolocation call production mechanisms in the bat are highly correlated with the respiratory cycle. In contrast, call intervals in the mouse were directly correlated with call duration. Importantly, call duration was not, or was only slightly, correlated with inter-call intervals, consistent with the idea that vocal production in the mouse is largely independent of the respiratory cycle. Conclusions Our findings suggest that ultrasonic vocalizations in mice are produced by call-pattern generating mechanisms that seem to be similar to those that have been found in primates. This is in contrast to the production mechanisms of ultrasonic echolocation calls in horseshoe bats. These results are particularly interesting, especially since mouse vocalizations have recently attracted increased attention as potential indicators for the degree of progression of several disease patterns in mouse models for neurodegenerative and neurodevelopmental disorders of humans. PMID:24020588

  6. A diet rich in OMEGA-6 polyunsaturated fat and sucrose reproduces key features of metabolic syndrome in C57BL/6 mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine whether a diet enriched in v-6 fatty acids and sucrose will reproduce features of metabolic syndrome in C57BL/6 mice. 4- to 7-week-old male C57BL/6 mice were randomized to chow (13% kcal fat, lard and corn oil) or high fat/high sucrose (HF/HS) diet (48% kcal fat, corn oil) for a period ...

  7. Distinctive infrared spectral features in liver tumor tissues of mice: evidence of structural modifications at the molecular level.

    PubMed

    Wong, P T; Cadrin, M; French, S W

    1991-12-01

    Mice were treated with griseofulvin (GF) containing diet or control diet for 12 months. The livers from mice fed griseofulvin showed large tumors that were excised and used for analysis. The infrared spectra from control liver tissue and tumor tissue from GF livers were measured and compared as a function of pressure up to 27 kbar. Many changes in the infrared spectral features of the tumor tissue were observed. Results showed that neoplasm formation involved structural modifications of nucleic acids, lipids, carbohydrates, and proteins in the liver cells, which were detected from the abnormal vibrations of the functional groups in these biomolecules. The amount of glycogen was dramatically decreased in the tumor tissue compared to the control tissue. Important changes in the strength of hydrogen-bondings in the phosphodiester backbone of the nucleic acids and in the C-O groups of tissue proteins and carbohydrates were observed. Stronger interchain interactions and thus close interchain packing among the lipids in the GF liver were evident. These results showed very close similarities with those obtained with other types of tumors such as human colon cancer, suggesting that a common pattern of molecular changes has been identified in neoplastic transformation. PMID:1748216

  8. Features of renal vasculitis in autoimmune MRL lpr/lpr mice: phenotypes and functional properties of infiltrating cells.

    PubMed Central

    Tarkowski, A; Jonsson, R; Sanchez, R; Klareskog, L; Koopman, W J

    1988-01-01

    MRL lpr/lpr (MRL/1) mice spontaneously develop a widespread renal vasculitis. The majority of the cells in vasculitic lesions are bright Ly-1, L3T4 and la-positive in contrast to the cells found in lymph nodes and spleens of the old MRL/1 mice. However, despite differences in phenotypical patterns, B and T cells from arteritic lesions do not differ from mononuclear cells (MNC) eluted from MRL/1 lymph nodes with regard to the frequency of IgG secreting cells and the proliferative responses to Concanavalin A (Con A). Co-culture experiments with congeneic MRL+/+ (MRL/n) spleen cells indicate that the poor response to Con A of the MNC eluted from vasculitic lesions is, unlike the case of lymph node MNC, due to suppressive action of vasculitic cells on the indicator cell population. Further support for the activation status of infiltrating MHC in kidney vasculitic lesions, expressed by high in vivo uptake of 3H-thymidine, was obtained by autoradiography performed on frozen sections. The observed differences in phenotypic patterns and functional features between lymph node MNC and infiltrating vasculitic MNC indicate that different immune mechanisms may be responsible for the development of lymphadenopathy and vasculopathy, respectively in MRL/1 mouse. Images Fig. 2 Fig. 3 Fig. 4 PMID:3293853

  9. Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes

    PubMed Central

    Kueffer, Peter J.; Maitz, Charles A.; Khan, Aslam A.; Schuster, Seth A.; Shlyakhtina, Natalia I.; Jalisatgi, Satish S.; Brockman, John D.; Nigg, David W.; Hawthorne, M. Frederick

    2013-01-01

    The application of boron neutron capture therapy (BNCT) following liposomal delivery of a 10B-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na3[1-(2?-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice bearing right flank EMT6 tumors. Biodistribution studies indicated that two identical injections given 24 h apart resulted in tumor boron levels exceeding 67 µg/g tumor at 54 h—with tumor/blood boron ratios being greatest at 96 h (5.68:1; 43 µg boron/g tumor)—following the initial injection. For BNCT experiments, tumor-bearing mice were irradiated 54 h after the initial injection for 30 min with thermal neutrons, resulting in a total fluence of 1.6 × 1012 neutrons per cm2 (±7%). Significant suppression of tumor growth was observed in mice given BNCT vs. control mice (only 424% increase in tumor volume at 14 d post irradiation vs. 1551% in untreated controls). In a separate experiment in which mice were given a second injection/irradiation treatment 7 d after the first, the tumor growth was vastly diminished (186% tumor volume increase at 14 d). A similar response was obtained for mice irradiated for 60 min (169% increase at 14 d), suggesting that neutron fluence was the limiting factor controlling BNCT efficacy in this study. PMID:23536304

  10. Lineage targeted MHC-II transgenic mice demonstrate the role of dendritic cells in bacterial driven colitis

    PubMed Central

    Maggio-Price, Lillian; Seamons, Audrey; Bielefeldt-Ohmann, Helle; Zeng, Weiping; Brabb, Thea; Ware, Carol; Lei, Mingzu; Hershberg, Robert M.

    2012-01-01

    Background Inflammatory bowel disease (IBD) pathogenesis involves an inadequately controlled immune reaction to intestinal microbiota and CD4+ T cells, dependent upon MHC class II (MHC-II) processing and presentation by antigen presenting cells (APC), play important roles The role of professional APC (macrophages and dendritic cells (DC)) and nonprofessional APC (intestinal epithelial cells (IEC)) in microbial driven intestinal inflammation remains controversial. Methods We generated transgenic animals on a MHC-II?/? genetic background in which MHC-II is expressed on a) DC via the CD11c promoter (CD11cTg) or b) IEC via the fatty acid binding protein (liver) promoter (EpithTg). These mice were crossed with Rag2?/? mice to eliminate T and B cells (CD11cTg/Rag2?/? and EpithTg/Rag2?/?). Helicobacter bilis (Hb) infection and adoptive transfer (AT) of naïve CD4+ T cells were used to trigger IBD. Results CD11cTg/Rag2?/? mice infected with Hb+AT developed severe colitis within three weeks post AT, similar to disease in positive control Rag2?/? mice infected with Hb+AT. CD11cTg/Rag2?/? mice given AT alone or Hb alone had significantly less severe colitis. In contrast, EpithTg/Rag2?/? mice infected with Hb+AT developed mild colitis by three weeks and even after 16 weeks post adoptive transfer, had only mild lesions. Conclusions MHC-II expression restricted to DCs is sufficient to induce severe colitis in the presence of T cells and a microorganism such as Hb within three weeks of adoptive transfer. Expression of MHC-II solely on IEC in the presence of a microbial trigger and T cells was insufficient for triggering severe colitis. PMID:22619032

  11. Analysis of Multiple Positive Feedback Paradigms Demonstrates a Complete Absence of LH Surges and GnRH Activation in Mice Lacking Kisspeptin Signaling1

    PubMed Central

    Dror, Tal; Franks, Jennifer; Kauffman, Alexander S.

    2013-01-01

    ABSTRACT Kisspeptin stimulates gonadotropin-releasing hormone (GnRH) neurons via the kisspeptin receptor, Kiss1r. In rodents, estrogen-responsive kisspeptin neurons in the rostral hypothalamus have been postulated to mediate estrogen-induced positive feedback induction of the preovulatory luteinizing hormone (LH) surge. However, conflicting evidence exists regarding the ability of mice lacking Kiss1r to display LH surges in response to exogenous hormones. Whether the discrepancy reflects different mouse strains used and/or utilization of different surge-induction paradigms is unknown. Here, we tested multiple hormonal paradigms in one Kiss1r knockout (KO) model to see which paradigms, if any, could generate circadian-timed LH surges. Kiss1r KO and wild-type (WT) females were ovariectomized, given sex steroids in various modes, and assessed several days later for LH levels in the morning or evening (when surges occur). Serum LH levels were very low in all morning animals, regardless of genotype or hormonal paradigm. In each paradigm, virtually all WT females displayed clear LH surges in the evening, whereas none of the KO females demonstrated LH surges. The lack of LH surges in KO mice reflects a lack of GnRH secretion rather than diminished pituitary responsiveness from a lifetime lack of GnRH exposure because KO mice responded to GnRH priming with robust LH secretion. Moreover, high cfos-GnRH coexpression was detected in WT females in the evening, whereas low cfos-GnRH coexpression was present in KO females at all time points. Our findings conclusively demonstrate that WT females consistently display LH surges under multiple hormonal paradigms, whereas Kiss1r KO mice do not, indicating that kisspeptin-Kiss1r signaling is mandatory for GnRH/LH surge induction. PMID:23595904

  12. Plasma Biomarkers of Liver Injury and Inflammation Demonstrate a Lack of Apoptosis during Obstructive Cholestasis in Mice

    PubMed Central

    Woolbright, Benjamin L.; Antoine, Daniel J.; Jenkins, Rosalind E.; Bajt, Mary Lynn; Park, B. Kevin; Jaeschke, Hartmut

    2013-01-01

    Cholestasis is a pathological common component of numerous liver diseases that results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis due to direct toxicity of hydrophobic bile acid exposure, recent work suggests the injury occurs through inflammatory necrosis. In order to resolve this controversy, we used novel plasma biomarkers to assess the mechanisms of cell death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct ligation (BDL) for 6–72h, or sham operation. Another group of mice were given D-galactosamine and endotoxin as a positive control for apoptosis and inflammatory necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR-122) and high mobility group box-1 protein (HMGB1) increased progressively after BDL with peak levels observed after 48h. These results indicate extensive cell necrosis after BDL, which is supported by the time course of plasma alanine aminotransferase activities and histology. In contrast, plasma caspase-3 activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments (cK18) were not elevated at any time during BDL suggesting the absence of apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were elevated 6h after Gal/End treatment. In addition, acetylated HMGB1, a marker for macrophage and monocyte activation, was increased as early as 12h but mainly at 48–72h. However, progressive neutrophil accumulation in the area of necrosis started at 6h after BDL. In conclusion, these data indicate that early cholestatic liver injury in mice is an inflammatory event, and occurs through necrosis with little evidence for apoptosis. PMID:24096036

  13. Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice

    SciTech Connect

    Woolbright, Benjamin L. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Jenkins, Rosalind E. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Bajt, Mary Lynn [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2013-12-15

    Cholestasis is a pathological common component of numerous liver diseases that results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis due to direct toxicity of hydrophobic bile acid exposure, recent work suggests that the injury occurs through inflammatory necrosis. In order to resolve this controversy, we used novel plasma biomarkers to assess the mechanisms of cell death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct ligation (BDL) for 6–72 h, or sham operation. Another group of mice were given D-galactosamine and endotoxin as a positive control for apoptosis and inflammatory necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR-122) and high mobility group box-1 protein (HMGB1) increased progressively after BDL with peak levels observed after 48 h. These results indicate extensive cell necrosis after BDL, which is supported by the time course of plasma alanine aminotransferase activities and histology. In contrast, plasma caspase-3 activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments (cK18) were not elevated at any time during BDL suggesting the absence of apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were elevated 6 h after Gal/End treatment. In addition, acetylated HMGB1, a marker for macrophage and monocyte activation, was increased as early as 12 h but mainly at 48–72 h. However, progressive neutrophil accumulation in the area of necrosis started at 6 h after BDL. In conclusion, these data indicate that early cholestatic liver injury in mice is an inflammatory event, and occurs through necrosis with little evidence for apoptosis. - Highlights: • The mechanism of cell death during cholestasis remains a controversial topic. • Plasma biomarkers offer new insight into cell death after bile duct ligation. • Cytokeratin-18, microRNA-122 and HMGB1 levels implicate necrosis. • Acetylated HMGB1 levels rise late after BDL confirming inflammation. • BDL-induced liver injury involves mainly inflammation and necrosis but no apoptosis.

  14. The distorting effect of varying diets on fecal glucocorticoid measurements as indicators of stress: a cautionary demonstration using laboratory mice.

    PubMed

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

    2015-01-15

    The physiological stress response is frequently gauged in animals, non-invasively, through measuring glucocorticoids in excreta. A concern with this method is, however, the unknown effect of variations in diets on the measurements. With an energy dense diet, leading to reduced defecation, will low concentrations of glucocorticoids be artificially inflated? Can this effect be overcome by measuring the total output of glucocorticoids in excreta? In a controlled laboratory setting we explored the effect in mice. When standard mouse chow - high in dietary fiber - was replaced with a 17% more energy-dense diet, fecal mass was significantly reduced. As circulating levels of corticosterone and the total output of corticosterone metabolites over time remained unaffected, the result was an overestimation - more than a doubling - of the corticosterone metabolite excretion if expressed as concentrations. Similar results were obtained for testosterone metabolites. Although measuring the total output is not feasible in, for example, wildlife studies, the present findings highlight the perilousness of relying on concentrations of hormones in excreta with no associated information of the dietary intake as even moderate changes can exert a great influence. PMID:25555461

  15. Meta-analysis identifies gene-by-environment interactions as demonstrated in a study of 4,965 mice.

    PubMed

    Kang, Eun Yong; Han, Buhm; Furlotte, Nicholas; Joo, Jong Wha J; Shih, Diana; Davis, Richard C; Lusis, Aldons J; Eskin, Eleazar

    2014-01-01

    Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta-analysis approach is that our combined study has significantly higher power and improved resolution compared to any single study thus explaining the large number of loci discovered in the combined study. PMID:24415945

  16. Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 Mice

    PubMed Central

    Joo, Jong Wha J.; Shih, Diana; Davis, Richard C.; Lusis, Aldons J.; Eskin, Eleazar

    2014-01-01

    Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta-analysis approach is that our combined study has significantly higher power and improved resolution compared to any single study thus explaining the large number of loci discovered in the combined study. PMID:24415945

  17. Peyer's Patch-Deficient Mice Demonstrate That Mycobacterium avium subsp. paratuberculosis Translocates across the Mucosal Barrier via both M Cells and Enterocytes but Has Inefficient Dissemination ?

    PubMed Central

    Bermudez, Luiz E.; Petrofsky, Mary; Sommer, Sandra; Barletta, Raúl G.

    2010-01-01

    Mycobacterium avium subsp. paratuberculosis, the agent of Johne's disease, infects ruminant hosts by translocation through the intestinal mucosa. A number of studies have suggested that M. avium subsp. paratuberculosis interacts with M cells in the Peyer's patches of the small intestine. The invasion of the intestinal mucosa by M. avium subsp. paratuberculosis and Mycobacterium avium subsp. hominissuis, a pathogen known to interact with intestinal cells, was compared. M. avium subsp. paratuberculosis was capable of invading the mucosa, but it was significantly less efficient at dissemination than M. avium subsp. hominissuis. B-cell knockout (KO) mice, which lack Peyer's patches, were used to demonstrate that M. avium subsp. paratuberculosis enters the intestinal mucosa through enterocytes in the absence of M cells. In addition, the results indicated that M. avium subsp. paratuberculosis had equal abilities to cross the mucosa in both Peyer's patch and non-Peyer's patch segments of normal mice. M. avium subsp. paratuberculosis was also shown to interact with epithelial cells by an ?5?1 integrin-independent pathway. Upon translocation, dendritic cells ingest M. avium subsp. paratuberculosis, but this process does not lead to efficient dissemination of the infection. In summary, M. avium subsp. paratuberculosis interacts with the intestinal mucosa by crossing both Peyer's patches and non-Peyer's patch areas but does not translocate or disseminate efficiently. PMID:20498259

  18. Specific hybridization probes demonstrate fewer xenotropic than mink cell focus-forming murine leukemia virus env-related sequences in DNAs from inbred laboratory mice

    SciTech Connect

    O'Neill, R.R.; Khan, A.S.; Hoggan, D.; Hartley, J.W.; Martin, M.A.; Repaske, R.

    1986-05-01

    The authors have derived hybridization probes from analogous 100-base-pair segments located within the N-terminal region of gp70 coding sequences which differentiate xenotropic from mink cell focus-forming (MCF)-related murine leukemia virus (MuLV) DNAs. The MCF probe annealed to the integrated proviruses of all six MCF MuLV isolates tested; the xenotropic probe hybridized to the DNAs of all four xenotropic proviral isolates examined. No cross-hybridization was observed, and neither probe reacted with the env segments of amphotropic or ecotropic MuLV DNAs. Southern blot analysis of HindIII- or EcoRI-digested genomic DNAs from a variety of inbred laboratory mice demonstrated the presence of more MCF- than xenotropic MuLV-related segments in every strain tested.

  19. Demonstration of motionless Knudsen pump based micro-gas chromatography featuring micro-fabricated columns and on-column detectors.

    PubMed

    Liu, Jing; Gupta, Naveen K; Wise, Kensall D; Gianchandani, Yogesh B; Fan, Xudong

    2011-10-21

    This paper reports the investigation of a micro-gas chromatography (?GC) system that utilizes an array of miniaturized motionless Knudsen pumps (KPs) as well as microfabricated separation columns and optical detectors. A prototype system was built to achieve a flow rate of 1 mL min(-1) and 0.26 mL min(-1) for helium and dry air, respectively, when they were used as carrier gas. This system was then employed to evaluate GC performance compromises and demonstrate the ability to separate and detect gas mixtures containing analytes of different volatilities and polarities. Furthermore, the use of pressure programming of the KP array was demonstrated to significantly shorten the analysis time while maintaining a high detection resolution. Using this method, we obtained a high resolution detection of 5 alkanes of different volatilities within 5 min. Finally, we successfully detected gas mixtures of various polarities using a tandem-column ?GC configuration by installing two on-column optical detectors to obtain complementary chromatograms. PMID:21869988

  20. Design and operating features of the high-level waste vitrification system for the West Valley demonstration project

    SciTech Connect

    Siemens, D.H.; Beary, M.M.; Barnes, S.M.; Berger, D.N.; Brouns, R.A.; Chapman, C.C.; Jones, R.M.; Peters, R.D.; Peterson, M.E.

    1986-03-01

    A liquid-fed joule-heated ceramic melter system is the reference process for immobilization of the high-level liquid waste in the US and several foreign countries. This system has been under development for over ten years at Pacific Northwest Laboratory and other national laboratories operated for the US Department of Energy. Pacific Northwest Laboratory contributed to this research through its Nuclear Waste Treatment Program and used applicable data to design and test melters and related systems using remote handling of simulated radioactive wastes. This report describes the equipment designed in support of the high-level waste vitrification program at West Valley, New York. Pacific Northwest Laboratory worked closely with West Valley Nuclear Services Company to design a liquid-fed ceramic melter, a liquid waste preparation and feed tank and pump, an off-gas treatment scrubber, and an enclosed turntable for positioning the waste canisters. Details of these designs are presented including the rationale for the design features and the alternatives considered.

  1. Heterozygous deletion of the Williams-Beuren syndrome critical interval in mice recapitulates most features of the human disorder.

    PubMed

    Segura-Puimedon, Maria; Sahún, Ignasi; Velot, Emilie; Dubus, Pierre; Borralleras, Cristina; Rodrigues, Ana J; Valero, María C; Valverde, Olga; Sousa, Nuno; Herault, Yann; Dierssen, Mara; Pérez-Jurado, Luis A; Campuzano, Victoria

    2014-12-15

    Williams-Beuren syndrome is a developmental multisystemic disorder caused by a recurrent 1.55-1.83 Mb heterozygous deletion on human chromosome band 7q11.23. Through chromosomal engineering with the cre-loxP system, we have generated mice with an almost complete deletion (CD) of the conserved syntenic region on chromosome 5G2. Heterozygous CD mice were viable, fertile and had a normal lifespan, while homozygotes were early embryonic lethal. Transcript levels of most deleted genes were reduced 50% in several tissues, consistent with gene dosage. Heterozygous mutant mice showed postnatal growth delay with reduced body weight and craniofacial abnormalities such as small mandible. The cardiovascular phenotype was only manifested with borderline hypertension, mildly increased arterial wall thickness and cardiac hypertrophy. The neurobehavioral phenotype revealed impairments in motor coordination, increased startle response to acoustic stimuli and hypersociability. Mutant mice showed a general reduction in brain weight. Cellular and histological abnormalities were present in the amygdala, cortex and hippocampus, including increased proportion of immature neurons. In summary, these mice recapitulate most crucial phenotypes of the human disorder, provide novel insights into the pathophysiological mechanisms of the disease such as the neural substrates of the behavioral manifestations, and will be valuable to evaluate novel therapeutic approaches. PMID:25027326

  2. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L.

    1982-01-01

    Two demonstrations are described: (1) a sunset effect using a gooseneck lamp and 20 sheets of paper and (2) the preparation and determination of structural features of dimethyl sulfoxide (DMSO) by infrared spectroscopy. (SK)

  3. [Features of the B chromosome in Korean wood mice Apodemus peninsulae (Thomas, 1906) from Transbaikalia and the Far East identified by the FISH method].

    PubMed

    Rubtsov, N B; Kartavtseva, I V; Roslik, G V; Karamysheva, T V; Pavlenko, M V; Iwasa, M A; Koh, H S

    2015-03-01

    Korean field mice (Apodemus peninsulae) are widely distributed throughout northeastern Asia, including the Russian Far East, northern China, the Korean peninsula, Sakhalin, and Hokkaido. This mouse species is characterized by a high frequency of animals with B chromosomes differing in their number, morphology, and DNA composition in different geographical regions. For the first time a comparative analysis of DNA probes from B chromosomes with metaphase chromosomes of mice from Transbaikalia, the Far East (including the Russian Far East), Japan, and South Korea was conducted by in situ hybridization. B chromosomes in mice from the Russian Far East were shown to exhibit low variability in DNA content; however, the DNA composition of B chromosomes in species from Transbaikalia and Japan were highly variable. B chromosomes in A. peninsulae from the South Korean population demonstrate minor differences from those from the Russian Far East. We discuss the origin of B chromosomes in the studied region in comparison with previously obtained data for mice from Siberia and the Baikal region, as well as the dispersal routes of the Korean field mouse. PMID:26027373

  4. The effect of BSO-induced oxidative stress on histologic feature of testis: testosterone secretion and semen parameters in mice

    PubMed Central

    Sajjadian, Fakhrosadat; Roshangar, Leila; Hemmati, Alireza; Nori, Mohammad; Soleimani-Rad, Sara; Soleimani-Rad, Jafar

    2014-01-01

    Objective(s): Buthionine sulfoximine (BSO) inhibits synthesis of glutathione as the main intracellular antioxidant. The aim of the present study is to investigate the effect of BSO-induced oxidative stress on histological structure of testis, testosterone secretion and semen parameters. Materials and Methods: Thirty male BALB/c mice were divided into 3 groups. In control group, the mice did not receive any chemical. In the experimental group, the mice received 2 mmol/kg BSO for 35 days. In the sham group, the mice received the solvent of BSO (0.9% saline). After the treatment, the mice were sacrificed. Their testes were fixed in Buein's fixative, embedded in paraffin and prepared for histological studies. To assess semen parameters, the sperms were collected from cauda epididymis. Blood samples were used for determination of super oxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPX), glutathione (GSH), catalase (CAT) and the serum testosterone level. The data analyzed using ANOVA and Dunnett's tests and SPSS software, version11.5. P- values at 0.05 level considered significant. Results: Data showed that in experimental group in comparison to control group; the concentration of CAT, GPX, SOD,GSH and the total level of testosterone is reduced while MDA level is increased significantly. The number of sperms with progressive motility were decreased (P<0.001) but sperms with abnormal morphology were increased (P<0.001). Histological studies revealed that the values for tubal differentiation index and spermatogenic index in experimental group were reduced (P<0.001). Conclusion: It is concluded that exposure to oxidative stress induced by BSO could affect testicular structure and semen parameters. PMID:25422755

  5. Cutaneous barrier function after cold exposure in hairless mice: a model to demonstrate how cold interferes with barrier homeostasis among workers in the fish-processing industry.

    PubMed

    Halkier-Sørensen, L; Menon, G K; Elias, P M; Thestrup-Pedersen, K; Feingold, K R

    1995-03-01

    Dry skin and eczema only seldomly occur in workers in the Danish fish-processing industry (FPI) during work, when their fingers and palms have a low skin surface temperature, low transepidermal water loss (TEWL), and a high capacitance. However, shortly after work, when the skin temperature has become normal, TEWL levels increase to above normal, and capacitance decreases to below normal, followed by the development of dry skin or chapping, which subsequently revert to normal over a period of hours. These observations suggest that workers in the FPI may have a defect in skin barrier function, which is, however, masked by a low skin temperature, resulting in misleadingly low TEWL levels during work. To test this hypothesis, we disrupted the permeability barrier in hairless mice with topical acetone, and exposed the treated skin to ice for 3.5 h. Although TEWL rates immediately after cold exposure were low, suggesting normal barrier recovery, TEWL increased to levels slightly above pre-cold exposure levels (i.e. levels just after the barrier was disrupted with acetone) when the skin temperature reverted to normal (> or = 15 min). The changes in TEWL were paralleled by equivalent changes in percutaneous penetration of the electron-dense tracer lanthanum nitrate. This indicates that cold masks a defective barrier, and inhibits barrier repair. After a few hours at ambient temperatures, normal barrier recovery was observed. Electron microscopy revealed empty or partially empty lamellar bodies during the first 30 min post-cold exposure. After 1 h the majority of nascent LBs displayed normal morphology. Moreover, histochemical studies showed a delayed reappearance of stratum corneum intercellular lipids following cold exposure. These results demonstrate that cold exposure prevents barrier recovery after acetone disruption, and provide an explanation for the occupational dermatosis observed in the fish-processing industry and related occupations. PMID:7718455

  6. A Rodent Model of Chikungunya Virus Infection in RAG1 -/- Mice, with Features of Persistence, for Vaccine Safety Evaluation

    PubMed Central

    Leal, Grace; Alcorn, Maria D. H.; Weaver, Scott C.

    2015-01-01

    Chikungunya virus (CHIKV) is a positive sense, single stranded RNA virus in the genus Alphavirus, and the etiologic agent of epidemics of severe arthralgia in Africa, Asia, Europe and, most recently, the Americas. CHIKV causes chikungunya fever (CHIK), a syndrome characterized by rash, fever, and debilitating, often chronic arthritis. In recent outbreaks, CHIKV has been recognized to manifest more neurologic signs of illness in the elderly and those with co-morbidities. The syndrome caused by CHIKV is often self-limited; however, many patients develop persistent arthralgia that can last for months or years. These characteristics make CHIKV not only important from a human health standpoint, but also from an economic standpoint. Despite its importance as a reemerging disease, there is no licensed vaccine or specific treatment to prevent CHIK. Many studies have begun to elucidate the pathogenesis of CHIKF and the mechanism of persistent arthralgia, including the role of the adaptive immune response, which is still poorly understood. In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development. To address this deficiency, we used recombination activating gene 1 (RAG1-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model. Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate. PMID:26115459

  7. Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans

    PubMed Central

    Suganami, Takayoshi; Konuma, Kuniha; Marumoto, Yoshio; Terai, Shuji; Sakugawa, Hiroshi; Kanai, Sayaka; Hamaguchi, Miho; Fukaishi, Takahiro; Aoe, Seiichiro; Akiyoshi, Kazunari; Komohara, Yoshihiro; Takeya, Motohiro; Sakaida, Isao; Ogawa, Yoshihiro

    2013-01-01

    Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH) is poorly understood. Here we report the unique histological structure termed “hepatic crown-like structures (hCLS)” in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH. PMID:24349208

  8. A Rodent Model of Chikungunya Virus Infection in RAG1 -/- Mice, with Features of Persistence, for Vaccine Safety Evaluation.

    PubMed

    Seymour, Robert L; Adams, A Paige; Leal, Grace; Alcorn, Maria D H; Weaver, Scott C

    2015-06-01

    Chikungunya virus (CHIKV) is a positive sense, single stranded RNA virus in the genus Alphavirus, and the etiologic agent of epidemics of severe arthralgia in Africa, Asia, Europe and, most recently, the Americas. CHIKV causes chikungunya fever (CHIK), a syndrome characterized by rash, fever, and debilitating, often chronic arthritis. In recent outbreaks, CHIKV has been recognized to manifest more neurologic signs of illness in the elderly and those with co-morbidities. The syndrome caused by CHIKV is often self-limited; however, many patients develop persistent arthralgia that can last for months or years. These characteristics make CHIKV not only important from a human health standpoint, but also from an economic standpoint. Despite its importance as a reemerging disease, there is no licensed vaccine or specific treatment to prevent CHIK. Many studies have begun to elucidate the pathogenesis of CHIKF and the mechanism of persistent arthralgia, including the role of the adaptive immune response, which is still poorly understood. In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development. To address this deficiency, we used recombination activating gene 1 (RAG1-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model. Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate. PMID:26115459

  9. Cloning and sequencing of yajC and secD homologs of Brucella abortus and demonstration of immune responses to YajC in mice vaccinated with B. abortus RB51.

    PubMed

    Vemulapalli, R; Duncan, A J; Boyle, S M; Sriranganathan, N; Toth, T E; Schurig, G G

    1998-12-01

    To identify Brucella antigens that are potentially involved in stimulating a protective cell-mediated immune response, a gene library of Brucella abortus 2308 was screened for the expression of antigens reacting with immunoglobulin G2a antibodies from BALB/c mice vaccinated with B. abortus RB51. One selected positive clone (clone MCB68) contained an insert of 2.6 kb; nucleotide sequence analysis of this insert revealed two open reading frames (ORFs). The deduced amino acid sequences of the first and second ORFs had significant similarities with the YajC and SecD proteins, respectively, of several bacterial species. Both the YajC and SecD proteins were expressed in Escherichia coli as fusion proteins with maltose binding protein (MBP). In Western blots, sera from mice vaccinated with B. abortus RB51 recognized YajC but not SecD. Further Western blot analysis with purified recombinant YajC protein indicated that mice inoculated with B. abortus 19 or 2308 or B. melitensis RM1 also produced antibodies to YajC. In response to in vitro stimulation with recombinant MBP-YajC fusion protein, splenocytes from mice vaccinated with B. abortus RB51 were able to proliferate and produce gamma interferon but not interleukin-4. This study demonstrates, for the first time, the involvement of YajC protein in an immune response to an infectious agent. PMID:9826342

  10. Partial rescue of some features of Huntington Disease in the genetic absence of caspase-6 in YAC128 mice.

    PubMed

    Wong, Bibiana K Y; Ehrnhoefer, Dagmar E; Graham, Rona K; Martin, Dale D O; Ladha, Safia; Uribe, Valeria; Stanek, Lisa M; Franciosi, Sonia; Qiu, Xiaofan; Deng, Yu; Kovalik, Vlad; Zhang, Weining; Pouladi, Mahmoud A; Shihabuddin, Lamya S; Hayden, Michael R

    2015-04-01

    Huntington Disease (HD) is a progressive neurodegenerative disease caused by an elongated CAG repeat in the huntingtin (HTT) gene that encodes a polyglutamine tract in the HTT protein. Proteolysis of the mutant HTT protein (mHTT) has been detected in human and murine HD brains and is implicated in the pathogenesis of HD. Of particular importance is the site at amino acid (aa) 586 that contains a caspase-6 (Casp6) recognition motif. Activation of Casp6 occurs presymptomatically in human HD patients and the inhibition of mHTT proteolysis at aa586 in the YAC128 mouse model results in the full rescue of HD-like phenotypes. Surprisingly, Casp6 ablation in two different HD mouse models did not completely prevent the generation of this fragment, and therapeutic benefits were limited, questioning the role of Casp6 in the disease. We have evaluated the impact of the loss of Casp6 in the YAC128 mouse model of HD. Levels of the mHTT-586 fragment are reduced but not absent in the absence of Casp6 and we identify caspase 8 as an alternate enzyme that can generate this fragment. In vivo, the ablation of Casp6 results in a partial rescue of body weight gain, normalized IGF-1 levels, a reversal of the depression-like phenotype and decreased HTT levels. In the YAC128/Casp6-/- striatum there is a concomitant reduction in p62 levels, a marker of autophagic activity, suggesting increased autophagic clearance. These results implicate the HTT-586 fragment as a key contributor to certain features of HD, irrespective of the enzyme involved in its generation. PMID:25583186

  11. Poly (lactide-co-glycolide) encapsulated extract of Phytolacca decandra demonstrates better intervention against induced lung adenocarcinoma in mice and on A549 cells.

    PubMed

    Das, Jayeeta; Das, Sreemanti; Samadder, Asmita; Bhadra, Kakali; Khuda-Bukhsh, Anisur Rahman

    2012-09-29

    We tested relative efficacy of the extract of Phytolacca decandra (PD) and its PLGA nano-encapsulated form (NPD) in mice intoxicated with benzo[a]pyrene (BaP) (25 mg/kg b.w.) plus sodium-arsenite (SA) (10 mg/kg b.w.) and on A549 lung cancer cells in vitro. We characterized nanoparticles by physico-chemical and morphological studies using dynamic light scattering, scanning electron and atomic force microscopies. We also conducted FTIR and (1)H NMR studies to determine if NPD had a co-polymeric nature and analyzed drug-DNA interaction through circular dichroism spectra (CD) and melting temperature profiles (T(m)) taking calf thymus DNA as target. An oral dose of 0.3mg/kg b.w. for NPD and 30 mg/kg b.w. for PD in mice showed chemopreventive effects in regard to DNA fragmentation, comet tail length and toxicity biomarkers like ROS generation, NF??, p53, PARP, CYP1A1 and caspase 3. NPD showed greater effects than that by PD. Results of in vivo studies showed similar effects on A549 in regard to cell viability, DAPI and PI staining, Comet tail length, DNA fragmentation. To further confirm the biological molecule present in PD we analyzed its chromatographic fraction through mass spectroscopy, NMR and FT-IR studies and characterized it to be a tri-terpenoid, a derivative of betulinic acid with a molecular formula C(30)H(46)O(2.) Thus, overall results suggest that nano-encapsulation of PD (NPD) increases drug bioavailability and thereby has a better chemo-preventive action against lung cancer in vivo and on A549 cells in vitro than that of PD. PMID:22771545

  12. Zinc protoporphyrin IX, a heme oxygenase-1 inhibitor, demonstrates potent antitumor effects but is unable to potentiate antitumor effects of chemotherapeutics in mice

    PubMed Central

    Nowis, Dominika; Bugajski, Marek; Winiarska, Magdalena; Bil, Jacek; Szokalska, Angelika; Salwa, Pawel; Issat, Tadeusz; Was, Halina; Jozkowicz, Alicja; Dulak, Jozef; Stoklosa, Tomasz; Golab, Jakub

    2008-01-01

    Background HO-1 participates in the degradation of heme. Its products can exert unique cytoprotective effects. Numerous tumors express high levels of HO-1 indicating that this enzyme might be a potential therapeutic target. In this study we decided to evaluate potential cytostatic/cytotoxic effects of zinc protoporphyrin IX (Zn(II)PPIX), a selective HO-1 inhibitor and to evaluate its antitumor activity in combination with chemotherapeutics. Methods Cytostatic/cytotoxic effects of Zn(II)PPIX were evaluated with crystal violet staining and clonogenic assay. Western blotting was used for the evaluation of protein expression. Flow cytometry was used to evaluate the influence of Zn(II)PPIX on the induction of apoptosis and generation of reactive oxygen species. Knock-down of HO-1 expression was achieved with siRNA. Antitumor effects of Zn(II)PPIX alone or in combination with chemotherapeutics were measured in transplantation tumor models. Results Zn(II)PPIX induced significant accumulation of reactive oxygen species in tumor cells. This effect was partly reversed by administration of exogenous bilirubin. Moreover, Zn(II)PPIX exerted potent cytostatic/cytotoxic effects against human and murine tumor cell lines. Despite a significant time and dose-dependent decrease in cyclin D expression in Zn(II)PPIX-treated cells no accumulation of tumor cells in G1 phase of the cell cycle was observed. However, incubation of C-26 cells with Zn(II)PPIX increased the percentage of cells in sub-G1 phase of the cells cycle. Flow cytometry studies with propidium iodide and annexin V staining as well as detection of cleaved caspase 3 by Western blotting revealed that Zn(II)PPIX can induce apoptosis of tumor cells. B16F10 melanoma cells overexpressing HO-1 and transplanted into syngeneic mice were resistant to either Zn(II)PPIX or antitumor effects of cisplatin. Zn(II)PPIX was unable to potentiate antitumor effects of 5-fluorouracil, cisplatin or doxorubicin in three different tumor models, but significantly potentiated toxicity of 5-FU and cisplatin. Conclusion Inhibition of HO-1 exerts antitumor effects but should not be used to potentiate antitumor effects of cancer chemotherapeutics unless procedures of selective tumor targeting of HO-1 inhibitors are developed. PMID:18620555

  13. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1984-01-01

    Procedures for two demonstrations are presented. The first is a demonstration of chemiluminescence. The second is a demonstration using a secondary battery constructed from common household articles. (JN)

  14. Alcohol dependence and free-choice drinking in mice.

    PubMed

    Griffin, William C

    2014-05-01

    Alcohol dependence continues to be an important health concern and animal models are critical to furthering our understanding of this complex disease. A hallmark feature of alcoholism is a significant increase in alcohol drinking over time. While several different animal models of excessive alcohol (ethanol) drinking exist for mice and rats, a growing number of laboratories are using a model that combines chronic ethanol exposure procedures with voluntary ethanol drinking with mice as experimental subjects. Primarily, these studies use a chronic intermittent ethanol (CIE) exposure pattern to render mice dependent and a 2-h limited access procedure to evaluate drinking behavior. Compared to non-dependent mice that also drink ethanol, the ethanol-dependent mice demonstrate significant increases in voluntary ethanol drinking. The increased drinking significantly elevates blood and brain ethanol concentrations compared to the non-dependent control mice. Studies report that the increased drinking by dependent mice is driven by neuroadaptations in glutamatergic and corticotropin-releasing factor signaling in different brain regions known to be involved in alcohol-related behaviors. The dysregulation of these systems parallels findings in human alcoholics and treatments that demonstrate efficacy in alcoholics can also reduce drinking in this model. Moreover, preclinical findings have informed the development of human clinical trials, further highlighting the translational potential of the model. As a result of these features, the CIE exposure and free-choice drinking model is becoming more widely used and promises to provide more insight into mechanisms of excessive drinking that may be important for developing treatments for human alcoholics. The salient features and possible future considerations for CIE exposure and free-choice drinking in mice are discussed. PMID:24530006

  15. Specific suppression of insulin sensitivity in growth hormone receptor gene-disrupted (GHR-KO) mice attenuates phenotypic features of slow aging

    PubMed Central

    Arum, Oge; Boparai, Ravneet K; Saleh, Jamal K; Wang, Feiya; Dirks, Angela L; Turner, Jeremy G; Kopchick, John J; Liu, Jun-Li; Khardori, Romesh K; Bartke, Andrzej

    2014-01-01

    In addition to their extended lifespans, slow-aging growth hormone receptor/binding protein gene-disrupted (knockout) (GHR-KO) mice are hypoinsulinemic and highly sensitive to the action of insulin. It has been proposed that this insulin sensitivity is important for their longevity and increased healthspan. We tested whether this insulin sensitivity of the GHR-KO mouse is necessary for its retarded aging by abrogating that sensitivity with a transgenic alteration that improves development and secretory function of pancreatic ?-cells by expressing Igf-1 under the rat insulin promoter 1 (RIP::IGF-1). The RIP::IGF-1 transgene increased circulating insulin content in GHR-KO mice, and thusly fully normalized their insulin sensitivity, without affecting the proliferation of any non-?-cell cell types. Multiple (nonsurvivorship) longevity-associated physiological and endocrinological characteristics of these mice (namely beneficial blood glucose regulatory control, altered metabolism, and preservation of memory capabilities) were partially or completely normalized, thus supporting the causal role of insulin sensitivity for the decelerated senescence of GHR-KO mice. We conclude that a delayed onset and/or decreased pace of aging can be hormonally regulated. PMID:25244225

  16. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Presented are three demonstrations for chemical education. The activities include: (1) demonstration of vapor pressure; (2) a multicolored luminol-based chemiluminescence demonstration; and (3) a Charles's Law/Vapor pressure apparatus. (RH)

  17. Reflectance Demonstration.

    ERIC Educational Resources Information Center

    Kowalski, Frank

    1993-01-01

    Presents a demonstration in which a mirror "disappears" upon rotation. The author has used the demonstration with students from fourth grade up through college. Suggestions are given for making the demonstration into a permanent hallway display. (MVL)

  18. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1981-01-01

    Provides procedures for demonstrations: (1) the ferrioxalate actinometer, which demonstrates a photochemical reaction; and (2) the silver mirror, which demonstrates the reduction of a metal salt to the metal and/or the reducing power of sugars. (CS)

  19. Bone malformations in interleukin-18 transgenic mice.

    PubMed

    Kawase, Yusuke; Hoshino, Tomoaki; Yokota, Koichi; Kuzuhara, Akemi; Nakamura, Masanori; Maeda, Yu; Nishiwaki, Eiji; Zenmyo, Michihisa; Hiraoka, Koji; Aizawa, Hisamichi; Yoshino, Kohichiro

    2003-06-01

    The in vivo effects of IL-18 on bone metabolism were investigated by histopathology in IL-18 transgenic mice. Deformed cortical bone and decreased turnover rate of lumbar trabecular bone are consistent with increased expression of IFN-gamma and IL-18 in the bone marrow. Interleukin (IL)-18 has been demonstrated to inhibit osteoclastogenesis in an in vitro co-culture system. We investigated the effects of IL-18 overexpression on bone metabolism by comparing bone characteristics in male IL-18 transgenic (TG) mice, which secrete mature murine IL-18 from their B- and T-cells, and their wildtype littermates (WT). Histopathological analysis revealed that the cortical bone of the femur was thinner and more deformed in IL-18 TG mice. Bone histomorphometry showed that the cortical bone area of the mid-diaphysis of the femur and the trabecular bone volume of the lumbar vertebrae were significantly reduced in IL-18 TG mice. IL-18 TG mice also exhibited significantly fewer osteoclasts and a reduced bone formation rate in the trabecular bones of their lumbar vertebrae. Real-time reverse transcriptase-polymerase chain reaction amplification of bone marrow cell mRNA revealed that interferon (IFN)-gamma mRNA expression was significantly increased, whereas IL-4 mRNA expression was significantly reduced, in IL-18 TG mice. However, the expression ratio of receptor activator of NFkappaB ligand and osteoprotegerin mRNA was not significantly altered. Thus, deformed cortical bone and a decreased turnover rate of lumbar trabecular bone are characteristic of IL-18 TG mice, and these features might be associated with the increased expression of IFN-gamma and IL-18 in the bone marrow. PMID:12817749

  20. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1989-01-01

    Presented are two demonstrations including a variation of the iodine clock reaction, and a simple demonstration of refractive index. The materials, procedures, and a discussion of probable results are given for each. (CW)

  1. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1990-01-01

    Presented are two demonstrations; "Heat of Solution and Colligative Properties: An Illustration of Enthalpy and Entropy," and "A Vapor Pressure Demonstration." Included are lists of materials and experimental procedures. Apparatus needed are illustrated. (CW)

  2. Immunological response to re-infections with clones of the Colombian strain of Trypanosoma cruzi with different degrees of virulence: influence on pathological features during chronic infection in mice.

    PubMed

    Guerreiro, Marcos Lazaro da Silva; Morais, Isa Rita Brito; Andrade, Sonia Gumes

    2015-06-01

    Re-infections with Trypanosoma cruzi are an aggravating factor for Chagas disease morbidity. The Colombian strain of T. cruzi represents multiclonal populations formed by clonally propagating organisms with different tropisms and degrees of virulence. In the present study, the influence of successive inoculations with clones of the Colombian strain, exhibiting different degrees of virulence, on chronic myocarditis and the humoral and cellular immune responses (Col-C1 high virulence, Col-C8 medium virulence and Col-C5 low virulence) were demonstrated. Mice from three groups with a single infection were evaluated during the acute (14th-30th day) and chronic phases for 175 days. An immunofluorescence assay, ELISA and delayed type hypersensitivity (DTH) cutaneous test were also performed. Mice with a triple infection were studied on the 115th-175th days following first inoculation. The levels of IgM and IgG2a were higher in the animals with a triple infection. DTH showed a higher intensity in the inflammatory infiltrate based on the morphometric analysis during a 48 h period of the triple infection and at 24 h with a single infection. The histopathology of the heart demonstrated significant exacerbation of cardiac inflammatory lesions confirmed by the morphometric test. The humoral responses indicate a reaction to the triple infection, even with clones of the same strain. PMID:25946153

  3. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1985-01-01

    List of materials needed, procedures used, and results obtained are provided for two demonstrations. The first is an inexpensive and quick method for demonstrating column chromatography of plant pigments of spinach extract. The second is a demonstration of cathodic protection by impressed current. (JN)

  4. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Sands, Robert; And Others

    1982-01-01

    Procedures for two demonstrations are provided. The solubility of ammonia gas in water is demonstrated by introducing water into a closed can filled with the gas, collapsing the can. The second demonstration relates scale of standard reduction potentials to observed behavior of metals in reactions with hydrogen to produce hydrogen gas. (Author/JN)

  5. Inflammatory Dilated Cardiomyopathy in Abcg5 Deficient Mice

    PubMed Central

    Wilson, Dennis W.; Oslund, Karen L.; Lyons, Bonnie; Foreman, Oded; Burzenski, Lisa; Svenson, Karen L.; Chase, Thomas H.; Shultz, Leonard D.

    2014-01-01

    Dilated cardiomyopathy (DCM) in A/J mice homozygous for the spontaneous thrombocytopenia and cardiomyopathy (trac) mutation results from a single base pair change in the Abcg5 gene. A similar mutation in humans causes sitosterolemia with high plant sterol levels, hypercholesterolemia, and early onset atherosclerosis. Analyses of CD3+ and Mac-3+ cells and trichrome stainable collagen in hearts showed inflammation and myocyte degeneration in A/J-trac/trac mice beginning post-weaning and progressed to marked dilative and fibrosing cardiomyopathy by 140 days. TEM demonstrated myocyte vacuoles consistent with swollen ER. Myocytes with abundant cytoplasmic glycogen and less dense actinomyosin filament bundles formed mature intercalated discs with adjacent normal myocytes suggesting myocyte repair. A/J-trac/trac mice fed life long phytosterol-free diets did not develop cardiomyopathy. BALB/cByJ- trac/trac mice had lesser inflammatory infiltrates and later onset DCM. BALB/cByJ- trac/trac mice changed from normal to phytosterol-free diets after initiation of cadiomyopathy had lesser T cell infiltrates but persistent monocyte infiltrates and equivalent fibrosis to mice on normal diets. B and T cell deficient BALB/cBy-Rag1null trac/trac mice fed normal diets did not develop inflammatory infiltrates or DCM. We conclude that DCM in the trac/trac mouse shares many features of inflammatory DCM and that the reversibility of myocardial T cell infiltration provides a novel model for investigating the progression of myocardial fibrosis. PMID:23129576

  6. N88S seipin mutant transgenic mice develop features of seipinopathy/BSCL2-related motor neuron disease via endoplasmic reticulum stress.

    PubMed

    Yagi, Takuya; Ito, Daisuke; Nihei, Yoshihiro; Ishihara, Tadayuki; Suzuki, Norihiro

    2011-10-01

    Heterozygosity for mutations (N88S and P90L) in the N-glycosylation site of seipin/BSCL2 is associated with the autosomal dominant motor neuron diseases, spastic paraplegia 17 and distal hereditary motor neuropathy type V, referred to as 'seipinopathies'. Previous in vitro studies have shown that seipinopathy-linked mutations result in accumulation of unfolded proteins in the endoplasmic reticulum (ER), leading to the unfolded protein response and cell death, suggesting that seipinopathies is closely associated with ER stress. To further understand the molecular pathogenesis of seipinopathies, we generated a transgenic (tg) mouse line expressing the human N88S seipin mutant with the murine Thy-1 promoter to permit analyses of in vivo phenotypic changes. The N88S seipin tg mice develop a progressive spastic motor deficit, reactive gliosis in the spinal cord and neurogenic muscular atrophy, recapitulating the symptomatic and pathological phenotype in patients of seipinopathy. We also found that expression of mutant seipin in mice upregulated the ER stress marker, immunoglobulin-heavy-chain-binding protein, protein disulfide isomerase and X-box binding protein 1, but was not linked to significant neuronal loss in affected tissue, thereby indicating that ER stress is sufficient, while neuronal death is not necessary, for the development of motor phenotypes of seipinopathies. Our findings in the mutant seipin tg mouse provide clues to understand the relationship with ER stress and neurodegeneration, and the seipin tg mouse is a valid tool for the development of novel therapeutic strategies against ER stress-related diseases. PMID:21750110

  7. Isolation, purification, and structural features of a polysaccharide from Phellinus linteus and its hypoglycemic effect in alloxan-induced diabetic mice.

    PubMed

    Zhao, Chao; Liao, Zunsheng; Wu, Xiaoqi; Liu, Yanling; Liu, Xiaoyan; Lin, Zhanxi; Huang, Yifan; Liu, Bin

    2014-05-01

    Phellinus linteus is a medicinal mushroom that has been used in Oriental countries for centuries for its antitumor, antioxidant, immunomodulatory, and biological activity on hyperglycemia. A water-soluble crude polysaccharide was extracted using hot water from P. linteus mycelia grown under submerged culture. An orthogonal experiment was used to optimize the extraction conditions of P. linteus mycelia polysaccharides (PLP). The crude polysaccharide was purified using DEAE Sephadex A-50 and Sephadex G-200 chromatography. Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance ((1) H NMR) spectroscopy were used to investigate the structure of the purified P. linteus polysaccharide (PLP-I), revealing that it was mainly a branched-type glycan with both ?- and ?-linkages and a pyranoid sugar ring conformation. PLP orally administered at 100 mg/kg body weight/d could significantly reduce the blood glucose level by 35.60% in alloxan-induced diabetic mice. The results of an oral glucose tolerance test (OGTT) revealed that PLP had an effect on glucose disposal after 28 d of treatment. The result revealed that PLP from a submerged culture of P. linteus mycelia possessed potent hypoglycemic properties. The polysaccharide may be useful as a functional food additive and a hypoglycemic agent. PMID:24761950

  8. Immunological features and efficacy of a multi-epitope vaccine CTB-UE against H. pylori in BALB/c mice model.

    PubMed

    Guo, Le; Yin, Runting; Liu, Kunmei; Lv, Xiaobo; Li, Yonghong; Duan, Xiangguo; Chu, Yuankui; Xi, Tao; Xing, Yingying

    2014-04-01

    Epitope vaccine is a promising option for prophylactic and therapeutic vaccination against Helicobacter pylori infection. Urease is an essential virulence factor and colonization factor for H. pylori. In this study, we constructed a multi-epitope vaccine named CTB-UE with mucosal adjuvant cholera toxin B subunit (CTB) and tandem copies of Th and B cell epitopes from H. pylori urease A and B subunits. The immunogenicity, specificity, ability to induce neutralizing antibodies against H. pylori urease, and prophylactic and therapeutic efficacy of the CTB-UE vaccine were evaluated in BALB/c mice model after purification. The experimental results indicated that CTB-UE could induce comparatively high levels of specific antibodies against native H. pylori urease, UreA, UreB, or the selected B cell epitopes UreA??????? and UreB??????? involved with the active site of urease and showed an effectively inhibitory effect on the enzymatic activity of urease. Besides, oral prophylactic or therapeutic immunization with CTB-UE significantly decreased H. pylori colonization compared with oral immunization with rUreB or PBS, and the protection was correlated with antigen-specific CD4? T cells and IgG, IgA, and mucosal sIgA antibody responses. This CTB-UE vaccine may be a promising vaccine candidate for the control of H. pylori infection. PMID:24370888

  9. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1983-01-01

    Discusses a supplement to the "water to rose" demonstration in which a pink color is produced. Also discusses blood buffer demonstrations, including hydrolysis of sodium bicarbonate, simulated blood buffer, metabolic acidosis, natural compensation of metabolic acidosis, metabolic alkalosis, acidosis treatment, and alkalosis treatment. Procedures…

  10. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Describes two laboratory demonstrations in chemistry. One uses dry ice, freon, and freezer bags to demonstrate volume changes, vapor-liquid equilibrium, a simulation of a rain forest, and vaporization. The other uses the clock reaction technique to illustrate fast reactions and kinetic problems in releasing carbon dioxide during respiration. (TW)

  11. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1980-01-01

    Described is a demonstration utilized to measure the heat of vaporization using the Clausius-Clapeyron equation. Explained is that when measurement is made as part of a demonstration, it raises student's consciousness that chemistry is experimentally based. (Author/DS)

  12. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1990-01-01

    Described are demonstrations designed to reveal the important "nonsolvent" properties of water through its interaction with a toy called "Magic Sand" and other synthetic silica derivatives, especially those bonded with organic moities. The procedures for seven demonstrations along with a discussion of the effects are presented. (CW)

  13. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1980-01-01

    Two demonstrations are described: (1) a variant of preparing purple benzene by phase transfer catalysis with quaternary ammonium salts and potassium permanganate in which crown ethers are used; (2) a corridor or "hallway" demonstration in which unknown molecular models are displayed and prizes awarded to students correctly identifying the…

  14. Physics Demonstrations

    NSDL National Science Digital Library

    A collection of in-depth physics demonstrations with instructions for doing it yourself, videos that let you see how it's done, and suggestions for developing some of the demos into experiments. The demonstrations were developed and tested by The Science House, the mathematics and science learning outreach project of North Carolina State University.

  15. Microgravity Demonstrator

    NSDL National Science Digital Library

    This tool was designed by NASA engineers to demonstrate and teach principles of microgravity and its relationship to science and math. Teachers may perform a series of demonstrations to provide a visual, physical connection between free-fall and microgravity conditions and to understand why certain experiments are performed under microgravity conditions.

  16. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Presents three demonstrations suitable for undergraduate chemistry classes. Focuses on experiments with calcium carbide, the induction by iron of the oxidation of iodide by dichromate, and the classical iodine clock reaction. (ML)

  17. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Roffia, Sergio; And Others

    1988-01-01

    Reports two electrochemical demonstrations. Uses a hydrogen-oxygen fuel cell to power a clock. Includes description of methods and materials. Investigates the "potato clock" used with different fruits. Lists emf and current for various fruit and electrode combinations. (ML)

  18. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1980-01-01

    Presented is a Corridor Demonstration which can be set up in readily accessible areas such as hallways or lobbies. Equipment is listed for a display of three cells (solar cells, fuel cells, and storage cells) which develop electrical energy. (CS)

  19. Tested Demonstrations

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1977-01-01

    Describes the use of various indicators to demonstrate chemical reactions; the display of sodium as a shiny metal; and the illustration of the attainment of chemical equilibrium with beakers of chemicals and an overhead projector. (MLH)

  20. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1988-01-01

    Describes two demonstrations for use in college chemistry classes. Includes "Spectroscopy in Large Lecture Halls" and "The Endothermic Dissolution of Ammonium Nitrate." Gives materials lists and procedures as well as a discussion of the results. (CW)

  1. Demonstration Explosion

    NASA Astrophysics Data System (ADS)

    Lee, Charles "Skip"

    1998-05-01

    Last week I did a demonstration that produced a serious explosion. After putting methanol in a big glass carboy and rotating the carboy to build up some methanol vapor, I lit the mouth of the carboy. What normally happens is a "jet engine" effect out of the mouth of the carboy. In my case, the carboy exploded. Two polycarbonate blast shields were shattered and glass was blown as far as 15 feet away. I was not seriously cut and bruised, but had I not been using the two blast shields, I would have been severely injured. At this time, I am not sure what caused the explosion. I have done this demonstration around one hundred times with no problem using the exact same amount of methanol and technique. I think it is important to get the word out that this demonstration may be more dangerous than previously thought. I would also welcome any hypotheses concerning what caused the carboy to explode.

