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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. Phenotype detection in morphological mutant mice using deformation features.

    PubMed

    Roy, Sharmili; Liang, Xi; Kitamoto, Asanobu; Tamura, Masaru; Shiroishi, Toshihiko; Brown, Michael S

    2013-01-01

    Large-scale global efforts are underway to knockout each of the approximately 25,000 mouse genes and interpret their roles in shaping the mammalian embryo. Given the tremendous amount of data generated by imaging mutated prenatal mice, high-throughput image analysis systems are inevitable to characterize mammalian development and diseases. Current state-of-the-art computational systems offer only differential volumetric analysis of pre-defined anatomical structures between various gene-knockout mice strains. For subtle anatomical phenotypes, embryo phenotyping still relies on the laborious histological techniques that are clearly unsuitable in such big data environment. This paper presents a system that automatically detects known phenotypes and assists in discovering novel phenotypes in muCT images of mutant mice. Deformation features obtained from non-linear registration of mutant embryo to a normal consensus average image are extracted and analyzed to compute phenotypic and candidate phenotypic areas. The presented system is evaluated using C57BL/10 embryo images. All cases of ventricular septum defect and polydactyly, well-known to be present in this strain, are successfully detected. The system predicts potential phenotypic areas in the liver that are under active histological evaluation for possible phenotype of this mouse line. PMID:24505791

  3. 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

  4. Alzheimer's disease-like pathological features in transgenic mice expressing the APP

    E-print Network

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

  5. 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. PMID:26082754

  6. 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

  7. 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

  8. C9orf72 BAC Transgenic Mice Display Typical Pathologic Features of ALS/FTD.

    PubMed

    O'Rourke, Jacqueline G; Bogdanik, Laurent; Muhammad, A K M G; Gendron, Tania F; Kim, Kevin J; Austin, Andrew; Cady, Janet; Liu, Elaine Y; Zarrow, Jonah; Grant, Sharday; Ho, Ritchie; Bell, Shaughn; Carmona, Sharon; Simpkinson, Megan; Lall, Deepti; Wu, Kathryn; Daughrity, Lillian; Dickson, Dennis W; Harms, Matthew B; Petrucelli, Leonard; Lee, Edward B; Lutz, Cathleen M; Baloh, Robert H

    2015-12-01

    Noncoding expansions of a hexanucleotide repeat (GGGGCC) in the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Here we report transgenic mice carrying a bacterial artificial chromosome (BAC) containing the full human C9orf72 gene with either a normal allele (15 repeats) or disease-associated expansion (?100-1,000 repeats; C9-BACexp). C9-BACexp mice displayed pathologic features seen in C9orf72 expansion patients, including widespread RNA foci and repeat-associated non-ATG (RAN) translated dipeptides, which were suppressed by antisense oligonucleotides targeting human C9orf72. Nucleolin distribution was altered, supporting that either C9orf72 transcripts or RAN dipeptides promote nucleolar dysfunction. Despite early and widespread production of RNA foci and RAN dipeptides in C9-BACexp mice, behavioral abnormalities and neurodegeneration were not observed even at advanced ages, supporting the hypothesis that RNA foci and RAN dipeptides occur presymptomatically and are not sufficient to drive neurodegeneration in mice at levels seen in patients. PMID:26637796

  9. 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

  10. Ceruloplasmin/Hephaestin Knockout Mice Model Morphologic and Molecular Features of AMD

    PubMed Central

    Hadziahmetovic, Majda; Dentchev, Tzvete; Song, Ying; Haddad, Nadine; He, Xining; Hahn, Paul; Pratico, Domenico; Wen, Rong; Harris, Z. Leah; Lambris, John D.; Beard, John; Dunaief, Joshua L.

    2008-01-01

    Purpose Iron is an essential element in human metabolism but also is a potent generator of oxidative damage with levels that increase with age. Several studies suggest that iron accumulation may be a factor in age-related macular degeneration (AMD). In prior studies, both iron overload and features of AMD were identified in mice deficient in the ferroxidase ceruloplasmin (Cp) and its homologue hephaestin (Heph) (double knockout, DKO). In this study, the location and timing of iron accumulation, the rate and reproducibility of retinal degeneration, and the roles of oxidative stress and complement activation were determined. Methods Morphologic analysis and histochemical iron detection by Perls' staining was performed on retina sections from DKO and control mice. Immunofluorescence and immunohistochemistry were performed with antibodies detecting activated complement factor C3, transferrin receptor, L-ferritin, and macrophages. Tissue iron levels were measured by atomic absorption spectrophotometry. Isoprostane F2?-VI, a specific marker of oxidative stress, was quantified in the tissue by gas chromatography/mass spectrometry. Results DKOs exhibited highly reproducible age-dependent iron overload, which plateaued at 6 months of age, with subsequent progressive retinal degeneration continuing to at least 12 months. The degeneration shared some features of AMD, including RPE hypertrophy and hyperplasia, photoreceptor degeneration, subretinal neovascularization, RPE lipofuscin accumulation, oxidative stress, and complement activation. Conclusions DKOs have age-dependent iron accumulation followed by retinal degeneration modeling some of the morphologic and molecular features of AMD. Therefore, these mice are a good platform on which to test therapeutic agents for AMD, such as antioxidants, iron chelators, and antiangiogenic agents. PMID:18326691

  11. Senescence induced by RECQL4 dysfunction contributes to Rothmund–Thomson syndrome features in mice

    PubMed Central

    Lu, H; Fang, E F; Sykora, P; Kulikowicz, T; Zhang, Y; Becker, K G; Croteau, D L; Bohr, V A

    2014-01-01

    Cellular senescence refers to irreversible growth arrest of primary eukaryotic cells, a process thought to contribute to aging-related degeneration and disease. Deficiency of RecQ helicase RECQL4 leads to Rothmund–Thomson syndrome (RTS), and we have investigated whether senescence is involved using cellular approaches and a mouse model. We first systematically investigated whether depletion of RECQL4 and the other four human RecQ helicases, BLM, WRN, RECQL1 and RECQL5, impacts the proliferative potential of human primary fibroblasts. BLM-, WRN- and RECQL4-depleted cells display increased staining of senescence-associated ?-galactosidase (SA-?-gal), higher expression of p16INK4a or/and p21WAF1 and accumulated persistent DNA damage foci. These features were less frequent in RECQL1- and RECQL5-depleted cells. We have mapped the region in RECQL4 that prevents cellular senescence to its N-terminal region and helicase domain. We further investigated senescence features in an RTS mouse model, Recql4-deficient mice (Recql4HD). Tail fibroblasts from Recql4HD showed increased SA-?-gal staining and increased DNA damage foci. We also identified sparser tail hair and fewer blood cells in Recql4HD mice accompanied with increased senescence in tail hair follicles and in bone marrow cells. In conclusion, dysfunction of RECQL4 increases DNA damage and triggers premature senescence in both human and mouse cells, which may contribute to symptoms in RTS patients. PMID:24832598

  12. 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

  13. Vasoactive Intestinal Peptide–Null Mice Demonstrate Enhanced Sweet Taste Preference, Dysglycemia, and Reduced Taste Bud Leptin Receptor Expression

    PubMed Central

    Martin, Bronwen; Shin, Yu-Kyong; White, Caitlin M.; Ji, Sunggoan; Kim, Wook; Carlson, Olga D.; Napora, Joshua K.; Chadwick, Wayne; Chapter, Megan; Waschek, James A.; Mattson, Mark P.; Maudsley, Stuart; Egan, Josephine M.

    2010-01-01

    OBJECTIVE It is becoming apparent that there is a strong link between taste perception and energy homeostasis. Recent evidence implicates gut-related hormones in taste perception, including glucagon-like peptide 1 and vasoactive intestinal peptide (VIP). We used VIP knockout mice to investigate VIP's specific role in taste perception and connection to energy regulation. RESEARCH DESIGN AND METHODS Body weight, food intake, and plasma levels of multiple energy-regulating hormones were measured and pancreatic morphology was determined. In addition, the immunocytochemical profile of taste cells and gustatory behavior were examined in wild-type and VIP knockout mice. RESULTS VIP knockout mice demonstrate elevated plasma glucose, insulin, and leptin levels, with no islet ?-cell number/topography alteration. VIP and its receptors (VPAC1, VPAC2) were identified in type II taste cells of the taste bud, and VIP knockout mice exhibit enhanced taste preference to sweet tastants. VIP knockout mouse taste cells show a significant decrease in leptin receptor expression and elevated expression of glucagon-like peptide 1, which may explain sweet taste preference of VIP knockout mice. CONCLUSIONS This study suggests that the tongue can play a direct role in modulating energy intake to correct peripheral glycemic imbalances. In this way, we could view the tongue as a sensory mechanism that is bidirectionally regulated and thus forms a bridge between available foodstuffs and the intricate hormonal balance in the animal itself. PMID:20150284

  14. DJ-1 deficient mice demonstrate similar vulnerability to pathogenic Ala53Thr human ?-syn toxicity

    PubMed Central

    Ramsey, Chenere P.; Tsika, Elpida; Ischiropoulos, Harry; Giasson, Benoit I.

    2010-01-01

    Parkinson's disease (PD) is the most common neurodegenerative movement disorder. A pathological hallmark of PD is the presence of intraneuronal inclusions composed of fibrillized ?-synuclein (?-syn) in affected brain regions. Mutations in the gene, PARK7, which encodes DJ-1, can cause autosomal recessive early-onset PD. Although DJ-1 has been shown to be involved in diverse biological processes, several in vitro studies suggest that it can inhibit the formation and protect against the effects of ?-syn aggregation. We previously established and characterized transgenic mice expressing pathogenic Ala53Thr human ?-syn (M83 mice) that develop extensive ?-syn pathologies in the neuroaxis resulting in severe motor impairments and eventual fatality. In the current study, we have crossbred M83 mice on a DJ-1 null background (M83-DJnull mice) in efforts to determine the effects of the lack of DJ-1 in these mice. Animals were assessed and compared for survival rate, distribution of ?-syn inclusions, biochemical properties of ?-syn protein, demise and function of nigral dopaminergic neurons, and extent of gliosis in the neuroaxis. M83 and M83-DJnull mice displayed a similar onset of disease and pathological changes, and none of the analyses to assess for changes in pathogenesis revealed any significant differences between M83 and M83-DJnull mice. These findings suggest that DJ-1 may not function to directly modulate ?-syn nor does DJ-1 appear to play a role in protecting against the deleterious effects of expressing pathogenic Ala53Thr ?-syn in vivo. It is possible that ?-syn and DJ-1 mutations may lead to PD via independent mechanisms. PMID:20089532

  15. Experimental demonstration of cascaded AWG access network featuring bi-directional transmission and polarization multiplexing

    NASA Astrophysics Data System (ADS)

    Tsalamanis, Ioannis; Rochat, Etienne; Walker, Stuart D.; Parker, Michael C.; Holburn, D. M.

    2004-03-01

    We present the first experimental demonstration of a bidirectional cascaded arrayed-waveguide grating (AWG) access network combining one N×N AWG in the central office with multiple 1×N AWG's at the distribution points, such as to individually address N2 users with only N wavelengths. Downstream and upstream data share the same optical path. BER curves were measured using 2.5Gb/s data stream in each direction, and error free transmission achieved for downstream and upstream, with only 0.3dB power penalty for simultaneous transmission. The addition of two orthogonal polarization-multiplexed channels per wavelength doubled the number of possible end users. Error free transmission was achieved with simultaneous upstream and downstream transmission of a composite signal featuring eight 2.5Gb/s channels (2 polarizations × 4 wavelengths)

  16. Norepinephrine transporter variant A457P knock-in mice display key features of human postural orthostatic tachycardia syndrome.

    PubMed

    Shirey-Rice, Jana K; Klar, Rebecca; Fentress, Hugh M; Redmon, Sarah N; Sabb, Tiffany R; Krueger, Jessica J; Wallace, Nathan M; Appalsamy, Martin; Finney, Charlene; Lonce, Suzanna; Diedrich, André; Hahn, Maureen K

    2013-07-01

    Postural orthostatic tachycardia syndrome (POTS) is a common autonomic disorder of largely unknown etiology that presents with sustained tachycardia on standing, syncope and elevated norepinephrine spillover. Some individuals with POTS experience anxiety, depression and cognitive dysfunction. Previously, we identified a mutation, A457P, in the norepinephrine (NE; also known as noradrenaline) transporter (NET; encoded by SLC6A2) in POTS patients. NET is expressed at presynaptic sites in NE neurons and plays a crucial role in regulating NE signaling and homeostasis through NE reuptake into noradrenergic nerve terminals. Our in vitro studies demonstrate that A457P reduces both NET surface trafficking and NE transport and exerts a dominant-negative impact on wild-type NET proteins. Here we report the generation and characterization of NET A457P mice, demonstrating the ability of A457P to drive the POTS phenotype and behaviors that are consistent with reported comorbidities. Mice carrying one A457P allele (NET(+/P)) exhibited reduced brain and sympathetic NE transport levels compared with wild-type (NET(+/+)) mice, whereas transport activity in mice carrying two A457P alleles (NET(P/P)) was nearly abolished. NET(+/P) and NET(P/P) mice exhibited elevations in plasma and urine NE levels, reduced 3,4-dihydroxyphenylglycol (DHPG), and reduced DHPG:NE ratios, consistent with a decrease in sympathetic nerve terminal NE reuptake. Radiotelemetry in unanesthetized mice revealed tachycardia in NET(+/P) mice without a change in blood pressure or baroreceptor sensitivity, consistent with studies of human NET A457P carriers. NET(+/P) mice also demonstrated behavioral changes consistent with CNS NET dysfunction. Our findings support that NET dysfunction is sufficient to produce a POTS phenotype and introduces the first genetic model suitable for more detailed mechanistic studies of the disorder and its comorbidities. PMID:23580201

  17. Genetically engineered mice demonstrate that adenosine deaminase is essential for early postimplantation development.

    PubMed

    Blackburn, M R; Knudsen, T B; Kellems, R E

    1997-08-01

    Adenosine deaminase (ADA) is an essential enzyme of purine metabolism that is enriched at the maternal-fetal interface of mice throughout postimplantation development. During early postimplantation stages Ada is highly expressed in both maternally derived decidual cells and zygotically derived trophoblast cells. For the current study we utilized genetically modified mice to delineate the relative contribution and importance of decidual and trophoblast ADA at the maternal-fetal interface. In females genetically engineered to lack decidual ADA a striking pattern of expression was revealed in giant trophoblast cells that surround the early postimplantation embryo. Embryos within gestation sites lacking both decidual and trophoblast ADA died during the early postimplantation period, whereas expression in trophoblast cells alone was sufficient for survival through this period. Severe disturbances in purine metabolism were observed in gestation sites lacking decidual ADA, including the accumulation of the potentially toxic ADA substrates adenosine and 2'-deoxyadenosine. These experiments provide genetic evidence that Ada expression at the maternal-fetal interface is essential for early postimplantation development in mice. PMID:9272950

  18. 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

  19. Radiographic features of bone in several strains of laboratory mice and of their tumours induced by bone-seeking radionuclides.

    PubMed Central

    Loutit, J F; Corp, M J; Ardran, G M

    1976-01-01

    The natural radiographic appearance of the various bones of the skeleton are described for several strains of laboratory mice. The Harwell substrains of CBA, A and 101 are generally similar and become osteoporotic on ageing. Harwell C57BL have similar, but more delicately chiseled, bones. Harwell C3H mice have bones with stouter cortices and may show osteosclerosis on ageing. CF1 females (donated by Dr M. Finkel) showed osteosclerosis and osteophytic outgrowths when aged. NMRI mice (donated by Dr A. Luz) appeared larger than the pure-strain Harwell mice. In general, mouse bones are simple tubular structures with an ivory cortex and a marrow cavity. Cancellous trabecular bone is scanty, even in vertebrae, flat bones and the metaphyses of long bones. Bone-seeking radionuclides administered to mice lead to skeletal tumours: (a) osteosarcomata, which are commonly radio-opaque to a variable degree owing to calcified tumour bone, but which may be osteolytic, (b) primitive mesenchymal (angio-) sarcomata which are non-osteogenic and osteolytic, (c) fibrosarcomata--which also are osteolytic--and to local or general lymphomata from irradiation of parental cells in bone marrow, but no special radiological features have been found associated with these last-named tumours. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 PMID:1069700

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

    SciTech Connect

    Proia, R.L.; Yamanaka, S.; Johnson, M.D.

    1994-09-01

    Tay-Sachs disease, the prototype of the G{sub M2} 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 consequence of the enzyme deficiency, G{sub M2} ganglioside accumulates progressively, beginning early in fetal life, to excessive amounts in the central nervous system (CNS). Rapid mental and motor deterioration starting in the first year of life leads to death by 2 to 4 years of age. Through the targeted disruption of the Hexa gene in embryonic stem cells, we have produced mice with biochemical and neuropathologic features of Tay-Sachs disease. The mutant mice exhibited less than 1% of normal {beta}-hexosaminidase A activity and accumulated G{sub M2} ganglioside in their CNS 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 three to five 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 enzymes and genes into the CNS. This model may also be valuable for studying the biochemical and pathologic changes occurring during the course of the disease.

  1. IL-21-Driven Neoplasms in SJL Mice Mimic Some Key Features of Human Angioimmunoblastic T-Cell Lymphoma.

    PubMed

    Jain, Shweta; Chen, Jing; Nicolae, Alina; Wang, Hongsheng; Shin, Dong-Mi; Adkins, Elisabeth B; Sproule, Thomas J; Leeth, Caroline M; Sakai, Tomomi; Kovalchuk, Alexander L; Raffeld, Mark; Ward, Jerrold M; Rehg, Jerold E; Waldmann, Thomas A; Jaffe, Elaine S; Roopenian, Derry C; Morse, Herbert C

    2015-11-01

    SJL/J mice exhibit a high incidence of mature B-cell lymphomas that require CD4(+) T cells for their development. We found that their spleens and lymph nodes contained increased numbers of germinal centers and T follicular helper (TFH) cells. Microarray analyses revealed high levels of transcripts encoding IL-21 associated with high levels of serum IL-21. We developed IL-21 receptor (IL21R)-deficient Swiss Jim Lambart (SJL) mice to determine the role of IL-21 in disease. These mice had reduced numbers of TFH cells, lower serum levels of IL-21, and few germinal center B cells, and they did not develop B-cell tumors, suggesting IL-21-dependent B-cell lymphomagenesis. We also noted a series of features common to SJL disease and human angioimmunoblastic T-cell lymphoma (AITL), a malignancy of TFH cells. Gene expression analyses of AITL showed that essentially all cases expressed elevated levels of transcripts for IL21, IL21R, and a series of genes associated with TFH cell development and function. These results identify a mouse model with features of AITL and suggest that patients with the disease might benefit from therapeutic interventions that interrupt IL-21 signaling. PMID:26363366

  2. SDP_mharwit_1: Demonstration of HIFI Linear Polarization Analysis of Spectral Features

    NASA Astrophysics Data System (ADS)

    Harwit, M.

    2010-03-01

    We propose to observe the polarization of the 621 GHz water vapor maser in VY Canis Majoris to demonstrate the capability of HIFI to make polarization observations of Far-Infrared/Submillimeter spectral lines. The proposed Demonstration Phase would: - Show that HIFI is capable of interesting linear polarization measurements of spectral lines; - Test out the highest spectral resolving power to sort out closely spaced Doppler components; - Determine whether the relative intensities predicted by Neufeld and Melnick are correct; - Record the degree and direction of linear polarization for the closely-Doppler shifted peaks.

  3. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur

    SciTech Connect

    Klebig, M.L.; Woychik, R.P.; Wilkinson, J.E.; Geisler, J.G. |

    1995-05-23

    Mice that carry the lethal yellow (A{sup y}) or viable yellow (A{sup vy}) mutation, two dominant mutations of the agouti (a) gene in mouse chromosome 2, exhibit a phenotype that includes yellow fur, marked obesity, a form of type II diabetes associated with insulin resistance, and an increased susceptibility to tumor development. Molecular analyses of these and several other dominant {open_quotes}obese yellow{close_quotes} a-locus mutations suggested that ectopic expression of the normal agouti protein gives rise to this complex pleiotropic phenotype. We have now tested this hypothesis directly by generating transgenic mice that ectopically express an agouti cDNA clone encoding the normal agouti protein in all tissues examined. Transgenic mice of both sexes have yellow fur, become obese, and develop hyperinsulinemia. In addition, male transgenic mice develop hyperglycemia by 12-20 weeks of age. These results demonstrate conclusively that the ectopic agouti expression is responsible for most, if not all, of the phenotypic traits of the dominant, obese yellow mutants. 42 refs., 5 figs.

  4. 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

  5. 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

  6. Functional and morphological features of skeletal muscle from mutant mice lacking both type 1 and type 3 ryanodine receptors.

    PubMed Central

    Ikemoto, T; Komazaki, S; Takeshima, H; Nishi, M; Noda, T; Iino, M; Endo, M

    1997-01-01

    1. We generated mice with targeted disruptions in the genes for both ryanodine receptor type 1 (RyR-1) and type 3 (RyR-3) to study the functional roles of RyR subtypes in skeletal muscle. 2. In permeabilized myocytes lacking both the RyRs, the Ca(2+)-induced Ca2+ release (CICR) mechanism was completely lost, and caffeine failed to induce Ca2+ release. 3. Replacement of potassium methanesulphonate in an experimental intracellular solution with choline chloride resulted in Ca2+ release in the wild-type muscle but not in the mutant muscle lacking RyR-1. 4. The double-mutant mice exhibited more severe muscular degeneration than RyR-1-deficient mice with formation of large vacuoles and swollen mitochondria while structural coupling between T-tubules and the sarcoplasmic reticulum was retained. 5. These results demonstrate that CICR is mediated solely by RyR-1 and RyR-3 in skeletal muscle cells, and suggest that RyR-1 is involved in Cl(-)-induced Ca2+ release. The results also suggest the presence of molecular components other than RyRs responsible for the triad formation. RyR-3 may have a role in the normal morphogenesis of skeletal muscle cells, although functionally it can be replaced by RyR-1. Images Figure 4 PMID:9192302

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

    E-print Network

    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

    (manifested as the tend- ency to explore the same holes) was measured via the coefficient of exploratory variation, calculated as the ratio of the S.D. for each different hole over the mean for each mouse. This index (Geyer & Paulus, 1992) has been shown.... Significance threshold was set at 0.05. Results Behavioural alterations Although the behavioural profiles of MAOA and A/B KO mice have been partially described in previous reports (Cases et al. 1995; Chen et al. 2004; Shih et al. 1999a, b), neither line has...

  8. 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 ...

  9. Morphological and electrophysiological features of motor neurons and putative interneurons in the dorsal vagal complex of rats and mice

    PubMed Central

    Gao, Hong; Glatzer, Nicholas R.; Williams, Kevin W.; Derbenev, Andrei V.; Liu, Dan; Smith, Bret N.

    2009-01-01

    The dorsal motor nucleus of the vagus (DMV) contains preganglionic motor neurons that control viscera along the subdiaphragmatic digestive tract, but may also contain neurons that do not project to the viscera. Neurons that expressed EGFP 60-72 h subsequent to PRV-152 inoculation of vagal terminals in the stomach wall were targeted for whole-cell patch-clamp recording and biocytin filling in transverse brainstem slices from rats and their quantitative morphological and electrophysiological characteristics were compared with uninfected cells. Over 90% of PRV-152 labeled neurons were also labeled subsequent to intraperitoneal injection of FluoroGold, indicating most were preganglionic motor neurons. In reconstructed neurons with an identifiable axon trajectory, two cellular subtypes were distinguished. The axon projected ventrolaterally from the DMV in 44 of 49 cells and these were likely to be vagal motor neurons. Axons of other neurons ramified within the nucleus tractus solitarius (NTS) or DMV. These cells were smaller and otherwise morphologically distinct from putative motor neurons. Transgenic mice with GFP-expressing inhibitory neurons (i.e., GIN mice) were used to identify a GABAergic subset vagal neurons. These neurons had locally-ramifying axons and formed a morphologically distinct subset of DMV cells, which were similar in size and axon trajectory to GABAergic neurons in the NTS. Most neurons in the DMV therefore possess morphological features of motor neurons, but locally projecting cells and inhibitory neurons with distinct morphological features are also found within the DMV. These cells likely contribute to regulation of vagal function. PMID:19619517

  10. Of Mice, Birds, and Men: The Mouse Ultrasonic Song System Has Some Features Similar to Humans and Song-Learning Birds

    PubMed Central

    Arriaga, Gustavo; Zhou, Eric P.; Jarvis, Erich D.

    2012-01-01

    Humans and song-learning birds communicate acoustically using learned vocalizations. The characteristic features of this social communication behavior include vocal control by forebrain motor areas, a direct cortical projection to brainstem vocal motor neurons, and dependence on auditory feedback to develop and maintain learned vocalizations. These features have so far not been found in closely related primate and avian species that do not learn vocalizations. Male mice produce courtship ultrasonic vocalizations with acoustic features similar to songs of song-learning birds. However, it is assumed that mice lack a forebrain system for vocal modification and that their ultrasonic vocalizations are innate. Here we investigated the mouse song system and discovered that it includes a motor cortex region active during singing, that projects directly to brainstem vocal motor neurons and is necessary for keeping song more stereotyped and on pitch. We also discovered that male mice depend on auditory feedback to maintain some ultrasonic song features, and that sub-strains with differences in their songs can match each other's pitch when cross-housed under competitive social conditions. We conclude that male mice have some limited vocal modification abilities with at least some neuroanatomical features thought to be unique to humans and song-learning birds. To explain our findings, we propose a continuum hypothesis of vocal learning. PMID:23071596

  11. An Intradermal Inoculation Model of Scrub Typhus in Swiss CD-1 Mice Demonstrates More Rapid Dissemination of Virulent Strains of Orientia tsutsugamushi

    PubMed Central

    Sunyakumthorn, Piyanate; Paris, Daniel H.; Chan, Teik-Chye; Jones, Margaret; Luce-Fedrow, Alison; Chattopadhyay, Suchismita; Jiang, Ju; Anantatat, Tippawan; Turner, Gareth D. H.; Day, Nicholas P. J.; Richards, Allen L.

    2013-01-01

    Scrub typhus is an important endemic disease of the Asia-Pacific region caused by Orientia tsutsugamushi. To develop an effective vaccine to prevent scrub typhus infection, a better understanding of the initial host-pathogen interaction is needed. The objective of this study was to investigate early bacterial dissemination in a CD-1 Swiss outbred mouse model after intradermal injection of O. tsutsugamushi. Three human pathogenic strains of O. tsutsugamushi (Karp, Gilliam, and Woods) were chosen to investigate the early infection characteristics associated with bacterial virulence. Tissue biopsies of the intradermal injection site and draining lymph nodes were examined using histology and immunohistochemistry to characterize bacterial dissemination, and correlated with quantitative real-time PCR for O. tsutsugamushi in blood and tissue from major organs. Soluble adhesion molecules were measured to examine cellular activation in response to infection. No eschar formation was seen at the inoculation site and no clinical disease developed within the 7 day period of observation. However, O. tsutsugamushi was localized at the injection site and in the draining lymph nodes by day 7 post inoculation. Evidence of leukocyte and endothelial activation was present by day 7 with significantly raised levels of sL-selectin, sICAM-1 and sVCAM-1. Infection with the Karp strain was associated with earlier and higher bacterial loads and more extensive dissemination in various tissues than the less pathogenic Gilliam and Woods strains. The bacterial loads of O. tsutsugamushi were highest in the lungs and spleens of mice inoculated with Karp and Gilliam, but not Woods strains. Strains of higher virulence resulted in more rapid systemic infection and dissemination in this model. The CD-1 mouse intradermal inoculation model demonstrates features relevant to early scrub typhus infection in humans, including the development of regional lymphadenopathy, leukocyte activation and distant organ dissemination after low-dose intradermal injection with O. tsutsugamushi. PMID:23342173

  12. 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

  13. Subchronic and mild social defeat stress accelerates food intake and body weight gain with polydipsia-like features in mice.

    PubMed

    Goto, Tatsuhiko; Kubota, Yoshifumi; Tanaka, Yuki; Iio, Wataru; Moriya, Naoko; Toyoda, Atsushi

    2014-08-15

    Development and characterization of animal models of depression are essential for fully understanding the pathogenesis of depression in humans. We made and analyzed a mouse model exhibiting social deficit and hyperphagia-like behavior using a subchronic and mild social defeat stress (sCSDS) paradigm. The body weight, food and water intake of mice were monitored during a test period, and their behaviors and serum components were analyzed at two stages: immediately after the sCSDS period and 1 month after the sCSDS. The body weight and food intake of defeated mice were significantly higher than control mice at the sCSDS period, and these differences were sustained until 1 month after the sCSDS, whereas the water intake of defeated mice was significantly higher than control mice for the period of sCSDS only. Behavioral analyses revealed that the defeated mice exhibit significant social aversion to unfamiliar mice in a social interaction test and a trend of anxiety-like behavior in an elevated-plus maze test. Possibly due to polydipsia-like symptoms, defeated mice had significantly lower levels of albumin and blood urea nitrogen than control mice immediately after the sCSDS period but not at 1 month after sCSDS. The present study revealed that our sCSDS mice keep much more water in their body than control mice. This study reports the first step toward an understanding of the mechanisms of stress-induced overhydration, over-eating and resultant weight gain. PMID:24875770

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

    SciTech Connect

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

    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.

  15. Generation of N-Ethyl-N-nitrosourea (ENU) Diabetes Models in Mice Demonstrates Genotype-specific Action of Glucokinase Activators*

    PubMed Central

    Fenner, Deborah; Odili, Stella; Hong, Hee-Kyung; Kobayashi, Yumiko; Kohsaka, Akira; Siepka, Sandra M.; Vitaterna, Martha H.; Chen, Pan; Zelent, Bogumil; Grimsby, Joseph; Takahashi, Joseph S.; Matschinsky, Franz M.; Bass, Joseph

    2011-01-01

    We performed genome-wide mutagenesis in C57BL/6J mice using N-ethyl-N-nitrosourea to identify mutations causing high blood glucose early in life and to produce new animal models of diabetes. Of a total of 13 new lines confirmed by heritability testing, we identified two semi-dominant pedigrees with novel missense mutations (GckK140E and GckP417R) in the gene encoding glucokinase (Gck), the mammalian glucose sensor that is mutated in human maturity onset diabetes of the young type 2 and the target of emerging anti-hyperglycemic agents that function as glucokinase activators (GKAs). Diabetes phenotype corresponded with genotype (mild-to-severe: Gck+/+ < GckP417R/+, GckK140E/+ < GckP417R/P417R, GckP417R/K140E, and GckK140E/K140E) and with the level of expression of GCK in liver. Each mutant was produced as the recombinant enzyme in Escherichia coli, and analysis of kcat and tryptophan fluorescence (I320/360) during thermal shift unfolding revealed a correlation between thermostability and the severity of hyperglycemia in the whole animal. Disruption of the glucokinase regulatory protein-binding site (GCKK140E), but not the ATP binding cassette (GCKP417R), prevented inhibition of enzyme activity by glucokinase regulatory protein and corresponded with reduced responsiveness to the GKA drug. Surprisingly, extracts from liver of diabetic GCK mutants inhibited activity of the recombinant enzyme, a property that was also observed in liver extracts from mice with streptozotocin-induced diabetes. These results indicate a relationship between genotype, phenotype, and GKA efficacy. The integration of forward genetic screening and biochemical profiling opens a pathway for preclinical development of mechanism-based diabetes therapies. PMID:21921030

  16. Pituitary and ovarian abnormalities demonstrated by CT and ultrasound in children with features of the McCune-Albright syndrome

    SciTech Connect

    Rieth, K.G.; Comite, F.; Shawker, T.H.; Cutler, G.B. Jr.

    1984-11-01

    In a random series of 97 children referred to the National Institutes of Health with a presumptive diagnosis of precocious puberty, eight girls were found to have features of the McCune-Albright syndrome, including fibrous dysplasia of bone and/or skin lesions resembling cafe au lait spots. Radiographic evaluation of these patients included computed tomography of the head and pelvic ultrasound. The pituitary glands were suspicious for abnormality in five of the eight girls. Seven girls underwent pelvic ultrasound, and in all of them the ovaries were considered to be abnormal for their chronological age; in addition, two had functional ovarian cysts. The role of diagnostic radiological studies in the diagnosis of this syndrome is discussed.

  17. 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.

  18. Features of in vitro ultrasound biomicroscopic imaging and colonoscopy for detection of colon tumor in mice.

    PubMed

    Alves, Kelly Z; Borges, Helena L; Soletti, Rossana C; Viana, Anália L P; Petrella, Lorena I; Soldan, Mônica; Chagas, Vera L; Schanaider, Alberto; Machado, Joăo C

    2011-12-01

    The present work tested the capability of ultrasound biomicroscopy (UBM), at 45 MHz, to provide cross-sectional images with appropriate resolution and contrast to detect tumors and determine their penetration depths on the colon of mice, Mus musculus (Linnaeus 1758), treated with carcinogen for colon tumor induction. B-mode images were obtained, in vitro, from each animal (13 treated and 4 untreated) colon opened longitudinally and immersed in saline solution at room temperature. Prior to UBM inspection, all animals were also examined by colonoscopy. The layers of normal colon identified by UBM are: mucosa (hyperechoic), muscularis mucosae (hypoechoic), submucosa (hyperechoic) and muscularis externa (hypoechoic). UBM images of colon lesions presented structures corresponding to tumors (hyperechoic), lymphoid hyperplasia (hypoechoic) and polypoid tumors (hyperechoic). Additionally, tumoral lesion invasion through the colon was also identified. When compared with histopathologic analysis, all colon lesions detected by UBM were confirmed, while colonoscopic findings had two false negatives. PMID:22033129

  19. Lipidomic profiling of phosphocholine-containing brain lipids in mice with sensorimotor deficits and anxiety-like features after exposure to Gulf War agents.

    PubMed

    Abdullah, Laila; Evans, James E; Bishop, Alex; Reed, Jon M; Crynen, Gogce; Phillips, John; Pelot, Robert; Mullan, Myles A; Ferro, Austin; Mullan, Christopher M; Mullan, Michael J; Ait-Ghezala, Ghania; Crawford, Fiona C

    2012-12-01

    The central nervous system (CNS)-based symptoms of Gulf War Illness (GWI) include motor dysfunction, anxiety, and cognitive impairment. Gulf War (GW) agents, such as pyridostigmine bromide (PB), permethrin (PER), N,N-diethyl-meta-toluamide (DEET), and stress, are among the contributory factors to the pathobiology of GWI. This study characterizes disturbances in phosphocholine-containing lipids that accompany neurobehavioral and neuropathological features associated with GW agent exposure. Exposed mice received PB orally, dermal application of PER and DEET and restraint stress daily for 28 days, while controls received vehicle during this period. Neurobehavioral studies included the rotarod, open field, and Morris water maze tests. Histopathological assessments included glial fibrillary acid protein, CD45, and Nissl staining. Liquid chromatography/mass spectrometry with source collision-induced dissociation in negative and positive ionization scanning modes was performed to characterize brain phosphatidylcholine (PC) and sphingomyelin (SM). A significant increase in ether containing PC (ePC34:0, ePC36:2, and ePC36:1) or long-chain fatty acid-containing PC (38:1, 40:4, 40:2) was observed in exposed mice compared with controls. Among differentially expressed PCs, levels of those with monounsaturated fatty acids were more affected than those with saturated and polyunsaturated fatty acids. Sensorimotor deficits and anxiety, together with an increase in astrocytosis, were observed in exposed mice compared with controls. These lipid changes suggest that alterations in peroxisomal pathways and stearoyl-CoA desaturase activity accompany neurobehavioral and neuropathological changes after GW agent exposure and represent possible treatment targets for the CNS symptoms of GWI. PMID:22798222

  20. 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)

  1. 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

  2. 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

  3. 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-Sřrensen, 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

  4. STAT5A-deficient mice demonstrate a defect in granulocyte-macrophage colony-stimulating factor-induced proliferation and gene expression.

    PubMed

    Feldman, G M; Rosenthal, L A; Liu, X; Hayes, M P; Wynshaw-Boris, A; Leonard, W J; Hennighausen, L; Finbloom, D S

    1997-09-01

    Responses of cells to cytokines typically involve the activation of a family of latent DNA binding proteins, referred to as signal transducers and activators of transcription (STAT) proteins, which are critical for the expression of early response genes. Of the seven known STAT proteins, STAT5 (originally called mammary gland factor) has been shown to be activated by several cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5, which are known to play important roles in growth and differentiation of hematopoietic precursors. In this report we have used mice that are deficient in STAT5A (one of two homologues of STAT5) to study the role of STAT5A in GM-CSF stimulation of cells. When bone marrow-derived macrophages were generated by differentiation with macrophage-CSF (M-CSF), exposure of cells from wild-type mice to GM-CSF resulted in a typical pattern of assembly of DNA binding proteins specific for the gamma activation sequence (GAS) element within the beta-casein promoter. However, in cells from the STAT5A null mouse one of the shifted bands was absent. Immunoblotting analysis in the null mice showed that lack of STAT5A protein resulted in no alteration in activation of STAT5B by tyrosine phosphorylation. Proliferation experiments revealed that, when exposed to increasing concentrations of GM-CSF, cells derived from the null mice grew considerably more slowly than cells derived from the wild-type mice. Moreover, expression of GM-CSF-dependent genes, CIS and A1, was markedly inhibited in cells derived from null mice as compared with those of wild-type mice. The decreased expression observed with A1, a bcl-2 like gene, may account in part for the suppression of growth in cells from the null mice. These data suggest that the presence of STAT5A during the GM-CSF-induced assembly of STAT5 dimers is critical for the formation of competent transcription factors that are required for both gene expression and cell proliferation. PMID:9292509

  5. Development and functional evaluation of biomimetic silicone surfaces with hierarchical micro/nano-topographical features demonstrates favourable in vitro foreign body response of breast-derived fibroblasts.

    PubMed

    Kyle, Daniel J T; Oikonomou, Antonios; Hill, Ernie; Bayat, Ardeshir

    2015-06-01

    Reproducing extracellular matrix topographical cues, such as those present within acellular dermal matrix (ADM), in synthetic implant surfaces, may augment cellular responses, independent of surface chemistry. This could lead to enhanced implant integration and performance while reducing complications. In this work, the hierarchical micro and nanoscale features of ADM were accurately and reproducibly replicated in polydimethylsiloxane (PDMS), using an innovative maskless 3D grayscale fabrication process not previously reported. Human breast derived fibroblasts (n=5) were cultured on PDMS surfaces and compared to commercially available smooth and textured silicone implant surfaces, for up to one week. Cell attachment, proliferation and cytotoxicity, in addition to immunofluorescence staining, SEM imaging, qRT-PCR and cytokine array were performed. ADM PDMS surfaces promoted cell adhesion, proliferation and survival (p=<0.05), in addition to increased focal contact formation and spread fibroblast morphology when compared to commercially available implant surfaces. PCNA, vinculin and collagen 1 were up-regulated in fibroblasts on biomimetic surfaces while IL8, TNF?, TGF?1 and HSP60 were down-regulated (p=<0.05). A reduced inflammatory cytokine response was also observed (p=<0.05). This study represents a novel approach to the development of functionalised biomimetic prosthetic implant surfaces which were demonstrated to significantly attenuate the acute in vitro foreign body reaction to silicone. PMID:25818416

  6. Constitutive expression of Gs?R201C in mice produces a heritable, direct replica of human fibrous dysplasia bone pathology and demonstrates its natural history

    PubMed Central

    Saggio, Isabella; Remoli, Cristina; Spica, Emanuela; Cersosimo, Stefania; Sacchetti, Benedetto; Robey, Pamela G.; Holmbeck, Kenn; Cumano, Ana; Boyde, Alan; Bianco, Paolo; Riminucci, Mara

    2014-01-01

    Fibrous dysplasia of bone (FD) is a crippling skeletal disease associated with post zygotic mutations (R201C, R201H) of the gene encoding the ? subunit of the stimulatory G protein, Gs. By causing a characteristic structural subversion of bone and bone marrow, the disease results in deformity, hypomineralization, and fracture of the affected bones, with severe morbidity arising in childhood or adolescence. Lack of inheritance of the disease in humans is thought to reflect embryonic lethality of germline-transmitted activating Gs? mutations, which would only survive through somatic mosaicism. We have generated multiple lines of mice that express Gs?R201C constitutively and develop an inherited, histopathologically exact replica of human FD. Robust transgene expression in neonatal and embryonic tissues, and embryonic stem (ES) cells was associated with normal development of skeletal tissues and differentiation of skeletal cells. As in humans, FD lesions in mice developed only in the postnatal life; a defined spatial and temporal pattern characterized the onset and progression of lesions across the skeleton. In individual bones, lesions developed through a sequence of three distinct histopathological stages: a primary modeling phase defined by endosteal/medullary excess bone formation, and normal resorption; a secondary phase, with excess, inappropriate remodeling; and a tertiary fibrous dysplastic phase, which reproduced a full-blown replica of the human bone pathology in mice of age ?1 year. Gs? mutations are sufficient to cause FD, and are per se compatible with germline transmission and normal embryonic development in mice. Our novel murine lines constitute the first model of FD. PMID:24764158

  7. Mice with a selective impairment of IFN-? signaling in macrophage lineage cells demonstrate the critical role of IFN-? activated macrophages for the control of protozoan parasitic infections in vivo1, 2

    PubMed Central

    Lykens, Jennifer E.; Terrell, Catherine E.; Zoller, Erin E.; Divanovic, Senad; Trompette, Aurelien; Karp, Christopher L.; Aliberti, Julio; Flick, Matthew J.; Jordan, Michael B.

    2010-01-01

    IFN-? has long been recognized as a cytokine with potent and varied effects in the immune response. While its effects on specific cell types have been well studied in vitro, its in vivo effects are less clearly understood because of its diverse actions on many different cell types. While control of multiple protozoan parasites is thought to depend critically on the direct action of IFN-? on macrophages, this premise has never been directly proven in vivo. In order to more directly examine the effects of IFN-? on cells of the macrophage lineage in vivo, we generated mice called the ‘Macrophages Insensitive to Interferon Gamma’ (MIIG) mice, which express a dominant negative mutant IFN-? receptor in CD68+ cells: monocytes, macrophages, dendritic cells, and mast cells. Macrophage lineage cells and mast cells from these mice are unable to respond to IFN-? while other cells are able to produce and respond to this cytokine normally. When challenged in vitro, macrophages from MIIG mice were unable produce NO or kill Trypanosoma cruzi or Leishmania major after priming with IFN-?. Furthermore, MIIG mice demonstrated impaired parasite control and heightened mortality after T. cruzi, L. major, and Toxoplasma gondii infection, despite an appropriate IFN-? response. In contrast, MIIG mice displayed normal control of lymphocytic choriomeningitis virus, despite persistent insensitivity of macrophages to IFN-?. Thus, the MIIG mouse formally demonstrates for the first time in vivo, the specific importance of direct, IFN-? mediated activation of macrophages for controlling infection with multiple protozoan parasites. “This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org.” PMID:20018611

  8. First demonstration of transmissible spongiform encephalopathy-associated prion protein (PrPTSE) in extracellular vesicles from plasma of mice infected with mouse-adapted variant Creutzfeldt-Jakob disease by in vitro amplification.

    PubMed

    Saá, Paula; Yakovleva, Oksana; de Castro, Jorge; Vasilyeva, Irina; De Paoli, Silvia H; Simak, Jan; Cervenakova, Larisa

    2014-10-17

    The development of variant Creutzfeldt-Jakob disease (vCJD) in three recipients of non-leukoreduced red blood cells from asymptomatic donors who subsequently developed the disease has confirmed existing concerns about the possible spread of transmissible spongiform encephalopathies (TSEs) via blood products. In addition, the presence of disease-associated misfolded prion protein (PrP(TSE)), generally associated with infectivity, has been demonstrated in the blood of vCJD patients. However, its origin and distribution in this biological fluid are still unknown. Various studies have identified cellular prion protein (PrP(C)) among the protein cargo in human blood-circulating extracellular vesicles released from endothelial cells and platelets, and exosomes isolated from the conditioned media of TSE-infected cells have caused the disease when injected into experimental mice. In this study, we demonstrate the detection of PrP(TSE) in extracellular vesicles isolated from plasma samples collected during the preclinical and clinical phases of the disease from mice infected with mouse-adapted vCJD and confirm the presence of the exosomal marker Hsp70 in these preparations. PMID:25157106

  9. First Demonstration of Transmissible Spongiform Encephalopathy-associated Prion Protein (PrPTSE) in Extracellular Vesicles from Plasma of Mice Infected with Mouse-adapted Variant Creutzfeldt-Jakob Disease by in Vitro Amplification*

    PubMed Central

    Saá, Paula; Yakovleva, Oksana; de Castro, Jorge; Vasilyeva, Irina; De Paoli, Silvia H.; Simak, Jan; Cervenakova, Larisa

    2014-01-01

    The development of variant Creutzfeldt-Jakob disease (vCJD) in three recipients of non-leukoreduced red blood cells from asymptomatic donors who subsequently developed the disease has confirmed existing concerns about the possible spread of transmissible spongiform encephalopathies (TSEs) via blood products. In addition, the presence of disease-associated misfolded prion protein (PrPTSE), generally associated with infectivity, has been demonstrated in the blood of vCJD patients. However, its origin and distribution in this biological fluid are still unknown. Various studies have identified cellular prion protein (PrPC) among the protein cargo in human blood-circulating extracellular vesicles released from endothelial cells and platelets, and exosomes isolated from the conditioned media of TSE-infected cells have caused the disease when injected into experimental mice. In this study, we demonstrate the detection of PrPTSE in extracellular vesicles isolated from plasma samples collected during the preclinical and clinical phases of the disease from mice infected with mouse-adapted vCJD and confirm the presence of the exosomal marker Hsp70 in these preparations. PMID:25157106

  10. Follicular Thyroid Cancers Demonstrate Dual Activation of PKA and mTOR as Modeled by Thyroid-Specific Deletion of Prkar1a and Pten in Mice

    PubMed Central

    Pringle, Daphne R.; Vasko, Vasily V.; Yu, Lianbo; Manchanda, Parmeet K.; Lee, Audrey A.; Zhang, Xiaoli; Kirschner, Jessica M.; Parlow, Albert F.; Saji, Motoyasu; Jarjoura, David; Ringel, Matthew D.; La Perle, Krista M. D.