  2. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1985-01-01

    Describes two demonstrations that require almost no preparation time, are visually stimulating, and present a variety of material for class discussion (with sample questions provided). The first involves a sodium bicarbonate hydrochloric acid volcano; the second involves a dissolving polystyrene cup. Procedures used and information on…

  3. Tested Demonstrations

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1976-01-01

    Describes two demonstrations: one that illustrates the attainment of equilibrium in first-order reactions by changing the volumes of two beakers of water at a specified rate, and another that illustrates the role of indicators in showing pH changes in buffer solutions. (MLH)

  4. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1984-01-01

    Two demonstrations are described. The first shows the effect of polarity on solubility. The second is based on the unexpected formation of a precipitate of barium nitrate when barium carbonate or barium phosphate is treated with dilute nitric acid. List of materials needed and procedures used are included. (JN)

  5. ENCEPHALOMYELITIS OF MICE

    PubMed Central

    Theiler, Max; Gard, Sven

    1940-01-01

    1. In the feces of approximately two-thirds of normal mice 6 weeks of age an agent in all respects similar to the virus of mouse encephalomyelitis can be recovered. 2. In isolated mice, fed on sterile food and water, excretion of virus has been shown to persist up to 53 days after isolation. 3. In normal mice known to be virus carriers virus has been demonstrated in the gastro-intestinal tract but not in the central nervous system, thoracic or abdominal viscera, or any organs of the head. 4. The source of the virus excreted in the feces has been shown to be located in all probability in the intestinal wall. 5. Evidence is presented that the virus can invade the animal organism, as virus has been demonstrated in the mesenteric lymph glands. PMID:19871009

  6. Simulations/ Demonstrations

    NSDL National Science Digital Library

    Over twenty Java applets from Rice University are presented on this site. The applets cover most of the major points taught in an introductory statistics course. One quality that makes this site stand out from others is the excellent background information presented with many applets, which lets users read about a concept and see it visually at the same time. Topics include applications of the central limit theorem, regression, analysis of variance, and many more. The applets are all very easy to use, and they are certainly valuable demonstrations for any high school or college student in statistics.

  7. A single intramuscular injection of neuraminidase inhibitor peramivir demonstrates antiviral activity against novel pandemic A\\/California\\/04\\/2009 (H1N1) influenza virus infection in mice

    Microsoft Academic Search

    Shanta Bantia; Debra Kellogg; Cynthia Parker; Ramanda Upshaw; Natalia A. Ilyushina; Y. S. Babu

    2011-01-01

    New and emerging influenza virus strains, such as the pandemic influenza A (H1N1) virus require constant vigilance for antiviral drug sensitivity and resistance. Efficacy of intramuscularly (IM) administered neuraminidase (NA) inhibitor, peramivir, was evaluated in mice infected with recently isolated pandemic A\\/California\\/04\\/2009 (H1N1, swine origin, mouse adapted) influenza virus. A single IM injection of peramivir (four dose groups), given 1h

  8. Expansion in vitro of Transplantable Human Cord Blood Stem Cells Demonstrated Using a Quantitative Assay of their Lympho-Myeloid Repopulating Activity in Nonobese Diabetic-Scid\\/Scid Mice

    Microsoft Academic Search

    E. Conneally; J. Cashman; A. Petzer; C. Eaves

    1997-01-01

    Human hematopoiesis originates in a population of stem cells with transplantable lympho-myeloid reconstituting potential, but a method for quantitating such cells has not been available. We now described a simple assay that meets this need. It is based on the ability of sublethally irradiated immunodeficient nonobese diabetic--scid\\/scid (NOD\\/SCID) mice to be engrafted by intravenously injected human hematopoietic cells and uses

  9. Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps

    PubMed Central

    2011-01-01

    Background We and others have demonstrated previously that ghrelin receptor (GhrR) knock out (KO) mice fed a high fat diet (HFD) have increased insulin sensitivity and metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is the dramatic decrease in hepatic steatosis. To characterize further the underlying mechanisms of glucose homeostasis in GhrR KO mice, we conducted both hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI-E) clamps. Additionally, we investigated tissue glucose uptake and specifically examined liver insulin sensitivity. Results Consistent with glucose tolerance-test data, in HG clamp experiments, GhrR KO mice showed a reduction in glucose-stimulated insulin release relative to WT littermates. Nevertheless, a robust 1st phase insulin secretion was still achieved, indicating that a healthy ?-cell response is maintained. Additionally, GhrR KO mice demonstrated both a significantly increased glucose infusion rate and significantly reduced insulin requirement for maintenance of the HG clamp, consistent with their relative insulin sensitivity. In HI-E clamps, both LFD-fed and HFD-fed GhrR KO mice showed higher peripheral insulin sensitivity relative to WT littermates as indicated by a significant increase in insulin-stimulated glucose disposal (Rd), and decreased hepatic glucose production (HGP). HFD-fed GhrR KO mice showed a marked increase in peripheral tissue glucose uptake in a variety of tissues, including skeletal muscle, brown adipose tissue and white adipose tissue. GhrR KO mice fed a HFD also showed a modest, but significant decrease in conversion of pyruvate to glucose, as would be anticipated if these mice displayed increased liver insulin sensitivity. Additionally, the levels of UCP2 and UCP1 were reduced in the liver and BAT, respectively, in GhrR KO mice relative to WT mice. Conclusions These results indicate that improved glucose homeostasis of GhrR KO mice is characterized by robust improvements of glucose disposal in both normal and metabolically challenged states, relative to WT controls. GhrR KO mice have an intact 1st phase insulin response but require significantly less insulin for glucose disposal. Our experiments reveal that the insulin sensitivity of GhrR KO mice is due to both BW independent and dependent factors. We also provide several lines of evidence that a key feature of the GhrR KO mouse is maintenance of hepatic insulin sensitivity during metabolic challenge. PMID:21211044

  10. Deletion of IL-12p35 induces liver fibrosis in dominant negative transforming growth factor ? receptor type II mice

    PubMed Central

    Tsuda, Masanobu; Zhang, Weici; Yang, Guo-Xiang; Tsuneyama, Koichi; Ando, Yugo; Kawata, Kazuhito; Park, Ogyi; Leung, Patrick S.C.; Coppel, Ross L.; Ansari, Aftab A.; Ridgway, William M.; Gao, Bin; Lian, Zhe-Xiong; Flavell, Richard; He, Xiao-Song; Gershwin, M. Eric

    2012-01-01

    We have previously reported that mice with a dominant negative transforming growth factor ? receptor restricted to T cells (dnTGF?RII mice) develop an inflammatory biliary ductular disease that strongly resembles human primary biliary cirrhosis (PBC). Furthermore, deletion of the gene encoding interleukin (IL)-12p40 resulted in a strain (IL-12p40?/?dnTGF?RII) with dramatically reduced autoimmune cholangitis. To further investigate the role of the IL-12 cytokine family in dnTGF?RII autoimmune biliary disease, we deleted the gene encoding the IL-12p35 subunit from dnTGF?RII mice, resulting in an IL-12p35?/? dnTGF?RII strain which is deficient in two members of the IL-12 family, IL-12 and IL-35. In contrast to IL-12p40?/? mice, the IL-12p35?/? mice developed liver inflammation and bile duct damage with similar severity but delayed onset as the parental dnTGF?RII mice. The p35?/? mice also demonstrated a distinct cytokine profile characterized by a shift from a Th1 to a Th17 response. Strikingly, liver fibrosis was frequently observed in IL-12p35?/? mice. In conclusion, IL-12p35?/? dnTGF?RII mice, histologically and immunologically, reflect key features of PBC, providing a useful generic model to understand the immunopathology of human PBC. PMID:22576253

  11. Automatic Visual Tracking and Social Behaviour Analysis with Multiple Mice

    PubMed Central

    Giancardo, Luca; Sona, Diego; Huang, Huiping; Sannino, Sara; Managò, Francesca; Scheggia, Diego; Papaleo, Francesco; Murino, Vittorio

    2013-01-01

    Social interactions are made of complex behavioural actions that might be found in all mammalians, including humans and rodents. Recently, mouse models are increasingly being used in preclinical research to understand the biological basis of social-related pathologies or abnormalities. However, reliable and flexible automatic systems able to precisely quantify social behavioural interactions of multiple mice are still missing. Here, we present a system built on two components. A module able to accurately track the position of multiple interacting mice from videos, regardless of their fur colour or light settings, and a module that automatically characterise social and non-social behaviours. The behavioural analysis is obtained by deriving a new set of specialised spatio-temporal features from the tracker output. These features are further employed by a learning-by-example classifier, which predicts for each frame and for each mouse in the cage one of the behaviours learnt from the examples given by the experimenters. The system is validated on an extensive set of experimental trials involving multiple mice in an open arena. In a first evaluation we compare the classifier output with the independent evaluation of two human graders, obtaining comparable results. Then, we show the applicability of our technique to multiple mice settings, using up to four interacting mice. The system is also compared with a solution recently proposed in the literature that, similarly to us, addresses the problem with a learning-by-examples approach. Finally, we further validated our automatic system to differentiate between C57B/6J (a commonly used reference inbred strain) and BTBR T+tf/J (a mouse model for autism spectrum disorders). Overall, these data demonstrate the validity and effectiveness of this new machine learning system in the detection of social and non-social behaviours in multiple (>2) interacting mice, and its versatility to deal with different experimental settings and scenarios. PMID:24066146

  12. Mice Rule! (or Not)

    NSDL National Science Digital Library

    2014-09-18

    Students explore the relationships between genetics, biodiversity and evolution through a simple activity involving hypothetical wild mouse populations. First, students toss coins to determine what traits a set of mouse parents possesses, such as fur color, body size, heat tolerance and running speed. Next, they use coin tossing to determine the traits a mouse pup born to these parents possesses. These physical features are then compared to features that would be most adaptive in several different environmental conditions. Finally, students consider what would happen to the mouse offspring if those environmental conditions were to change. Which mice would be most likely to survive and produce the next generation?

  13. Improved establishment of embryonic stem (ES) cell lines from the Chinese Kunming mice by hybridization with 129 mice.

    PubMed

    Yu, Shumin; Yan, Xingrong; Liu, Huanhuan; Cai, Xin; Cao, Suizhong; Shen, Liuhong; Zuo, Zhicai; Deng, Junliang; Ma, Xiaoping; Wang, Ya; Ren, Zhihua

    2014-01-01

    Chinese Kunming mice (Mus musculus Km), widely used as laboratory animals throughout China, remain very refractory for embryonic stem (ES) cell isolation. The present study was aimed to evaluate the effects of hybridization with 129/Sv mice, and culture media containing fetal bovine serum (FBS) or Knockout serum replacement (KSR) on ES cell isolation from Kunming mice. The results demonstrated that ES cells had been effectively isolated from the hybrid embryos of Kunming and 129/Sv mice using all three media containing 15% FBS, 15% KSR and their mixture of 14% KSR and 1% FBS, individually. These isolated ES cells had maintained in vitro undifferentiated for a long time, exhibiting all features specific for mouse ES cells. In addition, the rates of ES cell isolation in the medium containing 14% KSR and 1% FBS, was 46.67% and significantly higher than those in another two media containing only FBS or KSR (p < 0.05). Contrarily, no ES cell line had been established from Kunming mouse inbred embryos using the same protocols. These results suggested that ES cells with long-term self-renewal ability could be efficiently generated from hybrid embryos of Kunming and 129/Sv mice, and a small volume of FBS was necessary to isolate ES cells in the KSR medium when embryos and early ES cells cultured. PMID:24573251

  14. The disease of the NZB mouse: examination of exchange ovum transplantation derived NZB and CFW mice

    PubMed Central

    Barnes, R. D.; Tuffrey, Maureen; Kingman, Jean; Risdon, R. A.

    1972-01-01

    Exchange ovum transplantation has been employed between the autoimmune NZB and normal CFW mice. The features of the disease in these mice have been examined together with a small group of milk fostered animals. Ovum transplanted NZB uterine nurtured to term from the CFW develop a positive Direct Coombs' Test (DCT) and, like normally derived NZB, this reaction, once positive, is usually maintained. Positive DCT reactions were also, on occasions, seen in the CFW uterine nurtured or milk fostered from the NZB, but these were always transient. Although anaemia and reticulocytosis characterize normal, ovum transplantation derived and milk fostered NZB, these changes could not be demonstrated in either the uterine nurtured or milk fostered CFW mice. Histological examination of the thymus, kidney and spleen of these CFW mice also failed to reveal any morphological feature present in either ovum transplantation or normally derived NZB. The fact that the disease in the NZB was not altered in spite of being uterine nurtured from a normal strain, suggests that the stimulus to develop the disease must be present prior to the stage of implantation. The transient nature of the positive DCT reactions in the CFW, and anaemia and morphological changes not being demonstrated, suggests that stimulation to develop autoantibodies might be common in mice but this process is normally suppressed and it is the age related failure of this recognition and suppression process that accounts for the progressive disease of the aged NZB. ImagesFig. 5Fig. 6 PMID:4537526

  15. Genetic and phenotypic properties of vero cell-adapted Japanese encephalitis virus SA14-14-2 vaccine strain variants and a recombinant clone, which demonstrates attenuation and immunogenicity in mice.

    PubMed

    Gromowski, Gregory D; Firestone, Cai-Yen; Bustos-Arriaga, José; Whitehead, Stephen S

    2015-01-01

    The live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine, produced in primary hamster kidney cells, is safe and effective. Past attempts to adapt this virus to replicate in cells that are more favorable for vaccine production resulted in mutations that significantly reduced immunogenicity. In this study, 10 genetically distinct Vero cell-adapted JEV SA14-14-2 variants were isolated and a recombinant wild-type JEV clone, modified to contain the JEV SA14-14-2 polyprotein amino acid sequence, was recovered in Vero cells. A single capsid protein mutation (S66L) was important for Vero cell-adaptation. Mutations were also identified that modulated virus sensitivity to type I interferon-stimulation in Vero cells. A subset of JEV SA14-14-2 variants and the recombinant clone were evaluated in vivo and exhibited levels of attenuation that varied significantly in suckling mice, but were avirulent and highly immunogenic in weanling mice and are promising candidates for the development of a second-generation, recombinant vaccine. PMID:25311701

  16. Impaired structural correlates of memory in Alzheimer's disease mice?

    PubMed Central

    Badhwar, AmanPreet; Lerch, Jason P.; Hamel, Edith; Sled, John G.

    2013-01-01

    The healthy adult brain demonstrates robust learning-induced neuroanatomical plasticity. While altered neuroanatomical plasticity is suspected to be a factor mitigating the progressive cognitive decline in Alzheimer's disease (AD), it is not known to what extent this plasticity is affected by AD. We evaluated whether spatial learning and memory-induced neuroanatomical plasticity are diminished in an adult mouse model of AD (APP mice) featuring amyloid beta-driven cognitive and cerebrovascular dysfunction. We also evaluated the effect of early, long-term pioglitazone-treatment on functional hyperemia, spatial learning and memory, and associated neuroanatomical plasticity. Using high-resolution post-mortem MRI and deformation-based morphometry, we demonstrate spatial learning and memory-induced focal volume increase in the hippocampus of wild-type mice, an effect that was severely attenuated in APP mice, consistent with their unsuccessful performance in the spatial Morris water maze. These findings implicate impaired neuroanatomical plasticity as an important contributing factor to cognitive deficits in the APP mouse model of AD. Pioglitazone-treatment in APP mice completely rescued functional hyperemia and exerted beneficial effects on spatial learning and memory-recall, but it did not improve hippocampal plasticity. PMID:24273714

  17. Self-tracking Energy Transfer for Neural Stimulation in Untethered Mice

    E-print Network

    Ho, John S; Iyer, Shrivats Mohan; Christensen, Amelia J; Grosenick, Logan; Deisseroth, Karl; Delp, Scott L; Poon, Ada S Y

    2015-01-01

    Optical or electrical stimulation of neural circuits in mice during natural behavior is an important paradigm for studying brain function. Conventional systems for optogenetics and electrical microstimulation require tethers or large head-mounted devices that disrupt animal behavior. We report a method for wireless powering of small-scale implanted devices based on the strong localization of energy that occurs during resonant interaction between a radio-frequency cavity and intrinsic modes in mice. The system features self-tracking over a wide (16 cm diameter) operational area, and is used to demonstrate wireless activation of cortical neurons with miniaturized stimulators (10 mm$^{3}$, 20 mg) fully implanted under the skin.

  18. Neutral aminoaciduria in cystathionine ?-synthase-deficient mice; an animal model of homocystinuria.

    PubMed

    Akahoshi, Noriyuki; Kamata, Shotaro; Kubota, Masashi; Hishiki, Takako; Nagahata, Yoshiko; Matsuura, Tomomi; Yamazaki, Chiho; Yoshida, Yuka; Yamada, Hidenori; Ishizaki, Yasuki; Suematsu, Makoto; Kasahara, Tadashi; Ishii, Isao

    2014-06-15

    The kidney is one of the major loci for the expression of cystathionine ?-synthase (CBS) and cystathionine ?-lyase (CTH). While CBS-deficient (Cbs(-/-)) mice display homocysteinemia/methioninemia and severe growth retardation, and rarely survive beyond the first 4 wk, CTH-deficient (Cth(-/-)) mice show homocysteinemia/cystathioninemia but develop with no apparent abnormality. This study examined renal amino acid reabsorption in those mice. Although both 2-wk-old Cbs(-/-) and Cth(-/-) mice had normal renal architecture, their serum/urinary amino acid profiles largely differed from wild-type mice. The most striking feature was marked accumulation of Met and cystathionine in serum/urine/kidney samples of Cbs(-/-) and Cth(-/-) mice, respectively. Levels of some neutral amino acids (Val, Leu, Ile, and Tyr) that were not elevated in Cbs(-/-) serum were highly elevated in Cbs(-/-) urine, and urinary excretion of other neutral amino acids (except Met) was much higher than expected from their serum levels, demonstrating neutral aminoaciduria in Cbs(-/-) (not Cth(-/-)) mice. Because the bulk of neutral amino acids is absorbed via a B(0)AT1 transporter and Met has the highest substrate affinity for B(0)AT1 than other neutral amino acids, hypermethioninemia may cause hyperexcretion of neutral amino acids. PMID:24761004

  19. A lymphatic defect causes ocular hypertension and glaucoma in mice.

    PubMed

    Thomson, Benjamin R; Heinen, Stefan; Jeansson, Marie; Ghosh, Asish K; Fatima, Anees; Sung, Hoon-Ki; Onay, Tuncer; Chen, Hui; Yamaguchi, Shinji; Economides, Aris N; Flenniken, Ann; Gale, Nicholas W; Hong, Young-Kwon; Fawzi, Amani; Liu, Xiaorong; Kume, Tsutomu; Quaggin, Susan E

    2014-10-01

    Glaucoma is a leading cause of blindness, afflicting more than 60 million people worldwide. Increased intraocular pressure (IOP) due to impaired aqueous humor drainage is a major risk factor for the development of glaucoma. Here, we demonstrated that genetic disruption of the angiopoietin/TIE2 (ANGPT/TIE2) signaling pathway results in high IOP, buphthalmos, and classic features of glaucoma, including retinal ganglion degeneration and vision loss. Eyes from mice with induced deletion of Angpt1 and Angpt2 (A1A2Flox(WB) mice) lacked drainage pathways in the corneal limbus, including Schlemm's canal and lymphatic capillaries, which share expression of the PROX1, VEGFR3, and FOXC family of transcription factors. VEGFR3 and FOXCs have been linked to lymphatic disorders in patients, and FOXC1 has been linked to glaucoma. In contrast to blood endothelium, in which ANGPT2 is an antagonist of ANGPT1, we have shown that both ligands cooperate to regulate TIE2 in the lymphatic network of the eye. While A1A2Flox(WB) mice developed high IOP and glaucoma, expression of ANGPT1 or ANGPT2 alone was sufficient for ocular drainage. Furthermore, we demonstrated that loss of FOXC2 from lymphatics results in TIE2 downregulation, suggesting a mechanism for ocular defects in patients with FOXC mutations. These data reveal a pathogenetic and molecular basis for glaucoma and demonstrate the importance of angiopoietin ligand cooperation in the lymphatic endothelium. PMID:25202984

  20. A lymphatic defect causes ocular hypertension and glaucoma in mice

    PubMed Central

    Thomson, Benjamin R.; Heinen, Stefan; Jeansson, Marie; Ghosh, Asish K.; Fatima, Anees; Sung, Hoon-Ki; Onay, Tuncer; Chen, Hui; Yamaguchi, Shinji; Economides, Aris N.; Flenniken, Ann; Gale, Nicholas W.; Hong, Young-Kwon; Fawzi, Amani; Liu, Xiaorong; Kume, Tsutomu; Quaggin, Susan E.

    2014-01-01

    Glaucoma is a leading cause of blindness, afflicting more than 60 million people worldwide. Increased intraocular pressure (IOP) due to impaired aqueous humor drainage is a major risk factor for the development of glaucoma. Here, we demonstrated that genetic disruption of the angiopoietin/TIE2 (ANGPT/TIE2) signaling pathway results in high IOP, buphthalmos, and classic features of glaucoma, including retinal ganglion degeneration and vision loss. Eyes from mice with induced deletion of Angpt1 and Angpt2 (A1A2FloxWB mice) lacked drainage pathways in the corneal limbus, including Schlemm’s canal and lymphatic capillaries, which share expression of the PROX1, VEGFR3, and FOXC family of transcription factors. VEGFR3 and FOXCs have been linked to lymphatic disorders in patients, and FOXC1 has been linked to glaucoma. In contrast to blood endothelium, in which ANGPT2 is an antagonist of ANGPT1, we have shown that both ligands cooperate to regulate TIE2 in the lymphatic network of the eye. While A1A2FloxWB mice developed high IOP and glaucoma, expression of ANGPT1 or ANGPT2 alone was sufficient for ocular drainage. Furthermore, we demonstrated that loss of FOXC2 from lymphatics results in TIE2 downregulation, suggesting a mechanism for ocular defects in patients with FOXC mutations. These data reveal a pathogenetic and molecular basis for glaucoma and demonstrate the importance of angiopoietin ligand cooperation in the lymphatic endothelium. PMID:25202984

  1. Mice with human livers.

    PubMed

    Grompe, Markus; Strom, Stephen

    2013-12-01

    Animal models are used to study many aspects of human disease and to test therapeutic interventions. However, some very important features of human biology cannot be replicated in animals, even in nonhuman primates or transgenic rodents engineered with human genes. Most human microbial pathogens do not infect animals and the metabolism of many xenobiotics is different between human beings and animals. The advent of transgenic immune-deficient mice has made it possible to generate chimeric animals harboring human tissues and cells, including hepatocytes. The liver plays a central role in many human-specific biological processes and mice with humanized livers can be used to model human metabolism, liver injury, gene regulation, drug toxicity, and hepatotropic infections. PMID:24042096

  2. Maintenance of donor phenotype after full-thickness skin transplantation from mice with chronic proliferative dermatitis (cpdm/cpdm) to C57BL/Ka and nude mice and vice versa.

    PubMed

    Gijbels, M J; HogenEsch, H; Bruijnzeel, P L; Elliott, G R; Zurcher, C

    1995-12-01

    Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm) and is characterized by epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To elucidate whether these pathologic features are the result of a local (skin) process or a consequence of a systemic disorder, transplantations were performed of full-thickness grafts of affected skin from cpdm/cpdm mice and normal skin from control (C57BL/Ka) mice on the back of cpdm/cpdm, C57BL/Ka and athymic nude mice. After 3 months, the grafts maintained the histologic phenotype of the donor animal. Intercellular adhesion molecule-1 continued to be expressed by basal keratinocytes of the cpdm/cpdm grafts after transplantation. In contrast, the basal keratinocytes of the C57BL/Ka grafts onto cpdm/cpdm mice remained negative for intercellular adhesion molecule-1 3 months after transplantation. An increased number of proliferating keratinocytes was present in the cpdm/cpdm skin-graft transplanted to nudes or to C57BL/Ka mice based on short-term bromodeoxyuridine labeling. The bromodeoxyuridine incorporation in the keratinocytes of the control C57BL/Ka skin grafts transplanted to cpdm/cpdm, nude, or C57BL/Ka mice was the same as in the keratinocytes of normal C57BL/Ka mice. This study demonstrates that the pathologic features found in the cpdm/cpdm mice are the result of a disorder in the epidermis or dermis and not due to a systemic defect. PMID:7490470

  3. Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

    PubMed

    Berman-Booty, Lisa D; Thomas-Ahner, Jennifer M; Bolon, Brad; Oglesbee, Michael J; Clinton, Steven K; Kulp, Samuel K; Chen, Ching-Shih; La Perle, Krista M D

    2015-02-01

    Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of preneoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice and in male TRAMP mice without histologically apparent prostate tumors. In this article, we also calculate the incidences of the urethral carcinomas and renal tubuloacinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice. PMID:24742627

  4. Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase-deficient mice during acute inflammation.

    PubMed

    Kubala, Lukas; Schmelzer, Kara R; Klinke, Anna; Kolarova, Hana; Baldus, Stephan; Hammock, Bruce D; Eiserich, Jason P

    2010-05-15

    Acute inflammation is a common feature of many life-threatening pathologies, including septic shock. One hallmark of acute inflammation is the peroxidation of polyunsaturated fatty acids forming bioactive products that regulate inflammation. Myeloperoxidase (MPO) is an abundant phagocyte-derived hemoprotein released during phagocyte activation. Here, we investigated the role of MPO in modulating biologically active arachidonic acid (AA) and linoleic acid (LA) metabolites during acute inflammation. Wild-type and MPO-knockout (KO) mice were exposed to intraperitoneally injected endotoxin for 24 h, and plasma LA and AA oxidation products were comprehensively analyzed using a liquid chromatography-mass spectrometry method. Compared to wild-type mice, MPO-KO mice had significantly lower plasma levels of LA epoxides and corresponding LA- and AA-derived fatty acid diols. AA and LA hydroxy intermediates (hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids) were also significantly lower in MPO-KO mice. Conversely, MPO-deficient mice had significantly higher plasma levels of cysteinyl-leukotrienes with well-known proinflammatory properties. In vitro experiments revealed significantly lower amounts of AA and LA epoxides, LA- and AA-derived fatty acid diols, and AA and LA hydroxy intermediates in stimulated polymorphonuclear neutrophils isolated from MPO-KO mice. Our results demonstrate that MPO modulates the balance of pro- and anti-inflammatory lipid mediators during acute inflammation and, in this way, may control acute inflammatory diseases. PMID:20156554

  5. Modulation of arachidonic and linoleic acid metabolites in myeloperoxidase deficient mice during acute inflammation

    PubMed Central

    Kubala, Lukas; Schmelzer, Kara R.; Klinke, Anna; Kolarova, Hana; Baldus, Stephan; Hammock, Bruce D.; Eiserich, Jason P.

    2010-01-01

    Acute inflammation is a common feature of many life-threatening pathologies, including septic shock. One hallmark of acute inflammation is the peroxidation of polyunsaturated fatty acids forming bioactive products, which regulate inflammation. Myeloperoxidase (MPO) is an abundant phagocyte-derived hemoprotein released during phagocyte activation. Here, we investigated the role of MPO in modulating biologically active arachidonic acid (AA) and linoleic acid (LA) metabolites during acute inflammation. Wild-type and MPO-knockout (KO) mice were exposed to intraperitoneally injected endotoxin for 24 h, and plasma LA and AA oxidation products were comprehensively analyzed using a liquid chromatography-mass spectrometry method. Compared to wild-type mice, MPO-KO mice had significantly lower plasma levels of LA epoxides and corresponding LA- and AA-derived fatty acid diols. AA and LA hydroxy intermediates (hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids) were also significantly lower in MPO-KO mice. Conversely, MPO-deficient mice had significantly higher plasma levels of cysteinyl-leukotrienes with well-known pro-inflammatory properties. In vitro experiments revealed significantly lower amounts of AA and LA epoxides, LA- and AA-derived fatty acid diols, and AA and LA hydroxy intermediates in stimulated polymorphonuclear neutrophils isolated from MPO-KO mice. Our results demonstrate that MPO modulates the balance of pro- and anti-inflammatory lipid mediators during acute inflammation. In this way, may control acute inflammatory diseases. PMID:20156554

  6. Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability

    PubMed Central

    Yu, Y. Eugene; Wen, Lei; Silva, Jeane; Li, Zhongyou; Head, Karen; Sossey-Alaoui, Khalid; Pao, Annie; Mei, Lin; Cowell, John K.

    2010-01-01

    LGI1 in humans is responsible for a predisposition to autosomal dominant partial epilepsy with auditory features (ADPEAF). However, mechanisms of how LGI1 mutations cause epilepsy remain unclear. We have used a mouse chromosome engineering strategy to create a null mutation for the gene ortholog encoding LGI1. The Lgi1 null mutant mice show no gross overall developmental abnormalities from routine histopathological analysis. After 12–18 days of age, the homozygous mutant mice all exhibit myoclonic seizures accompanied by rapid jumping and running and die shortly thereafter. The heterozygous mutant mice do not develop seizures. Electrophysiological analysis demonstrates an enhanced excitatory synaptic transmission by increasing the release of the excitatory neurotransmitter glutamate, suggesting a basis for the seizure phenotype. This mouse model, therefore, provides novel insights into the mechanism behind ADPEAF and offers a new opportunity to study the mechanism behind the role of LGI1 in susceptibility to myoclonic seizures. PMID:20130004

  7. Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability.

    PubMed

    Yu, Y Eugene; Wen, Lei; Silva, Jeane; Li, Zhongyou; Head, Karen; Sossey-Alaoui, Khalid; Pao, Annie; Mei, Lin; Cowell, John K

    2010-05-01

    LGI1 in humans is responsible for a predisposition to autosomal dominant partial epilepsy with auditory features (ADPEAF). However, mechanisms of how LGI1 mutations cause epilepsy remain unclear. We have used a mouse chromosome engineering strategy to create a null mutation for the gene ortholog encoding LGI1. The Lgi1 null mutant mice show no gross overall developmental abnormalities from routine histopathological analysis. After 12-18 days of age, the homozygous mutant mice all exhibit myoclonic seizures accompanied by rapid jumping and running and die shortly thereafter. The heterozygous mutant mice do not develop seizures. Electrophysiological analysis demonstrates an enhanced excitatory synaptic transmission by increasing the release of the excitatory neurotransmitter glutamate, suggesting a basis for the seizure phenotype. This mouse model, therefore, provides novel insights into the mechanism behind ADPEAF and offers a new opportunity to study the mechanism behind the role of LGI1 in susceptibility to myoclonic seizures. PMID:20130004

  8. Enhanced Susceptibility to Pulmonary Infection with Burkholderia cepacia in Cftr?/? Mice

    PubMed Central

    Sajjan, Uma; Thanassoulis, George; Cherapanov, Vera; Lu, Annie; Sjolin, Carola; Steer, Brent; Wu, Yi Jun; Rotstein, Ori D.; Kent, Geraldine; McKerlie, Colin; Forstner, Janet; Downey, Gregory P.

    2001-01-01

    Progressive pulmonary infection is the dominant clinical feature of cystic fibrosis (CF), but the molecular basis for this susceptibility remains incompletely understood. To study this problem, we developed a model of chronic pneumonia by repeated instillation of a clinical isolate of Burkholderia cepacia (genomovar III, ET12 strain), an opportunistic gram-negative bacterium, from a case of CF into the lungs of Cftr m1unc?/? (Cftr?/?) and congenic Cftr+/+ controls. Nine days after the last instillation, the CF transmembrane regulator knockout mice showed persistence of viable bacteria with chronic severe bronchopneumonia while wild-type mice remained healthy. The histopathological changes in the lungs of the susceptible Cftr?/? mice were characterized by infiltration of a mixed inflammatory-cell population into the peribronchiolar and perivascular spaces, Clara cell hyperplasia, mucus hypersecretion in airways, and exudation into alveolar airspaces by a mixed population of macrophages and neutrophils. An increased proportion of neutrophils was observed in bronchoalveolar lavage fluid from the Cftr?/? mice, which, despite an increased bacterial load, demonstrated minimal evidence of activation. Alveolar macrophages from Cftr?/? mice also demonstrated suboptimal activation. These observations suggest that the pulmonary host defenses are compromised in lungs from animals with CF, as manifested by increased susceptibility to bacterial infection and lung injury. This murine model of chronic pneumonia thus reflects, in part, the situation in human patients and may help elucidate the mechanisms leading to defective host defense in CF. PMID:11447196

  9. Studies of mdx mice.

    PubMed

    Vajda, Z; Pedersen, M; Doczi, T; Sulyok, E; Nielsen, S

    2004-01-01

    Cerebral water accumulation-clinically denoted as brain edema-is a potentially life threatening complication of almost every intracranial neuropathological state. The molecular membrane water channel aquaporin-4 (AQP4) has been shown to be present at the blood-brain barrier (BBB) where it plays pivotal role in the transport of water between the tissue water compartments of the brain. Accumulating evidence indicates that the blockade of AQP4 function at the BBB would be a new therapeutic approach to the treatment and prevention of brain swelling. The cytoskeletal protein dystrophin has been shown to be involved in the maintenance of the polarized expression of AQP4 at the BBB. In order to further elucidate the mechanisms responsible for the highly polarized AQP4 expression, we studied brain tissue water accumulation during induction of brain edema in dystrophin-null transgenic mice (mdx-bgeo) and control mice. Immunofluorescence and immunoelectron microscopic analyses of dystrophin-null brains revealed a dramatic reduction of AQP4 in astroglial end-feet surrounding capillaries (BBB) and at the glia limitans (cerebrospinal fluid-brain interface). The AQP4 protein is mislocalized, because immunoblotting showed that the total AQP4 protein abundance was unaltered. Brain edema was induced by i.p. injection of distilled water and 8-deamino-arginine vasopressin. Changes in cerebral water compartments were assessed by diffusion-weighted MRI (DWI) with determination of the apparent diffusion coefficient (ADC). In dystrophin-null mice and control mice, ADC gradually decreased by 5-6% from baseline levels during the first 35 min, indicating the initial phase of intracellular water accumulation is similar in the two groups. At this point, the control mice sustained an abrupt, rapid decline in ADC to 58%+/-2.2% of the baseline at 52.5 min, and all of the animals were dead by 56 min. After a consistent delay, the dystrophin-null mice sustained a similar decline in ADC to 55%+/-3.4% at 66.5 min, when all of the mice were dead. These results demonstrate that dystrophin is necessary for polarized distribution of AQP4 protein in brain where facilitated movements of water occur across the BBB and cerebrospinal fluid-brain interface. Moreover, these results predict that interference with the subcellular localization of AQP4 may have therapeutic potential for delaying the onset of impending brain edema. PMID:15561414

  10. Olfactory discrimination largely persists in mice with defects in odorant receptor expression and axon guidance

    PubMed Central

    2012-01-01

    Background The defining feature of the main olfactory system in mice is that each olfactory sensory neuron expresses only one of more than a thousand different odorant receptor genes. Axons expressing the same odorant receptor converge onto a small number of targets in the olfactory bulb such that each glomerulus is made up of axon terminals expressing just one odorant receptor. It is thought that this precision in axon targeting is required to maintain highly refined odor discrimination. We previously showed that ?3GnT2?/? mice have severe developmental and axon guidance defects. The phenotype of these mice is similar to adenylyl cyclase 3 (AC3) knockout mice largely due to the significant down-regulation of AC3 activity in ?3GnT2?/? neurons. Results Microarray analysis reveals that nearly one quarter of all odorant receptor genes are down regulated in ?3GnT2?/? mice compared to controls. Analysis of OR expression by quantitative PCR and in situ hybridization demonstrates that the number of neurons expressing some odorant receptors, such as mOR256-17, is increased by nearly 60% whereas for others such as mOR28 the number of neurons is decreased by more than 75% in ?3GnT2?/? olfactory epithelia. Analysis of axon trajectories confirms that many axons track to inappropriate targets in ?3GnT2?/? mice, and some glomeruli are populated by axons expressing more than one odorant receptor. Results show that mutant mice perform nearly as well as control mice in an odor discrimination task. In addition, in situ hybridization studies indicate that the expression of several activity dependent genes is unaffected in ?3GnT2?/? olfactory neurons. Conclusions Results presented here show that many odorant receptors are under-expressed in ?3GnT2?/? mice and further demonstrate that additional axon subsets grow into inappropriate targets or minimally innervate glomeruli in the olfactory bulb. Odor evoked gene expression is unchanged and ?3GnT2?/? mice exhibit a relatively small deficit in their ability to discriminate divergent odors. Results suggest that despite the fact that ?3GnT2?/? mice have decreased AC3 activity, decreased expression of many ORs, and display many axon growth and guidance errors, odor-evoked activity in cilia of mutant olfactory neurons remains largely intact. PMID:22559903

  11. Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

    PubMed

    Lauer, Peter; Metzner, Hubert J; Zettlmeissl, Gerd; Li, Meng; Smith, Austin G; Lathe, Richard; Dickneite, Gerhard

    2002-12-01

    Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies. PMID:12529747

  12. The MICE Run Control System

    NASA Astrophysics Data System (ADS)

    Hanlet, Pierrick; Mice Collaboration

    2014-06-01

    The Muon Ionization Cooling Experiment (MICE) is a demonstration experiment to prove the feasibility of cooling a beam of muons for use in a Neutrino Factory and/or Muon Collider. The MICE cooling channel is a section of a modified Study II cooling channel which will provide a 10% reduction in beam emittance. In order to ensure a reliable measurement, MICE will measure the beam emittance before and after the cooling channel at the level of 1%, or a relative measurement of 0.001. This renders MICE a precision experiment which requires strict controls and monitoring of all experimental parameters in order to control systematic errors. The MICE Controls and Monitoring system is based on EPICS and integrates with the DAQ, Data monitoring systems, and a configuration database. The new MICE Run Control has been developed to ensure proper sequencing of equipment and use of system resources to protect data quality. A description of this system, its implementation, and performance during recent muon beam data collection will be discussed.

  13. Blind Mice

    NSDL National Science Digital Library

    This is a lesson about solar system exploration. Learners will understand that combining information gathered by a variety of robots gives us a more comprehensive understanding of our solar system. Learners will explore a planet made up of a combination of materials while simulating the perspective of different missions: pre-launch reconnaissance, fly-by, orbit, and landing. Learners will record and share their observations. Requires the book "Seven Blind Mice" by Ed Young. This is lesson 8 of 16 in the MarsBots learning module. This lesson is adapted from "Strange New Planet," an activity in the "Mars Activity Book."

  14. Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice.

    PubMed

    Hafler, Brian P; Klein, Zoe A; Jimmy Zhou, Z; Strittmatter, Stephen M

    2014-11-01

    Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn(-/-) mice develop degenerative pathology similar to features of human CLN11. PMID:25234724

  15. Coexistence of white-footed mice and deer mice may be mediated by fluctuating environmental conditions

    Microsoft Academic Search

    Jerry O. Wolff

    1996-01-01

    White-footed mice, Peromyscus leucopus noveboracensis, and deer mice, P. maniculatus nubiterrae, occur sympatically throughout much of the Appalachian Mountains of the eastern United States. Previous studies have shown that these two species are behaviorally and ecologically similar and do not partition food or microhabitat. In this paper I use a 14-year data set to demonstrate that the two species have

  16. Weighting Features

    Microsoft Academic Search

    Dietrich Wettschereck I; David W. Aha

    1995-01-01

    . Many case-based reasoning algorithms retrieve cases using aderivative of the k-nearest neighbor (k-NN) classifier, whose similarityfunction is sensitive to irrelevant, interacting, and noisy features. Manyproposed methods for reducing this sensitivity parameterize k-NN's similarityfunction with feature weights. We focus on methods that automaticallyassign weight settings using little or no domain-specific knowledge.Our goal is to predict the relative capabilities of these

  17. Evaluation of Renal Hypoxia in Diabetic Mice by BOLD MRI

    PubMed Central

    Prasad, Pottumarthi; Li, Lu-Ping; Halter, Sarah; Cabray, JoAnn; Ye, Minghao; Batlle, Daniel

    2015-01-01

    Objective Renal hypoxia has been proposed to be a pathophysiologic feature of diabetic kidney disease but it has been difficult to demonstrate in vivo, particularly in mouse models of diabetes. The objective of this work was to examine the sensitivity of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) to assess renal oxygenation in vivo in a mouse model of diabetic kidney disease, the db/db mice. Research Design and Methods Kidney BOLD MRI studies were performed on a 3.0 T scanner using multiple gradient echo sequence with a custom-designed surface coil to acquire T2*-weighted images. Studies were performed in 10-week-old db/db mice (n = 7) and db/m controls (n = 6). Results R2* is a measure of the tissue deoxyhemoglobin concentration and higher values of R2* are associated with hypoxia. The db/db mice had higher medullary (43.1 ± 5.1 s?1 vs. 32.3 ± 3.7 s?1, P = 0.001) and cortical R2* (31.7 ± 3.1 s?1 vs. 27.1 ± 4.1 s?1, P = 0.04) values. Using pimonidazole staining as a marker of kidney hypoxia, in kidney sections from 10-week-old db/db mice neither cortex nor medulla had significant differences as compared with 10-week-old db/m mice (cortex: db/db 2.14 ± 0.05 vs. db/m 2.02 ± 0.28, medulla: db/db 2.81 ± 0.08 vs. db/m 2.6 ± 0.08). The db/db mice demonstrated further increased cortical and medullary hypoxia when scanned again at 15 weeks of age. Conclusions The report shows that renal BOLD MRI is a sensitive method for the in vivo evaluation of renal hypoxia in a mouse model of diabetic kidney disease where progressive renal hypoxia can be documented over time. BOLD MRI may be useful to monitor therapeutic interventions that may improve tissue hypoxia in the diabetic kidney. PMID:20829708

  18. Smoking p66Shc Knocked Out Mice Develop Respiratory Bronchiolitis with Fibrosis but Not Emphysema

    PubMed Central

    Cavarra, Eleonora; Fineschi, Silvia; Bartalesi, Barbara; Lungarella, Giuseppe; Lucattelli, Monica

    2015-01-01

    The adaptor protein p66Shc regulates intracellular oxidant levels through the modulation of a forkhead-related transcription factor (FOXO3a). The genetic ablation of p66Shc (p66Shc–/–) renders mice resistant to oxidative stress and p53-dependent apoptosis. We investigated whether p66Shc ablation in mice modifies lung cellular and molecular responses to cigarette smoke (CS) exposure. No differences between wild type (WT) and p66Shc–/– mice were observed in terms of inflammation and oxidant burden after acute CS exposure; however,p66Shc ablation modifies specific features of chronic inflammation induced by repeated exposure to CS. Unlike WT mice, p66Shc–/– mice did not develop emphysema, showing protection toward oxidative damage to DNA and apoptosis as revealed by a trivial 8-hydroxyguanosine staining and faint TUNEL and caspase-3 positivity on alveolar epithelial cells. Unexpectedly, CS exposure in p66Shc–/– mice resulted in respiratory bronchiolitis with fibrosis in surrounded alveoli. Respiratory bronchiolitis was characterized by peribronchiolar infiltrates of lymphocytes and histiocytes, accumulation of ageing pigmented macrophages within and around bronchioles, and peribronchiolar fibrosis. The blockage of apoptosis interferes with the macrophage “clearance” from alveolar spaces, favouring the accumulation of aging macrophages into alveoli and the progressive accumulation of iron pigment in long-lived senescent cells. The presence of areas of interstitial and alveolar fibrosis in peripheral parenchyma often accompanied the bronchiolar changes. Macrophages from smoking p66Shc–/– mice elaborate M2 cytokines (i.e., IL-4 and IL-13) and enzymes (i.e., chitinase and arginase I), which can promote TGF-beta expression, collagen deposition, and fibrosis in the surrounding areas. We demonstrate here that resistance to oxidative stress and p53-dependent apoptosis can modify tissue responses to CS caused by chronic inflammation without influencing early inflammatory response to CS exposure. PMID:25790295

  19. Elevated plus maze for mice.

    PubMed

    Komada, Munekazu; Takao, Keizo; Miyakawa, Tsuyoshi

    2008-01-01

    Although the mouse genome is now completely sequenced, the functions of most of the genes expressed in the brain are not known. The influence of a given gene on a specific behavior can be determined by behavioral analysis of mutant mice. If a target gene is expressed in the brain, behavioral phenotype of the mutant mice could elucidate the genetic mechanism of normal behaviors. The elevated plus maze test is one of the most widely used tests for measuring anxiety-like behavior. The test is based on the natural aversion of mice for open and elevated areas, as well as on their natural spontaneous exploratory behavior in novel environments. The apparatus consists of open arms and closed arms, crossed in the middle perpendicularly to each other, and a center area. Mice are given access to all of the arms and are allowed to move freely between them. The number of entries into the open arms and the time spent in the open arms are used as indices of open space-induced anxiety in mice. Unfortunately, the procedural differences that exist between laboratories make it difficult to duplicate and compare results among laboratories. Here, we present a detailed movie demonstrating our protocol for the elevated plus maze test. In our laboratory, we have assessed more than 90 strains of mutant mice using the protocol shown in the movie. These data will be disclosed as a part of a public database that we are now constructing. Visualization of the protocol will promote better understanding of the details of the entire experimental procedure, allowing for standardization of the protocols used in different laboratories and comparisons of the behavioral phenotypes of various strains of mutant mice assessed using this test. PMID:19229173

  20. Muscle-specific expression of LARGE restores neuromuscular transmission deficits in dystrophic LARGEmyd mice

    PubMed Central

    Gumerson, Jessica D.; Davis, Carol S.; Kabaeva, Zhyldyz T.; Hayes, John M.; Brooks, Susan V.; Michele, Daniel E.

    2013-01-01

    Mutations in several glycosyltransferases underlie a group of muscular dystrophies known as glycosylation-deficient muscular dystrophy. A common feature of these diseases is loss of glycosylation and consequent dystroglycan function that is correlated with severe pathology in muscle, brain and other tissues. Although glycosylation of dystroglycan is essential for function in skeletal muscle, whether glycosylation-dependent function of dystroglycan is sufficient to explain all complex pathological features associated with these diseases is less clear. Dystroglycan glycosylation is defective in LARGEmyd (myd) mice as a result of a mutation in like-acetylglucosaminyltransferase (LARGE), a glycosyltransferase known to cause muscle disease in humans. We generated animals with restored dystroglycan function exclusively in skeletal muscle by crossing myd animals to a recently created transgenic line that expresses LARGE selectively in differentiated muscle. Transgenic myd mice were indistinguishable from wild-type littermates and demonstrated an amelioration of muscle disease as evidenced by an absence of muscle pathology, restored contractile function and a reduction in serum creatine kinase activity. Moreover, although deficits in nerve conduction and neuromuscular transmission were observed in myd animals, these deficits were fully rescued by muscle-specific expression of LARGE, which resulted in restored structure of the neuromuscular junction (NMJ). These data demonstrate that, in addition to muscle degeneration and dystrophy, impaired neuromuscular transmission contributes to muscle weakness in dystrophic myd mice and that the noted defects are primarily due to the effects of LARGE and glycosylated dystroglycan in stabilizing the endplate of the NMJ. PMID:23222475

  1. Web Features

    NSDL National Science Digital Library

    Web Features, presented by the Economic Policy Institute (EPI), is a collection of online resources for consumers about public opinion data. An economic snapshot, updated weekly, provides graphs and charts to highlight an economic issue, and this site also includes a selection of opinions from the EPI staff and their analysis of current economic data written in layperson's terms.

  2. Restoration of immune competence in tolerant mice by parabiosis to normal mice.

    PubMed

    Zolla, S; Naor, D

    1974-11-01

    These studies demonstrate that mice tolerant to human gamma globulin (HGG) regain their ability to make antibody to HGG after parabiosis to normal mice. This can be demonstrated by enumeration of PFC in the spleens of both the normal and tolerant partners. Hemagglutinin titers of normal-tolerant parabionts, however, are exceptionally low; serum antibody appears to be neutralized by circulating HGG present originally in the serum of the tolerant partner. These data support the hypothesis that tolerance to HGG in mice is a "defective" state due to the absence of cells capable of responding to this antigen. PMID:4138703

  3. RESTORATION OF IMMUNE COMPETENCE IN TOLERANT MICE BY PARABIOSIS TO NORMAL MICE

    PubMed Central

    Zolla, Susan; Naor, David

    1974-01-01

    These studies demonstrate that mice tolerant to human gamma globulin (HGG) regain their ability to make antibody to HGG after parabiosis to normal mice. This can be demonstrated by enumeration of PFC in the spleens of both the normal and tolerant partners. Hemagglutinin titers of normal-tolerant parabionts, however, are exceptionally low; serum antibody appears to be neutralized by circulating HGG present originally in the serum of the tolerant partner. These data support the hypothesis that tolerance to HGG in mice is a "defective" state due to the absence of cells capable of responding to this antigen. PMID:4138703

  4. Laithwaite's Heavy Spinning Disk Demonstration

    NASA Astrophysics Data System (ADS)

    Cross, Rod

    2014-09-01

    In 1974, Professor Eric Laithwaite demonstrated an unusually heavy gyroscope at a Royal Institution lecture in London. The demonstration was televised and can be viewed on YouTube.1 A recent version of the same experiment, together with partial explanations, attracted two million YouTube views in the first few months.2 In both cases, the gyroscope consisted of a 40-lb (18-kg) spinning disk on the end of a 3-ft (0.91-m) long axle. The most remarkable feature of the demonstration was that Laithwaite was able to lift the disk over his head with one hand, holding onto the far end of the axle. The impression was given that the 40-lb disk was almost weightless, or "as light as a feather" according to Laithwaite.

  5. Anticonvulsant Effects of ?-Hydroxybutyrate in Mice

    PubMed Central

    Yum, Mi-Sun; Ko, Tae-Sung; Kim, Dong Wook

    2012-01-01

    Background and Purpose: The ketogenic diet was formulated to mimic the biochemical changes seen upon fasting, specifically the formation of ketone bodies. Recent research data suggest that the anticonvulsant efficacy of the KD may be due in part to the direct actions of ketone bodies. This study was designed to investigate the anticonvulsant effects of ?-hydroxybutyrate (BHB) on pilocarpine-induced seizures in mature mice. Methods: Eighty-two male ICR mice at postnatal day 49 were used. All mice were pretreated with scopolamine methylbromide prior to pilocarpine injection. Experimental mice (n=42) were injected intraperitoneally with BHB (20 mmol/kg) 15 min prior to pilocarpine administration, while control animals (n=40) with normal saline. Pilocarpine (300 mg/kg) was administered intraperitoneally and mice were monitored for 2 h after pilocarpine injection. Results: All mice developed typical seizure behaviors. The mean (±SD) latency to the onset of seizures was significantly prolonged in the BHB-treated mice compared with controls (4.83±1.95 min vs. 3.67±1.90 min, p<0.01). Conclusions: This study demonstrates that treatment with BHB prolongs the latency to the onset of seizures induced by pilocarpine in mature mice and suggests that BHB, one of the ketone bodies, may have direct anticonvulsant effects. PMID:24649459

  6. Cutaneous ultrastructural features of the flaky skin (fsn) mouse mutation

    Microsoft Academic Search

    K Morita; M E Hogan; L B Nanney; L E King; M Manabe; T T Sun; J P Sundberg

    1995-01-01

    An autosomal recessive genetic disease with clinical and histopathological skin features resembling human psoriasis vulgaris occurs naturally in flaky skin mice (fsn\\/fsn). Affected mice are normal at birth, except for a hypochromic anemia. Subsequently, they develop hyperkeratotic plaques and acanthosis with elongation of rete ridges. Scanning electron microscopic examination revealed a greatly thickened epidermis, a sparsity of hairs and scale

  7. Favorite Demonstration: An Inexpensive Resonance Demonstration

    NSDL National Science Digital Library

    Phillip Dukes

    2005-01-01

    Resonance is commonplace and easy to recognize when it occurs. Yet it is also one of the most impressive and often unexpected phenomenon in all of physics. This article describes a visually appealing resonance demonstrator that uses readily available and inexpensive parts.

  8. ORION II bus demonstration. Demonstration report (Final)

    Microsoft Academic Search

    Shanley

    1989-01-01

    The Central New York Regional Transportation Authority conducted an 18-month demonstration to determine how the ORION II bus operates in actual service. The ORION II vehicle is a small low floor, accessible heavy duty, diesel-powered transit bus designed to meet the needs of the elderly and handicapped. It has the capacity to seat 26 passengers with 4 wheelchair lockdowns. Side

  9. Icariin, a phosphodiesterase-5 inhibitor, improves learning and memory in APP/PS1 transgenic mice by stimulation of NO/cGMP signalling.

    PubMed

    Jin, Feng; Gong, Qi-Hai; Xu, Ya-Sha; Wang, Li-Na; Jin, Hai; Li, Fei; Li, Li-Sheng; Ma, Yue-Ming; Shi, Jing-Shan

    2014-06-01

    Phosphodiesterase-5 (PDE5) inhibitors are predominantly used in the treatment of erectile dysfunction, and have been recently shown to have a potential therapeutic effect for the treatment of Alzheimer's disease (AD) through stimulation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling by elevating cGMP, which is a secondary messenger involved in processes of neuroplasticity. In the present study, the effects of a PDE5 inhibitor, icarrin (ICA), on learning and memory as well as the pathological features in APP/PS1 transgenic AD mice were investigated. Ten-month-old APP/PS1 transgenic mice overexpressing human amyloid precursor protein (APP695swe) and presenilin 1 (PS1-dE9) were given ICA (30 and 60 mg/kg) or sildenafil (SIL) (2 mg/kg), age-matched wild-type (WT) mice were given ICA (60 mg/kg), and APP/PS1 and WT control groups were given an isovolumic vehicle orally twice a day for four months. Results demonstrated that ICA treatments significantly improved learning and memory of APP/PS1 transgenic mice in Y-maze tasks. The amyloid precursor protein (APP), amyloid-beta (A?1-40/42) and PDE5 mRNA and/or protein levels were increased in the hippocampus and cortex of APP/PS1 mice, and ICA treatments decreased these physiopathological changes. Furthermore, ICA-treated mice showed an increased expression of three nitric oxide synthase (NOS) isoforms at both mRNA and protein levels, together with increased NO and cGMP levels in the hippocampus and cortex of mice. These findings demonstrate that ICA improves learning and memory functions in APP/PS1 transgenic mice possibly through the stimulation of NO/cGMP signalling and co-ordinated induction of NOS isoforms. PMID:24513083

  10. Molecular, Physiological, and Motor Performance Defects in DMSXL Mice Carrying >1,000 CTG Repeats from the Human DM1 Locus

    PubMed Central

    Huguet, Aline; Medja, Fadia; Nicole, Annie; Vignaud, Alban; Guiraud-Dogan, Céline; Ferry, Arnaud; Decostre, Valérie; Hogrel, Jean-Yves; Metzger, Friedrich; Hoeflich, Andreas; Baraibar, Martin; Gomes-Pereira, Mário; Puymirat, Jack; Bassez, Guillaume; Furling, Denis; Munnich, Arnold; Gourdon, Geneviève

    2012-01-01

    Myotonic dystrophy type 1 (DM1) is caused by an unstable CTG repeat expansion in the 3?UTR of the DM protein kinase (DMPK) gene. DMPK transcripts carrying CUG expansions form nuclear foci and affect splicing regulation of various RNA transcripts. Furthermore, bidirectional transcription over the DMPK gene and non-conventional RNA translation of repeated transcripts have been described in DM1. It is clear now that this disease may involve multiple pathogenic pathways including changes in gene expression, RNA stability and splicing regulation, protein translation, and micro–RNA metabolism. We previously generated transgenic mice with 45-kb of the DM1 locus and >300 CTG repeats (DM300 mice). After successive breeding and a high level of CTG repeat instability, we obtained transgenic mice carrying >1,000 CTG (DMSXL mice). Here we described for the first time the expression pattern of the DMPK sense transcripts in DMSXL and human tissues. Interestingly, we also demonstrate that DMPK antisense transcripts are expressed in various DMSXL and human tissues, and that both sense and antisense transcripts accumulate in independent nuclear foci that do not co-localize together. Molecular features of DM1-associated RNA toxicity in DMSXL mice (such as foci accumulation and mild missplicing), were associated with high mortality, growth retardation, and muscle defects (abnormal histopathology, reduced muscle strength, and lower motor performances). We have found that lower levels of IGFBP-3 may contribute to DMSXL growth retardation, while increased proteasome activity may affect muscle function. These data demonstrate that the human DM1 locus carrying very large expansions induced a variety of molecular and physiological defects in transgenic mice, reflecting DM1 to a certain extent. As a result, DMSXL mice provide an animal tool to decipher various aspects of the disease mechanisms. In addition, these mice can be used to test the preclinical impact of systemic therapeutic strategies on molecular and physiological phenotypes. PMID:23209425

  11. Experimental Demonstrations in Teaching Chemical Reactions.

    ERIC Educational Resources Information Center

    Hugerat, Muhamad; Basheer, Sobhi

    2001-01-01

    Presents demonstrations of chemical reactions by employing different features of various compounds that can be altered after a chemical change occurs. Experimental activities include para- and dia-magnetism in chemical reactions, aluminum reaction with base, reaction of acid with carbonates, use of electrochemical cells for demonstrating chemical…

  12. Controlling Rats and Mice 

    E-print Network

    Texas Wildlife Services

    2007-03-13

    House rats and mice eat and contaminate human and animal food, and they damage and destroy property. This leaflet explains how to identify rats and mice by their droppings, runways, food crumbs and noises. Various control methods are discussed....

  13. Infant CPR Video Demonstration

    MedlinePLUS

    Infant CPR Video Demonstration Video demonstration of CPR instruction for infants. RETURN TO MAIN PAGE These Videos Are For Educational Use Only And Are Not Authorized for Commercial Use. © 1998 - 2011 ...

  14. Cardio Lab Powerpoint Demonstration

    NSDL National Science Digital Library

    Ms. Jeannette K Hafey (Springfield College Biology/Chemistry)

    2010-05-24

    Powerpoint presentation utilizing a Functional Heart Model to demonstrate the relationships among stroke volume, heart rate, and cardiac output. Demonstration also includes blood vessel radius and flow-pressure relationships. Oxygen consumption and VO2 MAX is discussed.

  15. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1989-01-01

    Described are demonstrations of the optical activity of two sugar solutions, and the effects of various substituents on acid strength using an overhead projector. Materials and procedures for each demonstration are discussed. (CW)

  16. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1987-01-01

    Describes several chemistry demonstrations that use an overhead projector. Some of the demonstrations deal with electrochemistry, and another deals with the reactions of nonvolatile immiscible liquid in water. (TW)

  17. LIMB Demonstration Project Extension and Coolside Demonstration

    SciTech Connect

    Goots, T.R.; DePero, M.J.; Nolan, P.S.

    1992-11-10

    This report presents results from the limestone Injection Multistage Burner (LIMB) Demonstration Project Extension. LIMB is a furnace sorbent injection technology designed for the reduction of sulfur dioxide (SO[sub 2]) and nitrogen oxides (NO[sub x]) emissions from coal-fired utility boilers. The testing was conducted on the 105 Mwe, coal-fired, Unit 4 boiler at Ohio Edison's Edgewater Station in Lorain, Ohio. In addition to the LIMB Extension activities, the overall project included demonstration of the Coolside process for S0[sub 2] removal for which a separate report has been issued. The primary purpose of the DOE LIMB Extension testing, was to demonstrate the generic applicability of LIMB technology. The program sought to characterize the S0[sub 2] emissions that result when various calcium-based sorbents are injected into the furnace, while burning coals having sulfur content ranging from 1.6 to 3.8 weight percent. The four sorbents used included calcitic limestone, dolomitic hydrated lime, calcitic hydrated lime, and calcitic hydrated lime with a small amount of added calcium lignosulfonate. The results include those obtained for the various coal/sorbent combinations and the effects of the LIMB process on boiler and plant operations.

  18. General features

    SciTech Connect

    Wallace, R.E.

    1990-01-01

    The San Andreas fault system, a complex of faults that display predominantly large-scale strike slip, is part of an even more complex system of faults, isolated segments of the East Pacific Rise, and scraps of plates lying east of the East Pacific Rise that collectively separate the North American plate from the Pacific plate. This chapter briefly describes the San Andreas fault system, its setting along the Pacific Ocean margin of North America, its extent, and the patterns of faulting. Only selected characteristics are described, and many features are left for depictions on maps and figures.

  19. Altered lipid metabolism in Hfe-knockout mice promotes severe NAFLD and early fibrosis.

    PubMed

    Tan, Terrence C H; Crawford, Darrell H G; Jaskowski, Lesley A; Murphy, Therese M; Heritage, Mandy L; Subramaniam, V Nathan; Clouston, Andrew D; Anderson, Gregory J; Fletcher, Linda M

    2011-11-01

    The HFE protein plays a crucial role in the control of cellular iron homeostasis. Steatosis is commonly observed in HFE-related iron-overload disorders, and current evidence suggests a causal link between iron and steatosis. Here, we investigated the potential contribution of HFE mutations to hepatic lipid metabolism and its role in the pathogenesis of nonalcoholic fatty liver disease. Wild-type (WT) and Hfe knockout mice (Hfe(-/-)) were fed either standard chow, a monounsaturated low fat, or a high-fat, high-carbohydrate diet (HFD) and assessed for liver injury, body iron status, and markers of lipid metabolism. Despite hepatic iron concentrations and body weights similar to WT controls, Hfe(-/-) mice fed the HFD developed severe hypoxia-related steatohepatitis, Tnf-? activation, and mitochondrial respiratory complex and antioxidant dysfunction with early fibrogenesis. These features were associated with an upregulation in the expression of genes involved in intracellular lipid synthesis and trafficking, while transcripts for mitochondrial fatty acid ?-oxidation and adiponectin signaling-related genes were significantly attenuated. In contrast, HFD-fed WT mice developed bland steatosis only, with no inflammation or fibrosis and no upregulation of lipogenesis-related genes. A HFD led to reduced hepatic iron in Hfe(-/-) mice compared with chow-fed mice, despite higher serum iron, decreased hepcidin expression, and increased duodenal ferroportin mRNA. In conclusion, our results demonstrate that Hfe(-/-) mice show defective hepatic-intestinal iron and lipid signaling, which predispose them toward diet-induced hepatic lipotoxicity, accompanied by an accelerated progression of injury to fibrosis. PMID:21817060

  20. Edible Astronomy Demonstrations

    Microsoft Academic Search

    Donald A. Lubowich

    2007-01-01

    Astronomy demonstrations with edible ingredients are an effective way to increase student interest and knowledge of astronomical concepts. This approach has been successful with all age groups from elementary school through college students - and the students remember these demonstrations after they are presented. In this poster I describe edible demonstrations I have created to simulate the expansion of the

  1. Classroom Demonstrations: Individual Differences.

    ERIC Educational Resources Information Center

    Singer, Sandra M.

    These demonstrations stress individual differences, a concept becoming increasingly important in psychological research. Intended for use in undergraduate psychology courses, four demonstrations that illustrate common examples of human variation are described. The demonstrations deal with the following individual differences: taste blindness,…

  2. Stress inoculation modeled in mice

    PubMed Central

    Brockhurst, J; Cheleuitte-Nieves, C; Buckmaster, C L; Schatzberg, A F; Lyons, D M

    2015-01-01

    Stress inoculation entails intermittent exposure to mildly stressful situations that present opportunities to learn, practice and improve coping in the context of exposure psychotherapies and resiliency training. Here we investigate behavioral and hormonal aspects of stress inoculation modeled in mice. Mice randomized to stress inoculation or a control treatment condition were assessed for corticosterone stress hormone responses and behavior during open-field, object-exploration and tail-suspension tests. Stress inoculation training sessions that acutely increased plasma levels of corticosterone diminished subsequent immobility as a measure of behavioral despair on tail-suspension tests. Stress inoculation also decreased subsequent freezing in the open field despite comparable levels of thigmotaxis in mice from both treatment conditions. Stress inoculation subsequently decreased novel-object exploration latencies and reduced corticosterone responses to repeated restraint. These results demonstrate that stress inoculation acutely stimulates glucocorticoid signaling and then enhances subsequent indications of active coping behavior in mice. Unlike mouse models that screen for the absence of vulnerability to stress or presence of traits that occur in resilient individuals, stress inoculation training reflects an experience-dependent learning-like process that resembles interventions designed to build resilience in humans. Mouse models of stress inoculation may provide novel insights for new preventive strategies or therapeutic treatments of human psychiatric disorders that are triggered and exacerbated by stressful life events. PMID:25826112

  3. Light/dark transition test for mice.

    PubMed

    Takao, Keizo; Miyakawa, Tsuyoshi

    2006-12-01

    Although all of the mouse genome sequences have been determined, we do not yet know the functions of most of these genes. Gene-targeting techniques, however, can be used to delete or manipulate a specific gene in mice. The influence of a given gene on a specific behavior can then be determined by conducting behavioral analyses of the mutant mice. As a test for behavioral phenotyping of mutant mice, the light/dark transition test is one of the most widely used tests to measure anxiety-like behavior in mice. The test is based on the natural aversion of mice to brightly illuminated areas and on their spontaneous exploratory behavior in novel environments. The test is sensitive to anxiolytic drug treatment. The apparatus consists of a dark chamber and a brightly illuminated chamber. Mice are allowed to move freely between the two chambers. The number of entries into the bright chamber and the duration of time spent there are indices of bright-space anxiety in mice. To obtain phenotyping results of a strain of mutant mice that can be readily reproduced and compared with those of other mutants, the behavioral test methods should be as identical as possible between laboratories. The procedural differences that exist between laboratories, however, make it difficult to replicate or compare the results among laboratories. Here, we present our protocol for the light/dark transition test as a movie so that the details of the protocol can be demonstrated. In our laboratory, we have assessed more than 60 strains of mutant mice using the protocol shown in the movie. Those data will be disclosed as a part of a public database that we are now constructing. Visualization of the protocol will facilitate understanding of the details of the entire experimental procedure, allowing for standardization of the protocols used across laboratories and comparisons of the behavioral phenotypes of various strains of mutant mice assessed using this test. PMID:18704188

  4. Estradiol-Treated Female Mice as Surrogate Hosts for Neisseria gonorrhoeae Genital Tract Infections

    PubMed Central

    Jerse, Ann E.; Wu, Hong; Packiam, Mathanraj; Vonck, Rachel A.; Begum, Afrin A.; Garvin, Lotisha E.

    2011-01-01

    Historically, animal modeling of gonorrhea has been hampered by the exclusive adaptation of Neisseria gonorrhoeae to humans. Genital tract infection can be established in female mice that are treated with 17?-estradiol, however, and many features of experimental murine infection mimic human infection. Here we review the colonization kinetics and host response to experimental murine gonococcal infection, including mouse strain differences and evidence that IL-17 responses, toll-like receptor 4, and T regulatory cells play a role in infection. We also discuss the strengths and limitations of the mouse system and the potential of transgenic mice to circumvent host restrictions. Additionally, we review studies with genetically defined mutants that demonstrated a role for sialyltransferase and the MtrC–MtrD–MtrE active efflux pump in evading innate defenses in vivo, but not for factors hypothesized to protect against the phagocytic respiratory burst and H2O2-producing lactobacilli. Studies using estradiol-treated mice have also revealed the existence of non-host-restricted iron sources in the female genital tract and the influence of hormonal factors on colonization kinetics and selection for opacity (Opa) protein expression. Recent work by others with estradiol-treated mice that are transgenic for human carcinoembryonic adhesion molecules (CEACAMs) supports a role for Opa proteins in enhancing cellular attachment and thus reduced shedding of N. gonorrhoeae. Finally we discuss the use of the mouse model in product testing and a recently developed gonorrhea chlamydia coinfection model. PMID:21747807

  5. Edible Astronomy Demonstrations

    NASA Astrophysics Data System (ADS)

    Lubowich, D. A.

    2006-08-01

    By using astronomy demonstrations with edible ingredients, I have been able to increase student interest and knowledge of astronomical concepts. This approach has been successful with all age groups from elementary school through college students. I will present some of the edible demonstrations I have created including using popcorn to simulate radioactivity; using chocolate, nuts, and marshmallows to illustrate density and differentiation during the formation of the planets; and making big-bang brownies or chocolate chip-cookies to illustrate the expansion of the Universe. Sometimes the students eat the results of the astronomical demonstrations. These demonstrations are an effective teaching tool and the students remember these demonstrations after they are presented.

  6. Strategy Guideline: Demonstration Home

    SciTech Connect

    Savage, C.; Hunt, A.

    2012-12-01

    This guideline will provide a general overview of the different kinds of demonstration home projects, a basic understanding of the different roles and responsibilities involved in the successful completion of a demonstration home, and an introduction into some of the lessons learned from actual demonstration home projects. Also, this guideline will specifically look at the communication methods employed during demonstration home projects. And lastly, we will focus on how to best create a communication plan for including an energy efficient message in a demonstration home project and carry that message to successful completion.

  7. Data surety demonstrations

    SciTech Connect

    Draelos, T.; Harris, M.; Herrington, P.; Kromer, D.

    1998-08-01

    The use of data surety within the International Monitoring System (IMS) is designed to offer increased trust of acquired sensor data at a low cost. The demonstrations discussed in the paper illustrate the feasibility of hardware authentication for sensor data and commands in a retrofit environment and a new system and of the supporting key management system. The individual demonstrations which are summarized in the paper are: (1) demonstration of hardware authentication for communication authentication in a retrofit environment; (2)demonstration of hardware authentication in a new system; and (3) demonstration of key management for sensor data and command authentication.

  8. Otitis Media in Sperm-Associated Antigen 6 (Spag6)-Deficient Mice

    PubMed Central

    Li, Xiaofei; Xu, Lei; Li, Jianfeng; Li, Boqin; Bai, Xiaohui; Strauss, Jerome F.; Zhang, Zhibing; Wang, Haibo

    2014-01-01

    Mammalian SPAG6 protein is localized to the axoneme central apparatus, and it is required for normal flagella and cilia motility. Recent studies demonstrated that the protein also regulates ciliogenesis and cilia polarity in the epithelial cells of brain ventricles and trachea. Motile cilia are also present in the epithelial cells of the middle ear and Eustachian tubes, where the ciliary system participates in the movement of serous fluid and mucus in the middle ear. Cilia defects are associated with otitis media (OM), presumably due to an inability to efficiently transport fluid, mucus and particles including microorganisms. We investigated the potential role of SPAG6 in the middle ear and Eustachian tubes by studying mice with a targeted mutation in the Spag6 gene. SPAG6 is expressed in the ciliated cells of middle ear epithelial cells. The orientation of the ciliary basal feet was random in the middle ear epithelial cells of Spag6-deficient mice, and there was an associated disrupted localization of the planar cell polarity (PCP) protein, FZD6. These features are associated with disordered cilia orientation, confirmed by scanning electron microscopy, which leads to uncoordinated cilia beating. The Spag6 mutant mice were also prone to develop OM. However, there were no significant differences in bacterial populations, epithelial goblet cell density, mucin expression and Eustachian tube angle between the mutant and wild-type mice, suggesting that OM was due to accumulation of fluid and mucus secondary to the ciliary dysfunction. Our studies demonstrate a role for Spag6 in the pathogenesis of OM in mice, possibly through its role in the regulation of cilia/basal body polarity through the PCP-dependent mechanisms in the middle ear and Eustachian tubes. PMID:25393619

  9. IL-4 Knock Out Mice Display Anxiety-Like Behavior.

    PubMed

    Moon, Morgan L; Joesting, Jennifer J; Blevins, Neil A; Lawson, Marcus A; Gainey, Stephen J; Towers, Albert E; McNeil, Leslie K; Freund, Gregory G

    2015-07-01

    Inflammation is a recognized antecedent and coincident factor when examining the biology of anxiety. Little is known, however, about how reductions in endogenous anti-inflammatory mediators impact anxiety. Therefore, mood- cognition- and anxiety-associated/like behaviors were examined in IL-4 knock out (KO) mice and wild-type (WT) mice. In comparison to WT mice, IL-4 KO mice demonstrated decreased burrowing and increased social exploration. No differences were seen in forced swim or saccharine preference testing. IL-4 KO mice had similar performance to WT mice in the Morris water maze and during object location and novel object recognition. In the elevated zero-maze, IL-4 KO mice, in comparison to WT mice, demonstrated anxiety-like behavior. Anxiety-like behavior in IL-4 KO mice was not observed, however, during open-field testing. Taken together, these data indicate that IL-4 KO mice display state, but not trait, anxiety suggesting that reductions in endogenous anti-inflammatory bioactives can engender subtypes of anxiety. PMID:25772794

  10. Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis

    PubMed Central

    ALVAREZ, Nadine; INFANTE, Juan Francisco; BORRERO, Reinier; MATA, Dulce; PAYAN, JORGE BARRIOS-; HOSSAIN, Md. Murad; MOHD NOR, Norazmi; SARMIENTO, María Elena; HERNANDEZ-PANDO, Rogelio; ACOSTA, Armando

    2014-01-01

    Background: Humoral and cellular immune responses are associated with protection against extracellular and intracellular pathogens, respectively. In the present study, we evaluated the effect of receiving human secretory immunoglobulin A (hsIgA) on the histopathology of the lungs of mice challenged with virulent Mycobacterium tuberculosis. Methods: The hsIgA was purified from human colostrum and administered to Balb/c mice by the intranasal route prior to infection with M. tuberculosis or in a pre-incubated formulation with mycobacteria, with the principal aim to study its effect on qualitative pulmonary histopathology. Results: The intranasal administration of hsIgA and the pre-incubation of mycobacteria with this preparation was associated with the presence of organised granulomas with signs of immune activation and histological features related to efficient disease control. This effect was highly evident during the late stage of infection (60 days), as demonstrated by numerous organised granulomas with numerous activated macrophages in the lungs of treated mice. Conclusion: The administration of hsIgA to mice before intratracheal infection with M. tuberculosis or the pre-incubation of the bacteria with the antibody formulation induced the formation of well-organised granulomas and inflammatory lesions in lungs compared with non-treated animals which correlates with the protective effect already demonstrated by these antibody formulations. PMID:25246833

  11. NC State Physics Demonstrations

    NSDL National Science Digital Library

    The physics department at North Carolina State University has created this very fine list of online physics demonstration manuals that will be quite a boon to physics educators in high schools and colleges. Visitors can search 28 online demonstration manuals simultaneously or they can also choose to look over a demonstrations bibliography that contains over 7500 references. Those who just wish to browse around can scroll down the page to look within each manual separately. Also, visitors may also wish to check out the public lecture demonstration shows offered on the site, along with a collection of links to professional organizations, including The American Association of Physics Teachers.

  12. Diverging neural pathways assemble a behavioural state from separable features in anxiety.

    PubMed

    Kim, Sung-Yon; Adhikari, Avishek; Lee, Soo Yeun; Marshel, James H; Kim, Christina K; Mallory, Caitlin S; Lo, Maisie; Pak, Sally; Mattis, Joanna; Lim, Byung Kook; Malenka, Robert C; Warden, Melissa R; Neve, Rachael; Tye, Kay M; Deisseroth, Karl

    2013-04-11

    Behavioural states in mammals, such as the anxious state, are characterized by several features that are coordinately regulated by diverse nervous system outputs, ranging from behavioural choice patterns to changes in physiology (in anxiety, exemplified respectively by risk-avoidance and respiratory rate alterations). Here we investigate if and how defined neural projections arising from a single coordinating brain region in mice could mediate diverse features of anxiety. Integrating behavioural assays, in vivo and in vitro electrophysiology, respiratory physiology and optogenetics, we identify a surprising new role for the bed nucleus of the stria terminalis (BNST) in the coordinated modulation of diverse anxiety features. First, two BNST subregions were unexpectedly found to exert opposite effects on the anxious state: oval BNST activity promoted several independent anxious state features, whereas anterodorsal BNST-associated activity exerted anxiolytic influence for the same features. Notably, we found that three distinct anterodorsal BNST efferent projections-to the lateral hypothalamus, parabrachial nucleus and ventral tegmental area-each implemented an independent feature of anxiolysis: reduced risk-avoidance, reduced respiratory rate, and increased positive valence, respectively. Furthermore, selective inhibition of corresponding circuit elements in freely moving mice showed opposing behavioural effects compared with excitation, and in vivo recordings during free behaviour showed native spiking patterns in anterodorsal BNST neurons that differentiated safe and anxiogenic environments. These results demonstrate that distinct BNST subregions exert opposite effects in modulating anxiety, establish separable anxiolytic roles for different anterodorsal BNST projections, and illustrate circuit mechanisms underlying selection of features for the assembly of the anxious state. PMID:23515158

  13. Mathematical modeling of left ventricular dimensional changes in mice during aging

    PubMed Central

    2012-01-01

    Cardiac aging is characterized by diastolic dysfunction of the left ventricle (LV), which is due in part to increased LV wall stiffness. In the diastolic phase, myocytes are relaxed and extracellular matrix (ECM) is a critical determinant to the changes of LV wall stiffness. To evaluate the effects of ECM composition on cardiac aging, we developed a mathematical model to predict LV dimension and wall stiffness changes in aging mice by integrating mechanical laws and our experimental results. We measured LV dimension, wall thickness, LV mass, and collagen content for wild type (WT) C57/BL6J mice of ages ranging from 7.3 months to those of 34.0 months. The model was established using the thick wall theory and stretch-induced tissue growth to an isotropic and homogeneous elastic composite with mixed constituents. The initial conditions of the simulation were set based on the data from the young mice. Matlab simulations of this mathematical model demonstrated that the model captured the major features of LV remodeling with age and closely approximated experimental results. Specifically, the temporal progression of the LV interior and exterior dimensions demonstrated the same trend and order-of-magnitude change as our experimental results. In conclusion, we present here a validated mathematical model of cardiac aging that applies the thick-wall theory and stretch-induced tissue growth to LV remodeling with age. PMID:23281647

  14. Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate.

    PubMed

    Irie, Fumitoshi; Badie-Mahdavi, Hedieh; Yamaguchi, Yu

    2012-03-27

    Heparan sulfate regulates diverse cell-surface signaling events, and its roles in the development of the nervous system recently have been increasingly uncovered by studies using genetic models carrying mutations of genes encoding enzymes for its synthesis. On the other hand, the role of heparan sulfate in the physiological function of the adult brain has been poorly characterized, despite several pieces of evidence suggesting its role in the regulation of synaptic function. To address this issue, we eliminated heparan sulfate from postnatal neurons by conditionally inactivating Ext1, the gene encoding an enzyme essential for heparan sulfate synthesis. Resultant conditional mutant mice show no detectable morphological defects in the cytoarchitecture of the brain. Remarkably, these mutant mice recapitulate almost the full range of autistic symptoms, including impairments in social interaction, expression of stereotyped, repetitive behavior, and impairments in ultrasonic vocalization, as well as some associated features. Mapping of neuronal activation by c-Fos immunohistochemistry demonstrates that neuronal activation in response to social stimulation is attenuated in the amygdala in these mice. Electrophysiology in amygdala pyramidal neurons shows an attenuation of excitatory synaptic transmission, presumably because of the reduction in the level of synaptically localized AMPA-type glutamate receptors. Our results demonstrate that heparan sulfate is critical for normal functioning of glutamatergic synapses and that its deficiency mediates socio-communicative deficits and stereotypies characteristic for autism. PMID:22411800

  15. Ganges Features

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Context image for PIA03285 Ganges Features

    This image shows part of Ganges Chasma. Several landslides occur at the top of the image, while dunes and canyon floor deposits are visible at the bottom of the image.

    Image information: VIS instrument. Latitude -6.8N, Longitude 312.2E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  16. Token Ring Demonstration

    NSDL National Science Digital Library

    This applet demonstrates a Token Ring. Users may add or delete stations (or computers) from the ring. The applet allows the user to show data being circulated around the ring. Users may also select to demonstrate the cases when one of the stations is switched off, or monitoring. (UNC E-Learning Grant)

  17. A Greener Chemiluminescence Demonstration

    ERIC Educational Resources Information Center

    Jilani, Osman; Donahue, Trisha M.; Mitchell, Miguel O.

    2011-01-01

    Because they are dramatic and intriguing, chemiluminescence demonstrations have been used for decades to stimulate interest in chemistry. One of the most intense chemiluminescent reactions is the oxidation of diaryl oxalate diesters with hydrogen peroxide in the presence of a fluorescer. In typical lecture demonstrations, the commercially…

  18. Newton's Laws Demonstrations

    NSDL National Science Digital Library

    Don Rathjen

    2007-01-01

    In this collection of demonstrations, learners explore Newton's Laws of Motion. These seventeen quick activities investigate air resistance, acceleration, terminal velocity, inertia, action-reaction, and other key concepts related to forces and motion. These demonstrations can be coupled together or conducted individually.

  19. FDDI Ring Demonstration

    NSDL National Science Digital Library

    This applet demonstrates an FDDI ring. Users may add or delete stations (or computers) from the ring. The applet allows the user to show data being circulated around the ring. Users may also select to demonstrate the cases when the ring becomes broken or when one of the stations is switched off. (UNC E-Learning Grant)

  20. ?-Arrestin-1 Deficiency Protects Mice from Experimental Colitis

    PubMed Central

    Lee, Taehyung; Lee, Eunhee; Irwin, Regina; Lucas, Peter C.; McCabe, Laura R.; Parameswaran, Narayanan

    2014-01-01

    ?-Arrestins are intracellular scaffolding proteins that modulate specific cell signaling pathways. Recent studies, in both cell culture and in vivo models, have demonstrated an important role for ?-arrestin-1 in inflammation. However, the role of ?-arrestin-1 in the pathogenesis of inflammatory bowel disease (IBD) is not known. Our goal was to investigate the role of ?-arrestin-1 in IBD using mouse models of colitis. To this end, we subjected wild-type (WT) and ?-arrestin-1 knockout (?-arr-1?/?) mice to colitis induced by trinitrobenzenesulfonic acid or dextran sulfate sodium and examined the clinical signs, gross pathology, and histopathology of the colon, as well as inflammatory components. The ?-arr-1?/? mice displayed significantly attenuated colitis, compared with WT mice, in both models. Consistent with the phenotypic observations, histological examination of the colon revealed attenuated disease pathology in the ?-arr-1?/? mice. Our results further demonstrate that ?-arr-1?/? mice are deficient in IL-6 expression in the colon, but have higher expression of the anti-inflammatory IL-10 family of cytokines. Our results also demonstrate diminished ERK and NF?B pathways in the colons of ?-arr-1?/? mice, compared with WT mice. Taken together, our results demonstrate that decreased IL-6 production and enhanced IL-10 and IL-22 production in ?-arrestin-1–deficient mice likely lead to attenuated gut inflammation. PMID:23395087

  1. Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice.

    PubMed

    Kaul, D K; Hebbel, R P

    2000-08-01

    In sickle cell anemia, the initiation, progression, and resolution of a vasoocclusive episode may present features of ischemia-reperfusion injury, with recurrent episodes of ischemia/hypoxia and reoxygenation promoting inflammation. Here, we have tested the hypothesis that hypoxia/reoxygenation triggers inflammation in the transgenic sickle mouse. In these mice, even at ambient air, peripheral leukocyte counts are elevated by 1.7-fold and neutrophil counts by almost 3-fold. Two hours of hypoxia, followed by reoxygenation, induced a greater than normal rolling flux and adhesion of leukocytes in these mice, but no leukocyte extravasation. When 3 hours of hypoxia was followed by reoxygenation, sickle mice, but not normal mice, showed a distinct inflammatory response characterized by an increased number of adherent and emigrated leukocytes. Because these events, which are exaggerated in sickle mice, are not seen in response to hypoxia alone, we conclude that they represent a form of reperfusion injury. Studies using an H(2)O(2)-sensitive probe revealed clear evidence of oxidant production in vascular endothelial cells after hypoxia/reoxygenation in sickle mice. Infusion of an anti-P-selectin antibody, but not an anti-E-selectin antibody, completely inhibited this inflammatory response and significantly increased wall shear rates. These findings suggest that leukocyte-endothelium interaction contribute to vasoocclusive events in the sickle mice and perhaps in human sickle disease. PMID:10930444

  2. Teaching Chemistry through Observation--The Exploding Can Demonstration.

    ERIC Educational Resources Information Center

    Golestaneh, Kamran

    1998-01-01

    Describes procedures for a demonstration that features an exploding can. This demonstration prompts students to critically analyze the release of energy in an exothermic reaction, the work done in such a reaction, and the enthalpy. (DDR)

  3. Fabrication, Testing and Modeling of the MICE Superconducting Spectrometer Solenoids

    SciTech Connect

    Virostek, S.P.; Green, M.A.; Trillaud, F.; Zisman, M.S.

    2010-05-16

    The Muon Ionization Cooling Experiment (MICE), an international collaboration sited at Rutherford Appleton Laboratory in the UK, will demonstrate ionization cooling in a section of realistic cooling channel using a muon beam. A five-coil superconducting spectrometer solenoid magnet will provide a 4 tesla uniform field region at each end of the cooling channel. Scintillating fiber trackers within the 400 mm diameter magnet bore tubes measure the emittance of the beam as it enters and exits the cooling channel. Each of the identical 3-meter long magnets incorporates a three-coil spectrometer magnet section and a two-coil section to match the solenoid uniform field into the other magnets of the MICE cooling channel. The cold mass, radiation shield and leads are currently kept cold by means of three two-stage cryocoolers and one single-stage cryocooler. Liquid helium within the cold mass is maintained by means of a re-condensation technique. After incorporating several design changes to improve the magnet cooling and reliability, the fabrication and acceptance testing of the spectrometer solenoids have proceeded. The key features of the spectrometer solenoid magnets, the development of a thermal model, the results of the recently completed tests, and the current status of the project are presented.

  4. Tested Demonstrations: Spectroscopy Illustrated.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1983-01-01

    Background information and procedures are provided for an experiment to prepare three metal derivatives of dimethyl sulfoxide (DMSO) and to determine some structural features of these derivatives based on their infrared spectra. Results and discussion of reactions involved are also provided. (JN)

  5. Evaluation of the Medicaid Competition Demonstrations

    PubMed Central

    Freund, Deborah A.; Rossiter, Louis F.; Fox, Peter D.; Meyer, Jack A.; Hurley, Robert E.; Carey, Timothy S.; Paul, John E.

    1989-01-01

    In 1983, the Health Care Financing Administration funded a multiyear evaluation of Medicaid demonstrations in six States. The alternative delivery systems represented by the demonstrations contained a number of innovative features, most notably capitation, case management, limitations on provider choice, and provider competition. Implementation and operation issues as well as demonstration effects on utilization and cost of care, administrative costs, rate setting, biased selection, quality of care, and access and satisfaction were evaluated. Both primary and secondary data sources were used in the evaluation. This article contains an overview and summary of evaluation findings on the effects of the demonstrations. PMID:10313460

  6. Demonstrating environmental compliance

    SciTech Connect

    Pankratz, R.H. [Battelle Pantex, Amarillo, TX (United States)

    1995-12-31

    Almost every company, plant, or government entity wants to be in compliance with environmental statutes, regulations, and permit provisions. Today wanting is not enough. At the Pantex Plant, we have taken the approach, that unless we can demonstrate compliance, we are not necessarily in compliance. This paper is intended to illustrate how the Pantex Plant has designed its various programs to demonstrate compliance with environmental statutes, regulations, and permit provisions. A major emphasis is to have permit provisions that are objective and measurable so as to aid in demonstrating compliance. In conjunction with unambiguous permit provisions, appropriate management systems are required to provide the necessary records for this documentation.

  7. Favorite Demonstration: Biological Membranes

    NSDL National Science Digital Library

    Gilbert Ellis

    2009-01-01

    This demonstration provides an excellent example of how eukaryotic cells are compartmentalized and how important the bilipid layer of the endomembrane system is in providing this sectioned architecture. This demonstration also effectively depicts how lipid barriers exhibit a hydrophobic response to polar substances such as the cytoplasm and the nucleoplasm. By disrupting the various membranes during the demonstration, students can observe the amphipathetic nature of the membranes. Although this is not a true lipid bilayer, the characteristics of the lipid fluidity in membranes is clearly exemplified.

  8. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1989-01-01

    Described are two demonstrations for teaching chemistry using the overhead projector. Included are "Oxidation of Cyclohexanol--An Amoebalike Reaction," and "A Diels-Alder Reaction for the Overhead Projector." Materials and procedures are detailed. (CW)

  9. Copper Extraction Demonstration

    NSDL National Science Digital Library

    Summary This demonstration uses sulfuric acid and crushed copper ore (malachite) to produce a solution of copper sulfate and carbonic acid in a beaker. When a freshly sanded nail is dropped into the copper sulfate ...

  10. Thermal Conductivity Demonstrations

    NSDL National Science Digital Library

    Summary Here are three ideas for demonstrating thermal conductivity to your students. I. Heat flow down a metal rod (or rods) is timed by seeing wax melt at different locations along the rod. II. A rod made of ...

  11. Remote Agent Demonstration

    NASA Technical Reports Server (NTRS)

    Dorais, Gregory A.; Kurien, James; Rajan, Kanna

    1999-01-01

    We describe the computer demonstration of the Remote Agent Experiment (RAX). The Remote Agent is a high-level, model-based, autonomous control agent being validated on the NASA Deep Space 1 spacecraft.

  12. Projectile Demonstration 2

    NSDL National Science Digital Library

    Wolfgang Christian

    For this demonstration, the launch speed has been selected so that the projectile will hit the target. Type a new value of gravitational field in the associated field. Gun altitude may also be changed.

  13. A deficit of functional GABA A receptors in neurons of ? 3 subunit knockout mice

    Microsoft Academic Search

    Matthew D Krasowski; Caroline E Rick; Neil L Harrison; Leonard L Firestone; Gregg E Homanics

    1998-01-01

    Mice whose ?-aminobutyric acid type A (GABAA) ?3 subunit gene is inactivated (`?3 knockout mice') have been previously shown to have epilepsy, hypersensitive behavior, cleft palate, and a high incidence of neonatal mortality. In this study, we analyze whole-cell responses to GABA in neurons from ?3+\\/+, ?3+\\/? and ?3?\\/? mice. We demonstrate markedly decreased responses to GABA in both hippocampal

  14. BIOSYNTHESIS OF DIMETHYLNITROSAMINE IN DIMETHYLAMINE-TREATED MICE AFTER EXPOSURE TO NITROGEN DIOXIDE

    EPA Science Inventory

    These studies demonstrate the nitrosating potential of NO2 in vivo in 1CR mice. Groups of mice were gavaged with 2 mg dimethylamine (DMA) and exposed to NO2 at levels from 0.04 to 44.5 ppm for periods up to 4 hours. Mice were individually frozen and blended to a powder, aliquots ...

  15. Education Payload Operation - Demonstrations

    NASA Technical Reports Server (NTRS)

    Keil, Matthew

    2009-01-01

    Education Payload Operation - Demonstrations (EPO-Demos) are recorded video education demonstrations performed on the International Space Station (ISS) by crewmembers using hardware already onboard the ISS. EPO-Demos are videotaped, edited, and used to enhance existing NASA education resources and programs for educators and students in grades K-12. EPO-Demos are designed to support the NASA mission to inspire the next generation of explorers.

  16. Edible Astronomy Demonstrations

    NASA Astrophysics Data System (ADS)

    Lubowich, Donald A.

    2007-12-01

    Astronomy demonstrations with edible ingredients are an effective way to increase student interest and knowledge of astronomical concepts. This approach has been successful with all age groups from elementary school through college students - and the students remember these demonstrations after they are presented. In this poster I describe edible demonstrations I have created to simulate the expansion of the universe (using big-bang chocolate chip cookies); differentiation during the formation of the Earth and planets (using chocolate or chocolate milk with marshmallows, cereal, candy pieces or nuts); and radioactivity/radioactive dating (using popcorn). Other possible demonstrations include: plate tectonics (crackers with peanut butter and jelly); convection (miso soup or hot chocolate); mud flows on Mars (melted chocolate poured over angel food cake); formation of the Galactic disk (pizza); formation of spiral arms (coffee with cream); the curvature of Space (Pringles); constellations patterns with chocolate chips and chocolate chip cookies; planet shaped cookies; star shaped cookies with different colored frostings; coffee or chocolate milk measurement of solar radiation; Oreo cookie lunar phases. Sometimes the students eat the results of the astronomical demonstrations. These demonstrations are an effective teaching tool and can be adapted for cultural, culinary, and ethnic differences among the students.

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

    PubMed Central

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

    2013-01-01

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

  18. Vaccination against Pseudomonas aeruginosa Pneumonia in Immunocompromised Mice?

    PubMed Central

    Scarff, Jennifer M.; Goldberg, Joanna B.

    2008-01-01

    Immunocompromised patients are highly susceptible to infection with Pseudomonas aeruginosa. Our laboratory previously showed that intranasal administration of an attenuated Salmonella strain expressing the P. aeruginosa lipopolysaccharide O antigen was effective in clearing bacteria and preventing mortality in wild-type mice after intranasal challenge. We were interested in investigating the efficacy of this vaccine strategy in immunocompromised mice. Mice rendered leukopenic or neutropenic by intraperitoneal treatment with cyclophosphamide (Cy) or RB6-8C5 antibody, respectively, were more susceptible to P. aeruginosa pneumonia than their nontreated counterparts, demonstrating 50% lethal doses several logs lower than that in wild-type mice. This hypersusceptiblity was also associated with bacterial dissemination to the liver and spleen and increased lung permeability in Cy mice. Vaccination of the mice prior to treatment resulted in better survival and lower bacterial loads compared to vector-immunized mice. Although the treatments had no effect on antibody titers, this level of protection was still lower than that seen in untreated vaccinated mice. Administration of antibodies directly to the site of infection at the time of bacterial delivery prolonged survival and lowered bacterial loads in the immunocompromised mice. These results demonstrate the importance of white blood cells while still suggesting a critical role for antibodies in protection against P. aeruginosa infection. PMID:18094113

  19. Autophagy Controls Acquisition of Aging Features in Macrophages

    PubMed Central

    Stranks, Amanda J.; Hansen, Anne Louise; Panse, Isabel; Mortensen, Monika; Ferguson, David J.P.; Puleston, Daniel J.; Shenderov, Kevin; Watson, Alexander Scarth; Veldhoen, Marc; Phadwal, Kanchan; Cerundolo, Vincenzo; Simon, Anna Katharina

    2015-01-01

    Macrophages provide a bridge linking innate and adaptive immunity. An increased frequency of macrophages and other myeloid cells paired with excessive cytokine production is commonly seen in the aging immune system, known as ‘inflamm-aging’. It is presently unclear how healthy macrophages are maintained throughout life and what connects inflammation with myeloid dysfunction during aging. Autophagy, an intracellular degradation mechanism, has known links with aging and lifespan extension. Here, we show for the first time that autophagy regulates the acquisition of major aging features in macrophages. In the absence of the essential autophagy gene Atg7, macrophage populations are increased and key functions such as phagocytosis and nitrite burst are reduced, while the inflammatory cytokine response is significantly increased – a phenotype also observed in aged macrophages. Furthermore, reduced autophagy decreases surface antigen expression and skews macrophage metabolism toward glycolysis. We show that macrophages from aged mice exhibit significantly reduced autophagic flux compared to young mice. These data demonstrate that autophagy plays a critical role in the maintenance of macrophage homeostasis and function, regulating inflammation and metabolism and thereby preventing immunosenescence. Thus, autophagy modulation may prevent excess inflammation and preserve macrophage function during aging, improving immune responses and reducing the morbidity and mortality associated with inflamm-aging. PMID:25359593

  20. Diet-induced obese mice retain endogenous leptin action.

    PubMed

    Ottaway, Nickki; Mahbod, Parinaz; Rivero, Belen; Norman, Lee Ann; Gertler, Arieh; D'Alessio, David A; Perez-Tilve, Diego

    2015-06-01

    Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice. PMID:25980347

  1. Bex1 knock out mice show altered skeletal muscle regeneration

    SciTech Connect

    Koo, Jae Hyung [Department of Anatomy and Neurobiology, School of Medicine, University of Maryland Baltimore, Baltimore, MD 21201 (United States)], E-mail: jkoo001@umaryland.edu; Smiley, Mark A. [Department of Anatomy and Neurobiology, School of Medicine, University of Maryland Baltimore, Baltimore, MD 21201 (United States); Lovering, Richard M. [Department of Physiology, School of Medicine, University of Maryland Baltimore, Baltimore, MD 21201 (United States); Margolis, Frank L. [Department of Anatomy and Neurobiology, School of Medicine, University of Maryland Baltimore, Baltimore, MD 21201 (United States)

    2007-11-16

    Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca{sup 2+}/CaM may be involved in skeletal muscle regeneration.

  2. Spontaneous unilateral brainstem infarction in Swiss mice.

    PubMed

    Southard, T; Brayton, C F

    2011-05-01

    Spontaneous vestibular syndrome in mice, characterized clinically by head tilt, circling or rolling, can be caused by otitis media, arteritis or central nervous system lesions. Postmortem examination of eleven non-inbred Swiss mice submitted for necropsy due to acute onset of vestibular signs revealed lesions consistent with brainstem infarction. The lesions were characterized by unilateral, well-demarcated areas of necrosis, malacia, and gliosis, with variable amounts of hemorrhage, in the lateral aspect of the medulla and caudal pons. The affected area included the medial, lateral and superior vestibular nuclei, the facial nucleus and the spinal trigeminal nucleus. While vestibular disease secondary to otitis media, periarteritis, and central nervous system neoplasia has been reported in many mouse strains, these unilateral brainstem infarctions were only seen in Swiss mice. These lesions share features with Wallenberg's Lateral Medullary Syndrome, the most common type of brainstem infarct in humans. PMID:20466861

  3. Demonstrations in Introductory Geophysics

    NASA Astrophysics Data System (ADS)

    Schramm, K. A.; Stein, S.; van der Lee, S.; Swafford, L.; Klosko, E.; Delaughter, J.; Wysession, M.

    2005-12-01

    Geophysical concepts are challenging to teach at introductory levels, because students need to understand both the underlying physics and its geological application. To address this, our introductory courses include class demonstrations and experiments to demonstrate underlying physical principles and their geological applications. Demonstrations and experiments have several advantages over computer simulations. First, computer simulations "work" even if the basic principle is wrong. In contrast, simple demonstrations show that a principle is physically correct, rather than a product of computer graphics. Second, many students are unfamiliar with once-standard experiments demonstrating ideas of classical physics used in geophysics. Demonstrations are chosen that we consider stimulating, relevant, inexpensive, and easy to conduct in a non-lab classroom. These come in several groups. Many deal with aspects of seismic waves, using springs, light beams, and other methods such as talking from outside the room to illustrate the frequency dependence of diffraction (hearing but not seeing around a corner). Others deal with heat and mass transfer, such as illustrating fractional crystallization with apple juice and the surface/volume effect in planetary evolution with ice. Plate motions are illustrated with paper cutouts showing effects like motion on transform faults and how the Euler vector geometry changes a plate boundary from spreading, to strike-slip, to convergence along the Pacific-North America boundary from the Gulf of California to Alaska. Radioactive decay is simulated by having the class rise and sit down as a result of coin flips (one tail versus two gives different decay rates and hence half lives). This sessions' goal of exchanging information about demonstrations is an excellent idea: some of ours are described on http://www.earth.nwu.edu/people/seth/202.

  4. Feature Subset Selection Using a Genetic Algorithm

    Microsoft Academic Search

    Jihoon Yang; Vasant Honavar

    1998-01-01

    Practical pattern classification and knowledge discovery problems require selection of a subset of attributes or features (from a much larger set) to represent the patterns to be classified. This paper presents an approach to the multi-criteria optimization problem of feature subset selection using a genetic algorithm. Our experiments demonstrate the feasibility of this approach for feature subset selection in the

  5. The demonstration of recurrent demyelination and remyelination of axons in the central nervous system.

    PubMed

    Johnson, E S; Ludwin, S K

    1981-01-01

    A model for studying recurrent demyelination and remyelination in the central nervous system was developed by means of repeated administration of Cuprizone to mice. In contrast to the demyelination seen during the first course of Cuprizone, the recurrent demyelination was markedly protracted, displayed features of a "dying-back" gliopathy, and resulted in a greatly reduced inflammatory and glial reaction. The repeat remyelination also occurred at a slower tempo, varied markedly in completeness, and was associated with a diminished regeneration of oligodendrocytes. These results demonstrated that axons of the central nervous system in this model can be recurrently remyelinated if oligodendrocytes are available, that regeneration of oligodendrocytes is dependent upon the tissue reaction to demyelination, and that remyelinated axons are not more susceptible to demyelination than normal ones. PMID:7211208

  6. UWB feature localization for imaging

    Microsoft Academic Search

    Jochen Seitz; Markus Schaub; Ole Hirsch; Rudolf Zetik; T. Deissler; R. Thoma; J. Thielecke

    2008-01-01

    Object recognition, localization and imaging capabilities of ultra-wideband signals are demonstrated in this contribution. Resembling a bat, the experimental setup comprises one transmitter and two receivers. Instead of ultrasound, electromagnetic ultra-wideband (UWB) signals are used to recognize and localize features of the surroundings like e.g. walls, edges or corners. Each feature corresponds to a hypothesis on the dominant reflection and

  7. Fish Oil Has Beneficial Effects on Allergen-Induced Airway Inflammation and Hyperreactivity in Mice

    PubMed Central

    Bargut, Thereza Cristina Lonzetti; Ferreira, Tatiana Paula Teixeira; Daleprane, Julio Beltrame; Martins, Marco Aurélio; Silva, Patrícia Machado Rodrigues; Aguila, Marcia Barbosa

    2013-01-01

    Background Fish oil (FO) is rich in n-3 polyunsaturated fatty acids (PUFA), which have been suggested to be anti-inflammatory and are associated with improvement of several inflammatory diseases. In this study, we investigated the influence of FO on allergen-induced lung inflammation and airway hyperreactivity in mice. Methods Male A/J mice were fed either a standard-chow (SC) or a FO diet (FO) for 8 weeks. After 4 weeks, each group was further randomized for ovalbumin (SC-OVA and FO-OVA) or saline (SC-SAL and FO-SAL) challenge. Resistance and elastance were measured at baseline and after aerosolized methacholine, 24h after the last challenge. Bronchoalveolar lavage (BAL) was performed for leukocyte counts. Lung tissue mucus deposition, peribronchiolar matrix deposition and eosinophil infiltration were quantified. Serum immunoglobulin E (IgE) and IgG1 (ref 2.2), lung IL-4, IL-5, IL-10, IL-13, IL-17, INF? and eotaxin-1 and 2 were detected by ELISA and nuclear factor kappa B (NF?B), GATA-3 and peroxisome proliferator-activated receptor gamma (PPAR?) expression was measured by Western blot. Results Levels of serum IgE and IgG1 were significantly higher in OVA sensitized mice. OVA challenge resulted in increased eosinophil infiltration, increased inflammatory cytokine production, peribronchiolar matrix and mucus deposition and airway hyperreactivity to aerosolized methacholine. Elevated lung NF?B and GATA-3 expression was noted in OVA-challenged mice. These changes were attenuated in mice fed with FO diet. Higher PPAR? expression was also detected in the lungs from the FO-fed groups. Conclusion Our results demonstrate that FO intake attenuated classical asthma features by suppressing the systemic sensitization, thus providing evidence that FO might be a prophylactic alternative for asthma prevention. PMID:24040386

  8. Innovative technology demonstrations

    SciTech Connect

    Anderson, D.B.; Hartley, J.N.; Luttrell, S.P.

    1992-04-01

    Currently, several innovative technologies are being demonstrated at Tinker Air Force Base (TAFB) to address specific problems associated with remediating two contaminated test sites at the base. Cone penetrometer testing (CPT) is a form of testing that can rapidly characterize a site. This technology was selected to evaluate its applicability in the tight clay soils and consolidated sandstone sediments found at TAFB. Directionally drilled horizontal wells have been successfully installed at the US Department of Energy's (DOE) Savannah River Site to test new methods of in situ remediation of soils and ground water. This emerging technology was selected as a method that may be effective in accessing contamination beneath Building 3001 without disrupting the mission of the building, and in enhancing the extraction of contamination both in ground water and in soil. A soil gas extraction (SGE) demonstration, also known as soil vapor extraction, will evaluate the effectiveness of SGE in remediating fuels and TCE contamination contained in the tight clay soil formations surrounding the abandoned underground fuel storage vault located at the SW Tanks Site. In situ sensors have recently received much acclaim as a technology that can be effective in remediating hazardous waste sites. Sensors can be useful for determining real-time, in situ contaminant concentrations during the remediation process for performance monitoring and in providing feedback for controlling the remediation process. A demonstration of two in situ sensor systems capable of providing real-time data on contamination levels will be conducted and evaluated concurrently with the SGE demonstration activities. Following the SGE demonstration, the SGE system and SW Tanks test site will be modified to demonstrate bioremediation as an effective means of degrading the remaining contaminants in situ.

  9. Innovative technology demonstrations

    SciTech Connect

    Anderson, D.B.; Hartley, J.N.; Luttrell, S.P.

    1992-04-01

    Currently, several innovative technologies are being demonstrated at Tinker Air Force Base (TAFB) to address specific problems associated with remediating two contaminated test sites at the base. Cone penetrometer testing (CPT) is a form of testing that can rapidly characterize a site. This technology was selected to evaluate its applicability in the tight clay soils and consolidated sandstone sediments found at TAFB. Directionally drilled horizontal wells have been successfully installed at the US Department of Energy`s (DOE) Savannah River Site to test new methods of in situ remediation of soils and ground water. This emerging technology was selected as a method that may be effective in accessing contamination beneath Building 3001 without disrupting the mission of the building, and in enhancing the extraction of contamination both in ground water and in soil. A soil gas extraction (SGE) demonstration, also known as soil vapor extraction, will evaluate the effectiveness of SGE in remediating fuels and TCE contamination contained in the tight clay soil formations surrounding the abandoned underground fuel storage vault located at the SW Tanks Site. In situ sensors have recently received much acclaim as a technology that can be effective in remediating hazardous waste sites. Sensors can be useful for determining real-time, in situ contaminant concentrations during the remediation process for performance monitoring and in providing feedback for controlling the remediation process. A demonstration of two in situ sensor systems capable of providing real-time data on contamination levels will be conducted and evaluated concurrently with the SGE demonstration activities. Following the SGE demonstration, the SGE system and SW Tanks test site will be modified to demonstrate bioremediation as an effective means of degrading the remaining contaminants in situ.

  10. Standing Wave Demonstration

    NSDL National Science Digital Library

    This demonstration is intended to help students better understand the electromagnetic spectrum. At the end of this activity students will be able to explain that energy travels from the sun to the earth by means of electromagnetic waves, and that the shorter the wavelength, the higher the energy per photon. They will understand why shorter wavelengths of electromagnetic energy carry more energy than longer wavelengths. Students will also be able to demonstrate how wavelength is measured. The teacher's guide contains detailed background material, learning goals, alignment to national standards, grade level/time, details on materials and preparation, procedure, assessment ideas, and modifications for alternative learners.

  11. Demonstrating marketing accountability.

    PubMed

    Gombeski, William R; Britt, Jason; Taylor, Jan; Riggs, Karen; Wray, Tanya; Adkins, Wanda; Springate, Suzanne

    2008-01-01

    Pressure on health care marketers to demonstrate effectiveness of their strategies and show their contribution to organizational goals is growing. A seven-tiered model based on the concepts of structure (having the right people, systems), process (doing the right things in the right way), and outcomes (results) is discussed. Examples of measures for each tier are provided and the benefits of using the model as a tool for measuring, organizing, tracking, and communicating appropriate information are provided. The model also provides a framework for helping management understand marketing's value and can serve as a vehicle for demonstrating marketing accountability. PMID:19064476

  12. DEMONSTRATION OF MICROFILTRATION TECHNOLOGY

    EPA Science Inventory

    The U.S. Environmental Protection Agency, under the Superfund Innovative Technology Evaluation (SITE) program in cooperation with E.I. DuPont de Nemours & Company, Inc. (DuPont) and the Oberlin Filter Company (Oberlin), undertook a field demonstration project to evaluate microfil...

  13. ARJIS satellite demonstration project

    Microsoft Academic Search

    Steve Severance; Carl Williams

    2005-01-01

    In 2003, the California Space Authority (CSA) was provided funding by the U. S. Congress through the Defense Appropriations Act to develop a project that would demonstrate the U.S. space enterprise capability that would contribute to the effectiveness of those engaged in Homeland Security. The project was given broad latitude in selecting the area of Homeland Security to be addressed

  14. Tidd PFBC Demonstration Project

    SciTech Connect

    Not Available

    1992-07-01

    This is the 21st Technical Progress Report submitted to the Department of energy in connection with the Cooperative Agreement between the DOE and the Ohio Power Company for the Tidd PFBC Demonstration Plant. This report covers the period from April 1, 1992--June 30, 1992.

  15. The Breaking Broomstick Demonstration.

    ERIC Educational Resources Information Center

    Mamola, Karl C.; Pollock, Joseph T.

    1993-01-01

    Describes and explains the breaking broomstick demonstration first reported in 1532. A needle is fixed at each end of the broomstick, and these needles are made to rest on two glasses, placed on chairs. If the broomstick is struck violently with another stout stick, the former will be broken, but the glasses will remain intact. (PR)

  16. Why Demonstrations Matter

    ERIC Educational Resources Information Center

    Black, Richard

    2005-01-01

    The author remembers how exciting it was when the teacher had "stuff" on the front desk: unfamiliar objects and other things out of place in the traditional classroom. Years later, as a new teacher, the author learned the importance of building lessons around concepts and that demonstrations are an integral part of concept development in science.…

  17. Musical acoustics demonstrations

    NASA Astrophysics Data System (ADS)

    Hoekje, P. L.

    2003-10-01

    The ASA Musical Acoustics Demonstrations website (trial version at http://www.bw.edu/~phoekje) includes sound files, video clips, program code listings, and other material for demonstrations related to musical acoustics. Many of the sound demonstrations may be experienced either as expositions, in which the phenomena are explained before they are presented, or as experiments, in which the explanation comes after listeners have had the opportunity to draw their own conclusions. Suggestions are provided for apparatus construction and classroom experiments, as well as for building simple musical instruments. Software is recommended if it is available free and compatible with multiple personal computer operating systems. For example, Audacity (http://audacity.sourceforce.net) is a sound file editor and analyzer that can be used to visually represent sounds and manipulate them. Source files are included for the synthesized sound examples, which were created in Csound (http://csounds.com), so that interested users may create their own variations. Source code is also included for visual demonstrations created in Visual Python and Python (http://www.python.org), an efficient, high level programming language. Suggestions, criticisms, and contributions are always welcome! [Work supported by ASA and Baldwin-Wallace College.

  18. New Technology Demonstration Program

    E-print Network

    New Technology Demonstration Program Technical Brief FEMPFederal Energy Management Program Tom for saving energy in refrigerated walk-in coolers, and to evaluate the potential for this technology in Federal facilities. The focus of this study was on a single manufacturer of the technology, Nevada Energy

  19. ALASKA VILLAGE DEMONSTRATION PROJECTS

    EPA Science Inventory

    Two demonstration projects were built as authorized by Section 113 of PL 92-500. Modular construction was used to provide central utility systems which included water supply, laundry, bathing, saunas, and wastewater treatment. Service to homes was by vehicular delivery. Fire dest...

  20. Demonstration Road Show

    NSDL National Science Digital Library

    2009-04-06

    The Idaho State University Department of Physics conducts science demonstration shows at S. E. Idaho schools. Four different presentations are currently available; "Forces and Motion", "States of Matter", "Electricity and Magnetism", and "Sound and Waves". Information provided includes descriptions of the material and links to other resources.

  1. SOIL BIOVENTING DEMONSTRATION PROJECT

    EPA Science Inventory

    A pilot scale demonstration project of a soil bioventing system, which utilizes the biodegradation in soil and physical removal of VOC by induced air flow, is in operation at the U.S. Coast Guard Aviation Field in Traverse City, Michigan. he system is being tested to determine it...

  2. A Fruity Biochemistry Demonstration

    ERIC Educational Resources Information Center

    Shmaefsky, Brian R.

    2005-01-01

    Classroom demonstrations are a great vehicle for getting students to apply information they have heard in a lecture. Educational research is replete with data showing that concept application in an inquiry setting reinforces long-term science content retention. This means that students learn best when they experience applications of concepts and…

  3. A Magnetic Circuit Demonstration.

    ERIC Educational Resources Information Center

    Vanderkooy, John; Lowe, June

    1995-01-01

    Presents a demonstration designed to illustrate Faraday's, Ampere's, and Lenz's laws and to reinforce the concepts through the analysis of a two-loop magnetic circuit. Can be made dramatic and challenging for sophisticated students but is suitable for an introductory course in electricity and magnetism. (JRH)

  4. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1988-01-01

    Provides two demonstrations: (1) electrolyte migration of ions using colored ions which cross a strip of gelatin allowing for noticeable migration; and (2) photochemical reduction of Fe+3 by the citrate ion. Points out both reactions can be done in a Petri dish using common lab materials. (MVL)

  5. Santa Clara Demonstration Status

    Microsoft Academic Search

    Anthony J. Leo; Andrew J. Skok; Thomas P. OShea

    1996-01-01

    Fuel Cell Engineering Corporation (FCE) is in the fourth year of a DOE Cooperative Agreement Program (private-sector cost-shared) aimed at the demonstration of ERC's direct carbonate fuel cell (DFC) technology at full scale. FCE is a wholly owned subsidiary of Energy Research Corporation (ERC), which has been pursuing the development of the DFC for commercialization near the end of this

  6. Repository Drift Backfilling Demonstrator

    SciTech Connect

    Londe, I.; Dubois, J.Ph.; Bauer, C. [Agence Nationale pour la Gestion des Dechets Radioactifs (ANDRA), 92 - Chatenay Malabry (France)

    2008-07-01

    The 'Backfilling Demonstrator' is one of the technological demonstrators developed by ANDRA in the framework of the feasibility studies for a geological repository for high-level long-lived (HL-LL waste) within a clay formation. The demonstrator concerns the standard and supporting backfills as defined in Andra's 2005 design. The standard backfill is intended to fill up almost all drifts of the underground repository in order to limit any deformation of the rock after the degradation of the drift lining. The supporting backfill only concerns a small portion of the volume to be backfilled in order to counter the swelling pressure of the swelling clay contained in the sealing structures. The first objective of the demonstrator was to show the possibility of manufacturing a satisfactory backfill, in spite of the exiguity of the underground structures, and of reusing as much as possible the argillite muck. For the purpose of this experiment, the argillite muck was collected on Andra's work-site for the implementation of an underground research laboratory. Still ongoing, the second objective is to follow up the long-term evolution of the backfill. Approximately 200 m{sup 3} of compacted backfill material have been gathered in a large concrete tube simulating a repository drift. The standard backfill was manufactured exclusively with argillite. The supporting backfill was made by forming a mixture of argillite and sand. Operations were carried out mostly at Richwiller, close to Mulhouse, France. The objectives of the demonstrator were met: an application method was tested and proven satisfactory. The resulting dry densities are relatively high, although the moduli of deformation do not always reach the set goal. The selected objective for the demonstrator was a dry density corresponding to a relatively high compaction level (95% of the standard Proctor optimum [SPO]), for both pure argillite and the argillite-sand mixture. The plate-percussion compaction technique was used and proved satisfactory. The measured dry densities are higher than the 95%-SPO objective. The implementation rates remain very low due to the experimental conditions involved. The metal supply mode would need to be revised before any industrial application is contemplated. The Demonstrator Program started in August 2004 and is followed up today over the long term. With that objective in mind, sensors and a water-saturation system have been installed. (author)

  7. Demonstration of Berry Phase in Optical Spectroscopy

    NASA Technical Reports Server (NTRS)

    Xia, Hui-Rong; Zhang, Yong; Jiang, Hong-Ji; Ding, Liang-En

    1996-01-01

    In this paper we demonstrate that the observed phase shift of the RF signal and its intensity dependence under extreme low pump and probe laser field conditions are dominated by Berry phase effect in optical spectroscopy with good adiabatic approximation, which provides all features' agreements between the theoretical and the experimental results.