    2014-01-01

    Context: Thyroid cancer is the most common form of endocrine cancer, and it is a disease whose incidence is rapidly rising. Well-differentiated epithelial thyroid cancer can be divided into papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Although FTC is less common, patients with this condition have more frequent metastasis and a poorer prognosis than those with PTC. Objective: The objective of this study was to characterize the molecular mechanisms contributing to the development and metastasis of FTC. Design: We developed and characterized mice carrying thyroid-specific double knockout of the Prkar1a and Pten tumor suppressor genes and compared signaling alterations observed in the mouse FTC to the corresponding human tumors. Setting: The study was conducted at an academic research laboratory. Human samples were obtained from academic hospitals. Patients: Deidentified, formalin-fixed, paraffin-embedded (FFPE) samples were analyzed from 10 control thyroids, 30 PTC cases, five follicular variant PTC cases, and 10 FTC cases. Interventions: There were no interventions. Main outcome measures: Mouse and patient samples were analyzed for expression of activated cAMP response element binding protein, AKT, ERK, and mammalian target of rapamycin (mTOR). Murine FTCs were analyzed for differential gene expression to identify genes associated with metastatic progression. Results: Double Prkar1a-Pten thyroid knockout mice develop FTC and recapitulate the histology and metastatic phenotype of the human disease. Analysis of signaling pathways in FTC showed that both human and mouse tumors exhibited strong activation of protein kinase A and mTOR. The development of metastatic disease was associated with the overexpression of genes required for cell movement Conclusions: These data imply that the protein kinase A and mTOR signaling cascades are important for the development of follicular thyroid carcinogenesis and may suggest new targets for therapeutic intervention. Mouse models paralleling the development of the stages of human FTC should provide important new tools for understanding the mechanisms of FTC development and progression and for evaluating new therapeutics. PMID:24512487

  11. TU-A-12A-04: Quantitative Texture Features Calculated in Lung Tissue From CT Scans Demonstrate Consistency Between Two Databases From Different Institutions

    SciTech Connect

    Cunliffe, A; Armato, S; Castillo, R; Pham, N; Guerrero, T; Al-Hallaq, H

    2014-06-15

    Purpose: To evaluate the consistency of computed tomography (CT) scan texture features, previously identified as stable in a healthy patient cohort, in esophageal cancer patient CT scans. Methods: 116 patients receiving radiation therapy (median dose: 50.4Gy) for esophageal cancer were retrospectively identified. For each patient, diagnostic-quality pre-therapy (0-183 days) and post-therapy (5-120 days) scans (mean voxel size: 0.8mm×0.8mm×2.5mm) and a treatment planning scan and associated dose map were collected. An average of 501 32x32-pixel ROIs were placed randomly in the lungs of each pre-therapy scan. ROI centers were mapped to corresponding locations in post-therapy and planning scans using the displacement vector field output by demons deformable registration. Only ROIs with mean dose <5Gy were analyzed, as these were expected to contain minimal post-treatment damage. 140 texture features were calculated in pre-therapy and post-therapy scan ROIs and compared using Bland-Altman analysis. For each feature, the mean feature value change and the distance spanned by the 95% limits of agreement were normalized to the mean feature value, yielding normalized range of agreement (nRoA) and normalized bias (nBias). Using Wilcoxon signed rank tests, nRoA and nBias were compared with values computed previously in 27 healthy patient scans (mean voxel size: 0.67mm×0.67mm×1mm) acquired at a different institution. Results: nRoA was significantly (p<0.001) larger in cancer patients than healthy patients. Differences in nBias were not significant (p=0.23). The 20 features identified previously as having nRoA<20% for healthy patients had the lowest nRoA values in the current database, with an average increase of 5.6%. Conclusion: Despite differences in CT scanner type, scan resolution, and patient health status, the same 20 features remained stable (i.e., low variability and bias) in the absence of disease changes for databases from two institutions. Identification of these features is the first step towards quantifying radiation-induced changes between preand post-therapy scans. Supported, in part, by NIH Grant Nos. S10 RR021039, and P30 CA14599, the Virginia and D. K. Ludwig Fund for Cancer Research, Imaging Research Institute, Biological Sciences Division, The University of Chicago, and The Institute for Translational Medicine Pilot Award, The University of Chicago.

  12. 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

  13. [Features of behavioral reactions of chronically irradiated mice in the raised crosswise labyrinth with various genetically determined radiosensitivity and possibilities of their modification by the fungal biopolymer complex].

    PubMed

    Seniuk, O F; Gorovo?, L F; Kovalev, V A; Palamar, L A; Krul', N I; Zhidkov, A V; Chemerski?, G F; Kireev, S I; Khatuntseva, I V

    2013-01-01

    Structural elements of the central nervous system--neurons, along with the higher neuroendocrine structures and the hypothalamus centres, show high sensitivity to a chronic action of low doses of ionizing radiation (IR) in view of their extreme enrichment by phospholipids and intensive supply by oxygen, creating favorable conditions for the development of oxidizing stress. Stressful influences cause negative emotions in the behaviour of animals manifested as fear or uneasiness. The study represents the results of comparative research into the behavioral reactions characterized by uneasiness in the Balb/c and C57bl/6 mice exposed to a chronic irradiation at low doses. The chitin-melanin-glucan complex from fungi Fomes fomentarius (ChMG) was approved as an adaptive agent. It has been shown that under identical conditions, deposition levels of radionuclides 137Cs and 90Sr are raised in mice with IR hypersensitivity--line Balb/c, in comparison with less radio sensitive mice--line C57bl/6. Simultaneously, Balb/c mice were observed to exhibit the signs of a more anxious behaviour in the new environment. Chronic external and internal radiation exposure to rare ionizing radiation at low doses promotes strengthening of anxiety and phobic reactions in mice with IR hypersensitivity. The use of ChMG in animals neutralized the increase in anxiety and phobic reactions after a prolonged irradiation, thus indicating the presence in ChMG of the anxiolitic activity along with the above mentioned powerful radiosorbent, antioxidant, gene protective and immunomodulatory properties. PMID:23786031

  14. Green coffee polyphenols do not attenuate features of the metabolic syndrome and improve endothelial function in mice fed a high fat diet.

    PubMed

    Li Kwok Cheong, J D; Croft, K D; Henry, P D; Matthews, V; Hodgson, J M; Ward, N C

    2014-10-01

    We have investigated the effects of the major polyphenol in coffee, chlorogenic acid (CGA), on obesity, glucose intolerance, insulin resistance, systemic oxidative stress and endothelial dysfunction in a mouse model of the metabolic syndrome. Thirty C57BL6 mice were randomly divided into (n=10/group) (i) normal diet (ND), (ii) high fat diet (HFD), or (iii) high fat diet supplemented with 0.5% w/w green coffee bean extract (GCE) rich in chlorogenic acid (HFD+GCE). The high fat diet consisted of 28% fat and all animals were maintained on their diets for 12 weeks. The mice fed a HFD and HFD+GCE displayed symptoms of the metabolic syndrome compared to their normal fed counterparts, although no endothelial dysfunction was detected in the abdominal aortas after 12 weeks. GCE did not attenuate HFD-induced obesity, glucose intolerance, insulin resistance or systemic oxidative stress. Furthermore, GCE did not protect against ex vivo oxidant (hypochlorous acid)-induced endothelial dysfunction. PMID:24583266

  15. A preclinical orthotopic model for glioblastoma recapitulates key features of human tumors and demonstrates sensitivity to a combination of MEK and PI3K pathway inhibitors.

    PubMed

    El Meskini, Rajaa; Iacovelli, Anthony J; Kulaga, Alan; Gumprecht, Michelle; Martin, Philip L; Baran, Maureen; Householder, Deborah B; Van Dyke, Terry; Weaver Ohler, Zoë

    2015-01-01

    Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Previous work describes a genetically engineered mouse (GEM) model that contains perturbations in the most frequently dysregulated networks in GBM (driven by RB, KRAS and/or PI3K signaling and PTEN) that induce development of Grade IV astrocytoma with properties of the human disease. Here, we developed and characterized an orthotopic mouse model derived from the GEM that retains the features of the GEM model in an immunocompetent background; however, this model is also tractable and efficient for preclinical evaluation of candidate therapeutic regimens. Orthotopic brain tumors are highly proliferative, invasive and vascular, and express histology markers characteristic of human GBM. Primary tumor cells were examined for sensitivity to chemotherapeutics and targeted drugs. PI3K and MAPK pathway inhibitors, when used as single agents, inhibited cell proliferation but did not result in significant apoptosis. However, in combination, these inhibitors resulted in a substantial increase in cell death. Moreover, these findings translated into the in vivo orthotopic model: PI3K or MAPK inhibitor treatment regimens resulted in incomplete pathway suppression and feedback loops, whereas dual treatment delayed tumor growth through increased apoptosis and decreased tumor cell proliferation. Analysis of downstream pathway components revealed a cooperative effect on target downregulation. These concordant results, together with the morphologic similarities to the human GBM disease characteristics of the model, validate it as a new platform for the evaluation of GBM treatment. PMID:25431423

  16. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice.

    PubMed

    Soenjaya, Y; Foster, B L; Nociti, F H; Ao, M; Holdsworth, D W; Hunter, G K; Somerman, M J; Goldberg, H A

    2015-09-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp(-/-)) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp(-/-) mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp(-/-) mice. This hypothesis was tested by comparing Bsp(-/-) and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro-computed tomography. By 8 wk of age, Bsp(-/-) mice exhibited molar and incisor malocclusion regardless of diet. Bsp(-/-) mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp(-/-) mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp(-/-) mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp(-/-) mice. Bsp(-/-) incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP in maintaining proper periodontal function and alveolar bone remodeling and point to dental dysfunction as causative factor of skeletal defects observed in Bsp(-/-) mice. PMID:26130257

  17. H9c2 and HL-1 cells demonstrate distinct features of energy metabolism, mitochondrial function and sensitivity to hypoxia-reoxygenation

    PubMed Central

    Kuznetsov, Andrey V.; Javadov, Sabzali; Sickinger, Stephan; Frotschnig, Sandra; Grimm, Michael

    2015-01-01

    Dysfunction of cardiac energy metabolism plays a critical role in many cardiac diseases, including heart failure, myocardial infarction and ischemia–reperfusion injury and organ transplantation. The characteristics of these diseases can be elucidated in vivo, though animal-free in vitro experiments, with primary adult or neonatal cardiomyocytes, the rat ventricular H9c2 cell line or the mouse atrial HL-1 cells, providing intriguing experimental alternatives. Currently, it is not clear how H9c2 and HL-1 cells mimic the responses of primary cardiomyocytes to hypoxia and oxidative stress. In the present study, we show that H9c2 cells are more similar to primary cardiomyocytes than HL-1 cells with regard to energy metabolism patterns, such as cellular ATP levels, bioenergetics, metabolism, function and morphology of mitochondria. In contrast to HL-1, H9c2 cells possess beta-tubulin II, a mitochondrial isoform of tubulin that plays an important role in mitochondrial function and regulation. We demonstrate that H9c2 cells are significantly more sensitive to hypoxia-reoxygenation injury in terms of loss of cell viability and mitochondrial respiration, whereas HL-1 cells were more resistant to hypoxia as evidenced by their relative stability. In comparison to HL-1 cells, H9c2 cells exhibit a higher phosphorylation (activation) state of AMP-activated protein kinase, but lower peroxisome proliferator-activated receptor gamma coactivator 1-alpha levels, suggesting that each cell type is characterized by distinct regulation of mitochondrial biogenesis. Our results provide evidence that H9c2 cardiomyoblasts are more energetically similar to primary cardiomyocytes than are atrial HL-1 cells. H9c2 cells can be successfully used as an in vitro model to simulate cardiac ischemia–reperfusion injury. PMID:25450968

  18. H9c2 and HL-1 cells demonstrate distinct features of energy metabolism, mitochondrial function and sensitivity to hypoxia-reoxygenation.

    PubMed

    Kuznetsov, Andrey V; Javadov, Sabzali; Sickinger, Stephan; Frotschnig, Sandra; Grimm, Michael

    2015-02-01

    Dysfunction of cardiac energy metabolism plays a critical role in many cardiac diseases, including heart failure, myocardial infarction and ischemia-reperfusion injury and organ transplantation. The characteristics of these diseases can be elucidated in vivo, though animal-free in vitro experiments, with primary adult or neonatal cardiomyocytes, the rat ventricular H9c2 cell line or the mouse atrial HL-1 cells, providing intriguing experimental alternatives. Currently, it is not clear how H9c2 and HL-1 cells mimic the responses of primary cardiomyocytes to hypoxia and oxidative stress. In the present study, we show that H9c2 cells are more similar to primary cardiomyocytes than HL-1 cells with regard to energy metabolism patterns, such as cellular ATP levels, bioenergetics, metabolism, function and morphology of mitochondria. In contrast to HL-1, H9c2 cells possess beta-tubulin II, a mitochondrial isoform of tubulin that plays an important role in mitochondrial function and regulation. We demonstrate that H9c2 cells are significantly more sensitive to hypoxia-reoxygenation injury in terms of loss of cell viability and mitochondrial respiration, whereas HL-1 cells were more resistant to hypoxia as evidenced by their relative stability. In comparison to HL-1 cells, H9c2 cells exhibit a higher phosphorylation (activation) state of AMP-activated protein kinase, but lower peroxisome proliferator-activated receptor gamma coactivator 1-alpha levels, suggesting that each cell type is characterized by distinct regulation of mitochondrial biogenesis. Our results provide evidence that H9c2 cardiomyoblasts are more energetically similar to primary cardiomyocytes than are atrial HL-1 cells. H9c2 cells can be successfully used as an in vitro model to simulate cardiac ischemia-reperfusion injury. PMID:25450968

  19. 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 Central

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

    2015-01-01

    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

  20. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1979-01-01

    Presents two demonstrations which are intended for chemistry college students. These demonstrations are: (1) enhancement of concentration quenching by micelles; and (2) the thermite lecture demonstration. (HM)

  1. 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)

  2. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1988-01-01

    Details three demonstrations for use in chemistry classrooms. Includes: "A Demonstration of Corrosion by Differential Aeration"; "A Simple Demonstration of the Activation Energy Concept"; and "A Boiling Demonstration at Room Temperature." Each description includes equipment, materials, and methods. (CW)

  3. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1988-01-01

    Describes two chemistry demonstrations including a demonstration of chemical inhibition and "The Rayleigh Fountain" which demonstrates the polarity of the water molecule. Provides instructions and explanations for each demonstration. (CW)

  4. 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

  5. Partial Return Yoke for MICE

    SciTech Connect

    Witte H.; Plate, S; ,

    2013-05-03

    The international Muon Ionization Cooling Experiment (MICE) is a large scale experiment which is presently assembled at the Rutherford Appleton Laboratory in Didcot, UK. The purpose of MICE is to demonstrate the concept of ionization cooling experimentally. Ionization cooling is an important accelerator concept which will be essential for future HEP experiments such as a potential Muon Collider or a Neutrino Factory. The MICE experiment will house up to 18 superconducting solenoids, all of which produce a substantial amount of magnetic flux. Recently it was realized that this magnetic flux leads to a considerable stray magnetic field in the MICE hall. This is a concern as technical equipment in the MICE hall may may be compromised by this. In July 2012 a concept called partial return yoke was presented to the MICE community, which reduces the stray field in the MICE hall to a safe level. This report summarizes the general concept, engineering considerations and the expected shielding performance.

  6. 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)

  7. 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)

  8. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1982-01-01

    Three chemistry demonstrations are described: (1) partition coefficients; (2) Rutherford simulation experiment; and (3) demonstration of the powerful oxidizing property of dimanganeseheptoxide. Background information, materials needed, and procedures are provided for each demonstration. (JN)

  9. Immunopathogenesis of environmentally induced lupus in mice.

    PubMed Central

    Shaheen, V M; Satoh, M; Richards, H B; Yoshida, H; Shaw, M; Jennette, J C; Reeves, W H

    1999-01-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome defined by clinical and serologic features, including arthritis, glomerulonephritis, and certain autoantibodies such as anti-nuclear ribonucleoprotein (nRNP)/Smith antigen (Sm), DNA, and ribosomal P. Although lupus is considered primarily a genetic disorder, we recently demonstrated the induction of a syndrome strikingly similar to spontaneous lupus in many nonautoimmune strains of mice exposed to the isoprenoid alkane pristane (2,6,10,14-tetramethylpentadecane), a component of mineral oil. Intraperitoneal injection of pristane leads to the formation of lipogranulomas consisting of phagocytic cells that have engulfed the oil and collections of lymphocytes. Subsequently, pristane-treated BALB/c and SJL mice develop autoantibodies characteristic of SLE, including anti-nRNP/Sm, antiribosomal P, anti-Su, antichromatin, anti-single-stranded DNA, and anti-double-stranded DNA. This is accompanied by a severe glomerulonephritis with immune complex deposition, mesangial or mesangiocapillary proliferation, and proteinuria. All inbred mice examined appear to be susceptible to this novel form of chemically induced lupus. Pristane-induced lupus is the only inducible model of autoimmunity associated with the clinical syndrome as well as with the characteristic serologic abnormalities of SLE. Defining the immunopathogenesis of pristane-induced lupus in mice may provide insight into the causes of spontaneous (idiopathic) lupus and also may lead to information concerning possible risks associated with the ingestion or inhalation of mineral oil and exposure to hydrocarbons in the environment. Images Figure 1 Figure 2 Figure 3 PMID:10502537

  10. Tested Demonstrations

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1977-01-01

    Three demonstrations are described: paramagnetic properties of Fe(11) and Fe(111), the preparation of polyurethane foam: a lecture demonstration and the electrolysis of water-fuel cell reactions. A small discussion of the concepts demonstrated is included in each demonstration's description. (MR)

  11. Acoustic basis of directional acuity in laboratory mice.

    PubMed

    Lauer, Amanda M; Slee, Sean J; May, Bradford J

    2011-10-01

    The acoustic basis of auditory spatial acuity was investigated in CBA/129 mice by relating patterns of behavioral errors to directional features of the head-related transfer function (HRTF). Behavioral performance was assessed by training the mice to lick a water spout during sound presentations from a "safe" location and to suppress the response during presentations from "warning" locations. Minimum audible angles (MAAs) were determined by delivering the safe and warning sounds from different locations in the inter-aural horizontal and median vertical planes. HRTFs were measured at the same locations by implanting a miniature microphone and recording the gain of sound energy near the ear drum relative to free field. Mice produced an average MAA of 31° when sound sources were located in the horizontal plane. Acoustic measures indicated that binaural inter-aural level differences (ILDs) and monaural spectral features of the HRTF change systematically with horizontal location and therefore may have contributed to the accuracy of behavioral performance. Subsequent manipulations of the auditory stimuli and the directional properties of the ear produced errors that suggest the mice primarily relied on ILD cues when discriminating changes in azimuth. The MAA increased beyond 80° when the importance of ILD cues was minimized by testing in the median vertical plane. Although acoustic measures demonstrated a less robust effect of vertical location on spectral features of the HRTF, this poor performance provides further evidence for the insensitivity to spectral cues that was noted during behavioral testing in the horizontal plane. PMID:21717290

  12. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1981-01-01

    Two demonstrations are described: (1) red cabbage and electrolysis of water to bring together acid/base and electrochemical concepts; and (2) a model to demonstrate acid/base conjugate pairs utilizing magnets. (SK)

  13. 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)

  14. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1978-01-01

    Presents two demonstrations; one on Boyle's Law, to illustrate the gas law and serve as a challenging problem for the students; the other is a modified Color Blind Traffic Light demonstration in which the oscillating reactions were speeded up. (GA)

  15. 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)

  16. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1981-01-01

    Presents: (1) a simple demonstration which illustrates the driving force of entropy using the familiar effects of the negative thermal expansion coefficient of rubber; and (2) a demonstration of tetrahedral bonding using soap films. (CS)

  17. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1978-01-01

    Two demonstrations are described which are suitable for introductory chemistry classes. The first involves the precipitation of silver, and the second is a demonstration of the relationship between rate constants and equilibrium constants using water and beakers. (BB)

  18. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Provides instructions on conducting four demonstrations for the chemistry classroom. Outlines procedures for demonstrations dealing with coupled oscillations, the evaporation of liquids, thioxanthone sulfone radical anion, and the control of variables and conservation of matter. (TW)

  19. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Describes two classroom chemistry demonstrations which focus on the descriptive chemistry of bromine and iodine. Outlines the chemicals and equipment needed, experimental procedures, and discussion of one demonstration of the oxidation states of bromine and iodine, and another demonstration of the oxidation states of iodine. (TW)

  20. Demonstrating Diffusion

    ERIC Educational Resources Information Center

    Foy, Barry G.

    1977-01-01

    Two demonstrations are described. Materials and instructions for demonstrating movement of molecules into cytoplasm using agar blocks, phenolphthalein, and sodium hydroxide are given. A simple method for demonstrating that the rate of diffusion of a gas is inversely proportional to its molecular weight is also presented. (AJ)

  1. 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)

  2. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Describes a demonstration involving the controlled combustion of a mixture of metals with black and smokeless powder in a small Erlenmeyer flask. Also describes demonstrations using a device that precludes breathing of hazardous vapors during class demonstrations; the device is easy to transport and use in rooms without sinks. (JN)

  3. 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)

  4. Feature extraction Feature extraction

    E-print Network

    Giger, Christine

    Feature extraction #12;Feature extraction ! · Image interpretation: extract information from images · but the desired information may not be explicit in the raw observed pixel intensities · Transform image to make (hyperspectral sensors) Meteosat thermal IR channel hyperspectral "image cube" #12;Raw intensities ! · Pros

  5. Feature extraction Feature extraction

    E-print Network

    Giger, Christine

    Feature extraction #12;Feature extraction · Image interpretation: extract information from images · but the desired information may not be explicit in the raw observed pixel intensities · Transform image to make (hyperspectral sensors) Meteosat thermal IR channel hyperspectral "image cube" #12;Raw intensities · Pros

  6. 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

  7. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1989-01-01

    Presented are two chemistry demonstrations: (1) an alternative method for the demonstration of the properties of alkali metals, water is added to small amounts of metal; (2) an exploration of the properties of hydrogen, helium, propane, and carbon dioxide using an open trough and candle. (MVL)

  8. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1984-01-01

    Background information and procedures are provided for a second part to the dichromate volcano demonstration. The green ash produced during the demonstration is reduced to metal using aluminothermy (Goldschmide process). Also describes suitable light sources and spectroscopes for student observation of emission spectra in lecture halls. (JN)

  9. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Discusses the photochromic behavior of mercury(II) bis(dithizonate) in providing a colorful demonstration of the effect that visible light can have on the conformation and bonding of molecules in solution. Provides a description of the demonstration itself, along with the preparation needed to complete it. (TW)

  10. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Provides three descriptions of demonstrations used in various chemistry courses. Includes the use of a simple demonstration model to illustrate principles of chromatography, techniques for using balloons to teach about the behavior of gases, and the use of small concentrations of synthetic polyelectrolytes to induce the flocculation hydrophobic…

  11. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Describes two demonstrations designed to help chemistry students visualize certain chemical properties. One experiment uses balloons to illustrate the behavior of gases under varying temperatures and pressures. The other uses a makeshift pea shooter and a commercial model to demonstrate atomic structure and the behavior of high-speed particles.…

  12. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Outlines a simple, inexpensive way of demonstrating electroplating using the reaction between nickel ions and copper metal. Explains how to conduct a demonstration of the electrolysis of water by using a colored Na2SO4 solution as the electrolyte so that students can observe the pH changes. (TW)

  13. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1983-01-01

    Provides directions for setup and performance of two demonstrations. The first demonstrates the principles of Raoult's Law; using a simple apparatus designed to measure vapor pressure. The second illustrates the energy available from alcohol combustion (includes safety precautions) using an alcohol-fueled missile. (JM)

  14. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1979-01-01

    Presents two demonstrations for classroom use related to precipitation of ferrous hydroxide and to variation of vapor pressure with temperature. The former demonstration is simple and useful when discussing solubility of ionic compounds electrode potential of transition elements, and mixed valence compounds. (Author/SA)

  15. 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)

  16. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1982-01-01

    Three chemistry demonstrations are described: (1) modification of copper catalysis demonstration apparatus; (2) experiments in gas-liquid chromatography with simple gas chromatography at room temperature; and (3) equilibria in silver arsenate-arsenic acid and silver phosphate-phosphoric acid systems. Procedures and materials needed are provided.…

  17. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1983-01-01

    Describes a lecture demonstration of a solid state phase transition using a thermodynamic material which changes state at room temperature. Also describes a demonstration on kinetics using a "Big Bang" (trade mark) calcium carbide cannon. Indicates that the cannon is safe to use. (JN)

  18. 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…

  19. 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)

  20. 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)

  1. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1989-01-01

    Provided are two demonstrations for an introductory course in chemistry. The first one emphasizes the observation and the interpretation of facts to form hypotheses during the heating of a beaker of water. The second demonstration shows the liquid phase of carbon dioxide using dry ice and a pressure gauge. (YP)

  2. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1990-01-01

    Presented are three demonstrations: "The Construction and Use of Commercial Voltaic Cell Displays in Freshman Chemistry"; Dramatizing Isotopes: Deuterated Ice Cubes Sink"; and "A Simple Apparatus to Demonstrate Differing Gas Diffusion Rates (Graham's Law)." Materials, procedures, and safety considerations are discussed. (CW)

  3. 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…

  4. 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)

  5. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1979-01-01

    Presents a recipe for the Nylon Rope Trick, which is considered to be one of the most spectacular demonstrations in chemistry. Materials for growing the polymer and some safety precautions are given. (SA)

  6. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L.

    1990-01-01

    Included are three demonstrations that include the phase change of ice when under pressure, viscoelasticity and colloid systems, and flame tests for metal ions. The materials, procedures, probable results, and applications to real life situations are included. (KR)

  7. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1986-01-01

    Background information, list of materials needed, and procedures used are provided for a demonstration involving the transformation of a hydrophobic liquid to a partially hydrophobic semisolid. Safety considerations are noted. (JN)

  8. 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)

  9. 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)

  10. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Rehfeld, D. W.; And Others

    1988-01-01

    Describes two demonstrations (1) a dust explosion using a coffee can, candle, rubber tubing, and cornstarch and (2) forming a silicate-polyvinyl alcohol polymer which can be pressed into plastic sheets or molded. Gives specific instructions. (MVL)

  11. 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)

  12. 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)

  13. A Method of Separating the Lymph-Node Cells, of C57 BL Mice Allergized with BP8 Ascites Tumour, into Two Fractions with a Fast and Slow Electrophoretic Mobility: Demonstration that only the “Fast LNC” will Protect C3H Mice Against Challenge with the Tumour

    PubMed Central

    Thomas, Catherine B.; Cater, D. B.

    1972-01-01

    Lymph-node cells (LNC) from C57 Bl mice, allergized with BP8 ascites tumour, were separated in vitro into 2 populations on the basis of the charge on their plasma membranes. The population with a lower electrophoretic mobility (“slow LNC”) were agglutinated at zero zeta potential by a critical dose of poly-l-lysine leaving the “fast LNC” in suspension. Only the “fast LNC” protected C3H mice against fatal challenge with BP8 tumour in vivo. PMID:5032087

  14. Ovariectomy is associated with metabolic impairments and enhanced mammary tumor growth in MKR mice.

    PubMed

    Ben-Shmuel, Sarit; Scheinman, Eyal J; Rashed, Rola; Orr, Zila Shen; Gallagher, Emily J; LeRoith, Derek; Rostoker, Ran

    2015-12-01

    Obesity and type 2 diabetes (T2D) are associated with an increased risk of breast cancer incidence and mortality. Common features of obesity and T2D are insulin resistance and hyperinsulinemia. A mammary tumor promoting effect of insulin resistance and hyperinsulinemia was demonstrated in the transgenic female MKR mouse model of pre-diabetes inoculated with mammary cancer cells. Interestingly, in MKR mice, as well as in other diabetic mouse models, males exhibit severe hyperglycemia, while females display insulin resistance and hyperinsulinemia with only a mild increase in blood glucose levels. This gender-specific protection from hyperglycemia may be attributed to estradiol, a key player in the regulation of the metabolic state, including obesity, glucose homeostasis, insulin resistance, and lipid profile. The aim of this study was to investigate the effects of ovariectomy (including the removal of endogenous estradiol) on the metabolic state of MKR female mice and subsequently on the growth of Mvt-1 mammary cancer cells, inoculated into the mammary fat pad of ovariectomized mice, compared with sham-operated mice. The results showed an increase in body weight, accompanied by increased fat mass, elevated blood glucose levels, and hypercholesterolemia, in ovariectomized MKR mice. In addition, mammary tumor growth was significantly higher in these mice. The results suggest that ovarian hormone deficiency may promote impaired metabolic homeostasis in the hyperinsulinemic MKR female mice, which in turn is associated with an increased growth of mammary tumors. PMID:26383532

  15. Self-Tracking Energy Transfer for Neural Stimulation in Untethered Mice

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    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 mm3 , 20 mg) fully implanted under the skin.

  16. 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.

  17. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Cliche, Jean-Marie; And Others

    1988-01-01

    Describes two demonstrations: 1) the effect of polarity on solubility using sodium dichromate, TTE, ligroin, and water to form nonpolar-polar-nonpolar layers with the polar layer being colored; 2) determination of egg whites to be yellow by determining the content of yellow colored riboflavin in the egg white. (MVL)

  18. 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)

  19. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1981-01-01

    Provides instructions and a list of materials needed to demonstrate: (1) a model of the quantum mechanical atom; (2) principles involved in metal corrosion and in the prevention of this destructive process by electrochemical means; and (3) a Thermit reaction, modified to make it more dramatic and interesting for students. (SK)

  20. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Describes two demonstrations to illustrate characteristics of substances. Outlines a method to detect the changes in pH levels during the electrolysis of water. Uses water pistols, one filled with methane gas and the other filled with water, to illustrate the differences in these two substances. (TW)

  1. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L.

    1983-01-01

    An apparatus is described in which effects of pressure, volume, and temperature changes on a gas can be observed simultaneously. Includes use of the apparatus in demonstrating Boyle's, Gay-Lussac's, and Charles' Laws, attractive forces, Dalton's Law of Partial pressures, and in illustrating measurable vapor pressures of liquids and some solids.…

  2. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1985-01-01

    Background information, procedures, and typical results obtained are provided for two demonstrations. The first involves the colorful complexes of copper(II). The second involves reverse-phase separation of Food, Drug, and Cosmetic (FD & C) dyes using a solvent gradient. (JN)

  3. 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…

  4. Tested Demonstrations.

    ERIC Educational Resources Information Center

    Gilbert, George L., Ed.

    1987-01-01

    Describes two demonstrations for use in chemistry instruction. The first illustrates the preparation of a less common oxide of iron, showing why this oxide is rare. The second is an explosion reaction of hydrogen and oxygen that is recommended for use as an attention-getting device. (TW)

  5. 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)

  6. Vapb/Amyotrophic lateral sclerosis 8 knock-in mice display slowly progressive motor behavior defects accompanying ER stress and autophagic response.

    PubMed

    Larroquette, Frédérique; Seto, Lesley; Gaub, Perrine L; Kamal, Brishna; Wallis, Deeann; Larivičre, Roxanne; Vallée, Joanne; Robitaille, Richard; Tsuda, Hiroshi

    2015-11-15

    Missense mutations (P56S) in Vapb are associated with autosomal dominant motor neuron diseases: amyotrophic lateral sclerosis and lower motor neuron disease. Although transgenic mice overexpressing the mutant vesicle-associated membrane protein-associated protein B (VAPB) protein with neuron-specific promoters have provided some insight into the toxic properties of the mutant proteins, their role in pathogenesis remains unclear. To identify pathological defects in animals expressing the P56S mutant VAPB protein at physiological levels in the appropriate tissues, we have generated Vapb knock-in mice replacing wild-type Vapb gene with P56S mutant Vapb gene and analyzed the resulting pathological phenotypes. Heterozygous P56S Vapb knock-in mice show mild age-dependent defects in motor behaviors as characteristic features of the disease. The homozygous P56S Vapb knock-in mice show more severe defects compared with heterozygous mice reflecting the dominant and dose-dependent effects of P56S mutation. Significantly, the knock-in mice demonstrate accumulation of P56S VAPB protein and ubiquitinated proteins in cytoplasmic inclusions, selectively in motor neurons. The mutant mice demonstrate induction of ER stress and autophagic response in motor neurons before obvious onset of behavioral defects, suggesting that these cellular biological defects might contribute to the initiation of the disease. The P56S Vapb knock-in mice could be a valuable tool to gain a better understanding of the mechanisms by which the disease arises. PMID:26362257

  7. 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

  8. Status of MICE

    SciTech Connect

    Soler, F. J. P.

    2010-03-30

    The Muon Ionization Cooling Experiment (MICE) is an experiment currently under construction at the Rutherford Appleton Laboratory (RAL) in the UK. The aim of the experiment is to demonstrate the concept of ionization cooling for a beam of muons, crucial for the requirements of a Neutrino Factory and a Muon Collider. Muon cooling is achieved by measuring the reduction of the four dimensional transverse emittance for a beam of muons passing through low density absorbers and then accelerating the longitudinal component of the momentum using RF cavities. The absorbers are maintained in a focusing magnetic field to reduce the beta function of the beam and the RF cavities are kept inside coupling coils. The main goal of MICE is to measure a fractional drop in emittance, of order -10% for large emittance beams, with an accuracy of 1%(which imposes a requirement that the absolute emittance be measured with an accuracy of 0.1%). This paper will discuss the status of MICE, including the progress in commissioning the muon beam line at the ISIS accelerator at RAL, the construction of the different detector elements in MICE and the prospects for the future.

  9. RAP-011, an activin receptor ligand trap, increases hemoglobin concentration in hepcidin transgenic mice.

    PubMed

    Langdon, Jacqueline M; Barkataki, Sangjucta; Berger, Alan E; Cheadle, Chris; Xue, Qian-Li; Sung, Victoria; Roy, Cindy N

    2015-01-01

    Over expression of hepcidin antimicrobial peptide is a common feature of iron-restricted anemia in humans. We investigated the erythroid response to either erythropoietin or RAP-011, a "murinized" ortholog of sotatercept, in C57BL/6 mice and in hepcidin antimicrobial peptide 1 over expressing mice. Sotatercept, a soluble, activin receptor type IIA ligand trap, is currently being evaluated for the treatment of anemias associated with chronic renal disease, myelodysplastic syndrome, ?-thalassemia, and Diamond Blackfan anemia and acts by inhibiting signaling downstream of activin and other Transforming Growth Factor-? superfamily members. We found that erythropoietin and RAP-011 increased hemoglobin concentration in C57BL/6 mice and in hepcidin antimicrobial peptide 1 over expressing mice. While erythropoietin treatment depleted splenic iron stores in C57BL/6 mice, RAP-011 treatment did not deplete splenic iron stores in mice of either genotype. Bone marrow erythroid progenitors from erythropoietin-treated mice exhibited iron-restricted erythropoiesis, as indicated by increased median fluorescence intensity of transferrin receptor immunostaining by flow cytometry. In contrast, RAP-011-treated mice did not exhibit the same degree of iron-restricted erythropoiesis. In conclusion, we have demonstrated that RAP-011 can improve hemoglobin concentration in hepcidin antimicrobial peptide 1 transgenic mice. Our data support the hypothesis that RAP-011 has unique biologic effects which prevent or circumvent depletion of mouse splenic iron stores. RAP-011 may, therefore, be an appropriate therapeutic for trials in human anemias characterized by increased expression of hepcidin antimicrobial peptide and iron-restricted erythropoiesis. PMID:25236856

  10. Interventional effects of squid ink polysaccharides on cyclophosphamide-associated testicular damage in mice.

    PubMed

    Le, X Y; Luo, P; Gu, Y P; Tao, Y X; Liu, H Z

    2015-01-01

    Cyclophosphamide (CP) is a commonly used antitumour and immunosuppressive drug, but it is inevitable that the chemotherapeutic agent may cause long-term or permanent reproductive damage on young male patients through inducing oxidative stress in the testes. Squid ink polysaccharides (SIP), a newly found marine glycosaminoglycon have been proved to have antioxidant capabilities and chemotherapy-protective activities on model animals in our recent investigations. This study was conducted to assess whether or not SIP could protect male mice against gonadotoxicity during CP exposure. Sexually mature male Kunming mice were allocated to one of four groups. CP was abdominally administered at dose of 15 mg/kg body weight to two groups of mice for ten weeks, once a week, one group of mice received SIP at dose of 80 mg/kg body weight by gavage for ten weeks, once a day. The other two groups comprised a vehicle treated group and an SIP treated group. Toxicity of CP and protective activity of SIP on the testes were assessed by: sperm parameters, organ index, testicular antioxidant ability, activities of marker enzymes, sex hormone content, and histopathological features. Data showed CP-induced, serious negative changes on murine sperm parameters, organ index, testicular antioxidant ability, activities of marker enzymes, sexual hormone contents, and histopathological features which were all significantly impaired by SIP. This study found that SIP were demonstrated to offer protective effects against CP-induced toxicity on testes in mice (Tab. 2, Fig. 3, Ref. 29). PMID:25924645

  11. Thymic epithelium determines a spontaneous chronic neuritis in Icam1(tm1Jcgr)NOD mice.

    PubMed

    Meyer zu Horste, Gerd; Mausberg, Anne K; Cordes, Steffen; El-Haddad, Houda; Partke, Hans-Joachim; Leussink, Verena I; Roden, Michael; Martin, Stephan; Steinman, Lawrence; Hartung, Hans-Peter; Kieseier, Bernd C

    2014-09-15

    The NOD mouse strain spontaneously develops autoimmune diabetes. A deficiency in costimulatory molecules, such as B7-2, on the NOD genetic background prevents diabetes but instead triggers an inflammatory peripheral neuropathy. This constitutes a shift in the target of autoimmunity, but the underlying mechanism remains unknown. In this study, we demonstrate that NOD mice deficient for isoforms of ICAM-1, which comediate costimulatory functions, spontaneously develop a chronic autoimmune peripheral neuritis instead of diabetes. The disease is transferred by CD4(+) T cells, which infiltrate peripheral nerves together with macrophages and B cells and are autoreactive against peripheral myelin protein zero. These Icam1(tm1Jcgr)NOD mice exhibit unaltered numbers of regulatory T cells, but increased IL-17-producing T cells, which determine the severity, but not the target specificity, of autoimmunity. Ab-mediated ICAM-1 blockade triggers neuritis only in young NOD mice. Thymic epithelium from Icam1(tm1Jcgr)NOD mice features an altered expression of costimulatory molecules and induces neuritis and myelin autoreactivity after transplantation into nude mice in vivo. Icam1(tm1Jcgr)NOD mice exhibit a specifically altered TCR repertoire. Our findings introduce a novel animal model of chronic inflammatory neuropathies and indicate that altered expression of ICAM-1 on thymic epithelium shifts autoimmunity specifically toward peripheral nerves. This improves our understanding of autoimmunity in the peripheral nervous system with potential relevance for human diseases. PMID:25108020

  12. 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

  13. Progress of the MICE experiment

    E-print Network

    Bonesini, M

    2015-01-01

    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling of a muon beam. The demonstration is based on a simplified version of a neutrino factory cooling channel. As the emittance measurement will be done on a particle-by-particle basis, sophisticated beam instrumentation has been developed to measure particle coordinates and timing vs RF. The muon beamline has been characterized and a preliminary measure of the beam emittance, using a particle-by-particle method with only the TOF detector system, has been performed (MICE STEP I). Data taking for the study of the properties that determine the cooling performance (MICE Step IV) has just started in 2015, while the demonstration of ionization cooling with re-acceleration is foreseen for 2017.

  14. Dental and Cranial Pathologies in Mice Lacking the Cl(-) /H(+) -Exchanger ClC-7.

    PubMed

    Wen, Xin; Lacruz, Rodrigo S; Paine, Michael L

    2015-08-01

    ClC-7 is a 2Cl(-) /1H(+) -exchanger expressed at late endosomes and lysosomes, as well as the ruffled border of osteoclasts. ClC-7 deficiencies in mice and humans lead to impaired osteoclast function and therefore osteopetrosis. Failure of tooth eruption is also apparent in ClC-7 mutant animals, and this has been attributed to the osteoclast dysfunction and the subsequent defect in alveolar bone resorptive activity surrounding tooth roots. Ameloblasts also express ClC-7, and this study aims to determine the significance of ClC-7 in enamel formation by examining the dentitions of ClC-7 mutant mice. Micro-CT analysis revealed that the molar teeth of 3-week old ClC-7 mutant mice had no roots, and the incisors were smaller than their age-matched controls. Despite these notable developmental differences, the enamel and dentin densities of the mutant mice were comparable to those of the wild-type littermates. Scanning electron microscopy showed normal enamel crystallite and prismatic organization in the ClC-7 mutant mice, although the enamel was thinner (hypoplastic) than in controls. These results suggested that ClC-7 was not critical to enamel and dentin formation, and the observed tooth defects may be related more to a resulting alveolar bone phenotype. Micro-CT analysis also revealed abnormal features in the calvarial bones of the mutant mice. The cranial sutures in ClC-7 mutant mice remained open compared to the closed sutures seen in the control mice at 3 weeks. These data demonstrate that ClC-7 deficiency impacts the development of the dentition and calvaria, but does not significantly disrupt amelogenesis. PMID:25663454

  15. Macrophages largely contribute to heterologous anti-Propionibacterium acnes antibody-mediated protection from Actinobacillus pleuropneumoniae infection in mice.

    PubMed

    Ma, Qiuyue; Sun, Changjiang; Yang, Feng; Wang, Lei; Qin, Wanhai; Xia, Xiaojing; Feng, Xin; Du, Chongtao; Gu, Jingmin; Han, Wenyu; Lei, Liancheng

    2015-03-01

    Actinobacillus pleuropneumoniae is the causative agent of acute and chronic pleuropneumonia. Propionibacterium acnes is a facultative anaerobic gram-positive corynebacterium. We have previously found that anti-P. acnes antibodies can prevent A. pleuropneumoniae infections in mice. To investigate the role of macrophages in this process, affinity-purified anti-P. acnes IgG and anti-A. pleuropneumoniae IgG were used in opsonophagocytosis assays. Additionally, the efficacy of passive immunization with P. acnes serum against A. pleuropneumoniae was tested in macrophage-depleted mice. It was found that anti-P. acnes IgG had an effect similar to that of anti-A. pleuropneumoniae IgG (P > 0.05), which significantly promotes phagocytosis of A. pleuropneumoniae by macrophages (P < 0.01). It was also demonstrated that, after passive immunization with anti-P. acnes serum, macrophage-replete mice had the highest survival rate (90%), whereas the survival rate of macrophage-depleted mice was only 40% (P < 0.05). However, macrophage-depleted mice that had been passively immunized with naďve serum had the lowest survival rate (20%), this rate being lower than that of macrophage-replete mice that had been passively immunized with naďve serum. Overall, anti-P. acnes antibodies did not prevent A. pleuropneumoniae infection under conditions of macrophage depletion (P > 0.05). Furthermore, in mice that had been passively immunized with anti-P. acnes serum, macrophage depletion resulted in a greater A. pleuropneumoniae burden and more severe pathological features of pneumonia in lung tissues than occurred in macrophage-replete mice. It was concluded that macrophages are essential for the process by which anti-P. acnes antibody prevents A. pleuropneumoniae infection in mice. PMID:25644652

  16. Temporal distribution of distinct mast cell phenotypes during intestinal schistosomiasis in mice.

    PubMed

    De Jonge, Frederik; Van Nassauw, Luc; Van Meir, Frans; Miller, Hugh R P; Van Marck, Eric; Timmermans, Jean-Pierre

    2002-05-01

    Mastocytosis is a common feature of helminth infection in most host species. We examined the temporal distribution and phenotype of mast cells during intestinal schistosomiasis in mice, using antibodies directed against histamine, a general mast cell marker, against mouse mast cell protease-1 (MMCP-1), a mucosal mast cell (MMC) marker, and against tryptase, a predominantly connective tissue mast cell (CTMC) marker. Ileal paraffin and/or cryosections of control, 8- and 15-week-infected mice were quantitatively analysed. In the intestinal wall of non- and unisexual infected mice, a few dispersed mast cells were detected. In infected mice, a transient increase of mast cells in the mucosa and a gradual increase in the outer muscle layer were observed. MMCP-1 expressing MMCs were predominantly present in the mucosa during the acute phase [8 weeks postinfection (p.i.)], while tryptase and histamine immunoreactivity demonstrated that two subsets of CTMCs were predominantly present in the outer muscle layer at 15 weeks p.i. (chronic phase). In conclusion, these results reveal that, in mice, both MMCs and CTMCs are involved in the inflammatory response during schistosomiasis. The recruitment of each mast cell population is time-dependent and occurs at different locations. These data suggest that mastocytosis is associated with motility-related gastrointestinal symptoms and egg excretion. PMID:12060316

  17. Cerebellar-Dependent Expression of Motor Learning during Eyeblink Conditioning in Head-Fixed Mice

    PubMed Central

    Heiney, Shane A.; Wohl, Margot P.; Chettih, Selmaan N.; Ruffolo, Luis I.

    2014-01-01

    Eyeblink conditioning in restrained rabbits has served as an excellent model of cerebellar-dependent motor learning for many decades. In mice, the role of the cerebellum in eyeblink conditioning is less clear and remains controversial, partly because learning appears to engage fear-related circuits and lesions of the cerebellum do not abolish the learned behavior completely. Furthermore, experiments in mice are performed using freely moving systems, which lack the stability necessary for mapping out the essential neural circuitry with electrophysiological approaches. We have developed a novel apparatus for eyeblink conditioning in head-fixed mice. Here, we show that the performance of mice in our apparatus is excellent and that the learned behavior displays two hallmark features of cerebellar-dependent eyeblink conditioning in rabbits: (1) gradual acquisition; and (2) adaptive timing of conditioned movements. Furthermore, we use a combination of pharmacological inactivation, electrical stimulation, single-unit recordings, and targeted microlesions to demonstrate that the learned behavior is completely dependent on the cerebellum and to pinpoint the exact location in the deep cerebellar nuclei that is necessary. Our results pave the way for using eyeblink conditioning in head-fixed mice as a platform for applying next-generation genetic tools to address molecular and circuit-level questions about cerebellar function in health and disease. PMID:25378152

  18. Clonal Structure of Carcinogen-induced Intestinal Tumors in Mice

    PubMed Central

    Thliveris, Andrew T.; Clipson, Linda; White, Alanna; Waggoner, Jesse; Plesh, Lauren; Skinner, Bridget L.; Zahm, Christopher D.; Sullivan, Ruth; Dove, William F.; Newton, Michael A.; Halberg, Richard B.