  8. Observations in APP Bitransgenic Mice Suggest that Diffuse and Compact Plaques Form via Independent Processes in Alzheimer's Disease

    PubMed Central

    Lord, Anna; Philipson, Ola; Klingstedt, Therése; Westermark, Gunilla; Hammarström, Per; Nilsson, K. Peter R.; Nilsson, Lars N.G.

    2011-01-01

    Studies of familial Alzheimer's disease suggest that misfolding and aggregation of amyloid-? (A?) peptides initiate the pathogenesis. The Arctic mutation of A? precursor protein (APP) results in AD, and Arctic A? is more prone to form A? protofibrils and extracellular deposits. Herein is demonstrated that the burden of diffuse A? deposits but not compact plaques is increased when tg-Swe mice are crossed with tg-ArcSwe mice synthesizing low levels of Arctic A?. The diffuse deposits in bitransgenic mice, which contain primarily wild-type A?42, accumulate in regions both with and without transgene expression. However, APP processing, when compared with tg-Swe, remains unchanged in young bitransgenic mice, whereas wild-type A?42 aggregation is accelerated and fibril architecture is altered in vitro and in vivo when a low level of Arctic A?42 is introduced. Thus, the increased number of diffuse deposits is likely due to physical interactions between Arctic A? and wild-type A?42. The selective increase of a single type of parenchymal A? deposit suggests that different pathways lead to formation of diffuse and compact plaques. These findings could have general implications for Alzheimer's disease pathogenesis and particular relevance to patients heterozygous for the Arctic APP mutation. Moreover, it further illustrates how A? neuropathologic features can be manipulated in vivo by mechanisms similar to those originally conceptualized in prion research. PMID:21514441

  9. Mice Lacking Natural Killer T Cells Are More Susceptible to Metabolic Alterations following High Fat Diet Feeding

    PubMed Central

    Wang, Hong; De La Houssaye, Becky A.; Reilly, Timothy P.; Friedman, Jacob E.; Ju, Cynthia

    2014-01-01

    Current estimates suggest that over one-third of the adult population has metabolic syndrome and three-fourths of the obese population has non-alcoholic fatty liver disease (NAFLD). Inflammation in metabolic tissues has emerged as a universal feature of obesity and its co-morbidities, including NAFLD. Natural Killer T (NKT) cells are a subset of innate immune cells that abundantly reside within the liver and are readily activated by lipid antigens. There is general consensus that NKT cells are pivotal regulators of inflammation; however, disagreement exists as to whether NKT cells exert pathogenic or suppressive functions in obesity. Here we demonstrate that CD1d?/? mice, which lack NKT cells, were more susceptible to weight gain and fatty liver following high fat diet (HFD) feeding. Compared with their WT counterparts, CD1d?/? mice displayed increased adiposity and greater induction of inflammatory genes in the liver suggestive of the precursors of NAFLD. Calorimetry studies revealed a significant increase in food intake and trends toward decreased metabolic rate and activity in CD1d?/? mice compared with WT mice. Based on these findings, our results suggest that NKT cells play a regulatory role that helps to prevent diet-induced obesity and metabolic dysfunction and may play an important role in mechanisms governing cross-talk between metabolism and the immune system to regulate energy balance and liver health. PMID:24465369

  10. Ablation of the GNB3 gene in mice does not affect body weight, metabolism or blood pressure, but causes bradycardia.

    PubMed

    Ye, Yuanchao; Sun, Zhizeng; Guo, Ang; Song, Long-Sheng; Grobe, Justin L; Chen, Songhai

    2014-11-01

    G protein ?3 (G?3) is an isoform of heterotrimeric G protein ? subunits involved in transducing G protein coupled receptor (GPCR) signaling. Polymorphisms in G?3 (GNB3) are associated with many human disorders (e.g. hypertension, diabetes and obesity) but the role of GNB3 in these pathogeneses remains unclear. Here, G?3-null mice (GNB3(-/-)) were characterized to determine how G?3 functions to regulate blood pressure, body weight and metabolism. We found G?3 expression restricted to limited types of tissues, including the retina, several regions of the brain and heart ventricles. G?3-deficient mice were normal as judged by body weight gain by age or by feeding with high-fat diet (HFD); glucose tolerance and insulin sensitivity; baseline blood pressure and angiotensin II infusion-induced hypertension. During tail-cuff blood pressure measurements, however, G?3-null mice had slower heart rates (~450 vs ~500 beats/min). This bradycardia was not observed in isolated and perfused G?3-null mouse hearts. Moreover, mouse hearts isolated from GNB3(-/-) and controls responded equivalently to muscarinic receptor- and ?-adrenergic receptor-stimulated bradycardia and tachycardia, respectively. Since no difference was seen in isolated hearts, G?3 is unlikely to be involved directly in the GPCR signaling activity that controls heart pacemaker activity. These results demonstrate that although G?3 appears dispensable in mice for the regulation of blood pressure, body weight and metabolic features associated with obesity and diabetes, G?3 may regulate heart rate. PMID:25093805

  11. Effect of Leptin on Fatless Mice

    Microsoft Academic Search

    I. Shimomura

    \\u000a Generalized lipodystrophy (GL) is a disorder characterized by a paucity of adipose (fat) tissue that is accompanied by a severe\\u000a resistance to insulin, leading to hyperinsulinemia, hyperglycemia, and enlarged fatty liver. Our laboratory have developed\\u000a a mouse model that mimics these features of generalized lipodystrophy: the syndrome occurs in transgenic mice expressing a\\u000a truncated version of a nuclear protein known

  12. Nucla CFB Demonstration Project

    SciTech Connect

    Not Available

    1990-12-01

    This report documents Colorado-Ute Electric Association's Nucla Circulating Atmospheric Fluidized-Bed Combustion (AFBC) demonstration project. It describes the plant equipment and system design for the first US utility-size circulating AFBC boiler and its support systems. Included are equipment and system descriptions, design/background information and appendices with an equipment list and selected information plus process flow and instrumentation drawings. The purpose of this report is to share the information gathered during the Nucla circulating AFBC demonstration project and present it so that the general public can evaluate the technical feasibility and cost effectiveness of replacing pulverized or stoker-fired boiler units with circulating fluidized-bed boiler units. (VC)

  13. Defective response inhibition and collicular noradrenaline enrichment in mice with duplicated retinotopic map in the superior colliculus.

    PubMed

    Mathis, Chantal; Savier, Elise; Bott, Jean-Bastien; Clesse, Daniel; Bevins, Nicholas; Sage-Ciocca, Dominique; Geiger, Karin; Gillet, Anaïs; Laux-Biehlmann, Alexis; Goumon, Yannick; Lacaud, Adrien; Lelièvre, Vincent; Kelche, Christian; Cassel, Jean-Christophe; Pfrieger, Frank W; Reber, Michael

    2015-05-01

    The superior colliculus is a hub for multisensory integration necessary for visuo-spatial orientation, control of gaze movements and attention. The multiple functions of the superior colliculus have prompted hypotheses about its involvement in neuropsychiatric conditions, but to date, this topic has not been addressed experimentally. We describe experiments on genetically modified mice, the Isl2-EphA3 knock-in line, that show a well-characterized duplication of the retino-collicular and cortico-collicular axonal projections leading to hyperstimulation of the superior colliculus. To explore the functional impact of collicular hyperstimulation, we compared the performance of homozygous knock-in, heterozygous knock-in and wild-type mice in several behavioral tasks requiring collicular activity. The light/dark box test and Go/No-Go conditioning task revealed that homozygous mutant mice exhibit defective response inhibition, a form of impulsivity. This defect was specific to attention as other tests showed no differences in visually driven behavior, motivation, visuo-spatial learning and sensorimotor abilities among the different groups of mice. Monoamine quantification and gene expression profiling demonstrated a specific enrichment of noradrenaline only in the superficial layers of the superior colliculus of Isl2-EphA3 knock-in mice, where the retinotopy is duplicated, whereas transcript levels of receptors, transporters and metabolic enzymes of the monoaminergic pathway were not affected. We demonstrate that the defect in response inhibition is a consequence of noradrenaline imbalance in the superficial layers of the superior colliculus caused by retinotopic map duplication. Our results suggest that structural abnormalities in the superior colliculus can cause defective response inhibition, a key feature of attention-deficit disorders. PMID:24647754

  14. The Blowgun Demonstration Experiment

    ERIC Educational Resources Information Center

    Tsukamoto, Koji; Uchino, Masanori

    2008-01-01

    We have found that a simple demonstration experiment using a match or a cotton swab and a drinking straw or an acrylic pipe serves as an effective introduction to dynamics. The most basic apparatus has a cotton swab serving as a dart and the straw as the blowgun. When blown from a starting point near the exit end of the straw, the cotton swab does…

  15. Multiwire slurry wafering demonstrations

    Microsoft Academic Search

    C. P. Chen

    1978-01-01

    Ten slicing demonstrations on a multi-wire slurry saw, made to evaluate the silicon ingot wafering capabilities, reveal that the present sawing capabilities can provide usable wafer area from an ingot 1.05m\\/kg (e.g. kerf width 0.135 mm and wafer thickness 0.265 mm). Satisfactory surface qualities and excellent yield of silicon wafers were found. One drawback is that the add-on cost of

  16. Space Fabrication Demonstration System

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The completion of assembly of the beam builder and its first automatic production of truss is discussed. A four bay, hand assembled, roll formed members truss was built and tested to ultimate load. Detail design of the fabrication facility (beam builder) was completed and designs for subsystem debugging are discussed. Many one bay truss specimens were produced to demonstrate subsystem operation and to detect problem areas.

  17. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris

    1988-01-01

    Describes two oscillating reactions: the Briggs-Raucher reaction using H202, KIO3, malonic acid, and MnSO4 which changes from yellow to blue, and the Belousov-Zhabotinskii reaction uses NaBrO3, NaBr, malonic acid, and ferroin solution and changes from red to blue. Includes a third color demonstration on the six oxidation states of manganese. (MVL)

  18. The evolution of hod mice The evolution of hod mice

    E-print Network

    Koellner, Peter

    The evolution of hod mice The evolution of hod mice Grigor Sargsyan UCLA Harvard Mamls February 20, 2011 Cambridge, Massachusetts The evolution of hod mice Grigor Sargsyan #12;The evolution of hod mice The beginnings CH in HOD Theorem (Harrington-Kechris) Assume V = L(R) + AD. Then HOD CH. The evolution of hod

  19. Defective microglial development in the hippocampus of Cx3cr1 deficient mice.

    PubMed

    Pagani, Francesca; Paolicelli, Rosa C; Murana, Emanuele; Cortese, Barbara; Angelantonio, Silvia Di; Zurolo, Emanuele; Guiducci, Eva; Ferreira, Tiago A; Garofalo, Stefano; Catalano, Myriam; D'Alessandra, Giuseppina; Porzia, Alessandra; Peruzzi, Giovanna; Mainiero, Fabrizio; Limatola, Cristina; Gross, Cornelius T; Ragozzino, Davide

    2015-01-01

    Microglial cells participate in brain development and influence neuronal loss and synaptic maturation. Fractalkine is an important neuronal chemokine whose expression increases during development and that can influence microglia function via the fractalkine receptor, CX3CR1. Mice lacking Cx3cr1 show a variety of neuronal defects thought to be the result of deficient microglia function. Activation of CX3CR1 is important for the proper migration of microglia to sites of injury and into the brain during development. However, little is known about how fractalkine modulates microglial properties during development. Here we examined microglial morphology, response to ATP, and K(+) current properties in acute brain slices from Cx3cr1 knockout mice across postnatal hippocampal development. We found that fractalkine signaling is necessary for the development of several morphological and physiological features of microglia. Specifically, we found that the occurrence of an outward rectifying K(+) current, typical of activated microglia, that peaked during the second and third postnatal week, was reduced in Cx3cr1 knockout mice. Fractalkine signaling also influenced microglial morphology and ability to extend processes in response to ATP following its focal application to the slice. Our results reveal the developmental profile of several morphological and physiological properties of microglia and demonstrate that these processes are modulated by fractalkine signaling. PMID:25873863

  20. Lafora bodies and neurological defects in malin-deficient mice correlate with impaired autophagy.

    PubMed

    Criado, Olga; Aguado, Carmen; Gayarre, Javier; Duran-Trio, Lara; Garcia-Cabrero, Ana M; Vernia, Santiago; San Millán, Beatriz; Heredia, Miguel; Romá-Mateo, Carlos; Mouron, Silvana; Juana-López, Lucía; Domínguez, Mercedes; Navarro, Carmen; Serratosa, Jose M; Sanchez, Marina; Sanz, Pascual; Bovolenta, Paola; Knecht, Erwin; Rodriguez de Cordoba, Santiago

    2012-04-01

    Lafora disease (LD), a fatal neurodegenerative disorder characterized by the presence of intracellular inclusions called Lafora bodies (LBs), is caused by loss-of-function mutations in laforin or malin. Previous studies suggested a role of these proteins in the regulation of glycogen biosynthesis, in glycogen dephosphorylation and in the modulation of the intracellular proteolytic systems. However, the contribution of each of these processes to LD pathogenesis is unclear. We have generated a malin-deficient (Epm2b-/-) mouse with a phenotype similar to that of LD patients. By 3-6 months of age, Epm2b-/- mice present neurological and behavioral abnormalities that correlate with a massive presence of LBs in the cortex, hippocampus and cerebellum. Sixteen-day-old Epm2b-/- mice, without detectable LBs, show an impairment of macroautophagy (hereafter called autophagy), which remains compromised in adult animals. These data demonstrate similarities between the Epm2a-/- and Epm2b-/- mice that provide further insights into LD pathogenesis. They illustrate that the dysfunction of autophagy is a consequence of the lack of laforin-malin complexes and a common feature of both mouse models of LD. Because this dysfunction precedes other pathological manifestations, we propose that decreased autophagy plays a primary role in the formation of LBs and it is critical in LD pathogenesis. PMID:22186026

  1. Xyloketal B Attenuates Atherosclerotic Plaque Formation and Endothelial Dysfunction in Apolipoprotein E Deficient Mice

    PubMed Central

    Zhao, Li-Yan; Li, Jie; Yuan, Feng; Li, Mei; Zhang, Quan; Huang, Yun-Ying; Pang, Ji-Yan; Zhang, Bin; Sun, Fang-Yun; Sun, Hong-Shuo; Li, Qian; Cao, Lu; Xie, Yu; Lin, Yong-Cheng; Liu, Jie; Tan, Hong-Mei; Wang, Guan-Lei

    2015-01-01

    Our previous studies demonstrated that xyloketal B, a novel marine compound with a unique chemical structure, has strong antioxidant actions and can protect against endothelial injury in different cell types cultured in vitro and model organisms in vivo. The oxidative endothelial dysfunction and decrease in nitric oxide (NO) bioavailability are critical for the development of atherosclerotic lesion. We thus examined whether xyloketal B had an influence on the atherosclerotic plaque area in apolipoprotein E-deficient (apoE?/?) mice fed a high-fat diet and investigated the underlying mechanisms. We found in our present study that the administration of xyloketal B dose-dependently decreased the atherosclerotic plaque area both in the aortic sinus and throughout the aorta in apoE?/? mice fed a high-fat diet. In addition, xyloketal B markedly reduced the levels of vascular oxidative stress, as well as improving the impaired endothelium integrity and NO-dependent aortic vasorelaxation in atherosclerotic mice. Moreover, xyloketal B significantly changed the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt without altering the expression of total eNOS and Akt in cultured human umbilical vein endothelial cells (HUVECs). Here, it increased eNOS phosphorylation at the positive regulatory site of Ser-1177, while inhibiting phosphorylation at the negative regulatory site of Thr-495. Taken together, these findings indicate that xyloketal B has dramatic anti-atherosclerotic effects in vivo, which is partly due to its antioxidant features and/or improvement of endothelial function. PMID:25874925

  2. Defective microglial development in the hippocampus of Cx3cr1 deficient mice

    PubMed Central

    Pagani, Francesca; Paolicelli, Rosa C.; Murana, Emanuele; Cortese, Barbara; Di Angelantonio, Silvia; Zurolo, Emanuele; Guiducci, Eva; Ferreira, Tiago A.; Garofalo, Stefano; Catalano, Myriam; D’Alessandro, Giuseppina; Porzia, Alessandra; Peruzzi, Giovanna; Mainiero, Fabrizio; Limatola, Cristina; Gross, Cornelius T.; Ragozzino, Davide

    2015-01-01

    Microglial cells participate in brain development and influence neuronal loss and synaptic maturation. Fractalkine is an important neuronal chemokine whose expression increases during development and that can influence microglia function via the fractalkine receptor, CX3CR1. Mice lacking Cx3cr1 show a variety of neuronal defects thought to be the result of deficient microglia function. Activation of CX3CR1 is important for the proper migration of microglia to sites of injury and into the brain during development. However, little is known about how fractalkine modulates microglial properties during development. Here we examined microglial morphology, response to ATP, and K+ current properties in acute brain slices from Cx3cr1 knockout mice across postnatal hippocampal development. We found that fractalkine signaling is necessary for the development of several morphological and physiological features of microglia. Specifically, we found that the occurrence of an outward rectifying K+ current, typical of activated microglia, that peaked during the second and third postnatal week, was reduced in Cx3cr1 knockout mice. Fractalkine signaling also influenced microglial morphology and ability to extend processes in response to ATP following its focal application to the slice. Our results reveal the developmental profile of several morphological and physiological properties of microglia and demonstrate that these processes are modulated by fractalkine signaling. PMID:25873863

  3. Effect of low frequency low energy pulsing electromagnetic fields on mice injected with cyclophosphamide

    SciTech Connect

    Cadossi, R.; Zucchini, P.; Emilia, G.; Franceschi, C.; Cossarizza, A.; Santantonio, M.; Mandolini, G.; Torelli, G. (Univ. of Modena (Italy))

    1991-03-01

    C3H mice have been used to investigate the effect of a combination of cyclophosphamide (CY) and electromagnetic fields (PEMF). Mice were injected i.p. with a single dose of 200 mg/kg body weight of CY and then exposed to PEMF 24 h per day. In an initial series of experiments immediately after CY injection mice were exposed to PEMF until sacrifice. WBC counts in the peripheral blood demonstrated a quicker decline in WBC at days 1 and 2 in mice exposed to PEMF. Groups of mice were sacrificed at days 1, 4, 6, 8, and 10 after CY injection. In mice exposed to PEMF the spleen weight was less than in controls at days 6, 8, and 10. Autoradiographic studies demonstrated that the labeling index of bone marrow smears did not significantly differ between controls and experimental mice exposed to PEMF, whereas the spleen labeling index proved to be higher among control mice versus mice exposed to PEMF at day 6, and higher among mice exposed to PEMF versus controls at day 8. In a second series of experiments mice were exposed to PEMF only over the 24 h following CY injection. We found that the spleens of mice exposed to PEMF weighed less than those of controls at days 6 and 8. The labeling index of bone marrow did evidence a slight decrease among mice exposed to PEMF at days 8 and 10 after CY injection versus control mice. The spleen labeling index proved to be lower in experimental mice exposed to PEMF than in controls at days 4, 6, and 8. Mice were then injected with CY, half were exposed to PEMF, and 24 h later bone marrow was recovered from both groups of animals. The same number of bone marrow cells was injected via the tail vein into recipient mice irradiated to 8.5 Gy.

  4. The selective advantage of crypsis in mice.

    PubMed

    Vignieri, Sacha N; Larson, Joanna G; Hoekstra, Hopi E

    2010-07-01

    The light color of mice that inhabit the sandy dunes of Florida's coast have served as a textbook example of adaptation for nearly a century, despite the fact that the selective advantage of crypsis has never been directly tested or quantified in nature. Using plasticine mouse models of light and dark color, we demonstrate a strong selective advantage for mice that match their local background substrate. Further our data suggest that stabilizing selection maintains color matching within a single habitat, as models that are both lighter and darker than their local environment are selected against. These results provide empirical evidence in support of the hypothesis that visual hunting predators shape color patterning in Peromyscus mice and suggest a mechanism by which selection drives the pronounced color variation among populations. PMID:20163447

  5. Eosinophils control the resolution of inflammation and draining lymph node hypertrophy through the proresolving mediators and CXCL13 pathway in mice.

    PubMed

    Tani, Yukako; Isobe, Yosuke; Imoto, Yuki; Segi-Nishida, Eri; Sugimoto, Yukihiko; Arai, Hiroyuki; Arita, Makoto

    2014-09-01

    Resolution of inflammation is critical to restoration of tissue function after an inflammatory response. We previously demonstrated that 12/15-lipoxygenase (12/15-LOX)-expressing eosinophils contribute to this process in murine zymosan-induced peritonitis. In this study, eosinophils promoted resolution by regulating expression of macrophage CXCL13. Microarray analysis revealed that eosinophils significantly increased (?3-fold) the expression of macrophage CXCL13 by a 12/15-LOX-dependent mechanism. CXCL13 depletion caused a resolution defect, with the reduced appearance of phagocytes carrying engulfed zymosan in the draining lymph nodes. Inflamed lymph node hypertrophy, a critical feature of the resolution process, was reduced by ?60% in eosinophil-deficient mice, and adoptive transfer of eosinophils or administration of CXCL13 corrected this defect. Administration of the 12/15-LOX-derived mediator lipoxin A4 (LXA4) increased the expression of CXCL13 and restored the defect of lymph node hypertrophy in eosinophil-deficient mice. These results demonstrate that eosinophils control the resolution of inflammation and draining lymph node hypertrophy through proresolving lipid mediators and the CXCL13 pathway in mice.-Tani, Y., Isobe, Y., Imoto, Y., Segi-Nishida, E., Sugimoto, Y., Arai, H., Arita, M. Eosinophils control the resolution of inflammation and draining lymph node hypertrophy through the proresolving mediators and CXCL13 pathway in mice. PMID:24891522

  6. Floating Pennies Demonstration

    NSDL National Science Digital Library

    The Materials Science and Technology Teacher's Workshop (MAST) provides this demonstration on the different reactivities of copper and zinc to hydrochloric acid. In this module, the reactivities of copper and zinc to hydrochloric acid will be used to separate the two metals in a post-1983 penny. The percent of zinc and of copper can be calculated as well as the economic value of each. The lesson includes a step by step explanation of the laboratory procedure. Discussion questions and a video clip are also included.

  7. NAVAJO ELECTRIFICATION DEMONSTRATION PROJECT

    SciTech Connect

    Terry W. Battiest

    2008-06-11

    The Navajo Electrification Demonstration Project (NEDP) is a multi-year project which addresses the electricity needs of the unserved and underserved Navajo Nation, the largest American Indian tribe in the United States. The program serves to cumulatively provide off-grid electricty for families living away from the electricty infrastructure, line extensions for unserved families living nearby (less than 1/2 mile away from) the electricity, and, under the current project called NEDP-4, the construction of a substation to increase the capacity and improve the quality of service into the central core region of the Navajo Nation.

  8. Santa Clara Demonstration Status

    SciTech Connect

    Leo, Anthony J.; Skok, Andrew J.; O'Shea, Thomas P.

    1996-08-01

    Fuel Cell Engineering Corporation (FCE) is in the fourth year of a DOE Cooperative Agreement Program (private-sector cost-shared) aimed at the demonstration of ERC's direct carbonate fuel cell (DFC) technology at full scale. FCE is a wholly owned subsidiary of Energy Research Corporation (ERC), which has been pursuing the development of the DFC for commercialization near the end of this decade. The DFC produces power directly from hydrocarbon fuels electrochemically, without the need for external reforming or intermediate mechanical conversion steps. As a result, the DFC has the potential to achieve very high efficiency with very low levels of environmental emissions. Modular DFC power plants, which can be shop-fabricated and sited near the user, are ideally suited for distributed generation, cogeneration, industrial, and defense applications. This project is an integral part of the ERC effort to commercialize the technology to serve these applications. Potential users of the commercial DFC power plant under development at ERC will require that the technology be demonstrated at or near the full scale of the commercial products. The objective of the Santa Clara Demonstration Project (SCDP) is to provide the first such demonstration of the technology. The approach ERC has taken in the commercialization of the DFC is described in detail elsewhere [1]. Briefly, an aggressive core technology development program is in place which is focused by ongoing contact with customers and vendors to optimize the design of the commercial power plant. ERC has selected a 2.85 MW power plant unit for initial market entry. Two ERC subsidiaries are supporting the commercialization effort: The Fuel Cell Manufacturing Corporation (FCMC) and the Fuel Cell Engineering Corporation (FCE). FCMC manufactures carbonate stacks and multi-stack modules, currently from its manufacturing facility in Torrington, CT. FCE is responsible for power plant design, integration of all subsystems, sales/marketing, and client services. The commercial product specifications have been developed by working closely with the Fuel Cell Commercialization Group (FCCG). FCCG members include municipal utilities, rural electric co-ops, and investor owned utilities who have expressed interest in being the initial purchasers of the first commercial DFC power plants. The utility participants in the SCDP have been drawn from the membership of FCCG. FCE is serving as the prime contractor for the design, construction, and testing of the SCDP Plant, and FCMC has manufactured the multi-stack submodules used in the DC power section of the plant. Fluor Daniel Inc. (FDI) served as the architect-engineer for the design and construction of the plant, and also provided support to the design of the multi-stack submodules. FDI is also assisting the ERC companies in commercial power plant design.

  9. Slime: Classroom Demonstration

    NSDL National Science Digital Library

    Goodwin, Debbie

    The Materials Education Resource Center has provided this hands on lab activity created by Andrew Nydam and Debbie Goodwin. The activity demonstrates property change due to crosslinking in slime formed from mixing PVA and Borax solution. This lab will teach the students the important concepts of plastic flow vs. elastic flow, hydrogen bonding, and viscosity. This pdf document provides instructions for the instructor, recommendations to ensure the experiment goes smoothly for both students and teacher, and an evaluation packet for the students to complete once the lab is finished. All in all, this is a fun and education tool for any high school or community college science classroom.

  10. Statistic Simulations and Demonstrations

    NSDL National Science Digital Library

    Over twenty Java applets from Online Statistics are presented on this site. The applets cover most of the major points taught in an introductory statistics course. One quality that makes this site stand out from others is the excellent background information presented with many applets, which lets users read about a concept and see it visually at the same time. Topics include applications of the central limit theorem, regression, analysis of variance, and many more. The applets are all very easy to use, and they are certainly valuable demonstrations for any high school or college student in statistics.

  11. Defective generation of a humoral immune response is associated with a reduced incidence and severity of collagen-induced arthritis in microsomal prostaglandin E synthase-1 null mice.

    PubMed

    Kojima, Fumiaki; Kapoor, Mohit; Yang, Lihua; Fleishaker, Erica L; Ward, Martin R; Monrad, Seetha U; Kottangada, Ponnappa C; Pace, Charles Q; Clark, James A; Woodward, Jerold G; Crofford, Leslie J

    2008-06-15

    Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH(2) to PGE(2). The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clinical model of bovine collagen-induced arthritis. mPGES-1 null and heterozygous mice exhibited decreased incidence and severity of arthritis compared with wild-type mice in a gene dose-dependent manner. Histopathological examination revealed significant reduction in lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type littermates. mPGES-1 deficient mice also exhibited attenuation of mechanical nociception in a gene dose-dependent manner. In addition, mPGES-1 null and heterozygous mice showed a marked reduction of serum IgG against type II collagen, including subclasses IgG1, IgG2a, IgG2b, IgG2c, and IgG3, compared with wild-type mice, which correlated with the reduction in observed inflammatory features. These results demonstrate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced arthritis, at least in part, by blocking the development of a humoral immune response against type II collagen. Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis. PMID:18523303

  12. The IBL BOC Demonstrator

    E-print Network

    Ancu, J; The ATLAS collaboration; Falchieri, D; Flick, T; Gabrielli, A; Grosse-Knetter, J; Heim, T; Joseph, J; Krieger, N; Kugel, A; Morettini, P; Neumann, M; Polini, A; Schneider, B; Schroer, N

    2011-01-01

    The IBL is a new pixel detector layer to be installed at the ATLAS experiment at the LHC, CERN in 2013. It will be integrated into the general pixel readout and software framework, hence the off-detector readout electronics has to support the new front-end electronics whilst maintaining a high degree of interoperability to the components of the existing system. The off-detector readout is realised using a number of VME card pairs – ROD and BOC – plus a VME crate controller and a custom timing distribution system. The main elements of the new BOC design comprise optical interfaces towards the detector, signal conditioning and data recovery logic. We present the demonstrator used to verify the design approach. The demonstrator is based on a XILINX SP605 FPGA evaluation board and uses a Microblaze processor inside the FPGA to provide easy and flexible access to all essential BOC functions and the corresponding emulator modules, which enable full test of the entire BOC functionality even without any external ...

  13. Vault demonstration program. [Near surface vault storage

    SciTech Connect

    Scott, S.H.

    1987-01-01

    There is a continuing expansion of the threats that must be countered at weapon storage areas with respect to both the security and survivability of the stored weapons. These threats will continue to evolve into the 21st century. One approach to counter these threats is to increase the storage hardness for the stored materials. The goal of this program, which is sponsored and funded by the Defense Nuclear Agency, is to demonstrate near-surface vault storage for a variety of stored materials. Two vault designs are being demonstrated as part of the program. A full feature vault incorporates many features to enhance the vault operational capabilities. These include a self-contained internal lift, a back-up drive system, flexible interior storage, and sensors with alarm status reporting. The Simplified Storage Vault (SSV) eliminates many of these features to reduce to a minimum the installed cost of vault storage. Features to enhance the survivability hardness of stored materials are incorporated into both vault designs. The full feature vault installation is complete and is undergoing engineering test and evaluation. The SSV installation is to be completed in August 1987. Both vault designs and evaluation results to date are described. 3 refs., 5 figs.

  14. ApoE-Deficient Mice Develop Lesions of All Phases of Atherosclerosis Throughout the Arterial Tree

    Microsoft Academic Search

    Yutaka Nakashima; Andrew S. Plump; Elaine W. Raines; Jan L. Breslow; Russell Ross

    2010-01-01

    Initial description of apolipoprotein (apo) E-de- ficient transgenic mice demonstrated the development of severe hypercholesterolemia due to probable delayed clear- ance of large atherogenic particles from the circulation. Ex- amination of these mice demonstrated foam cell accumulation in the aortic root and pulmonary arteries by 10 weeks of age. In the present study, the animals were fed either chow or

  15. Electrodynamic Dust Shield Demonstrator

    NASA Technical Reports Server (NTRS)

    Stankie, Charles G.

    2013-01-01

    The objective of the project was to design and manufacture a device to demonstrate a new technology developed by NASA's Electrostatics and Surface Physics Laboratory. The technology itself is a system which uses magnetic principles to remove regolith dust from its surface. This project was to create an enclosure that will be used to demonstrate the effectiveness of the invention to The Office of the Chief Technologist. ONE of the most important challenges of space exploration is actually caused by something very small and seemingly insignificant. Dust in space, most notably on the moon and Mars, has caused many unforeseen issues. Dirt and dust on Earth, while a nuisance, can be easily cleaned and kept at bay. However, there is considerably less weathering and erosion in space. As a result, the microscopic particles are extremely rough and abrasive. They are also electrostatically charged, so they cling to everything they make contact with. This was first noted to be a major problem during the Apollo missions. Dust would stick to the spacesuits, and could not be wiped off as predicted. Dust was brought back into the spacecraft, and was even inhaled by astronauts. This is a major health hazard. Atmospheric storms and other events can also cause dust to coat surfaces of spacecraft. This can cause abrasive damage to the craft. The coating can also reduce the effectiveness of thermal insulation and solar panels.' A group of engineers at Kennedy Space Center's Electrostatics and Surface Physics Laboratory have developed a new technology, called the Electrodynamic Dust Shield, to help alleviate these problems. It is based off of the electric curtain concept developed at NASA in 1967. "The EDS is an active dust mitigation technology that uses traveling electric fields to transport electrostatically charged dust particles along surfaces. To generate the traveling electric fields, the EDS consists of a multilayer dielectric coating with an embedded thin electrode grid running a multiphase low frequency AC signal. Electrostatically charged particles, such as those encountered on the moon, Mars, or an asteroid, are carried along by the traveling field due to the action of Coulomb and dielectrophoretic forces."2 The technical details have been described in a separate article. This document details the design and construction process of a small demonstration unit. Once finished, this device will go to the Office of the ChiefTechnologist at NASA headquarters, where it will be used to familiarize the public with the technology. 1 NASA KSC FO Intern, Prototype Development Laboratory, Kennedy Space Center, University of Central Florida Kennedy Space

  16. Fusion Power Demonstration III

    SciTech Connect

    Lee, J.D. (ed.)

    1985-07-01

    This is the third in the series of reports covering the Fusion Power Demonstration (FPD) design study. This volume considers the FPD-III configuration that incorporates an octopole end plug. As compared with the quadrupole end-plugged designs of FPD-I and FPD-II, this octopole configuration reduces the number of end cell magnets and shortens the minimum ignition length of the central cell. The end-cell plasma length is also reduced, which in turn reduces the size and cost of the end cell magnets and shielding. As a contiuation in the series of documents covering the FPD, this report does not stand alone as a design description of FPD-III. Design details of FPD-III subsystems that do not differ significantly from those of the FPD-II configuration are not duplicated in this report.

  17. Demonstrating An Epidemic

    NSDL National Science Digital Library

    M. Beth Powel

    2009-01-01

    This experiment allows learners to experience a small scale "epidemic," demonstrating the ease with which disease organisms are spread, and enables learners to determine the originator of the "epidemic." Learners will transfer live bacteria by hand contact, then transfer an inoculum to a nutrient agar plate for 24 hour incubation. After incubation, plates are observed for growth of the microbial agent. By arranging the plates in the order of hand contact, it can be determined which individual received the original contaminant and started the "epidemic," which individuals transferred the organism yet did not grow it out (carriers), and how dosage, or amount of contamination, affects getting a disease. Other means of microbial transmission (air, water, body fluids, fomites) may also be discussed. This lesson guide includes safety precautions, questions, and an additional activity to simulate vaccination.

  18. The GLORIA demonstrator experiment

    NASA Astrophysics Data System (ADS)

    Majcher, A.; ?wiek, A.; ?wiok, M.; Mankiewicz, L.; Zaremba, M.; ?arnecki, A. F.

    2013-10-01

    GLORIA stands for "GLObal Robotic-telescopes Intelligent Array" and it is the first free and open-access network of robotic telescopes on the world. Based on a Web 2.0 environment amateur and professional users can do research in astronomy by observing with robotic telescopes, and/or analyzing data acquired with GLORIA, or from other free access databases. GLORIA project develops free standards, protocols and tools for controlling Robotic Telescopes and related instrumentation, for scheduling observations in the telescope network, and for conducting so-called off-line experiments based on the analysis of astronomical data. This contribution summarizes the implementation and results from the first research level off-line demonstrator experiment implemented in GLORIA, which was base on the data collected with the "Pi of the Sky" telescope in Chile.

  19. Shuttle bay telerobotics demonstration

    NASA Technical Reports Server (NTRS)

    Chun, W.; Cogeos, P.

    1987-01-01

    A demonstration of NASA's robotics capabilities should be a balanced agenda of servicing and assembly tasks combined with selected key technical experiments. The servicing tasks include refueling and module replacement. Refueling involves the mating of special fluid connectors while module replacement requires an array of robotic technologies such as special tools, the arm of a logistics tool, and the precision mating of orbital replacement units to guides. The assembly task involves the construction of a space station node and truss structure. The technological experiments will focus on a few important issues: the precision manipulation of the arms by a teleoperator, the additional use of several mono camera views in conjunction with the stereo system, the use of a general purpose end effector versus a caddy of tools, and the dynamics involved with using a robot with a stabilizer.

  20. Jennings Demonstration PLant

    SciTech Connect

    Russ Heissner

    2010-08-31

    Verenium operated a demonstration plant with a capacity to produce 1.4 million gallons of cellulosic ethanol from agricultural resiues for about two years. During this time, the plant was able to evaluate the technical issues in producing ethanol from three different cellulosic feedstocks, sugar cane bagasse, energy cane, and sorghum. The project was intended to develop a better understanding of the operating parameters that would inform a commercial sized operation. Issues related to feedstock variability, use of hydrolytic enzymes, and the viability of fermentative organisms were evaluated. Considerable success was achieved with pretreatment processes and use of enzymes but challenges were encountered with feedstock variability and fermentation systems. Limited amounts of cellulosic ethanol were produced.

  1. Emergent feature modularization

    Microsoft Academic Search

    Márcio Ribeiro; Humberto Pacheco; Leopoldo Teixeira; Paulo Borba

    2010-01-01

    Virtual Separation of Concerns reduces the drawbacks of implementing product line variability with preprocessors. Developers can focus on certain features and hide others of no interest. However, these features eventually share elements between them, which might break feature modularization, since modifications in a feature result in problems for another. We present the concept of emergent feature modularization, which aims to

  2. Mapping Pathological Phenotypes in Reelin Mutant Mice

    PubMed Central

    Michetti, Caterina; Romano, Emilia; Altabella, Luisa; Caruso, Angela; Castelluccio, Paolo; Bedse, Gaurav; Gaetani, Silvana; Canese, Rossella; Laviola, Giovanni; Scattoni, Maria Luisa

    2014-01-01

    Autism Spectrum Disorders (ASD) are neurodevelopmental disorders with multifactorial origin characterized by social communication deficits and the presence of repetitive behaviors/interests. Several studies showed an association between the reelin gene mutation and increased risk of ASD and a reduced reelin expression in some brain regions of ASD subjects, suggesting a role for reelin deficiency in ASD etiology. Reelin is a large extracellular matrix glycoprotein playing important roles during development of the central nervous system. To deeply investigate the role of reelin dysfunction as vulnerability factor in ASD, we assessed the behavioral, neurochemical, and brain morphological features of reeler male mice. We recently reported a genotype-dependent deviation in the ultrasonic vocal repertoire and a general delay in motor development of reeler pups. We now report that adult male heterozygous (Het) reeler mice did not show social behavior and communication deficits during male–female social interactions. Wildtype and Het mice showed a typical light/dark locomotor activity profile, with a peak during the central interval of the dark phase. However, when faced with a mild stressful stimulus (a saline injection) only Het mice showed an over response to stress. In addition to the behavioral studies, we conducted high performance liquid chromatography and magnetic resonance imaging and spectroscopy to investigate whether reelin mutation influences brain monoamine and metabolites levels in regions involved in ASD. Low levels of dopamine in cortex and high levels of glutamate and taurine in hippocampus were detected in Het mice, in line with clinical data collected on ASD children. Altogether, our data detected subtle but relevant neurochemical abnormalities in reeler mice supporting this mutant line, particularly male subjects, as a valid experimental model to estimate the contribution played by reelin deficiency in the global ASD neurobehavioral phenotype. PMID:25237666

  3. Oxidative stress in mice

    Microsoft Academic Search

    Robert Domitrovi?; Marin Tota; ?edomila Milin

    2006-01-01

    The aim of this study was to analyze the effect of high dietary Fe on liver antioxidant status in mice fed a corn-oil-enriched\\u000a diet. Male Balb\\/c mice were fed for 3 wk with a standard diet enriched with 5% by weight of corn oil with adequate Fe (FCO\\u000a diet) or supplemented with 1% carbonyl Fe (FCOFe diet). The control group

  4. Transgenic knockout mice with exclusively human sickle hemoglobinand sickle cell disease

    SciTech Connect

    Paszty, C.; Brion, C.; Manci, E.; Witkowska, E.; Stevens, M.; Narla, M.; Rubin, E.

    1997-06-13

    To create mice expressing exclusively human sicklehemoglobin (HbS), transgenic mice expressing human alpha-, gamma-, andbeta[S]-globin were generated and bred with knockout mice that haddeletions of the murine alpha- and beta-globin genes. These sickle cellmice have the major features (irreversibly sickled red cells, anemia,multiorgan pathology) found in humans with sickle cell disease and, assuch, represent a useful in vivo system to accelerate the development ofimproved therapies for this common genetic disease.

  5. Quinolones potentiate cefazolin-induced seizures in DBA/2 mice.

    PubMed

    De Sarro, A; Zappalá, M; Chimirri, A; Grasso, S; De Sarro, G B

    1993-07-01

    The behavioral and convulsant effects of cefazolin, a beta-lactam derivative, were studied after intraperitoneal administration to DBA/2 mice, a strain genetically susceptible to sound-induced seizures, and Swiss mice. DBA/2 mice were more susceptible to seizures induced by cefazolin than were Swiss mice. The proconvulsant effects of some quinolones on seizures evoked by intraperitoneal administration of cefazolin were also evaluated in DBA/2 mice. Our study also demonstrated that the order of proconvulsant activity in our epileptic model was pefloxacin > enoxacin > ofloxacin > rufloxacin > norfloxacin > cinoxacin > ciprofloxacin > nalidixic acid. The relationships between the chemical structures and proconvulsant activities of quinolone derivatives were studied. The relationship between lipophilicity and proconvulsant activity was also investigated. PMID:8395790

  6. Quinolones potentiate cefazolin-induced seizures in DBA/2 mice.

    PubMed Central

    De Sarro, A; Zappalá, M; Chimirri, A; Grasso, S; De Sarro, G B

    1993-01-01

    The behavioral and convulsant effects of cefazolin, a beta-lactam derivative, were studied after intraperitoneal administration to DBA/2 mice, a strain genetically susceptible to sound-induced seizures, and Swiss mice. DBA/2 mice were more susceptible to seizures induced by cefazolin than were Swiss mice. The proconvulsant effects of some quinolones on seizures evoked by intraperitoneal administration of cefazolin were also evaluated in DBA/2 mice. Our study also demonstrated that the order of proconvulsant activity in our epileptic model was pefloxacin > enoxacin > ofloxacin > rufloxacin > norfloxacin > cinoxacin > ciprofloxacin > nalidixic acid. The relationships between the chemical structures and proconvulsant activities of quinolone derivatives were studied. The relationship between lipophilicity and proconvulsant activity was also investigated. PMID:8395790

  7. Long-Term Effects of Ovariectomy on Osteoporosis and Obesity in Estrogen-Receptor-?–Deleted Mice

    PubMed Central

    Seidlova-Wuttke, Dana; Nguyen, Ba Tiep; Wuttke, Wolfgang

    2012-01-01

    Untreated BERKO mice demonstrate few abnormalities in bone phenotype and recent ovariectomy has few effects on various bone characteristics in these mice. Long-term studies on the bone phenotype of intact and ovariectomized mice are unavailable. Using quantitative computed tomography (qCT), we determined various parameters of the metaphysis of the tibia in sham-ovariectomized (intact) and ovariectomized BERKO and wildtype mice. Body weight and estrogen-regulated fat were also measured. Mice underwent surgery (ovariectomy or sham) at 3 mo of age, and qCT analysis was performed every 2 to 4 mo until mice were 12 mo old. Ovariectomized wildtype mice gained body weight and their fat depot increased in size within 2 mo after ovariectomy. Obesity developed later in ovariectomized BERKO mice, which became significantly heavier than their wildtype counterparts. Ovariectomized wildtype mice lost trabecular density more rapidly than did ovariectomized BERKO mice, which did not show similar loss in trabecular density until at least 7 mo after ovariectomy. At the latest studied time point (9 mo after surgery), cortical area was significantly larger in ovariectomized BERKO mice than ovariectomized wildtype mice. The absence of ER? in ovariectomized BERKO mice during the first 3 to 5 mo after ovariectomy had protective effects against obesity and trabecular rarification; this protective effect disappeared at later time points. PMID:22330645

  8. Long-term effects of ovariectomy on osteoporosis and obesity in estrogen-receptor-?-deleted mice.

    PubMed

    Seidlova-Wuttke, Dana; Nguyen, Ba Tiep; Wuttke, Wolfgang

    2012-02-01

    Untreated BERKO mice demonstrate few abnormalities in bone phenotype and recent ovariectomy has few effects on various bone characteristics in these mice. Long-term studies on the bone phenotype of intact and ovariectomized mice are unavailable. Using quantitative computed tomography (qCT), we determined various parameters of the metaphysis of the tibia in sham-ovariectomized (intact) and ovariectomized BERKO and wildtype mice. Body weight and estrogen-regulated fat were also measured. Mice underwent surgery (ovariectomy or sham) at 3 mo of age, and qCT analysis was performed every 2 to 4 mo until mice were 12 mo old. Ovariectomized wildtype mice gained body weight and their fat depot increased in size within 2 mo after ovariectomy. Obesity developed later in ovariectomized BERKO mice, which became significantly heavier than their wildtype counterparts. Ovariectomized wildtype mice lost trabecular density more rapidly than did ovariectomized BERKO mice, which did not show similar loss in trabecular density until at least 7 mo after ovariectomy. At the latest studied time point (9 mo after surgery), cortical area was significantly larger in ovariectomized BERKO mice than ovariectomized wildtype mice. The absence of ER? in ovariectomized BERKO mice during the first 3 to 5 mo after ovariectomy had protective effects against obesity and trabecular rarification; this protective effect disappeared at later time points. PMID:22330645

  9. Plug cluster module demonstration

    NASA Technical Reports Server (NTRS)

    Rousar, D. C.

    1978-01-01

    The low pressure, film cooled rocket engine design concept developed during two previous ALRC programs was re-evaluated for application as a module for a plug cluster engine capable of performing space shuttle OTV missions. The nominal engine mixture ratio was 5.5 and the engine life requirements were 1200 thermal cycles and 10 hours total operating life. The program consisted of pretest analysis; engine tests, performed using residual components; and posttest analysis. The pretest analysis indicated that operation of the operation of the film cooled engine at O/F = 5.5 was feasible. During the engine tests, steady state wall temperature and performance measurement were obtained over a range of film cooling flow rates, and the durability of the engine was demonstrated by firing the test engine 1220 times at a nominal performance ranging from 430 - 432 seconds. The performance of the test engine was limited by film coolant sleeve damage which had occurred during previous testing. The post-test analyses indicated that the nominal performance level can be increased to 436 seconds.

  10. Apollo 14 composite casting demonstration

    NASA Technical Reports Server (NTRS)

    1971-01-01

    This program assisted in the design and implementation of the composite casting demonstration for the Apollo 14 mission. Both flight and control samples were evaluated. Some conclusions resulting from a comparison of the flight and control samples were: (1) Solidification in neither the flight nor control samples was truly directional. (2) Apparent intermittent contact of the melt with the container in the flight samples led to unusual nucleation and growth structures. (3) There was greater uniformity, on a macro scale, of both pores and structural features in the flight sample; presumably the result of the reduced gravity conditions. (4) It seems quite feasible to produce enhanced dispersions of gases and dense phases in a melt which is solidified in reduced gravity. (5) A two-stage heating/cooling cycle may help directional solidification. (6) Sample materials should be selected from materials in which the dispersant fully wets the matrix material. (7) Experiments should be conducted in two modes: (1) where the melt is in good thermal contact with the container, and (2) where the melt is in a free-float condition.

  11. Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumors in patients

    PubMed Central

    Grisanzio, Chiara; Seeley, Apryle; Chang, Michelle; Collins, Michael; Di Napoli, Arianna; Cheng, Su-Chun; Percy, Andrew; Beroukhim, Rameen; Signoretti, Sabina

    2013-01-01

    Renal cell carcinoma (RCC) is an aggressive malignancy with limited responsiveness to existing treatments. In vivo models of human cancer, including RCC, are critical for developing more effective therapies. Unfortunately, current RCC models do not accurately represent relevant properties of the human disease. The goal of this study was to develop clinically relevant animal models of RCC for preclinical investigations. We transplanted intact human tumor tissue fragments orthotopically in immunodeficient mice. The xenografts were validated by comparing the morphologic, phenotypic, and genetic characteristics of the kidney tumor tissues before and after implantation. Twenty kidney tumors were transplanted into mice. Successful tumor growth was detected in 19 cases (95%). The histopathologic and immunophenotypic features of the xenografts and those of the original tumors largely overlapped in all the cases. Evaluation of genetic alterations in a subset of 10 cases demonstrated that the grafts largely retained the genetic features of the pre-implantation RCC tissues. Indeed, primary tumors and corresponding grafts displayed identical VHL mutations. Moreover, an identical pattern of DNA copy amplification or loss was observed in 6 of 10 cases (60%). In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients. These models will be invaluable for in vivo preclinical drug testing, and for deeper understanding of kidney carcinogenesis. PMID:21710693

  12. MODELING METRIC DISTANCES OF DENDRITE SPINES OF MICE BASED ON MORPHOMETRIC MEASURES

    E-print Network

    Hurdal, Monica K.

    MODELING METRIC DISTANCES OF DENDRITE SPINES OF MICE BASED ON MORPHOMETRIC MEASURES E. Ceyhan1* , R of mice based on various morphometric (shape and size related) measures, condition, and type of the spines numerical morphomet- ric measures to obtain uncorrelated morphometric features, since PCA provides

  13. Favorite Demonstrations: Gaseous Diffusion: A Demonstration of Graham's Law.

    ERIC Educational Resources Information Center

    Kauffman, George B.; Ebner, Ronald D.

    1985-01-01

    Describes a demonstration in which gaseous ammonia and hydrochloric acid are used to illustrate rates of diffusion (Graham's Law). Simple equipment needed for the demonstration include a long tube, rubber stoppes, and cotton. Two related demonstrations are also explained. (DH)

  14. The chemokine CCL5 induces CCR1-mediated hyperalgesia in mice inoculated with NCTC 2472 tumoral cells.

    PubMed

    Pevida, M; Lastra, A; Meana, Á; Hidalgo, A; Baamonde, A; Menéndez, Luis

    2014-02-14

    Although the expression of the chemokine receptor CCR1 has been demonstrated in several structures related to nociception, supporting the nociceptive role of chemokines able to activate it, the involvement of CCR1 in neoplastic pain has not been previously assessed. We have assayed the effects of a CCR1 antagonist, J113863, in two murine models of neoplastic hyperalgesia based on the intratibial injection of either NCTC 2472 fibrosarcoma cells, able to induce osteolytic bone injury, or B16-F10 melanoma cells, associated to mixed osteolytic/osteoblastic bone pathological features. The systemic administration of J113863 inhibited thermal and mechanical hyperalgesia but not mechanical allodynia in mice inoculated with NCTC 2472 cells. Moreover, in these mice, thermal hyperalgesia was counteracted following the peritumoral (10-30?g) but not spinal (3-5?g) administration of J113863. In contrast, hyperalgesia and allodynia measured in mice inoculated with B16-F10 cells remained unaffected after the administration of J113863. The inoculation of tumoral cells did not modify the levels of CCL3 at tumor or spinal cord. In contrast, although the concentration of CCL5 remained unmodified in mice inoculated with B16-F10 cells, increased levels of this chemokine were measured in tumor-bearing limbs, but not the spinal cord, of mice inoculated with NCTC 2472 cells. Increased levels of CCL5 were also found following the incubation of NCTC 2472, but not B16-F10, cells in the corresponding culture medium. The intraplantar injection of CCL5 (0.5ng) to naïve mice evoked thermal hyperalgesia prevented by the coadministration of J113863 or the CCR5 antagonist, d-Ala-peptide T-amide (DAPTA), demonstrating that CCL5 can induce thermal hyperalgesia in mice through the activation of CCR1 or CCR5. However, contrasting with the inhibitory effect evoked by J113863, the systemic administration of DAPTA did not prevent tumoral hyperalgesia. Finally, the peritumoral administration of an anti-CCL5 antibody completely inhibited thermal hyperalgesia evoked by the inoculation of NCTC 2472 cells. PMID:24316469

  15. Lumican overexpression exacerbates lipopolysaccharide-induced renal injury in mice.

    PubMed

    Lu, Xiao-Mei; Ma, Ling; Jin, Yu-Nan; Yu, Yan-Qiu

    2015-09-01

    The present study aimed to investigate the role of lumican in mice with endotoxin-induced acute renal failure (ARF). Lumican transgenic mice and wild?type mice were injected with lipopolysaccharide (LPS; 10 mg/kg) to establish a model of ARF. The mice were sacrificed at 24 h and the blood and renal tissue samples were collected. The value of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured to determine renal function. An ELISA was used to determined the concentrations of renal cytokines, including tumor necrosis factor (TNF)?, interleukin (IL)?6, IL?4 and IL?10. The protein expression levels of Toll-like receptor (TLR4) and nuclear factor (NF)?B in renal tissues were assessed using western blot analysis. Terminal deoxynucleotidyl transferase?mediated dUTP nick end labeling was performed to monitor apoptosis of renal tissue. Light microscopy and electron microscopy were used to observe structural changes in the renal tissues. Following the administration of LPS, the SCr and BUN values of mice in the lumican transgenic group were higher compared with those in the control group. The expression levels of renal TLR4, NF?B, TNF?, IL?6, IL?4 and IL?10 were upregulated in the lumican transgenic mice compared with those in the wild?type control group. Apoptosis was detected predominantly on the renal tubule. There was a significant difference in the optical density of apoptotic bodies between the control mice and the lumican transgenic mice. Light and electron microscopy demonstrated more severe renal tissue injury in the lumican transgenic mice compared with that in the control mice. In conclusion, LPS may cause excessive apoptosis in the renal tubular cells via the TLR4 signal transduction pathway, a decrease in the number of renal tubular cells and ARF. Lumican may be important in mice with LPS-induced ARF. PMID:26081832

  16. Experimental infection of mice with bovine viral diarrhea virus.

    PubMed

    Seong, Giyong; Oem, Jae-Ku; Lee, Kyung-Hyun; Choi, Kyoung-Seong

    2015-06-01

    The objective of this study was to test the ability of bovine viral diarrhea virus (BVDV) to infect mice. Two mice each were either mock infected or inoculated with one of three BVDV strains by the intraperitoneal (IP) (n = 8) or intranasal (IN) (n = 8) route. All mice were euthanized at day 7 postinfection (p.i.). None of the infected mice exhibited any clinical signs of illness; however, the tissues harvested after BVDV challenge showed significant histopathological changes. Blood samples from five mice that were injected IP and one mouse that was inoculated IN were positive for BVDV by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry (IHC) was used to assess the presence of viral antigen in the organs of mice infected with three BVDV strains. In IP-injected mice, BVDV antigen was detected in the spleen (5/6), mesenteric lymph nodes (4/6), lymphatic tissue of the lung (3/6), lung (1/6), and stomach (1/6) of the infected mice; however, it was not detected in the liver (0/6) or kidney (0/6). In IN-inoculated mice, BVDV antigen was detected in the lung and mesenteric lymph nodes of one BVDV-infected mouse but was not detected in other tissues. The results of this study suggest that the spleen is the most reliable tissue for BVDV antigen detection using IHC in the IP-injected group. Our study demonstrates that mice can be infected by BVDV. This is the first report of BVDV infection in mice. PMID:25850760

  17. Immune Responses to Candida albicans in Genetically Distinct Mice

    PubMed Central

    Hector, Richard F.; Domer, Judith E.; Carrow, Emily W.

    1982-01-01

    Mice from six genetically distinct strains were examined for their immune responses to Candida albicans in in vitro and in vivo assays, and naive mice and mice immunized with the fungus were challenged intravenously with three different doses of C. albicans to determine differences in susceptibility. Naive mice from the six groups showed substantial differences in resistance to challenge based on mortalities and quantitative cultures of kidneys, with mice from strains C57BL/6J and BALB/cByJ showing the most resistance; mice from strains A/J, C3H/HeJ, and CBA/J showing moderate susceptibility; and mice from strain DBA/2J showing the highest degree of susceptibility to challenge. Unimmunized mice from strains C57BL/6J and BALB/cByJ did not produce detectable levels of Candida-specific antibody by the end of the 28-day observation period when challenged intravenously, but the other strains did. Immunized mice showed a degree of protection to challenge, with all groups except mice from strain BALB/cByJ showing a reduction of two to three log units in the level of colonization in their kidneys and all strains producing significant levels of antibody. Additionally, the immunized mice of all strains developed substantial levels of delayed-type hypersensitivity and demonstrated nearly identical lymphocyte proliferative responses to Candida antigens. The results indicate that resistance to systemic candidiasis is dependent upon a combination of innate factors, predominately an intact complement system, and the acquisition of an immune response, most likely of a cell-mediated type. Additionally, the findings suggest that genetic control of acquired resistance to C. albicans may not be associated with the H-2 complex. PMID:6759403

  18. Immune Destruction of Larval Taenia crassiceps in Mice

    PubMed Central

    Mooney, K. A.; Spolski, R. J.; See, E. J.; Kuhn, R. E.

    2000-01-01

    Immune destruction of larval Taenia crassiceps was examined by first injecting BALB/cJ mice subcutaneously with larval buds and 30 to 60 days later challenging the mice with larvae injected into the peritoneal cavity. The larvae injected intraperitoneally (i.p.) secondarily are killed by host cells that completely encase the larvae in a thick sheath. The peritoneal exudate cells and the cytokines they produced were characterized by flow cytometry, enzyme-linked immunosorbent assays (ELISAs), and reverse transcription PCR (RT-PCR). No changes in percentage of CD4+ T cells, CD8+ T cells, B1 cells, or macrophages were detected in the peritoneal cavities of mice that were killing larvae compared to mice with a primary 7-day infection i.p. Both RT-PCR and ELISA demonstrated a decrease in cytokines including gamma interferon (IFN-?), interleukin-4 (IL-4), and IL-10 in mice that were killing the larvae compared to control mice infected for 30 to 60 days i.p. alone, although there was little difference compared to mice infected for 7 days i.p. alone. Serum cytokine levels in mice that were killing the larvae showed a decrease in IFN-? and IL-4, an increase in IL-10 when compared to mice infected for 30 to 60 days i.p. alone, and increases in all cytokines compared to mice infected for 7 days i.p. alone. Inhibition of nitric oxide production did not significantly affect the number or the viability of larvae in the peritoneal cavity of mice that were killing larvae during secondary infection. PMID:10768922

  19. Status of the Medicaid competition demonstrations

    PubMed Central

    Hurley, Robert E.

    1986-01-01

    In 1982, the Health Care Financing Administration approved funding for demonstration programs in six States to test a variety of alternative delivery strategies for Medicaid recipients. A number of innovative health service delivery features have been used in these programs, including competition, capitation, case management, and limitations on provider choice. These strategies have been tried in order to address the key Medicaid problems of cost containment and access to appropriate and high quality care. This article provides an overview of how the demonstration sites have approached the task of designing, developing, and implementing their various programs. PMID:10312013

  20. Satellite Feature Identification: Atmospheric Rivers

    NSDL National Science Digital Library

    2014-09-14

    The Satellite Feature Identification: Atmospheric Rivers module presents the global moisture transport phenomenon known as the Atmospheric River (AR). ARs are responsible for transporting the majority of maritime moisture from low to middle latitudes. Advanced satellite products, including Integrated Water Vapor and Total Precipitable Water, provide excellent observations of AR development and evolution.. This module demonstrates the usefulness of these products in forecasting the impacts of ARs, especially when they are combined with numerical weather prediction products. Several AR case studies highlight the importance of using satellite information regarding ARs and allow the user to practice forecasting their impacts. This module is part of the series: "Dynamic Feature Identification: The Satellite Palette".

  1. Effects of Simulated Heat Waves on ApoE-/- Mice

    PubMed Central

    Wang, Chunling; Zhang, Shuyu; Tian, Ying; Wang, Baojian; Shen, Shuanghe

    2014-01-01

    The effects of simulated heat waves on body weight, body temperature, and biomarkers of cardiac function in ApoE-/- mice were investigated. Heat waves were simulated in a meteorological environment simulation chamber according to data from a heat wave that occurred in July 2001 in Nanjing, China. Eighteen ApoE-/- mice were divided into control group, heat wave group, and heat wave BH4 group. Mice in the heat wave and BH4 groups were exposed to simulated heat waves in the simulation chamber. Mice in BH4 group were treated with gastric lavage with BH4 2 h prior to heat wave exposure. Results showed that the heat waves did not significantly affect body weight or ET-1 levels. However, mice in the heat wave group had significantly higher rectal temperature and NO level and lower SOD activity compared with mice in the control group (p < 0.01), indicating that heat wave had negative effects on cardiac function in ApoE-/- mice. Gastric lavage with BH4 prior to heat wave exposure significantly reduced heat wave-induced increases in rectal temperature and decreases in SOD activity. Additionally, pretreatment with BH4 further increased NO level in plasma. Collectively, these beneficial effects demonstrate that BH4 may potentially mitigate the risk of coronary heart disease in mice under heat wave exposure. These results may be useful when studying the effects of heat waves on humans. PMID:24477215

  2. Feature Clustering for Accelerating Parallel Coordinate Descent

    SciTech Connect

    Scherrer, Chad; Tewari, Ambuj; Halappanavar, Mahantesh; Haglin, David J.

    2012-12-06

    We demonstrate an approach for accelerating calculation of the regularization path for L1 sparse logistic regression problems. We show the benefit of feature clustering as a preconditioning step for parallel block-greedy coordinate descent algorithms.

  3. Muscleblind-like 2 (Mbnl2) -deficient mice as a model for myotonic dystrophy.

    PubMed

    Hao, Minqi; Akrami, Kevan; Wei, Ke; De Diego, Carlos; Che, Nam; Ku, Jeong-Hee; Tidball, James; Graves, Michael C; Shieh, Perry B; Chen, Fabian

    2008-02-01

    Myotonic dystrophy (DM), the most common adult-onset muscular dystrophy, is caused by CTG or CCTG microsatellite repeat expansions. Expanded DM mRNA microsatellite repeats are thought to accumulate in the nucleus, sequester Muscleblind proteins, and interfere with alternative mRNA splicing. Muscleblind2 (Mbnl2) is a member of the family of Muscleblind RNA binding proteins (that also include Mbnl1 and Mbnl3) that are known to bind CTG/CCTG RNA repeats. Recently, it was demonstrated that Mbnl1-deficient mice have characteristic features of human DM, including myotonia and defective chloride channel expression. Here, we demonstrate that Mbnl2-deficient mice also develop myotonia and have skeletal muscle pathology consistent with human DM. We also find defective expression and mRNA splicing of the chloride channel (Clcn1) in skeletal muscle that likely contributes to the myotonia phenotype. Our results support the hypothesis that Muscleblind proteins and specifically MBNL2 contribute to the pathogenesis of human DM. PMID:18213585

  4. Preference aversion in mice to bitter substance.

    PubMed

    WARREN, R P

    1963-05-17

    Preference-aversion functions demonstrable for sweet and salty stimuli have been found for a "bitter" substance, sucrose octaacetate, at individually specific concentrations for mice. The data support Schneirla's views correlating stimulus magnitudes and approach-withdrawal. The positive reinforcing value of this bitter substance as a weak stimulus is diminished with continuous exposure and no secondary reinforcement. Avoidance is related to intensity of stimulation rather than modality or postingestion effects. PMID:13998994

  5. Bacterial Conjunctivitis in Mucl Null Mice

    Microsoft Academic Search

    Rachele Kardon; Roger E. Price; JoAnne Julian; Errin Lagow; Scheffer C. G. Tseng; Sandra J. Gendler; Daniel D. Carson

    1999-01-01

    RESULTS. Student's unpaired t-test performed on the eye inflammation frequency of Mucl null mice confirmed a statistical significance (P < 0.01) when compared to wild-type background animals housed in the same room. Analysis of blood samples from affected Mucl null animals detected no common murine viral pathogens. Bacterial analysis of conjunctival swabs and whole eye prepara- tions demonstrated the presence

  6. Atp13a2-deficient mice exhibit neuronal ceroid lipofuscinosis, limited ?-synuclein accumulation and age-dependent sensorimotor deficits

    PubMed Central

    Schultheis, Patrick J.; Fleming, Sheila M.; Clippinger, Amy K.; Lewis, Jada; Tsunemi, Taiji; Giasson, Benoit; Dickson, Dennis W.; Mazzulli, Joseph R.; Bardgett, Mark E.; Haik, Kristi L.; Ekhator, Osunde; Chava, Anil Kumar; Howard, John; Gannon, Matt; Hoffman, Elizabeth; Chen, Yinhuai; Prasad, Vikram; Linn, Stephen C.; Tamargo, Rafael J.; Westbroek, Wendy; Sidransky, Ellen; Krainc, Dimitri; Shull, Gary E.

    2013-01-01

    Mutations in ATP13A2 (PARK9), encoding a lysosomal P-type ATPase, are associated with both Kufor–Rakeb syndrome (KRS) and neuronal ceroid lipofuscinosis (NCL). KRS has recently been classified as a rare genetic form of Parkinson's disease (PD), whereas NCL is a lysosomal storage disorder. Although the transport activity of ATP13A2 has not been defined, in vitro studies show that its loss compromises lysosomal function, which in turn is thought to cause neuronal degeneration. To understand the role of ATP13A2 dysfunction in disease, we disrupted its gene in mice. Atp13a2?/? and Atp13a2+/+ mice were tested behaviorally to assess sensorimotor and cognitive function at multiple ages. In the brain, lipofuscin accumulation, ?-synuclein aggregation and dopaminergic pathology were measured. Behaviorally, Atp13a2?/? mice displayed late-onset sensorimotor deficits. Accelerated deposition of autofluorescent storage material (lipofuscin) was observed in the cerebellum and in neurons of the hippocampus and the cortex of Atp13a2?/? mice. Immunoblot analysis showed increased insoluble ?-synuclein in the hippocampus, but not in the cortex or cerebellum. There was no change in the number of dopaminergic neurons in the substantia nigra or in striatal dopamine levels in aged Atp13a2?/? mice. These results show that the loss of Atp13a2 causes sensorimotor impairments, ?-synuclein accumulation as occurs in PD and related synucleinopathies, and accumulation of lipofuscin deposits characteristic of NCL, thus providing the first direct demonstration that null mutations in Atp13a2 can cause pathological features of both diseases in the same organism. PMID:23393156

  7. Impaired vibration of auditory ossicles in osteopetrotic mice.

    PubMed

    Kanzaki, Sho; Takada, Yasunari; Niida, Shumpei; Takeda, Yoshihiro; Udagawa, Nobuyuki; Ogawa, Kaoru; Nango, Nobuhito; Momose, Atsushi; Matsuo, Koichi

    2011-03-01

    In the middle ear, a chain of three tiny bones (ie, malleus, incus, and stapes) vibrates to transmit sound from the tympanic membrane to the inner ear. Little is known about whether and how bone-resorbing osteoclasts play a role in the vibration of auditory ossicles. We analyzed hearing function and morphological features of auditory ossicles in osteopetrotic mice, which lack osteoclasts because of the deficiency of either cytokine RANKL or transcription factor c-Fos. The auditory brainstem response showed that mice of both genotypes experienced hearing loss, and laser Doppler vibrometry revealed that the malleus behind the tympanic membrane failed to vibrate. Histological analysis and X-ray tomographic microscopy using synchrotron radiation showed that auditory ossicles in osteopetrotic mice were thicker and more cartilaginous than those in control mice. Most interestingly, the malleal processus brevis touched the medial wall of the tympanic cavity in osteopetrotic mice, which was also the case for c-Src kinase-deficient mice (with normal numbers of nonresorbing osteoclasts). Osteopetrotic mice showed a smaller volume of the tympanic cavity but had larger auditory ossicles compared with controls. These data suggest that osteoclastic bone resorption is required for thinning of auditory ossicles and enlargement of the tympanic cavity so that auditory ossicles vibrate freely. PMID:21356377

  8. Unsupervised feature evaluation: a neuro-fuzzy approach

    Microsoft Academic Search

    Sankar K. Pal; Rajat K. De; Jayanta Basak

    2000-01-01

    Demonstrates a way of formulating neuro-fuzzy approaches for both feature selection and extraction under unsupervised learning. A fuzzy feature evaluation index for a set of features is defined in terms of degree of similarity between two patterns in both the original and transformed feature spaces. A concept of flexible membership function incorporating weighted distance is introduced for computing membership values

  9. Designing using manufacturing features

    NASA Astrophysics Data System (ADS)

    Szecsi, T.; Hoque, A. S. M.

    2012-04-01

    This paper presents a design system that enables the composition of a part using manufacturing features. Features are selected from feature libraries. Upon insertion, the system ensures that the feature does not contradict the design-for-manufacture rules. This helps eliminating costly manufacturing problems. The system is developed as an extension to a commercial CAD/CAM system Pro/Engineer.

  10. Towards feature modularization

    Microsoft Academic Search

    Márcio Ribeiro; Paulo Borba

    2010-01-01

    Virtual Separation of Concerns was introduced as a way to reduce drawbacks of implementing product line variability with preprocessors. Developers can focus on certain features and hide others of no interest. However, features eventually share elements, which might break feature modularity, since modifications in a feature result in problems for another. In this thesis we propose the concept of emergent

  11. Human malignant melanoma heterotransplanted to nude mice.

    PubMed

    Tropé, C; Johnsson, J E; Alm, P; Landberg, T; Olsson, H; Wennerberg, J

    1981-01-01

    Five different human malignant melanoma were heterotransplanted subcutaneously to nude mice. When small tissue pieces were used 3 out of 5 tumors grew. Subcutaneous injections of suspended tumor cells were also made, but all failed to take. Metastatic or infiltrative growth was never seen in the mice observed for up to 2.5 months. The successful grafts largely retained the original morphologicaL features. The three successfully transplanted tumors could all be serially transferred with 100% tumor take. In one case passage time was reduced from 40 days to 15 days. As measured with 3H-thymidine incorporation the proliferation rate increased during the passages. These changes might be due to a selection of more rapidly growing tumor cells in the nudes. PMID:7312076

  12. Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease.

    PubMed

    Holland, Philip R; Searcy, James L; Salvadores, Natalia; Scullion, Gillian; Chen, Guiquan; Lawson, Greig; Scott, Fiona; Bastin, Mark E; Ihara, Masafumi; Kalaria, Rajesh; Wood, Emma R; Smith, Colin; Wardlaw, Joanna M; Horsburgh, Karen

    2015-06-01

    Cerebral small vessel disease (SVD) is a major cause of age-related cognitive impairment and dementia. The pathophysiology of SVD is not well understood and is hampered by a limited range of relevant animal models. Here, we describe gliovascular alterations and cognitive deficits in a mouse model of sustained cerebral hypoperfusion with features of SVD (microinfarcts, hemorrhage, white matter disruption) induced by bilateral common carotid stenosis. Multiple features of SVD were determined on T2-weighted and diffusion-tensor magnetic resonance imaging scans and confirmed by pathologic assessment. These features, which were absent in sham controls, included multiple T2-hyperintense infarcts and T2-hypointense hemosiderin-like regions in subcortical nuclei plus increased cerebral atrophy compared with controls. Fractional anisotropy was also significantly reduced in several white matter structures including the corpus callosum. Investigation of gliovascular changes revealed a marked increase in microvessel diameter, vascular wall disruption, fibrinoid necrosis, hemorrhage, and blood-brain barrier alterations. Widespread reactive gliosis, including displacement of the astrocytic water channel, aquaporin 4, was observed. Hypoperfused mice also demonstrated deficits in spatial working and reference memory tasks. Overall, gliovascular disruption is a prominent feature of this mouse, which could provide a useful model for early-phase testing of potential SVD treatment strategies. PMID:25669904

  13. Long-lived crowded-litter mice exhibit lasting effects on insulin sensitivity and energy homeostasis.

    PubMed

    Sadagurski, Marianna; Landeryou, Taylor; Blandino-Rosano, Manuel; Cady, Gillian; Elghazi, Lynda; Meister, Daniel; See, Lauren; Bartke, Andrzej; Bernal-Mizrachi, Ernesto; Miller, Richard A

    2014-06-01

    The action of nutrients on early postnatal growth can influence mammalian aging and longevity. Recent work has demonstrated that limiting nutrient availability in the first 3 wk of life [by increasing the number of pups in the crowded-litter (CL) model] leads to extension of mean and maximal lifespan in genetically normal mice. In this study, we aimed to characterize the impact of early-life nutrient intervention on glucose metabolism and energy homeostasis in CL mice. In our study, we used mice from litters supplemented to 12 or 15 pups and compared those to control litters limited to eight pups. At weaning and then throughout adult life, CL mice are significantly leaner and consume more oxygen relative to control mice. At 6 mo of age, CL mice had low fasting leptin concentrations, and low-dose leptin injections reduced body weight and food intake more in CL female mice than in controls. At 22 mo, CL female mice also have smaller adipocytes compared with controls. Glucose and insulin tolerance tests show an increase in insulin sensitivity in 6 mo old CL male mice, and females become more insulin sensitive later in life. Furthermore, ?-cell mass was significantly reduced in the CL male mice and was associated with reduction in ?-cell proliferation rate in these mice. Together, these data show that early-life nutrient intervention has a significant lifelong effect on metabolic characteristics that may contribute to the increased lifespan of CL mice. PMID:24735888

  14. Long-lived crowded-litter mice exhibit lasting effects on insulin sensitivity and energy homeostasis

    PubMed Central

    Landeryou, Taylor; Blandino-Rosano, Manuel; Cady, Gillian; Elghazi, Lynda; Meister, Daniel; See, Lauren; Bartke, Andrzej; Bernal-Mizrachi, Ernesto; Miller, Richard A.

    2014-01-01

    The action of nutrients on early postnatal growth can influence mammalian aging and longevity. Recent work has demonstrated that limiting nutrient availability in the first 3 wk of life [by increasing the number of pups in the crowded-litter (CL) model] leads to extension of mean and maximal lifespan in genetically normal mice. In this study, we aimed to characterize the impact of early-life nutrient intervention on glucose metabolism and energy homeostasis in CL mice. In our study, we used mice from litters supplemented to 12 or 15 pups and compared those to control litters limited to eight pups. At weaning and then throughout adult life, CL mice are significantly leaner and consume more oxygen relative to control mice. At 6 mo of age, CL mice had low fasting leptin concentrations, and low-dose leptin injections reduced body weight and food intake more in CL female mice than in controls. At 22 mo, CL female mice also have smaller adipocytes compared with controls. Glucose and insulin tolerance tests show an increase in insulin sensitivity in 6 mo old CL male mice, and females become more insulin sensitive later in life. Furthermore, ?-cell mass was significantly reduced in the CL male mice and was associated with reduction in ?-cell proliferation rate in these mice. Together, these data show that early-life nutrient intervention has a significant lifelong effect on metabolic characteristics that may contribute to the increased lifespan of CL mice. PMID:24735888

  15. Thrombospondin1 Deficiency Attenuates Obesity-Associated Microvascular Complications in ApoE-/- Mice

    PubMed Central

    Maimaitiyiming, Hasiyeti; Clemons, Kate; Zhou, Qi; Norman, Heather; Wang, Shuxia

    2015-01-01

    Obesity is associated with insulin resistance and the increased development of vascular complications. Previously, we have demonstrated that thrombospondin1 (TSP1) regulates macrophage function and contributes to obesity associated inflammation and insulin resistance. However, the role of TSP1 in the development of obesity associated vascular complications is not clear. Therefore, in the current study, we investigated whether TSP1 deficiency protects mice from obesity associated micro as well as macro-vascular complications in ApoE-/- mice. In this study, male ApoE-/- mice and ApoE-/-TSP1-/- mice were fed with a low-fat (LF) or a high-fat (HF) diet for 16 weeks. We found that body weight and fat mass increased similarly between the ApoE-/-TSP1-/- mice and ApoE-/- mice under HF feeding conditions. However, as compared to obese ApoE-/- mice, obese ApoE-/-TSP1-/- mice had improved glucose tolerance, increased insulin sensitivity, and reduced systemic inflammation. Aortic atherosclerotic lesion formation was similar in these two groups of mice. In contrast, albuminuria was attenuated and kidney fibrosis was reduced in obese ApoE-/-TSP1-/- mice compared to obese ApoE-/- mice. The improved kidney function in obese ApoE-/-TSP1-/- mice was associated with decreased renal lipid accumulation. Together, these data suggest that TSP1 deficiency did not affect the development of obesity associated macro-vascular complication, but attenuated obesity associated micro-vascular complications. PMID:25803585

  16. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor

    PubMed Central

    Kato, Masaki; Patel, Millan S.; Levasseur, Regis; Lobov, Ivan; Chang, Benny H.-J.; Glass, Donald A.; Hartmann, Christine; Li, Lan; Hwang, Tae-Ho; Brayton, Cory F.; Lang, Richard A.; Karsenty, Gerard; Chan, Lawrence

    2002-01-01

    The low-density lipoprotein receptor–related protein (Lrp)-5 functions as a Wnt coreceptor. Here we show that mice with a targeted disruption of Lrp5 develop a low bone mass phenotype. In vivo and in vitro analyses indicate that this phenotype becomes evident postnatally, and demonstrate that it is secondary to decreased osteoblast proliferation and function in a Cbfa1-independent manner. Lrp5 is expressed in osteoblasts and is required for optimal Wnt signaling in osteoblasts. In addition, Lrp5-deficient mice display persistent embryonic eye vascularization due to a failure of macrophage-induced endothelial cell apoptosis. These results implicate Wnt proteins in the postnatal control of vascular regression and bone formation, two functions affected in many diseases. Moreover, these features recapitulate human osteoporosis-pseudoglioma syndrome, caused by LRP5 inactivation. PMID:11956231

  17. Juxta-articular joint-capsule mineralization in CD73 deficient mice: similarities to patients with NT5E mutations.

    PubMed

    Li, Qiaoli; Price, Thea P; Sundberg, John P; Uitto, Jouni

    2014-01-01

    Arterial calcification due to CD73 deficiency (ACDC), an autosomal recessive disorder, manifests with extensive mineralization of the lower-extremity arteries as well as of hand and foot joint-capsules. This disease is caused by mutations in the NT5E gene which encodes CD73, a membrane-bound ecto-5'-nucleotidase hydrolyzing 5'-AMP into adenosine and Pi. To gain insight into the pathophysiologic details of ACDC, we have characterized a Nt5e(-/-) knock out mouse (Nt5e(tm1Jgsc)) deficient in CD73. These mice, when maintained on appropriate strain background, demonstrated stiffening of the joints and micro CT revealed distinct changes in the thoracic skeletal structure with evidence of mineralization at the costochondral junctions. Mineralization was also noted in the juxta-articular spaces of the lower extremities as well as of ligaments and capsules adjacent to the bony structures. No evidence of vascular mineralization was noted either by CT or by microdissection of arteries in the thoracic area or in lower extremities. The Nt5e(-/-) mutant mice demonstrated significantly increased Pi levels in the serum and significantly reduced PPi concentration in the heparinized plasma, resulting in markedly increased Pi/PPi ratio, thus creating a pro-mineralization environment. In conclusion, the Nt5e(-/-) targeted mutant mice recapitulate some, but not all, features of ACDC and serve as a model system to study pharmacologic interventions for ectopic mineralization. Collectively, this mouse model deficient in CD73, with other targeted mutant mice with vascular mineralization, attests to the presence of a complex pro-mineralization/anti-mineralization network that under physiologic homeostatic conditions prevents ectopic tissue mineralization. PMID:25486201

  18. DEMONSTRATION wcec.ucdavis.edu

    E-print Network

    California at Davis, University of

    · Supply air flow adjustment · Evaporator or condenser coil cleaning · Refrigerant valve cap replacement Demonstration WCEC is working with PECI, Cooper Oates Air Conditioning (COAC), and UC Davis FacilitiesDEMONSTRATION wcec.ucdavis.edu FOR MORE INFORMATION: DEMONSTRATION Demonstration AirCare PlusTM Air

  19. Salty taste deficits in CALHM1 knockout mice.

    PubMed

    Tordoff, Michael G; Ellis, Hillary T; Aleman, Tiffany R; Downing, Arnelle; Marambaud, Philippe; Foskett, J Kevin; Dana, Rachel M; McCaughey, Stuart A

    2014-07-01

    Genetic ablation of calcium homeostasis modulator 1 (CALHM1), which releases adenosine triphosphate from Type 2 taste cells, severely compromises the behavioral and electrophysiological responses to tastes detected by G protein-coupled receptors, such as sweet and bitter. However, the contribution of CALHM1 to salty taste perception is less clear. Here, we evaluated several salty taste-related phenotypes of CALHM1 knockout (KO) mice and their wild-type (WT) controls: 1) In a conditioned aversion test, CALHM1 WT and KO mice had similar NaCl avoidance thresholds. 2) In two-bottle choice tests, CALHM1 WT mice showed the classic inverted U-shaped NaCl concentration-preference function but CALHM1 KO mice had a blunted peak response. 3) In brief-access tests, CALHM1 KO mice showed less avoidance than did WT mice of high concentrations of NaCl, KCl, NH(4)Cl, and sodium lactate (NaLac). Amiloride further ameliorated the NaCl avoidance of CALHM1 KO mice, so that lick rates to a mixture of 1000 mM NaCl + 10 µM amiloride were statistically indistinguishable from those to water. 4) Relative to WT mice, CALHM1 KO mice had reduced chorda tympani nerve activity elicited by oral application of NaCl, NaLac, and sucrose but normal responses to HCl and NH(4)Cl. Chorda tympani responses to NaCl and NaLac were amiloride sensitive in WT but not KO mice. These results reinforce others demonstrating that multiple transduction pathways make complex, concentration-dependent contributions to salty taste perception. One of these pathways depends on CALHM1 to detect hypertonic NaCl in the mouth and signal the aversive taste of concentrated salt. PMID:24846212

  20. Experimental demonstration of composite adiabatic passage

    NASA Astrophysics Data System (ADS)

    Schraft, Daniel; Halfmann, Thomas; Genov, Genko T.; Vitanov, Nikolay V.

    2013-12-01

    We report an experimental demonstration of composite adiabatic passage (CAP) for robust and efficient manipulation of two-level systems. The technique represents a altered version of rapid adiabatic passage (RAP), driven by composite sequences of radiation pulses with appropriately chosen phases. We implement CAP with radio-frequency pulses to invert (i.e., to rephase) optically prepared spin coherences in a Pr3+:Y2SiO5 crystal. We perform systematic investigations of the efficiency of CAP and compare the results with conventional ? pulses and RAP. The data clearly demonstrate the superior features of CAP with regard to robustness and efficiency, even under conditions of weakly fulfilled adiabaticity. The experimental demonstration of composite sequences to support adiabatic passage is of significant relevance whenever a high efficiency or robustness of coherent excitation processes need to be maintained, e.g., as required in quantum information technology.

  1. Effects of short-term Western diet on cerebral oxidative stress and diabetes related factors in APP x PS1 knock-in mice.

    PubMed

    Studzinski, Christa M; Li, Feng; Bruce-Keller, Annadora J; Fernandez-Kim, Sun Ok; Zhang, Le; Weidner, Adam M; Markesbery, William R; Murphy, M Paul; Keller, Jeffrey N

    2009-02-01

    A chronic high fat Western diet (WD) promotes a variety of morbidity factors although experimental evidence for short-term WD mediating brain dysfunction remains to be elucidated. The amyloid precursor protein and presenilin-1 (APP x PS1) knock-in mouse model has been demonstrated to recapitulate some key features of Alzheimer's disease pathology, including amyloid-beta (Abeta) pathogenesis. In this study, we placed 1-month-old APP x PS1 mice and non-transgenic littermates on a WD for 4 weeks. The WD resulted in a significant elevation in protein oxidation and lipid peroxidation in the brain of APP x PS1 mice relative to non-transgenic littermates, which occurred in the absence of increased Abeta levels. Altered adipokine levels were also observed in APP x PS1 mice placed on a short-term WD, relative to non-transgenic littermates. Taken together, these data indicate that short-term WD is sufficient to selectively promote cerebral oxidative stress and metabolic disturbances in APP x PS1 knock-in mice, with increased oxidative stress preceding alterations in Abeta. These data have important implications for understanding how WD may potentially contribute to brain dysfunction and the development of neurodegenerative disorders such as Alzheimer's disease. PMID:19046405

  2. Genetic Deletion and Pharmacological Inhibition of PI3K? Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease

    PubMed Central

    Galluzzo, Maria; Ciraolo, Elisa; Lucattelli, Monica; Hoxha, Eriola; Ulrich, Martina; Campa, Carlo Cosimo; Lungarella, Giuseppe; Doring, Gerd; Zhou-Suckow, Zhe; Mall, Marcus; Hirsch, Emilio; De Rose, Virginia

    2015-01-01

    Purpose. Neutrophil-dominated airway inflammation is a key feature of progressive lung damage in cystic fibrosis (CF). Thus, reducing airway inflammation is a major goal to prevent lung damage in CF. However, current anti-inflammatory drugs have shown several limits. PI3K? plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3K? on airway inflammation and structural lung damage in a mouse model of CF lung disease. Methods. ?ENaC overexpressing mice (?ENaC-Tg) were backcrossed with PI3K?-deficient (PI3K?KO) mice. Tissue damage was assessed by histology and morphometry and inflammatory cell number was evaluated in bronchoalveolar lavage fluid (BALF). Furthermore, we assessed the effect of a specific PI3K? inhibitor (AS-605240) on inflammatory cell number in BALF. Results. Genetic deletion of PI3K? decreased neutrophil numbers in BALF of PI3K?KO/?ENaC-Tg mice, and this was associated with reduced emphysematous changes. Treatment with the PI3K? inhibitor AS-605240 decreased the number of neutrophils in BALF of ?ENaC-Tg mice, reproducing the effect observed with genetic deletion of the enzyme. Conclusions. These results demonstrate the biological efficacy of both genetic deletion and pharmacological inhibition of PI3K? in reducing chronic neutrophilic inflammation in CF-like lung disease in vivo. PMID:26185363

  3. Yersinia enterocolitica infection in resistant and susceptible strains of mice.

    PubMed Central

    Hancock, G E; Schaedler, R W; MacDonald, T T

    1986-01-01

    We investigated natural resistance in mice to Yersinia enterocolitica, an enteric bacterial pathogen of humans, with a view to determine host genetic factors that are important in resistance. Most mouse strains studied (C3H/HeN, BALB/c, BALB.B, DBA/2, A, Swiss, and SWR) were highly susceptible to infection (50% lethal dose [LD50], 2 X 10(2) to 6 X 10(2) Y. enterocolitica administered intravenously [i.v.]). In contrast, C57BL/6 mice were highly resistant (LD50, 2 X 10(5) Y. enterocolitica administered i.v.). Resistance to i.v. Yersinia infection did not appear to be related to the Ity locus (which codes for resistance to Salmonella typhimurium and other pathogens) because Ityr mice (C3H/HeN, DBA/2, A, and SWR) were more susceptible to Y. enterocolitica than were Itys (C57BL/6) mice. In addition, because BALB.B mice (congenic to C57BL/6 mice at the H-2 locus) were susceptible, resistance was probably not H-2 linked. BALB/c X C57BL/6 F1 mice were intermediate in their resistance to Y. enterocolitica infection (LD50, 3 X 10(4) organisms administered i.v.), suggesting that resistance to Y. enterocolitica depends on a gene dosage affect or a resistance gene(s) interaction between susceptible and resistant parents. Further studies with C57BL/6 and BALB/c mice as prototype resistant and susceptible strains were undertaken. A time course study of Y. enterocolitica growth in various organs following i.v. infection revealed no strain difference in bacterial growth during the first 48 h of infection. Thereafter, however, C57BL/6 mice were capable of restricting Y. enterocolitica growth in all tissues (liver, lung, spleen, kidneys), whereas extensive bacterial proliferation occurred in BALB/c mice tissues. BALB/c mice were also more susceptible to oral Y. enterocolitica infection than were C57BL/6 mice, demonstrating increased mortality and greater numbers of bacteria in the Peyer's patches. Finally, whereas thymus-bearing C57BL/6 X BALB/c F1 mice were resistant to infection, athymic (nude) C57BL/6 X BALB/c F1 mice were susceptible. These studies provide a model to investigate natural immunity to enteric pathogens at mucosal surfaces, as well as provide the basis for clarifying the role of host genotype in Y. enterocolitica resistance. PMID:3721579

  4. Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background

    PubMed Central

    Koenig, Sara N.; Bosse, Kevin M.; Nadorlik, Holly A.; Lilly, Brenda; Garg, Vidu

    2015-01-01

    Thoracic aortic aneurysms (TAA) are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV) and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1+/?; Nos3?/? mice. Echocardiographic analysis of Notch1+/?; Nos3?/? mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1+/?; Nos3?/? mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta. PMID:25914885

  5. Colorful Kindergarten Mice

    ERIC Educational Resources Information Center

    Bobick, Bryna; Wheeler, Elizabeth

    2008-01-01

    Developing kindergarten lessons can be very challenging, especially at the beginning of the school year when many students are just learning to cut paper and hold crayons. The author's favorite beginning unit of the year is "mice paintings," a practical introduction to drawing, color theory, and painting. This unit also incorporates children's…

  6. Conditional RNAi in mice

    Microsoft Academic Search

    Aljoscha Kleinhammer; Jan Deussing; Wolfgang Wurst; Ralf Kühn

    2011-01-01

    RNA interference (RNAi)-mediated gene knockdown has developed into a routine method to assess gene function in cultured mammalian cells in a fast and easy manner. For the use of RNAi in mice, short hairpin (sh) RNAs expressed stably from the genome are a fast alternative to conventional knockout approaches. We developed a strategy for complete or conditional gene knockdown in

  7. Favorite Demonstration: Forensic Analysis Demonstration via Hawaii Five-O

    NSDL National Science Digital Library

    Brian R. Shmaefsky

    2006-09-01

    The interdisciplinary nature of a forensics-based demonstration encourages science majors to move beyond their own narrow fields of study. The demonstration described in this column emphasizes the interconnectedness of biology, chemistry, and geology. Forensic-based demonstrations such as this can also be used to introduce the protocols governing the application of discipline specific information to other fields of study.

  8. A single neurotoxic dose of methamphetamine induces a long-lasting depressive-like behaviour in mice.

    PubMed

    Silva, Carlos D; Neves, Ana F; Dias, Ana I; Freitas, Hugo J; Mendes, Sheena M; Pita, Inês; Viana, Sofia D; de Oliveira, Paulo A; Cunha, Rodrigo A; Fontes Ribeiro, Carlos A; Prediger, Rui D; Pereira, Frederico C

    2014-04-01

    Methamphetamine (METH) triggers a disruption of the monoaminergic system and METH abuse leads to negative emotional states including depressive symptoms during drug withdrawal. However, it is currently unknown if the acute toxic dosage of METH also causes a long-lasting depressive phenotype and persistent monoaminergic deficits. Thus, we now assessed the depressive-like behaviour in mice at early and long-term periods following a single high METH dose (30 mg/kg, i.p.). METH did not alter the motor function and procedural memory of mice as assessed by swimming speed and escape latency to find the platform in a cued version of the water maze task. However, METH significantly increased the immobility time in the tail suspension test at 3 and 49 days post-administration. This depressive-like profile induced by METH was accompanied by a marked depletion of frontostriatal dopaminergic and serotonergic neurotransmission, indicated by a reduction in the levels of dopamine, DOPAC and HVA, tyrosine hydroxylase and serotonin, observed at both 3 and 49 days post-administration. In parallel, another neurochemical feature of depression--astroglial dysfunction--was unaffected in the cortex and the striatal levels of the astrocytic protein marker, glial fibrillary acidic protein, were only transiently increased at 3 days. These findings demonstrate for the first time that a single high dose of METH induces long-lasting depressive-like behaviour in mice associated with a persistent disruption of frontostriatal dopaminergic and serotonergic homoeostasis. PMID:24072398

  9. Thermosensitive phenotype of transgenic mice overproducing human glutathione peroxidases.

    PubMed Central

    Mirochnitchenko, O; Palnitkar, U; Philbert, M; Inouye, M

    1995-01-01

    Exposure of humans and other mammals to hyperthermic conditions elicits many physiological responses to stress in various tissues leading to profound injuries, which eventually result in death. It has been suggested that hyperthermia may increase oxidative stress in tissues to form reactive oxygen species harmful to cellular functions. By using transgenic mice with human antioxidant genes, we demonstrate that the overproduction of glutathione peroxidase (GP, both extracellular and intracellular) leads to a thermosensitive phenotype, whereas the overproduction of Cu,Zn-superoxide dismutase has no effect on the thermosensitivity of transgenic mice. Induction of HSP70 in brain, lung, and muscle in GP transgenic mice at elevated temperature was significantly inhibited in comparison to normal animals. Measurement of peroxide production in regions normally displaying induction of HSP70 under hyperthermia revealed high levels of peroxides in normal mice and low levels in GP transgenic mice. There was also a significant difference between normal and intracellular GP transgenic mice in level of prostaglandin E2 in hypothalamus and cerebellum. These data suggest direct participation of peroxides in induction of cytoprotective proteins (HSP70) and cellular mechanisms regulating body temperature. GP transgenic mice provide a model for studying thermoregulation and processes involving actions of hydroxy and lipid peroxides in mammals. Images Fig. 2 Fig. 4 Fig. 5 PMID:7667255

  10. Studies of macrophage function during Trichinella spiralis infection in mice.

    PubMed Central

    Wing, E J; Krahenbuhl, J L; Remington, J S

    1979-01-01

    Studies were made to investigate the quantitative and functional changes which occur in peritoneal macrophage populations obtained from mice infected orally with Trichinella spiralis larvae. C57BL/6 mice infected with T. spiralis larvae became parasitized with adult worms which were rejected from the intestine from 14 to 20 days after infection. Infected mice developed a striking increase in peritoneal exudate cells, composed largely of macrophages, which was maximal at from 16 to 18 days after infection. T. spiralis larvae and eosinophils were not seen in the peritoneal exudates. Macrophages from mice infected more than 11 days earlier inhibited DNA synthesis of syngeneic and allogeneic tumour cells, a property atributed to activated macrophages. In addition, macrophages from T. spiralis-infected mice had the functional ability to kill EL-4 tumour cells as measured by 51Cr release. Unlike activated macrophages, however, macrophages from infected mice did not develop the ability to inhibit multiplication of the intracellular pathogen Toxoplasma gondii. These studies demonstrate that T. spiralis infection in mice induces changes in macrophage function that differ from changes associated with infections by intracellular pathogens. PMID:437839

  11. IL-12 Inhibits Lipopolysaccharide Stimulated Osteoclastogenesis in Mice

    PubMed Central

    Yoshimatsu, Masako; Fujimura, Yuji; Kohara, Haruka; Morita, Yukiko; Yoshida, Noriaki

    2015-01-01

    Lipopolysaccharide (LPS) is related to osteoclastogenesis in osteolytic diseases. Interleukin- (IL-) 12 is an inflammatory cytokine that plays a critical role in host defense. In this study, we investigated the effects of IL-12 on LPS-induced osteoclastogenesis. LPS was administered with or without IL-12 into the supracalvariae of mice, and alterations in the calvarial suture were evaluated histochemically. The number of osteoclasts in the calvarial suture and the mRNA level of tartrate-resistant acid phosphatase (TRAP), an osteoclast marker, were lower in mice administered LPS with IL-12 than in mice administered LPS alone. The serum level of tartrate-resistant acid phosphatase 5b (TRACP 5b), a bone resorption marker, was also lower in mice administered LPS with IL-12 than in mice administered LPS alone. These results revealed that IL-12 might inhibit LPS-induced osteoclastogenesis and bone resorption. In TdT-mediated dUTP-biotin nick end-labeling (TUNEL) assays, apoptotic changes in cells were recognized in the calvarial suture in mice administered LPS with IL-12. Furthermore, the mRNA levels of both Fas and FasL were increased in mice administered LPS with IL-12. Taken together, the findings demonstrate that LPS-induced osteoclastogenesis is inhibited by IL-12 and that this might arise through apoptotic changes in osteoclastogenesis-related cells induced by Fas/FasL interactions.

  12. Thermal latency studies in opiate-treated mice

    PubMed Central

    Schildhaus, Noam; Trink, Eliana; Polson, Chirs; DeTolla, Louis; Tyler, Betty M.; Jallo, George I.; Tok, Sino; Guarnieri, Michael

    2014-01-01

    Background: The change in the reaction time of a tail or paw exposed to a thermal stimulus is a measure of nociceptive activity in laboratory animals. Tail-flick and plantar thermal sensitivity (Hargreaves) tests are non-invasive, minimize stress, and can be used to screen animals for phenotype and drug activity. Objective: Hargreaves testing has been widely used in rats. We investigated its use to measure the activity of opiate analgesia in mice. Methods: Mice were used in thermal stimulus studies at 1-5 hours and 1-5 days to test acute and extended release preparations of buprenorphine. Results: Hargreaves testing had limited value at 1-5 hours because mice can have an obtunded response to opiate therapy. Tail-flick studies with restrained mice are not affected by the initial locomotor stimulation. Discussion: The present report describes a simple restraint system for mice. The utility of the system is demonstrated by examining the efficacy of acute and extended release buprenorphine injections in Balb/c and Swiss mice. Conclusion: Standardized tail-flick testing provides a sensitive robust method to monitor opiate activity in mice. PMID:24459403

  13. Analysis of PFOA in Dosed CD-1 Mice Part 2: Disposition of PFOA in Tissues and fluids from pregnant and lactating mice and their pups

    EPA Science Inventory

    Previous studies in mice with multiple gestational exposures to perfluorooctanoic acid (PFOA) demonstrate numerous dose dependent growth and developmental effects which appeared to worsen if offspring exposed in utero nursed from PFOA-exposed dams. To evaluate the disposition of ...

  14. Antigen binding and capping by lymphocytes of genetic nonresponder mice.

    PubMed

    Dunham, E K; Unanue, E R; Benacerraf, B

    1972-08-01

    Radioautographic study of the binding of GAT-(125)I to spleen cells of genetic responder and nonresponder mice demonstrates that among mice not injected with antigen all strains have approximately the same number of antigen-binding cells; after injection with antigen the number of antigen-binding cells increases in responders but not in nonresponders. Nonresponders are shown to make antibody after injection with GAT complexed with an immunogenic carrier, demonstrating the presence of potentially functional B cells in responders and nonresponders alike. When incubated in the warm, antigen-binding cells of both responders and nonresponders concentrate antigen at one pole of the cell, forming caps. PMID:5043419

  15. Transgenic expression of human signal regulatory protein alpha in Rag2-/-gamma(c)-/- mice improves engraftment of human hematopoietic cells in humanized mice.

    PubMed

    Strowig, Till; Rongvaux, Anthony; Rathinam, Chozhavendan; Takizawa, Hitoshi; Borsotti, Chiara; Philbrick, William; Eynon, Elizabeth E; Manz, Markus G; Flavell, Richard A

    2011-08-01

    Transplantation of human hematopoietic stem cells into severely immunocompromised newborn mice allows the development of a human hematopoietic and immune system in vivo. NOD/scid/?(c)(-/-) (NSG) and BALB/c Rag2(-/-)?(c)(-/-) mice are the most commonly used mouse strains for this purpose and a number of studies have demonstrated the high value of these model systems in areas spanning from basic to translational research. However, limited cross-reactivity of many murine cytokines on human cells and residual host immune function against the xenogeneic grafts results in defective development and maintenance of human cells in vivo. Whereas NSG mice have higher levels of absolute human engraftment than similar mice on a BALB/c background, they have a shorter lifespan and NOD ES cells are unsuitable for the complex genetic engineering that is required to improve human hematopoiesis and immune responses by transgenesis or knockin of human genes. We have generated mice that faithfully express a transgene of human signal regulatory protein alpha (SIRPa), a receptor that negatively regulates phagocytosis, in Rag2(-/-)?(c)(-/-) mice on a mixed 129/BALB/c background, which can easily be genetically engineered. These mice allow significantly increased engraftment and maintenance of human hematopoietic cells reaching levels comparable to NSG mice. Furthermore, we found improved functionality of the human immune system in these mice. In summary, hSIRPa-transgenic Rag2(-/-)?(c)(-/-) mice represent a unique mouse strain supporting high levels of human cell engraftment, which can easily be genetically manipulated. PMID:21788509

  16. Features of the Sun

    NSDL National Science Digital Library

    Beverly Meier

    In this activity students study various features of the Sun in order to understand how the Sun varies. Students will learn that the Sun contains many complex features and compare this to their own prior knowledge about the Sun. Features studied include sunspots, plages, solar flares, prominences, filaments, the corona, helmet streamers, and coronal holes.

  17. Visual Navigation Visual Features

    E-print Network

    Zhang, Hong

    : Scale-Invariant Feature Transform § SIFT Keypoints ­ local intensity extrema (minima or maxima) in both space and scale § Extrema in space are translation-invariant. § Extrema in scale are scale-invariant1 Visual Navigation Visual Features 2 3 What are visual features? SA-1 A small image patch 4 91 85

  18. Advanced Features Jana Kosecka

    E-print Network

    Kosecka, Jana

    , International Journal of Computer Vision, 60, 2 (2004), pp. 91-110. SIFT = Scale Invariant Feature Transform #12 - NO Feature Matching with templates #12;5 9 Scale Invariance: Image Pyramid 10 Aliasing Effects Constructing Yes 14 SIFT Reference Distinctive image features from scale-invariant keypoints. David G. Lowe

  19. Scalable reward learning from demonstration

    E-print Network

    Michini, Bernard

    Reward learning from demonstration is the task of inferring the intents or goals of an agent demonstrating a task. Inverse reinforcement learning methods utilize the Markov decision process (MDP) framework to learn rewards, ...

  20. Revisiting the Electric Pickle Demonstration

    ERIC Educational Resources Information Center

    Journal of Chemical Education, 2005

    2005-01-01

    The electric pickle is a classic demonstration that is widely used in both high school and college settings to explain the general principles behind atomic emission. The demonstration fails to provide an interesting multi-line spectrum.

  1. Defective Generation of a Humoral Immune Response Is Associated with a Reduced Incidence and Severity of Collagen-Induced Arthritis in Microsomal Prostaglandin E Synthase-1 Null Mice1

    PubMed Central

    Kojima, Fumiaki; Kapoor, Mohit; Yang, Lihua; Fleishaker, Erica L.; Ward, Martin R.; Monrad, Seetha U.; Kottangada, Ponnappa C.; Pace, Charles Q.; Clark, James A.; Woodward, Jerold G.; Crofford, Leslie J.

    2008-01-01

    Microsomal PGE synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase and specifically catalyzes the conversion of PGH2 to PGE2. The present study demonstrates the effect of genetic deletion of mPGES-1 on the developing immunologic responses and its impact on the clinical model of bovine collagen-induced arthritis. mPGES-1 null and heterozygous mice exhibited decreased incidence and severity of arthritis compared with wild-type mice in a gene dose-dependent manner. Histopathological examination revealed significant reduction in lining hyperplasia and tissue destruction in mPGES-1 null mice compared with their wild-type littermates. mPGES-1 deficient mice also exhibited attenuation of mechanical nociception in a gene dose-dependent manner. In addition, mPGES-1 null and heterozygous mice showed a marked reduction of serum IgG against type II collagen (CII), including subclasses IgG1, IgG2a, IgG2b, IgG2c, and IgG3, compared with wild-type mice, which correlated with the reduction in observed inflammatory features. These results demonstrate for the first time that deficiency of mPGES-1 inhibits the development of collagen-induced arthritis, at least in part, by blocking the development of a humoral immune response against type II collagen. Pharmacologic inhibition of mPGES-1 may therefore impact both the inflammation and the autoimmunity associated with human diseases such as rheumatoid arthritis. PMID:18523303

  2. Mice Drawer System

    NASA Technical Reports Server (NTRS)

    Cancedda, Ranieri

    2008-01-01

    The Mice Drawer System (MDS) is an Italian Space Agency (ASI) facility which is able to support mice onboard the International Space Station during long-duration exploration missions (from 100 to 150-days) by living space, food, water, ventilation and lighting. Mice can be accommodated either individually (maximum 6) or in groups (4 pairs). MDS is integrated in the Space Shuttle middeck during transportation (uploading and downloading) to the ISS and in an EXPRESS Rack in Destiny, the US Laboratory during experiment execution. Osteoporosis is a debilitating disease that afflicts millions of people worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton. This bone loss experienced by astronauts is similar to osteoporosis in the elderly population. MDS will help investigate the effects of unloading on transgenic (foreign gene that has been inserted into its genome to exhibit a particular trait) mice with the Osteoblast Stimulating Factor-1, OSF-1, a growth and differentiation factor, and to study the genetic mechanisms underlying the bone mass pathophysiology. MDS will test the hypothesis that mice with an increased bone density are likely to be more protected from osteoporosis, when the increased bone mass is a direct effect of a gene involved in skeletogenesis (skeleton formation). Osteoporosis is a debilitating disease that afflicts millions worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton, a loss that is similar to osteoporosis in the elderly population on Earth. Osteoblast Stimulating Factor-1 (OSF-1), also known as pleiotrophin (PTN) or Heparin-Binding Growth- Associated Molecule (HB-GAM) belongs to a family of secreted heparin binding proteins..OSF-1 is an extracellular matrix-associated growth and differentiation factor that is normally expressed in cartilage; it can stimulate the proliferation and differentiation of human osteoprogenitor cells (cell that differentiate into an osteoblast) in vitro. The Mice Drawer System will study the effects of microgravity on transgenic mouse bones in order to identify genetic mechanisms playing a role in the reduction of the bone mass observed in humans and animals as a consequence of long-duration (greater than 100 days) microgravity exposure. Onboard the ISS, MDS is relatively self-sufficient; a crewmember will check the health status of the rodents on a daily basis, by assessing them through the viewing window. Water levels will be assessed by the crew daily and refilled as needed. Replacement of the food bars and replacement of the waste filters will be conducted inflight by crewmembers every 20-days.

  3. Aggravated experimental autoimmune encephalomyelitis in IL-15 knockout mice.

    PubMed

    Gomez-Nicola, Diego; Spagnolo, Alessandra; Guaza, Carmen; Nieto-Sampedro, Manuel

    2010-04-01

    IL-15 initially identified as a T proliferating cytokine has several structural and biological similarities with IL-2 and has been associated with a number of autoimmune diseases. Because of the scarcity of information available on the role of IL-15 in MS pathogenesis, we have investigated how the absence of IL-15 affected the development of experimental autoimmune encephalomyelitis, a mouse model of MS. Following immunization of IL-15(-/-) and C57BL/6 mice with MOG(35-55), we observed a more severe neurological impairment in the IL-15 knockout mice than in the wild-type group. The enhanced disease severity in IL-15(-/-) mice was associated with greater demyelination in the spinal cord, increased immune cell infiltration and inflammation. These events may be related to the higher CD4/CD8 ratio and the almost absent NK cell activity, congenital immune features of IL-15KO mice. Moreover, we found that the fractalkine receptor CX3CR1 was overexpressed in the spinal cord of IL-15(-/-) mice, mainly localized on infiltrating CD8(+) T cells. How these findings are contributing to the aggravated EAE development in IL-15 KO mice remain unclear and need to be further investigated. PMID:20070942

  4. Transplacental transfer of immune antibodies in the mouse demonstrated by antibody labeled in vivo with tritium 

    E-print Network

    McKinney, Hubert Eugene

    1971-01-01

    of the requirement for the degree of MASTER OF SCIENCE August 1971 Major Sub] ect: Laboratory Animal Medicine TRAYSPLACENTAL TRANSFER OF IMMUNE ANTIBODIES IN THE MOUSE DEMONSTRATED BY ANTIBODY LABELED IN VIVO WITH TRITIUM A Thesis by HUBERT EUGENE MCKINNEY.... Pooled sera of stock mice, from which the animals used in this study originated, did not neutralize the immuniz- ing virus in any dilution. Serum collected from passively immunized mice 6 or more days after immunization did not neutralize the immuniz...

  5. Constitutive NF-kappaB activation, normal Fas-induced apoptosis, and increased incidence of lymphoma in human herpes virus 8 K13 transgenic mice.

    PubMed

    Chugh, Priti; Matta, Hittu; Schamus, Sandra; Zachariah, Sunny; Kumar, Arvind; Richardson, James A; Smith, Alice L; Chaudhary, Preet M

    2005-09-01

    Human herpesvirus 8 (HHV-8, also called Kaposi's sarcoma-associated herpes virus) has been linked to Kaposi's sarcoma and primary effusion lymphoma. HHV-8-encoded viral Fas-associated death domain-like IL-1-converting enzyme inhibitory protein (vFLIP) is one of the few viral proteins to be expressed in latently infected cells and plays a key role in the survival and proliferation of primary effusion lymphoma cells. Two main functions have been ascribed to HHV-8 vFLIP, inhibition of caspase 8/Fas-associated death domain-like IL-1-converting enzyme and activation of NF-kappaB. In this article, we demonstrate that vFLIP-expressing transgenic mice lack any of the features seen in mice deficient in caspase 8 or Fas-associated death domain protein and are not resistant to Fas-induced apoptosis. On the other hand, these mice display constitutive activation of classical and alternative NF-kappaB pathways, enhanced response to mitogenic stimuli, and increased incidence of lymphoma. Collectively, our results demonstrate that HHV-8 vFLIP is an oncogenic protein that mimics the signaling activities of caspase 8 during antigen receptor signaling and could contribute to the development of lymphoproliferative disorders via constitutive NF-kappaB activation independent of inhibition of Fas-induced apoptosis. PMID:16120683

  6. Aromatase-null mice expressing enhanced green fluorescent protein in germ cells provide a model system to assess estrogen-dependent ovulatory responses.

    PubMed

    Toda, Katsumi; Hayashi, Yoshihiro; Yamashita, Atsuko; Okabe, Masaru; Ono, Masafumi; Saibara, Toshiji

    2014-04-01

    Enhanced green fluorescent protein (EGFP) has provided us with valuable approaches for tracking living cells. We established a novel line of transgenic mice, which express EGFP in the testis and ovary. Histological analysis demonstrated that spermatids in the testis and oocytes in ovarian follicles beyond preantral stages were positive for EGFP. By exploiting these features, we evaluated ovulatory responses of aromatase-gene (Cyp19a) knockout mouse expressing the EGFP transgene, which is totally anovulatory due to 17?-estradiol (E2) deficiency. Ovulation in the knockout mice was induced by sequential injections of E2 on days 1, 4 and 5, pregnant mare serum gonadotropin on day 4 and human chorionic gonadotropin on day 6. Fluorescent oocytes were readily detectable at 15 h after the last gonadotropin injection in the oviduct under a fluorescence stereomicroscope, even when only one oocyte was present. However, when E2 supplementation on day 4 or day 5 in the regimen was omitted, no ovulated oocytes were detected, indicating that exogenous E2 supplementation at the time of gonadotropin stimulation is necessary to induce ovulation in aromatase-gene knockout mice. Our results further demonstrated that the current mouse line can provide an alternative tool to study germ cell biology, including oogenesis, ovulation and senescence. PMID:24272335

  7. Selenium status alters the immune response and expulsion of adult Heligmosomodies bakeri in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heligmosomoides bakeri is a nematode with parasitic development exclusively in the small intestine of infected mice that induces a potent STAT6-dependent Th2 immune response. We previously demonstrated that host protective expulsion of adult H. bakeri was delayed in selenium (Se) deficient mice. ...

  8. Superior Neutralizing Antibody Response and Protection in Mice Vaccinated with Heterologous DNA Prime and

    E-print Network

    Boyer, Edmond

    HPAI H5N1 viruses in mice. We demonstrate that DNA-VLP elicits the highest neutralizing antibody titersSuperior Neutralizing Antibody Response and Protection in Mice Vaccinated with Heterologous DNA Prime and Virus Like Particle Boost against HPAI H5N1 Virus Heng Ding1. , Cheguo Tsai1. , Ramona

  9. Novel Arterial Pathology in Mice and Humans Hemizygous for Elastin 1783 J. Clin. Invest.

    E-print Network

    Mecham, Robert

    Novel Arterial Pathology in Mice and Humans Hemizygous for Elastin 1783 J. Clin. Invest, November 1998, 1783­1787 http://www.jci.org Novel Arterial Pathology in Mice and Humans Hemizygous demonstrated that loss-of-function mu- tations in one elastin allele cause an inherited obstructive arterial

  10. State Machine Operation of the MICE Cooling Channel

    NASA Astrophysics Data System (ADS)

    Hanlet, Pierrick; Mice Collaboration

    2014-06-01

    The Muon Ionization Cooling Experiment (MICE) is a demonstration experiment to prove the feasibility of cooling a beam of muons for use in a Neutrino Factory and/or Muon Collider. The MICE cooling channel is a section of a modified Study II cooling channel which will provide a 10% reduction in beam emittance. In order to ensure a reliable measurement, MICE will measure the beam emittance before and after the cooling channel at the level of 1%, a relative measurement of 0.001. This renders MICE a precision experiment which requires strict controls and monitoring of all experimental parameters in order to control systematic errors. The MICE Controls and Monitoring system is based on EPICS and integrates with the DAQ, Data monitoring systems, and a configuration database. The cooling channel for MICE has between 12 and 18 superconductnig solenoid coils in 3 to 7 magnets, depending on the staged development of the experiment. The magnets are coaxial and in close proximity which requires coordinated operation of the magnets when ramping, responding to quench conditions, and quench recovery. To reliably manage the operation of the magnets, MICE is implementing state machines for each magnet and an over-arching state machine for the magnets integrated in the cooling channel. The state machine transitions and operating parameters are stored/restored to/from the configuration database and coupled with MICE Run Control. Proper implementation of the state machines will not only ensure safe operation of the magnets, but will help ensure reliable data quality. A description of MICE, details of the state machines, and lessons learned from use of the state machines in recent magnet training tests will be discussed.