    2011-01-01

    Previous studies have demonstrated that intestinal tumors from ApcMin/+ (Min) mice and Familial adenomatous polyposis (FAP) patients are often polyclonal. We sought to determine whether polyclonality is unique to tumors arising from hereditary predispositions or, instead, is a common feature of intestinal tumorigenesis in other pathways to tumorigenesis. Ethylnitrosourea-induced intestinal tumors from mice wildtype at the Apc locus and chimeric for the Rosa26 lineage marker were analyzed. Many were overtly polyclonal, being composed of a mixture of Rosa26+ and Rosa26? neoplastic cells. Statistical analyses revealed that polyclonality could be explained by interactions between two initiated clones separated by a very short distance. The frequency of overtly polyclonal tumors and the range of interactions estimated in this model are similar to those observed when analyzing familial tumors from Min mice. Thus, polyclonality does not depend on the familial pathway to tumorigenesis. Interactions between two initiated clones might provide a selective advantage during the early stages of intestinal tumorigenesis. PMID:21636550

  19. 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

  20. Adenosine-dependent pulmonary fibrosis in adenosine deaminase-deficient mice.

    PubMed

    Chunn, Janci L; Molina, Jose G; Mi, Tiejuan; Xia, Yang; Kellems, Rodney E; Blackburn, Michael R

    2005-08-01

    Pulmonary fibrosis is a common feature of numerous lung disorders, including interstitial lung diseases, asthma, and chronic obstructive pulmonary disease. Despite the prevalence of pulmonary fibrosis, the molecular mechanisms governing inflammatory and fibroproliferative aspects of the disorder are not clear. Adenosine is a purine-signaling nucleoside that is generated in excess during cellular stress and damage. This signaling molecule has been implicated in the regulation of features of chronic lung disease; however, the impact of adenosine on pulmonary fibrosis is not well understood. The goal of this study was to explore the impact of endogenous adenosine elevations on pulmonary fibrosis. To accomplish this, adenosine deaminase (ADA)-deficient mice were treated with various levels of ADA enzyme replacement therapy to regulate endogenous adenosine levels in the lung. Maintaining ADA-deficient mice on low dosages of ADA enzyme therapy led to chronic elevations in lung adenosine levels that were associated with pulmonary inflammation, expression of profibrotic molecules, collagen deposition, and extreme alteration in airway structure. These features could be blocked by preventing elevations in lung adenosine. Furthermore, lowering lung adenosine levels after the establishment of pulmonary fibrosis resulted in a resolution of fibrosis. These findings demonstrate that chronic adenosine elevations are associated with pulmonary fibrosis in ADA-deficient mice and suggest that the adenosine functions as a profibrotic signal in the lung. PMID:16034138

  1. Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice[S

    PubMed Central

    Babaev, Vladimir R.; Hebron, Katie E.; Wiese, Carrie B.; Toth, Cynthia L.; Ding, Lei; Zhang, Youmin; May, James M.; Fazio, Sergio; Vickers, Kasey C.; Linton, MacRae F.

    2014-01-01

    Macrophages play crucial roles in the formation of atherosclerotic lesions. Akt, a serine/threonine protein kinase B, is vital for cell proliferation, migration, and survival. Macrophages express three Akt isoforms, Akt1, Akt2, and Akt3, but the roles of Akt1 and Akt2 in atherosclerosis in vivo remain unclear. To dissect the impact of macrophage Akt1 and Akt2 on early atherosclerosis, we generated mice with hematopoietic deficiency of Akt1 or Akt2. After 8 weeks on Western diet, Ldlr?/? mice reconstituted with Akt1?/? fetal liver cells (Akt1?/??Ldlr?/?) had similar atherosclerotic lesion areas compared with control mice transplanted with WT cells (WT?Ldlr?/?). In contrast, Akt2?/??Ldlr?/? mice had dramatically reduced atherosclerotic lesions compared with WT?Ldlr?/? mice of both genders. Similarly, in the setting of advanced atherosclerotic lesions, Akt2?/??Ldlr?/? mice had smaller aortic lesions compared with WT?Ldlr?/? and Akt1?/??Ldlr?/? mice. Importantly, Akt2?/??Ldlr?/? mice had reduced numbers of proinflammatory blood monocytes expressing Ly-6Chi and chemokine C-C motif receptor 2. Peritoneal macrophages isolated from Akt2?/? mice were skewed toward an M2 phenotype and showed decreased expression of proinflammatory genes and reduced cell migration. Our data demonstrate that loss of Akt2 suppresses the ability of macrophages to undergo M1 polarization reducing both early and advanced atherosclerosis. PMID:25240046

  2. 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....

  3. Urinary Bladder Dysfunction in Transgenic Sickle Cell Disease Mice

    PubMed Central

    Claudino, Mário Angelo; Leiria, Luiz Osório Silveira; da Silva, Fábio Henrique; Alexandre, Eduardo Costa; Renno, Andre; Mónica, Fabiola Zakia; de Nucci, Gilberto; Fertrin, Kleber Yotsumoto; Antunes, Edson; Costa, Fernando Ferreira; Franco-Penteado, Carla Fernanda

    2015-01-01

    Background Urological complications associated with sickle cell disease (SCD), include nocturia, enuresis, urinary infections and urinary incontinence. However, scientific evidence to ascertain the underlying cause of the lower urinary tract symptoms in SCD is lacking. Objective Thus, the aim of this study was to evaluate urinary function, in vivo and ex vivo, in the Berkeley SCD murine model (SS). Methods Urine output was measured in metabolic cage for both wild type and SS mice (25-30 g). Bladder strips and urethra rings were dissected free and mounted in organ baths. In isolated detrusor smooth muscle (DSM), relaxant response to mirabegron and isoproterenol (1nM-10?M) and contractile response to (carbachol (CCh; 1 nM-100?M), KCl (1 mM-300mM), CaCl2 (1?M-100mM), ?,?-methylene ATP (1, 3 and 10 ?M) and electrical field stimulation (EFS; 1-32 Hz) were measured. Phenylephrine (Phe; 10nM-100?M) was used to evaluate the contraction mechanism in the urethra rings. Cystometry and histomorphometry were also performed in the urinary bladder. Results SS mice present a reduced urine output and incapacity to produce typical bladder contractions and bladder emptying (ex vivo), compared to control animals. In DSM, relaxation in response to a selective ?3-adrenergic agonist (mirabegron) and to a non-selective ?-adrenergic (isoproterenol) agonist were lower in SS mice. Additionally, carbachol, ?, ?-methylene ATP, KCl, extracellular Ca2+ and electrical-field stimulation promoted smaller bladder contractions in SS group. Urethra contraction induced by phenylephrine was markedly reduced in SS mice. Histological analyses of SS mice bladder revealed severe structural abnormalities, such as reductions in detrusor thickness and bladder volume, and cell infiltration. Conclusions Taken together, our data demonstrate, for the first time, that SS mice display features of urinary bladder dysfunction, leading to impairment in urinary continence, which may have an important role in the pathogenesis of the enuresis and infections observed the SCD patients. PMID:26241312

  4. 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

  5. Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice

    PubMed Central

    Galli, Soledad; Lopes, Douglas M.; Ammari, Rachida; Kopra, Jaakko; Millar, Sarah E.; Gibb, Alasdair; Salinas, Patricia C.

    2014-01-01

    Synapse degeneration is an early and invariant feature of neurodegenerative diseases. Indeed, synapse loss occurs prior to neuronal degeneration and correlates with the symptom severity of these diseases. However, the molecular mechanisms that trigger synaptic loss remain poorly understood. Here we demonstrate that deficient Wnt signalling elicits synaptic degeneration in the adult striatum. Inducible expression of the secreted Wnt antagonist Dickkopf1 (Dkk1) in adult mice (iDkk1) decreases the number of cortico-striatal glutamatergic synapses and of D1 and D2 dopamine receptor clusters. Synapse loss occurs in the absence of axon retraction or cell death. The remaining excitatory terminals contain fewer synaptic vesicles and have a reduced probability of evoked transmitter release. IDkk1 mice show impaired motor coordination and are irresponsive to amphetamine. These studies identify Wnts as key endogenous regulators of synaptic maintenance and suggest that dysfunction in Wnt signalling contributes to synaptic degeneration at early stages in neurodegenerative diseases. PMID:25318560

  6. Inflammatory responses to pneumovirus infection in IFN-alpha beta R gene-deleted mice.

    PubMed

    Garvey, Tara L; Dyer, Kimberly D; Ellis, John A; Bonville, Cynthia A; Foster, Barbara; Prussin, Calman; Easton, Andrew J; Domachowske, Joseph B; Rosenberg, Helene F

    2005-10-01

    Pneumonia virus of mice (PVM; family Paramyxoviridae) is a natural pathogen of rodents that reproduces important clinical features of severe respiratory syncytial virus infection in humans. As anticipated, PVM infection induces transcription of IFN antiviral response genes preferentially in wild-type over IFN-alphabetaR gene-deleted (IFN-alphabetaR-/-) mice. However, we demonstrate that PVM infection results in enhanced expression of eotaxin-2 (CCL24), thymus and activation-regulated chemokine (CCL17), and the proinflammatory RNase mouse eosinophil-associated RNase (mEar) 11, and decreased expression of monocyte chemotactic protein-5, IFN-gamma-inducible protein-10, and TLR-3 in lung tissue of IFN-alphabetaR-/- mice when compared with wild type. No differential expression of chemokines MIP-1alpha or MIP-2 or Th2 cytokines IL-4 or IL-5 was observed. Differential expression of proinflammatory mediators was associated with distinct patterns of lung pathology. The widespread granulocytic infiltration and intra-alveolar edema observed in PVM-infected, wild-type mice are replaced with patchy, dense inflammatory foci localized to the periphery of the larger blood vessels. Bronchoalveolar lavage fluid from IFN-alphabetaR-/- mice yielded 7- to 8-fold fewer leukocytes overall, with increased percentages of eosinophils, monocytes, and CD4+ T cells, and decreased percentage of CD8+ T cells. Differential pathology is associated with prolonged survival of the IFN-alphabetaR-/- mice (50% survival at 10.8 +/- 0.6 days vs the wild type at 9.0 +/- 0.3 days; p < 0.02) despite increased virus titers. Overall, our findings serve to identify novel transcripts that are differentially expressed in the presence or absence of IFN-alphabetaR-mediated signaling, further elucidating interactions between the IFN and antiviral inflammatory responses in vivo. PMID:16177121

  7. Toll-like receptor-deficient mice reveal how innate immune signaling influences Salmonella virulence strategies.

    PubMed

    Sivick, Kelsey E; Arpaia, Nicholas; Reiner, Gabrielle L; Lee, Bettina L; Russell, Bethany R; Barton, Gregory M

    2014-02-12

    Pathogens utilize features of the host response as cues to regulate virulence gene expression. Salmonella enterica serovar Typhimurium (ST) sense Toll-like receptor (TLR)-dependent signals to induce Salmonella Pathogenicity Island 2 (SPI2), a locus required for intracellular replication. To examine pathogenicity in the absence of such cues, we evaluated ST virulence in mice lacking all TLR function (Tlr2(-/-)xTlr4(-/-)xUnc93b1(3d/3d)). When delivered systemically to TLR-deficient mice, ST do not require SPI2 and maintain virulence by replicating extracellularly. In contrast, SPI2 mutant ST are highly attenuated after oral infection of the same mice, revealing a role for SPI2 in the earliest stages of infection, even when intracellular replication is not required. This early requirement for SPI2 is abolished in MyD88(-/-)xTRIF(-/-) mice lacking both TLR- and other MyD88-dependent signaling pathways, a potential consequence of compromised intestinal permeability. These results demonstrate how pathogens use plasticity in virulence strategies to respond to different host immune environments. PMID:24528866

  8. Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis.

    PubMed

    Iff, Joël; Wang, Wei; Sajic, Tatjana; Oudry, Nathalie; Gueneau, Estelle; Hopfgartner, Gérard; Varesio, Emmanuel; Szanto, Ildiko

    2009-10-01

    Increased inflammatory signaling is a key feature of metabolic disorders. In this context, the role of increased pro-inflammatory signals has been extensively studied. By contrast, no efforts have been dedicated to study the contrasting scenario: the attenuation of anti-inflammatory signals and their role in metabolic homeostasis. IL-4 and IL-13 are anti-inflammatory cytokines signaling through the Signal Transducer and Activator of Transcription 6 (STAT6). Our study was aimed at evaluating the lack of STAT6 signaling on liver homeostasis. To this end we analyzed the liver proteome of wild type and STAT6 knock-out mice using 2D nanoscale LC-MS/MS with iTRAQ labeling technique. The coordinated changes in proteins identified by this quantitative proteome analysis indicated disturbed lipid homeostasis and a state of hepatocellular stress. Most significantly, the expression of the liver fatty acid binding protein (FABP1) was increased in the knock-out mice. In line with the elevated FABP1 expression we found latent liver lipid accumulation in the STAT6-deficient mice which was further aggravated when mice were challenged by a high fat diet. In conclusion, our study revealed a so far uncharacterized role for STAT6 in regulating liver lipid homeostasis and demonstrates the importance of anti-inflammatory signaling in the defense against the development of liver steatosis. PMID:19663508

  9. The effects of hypermuscularity on shoulder morphology in myostatin-deficient mice

    PubMed Central

    Green, David J; Hamrick, Mark W; Richmond, Brian G

    2011-01-01

    Mechanical loads, particularly those generated by skeletal muscle, play a significant role in determining long-bone shape and strength, but it is less clear how these loads influence the morphology of flat bones like the scapula. While scapular morphology has been shown to vary with locomotor mode in mammals, this study seeks to better understand whether genetically modified muscle size can influence scapular shape in the absence of significant locomotor differences. The soft- and hard-tissue morphological characteristics were examined in 11 hypermuscular, mutant (myostatin-deficient), 20 heterozygote, and 15 wild-type mouse shoulders. Body mass did not significantly differ among the genotype groups, but homozygous mutant and heterozygote mice had significantly larger shoulder muscles than wild-type mice. Mutant mice also differed significantly from the wild-type controls in several aspects of scapular size and shape, including glenohumeral joint orientation, total scapular length, superior border length, and supraspinous and infraspinous fossa length. Conversely, several traits describing superoinferior scapular breadth measures (e.g. total breadth and dorsal scapular fossa breadth) did not significantly differ between mutant and wild-type mice. Since the intrinsic musculature of the scapula is oriented in a mediolateral fashion, it follows that mediolaterally configured hard-tissue features like scapular length were most distinct among genotype groups. As had been noted previously with long bones, this study demonstrates that genetically enhanced muscle size has marked effects on the morphological characteristics of the shoulder. PMID:21332716

  10. Functional consequences of EpCam mutation in mice and men.

    PubMed

    Mueller, James L; McGeough, Matthew D; Peńa, Carla A; Sivagnanam, Mamata

    2014-02-15

    Congenital tufting enteropathy (CTE) is a severe diarrheal disease of infancy characterized by villous changes and epithelial tufts. We previously identified mutations in epithelial cell adhesion molecule (EpCAM) as the cause of CTE. We developed an in vivo mouse model of CTE based on EpCAM mutations found in patients with the aim to further elucidate the in vivo role of EpCAM and allow for a direct comparison to human CTE. Using Cre-LoxP recombination technology, we generated a construct lacking exon 4 in Epcam. Epcam(?4/?4) mice and CTE patient intestinal tissue integrity was analyzed by histology using both light immunohistochemistry and electron microscopy. Epcam(?4/?4) mice demonstrate neonatal lethality and growth retardation with pathological features, including epithelial tufts, enterocyte crowding, altered desmosomes, and intercellular gaps, similar to human CTE patients. Mutant EpCAM protein is present at low levels and is mislocalized in the intestine of Epcam(?4/?4) mice and CTE patients. Deletion of exon 4 was found to decrease expression of both EpCAM and claudin-7 causing a loss of colocalization, functionally disrupting the EpCAM/claudin-7 complex, a finding for the first time confirmed in CTE patients. Furthermore, compared with unaffected mice, mutation of Epcam leads to enhanced permeability and intestinal cell migration, uncovering underlying disease mechanisms. PMID:24337010

  11. Functional consequences of EpCam mutation in mice and men

    PubMed Central

    Mueller, James L.; McGeough, Matthew D.; Peńa, Carla A.

    2013-01-01

    Congenital tufting enteropathy (CTE) is a severe diarrheal disease of infancy characterized by villous changes and epithelial tufts. We previously identified mutations in epithelial cell adhesion molecule (EpCAM) as the cause of CTE. We developed an in vivo mouse model of CTE based on EpCAM mutations found in patients with the aim to further elucidate the in vivo role of EpCAM and allow for a direct comparison to human CTE. Using Cre-LoxP recombination technology, we generated a construct lacking exon 4 in Epcam. Epcam?4/?4 mice and CTE patient intestinal tissue integrity was analyzed by histology using both light immunohistochemistry and electron microscopy. Epcam?4/?4 mice demonstrate neonatal lethality and growth retardation with pathological features, including epithelial tufts, enterocyte crowding, altered desmosomes, and intercellular gaps, similar to human CTE patients. Mutant EpCAM protein is present at low levels and is mislocalized in the intestine of Epcam?4/?4 mice and CTE patients. Deletion of exon 4 was found to decrease expression of both EpCAM and claudin-7 causing a loss of colocalization, functionally disrupting the EpCAM/claudin-7 complex, a finding for the first time confirmed in CTE patients. Furthermore, compared with unaffected mice, mutation of Epcam leads to enhanced permeability and intestinal cell migration, uncovering underlying disease mechanisms. PMID:24337010

  12. 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.

  13. Running endurance abnormality in mdx mice.

    PubMed

    Hara, Hajime; Nolan, Patrick M; Scott, Marion O; Bucan, Maja; Wakayama, Yoshihiro; Fischbeck, Kenneth H

    2002-02-01

    The mdx mouse lacks dystrophin and has histological features of Duchenne muscular dystrophy but little weakness in the first year of life. We report here an early deficit in voluntary wheel running, as assayed with a computerized wheel. All mdx mice showed an intermittent running pattern, in contrast to the continuous running seen in controls. The average continuous running time differed significantly between mdx and control mice at all ages tested (5-21 weeks). This assay is noninvasive, has the advantage of unbiased automatic data collection, and should be useful for quantifying the mdx deficit in therapeutic studies. PMID:11870688

  14. A Fluorescence Lecture Demonstration.

    ERIC Educational Resources Information Center

    Bozzelli, Joseph W.; Kemp, Marwin

    1982-01-01

    Describes fluorescence demonstrations related to several aspects of molecular theory and quantitized energy levels. Demonstrations use fluorescent chemical solutions having luminescence properties spanning the visible spectrum. Also describes a demonstration of spontaneous combustion of familiar substances in chlorine. (JN)

  15. Partial return yoke for MICE step IV and final step

    SciTech Connect

    Witte, H.; Plate, S.; Berg, J. S.; Tarrant, J.; Bross, A.

    2015-05-03

    This paper reports on the progress of the design and construction of a retro-fitted return yoke for the international Muon Ionization Cooling Experiment (MICE). MICE is a proof-of-principle experiment aiming to demonstrate ionization cooling experimentally. In earlier studies we outlined how a partial return yoke can be used to mitigate stray magnetic field in the experimental hall; we report on the progress of the construction of the partial return yoke for MICE Step IV. We also discuss an extension of the Partial Return Yoke for the final step of MICE; we show simulation results of the expected performance.

  16. 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.

  17. Adult mice expressing a Braf Q241R mutation on an ICR/CD-1 background exhibit a cardio-facio-cutaneous syndrome phenotype.

    PubMed

    Moriya, Mitsuji; Inoue, Shin-Ichi; Miyagawa-Tomita, Sachiko; Nakashima, Yasumi; Oba, Daiju; Niihori, Tetsuya; Hashi, Misato; Ohnishi, Hiroshi; Kure, Shigeo; Matsubara, Yoichi; Aoki, Yoko

    2015-12-20

    Activation of the RAS pathway has been implicated in oncogenesis and developmental disorders called RASopathies. Germline mutations in BRAF have been identified in 50-75% of patients with cardio-facio-cutaneous (CFC) syndrome, which is characterized by congenital heart defects, distinctive facial features, short stature and ectodermal abnormalities. We recently demonstrated that mice expressing a Braf Q241R mutation, which corresponds to the most frequent BRAF mutation (Q257R) in CFC syndrome, on a C57BL/6J background are embryonic/neonatal lethal, with multiple congenital defects, preventing us from analyzing the phenotypic consequences after birth. Here, to further explore the pathogenesis of CFC syndrome, we backcrossed these mice onto a BALB/c or ICR/CD-1 genetic background. On a mixed (BALB/c and C57BL/6J) background, all heterozygous Braf(Q241R/+) mice died between birth and 24 weeks and exhibited growth retardation, sparse and ruffled fur, liver necrosis and atrial septal defects (ASDs). In contrast, 31% of the heterozygous Braf(Q241R/+) ICR mice survived over 74 weeks. The surviving Braf(Q241R/+) ICR mice exhibited growth retardation, sparse and ruffled fur, a hunched appearance, craniofacial dysmorphism, long and/or dystrophic nails, extra digits and ovarian cysts. The Braf(Q241R/+) ICR mice also showed learning deficits in the contextual fear-conditioning test. Echocardiography indicated the presence of pulmonary stenosis and ASDs in the Braf(Q241R/+) ICR mice, which were confirmed by histological analysis. These data suggest that the heterozygous Braf(Q241R/+) ICR mice show similar phenotypes as CFC syndrome after birth and will be useful for elucidating the pathogenesis and potential therapeutic strategies for RASopathies. PMID:26472072

  18. Developmental consequences of in utero sodium arsenate exposure in mice with folate transport deficiencies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have demonstrated that mice lacking a functional folate binding protein 2 gene (Folbp2'/') were significantly more sensitive to in utero arsenic exposure than were the wild-type mice similarly exposed. When these mice were fed a folate-deficient diet, the embryotoxic effect of arsen...

  19. 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 ...

  20. 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.

  1. Insulin sensitivity in long-living Ames dwarf mice.

    PubMed

    Wiesenborn, Denise S; Ayala, Julio E; King, Emily; Masternak, Michal M

    2014-01-01

    Long-living Ames dwarf mice (df/df) characterized by growth hormone (GH) deficiency are widely used in aging research because of their 40-60 % lifespan extension compared to normal (N) littermates. Importantly, these mice not only live longer but are also protected from age-related diseases including insulin resistance. Several studies demonstrate that df/df mice have enhanced insulin signaling in different insulin-sensitive tissues and suggest that this is a mechanism for extended lifespan. However, it is unknown whether the enhanced insulin signaling in df/df mice translates to improved insulin action on hepatic glucose production and tissue glucose uptake. We performed hyperinsulinemic-euglycemic clamps to assess tissue-specific insulin action in vivo for the first time in these small long-living dwarfs. Our results demonstrate that the glucose infusion rate required to maintain euglycemia was ?2-fold higher in df/df mice compared to N controls. Insulin-mediated glucose production was completely suppressed in dwarf mice, and stimulation of gastrocnemius and vastus muscle and adipose tissue glucose uptake was also enhanced in df/df mice (100, 86, and 65 %, respectively). These findings show that improved insulin signaling in df/df mice is associated with enhanced tissue-specific insulin action in vivo. This improved functionality of insulin action and glucose homeostasis may play a key role in promoting healthy aging and longer lifespan in df/df mice. PMID:25163655

  2. Contact hypersensitivity response to isophorone diisocyanate in mice

    SciTech Connect

    Stern, M.L.; Brown, T.A.; Brown, R.D.; Munson, A.E. )

    1989-09-01

    Isophorone diisocyanate was evaluated for its potential as a sensitizing agent for allergic contact hypersensitivity in mice. Female B6C3F1 mice were sensitized with 0.1, 0.3, and 1.0% isophorone diisocyanate and challenged with 3.0% isophorone diisocyanate. Doses of isophorone diisocyanate were selected from assays for primary irritancy. Mice received 20 microliters by direct dermal application, for 5 days, to sites prepared by shaving, dermabrading and, in some mice, with intra dermal injection of complete Freund's adjuvant. The rest period was 7 days. Measurement of the contact hypersensitivity response in mice was by radioisotopic assay two days after challenge and mouse ear swelling one and two days after challenge. Mice demonstrated statistically significant dose-dependent contact hypersensitivity responses to isophorone diisocyanate with or without adjuvant pretreatment.

  3. Bex1 knock out mice show altered skeletal muscle regeneration

    SciTech Connect

    Koo, Jae Hyung Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

    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.

  4. Why Demonstrations Matter

    ERIC Educational Resources Information Center

    Black, Richard

    2005-01-01

    With the current focus on constructivist perspectives, science demonstrations have fallen out of favor in some circles. Demonstrations are easy to do and offer many benefits and unique opportunities in the constructivist classroom. With careful use, demonstrations can be powerful teaching tools. A wonderful quality of a demonstration (or a series…

  5. 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…

  6. METCAN demonstration manual, version 1.0

    NASA Technical Reports Server (NTRS)

    Lee, H.-J.; Murthy, P. L. N.

    1992-01-01

    The various features of the Metal Matrix Composite Analyzer (METCAN) computer program to simulate the high temperature nonlinear behavior of continuous fiber reinforced metal matrix composites are demonstrated. Different problems are used to demonstrate various capabilities of METCAN for both static and cyclic analyses. A complete description of the METCAN output file is also included to help interpret results.

  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. Melancholic-Like Behaviors and Circadian Neurobiological Abnormalities in Melatonin MT1 Receptor Knockout Mice

    PubMed Central

    Comai, Stefano; Ochoa-Sanchez, Rafael; Dominguez-Lopez, Sergio; Bambico, Francis Rodriguez

    2015-01-01

    Background: Melancholic depression, described also as endogenous depression, is a mood disorder with distinctive specific psychopathological features and biological homogeneity, including anhedonia, circadian variation of mood, psychomotor activation, weight loss, diurnal cortisol changes, and sleep disturbances. Although several hypotheses have been proposed, the etiology of this disorder is still unknown. Methods: Behavioral, electrophysiological and biochemical approaches were used to characterize the emotional phenotype, serotonergic and noradrenergic electrical activity, and corticosterone in melatonin MT1 receptor knockout mice and their wild type counterparts, during both light and dark phases. Results: Melatonin MT1 receptor knockout mice have decreased mobility in the forced swim and tail suspension tests as well as decreased sucrose consumption, mostly during the dark/inactive phase. These mood variations are reversed by chronic treatment with the tricyclic antidepressant desipramine. In addition, MT1 receptor knockout mice exhibit psychomotor disturbances, higher serum levels of corticosterone the dark phase, and a blunted circadian variation of corticosterone levels. In vivo electrophysiological recordings show a decreased burst-firing activity of locus coeruleus norepinephrine neurons during the dark phase. The circadian physiological variation in the spontaneous firing activity of high-firing neuronal subpopulations of both norepinephrine neurons and dorsal raphe serotonin neurons are abolished in MT1 knockout mice. Conclusions: These data demonstrate that melatonin MT1 receptor knockout mice recapitulate several behavioral and neurobiological circadian changes of human melancholic depression and, for the first time, suggest that the MT1 receptor may be implicated in the pathogenesis of melancholic depression and is a potential pharmacological target for this mental condition. PMID:25638817

  9. Dehydration parameters and standards for laboratory mice.

    PubMed

    Bekkevold, Christine M; Robertson, Kimberly L; Reinhard, Mary K; Battles, August H; Rowland, Neil E

    2013-01-01

    Water deprivation and restriction are common features of many physiologic and behavioral studies; however, there are no data-driven humane standards regarding mice on water deprivation or restriction studies to guide IACUC, investigators, and veterinarians. Here we acutely deprived outbred CD1 mice of water for as long as 48 h or restricted them to a 75% or 50% water ration; physical and physiologic indicators of dehydration were measured. With acute water deprivation, the appearance and attitude of mice deteriorated after 24 h, and weight loss exceeded 15%. Plasma osmolality was increased, and plasma volume decreased with each time interval. Plasma corticosterone concentration increased with duration of deprivation. There were no differences in any dehydration measures between mice housed in conventional static cages or ventilated racks. Chronic water restriction induced no significant changes compared with ad libitum availability. We conclude that acute water deprivation of as long as 24 h produces robust physiologic changes; however, deprivation in excess of 24 h is not recommended in light of apparent animal distress. Although clearly thirsty, mice adapt to chronic water restriction of as much as 50% of the ad libitum daily ration that is imposed over an interval of as long as 8 d. PMID:23849404

  10. Polarized Light Corridor Demonstrations.

    ERIC Educational Resources Information Center

    Davies, G. R.

    1990-01-01

    Eleven demonstrations of light polarization are presented. Each includes a brief description of the apparatus and the effect demonstrated. Illustrated are strain patterns, reflection, scattering, the Faraday Effect, interference, double refraction, the polarizing microscope, and optical activity. (CW)

  11. 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)

  12. 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.

  13. 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,…

  14. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1988-01-01

    Details two demonstrations for use with an overhead projector in a chemistry lecture. Includes "A Very Rapidly Growing Silicate Crystal" and "A Colorful Demonstration to Simulate Orbital Hybridization." The materials and directions for each demonstration are included as well as a brief explanation of the essential learning involved. (CW)

  15. Knockout of Epstein-Barr Virus BPLF1 Retards B-Cell Transformation and Lymphoma Formation in Humanized Mice

    PubMed Central

    Li, Guangming; Montgomery, Stephanie A.; Montgomery, Nathan D.; Su, Lishan; Pagano, Joseph S.

    2015-01-01

    ABSTRACT BPLF1 of Epstein-Barr virus (EBV) is classified as a late lytic cycle protein but is also found in the viral tegument, suggesting its potential involvement at both initial and late stages of viral infection. BPLF1 possesses both deubiquitinating and deneddylating activity located in its N-terminal domain and is involved in processes that affect viral infectivity, viral DNA replication, DNA repair, and immune evasion. A recently constructed EBV BPLF1-knockout (KO) virus was used in conjunction with a humanized mouse model that can be infected with EBV, enabling the first characterization of BPLF1 function in vivo. Results demonstrate that the BPLF1-knockout virus is approximately 90% less infectious than wild-type (WT) virus. Transformation of human B cells, a hallmark of EBV infection, was delayed and reduced with BPLF1-knockout virus. Humanized mice infected with EBV BPLF1-knockout virus showed less weight loss and survived longer than mice infected with equivalent infectious units of WT virus. Additionally, splenic tumors formed in 100% of mice infected with WT EBV but in only 25% of mice infected with BPLF1-KO virus. Morphological features of spleens containing tumors were similar to those in EBV-induced posttransplant lymphoproliferative disease (PTLD) and were almost identical to cases seen in human diffuse large B-cell lymphoma. The presence of EBV genomes was detected in all mice that developed tumors. The results implicate BPLF1 in human B-cell transformation and tumor formation in humanized mice. PMID:26489865

  16. Nitric oxide as an inflammatory mediator in autoimmune MRL-lpr/lpr mice.

    PubMed Central

    Weinberg, J B

    1998-01-01

    Nitric oxide (.NO) may exhibit proinflammatory features. .NO synthase type 2 (NOS2) is overexpressed and .NO overproduced in rodent models of induced inflammation. Blockage of .NO production by administration of NOS inhibitors prevents or reduces various types of induced inflammation in mice and rats. We have shown that autoimmune MRL-lpr/lpr mice overexpress NOS2 and overproduce .NO in an age-dependent fashion that parallels expression of arthritis, glomerulonephritis, and vasculitis. Blocking .NO production by oral administration of the NOS inhibitor NG-monomethyl-L-arginine reduced the arthritis, glomerulonephritis, and vasculitis, but it did not modify serum anti-DNA antibody levels or glomerular deposition of immune complexes. When mice with genetically disrupted NOS2 were backcrossed to MRL-lpr/lpr mice, the resultant (-/-) mice expressed no NOS2 and produced no .NO, the wild-type (+/+) mice overexpressed NOS2 and overproduced .NO (in comparison to normal, control mice), and the heterozygous (+/-) mice expressed and produced intermediate levels. Nephritis and arthritis in the (-/-) mice were comparable to that in MRL-lpr/lpr mice, but vasculitis was markedly decreased. Levels of anti-DNA antibodies were comparable in all mice, but IgG rheumatoid factor production was markedly reduced in the (-/-) mice. These results of studies in MRL-lpr/lpr mice with genetically disrupted NOS2 highlight the heterogeneity and complexity of the role of NOS2 and .NO in inflammation. PMID:9788887

  17. 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

  18. Strategy Guideline. Demonstration Home

    SciTech Connect

    Hunt, A.; Savage, C.

    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.

  19. 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.

  20. Reversal of reduced parvalbumin neurons in hippocampus and amygdala of Angelman syndrome model mice by chronic treatment of fluoxetine.

    PubMed

    Godavarthi, Swetha K; Sharma, Ankit; Jana, Nihar Ranjan

    2014-08-01

    Angelman syndrome (AS) is a neuropsychiatric disorder characterized by autism, intellectual disability and motor disturbances. The disease is primarily caused by the loss of function of maternally inherited UBE3A. Ube3a maternal-deficient mice recapitulates many essential feature of AS. These AS mice have been shown to be under chronic stress and exhibits anxiety-like behaviour because of defective glucocorticoid receptor signalling. Here, we demonstrate that chronic stress in these mice could lead to down-regulation of parvalbumin-positive interneurons in the hippocampus and basolateral amygdala from early post-natal days. Down-regulation of parvalbumin-positive interneurons number could be because of decrease in the expression of parvalbumin in these neurons. We also find that treatment with fluoxetine, a selective serotonin reuptake inhibitor, results in restoration of impaired glucocorticoid signalling, elevated serum corticosterone level, parvalbumin-positive interneurons and anxiety-like behaviours. Our findings suggest that impaired glucocorticod signalling in hippocampus and amygdala of AS mice is critical for the decrease in parvalbumin interneurons number, emergence of anxiety and other behavioural deficits and highlights the importance of fluoxetine in the recovery of these abnormalities. PMID:24678582

  1. Ablation of TNF-RI/RII Expression in Alzheimer's Disease Mice Leads to an Unexpected Enhancement of Pathology

    PubMed Central

    Montgomery, Sara L.; Mastrangelo, Michael A.; Habib, Diala; Narrow, Wade C.; Knowlden, Sara A.; Wright, Terry W.; Bowers, William J.

    2011-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe memory loss and cognitive impairment. Neuroinflammation, including the extensive production of pro-inflammatory molecules and the activation of microglia, has been implicated in the disease process. Tumor necrosis factor (TNF)-?, a prototypic pro-inflammatory cytokine, is elevated in AD, is neurotoxic, and colocalizes with amyloid plaques in AD animal models and human brains. We previously demonstrated that the expression of TNF-? is increased in AD mice at ages preceding the development of hallmark amyloid and tau pathological features and that long-term expression of this cytokine in these mice leads to marked neuronal death. Such observations suggest that TNF-? signaling promotes AD pathogenesis and that therapeutics suppressing this cytokine's activity may be beneficial. To dissect TNF-? receptor signaling requirements in AD, we generated triple-transgenic AD mice (3xTg-AD) lacking both TNF-? receptor 1 (TNF-RI) and 2 (TNF-RII), 3xTg-ADxTNF-RI/RII knock out, the cognate receptors of TNF-?. These mice exhibit enhanced amyloid and tau-related pathological features by the age of 15 months, in stark contrast to age-matched 3xTg-AD counterparts. Moreover, 3xTg-ADxTNF-RI/RII knock out–derived primary microglia reveal reduced amyloid-? phagocytic marker expression and phagocytosis activity, indicating that intact TNF-? receptor signaling is critical for microglial-mediated uptake of extracellular amyloid-? peptide pools. Overall, our results demonstrate that globally ablated TNF receptor signaling exacerbates pathogenesis and argues against long-term use of pan-anti-TNF-? inhibitors for the treatment of AD. PMID:21835156

  2. Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animals

    PubMed Central

    Weinshenker, David; Miller, Nicole S.; Blizinsky, Katherine; Laughlin, Marc L.; Palmiter, Richard D.

    2002-01-01

    Acute pharmacological blockade of ?1 adrenoreceptors (ARs) attenuates the locomotor response to amphetamine (LRA). We took a genetic approach to study how norepinephrine (NE) signaling modulates psychostimulant responses by testing LRA in dopamine ?-hydroxylase knockout (Dbh?/?) mice that lack NE. Surprisingly, Dbh?/? animals were hypersensitive to the behavioral effects of amphetamine. Amphetamine (2 mg/kg) elicited greater locomotor activity in Dbh?/? mice compared to controls, whereas 5 mg/kg caused stereotypy in Dbh?/? mice, which is only observed in control mice at higher doses. Prazosin, an ?1AR antagonist, attenuated LRA in Dbh+/? mice but had no effect in Dbh?/? mice. Changes in the sensitivity of dopamine (DA)-signaling pathways may contribute to the altered amphetamine responses of Dbh?/? mice because they were relatively insensitive to a D1 agonist and hypersensitive to a D2 agonist. Daily amphetamine administration resulted in behavioral sensitization in both Dbh+/? and Dbh?/? mice, demonstrating that NE is not required for the development or expression of behavioral sensitization. Daily prazosin administration blunted but did not completely block locomotor sensitization in Dbh+/? mice, suggesting that ?1AR signaling contributes to, but is not required for sensitization in Dbh+/? control animals. We conclude that in contrast to acute ?1AR blockade, chronic NE deficiency induces changes similar to sensitization, perhaps by altering DA-signaling pathways. PMID:12370425

  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. )

    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. Estrogen Receptor-? Knockout Mice.

    PubMed

    Antonson, Per; Humire, Patricia; Gustafsson, Jan-Ĺke

    2016-01-01

    Tissue specific knockout mice are valuable tools to study gene function in vivo. The method uses the Cre/loxP system in which loxP sites are cloned into the genome surrounding one or more exons of a gene and the targeted exon(s) are deleted when the Cre enzyme is expressed. Mouse lines that are prepared for the generation of knockout ER? mice have been developed independently by many research groups and the number of available transgenic mouse lines that express Cre under tissue specific promoters is large. Here, we describe how tissue specific ER? knockout mice are generated. PMID:26585154

  5. Behavior and the cholinergic parameters in olfactory bulbectomized female rodents: Difference between rats and mice.

    PubMed

    Stepanichev, Mikhail; Markov, Daniil; Pasikova, Natalia; Gulyaeva, Natalia

    2016-01-15

    Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional disturbances, including behavioral, neurochemical, and neuromorphological alterations. We have examined the effects of OBX on behavior and the parameters of the cholinergic system in female rats and mice. In rats, OBX resulted in the appearance of some depressive-like behavioral marks, such as the decreased sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like behavioral features, such as shortened presence in the center of the open field arena or open arms of the elevated plus-maze and an enhancement of avoidance behavior. These behavioral abnormalities could be associated with disturbances in hippocampal function, this suggestion being supported by the presence of cellular changes in this brain structure. No effect of OBX on the number of cholinergic neurons in the medial septum-diagonal band as well as on the acetylcholine content and acetylcholinesterase activity in the septum, hippocampus, and neocortex could be detected. In contrast, in mice, OBX impaired spontaneous alternation behavior and decreased the number of cholinergic neurons in the medial septum-diagonal band. These data demonstrate that rats and mice differently respond to OBX, in particular, OBX does not significantly affect the cholinergic system in rats. PMID:26431763

  6. 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

  7. Lipid transport in cholecystokinin knockout mice.

    PubMed

    King, Alexandra; Yang, Qing; Huesman, Sarah; Rider, Therese; Lo, Chunmin C

    2015-11-01

    Cholecystokinin (CCK) is released in response to lipid feeding and regulates pancreatic digestive enzymes vital to the absorption of nutrients. Our previous reports demonstrated that cholecystokinin knockout (CCK-KO) mice fed for 10 weeks of HFD had reduced body fat mass, but comparable glucose uptake by white adipose tissues and skeletal muscles. We hypothesized that CCK is involved in energy homeostasis and lipid transport from the small intestine to tissues in response to acute treatment with dietary lipids. CCK-KO mice with comparable fat absorption had increased energy expenditure and were resistant to HFD-induced obesity. Using intraduodenal infusion of butter fat and intravenous infusion using Liposyn III, we determined the mechanism of lipid transport from the small intestine to deposition in lymph and adipocytes in CCK-KO mice. CCK-KO mice had delayed secretion of Apo B48-chylomicrons, lipid transport to the lymphatic system, and triglyceride (TG)-derived fatty acid uptake by epididymal fat in response to acute treatment of intraduodenal lipids. In contrast, CCK-KO mice had comparable TG clearance and lipid uptake by white adipocytes in response to TGs in chylomicron-like emulsion. Thus, we concluded that CCK is important for lipid transport and energy expenditure to control body weight in response to dietary lipid feeding. PMID:26171590

  8. [Cardiac tumors: CT and MR imaging features].

    PubMed

    Moskovitch, G; Chabbert, V; Escourrou, G; Desloques, L; Otal, P; Glock, Y; Rousseau, H

    2010-09-01

    The CT and MR imaging features of the main cardiac tumors will be reviewed. Cross-sectional imaging features may help differentiate between cardiac tumors and pseudotumoral lesions and identify malignant features. Based on clinical features, imaging findings are helpful to further characterize the nature of the lesion. CT and MR imaging can demonstrate the relationship of the tumor with adjacent anatomical structures and are invaluable in the presurgical work-up and postsurgical follow-up. PMID:20814374

  9. Hepatic Mttp deletion reverses gallstone susceptibility in L-Fabp knockout mice.

    PubMed

    Xie, Yan; Fung, Ho Yee Joyce; Newberry, Elizabeth P; Kennedy, Susan; Luo, Jianyang; Crooke, Rosanne M; Graham, Mark J; Davidson, Nicholas O

    2014-03-01

    Previous studies demonstrated that L-Fabp KO mice are more susceptible to lithogenic diet (LD)-induced gallstones because of altered hepatic cholesterol metabolism and increased canalicular cholesterol secretion. Other studies demonstrated that liver-specific deletion of microsomal triglyceride transfer protein (Mttp-LKO) reduced LD-induced gallstone formation by increasing biliary phospholipid secretion. Here we show that mice with combined deletion (i.e., DKO mice) are protected from LD-induced gallstone formation. Following 2 weeks of LD feeding, 73% of WT and 100% of L-Fabp KO mice developed gallstones versus 18% of Mttp-LKO and 23% of DKO mice. This phenotype was recapitulated in both WT and L-Fabp KO mice treated with an Mttp antisense oligonucleotide (M-ASO). Biliary cholesterol secretion was increased in LD-fed L-Fabp KO mice and decreased in DKO mice. However, phospholipid secretion was unchanged in LD-fed Mttp-LKO and DKO mice as well as in M-ASO-treated mice. Expression of the canalicular export pump ABCG5/G8 was reduced in LD-fed DKO mice and in M-ASO-treated L-Fabp KO mice. We conclude that liver-specific Mttp deletion not only eliminates apical lipoprotein secretion from hepatocytes but also attenuates canalicular cholesterol secretion, which in turn decreases LD-induced gallstone susceptibility. PMID:24474819

  10. Effect of Weight-Reduction in Obese Mice Lacking Toll-Like Receptor 5 and C57BL/6 Mice Fed a Low-Fat Diet

    PubMed Central

    Wu, Shao-Chun; Rau, Cheng-Shyuan; Lu, Tsu-Hsiang; Tzeng, Siou-Ling; Wu, Yi-Chan; Wu, Chia-Jung; Lin, Chia-Wei; Hsieh, Ching-Hua

    2015-01-01

    Background. This study aims to investigate the effect of feeding low-fat diet (LFD) to diet-induced obesity (DIO) mice lacking TLR5 (TLR5?/?), which have a tendency to develop glucose intolerance with increased adiposity, compared to that in C57BL/6 mice. Results. TLR5?/? and C57BL/6 male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5?kcal%) diet for 12 weeks; (2) DIO, mice were fed a 58?kcal% high-fat diet (HFD) for 12 weeks; and (3) diet, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5?kcal% LFD for 4 weeks. The glucose intolerance in DIO TLR5?/? mice was more significant than that in DIO C57BL/6 mice and was not attenuated by a switch to the LFD. Weight-reduction with LFD had significantly decreased the epididymal fat mass in C57BL/6 mice but not in TLR5?/? mice. In addition, the LFD-fed TLR5?/? mice showed significantly higher expression of ghrelin in the serum and resistin in the epididymal fat than that in C57BL/6 mice. Conclusions. This study demonstrated that TLR5 gene knockout impairs some effects of weight-reduction in DIO. PMID:26681840

  11. Better Ira Remsen Demonstration

    ERIC Educational Resources Information Center

    Dalby, David K.; Maynard, James H.; Moore, John W.

    2011-01-01

    Many versions of the classic Ira Remsen experience involving copper and concentrated nitric acid have been used as lecture demonstrations. Remsen's original reminiscence from 150 years ago is included in the Supporting Information, and his biography can be found on the Internet. This article presents a new version that makes the demonstration more…

  12. A Stellar Demonstrator

    ERIC Educational Resources Information Center

    Ros, Rosa M.

    2009-01-01

    The main purpose of the stellar demonstrator is to help explain the movement of stars. In particular, students have difficulties understanding why, if they are living in the Northern Hemisphere, they may observe starts in the Southern Hemisphere, or why circumpolar stars are not the same in different parts of Europe. Using the demonstrator, these…

  13. Levitation Kits Demonstrate Superconductivity.

    ERIC Educational Resources Information Center

    Worthy, Ward

    1987-01-01

    Describes the "Project 1-2-3" levitation kit used to demonstrate superconductivity. Summarizes the materials included in the kit. Discusses the effect demonstrated and gives details on how to obtain kits. Gives an overview of the documentation that is included. (CW)

  14. Demonstrating Phase Changes.

    ERIC Educational Resources Information Center

    Rohr, Walter

    1995-01-01

    Presents two experiments that demonstrate phase changes. The first experiment explores phase changes of carbon dioxide using powdered dry ice sealed in a piece of clear plastic tubing. The second experiment demonstrates an equilibrium process in which a crystal grows in equilibrium with its saturated solution. (PVD)

  15. 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…

  16. Demonstrating Newton's Second Law.

    ERIC Educational Resources Information Center

    Fricker, H. S.

    1994-01-01

    Describes an apparatus for demonstrating the second law of motion. Provides sample data and discusses the merits of this method over traditional methods of supplying a constant force. The method produces empirical best-fit lines which convincingly demonstrate that for a fixed mass, acceleration is proportional to force. (DDR)

  17. Manufacturing Demonstration Facility

    E-print Network

    for American workers and regional economic development. Technology Areas · Additive Manufacturing utilizingContact Manufacturing Demonstration Facility Craig Blue, Ph.D. Director, Manufacturing Demonstration Facility (865) 574-4351 blueca@ornl.gov INNOVATIONS IN MANUFACTURING www.ornl.gov/manufacturing

  18. USFWS demonstration fees

    USGS Publications Warehouse

    Taylor, Jonathan; Vaske, Jerry; Donnelly, Maureen; Shelby, Lori

    2002-01-01

    This study examined National Wildlife Refuge (NWR) visitors' reactions to changes in fees implemented as part of the fee demonstration program. Visitors' evaluations of the fees paid were examined in addition to their beliefs about fees and the fee demonstration program, and the impact of fees paid on their intention to return. All results were analyzed relative to socio-demographic characteristics.