  11. Assessment of a non-invasive high-throughput classifier for behaviours associated with sleep and wake in mice

    PubMed Central

    Donohue, Kevin D; Medonza, Dharshan C; Crane, Eli R; O'Hara, Bruce F

    2008-01-01

    This work presents a non-invasive high-throughput system for automatically detecting characteristic behaviours in mice over extended periods of time, useful for phenotyping experiments. The system classifies time intervals on the order of 2 to 4 seconds as corresponding to motions consistent with either active wake or inactivity associated with sleep. A single Polyvinylidine Difluoride (PVDF) sensor on the cage floor generates signals from motion resulting in pressure. This paper develops a linear classifier based on robust features extracted from normalized power spectra and autocorrelation functions, as well as novel features from the collapsed average (autocorrelation of complex spectrum), which characterize transient and periodic properties of the signal envelope. Performance is analyzed through an experiment comparing results from direct human observation and classification of the different behaviours with an automatic classifier used in conjunction with this system. Experimental results from over 28.5 hours of data from 4 mice indicate a 94% classification rate relative to the human observations. Examples of sequential classifications (2 second increments) over transition regions between sleep and wake behaviour are also presented to demonstrate robust performance to signal variation and explain performance limitations. PMID:18405376

  12. LXR? is required for glucocorticoid-induced hyperglycemia and hepatosteatosis in mice

    PubMed Central

    Patel, Rucha; Patel, Monika; Tsai, Ricky; Lin, Vicky; Bookout, Angie L.; Zhang, Yuan; Magomedova, Lilia; Li, Tingting; Chan, Jessica F.; Budd, Conrad; Mangelsdorf, David J.; Cummins, Carolyn L.

    2010-01-01

    Although widely prescribed for their potent antiinflammatory actions, glucocorticoid drugs (e.g., dexamethasone) cause undesirable side effects that are features of the metabolic syndrome, including hyperglycemia, fatty liver, insulin resistance, and type II diabetes. Liver x receptors (LXRs) are nuclear receptors that respond to cholesterol metabolites and regulate the expression of a subset of glucocorticoid target genes. Here, we show LXR? is required to mediate many of the negative side effects of glucocorticoids. Mice lacking LXR? (but not LXR?) were resistant to dexamethasone-induced hyperglycemia, hyperinsulinemia, and hepatic steatosis, but remained sensitive to dexamethasone-dependent repression of the immune system. In vivo, LXR?/? knockout mice demonstrated reduced dexamethasone-induced expression of the key hepatic gluconeogenic gene, phosphoenolpyruvate carboxykinase (PEPCK). In perfused liver and primary mouse hepatocytes, LXR? was required for glucocorticoid-induced recruitment of the glucocorticoid receptor to the PEPCK promoter. These findings suggest a new avenue for the design of safer glucocorticoid drugs through a mechanism of selective glucocorticoid receptor transactivation. PMID:21123945

  13. Progress on the Fabrication and Testing of the MICE Spectrometer Solenoids

    SciTech Connect

    Virostek, Steve; Green, M.A.; Li, Derun; Zisman, Michael

    2009-05-19

    The Muon Ionization Cooling Experiment (MICE) is an international collaboration that will demonstrate ionization cooling in a section of a realistic cooling channel using a muon beam at Rutherford Appleton Laboratory (RAL) in the UK. At each end of the cooling channel a spectrometer solenoid magnet consisting of five superconducting coils will provide a 4 tesla uniform field region. The scintillating fiber tracker within the magnet bore will measure the muon beam emittance as it enters and exits the cooling channel. The 400 mm diameter warm bore, 3 meter long magnets incorporate a cold mass consisting of two coil sections wound on a single aluminum mandrel: a three-coil spectrometer magnet and a two-coil section that matches the solenoid uniform field into the MICE cooling channel. The fabrication of the first of two spectrometer solenoids has been completed, and preliminary testing of the magnet is nearly complete. The key design features of the spectrometer solenoid magnets are presented along with a summary of the progress on the training and testing of the first magnet.

  14. A forward genetic screen in mice identifies mutants with abnormal cortical patterning.

    PubMed

    Ha, Seungshin; Stottmann, Rolf W; Furley, Andrew J; Beier, David R

    2015-01-01

    Formation of a 6-layered cortical plate and axon tract patterning are key features of cerebral cortex development. Abnormalities of these processes may be the underlying cause for a range of functional disabilities seen in human neurodevelopmental disorders. To identify mouse mutants with defects in cortical lamination or corticofugal axon guidance, N-ethyl-N-nitrosourea (ENU) mutagenesis was performed using mice expressing LacZ reporter genes in layers II/III and V of the cortex (Rgs4-lacZ) or in corticofugal axons (TAG1-tau-lacZ). Four lines with abnormal cortical lamination have been identified. One of these was a splice site mutation in reelin (Reln) that results in a premature stop codon and the truncation of the C-terminal region (CTR) domain of reelin. Interestingly, this novel allele of Reln did not display cerebellar malformation or ataxia, and this is the first report of a Reln mutant without a cerebellar defect. Four lines with abnormal cortical axon development were also identified, one of which was found by whole-genome resequencing to carry a mutation in Lrp2. These findings demonstrated that the application of ENU mutagenesis to mice carrying transgenic reporters marking cortical anatomy is a sensitive and specific method to identify mutations that disrupt patterning of the developing brain. PMID:23968836

  15. Scale- and affine-invariant fan feature.

    PubMed

    Cui, Chunhui; Ngan, King Ngi

    2011-06-01

    Most existing feature detectors assume no surface discontinuity within the keypoints' support regions and, hence, have little chance to match the keypoints located on or near the surface boundaries. These keypoints, though not many, are salient and representative. In this paper, we show that they can be successfully matched by using the proposed scale- and affine-invariant Fan features. Specifically, the image neighborhood of a keypoint is depicted by multiple fan subregions, namely Fan features, to provide robustness to surface discontinuity and background change. These Fan features are made scale-invariant by using the automatic scale selection method based on the Fan Laplacian of Gaussian (FLOG). Affine invariance is further introduced to the Fan features based on the affine shape diagnosis of the mirror-predicted surface patch. The Fan features are then described by Fan-SIFT, which is an extension of the famous scale-invariant feature transform (SIFT) descriptor. Experimental results of quantitative comparisons show that the proposed Fan feature has good repeatability that is comparable to the state-of-the-art features for general structured scenes. Moreover, by using Fan features, we can successfully match image structures near surface discontinuities despite significant scale, viewpoint, and background changes. These structures are complementary to those found by the traditional methods and are especially useful for describing weakly textured scenes, which is demonstrated in our experiments on image matching and object rendering. PMID:21224174

  16. Experimental demonstration of blind quantum computing

    NASA Astrophysics Data System (ADS)

    Barz, Stefanie; Kashefi, Elham; Broadbent, Anne; Fitzsimons, Joe; Zeilinger, Anton; Walther, Philip

    2012-02-01

    Quantum computers are among the most promising applications of quantum-enhanced technologies. Quantum effects such as superposition and entanglement enable computational speed-ups that are unattainable using classical computers. The challenges in realising quantum computers suggest that in the near future, only a few facilities worldwide will be capable of operating such devices. In order to exploit these computers, users would seemingly have to give up their privacy. It was recently shown that this is not the case and that, via the universal blind quantum computation protocol, quantum mechanics provides a way to guarantee that the user's data remain private. Here, we demonstrate the first experimental version of this protocol using polarisation-entangled photonic qubits. We demonstrate various blind one- and two-qubit gate operations as well as blind versions of the Deutsch's and Grover's algorithms. When the technology to build quantum computers becomes available, this will become an important privacy-preserving feature of quantum information processing.

  17. Unsupervised Feature Selection Using Feature Similarity

    E-print Network

    Mitra, Pabitra

    index, is introduced. The algorithm is generic in nature and has the capability of multiscale among them. The index usually measures the capability of the respective subsets in classification redundancy and information loss in feature selection can be quantified with an entropy measure. Index Terms

  18. Subacute exposure to 50-Hz electromagnetic fields affect prenatal and neonatal mice's motor coordination

    NASA Astrophysics Data System (ADS)

    Sakhnini, Lama; Ali, Hassan Al; Qassab, Narjis Al; Arab, Eman Al; Kamal, Amer

    2012-04-01

    In this study, we investigate the possible effect of ELF-EMFs on motor performance in mice (prenatal and neonatal exposed mice). The mice performance is evaluated after 5 days of subacute exposure. Immature mice have been chosen for this study because the immature rodent brain still has the capacity to undergo proliferation, differentiation, and reorganization. Results from the rotarod experiments demonstrated a pronounced deficit in the learning abilities of the prenatal exposed groups, but no pronounced effect was observed for the neonatal exposed group.

  19. The Genetic Landscape of Hematopoietic Stem Cell Frequency in Mice.

    PubMed

    Zhou, Xiaoying; Crow, Amanda L; Hartiala, Jaana; Spindler, Tassja J; Ghazalpour, Anatole; Barsky, Lora W; Bennett, Brian J; Parks, Brian W; Eskin, Eleazar; Jain, Rajan; Epstein, Jonathan A; Lusis, Aldons J; Adams, Gregor B; Allayee, Hooman

    2015-07-14

    Prior efforts to identify regulators of hematopoietic stem cell physiology have relied mainly on candidate gene approaches with genetically modified mice. Here we used a genome-wide association study (GWAS) strategy with the hybrid mouse diversity panel to identify the genetic determinants of hematopoietic stem/progenitor cell (HSPC) frequency. Among 108 strains, we observed ?120- to 300-fold variation in three HSPC populations. A GWAS analysis identified several loci that were significantly associated with HSPC frequency, including a locus on chromosome 5 harboring the homeodomain-only protein gene (Hopx). Hopx previously had been implicated in cardiac development but was not known to influence HSPC biology. Analysis of the HSPC pool in Hopx(-/-) mice demonstrated significantly reduced cell frequencies and impaired engraftment in competitive repopulation assays, thus providing functional validation of this positional candidate gene. These results demonstrate the power of GWAS in mice to identify genetic determinants of the hematopoietic system. PMID:26050929

  20. Favorite Demonstration: Demonstrating an Interactive Genetic Drift Exercise

    NSDL National Science Digital Library

    Ashley J. R. Carter

    2003-03-01

    The exercise presented here is a hands-on demonstration of the phenomenon of genetic drift in populations. In particular, it reinforces the random nature of drift and demonstrates the effect that population size can have on the mean frequency of an allele

  1. Demonstrations with a Vacuum: Old Demonstrations for New Vacuum Pumps.

    ERIC Educational Resources Information Center

    Greenslade, Thomas B., Jr.

    1989-01-01

    Explains mechanisms of 19th-century vacuum pumps. Describes demonstrations using the pump including guinea and feather tube, aurora tube, electric egg, Gassiots cascade, air mill, bell in vacuum, density and buoyancy of air, fountain in vacuum, mercury shower, palm and bladder glasses, Bacchus demonstration, pneumatic man-lifter, and Magdeburg…

  2. The demonstration of recurrent demyelination and remyelination of axons in the central nervous system

    Microsoft Academic Search

    E. Stidworthy Johnson; S. K. Ludwin

    1981-01-01

    A model for studying recurrent demyelination and remyelination in the central nervous system was developed by means of repeated administration of Cuprizone to mice. In contrast to the demyelination seen during the first course of Cuprizone, the recurrent demyelination was markedly protracted, displayed features of a “dying-back” gliopathy, and resulted in a greatly reduce inflammatory and glial reaction. The repeat

  3. Multiscale multifractal analysis of 12-lead ECG signals of mice based on wavelet transform and coarse-grained approach

    Microsoft Academic Search

    Chengyu Huo; Xiaofei Ma; Xiaolin Huang; Xinbao Ning; Jun Wang; Xiaojun Qiu

    2011-01-01

    In recent years, the nonlinear analysis of electrocardiogram (ECG) signals using multifractal theory has been proved to be effective. In order to further study the features in normal and pathological ECG signals with multifractal analysis, drugs experiments were conducted on mice. Mice received various drugs to imitate different physiological and pathological conditions, and the distributions of the singularity strength range

  4. Adaptive feature extraction expert

    SciTech Connect

    Yuschik, M.

    1983-01-01

    The identification of discriminatory features places an upper bound on the recognition rate of any automatic speech recognition (ASR) system. One way to structure the extraction of features is to construct an expert system which applies a set of rules to identify particular properties of the speech patterns. However, these patterns vary for an individual speaker and from speaker to speaker so that another expert is actually needed to learn the new variations. The author investigates the problem by using sets of discriminatory features that are suggested by a feature generation expert, improves the selectivity of these features with a training expert, and finally develops a minimally spanning feature set with a statistical selection expert. 12 references.

  5. Pacific Northwest Resources Inventory Demonstration

    NASA Technical Reports Server (NTRS)

    Nichols, J. D.

    1976-01-01

    The Pacific Northwest Land Resource Inventory Demonstration project is designed to demonstrate to users from state and local agencies in Washington, Oregon, and Idaho the cost effective role that Landsat derived information can play in natural resource planning and management when properly supported by ground and aircraft data. The project has been organized into five main phases: (1) maps and overlays, (2) early digital image analysis, (3) demonstration of applications using interactive image analysis, (4) Landsat products and land resources information systems, and (5) documentation. The demonstration project has been applied to Washington forestry, water inventory in southern Idaho, and monitoring of tansy ragwort in western Oregon.

  6. Demonstration Wetland at Henderson, Nevada

    USGS Multimedia Gallery

    Demonstration wetland at Henderson, Nevada, where vegetated hummocks were built into the wastewater treatment wetland to improve its effectiveness and sustainability, as well as provide quality wildlife habitat....

  7. Local inflammatory reaction induced by Scolopendra viridicornis centipede venom in mice.

    PubMed

    Kimura, Louise Faggionato; Prezotto-Neto, José Pedro; Távora, Bianca de Carvalho Lins Fernandes; Antoniazzi, Marta Maria; Knysak, Irene; Gióia Guizze, Samuel Paulo; Santoro, Marcelo Larami; Barbaro, Katia Cristina

    2013-12-15

    Centipede envenomation is generally mild, and human victims usually manifest burning pain, erythema and edema. Despite the abundance and ubiquity of these animals, centipede venom has been poorly characterized in literature. For this reason, the aim of this work was to investigate local inflammatory features induced by Scolopendra viridicornis centipede envenomation in mice, evaluating edema formation, leukocyte infiltration, production of inflammatory mediators, and also performing histological analysis. The highest edematogenic activity induced by the venom, determined by plethysmometry, was noticed 0.5 h after injection in mice footpad. At 24 h, edema was still detected in animals that received 15 and 60 ?g of venom, and at 48 h, only in animals injected with 60 ?g of venom. In relation to leukocyte count, S. viridicornis venom induced cell recruitment, mainly neutrophils and monocytes/macrophages, in all doses and time periods analyzed in comparison with PBS-injected mice. An increase in lymphocytes was detected especially between 1 and 24 h at 60 ?g dose. Besides, eosinophil recruitment was observed mainly for 15 and 60 ?g doses in early time periods. Edema formation and cell recruitment were also confirmed by histological analysis. Moreover, S. viridicornis venom stimulated the release of IL-6, MCP-1, KC, and IL-1?. Conversely, S. viridicornis venom did not induce the release of detectable levels of TNF-?. We demonstrated that the edematogenic activity induced by S. viridicornis venom was of rapid onset, and the venom stimulated secretion of pro-inflammatory mediators which contribute to the inflammatory reaction induced by S. viridicornis venom in an experimental model. PMID:24140924

  8. Feature parsing: feature cue mapping in spoken word recognition.

    PubMed

    Gow, David W

    2003-05-01

    For listeners to recognize words, they must map temporally distributed phonetic feature cues onto higher order phonological representations. Three experiments are reported that were performed to examine what information listeners extract from assimilated segments (e.g., place-assimilated tokens of cone that resemble comb) and how they interpret it. Experiment 1 employed form priming to demonstrate that listeners activate the underlying form of CONE, but not of its neighbor (COMB). Experiment 2 employed phoneme monitoring to show that the same assimilated tokens facilitate the perception of postassimilation context. Together, the results of these two experiments suggest that listeners recover both the underlying place of the modified item and information about the subsequent item from the same modified segment. Experiment 3 replicated Experiment 1, using different postassimilation contexts to demonstrate that context effects do not reflect familiarity with a given assimilation process. The results are discussed in the context of general auditory grouping mechanisms. PMID:12812280

  9. Scn3b knockout mice exhibit abnormal ventricular electrophysiological properties.

    PubMed

    Hakim, Parvez; Gurung, Iman S; Pedersen, Thomas H; Thresher, Rosemary; Brice, Nicola; Lawrence, Jason; Grace, Andrew A; Huang, Christopher L-H

    2008-01-01

    We report for the first time abnormalities in cardiac ventricular electrophysiology in a genetically modified murine model lacking the Scn3b gene (Scn3b(-/-)). Scn3b(-/-) mice were created by homologous recombination in embryonic stem (ES) cells. RT-PCR analysis confirmed that Scn3b mRNA was expressed in the ventricles of wild-type (WT) hearts but was absent in the Scn3b(-/-) hearts. These hearts also showed increased expression levels of Scn1b mRNA in both ventricles and Scn5a mRNA in the right ventricles compared to findings in WT hearts. Scn1b and Scn5a mRNA was expressed at higher levels in the left than in the right ventricles of both Scn3b(-/-) and WT hearts. Bipolar electrogram and monophasic action potential recordings from the ventricles of Langendorff-perfused Scn3b(-/-) hearts demonstrated significantly shorter ventricular effective refractory periods (VERPs), larger ratios of electrogram duration obtained at the shortest and longest S(1)-S(2) intervals, and ventricular tachycardias (VTs) induced by programmed electrical stimulation. Such arrhythmogenesis took the form of either monomorphic or polymorphic VT. Despite shorter action potential durations (APDs) in both the endocardium and epicardium, Scn3b(-/-) hearts showed DeltaAPD(90) values that remained similar to those shown in WT hearts. The whole-cell patch-clamp technique applied to ventricular myocytes isolated from Scn3b(-/-) hearts demonstrated reduced peak Na(+) current densities and inactivation curves that were shifted in the negative direction, relative to those shown in WT myocytes. Together, these findings associate the lack of the Scn3b gene with arrhythmic tendencies in intact perfused hearts and electrophysiological features similar to those in Scn5a(+/-) hearts. PMID:19351516

  10. Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice

    PubMed Central

    Singh, Vijay K.; Wise, Stephen Y.; Fatanmi, Oluseyi O.; Beattie, Lindsay A.; Ducey, Elizabeth J.; Seed, Thomas M.

    2014-01-01

    The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans. PMID:23814114

  11. Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice.

    PubMed

    Singh, Vijay K; Wise, Stephen Y; Fatanmi, Oluseyi O; Beattie, Lindsay A; Ducey, Elizabeth J; Seed, Thomas M

    2014-01-01

    The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5-12.5 Gy) of (60)Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans. PMID:23814114

  12. CD14 transgenic mice expressing membrane and soluble forms: comparisons of levels of cytokines and lethalities in response to lipopolysaccharide between transgenic and non-transgenic mice.

    PubMed

    Tamura, Y; Higuchi, Y; Kataoka, M; Akizuki, S; Matsuura, K; Yamamoto, S

    1999-03-01

    Two different metallothionein promoter-mouse CD14 fusion genes were constructed. The membrane form of the CD14 fusion gene, designated M14M, contained the full-length CD14 cDNA sequence, whereas the soluble form of the fusion gene, designated M14S, was truncated to lack the sequence for the phosphatidylinositol-anchoring site. Expression of transgenic RNA in M14M and M14S mice on the basal diet was abundant in the liver. After maintenance with water containing ZnSO4 (50 mM) for 4 days, expression of transgenic RNA in M14M and M14S mice was strong in the small intestine. Immunohistochemical analysis demonstrated CD14 expression in these organs in M14S and M14M mice. Levels of CD14 in sera from M14S mice after zinc administration were significantly higher than these animals maintained with normal water, M14M mice after zinc administration and non-transgenic mice. Sera from M14S and M14M mice after stimulation with lipopolysaccharide LPS (LPS) demonstrated significantly lower levels of tumor necrosis factor-alpha and IL-6 than those from non-transgenic mice. Lethality in endotoxin shock produced by i.p. injection of 30-40 microg/g body wt LPS was not different between M14S, M14M and non-transgenic mice. However, survival rates in the lethal Shwartzman reaction induced by priming and challenge injections of LPS were significantly higher in M14M and M14S mice than in non-transgenic mice. PMID:10221645

  13. Disposition of Perfluorooctanoic Acid (PFOA) in Pregnant and Lactating CD-1 Mice and Their Pups

    EPA Science Inventory

    Previous studies in mice prenatally-exposed to PFOA demonstrate growth and developmental effects, including impaired body weight gain and mammary gland development, delayed eye opening, and increased mortality. Those dose dependent effects appeared to worsen if offspring exposed ...

  14. Rotation and scaling invariant feature lines for image matching

    Microsoft Academic Search

    Zhang Ye; Wang Yanjie; Qu Hongsong Changchun

    2011-01-01

    Image matching has been one of the most fundamental issues computer vision over the decades.In this paper we propose a novel method based on making use of feature lines in order to achieve more robust image matching. The feature lines have the properties of rotation and scaling invariance?» coined RIFLT(Rotation invariant feature line transform). Experimental results demonstrate the effectiveness and

  15. A comparative analysis of DNA barcode microarray feature size

    Microsoft Academic Search

    Ron Ammar; Andrew M Smith; Lawrence E Heisler; Guri Giaever; Corey Nislow

    2009-01-01

    BACKGROUND: Microarrays are an invaluable tool in many modern genomic studies. It is generally perceived that decreasing the size of microarray features leads to arrays with higher resolution (due to greater feature density), but this increase in resolution can compromise sensitivity. RESULTS: We demonstrate that barcode microarrays with smaller features are equally capable of detecting variation in DNA barcode intensity

  16. Characteristics of antibody responses induced in mice by protein allergens

    Microsoft Academic Search

    J. Hilton; R. J. Dearman; N. Sattar; D. A. Basketter; I. Kimber

    1997-01-01

    Whereas many foreign proteins are immunogenic, only a proportion is also allergenic, having the capacity to induce the quality of immune response necessary to support the production of IgE antibody. We have demonstrated previously that intraperitoneal administration to mice of proteins such as ovalbumin (OVA) or the industrial enzyme A. oryzae lipase, which possess significant allergenic potential, stimulates the production

  17. Treatment of fatal disseminated vaccinia virus infection in immunosuppressed mice.

    PubMed

    Worthington, M; Conliffe, M

    1977-08-01

    Studies were performed to compare the therapeutic effectiveness of three antiviral drugs (ARA-A, ARA-C and IDU) on the course of fatal disseminated vaccinia virus infection in immunosuppressed mice. Treatment with ARA-A begun as late as 7 days after virus infection was significantly effective in preventing death; no antiviral effect of the other two drugs was demonstrated. PMID:302323

  18. Genetically Engineered Mice: Tools To Understand Craniofacial Development

    Microsoft Academic Search

    Michael A. Ignelzi; Yi-Hsin Liu; Robert E. Maxson; Malcolm L. Snead

    1995-01-01

    In this review, we provide a survey of the experimental approaches used to generate genetically engineered mice. Two specific examples are presented that demonstrate the applicability of these approaches to craniofacial development. In the first, a promoter analysis of the Msx2 gene is presented which illustrates the cis regulatory interactions that define cell-specific gene expression. In the second, a mouse

  19. Effects of feeding lactobacillus GG on lethal irradiation in mice

    Microsoft Academic Search

    M. Y. Dong; T. W. Chang; S. L. Gorbach

    1987-01-01

    Mice exposed to 1400 rads of total body irradiation experienced 80%-100% mortality in 2 wk. Bacteremia was demonstrated in all dead animals. Feeding Lactobacillus GG strain reduced Pseudomonas bacteremia and prolonged survival time in animals colonized with this organism. In animals not colonized with Pseudomonas, feeding Lactobacillus GG also produced some reduction in early deaths, and there was less Gram-negative

  20. A Demonstration on Every Exam.

    ERIC Educational Resources Information Center

    Julian, Glenn M.

    1995-01-01

    Argues that inclusion of demonstrations on examinations increases students' ability to observe carefully the physical world around them, translate from observation in terms of models, and make quantitative estimates and physicist-type "back-of-the-envelope" calculations. Presents demonstration ideas covering the following topics: mechanics,…

  1. Favorite Demonstration: MOM Teaches Chemistry

    NSDL National Science Digital Library

    Rich Smierciak

    2004-09-01

    Bring in an expert to demonstrate simple chemistry concepts--MOM! Milk of Magnesia (MOM) is used in this practical demonstration that is simple to do, safe to perform, and engages students as they try to figure out and hypothesize what's going on. Finally,

  2. Rocket Ignition Demonstrations Using Silane

    NASA Technical Reports Server (NTRS)

    Pal, Sibtosh; Santoro, Robert; Watkins, William B.; Kincaid, Kevin

    1998-01-01

    Rocket ignition demonstration tests using silane were performed at the Penn State Combustion Research Laboratory. A heat sink combustor with one injection element was used with gaseous propellants. Mixtures of silane and hydrogen were used as fuel, and oxygen was used as oxidizer. Reliable ignition was demonstrated using fuel lead and and a swirl injection element.

  3. Deployable optical telescope ground demonstration

    Microsoft Academic Search

    Kevin D. Bell; Ruth L. Moser; Michael K. Powers; R. Scott Erwin

    2000-01-01

    The deployable optical telescope, the second project of the Air Force Research Laboratory's Integrated Ground Demonstration Laboratory, will demonstrate critical integration technologies associated with the next generation of beam expanders for space-based laser systems and large apertures for tactical surveillance systems. AFRL's development will be carried in cooperation with the contractor community and have direct ties to the future program

  4. The Energy Network & Demonstration Site

    E-print Network

    Su, Xiao

    , [60 Kg] Other: · Storage Supper Cap.: 48VDC, Maxwell DMOD 0165, 164F [14 Kg] Flywheel: 540V Libert FS1 The Energy Network & Demonstration Site A First Step Peter Reischl Electrical Engineering Power · The Energy Network · Demonstration Site, phase 1/first step · Accomplishments · Next step/how build

  5. Autobacteriographic studies of clarithromycin and erythromycin in mice

    SciTech Connect

    Kohno, Y.; Ohta, K.; Suwa, T.; Suga, T. (Taisho Pharmaceutical Co., Ltd., Ohmiya (Japan))

    1990-04-01

    The antimicrobial activity of clarithromycin was compared with that of erythromycin in experimentally infected mice by whole-body autobacteriography. In mice with systemic staphylococcal infections, the number of vital microbes in the body was relatively low in the early period after oral administration of erythromycin, but increased thereafter to the levels found in nonmedicated control mice. On the other hand, with clarithromycin treatment, a significantly smaller number of microbes was evident throughout the body. The microbes were scarcely seen in the parenchyma of any organs during the examination period. This potent antimicrobial activity of clarithromycin compared with that of erythromycin was further demonstrated in mice with respiratory infections. On the other hand, to examine the distribution properties of both antibiotics in the whole body, an autoradiographic study was carried out with (N-methyl-14C)clarithromycin and (N-methyl-14C)erythromycin. Both labeled antibiotics were distributed widely throughout the body after oral administration in both uninfected control mice and mice with systemic infections. However, the radioactivity was more marked and persistent for (14C)clarithromycin than it was for (14C)erythromycin, particularly in the lungs. The observations described above indicate the superior in vivo antimicrobial activity of clarithromycin compared with that of erythromycin and suggest that the superiority of clarithromycin is largely attributed to its favorable distribution properties. The advantages of whole-body autobacteriography, coupled with whole-body autoradiography, are discussed.

  6. Enhanced malignant tumorigenesis in Cdk4 transgenic mice.

    PubMed

    Miliani de Marval, Paula L; Macias, Everardo; Conti, Claudio J; Rodriguez-Puebla, Marcelo L

    2004-03-11

    In a previous study, we reported that overexpression of cyclin-dependent kinase-4 (CDK4) in mouse epidermis results in epidermal hyperplasia, hypertrophy and severe dermal fibrosis. In this study, we have investigated the susceptibility to skin tumor formation by forced expression of CDK4. Skin tumors from transgenic mice showed a dramatic increase in the rate of malignant progression to squamous cell carcinomas (SCC) in an initiation-promotion protocol. Histopathological analysis of papillomas from transgenic mice showed an elevated number of premalignant lesions characterized by dysplasia and marked atypia. Interestingly, transgenic mice also developed tumors in initiated but not promoted skin, demonstrating that CDK4 replaced the action of tumor promoters. These results suggest that expression of cyclin D1 upon ras activation synergizes with CDK4 overexpression. However, cyclin D1 transgenic mice and double transgenic mice for cyclin D1 and CDK4 did not show increased malignant progression in comparison to CDK4 transgenic mice. Biochemical analysis of tumors showed that CDK4 sequesters the CDK2 inhibitors p27Kip1 and p21Cip1, suggesting that indirect activation of CDK2 plays an important role in tumor development. These results indicate that, contrary to the general assumption, the catalytic subunit, CDK4, has higher oncogenic activity than cyclin D1, revealing a potential use of CDK4 as therapeutic target. PMID:14647432

  7. Therapeutic Effects of Bupleurum Polysaccharides in Streptozotocin Induced Diabetic Mice

    PubMed Central

    Li, Hong; Liu, Zhenzhen; Xu, Yanyan; Zhou, Chunjiao; Lu, Xiaoxiao; Su, Xiaoyu; Zhang, Yunyi; Chen, Daofeng

    2015-01-01

    Diabetes mellitus is related to low-grade chronic inflammation and oxidative stress. Bupleurum Polysaccharides (BPs), isolated from Bupleurum smithii var. parvifolium has anti-inflammatory and anti-oxidative properties. However, little is known about its therapeutic effects on diabetes. In this experiment, the effects of BPs on alleviation of diabetes and the underlying mechanisms were investigated. Diabetic mice model was established via successive intraperitoneal injections of streptozotocin (100 mg/kg body weight) for two days. Mice with blood glucose levels higher than 16.8mmol/L were selected for experiments. The diabetic mice were orally administered with BPs (30 and 60 mg/kg) once a day for 35 days. BPs not only significantly decreased levels of blood glucose, but also increased those of serum insulin and liver glycogen in diabetic mice compared to model mice. Additionally, BPs adminstration improved the insulin expression and suppressed the apoptosis in pancreas of the diabetic mice. Histopathological observations further demonstrated that BPs protected the pancreas and liver from oxidative and inflammatory damages. These results suggest that BPs protect pancreatic ? cells and liver hepatocytes and ameliorate diabetes, which is associated with its anti-oxidative and anti-inflammatory properties. PMID:26176625

  8. Antifatigue effect of Gracilaria eucheumoides in mice

    PubMed Central

    SHAO, JIN-TING; WANG, MEI-YAN; ZHENG, LU-BIN

    2013-01-01

    Gracilaria eucheumoides Linn (Gracilariaceae; G. eucheumoides) is abundant in dietary fiber, which aids the clearance of excess cholesterol from the blood and maintains stable blood glucose levels. The aim of the present study was to investigate the antifatigue effect of G. eucheumoides in mice and the physiological and molecular mechanisms underlying this effect. Mice were randomly divided into four groups and three of the groups were administered different doses of G. eucheumoides extract. A loaded swimming test demonstrated that the swimming times of the low-, medium- and high-dose groups were longer than those of the control group. Examinations revealed that the liver and muscle glycogen, lactate dehydrogenase and blood glucose concentration levels of the treatment groups were higher than those of the control group (P<0.05). However, this was not the case for lactic acid concentration (P>0.05). Quantitative polymerase chain reaction showed that the gene expression levels of glucose transport protein 4 and AMP-activated protein kinase in the medium-dose group exhibited the largest increases, compared with the other treatment groups, and were 3.0- and 1.8-fold higher than those in the control group, respectively. The results of the present study indicated that G. eucheumoides exerts an antifatigue effect on mice. PMID:24255683

  9. Circadian behaviour in neuroglobin deficient mice.

    PubMed

    Hundahl, Christian A; Fahrenkrug, Jan; Hay-Schmidt, Anders; Georg, Birgitte; Faltoft, Birgitte; Hannibal, Jens

    2012-01-01

    Neuroglobin (Ngb), a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN). The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP) and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night. PMID:22496809

  10. Buried Waste Integrated Demonstration: Selection of potential demonstration locations

    SciTech Connect

    Arrenholz, D.A.; Knight, J.L.

    1991-11-01

    The first step towards identifying primary Buried Waste Integrated Demonstration locations is the selection of potential demonstration sites within the Subsurface Disposal Area. The sites selected are Pits 4, 5, 6, and 9, containing transuranic waste of Rocky Flats origin, the Acid Pit, and Pad A. The criteria and methodology for selection of these sites, as well as a description of the wastes present in each area, are included in this report. At a later date, technology-specific demonstration locations will be selected from these six potential sites. The selected locations will be used as necessary to demonstrate technologies whose potential abilities may be optimal on waste forms present at these identified locations.

  11. Video tracking using learned hierarchical features.

    PubMed

    Li Wang; Ting Liu; Gang Wang; Kap Luk Chan; Qingxiong Yang

    2015-04-01

    In this paper, we propose an approach to learn hierarchical features for visual object tracking. First, we offline learn features robust to diverse motion patterns from auxiliary video sequences. The hierarchical features are learned via a two-layer convolutional neural network. Embedding the temporal slowness constraint in the stacked architecture makes the learned features robust to complicated motion transformations, which is important for visual object tracking. Then, given a target video sequence, we propose a domain adaptation module to online adapt the pre-learned features according to the specific target object. The adaptation is conducted in both layers of the deep feature learning module so as to include appearance information of the specific target object. As a result, the learned hierarchical features can be robust to both complicated motion transformations and appearance changes of target objects. We integrate our feature learning algorithm into three tracking methods. Experimental results demonstrate that significant improvement can be achieved using our learned hierarchical features, especially on video sequences with complicated motion transformations. PMID:25700445

  12. Histochemical demonstration of methamphetamine by immunocytochemistry.

    PubMed

    Ishiyama, I; Mukaida, M; Yoshii, T; Suyama, H

    1987-05-01

    A method for the demonstration of methamphetamine (MA) by immunocytochemistry was established. The tissues of intoxicated mice, administered various amounts of MA in single doses of from 0.01 to 1 mg of MA-HCl, were fixed in glutaraldehyde-containing fixatives. Cryostat and paraffin slices gave a positive reaction of MA localization by staining the brain, liver, kidney, lung, stomach, spleen, and so forth, with the aid of the indirect immunoperoxidase technique. Those of animals administered a single dose of 0.1 mg or more (over 3 to 4 mg/kg--the usual dose of MA in acute intoxication death in forensic medicine), in particular, gave a strong strong reaction, so that the diagnosis of MA intoxication can be performed by macroscopic observation of stained slices. The histochemical diagnosis of MA intoxication in clinical toxicology and pathology might be regarded as a useful tool, especially in forensic pathology. The following cells gave a strong positive reaction: nerve cells and myelin sheaths, hepatocytes, epithelial cells of the distal part of the renal tubule and of the collecting tubule, alveolar and bronchial epithelial cells of the lung, chief and parietal cells of the gastric gland, capillaries of the renal glomerulus, macrophages in the blood and tissues, and striated muscle cells including cardiocytes. The morphological evidence of the pharmacodynamics and pharmacokinetics of MA can be determined at the cellular level by immunocytochemistry. PMID:2439648

  13. Linear and Planar Features

    NSDL National Science Digital Library

    Carol Ormand

    Students gesture the orientations of linear and planar features. In the first part of the exercise, students can only see one surface of a wooden block, and are asked to speculate about how planar features penetrate through the interior. Later, they uncover the other faces of the block and gesture the actual orientations.

  14. Formation of Oceanic Features

    NSDL National Science Digital Library

    Katlyn Wicks

    2012-07-16

    This is a picture inquiry based lesson for students to explore four specific oceanic features (mid-ocean ridge, trench, seamount, and continental shelf). Groups of three students will observe and explain features found in pictures and share ideas with their peers.

  15. Feature Selection for Classification

    Microsoft Academic Search

    Manoranjan Dash; Huan Liu

    1997-01-01

    Feature selection has been the focus of interest for quite some time and much work has been done. With the creation of huge databases and the consequent requirements for good machine learning techniques, new problems arise and novel approaches to feature selection are in demand. This survey is a comprehensive overview of many existing methods from the 1970's to the

  16. Beamer Features Michael Lacey

    E-print Network

    Haase, Markus

    Beamer Features Michael Lacey Georgia Institute of Technology October 16, 2004 Michael Lacey Specifications 4 Graphics Michael Lacey (Georgia Tech) Beamer Features October 16, 2004 2 / 20 #12;What is Beamer? A Latex package to create structured powerpoint style presentations. Michael Lacey (Georgia Tech) Beamer

  17. FREL: A Stable Feature Selection Algorithm.

    PubMed

    Li, Yun; Si, Jennie; Zhou, Guojing; Huang, Shasha; Chen, Songcan

    2015-07-01

    Two factors characterize a good feature selection algorithm: its accuracy and stability. This paper aims at introducing a new approach to stable feature selection algorithms. The innovation of this paper centers on a class of stable feature selection algorithms called feature weighting as regularized energy-based learning (FREL). Stability properties of FREL using L1 or L2 regularization are investigated. In addition, as a commonly adopted implementation strategy for enhanced stability, an ensemble FREL is proposed. A stability bound for the ensemble FREL is also presented. Our experiments using open source real microarray data, which are challenging high dimensionality small sample size problems demonstrate that our proposed ensemble FREL is not only stable but also achieves better or comparable accuracy than some other popular stable feature weighting methods. PMID:25134091

  18. Modified Protein Improves Vitiligo Symptoms in Mice

    MedlinePLUS

    ... to mice that had already begun to lose pigment. They found that the vitiligo-prone mice did ... disorder at all, and 76 percent of normal pigment returned among the vitiligo-affected mice, essentially reversing ...

  19. Autoreactive human T-cell receptor initiates insulitis and impaired glucose tolerance in HLA DR4 transgenic mice.

    PubMed

    Gebe, John A; Unrath, Kellee A; Yue, Betty B; Miyake, Tom; Falk, Ben A; Nepom, Gerald T

    2008-06-01

    A human T-cell receptor (TcR) derived from an autoreactive T-cell specific for GAD65, from a subject at high risk for autoimmune diabetes, was introduced into HLA-DR4 transgenic mice. The source of TcR was a CD4(+) T(H)1(+) T-cell clone which responded to an immunodominant epitope of the human islet protein GAD65, an epitope shared with both GAD65 and GAD67 in the mouse. The resulting HLA-DR4/GAD-TcR transgenic mice on a Rag2(o/o)/I-Ab(o/o)/B6 background exhibited a CD4(+) infiltrate into pancreatic islets that correlated with a loss of insulin in infiltrated islets. These mice also exhibited a subclinical impaired tolerance to exogenously fed glucose as assayed by an intraperitoneal glucose tolerance test. T cells containing the GAD65/67 (555-567) responsive TcR undergo strong negative selection as evidenced by a 10-fold lower thymocyte cellularity compared to non-TcR transgenic mice, and clonotype peripheral T cells represented approximately 1% of CD4(+) T cells in Rag2 sufficient mice. Upon in vitro stimulation, GAD65/67 555-567 responsive T cells secrete interferon-gamma, minimal interleukin (IL)-2 and tumor necrosis factor-alpha, and no IL-4, IL-5, IL-10, or IL-17, consistent with a T(H)1 profile. These data demonstrate that CD4(+) T cells specific for a naturally processed epitope within GAD can specifically home to pancreatic islets and lead to impaired islet beta-cell function in diabetes-associated HLA-DR4 transgenic mice on the relatively non-autoimmune C57BL/6 background. The relatively slow progression and patchy insulitis are reminiscent of the chronic pre-clinical phase similar to a majority of human at-risk subjects, and models these indolent features of human T1D. PMID:17949947

  20. Bardoxolone methyl prevents fat deposition and inflammation in the visceral fat of mice fed a high-fat diet.

    PubMed

    Dinh, Chi H L; Szabo, Alexander; Camer, Danielle; Yu, Yinghua; Wang, Hongqin; Huang, Xu-Feng

    2015-03-01

    Key features of diet-induced obesity are visceral fat deposition, macrophage infiltration and inflammation that can lead to metabolic disorders. This study examined the effects of bardoxolone methyl (BARD) in preventing obesity and inflammation in the visceral fat of mice fed high-fat diet. Male C57BL/6J mice were fed a high-fat diet (HFD), a low-fat diet (LFD, i.e., lab chow diet) or a high-fat diet supplemented with BARD (HFD/BARD) for 21weeks. BARD at a dosage of 10mg/kg body weight was administered orally in drinking water. Histology, immunohistochemistry and Western blot were used for the analysis of epididymal adipose tissue. Morphological results demonstrated that HFD fed mice treated with BARD had smaller adipocytes and fewer macrophages present in epididymal adipose tissue than the HFD group. Furthermore, BARD administration reduced the inflammatory profile in this tissue by increasing the expression of nuclear factor of kappa-light-polypeptide gene enhancer in B-cells inhibitor, alpha (I?B-?) protein and decreasing the protein expression of tumour necrosis factor alpha (TNF-?). BARD also prevented oxidative stress reflected by a reduction in stress activated proteins, including signal transducer and activator of transcription 3 (STAT3), protein kinase B (Akt), extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). BARD administration activated the sympathetic nervous system in epididymal adipose tissue assessed by the increased synthesis of tyrosine hydroxylase (TH) and uncoupling protein 2 (UCP2). The expression of inflammatory and sympathetic nervous system proteins in BARD mice fed a HFD was equivalent to that of the LFD control mice, indicating the anti-inflammatory and anti-obesity properties of this drug. In conclusion, the oral administration of BARD in HFD mice prevented fat deposition, inflammation and oxidative stress, and improved sympathetic activity in visceral fat. This study suggests a potential therapeutic role of BARD in preventing the development of obesity. PMID:25637688

  1. Abnormal fluid homeostasis in apelin receptor knockout mice

    PubMed Central

    Roberts, Emma M; Newson, Michael J F; Pope, George R; Landgraf, Rainer; Lolait, Stephen J; O'Carroll, Anne-Marie

    2009-01-01

    The apelinergic system, comprised of apelin and its G protein-coupled receptor (APJ; APLNR as given in MGI Database), is expressed within key regions of the central nervous system associated with arginine vasopressin (AVP) synthesis and release as well as in structures involved in the control of drinking behaviour, including the magnocellular neurones of the hypothalamus, circumventricular organs, and the pituitary gland. This localisation is indicative of a possible functional role in fluid homeostasis. We investigated a role for APJ in the regulation of fluid balance using mice deficient for the receptor. Male APJ wild-type and knockout (APJ?/?) mice were housed in metabolic cages to allow determination of water intake and urine volume and osmolality. When provided with free access to water, APJ?/? mice drank significantly less than wild-types, while their urine volume and osmolality did not differ. Water deprivation for 24?h significantly reduced urine volume and increased osmolality in wild-type but not in APJ?/? mice. Baseline plasma AVP concentration increased comparably in both wild-type and APJ?/? mice following dehydration; however, APJ?/? mice were unable to concentrate their urine to the same extent as wild-type mice in response to the V2 agonist desmopressin. Analysis of c-fos (Fos as given in MGI Database) mRNA expression in response to dehydration showed attenuation of expression within the subfornical organ, accentuated expression in the paraventricular nucleus, but no differences in expression in the supraoptic nucleus nor median pre-optic nucleus in APJ?/? mice compared with wild-type. These findings demonstrate a physiological role for APJ in mechanisms of water intake and fluid retention and suggest an anti-diuretic effect of apelin in vivo. PMID:19578099

  2. Caveolin-1 null (-/-) mice show dramatic reductions in life span.

    PubMed

    Park, David S; Cohen, Alex W; Frank, Philippe G; Razani, Babak; Lee, Hyangkyu; Williams, Terence M; Chandra, Madhulika; Shirani, Jamshid; De Souza, Andrea P; Tang, Baiyu; Jelicks, Linda A; Factor, Stephen M; Weiss, Louis M; Tanowitz, Herbert B; Lisanti, Michael P

    2003-12-30

    Caveolae are 50-100 nm flask-shaped invaginations of the plasma membrane found in most cell types. Caveolin-1 is the principal protein component of caveolae membranes in nonmuscle cells. The recent development of Cav-1-deficient mice has allowed investigators to study the in vivo functional role of caveolae in the context of a whole animal model, as these mice lack morphologically detectable caveolae membrane domains. Surprisingly, Cav-1 null mice are both viable and fertile. However, it remains unknown whether loss of caveolin-1 significantly affects the overall life span of these animals. To quantitatively determine whether loss of Cav-1 gene expression confers any survival disadvantages with increasing age, we generated a large cohort of mice (n = 180), consisting of Cav-1 wild-type (+/+) (n = 53), Cav-1 heterozygous (+/-) (n = 70), and Cav-1 knockout (-/-) (n = 57) animals, and monitored their long-term survival over a 2 year period. Here, we show that Cav-1 null (-/-) mice exhibit an approximately 50% reduction in life span, with major declines in viability occurring between 27 and 65 weeks of age. However, Cav-1 heterozygous (+/-) mice did not show any changes in long-term survival, indicating that loss of both Cav-1 alleles is required to mediate a reduction in life span. Mechanistically, these dramatic reductions in life span appear to be secondary to a combination of pulmonary fibrosis, pulmonary hypertension, and cardiac hypertrophy in Cav-1 null mice. Taken together, our results provide the first demonstration that loss of Cav-1 gene expression and caveolae organelles dramatically affects the long-term survival of an organism. In addition, aged Cav-1 null mice may provide a new animal model to study the pathogenesis and treatment of progressive hypertrophic cardiomyopathy and sudden cardiac death syndrome. PMID:14690422

  3. Abnormal fluid homeostasis in apelin receptor knockout mice.

    PubMed

    Roberts, Emma M; Newson, Michael J F; Pope, George R; Landgraf, Rainer; Lolait, Stephen J; O'Carroll, Anne-Marie

    2009-09-01

    The apelinergic system, comprised of apelin and its G protein-coupled receptor (APJ; APLNR as given in MGI Database), is expressed within key regions of the central nervous system associated with arginine vasopressin (AVP) synthesis and release as well as in structures involved in the control of drinking behaviour, including the magnocellular neurones of the hypothalamus, circumventricular organs, and the pituitary gland. This localisation is indicative of a possible functional role in fluid homeostasis. We investigated a role for APJ in the regulation of fluid balance using mice deficient for the receptor. Male APJ wild-type and knockout (APJ(-/-)) mice were housed in metabolic cages to allow determination of water intake and urine volume and osmolality. When provided with free access to water, APJ(-/-) mice drank significantly less than wild-types, while their urine volume and osmolality did not differ. Water deprivation for 24 h significantly reduced urine volume and increased osmolality in wild-type but not in APJ(-/-) mice. Baseline plasma AVP concentration increased comparably in both wild-type and APJ(-/-) mice following dehydration; however, APJ(-/-) mice were unable to concentrate their urine to the same extent as wild-type mice in response to the V2 agonist desmopressin. Analysis of c-fos (Fos as given in MGI Database) mRNA expression in response to dehydration showed attenuation of expression within the subfornical organ, accentuated expression in the paraventricular nucleus, but no differences in expression in the supraoptic nucleus nor median pre-optic nucleus in APJ(-/-) mice compared with wild-type. These findings demonstrate a physiological role for APJ in mechanisms of water intake and fluid retention and suggest an anti-diuretic effect of apelin in vivo. PMID:19578099

  4. Immune response to intrapharyngeal LPS in neonatal and juvenile mice.

    PubMed

    McGrath-Morrow, Sharon A; Lee, Seakwoo; Gibbs, Kevin; Lopez, Armando; Collaco, Joseph M; Neptune, Enid; Soloski, Mark J; Scott, Alan; D'Alessio, Franco

    2015-03-01

    Neonates and infants have a higher morbidity and mortality associated with lower respiratory tract illnesses compared with older children. To identify age-related and longitudinal differences in the cellular immune response to acute lung injury (ALI), neonatal and juvenile mice were given Escherichia coli LPS using a novel, minimally invasive aspiration technique. Neonatal and juvenile mice received between 3.75 and 7.5 mg/kg LPS by intrapharyngeal aspiration. Airway and lung cells were isolated and characterized by flow cytometry, cytokine/chemokine mRNA expression from lung homogenates was quantified, and lung morphometry and injury scores were performed. LPS-treated neonatal mice underwent adoptive transfer with adult T regulatory cells (Tregs). After LPS aspiration, lung monocytes isolated from neonatal mice had a predominant M2 phenotype, whereas lung monocytes from juvenile mice displayed a mixed M1/M2 phenotype. At 72 hours after LPS exposure, neonatal lungs were slower to resolve inflammation and expressed lower mRNA levels of CCL2, CCL5, CXCL10, and IL-10. Juvenile, but not neonatal, mice demonstrated a significant increase in airway Tregs after LPS exposure. Adoptive transfer of adult Tregs into LPS-challenged neonatal mice resulted in reduced lung inflammation and improved weight gain. These findings underscore several vulnerabilities in the neonatal immune response to LPS-induced ALI. Most striking was the deficiency in airway Tregs after LPS aspiration. Adoptive transfer of adult Tregs mitigated LPS-induced ALI in neonatal mice, highlighting the importance of age-related differences in Tregs and their response to ALI during early postnatal development. PMID:25068533

  5. Endocranial and masticatory muscle volumes in myostatin-deficient mice

    PubMed Central

    Jeffery, Nathan; Mendias, Christopher

    2014-01-01

    Structural and functional trade-offs are integral to the evolution of the mammalian skull and its development. This paper examines the potential for enlargement of the masticatory musculature to limit the size of the endocranial cavity by studying a myostatin-deficient mouse model of hypermuscularity (MSTN?/?). The study tests the null prediction that the larger MSTN?/? mice have larger brains compared with wild-type (WT) mice in order to service the larger muscles. Eleven post-mortem MSTN?/? mice and 12 WT mice were imaged at high resolution using contrast enhanced micro-CT. Masticatory muscle volumes (temporalis, masseter, internal and external pterygoids) and endocranial volumes were measured on the basis of two-dimensional manual tracings and the Cavalieri principle. Volumes were compared using Kruskal–Wallis and Student's t-tests. Results showed that the masticatory muscles of the MSTN?/? mice were significantly larger than in the WT mice. Increases were in the region of 17–36% depending on the muscle. Muscles increased in proportion to each other, maintaining percentages in the region of 5, 10, 21 and 62% of total muscle volume for the external ptyergoid, internal pterygoid, temporalis and masseter, respectively. Kruskal–Wallis and t-tests demonstrated that the endocranial volume was significantly larger in the WT mice, approximately 16% larger on average than that seen in the MSTN?/? mice. This comparative reduction of MSTN?/? endocranial size could not be explained in terms of observer bias, ageing, sexual dimorphism or body size scaling. That the results showed a reduction of brain size associated with an increase of muscle size falsifies the null prediction and lends tentative support to the view that the musculature influences brain growth. It remains to be determined whether the observed effect is primarily physical, nutritional, metabolic or molecular in nature.

  6. Cerebral ?-Amyloidosis in Mice Investigated by Ultramicroscopy

    PubMed Central

    Jährling, Nina; Becker, Klaus; Wegenast-Braun, Bettina M.; Grathwohl, Stefan A.; Jucker, Mathias; Dodt, Hans-Ulrich

    2015-01-01

    Alzheimer´s disease (AD) is the most common neurodegenerative disorder. AD neuropathology is characterized by intracellular neurofibrillary tangles and extracellular ?-amyloid deposits in the brain. To elucidate the complexity of AD pathogenesis a variety of transgenic mouse models have been generated. An ideal imaging system for monitoring ?-amyloid plaque deposition in the brain of these animals should allow 3D-reconstructions of ?-amyloid plaques via a single scan of an uncropped brain. Ultramicroscopy makes this possible by replacing mechanical slicing in standard histology by optical sectioning. It allows a time efficient analysis of the amyloid plaque distribution in the entire mouse brain with 3D cellular resolution. We herein labeled ?-amyloid deposits in a transgenic mouse model of cerebral ?-amyloidosis (APPPS1 transgenic mice) with two intraperitoneal injections of the amyloid-binding fluorescent dye methoxy-X04. Upon postmortem analysis the total number of ?-amyloid plaques, the ?-amyloid load (volume percent) and the amyloid plaque size distributions were measured in the frontal cortex of two age groups (2.5 versus 7-8.5 month old mice). Applying ultramicroscopy we found in a proof-of-principle study that the number of ?-amyloid plaques increases with age. In our experiments we further observed an increase of large plaques in the older age group of mice. We demonstrate that ultramicroscopy is a fast, and accurate analysis technique for studying ?-amyloid lesions in transgenic mice allowing the 3D staging of ?-amyloid plaque development. This in turn is the basis to study neural network degeneration upon cerebral ?-amyloidosis and to assess A? -targeting therapeutics. PMID:26017149

  7. Delayed toxicity of cyclophosphamide in normal mice.

    PubMed Central

    Anton, E.

    1987-01-01

    Delayed toxicity of a single dose of 300 mg/kg cyclophosphamide (CP) was investigated in female DBA/2 mice. Lethality was low up to 30 days but increased markedly afterwards reaching a peak of 50% between 50-70 days with a total mortality of more than 80% by day 120 after CP. One week before death, the mice suffered a sharp loss of weight and showed typical signs of wasting disease. There was a decrease in the white cell count and lymphocyte neutrophil ratio was reversed as a result of lymphocyte depletion whereas neutrophil count remained similar to the controls. Profound lymphocyte depletion was also observed in light and electron microscopy preparations of thymus from mice with CP-induced wasting disease. Histochemical methods demonstrated increased activity of four lysosomal enzymes, acid phosphatase, beta-glucuronidase, E600 resistant esterase and n-acetyl-beta-glucosaminidase, in the thymus of treated mice. Acid phosphatase was notably active in thymus epithelial cells; the reaction product was localized in multiple primary Golgi lysosomes, Golgi cisternae, cisternae of the endoplasmic reticulum, and secondary lysosomes. The appearance of numerous cystic formations, as well as the activation of the lysosomal system and the presence of large areas of degradation support the assumption that CP-delayed toxicity is accompanied by thymus involution. Delayed mortality was partially prevented when syngenic bone marrow cells were injected as early as 24 h after CP injection. On the other hand thymus transplants were incapable of reducing delayed lethality. It is suggested that CP provokes a delayed wasting syndrome with thymic involution that is not caused by a direct effect on specific thymus structures but rather secondary to a primary injury to pre T cells in bone marrow. Images Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 PMID:3555594

  8. JCE Feature Columns

    NASA Astrophysics Data System (ADS)

    Holmes, Jon L.

    1999-05-01

    The Features area of JCE Online is now readily accessible through a single click from our home page. In the Features area each column is linked to its own home page. These column home pages also have links to them from the online Journal Table of Contents pages or from any article published as part of that feature column. Using these links you can easily find abstracts of additional articles that are related by topic. Of course, JCE Online+ subscribers are then just one click away from the entire article. Finding related articles is easy because each feature column "site" contains links to the online abstracts of all the articles that have appeared in the column. In addition, you can find the mission statement for the column and the email link to the column editor that I mentioned above. At the discretion of its editor, a feature column site may contain additional resources. As an example, the Chemical Information Instructor column edited by Arleen Somerville will have a periodically updated bibliography of resources for teaching and using chemical information. Due to the increase in the number of these resources available on the WWW, it only makes sense to publish this information online so that you can get to these resources with a simple click of the mouse. We expect that there will soon be additional information and resources at several other feature column sites. Following in the footsteps of the Chemical Information Instructor, up-to-date bibliographies and links to related online resources can be made available. We hope to extend the online component of our feature columns with moderated online discussion forums. If you have a suggestion for an online resource you would like to see included, let the feature editor or JCE Online (jceonline@chem.wisc.edu) know about it. JCE Internet Features JCE Internet also has several feature columns: Chemical Education Resource Shelf, Conceptual Questions and Challenge Problems, Equipment Buyers Guide, Hal's Picks, Mathcad in the Chemistry Curriculum, and WWW Site Review. These columns differ from the print feature columns in that they use the Internet as the publication medium. Doing so allows these features to include continually updated information, digital components, and links to other online resources. The Conceptual Questions and Challenge Problems feature of JCE Internet serves as a good example for the kinds of resources that you can expect to find in an online feature column. Like other columns it contains a mission statement that defines the role of the column. It includes a digital library of continually updated examples of conceptual questions and challenge problems. (As I write this we have just added several new questions to the library.) It also includes a list of links to related online resources, information for authors about how to write questions and problems, and information for teachers about how to use conceptual questions and challenge problems. Teaching with Technology home page at JCE Online. One-Stop Feature Shop The updated Feature area of JCE Online offers information about all JCE feature columns in one place. It gives you a quick and convenient way to access a group of articles in a particular subject area. It provides authors and readers with a good definition of the column and its mission. It complements the print feature columns with online resources. It provides up-to-date bibliographies for selected areas of interest. And last, but not least, it provides that email address you can use to send that message of appreciation to the feature editor for his or her contribution to JCE and the chemical education community.

  9. FeaturePlugin: feature modeling plug-in for Eclipse

    Microsoft Academic Search

    Michal Antkiewicz; Krzysztof Czarnecki

    2004-01-01

    Feature modeling is a key technique used in product-line development to model commonalities and variabilities of product-line members. In this paper, we present FeaturePlugin, a feature modeling plug-in for Eclipse. The tool supports cardinality-based feature modeling, specialization of feature diagrams, and configuration based on feature diagrams.

  10. Notional Airspace Operations Demonstration Plan

    NASA Technical Reports Server (NTRS)

    Trongale, Nicholas A.

    2006-01-01

    The airspace operations demonstration (AOD) is intended to show that the Access 5 Step 1 functional requirements can be met. The demonstration will occur in two phases. The initial on-range phase will be carried out in restricted airspace to demonstrate the cooperative collision avoidance (CCA) functional requirements and to provide risk-reduction for the AOD by allowing the test team to rehearse some elements of the demonstration mission. The CCA system to be used in these flights is based on Automatic Dependent Surveillance-Broadcast (ADS-B) which is a commercially-available system by which airplanes constantly broadcast their current position and altitude to other aircraft and ground resources over a dedicated radio datalink. The final phase will occur in the national airspace (NAS) and will be the formal demonstration of the remainder of the proposed functional requirements. The general objectives of the AOD are as follows: (1) Demonstrate that the UAS can aviate in the NAS (2) Demonstrate that the UAS can navigate in the NAS (3) Demonstrate that the UAS can communicate with the NAS (4) Demonstrate that the UAS can perform selected collision avoidance functions in the NAS (5) Demonstrate that the UAS can evaluate and avoid weather conflicts in the NAS (6) Demonstrate that the UAS can provide adequate command and control in the NAS In addition to the stated objectives, there are a number of goals for the flight demonstration. The demo can be accomplished successfully without achieving these goals, but these goals are to be used as a guideline for preparing for the mission. The goals are: (1) Mission duration of at least 24 hours (2) Loiter over heavy traffic to evaluate the data block issue identified during the Access 5 Airspace Operations Simulations (3) Document the contingency management process and lessons learned (4) Document the coordination process for Ground Control Stations (GCS) handoff (5) Document lessons learned regarding the process of flying in the NAS Preliminary planning for a notional mission to achieve the objectives and goals has been prepared. The planning is intended to serve as a guide for detailed planning of the AOD.

  11. Novel cerebrovascular pathology in mice fed a high cholesterol diet

    PubMed Central

    Franciosi, Sonia; Gama Sosa, Miguel A; English, Daniel F; Oler, Elizabeth; Oung, Twethida; Janssen, William GM; De Gasperi, Rita; Schmeidler, James; Dickstein, Dara L; Schmitz, Christoph; Gandy, Sam; Hof, Patrick R; Buxbaum, Joseph D; Elder, Gregory A

    2009-01-01

    Background Hypercholesterolemia causes atherosclerosis in medium to large sized arteries. Cholesterol is less known for affecting the microvasculature and has not been previously reported to induce microvascular pathology in the central nervous system (CNS). Results Mice with a null mutation in the low-density lipoprotein receptor (LDLR) gene as well as C57BL/6J mice fed a high cholesterol diet developed a distinct microvascular pathology in the CNS that differs from cholesterol-induced atherosclerotic disease. Microvessel diameter was increased but microvascular density and length were not consistently affected. Degenerative changes and thickened vascular basement membranes were present ultrastructurally. The observed pathology shares features with the microvascular pathology of Alzheimer's disease (AD), including the presence of string-like vessels. Brain apolipoprotein E levels which have been previously found to be elevated in LDLR-/- mice were also increased in C57BL/6J mice fed a high cholesterol diet. Conclusion In addition to its effects as an inducer of atherosclerosis in medium to large sized arteries, hypercholesterolemia also induces a microvascular pathology in the CNS that shares features of the vascular pathology found in AD. These observations suggest that high cholesterol may induce microvascular disease in a range of CNS disorders including AD. PMID:19852847

  12. Uncovering Novel Reproductive Defects in Neurokinin B Receptor Null Mice: Closing the Gap Between Mice and Men

    PubMed Central

    Yang, Jasmine J.; Caligioni, Claudia S.; Chan, Yee-Ming

    2012-01-01

    Patients bearing mutations in TAC3 and TACR3 (which encode neurokinin B and its receptor, respectively) have sexual infantilism and infertility due to GnRH deficiency. In contrast, Tacr3?/? mice have previously been reported to be fertile. Because of this apparent phenotypic discordance between mice and men bearing disabling mutations in Tacr3/TACR3, Tacr3 null mice were phenotyped with close attention to pubertal development, estrous cyclicity, and fertility. Tacr3?/? mice demonstrated normal timing of preputial separation and day of first estrus, markers of sexual maturation. However, at postnatal d 60, Tacr3?/? males had significantly smaller testes and lower FSH levels than their wild-type littermates. Tacr3?/? females had lower uterine weights and abnormal estrous cyclicity. Approximately half of Tacr3?/? females had no detectable corpora lutea on ovarian histology at postnatal d 60. Despite this apparent ovulatory defect, all Tacr3?/? females achieved fertility when mated. However, Tacr3?/? females were subfertile, having both reduced numbers of litters and pups per litter. The subfertility of these animals was not due to a primary ovarian defect, because they demonstrated a robust response to exogenous gonadotropins. Thus, although capable of fertility, Tacr3-deficient mice have central reproductive defects. The remarkable ability of acyclic female Tacr3 null mice to achieve fertility is reminiscent of the reversal of hypogonadotropic hypogonadism seen in a high proportion of human patients bearing mutations in TACR3. Tacr3 mice are a useful model to examine the mechanisms by which neurokinin B signaling modulates GnRH release. PMID:22253416

  13. Disease course in mdx:utrophin+/- mice: comparison of three mouse models of Duchenne muscular dystrophy.

    PubMed

    McDonald, Abby A; Hebert, Sadie L; Kunz, Matthew D; Ralles, Steven J; McLoon, Linda K

    2015-04-01

    The mdx mouse model of Duchenne muscular dystrophy (DMD) is used to study disease mechanisms and potential treatments, but its pathology is less severe than DMD patients. Other mouse models were developed to more closely mimic the human disease based on knowledge that upregulation of utrophin has a protective effect in mdx muscle. An mdx:utrophin(-/-) (dko) mouse was created, which had a severe disease phenotype and a shortened life span. An mdx:utrophin(+/-) mouse was also created, which had an intermediate disease phenotype compared to the mdx and dko mice. To determine the usefulness of mdx:utrophin(+/-) mice for long-term DMD studies, limb muscle pathology and function were assessed across the life span of wild-type, mdx, mdx:utrophin(+/-), and dko mice. Muscle function assessment, specifically grip duration and rotarod performance, demonstrated that mdx:utrophin(+/-) mice were weaker for a longer time than mdx mice. Mean myofiber area was smaller in mdx:utrophin(+/-) mice compared to mdx mice at 12 months. Mdx:utrophin(+/-) mice had a higher percentage of centrally nucleated myofibers compared to mdx mice at 6 and 12 months. Collagen I and IV density was significantly higher in mdx:utrophin(+/-) muscle compared to mdx at most ages examined. Generally, mdx:utrophin(+/-) mice showed an intermediate disease phenotype over a longer time course compared to the mdx and dko mice. While they do not genetically mirror human DMD, mdx:utrophin(+/-) mice may be a more useful animal model than mdx or dko mice for investigating long-term efficacy of potential treatments when fibrosis or muscle function is the focus. PMID:25921779

  14. The individuality of mice.

    PubMed

    Lathe, R

    2004-12-01

    Mutant mice simulating human CNS disorders are used as models for therapeutic drug development. Drug evaluation requires a coherent correlation between behavioral phenotype and drug status. Variations in behavioral responses could mask such correlations, a problem highlighted by the three-site studies of Crabbe et al. (1999) and Wahlsten et al. (2003a). Factors contributing to variation are considered, focusing on differences between individual animals. Genetic differences due to minisatellite variation suggest that each mouse is genetically distinct. Effects during gestation, including maternal stress, influence later life behavior; while endocrine exchanges between fetus and parent, and between male and female fetuses dependent on intrauterine position, also contribute. Pre and perinatal nutrition and maternal attention also play a role. In adults, endocrine cyclicity in females is a recognized source of behavioral diversity. Notably, there is increasing recognition that groups of wild and laboratory mice have complex social structures, illustrated through consideration of Crowcroft (1966). Dominance status can markedly modify behavior in test paradigms addressing anxiety, locomotion and aggressiveness, to an extent comparable to mutation or drug status. Understanding how such effects amplify the behavioral spectrum displayed by otherwise identical animals will improve testing. PMID:15544575

  15. Ultrasonic Songs of Male Mice

    Microsoft Academic Search

    Timothy E Holy; Zhongsheng Guo

    2005-01-01

    Previously it was shown that male mice, when they encounter female mice or their pheromones, emit ultrasonic vocalizations with frequencies ranging over 30–110 kHz. Here, we show that these vocalizations have the characteristics of song, consisting of several different syllable types, whose temporal sequencing includes the utterance of repeated phrases. Individual males produce songs with characteristic syllabic and temporal structure.

  16. Cbf? deletion in mice recapitulates cleidocranial dysplasia and reveals multiple functions of Cbf? required for skeletal development.

    PubMed

    Chen, Wei; Ma, Junqing; Zhu, Guochun; Jules, Joel; Wu, Mengrui; McConnell, Matthew; Tian, Fei; Paulson, Christie; Zhou, Xuedong; Wang, Lin; Li, Yi-Ping

    2014-06-10

    The pathogenesis of cleidocranial dysplasia (CCD) as well as the specific role of core binding factor ? (Cbf?) and the Runt-related transcription factor (RUNX)/Cbf? complex in postnatal skeletogenesis remain unclear. We demonstrate that Cbf? ablation in osteoblast precursors, differentiating chondrocytes, osteoblasts, and odontoblasts via Osterix-Cre, results in severe craniofacial dysplasia, skeletal dysplasia, abnormal teeth, and a phenotype recapitulating the clinical features of CCD. Cbf?(f/f)Osterix-Cre mice have fewer proliferative and hypertrophic chondrocytes, fewer osteoblasts, and almost absent trabecular bone, indicating that Cbf? may maintain trabecular bone formation through its function in hypertrophic chondrocytes and osteoblasts. Cbf?(f/f)Collagen, type 1, alpha 1 (Col1?1)-Cre mice show decreased bone mineralization and skeletal deformities, but no radical deformities in teeth, mandibles, or cartilage, indicating that osteoblast lineage-specific ablation of Cbf? results in milder bone defects and less resemblance to CCD. Activating transcription factor 4 (Atf4) and Osterix protein levels in both mutant mice are dramatically reduced. ChIP assays show that Cbf? directly associates with the promoter regions of Atf4 and Osterix. Our data further demonstrate that Cbf? highly up-regulates the expression of Atf4 at the transcriptional regulation level. Overall, our genetic dissection approach revealed that Cbf? plays an indispensable role in postnatal skeletal development and homeostasis in various skeletal cell types, at least partially by up-regulating the expression of Atf4 and Osterix. It also revealed that CCD may result from functional defects of the Runx2/Cbf? heterodimeric complex in various skeletal cells. These insights into the role of Cbf? in postnatal skeletogenesis and CCD pathogenesis may assist in the development of new therapies for CCD and osteoporosis. PMID:24850862

  17. Toluene Induces Depression-Like Behaviors in Adult Mice

    PubMed Central

    Yang, Miyoung; Kim, Sung-Ho; Kim, Jong-Choon; Shin, Taekyun

    2010-01-01

    It has been clinically reported that toluene causes mental depression in humans. However, the detrimental effects of toluene exposure on brain function and the relation between features of mental depression and toluene exposure are poorly understood. This study evaluated depression-like behaviors in adult C57BL/6 mice after administration of toluene, and elucidated the effects of classical antidepressants on the depression-like behaviors. For the estimation of depression-like behaviors, tail suspension test (TST) and forcedswim test (FST) were performed 1, 4 and 16 days after toluene (0~1000 mg/kg bw) treatment. In addition, classical antidepressants such as fluoxetine (FLX, 20 mg/kg bw) and imipramine (IMI, 40 mg/kg bw) were administered 12 h and 1 h before the tests. In the TST and FST, toluene-treated mice exhibited a longer duration of immobility than vehicle-treated mice 1 and 4 days after toluene treatment. The depression-like behaviors were significantly reversed by FLX and IMI. The weight of the adrenal gland and the size of adrenocortical cells were significantly higher in toluene-treated mice compared to vehicle-treated controls. It is suggested that acute toluene exposure of adult mice is sufficiently detrimental to induce depression. In addition, this study has established a mouse model for a depressive state induced by toluene treatment. PMID:24278539

  18. Demonstrating and Calculating Electrostatic Forces

    NSDL National Science Digital Library

    Rosen, Robert

    This lesson plan from the Beacon Learning Center educates students on the topic of demonstrating and calculating electrostatic forces. The lesson focuses on how electrostatic forces exist between charged objects. Florida state educational standards which the experiment exemplifies are included.

  19. CT Demonstration of Caput Medusae

    ERIC Educational Resources Information Center

    Weber, Edward C.; Vilensky, Joel A.

    2009-01-01

    Maximum intensity and volume rendered CT displays of caput medusae are provided to demonstrate both the anatomy and physiology of this portosystemic shunt associated with portal hypertension. (Contains 2 figures.)

  20. Rotating Cylinder Treatment System Demonstration

    EPA Science Inventory

    In August 2008, a rotating cylinder treatment system (RCTSTM) demonstration was conducted near Gladstone, CO. The RCTSTM is a novel technology developed to replace the aeration/oxidation and mixing components of a conventional lime precipitation treatment s...

  1. Cardiovascular Interactions Model and Demonstration

    NSDL National Science Digital Library

    PhD Carl F. Rothe (Indiana University School of Medicine Department of Cellular and Integrative Physiology)

    2005-06-22

    The Cardiovascular Interactions Project is an electronic active learning tool that demonstrates the complex and intricate interactions between the functions of the heart and peripheral circulation to provide an adequate cardiac output during various stresses.

  2. Demonstrating Forces between Parallel Wires.

    ERIC Educational Resources Information Center

    Baker, Blane

    2000-01-01

    Describes a physics demonstration that dramatically illustrates the mutual repulsion (attraction) between parallel conductors using insulated copper wire, wooden dowels, a high direct current power supply, electrical tape, and an overhead projector. (WRM)

  3. Rubens Flame-Tube Demonstration.

    ERIC Educational Resources Information Center

    Ficken, George W.; Stephenson, Francis C.

    1979-01-01

    Investigates and explains the phenomenon associated with Rubens flame-tube demonstration, specifically the persistance of flames at regular intervals along the tube for few minutes after the gas is turned off. (GA)

  4. Favorite Demonstrations for College Science

    NSDL National Science Digital Library

    2004-01-01

    Peer-reviewed, classroom-tested, and tailored specifically for introductory science courses, Favorite Demonstrations is an essential complement to every college instructor's lesson plans. The book is an all-in-one compilation of 36 popular classroom demonstrations published since 1993 in the "Favorite Demonstration" column of NSTA's Journal of College Science Teaching. The collection begins with a chapter on safety, "The Rules of Research." From there, chapters emphasize conveying scientific principles while making them memorable. The demonstrations cover general science, biology, chemistry, Earth science, and physics while many illustrate the interdisciplinary nature of science by showing how the various subjects contribute to each other's knowledge base. Most are simple to prepare; use low-cost, readily available materials; and can be repeated throughout the day for back-to-back classes.

  5. Classroom Demonstrations of Auditory Perception.

    ERIC Educational Resources Information Center

    Haws, LaDawn; Oppy, Brian J.

    2002-01-01

    Presents activities to help students gain understanding about auditory perception. Describes demonstrations that cover topics, such as sound localization, wave cancellation, frequency/pitch variation, and the influence of media on sound propagation. (CMK)

  6. Energy Research, Development and Demonstration

    E-print Network

    Ray, R. R., Jr.

    1980-01-01

    , and demonstration. The Technology Development Section carries out these functions by maintaining contact with recognized technical experts; monitoring state, federal, and other energy-related technology development; providing staff support to Council advisory...

  7. Status of the MAJORANA Demonstrator

    E-print Network

    C. Cuesta; N. Abgrall; I. J. Arnquist; F. T. Avignone III; A. S. Barabash; F. E. Bertrand; V. Brudanin; M. Busch; M. Buuck; D. Byram; A. S. Caldwell; Y-D. Chan; C. D. Christofferson; J. A. Detwiler; Yu. Efremenko; H. Ejiri; S. R. Elliott; A. Galindo-Uribarri; G. K. Giovanetti; J. Goett; M. P. Greenn; J. Gruszko; I. S. Guinn; V. E. Guiseppe; R. Henning; E. W. Hoppe; S. Howard; M. A. Howe; B. R. Jasinski; K. J. Keeter; M. F. Kidd; S. I. Konovalov; R. T. Kouzes; B. D. LaFerriere; J. Leon; J. MacMullin; R. D. Martin; S. J. Meijer; S. Mertens; J. L. Orrell; C. O'Shaughnessy; N. R. Overman; A. W. P. Poon; D. C. Radford; J. Rager; K. Rielage; R. G. H. Robertson; E. Romero-Romero; C. Schmitt; B. Shanks; M. Shirchenko; N. Snyder; A. M. Suriano; D. Tedeschi; V. Timkin; J. E. Trimble; R. L. Varner; S. Vasilyev; K. Vetter; K. Vorren; B. R. White; J. F. Wilkerson; C. Wiseman; W. Xu; E. Yakushev; C. -H. Yu; V. Yumatov

    2015-01-07

    The MAJORANA Collaboration is constructing the MAJORANA Demonstrator, an ultra-low background, 40-kg modular high purity Ge detector array to search for neutrinoless double-beta decay in Ge. In view of the next generation of tonne-scale Ge-based neutrinoless double-beta decay searches that will probe the neutrino mass scale in the inverted-hierarchy region, a major goal of the Demonstrator is to demonstrate a path forward to achieving a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value at 2039 keV. The current status of the Demonstrator is discussed, as are plans for its completion.

  8. Yo-Yo Pull Demonstration

    ERIC Educational Resources Information Center

    Layton, William

    2013-01-01

    A popular demonstration involves placing a yo-yo on a level table and gently pulling the string horizontally when it is wrapped to come out below the center of the yo-yo's axis. Students are then asked to predict which way the yo-yo will move. A similar demonstration is performed with a tricycle by pulling forward on a pedal with the pedal down in…

  9. Wave rotor demonstrator engine assessment

    NASA Technical Reports Server (NTRS)

    Snyder, Philip H.

    1996-01-01

    The objective of the program was to determine a wave rotor demonstrator engine concept using the Allison 250 series engine. The results of the NASA LERC wave rotor effort were used as a basis for the wave rotor design. A wave rotor topped gas turbine engine was identified which incorporates five basic requirements of a successful demonstrator engine. Predicted performance maps of the wave rotor cycle were used along with maps of existing gas turbine hardware in a design point study. The effects of wave rotor topping on the engine cycle and the subsequent need to rematch compressor and turbine sections in the topped engine were addressed. Comparison of performance of the resulting engine is made on the basis of wave rotor topped engine versus an appropriate baseline engine using common shaft compressor hardware. The topped engine design clearly demonstrates an impressive improvement in shaft horsepower (+11.4%) and SFC (-22%). Off design part power engine performance for the wave rotor topped engine was similarly improved including that at engine idle conditions. Operation of the engine at off design was closely examined with wave rotor operation at less than design burner outlet temperatures and rotor speeds. Challenges identified in the development of a demonstrator engine are discussed. A preliminary design was made of the demonstrator engine including wave rotor to engine transition ducts. Program cost and schedule for a wave rotor demonstrator engine fabrication and test program were developed.

  10. Clostridium difficile infection aggravates colitis in interleukin 10-deficient mice

    PubMed Central

    Kim, Mi Na; Koh, Seong-Joon; Kim, Jung Mogg; Im, Jong Pil; Jung, Hyun Chae; Kim, Joo Sung

    2014-01-01

    AIM: To investigate the effect of Clostridium difficile (C. difficile) infection in an interleukin 10-deficient (IL-10-/-) mouse model of inflammatory bowel disease. METHODS: Bone marrow-derived dendritic cells isolated from wild type (WT) and IL-10-/-mice were stimulated for 4 h with C. difficile toxin A (200 ?g/mL), and gene expression of interferon (IFN)-?, IL-12 and IL-23 was determined by real-time reverse transcription polymerase chain reaction. WT and IL-10-/- mice (n = 20 each) were exposed to an antibiotic cocktail for three days and then were injected with clindamycin (i.p.). Mice (n = 10 WT, 10 IL-10-/-) were then challenged with oral administration of C. difficile (1 × 105 colony forming units of strain VPI 10463). Animals were monitored daily for 7 d for signs of colitis. Colonic tissue samples were evaluated for cytokine gene expression and histopathologic analysis. RESULTS: C. difficile toxin A treatment induced IFN-? gene expression to a level that was significantly higher in BDMCs from IL-10-/- compared to those from WT mice (P < 0.05). However, expression of IL-12 and IL-23 was not different among the groups. Following C. difficile administration, mice developed diarrhea and lost weight within 2-3 d. Weight loss was significantly greater in IL-10-/- compared to WT mice (P < 0.05). C. difficile infection induced histopathologic features typical of colitis in both IL-10-/- and WT mice. The histopathologic severity score was significantly higher in the IL-10-/- than in WT mice (mean ± standard error; 5.50 ± 0.53 vs 2.44 ± 0.46; P < 0.05). This was accompanied by a significantly greater increase in IFN-? gene expression in colonic tissues from IL-10-/- than from WT mice challenged with C. difficile (P < 0.05). CONCLUSION: These results indicate that colitis is more severe after C. difficile infection in IL-10-/-mice, and that IFN-? expression is involved in this process. PMID:25493020

  11. Satellite Feature Identification: Cyclogenesis

    NSDL National Science Digital Library

    COMET

    2012-08-17

    This module, Satellite Feature Identification: Cyclogenesis, uses water vapor satellite imagery to present a satellite perspective of basic features associated with the formation and development of extratropical cyclones. First, through an initial case study, the precursor elements leading to cyclogenesis are identified. Then three conceptual views of different ways cyclogenesis can evolve are presented along with additional examples to illustrate the concepts. Finally a series of exercises, again using real case studies, are used to emphasize the important points and provide realistic scenarios describing some of the many ways cyclogenesis reveals itself on satellite imagery. This module is part of the series: 'Dynamic Feature Identification: The Satellite Palette'.

  12. Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice

    Microsoft Academic Search

    Guo-Xing Zhang; Koji Ohmori; Yukiko Nagai; Yoshihide Fujisawa; Akira Nishiyama; Youichi Abe; Shoji Kimura

    2007-01-01

    Elevated activities of the sympathetic nerve and renin–angiotensin systems are common features of heart failure. This study was designed to investigate the roles of the AT1 receptor in cardiac hypertrophy and oxidative stress during excessive ?-adrenoceptor stimulation using an AT1 receptor antagonist (ARB) and AT1a receptor-deficient (AT1aR?\\/?) mice. Isoproterenol (ISO) was given to C57BL mice with or without ARB (olmesartan)

  13. Susceptibility to re-infection in C57BL/6 mice with recombinant strains of Toxoplasma gondii.

    PubMed

    Brandão, Geane P; Melo, Maria N; Caetano, Braulia C; Carneiro, Cláudia M; Silva, Letícia A; Vitor, Ricardo W A

    2011-08-01

    This work reports results of re-infection of BALB/c and C57BL/6 mice with different recombinant strains of Toxoplasma gondii. Mice were prime-infected with the non-virulent D8 strain and challenged with virulent strains. PCR-RFLP of cS10-A6 genetic marker of T. gondii demonstrated that BALB/c mice were re-infected with the EGS strain, while C57BL/6 mice were re-infected with the EGS and CH3 strains. Levels of IFN-? and IL-10 after D8 prime-infection were lower in C57BL/6 than in BALB/c mice. Brain inflammation after D8 prime-infection was more intense in C57BL/6 than in BALB/c mice. It was shown that re-infection depends on mice lineage and genotype of the strain used in the challenge. PMID:21640105

  14. Angiotensin II inhibitor facilitates epidermal wound regeneration in diabetic mice

    PubMed Central

    Kamber, Maria; Papalazarou, Vasileios; Rouni, Georgia; Papageorgopoulou, Evagelia; Papalois, Apostolos; Kostourou, Vassiliki

    2015-01-01

    Tissue regeneration and wound healing are severely impaired in diabetes and are associated with poor circulation and dysfunctional blood vessels. Angiotensin II inhibitors are anti-hypertensive drugs used in clinical practice to regulate blood pressure and could affect tissue remodeling. We hypothesize that blocking angiotensin II, using Losartan, could facilitate tissue regeneration in diabetic mice. To this end, we established an experimental model of wound healing in streptozotocin-induced diabetic mice. Our data demonstrated that Losartan accelerates wound repair and normalizes wound stromal responses, having a beneficial role in wounds of diabetic individuals. Our findings highlight a potential therapeutic use of Losartan in improving wound repair in diabetic conditions.

  15. Radioimaging of human ovarian carcinoma xenograft in nude mice

    SciTech Connect

    Manetta, A.; Satyaswaroop, P.G.; Hamilton, T.; Ozols, R.; Mortel, R.

    1987-11-01

    Human ovarian carcinomas in nude mice were radioimaged using a well-characterized antibody against a tumor-associated antigen (CA 125) and three transplantable human ovarian carcinoma tumor lines: NIH:OVCAR 3, NIH:OVCAR 5, and NIH:OVCAR 9. Radioiodinated monoclonal antibody OC125 was used in these studies. In order to establish the optimal conditions for imaging, tumor/blood ratios were determined. Gamma scintigraphy of nude mice bearing subcutaneous transplants of human ovarian carcinomas 3-4 days after /sup 131/I-OC125 administration demonstrated selective localization of the radiolabeled monoclonal antibody by these tumors without need for any background subtraction techniques.

  16. Visualizing object detection features

    E-print Network

    Vondrick, Carl (Carl Martin)

    2013-01-01

    We introduce algorithms to visualize feature spaces used by object detectors. The tools in this paper allow a human to put on 'HOG goggles' and perceive the visual world as a HOG based object detector sees it. We found ...

  17. DCTD — Featured Trials

    Cancer.gov

    Skip to Content Click here to view the Site Map Home | Sitemap | Contact DCTD Search this site Featured Trials Funding Opportunities Partnerships DCTD Programs Cancer Diagnosis Program Cancer Imaging Program Cancer Therapy Evaluation Program Developmental

  18. Rapid Vascular Responses to Anthrax Lethal Toxin in Mice Containing a Segment of Chromosome 11 from the CAST/Ei Strain on a C57BL/6 Genetic Background

    PubMed Central

    Weigel, Kelsey J.; Rues, Laura; Doyle, Edward J.; Buchheit, Cassandra L.; Wood, John G.; Gallagher, Ryan J.; Kelly, Laura E.; Radel, Jeffrey D.; Bradley, Kenneth A.; LeVine, Steven M.

    2012-01-01

    Host allelic variation controls the response to B. anthracis and the disease course of anthrax. Mouse strains with macrophages that are responsive to anthrax lethal toxin (LT) show resistance to infection while mouse strains with LT non-responsive macrophages succumb more readily. B6.CAST.11M mice have a region of chromosome 11 from the CAST/Ei strain (a LT responsive strain) introgressed onto a LT non-responsive C57BL/6J genetic background. Previously, B6.CAST.11M mice were found to exhibit a rapid inflammatory reaction to LT termed the early response phenotype (ERP), and displayed greater resistance to B. anthracis infection compared to C57BL/6J mice. Several ERP features (e.g., bloat, hypothermia, labored breathing, dilated pinnae vessels) suggested vascular involvement. To test this, Evan’s blue was used to assess vessel leakage and intravital microscopy was used to monitor microvascular blood flow. Increased vascular leakage was observed in lungs of B6.CAST.11M mice compared to C57BL/6J mice 1 hour after systemic administration of LT. Capillary blood flow was reduced in the small intestine mesentery without concomitant leukocyte emigration following systemic or topical application of LT, the latter suggesting a localized tissue mechanism in this response. Since LT activates the Nlrp1b inflammasome in B6.CAST.11M mice, the roles of inflammasome products, IL-1? and IL-18, were examined. Topical application to the mesentery of IL-1? but not IL-18 revealed pronounced slowing of blood flow in B6.CAST.11M mice that was not present in C57BL/6J mice. A neutralizing anti-IL-1? antibody suppressed the slowing of blood flow induced by LT, indicating a role for IL-1? in the response. Besides allelic differences controlling Nlrp1b inflammasome activation by LT observed previously, evidence presented here suggests that an additional genetic determinant(s) could regulate the vascular response to IL-1?. These results demonstrate that vessel leakage and alterations to blood flow are part of the rapid response in mice resistant to B. anthracis infection. PMID:22792226

  19. Suppression of NMDA receptor function in mice prenatally exposed to valproic acid improves social deficits and repetitive behaviors

    PubMed Central

    Kang, Jaeseung; Kim, Eunjoon

    2015-01-01

    Animals prenatally exposed to valproic acid (VPA), an antiepileptic agent, have been used as a model for autism spectrum disorders (ASDs). Previous studies have identified enhanced NMDA receptor (NMDAR) function in the brain of VPA rats, and demonstrated that pharmacological suppression of NMDAR function normalizes social deficits in these animals. However, whether repetitive behavior, another key feature of ASDs, can be rescued by NMDAR inhibition remains unknown. We report here that memantine, an NMDAR antagonist, administered to VPA mice rescues both social deficits and repetitive behaviors such as self-grooming and jumping. These results suggest that suppression of elevated NMDAR function in VPA animals normalizes repetitive behaviors in addition to social deficits. PMID:26074764

  20. Molecular Imaging of Neuroblastoma Progression in TH-MYCN Transgenic Mice

    PubMed Central

    Quarta, Carmelo; Cantelli, Erika; Nanni, Cristina; Ambrosini, Valentina; D’ambrosio, Daniela; Di Leo, Korinne; Angelucci, Silvia; Zagni, Federico; Lodi, Filippo; Marengo, Mario; Weiss, William A.; Pession, Andrea; Tonelli, Roberto; Fanti, Stefano

    2012-01-01

    Purpose TH-MYCN transgenic mice represent a valuable preclinical model of neuroblastoma. Current methods to study tumor progression in these mice are inaccurate or invasive, limiting the potential of this murine model. The aim of our study was to assess the potential of small animal positron emission tomography (SA-PET) to study neuroblastoma progression in TH-MYCN mice. Procedure Serial SA-PET scans using the tracer 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) have been performed in TH-MYCN mice. Image analysis of tumor progression has been compared with ex vivo evaluation of tumor volumes and histological features. Results [18F]FDG-SA-PET allowed to detect early staged tumors in almost 100 % of TH-MYCN mice positive for disease. Image analysis of tumor evolution reflected the modifications of the tumor volume, histological features, and malignancy during disease progression. Image analysis of TH-MYCN mice undergoing chemotherapy treatment against neuroblastoma provided information on drug-induced alterations in tumor metabolic activity. Conclusions These data show for the first time that [18F]FDG-SA-PET is a useful tool to study neuroblastoma presence and progression in TH-MYCN transgenic mice. PMID:22777578

  1. Tested Demonstrations. Brownian Motion: A Classroom Demonstration and Student Experiment.

    ERIC Educational Resources Information Center

    Kirksey, H. Graden; Jones, Richard F.

    1988-01-01

    Shows how video recordings of the Brownian motion of tiny particles may be made. Describes a classroom demonstration and cites a reported experiment designed to show the random nature of Brownian motion. Suggests a student experiment to discover the distance a tiny particle travels as a function of time. (MVL)

  2. Demonstration Extension: Copper-to-Silver-to-Gold Penny Demonstration

    ERIC Educational Resources Information Center

    Vitz, Ed

    2008-01-01

    This demonstration, if done in the original way, can lead to fires in waste containers (sometimes in the middle of the night after the experiment has been conducted), because pyrophoric zinc is generated by suspending powdered zinc in hot sodium hydroxide. This is avoided by using hot ZnSO[subscript 4].

  3. LIMB demonstration project extension and Coolside demonstration: A DOE assessment

    SciTech Connect

    National Energy Technology Laboratory

    2000-04-30

    The goal of the US Department of Energy (DOE) Clean Coal Technology (CCT) program is to furnish the energy marketplace with a number of advanced, more efficient, and environmentally responsible coal utilization technologies through demonstration projects. These projects seek to establish the commercial feasibility of the most promising advanced coal technologies that have already reached the proof-of-concept stage. This document serves as a DOE post-project assessment of the CCT Round 1 project ``LIMB Demonstration Project Extension and Coolside Demonstration'', described in a report to Congress (Babcock and Wilcox 1987), a paper by DePero et al. (1992), and in a report by Goots et al. (1992). The original limestone injection multistage burner (LIMB) demonstration work was conducted by Babcock and Wilcox Company (B and W) beginning in 1984, under the sponsorship of the US Environmental Protection Agency (EPA) and the State of Ohio Coal Development Office (OCDO). In 1987, B and W and the Ohio Edison Company agreed to extend the full-scale demonstration of LIMB technology under the sponsorship of DOE through its CCT Program, and with support from OCDO and Consolidation Coal Company, now known as CONSOL. In a separate effort, CONSOL had been developing another flue gas desulfurization (FGD) technology known as the Coolside process. Both LIMB and Coolside use sorbent injection to remove SO{sub 2}. The LIMB process injects the sorbent into the furnace and the Coolside injects the sorbent into the flue gas duct. In addition, LIMB uses low-NO{sub x} burners to reduce NO{sub x} emissions; hence it is categorized as a combination SO{sub 2}/NO{sub x} control technology. To take advantage of synergism between the two processes, the CCT project was structured to incorporate demonstration of both the LIMB and Coolside processes. Coolside testing was accomplished between July 1989 and February 1990, and the LIMB Extension test program was conducted between April 1990 and August 1991. The host site for both tests was the 105 MWe coal-fired Unit 4 at Ohio Edison's Edgewater Station in Lorain, Ohio. The major performance objectives of this project were successfully achieved, with SO{sub 2} emissions reductions of up to 70% demonstrated in both processes.

  4. Demonstration of Active Combustion Control

    NASA Technical Reports Server (NTRS)

    Lovett, Jeffrey A.; Teerlinck, Karen A.; Cohen, Jeffrey M.

    2008-01-01

    The primary objective of this effort was to demonstrate active control of combustion instabilities in a direct-injection gas turbine combustor that accurately simulates engine operating conditions and reproduces an engine-type instability. This report documents the second phase of a two-phase effort. The first phase involved the analysis of an instability observed in a developmental aeroengine and the design of a single-nozzle test rig to replicate that phenomenon. This was successfully completed in 2001 and is documented in the Phase I report. This second phase was directed toward demonstration of active control strategies to mitigate this instability and thereby demonstrate the viability of active control for aircraft engine combustors. This involved development of high-speed actuator technology, testing and analysis of how the actuation system was integrated with the combustion system, control algorithm development, and demonstration testing in the single-nozzle test rig. A 30 percent reduction in the amplitude of the high-frequency (570 Hz) instability was achieved using actuation systems and control algorithms developed within this effort. Even larger reductions were shown with a low-frequency (270 Hz) instability. This represents a unique achievement in the development and practical demonstration of active combustion control systems for gas turbine applications.

  5. Iterative feature removal yields highly discriminative pathways

    PubMed Central

    2013-01-01

    Background We introduce Iterative Feature Removal (IFR) as an unbiased approach for selecting features with diagnostic capacity from large data sets. The algorithm is based on recently developed tools in machine learning that are driven by sparse feature selection goals. When applied to genomic data, our method is designed to identify genes that can provide deeper insight into complex interactions while remaining directly connected to diagnostic utility. We contrast this approach with the search for a minimal best set of discriminative genes, which can provide only an incomplete picture of the biological complexity. Results Microarray data sets typically contain far more features (genes) than samples. For this type of data, we demonstrate that there are many equivalently-predictive subsets of genes. We iteratively train a classifier using features identified via a sparse support vector machine. At each iteration, we remove all the features that were previously selected. We found that we could iterate many times before a sustained drop in accuracy occurs, with each iteration removing approximately 30 genes from consideration. The classification accuracy on test data remains essentially flat even as hundreds of top-genes are removed. Our method identifies sets of genes that are highly predictive, even when comprised of genes that individually are not. Through automated and manual analysis of the selected genes, we demonstrate that the selected features expose relevant pathways that other approaches would have missed. Conclusions Our results challenge the paradigm of using feature selection techniques to design parsimonious classifiers from microarray and similar high-dimensional, small-sample-size data sets. The fact that there are many subsets of genes that work equally well to classify the data provides a strong counter-result to the notion that there is a small number of “top genes” that should be used to build classifiers. In our results, the best classifiers were formed using genes with limited univariate power, thus illustrating that deeper mining of features using multivariate techniques is important. PMID:24274115

  6. Improved Engraftment of Human Spleen Cells in NOD/LtSz-scid/scid Mice as Compared with C.B-17-scid/scid Mice

    PubMed Central

    Greiner, Dale L.; Shultz, Leonard D.; Yates, Jon; Appel, Michael C.; Perdrizet, George; Hesselton, RuthAnn M.; Schweitzer, Isabelle; Beamer, Wes G.; Shultz, Kathryn L.; Pelsue, Stephen C.; Leif, Jean H.; Rajan, Thiruchandurai V.

    1995-01-01

    T and B lymphocyte-deficient mice homozygous for the severe combined immunodeficiency (SCID) mutation can be immunologically engrafted with human lymphocytes. However, low levels of human peripheral blood mononuclear cell engraftment are commonly observed, impeding full use of this model We now demonstrate that strain background in mice homozygous for the scid mutation is a strong determinant of levels of human lymphocyte engraftment. NOD/LtSz-scid/scid mice support higher levels of engraftment of both human spleen and peripheral blood mononuclear cells than do C.B-17-scid/scid mice. We observed, using human spleen cell injected scid mice, 1), high levels of engraftment of the host peripheral lymphoid tissues with human CD45+ (leukocytes), CD3+ (T cells), CD4+ (helper/inducer), and CD8+ (suppressor/cytotoxic) lymphoid cells for up to 24 weeks in NOD/LtSz-scid/scid mice; 2), migration of high numbers of human lymphocytes to peripheral lymphoid and nonlymphoid organs in NOD/LtSz-scid/scid, but not in C.B-17-scid/scid mice; 3), higher levels of serum immunoglobulin of human origin in NOD/LtSz-scid/scid mice than in C.B-17-scid/scid mice; 4), histological lesions character-istic of human anti-mouse xenoreactivity in NOD/LtSz-scid/scid mice; and 5), human origin antibodies against filarial antigens after engraftment with naive human spleen cells. The use of NOD/LtSz-scid/scid mice as recipients to achieve significantly enhanced human lymphopoietic cell engraftment will now enable human immunity to be more easily studied in animal models. ImagesFigure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 12 PMID:7717456

  7. Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice.

    PubMed

    Mirsoian, Annie; Bouchlaka, Myriam N; Sckisel, Gail D; Chen, Mingyi; Pai, Chien-Chun Steven; Maverakis, Emanuel; Spencer, Richard G; Fishbein, Kenneth W; Siddiqui, Sana; Monjazeb, Arta M; Martin, Bronwen; Maudsley, Stuart; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L; Blazar, Bruce R; Wiltrout, Robert H; Taub, Dennis D; Murphy, William J

    2014-11-17

    Aging is a contributing factor in cancer occurrence. We recently demonstrated that systemic immunotherapy (IT) administration in aged, but not young, mice resulted in induction of rapid and lethal cytokine storm. We found that aging was accompanied by increases in visceral fat similar to that seen in young obese (ob/ob or diet-induced obese [DIO]) mice. Yet, the effects of aging and obesity on inflammatory responses to immunotherapeutics are not well defined. We determine the effects of adiposity on systemic IT tolerance in aged compared with young obese mice. Both young ob/ob- and DIO-generated proinflammatory cytokine levels and organ pathologies are comparable to those in aged ad libitum mice after IT, culminating in lethality. Young obese mice exhibited greater ratios of M1/M2 macrophages within the peritoneal and visceral adipose tissues and higher percentages of TNF(+) macrophages in response to ?CD40/IL-2 as compared with young lean mice. Macrophage depletion or TNF blockade in conjunction with ?CD40/IL-2 prevented cytokine storms in young obese mice and protected from lethality. Calorie-restricted aged mice contain less visceral fat and displayed reduced cytokine levels, protection from organ pathology, and protection from lethality upon ?CD40/IL-2 administration. Our data demonstrate that adiposity is a critical factor in the age-associated pathological responses to systemic anti-cancer IT. PMID:25366964

  8. CALHM1 Deletion in Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, and Life Span.

    PubMed

    Hellekant, Göran; Schmolling, Jared; Marambaud, Philippe; Rose-Hellekant, Teresa A

    2015-07-01

    Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, food intake, body weight, and life span. KO mice have no NG response to sweet and a suppressed response to bitter compared with control (wild-type [WT]) mice. KO mice showed some NG response to umami, suggesting that umami taste involves both CALHM1- and non-CALHM1-modulated signals. NG responses to sour and salty were not significantly different between KO and WT mice. Behavioral data conformed in general with the NG data. Adult KO mice consumed less food, weighed significantly less, and lived almost a year longer than WT mice. Taken together, these data demonstrate that sweet taste majorly influences food intake, body weight, and life span. PMID:25855639

  9. Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice

    PubMed Central

    Mirsoian, Annie; Bouchlaka, Myriam N.; Sckisel, Gail D.; Chen, Mingyi; Pai, Chien-Chun Steven; Maverakis, Emanuel; Spencer, Richard G.; Fishbein, Kenneth W.; Siddiqui, Sana; Monjazeb, Arta M.; Martin, Bronwen; Maudsley, Stuart; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L.; Blazar, Bruce R.; Wiltrout, Robert H.; Taub, Dennis D.

    2014-01-01

    Aging is a contributing factor in cancer occurrence. We recently demonstrated that systemic immunotherapy (IT) administration in aged, but not young, mice resulted in induction of rapid and lethal cytokine storm. We found that aging was accompanied by increases in visceral fat similar to that seen in young obese (ob/ob or diet-induced obese [DIO]) mice. Yet, the effects of aging and obesity on inflammatory responses to immunotherapeutics are not well defined. We determine the effects of adiposity on systemic IT tolerance in aged compared with young obese mice. Both young ob/ob- and DIO-generated proinflammatory cytokine levels and organ pathologies are comparable to those in aged ad libitum mice after IT, culminating in lethality. Young obese mice exhibited greater ratios of M1/M2 macrophages within the peritoneal and visceral adipose tissues and higher percentages of TNF+ macrophages in response to ?CD40/IL-2 as compared with young lean mice. Macrophage depletion or TNF blockade in conjunction with ?CD40/IL-2 prevented cytokine storms in young obese mice and protected from lethality. Calorie-restricted aged mice contain less visceral fat and displayed reduced cytokine levels, protection from organ pathology, and protection from lethality upon ?CD40/IL-2 administration. Our data demonstrate that adiposity is a critical factor in the age-associated pathological responses to systemic anti-cancer IT. PMID:25366964

  10. Cystitis induced by infection with the Lyme disease spirochete, Borrelia burgdorferi, in mice.

    PubMed Central

    Czub, S.; Duray, P. H.; Thomas, R. E.; Schwan, T. G.

    1992-01-01

    Previous studies have demonstrated that the urinary bladder is a consistent source for isolating the Lyme disease spirochete, Borrelia burgdorferi, from both experimentally infected and naturally exposed rodents. We examined histopathologic changes in the urinary bladder of different types of rodents experimentally infected with Lyme spirochetes, including BALB/c mice (Mus musculus), nude mice (M. musculus), white-footed mice (Peromyscus leucopus), and grasshopper mice (Onychomys leucogaster). Animals were inoculated intraperitoneally, subcutaneously, or intranasally with low-passaged spirochetes, high-passaged spirochetes, or phosphate-buffered saline. At various times after inoculation, animals were killed and approximately one-half of each urinary bladder and kidney were cultured separately in BSK-II medium while the other half of each organ was prepared for histologic examination. Spirochetes were cultured from the urinary bladder of all 35 mice inoculated with low-passaged spirochetes while we were unable to isolate spirochetes from any kidneys of the same mice. The pathologic changes observed most frequently in the urinary bladder of the infected mice were the presence of lymphoid aggregates, vascular changes, including an increase in the number of vessels and thickening of the vessel walls, and perivascular infiltrates. Our results demonstrate that nearly all individuals (93%) of the four types of mice examined had a cystitis associated with spirochetal infection. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1443051

  11. Cystitis induced by infection with the Lyme disease spirochete, Borrelia burgdorferi, in mice.

    PubMed

    Czub, S; Duray, P H; Thomas, R E; Schwan, T G

    1992-11-01

    Previous studies have demonstrated that the urinary bladder is a consistent source for isolating the Lyme disease spirochete, Borrelia burgdorferi, from both experimentally infected and naturally exposed rodents. We examined histopathologic changes in the urinary bladder of different types of rodents experimentally infected with Lyme spirochetes, including BALB/c mice (Mus musculus), nude mice (M. musculus), white-footed mice (Peromyscus leucopus), and grasshopper mice (Onychomys leucogaster). Animals were inoculated intraperitoneally, subcutaneously, or intranasally with low-passaged spirochetes, high-passaged spirochetes, or phosphate-buffered saline. At various times after inoculation, animals were killed and approximately one-half of each urinary bladder and kidney were cultured separately in BSK-II medium while the other half of each organ was prepared for histologic examination. Spirochetes were cultured from the urinary bladder of all 35 mice inoculated with low-passaged spirochetes while we were unable to isolate spirochetes from any kidneys of the same mice. The pathologic changes observed most frequently in the urinary bladder of the infected mice were the presence of lymphoid aggregates, vascular changes, including an increase in the number of vessels and thickening of the vessel walls, and perivascular infiltrates. Our results demonstrate that nearly all individuals (93%) of the four types of mice examined had a cystitis associated with spirochetal infection. PMID:1443051

  12. Immunization with hepatitis C virus-like particles protects mice from recombinant hepatitis C virus-vaccinia infection

    Microsoft Academic Search

    Kazumoto Murata; Martin Lechmann; Ming Qiao; Toshiaki Gunji; Harvey J. Alter; T. Jake Liang

    2003-01-01

    We have recently demonstrated that immunization with hepatitis C virus-like particles (HCV-LPs) generated in insect cells can elicit both humoral and cellular immune responses in BALB\\/c mice. Here, we evaluate the immunogenicity of HCV-LPs in HLA2.1 transgenic (AAD) mice in comparison to DNA immunization. HCV-LP immunization elicited a significantly stronger humoral immune response than DNA immunization. HCV-LP-immunized mice also developed

  13. SECURES: Austin, Texas demonstration results

    NASA Astrophysics Data System (ADS)

    Lewis, Glynn; Shaw, Scott; Scharf, Peter; Stellingworth, Bob

    2003-09-01

    The Law Enforcement technology development community has a growing interest in the technologies associated with gunshot detection and localization. These interests revolve around community-oriented policing. Technologies of interest include those associated with muzzle blast and bullet shockwave detection and the inter-netting of these acoustic sensors with electro-optic sensors. To date, no one sensor technology has proven totally effective for a complete solution. PSI has a muzzle blast detection and localization product which is wireless, highly mobile and reconfigurable, with a user-friendly laptop processor and display unit, which completed a one-year demonstration in Austin, Texas on July 6, 2002. This demonstration was conducted under a Cooperative Agreement with the National Institute of Justice and in cooperation with the Austin Police Department. This paper will discuss the details of the demonstrations, provide a summarized evaluation, elucidate the lessons learned, make recommendations for future deployments and discuss the developmental directions indicated for the future.

  14. Propane Vehicle Demonstration Grant Program

    SciTech Connect

    Jack Mallinger

    2004-08-27

    Project Description: Propane Vehicle Demonstration Grants The Propane Vehicle Demonstration Grants was established to demonstrate the benefits of new propane equipment. The US Department of Energy, the Propane Education & Research Council (PERC) and the Propane Vehicle Council (PVC) partnered in this program. The project impacted ten different states, 179 vehicles, and 15 new propane fueling facilities. Based on estimates provided, this project generated a minimum of 1,441,000 new gallons of propane sold for the vehicle market annually. Additionally, two new off-road engines were brought to the market. Projects originally funded under this project were the City of Portland, Colorado, Kansas City, Impco Technologies, Jasper Engines, Maricopa County, New Jersey State, Port of Houston, Salt Lake City Newspaper, Suburban Propane, Mutual Liquid Propane and Ted Johnson.

  15. Classroom demonstrations of acoustic beamforming.

    PubMed

    Carman, Jessie C

    2012-03-01

    A tabletop apparatus permitting demonstrations and hands-on student exercises in the acoustic beamforming of linear arrays is described. The apparatus can be used to demonstrate how interference effects from two or more linearly arranged sources produce patterns of maxima and minima as described by theory. A transmitting array is attached to the top of a rotating table and a receiving transducer provides voltages to a signal processor. Students measure the angular speed of the rotating table and the voltages produced by the receiving transducer as a function of time. These data can be analyzed in a spreadsheet program and compared to theory. The angles at which signal maxima occur correspond well to theory and useful teaching discussions result from comparisons of signal maxima magnitudes. The spreadsheet analysis can also provide the students a graphical demonstration of l'Hôpital's rule. PMID:22423786

  16. Performance demonstration in the USA

    SciTech Connect

    Spanner, J. [Electric Power Research Inst., Charlotte, NC (United States); Sheffel, B. [Detroit Edison, Newport, MI (United States); Becker, L. [NDE Center, Charlotte, NC (United States)

    1995-12-01

    In the 1989 Addenda of ASME Boiler and Pressure Vessel Code Section 11, Appendix 8, the rules for qualifying ultrasonic (UT) systems (personnel, equipment and procedures) were published. Representatives from American utilities organized the Performance Demonstration Initiative Steering Committee (PDI) to implement Appendix 8 in response to the new requirements. The utilities collaborated their resources to provide a unified approach that is economical and utility directed. Nearly all of the samples containing the flaws have been fabricated and are being used for the demonstrations. Pipe samples removed from service containing intergranular Stress Corrosion Cracking (IGSCC) have also been included in the program. The results of these initial demonstrations are summarized in this paper. Samples represented BWRs and PWRs.

  17. Demonstration of blind quantum computing.

    PubMed

    Barz, Stefanie; Kashefi, Elham; Broadbent, Anne; Fitzsimons, Joseph F; Zeilinger, Anton; Walther, Philip

    2012-01-20

    Quantum computers, besides offering substantial computational speedups, are also expected to preserve the privacy of a computation. We present an experimental demonstration of blind quantum computing in which the input, computation, and output all remain unknown to the computer. We exploit the conceptual framework of measurement-based quantum computation that enables a client to delegate a computation to a quantum server. Various blind delegated computations, including one- and two-qubit gates and the Deutsch and Grover quantum algorithms, are demonstrated. The client only needs to be able to prepare and transmit individual photonic qubits. Our demonstration is crucial for unconditionally secure quantum cloud computing and might become a key ingredient for real-life applications, especially when considering the challenges of making powerful quantum computers widely available. PMID:22267806

  18. Yo-yo Pull Demonstration

    NASA Astrophysics Data System (ADS)

    Layton, William

    2013-03-01

    A popular demonstration involves placing a yo-yo on a level table and gently pulling the string horizontally when it is wrapped to come out below the center of the yo-yo's axis. Students are then asked to predict which way the yo-yo will move. A similar demonstration is performed with a tricycle by pulling forward on a pedal with the pedal down in its lowest position.2,3 As well as pulling the yo-yo horizontally, often the string is lifted until the angle it makes with the table causes no motion. This occurs when the line extended from the string intersects the point of contact of the yo-yo with the table.4 This paper describes an apparatus that extends these demonstrations to the situation where the force pulling the yo-yo is still horizontal yet is below the level of the table.

  19. In vivo ketogenic diet treatment attenuates pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices from epileptic Kv 1.1? knockout mice.

    PubMed

    Simeone, Timothy A; Samson, Kaeli K; Matthews, Stephanie A; Simeone, Kristina A

    2014-05-01

    The ketogenic diet (KD) is an effective therapy for pediatric refractory epilepsies; however, whether the KD changes the pathologic network oscillations generated by an epileptic brain remains unknown. We have reported that hippocampal CA3 regions of epileptic Kv1.1? knockout (KO) mice generate pathologic sharp waves (SPWs) and high-frequency oscillations (HFOs) that have higher incidence, longer duration, and fast ripples compared to wild-type (WT). Synaptic activity of hyperexcitable KO mossy fibers significantly decreased CA3 principal cell spike-timing reliability, which contributed to this network pathology. In addition, we have demonstrated that the KD reduces seizures by 75% in KO mice. Here, we determined whether 10- to 14-day in vivo KD treatment exerts disease-modifying effects that alter the spontaneous SPW-HFO complexes generated by the hippocampal CA3 region of KO mice in vitro using extracellular multielectrode array recordings. We found that KD treatment significantly attenuated the pathologic features of KO SPWs and ripples and reduced the incidence of fast ripples. The KD also improved spike-timing reliability of KO CA3 principal cells, decreased mossy fiber excitability, increased mossy fiber-CA3 paired-pulse ratios, and reduced coupling of field excitatory postsynaptic potentials and population spikes in the CA3 region. Collectively, these data indicate that KD treatment modulates CA3-generated pathologic oscillations by dampening hyperactive mossy fiber synapses. PMID:24702645

  20. Saccharomyces boulardii Administration Changes Gut Microbiota and Reduces Hepatic Steatosis, Low-Grade Inflammation, and Fat Mass in Obese and Type 2 Diabetic db/db Mice

    PubMed Central

    Everard, Amandine; Matamoros, Sébastien; Geurts, Lucie; Delzenne, Nathalie M.

    2014-01-01

    ABSTRACT Growing evidence shows that gut microbes are key factors involved in the regulation of energy homeostasis, metabolic inflammation, lipid metabolism, and glucose metabolism. Therefore, gut microbiota modulations caused by selectively fermented oligosaccharides or probiotic bacteria constitute an interesting target in the physiopathology of obesity. However, to date, no probiotic yeast has been investigated in this context. Therefore, our study aimed to evaluate the impact of the most-studied probiotic yeast (i.e., Saccharomyces boulardii Biocodex) on obesity and associated metabolic features, such as fat mass development, hepatic steatosis, and low-grade inflammation, in obese mice. S. boulardii was administered daily by oral gavage to leptin-resistant obese and type 2 diabetic mice (db/db) for 4 weeks. We found that S. boulardii-treated mice exhibited reduced body weight, fat mass, hepatic steatosis, and inflammatory tone. Interestingly, these effects of S. boulardii on host metabolism were associated with local effects in the intestine. S. boulardii increased cecum weight and cecum tissue weight but also induced dramatic changes in the gut microbial composition at the phylum, family, and genus levels. These gut microbiota changes in response to S. boulardii may also be correlated with the host metabolism response. In conclusion, this study demonstrates for the first time that S. boulardii may act as a beneficial probiotic treatment in the context of obesity and type 2 diabetes. PMID:24917595

  1. Demonstration of portable solar adaptive optics system

    NASA Astrophysics Data System (ADS)

    Ren, Deqing; Dong, Bing

    2012-10-01

    Solar-adaptive optics (AO) are more challenging than night-time AO, in some aspects. A portable solar adaptive optics (PSAO) system featuring compact physical size, low cost, and good performance has been proposed and developed. PSAO can serve as a visiting instrument for any existing ground-based solar telescope to improve solar image quality by replacing just a few optical components. High-level programming language, LabVIEW, is used to develop the wavefront sensing and control software, and general purpose computers are used to drive the whole system. During October 2011, the feasibility and good performance of PSAO was demonstrated with the 61-cm solar telescope at San Fernando Observatory. The image contrast and resolution are noticeably improved after AO correction.

  2. A Demonstration Database For Document Images

    NASA Astrophysics Data System (ADS)

    Cookson, John

    1984-08-01

    This paper reports on a recent effort at the Lister Hill National Center for Biomedical Communications where it is shown that a medical bibliographic database, when linked to a mini-computer's file handling software, can be used to build a demonstration database of document images. The images of the tables of contents from approximately fifty medical books were stored on magnetic disks. The medical bibliographic database, hosted on a remote mainframe computer, was linked to the minicomputer controlling the magnetic disks. The result is that users who do bibliographic searches on a particular medical subject may view, at their work station, the tables of contents and title page from selected citations. The result is also that the document image database is accessed and managed using pre-existing features of the bibliographic database and the minicomputer's operating system.

  3. Probability of Detection Demonstration Transferability

    NASA Technical Reports Server (NTRS)

    Parker, Bradford H.