  19. Kinetics and Catalysis Demonstrations.

    ERIC Educational Resources Information Center

    Falconer, John L.; Britten, Jerald A.

    1984-01-01

    Eleven videotaped kinetics and catalysis demonstrations are described. Demonstrations include the clock reaction, oscillating reaction, hydrogen oxidation in air, hydrogen-oxygen explosion, acid-base properties of solids, high- and low-temperature zeolite reactivity, copper catalysis of ammonia oxidation and sodium peroxide decomposition, ammonia…

  20. 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.

  1. Microgravity Plant Growth Demonstration

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Two visitors watch a TV monitor showing plant growth inside a growth chamber designed for operation aboard the Space Shuttle as part of NASA's Space Product Development program. The exhibit, featuring work by the Wisconsin Center for Space Automation and Robotics, was at AirVenture 2000 sponsored by the Experimental Aircraft Association in Oshkosh, WI.

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

    PubMed Central

    LU, XIAO-MEI; MA, LING; JIN, YU-NAN; YU, YAN-QIU

    2015-01-01

    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

  3. 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.

  4. Methanol Cannon Demonstrations Revisited.

    ERIC Educational Resources Information Center

    Dolson, David A.; And Others

    1995-01-01

    Describes two variations on the traditional methanol cannon demonstration. The first variation is a chain reaction using real metal chains. The second example involves using easily available components to produce sequential explosions that can be musical in nature. (AIM)

  5. Floating Magnet Demonstration.

    ERIC Educational Resources Information Center

    Wake, Masayoshi

    1990-01-01

    A room-temperature demonstration of a floating magnet using a high-temperature superconductor is described. The setup and operation of the apparatus are described. The technical details of the effect are discussed. (CW)

  6. Demonstration of Surface Tension.

    ERIC Educational Resources Information Center

    Rosenthal, Andrew J.

    2001-01-01

    Surface tension is a fundamental obstacle in the spontaneous formation of bubbles, droplets, and crystal nuclei in liquids. Describes a simple overhead projector demonstration that illustrates the power of surface tension that can prevent so many industrial processes. (ASK)

  7. Spacecraft servicing demonstration plan

    NASA Technical Reports Server (NTRS)

    Bergonz, F. H.; Bulboaca, M. A.; Derocher, W. L., Jr.

    1984-01-01

    A preliminary spacecraft servicing demonstration plan is prepared which leads to a fully verified operational on-orbit servicing system based on the module exchange, refueling, and resupply technologies. The resulting system can be applied at the space station, in low Earth orbit with an orbital maneuvering vehicle (OMV), or be carried with an OMV to geosynchronous orbit by an orbital transfer vehicle. The three phase plan includes ground demonstrations, cargo bay demonstrations, and free flight verifications. The plan emphasizes the exchange of multimission modular spacecraft (MMS) modules which involves space repairable satellites. Three servicer mechanism configurations are the engineering test unit, a protoflight quality unit, and two fully operational units that have been qualified and documented for use in free flight verification activity. The plan balances costs and risks by overlapping study phases, utilizing existing equipment for ground demonstrations, maximizing use of existing MMS equipment, and rental of a spacecraft bus.

  8. EVA Retriever Demonstration

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The EVA retriever is demonstrated in the Manipulator Development Facility (MDF). The retriever moves on the air bearing table 'searching' for its target, in this case tools 'dropped' by astronauts on orbit.

  9. Classroom Demonstration of Sunspots.

    ERIC Educational Resources Information Center

    Callaway, Thomas O.; And Others

    1982-01-01

    An overhead projector, projection screen, and clear tungsten Filament light bulb operated through a dimmer or variac switch are used to demonstrate the fact that black appearance of sunspots is due only to contrast and that sunspots are bright. (SK)

  10. Innovative technology demonstration

    SciTech Connect

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

    1992-04-01

    The Innovative Technology Demonstration (ITD) program at Tinker Air Force Base (TAFB), Oklahoma City, Oklahoma, will demonstrate the overall utility and effectiveness of innovative technologies for site characterization, monitoring, and remediation of selected contaminated test sites. The current demonstration test sites include a CERCLA site on the NPL list, located under a building (Building 3001) that houses a large active industrial complex used for rebuilding military aircraft, and a site beneath and surrounding an abandoned underground tank vault used for storage of jet fuels and solvents. The site under Building 3001 (the NW Test Site) is contaminated with TCE and Cr{sup {plus}6}; the site with the fuel storage vault (the SW Tanks Site) is contaminated with fuels, BTEX and TCE. These sites and others have been identified for cleanup under the Air Force`s Installation Restoration Program (IRP). This document describes the demonstrations that have been conducted or are planned for the TAFB.

  11. Innovative technology demonstration

    SciTech Connect

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

    1992-04-01

    The Innovative Technology Demonstration (ITD) program at Tinker Air Force Base (TAFB), Oklahoma City, Oklahoma, will demonstrate the overall utility and effectiveness of innovative technologies for site characterization, monitoring, and remediation of selected contaminated test sites. The current demonstration test sites include a CERCLA site on the NPL list, located under a building (Building 3001) that houses a large active industrial complex used for rebuilding military aircraft, and a site beneath and surrounding an abandoned underground tank vault used for storage of jet fuels and solvents. The site under Building 3001 (the NW Test Site) is contaminated with TCE and Cr{sup {plus}6}; the site with the fuel storage vault (the SW Tanks Site) is contaminated with fuels, BTEX and TCE. These sites and others have been identified for cleanup under the Air Force's Installation Restoration Program (IRP). This document describes the demonstrations that have been conducted or are planned for the TAFB.

  12. Gata5 Deficiency Causes Airway Constrictor Hyperresponsiveness in Mice

    PubMed Central

    Chen, Bohao; Moore, Tamson V.; Li, Zhenping; Sperling, Anne I.; Zhang, Chunling; Andrade, Jorge; Rodriguez, Alex; Bahroos, Neil; Huang, Yong; Morrisey, Edward E.; Gruber, Peter J.

    2014-01-01

    Gata5 is a transcription factor expressed in the lung, but its physiological role is unknown. To test whether and how Gata5 regulates airway constrictor responsiveness, we studied Gata5?/?, Gata5+/?, and wild-type mice on the C57BL/6J background. Cholinergic airway constrictor responsiveness was assessed invasively in mice without and with induction of allergic airway inflammation through ovalbumin sensitization and aerosol exposure. Gata5-deficient mice displayed native airway constrictor hyperresponsiveness (AHR) in the absence of allergen-induced inflammation. Gata5-deficient mice retained their relatively greater constrictor responsiveness even in ovalbumin-induced experimental asthma. Gata5 deficiency did not alter the distribution of cell types in bronchoalveolar lavage fluid, but bronchial epithelial mucus metaplasia was more prominent in Gata5?/? mice after allergen challenge. Gene expression profiles revealed that apolipoprotein E (apoE) was the fifth most down-regulated transcript in Gata5-deficient lungs, and quantitative RT-PCR and immunostaining confirmed reduced apoE expression in Gata5?/? mice. Quantitative RT-PCR also revealed increased IL-13 mRNA in the lungs of Gata5-deficient mice. These findings for the first time show that Gata5 regulates apoE and IL-13 expression in vivo and that its deletion causes AHR. Gata5-deficient mice exhibit an airway phenotype that closely resembles that previously reported for apoE?/? mice: both exhibit cholinergic AHR in native and experimental asthma states, and there is excessive goblet cell metaplasia after allergen sensitization and challenge. The Gata5-deficient phenotype also shares features that were previously reported for IL-13–treated mice. Together, these results indicate that Gata5 deficiency induces AHR, at least in part, by blunting apoE and increasing IL-13 expression. PMID:24199649

  13. Gata5 deficiency causes airway constrictor hyperresponsiveness in mice.

    PubMed

    Chen, Bohao; Moore, Tamson V; Li, Zhenping; Sperling, Anne I; Zhang, Chunling; Andrade, Jorge; Rodriguez, Alex; Bahroos, Neil; Huang, Yong; Morrisey, Edward E; Gruber, Peter J; Solway, Julian

    2014-04-01

    Gata5 is a transcription factor expressed in the lung, but its physiological role is unknown. To test whether and how Gata5 regulates airway constrictor responsiveness, we studied Gata5(-/-), Gata5(+/-), and wild-type mice on the C57BL/6J background. Cholinergic airway constrictor responsiveness was assessed invasively in mice without and with induction of allergic airway inflammation through ovalbumin sensitization and aerosol exposure. Gata5-deficient mice displayed native airway constrictor hyperresponsiveness (AHR) in the absence of allergen-induced inflammation. Gata5-deficient mice retained their relatively greater constrictor responsiveness even in ovalbumin-induced experimental asthma. Gata5 deficiency did not alter the distribution of cell types in bronchoalveolar lavage fluid, but bronchial epithelial mucus metaplasia was more prominent in Gata5(-/-) mice after allergen challenge. Gene expression profiles revealed that apolipoprotein E (apoE) was the fifth most down-regulated transcript in Gata5-deficient lungs, and quantitative RT-PCR and immunostaining confirmed reduced apoE expression in Gata5(-/-) mice. Quantitative RT-PCR also revealed increased IL-13 mRNA in the lungs of Gata5-deficient mice. These findings for the first time show that Gata5 regulates apoE and IL-13 expression in vivo and that its deletion causes AHR. Gata5-deficient mice exhibit an airway phenotype that closely resembles that previously reported for apoE(-/-) mice: both exhibit cholinergic AHR in native and experimental asthma states, and there is excessive goblet cell metaplasia after allergen sensitization and challenge. The Gata5-deficient phenotype also shares features that were previously reported for IL-13-treated mice. Together, these results indicate that Gata5 deficiency induces AHR, at least in part, by blunting apoE and increasing IL-13 expression. PMID:24199649

  14. 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.

  15. Impact of loss of NF-?B1, NF-?B2 or c-REL on SLE-like autoimmune disease and lymphadenopathy in Fas(lpr/lpr) mutant mice.

    PubMed

    Low, J T; Hughes, P; Lin, A; Siebenlist, U; Jain, R; Yaprianto, K; Gray, D H D; Gerondakis, S; Strasser, A; O'Reilly, L A

    2016-01-01

    Defects in apoptosis can cause autoimmune disease. Loss-of-function mutations in the 'death receptor' FAS impair the deletion of autoreactive lymphocytes in the periphery, leading to progressive lymphadenopathy and systemic lupus erythematosus-like autoimmune disease in mice (Fas(lpr/lpr) (mice homozygous for the lymphoproliferation inducing spontaneous mutation)) and humans. The REL/nuclear factor-?B (NF-?B) transcription factors regulate a broad range of immune effector functions and are also implicated in various autoimmune diseases. We generated compound mutant mice to investigate the individual functions of the NF-?B family members NF-?B1, NF-?B2 and c-REL in the various autoimmune pathologies of Fas(lpr/lpr) mutant mice. We show that loss of each of these transcription factors resulted in amelioration of many classical features of autoimmune disease, including hypergammaglobulinaemia, anti-nuclear autoantibodies and autoantibodies against tissue-specific antigens. Remarkably, only c-REL deficiency substantially reduced immune complex-mediated glomerulonephritis and extended the lifespan of Fas(lpr/lpr) mice. Interestingly, compared with the Fas(lpr/lpr) animals, Fas(lpr/lpr)nfkb2(-/-) mice presented with a dramatic acceleration and augmentation of lymphadenopathy that was accompanied by severe lung pathology due to extensive lymphocytic infiltration. The Fas(lpr/lpr)nfkb1(-/-) mice exhibited the combined pathologies caused by defects in FAS-mediated apoptosis and premature ageing due to loss of NF-?B1. These findings demonstrate that different NF-?B family members exert distinct roles in the development of the diverse autoimmune and lymphoproliferative pathologies that arise in Fas(lpr/lpr) mice, and suggest that pharmacological targeting of c-REL should be considered as a strategy for therapeutic intervention in autoimmune diseases. PMID:26084385

  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. Crybb2 deficiency impairs fertility in female mice.

    PubMed

    Gao, Qian; Sun, Li-Li; Xiang, Fen-Fen; Gao, Li; Jia, Yin; Zhang, Jian-Rong; Tao, Hai-Bo; Zhang, Jun-Jie; Li, Wen-Jie

    2014-10-10

    Beta-B2-crystallin (CRYBB2), encoded by Crybb2 gene, is a major protein in the mammalian eye lens that plays an important role in maintaining the transparency of the ocular lens. However, CRYBB2 also plays important roles in many extra-lenticular tissues and organs such as the retina, brain and testis. Our previous studies demonstrated that male Crybb2 deficient (Crybb2(-/-)) mice have reduced fertility compared with wild-type (WT) mice, while female Crybb2(-/-) mice exhibited reduced ovary weights and shorter estrous cycle percentages. Here we specifically investigated the role of CRYBB2 in the female reproductive system. Our studies revealed that ovaries from female Crybb2(-/-) mice exhibited significantly reduced numbers of primordial, secondary and pre-ovulatory follicles when compared with WT mice, while the rate of atretic follicles was also increased. Additionally, fewer eggs were collected from the oviduct of Crybb2(-/-) female mice after superovulation. Estrogen levels were higher in the metestrus and diestrus cycles of female Crybb2(-/-) mice, while progesterone levels were lower in diestrus cycles. Furthermore, the expression of survival and cell cycle genes, Bcl-2, Cdk4 and Ccnd2, were significantly decreased in granulosa cells isolated from female Crybb2(-/-) mice, consistent with the predominant expression of CRYBB2 in ovarian granulosa cells. Our results reveal a critical role for CRYBB2 in female fertility and specific effects on the proliferation and survival status of ovarian granulosa cells. PMID:25245288

  18. Phenotypic characterization of Ggt1(dwg/dwg) mice,a mouse model for hereditary ?-glutamyltransferase deficiency.

    PubMed

    Yamada, Kaoru; Tsuji, Takehito; Kunieda, Tetsuo

    2013-01-01

    Ggt1(dwg/dwg) mice are spontaneous mutant mice with a nucleotide deletion in the Ggt1 gene. They are characterized by dwarfism, cataract, and coat color abnormality. These abnormalities in the external appearance of Ggt1(dwg/dwg) mice closely resemble those of previously reported GGT1-deficient mice, Ggt1(tm1Zuk/tm1Zuk) (Ggt1(-/-)) and Ggt1(enu1/enu1), generated by gene targeting or ENU mutagenesis. However, whether the pathological features of Ggt1(dwg/dwg) mice are also similar to those of the Ggt1(-/-) and Ggt1(enu1/enu1) mice remains unclear. To clarify the pathogenesis of Ggt1(dwg/dwg) mice, we physiologically and histologically investigated the abnormalities of Ggt1(dwg/dwg) mice in this study. First, we analyzed the activity of GGT1 and GSH levels in Ggt1(dwg/dwg) mice. GGT1 activity in the Ggt1(dwg/dwg) mice was reduced to approximately 4.0% of that in the wild-type mice. Plasma and kidney GSH levels were markedly increased, while eye and liver GSH levels were markedly decreased, in the Ggt1(dwg/dwg) mice. Notably, no significant difference in survival rate was observed between the Ggt1(dwg/dwg) and wild-type mice, whereas high mortality was reported in the Ggt1(-/-) and Ggt1(enu1/enu1) mice. Growth retardation, degeneration of lens fibers, and an increased number of osteoclasts in the Ggt1(dwg/dwg) mice were reversed by administration of N-acetyl-L-cysteine, a precursor of GSH synthesis. Thus, we conclude that the abnormalities of Ggt1(dwg/dwg) mice are caused by alteration of the GSH levels due to the depression of GGT1 activity and that Ggt1(dwg/dwg) mice will be a useful model for GGT deficiency with peculiar features. PMID:23615310

  19. 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.

  20. Feature and Feature Interaction Modeling with Feature-Solution Graphs

    E-print Network

    van Vliet, Hans

    and evaluation process. 1 Introduction The architecture of a software system captures early design decisions reference architecture is 1A detailed discussion can be found in our paper presented at GCSE'2001: Scenario-Based Generation and Evaluation of Software Architectures. 1 #12;Feature-Soulution Graph Features: Functional

  1. Pregnancy-induced changes in renin gene expression in mice.

    PubMed

    Xia, Yang; Wen, Hong; Prashner, Heather R; Chen, Rong; Inagami, Tadashi; Catanzaro, Daniel F; Kellems, Rodney E

    2002-01-01

    A puzzling feature of the renin-angiotensin system during pregnancy is the appearance in the maternal circulation of a large increase in the concentration of prorenin and renin. The physiologic role of these changes is not understood. We determined that high levels of renin protein occur in the circulation of pregnant mice, thereby establishing the mouse as a valuable model for understanding gestation-induced changes in the renin-angiotensin system. We used the murine model to show that high levels of renin gene expression occur at the mother-fetus interface, first in maternal decidua and subsequently in placentas. These results were obtained using ICR mice that have 2 related renin genes, Ren1 and Ren2. We also examined renin gene expression in C57Bl/6 mice that have only the Ren1 gene. In these mice, very little renin gene expression was observed in placentas but instead was upregulated in kidneys during pregnancy. In both ICR and C57Bl/6 mice, there is an increase in renin protein in the maternal circulation during pregnancy. However, these mice differ with regard to gestation-induced sites of increased renin gene expression. These studies suggest that mice are a convenient and valuable model for studying renin gene expression during pregnancy. PMID:11751275

  2. Trypanosoma musculi infection in B-cell-deficient mice.

    PubMed Central

    Vargas, F D; Viens, P; Kongshavn, P A

    1984-01-01

    The course of infection with Trypanosoma musculi was assessed in mice deprived of B-lymphocytes by administration, from birth, of rabbit antiserum to mouse immunoglobulin M (IgM). Initial control of parasitemia leading to the first crisis and establishment of the plateau phase was unaffected by lack of B-lymphocyte function, although multiplicative forms persisted throughout the infection in anti-IgM-treated mice, instead of disappearing after the first crisis as in intact mice. Elimination of trypanosomes after the second crisis was not observed in anti-IgM-treated mice, which maintained high numbers of parasites in the blood and peritoneal cavity, resulting in some mortality. A temporary reduction in parasitemia was achieved in anti-IgM-treated mice by transfusion of immune plasma. Immunodepression, as measured by splenic mitogen responsiveness, and splenomegaly were both observed in anti-IgM-treated as well as in intact mice, indicating that these features of murine trypanosomiasis are independent of B-lymphocyte function. Since in T. musculi infection parasitemia can be controlled initially but not eliminated in mice lacking B-cell function, the only crucial protection provided by antibody would appear to be in curing the infection after the second crisis. PMID:6608496

  3. Search for an Endogenous Bombesin-Like Receptor 3 (BRS-3) Ligand Using Parabiotic Mice

    PubMed Central

    Lateef, Dalya M.; Xiao, Cuiying; Reitman, Marc L.

    2015-01-01

    Bombesin-like receptor 3 (BRS-3) is an X-linked G protein-coupled receptor involved in the regulation of energy homeostasis. Brs3 null (Brs3-/y) mice become obese. To date, no high affinity endogenous ligand has been identified. In an effort to detect a circulating endogenous BRS-3 ligand, we generated parabiotic pairs of mice between Brs3-/y and wild type (WT) mice or between WT controls. Successful parabiosis was demonstrated by circulatory dye exchange. The Brs3-/y-WT and WT-WT pairs lost similar weight immediately after surgery. After 9 weeks on a high fat diet, the Brs3-/y-WT pairs weighed more than the WT-WT pairs. Within the Brs3-/y-WT pairs, the Brs3-/y mice had greater adiposity than the WT mice, but comparable lean and liver weights. Compared to WT mice in WT-WT pairs, Brs3-/y and WT mice in Brs3-/y-WT pairs each had greater lean mass, and the Brs3-/y mice also had greater adiposity. These results contrast to those reported for parabiotic pairs of leptin receptor null (Leprdb/db) and WT mice, where high leptin levels in the Leprdb/db mice cause the WT parabiotic partners to lose weight. Our data demonstrate that a circulating endogenous BRS-3 ligand, if present, is not sufficient to reduce adiposity in parabiotic partners of Brs3-/y mice. PMID:26562312

  4. TRUEX hot demonstration

    SciTech Connect

    Chamberlain, D.B.; Leonard, R.A.; Hoh, J.C.; Gay, E.C.; Kalina, D.G.; Vandegrift, G.F.

    1990-04-01

    In FY 1987, a program was initiated to demonstrate technology for recovering transuranic (TRU) elements from defense wastes. This hot demonstration was to be carried out with solution from the dissolution of irradiated fuels. This recovery would be accomplished with both PUREX and TRUEX solvent extraction processes. Work planned for this program included preparation of a shielded-cell facility for the receipt and storage of spent fuel from commercial power reactors, dissolution of this fuel, operation of a PUREX process to produce specific feeds for the TRUEX process, operation of a TRUEX process to remove residual actinide elements from PUREX process raffinates, and processing and disposal of waste and product streams. This report documents the work completed in planning and starting up this program. It is meant to serve as a guide for anyone planning similar demonstrations of TRUEX or other solvent extraction processing in a shielded-cell facility.

  5. Neuropathological Differences Between Rats and Mice after Spinal Cord Injury

    PubMed Central

    Byrnes, Kimberly R.; Fricke, Stanley T.; Faden, Alan I.

    2010-01-01

    Purpose To investigate the utility of noninvasive magnetic resonance imaging (MRI) protocols to demonstrate pathological differences between rats and mice after SCI. Rats and mice are commonly used to model spinal cord injury (SCI), however histology and immunohistochemistry have shown differences in neuropathology between the two species, including cavity formation and scar/inflammatory responses. Materials and Methods Moderate contusion SCI was performed on adult male rats and mice. At 28 days post-injury, animals underwent T1-weighted (T1W), with or without gadolinium contrast, or T2-weighted (T2W) MRI, to be compared with histology at the same time point. Results In both species, all MRI methods demonstrated changes in spinal cord anatomy. Immunohistochemistry indicated that T2W accurately reflected areas of inflammation and glial scar formation in rats and mice. Quantitation of lesion volume by histology and functional performance correlated best with T2W measurements in both species. Gadolinium contrast accurately reflected the blood-spinal cord-barrier permeability in both species, which appeared greater in rats than in mice. Conclusion These data demonstrate that MRI, with either a T1W or T2W protocol, can effectively distinguish pathological differences between rats and mice. PMID:20882614

  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. Innovative technology demonstrations

    SciTech Connect

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

    1992-08-01

    Environmental Management Operations (EMO) is conducting an Innovative Technology Demonstration Program for Tinker Air Force Base (TAFB). Several innovative technologies are being demonstrated 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 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. 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. The bioremediation demonstration will evaluate a bioventing process in which the naturally occurring consortium of soil bacteria will be stimulated to aerobically degrade soil contaminants, including fuel and TCE, in situ.

  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. 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.

  11. Technology Tips: Building Interactive Demonstrations with Sage

    ERIC Educational Resources Information Center

    Murray, Maura

    2013-01-01

    Sage is an open-source software package that can be used in many different areas of mathematics, ranging from algebra to calculus and beyond. One of the most exciting pedagogical features of Sage (http://www.sagemath.org) is its ability to create interacts--interactive examples that can be used in a classroom demonstration or by students in a…

  12. Demonstrating Group Process Using "12 Angry Men"

    ERIC Educational Resources Information Center

    Armstrong, Stephen A.; Berg, Robert C.

    2005-01-01

    The feature film "12 Angry Men" focuses on an organizational task group that demonstrates the dynamics of a working group. The film is discussed as an effective tool for illuminating group process. The authors describe their experiences using the movie as a teaching tool and provide examples of how it can be used to depict critical incidents, the…

  13. Gigashot Optical Laser Demonstrator

    SciTech Connect

    Deri, R. J.

    2015-10-13

    The Gigashot Optical Laser Demonstrator (GOLD) project has demonstrated a novel optical amplifier for high energy pulsed lasers operating at high repetition rates. The amplifier stores enough pump energy to support >10 J of laser output, and employs conduction cooling for thermal management to avoid the need for expensive and bulky high-pressure helium subsystems. A prototype amplifier was fabricated, pumped with diode light at 885 nm, and characterized. Experimental results show that the amplifier provides sufficient small-signal gain and sufficiently low wavefront and birefringence impairments to prove useful in laser systems, at repetition rates up to 60 Hz.

  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. Solar Energy Demonstrations

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Solar energy furnishes all of the heating and hot water needs, plus 80 percent of the air conditioning, for the two-story Reedy Creek building. A unique feature of this installation is that the 16 semi-cylindrical solar collectors (center photo on opposite page with closeup of a single collector below it) are not mounted atop the roof as is customary, they actually are the roof. This arrangement eliminates the usual trusses, corrugated decking and insulating concrete in roof construction; that, in turn, reduces overall building costs and makes the solar installation more attractive economically. The Reedy Creek collectors were designed and manufactured by AAI Corporation of Baltimore, Maryland.

  16. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1989-01-01

    Presents two demonstrations using the overhead projector: (1) describes how to build a projecting voltmeter and presents uses for the classroom; and (2) investigates the color of fluorescent solutions by studying the absorption and transmission of light through the solutions. (MVL)

  17. 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...

  18. Demonstrating carbon capture

    SciTech Connect

    Qader, A.; Hooper, B.; Stevens, G.

    2009-11-15

    Australia is at the forefront of advancing CCS technology. The CO2CRC's H3 (Post-combustion) and Mulgrave (pre-combustion) capture projects are outlined. The capture technologies for these 2 demonstration projects are described. 1 map., 2 photos.

  19. Calculus Demonstrations Using MATLAB

    ERIC Educational Resources Information Center

    Dunn, Peter K.; Harman, Chris

    2002-01-01

    The note discusses ways in which technology can be used in the calculus learning process. In particular, five MATLAB programs are detailed for use by instructors or students that demonstrate important concepts in introductory calculus: Newton's method, differentiation and integration. Two of the programs are animated. The programs and the…

  20. Participatory Lecture Demonstrations.

    ERIC Educational Resources Information Center

    Battino, Rubin

    1979-01-01

    The use of participatory lecture demonstrations in the classroom is described. Examples are given for the following topics: chromatography, chemical kinetics, balancing equations, the gas laws, kinetic molecular theory, Henry's law of gas solubility, electronic energy levels in atoms, and translational, vibrational, and rotational energies of…

  1. 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…

  2. 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...

  3. Polarized Light: Three Demonstrations.

    ERIC Educational Resources Information Center

    Goehmann, Ruth; Welty, Scott

    1984-01-01

    Describes three demonstrations used in the Chicago Museum of Science and Industry polarized light show. The procedures employed are suitable for the classroom by using smaller polarizers and an overhead projector. Topic areas include properties of cellophane tape, nondisappearing arrows, and rope through a picket fence. (JN)

  4. Demonstrations: Atwood's machine

    E-print Network

    Boal, David

    Demonstrations: ·Atwood's machine ·giant yo-yo on a table ·cylinders on an incline plane Text + vaxle orientation from v = x r In magnitude, vaxle = vwheel Wheel Rolling Down Incline Plane · N that a is positive when m2 > m1, as expected. In general: around pulley axis: 1 = - R T1 (into plane) 2 = R T2 (out

  5. 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)

  6. Astronomy Demonstrations and Models.

    ERIC Educational Resources Information Center

    Eckroth, Charles A.

    Demonstrations in astronomy classes seem to be more necessary than in physics classes for three reasons. First, many of the events are very large scale and impossibly remote from human senses. Secondly, while physics courses use discussions of one- and two-dimensional motion, three-dimensional motion is the normal situation in astronomy; thus,…

  7. 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...

  8. Overhead Projector Demonstrations.

    ERIC Educational Resources Information Center

    Kolb, Doris, Ed.

    1989-01-01

    Described are three chemistry demonstrations: (1) a simple qualitative technique for taste pattern recognition in structure-activity relationships; (2) a microscale study of gaseous diffusion using bleach, HCl, ammonia, and phenolphthalein; and (3) the rotation of polarized light by stereoisomers of limonene. (MVL)

  9. Demonstrating the Gas Laws.

    ERIC Educational Resources Information Center

    Holko, David A.

    1982-01-01

    Presents a complete computer program demonstrating the relationship between volume/pressure for Boyle's Law, volume/temperature for Charles' Law, and volume/moles of gas for Avagadro's Law. The programing reinforces students' application of gas laws and equates a simulated moving piston to theoretical values derived using the ideal gas law.…

  10. Serum Amyloid A Facilitates Early Lesion Development in Ldlr?/? Mice

    PubMed Central

    Krishack, Paulette A; Bhanvadia, Clarissa V; Lukens, John; Sontag, Timothy J; De Beer, Maria C; Getz, Godfrey S; Reardon, Catherine A

    2015-01-01

    Background Atherosclerosis is a chronic inflammatory disorder, and several studies have demonstrated a positive association between plasma serum amyloid A (SAA) levels and cardiovascular disease risk. The aim of the study was to examine whether SAA has a role in atherogenesis, the underlying basis of most cardiovascular disease. Methods and Results Mice globally deficient in acute-phase isoforms Saa1 and Saa2 (Saa?/?) were crossed to Ldlr?/? mice (Saa?/?Ldlr?/?). Saa?/?Ldlr?/? mice demonstrated a 31% reduction in lesional area in the ascending aorta but not in the aortic root or innominate artery after consuming a high-fat, high-cholesterol Western-type diet for 6 weeks. The lesions were predominantly macrophage foam cells. The phenotype was lost in more mature lesions in mice fed a Western-type diet for 12 weeks, suggesting that SAA is involved in early lesion development. The decreased atherosclerosis in the Saa?/?Ldlr?/? mice occurred despite increased levels of blood monocytes and was independent of plasma lipid levels. SAA is produced predominantly by hepatocytes and macrophages. To determine which source of SAA may have a dominant role in lesion development, bone marrow transplantation was performed. Ldlr?/? mice that received bone marrow from Saa?/?Ldlr?/? mice had slightly reduced ascending aorta atherosclerosis compared with Saa?/?Ldlr?/? mice receiving bone marrow from Ldlr?/? mice, indicating that the expression of SAA by macrophages may have an important influence on atherogenesis. Conclusions The results indicate that SAA produced by macrophages promotes early lesion formation in the ascending aorta. PMID:26187995

  11. Significance of higher drug concentration in erythrocytes of mice infected with Schistosoma japonicum and treated orally with mefloquine at single doses.

    PubMed

    Tao, Yi; Xue, Jian; Jiang, Bin; Zhang, Hao-Bing; Xiao, Shu-Hua

    2015-12-01

    The purpose of the present study is to understand the pharmacokinetic feature of mefloquine measured by erythrocytes and plasma in Schistosoma japonicum (S. j.)-infected mice and non-infected mice after oral administration of the drug at single doses. A high-performance liquid chromatography (HPLC) method was used to measure the plasma and erythrocyte concentrations of mefloquine at varying intervals posttreatment. Our results demonstrated that in non-infected mice treated orally with mefloquine at an ineffective dose of 50 mg/kg or effective dose of 200 mg/kg for 2-72 h, the erythrocyte-to-plasma ratios of mefloquine were 5.8-11.2 or 2-14.2. On the other hand, in S. j.-infected mice treated with the same single doses of the drug, the erythrocyte and plasma drug concentration ratios were 3.1-4.6 or 2.9-8.5, manifesting that either in infected mice or in non-infected mice that received oral mefloquine resulted in higher concentration of mefloquine in erythrocytes than that in plasma. Unexpectedly, under oral administration of mefloquine at a higher single dose of 200 mg/kg, the pharmacokinetic parameter C max values for plasma from S. j.-infected and non-infected mice were 1.6?±?0.3 and 2.0?±?0.4 ?g/mL, respectively, which were below the determined in vitro LC50 (50 % lethal concentration) value of 4.93 ?g/mL. Therefore, the plasma concentration of mefloquine may display a little effect against schistosomes during the treatment. Although the values of T 1/2 and AUC0-? for erythrocytes were significantly longer and higher in infected mice than those of corresponding non-infect mice that received the same single mefloqine dose of 50 mg/kg, the C max value was only 2.6?±?0.4 ?g/mL lower than the determined in vitro LC50, which may explain why this low single dose is ineffective against schistosomes in vivo. After administration of higher mefloquine dose of 200 mg/kg, the C max value for erythrocytes in infected mice was 30 % (7.4?±?0.7 versus 10.7?±?2.7 ?g/mL) lower than that in the corresponding non-infected mice, but its level was above the determined in vitro LC95 (95 % lethal concentration) value of 6.12 ?g/mL. Meanwhile, longer T 1/2 value of 159.2?±?129.3 h in infected mice led to significant increase in AUC0-? value (1969.3?±?1057.7 vs 486.4?±?53.0 ?g/mL·h), relative to corresponding non-infected mice. In addition, the mean residence time (MRT0-?) in infected mice was also significantly longer than that in non-infected mice. All these results may beneficial for the treatment. According to the results, we suggest that higher ratios of mefloquine concentration in erythrocytes to plasma may offer a way to transport mefloquine to the worm gut through ingestion of erythrocytes by the worms, where the gut is the site for displaying the effect by mefloquine. PMID:26341799

  12. Behavior of captive white-footed mice.

    PubMed

    Kavanau, J L

    1967-03-31

    Detailed studies of the behavior of captive white-footed mice have cast a number of old problems in new perspectives. Many responses of small captive mammals cannot be interpreted at face value because of severe distortions of behavior that are caused by depriving the wild animal of natural outlets for activity. Confined animals are likely to seize upon and repeatedly exercise virtually any opportunities to modify (and alter their relationships with) their surroundings. In addition they have a strong tendency to counteract nonvolitional and "unexpected" deviations from the status quo. As a result, their responses do not bear an immutable relationship to the nature of the stimulus or other variable being modified; stimuli and activities that are rewarding in certain circumstances are avoided in others. These aspects of behavior have been illustrated by studies of nest occupancy, running in motordriven wheels, and control of intensity of illumination. The results of the control-of-illumination studies suggest the complex interplay of tendencies to modify features of the environment, to avoid conditions imposed compulsorily, and to select preferred levels of illumination. The importance of split-second timing, coordination, and quick reflex actions in the running of activity wheels is indicated by the fact that experienced white-footed mice prefer running in square "wheels" and wheels with hurdles to running in plain round wheels. The relatively conservative behavior of these mice in selecting between multiple sources of food and water and different types of activity wheels suggests the need for careful experimental design in free-choice studies with inexperienced animals. The tendency of trained animals to give some so-called "incorrect" responses even after long experience can be interpreted most reasonably in terms of the adaptive value of a certain degree of variability of behavior in the wild. White-footed mice readily master complex regimes in which several different levers and shutters must be pressed or rotated in certain sequences within seconds for different rewards. They quickly learn to traverse mazes containing hundreds of blind alleys and do so frequently without extrinsic reward. It is unlikely that these remarkable learning performances even begin to approach the capacities of the animals. When two female mice having markedly different solitary behavior patterns were placed in consort, the behavior of each changed, becoming more like that of the other, and the animals showed a strong tendency to remain in each other's company. The behavior of mice in enclosures of great extent casts doubt upon the postulate that hunger and thirst play leading roles in the motivation of wide-ranging locomotor movements. Accordingly, studies of deprived domestic animals in simple mazes may have but limited significance for understanding the behavior of wild and relatively unconfined animals. The existence of marked individual differences between mice selected at random from wild populations sounds the need for a cautious approach in the interpretation of results obtained with highly inbred domestic animals. The relatively uniform behavior of inbred strains represents only a small fragment of the total response spectrum for the species and probably has minimal significance for adaptation and evolution in the wild. When allowed to control the intensity of illumination by operating a series of switches, white-footed mice establish a roughly 24-hour regime consistent with that experienced in the wild, namely dim light during periods of activity and very dim light during periods of inactivity. Consistent with this finding, when exposed to a dim-dark light cycle, the mice are active during the dim phase, not in darkness. Artificial twilight transitions of both constant and varying color temperature have several marked effects upon the activity of white-footed mice. The existence of a strong orienting influence of dim light on the direction of wheel-running suggests that mice in the wild use the twilight

  13. Reduced Choroidal Neovascular Membrane Formation in Cyclooxygenase-2 Null Mice

    PubMed Central

    Rezaei, Kasra A.; Toma, Hassanain S.; Cai, Jiyang; Penn, John S.; Sternberg, Paul

    2011-01-01

    Purpose. To assess the degree of laser-induced choroidal neovascular membrane formation in wild-type (WT) and COX-2 null mice and to measure vascular endothelial growth factor (VEGF), interleukin (IL)-1?, and tumor necrosis factor (TNF)-? levels in the retina and choroid. Methods. Four laser burns were placed in each eye of WT and COX-2 null mice to induce choroidal neovascularization. Fluorescein angiography (FA) was performed at 14 days, and retinal pigment epithelium-choroid-sclera (choroidal) flat mounts were prepared. The retina and choroid were isolated from WT and COX-2 null mice at 24, 72, and 168 hours after laser photocoagulation and from unlasered eyes and were tested for VEGF, IL-1?, and TNF-?. Results. COX-2 null mice demonstrated 58% (P = 0.001) and 48% (P = 0.001) reductions in CNV formation on FA and choroidal flat mounts, respectively, compared with WT mice. For unlasered mice, mean VEGF concentrations in the retina and choroid were 1.2 ± 0.42 pg/mg protein for WT but only 0.42 ± 0.2 pg/mg protein for COX-2 null mice (P < 0.05). After laser photocoagulation, WT mice showed significantly greater VEGF and IL-? expression in the retina and choroid by 168 hours (P < 0.05) and 72 hours (P < 0.05), respectively, compared with COX-2 null mice. Conclusions. COX-2 null mice exhibited significantly less choroidal neovascular membrane formation associated with reduced expression of VEGF. The results of this study suggest that COX-2 modulates VEGF expression in CNV and implicates a potential therapeutic role for nonsteroidal anti-inflammatory drugs. PMID:20881304

  14. Skeletal muscle weakness in osteogeneis imperfecta mice

    PubMed Central

    Gentry, Bettina A; Ferreira, J. Andries; McCambridge, Amanda J.; Brown, Marybeth; Phillips, Charlotte L.

    2010-01-01

    Exercise intolerance, muscle fatigue and weakness are often-reported, little-investigated concerns of patients with osteogenesis imperfecta (OI). OI is a heritable connective tissue disorder hallmarked by bone fragility resulting primarily from dominant mutations in the pro?1(I) or pro?2(I) collagen genes and the recently discovered recessive mutations in post-translational modifying proteins of type I collagen. In this study we examined the soleus (S), plantaris (P), gastrocnemius (G), tibialis anterior (TA) and quadriceps (Q) muscles of mice expressing mild (+/oim) and moderately severe (oim/oim) OI for evidence of inherent muscle pathology. In particular, muscle weight, fiber cross-sectional area (CSA), fiber type, fiber histomorphology, fibrillar collagen content, absolute, relative and specific peak tetanic force (Po, Po/mg and Po/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased Po and an inability to sustain Po for the 300 ms testing duration for specific muscles; +/oim mice had a similar but milder skeletal muscle phenotype. +/oim mice had mild weakness of specific muscles but were less affected than their oim/oim counterparts which demonstrated readily apparent skeletal muscle pathology. Therefore muscle weakness in oim mice reflects inherent skeletal muscle pathology. PMID:20619344

  15. Heat-killed yeast protects diabetic ketoacidotic-steroid treated mice from pulmonary mucormycosis.

    PubMed

    Luo, Guanpingsheng; Gebremariam, Teclegiorgis; Clemons, Karl V; Stevens, David A; Ibrahim, Ashraf S

    2014-06-17

    Previous studies have shown that vaccination with heat-killed yeast, Saccharomyces cerevisiae (HKY), protects mice against systemic candidiasis, aspergillosis, cryptococcosis or coccidioidomycosis. Here we sought to define the potential use of HKY as a vaccine to protect mice from mucormycosis. Mice were vaccinated with different regimens of HKY prior to induction of diabetes. Diabetic ketoacidotic (DKA) mice were then treated with steroids prior to intratracheal challenge with Rhizopus oryzae. All regimens of HKY vaccine improved survival of DKA mice and reduced fungal burden in the primary target organ, lungs, as determined by qPCR. Furthermore, compared to mice vaccinated with diluent, vaccination with HKY substantially increased the mouse immune response as determined by detection of increased anti-Rhizopus antibody titers. Our results show that HKY protects steroid-treated DKA mice from pulmonary R. oryzae infection. Considering its demonstrated efficacy against other fungal infections, HKY is a promising candidate for development as a panfungal vaccine. PMID:24814556

  16. Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice

    PubMed Central

    Fujita, Kosuke; Kuge, Katsunori; Ozawa, Noriyasu; Sahara, Shunya; Zaiki, Kaori; Nakaoji, Koichi; Hamada, Kazuhiko; Takenaka, Yukiko; Tanahashi, Takao; Tamai, Katsuto; Kaneda, Yasufumi; Maeda, Akito

    2015-01-01

    Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on mesenchymal stem cell migration. PMID:26657737

  17. Repetitive behavior and increased activity in mice with Purkinje cell loss: a model for understanding the role of cerebellar pathology in autism

    PubMed Central

    Martin, Loren A.; Goldowitz, Dan; Mittleman, Guy

    2010-01-01

    Repetitive behaviors and hyperactivity are common features of developmental disorders, including autism. Neuropathology of the cerebellum is also a frequent occurrence in autism and other developmental disorders. Recent studies have indicated that cerebellar pathology may play a causal role in the generation of repetitive and hyperactive behaviors. In this study, we examined the relationship between cerebellar pathology and these behaviors in a mouse model of Purkinje cell loss. Specifically, we made aggregation chimeras between Lc/+ mutant embryos and +/+ embryos. Lc/+ mice lose 100% of their Purkinje cells postnatally due to a cell-intrinsic gain-of-function mutation. Through our histological examination, we demonstrated that Lc/+?+/+ chimeric mice have Purkinje cells ranging from zero to normal numbers. Our analysis of these chimeric cerebella confirmed previous studies on Purkinje cell lineage. The results of both open-field activity and hole-board exploration testing indicated negative relationships between Purkinje cell number and measures of activity and investigatory nose-poking. Additionally, in a progressive-ratio operant paradigm, we found that Lc/+ mice lever-pressed significantly less than +/+ controls, which led to significantly lower breakpoints in this group. In contrast, chimeric mice lever-pressed significantly more than controls and this repetitive lever-pressing behavior was significantly and negatively correlated with total Purkinje cell numbers. Although the performance of Lc/+ mice is probably related to their motor deficits, the significant relationships between Purkinje cell number and repetitive lever-pressing behavior as well as open-field activity measures provide support for a role of cerebellar pathology in generating repetitive behavior and increased activity in chimeric mice. PMID:20105240

  18. Repetitive behavior and increased activity in mice with Purkinje cell loss: a model for understanding the role of cerebellar pathology in autism.

    PubMed

    Martin, Loren A; Goldowitz, Dan; Mittleman, Guy

    2010-02-01

    Repetitive behaviors and hyperactivity are common features of developmental disorders, including autism. Neuropathology of the cerebellum is also a frequent occurrence in autism and other developmental disorders. Recent studies have indicated that cerebellar pathology may play a causal role in the generation of repetitive and hyperactive behaviors. In this study, we examined the relationship between cerebellar pathology and these behaviors in a mouse model of Purkinje cell loss. Specifically, we made aggregation chimeras between Lc/+ mutant embryos and +/+ embryos. Lc/+ mice lose 100% of their Purkinje cells postnatally due to a cell-intrinsic gain-of-function mutation. Through our histological examination, we demonstrated that Lc/+<-->+/+ chimeric mice have Purkinje cells ranging from zero to normal numbers. Our analysis of these chimeric cerebella confirmed previous studies on Purkinje cell lineage. The results of both open-field activity and hole-board exploration testing indicated negative relationships between Purkinje cell number and measures of activity and investigatory nose-poking. Additionally, in a progressive-ratio operant paradigm, we found that Lc/+ mice lever-pressed significantly less than +/+ controls, which led to significantly lower breakpoints in this group. In contrast, chimeric mice lever-pressed significantly more than controls and this repetitive lever-pressing behavior was significantly and negatively correlated with total Purkinje cell numbers. Although the performance of Lc/+ mice is probably related to their motor deficits, the significant relationships between Purkinje cell number and repetitive lever-pressing behavior as well as open-field activity measures provide support for a role of cerebellar pathology in generating repetitive behavior and increased activity in chimeric mice. PMID:20105240

  19. 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.

  20. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1989-06-15

    The basic goal of the Limestone Injection Multistage Burner (LIMB) demonstration is to extend LIMB technology development to a full- scale application on a representative wall-fired utility boiler. The successful retrofit of LIMB to an existing boiler is expected to demonstrate that (a) reductions of 50 percent or greater in SO{sub x} and NO{sub x} emissions can be achieved at a fraction of the cost of add-on FGD systems, (b) boiler reliability, operability, and steam production can be maintained at levels existing prior to LIMB retrofit, and (c) technical difficulties attributable to LIMB operation, such as additional slagging and fouling, changes in ash disposal requirements, and an increased particulate load, can be resolved in a cost-effective manner. The primary fuel to be used will be an Ohio bituminous coal having a nominal sulfur content of 3 percent or greater.

  1. AVNG system demonstration

    SciTech Connect

    Thron, Jonathan Louis; Mac Arthur, Duncan W; Kondratov, Sergey; Livke, Alexander; Razinkov, Sergey

    2010-01-01

    An attribute measurement system (AMS) measures a number of unclassified attributes of potentially classified material. By only displaying these unclassified results as red or green lights, the AMS protects potentially classified information while still generating confidence in the measurement result. The AVNG implementation that we describe is an AMS built by RFNC - VNIIEF in Sarov, Russia. To provide additional confidence, the AVNG was designed with two modes of operation. In the secure mode, potentially classified measurements can be made with only the simple red light/green light display. In the open mode, known unclassified material can be measured with complete display of the information collected from the radiation detectors. The AVNG demonstration, which occurred in Sarov, Russia in June 2009 for a joint US/Russian audience, included exercising both modes of AVNG operation using a number of multi-kg plutonium sources. In addition to describing the demonstration, we will show photographs and/or video taken of AVNG operation.

  2. 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)

  3. Chemical Domino Demonstration

    NASA Astrophysics Data System (ADS)

    Alexander, M. Dale

    1998-04-01

    The Chemical Domino Demonstration is both educational and entertaining. It provides an excellent means for a review of chemical concepts at the conclusion of a general chemistry course. This demonstration consists of a number of different chemical reactions occurring in sequence in a Rube Goldberg-type apparatus. These reactions include the reduction of water by an active metal, the oxidation of a moderately active metal by an acid, reduction of metallic ions by a metal of greater activity, acid-base neutralization reactions in solution monitored with indicators, a gas-phase acid-base neutralization reaction, decomposition of a compound, precipitation of an insoluble salt, substitution reactions of coordination complexes, and pyrotechnic oxidation-reduction reactions including a hypergolic oxidation-reduction reaction, an intramolecular oxidation-reduction reaction, and the combustion of a flammable gas.