    2008-01-01

    The ongoing Mars Science Laboratory (MSL) Propellant Tank Penetrant Nondestructive Evaluation (NDE) Probability of Detection (POD) Assessment (NESC activity) has surfaced several issues associated with liquid penetrant POD demonstration testing. This presentation lists factors that may influence the transferability of POD demonstration tests. Initial testing will address the liquid penetrant inspection technique. Some of the factors to be considered in this task are crack aspect ratio, the extent of the crack opening, the material and the distance between the inspection surface and the inspector's eye.

  4. Temporal Data Mining in Dynamic Feature Spaces

    Microsoft Academic Search

    Brent Wenerstrom; Christophe G. Giraud-carrier

    2006-01-01

    Many interesting real-world applications for temporal data mining are hindered by concept drift. One particular form of concept drift is characterized by changes to the underlying feature space. Seemingly little has been done in this area. This paper presents FAE, an incremental ensemble approach to mining data subject to such concept drift. Empirical results on large data streams demonstrate promise.

  5. Phytol induced hepatotoxicity in mice

    PubMed Central

    Mackie, John T.; Atshaves, Barbara P.; Payne, H. Ross; McIntosh, Avery L.; Schroeder, Friedhelm; Kier, Ann B.

    2010-01-01

    Phytanic acid is a branched-chain, saturated fatty acid present in high concentrations in dairy products and ruminant fat. Some other dietary fats contain lower levels of phytol, which is readily converted to phytanic acid after absorption. Phytanic acid is a peroxisome proliferator binding the nuclear transcription factor peroxisome proliferator-activated receptor ? (PPAR?) to induce expression of genes encoding enzymes of fatty acid oxidation in peroxisomes and mitochondria. Administration of dietary phytol (0.5% or 1%) to normal mice for twelve to eighteen days caused consistent PPAR ? -mediated responses, such as lower body weights, higher liver weights, peroxisome proliferation, increased catalase expression, and hepatocellular hypertrophy and hyperplasia. Female mice fed 0.5% phytol and male and female mice fed 1% phytol exhibited midzonal hepatocellular necrosis, periportal hepatocellular fatty vacuolation, and corresponding increases in liver levels of the phytol metabolites phytanic acid and pristanic acid. Hepatic expression of sterol carrier protein-x (SCP-x) was five- to twelve-fold lower in female mice than in male mice. These results suggest that phytol may cause selective midzonal hepatocellular necrosis in mice, an uncommon pattern of hepatotoxic injury, and that the greater susceptibility of female mice may reflect a lower capacity to oxidize phytanic acid because of their intrinsically lower hepatic expression of SCP-x. PMID:19188468

  6. Heterozygosity for Nuclear Factor One X Affects Hippocampal-Dependent Behaviour in Mice

    PubMed Central

    Harris, Lachlan; Dixon, Chantelle; Cato, Kathleen; Heng, Yee Hsieh Evelyn; Kurniawan, Nyoman D.; Ullmann, Jeremy F. P.; Janke, Andrew L.; Gronostajski, Richard M.; Richards, Linda J.; Burne, Thomas H. J.; Piper, Michael

    2013-01-01

    Identification of the genes that regulate the development and subsequent functioning of the hippocampus is pivotal to understanding the role of this cortical structure in learning and memory. One group of genes that has been shown to be critical for the early development of the hippocampus is the Nuclear factor one (Nfi) family, which encodes four site-specific transcription factors, NFIA, NFIB, NFIC and NFIX. In mice lacking Nfia, Nfib or Nfix, aspects of early hippocampal development, including neurogenesis within the dentate gyrus, are delayed. However, due to the perinatal lethality of these mice, it is not clear whether this hippocampal phenotype persists to adulthood and affects hippocampal-dependent behaviour. To address this we examined the hippocampal phenotype of mice heterozygous for Nfix (Nfix+/?), which survive to adulthood. We found that Nfix+/? mice had reduced expression of NFIX throughout the brain, including the hippocampus, and that early hippocampal development in these mice was disrupted, producing a phenotype intermediate to that of wild-type mice and Nfix?/? mice. The abnormal hippocampal morphology of Nfix+/? mice persisted to adulthood, and these mice displayed a specific performance deficit in the Morris water maze learning and memory task. These findings demonstrate that the level of Nfix expression during development and within the adult is essential for the function of the hippocampus during learning and memory. PMID:23776487

  7. Testosterone is essential for skeletal muscle growth in aged mice in a heterochronic parabiosis model.

    PubMed

    Sinha, Indranil; Sinha-Hikim, Amiya P; Wagers, Amy J; Sinha-Hikim, Indrani

    2014-09-01

    As humans age, they lose both muscle mass and strength (sarcopenia). Testosterone, a circulating hormone, progressively declines in aging and is associated with loss of muscle mass and strength. The surgical joining of a young and old mouse (heterochronic parabiosis) activates Notch signaling and restores muscle regenerative potential in aged mice. We hypothesize that testosterone is at least one of the factors required for the improvement seen in muscles in old mice in heterochronic parabiosis with young mice. To test this hypothesis, we established the following heterochronic parabioses between young (Y; 5 months old) and old (O; 22-23 months old) C57BL6 male mice: (1) Y:O; (2) castrated Y:O (ØY:O); (3) castrated + testosterone-treated Y:O (ØY + T:O). A group of normal young mice received empty implants, and old mice were used as controls. Parabiotic pairings were maintained for 4 weeks prior to analysis. Serum testosterone levels were three-fold higher in young than in old mice. The ØY + T:O pairing demonstrated significantly elevated levels of serum testosterone and an improvement in gastrocnemius muscle weight, muscle ultrastructure, muscle fiber cross-sectional area, and Notch-1 expression in old mice. These changes were not present in aged mice in the ØY:O pairing. These data indicate that testosterone has a critical role in mediating the improved muscle mass and ultrastructure seen in an experimental model of heterochronic parabiosis. PMID:24859218

  8. Dietary methionine restriction in mice elicits an adaptive cardiovascular response to hyperhomocysteinemia.

    PubMed

    Ables, Gene P; Ouattara, Amadou; Hampton, Thomas G; Cooke, Diana; Perodin, Frantz; Augie, Ines; Orentreich, David S

    2015-01-01

    Dietary methionine restriction (MR) in rodents increased lifespan despite higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia, which are symptoms associated with increased risk for cardiovascular disease. We investigated this paradoxical effect of MR on cardiac function using young, old, and apolipoprotein E-deficient (ApoE-KO) mice. Indeed, MR animals exhibited higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia with a molecular pattern consistent with cardiac stress while maintaining the integrity of cardiac structure. Baseline cardiac function, which was measured by non-invasive electrocardiography (ECG), showed that young MR mice had prolonged QRS intervals compared with control-fed (CF) mice, whereas old and ApoE-KO mice showed similar results for both groups. Following ?-adrenergic challenge, responses of MR mice were either similar or attenuated compared with CF mice. Cardiac contractility, which was measured by isolated heart retrograde perfusion, was similar in both groups of old mice. Finally, the MR diet induced secretion of cardioprotective hormones, adiponectin and fibroblast growth factor 21 (FGF21), in MR mice with concomitant alterations in cardiac metabolic molecular signatures. Our findings demonstrate that MR diet does not alter cardiac function in mice despite the presence of hyperhomocysteinemia because of the adaptive responses of increased adiponectin and FGF21 levels. PMID:25744495

  9. Dietary Methionine Restriction in Mice Elicits an Adaptive Cardiovascular Response to Hyperhomocysteinemia

    PubMed Central

    Ables, Gene P.; Ouattara, Amadou; Hampton, Thomas G.; Cooke, Diana; Perodin, Frantz; Augie, Ines; Orentreich, David S.

    2015-01-01

    Dietary methionine restriction (MR) in rodents increased lifespan despite higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia, which are symptoms associated with increased risk for cardiovascular disease. We investigated this paradoxical effect of MR on cardiac function using young, old, and apolipoprotein E-deficient (ApoE-KO) mice. Indeed, MR animals exhibited higher heart-to-body weight ratio (w/w) and hyperhomocysteinemia with a molecular pattern consistent with cardiac stress while maintaining the integrity of cardiac structure. Baseline cardiac function, which was measured by non-invasive electrocardiography (ECG), showed that young MR mice had prolonged QRS intervals compared with control-fed (CF) mice, whereas old and ApoE-KO mice showed similar results for both groups. Following ?-adrenergic challenge, responses of MR mice were either similar or attenuated compared with CF mice. Cardiac contractility, which was measured by isolated heart retrograde perfusion, was similar in both groups of old mice. Finally, the MR diet induced secretion of cardioprotective hormones, adiponectin and fibroblast growth factor 21 (FGF21), in MR mice with concomitant alterations in cardiac metabolic molecular signatures. Our findings demonstrate that MR diet does not alter cardiac function in mice despite the presence of hyperhomocysteinemia because of the adaptive responses of increased adiponectin and FGF21 levels. PMID:25744495

  10. Early Adaptive Responses of the Vascular Wall during Venous Arterialization in Mice

    PubMed Central

    Kwei, Stephanie; Stavrakis, George; Takahas, Masaya; Taylor, George; Folkman, M. Judah; Gimbrone, Michael A.; García-Cardeña, Guillermo

    2004-01-01

    Venous arterialization occurs when a vein segment is transposed as a bypass graft into the arterial circulation, resulting in a structural and functional reorganization of the vascular wall in response to the new local biomechanical environment. Although the anatomical changes of venous arterialization have been well characterized, the molecular mechanisms of vascular remodeling remain incompletely understood. Here, we present a novel model of venous arterialization in mice wherein the external jugular vein is connected to the common carotid artery. The hemodynamic characteristics of the arterialized vein, as assessed by ultrasound and magnetic resonance imaging, resemble features of the arterial circulation. Temporal analyses of the morphological changes in the venous segment at 1, 3, and 7 days after surgery demonstrate preservation of the endothelium at all time points and formation of multiple smooth muscle layers by day 7. Expression of endothelial E-selectin and VCAM-1 was documented at early time points, concomitant with the presence of neutrophils and monocytes/macrophages in the vascular wall. In addition, endothelium-dependent permeability was decreased in the arterialized vein when compared to the contralateral control vein. Thus, this novel mouse model of venous arterialization displays anatomical and cellular features present in other species, and should help to characterize the molecular mechanisms of this adaptive response of the vascular wall to changes in its biomechanical environment. PMID:14695322

  11. Effect of Environment on Staphylococcal Lesions in Mice

    PubMed Central

    Schmidt, Jerome P.; Cordaro, Joseph T.; Ball, Robert J.

    1967-01-01

    The influence of reduced barometric pressure on the development and healing of staphylococcal skin lesions in mice was investigated by exposing groups of animals to the test environment before, after, or before and after subcutaneous inoculation with 3.5 × 108 colony-forming units of a phage type 80 strain of Staphylococcus aureus. Similarly infected control animals were not exposed to the experimental environment. The results indicate that the lesions which developed in mice exposed to the test environment prior to infectious challenge were larger and healed at a slower rate than those in mice maintained at ground level before infection. Exposure after inoculation produced no demonstrable effect in the size or healing rate of the experimental lesions. Images Fig. 2 PMID:16349767

  12. Repeated positive fighting experience in male inbred mice.

    PubMed

    Kudryavtseva, Natalia N; Smagin, Dmitry A; Kovalenko, Irina L; Vishnivetskaya, Galina B

    2014-11-01

    Repeated aggression is a frequent symptom of many psychiatric and neurological disorders, including obsessive-compulsive and attention deficit hyperactivity disorders, bipolar and post-traumatic stress disorders, epilepsy, autism, schizophrenia and drug abuse. However, repeated aggression is insufficiently studied because there is a lack of adequate models in animals. The sensory contact model (SCM), widely used to study the effects of chronic social defeat stress, can also be used to investigate the effects of repeated aggression. Mice with repeated positive fighting experience in daily agonistic interactions in this model develop pronounced aggressiveness, anxiety and impulsivity, disturbances in motivated and cognitive behaviors, and impairments of sociability; they also demonstrate hyperactivity, attention-deficit behavior, motor dysfunctions and repetitive stereotyped behaviors, such as jerks, rotations and head twitches. In this protocol, we describe how to apply the SCM to study repeated aggression in mice. Severe neuropathology develops in male mice after 20-21 d of agonistic interactions. PMID:25340443

  13. Spontaneous Generation of Infectious Prion Disease in Transgenic Mice

    PubMed Central

    Castilla, Joaquín; Pintado, Belén; Gutiérrez-Adan, Alfonso; Andréoletti, Olivier; Aguilar-Calvo, Patricia; Arroba, Ana-Isabel; Parra-Arrondo, Beatriz; Ferrer, Isidro; Manzanares, Jorge; Espinosa, Juan-Carlos

    2013-01-01

    We generated transgenic mice expressing bovine cellular prion protein (PrPC) with a leucine substitution at codon 113 (113L). This protein is homologous to human protein with mutation 102L, and its genetic link with Gerstmann–Sträussler–Scheinker syndrome has been established. This mutation in bovine PrPC causes a fully penetrant, lethal, spongiform encephalopathy. This genetic disease was transmitted by intracerebral inoculation of brain homogenate from ill mice expressing mutant bovine PrP to mice expressing wild-type bovine PrP, which indicated de novo generation of infectious prions. Our findings demonstrate that a single amino acid change in the PrPC sequence can induce spontaneous generation of an infectious prion disease that differs from all others identified in hosts expressing the same PrPC sequence. These observations support the view that a variety of infectious prion strains might spontaneously emerge in hosts displaying random genetic PrPC mutations. PMID:24274622

  14. [Behavior of mice from different strains: modifications produced by noopept].

    PubMed

    Bel'nik, A P; Ostrovskaia, R U; Poletaeva, I I

    2007-01-01

    Genotype-dependent behavioral effects were demonstrated in BALB/c, C57BL/6J [Russian character: see text] DBA/2J mice after injections of nootropic drug Noopept. In an elevated plus maze, drug administration induced an increase in the number of enterings into bright arms in BALB/c mice, whereas the opposite effect was observed in C57BL/6J. After the Noopept administration, animals from all the three strains increased the number of active avoidance reactions in stress-inducing slip-funnel test. A significant intensification of exploration behavior was observed in a closed plus-maze in BALB/c and C57BL/6J. The Noopept affected weakly or had no effect on the behavior of DBA/2J mice. PMID:18064900

  15. Lung disease in mice with cystic fibrosis.

    PubMed Central

    Kent, G; Iles, R; Bear, C E; Huan, L J; Griesenbach, U; McKerlie, C; Frndova, H; Ackerley, C; Gosselin, D; Radzioch, D; O'Brodovich, H; Tsui, L C; Buchwald, M; Tanswell, A K

    1997-01-01

    The leading cause of mortality and morbidity in humans with cystic fibrosis is lung disease. Advances in our understanding of the pathogenesis of the lung disease of cystic fibrosis, as well as development of innovative therapeutic interventions, have been compromised by the lack of a natural animal model. The utility of the CFTR-knockout mouse in studying the pathogenesis of cystic fibrosis has been limited because of their failure, despite the presence of severe intestinal disease, to develop lung disease. Herein, we describe the phenotype of an inbred congenic strain of CFTR-knockout mouse that develops spontaneous and progressive lung disease of early onset. The major features of the lung disease include failure of effective mucociliary transport, postbronchiolar over inflation of alveoli and parenchymal interstitial thickening, with evidence of fibrosis and inflammatory cell recruitment. We speculate that the basis for development of lung disease in the congenic CFTR-knockout mice is their observed lack of a non-CFTR chloride channel normally found in CFTR-knockout mice of mixed genetic background. PMID:9399953

  16. Favorite Demonstration: Demonstrating Translation With a Student-Centered Activity

    NSDL National Science Digital Library

    Therese M. Poole

    2006-03-01

    The process of protein synthesis translation is difficult for many students to understand. The reasons for this include the fact that it is difficult to visualize the process since the components involved in the process are not observable. Also, there are many details, often dependent on each other and difficult to grasp independently that are necessary to know in order to understand the process. With that in mind, an interactive group demonstration was developed to help students vizualize the process of translation.

  17. Preventive effect of polysaccharides from the large yellow croaker swim bladder on HCl/ethanol induced gastric injury in mice.

    PubMed

    Chen, Shaocheng; Zhu, Kai; Wang, Rui; Zhao, Xin

    2014-07-01

    In the present study the preventive effect of polysaccharides from the large yellow croaker swim bladder (PLYCSB) on HCl/ethanol-induced gastric injury in ICR mice was investigated. A high dose of PLYCSB (50 mg/kg) was found to reduce the levels of the serum proinflammatory cytokines interleukin (IL)-1?, IL-6, IL-8, as well as increase the levels of IL-4 compared with those in mice treated with a low dose of PLYCSB (25 mg/kg) and control mice. The somatostatin and vasoactive intestinal peptide serum levels in PLYCSB-treated mice were higher compared with those in control mice, whilst motilin and substance P serum levels were lower compared with those in control mice. The extent of the gastric injury in the mice treated with PLYCSB was lower compared with that in the control mice; however, the results obtained for mice treated with a high dose of PLYCSB were similar to those for omeprazole-treated mice. In addition, the superoxide dismutase and glutathione peroxidase activities of PLYCSB-treated mice were higher compared with those of the control mice, and similar to those observed in normal and omeprazole-treated mice. Furthermore, PLYCSB-treated mice showed levels of nitric oxide and malondialdehyde that were similar to those in the normal group. Using PCR and western blot analysis, it was demonstrated that PLYCSB significantly inhibited inflammation in the tissues of the HCl/ethanol induced gastric injury mice by downregulating the expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-? and IL-1?. These results suggest that PLYCSB has an inhibitory effect against gastric injury that is comparable to that of the gastric injury drug omeprazole. Therefore, PLYCSB has the potential to be used as a natural therapeutic drug. PMID:24944640

  18. Preventive effect of polysaccharides from the large yellow croaker swim bladder on HCl/ethanol induced gastric injury in mice

    PubMed Central

    CHEN, SHAOCHENG; ZHU, KAI; WANG, RUI; ZHAO, XIN

    2014-01-01

    In the present study the preventive effect of polysaccharides from the large yellow croaker swim bladder (PLYCSB) on HCl/ethanol-induced gastric injury in ICR mice was investigated. A high dose of PLYCSB (50 mg/kg) was found to reduce the levels of the serum proinflammatory cytokines interleukin (IL)-1?, IL-6, IL-8, as well as increase the levels of IL-4 compared with those in mice treated with a low dose of PLYCSB (25 mg/kg) and control mice. The somatostatin and vasoactive intestinal peptide serum levels in PLYCSB-treated mice were higher compared with those in control mice, whilst motilin and substance P serum levels were lower compared with those in control mice. The extent of the gastric injury in the mice treated with PLYCSB was lower compared with that in the control mice; however, the results obtained for mice treated with a high dose of PLYCSB were similar to those for omeprazole-treated mice. In addition, the superoxide dismutase and glutathione peroxidase activities of PLYCSB-treated mice were higher compared with those of the control mice, and similar to those observed in normal and omeprazole-treated mice. Furthermore, PLYCSB-treated mice showed levels of nitric oxide and malondialdehyde that were similar to those in the normal group. Using PCR and western blot analysis, it was demonstrated that PLYCSB significantly inhibited inflammation in the tissues of the HCl/ethanol induced gastric injury mice by downregulating the expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-? and IL-1?. These results suggest that PLYCSB has an inhibitory effect against gastric injury that is comparable to that of the gastric injury drug omeprazole. Therefore, PLYCSB has the potential to be used as a natural therapeutic drug. PMID:24944640

  19. Myriad innovations mark scrubber demonstration

    SciTech Connect

    Not Available

    1994-04-01

    This article reviews a demonstration of the CT-121 flue gas scrubber process at Georgia Power Company's Plant Yates. The topics of the article include scrubber performance and reliability, a brief description of the absorption module, eliminating reheat of the flue gas before exiting the scrubber, and the extensive use of fiberglass reinforced plastic.

  20. Satellite Technology Demonstration; Final Report.

    ERIC Educational Resources Information Center

    Federation of Rocky Mountain States, Inc., Denver, CO.

    The goal of the Satellite Technology Demonstration project (STD) was to show the feasibility of a satellite-based media system for isolated, rural populations and to test and evaluate user acceptance and the cost of various delivery modes using a variety of materials. The STD amalgamated the resources of government, health, education, and…

  1. Binary Quantum Receiver Concept Demonstration

    Microsoft Academic Search

    C.-W. Lau; V. A. Vilnrotter; S. Dolinar; J. M. Geremia; H. Mabuchi

    2006-01-01

    An experimental demonstration of a quantum optimal receiver for optical bi- nary signals, developed as a joint effort by the Jet Propulsion Laboratory and the California Institute of Technology, is described in this article. A brief summary of the classical, quantum optimal, and quantum near-optimal solutions for detecting binary signals is first presented. The components and experimental setup used to

  2. Demonstrating Fermat's Principle in Optics

    ERIC Educational Resources Information Center

    Paleiov, Orr; Pupko, Ofir; Lipson, S. G.

    2011-01-01

    We demonstrate Fermat's principle in optics by a simple experiment using reflection from an arbitrarily shaped one-dimensional reflector. We investigated a range of possible light paths from a lamp to a fixed slit by reflection in a curved reflector and showed by direct measurement that the paths along which light is concentrated have either…

  3. Demonstrations with an "LCR" Circuit

    ERIC Educational Resources Information Center

    Kraftmakher, Yaakov

    2011-01-01

    The "LCR" circuit is an important topic in the course of electricity and magnetism. Papers in this field consider mainly the forced oscillations and resonance. Our aim is to show how to demonstrate the free and self-excited oscillations in an "LCR" circuit. (Contains 4 figures.)

  4. Demonstrations To Save the World.

    ERIC Educational Resources Information Center

    Brown, Tom; Dias, Michael

    2003-01-01

    Presents two environmental modeling activities, biosphere bubbles and a crystal ball of population growth, along with a related online exercise and explains proven teaching methods that make demonstrations less teacher-centered and more engaging for groups of collaborating students. (KHR)

  5. Launch Vehicle Dynamics Demonstrator Model

    NASA Technical Reports Server (NTRS)

    1963-01-01

    Launch Vehicle Dynamics Demonstrator Model. The effect of vibration on launch vehicle dynamics was studied. Conditions included three modes of instability. The film includes close up views of the simulator fuel tank with and without stability control. [Entire movie available on DVD from CASI as Doc ID 20070030984. Contact help@sti.nasa.gov

  6. AARD - Autonomous Airborne Refueling Demonstration

    NASA Technical Reports Server (NTRS)

    Ewers, Dick

    2007-01-01

    This viewgraph document reviews the Autonomous Airborne Refueling Demonstration program, and NASA Dryden's work in the program. The primary goal of the program is to make one fully automatic probe-to-drogue engagement using the AARD system. There are pictures of the aircraft approaching to the docking.

  7. Optical demonstrations though science fairs

    Microsoft Academic Search

    G. Groot Gregory; David P. Biss; Barbara Darnell

    2010-01-01

    The New England Section of the Optical Society of America (NES\\/OSA), founded in 1949, provides programming for the promotion of science and optics education. In recent years, the NES\\/OSA has combined funding to provide demonstrations during the Massachusetts Science Fairs for Middle and High School age groups and award prizes to the winners. This funding is supplied from the Section's

  8. Demonstrating Sound Impulses in Pipes.

    ERIC Educational Resources Information Center

    Raymer, M. G.; Micklavzina, Stan

    1995-01-01

    Describes a simple, direct method to demonstrate the effects of the boundary conditions on sound impulse reflections in pipes. A graphical display of the results can be made using a pipe, cork, small hammer, microphone, and fast recording electronics. Explains the principles involved. (LZ)

  9. Unmanned space vehicle technology demonstrator

    NASA Astrophysics Data System (ADS)

    Tancredi, U.; Accardo, D.; Grassi, M.; Curreri, F.

    2007-02-01

    The unmanned space vehicle (USV) program has been undertaken by the Italian Center for Aerospace Research with the aim of developing flying test beds of next generation reentry launch vehicles. In this framework, the development of small demonstrators is also foreseen to validate technological and operational aspects of full-scale vehicles and missions. In this paper, a small-scale demonstrator of the sub-orbital re-entry test mission of the USV program is described. Both mission profile and objectives are very challenging in terms of demonstrator guidance, navigation and control. After a short description of the mission and demonstrator architectures, particular emphasis is given to the guidance and navigation analysis. To this end, mission objectives and reduced-scale system constaints are integrated and translated into innovative guidance solutions relying on optimization techniques. Then, performance of a commercial-off-the-shelf GPS-aided, miniature inertial navigation system over the proposed trajectories is evaluated by Monte Carlo analysis. Standalone inertial and GPS-aided inertial navigation performance is also compared considering GPS loss conditions due to antenna plasma effects.

  10. GLOBAL EMISSIONS DATABASE (GLOED) DEMONSTRATION

    EPA Science Inventory

    The paper describes the EPA-developed Global Emissions Database (GloED) and how it works. t was prepared to accompany a demonstration of GloED, a powerful software package. loED is a user-friendly, menu-driven tool for storing and retriEving emissions factors and activity data on...

  11. A Demonstration and a Souvenir

    ERIC Educational Resources Information Center

    Lentz, Randy

    1978-01-01

    Describes an activity using interchangeable, preset tool holders to provide a demonstration for parents or students attending a school's open house session that produces a small souvenir (an aluminum mini-chalice) for them. A procedure sheet for the school's individual lathe and specification diagrams for making the cup are provided. (TA)

  12. George Arcement Demonstrates the ADCP

    USGS Multimedia Gallery

    USGS Water Science Center Director George Arcement demonstrates the Acoustic Doppler Current Profiler (ADCP) to legislative staffers. USGS uses the ADCP to make streamflow measurements. The ADCP emits soundwaves through the water column, which rebound off particles in the water until they reach ...

  13. Weed Identification Field Training Demonstrations.

    ERIC Educational Resources Information Center

    Murdock, Edward C.; And Others

    1986-01-01

    Reviews efforts undertaken in weed identification field training sessions for agriprofessionals in South Carolina. Data over a four year period (1980-1983) revealed that participants showed significant improvement in their ability to identify weeds. Reaffirms the value of the field demonstration technique. (ML)

  14. Classroom Demonstrations of Polymer Principles.

    ERIC Educational Resources Information Center

    Rodriguez, F.; And Others

    1987-01-01

    Describes several techniques to help students visualize the principles of polymer chemistry. Outlines demonstrations using simple materials (such as pop-it beads, thread, and wire) to illustrate the size of macromolecules, the composition of copolymers, and the concept of molecular mass. (TW)

  15. Programming shell scripts by demonstration

    Microsoft Academic Search

    Tessa Lau; Lawrence Bergman; Vittorio Castelli; Daniel Oblinger

    Command-line interfaces are heavily used by system admin- istrators to manage computer systems. Tasks performed at a command line may often be repetitive, leading to a desire for automation. However, the critical nature of system adminis- tration suggests that humans also need to supervise an auto- mated system's behavior. This paper presents a programming by demonstration approach to capturing repetitive

  16. A Demonstration of Simultaneous Electrochemiluminescence

    ERIC Educational Resources Information Center

    Ibanez, Jorge G.; Zavala-Araiza, Daniel; Sotomayor-Martinez Barranco, Biaani; Torres-Perez, Jonatan; Camacho-Zuniga, Claudia; Bohrmann-Linde, Claudia; Tausch, Michael W.

    2013-01-01

    Paired (simultaneous) electrochemical processes can increase energy savings in selected cases by using the reactions at both electrodes of an electrochemical cell to perform a desired process, as is the case in the commercially successful chlor-alkali process. In the demonstration described herein, simultaneous blue electrochemiluminescence (ECL)…

  17. Augmenting a Classical Electrochemical Demonstration.

    ERIC Educational Resources Information Center

    Yochum, Susan M.; Luoma, John R.

    1995-01-01

    Presents an augmentation of a classical electrochemical demonstration that addresses the learning styles of the students and teaches electrochemistry in a concrete manner. Enables each student to see each event clearly, repeatedly, or in stop-action mode and enables students to improve their own mental models by providing them with a visually…

  18. LIMB Demonstration Project Extension and Coolside Demonstration. [Final report

    SciTech Connect

    Goots, T.R.; DePero, M.J.; Nolan, P.S.

    1992-11-10

    This report presents results from the limestone Injection Multistage Burner (LIMB) Demonstration Project Extension. LIMB is a furnace sorbent injection technology designed for the reduction of sulfur dioxide (SO{sub 2}) and nitrogen oxides (NO{sub x}) emissions from coal-fired utility boilers. The testing was conducted on the 105 Mwe, coal-fired, Unit 4 boiler at Ohio Edison`s Edgewater Station in Lorain, Ohio. In addition to the LIMB Extension activities, the overall project included demonstration of the Coolside process for S0{sub 2} removal for which a separate report has been issued. The primary purpose of the DOE LIMB Extension testing, was to demonstrate the generic applicability of LIMB technology. The program sought to characterize the S0{sub 2} emissions that result when various calcium-based sorbents are injected into the furnace, while burning coals having sulfur content ranging from 1.6 to 3.8 weight percent. The four sorbents used included calcitic limestone, dolomitic hydrated lime, calcitic hydrated lime, and calcitic hydrated lime with a small amount of added calcium lignosulfonate. The results include those obtained for the various coal/sorbent combinations and the effects of the LIMB process on boiler and plant operations.

  19. Distinct mechanisms are responsible for osteopenia and growth retardation in OASIS-deficient mice.

    PubMed

    Murakami, Tomohiko; Hino, Shin-Ichiro; Nishimura, Riko; Yoneda, Toshiyuki; Wanaka, Akio; Imaizumi, Kazunori

    2011-03-01

    Old astrocyte specifically induced substance (OASIS), which is a new type of endoplasmic reticulum (ER) stress transducer, is a basic leucine zipper transcription factor of the CREB/ATF family that contains a transmembrane domain and is processed by regulated intramembrane proteolysis in response to ER stress. OASIS is selectively expressed in certain types of cells such as astrocytes and osteoblasts. We have previously demonstrated that OASIS activates transcription of the type I collagen gene Col1a1 and contributes to the secretion of bone matrix proteins in osteoblasts, and that OASIS-/- mice exhibit osteopenia and growth retardation. In the present study, we examined whether osteopenia in OASIS-/- mice is rescued by OASIS introduction into osteoblasts. We generated OASIS-/- mice that specifically expressed OASIS in osteoblasts using a 2.3-kb osteoblast-specific type I collagen promoter (OASIS-/-;Tg mice). Histological analysis of OASIS-/-;Tg mice revealed that osteopenia in OASIS-/- mice was rescued by osteoblast-specific expression of the OASIS transgene. The decreased expression levels of type I collagen mRNAs in the bone tissues of OASIS-/- mice were recovered by the OASIS transgene accompanied by the rescue of an abnormal expansion of the rough ER in OASIS-/- osteoblasts. In contrast, growth retardation in OASIS-/- mice did not improve in OASIS-/-;Tg mice. Interestingly, the serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-1 were downregulated in OASIS-/- mice compared with those in wild-type mice. These decreased GH and IGF-1 levels in OASIS-/- mice did not change when OASIS was introduced into osteoblasts. Taken together, these results indicate that OASIS regulates skeletal development by osteoblast-dependent and -independent mechanisms. PMID:21047569

  20. Immune response against lymphocytic choriomeningitis virus infection in mice without CD8 expression

    PubMed Central

    1991-01-01

    The immune response against lymphocytic choriomeningitis virus (LCMV) was studied in a mutant mouse strain that does not possess CD8+ T lymphocytes. Virus-specific cytotoxic T cell activity was generated in spleens of wild-type mice in an acute LCMV infection but was not measurable in mutant mice. Injection of replicating LCMV into footpads of wild-type mice induced a CD8+ T cell-mediated swelling that peaked on day 8, followed by a CD4+ T cell-mediated swelling that peaked on day 11, whereas mutant mice exhibited only the CD4+ T cell-mediated swelling. After intracerebral inoculation with LCMV-Armstrong, all wild- type mice died of classical CD8+ T cell-dependent choriomeningitis in 8- 10 days. Mutant mice showed symptoms of general malaise but most of them survived. Mutant mice depleted of CD4+ T cells by monoclonal antibody treatment showed no clinical signs of sickness. On day 9 after intravenous infection with LCMV-WE, virus was detected at high titers in spleens and livers of mutant mice but not in those of wild-type mice. On day 70 after injection of LCMV-WE into footpads, virus was not detected in wild-type mice and in one of the three mutant mice tested, but was still measurable in kidneys of the other two mutant mice. These results confirm in a new animal model that CD8+ T cell-mediated immunity is crucial in LCMV clearance and in the immunopathological disease during LCMV infection. In addition, our results demonstrated a less severe form of choriomeningitis mediated by CD4+ T cells and slow clearance of LCMV by alternative pathways independent of CD8+ T cells. PMID:1683893

  1. Osteoblast-Specific ?-Glutamyl Carboxylase-Deficient Mice Display Enhanced Bone Formation With Aberrant Mineralization.

    PubMed

    Azuma, Kotaro; Shiba, Sachiko; Hasegawa, Tomoka; Ikeda, Kazuhiro; Urano, Tomohiko; Horie-Inoue, Kuniko; Ouchi, Yasuyoshi; Amizuka, Norio; Inoue, Satoshi

    2015-07-01

    Vitamin K is a fat-soluble vitamin that is necessary for blood coagulation. In addition, it has bone-protective effects. Vitamin K functions as a cofactor of ?-glutamyl carboxylase (GGCX), which activates its substrates by carboxylation. These substrates are found throughout the body and examples include hepatic blood coagulation factors. Furthermore, vitamin K functions as a ligand of the nuclear receptor known as steroid and xenobiotic receptor (SXR) and its murine ortholog, pregnane X receptor (PXR). We have previously reported on the bone-protective role of SXR/PXR signaling by demonstrating that systemic Pxr-knockout mice displayed osteopenia. Because systemic Ggcx-knockout mice die shortly after birth from severe hemorrhage, the GGCX-mediated effect of vitamin K on bone metabolism has been difficult to evaluate. In this work, we utilized Ggcx-floxed mice to generate osteoblast-specific GGCX-deficient (Ggcx(?obl/?obl) ) mice by crossing them with Col1-Cre mice. The bone mineral density (BMD) of Ggcx(?obl/?obl) mice was significantly higher than that of control Col1-Cre (Ggcx(+/+) ) mice. Histomorphometrical analysis of trabecular bones in the proximal tibia showed increased osteoid volume and a higher rate of bone formation in Ggcx(?obl/?obl) mice. Histomorphometrical analysis of cortical bones revealed a thicker cortical width and a higher rate of bone formation in Ggcx(?obl/?obl) mice. Electron microscopic examination revealed disassembly of mineralized nodules and aberrant calcification of collagen fibers in Ggcx(?obl/?obl) mice. The mechanical properties of bones from Ggcx(?obl/?obl) mice tended to be stronger than those from control Ggcx(+/+) mice. These results suggest that GGCX in osteoblasts functions to prevent abnormal mineralization in bone formation, although this function may not be a prerequisite for the bone-protective effect of vitamin K. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research. PMID:25600070

  2. Ferroportin deficiency impairs manganese metabolism in flatiron mice.

    PubMed

    Seo, Young Ah; Wessling-Resnick, Marianne

    2015-07-01

    We examined the physiologic role of ferroportin (Fpn) in manganese (Mn) export using flatiron (ffe/+) mice, a genetic model of Fpn deficiency. Blood (0.0123 vs. 0.0107 mg/kg; P = 0.0003), hepatic (1.06 vs. 0.96 mg/kg; P = 0.0125), and bile Mn levels (79 vs. 38 mg/kg; P = 0.0204) were reduced in ffe/+ mice compared to +/+ controls. Erythrocyte Mn-superoxide dismutase was also reduced at 6 (0.154 vs. 0.096, P = 0.0101), 9 (0.131 vs. 0.089, P = 0.0162), and 16 weeks of age (0.170 vs. 0.090 units/mg protein/min; P < 0.0001). (54)Mn uptake after intragastric gavage was markedly reduced in ffe/+ mice (0.0187 vs. 0.0066% dose; P = 0.0243), while clearance of injected isotope was similar in ffe/+ and +/+ mice. These values were compared to intestinal absorption of (59)Fe, which was significantly reduced in ffe/+ mice (8.751 vs. 3.978% dose; P = 0.0458). The influence of the ffe mutation was examined in dopaminergic SH-SY5Y cells and human embryonic HEK293T cells. While expression of wild-type Fpn reversed Mn-induced cytotoxicity, ffe mutant H32R failed to confer protection. These combined results demonstrate that Fpn plays a central role in Mn transport and that flatiron mice provide an excellent genetic model to explore the role of this exporter in Mn homeostasis.-Seo, Y. A., Wessling-Resnick, M. Ferroportin deficiency impairs manganese metabolism in flatiron mice. PMID:25782988

  3. Autism-related behavioral abnormalities in synapsin knockout mice

    PubMed Central

    Greco, Barbara; Managò, Francesca; Tucci, Valter; Kao, Hung-Teh; Valtorta, Flavia; Benfenati, Fabio

    2013-01-01

    Several synaptic genes predisposing to autism-spectrum disorder (ASD) have been identified. Nonsense and missense mutations in the SYN1 gene encoding for Synapsin I have been identified in families segregating for idiopathic epilepsy and ASD and genetic mapping analyses have identified variations in the SYN2 gene as significantly contributing to epilepsy predisposition. Synapsins (Syn I/II/III) are a multigene family of synaptic vesicle-associated phosphoproteins playing multiple roles in synaptic development, transmission and plasticity. Lack of SynI and/or SynII triggers a strong epileptic phenotype in mice associated with mild cognitive impairments that are also present in the non-epileptic SynIII?/? mice. SynII?/? and SynIII?/? mice also display schizophrenia-like traits, suggesting that Syns could be involved in the regulation of social behavior. Here, we studied social interaction and novelty, social recognition and social dominance, social transmission of food preference and social memory in groups of male SynI?/?, SynII?/? and SynIII?/? mice before and after the appearance of the epileptic phenotype and compared their performances with control mice. We found that deletion of Syn isoforms widely impairs social behaviors and repetitive behaviors, resulting in ASD-related phenotypes. SynI or SynIII deletion altered social behavior, whereas SynII deletion extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming. Social impairments of SynI?/? and SynII?/? mice were evident also before the onset of seizures. The results demonstrate an involvement of Syns in generation of the behavioral traits of ASD and identify Syn knockout mice as a useful experimental model of ASD and epilepsy. PMID:23280234

  4. Natural Hazard Demonstrations for Teaching

    NASA Astrophysics Data System (ADS)

    Malamud, B. D.

    2005-12-01

    This paper presents several demonstrations that have been developed or gathered from other sources in the general area of natural hazards (e.g. landslides, earthquakes, volcanoes, wildfires, tsunamis, mass movements, asteroid impacts, etc.). There are many methods of teaching, but as university lecturers, particularly for large class sizes, we find ourselves too often presenting material to students by direct speaking, or some combination of blackboard/whiteboard/slide projector/digital projector. There are certainly a number of techniques to more actively involve students, so that teaching is not just `receiving of information', including breaking up students into small group discussions, encouraging students to actively participate in class through comments and questions, and/or some combination of hands-on activities and demonstrations. It is this latter which is concentrated on here. As a teaching tool, the students themselves became much more excited about what they are learning if use is made of 5--10 minute demonstrations, even if only peripherally related to the subject at hand. The resultant discussion with questions and comments by students keeps both the students and the lecturer (in this case the author) motivated and intrigued about the subjects being discussed. Days, weeks, and months later, the students remember these `demonstrations', but to set these up takes time, effort, and resources of equipment, although not necessarily a large amount of the latter. Several natural hazards demonstrations are presented here, most inexpensive, that have been used in front of large university classes and smaller `break-out groups', and which can also be adapted for secondary-school students.

  5. A Classroom Demonstration of Taste-Aversion Learning.

    ERIC Educational Resources Information Center

    Best, Michael R.; Batsell, Jr., W. Robert

    1998-01-01

    Describes a demonstration that recreates the central features of taste aversion (learning to avoid distinctively flavored food or drink paired with gastrointestinal illness) research. Rats are allowed to drink a saccharine flavored solution and then are given an injection of sodium chloride. They associate the unpleasant effects with the solution.…

  6. Demonstration Dock Designed to Benefit Eelgrass Habitat Restoration (Washington)

    Microsoft Academic Search

    Heida L. Diefenderfer; Susan L. Sargeant; Ronald M. Thom; Amy B. Borde; Perry F. Gayaldo; Craig A. Curtis; Brian L. Court; David M. Pierce; David S. Robison

    2004-01-01

    The derelict Thomas Oil Dock on state tidelands in Port Townsend, Washington, was redesigned for the Northwest Maritime Center by a committee including marine scientists, architects, engineers, educators, regulators, and user groups. The committee's objectives were to create a ''demonstration dock'' using the best-available technologies and design features to restore nearshore habitat functions, particularly for threatened fisheries resources, while accommodating

  7. Illustration of the X-37 Advanced Technology Demonstrator during flight

    NASA Technical Reports Server (NTRS)

    1999-01-01

    An artist's conception of the X-37 Advanced Technology Demonstrator as it glides to a landing on earth. Its design features a rounded fuselage topped by an experiment bay; short, double delta wings (like those of the Shuttle orbiter); and two stabilizers (that form a V-shape) at the rear of the vehicle.

  8. Acceleration of bone development and regeneration through the Wnt/?-catenin signaling pathway in mice heterozygously deficient for GSK-3?

    SciTech Connect

    Arioka, Masaki [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan) [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Takahashi-Yanaga, Fumi, E-mail: yanaga@clipharm.med.kyushu-u.ac.jp [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan) [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Global Medical Science Education Unit, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Sasaki, Masanori [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan)] [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Yoshihara, Tatsuya; Morimoto, Sachio [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan)] [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan); Takashima, Akihiko [Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Oobu (Japan)] [Department of Aging Neurobiology, National Center for Geriatrics and Gerontology, Oobu (Japan); Mori, Yoshihide [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan)] [Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka (Japan); Sasaguri, Toshiyuki [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan)] [Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka (Japan)

    2013-11-01

    Highlights: •The Wnt/?-catenin signaling pathway was activated in GSK-3?{sup +/?} mice. •The cortical and trabecular bone volumes were increased in GSK-3?{sup +/?} mice. •Regeneration of a partial bone defect was accelerated in GSK-3?{sup +/?} mice. -- Abstract: Glycogen synthase kinase (GSK)-3? plays an important role in osteoblastogenesis by regulating the Wnt/?-catenin signaling pathway. Therefore, we investigated whether GSK-3? deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3? (GSK-3?{sup +/?}). The amounts of ?-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3?{sup +/?} mice were significantly increased compared with those of wild-type mice, indicating that Wnt/?-catenin signals were enhanced in GSK-3?{sup +/?} mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3?{sup +/?} mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3? deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3?{sup +/?} mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3?, probably through activation of the Wnt/?-catenin signaling pathway.

  9. Schizophrenia classification using functional network features

    NASA Astrophysics Data System (ADS)

    Rish, Irina; Cecchi, Guillermo A.; Heuton, Kyle

    2012-03-01

    This paper focuses on discovering statistical biomarkers (features) that are predictive of schizophrenia, with a particular focus on topological properties of fMRI functional networks. We consider several network properties, such as node (voxel) strength, clustering coefficients, local efficiency, as well as just a subset of pairwise correlations. While all types of features demonstrate highly significant statistical differences in several brain areas, and close to 80% classification accuracy, the most remarkable results of 93% accuracy are achieved by using a small subset of only a dozen of most-informative (lowest p-value) correlation features. Our results suggest that voxel-level correlations and functional network features derived from them are highly informative about schizophrenia and can be used as statistical biomarkers for the disease.

  10. Massage-like stroking boosts the immune system in mice.

    PubMed

    Major, Benjamin; Rattazzi, Lorenza; Brod, Samuel; Pilipovi?, Ivan; Leposavi?, Gordana; D'Acquisto, Fulvio

    2015-01-01

    Recent clinical evidence suggests that the therapeutic effect of massage involves the immune system and that this can be exploited as an adjunct therapy together with standard drug-based approaches. In this study, we investigated the mechanisms behind these effects exploring the immunomodulatory function of stroking as a surrogate of massage-like therapy in mice. C57/BL6 mice were stroked daily for 8 days either with a soft brush or directly with a gloved hand and then analysed for differences in their immune repertoire compared to control non-stroked mice. Our results show that hand- but not brush-stroked mice demonstrated a significant increase in thymic and splenic T cell number (p?mice support the hypothesis that massage-like therapies might be of therapeutic value in the treatment of immunodeficiencies and related disorders and suggest a reduction of the inhibitory noradrenergic tone in lymphoid organs as one of the possible explanations for their immunomodulatory function. PMID:26046935

  11. Diffuse optical monitoring of repeated cerebral ischemia in mice

    PubMed Central

    Shang, Yu; Chen, Lei; Toborek, Michal; Yu, Guoqiang

    2011-01-01

    Occlusions of bilateral common carotid arteries (bi-CCA) in mice are popular models for the investigation of transient forebrain ischemia. Currently available technologies for assessing cerebral blood flow (CBF) and oxygenation in ischemic mice have limitations. This study tests a novel near-infrared diffuse correlation spectroscopy (DCS) flow-oximeter for monitoring both CBF and cerebral oxygenation in mice undergoing repeated transient forebrain ischemia. Concurrent flow measurements in a mouse brain were first conducted for validation purposes; DCS measurement was found highly correlated with laser Doppler measurement (R2 = 0.94) and less susceptible to motion artifacts. With unique designs in experimental protocols and fiber-optic probes, we have demonstrated high sensitivities of DCS flow-oximeter in detecting the regional heterogeneity of CBF responses in different hemispheres and global changes of both CBF and cerebral oxygenation across two hemispheres in mice undergoing repeated 2-minute bi-CCA occlusions over 5 days. More than 75% CBF reductions were found during bi-CCA occlusions in mice, which may be considered as a threshold to determine a successful bi-CCA occlusion. With the progress of repeated 2-minute bi-CCA occlusions over days, a longitudinal decline in the magnitudes of CBF reduction was observed, indicating the brain adaptation to cerebral ischemia through the repeated preconditioning. PMID:21997041

  12. Platelet neuropeptide Y is critical for ischemic revascularization in mice.

    PubMed

    Tilan, Jason U; Everhart, Lindsay M; Abe, Ken; Kuo-Bonde, Lydia; Chalothorn, Dan; Kitlinska, Joanna; Burnett, Mary Susan; Epstein, Stephen E; Faber, James E; Zukowska, Zofia

    2013-06-01

    We previously reported that the sympathetic neurotransmitter neuropeptide Y (NPY) is potently angiogenic, primarily through its Y2 receptor, and that endogenous NPY is crucial for capillary angiogenesis in rodent hindlimb ischemia. Here we sought to identify the source of NPY responsible for revascularization and its mechanisms of action. At d 3, NPY(-/-) mice demonstrated delayed recovery of blood flow and limb function, consistent with impaired collateral conductance, while ischemic capillary angiogenesis was reduced (~70%) at d 14. This biphasic temporal response was confirmed by 2 peaks of NPY activation in rats: a transient early increase in neuronally derived plasma NPY and increase in platelet NPY during late-phase recovery. Compared to NPY-null platelets, collagen-activated NPY-rich platelets were more mitogenic (~2-fold vs. ~1.6-fold increase) for human microvascular endothelial cells, and Y2/Y5 receptor antagonists ablated this difference in proliferation. In NPY(+/+) mice, ischemic angiogenesis was prevented by platelet depletion and then restored by transfusion of platelets from NPY(+/+) mice, but not NPY(-/-) mice. In thrombocytopenic NPY(-/-) mice, transfusion of wild-type platelets fully restored ischemia-induced angiogenesis. These findings suggest that neuronally derived NPY accelerates the early response to femoral artery ligation by promoting collateral conductance, while platelet-derived NPY is critical for sustained capillary angiogenesis. PMID:23457218

  13. Exacerbated Experimental Colitis in TNFAIP8-Deficient Mice.

    PubMed

    Sun, Honghong; Lou, Yunwei; Porturas, Thomas; Morrissey, Samantha; Luo, George; Qi, Ji; Ruan, Qingguo; Shi, Songlin; Chen, Youhai H

    2015-06-15

    The TNF-?-induced protein 8 (TNFAIP8 or TIPE) is a risk factor for cancer and bacterial infection, and its expression is upregulated in a number of human cancers. However, its physiologic and pathologic functions are unclear. In this study, we describe the generation of TIPE-deficient mice and their increased sensitivity to colonic inflammation. TIPE-deficient mice were generated by germ line gene targeting and were born without noticeable developmental abnormalities. Their major organs, including lymphoid organs and intestines, were macroscopically and microscopically normal. However, after drinking dextran sodium sulfate-containing water, TIPE-deficient mice developed more severe colitis than wild type mice did, as demonstrated by decreased survival rates, increased body weight loss, and enhanced leukocyte infiltration, bacterial invasion, and inflammatory cytokine production in the colon. Bone marrow chimeric experiments revealed that TIPE deficiency in nonhematopoietic cells was responsible for the exacerbated colitis in TIPE-deficient mice. Consistent with this result, TIPE-deficient intestinal epithelial cells had increased rate of cell death and decreased rate of proliferation as compared with wild type controls. These findings indicate that TIPE plays an important role in maintaining colon homeostasis and in protecting against colitis. PMID:25948814

  14. Immune enhancement during chronic ethanol feeding in mice - Autoimmune phenomena

    SciTech Connect

    Honchel, R.; Rhoads, C.A.; Fitzpatrick, E.A.; McClain, C.J.; Kaplan, A.M.; Cohen, D.A. (Univ. of Kentucky, Lexington (United States))

    1991-03-11

    Chronic alcohol abuse in humans is often associated with diminished immune reactivity and enhanced susceptibility to infections. However, many alcohol-dependent individuals display signs of autoimmunity, which has been implicated in alcohol-associated liver damage. This study demonstrates that C57Bl/6 mice placed on the Lieber-DeCarli liquid ethanol diet for up to 9 weeks displayed augmented immune reactivity as compared to mice placed on an isocaloric control diet. Spleen cells were significantly more responsive to the mitogens, LPS and ConA, as early as 3 weeks after initiation of EtOH feeding and this hyperresponsiveness persisted throughout the 9 week feeding period. Similar enhancement of the mixed lymphocyte response was also seen in EtOH fed mice. The enhancement of immune responsiveness was not related to a change in the numbers or percentages of B cells, T cells, or in the CD4/CD8 T cell ratios as determined by flow cytometry. These studies indicate that under certain conditions of ethanol feeding in mice, enhancement rather than suppression of the immune system may occur. This system may be a model to evaluate possible induction of autoimmune responses during chronic ethanol abuse. Studies are underway to measure the presence of auto-antibodies in the sera of these ethanol fed mice.

  15. Immunobiology of Germfree Mice Infected with Nocardia asteroides

    PubMed Central

    Beaman, Blaine L.; Gershwin, M. Eric; Scates, Steven S.; Ohsugi, Yoshiyuki

    1980-01-01

    Nocardia asteroides GUH-2 was administered either intranasally or by intravenous inoculation into (i) conventionally grown, (ii) germfree, and (iii) lipopolysaccharide-treated germfree NIH:S mice. The number of bacteria within the lungs, brain, kidneys, adrenals, liver, spleen, and blood was quantitated at 3, 24, 72, and 168 h after infection. Further, the histological changes that occurred in each of these organs after infection were studied. The data demonstrated that germfree mice were significantly more susceptible to the acute phase of infection caused by N. asteroides than the conventionally grown animals. The brains and lungs of these mice were affected most dramatically. Pretreatment of the germfree mice with lipopolysaccharide completely reversed this enhanced susceptibility and rendered the animals more resistant to infection than the conventionally grown mice. These observations establish further the role of macrophage activation and the development of cell-mediated immunity in host resistance to nocardia. In addition, the presence of a resident microflora within the host appears to be important in the development of resistance to systemic nocardial infections. ImagesFig. 2Fig. 3 PMID:7011984

  16. Exocrine pancreatic disorders in transsgenic mice expressing human keratin 8

    PubMed Central

    Casanova, M. Llanos; Bravo, Ana; Ramírez, Angel; Escobar, Gabriela Morreale de; Were, Felipe; Merlino, Glenn; Vidal, Miguel; Jorcano, José L.

    1999-01-01

    Keratins K8 and K18 are the major components of the intermediate-filament cytoskeleton of simple epithelia. Increased levels of these keratins have been correlated with various tumor cell characteristics, including progression to malignancy, invasive behavior, and drug sensitivity, although a role for K8/K18 in tumorigenesis has not yet been demonstrated. To examine the function of these keratins, we generated mice expressing the human K8 (hk8) gene, which leads to a moderate keratin-content increase in their simple epithelia. These mice displayed progressive exocrine pancreas alterations, including dysplasia and loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine by adipose tissue, as well as increased cell proliferation and apoptosis. Histological changes were not observed in other simple epithelia, such as the liver. Electron microscopy showed that transgenic acinar cells have keratins organized in abundant filament bundles dispersed throughout the cytoplasm, in contrast to control acinar cells, which have scarce and apically concentrated filaments. The phenotype found was very similar to that reported for transgenic mice expressing a dominant-negative mutant TGF-? type II receptor (TGF?RII mice). We show that these TGF?RII mutant mice also have elevated K8/K18 levels. These results indicate that simple epithelial keratins play a relevant role in the regulation of exocrine pancreas homeostasis and support the idea that disruption of mechanisms that normally regulate keratin expression in vivo could be related to inflammatory and neoplastic pancreatic disorders. PMID:10359568

  17. Cadmium modulates adipocyte functions in metallothionein-null mice.

    PubMed

    Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito; Sato, Masao; Inoue, Masahisa; Suzuki, Shinya

    2013-11-01

    Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT(-/-)) mice, which cannot form atoxic Cd-MT complexes and are used for evaluating Cd as free ions, and wild type (MT(+/+)) mice. Cd administration more significantly reduced the adipocyte size of MT(-/-) mice than that of MT(+/+) mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT(-/-) mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. PMID:23921151

  18. Iron Status in Mice Carrying a Targeted Disruption of Lactoferrin

    PubMed Central

    Ward, Pauline P.; Mendoza-Meneses, Marisela; Cunningham, Grainne A.; Conneely, Orla M.

    2003-01-01

    Lactoferrin is a member of the transferrin family of iron-binding glycoproteins present in milk, mucosal secretions, and the secondary granules of neutrophils. While several physiological functions have been proposed for lactoferrin, including the regulation of intestinal iron uptake, the exact function of this protein in vivo remains to be established. To directly assess the physiological functions of lactoferrin, we have generated lactoferrin knockout (LFKO?/?) mice by homologous gene targeting. LFKO?/? mice are viable and fertile, develop normally, and display no overt abnormalities. A comparison of the iron status of suckling offspring from LFKO?/? intercrosses and from wild-type (WT) intercrosses showed that lactoferrin is not essential for iron delivery during the postnatal period. Further, analysis of adult mice on a basal or a high-iron diet revealed no differences in transferrin saturation or tissue iron stores between WT and LFKO?/? mice on either diet, although the serum iron levels were slightly elevated in LFKO-/- mice on the basal diet. Consistent with the relatively normal iron status, in situ hybridization analysis demonstrated that lactoferrin is not expressed in the postnatal or adult intestine. Collectively, these results support the conclusion that lactoferrin does not play a major role in the regulation of iron homeostasis. PMID:12482971

  19. Three featured plenary sessions

    NASA Astrophysics Data System (ADS)

    2012-07-01

    The conference included three plenary sessions. The plenary on Governance, Security, Economy, and the Ecosystem of the Changing Arctic featured Vera Alexander, president, Arctic Research Consortium of the U.S.; Alan Thornhill, chief environmental officer, U.S. Department of the Interior's Bureau of Ocean Energy Management; and Fran Ulmer, chair, U.S. Arctic Research Commission. A plenary on the U.N. Convention on the Law of the Sea featured Ambassador David Balton, deputy assistant secretary for oceans and fisheries, U.S. Department of State; and Rear Admiral Frederick Kenney Jr., judge advocate general and chief counsel, U.S. Coast Guard. The plenary on Science and the 21st Century featured Phil Keslin, chief technology officer, small lab within Google.

  20. Passive Safety Features for Small Modular Reactors

    SciTech Connect

    Ingersoll, Daniel T [ORNL] [ORNL

    2010-01-01

    The rapid growth in the size and complexity of commercial nuclear power plants in the 1970s spawned an interest in smaller, simpler designs that are inherently or intrinsically safe through the use of passive design features. Several designs were developed, but none were ever built, although some of their passive safety features were incorporated into large commercial plant designs that are being planned or built today. In recent years, several reactor vendors are actively redeveloping small modular reactor (SMR) designs with even greater use of passive features. Several designs incorporate the ultimate in passive safety they completely eliminate specific accident initiators from the design. Other design features help to reduce the likelihood of an accident or help to mitigate the accident s consequences, should one occur. While some passive safety features are common to most SMR designs, irrespective of the coolant technology, other features are specific to water, gas, or liquid-metal cooled SMR designs. The extensive use of passive safety features in SMRs promise to make these plants highly robust, protecting both the general public and the owner/investor. Once demonstrated, these plants should allow nuclear power to be used confidently for a broader range of customers and applications than will be possible with large plants alone.