  4. 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…

  5. The Majorana Demonstrator

    E-print Network

    E. Aguayo; J. E. Fast; E. W. Hoppe; M. E. Keillor; J. D. Kephart; R. T. Kouzes; B. D. LaFerriere; J. Merriman; J. L. Orrell; N. R. Overman; F. T. Avignone III; H. O. Back; D. C. Combs; L. E. Leviner; A. R. Young; A. S. Barabash; S. I. Konovalov; I. Vanyushin; V. Yumatov; M. Bergevin; Y-D. Chan; J. A. Detwiler; J. C. Loach; R. D. Martin; A. W. P. Poon; G. Prior; K. Vetter; F. E. Bertrand; R. J. Cooper; D. C. Radford; R. L. Varner; C. -H. Yu; M. Boswell; S. R. Elliott; V. M. Gehman; A. Hime; M. F. Kidd; B. H. LaRoque; K. Rielage; M. C. Ronquest; D. Steele; V. Brudanin; V. Egorov; K. Gusey; O. Kochetov; M. Shirchenko; V. Timkin; E. Yakushev; M. Busch; J. Esterline; W. Tornow; C. D. Christofferson; M. Horton; S. Howard; V. Sobolev; J. I. Collar; N. Fields; R. J. Creswick; P. J. Doe; R. A. Johnson; A. Knecht; J. Leon; M. G. Marino; M. L. Miller; R. G. H. Robertson; A. G. Schubert; B. A. Wolfe; Yu. Efremenko; H. Ejiri; R. Hazama; M. Nomachi; T. Shima; P. Finnerty; F. M. Fraenkle; G. K. Giovanetti; M. P. Green; R. Henning; M. A. Howe; S. MacMullin; D. G. Phillips II; K. J. Snavely; J. Strain; K. Vorren; V. E. Guiseppe; C. Keller; D. -M. Mei; G. Perumpilly; K. Thomas; C. Zhang; A. L. Hallin; K. J. Keeter; L. Mizouni; J. F. Wilkerson

    2011-09-30

    A brief review of the history and neutrino physics of double beta decay is given. A description of the MAJORANA DEMONSTRATOR research and development program including background reduction techniques is presented in some detail. The application of point contact (PC) detectors to the experiment is discussed, including the effectiveness of pulse shape analysis. The predicted sensitivity of a PC detector array enriched to 86% in 76Ge is given.

  6. Joined Beryllium Mirror Demonstrator

    NASA Technical Reports Server (NTRS)

    Stahl, H. Philip; Parsonage, Tom; Burdine, Robert (Technical Monitor)

    2001-01-01

    Fabrications of large Beryllium optical components are fundamentally limited by available facility capabilities. To overcome this limitation, NASA funded Brush Wellman Corp to study a Be joining process. Four 76 mm diameters samples and a 0.5 mm diameter Joined Beryllium Mirror Demonstrator (JBMD) were fabricated. This presentation will review the fabrication of these samples and summarize the results of their cryogenic testing at MSFCs XRCF.

  7. LIMB Demonstration Project Extension

    SciTech Connect

    Not Available

    1990-09-21

    The DOE LIMB Demonstration Project Extension is a continuation of the EPA Limestone Injection Multistage Burner (LIMB) Demonstration. EPA ultimately expects to show that LIMB is a low cost control technology capable of producing moderate SO{sub x} and NO{sub x} control (50--60 percent) with applicability for retrofit to the major portion of the existing coal-fired boiler population. The current EPA Wall-Fired LIMB Demonstration is a four-year project that includes design and installation of a LIMB system at the 105-MW Unit 4 boiler at Ohio Edison's Edgewater Station in Lorain, Ohio. LIMB Extension testing continued during the quarter with lignosulfonated hydrated lime, pulverized limestone, and hydrated dolomitic lime while firing 1.8% and 3% sulfur coals. Sulfur dioxide removal efficiencies were equivalent to the results found during EPA, base LIMB testing. Sulfur dioxide removal efficiencies were lower than expected while testing with pulverized limestone without humidification. A slight increase in sulfur capture was noted while injecting pulverized limestone at the 187' elevation and with the humidifier outlet temperature at 145{degree}F.

  8. Lunar Water Resource Demonstration

    NASA Technical Reports Server (NTRS)

    Muscatello, Anthony C.

    2008-01-01

    In cooperation with the Canadian Space Agency, the Northern Centre for Advanced Technology, Inc., the Carnegie-Mellon University, JPL, and NEPTEC, NASA has undertaken the In-Situ Resource Utilization (ISRU) project called RESOLVE. This project is a ground demonstration of a system that would be sent to explore permanently shadowed polar lunar craters, drill into the regolith, determine what volatiles are present, and quantify them in addition to recovering oxygen by hydrogen reduction. The Lunar Prospector has determined these craters contain enhanced hydrogen concentrations averaging about 0.1%. If the hydrogen is in the form of water, the water concentration would be around 1%, which would translate into billions of tons of water on the Moon, a tremendous resource. The Lunar Water Resource Demonstration (LWRD) is a part of RESOLVE designed to capture lunar water and hydrogen and quantify them as a backup to gas chromatography analysis. This presentation will briefly review the design of LWRD and some of the results of testing the subsystem. RESOLVE is to be integrated with the Scarab rover from CMIJ and the whole system demonstrated on Mauna Kea on Hawaii in November 2008. The implications of lunar water for Mars exploration are two-fold: 1) RESOLVE and LWRD could be used in a similar fashion on Mars to locate and quantify water resources, and 2) electrolysis of lunar water could provide large amounts of liquid oxygen in LEO, leading to lower costs for travel to Mars, in addition to being very useful at lunar outposts.

  9. A novel phosphodiesterase-5 Inhibitor: Yonkenafil modulates neurogenesis, gliosis to improve cognitive function and ameliorates amyloid burden in an APP/PS1 transgenic mice model.

    PubMed

    Zhu, Lei; Yang, Jing-Yu; Xue, Xue; Dong, Ying-Xu; Liu, Yang; Miao, Feng-Rong; Wang, Yong-Feng; Xue, Hong; Wu, Chun-Fu

    2015-09-01

    In Alzheimer's disease (AD), activated microglia invade and surround ?-amyloid plaques, possibly contributing to the aggregation of amyloid ? (A?), which affect the survival of neurons and lead to memory loss. Phosphodiesterase-5 (PDE-5) inhibitors have recently been shown a potential therapeutic effect on AD. In this study, the effects of yonkenafil (yonk), a novel PDE-5 inhibitor, on cognitive behaviors as well as the pathological features in transgenic AD mice were investigated. Seven-month-old APP/PS1 transgenic mice were treated with yonk (2, 6, or 18mg/kg, intraperitoneal injection (i.p.)) or sildenafil (sild) (6mg/kg, i.p.) daily for 3 months and then behavioral tests were performed. The results demonstrated that yonk improved nesting-building ability, ameliorated working memory deficits in the Y-maze tasks, and significantly improved learning and memory function in the Morris water maze (MWM) tasks. In addition, yonk reduced the area of A? plaques, and inhibited over-activation of microglia and astrocytes. Furthermore, yonk increased neurogenesis in the dentate granule brain region of APP/PS1 mice, indicated by increased BrdU(+)/NeuN(+) and BrdU(+)/DCX(+) cells compared to vehicle-treated transgenic mice. These results suggest that yonk could rescue cognitive deficits by ameliorated amyloid burden through regulating APP processing, inhibited the over-activation of microglia and astrocytes as well as restored neurogenesis. PMID:26200391

  10. Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2R?null mice

    PubMed Central

    Singh, Maneesh; Singh, Pratibha; Vaira, Dolores; Amand, Mathieu; Rahmouni, Souad; Moutschen, Michel

    2014-01-01

    More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T-cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB-HPCs) -transplanted humanized NOD/LtsZ-scidIL-2R?null mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up-regulation of several T-cell immune activation markers such as CD38, HLA-DR, CD69 and co-receptor CCR5. T-cell exhaustion markers PD-1 and CTLA-4 were found to be significantly up-regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin-10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T-cell counts in HIV-infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low-cost adjunctive treatment to regulate chronic immune activation and replication of HIV. PMID:24409837

  11. Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2R?(null) mice.

    PubMed

    Singh, Maneesh; Singh, Pratibha; Vaira, Dolores; Amand, Mathieu; Rahmouni, Souad; Moutschen, Michel

    2014-08-01

    More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T-cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB-HPCs) -transplanted humanized NOD/LtsZ-scidIL-2R?(null) mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up-regulation of several T-cell immune activation markers such as CD38, HLA-DR, CD69 and co-receptor CCR5. T-cell exhaustion markers PD-1 and CTLA-4 were found to be significantly up-regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin-10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T-cell counts in HIV-infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low-cost adjunctive treatment to regulate chronic immune activation and replication of HIV. PMID:24409837

  12. Ameliorative effect of vanadyl(IV)-ascorbate complex on high-fat high-sucrose diet-induced hyperglycemia, insulin resistance, and oxidative stress in mice.

    PubMed

    Liu, Yanjun; Xu, Jie; Guo, Yongli; Xue, Yong; Wang, Jingfeng; Xue, Changhu

    2015-10-01

    There is mounting evidence demonstrating causative links between hyperglycemia, oxidative stress, and insulin resistance, the core pathophysiological features of type 2 diabetes mellitus. Using a combinational approach, we synthesized a vanadium-antioxidant (i.e., l-ascorbic acid) complex and examined its effect on insulin resistance and oxidative stress. This study was designed to examine whether vanadyl(IV)-ascorbate complex (VOAsc) would reduce oxidative stress, hyperglycemia, and insulin resistance in high-fat high-sucrose diet (HFSD)-induced type 2 diabetes in mice. Male C57BL/6J mice were fed a HFSD for 12 weeks to induce insulin resistance, rendering them diabetic. Diabetic mice were treated with rosiglitazone, sodium l-ascorbate, or VOAsc. At the end of treatment, fasting blood glucose, fasting serum insulin, homeostasis model assessment-insulin resistance index, and serum adipocytokine levels were measured. Serum levels of nitric oxide (NO) parameters were also determined. The liver was isolated and used for determination of malondialdehyde, reduced glutathione, and catalase levels, and superoxide dismutase and glutathione peroxidase activities. VOAsc groups exhibited significant reductions in serum adipocytokine and NO levels, and oxidative stress parameters compared to the corresponding values in the untreated diabetic mice. The results indicated that VOAsc is non-toxic. In conclusion, we identified VOAsc as a potentially effective adjunct therapy for the management of type 2 diabetes. PMID:26302923

  13. 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

  14. CCK Response Deficiency in Synphilin-1 Transgenic Mice

    PubMed Central

    Smith, Wanli W.; Smith, Megan; Yang, Dejun; Choi, Pique P.; Moghadam, Alexander; Li, Tianxia; Moran, Timothy H.

    2015-01-01

    Previously, we have identified a novel role for the cytoplasmic protein, synphilin-1(SP1), in the controls of food intake and body weight in both mice and Drosophila. Ubiquitous overexpression of human SP1 in brain neurons in transgenic mice results in hyperphagia expressed as an increase in meal size. However, the mechanisms underlying this action of SP1 remain to be determined. Here we investigate a potential role for altered gut feedback signaling in the effects of SP1 on food intake. We examined responses to peripheral administration of cholecytokinin (CCK), amylin, and the glucagon like peptide-1 (GLP-1) receptor agonist, exendin-4. Intraperitoneal administration of CCK at doses ranging from 1–10 nmol/kg significantly reduced glucose intake in wild type (WT) mice, but failed to affect intake in SP1 transgenic mice. Moreover, there was a significant attenuation of CCK-induced c-Fos expression in the dorsal vagal complex in SP1 transgenic mice. In contrast, WT and SP1 transgenic mice were similarly responsive to both amylin and exendin-4 treatment. These studies demonstrate that SP1 results in a CCK response deficiency that may contribute to the increased meal size and overall hyperphagia in synphillin-1 transgenic mice. PMID:26569394

  15. 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

  16. The LRF transcription factor regulates mature B cell development and the germinal center response in mice

    PubMed Central

    Sakurai, Nagisa; Maeda, Manami; Lee, Sung-Uk; Ishikawa, Yuichi; Li, Min; Williams, John C.; Wang, Lisheng; Su, Leila; Suzuki, Mai; Saito, Toshiki I.; Chiba, Shigeru; Casola, Stefano; Yagita, Hideo; Teruya-Feldstein, Julie; Tsuzuki, Shinobu; Bhatia, Ravi; Maeda, Takahiro

    2011-01-01

    B cells play a central role in immune system function. Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therapies for autoimmune diseases and B cell malignancies. Employing B cell–specific conditional knockout mice, we have demonstrated here that the transcription factor leukemia/lymphoma-related factor (LRF) forms an obligate dimer in B cells and regulates mature B cell lineage fate and humoral immune responses via distinctive mechanisms. Moreover, LRF inactivation in transformed B cells attenuated their growth rate. These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies. PMID:21646720

  17. The Unfolded Protein Response and Chemical Chaperones Reduce Protein Misfolding and Colitis in Mice

    PubMed Central

    CAO, STEWART SIYAN; ZIMMERMANN, ELLEN M.; CHUANG, BRANDY–MENGCHIEH; SONG, BENBO; NWOKOYE, ANOSIKE; WILKINSON, J. ERBY; EATON, KATHRYN A.; KAUFMAN, RANDAL J.

    2013-01-01

    BACKGROUND & AIMS Endoplasmic reticulum (ER) stress has been associated with development of inflammatory bowel disease. We examined the effects of ER stress–induced chaperone response and the orally active chemical chaperones tauroursodeoxycholate (TUDCA) and 4-phenylbutyrate (PBA), which facilitate protein folding and reduce ER stress, in mice with colitis. METHODS We used dextran sulfate sodium (DSS) to induce colitis in mice that do not express the transcription factor ATF6? or the protein chaperone P58IPK. We examined the effects of TUDCA and PBA in cultured intestinal epithelial cells (IECs); in wild-type, P58IPK?/?, and Atf6??/? mice with colitis; and in Il10?/? mice. RESULTS P58IPK?/? and Atf6??/? mice developed more severe colitis following administration of DSS than wild-type mice. IECs from P58IPK?/? mice had excessive ER stress, and apoptotic signaling was activated in IECs from Atf6??/? mice. Inflammatory stimuli induced ER stress signals in cultured IECs, which were reduced by incubation with TUDCA or PBA. Oral administration of either PBA or TUDCA reduced features of DSS-induced acute and chronic colitis in wild-type mice, the colitis that develops in Il10?/? mice, and DSS-induced colitis in P58IPK?/? and Atf6??/? mice. Reduced signs of colonic inflammation in these mice were associated with significantly decreased ER stress in colonic epithelial cells. CONCLUSIONS The unfolded protein response induces expression of genes that encode chaperones involved in ER protein folding; these factors prevent induction of colitis in mice. Chemical chaperones such as TUDCA and PBA alleviate different forms of colitis in mice and might be developed for treatment of inflammatory bowel diseases. PMID:23336977

  18. Z Section feature, parents: toolkit Concept : P Feature

    E-print Network

    Li, Yuan-Fang

    Z Section feature, parents: toolkit [Feature] Concept : P Feature holds : Concept Feature disabled grule holdsSelf c : Concept · (c, c) holds mandatory : Concept (Feature × P Feature) disabled rule Feature) disabled rule optionalDef c : Concept; pf : Feature; s : P Feature · c optional (pf , s) pf

  19. Space Research Benefits Demonstrated

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Angie Jackman, a NASA project manager in microgravity research, demonstrates the enhanced resilience of undercooled metal alloys as compared to conventional alloys. Experiments aboard the Space Shuttle helped scientists refine their understanding of the physical properties of certain metal alloys when undercooled (i.e., kept liquid below their normal solidification temperature). This new knowledge then allowed scientists to modify a terrestrial production method so they can now make limited quantities marketed under the Liquid Metal trademark. The exhibit was a part of the NASA outreach activity at AirVenture 2000 sponsored by the Experimental Aircraft Association in Oshkosh, WI.

  20. Demonstration of optical microfluidics

    NASA Astrophysics Data System (ADS)

    Kotz, Kenneth T.; Kalogerakis, Konstantinos S.; Noble, Kyle A.; Smith, Sarah E.; Faris, Gregory W.

    2004-06-01

    We demonstrate a novel method for the control of small droplets using laser-based heating. Temperature dependent interfacial surface tensions were the primary force used to move droplets. With this approach, ~1.7 ?L to 14 pL droplets were moved on a bare, unmodified polystyrene surface, at speeds of up to 3 mm/s. Upon contact, droplets spontaneously fused and rapidly mixed within 33 ms. We performed an optical absorption-based protein assay using horseradish peroxidase and a chromogenic substrate (ABTS), and readily detected as little as ~125 attomoles of reacting enzyme.

  1. 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.

  2. Exploration Medical System Demonstration

    NASA Technical Reports Server (NTRS)

    Rubin, D. A.; Watkins, S. D.

    2014-01-01

    BACKGROUND: Exploration class missions will present significant new challenges and hazards to the health of the astronauts. Regardless of the intended destination, beyond low Earth orbit a greater degree of crew autonomy will be required to diagnose medical conditions, develop treatment plans, and implement procedures due to limited communications with ground-based personnel. SCOPE: The Exploration Medical System Demonstration (EMSD) project will act as a test bed on the International Space Station (ISS) to demonstrate to crew and ground personnel that an end-to-end medical system can assist clinician and non-clinician crew members in optimizing medical care delivery and data management during an exploration mission. Challenges facing exploration mission medical care include limited resources, inability to evacuate to Earth during many mission phases, and potential rendering of medical care by non-clinicians. This system demonstrates the integration of medical devices and informatics tools for managing evidence and decision making and can be designed to assist crewmembers in nominal, non-emergent situations and in emergent situations when they may be suffering from performance decrements due to environmental, physiological or other factors. PROJECT OBJECTIVES: The objectives of the EMSD project are to: a. Reduce or eliminate the time required of an on-orbit crew and ground personnel to access, transfer, and manipulate medical data. b. Demonstrate that the on-orbit crew has the ability to access medical data/information via an intuitive and crew-friendly solution to aid in the treatment of a medical condition. c. Develop a common data management framework that can be ubiquitously used to automate repetitive data collection, management, and communications tasks for all activities pertaining to crew health and life sciences. d. Ensure crew access to medical data during periods of restricted ground communication. e. Develop a common data management framework that allows for scalability, extensibility, and interoperability of data sources and data users. f. Lower total cost of ownership for development and sustainment of peripheral hardware and software that use EMSD for data management. g. Provide a better standard of healthcare for crew members through reductions in the time required by crew and ground personnel to provide medical treatment and the number of crew errors experienced during treatment.

  3. 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.

  4. Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice

    PubMed Central

    Qiu, Shuiqing; Mintz, James D.; Salet, Christina D.; Han, Weihong; Giannis, Athanassios; Chen, Feng; Yu, Yanfang; Su, Yunchao; Fulton, David J.; Stepp, David W.

    2014-01-01

    Background A sedentary lifestyle is an independent risk factor for cardiovascular disease and exercise has been shown to ameliorate this risk. Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training. The relationship between muscle mass and vascular function is poorly defined. The aims of the current study were to determine whether increasing muscle mass by genetic deletion of myostatin, a negative regulator of muscle growth, can influence vascular function in mesenteric arteries from obese db/db mice. Methods and Results Myostatin expression was elevated in skeletal muscle of obese mice and associated with reduced muscle mass (30% to 50%). Myostatin deletion increased muscle mass in lean (40% to 60%) and obese (80% to 115%) mice through increased muscle fiber size (P<0.05). Myostatin deletion decreased adipose tissue in lean mice, but not obese mice. Markers of insulin resistance and glucose tolerance were improved in obese myostatin knockout mice. Obese mice demonstrated an impaired endothelial vasodilation, compared to lean mice. This impairment was improved by superoxide dismutase mimic Tempol. Deletion of myostatin improved endothelial vasodilation in mesenteric arteries in obese, but not in lean, mice. This improvement was blunted by nitric oxide (NO) synthase inhibitor l?NG?nitroarginine methyl ester (l?NAME). Prostacyclin (PGI2)? and endothelium?derived hyperpolarizing factor (EDHF)?mediated vasodilation were preserved in obese mice and unaffected by myostatin deletion. Reactive oxygen species) was elevated in the mesenteric endothelium of obese mice and down?regulated by deletion of myostatin in obese mice. Impaired vasodilation in obese mice was improved by NADPH oxidase inhibitor (GKT136901). Treatment with sepiapterin, which increases levels of tetrahydrobiopterin, improved vasodilation in obese mice, an improvement blocked by l?NAME. Conclusions Increasing muscle mass by genetic deletion of myostatin improves NO?, but not PGI2? or EDHF?mediated vasodilation in obese mice; this vasodilation improvement is mediated by down?regulation of superoxide. PMID:24965025

  5. 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.

  6. 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 ...

  7. FGF21 mediates alcohol-induced adipose tissue lipolysis by activation of systemic release of catecholamine in mice[S

    PubMed Central

    Zhao, Cuiqing; Liu, Yanlong; Xiao, Jian; Liu, Liming; Chen, Shaoyu; Mohammadi, Moosa; McClain, Craig J.; Li, Xiaokun; Feng, Wenke

    2015-01-01

    Alcohol consumption leads to adipose tissue lipoatrophy and mobilization of FFAs, which contributes to hepatic fat accumulation in alcoholic liver disease. This study aimed to investigate the role of fibroblast growth factor (FGF)21, a metabolic regulator, in the regulation of chronic-binge alcohol-induced adipose tissue lipolysis. FGF21 KO mice were subjected to chronic-binge alcohol exposure, and epididymal white adipose tissue lipolysis and liver steatosis were investigated. Alcohol exposure caused adipose intracellular cAMP elevation and activation of lipolytic enzymes, leading to FFA mobilization in both WT and FGF21 KO mice. However, alcohol-induced systemic elevation of catecholamine, which is known to be a major player in adipose lipolysis by binding to the ?-adrenergic receptor, was markedly inhibited in KO mice. Supplementation with recombinant human FGF21 to alcohol-exposed FGF21 KO mice resulted in an increase in fat loss in parallel with an increase of circulating norepinephrine concentration. Furthermore, alcohol consumption-induced fatty liver was blunted in the KO mice, indicating an inhibition of fatty acid reverse transport from adipose to the liver in the KO mice. Taken together, our studies demonstrate that FGF21 KO mice are protected from alcohol-induced adipose tissue excess-lipolysis through a mechanism involving systemic catecholamine release. PMID:26092866

  8. Feature-by-Feature – Evaluating De Novo Sequence Assembly

    PubMed Central

    Vezzi, Francesco; Narzisi, Giuseppe; Mishra, Bud

    2012-01-01

    The whole-genome sequence assembly (WGSA) problem is among one of the most studied problems in computational biology. Despite the availability of a plethora of tools (i.e., assemblers), all claiming to have solved the WGSA problem, little has been done to systematically compare their accuracy and power. Traditional methods rely on standard metrics and read simulation: while on the one hand, metrics like N50 and number of contigs focus only on size without proportionately emphasizing the information about the correctness of the assembly, comparisons performed on simulated dataset, on the other hand, can be highly biased by the non-realistic assumptions in the underlying read generator. Recently the Feature Response Curve (FRC) method was proposed to assess the overall assembly quality and correctness: FRC transparently captures the trade-offs between contigs' quality against their sizes. Nevertheless, the relationship among the different features and their relative importance remains unknown. In particular, FRC cannot account for the correlation among the different features. We analyzed the correlation among different features in order to better describe their relationships and their importance in gauging assembly quality and correctness. In particular, using multivariate techniques like principal and independent component analysis we were able to estimate the “excess-dimensionality” of the feature space. Moreover, principal component analysis allowed us to show how poorly the acclaimed N50 metric describes the assembly quality. Applying independent component analysis we identified a subset of features that better describe the assemblers performances. We demonstrated that by focusing on a reduced set of highly informative features we can use the FRC curve to better describe and compare the performances of different assemblers. Moreover, as a by-product of our analysis, we discovered how often evaluation based on simulated data, obtained with state of the art simulators, lead to not-so-realistic results. PMID:22319599

  9. Residential Transactive Control Demonstration

    SciTech Connect

    Widergren, Steven E.; Fuller, Jason C.; Marinovici, Maria C.; Somani, Abhishek

    2014-02-19

    Arguably the most exciting aspect of the smart grid vision is the full participation of end-use resources with all forms of generation and energy storage in the reliable and efficient operation of an electric power system. Engaging all of these resources in a collaborative manner that respects the objectives of each resource, is sensitive to the system and local constraints of electricity flow, and scales to the large number of devices and systems participating is a grand challenge. Distributed decision-making system approaches have been presented and experimentation is underway. This paper reports on the preliminary findings of a residential demand response demonstration that uses the bidding transactions of supply and end-use air conditioning resources communicating with a real-time, 5 minute market to balance the various needs of the participants on a distribution feeder. The nature of the demonstration, the value streams being explored, and the operational scenarios implemented to characterize the system response are summarized along with preliminary findings.

  10. Reactor vessel sectioning demonstration

    SciTech Connect

    Lundgren, R.A.

    1981-09-01

    A technical demonstration was successfully completed of simulated reactor vessel sectioning using the combined techniques of air arc gouging and flame cutting. A 4-ft x 3-ft x 9-in. thick sample was fabricated of A36 carbon steel to simulate a reactor vessel wall. A 1/4-in. layer of stainless steel (SS) was tungsten inert gas (TIG)-welded to the carbon steel. Several techniques were considered to section the simulated reactor vessel; air arc gouging was selected to penetrate the stainless steel, and flame cutting was selected to sever the carbon steel. Three sectioning operations were demonstrated. For all three, the operating parameters were the same; but the position of the sample was varied. For the first cut, the sample was placed in a horizontal position, and it was successfully severed from the SS side. For the second cut, the sample was turned over and cut from the carbon steel side. Cutting from the carbon steel side has the advantages of cost reduction

  11. PFBC Utility Demonstration Project

    SciTech Connect

    Not Available

    1992-11-01

    This report provides a summary of activities by American Electric Power Service Corporation during the first budget period of the PFBC Utility Demonstration Project. In April 1990, AEP signed a Cooperative Agreement with the US Department of Energy to repower the Philip Sporn Plant, Units 3 4 in New Haven, West Virginia, with a 330 KW PFBC plant. The purpose of the program was to demonstrate and verify PFBC in a full-scale commercial plant. The technical and cost baselines of the Cooperative Agreement were based on a preliminary engineering and design and a cost estimate developed by AEP subsequent to AEP's proposal submittal in May 1988, and prior to the signing of the Cooperative Agreement. The Statement of Work in the first budget period of the Cooperative Agreement included a task to develop a preliminary design and cost estimate for erecting a Greenfield plant and to conduct a comparison with the repowering option. The comparative assessment of the options concluded that erecting a Greenfield plant rather than repowering the existing Sporn Plant could be the technically and economically superior alternative. The Greenfield plant would have a capacity of 340 MW. The ten additional MW output is due to the ability to better match the steam cycle to the PFBC system with a new balance of plant design. In addition to this study, the conceptual design of the Sporn Repowering led to several items which warranted optimization studies with the goal to develop a more cost effective design.

  12. Olfactory discrimination learning in mice lacking the fragile X mental retardation protein.

    PubMed

    Larson, John; Kim, Daniel; Patel, Roseanne C; Floreani, Christina

    2008-07-01

    An automated training system was used to compare the behavior of knockout (KO) mice lacking the fragile X mental retardation protein with that of wild-type (WT) mice (C57Bl/6 strain) in the acquisition and retention of olfactory discriminations. KO and WT mice did not differ in the acquisition of a four-stage nose poke shaping procedure. In two separate experiments, mutant mice required substantially more training to acquire a series of novel olfactory discrimination problems than did control mice. The KO mice required significantly more sessions to reach criterion performance, made significantly more errors during training, and more often failed to acquire discriminations. Both KO and WT mice showed similar error patterns when learning novel discriminations and both groups showed evidence of more rapid learning of later discriminations in the problem series. Both groups showed significant long-term memory two or four weeks after training but WT and KO mice did not differ in this regard. A group of well-trained mice were given training on novel odors in sessions limited to 20-80 trials. Memory of these problems at two day delays did not differ between WT and KO mice. Tests using ethyl acetate demonstrated that WT and KO mice had similar odor detection thresholds. PMID:18289890

  13. Smart Grid Demonstration Project

    SciTech Connect

    Miller, Craig; Carroll, Paul; Bell, Abigail

    2015-03-11

    The National Rural Electric Cooperative Association (NRECA) organized the NRECA-U.S. Department of Energy (DOE) Smart Grid Demonstration Project (DE-OE0000222) to install and study a broad range of advanced smart grid technologies in a demonstration that spanned 23 electric cooperatives in 12 states. More than 205,444 pieces of electronic equipment and more than 100,000 minor items (bracket, labels, mounting hardware, fiber optic cable, etc.) were installed to upgrade and enhance the efficiency, reliability, and resiliency of the power networks at the participating co-ops. The objective of this project was to build a path for other electric utilities, and particularly electrical cooperatives, to adopt emerging smart grid technology when it can improve utility operations, thus advancing the co-ops’ familiarity and comfort with such technology. Specifically, the project executed multiple subprojects employing a range of emerging smart grid technologies to test their cost-effectiveness and, where the technology demonstrated value, provided case studies that will enable other electric utilities—particularly electric cooperatives— to use these technologies. NRECA structured the project according to the following three areas: Demonstration of smart grid technology; Advancement of standards to enable the interoperability of components; and Improvement of grid cyber security. We termed these three areas Technology Deployment Study, Interoperability, and Cyber Security. Although the deployment of technology and studying the demonstration projects at coops accounted for the largest portion of the project budget by far, we see our accomplishments in each of the areas as critical to advancing the smart grid. All project deliverables have been published. Technology Deployment Study: The deliverable was a set of 11 single-topic technical reports in areas related to the listed technologies. Each of these reports has already been submitted to DOE, distributed to co-ops, and posted for universal access at www.nreca.coop/smartgrid. This research is available for widespread distribution to both cooperative members and non-members. These reports are listed in Table 1.2. Interoperability: The deliverable in this area was the advancement of the MultiSpeak™ interoperability standard from version 4.0 to version 5.0, and improvement in the MultiSpeak™ documentation to include more than 100 use cases. This deliverable substantially expanded the scope and usability of MultiSpeak, ™ the most widely deployed utility interoperability standard, now in use by more than 900 utilities. MultiSpeak™ documentation can be accessed only at www.multispeak.org. Cyber Security: NRECA’s starting point was to develop cyber security tools that incorporated succinct guidance on best practices. The deliverables were: cyber security extensions to MultiSpeak,™ which allow more security message exchanges; a Guide to Developing a Cyber Security and Risk Mitigation Plan; a Cyber Security Risk Mitigation Checklist; a Cyber Security Plan Template that co-ops can use to create their own cyber security plans; and Security Questions for Smart Grid Vendors.

  14. Pancreatic Neuroendocrine Tumors in Mice Deficient in Proglucagon-Derived Peptides

    PubMed Central

    Takano, Yuko; Kasai, Kenji; Takagishi, Yoshiko; Kikumori, Toyone; Imai, Tsuneo; Murata, Yoshiharu; Hayashi, Yoshitaka

    2015-01-01

    Animal models with defective glucagon action show hyperplasia of islet ?-cells, however, the regulatory mechanisms underlying the proliferation of islet endocrine cells remain largely to be elucidated. The Gcggfp/gfp mice, which are homozygous for glucagon/green fluorescent protein knock-in allele (GCGKO), lack all proglucagon-derived peptides including glucagon and GLP-1. The present study was aimed to characterize pancreatic neuroendocrine tumors (panNETs), which develop in the GCGKO mice. At 15 months of age, macroscopic GFP-positive tumors were identified in the pancreas of all the GCGKO mice, but not in that of the control heterozygous mice. The tumor manifested several features that were consistent with pancreatic neuroendocrine tumors (panNETs), such as organoid structures with trabecular and cribriform patterns, and the expression of chromogranin A and synaptophysin. Dissemination of GFP-positive cells was observed in the liver and lungs in 100% and 95%, respectively, of 15-month-old GCGKO mice. To elucidate the regulatory mechanism for tumor growth, PanNET grafts were transplanted into subrenal capsules in GCGKO and control mice. Ki-67 positive cells were identified in panNET grafts transplanted to GCGKO mice 1 month after transplantation, but not in those to control mice. These results suggest that humoral factors or conditions specific to GCGKO mice, are involved in the proliferation of panNETs. Taken together, GCGKO mice are novel animal model for studying the development, pathogenesis, and metastasis panNETs. PMID:26192435

  15. Decreased albumin mRNA in immunodeficient wasted' mice

    SciTech Connect

    Libertin, C.R.; Buczek, N.; Weaver, P.; Mobarhan, S.; Woloschak, G.E. Argonne National Lab., IL )

    1991-03-15

    Mice bearing the autosomal recessive gene wst (wst/wst) develop a wasting syndrome' that leads to death by 28-32 days of age. These mice have faulty repair of damage induced by ionizing radiation, immunodeficiency at secretory sites, and neurologic abnormalities. In addition to a progressively more apparent wasted phenotype, wst/wst mice show other features of failure to thrive and malnutrition. Daily body weights of the animals revealed a loss in weight between 25 and 30 days of age, a time during which normal littermates were progressively and rapidly gaining weight. Albumin mRNA levels were measured by dilution dot blot hybridizations of liver-derived RNA preparations from wasted mice, littermates, and parental controls. In all wasted mice, albumin mRNA levels were reduced 5 to 10 fold compared to controls. Northern blots revealed that the albumin mRNA present in wasted mice was normal in length though reduced in amount. These results suggest there may be a relationship between low albumin synthesis and the wasting syndrome of the wst/wst mouse.

  16. Solar Thermal Demonstration Project

    SciTech Connect

    Biesinger, K.; Cuppett, D.; Dyer, D.

    2012-01-30

    HVAC Retrofit and Energy Efficiency Upgrades at Clark High School, Las Vegas, Nevada The overall objectives of this project are to increase usage of alternative/renewable fuels, create a better and more reliable learning environment for the students, and reduce energy costs. Utilizing the grant resources and local bond revenues, the District proposes to reduce electricity consumption by installing within the existing limited space, one principal energy efficient 100 ton adsorption chiller working in concert with two 500 ton electric chillers. The main heating source will be primarily from low nitrogen oxide (NOX), high efficiency natural gas fired boilers. With the use of this type of chiller, the electric power and cost requirements will be greatly reduced. To provide cooling to the information technology centers and equipment rooms of the school during off-peak hours, the District will install water source heat pumps. In another measure to reduce the cooling requirements at Clark High School, the District will replace single pane glass and metal panels with â??Kalwallâ?? building panels. An added feature of the â??Kalwallâ?ť system is that it will allow for natural day lighting in the student center. This system will significantly reduce thermal heat/cooling loss and control solar heat gain, thus delivering significant savings in heating ventilation and air conditioning (HVAC) costs.

  17. 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

  18. 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.

  19. Neurogenic inflammation in mice deficient in heparin-synthesizing enzyme.

    PubMed

    Karlsen, Tine V; Iversen, Vegard V; Forsberg, Erik; Kjellén, Lena; Reed, Rolf K; Gjerde, Eli-Anne B

    2004-03-01

    Mast cell activation, or neurogenic inflammation, is known to induce lowering of interstitial fluid pressure (P(if)) and plasma protein extravasation (PPE) in several tissues from both rats and mice. To examine a possible role of connective tissue mast cells (CTMCs) in these inflammatory responses, we used mice with dysfunctional CTMCs due to lack of the N-deacetylase/N-sulfotransferase-2 enzyme (NDST-2(-/-)). P(if) and PPE were measured after challenge with compound 48/80 (C48/80), and P(if) alone was measured after treatment either with capsaicin, substance P (SP), or calcitonin gene-related peptide (CGRP). Measurements of P(if) in anesthetized (fentanyl/fluanison and midazolam, 1:1) mice were performed in paw skin with glass capillaries connected to a servo-controlled counterpressure system. PPE was measured with microdialysis by using hollow plasmapheresis fibers (cutoff at 3,000 kDa) placed subcutaneously on the back. Intravenous administration of C48/80 lowered P(if) significantly (P < 0.05) in NDST-2(-/-) mice (-1.67 +/- 0.42 mmHg) compared with vehicle (-0.57 +/- 0.17 mmHg) but the lowering was significantly (P < 0.05) less compared with that of the NDST-2(+/+) mice (-2.31 +/- 0.47 mmHg). PPE was increased 300% after treatment with C48/80 in NDST-2(+/+) mice, whereas there was no increase in PPE in NDST-2(-/-) mice. Capsaicin, SP, and CGRP lowered P(if) significantly (P < 0.05) compared with vehicle and to the same extent in both NDST-2(+/+) and NDST-2(-/-) mice. We can conclude that although NDST-2(-/-) mice demonstrate an altered response in P(if) after mast cell activation, there was no similar alteration after neurogenic inflammation. Therefore, we suggest that neurogenic inflammation in mouse skin is not exclusively dependent on intact CTMCs. PMID:14604857

  20. Caveolin-2-deficient mice show increased sensitivity to endotoxemia

    PubMed Central

    de Almeida, Cecilia J; Witkiewicz, Agnieszka K; Jasmin, Jean-François; Tanowitz, Herbert B; Sotgia, Federica; Frank, Philippe G

    2011-01-01

    Caveolin proteins are structural components of caveolae and are involved in the regulation of many biological processes. Recent studies have shown that caveolin-1 modulates inflammatory responses and is important for sepsis development. In the present study, we show that caveolin-1 and caveolin-2 have opposite roles in lipopolysaccharide (LPS)-induced sepsis using caveolin-deficient (Cav-1-/- and Cav-2-/-) mice for each of these proteins. While Cav-1-/- mice displayed delayed mortality following challenge with LPS, Cav-2-/- mice were more sensitive to LPS compared to wild-type (WT). With Cav-2-/- mice, this effect was associated with increased intestinal injury and increased intestinal permeability. This negative outcome was also correlated with enhanced expression of iNOS in intestinal epithelial cells, and enhanced production of nitric oxide (NO). By contrast, Cav-1-/- mice demonstrated a decrease in iNOS expression with decreased NO production, but no alteration in intestinal permeability. The differential expression of iNOS was associated with a significant increase in STAT-1 activation in these mice. Intestinal cells of Cav-2-/- mice showed increased phosphorylation of STAT-1 at tyrosine 701 compared to wild-type. However, Cav-1-/- mice-derived intestinal cells showed decreased levels of phosphorylation of STAT-1 at tyrosine 701. Since caveolin-2 is almost completely absent in Cav-1-/- mice, we conclude that it is not just the absence of caveolin-2 that is responsible for the observed effects, but that the balance between caveolin-1 and caveolin-2 is important for iNOS expression and ultimately for sepsis outcome. PMID:21670588

  1. Identification of a neurovascular signaling pathway regulating seizures in mice

    PubMed Central

    Fredriksson, Linda; Stevenson, Tamara K; Su, Enming J; Ragsdale, Margaret; Moore, Shannon; Craciun, Stefan; Schielke, Gerald P; Murphy, Geoffrey G; Lawrence, Daniel A

    2015-01-01

    Objective A growing body of evidence suggests that increased blood–brain barrier (BBB) permeability can contribute to the development of seizures. The protease tissue plasminogen activator (tPA) has been shown to promote BBB permeability and susceptibility to seizures. In this study, we examined the pathway regulated by tPA in seizures. Methods An experimental model of kainate-induced seizures was used in genetically modified mice, including mice deficient in tPA (tPA?/?), its inhibitor neuroserpin (Nsp?/?), or both (Nsp:tPA?/?), and in mice conditionally deficient in the platelet-derived growth factor receptor alpha (PDGFR?). Results Compared to wild-type (WT) mice, Nsp?/? mice have significantly reduced latency to seizure onset and generalization; whereas tPA?/? mice have the opposite phenotype, as do Nsp:tPA?/? mice. Furthermore, interventions that maintain BBB integrity delay seizure propagation, whereas osmotic disruption of the BBB in seizure-resistant tPA?/? mice dramatically reduces the time to seizure onset and accelerates seizure progression. The phenotypic differences in seizure progression between WT, tPA?/?, and Nsp?/? mice are also observed in electroencephalogram recordings in vivo, but absent in ex vivo electrophysiological recordings where regulation of the BBB is no longer necessary to maintain the extracellular environment. Finally, we demonstrate that these effects on seizure progression are mediated through signaling by PDGFR? on perivascular astrocytes. Interpretation Together, these data identify a specific molecular pathway involving tPA-mediated PDGFR? signaling in perivascular astrocytes that regulates seizure progression through control of the BBB. Inhibition of PDGFR? signaling and maintenance of BBB integrity might therefore offer a novel clinical approach for managing seizures. PMID:26273685

  2. 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.

  3. Space Research Benefits Demonstrated

    NASA Technical Reports Server (NTRS)

    2000-01-01

    An entranced youngster watches a demonstration of the enhanced resilience of undercooled metal alloys as compared to conventional alloys. Steel bearings are dropped onto plates made of steel, titanium alloy, and zirconium liquid metal alloy, so-called because its molecular structure is amorphous and not crystalline. The bearing on the liquid metal plate bounces for a minute or more longer than on the other plates. Experiments aboard the Space Shuttle helped scientists refine their understanding of the physical properties of certain metal alloys when undercooled (i.e., kept liquid below their normal solidification temperature). This new knowledge then allowed scientists to modify a terrestrial production method so they can now make limited quantities marketed under the Liquid Metal trademark. The exhibit was a part of the NASA outreach activity at AirVenture 2000 sponsored by the Experimental Aircraft Association in Oshkosh, WI.

  4. 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.

  5. 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.

  6. Fusion Power Demonstration III

    SciTech Connect

    Lee, J.D.

    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.

  7. ARJIS satellite demonstration project

    NASA Astrophysics Data System (ADS)

    Severance, Steve; Williams, Carl

    2005-06-01

    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 and the nature of the space technology to be applied. CSA became aware of a nascent law enforcement data-sharing project in the San Diego region known as the Automated Regional Justice Information System (ARJIS). First developed by the police departments in San Diego, ARJIS is an innovative system that shares criminal justice information among 50 federal, state, and local agencies. ARJIS was completing a pilot project that enabled officers to receive information on handheld computers, which was transmitted wirelessly through cellular networks. The accessed information came from several databases that collectively contained the entire region's crime and arrest reports, traffic citations, and incidents, as well as state and county wants and warrants. The fundamental limitations that plague all cellular-based devices caught CSA's attention and resulted in a cooperative effort to harden the communications link between the patrol officer and critical data. The principal goal of the SATCOM development task was to create a proof-of-concept application that would use SATCOM links to augment the current ARJIS handheld wireless (cellular) capability. The successful technical demonstration and the positive support for satellite communications from the law enforcement community showed that this project filled a need-both for improved information sharing and for highly reliable communications systems.

  8. 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. ...

  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. Mitochondrial Dysfunction and Apoptosis in Cumulus Cells of Type I Diabetic Mice

    E-print Network

    Mitochondrial Dysfunction and Apoptosis in Cumulus Cells of Type I Diabetic Mice Qiang Wang1 demonstrated in diabetic mice; however, the potential pathways by which maternal diabetes exerts its effects of maternal diabetes on the mitochondrial status in cumulus cells. We found an increased frequency

  11. COMPARISON OF THE EFFECTS OF ACUTE AND SUBACUTE TREATMENT OF PHENOBARBITAL IN DIFFERENT STARINS OF MICE

    EPA Science Inventory

    A strain specificity has been demonstrated for the effect of subsequent administration of phenobarbital, in which diethylnitrosamine initiated hepatocarcinogensis was promoted in C3H mice, inhibited in B6C3F1 (C57BL X C3H) and not affect in C57BL mice. herefore, we examined in th...

  12. COMPARISON OF THE EFFECTS OF ACUTE AND SUBACUTE TREATMENT OF PHENOBARBITAL IN DIFFERENT STRAINS OF MICE

    EPA Science Inventory

    A strain specificity has been demonstrated for the effect of subsequent administration of phenobarbital. n which diethylnitresamine-initiated hepatocarcinogenesis was presented in C3H mice, inhibited in B6C3F1 (C57BL X C3M) and not affected in C57BL mice. herefore, we examined in...

  13. Human Endometrial Side Population Cells Exhibit Genotypic, Phenotypic and Functional Features of Somatic Stem Cells

    PubMed Central

    Cervelló, Irene; Gil-Sanchis, Claudia; Mas, Aymara; Delgado-Rosas, Francisco; Martínez-Conejero, José Antonio; Galán, Amparo; Martínez-Romero, Alicia; Martínez, Sebastian; Navarro, Ismael; Ferro, Jaime; Horcajadas, José Antonio; Esteban, Francisco José; O'Connor, José Enrique; Pellicer, Antonio; Simón, Carlos

    2010-01-01

    During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC) population. Here we explore the hypothesis that human endometrial side population (SP) cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and characteristic telomerase pattern. We analyzed the clonogenic activity of SP cells under hypoxic conditions and the differentiation capacity in vitro to adipogenic and osteogenic lineages. Finally, we demonstrated the functional capability of endometrial SP to develop human endometrium after subcutaneous injection in NOD-SCID mice. Briefly, SP cells of human endometrium from epithelial and stromal compartments display genotypic, phenotypic and functional features of SSC. PMID:20585575

  14. 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

  15. Small sample feature selection 

    E-print Network

    Sima, Chao

    2007-09-17

    - tion. It does so for three classification rules: linear discriminant analysis (LDA), 3-nearest-neighbor classification (3NN), and classification trees (CART). Two mea- sures of performance are considered. One counts the number of the truly best feature...), and classification trees (CART). We will present detailed analysis for one case from each study. B. Ranking Feature Sets We consider two performance measures concerning how well feature ranking using the error estimators agrees with feature ranking based on the true...

  16. 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.

  17. Collaborative Writing Features

    ERIC Educational Resources Information Center

    Yong Mei Fung

    2010-01-01

    As part of a research study on collaborative writing, this paper discusses defining and facilitating features that occur during face-to-face collaboration, based on the literature and research. The defining features are mutual interaction, negotiations, conflict, and shared expertise. Facilitating features include affective factors, use of L1,…

  18. NASA Bioreactor Demonstration System

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Leland W. K. Chung (left), Director, Molecular Urology Therapeutics Program at the Winship Cancer Institute at Emory University, is principal investigator for the NASA bioreactor demonstration system (BDS-05). With him is Dr. Jun Shu, an assistant professor of Orthopedics Surgery from Kuming Medical University China. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: Emory University.

  19. Orbital construction demonstration study

    NASA Technical Reports Server (NTRS)

    1976-01-01

    A conceptual design and program plan for an Orbital Construction Demonstration Article (OCDA) was developed that can be used for evaluating and establishing practical large structural assembly operations. A flight plan for initial placement and continued utility is presented as a basic for an entirely new shuttle payload line-item having great future potential benefit for space applications. The OCDA is a three-axis stabilized platform in low-earth orbit with many structural nodals for mounting large construction and fabrication equipments. This equipment would be used to explore methods for constructing the large structures for future missions. The OCDA would be supported at regular intervals by the shuttle. Construction experiments and consumables resupply are performed during shuttle visit periods. A 250 kw solar array provides sufficient power to support the shuttle while attached to the OCDA and to run construction experiments at the same time. Wide band communications with a Telemetry and Data Relay Satellite compatible high gain antenna can be used between shuttle revisits to perform remote controlled, TV assisted construction experiments.

  20. 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)

  1. High-dimensional feature selection by feature-wise kernelized Lasso.

    PubMed

    Yamada, Makoto; Jitkrittum, Wittawat; Sigal, Leonid; Xing, Eric P; Sugiyama, Masashi

    2014-01-01

    The goal of supervised feature selection is to find a subset of input features that are responsible for predicting output values. The least absolute shrinkage and selection operator (Lasso) allows computationally efficient feature selection based on linear dependency between input features and output values. In this letter, we consider a feature-wise kernelized Lasso for capturing nonlinear input-output dependency. We first show that with particular choices of kernel functions, nonredundant features with strong statistical dependence on output values can be found in terms of kernel-based independence measures such as the Hilbert-Schmidt independence criterion. We then show that the globally optimal solution can be efficiently computed; this makes the approach scalable to high-dimensional problems. The effectiveness of the proposed method is demonstrated through feature selection experiments for classification and regression with thousands of features. PMID:24102126

  2. Monitoring breast tumor progression by photoacoustic measurements: a xenograft mice model study

    NASA Astrophysics Data System (ADS)

    Priya, Mallika; Satish Rao, Bola Sadashiva; Chandra, Subhash; Datta, Anirbit; Nayak, Subramanya G.; Mahato, Krishna Kishore

    2015-10-01

    The current study reports the photoacoustic spectroscopy-based assessment of breast tumor progression in a nude mice xenograft model. The tumor was induced through subcutaneous injection of MCF-7 cells in female nude mice and was monitored for 20 days until the tumor volume reached 1000 mm3. The tumor tissues were extracted at three different time points (days 10, 15, and 20) after tumor inoculation and subjected to photoacoustic spectral recordings in time domain ex vivo at 281 nm pulsed laser excitations. The spectra were converted into the frequency domain using the fast Fourier transformed tools of MATLAB® algorithms and further utilized to extract seven statistical features (mean, median, area under the curve, variance and standard deviation, skewness and kurtosis) from each time point sample to assess the tumor growth with wavelet principal component analysis based logistic regression analysis performed on the data. The prediction accuracies of the analysis for day 10 versus day 15, day 15 versus day 20, and day 10 versus day 20 were found to be 92.31, 87.5, and 95.2%, respectively. Also, receiver operator characteristics area under the curve analysis for day 10 versus day 15, day 15 versus day 20, and day 10 versus day 20 were found to be 0.95, 0.85, and 0.93, respectively. The ability of photoacoustic measurements in the objective assessment of tumor progression has been clearly demonstrated, indicating its clinical potential.

  3. Muscle Wasting and Impaired Myogenesis in Tumor Bearing Mice Are Prevented by ERK Inhibition

    PubMed Central

    Penna, Fabio; Costamagna, Domiziana; Fanzani, Alessandro; Bonelli, Gabriella; Baccino, Francesco M.; Costelli, Paola

    2010-01-01

    Background The onset of cachexia is a frequent feature in cancer patients. Prominent characteristic of this syndrome is the loss of body and muscle weight, this latter being mainly supported by increased protein breakdown rates. While the signaling pathways dependent on IGF-1 or myostatin were causally involved in muscle atrophy, the role of the Mitogen-Activated-Protein-Kinases is still largely debated. The present study investigated this point on mice bearing the C26 colon adenocarcinoma. Methodology/Principal Findings C26-bearing mice display a marked loss of body weight and muscle mass, this latter associated with increased phosphorylated (p)-ERK. Administration of the ERK inhibitor PD98059 to tumor bearers attenuates muscle depletion and weakness, while restoring normal atrogin-1 expression. In C26 hosts, muscle wasting is also associated with increased Pax7 expression and reduced myogenin levels. Such pattern, suggestive of impaired myogenesis, is reversed by PD98059. Increased p-ERK and reduced myosin heavy chain content can be observed in TNF?-treated C2C12 myotubes, while decreased myogenin and MyoD levels occur in differentiating myoblasts exposed to the cytokine. All these changes are prevented by PD98059. Conclusions/Significance These results demonstrate that ERK is involved in the pathogenesis of muscle wasting in cancer cachexia and could thus be proposed as a therapeutic target. PMID:21048967

  4. High fat diet induces specific pathological changes in hypothalamic orexin neurons in mice.

    PubMed

    Nobunaga, Mizuki; Obukuro, Kanae; Kurauchi, Yuki; Hisatsune, Akinori; Seki, Takahiro; Tsutsui, Masato; Katsuki, Hiroshi

    2014-12-01

    Loss of orexin neurons in the hypothalamus is a prominent feature of narcolepsy and several other neurological conditions. We have recently demonstrated that sleep deprivation stimulates local nitric oxide (NO) production by neuronal NO synthase in the lateral hypothalamus, which leads to selective degeneration of orexin neurons accompanied by formation of orexin-immunoreactive aggregates. Here we analyzed whether lifestyle-related conditions other than sleep deprivation could trigger similar pathological changes in orexin neurons. Four-week-old male C57BL/6 mice were fed with high fat diet (HFD) for 8 weeks. Immunohistochemical analysis revealed that the number of orexin-immunopositive neurons was significantly decreased by HFD intake, whereas the number of melanin-concentrating hormone-immunopositive neurons was unchanged. In addition, HFD promoted formation of intracellular orexin-immunoreactive aggregates in a subset of orexin neurons. We also confirmed that expression of inducible NO synthase (iNOS) in the hypothalamus was upregulated in response to HFD intake. Notably, loss of orexin-immunopositive neurons and formation of orexin-immunoreactive aggregates were not observed in iNOS knockout mice fed with HFD. These results indicate that inappropriate dietary conditions could trigger specific neuropathological events in orexin neurons in an iNOS-dependent manner. PMID:25195718

  5. 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.

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

    PubMed Central

    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

    2015-01-01

    Summary 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

  7. Kinesthetic Transverse Wave Demonstration

    NASA Astrophysics Data System (ADS)

    Pantidos, Panagiotis; Patapis, Stamatis

    2005-09-01

    This is a variation on the String and Sticky Tape demonstration "The Wave Game," suggested by Ron Edge. A group of students stand side by side, each one holding a card chest high with both hands. The teacher cues the first student to begin raising and lowering his card. When he starts lowering his card, the next student begins to raise his. As succeeding students move their cards up and down, a wave such as that shown in the figure is produced. To facilitate the process, students' motions were synchronized with the ticks of a metronome (without such synchronization it was nearly impossible to generate a satisfactory wave). Our waves typically had a frequency of about 1 Hz and a wavelength of around 3 m. We videotaped the activity so that the students could analyze the motions. The (17-year-old) students had not received any prior instruction regarding wave motion and did not know beforehand the nature of the exercise they were about to carry out. During the activity they were asked what a transverse wave is. Most of them quickly realized, without teacher input, that while the wave propagated horizontally, the only motion of the transmitting medium (them) was vertical. They located the equilibrium points of the oscillations, the crests and troughs of the waves, and identified the wavelength. The teacher defined for them the period of the oscillations of the motion of a card to be the total time for one cycle. The students measured this time and then several asserted that it was the same as the wave period. Knowing the length of the waves and the number of waves per second, the next step can easily be to find the wave speed.

  8. Adaptive unsupervised slow feature analysis for feature extraction

    NASA Astrophysics Data System (ADS)

    Gu, Xingjian; Liu, Chuancai; Wang, Sheng

    2015-03-01

    Slow feature analysis (SFA) extracts slowly varying features out of the input data and has been successfully applied on pattern recognition. However, SFA heavily relies on the constructed time series when SFA is applied on databases that neither have obvious temporal structure nor have label information. Traditional SFA constructs time series based on k-nearest neighborhood (k-NN) criterion. Specifically, the time series set constructed by k-NN criterion is likely to include noisy time series or lose suitable time series because the parameter k is difficult to determine. To overcome these problems, a method called adaptive unsupervised slow feature analysis (AUSFA) is proposed. First, AUSFA designs an adaptive criterion to generate time series for characterizing submanifold. The constructed time series have two properties: (1) two points of time series lie on the same submanifold and (2) the submanifold of the time series is smooth. Second, AUSFA seeks projections that simultaneously minimize the slowness scatter and maximize the fastness scatter to extract slow discriminant features. Extensive experimental results on three benchmark face databases demonstrate the effectiveness of our proposed method.

  9. Modulation of Recombinant Antigenic Constructs Containing Multi-Epitopes towards Effective Reduction of Atherosclerotic Lesion in B6;129S-Ldlrtm1HerApobtm2Sgy/J Mice

    PubMed Central

    Xia, Min; Chen, Daxin; Endresz, Valeria; Lantos, Ildiko; Szabo, Andrea; Kakkar, Vijay; Lu, Xinjie

    2015-01-01

    Atherosclerosis is increasingly recognized as a complex chronic inflammatory disease. Many more studies have extended vaccination against atherosclerosis by using epitopes from self-antigens or beyond and demonstrated that vaccination with antigens or derivatives could reduce the extent of the lesions in atherosclerosis-prone mice. Our previous study has demonstrated that construct AHHC [ApoB100688-707 + hHSP60303-312 + hHSP60153-163 + Cpn derived peptide (C)] significantly reduced atherosclerotic lesion. The aim of this study was to investigate whether AHHC can be modulated towards increased lesion reduction in mice by creating two other derivatives with a sequential epitope-substitution named RHHC in which A was replaced by an “R” (C5aR1-31) and RPHC with a further “H” (hHSP60303-312) conversion into “P” (protease-activated receptor-142-55) in mice. Antigenic epitopes were incorporated into a dendroaspin scaffold. Immunization of B6;129S-Ldlrtm1HerApobtm2Sgy/J mice with three constructs elicited production of high levels of antibodies against each epitope (apart from hHSP60153-163 and P which induced a low antibody response). Histological analyses demonstrated that the mice immunized with either RPHC or RHHC showed significant reductions in the size of atherosclerostic lesions compared to those with AHHC (69.5±1.1% versus 55.7±3.4%, P<0.01 or 65.6±1.3% versus 55.7±3.4%, P<0.01). Reduction of plaque size in the aortic sinus and descending aorta correlated with alterations in cellular immune responses when compared with controls. We conclude that a recombinant construct RPHC may provide new antigenic and structural features which are favorable for significant reduction in atherosclerotic lesion formation. This approach offers a novel strategy for developing anti-atherosclerotic agents. PMID:25830298

  10. Spatial Feature Evaluation for Aerial Scene Analysis

    SciTech Connect

    Swearingen, Thomas S; Cheriyadat, Anil M

    2013-01-01

    High-resolution aerial images are becoming more readily available, which drives the demand for robust, intelligent and efficient systems to process increasingly large amounts of image data. However, automated image interpretation still remains a challenging problem. Robust techniques to extract and represent features to uniquely characterize various aerial scene categories is key for automated image analysis. In this paper we examined the role of spatial features to uniquely characterize various aerial scene categories. We studied low-level features such as colors, edge orientations, and textures, and examined their local spatial arrangements. We computed correlograms representing the spatial correlation of features at various distances, then measured the distance between correlograms to identify similar scenes. We evaluated the proposed technique on several aerial image databases containing challenging aerial scene categories. We report detailed evaluation of various low-level features by quantitatively measuring accuracy and parameter sensitivity. To demonstrate the feature performance, we present a simple query-based aerial scene retrieval system.

  11. 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

  12. Studies on the correlation with olfactory dysfunction in a transgenic mice model of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Rasheed, Ameer; Lee, Ji Hye; Suh, Yoo-Hun; Moon, Cheil

    2013-05-01

    Alzheimer's disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the presence of proteinaceous deposits in the brain. AD often results in olfactory dysfunction and impaired olfactory perceptual acuity may be a potential biomarker for early diagnosis of AD. Until recently, there is no Alzheimer's nanoscope or any other high-end microscope developed to be capable of seeing buried feature of AD clearly. Modern neuroimaging techniques are more effective only after the occurrence of cognitive impairment. Therefore, early detection of Alzheimer's disease is critical in developing effective treatment of AD. H and E (Haematoxyline and Eosin) staining is performed for examining gross morphological changes, while TUNEL (transferase (TdT)-mediated dUTP nick end labeling) staining for monitoring neuronal death in the olfactory epithelium (OE). Furthermore, immunohistochemistry and western blot are performed to examine ?-amyloid protein expression. AD model animals were Tg2576 (transgenic mice that overexpress a mutated form of the A? precursor protein), and 6 month (before onset of AD symptoms) and 14 month (after onset of AD symptoms) old WT (wild type) and transgenic mice were compared in their olfactory system. We found that in OE of Tg2576 mice, thickness and total number of cells were decreased, while the numbers of TUNEL-positive neurons, caspase-3 activation were significantly increased compared with age-matched WT. Our results demonstrate that the olfactory system may get deteriorated before onset of AD symptoms. Our findings imply that an olfactory biopsy could be served as an early and relatively simple diagnostic tool for potential AD patients.

  13. Normal Development, Wound Healing, and Adenovirus Susceptibility in ?5-Deficient Mice

    PubMed Central

    Huang, Xiaozhu; Griffiths, Mark; Wu, Jianfeng; Farese, Robert V.; Sheppard, Dean

    2000-01-01

    Integrins have been shown to play important roles in embryonic development, wound healing, metastasis, and other biological processes. ?v?5 is a receptor for RGD-containing extracellular matrix proteins that has been suggested to be important in cutaneous wound healing and adenovirus infection. To examine the in vivo function of this receptor, we have generated mice lacking ?5 expression, using homologous recombination in embryonic stem cells. Mice homozygous for a null mutation of the ?5 subunit gene develop, grow, and reproduce normally. Keratinocytes harvested from ?5?/? mice demonstrate impaired migration on and adhesion to the ?v?5 ligand, vitronectin. However, the rate of healing of cutaneous wounds is not different in ?5?/? and ?5+/+ mice. Furthermore, keratinocytes and airway epithelial cells obtained from null mice show adenovirus infection efficiency equal to that from wild-type mice. These data suggest that ?v?5 is not essential for normal development, reproduction, adenovirus infection, or the healing of cutaneous wounds. PMID:10629031

  14. The role of normal flora in Giardia lamblia infections in mice.

    PubMed

    Singer, S M; Nash, T E

    2000-04-01

    The presence of normal bacterial flora in the intestinal tract is thought to protect against colonization by pathogens. Only a few specific examples of this protection have been demonstrated for bacterial pathogens and protozoan infections. Mice from one commercial breeding farm were found to be less susceptible to infection with Giardia lamblia than were isogenic mice from another facility. When mice were housed together, resistance to infection was readily transferred to normally susceptible mice. After resistant mice were treated with neomycin, differences in susceptibility to infection were shown to be due to differences in the resident flora present in these mice. These results suggest the possible use of probiotic therapy for prevention of G. lamblia infections and may help explain some of the variability of outcomes seen in G. lamblia infections in humans. PMID:10751141

  15. Pam heterozygous mice reveal essential role for Cu in amygdalar behavioral and synaptic function

    PubMed Central

    Gaier, Eric D; Eipper, Betty A; Mains, Richard E

    2014-01-01

    Cu is an essential element with many biological roles, but its roles in the mammalian nervous system are poorly understood. Mice deficient in the cuproenzyme peptidylglycine ?-amidating monooxygenase (PAM+/? mice) were initially generated to study neuropeptide amidation. PAM+/? mice exhibited profound deficits in a few behavioral tasks, including enhancements in innate fear along with deficits in acquired fear. Interestingly, several PAM+/? phenotypes were recapitulated in Cu restricted wildtype mice and rescued in Cu supplemented PAM+/? mice. These behaviors correspond to enhanced excitability and deficient synaptic plasticity in the amygdala of PAM+/? mice, which are also rescued by Cu supplementation. Cu and ATP7A are present at synapses, in key positions to respond to and influence synaptic activity. Further study demonstrated that extracellular Cu is necessary for wildtype synaptic plasticity and sufficient to rescue PAM+/? LTP. These experiments support roles for PAM in Cu homeostasis and for synaptic Cu in amygdalar function. PMID:24593825

  16. Chronic treatment in vivo with ?-adrenoceptor agonists induces dysfunction of airway ?2-adrenoceptors and exacerbates lung inflammation in mice

    PubMed Central

    Lin, Rui; Degan, Simone; Theriot, Barbara S; Fischer, Bernard M; Strachan, Ryan T; Liang, Jiurong; Pierce, Richard A; Sunday, Mary E; Noble, Paul W; Kraft, Monica; Brody, Arnold R; Walker, Julia KL

    2012-01-01

    BACKGROUND AND PURPOSE Inhalation of a ?-adrenoceptor agonist (?-agonist) is first-line asthma therapy, used for both prophylaxis against, and acute relief of, bronchoconstriction. However, repeated clinical use of ?-agonists leads to impaired bronchoprotection and, in some cases, adverse patient outcomes. Mechanisms underlying this ?2-adrenoceptor dysfunction are not well understood, due largely to the lack of a comprehensive animal model and the uncertainty as to whether or not bronchorelaxation in mice is mediated by ?2-adrenoceptors. Thus, we aimed to develop a mouse model that demonstrated functional ?-agonist-induced ?2-adrenoceptor desensitization in the context of allergic inflammatory airway disease. EXPERIMENTAL APPROACH We combined chronic allergen exposure with repeated ?-agonist inhalation in allergen-treated BALB/C mice and examined the contribution of ?2-adrenoceptors to albuterol-induced bronchoprotection using FVB/NJ mice with genetic deletion of ?2-adrenoceptors (KO). Associated inflammatory changes – cytokines (ELISA), cells in bronchoalevolar lavage and airway remodelling (histology) and ?2-adrenoceptor density (radioligand binding) – were also measured. KEY RESULTS ?2-Adrenoceptors mediated albuterol-induced bronchoprotection in mice. Chronic treatment with albuterol induced loss of bronchoprotection, associated with exacerbation of the inflammatory components of the asthma phenotype. CONCLUSIONS AND IMPLICATIONS This animal model reproduced salient features of human asthma and linked loss of bronchoprotection with airway pathobiology. Accordingly, the model offers an advanced tool for understanding the mechanisms of the effects of chronic ?- agonist treatment on ?-adrenoceptor function in asthma. Such information may guide the clinical use of ?-agonists and provide insight into development of novel ?-adrenoceptor ligands for the treatment of asthma. PMID:22013997

  17. A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice.

    PubMed

    Kauffman, Alexander S; Thackray, Varykina G; Ryan, Genevieve E; Tolson, Kristen P; Glidewell-Kenney, Christine A; Semaan, Sheila J; Poling, Matthew C; Iwata, Nahoko; Breen, Kellie M; Duleba, Antoni J; Stener-Victorin, Elisabet; Shimasaki, Shunichi; Webster, Nicholas J; Mellon, Pamela L

    2015-09-01

    Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition. PMID:26203175

  18. DIESEL PARTICLE INSTILLATION ENHANCES INFLAMMATORY AND NEUROTROPHIN RESPONSES IN THE LUNGS OF ALLERGIC BALB/C MICE

    EPA Science Inventory

    Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airways resistance and inflammation. Antibody blockade of NGF attenuates airways resistance associated with the allergen-specific airways responses in mice. ...

  19. Autobacteriographic studies of clarithromycin and erythromycin in mice

    SciTech Connect

    Kohno, Y.; Ohta, K.; Suwa, T.; Suga, T. )

    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.

  20. Caloric Restriction Enhances Fear Extinction Learning in Mice

    PubMed Central

    Riddle, Megan C; McKenna, Morgan C; Yoon, Yone J; Pattwell, Siobhan S; Santos, Patricia Mae G; Casey, B J; Glatt, Charles E

    2013-01-01

    Fear extinction learning, the ability to reassess a learned cue of danger as safe when it no longer predicts aversive events, is often dysregulated in anxiety disorders. Selective serotonin reuptake inhibitors (SSRI's) enhance neural plasticity and their ability to enhance fear extinction learning may explain their anxiolytic properties. Caloric restriction (CR) has SSRI-like effects on neural plasticity and anxiety-related behavior. We implemented CR in mice to determine its effects on conditioned-fear responses. Wild type and serotonin transporter (SERT) knockout mice underwent CR for 7 days leading to significant weight loss. Mice were then tested for cued fear learning and anxiety-related behavior. CR markedly enhanced fear extinction learning and its retention in adolescent female mice, and adults of both sexes. These effects of CR were absent in SERT knockout mice. Moreover, CR phenocopied behavioral and molecular effects of chronic fluoxetine, but there was no additive effect of CR in fluoxetine-treated mice. These results demonstrate that CR enhances fear extinction learning through a SERT-dependent mechanism. These results may have implications for eating disorders such as anorexia nervosa (AN), in which there is a high prevalence of anxiety before the onset of dietary restriction and support proposals that in AN, CR is a motivated effort to control dysregulated fear responses and elevated anxiety. PMID:23303073

  1. Norepinephrine transporter heterozygous knockout mice exhibit altered transport and behavior.

    PubMed

    Fentress, H M; Klar, R; Krueger, J J; Sabb, T; Redmon, S N; Wallace, N M; Shirey-Rice, J K; Hahn, M K

    2013-11-01

    The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET(+/-) ), demonstrating that they display an approximately 50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET(+/-) mouse establishes an activated state of existing surface NET proteins. The NET(+/-) mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris water maze. These data suggest that recovery of near basal activity in NET(+/-) mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET(+/-) mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders. PMID:24102798

  2. Host microbiota modulates development of social preference in mice

    PubMed Central

    Arentsen, Tim; Raith, Henrike; Qian, Yu; Forssberg, Hans; Heijtz, Rochellys Diaz

    2015-01-01

    Background Mounting evidence indicates that the indigenous gut microbiota exerts long-lasting programming effects on brain function and behaviour. Objective In this study, we used the germ-free (GF) mouse model, devoid of any microbiota throughout development, to assess the influence of the indigenous microbiota on social preference and repetitive behaviours (e.g. self-grooming). Methods and results Using the three-chambered social approach task, we demonstrate that when adult GF mice were given a choice to spend time with a novel mouse or object, they spent significantly more time sniffing and interacting with the stimulus mouse compared to conventionally raised mice (specific pathogen-free, SPF). Time spent in repetitive self-grooming behaviour, however, did not differ between GF and SPF mice. Real-time PCR–based gene expression analysis of the amygdala, a key region that is part of the social brain network, revealed a significant reduction in the mRNA levels of total brain-derived neurotrophic factor (BDNF), BDNF exon I-, IV-, VI-, IX-containing transcripts, and NGFI-A (a signalling molecule downstream of BDNF) in GF mice compared to SPF mice. Conclusion These results suggest that differential regulation of BDNF exon transcripts in the amygdala by the indigenous microbes may contribute to the altered social development of GF mice. PMID:26679775

  3. 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

  4. Norepinephrine Transporter Heterozygous Knockout Mice Exhibit Altered Transport and Behavior

    PubMed Central

    Fentress, HM; Klar, R; Krueger, JK; Sabb, T; Redmon, SN; Wallace, NM; Shirey-Rice, JK; Hahn, MK

    2013-01-01

    The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically-driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET+/?), demonstrating that they display an ~50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity, assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET+/? mouse establishes an activated state of existing, surface NET proteins. NET+/? mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris Water Maze. These data suggest recovery of near basal activity in NET+/? mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET+/? mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders. PMID:24102798

  5. Heart regeneration in adult MRL mice

    PubMed Central

    Leferovich, John M.; Bedelbaeva, Khamilia; Samulewicz, Stefan; Zhang, Xiang-Ming; Zwas, Donna; Lankford, Edward B.; Heber-Katz, Ellen

    2001-01-01

    The reaction of cardiac tissue to acute injury involves interacting cascades of cellular and molecular responses that encompass inflammation, hormonal signaling, extracellular matrix remodeling, and compensatory adaptation of myocytes. Myocardial regeneration is observed in amphibians, whereas scar formation characterizes cardiac ventricular wound healing in a variety of mammalian injury models. We have previously shown that the MRL mouse strain has an extraordinary capacity to heal surgical wounds, a complex trait that maps to at least seven genetic loci. Here, we extend these studies to cardiac wounds and demonstrate that a severe transmural, cryogenically induced infarction of the right ventricle heals extensively within 60 days, with the restoration of normal myocardium and function. Scarring is markedly reduced in MRL mice compared with C57BL/6 mice, consistent with both the reduced hydroxyproline levels seen after injury and an elevated cardiomyocyte mitotic index of 10–20% for the MRL compared with 1–3% for the C57BL/6. The myocardial response to injury observed in these mice resembles the regenerative process seen in amphibians. PMID:11493713

  6. 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

  7. Hepatotoxic effects of mycotoxin combinations in mice.

    PubMed

    Sun, Lv-Hui; Lei, Ming-yan; Zhang, Ni-Ya; Zhao, Ling; Krumm, Christopher Steven; Qi, De-Sheng

    2014-12-01

    This study was performed to assess the individual and combined toxic effects of aflatoxin B1 (AFB1), zearalenone (ZEA) and deoxynivalenol (DON) within the liver of mice. A total of 56 4-week-old weanling female mice were divided into seven groups (n?=?8). For 2 weeks, each group received an oral administration of either solvent (control), AFB1, ZEA, DON, AFB1?+?ZEA, AFB1?+?DON or ZEA?+?DON per day. The results showed that AFB1, ZEA and DON induced liver injury, indicated by elevated relative liver weight, activities of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), as well as decreased albumin (ALB) and/or total protein (TP) concentration in the serum. These mycotoxins also decreased hepatic total antioxidant capacity (T-AOC), and/or increased the concentration of malondialdehyde (MDA). Moreover, AFB1?+?DON displayed synergistic effects, while AFB1?+?ZEA displayed antagonistic effects on those parameters previously described. Furthermore, the apoptotic potential was demonstrated associated with an upregulation of the apoptotic genes Caspase-3 and Bax, along with a downregulation of the antiapoptotic gene Bcl-2 in liver. In conclusion, this study provides a better understanding of the toxic effects of AFB1, ZEA, DON, alone or in combinations on the liver of mice, which could contribute to the risk assessment of these mycotoxins in food and feed. PMID:25445755

  8. Antifatigue effect of Gracilaria eucheumoides in mice.

    PubMed

    Shao, Jin-Ting; Wang, Mei-Yan; Zheng, Lu-Bin

    2013-12-01

    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. 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 ...

  10. 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 ...

  11. Impact of T1r3 and Trpm5 on Carbohydrate Preference and Acceptance in C57BL/6 Mice

    PubMed Central

    2013-01-01

    Knockout (KO) mice missing the sweet taste receptor subunit T1r3 or the signaling protein Trpm5 have greatly attenuated sweetener preferences but learn to prefer sucrose in 24-h tests. Here, we examined 24-h preferences of T1r3 KO, Trpm5 KO, and C57BL/6J wild-type (WT) mice for glucose, fructose, galactose, and corn starch. Unlike glucose, fructose has little postoral reward effect in WT mice, whereas conflicting data have been obtained with galactose. Naďve KO mice were initially indifferent to dilute glucose solutions (0.5–4%) but exhibited strong preferences for 8–32% concentrations. In a second test, they strongly preferred (~90%) all glucose concentrations although they drank less sugar than WT mice. Naďve KO mice were indifferent to 0.5–8% fructose and avoided 16–32% fructose. However, the glucose-experienced KO mice displayed significant preferences for all fructose solutions. Naďve KO mice preferred only 8% galactose, whereas WT mice preferred 4–16% galactose, and all mice avoided 32% galactose. Galactose experience enhanced the preference for this sugar in KO and WT mice. Naďve T1r3 KO and WT mice displayed similar preferences for 0.5–32% corn starch, which were enhanced by starch experience. Naďve Trpm5 KO mice did not prefer starch but did so after 1-bottle starch experience. The results confirm the sweet taste deficits of T1r3 KO and Trpm5 KO mice but demonstrate their ability to develop strong glucose and milder galactose preferences attributed to the postoral actions of these sugars. The acquired preference for the non-sweet flavor properties of glucose generalized to those of fructose. The findings further demonstrate that although Trpm5 (but not T1r3) signaling is essential for starch preference, Trpm5 KO mice can learn to prefer starch based on its postoral effects. PMID:23547138

  12. The PGE2 EP3 Receptor Regulates Diet-Induced Adiposity in Male Mice.

    PubMed

    Ceddia, Ryan P; Lee, DaeKee; Maulis, Matthew F; Carboneau, Bethany A; Threadgill, David W; Poffenberger, Greg; Milne, Ginger; Boyd, Kelli L; Powers, Alvin C; McGuinness, Owen P; Gannon, Maureen; Breyer, Richard M

    2016-01-01

    Mice carrying a targeted disruption of the prostaglandin E2 (PGE2) E-prostanoid receptor 3 (EP3) gene, Ptger3, were fed a high-fat diet (HFD), or a micronutrient matched control diet, to investigate the effects of disrupted PGE2-EP3 signaling on diabetes in a setting of diet-induced obesity. Although no differences in body weight were seen in mice fed the control diet, when fed a HFD, EP3(-/-) mice gained more weight relative to EP3(+/+) mice. Overall, EP3(-/-) mice had increased epididymal fat mass and adipocyte size; paradoxically, a relative decrease in both epididymal fat pad mass and adipocyte size was observed in the heaviest EP3(-/-) mice. The EP3(-/-) mice had increased macrophage infiltration, TNF-?, monocyte chemoattractant protein-1, IL-6 expression, and necrosis in their epididymal fat pads as compared with EP3(+/+) animals. Adipocytes isolated from EP3(+/+) or EP3(-/-) mice were assayed for the effect of PGE2-evoked inhibition of lipolysis. Adipocytes isolated from EP3(-/-) mice lacked PGE2-evoked inhibition of isoproterenol stimulated lipolysis compared with EP3(+/+). EP3(-/-) mice fed HFD had exaggerated ectopic lipid accumulation in skeletal muscle and liver, with evidence of hepatic steatosis. Both blood glucose and plasma insulin levels were similar between genotypes on a control diet, but when fed HFD, EP3(-/-) mice became hyperglycemic and hyperinsulinemic when compared with EP3(+/+) fed HFD, demonstrating a more severe insulin resistance phenotype in EP3(-/-). These results demonstrate that when fed a HFD, EP3(-/-) mice have abnormal lipid distribution, developing excessive ectopic lipid accumulation and associated insulin resistance. PMID:26485614

  13. 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

  14. ROCK insufficiency attenuates ozone-induced airway hyperresponsiveness in mice.

    PubMed

    Kasahara, David I; Mathews, Joel A; Park, Chan Y; Cho, Youngji; Hunt, Gabrielle; Wurmbrand, Allison P; Liao, James K; Shore, Stephanie A

    2015-10-01

    Ozone causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Rho kinase (ROCK) is a key regulator of smooth muscle cell contraction and inflammatory cell migration. To determine the contribution of the two ROCK isoforms ROCK1 and ROCK2 to ozone-induced AHR, we exposed wild-type, ROCK1(+/-), and ROCK2(+/-) mice to air or ozone (2 ppm for 3 h) and evaluated mice 24 h later. ROCK1 or ROCK2 haploinsufficiency did not affect airway responsiveness in air-exposed mice but significantly reduced ozone-induced AHR, with a greater reduction in ROCK2(+/-) mice despite increased bronchoalveolar lavage (BAL) inflammatory cells in ROCK2(+/-) mice. Compared with wild-type mice, ozone-induced increases in BAL hyaluronan, a matrix protein implicated in ozone-induced AHR, were lower in ROCK1(+/-) but not ROCK2(+/-) mice. Ozone-induced increases in other inflammatory moieties reported to contribute to ozone-induced AHR (IL-17A, osteopontin, TNF?) were not different in wild-type vs. ROCK1(+/-) or ROCK2(+/-) mice. We also observed a dose-dependent reduction in ozone-induced AHR after treatment with the ROCK1/ROCK2 inhibitor fasudil, even though fasudil was administered after induction of inflammation. Ozone increased pulmonary expression of ROCK2 but not ROCK1 or RhoA. A ROCK2 inhibitor, SR3677, reduced contractile forces in primary human airway smooth muscle cells, confirming a role for ROCK2 in airway smooth muscle contraction. Our results demonstrate that ozone-induced AHR requires ROCK. Whereas ROCK1-dependent changes in hyaluronan may contribute to ROCK1's role in O3-induced AHR, the role of ROCK2 is downstream of inflammation, likely at the level of airway smooth muscle contraction. PMID:26276827

  15. 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

  16. Crybb2 deficiency impairs fertility in female mice

    SciTech Connect

    Gao, Qian; Sun, Li-Li; Xiang, Fen-Fen; Gao, Li; Jia, Yin; Zhang, Jian-Rong; Tao, Hai-Bo; Zhang, Jun-Jie; Li, Wen-Jie

    2014-10-10

    Highlights: • Crybb2 deletion impaired female fertility. • Crybb2 deletion dramatically affected the production of reproduction-related hormones and hormone response. • Crybb2 deletion impaired follicular development and inhibited the proliferation of granulosa cells. • Crybb2 deletion promoted follicular atresia and apoptosis in granulosa cells. - Abstract: Beta-B2-crystallin (CRYBB2), encoded by Crybb2 gene, is a major protein in the mammalian eye lens that plays an important role in maintaining the transparency of the ocular lens. However, CRYBB2 also plays important roles in many extra-lenticular tissues and organs such as the retina, brain and testis. Our previous studies demonstrated that male Crybb2 deficient (Crybb2{sup ?/?}) mice have reduced fertility compared with wild-type (WT) mice, while female Crybb2{sup ?/?} mice exhibited reduced ovary weights and shorter estrous cycle percentages. Here we specifically investigated the role of CRYBB2 in the female reproductive system. Our studies revealed that ovaries from female Crybb2{sup ?/?} mice exhibited significantly reduced numbers of primordial, secondary and pre-ovulatory follicles when compared with WT mice, while the rate of atretic follicles was also increased. Additionally, fewer eggs were collected from the oviduct of Crybb2{sup ?/?} female mice after superovulation. Estrogen levels were higher in the metestrus and diestrus cycles of female Crybb2{sup ?/?} mice, while progesterone levels were lower in diestrus cycles. Furthermore, the expression of survival and cell cycle genes, Bcl-2, Cdk4 and Ccnd2, were significantly decreased in granulosa cells isolated from female Crybb2{sup ?/?} mice, consistent with the predominant expression of CRYBB2 in ovarian granulosa cells. Our results reveal a critical role for CRYBB2 in female fertility and specific effects on the proliferation and survival status of ovarian granulosa cells.

  17. New BRAF knockin mice provide a pathogenetic mechanism of developmental defects and a therapeutic approach in cardio-facio-cutaneous syndrome.

    PubMed

    Inoue, Shin-Ichi; Moriya, Mitsuji; Watanabe, Yusuke; Miyagawa-Tomita, Sachiko; Niihori, Tetsuya; Oba, Daiju; Ono, Masao; Kure, Shigeo; Ogura, Toshihiko; Matsubara, Yoichi; Aoki, Yoko

    2014-12-15

    Cardio-facio-cutaneous (CFC) syndrome is one of the 'RASopathies', a group of phenotypically overlapping syndromes caused by germline mutations that encode components of the RAS-MAPK pathway. Germline mutations in BRAF cause CFC syndrome, which is characterized by heart defects, distinctive facial features and ectodermal abnormalities. To define the pathogenesis and to develop a potential therapeutic approach in CFC syndrome, we here generated new knockin mice (here Braf(Q241R/+)) expressing the Braf Q241R mutation, which corresponds to the most frequent mutation in CFC syndrome, Q257R. Braf(Q241R/+) mice manifested embryonic/neonatal lethality, showing liver necrosis, edema and craniofacial abnormalities. Histological analysis revealed multiple heart defects, including cardiomegaly, enlarged cardiac valves, ventricular noncompaction and ventricular septal defects. Braf(Q241R/+) embryos also showed massively distended jugular lymphatic sacs and subcutaneous lymphatic vessels, demonstrating lymphatic defects in RASopathy knockin mice for the first time. Prenatal treatment with a MEK inhibitor, PD0325901, rescued the embryonic lethality with amelioration of craniofacial abnormalities and edema in Braf(Q241R/+) embryos. Unexpectedly, one surviving pup was obtained after treatment with a histone 3 demethylase inhibitor, GSK-J4, or NCDM-32b. Combination treatment with PD0325901 and GSK-J4 further increased the rescue from embryonic lethality, ameliorating enlarged cardiac valves. These results suggest that our new Braf knockin mice recapitulate major features of RASopathies and that epigenetic modulation as well as the inhibition of the ERK pathway will be a potential therapeutic strategy for the treatment of CFC syndrome. PMID:25035421

  18. Budget constrained non-monotonic feature selection.

    PubMed

    Yang, Haiqin; Xu, Zenglin; Lyu, Michael R; King, Irwin

    2015-11-01

    Feature selection is an important problem in machine learning and data mining. We consider the problem of selecting features under the budget constraint on the feature subset size. Traditional feature selection methods suffer from the "monotonic" property. That is, if a feature is selected when the number of specified features is set, it will always be chosen when the number of specified feature is larger than the previous setting. This sacrifices the effectiveness of the non-monotonic feature selection methods. Hence, in this paper, we develop an algorithm for non-monotonic feature selection that approximates the related combinatorial optimization problem by a Multiple Kernel Learning (MKL) problem. We justify the performance guarantee for the derived solution when compared to the global optimal solution for the related combinatorial optimization problem. Finally, we conduct a series of empirical evaluation on both synthetic and real-world benchmark datasets for the classification and regression tasks to demonstrate the promising performance of the proposed framework compared with the baseline feature selection approaches. PMID:26433049

  19. Deletion of Fanca or Fancd2 dysregulates Treg in mice.

    PubMed

    Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C; Steinbrecher, Kris A; Davies, Stella M; Pang, Qishen

    2014-03-20

    Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca(-/-) or Fancd2(-/-) BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca(-/-) or Fancd2(-/-) mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25(+)Foxp3(+) Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25(+)Foxp3(+) Tregs of Fanca(-/-) or Fancd2(-/-) mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-?B activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients. PMID:24501220

  20. Comparison of interval timing behaviour in mice following dorsal or ventral hippocampal lesions with mice having ?-opioid receptor gene deletion

    PubMed Central

    Yin, Bin; Meck, Warren H.

    2014-01-01

    Mice with cytotoxic lesions of the dorsal hippocampus (DH) underestimated 15 s and 45 s target durations in a bi-peak procedure as evidenced by proportional leftward shifts of the peak functions that emerged during training as a result of decreases in both ‘start’ and ‘stop’ times. In contrast, mice with lesions of the ventral hippocampus (VH) displayed rightward shifts that were immediately present and were largely limited to increases in the ‘stop’ time for the 45 s target duration. Moreover, the effects of the DH lesions were congruent with the scalar property of interval timing in that the 15 s and 45 s functions superimposed when plotted on a relative timescale, whereas the effects of the VH lesions violated the scalar property. Mice with DH lesions also showed enhanced reversal learning in comparison to control and VH lesioned mice. These results are compared with the timing distortions observed in mice lacking ?-opioid receptors (Oprd1?/?) which were similar to mice with DH lesions. Taken together, these results suggest a balance between hippocampal–striatal interactions for interval timing and demonstrate possible functional dissociations along the septotemporal axis of the hippocampus in terms of motivation, timed response thresholds and encoding in temporal memory. PMID:24446500

  1. Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles.

    PubMed

    Gustafsson, Ĺsa; Bergström, Ulrika; Ĺgren, Lina; Österlund, Lars; Sandström, Thomas; Bucht, Anders

    2015-10-01

    The aim of this study was to investigate the inflammatory and immunological responses in airways and lung-draining lymph nodes (LDLNs), following lung exposure to iron oxide (hematite) nanoparticles (NPs). The responses to the hematite NPs were evaluated in both healthy non-sensitized mice, and in sensitized mice with an established allergic airway disease. The mice were exposed intratracheally to either hematite NPs or to vehicle (PBS) and the cellular responses were evaluated on days 1, 2, and 7, post-exposure. Exposure to hematite NPs increased the numbers of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on days 1 and 2 post-exposure; at these time points the number of lymphocytes was also elevated in the LDLNs. In contrast, exposing sensitized mice to hematite NPs induced a rapid and unspecific cellular reduction in the alveolar space on day 1 post-exposure; a similar decrease of lymphocytes was also observed in the LDLN. The results indicate that cells in the airways and in the LDLN of individuals with established airway inflammation undergo cell death when exposed to hematite NPs. A possible explanation for this toxic response is the extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways. This study demonstrates how sensitized and non-sensitized mice respond differently to hematite NP exposure, and it highlights the importance of including individuals with respiratory disorders when evaluating health effects of inhaled nanomaterials. PMID:26163175

  2. Reprogramming in vivo produces teratomas and iPS cells with totipotency features.

    PubMed

    Abad, María; Mosteiro, Lluc; Pantoja, Cristina; Cańamero, Marta; Rayon, Teresa; Ors, Inmaculada; Grańa, Osvaldo; Megías, Diego; Domínguez, Orlando; Martínez, Dolores; Manzanares, Miguel; Ortega, Sagrario; Serrano, Manuel

    2013-10-17

    Reprogramming of adult cells to generate induced pluripotent stem cells (iPS cells) has opened new therapeutic opportunities; however, little is known about the possibility of in vivo reprogramming within tissues. Here we show that transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs, implying that full reprogramming can occur in vivo. Analyses of the stomach, intestine, pancreas and kidney reveal groups of dedifferentiated cells that express the pluripotency marker NANOG, indicative of in situ reprogramming. By bone marrow transplantation, we demonstrate that haematopoietic cells can also be reprogrammed in vivo. Notably, reprogrammable mice present circulating iPS cells in the blood and, at the transcriptome level, these in vivo generated iPS cells are closer to embryonic stem cells (ES cells) than standard in vitro generated iPS cells. Moreover, in vivo iPS cells efficiently contribute to the trophectoderm lineage, suggesting that they achieve a more plastic or primitive state than ES cells. Finally, intraperitoneal injection of in vivo iPS cells generates embryo-like structures that express embryonic and extraembryonic markers. We conclude that reprogramming in vivo is feasible and confers totipotency features absent in standard iPS or ES cells. These discoveries could be relevant for future applications of reprogramming in regenerative medicine. PMID:24025773

  3. 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.

  4. Effects of oral genistein in mice.

    PubMed

    Bhandari, Anita; Crawford, Susan E; Huang, Lijun; Reenstra, William W

    2003-01-01

    In cell culture systems, genistein, a soy-derived isoflavone with chemopreventive and estrogenic effects, enhances cAMP-dependent activation of the most common cystic fibrosis-causing mutation, deltaF508-CFTR, by as much as 20-fold. DeltaF508-CFTR is present in the apical membrane at far lower levels than wild-type CFTR. If genistein can enhance cyclic AMP-dependent activity in vivo, the presence of deltaF508-CFTR, at even a few percent of wild-type levels, might permit genistein to be of therapeutic benefit to cystic fibrosis patients with this mutation. Before determining if oral genistein would be of benefit in mice with a deltaF508 mutation in the murine CFTR gene, a maximal dose of oral genistein with minimal side effects needed to be established. Accordingly, C57Bl/6 mice pups were randomly weaned onto soy-free diet, AIN-76, containing between 0 and 1.0 g/kg genistein and allowed to feed ad libitum for 3 weeks. Genistein had no significant effects on growth rates of either male or female mice. Histology of the lung, heart, kidney, liver, and intestine revealed no significant genistein-dependent changes in morphology. When mice on a 1.0 g/kg of genistein diet were sacrificed in the morning, the mean level of serum genistein was 1.4+/-0.2 micro moles/L. Serum genistein increased during the daylight hours reaching a maximum of 7.5+/-0.6 micro moles/L in the early evening. Our results demonstrate that dietary genistein is not inhibitory to growth or caloric intake and up to 1.0 g/kg ad libitum genistein causes no significant organ specific abnormalities. PMID:12556293

  5. MICE data handling on the Grid

    NASA Astrophysics Data System (ADS)

    Martyniak, J.; Mice Collaboration

    2014-06-01

    The international Muon Ionisation Cooling Experiment (MICE) is designed to demonstrate the principle of muon ionisation cooling for the first time, for application to a future Neutrino factory or Muon Collider. The experiment is currently under construction at the ISIS synchrotron at the Rutherford Appleton Laboratory (RAL), UK. In this paper we present a system - the Raw Data Mover, which allows us to store and distribute MICE raw data - and a framework for offline reconstruction and data management. The aim of the Raw Data Mover is to upload raw data files onto a safe tape storage as soon as the data have been written out by the DAQ system and marked as ready to be uploaded. Internal integrity of the files is verified and they are uploaded to the RAL Tier-1 Castor Storage Element (SE) and placed on two tapes for redundancy. We also make another copy at a separate disk-based SE at this stage to make it easier for users to access data quickly. Both copies are check-summed and the replicas are registered with an instance of the LCG File Catalog (LFC). On success a record with basic file properties is added to the MICE Metadata DB. The reconstruction process is triggered by new raw data records filled in by the mover system described above. Off-line reconstruction jobs for new raw files are submitted to RAL Tier-1 and the output is stored on tape. Batch reprocessing is done at multiple MICE enabled Grid sites and output files are shipped to central tape or disk storage at RAL using a custom File Transfer Controller.

  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. 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

  8. 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.

  9. Provision of a voluntary exercise environment enhances running activity and prevents obesity in Snark-deficient mice.

    PubMed

    Ichinoseki-Sekine, Noriko; Naito, Hisashi; Tsuchihara, Katsuya; Kobayashi, Ikumi; Ogura, Yuji; Kakigi, Ryo; Kurosaka, Mitsutoshi; Fujioka, Rumi; Esumi, Hiroyasu

    2009-05-01

    The present study was performed to investigate the involvement of SNARK in physical activity levels in mice. To examine the acute effect of SNARK deficiency on voluntary running, Snark-deficient mice (Snark(+/-): n = 16) and their wild-type counterparts (Snark(+/+): n = 16) were assigned to sedentary or exercise (1 wk voluntary wheel running) groups. In addition, to clarify the differences in voluntary running activity and its effect between genotypes, mice (Snark(+/+): n = 16; Snark(+/-): n = 16) were also kept in individual cages with/without a running wheel for 5 mo. Unexpectedly, in both voluntary running experiments, running distances were increased in Snark(+/-) mice compared with Snark(+/+) mice. Under sedentary conditions, body and white adipose tissue weights were increased significantly in Snark(+/-) mice. However, no significant differences were observed between the two genotypes under exercise conditions, and the values were significantly less than those under sedentary conditions in the long-term experiment. In the short-term experiment, serum interleukin-6 level in exercised Snark(+/+) mice was the same as that in sedentary Snark(+/+) mice, whereas that in sedentary Snark(+/-) mice was significantly lower than in the other groups. In contrast, serum leptin level was reduced significantly in exercised Snark(+/-) mice compared with sedentary Snark(+/-) mice. The results of this study demonstrated that exposure to an environment that allows voluntary exercise promotes increased running activity and prevents obesity in Snark-deficient mice. PMID:19276392

  10. Pitavastatin Reduces Inflammation in Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice with Late Stage Renal Disease

    PubMed Central

    Figueiredo, Jose-Luiz; New, Sophie E. P.; Quillard, Thibaut; Goettsch, Claudia; Koga, Jun-ichiro; Sonoki, Hiroyuki; Matsumoto, Jiro; Aikawa, Masanori; Aikawa, Elena

    2015-01-01

    Objectives Chronic renal disease (CRD) accelerates atherosclerosis and cardiovascular calcification. Statins reduce low-density lipoprotein-cholesterol levels in patients with CRD, however, the benefits of statins on cardiovascular disease in CRD remain unclear. This study has determined the effects of pitavastatin, the newest statin, on arterial inflammation and calcification in atherogenic mice with CRD. Methods and Results CRD was induced by 5/6 nephrectomy in cholesterol-fed apolipoprotein E-deficient mice. Mice were randomized into three groups: control mice, CRD mice, and CRD mice treated with pitavastatin. Ultrasonography showed that pitavastatin treatment significantly attenuated luminal stenosis in brachiocephalic arteries of CRD mice. Near-infrared molecular imaging and correlative Mac3 immunostaining demonstrated a significant reduction in macrophage accumulation in pitavastatin-treated CRD mice. Pitavastatin treatment reduced levels of osteopontin in plasma and atherosclerotic lesions in CRD mice, but did not produce a significant reduction in calcification in atherosclerotic plaques as assesses by histology. CRD mice had significantly higher levels of phosphate in plasma than did control mice, which did not change by pitavastatin. In vitro, pitavastatin suppressed the expression of osteopontin in peritoneal macrophages stimulated with phosphate or calcium/phosphate in concentrations similar to those found in human patients with CRD. Conclusion Our study provides in vivo evidence that pitavastatin reduces inflammation within atherosclerotic lesions in CRD mice. PMID:26367531

  11. Aberrant macrophages mediate defective kidney repair that triggers nephritis in lupus-susceptible mice.

    PubMed

    Iwata, Yasunori; Boström, Elisabeth A; Menke, Julia; Rabacal, Whitney A; Morel, Laurence; Wada, Takashi; Kelley, Vicki R

    2012-05-01

    CSF-1, required for macrophage (Mř) survival, proliferation, and activation, is upregulated in the tubular epithelial cells (TECs) during kidney inflammation. CSF-1 mediates Mř-dependent destruction in lupus-susceptible mice with nephritis and, paradoxically, Mř-dependent renal repair in lupus-resistant mice after transient ischemia/reperfusion injury (I/R). We now report that I/R leads to defective renal repair, nonresolving inflammation, and, in turn, early-onset lupus nephritis in preclinical MRL/MpJ-Faslpr/Fas(lpr) mice (MRL-Fas(lpr) mice). Moreover, defective renal repair is not unique to MRL-Fas(lpr) mice, as flawed healing is a feature of other lupus-susceptible mice (Sle 123) and MRL mice without the Fas(lpr) mutation. Increasing CSF-1 hastens renal healing after I/R in lupus-resistant mice but hinders healing, exacerbates nonresolving inflammation, and triggers more severe early-onset lupus nephritis in MRL-Fas(lpr) mice. Probing further, the time-related balance of M1 "destroyer" Mř shifts toward the M2 "healer" phenotype in lupus-resistant mice after I/R, but M1 Mř continue to dominate in MRL-Fas(lpr) mice. Moreover, hypoxic TECs release mediators, including CSF-1, that are responsible for stimulating the expansion of M1 Mř inherently poised to destroy the kidney in MRL-Fas(lpr) mice. In conclusion, I/R induces CSF-1 in injured TECs that expands aberrant Mř (M1 phenotype), mediating defective renal repair and nonresolving inflammation, and thereby hastens the onset of lupus nephritis. PMID:22467656

  12. Disease course in mdx:utrophin+/? mice: comparison of three mouse models of Duchenne muscular dystrophy

    PubMed Central

    McDonald, Abby A; Hebert, Sadie L; Kunz, Matthew D; Ralles, Steven J; McLoon, Linda K

    2015-01-01

    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

  13. Evidence for Persistence of Ectromelia Virus in Inbred Mice, Recrudescence Following Immunosuppression and Transmission to Naďve Mice

    PubMed Central

    Sakala, Isaac G.; Chaudhri, Geeta; Scalzo, Anthony A.; Eldi, Preethi; Newsome, Timothy P.; Buller, Robert M.; Karupiah, Gunasegaran

    2015-01-01

    Orthopoxviruses (OPV), including variola, vaccinia, monkeypox, cowpox and ectromelia viruses cause acute infections in their hosts. With the exception of variola virus (VARV), the etiological agent of smallpox, other OPV have been reported to persist in a variety of animal species following natural or experimental infection. Despite the implications and significance for the ecology and epidemiology of diseases these viruses cause, those reports have never been thoroughly investigated. We used the mouse pathogen ectromelia virus (ECTV), the agent of mousepox and a close relative of VARV to investigate virus persistence in inbred mice. We provide evidence that ECTV causes a persistent infection in some susceptible strains of mice in which low levels of virus genomes were detected in various tissues late in infection. The bone marrow (BM) and blood appeared to be key sites of persistence. Contemporaneous with virus persistence, antiviral CD8 T cell responses were demonstrable over the entire 25-week study period, with a change in the immunodominance hierarchy evident during the first 3 weeks. Some virus-encoded host response modifiers were found to modulate virus persistence whereas host genes encoded by the NKC and MHC class I reduced the potential for persistence. When susceptible strains of mice that had apparently recovered from infection were subjected to sustained immunosuppression with cyclophosphamide (CTX), animals succumbed to mousepox with high titers of infectious virus in various organs. CTX treated index mice transmitted virus to, and caused disease in, co-housed naďve mice. The most surprising but significant finding was that immunosuppression of disease-resistant C57BL/6 mice several weeks after recovery from primary infection generated high titers of virus in multiple tissues. Resistant mice showed no evidence of a persistent infection. This is the strongest evidence that ECTV can persist in inbred mice, regardless of their resistance status. PMID:26700306

  14. Combination of 3D skin surface texture features and 2D ABCD features for improved melanoma diagnosis.

    PubMed

    Ding, Yi; John, Nigel W; Smith, Lyndon; Sun, Jiuai; Smith, Melvyn

    2015-10-01

    Two-dimensional asymmetry, border irregularity, colour variegation and diameter (ABCD) features are important indicators currently used for computer-assisted diagnosis of malignant melanoma (MM); however, they often prove to be insufficient to make a convincing diagnosis. Previous work has demonstrated that 3D skin surface normal features in the form of tilt and slant pattern disruptions are promising new features independent from the existing 2D ABCD features. This work investigates that whether improved lesion classification can be achieved by combining the 3D features with the 2D ABCD features. Experiments using a nonlinear support vector machine classifier show that many combinations of the 2D ABCD features and the 3D features can give substantially better classification accuracy than using (1) single features and (2) many combinations of the 2D ABCD features. The best 2D and 3D feature combination includes the overall 3D skin surface disruption, the asymmetry and all the three colour channel features. It gives an overall 87.8 % successful classification, which is better than the best single feature with 78.0 % and the best 2D feature combination with 83.1 %. These demonstrate that (1) the 3D features have additive values to improve the existing lesion classification and (2) combining the 3D feature with all the 2D features does not lead to the best lesion classification. The two ABCD features not selected by the best 2D and 3D combination, namely (1) the border feature and (2) the diameter feature, were also studied in separate experiments. It found that inclusion of either feature in the 2D and 3D combination can successfully classify 3 out of 4 lesion groups. The only one group not accurately classified by either feature can be classified satisfactorily by the other. In both cases, they have shown better classification performances than those without the 3D feature in the combinations. This further demonstrates that (1) the 3D feature can be used to improve the existing 2D-based diagnosis and (2) including the 3D feature with subsets of the 2D features can be used in distinguishing different benign lesion classes from MM. It is envisaged that classification performance may be further improved if different 2D and 3D feature subsets demonstrated in this study are used in different stages to target different benign lesion classes in future studies. PMID:25947095

  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. Wedge absorber design and simulation for MICE Step IV

    SciTech Connect

    Rogers, C.T.; Snopok, P.; Coney, L.; Hanson, G.; /UC, Riverside

    2011-03-01

    In the Muon Ionization Cooling Experiment (MICE), muons are cooled by passing through material, then through RF cavities to compensate for the energy loss; which reduces the transverse emittance. It is planned to demonstrate longitudinal emittance reduction via emittance exchange in MICE by using a solid wedge absorber in Step IV. Based on the outcome of previous studies, the shape and material of the wedge were chosen. We address here further simulation efforts for the absorber of choice as well as engineering considerations in connection with the absorber support design.

  17. Characterization of lethal dengue virus type 4 (DENV-4) TVP-376 infection in mice lacking both IFN-?/? and IFN-? receptors (AG129) and comparison with the DENV-2 AG129 mouse model.

    PubMed

    Sarathy, Vanessa V; Infante, Ernesto; Li, Li; Campbell, Gerald A; Wang, Tian; Paessler, Slobodan; Robert Beatty, P; Harris, Eva; Milligan, Gregg N; Bourne, Nigel; Barrett, Alan D T

    2015-10-01

    Dengue is a mosquito-borne disease caused by four related but distinct dengue viruses, DENV-1 to DENV-4. Dengue is endemic in most tropical countries, and over a third of the world's population is at risk of being infected. Although the global burden is high, no vaccine or antiviral is licensed to combat this disease. An obstacle complicating dengue research is the lack of animal challenge models that mimic human disease. Advances in immunocompromised murine infection models resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice, which are deficient in both the IFN-?/? receptor (IFN-?/?R) and the IFN-? receptor (IFN-?R). These models mimic features of dengue disease in humans. Here, we characterized lethal infection of AG129 mice by DENV-4 strain TVP-376 and found that AG129 mice developed clinical signs of illness and high viral loads in multiple tissues and succumbed 5?days after infection. Moreover, the splenic and hepatic histopathology of TVP-376-infected mice demonstrated the presence of cell activation and destruction of tissue architecture. Furthermore, infected mice had heightened levels of circulating cytokines. Comparison of the virulence phenotypes of DENV-4 strain TVP-376 and DENV-2 strain D2S10 revealed that TVP-376-induced mortality occurred in the absence of both IFN-?/?R and IFN-?R signalling, but not with intact signalling from the IFN-?R, whereas D2S10 required the absence of IFN-?/?R signalling only, indicating that it is more virulent than TVP-376. In conclusion, TVP-376 is lethal in AG129 mice, and this model provides a useful platform to investigate vaccine candidates and antivirals against DENV-4. PMID:26296350

  18. [Mice myometrial contractility in conditions of mitochondrial functional changes].

    PubMed

    Ianchi?, R I; Kale?nikova, O M; Voznesens'ka, T Iu; Blashkiv, T V; Bidzilia, Iu P

    2013-01-01

    It has been investigated the temporal amplitude features of mice myometrium in conditions of action mitochondrial carriers inhibitor, the mitochondrial pore activator, calcium uniporters inhibitor. For the first time it is established that the functional condition of myometrium depends on a mitochondrial carriers functioning; the mitochondrial carrier is NO-dependent itself (on arginaze way of its formation); the carrier functions depending on mitochondrial membrane potential and mitochondrion nonspecific conductivity (mitochondrial pores). PMID:24175476

  19. 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

  20. Ontology patterns for complex topographic feature yypes

    USGS Publications Warehouse

    Varanka, Dalia E.

    2011-01-01

    Complex feature types are defined as integrated relations between basic features for a shared meaning or concept. The shared semantic concept is difficult to define in commonly used geographic information systems (GIS) and remote sensing technologies. The role of spatial relations between complex feature parts was recognized in early GIS literature, but had limited representation in the feature or coverage data models of GIS. Spatial relations are more explicitly specified in semantic technology. In this paper, semantics for topographic feature ontology design patterns (ODP) are developed as data models for the representation of complex features. In the context of topographic processes, component assemblages are supported by resource systems and are found on local landscapes. The topographic ontology is organized across six thematic modules that can account for basic feature types, resource systems, and landscape types. Types of complex feature attributes include location, generative processes and physical description. Node/edge networks model standard spatial relations and relations specific to topographic science to represent complex features. To demonstrate these concepts, data from The National Map of the U. S. Geological Survey was converted and assembled into ODP.

  1. Assessing Cognition in Mice.

    PubMed

    Hölter, Sabine M; Garrett, Lillian; Einicke, Jan; Sperling, Bettina; Dirscherl, Petra; Zimprich, Annemarie; Fuchs, Helmut; Gailus-Durner, Valerie; Hrab? de Angelis, Martin; Wurst, Wolfgang

    2015-01-01

    Genetically modified mouse models have proven useful to study learning and memory processes and the neurocircuitry and molecular mechanisms involved, as well as to develop therapies for diseases involving cognitive impairment. A variety of tests have been developed to measure cognition in mice, and here we present those established and regularly used in the German Mouse Clinic. The test paradigms have been carefully chosen according to reliability of results and disease relevance of the cognitive functions assessed. Further criteria were time efficiency and ease of application. All tests assess slightly different but also overlapping or interacting aspects of learning and memory so that they can be used to complement each other in a comprehensive assessment of cognitive function. The five protocols described are for spontaneous alternation in the Y-maze, social discrimination, object recognition, automated assessment of learning and memory using the IntelliCage, and olfactory discrimination learning. © 2015 by John Wiley & Sons, Inc. PMID:26629775

  2. Defeating feature fatigue.

    PubMed

    Rust, Roland T; Thompson, Debora Viana; Hamilton, Rebecca W

    2006-02-01

    Consider a coffeemaker that offers 12 drink options, a car with more than 700 features on the dashboard, and a mouse pad that's also a clock, calculator, and FM radio. All are examples of "feature bloat", or "featuritis", the result of an almost irresistible temptation to load products with lots of bells and whistles. The problem is that the more features a product boasts, the harder it is to use. Manufacturers that increase a product's capability--the number of useful functions it can perform--at the expense of its usability are exposing their customers to feature fatigue. The authors have conducted three studies to gain a better understanding of how consumers weigh a product's capability relative to its usability. They found that even though consumers know that products with more features are harder to use, they initially choose high-feature models. They also pile on more features when given the chance to customize a product for their needs. Once consumers have actually worked with a product, however, usability starts to matter more to them than capability. For managers in consumer products companies, these findings present a dilemma: Should they maximize initial sales by designing high-feature models, which consumers consistently choose, or should they limit the number of features in order to enhance the lifetime value of their customers? The authors' analytical model guides companies toward a happy middle ground: maximizing the net present value of the typical customer's profit stream. The authors also advise companies to build simpler products, help consumers learn which products suit their needs, develop products that do one thing very well, and design market research in which consumers use actual products or prototypes. PMID:16485808

  3. Factor VII Deficiency Impairs Cutaneous Wound Healing in Mice

    PubMed Central

    Xu, Zhi; Xu, Haifeng; Ploplis, Victoria A; Castellino, Francis J

    2010-01-01

    Skin keratinocytes express tissue factor (TF) and are highly associated with skin wound healing. Although it has been demonstrated that perivascular TF expression in granulation tissue formed after dermal injury is downregulated during healing, studies of the mechanism of factor (F) VII, a TF ligand, in skin wound healing are lacking. We reported the use of a dermal punch model to demonstrate that low-expressing FVII mice (~1% of wild type [WT]) exhibited impaired skin wound healing compared with WT controls. These low-FVII mice showed defective reepithelialization and reduced inflammatory cell infiltration at wound sites. This attenuated reepithelialization was associated with diminished expression of the transcription factor early growth response 1 (Egr-1). In vitro, Egr-1 was shown to be essential for the FVIIa-induced regulation of keratinocyte migration and inflammation. Both Egr-1 upregulation and downstream inflammatory cytokine appearance in keratinocytes depended on FVIIa/TF/protease-activated receptor 2 (PAR-2)-induced signaling and did not require subsequent generation of FXa and thrombin. The participation of Egr-1 in FVIIa-mediated regulation of keratinocyte function was confirmed by use of Egr-1–deficient mice, wherein a significant delay in skin wound healing after injury was observed, relative to WT mice. The results from these studies demonstrate an in vivo mechanistic relationship between FVIIa, Egr-1 and the inflammatory response in keratinocyte function during the wound healing process. PMID:20454518

  4. De novo 325 kb microdeletion in chromosome band 10q25.3 including ATRNL1 in a boy with cognitive impairment, autism and dysmorphic features.

    PubMed

    Stark, Zornitza; Bruno, Damien L; Mountford, Hayley; Lockhart, Paul J; Amor, David J

    2010-01-01

    We provide the first description of a patient with a heterozygous deletion of the Attractin-like (ATRNL1) gene. The patient presented with a novel and distinctive phenotype comprising dysmorphic facial appearance, ventricular septal defect, toe syndactyly, radioulnar synostosis, postnatal growth retardation, cognitive impairment with autistic features, and ataxia. A 325 kb de novo deletion in ATRNL1 was demonstrated using SNP microarray and confirmed by FISH analysis using BAC probes. Sequence analysis of the undeleted allele did not identify any alterations, suggesting that the phenotype was the result of haploinusfficiency. ATRNL1 and its paralog ATRN are highly conserved transmembrane proteins thought to be involved in cell adhesion and signalling events. The phenotype of mice with homozygous Atrn mutations overlaps considerably with the features observed in our patient. We therefore postulate that our patient's phenotype is caused by the deletion of ATRNL1, and provide further insight into the role of ATRNL1 in human development. PMID:20670697

  5. 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

    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

  6. Ablation of TNF-RI/RII expression in Alzheimer's disease mice leads to an unexpected enhancement of pathology: implications for chronic pan-TNF-? suppressive therapeutic strategies in the brain.

    PubMed

    Montgomery, Sara L; Mastrangelo, Michael A; Habib, Diala; Narrow, Wade C; Knowlden, Sara A; Wright, Terry W; Bowers, William J

    2011-10-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe memory loss and cognitive impairment. Neuroinflammation, including the extensive production of pro-inflammatory molecules and the activation of microglia, has been implicated in the disease process. Tumor necrosis factor (TNF)-?, a prototypic pro-inflammatory cytokine, is elevated in AD, is neurotoxic, and colocalizes with amyloid plaques in AD animal models and human brains. We previously demonstrated that the expression of TNF-? is increased in AD mice at ages preceding the development of hallmark amyloid and tau pathological features and that long-term expression of this cytokine in these mice leads to marked neuronal death. Such observations suggest that TNF-? signaling promotes AD pathogenesis and that therapeutics suppressing this cytokine's activity may be beneficial. To dissect TNF-? receptor signaling requirements in AD, we generated triple-transgenic AD mice (3xTg-AD) lacking both TNF-? receptor 1 (TNF-RI) and 2 (TNF-RII), 3xTg-ADxTNF-RI/RII knock out, the cognate receptors of TNF-?. These mice exhibit enhanced amyloid and tau-related pathological features by the age of 15 months, in stark contrast to age-matched 3xTg-AD counterparts. Moreover, 3xTg-ADxTNF-RI/RII knock out-derived primary microglia reveal reduced amyloid-? phagocytic marker expression and phagocytosis activity, indicating that intact TNF-? receptor signaling is critical for microglial-mediated uptake of extracellular amyloid-? peptide pools. Overall, our results demonstrate that globally ablated TNF receptor signaling exacerbates pathogenesis and argues against long-term use of pan-anti-TNF-? inhibitors for the treatment of AD. PMID:21835156

  7. JPEG image steganalysis using joint discrete cosine transform domain features

    NASA Astrophysics Data System (ADS)

    Xia, Zhihua; Sun, Xingming; Liang, Wei; Qin, Jiaohua; Li, Feng

    2010-04-01

    A JPEG image steganalysis scheme based on joint discrete cosine transform (DCT) domain features is proposed. Intrinsic characteristics of DCT coefficients, such as histogram, intrablock correlation, and interblock correlation, are exploited to construct three feature sets. Support vector machine is utilized to learn and discriminate the difference of features between cover and stego images. First, the three feature sets are investigated separately to reveal their individual capability of attacking steganographic methods. Second, the feature sets are combined to form a joint feature set with better performance. Experimental results demonstrate that all three feature sets individually succeed in attacking the four typical steganographic tools to some extent, with the intrablock feature set performing the best. Furthermore, the comparison experiments show that the jointed feature set not only outperforms the three individual feature sets but also proves to be better than a previous state-of-the-art steganalysis method.

  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. Feeding and Metabolism in Mice Lacking Pituitary Adenylate Cyclase-Activating Polypeptide

    PubMed Central

    Adams, Bruce A.; Gray, Sarah L.; Isaac, Emma R.; Bianco, Antonio C.; Vidal-Puig, Antonio J.; Sherwood, Nancy M.

    2008-01-01

    Disruption of the pituitary adenylate cyclase-activating polypeptide (PACAP) gene in mice has demonstrated a role for this highly conserved neuropeptide in the regulation of metabolism and temperature control. Localization of PACAP neurons within hypothalamic nuclei that regulate appetite suggest PACAP may affect feeding and thus energy balance. We used PACAP-null mice to address this question, examining both food intake and energy expenditure. PACAP-null mice were leaner than wild-type littermates due to decreased adiposity and displayed increased insulin sensitivity. The lean phenotype in the PACAP-null mice was completely eliminated if animals were fed a high-fat diet or housed near thermoneutrality (28 C). Further metabolic analyses of PACAP-null mice housed at 21 C indicated that the reduced body weight could not be explained by decreased food intake, increased metabolic rate, or increased locomotor activity. The thyroid hormone axis of PACAP-null mice was affected, because mRNA levels of hypothalamic TRH and brown adipose tissue type 2 deiodinase were reduced in PACAP-null mice housed at room temperature, and brain deiodinase activity was lower in PACAP-null mice after an acute cold challenge compared with wild-type controls. These results demonstrate that PACAP is not required for the regulation of food intake yet is necessary to maintain normal energy homeostasis, likely playing a role in central cold-sensing mechanisms. PMID:18162530

  11. Immmunophenotype of Spontaneous Hematolymphoid Tumors Occurring in Young and Aging Female CD-1 Mice.

    PubMed

    Rehg, Jerold E; Rahija, Richard; Bush, Dorothy; Bradley, Alys; Ward, Jerrold M

    2015-10-01

    A few reports indicated the incidence of hematolymphoid neoplasms in old CD-1 mice, but the cellular lineage of CD-1 mouse neoplasms has not been published. In this study, immunohistochemistry (IHC) was used to characterize the cellular lineage of spontaneous hematolymphoid neoplasms arising in 24 young female CD-1 mice used as health-monitoring sentinels and 32 aging female CD-1 mice used as controls in 80-week carcinogenesis studies. Lymphoblastic lymphomas of T-cell and B-cell lineage were common in mice aged 12 months or less, whereas a wide range of non-lymphoblastic B-cell lymphomas and lymphoblastic B-cell lymphomas were common in mice >12-mo-old. Renal hyaline droplets positive for lysozyme were observed in aged mice with a histiocytic-associated large B-cell lymphoma (HA-BCL) and a myeloid leukemia. Endogenous ecotropic mouse leukemia virus (MuLV) genes have been recovered from CD-1 mice, but MuLV protein expression has not been previously demonstrated. We reported for the first time the expression of a MuLV protein p30 by IHC in lymphomas and some normal tissues of both young and aging CD-1 mice. This report should help to differentiate spontaneous lymphomas and leukemias in CD-1 mice from those induced by chemicals and other methods. PMID:26224701

  12. Effects of Injected Iron and Siderophores on Infections in Normal and Immune Mice

    PubMed Central

    Kochan, Ivan; Wasynczuk, John; McCabe, Martha A.

    1978-01-01

    The fate of virulent and avirulent strains of Salmonella typhimurium in untreated and iron-injected mice and in transferrin-containing media demonstrated a direct relationship between bacterial virulence and the ability of bacteria to acquire transferrin-bound iron. Effects of injected iron on the development of infections with virulent and avirulent bacterial strains were determined in normal and immune mice by determinations of bacterial numbers in tissue homogenates and the mortality of infected animals. Results showed that infected and iron-injected mice died much more rapidly and frequently from overwhelming infections than infected and saline-injected mice. The infection-promoting effect of iron varied with the degree of bacterial virulence; the more virulent the bacteria, the more helpful was iron for the development of lethal infections. Siderophores promoted lethal infections in mice infected with virulent but not with avirulent bacteria. Experiments with vaccinated animals showed that iron exerted a deleterious effect on acquired immunity. Immune mice infected with virulent bacteria and injected with iron developed lethal infections as rapidly and nearly as frequently as similarly treated normal mice. Siderophores did not promote the development of lethal infections in immune mice. The effectiveness of iron, but not of siderophores, to promote bacterial infections in vaccinated mice revealed that acquired immunity is dependent upon the activity of an iron-neutralizable antibacterial system. Images PMID:365761

  13. 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

  14. MMIC Phased Array Demonstrations with ACTS

    NASA Technical Reports Server (NTRS)

    Raquet, Charles A. (Compiler); Martzaklis, Konstantinos (Compiler); Zakrajsek, Robert J. (Compiler); Andro, Monty (Compiler); Turtle, John P.

    1996-01-01

    Over a one year period from May 1994 to May 1995, a number of demonstrations were conducted by the NASA Lewis Research Center (LeRC) in which voice, data, and/or video links were established via NASA's advanced communications technology satellite (ACTS) between the ACTS link evaluation terminal (LET) in Cleveland, OH, and aeronautical and mobile or fixed Earth terminals having monolithic microwave integrated circuit (MMIC) phased array antenna systems. This paper describes four of these. In one, a duplex voice link between an aeronautical terminal on the LeRC Learjet and the ACTS was achieved. Two others demonstrated duplex voice (and in one case video as well) links between the ACTS and an Army vehicle. The fourth demonstrated a high data rate downlink from ACTS to a fixed terminal. Array antenna systems used in these demonstrations were developed by LeRC and featured LeRC and Air Force experimental arrays using gallium arsenide MMIC devices at each radiating element for electronic beam steering and distributed power amplification. The single 30 GHz transmit array was developed by NASA/LeRC and Texas Instruments. The three 20 GHz receive arrays were developed in a cooperative effort with the Air Force Rome Laboratory, taking advantage of existing Air Force array development contracts with Boeing and Lockheed Martin. The paper describes the four proof-of-concept arrays and the array control system. The system configured for each of the demonstrations is described, and results are discussed.

  15. 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.

  16. A Dramatic Flame Test Demonstration.

    ERIC Educational Resources Information Center

    Johnson, Kristin A.; Schreiner, Rodney

    2001-01-01

    Flame tests are used for demonstration of atomic structure. Describes a demonstration that uses spray bottles filled with methanol and a variety of salts to produce a brilliantly colored flame. (Contains 11 references.) (ASK)

  17. 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

  18. Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A2B adenosine receptor signaling.

    PubMed

    Wen, Jiaming; Jiang, Xianzhen; Dai, Yingbo; Zhang, Yujin; Tang, Yuxin; Sun, Hong; Mi, Tiejuan; Phatarpekar, Prasad V; Kellems, Rodney E; Blackburn, Michael R; Xia, Yang

    2010-03-01

    Priapism is a condition of persistent penile erection in the absence of sexual excitation. Of men with sickle cell disease (SCD), 40% display priapism. The disorder is a dangerous and urgent condition, given its association with penile fibrosis and eventual erectile dysfunction. Current strategies to prevent its progression are poor because of a lack of fundamental understanding of the molecular mechanisms for penile fibrosis in priapism. Here we demonstrate that increased adenosine is a novel causative factor contributing to penile fibrosis in two independent animal models of priapism, adenosine deaminase (ADA)-deficient mice and SCD transgenic mice. An important finding is that chronic reduction of adenosine by ADA enzyme therapy successfully attenuated penile fibrosis in both mouse models, indicating an essential role of increased adenosine in penile fibrosis and a novel therapeutic possibility for this serious complication. Subsequently, we identified that both mice models share a similar fibrotic gene expression profile in penile tissue (including procollagen I, TGF-beta(1), and plasminogen activator inhibitor-1 mRNA), suggesting that they share similar signaling pathways for progression to penile fibrosis. Thus, in an effort to decipher specific cell types and underlying mechanism responsible for adenosine-mediated penile fibrosis, we purified corpus cavernosal fibroblast cells (CCFCs), the major cell type involved in this process, from wild-type mice. Quantitative RT-PCR showed that the major receptor expressed in these cells is the adenosine receptor A(2B)R. Based on this fact, we further purified CCFCs from A(2B)R-deficient mice and demonstrated that A(2B)R is essential for excess adenosine-mediated penile fibrosis. Finally, we revealed that TGF-beta functions downstream of the A(2B)R to increase CCFC collagen secretion and proliferation. Overall, our studies identify an essential role of increased adenosine in the pathogenesis of penile fibrosis via A(2B)R signaling and offer a potential target for prevention and treatment of penile fibrosis, a dangerous complication seen in priapism.-Wen, J., Jiang, X., Dai, Y., Zhang, Y., Tang, Y., Sun, H., Mi, T., Phatarpekar, P. V., Kellems, R. E., Blackburn, M. R., Xia, Y. Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A(2B) adenosine receptor signaling. PMID:19858092

  19. Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A2B adenosine receptor signaling

    PubMed Central

    Wen, Jiaming; Jiang, Xianzhen; Dai, Yingbo; Zhang, Yujin; Tang, Yuxin; Sun, Hong; Mi, Tiejuan; Phatarpekar, Prasad V.; Kellems, Rodney E.; Blackburn, Michael R.; Xia, Yang

    2010-01-01

    Priapism is a condition of persistent penile erection in the absence of sexual excitation. Of men with sickle cell disease (SCD), 40% display priapism. The disorder is a dangerous and urgent condition, given its association with penile fibrosis and eventual erectile dysfunction. Current strategies to prevent its progression are poor because of a lack of fundamental understanding of the molecular mechanisms for penile fibrosis in priapism. Here we demonstrate that increased adenosine is a novel causative factor contributing to penile fibrosis in two independent animal models of priapism, adenosine deaminase (ADA)-deficient mice and SCD transgenic mice. An important finding is that chronic reduction of adenosine by ADA enzyme therapy successfully attenuated penile fibrosis in both mouse models, indicating an essential role of increased adenosine in penile fibrosis and a novel therapeutic possibility for this serious complication. Subsequently, we identified that both mice models share a similar fibrotic gene expression profile in penile tissue (including procollagen I, TGF-?1, and plasminogen activator inhibitor-1 mRNA), suggesting that they share similar signaling pathways for progression to penile fibrosis. Thus, in an effort to decipher specific cell types and underlying mechanism responsible for adenosine-mediated penile fibrosis, we purified corpus cavernosal fibroblast cells (CCFCs), the major cell type involved in this process, from wild-type mice. Quantitative RT-PCR showed that the major receptor expressed in these cells is the adenosine receptor A2BR. Based on this fact, we further purified CCFCs from A2BR-deficient mice and demonstrated that A2BR is essential for excess adenosine-mediated penile fibrosis. Finally, we revealed that TGF-? functions downstream of the A2BR to increase CCFC collagen secretion and proliferation. Overall, our studies identify an essential role of increased adenosine in the pathogenesis of penile fibrosis via A2BR signaling and offer a potential target for prevention and treatment of penile fibrosis, a dangerous complication seen in priapism.—Wen, J., Jiang, X., Dai, Y., Zhang, Y., Tang, Y., Sun, H., Mi, T., Phatarpekar, P. V., Kellems, R. E., Blackburn, M. R., Xia, Y. Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A2B adenosine receptor signaling. PMID:19858092

  20. The FVB/N mice: A well suited strain to study learning and memory processes using olfactory cues.

    PubMed

    Girard, Stéphane D; Escoffier, Guy; Khrestchatisky, Michel; Roman, François S

    2016-01-01

    The FVB/N mice are well suited to generate transgenic animals. These mice are also particularly sensitive to seizures and neurodegeneration induced by systemic administration of chemoconvulsants and are very useful to model epilepsy. However, previous studies report strong cognitive and visual impairments suggesting this background unsuitable for behavioral analysis. In this study, we assessed and compared learning abilities of FVB/N mice to the well characterized C57BL/6 strain using the olfactory tubing maze, a non-visual hippocampus-dependent task in which the mice were trained to learn odor-reward associations. Exploratory behavior and spontaneous locomotor activity were then compared using the open field test. We demonstrated that FVB/N mice were able to learn the task, reaching at the end of the test a high percentage of correct responses. Interestingly, the performance of the FVB/N mice was at least similar to that of the C57BL/6 mice. Moreover, in contrast to previous reports, the FVB/N mice displayed a spontaneous locomotor activity lower than C57BL/6 mice. Our study demonstrated that FVB/N mice are not cognitively impaired and that their learning and memory performance can be assessed when the task is based on olfaction rather than vision. PMID:26365456

  1. New features in MEDM.

    SciTech Connect

    Evans, K., Jr.

    1999-04-13

    MEDM, which is derived from Motif Editor and Display Manager, is the primary graphical interface to the EPICS control system. This paper describes new features that have been added to MEDM in the last two years. These features include new editing capabilities, a PV Info dialog box, a means of specifying limits and precision, a new implementation of the Cartesian Plot, new features for several objects, new capability for the Related Display, help, a user-configurable Execute Menu, reconfigured start-up options, and availability for Windows 95/98/NT. Over one hundred bugs have been fixed, and the program is quite stable and in extensive use.

  2. [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

  3. Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice

    SciTech Connect

    Ezaki, Hisao; Yoshida, Yuichi; Saji, Yukiko; Takemura, Takayo; Fukushima, Juichi; Matsumoto, Hitoshi; Kamada, Yoshihiro; Wada, Akira; Igura, Takumi; Kihara, Shinji; Funahashi, Tohru; Shimomura, Iichiro; Tamura, Shinji; Kiso, Shinichi Hayashi, Norio

    2009-01-02

    We previously demonstrated that adiponectin has anti-fibrogenic and anti-inflammatory effects in the liver of mouse models of various liver diseases. However, its role in liver regeneration remains unclear. The aim of this study was to determine the role of adiponectin in liver regeneration. We assessed liver regeneration after partial hepatectomy in wild-type (WT) and adiponectin knockout (KO) mice. We analyzed DNA replication and various signaling pathways involved in cell proliferation and metabolism. Adiponectin KO mice exhibited delayed DNA replication and increased lipid accumulation in the regenerating liver. The expression levels of peroxisome proliferator-activated receptor (PPAR) {alpha} and carnitine palmitoyltransferase-1 (CPT-1), a key enzyme in mitochondrial fatty acid oxidation, were decreased in adiponectin KO mice, suggesting possible contribution of altered fat metabolism to these phenomena. Collectively, the present results highlight a new role for adiponectin in the process of liver regeneration.

  4. 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

  5. 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

  6. Favorite Demonstrations for College Science

    ERIC Educational Resources Information Center

    Shmaefsky, Brian

    2004-01-01

    Peer-reviewed, classroom-tested, and tailored specifically for introductory science courses, Favorite Demonstrations is a 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 …

  7. Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice.

    PubMed

    Jadeja, Ravirajsinh N; Urrunaga, Nathalie H; Dash, Suchismita; Khurana, Sandeep; Saxena, Neeraj Kumar

    2015-09-01

    Withaferin-A (WA) has anti-oxidant activities however, its therapeutic potential in acetaminophen (APAP) hepatotoxicity is unknown. We performed a proof-of-concept study to assess the therapeutic potential of WA in a mouse model that mimics APAP-induced liver injury (AILI) in humans. Overnight fasted C57BL/6NTac (5-6 wk. old) male mice received 200 mg/kg APAP intraperitoneally (i.p.). After 1 h mice were treated with 40 mg/kg WA or vehicle i.p., and euthanized 4 and 16 h later; their livers were harvested and serum collected for analysis. At 4 h, compared to vehicle-treated mice, WA-treated mice had reduced serum ALT levels, hepatocyte necrosis and intrahepatic hemorrhage. All APAP-treated mice had reduced hepatic glutathione (GSH) levels however, reduction in GSH was lower in WA-treated when compared to vehicle-treated mice. Compared to vehicle-treated mice, livers from WA-treated mice had reduced APAP-induced JNK activation, mitochondrial Bax translocation, and nitrotyrosine generation. Compared to vehicle-treated mice, WA-treated mice had increased hepatic up-regulation of Nrf2, Gclc and Nqo1, and down-regulation of Il-6 and Il-1?. The hepatoprotective effect of WA persisted at 16 h. Compared to vehicle-treated mice, WA-treated mice had reduced hepatocyte necrosis and hepatic expression of Il-6, Tnf-? and Il-1?, increased hepatic Gclc and Nqo1 expression and GSH levels, and reduced lipid peroxidation. Finally, in AML12 hepatocytes, WA reduced H?O?-induced oxidative stress and necrosis by preventing GSH depletion. Collectively, these data show mechanisms whereby WA reduces necrotic hepatocyte injury, and demonstrate that WA has therapeutic potential in AILI. PMID:26212553

  8. Exacerbated venous thromboembolism in mice carrying a protein S K196E mutation.

    PubMed

    Banno, Fumiaki; Kita, Toshiyuki; Fernández, José A; Yanamoto, Hiroji; Tashima, Yuko; Kokame, Koichi; Griffin, John H; Miyata, Toshiyuki

    2015-11-01

    Protein S (PS) acts as an anticoagulant cofactor for activated protein C in regulation of blood coagulation. The K196E mutation in PS is a race-specific genetic risk factor for venous thromboembolism with a prevalence of ?2% within the Japanese population. To evaluate the thrombosis risk of the PS-K196E mutation, we generated PS-K196E knockin mice and heterozygous PS-deficient mice. We analyzed their thrombotic states, comparing with mice carrying the factor V Leiden mutation (FV-R504Q), a race-specific genetic risk for venous thrombosis in whites. PS-K196E mice grew normally but had decreased activated protein C cofactor activity in plasma. Purified recombinant murine PS-K196E showed the same decreased activated protein C cofactor activity. A deep vein thrombosis model of electrolytic inferior vena cava injury and pulmonary embolism models induced by infusion of tissue factor or polyphosphates revealed that PS-K196E mice, heterozygous PS-deficient mice, and FV-R504Q mice were much more susceptible to venous thrombosis compared with wild-type mice. Transient middle cerebral artery ischemia-reperfusion injury model studies demonstrated that both PS-K196E mice and heterozygous PS-deficient mice had cerebral infarction similar to wild-type mice, consistent with human observations. Our in vitro and in vivo results support a causal relationship between the PS-K196E mutation and venous thrombosis and indicate that PS-K196E mice can provide an in vivo evaluation system to help uncovering racial differences in thrombotic diseases. PMID:26251307

  9. Sudden Infant Death Syndrome in Mice with an Inherited Mutation in RyR2

    PubMed Central

    Mathur, Nitin; Sood, Subeena; Wang, Sufen; van Oort, Ralph J.; Sarma, Satyam; Li, Na; Skapura, Darlene G.; Bayle, J. Henri; Valderrábano, Miguel; Wehrens, Xander H.T.

    2009-01-01

    Background Mutations in the cardiac ryanodine receptor gene (RYR2) have been recently identified in victims of sudden infant death syndrome (SIDS). The aim of this study was to determine whether a gain-of-function mutation in RYR2 increases the propensity to cardiac arrhythmias and sudden death in young mice. Methods and Results Incidence of sudden death was monitored prospectively in heterozygous knock-in mice with mutation R176Q in Ryr2 (R176Q/+). Young R176Q/+ mice exhibited a higher incidence of sudden death compared with wild-type (WT) littermates. Optical mapping of membrane potentials and calcium levels in 1-7 day-old R176Q/+ and WT mice revealed an increased incidence of ventricular ectopy and spontaneous calcium releases in neonatal R176Q/+ mice. Surface ECGs in 3-10 day-old mice showed that R176Q/+ mice developed more ventricular arrhythmias following provocation with epinephrine and caffeine. Intracardiac pacing studies in 12-18 day-old mice revealed the presence of an arrhythmogenic substrate in R176Q/+ compared with WT mice. RT-PCR and Western blotting showed that expression levels of other calcium handling proteins were unaltered suggesting that calcium leak through mutant RyR2 underlies arrhythmogenesis and sudden death in young R176Q/+ mice. Conclusions Our findings demonstrate that a gain-of-function mutation in RyR2 confers an increased risk of cardiac arrhythmias and sudden death in young mice, and that young R176Q/+ mice may be used as a model for elucidating the complex interplay between genetic and environmental risk factors associated with SIDS. PMID:20009080

  10. Delayed Amyloid Plaque Deposition and Behavioral Deficits in Outcrossed A?PP/PS1 Mice

    PubMed Central

    Couch, Brian A.; Kerrisk, Meghan E.; Kaufman, Adam C.; Nygaard, Haakon B.; Strittmatter, Stephen M.; Koleske, Anthony J.

    2012-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid-? precursor protein (A?PP) and presenilin-1 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. A?PP/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4–9 months of age. We crossed A?PP/PS1 animals with mice of a mixed genetic background (C57BL/6 × 129/SvJ) and investigated the development of AD-like features in the resulting outcrossed mice. The onset of memory-based behavioral impairment is delayed considerably in outcrossed A?PP/PS1 mice relative to inbred mice on a C57BL/6 background. While inbred A?PP/PS1 mice develop deficits in radial-arm water maze performance and novel object recognition as early as 8 months, outcrossed A?PP/PS1 mice do not display defects until 18 months. Within the forebrain, we find that inbred A?PP/PS1 mice have significantly higher amyloid plaque burden at 12 months than outcrossed A?PP/PS1 mice of the same age. Surprisingly, inbred A?PP/PS1 mice at 8 months have low plaque burden suggesting that plaque burden alone cannot explain the accompanying behavioral deficits. Analysis of A?PP processing revealed that elevated levels of soluble A? correlate with the degree of behavioral impairment in both strains. Taken together, these findings suggest that animal behavior, amyloid plaque deposition, and A?PP processing are sensitive to genetic differences between mouse strains. PMID:23047754

  11. Selective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice

    PubMed Central

    Reber, Laurent L.; Marichal, Thomas; Mukai, Kaori; Kita, Yoshihiro; Tokuoka, Suzumi M.; Roers, Axel; Hartmann, Karin; Karasuyama, Hajime; Nadeau, Kari C.; Tsai, Mindy; Galli, Stephen J.

    2013-01-01

    Background Studies using c-kit mutant mast cell (MC)-deficient mice and antibody-mediated depletion of basophils suggest that both MCs and basophils can contribute to peanut-induced anaphylaxis (PIA). However, interpretation of data obtained using such approaches is complicated because c-kit mutant mice have several phenotypic abnormalities in addition to MC deficiency and basophil-depleting antibodies can also react with MCs. Objective We analyzed: (1) the changes in the features of PIA in mice after the selective and inducible ablation of MCs or basophils, and (2) the possible importance of effector cells other than MCs and basophils in the PIA response. Methods Wild-type (WT) and various mutant mice were orally sensitized with peanut extract and cholera toxin weekly for 4 weeks and challenged intraperitoneally with peanut extract 2 weeks later. Results Peanut-challenged MC-deficient KitW-sh/W-sh mice developed reduced immediate hypothermia, as well as a late phase drop in body temperature that was abrogated by antibody-mediated depletion of neutrophils. Diphtheria toxin-mediated selective depletion of MCs or basophils in Mcpt5-Cre; iDTR and Mcpt8DTR mice, respectively, and treatment of WT mice with the basophil-depleting antibody Ba103, significantly reduced peanut-induced hypothermia. Non-c-kit mutant MC- and basophil-deficient Cpa3-Cre; Mcl-1fl/fl mice developed reduced, but still significant, responses to peanut. Conclusion Inducible and selective ablation of MCs or basophils in non-c-kit mutant mice can significantly reduce PIA, but partial responses to peanut can still be observed in the virtual absence of both cell types. The neutrophilia in KitW-sh/W-sh mice may influence the responses of these mice in this PIA model. PMID:23915716

  12. Decreased thyroidal response to thyrotropin in diabetic mice

    SciTech Connect

    Bagchi, N.; Brown, T.R.; Shivers, B.; Lucas, S.; Mack, R.E.

    1981-11-01

    The effect of diabetes mellitus on the synthesis and secretion of thyroid hormone ws investigated in mice with streptozotocin-induced diabetes. Thyroid glands were labeled in vivo with 131I for 2 h. In control animals, TSH stimulated the synthesis of PB127I and 131I-labeled iodothyronines and simultaneously decreased the proportion of 131I-. These effects of TSH were not observed in diabetic animals but were demonstrable in diabetic animals treated with insulin. For studies of hormone secretion, labeled thyroid glands were cultured in vitro in medium containing 1 mM mononitrotyrosine. The rate of the hydrolysis of labeled thyroglobulin was measured as the proportion of 131I-labeled iodotyrosines and 131I-labeled iodothyronines recovered at the end of culture and was used as an index of thyroid secretion. TSH in vivo stimulated the rate of thyroglobulin hydrolysis for 6 h, with a peak occurring after 2 h. The diabetic mice had a diminished response to TSH, which improved on treatment with insulin. The addition of TSH and insulin to the culture medium significantly increased the rate of thyroglobulin hydrolysis in glands of diabetic mice over that resulting from the addition of dibutyryl cAMP alone. The generation of thyroidal cAMP in response to TSH was higher in diabetic mice than in controls. The rise in plasma T4 and T3 2 h after the administration of TSH was less in diabetic mice than in control mice or diabetic mice treated with insulin. Our studies, therefore, indicate that the thyroidal response to TSH is decreased in diabetes mellitus. The defect appears to be at a step beyond the generation of cAMP.

  13. Transmammary infection in BALB/c mice with chronic toxocariasis.

    PubMed

    de Souza Aguiar, Patricia; Furtado, Raquel Dutra; de Avila, Luciana Farias da Costa; de Lima Telmo, Paula; Martins, Lourdes Helena Rodrigues; Berne, Maria Elisabeth Aires; da Silva, Pedro Eduardo Almeida; Scaini, Carlos James

    2015-04-01

    Human toxocariasis is a neglected public health problem. Infection of humans generally results from the accidental ingestion of embryonated Toxocara canis eggs, but it is important to broaden knowledge about other forms of transmission. This study aimed to demonstrate the prevalence of transmammary transmission in mice with chronic toxocariasis. BALB/c mice in groups 1 (G1) and 3 (G3) were inoculated with 1200 T. canis eggs 60days before mating, whereas those of group 2 (G2) were not infected. After delivery, the G1 neonates were transferred to G2 females to be nursed, and vice versa. Thus, the mice generated by G2 females and breastfed by G1 females could be infected only during lactation. In the G3 group, offspring were not exchanged. The search for T. canis larvae in the bodies of the lactating females and their offspring was performed after weaning and at 60days old, respectively. The frequency of transmammary infection in the mice generated by G2 uninfected females and breastfed by G1 infected females was 19.8%, which was similar to that observed (19.6%) in the mice bred and fed by G3 females. The frequency of infection in the mice generated by G1 females and breastfed by G2 females was only 4.2%, which was lower than that of G1 (p=0.0064) and G3 (p=0.0062) groups. Transmammary infection by mice with chronic toxocariasis was found to be more prevalent than congenital infection. PMID:24837181

  14. Glycogen synthase kinase 3? regulates urine concentrating mechanism in mice.

    PubMed

    Nřrregaard, Rikke; Tao, Shixin; Nilsson, Line; Woodgett, James R; Kakade, Vijayakumar; Yu, Alan S L; Howard, Christiana; Rao, Reena

    2015-03-15

    In mammals, glycogen synthase kinase (GSK)3 comprises GSK3? and GSK3? isoforms. GSK3? has been shown to play a role in the ability of kidneys to concentrate urine by regulating vasopressin-mediated water permeability of collecting ducts, whereas the role of GSK3? has yet to be discerned. To investigate the role of GSK3? in urine concentration, we compared GSK3? knockout (GSK3?KO) mice with wild-type (WT) littermates. Under normal conditions, GSK3?KO mice had higher water intake and urine output. GSK3?KO mice also showed reduced urine osmolality and aquaporin-2 levels but higher urinary vasopressin. When water deprived, they failed to concentrate their urine to the same level as WT littermates. The addition of 1-desamino-8-d-arginine vasopressin to isolated inner medullary collecting ducts increased the cAMP response in WT mice, but this response was reduced in GSK3?KO mice, suggesting reduced responsiveness to vasopressin. Gene silencing of GSK3? in mpkCCD cells also reduced forskolin-induced aquaporin-2 expression. When treated with LiCl, an isoform nonselective inhibitor of GSK3 and known inducer of polyuria, WT mice developed significant polyuria within 6 days. However, in GSK3?KO mice, the polyuric response was markedly reduced. This study demonstrates, for the first time, that GSK3? could play a crucial role in renal urine concentration and suggest that GSK3? might be one of the initial targets of Li(+) in LiCl-induced nephrogenic diabetes insipidus. PMID:25608967

  15. Human Cancer Xenografts in Outbred Nude Mice Can Be Confounded by Polymorphisms in a Modifier of Tumorigenesis

    PubMed Central

    Zeineldin, Maged; Jensen, Derek; Paranjape, Smita R.; Parelkar, Nikhil K.; Jokar, Iman; Vielhauer, George A.; Neufeld, Kristi L.

    2014-01-01

    Tumorigenicity studies often employ outbred nude mice, in the absence of direct evidence that this mixed genetic background will negatively affect experimental outcome. Here we show that outbred nude mice carry two different alleles of Pla2g2a, a genetic modifier of intestinal tumorigenesis in mice. Here, we identify previous unreported linked polymorphisms in the promoter, noncoding and coding sequences of Pla2g2a and show that outbred nude mice from different commercial providers are heterogeneous for this polymorphic Pla2g2a allele. This heterogeneity even extends to mice obtained from a single commercial provider, which display mixed Pla2g2a genotypes. Notably, we demonstrated that the polymorphic Pla2g2a allele affects orthotopic xenograft establishment of human colon cancer cells in outbred nude mice. This finding establishes a non-cell-autonomous role for Pla2g2a in suppressing intestinal tumorigenesis. Using in vitro reporter assays and pharmacological inhibitors, we show promoter polymorphisms and nonsense-mediated RNA decay (NMD) as underlying mechanisms that lead to low Pla2g2a mRNA levels in tumor-sensitive mice. Together, this study provides mechanistic insight regarding Pla2g2a polymorphisms and demonstrates a non-cell-autonomous role for Pla2g2a in suppressing tumors. Moreover, our direct demonstration that mixed genetic backgrounds of outbred nude mice can significantly affect baseline tumorigenicity cautions against future use of outbred mice for tumor xenograft studies. PMID:24913681

  16. Sucrose-conditioned flavor preferences in sweet ageusic T1r3 and Calhm1 knockout mice

    PubMed Central

    Sclafani, Anthony; Marambaud, Philippe; Ackroff, Karen

    2014-01-01

    The present study compared the ability of sweet ageusic T1r3 knockout (KO) and Calhm1 KO mice to acquire preferences for a sucrose-paired flavor as well as for unflavored sucrose. The KO and wildtype (WT) mice were given 24-h one-bottle access to 8% sucrose containing one flavor (CS+, e.g., grape) and to water containing a different flavor (CS-, e.g., cherry) over 4 training days. In subsequent two-bottle tests with the flavors in water only, the T1r3 KO and Calhm1 KO mice, like WT mice, preferred the CS+ to the CS-. After training with flavored solutions, both KO groups also preferred unflavored 8% sucrose to water although Calhm1 KO mice required more sugar experience to match the preference of the T1r3 KO mice. These findings demonstrate that Calhm1 KO mice, like T1r3 KO mice and WT mice, are sensitive to the post-oral preference conditioning actions of sucrose and can discriminate sugar from water. Yet, despite their acquired sucrose preferences, the Calhm1 KO and T1r3 KO mice consumed only half as much sugar per day as did WT mice. Thus, sweet taste signaling elements are not needed in the gut for sugar conditioning, but sweet taste signaling in the mouth is essential for the full expression of sugar appetite. PMID:24384370

  17. 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 Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka ; Takahashi-Yanaga, Fumi; Global Medical Science Education Unit, Faculty of Medical Sciences, Kyushu University, Fukuoka ; Sasaki, Masanori; Yoshihara, Tatsuya; Morimoto, Sachio; Takashima, Akihiko; Mori, Yoshihide; Sasaguri, Toshiyuki

    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.

  18. Volcanic features of Io

    USGS Publications Warehouse

    Carr, M.H.; Masursky, H.; Strom, R.G.; Terrile, R.J.

    1979-01-01

    Volcanic activity is apparently higher on Io than on any other body in the Solar System. Its volcanic landforms can be compared with features on Earth to indicate the type of volcanism present on Io. ?? 1979 Nature Publishing Group.

  19. 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

  20. Computed tomographic features of esophageal intramural pseudodiverticulosis

    SciTech Connect

    Pearlberg, J.L.; Sandler, M.A.; Madrazo, B.L.

    1983-04-01

    A patient wit esophageal intramural pseudodiverticulosis (EIPD) was examined with computed tomography (CT). CT demonstrated marked thichening of the esophageal wall, diffuse irregularity of the esophageal lumen, and intramural gas collections-features typical of this entity. In the proper clinical setting, CT can confirm the diagnosis of EIPD, especially when other studies are equivocal. However, this case also demonstrates some of the limitations of CT in differentiating benign and malignant esophageal disorders.

  1. Feature Characterization Library

    Energy Science and Technology Software Center (ESTSC)

    2006-08-03

    FCLib is a data analysis toolkit constructed to meet the needs of data discovery in large-scale, spatio-temporal data such as finite element simulation data. FCLib is a C library toolkit of building blocks that can be assembled into complex analyses. Important features of FCLib include the following: (1) Support of feature-based analysis, (2) minimization of low-oevel processing, (3) ease of use, and (4) applicable to the wide variety of science domains.

  2. Transgenic mice in developmental toxicology

    SciTech Connect

    Woychik, R.P.

    1992-01-01

    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  3. Transgenic mice in developmental toxicology

    SciTech Connect

    Woychik, R.P.

    1992-12-31

    Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areas of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.

  4. Owls and Larks in Mice

    PubMed Central

    Pfeffer, Martina; Wicht, Helmut; von Gall, Charlotte; Korf, Horst-Werner

    2015-01-01

    Humans come in different chronotypes and, particularly, the late chronotype (the so-called owl) has been shown to be associated with several health risks. A number of studies show that laboratory mice also display various chronotypes. In mice as well as in humans, the chronotype shows correlations with the period length and rhythm stability. In addition, some mouse models for human diseases show alterations in their chronotypic behavior, which are comparable to those humans. Thus, analysis of the behavior of mice is a powerful tool to unravel the molecular and genetic background of the chronotype and the prevalence of risks and diseases that are associated with it. In this review, we summarize the correlation of chronotype with free-running period length and rhythm stability in inbred mouse strains, in mice with a compromised molecular clockwork, and in a mouse model for neurodegeneration. PMID:26029157

  5. Soluble epoxide hydrolase deficiency ameliorates acute pancreatitis in mice.

    PubMed

    Bettaieb, Ahmed; Morisseau, Christophe; Hammock, Bruce; Haj, Fawaz

    2014-10-01

    Acute pancreatitis (AP) is a frequent gastrointestinal disorder that causes significant morbidity and its incidence has been progressively increasing. AP starts as a local inflammation in the pancreas that often leads to systemic inflammatory response and complications. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition in murine models has beneficial effects in inflammatory diseases, but its significance in AP remains unexplored. To investigate whether sEH may have a causal role in AP we utilized sEH knockout (KO) mice to determine the effects of sEH deficiency on ceruelin- and arginine-induced AP. sEH expression increased at the protein and messenger RNA levels, as well as sEH activity in the early phase of cerulein- and arginine-induced AP in mice. In addition, amylase and lipase levels were lower in cerulein-treated sEH KO mice compared with non-treated controls. Moreover, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1ß and IL-6 were lower in sEH KO mice compared with controls. Further, sEH KO mice exhibited decreased cerulein- and arginine-induced NF-?B inflammatory response, MAPKs activation and decreased cell death. These findings demonstrate a novel role for sEH in the progression of cerulein- and arginine-induced AP. PMID:26461340

  6. Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice.

    PubMed

    Hirase, Tetsuaki; Hara, Hiromitsu; Miyazaki, Yoshiyuki; Ide, Noriko; Nishimoto-Hazuku, Ai; Fujimoto, Hirokazu; Saris, Christiaan J M; Yoshida, Hiroki; Node, Koichi

    2013-08-01

    Chronic inflammation in arterial wall that is driven by immune cells and cytokines plays pivotal roles in the development of atherosclerosis. Interleukin 27 (IL-27) is a member of the IL-12 family of cytokines that consists of IL-27p28 and Epstein-Barr virus induced gene 3 (EBI3) and has anti-inflammatory properties that regulate T cell polarization and cytokine production. IL-27-deficient (Ldlr-/-Ebi3-/-) and IL-27 receptor-deficient (Ldlr-/-WSX-1-/-) Ldlr-/- mice were generated and fed with a high-cholesterol diet to induce atherosclerosis. Roles of bone marrow-derived cells in vivo and macrophages in vitro were studied using bone marrow reconstitution by transplantation and cultured peritoneal macrophages, respectively. We demonstrate that mice lacking IL-27 or IL-27 receptor are more susceptible to atherosclerosis compared with wild type due to enhanced accumulation and activation of macrophages in arterial walls. The number of circulating proinflammatory Ly6C(hi) monocytes showed no significant difference between wild-type mice and mice lacking IL-27 or IL-27 receptor. Administration of IL-27 suppressed the development of atherosclerosis in vivo and macrophage activation in vitro that was indicated by increased uptake of modified low-density lipoprotein and augmented production of proinflammatory cytokines. These findings define a novel inhibitory role for IL-27 in atherosclerosis that regulates macrophage activation in mice. PMID:23729211

  7. Behavioral stress accelerates prostate cancer development in mice.

    PubMed

    Hassan, Sazzad; Karpova, Yelena; Baiz, Daniele; Yancey, Dana; Pullikuth, Ashok; Flores, Anabel; Register, Thomas; Cline, J Mark; D'Agostino, Ralph; Danial, Nika; Datta, Sandeep Robert; Kulik, George

    2013-02-01

    Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress-prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor involution both in phosphatase and tensin homolog-deficient (PTEN-deficient) prostate cancer xenografts treated with PI3K inhibitor and in prostate tumors of mice with prostate-restricted expression of c-MYC (Hi-Myc mice) subjected to androgen ablation therapy with bicalutamide. Additionally, stress accelerated prostate cancer development in Hi-Myc mice. The effects of stress were prevented by treatment with the selective ?2-adrenergic receptor (ADRB2) antagonist ICI118,551 or by inducible expression of PKA inhibitor (PKI) or of BCL2-associated death promoter (BAD) with a mutated PKA phosphorylation site (BADS112A) in xenograft tumors. Effects of stress were also blocked in Hi-Myc mice expressing phosphorylation-deficient BAD (BAD3SA). These results demonstrate interactions between prostate tumors and the psychosocial environment mediated by activation of an adrenaline/ADRB2/PKA/BAD antiapoptotic signaling pathway. Our findings could be used to identify prostate cancer patients who could benefit from stress reduction or from pharmacological inhibition of stress-induced signaling. PMID:23348742

  8. Massage-like stroking boosts the immune system in mice

    PubMed Central

    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

  9. 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

  10. Integrating electrostatics with demonstrations and interactive teaching

    NASA Astrophysics Data System (ADS)

    Chang, Wheijen

    2011-02-01

    Teaching electrostatics is challenging due to its complexity and high degree of abstraction. To facilitate students' understanding of the meanings and relations of the key terms, this paper describes a series of demonstrations and conceptual questions based on an interactive teaching approach. The context was an introductory university physics course for engineering and science students in Taiwan. Features of the teaching intervention include the utilization of a series of demonstrations for repeated practice applying the important concepts, the incorporation of derivations of equations and verbal elaboration of concepts, and the engagement of students in thinking and discussing. Data show that the teaching intervention benefited the students' academic performance and their satisfaction with the learning achievement.

  11. Feature correlation guidance in category visual search.

    PubMed

    Wu, Rachel; Pruitt, Zoe; Runkle, Megan; Meyer, Kristen; Scerif, Gaia; Aslin, Richard

    2015-09-01

    Compared to objects with uncorrelated features (e.g., jelly beans come in many colors), objects with correlated features (e.g., bananas tend to be yellow) enable more robust object and category representations (e.g., Austerweil & Griffiths, 2011; Wu et al., 2011; Younger & Cohen, 1986). It is unknown whether these more robust representations impact attentional templates (i.e., working memory representations guiding visual search). Adults participated in four visual search tasks (2x2 design) where targets were defined as either one item (a specific alien) or a category (any alien) with correlated features (e.g., circle belly shape, circle back spikes) or uncorrelated features (e.g., circle belly shape, triangle back spikes). We measured behavioral responses and the N2pc component, an event-related potential (ERP) marker for target selection. Behavioral responses were better for correlated items than uncorrelated items for both exemplar and category search. While the N2pc amplitude was larger for exemplar search compared to category search, the amplitude only differed based on feature correlation for category search: The N2pc was present for category search with correlated features, and not present in search for uncorrelated features. Our ERP results demonstrate that correlated (and not uncorrelated) features for novel categories provide a robust category representation that can guide visual search. Meeting abstract presented at VSS 2015. PMID:26326614

  12. Presenilin transgenic mice as models of Alzheimer’s disease

    PubMed Central

    Elder, Gregory A.; Sosa, Miguel A. Gama; De Gasperi, Rita; Dickstein, Dara L.; Hof, Patrick R.

    2012-01-01

    Mutations in presenilin-1 (PS1) and presenilin-2 (PS2) cause familial Alzheimer’s disease (FAD). Presenilins influence multiple molecular pathways and are best known for their role in the ?-secretase cleavage of type I transmembrane proteins including the amyloid precursor protein (APP). PS1 and PS2 FAD mutant transgenic mice have been generated using a variety of promoters. PS1-associated FAD mutations have also been knocked into the endogenous mouse gene. PS FAD mutant mice consistently show elevations of A?42 with little if any effect on A?40. When crossed with plaque forming APP FAD mutant lines, the PS1 FAD mutants cause earlier and more extensive plaque deposition. Although single transgenic PS1 or PS2 mice do not form plaques, they exhibit a number of pathological features including age-related neuronal and synaptic loss as well as vascular pathology. They also exhibit increased susceptibility to excitotoxic injury most likely on the basis of exaggerated calcium release from the endoplasmic reticulum. Electrophysiologically long-term potentiation in the hippocampus is increased in young PS1 FAD mutant mice but this effect appears to be lost with aging. In most studies neurogenesis in the adult hippocampus is also impaired by PS1 FAD mutants. Mice in which PS1 has been conditionally knocked out in adult forebrain on a PS2 null background (PS1/2 cDKO) develop a striking neurodegeneration that mimics AD neuropathology in being associated with neuronal and synaptic loss, astrogliosis and hyperphosphorylation of tau, although it is not accompanied by plaque deposits. The relevance of PS transgenic mice as models of AD is discussed. PMID:19921519

  13. The MICE grand challenge lightcone simulation - I. Dark matter clustering

    NASA Astrophysics Data System (ADS)

    Fosalba, P.; Crocce, M.; Gaztańaga, E.; Castander, F. J.

    2015-04-01

    We present a new N-body simulation from the Marenostrum Institut de Cičncies de l'Espai (MICE) collaboration, the MICE Grand Challenge (MICE-GC), containing about 70 billion dark matter particles in a (3 Gpc h-1)3 comoving volume. Given its large volume and fine spatial resolution, spanning over five orders of magnitude in dynamic range, it allows an accurate modelling of the growth of structure in the universe from the linear through the highly non-linear regime of gravitational clustering. We validate the dark matter simulation outputs using 3D and 2D clustering statistics, and discuss mass-resolution effects in the non-linear regime by comparing to previous simulations and the latest numerical fits. We show that the MICE-GC run allows for a measurement of the BAO feature with per cent level accuracy and compare it to state-of-the-art theoretical models. We also use sub-arcmin resolution pixelized 2D maps of the dark matter counts in the lightcone to make tomographic analyses in real and redshift space. Our analysis shows the simulation reproduces the Kaiser effect on large scales, whereas we find a significant suppression of power on non-linear scales relative to the real space clustering. We complete our validation by presenting an analysis of the three-point correlation function in this and previous MICE simulations, finding further evidence for mass-resolution effects. This is the first of a series of three papers in which we present the MICE-GC simulation, along with a wide and deep mock galaxy catalogue built from it. This mock is made publicly available through a dedicated web portal, http://cosmohub.pic.es.

  14. Tamoxifen administration to mice.

    PubMed

    Whitfield, Jonathan; Littlewood, Trevor; Soucek, Laura

    2015-03-01

    The strategy of fusing a protein of interest to a hormone-binding domain (HBD) of a steroid hormone receptor allows fine control of the activity of the fused protein. Such fusion proteins are inactive in the absence of ligand, because they are complexed with a variety of intracellular polypeptides. Upon ligand binding, the receptor is released from its inhibitory complex and the fusion protein becomes functional. In the murine estrogen receptor (ER) fusion system, proteins are fused to the HBD of the ER. The system relies on the use of a mutant ER known as ER(TAM). Compared to the wild-type HBD, ER(TAM) has 1000-fold lower affinity for estrogen, yet remains responsive to activation by the synthetic steroid 4-hydroxytamoxifen (4-OHT). Because 4-OHT is expensive, animals can be treated with the cheaper precursor tamoxifen, which is converted into 4-OHT by a liver enzyme. Here we present an overview of the methods used to deliver tamoxifen to mice. The most used method is intraperitoneal injection, because the amount of administered compound can be better controlled, but delivery by oral gavage is also possible. For short-term and immediate-effect studies or when conversion of tamoxifen by the liver is to be avoided, 4-OHT can be used directly. PMID:25734062

  15. Inborn anemias in mice

    SciTech Connect

    Bernstein, S.E.; Barker, J.E.; Russell, E.S.

    1981-06-01

    hereditary anemias of mice have been the chief objects of investigation. At present under study are four macrocytic anemias, five hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an ..cap alpha..-thalassemia, and a new target-cell anemia. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: (a) characterization of peripheral blood values, (b) determinations of radiosensitivity under a variety of conditions, (c) measurements of iron metabolism and heme synthesis, (d) histological and biochemical study of blood-forming tissue, (e) functional tests of the stem cell component, (f) examination of responses to erythroid stimuli, and (g) transplantation of tissue between individuals of differently affected genotypes.

  16. Functional knock down of VCAM1 in mice mediated by endoplasmatic reticulum retained intrabodies

    PubMed Central

    Marschall, Andrea LJ; Single, Frank N; Schlarmann, Katrin; Bosio, Andreas; Strebe, Nina; van den Heuvel, Joop; Frenzel, André; Dübel, Stefan

    2014-01-01

    Functional knockdowns mediated by endoplasmatic reticulum-retained antibodies (ER intrabodies) are a promising tool for research because they allow functional interference on the protein level. We demonstrate for the first time that ER intrabodies can induce a knock-down phenotype in mice. Surface VCAM1 was suppressed in bone marrow of heterozygous and homozygous ER intrabody mice (iER-VCAM1 mice). iER-VCAM1 mice did not have a lethal phenotype, in contrast to the constitutive knockout of VCAM1, but adult mice exhibited physiological effects in the form of aberrant distribution of immature B-cells in blood and bone marrow. The capability to regulate knock-down strength may spark a new approach for the functional study of membrane and plasma proteins, which may especially be valuable for generating mouse models that more closely resemble disease states than classic knockouts do. PMID:25484057

  17. In vivo auditory brain mapping in mice with Mn-enhanced MRI

    PubMed Central

    Yu, Xin; Wadghiri, Youssef Zaim; Sanes, Dan H; Turnbull, Daniel H

    2007-01-01

    There are currently no noninvasive imaging methods available for auditory brain mapping in mice, despite the increasing use of genetically engineered mice to study auditory brain development and hearing loss. We developed a manganese-enhanced MRI (MEMRI) method to map regions of accumulated sound-evoked activity in awake, normally behaving mice. To demonstrate its utility for high-resolution (100-?m) brain mapping, we used MEMRI to show the tonotopic organization of the mouse inferior colliculus. To test its efficacy in an experimental setting, we acquired data from mice experiencing unilateral conductive hearing loss at different ages. Larger and persistent changes in auditory brainstem activity resulted when hearing loss occurred before the onset of hearing, showing that early hearing loss biases the response toward the functional ear. Thus, MEMRI provides a sensitive and effective method for mapping the mouse auditory brainstem and has great potential for a range of functional neuroimaging studies in normal and mutant mice. PMID:15924136

  18. Progesterone receptor knockout mice have an improved glucose homeostasis secondary to -cell proliferation

    NASA Astrophysics Data System (ADS)

    Picard, Frédéric; Wanatabe, Mitsuhiro; Schoonjans, Kristina; Lydon, John; O'Malley, Bert W.; Auwerx, Johan

    2002-11-01

    Gestational diabetes coincides with elevated circulating progesterone levels. We show that progesterone accelerates the progression of diabetes in female db/db mice. In contrast, RU486, an antagonist of the progesterone receptor (PR), reduces blood glucose levels in both female WT and db/db mice. Furthermore, female, but not male, PR-/- mice had lower fasting glycemia than PR+/+ mice and showed higher insulin levels on glucose injection. Pancreatic islets from female PR-/- mice were larger and secreted more insulin consequent to an increase in -cell mass due to an increase in -cell proliferation. These findings demonstrate an important role of progesterone signaling in insulin release and pancreatic function and suggest that it affects the susceptibility to diabetes.

  19. The growth and development of Schistosoma mansoni in mice exposed to sublethal doses of radiation

    SciTech Connect

    Aitken, R.; Wilson, R.A. )

    1989-12-01

    The maturation of Schistosoma mansoni was studied in mice exposed to various sublethal doses of radiation. Although the treatment of mice with 500 rads of radiation prior to infection did not alter parasite maturation, doses in excess of 500 rads led to a reduction in worm burden. This could not be attributed to a delay in the arrival of parasites in the hepatic portal system. Worms developing in mice treated with 800 rads commenced egg-laying about 1 wk later than worms in intact mice, and the rate of egg deposition appeared to be lower in irradiated hosts. The data demonstrate that exposure of C57BL/6 mice to doses of radiation in excess of 500 rads impairs their ability to carry infections of S. mansoni. The findings do not support the hypothesis that primary worm burdens in the mouse are controlled by a host immune response.

  20. Danggui Buxue Tang Inhibits 2,4-Dinitrochlorobenzene: Induced Atopic Dermatitis in Mice

    PubMed Central

    Fang, Li-Wen; Cheng, Chao-Chun; Hwang, Tzann-Shun; Huang, Wen-Chung; Liou, Chian-Jiun; Chen, Wen-Chyuan; Wu, Shu-Ju

    2015-01-01

    Danggui Buxue Tang (DBT) is a herbal decoction that has been used in Chinese medicine to enhance qi and blood circulation. Previously, we found that DBT can suppress allergy-related asthma in mice, leading us to hypothesize that DBT might ameliorate allergy disease. In this study, we evaluated whether DBT can attenuate atopic dermatitis (AD) symptoms and have an anti-inflammatory effect on AD-like mice. The dorsal skin of female mice was shaved and sensitized cutaneously (skin smear) with 1-chloro-2,4-dinitrobenzene. Mice were then given various doses of DBT from days 14 to 29 cutaneously. DBT treatment suppressed ear swelling and skin inflammation and decreased mast cell and eosinophil infiltration into skin and ear tissue. DBT also inhibited levels of IgE and Th2-associated cytokine levels in serum. These results demonstrate that cutaneous administration of DBT reduced the development of AD-like skin lesions in mice. PMID:25861366

  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. Demonstration: Male Workers in Day Care. Demonstration Project Progress Report.

    ERIC Educational Resources Information Center

    McCandless, B. R.

    A demonstration project using young men as day care workers in the Early Learning and Child care centers in Atlanta is described. The proposal for the demonstration project and a progress report are given. Four white advantaged and four black disadvantaged male high school students were recruited to work as caregivers for black and white boys and…

  3. A Protocol for Housing Mice in an Enriched Environment

    PubMed Central

    Slater, Andrew M.; Cao, Lei

    2015-01-01

    Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent studies demonstrate that environmental enrichment decreases adiposity, increases energy expenditure, resists diet induced obesity, and causes cancer remission and inhibition in mice. EE typically consists of larger living space, a variety of ‘toys’ to interact with, running wheels, and can include a number of other novel environmental changes. All of this fosters a more complex social engagement, cognitive and physical stimulations. Importantly, the toy location and type of toy is changed regularly, which encourages the mice to adapt to a frequently changing and novel environment. Many variables can be manipulated in EE to promote health effects in mice. Thus these approaches are difficult to control and must be properly managed to successfully replicate the associated phenotypes. Therefore, the goal of this video is to demonstrate how EE is properly set up and maintained to assure a complex, challenging, and controlled environment so that other researchers can easily reproduce the protective effects of EE against obesity and cancer. PMID:26131694

  4. A Protocol for Housing Mice in an Enriched Environment.

    PubMed

    Slater, Andrew M; Cao, Lei

    2015-01-01

    Environmental enrichment (EE) is a housing environment for mice that boosts mental and physical health compared to standard laboratory housing. Our recent studies demonstrate that environmental enrichment decreases adiposity, increases energy expenditure, resists diet induced obesity, and causes cancer remission and inhibition in mice. EE typically consists of larger living space, a variety of 'toys' to interact with, running wheels, and can include a number of other novel environmental changes. All of this fosters a more complex social engagement, cognitive and physical stimulations. Importantly, the toy location and type of toy is changed regularly, which encourages the mice to adapt to a frequently changing and novel environment. Many variables can be manipulated in EE to promote health effects in mice. Thus these approaches are difficult to control and must be properly managed to successfully replicate the associated phenotypes. Therefore, the goal of this video is to demonstrate how EE is properly set up and maintained to assure a complex, challenging, and controlled environment so that other researchers can easily reproduce the protective effects of EE against obesity and cancer. PMID:26131694

  5. Feature Hashing for Large Scale Multitask Learning

    E-print Network

    Weinberger, Kilian; Attenberg, Josh; Langford, John; Smola, Alex

    2009-01-01

    Empirical evidence suggests that hashing is an effective strategy for dimensionality reduction and practical nonparametric estimation. In this paper we provide exponential tail bounds for feature hashing and show that the interaction between random subspaces is negligible with high probability. We demonstrate the feasibility of this approach with experimental results for a new use case -- multitask learning with hundreds of thousands of tasks.

  6. 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.

  7. 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....

  8. Contracting to Demonstrate Teacher Competencies.

    ERIC Educational Resources Information Center

    Lux, John E.

    1979-01-01

    The Lincoln, Nebraska, Teacher Corps' contracting process offers an effective model for team teaching, individualizing/personalizing instruction, and demonstrating both teacher and learner levels of competency. (JMF)

  9. Long-Lived ?MUPA Mice Show Attenuation of Cardiac Aging and Leptin-Dependent Cardioprotection

    PubMed Central

    Levy, Esther; Kornowski, Ran; Gavrieli, Reut; Fratty, Ilana; Greenberg, Gabriel; Waldman, Maayan; Birk, Einat; Shainberg, Asher; Akirov, Amit; Miskin, Ruth; Hochhauser, Edith

    2015-01-01

    ?MUPA transgenic mice spontaneously consume less food compared with their wild type (WT) ancestors due to endogenously increased levels of the satiety hormone leptin. ?MUPA mice share many benefits with mice under caloric restriction (CR) including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of ?MUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI) in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, ?MUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while ?MUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in ?MUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in ?MUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin) abrogated the ?MUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the ?MUPA myocardium. ?MUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of ?MUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in ?MUPA mice, indicating the attenuation of cardiac aging. ?MUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR. PMID:26673217

  10. Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice

    PubMed Central

    Lakritz, Jessica R; Poutahidis, Theofilos; Levkovich, Tatiana; Varian, Bernard J; Ibrahim, Yassin M; Chatzigiagkos, Antonis; Mirabal, Sheyla; Alm, Eric J; Erdman, Susan E

    2014-01-01

    Recent studies suggest health benefits including protection from cancer after eating fermented foods such as probiotic yogurt, though the mechanisms are not well understood. Here we tested mechanistic hypotheses using two different animal models: the first model studied development of mammary cancer when eating a Westernized diet, and the second studied animals with a genetic predilection to breast cancer. For the first model, outbred Swiss mice were fed a Westernized chow putting them at increased risk for development of mammary tumors. In this Westernized diet model, mammary carcinogenesis was inhibited by routine exposure to Lactobacillus reuteri ATCC-PTA-6475 in drinking water. The second model was FVB strain erbB2 (HER2) mutant mice, genetically susceptible to mammary tumors mimicking breast cancers in humans, being fed a regular (non-Westernized) chow diet. We found that oral supplement with these purified lactic acid bacteria alone was sufficient to inhibit features of mammary neoplasia in both models. The protective mechanism was determined to be microbially-triggered CD4+CD25+ lymphocytes. When isolated and transplanted into other subjects, these L. reuteri-stimulated lymphocytes were sufficient to convey transplantable anti-cancer protection in the cell recipient animals. These data demonstrate that host immune responses to environmental microbes significantly impact and inhibit cancer progression in distal tissues such as mammary glands, even in genetically susceptible mice. This leads us to conclude that consuming fermentative microbes such as L. reuteri may offer a tractable public health approach to help counteract the accumulated dietary and genetic carcinogenic events integral in the Westernized diet and lifestyle. What's new? Can eating fermented foods like yogurt ward off cancer? Recent studies have suggested it's possible. To find out how, these authors isolated the probiotic bacteria involved in fermentation and fed them to mice that were susceptible to mammary tumors. These mice either had genetic changes predisposing them to cancer or were fed a diet known to increase their likelihood of developing the tumors. Eating the lactic acid bacteria stimulated an immune response that delayed the onset of tumors in both models, suggesting a potential avenue to prevent the cancer in humans. PMID:24382758

  11. Healthy mice (HC) Infected mice (MC) Infected mice + CQ (MD) Spleen length (cm) 1.650.10 2.620.18 3.16 0.14

    E-print Network

    Dao, Ming

    S1A B Healthy mice (HC) Infected mice (MC) Infected mice + CQ (MD) Spleen length (cm) 1.65±0.10 2 than three experimental rounds have been performed separately for healthy and malarial mice during data acquisition. Spleen size and RBC deformability were compared and summarized among healthy mice, infected mice

  12. Prolactin rescues and primes autoreactive B cells directly and indirectly through dendritic cells in B6.Sle3 mice

    PubMed Central

    Gonzalez, J; Saha, S; Peeva, E

    2013-01-01

    The lupus susceptibility interval Sle3/5 confers responsiveness to prolactin in C57BL/6 (B6) mice and hyperprolactinaemia induces a lupus-like phenotype in B6.Sel3/5 mice. In this study, the immunostimulatory effects of prolactin in B6 mice containing the Sle3 portion of the Sel3/5 interval (B6.Sle3 mice) were dissected. Because of the Sle3 interval's involvement in activation of myeloid cells, the effect of dendritic cells (DCs) from prolactin-treated B6.Sle3 mice on the phenotype of B6 mice was also evaluated. B cells from prolactin-treated B6 and B6.Sle3 mice and from B6 recipients of prolactin-modulated DCs from B6.Sle3 mice were tested for DNA-reactivity and resistance to B cell receptor (BCR)-mediated apoptosis. The expression of co-stimulatory molecules on lymphocytes and myeloid cells was also evaluated. In prolactin-treated B6.Sle3 mice, transitional type 2 B cells increased while type 1 B cells decreased as a consequence of prolactin-induced resistance to BCR-mediated apoptosis leading to the survival of DNA-reactive B cells. Follicular B cells from prolactin-treated mice expressed increased levels of CD40, B7·2 and IAb, and DCs and monocytes had higher levels of CD44 and B7·2 than placebo-treated mice. Adoptive transfer of DCs from prolactin-treated B6.Sle3 mice to B6 recipients demonstrated the intrinsic ability of prolactin-modulated DCs to induce a development of lupus-like characteristics in B6 mice. Based on these results, prolactin accelerates the breakdown of immune tolerance in B6.Sle3 mice by promoting the survival, maturation and activation of autoreactive B cells, DCs and macrophages. PMID:23574327

  13. 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.

  14. Acute Starvation Protects Mice Against Listeria monocytogenes

    PubMed Central

    Wing, Edward J.; Young, James B.

    1980-01-01

    We investigated the effect of starvation on the course of Listeria monocytogenes infections in mice. Mice starved for 24, 48, or 72 h and then inoculated with a lethal dose of L. monocytogenes showed significantly less mortality than mice not starved (i.e., fed mice). The protective effect of 48 or 72 h of starvation began immediately after the starvation period and persisted for at least 48 h. Starved, infected mice had significantly fewer L. monocytogenes cells in their spleens 2, 3, and 4 days after infection than did fed mice. Neither changes in T-lymphocyte function nor serum factors appeared to be responsible for the protective effect. Delayed hypersensitivity responses to L. monocytogenes antigen were smaller in starved mice than in fed mice. Adoptive transfer of spleen cells from nonimmune starved mice did not protect against L. monocytogenes. Additional studies indicated that the serum of starved mice did not inhibit multiplication of L. monocytogenes in vitro, nor was it able to transfer protection against L. monocytogenes to normal mice. In contrast, peritoneal macrophages from starved mice inhibited deoxyribonucleic acid synthesis of P815 tumor cells compared with macrophages from control mice. Therefore, the resistance of starved mice to L. monocytogenes is most likely due to nonspecific factors, one of which may be activation of macrophages. PMID:6772566

  15. Knockout of the TauT Gene Predisposes C57BL/6 Mice to Streptozotocin-Induced Diabetic Nephropathy

    PubMed Central

    Han, Xiaobin; Patters, Andrea B.; Ito, Takashi; Schaffer, Stephen W.; Chesney, Russell W.

    2015-01-01

    Diabetic nephropathy is the leading cause of end stage renal disease in the world. Although tremendous efforts have been made, scientists have yet to identify an ideal animal model that can reproduce the characteristics of human diabetic nephropathy. In this study, we hypothesize that taurine insufficiency is a critical risk factor for development of diabetic nephropathy associated with diabetes mellitus. This hypothesis was tested in vivo in TauT heterozygous (TauT+/-) and homozygous (TauT-/-) knockout in C57BL/6 background mice. We have shown that alteration of the TauT gene (also known as SLC6A6) has a substantial effect on the susceptibility to development of extensive diabetic kidney disease in both TauT+/- and TauT-/-mouse models of diabetes. These animals developed histological changes characteristic of human diabetic nephropathy that included glomerulosclerosis, nodular lesions, arteriosclerosis, arteriolar dilation, and tubulointerstitial fibrosis. Immunohistochemical staining of molecular markers of smooth muscle actin, CD34, Ki67 and collagen IV further confirmed these observations. Our results demonstrated that both homozygous and heterozygous TauT gene deletion predispose C57BL/6 mice to develop end-stage diabetic kidney disease, which closely replicates the pathological features of diabetic nephropathy in human diabetic patients. PMID:25629817

  16. Exercise performance and peripheral vascular insufficiency improve with AMPK activation in high-fat diet-fed mice

    PubMed Central

    Baltgalvis, Kristen A.; White, Kathy; Li, Wei; Claypool, Mark D.; Lang, Wayne; Alcantara, Raniel; Singh, Baljit K.; Friera, Annabelle M.; McLaughlin, John; Hansen, Derek; McCaughey, Kelly; Nguyen, Henry; Smith, Ira J.; Godinez, Guillermo; Shaw, Simon J.; Goff, Dane; Singh, Rajinder; Markovtsov, Vadim; Sun, Tian-Qiang; Jenkins, Yonchu; Uy, Gerald; Li, Yingwu; Pan, Alison; Gururaja, Tarikere; Lau, David; Park, Gary; Hitoshi, Yasumichi; Payan, Donald G.

    2014-01-01

    Intermittent claudication is a form of exercise intolerance characterized by muscle pain during walking in patients with peripheral artery disease (PAD). Endothelial cell and muscle dysfunction are thought to be important contributors to the etiology of this disease, but a lack of preclinical models that incorporate these elements and measure exercise performance as a primary end point has slowed progress in finding new treatment options for these patients. We sought to develop an animal model of peripheral vascular insufficiency in which microvascular dysfunction and exercise intolerance were defining features. We further set out to determine if pharmacological activation of 5?-AMP-activated protein kinase (AMPK) might counteract any of these functional deficits. Mice aged on a high-fat diet demonstrate many functional and molecular characteristics of PAD, including the sequential development of peripheral vascular insufficiency, increased muscle fatigability, and progressive exercise intolerance. These changes occur gradually and are associated with alterations in nitric oxide bioavailability. Treatment of animals with an AMPK activator, R118, increased voluntary wheel running activity, decreased muscle fatigability, and prevented the progressive decrease in treadmill exercise capacity. These functional performance benefits were accompanied by improved mitochondrial function, the normalization of perfusion in exercising muscle, increased nitric oxide bioavailability, and decreased circulating levels of the endogenous endothelial nitric oxide synthase inhibitor asymmetric dimethylarginine. These data suggest that aged, obese mice represent a novel model for studying exercise intolerance associated with peripheral vascular insufficiency, and pharmacological activation of AMPK may be a suitable treatment for intermittent claudication associated with PAD. PMID:24561866

  17. 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.

  18. Escalator design features evaluation

    NASA Technical Reports Server (NTRS)

    Zimmerman, W. F.; Deshpande, G. K.

    1982-01-01

    Escalators are available with design features such as dual speed (90 and 120 fpm), mat operation and flat steps. These design features were evaluated based on the impact of each on capital and operating costs, traffic flow, and safety. A human factors engineering model was developed to analyze the need for flat steps at various speeds. Mat operation of escalators was found to be cost effective in terms of energy savings. Dual speed operation of escalators with the higher speed used during peak hours allows for efficient operation. A minimum number of flat steps required as a function of escalator speed was developed to ensure safety for the elderly.

  19. The Effects of Acute Blood Loss for Diagnostic Bloodwork and Fluid Replacement in Clinically Ill Mice.

    PubMed

    Marx, James O; Jensen, JanLee A; Seelye, Stacie; Walton, Raquel M; Hankenson, F Claire

    2015-06-01

    Despite the great value of diagnostic bloodwork for identifying disease in animals, the volume of blood required for these analyses limits its use in laboratory mice, particularly when they are clinically ill. We sought to determine the effects of acute blood loss (ABL) following blood collection for diagnostic bloodwork in healthy mice compared with streptozotocin-induced diabetic and dextran sulfate sodium (DSS)-treated dehydrated mice. ABL caused several mild changes in the control mice, with significant decreases in body weight, temperature, and activity in both experimental groups; increased dehydration and azotemia in the DSS-treated mice; and a significant drop in the blood pressure of the diabetic mice. To determine whether these negative outcomes could be ameliorated, we treated mice with intraperitoneal lactated Ringers solution either immediately after or 30 min before ABL. Notably, preABL administration of fluids helped prevent the worsening of the dehydration and azotemia in the DSS-treated mice and the changes in blood pressure in the diabetic mice. However, fluid administration provided no benefit in control of blood pressure when administered after ABL in the diabetic mice. Furthermore, fluid therapy did not prevent ABL-induced drops in body weight and activity. Although one mouse not receiving fluid therapy became moribund at the 24-h time point, no animals died during the 24-h study. This investigation demonstrates that blood for diagnostic bloodwork can be collected safely from clinically ill mice and that preemptive fluid therapy mitigates some of the negative changes associated with this blood loss. PMID:26141445

  20. Salivary Gland Hypofunction in tyrosylprotein sulfotransferase-2 Knockout Mice Is Due to Primary Hypothyroidism

    PubMed Central

    Westmuckett, Andrew D.; Siefert, Joseph C.; Tesiram, Yasvir A.; Pinson, David M.; Moore, Kevin L.

    2013-01-01

    Background Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). We reported that Tpst2-/- mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are euthyroid. While using magnetic resonance imaging (MRI) to look at the thyroid gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than in wild type mice. This prompted a detailed analysis to compare salivary gland structure and function in wild type, Tpst1-/-, and Tpst2 -/- mice. Methodology/Principal Findings Quantitative MRI imaging documented that salivary glands in Tpst2-/- females were ? 30% smaller than wild type or Tpst1-/- mice and that the granular convoluted tubules in Tpst2-/- submandibular glands were less prominent and were almost completely devoid of exocrine secretory granules compared to glands from wild type or Tpst1-/- mice. In addition, pilocarpine–induced salivary flow and salivary ?-amylase activity in Tpst2-/- mice of both sexes was substantially lower than in wild type and Tpst1-/- mice. Anti-sulfotyrosine Western blots of salivary gland extracts and saliva showed no differences between wild type, Tpst1-/-, and Tpst2-/- mice, suggesting that the salivary gland hypofunction is due to factor(s) extrinsic to the salivary glands. Finally, we found that all indicators of hypothyroidism (serum T4, body weight) and salivary gland hypofunction (salivary flow, salivary ?-amylase activity, histological changes) were restored to normal or near normal by thyroid hormone supplementation. Conclusions/Significance Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism. PMID:23951251

  1. M4 muscarinic receptor knockout mice display abnormal social behavior and decreased prepulse inhibition

    PubMed Central

    2012-01-01

    Background In the central nervous system (CNS), the muscarinic system plays key roles in learning and memory, as well as in the regulation of many sensory, motor, and autonomic processes, and is thought to be involved in the pathophysiology of several major diseases of the CNS, such as Alzheimer's disease, depression, and schizophrenia. Previous studies reveal that M4 muscarinic receptor knockout (M4R KO) mice displayed an increase in basal locomotor activity, an increase in sensitivity to the prepulse inhibition (PPI)-disrupting effect of psychotomimetics, and normal basal PPI. However, other behaviorally significant roles of M4R remain unclear. Results In this study, to further investigate precise functional roles of M4R in the CNS, M4R KO mice were subjected to a battery of behavioral tests. M4R KO mice showed no significant impairments in nociception, neuromuscular strength, or motor coordination/learning. In open field, light/dark transition, and social interaction tests, consistent with previous studies, M4R KO mice displayed enhanced locomotor activity compared to their wild-type littermates. In the open field test, M4R KO mice exhibited novelty-induced locomotor hyperactivity. In the social interaction test, contacts between pairs of M4R KO mice lasted shorter than those of wild-type mice. In the sensorimotor gating test, M4R KO mice showed a decrease in PPI, whereas in the startle response test, in contrast to a previous study, M4R KO mice demonstrated normal startle response. M4R KO mice also displayed normal performance in the Morris water maze test. Conclusions These findings indicate that M4R is involved in regulation of locomotor activity, social behavior, and sensorimotor gating in mice. Together with decreased PPI, abnormal social behavior, which was newly identified in the present study, may represent a behavioral abnormality related to psychiatric disorders including schizophrenia. PMID:22463818

  2. Chronic Toxoplasma gondii in Nurr1-Null Heterozygous Mice Exacerbates Elevated Open Field Activity

    PubMed Central

    Eells, Jeffrey B.; Varela-Stokes, Andrea; Guo-Ross, Shirley X.; Kummari, Evangel; Smith, Holly M.; Cox, Erin; Lindsay, David S.

    2015-01-01

    Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population) and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%), genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/-) mice and wild-type (+/+) mice were evaluate using an emergence test, activity in an open field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI) prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice. PMID:25855987

  3. Reduced Number and Morphofunctional Change of Alveolar Macrophages in MafB Gene-Targeted Mice

    PubMed Central

    Sato-Nishiwaki, Michiko; Aida, Yasuko; Abe, Shuichi; Shibata, Yoko; Kimura, Tomomi; Yamauchi, Keiko; Kishi, Hiroyuki; Igarashi, Akira; Inoue, Sumito; Sato, Masamichi; Nakajima, Osamu; Kubota, Isao

    2013-01-01

    Alveolar macrophages (AMs) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated that the transcription factor, MafB, increased in the AMs of mice exposed to cigarette smoke, and in those of human patients with COPD. The aim of this study was to evaluate the role of MafB in AMs using newly established transgenic (TG) mice that specifically express dominant negative (DN) MafB in macrophages under the control of macrophage scavenger receptor (MSR) enhancer-promoter. We performed cell differential analyses in bronchoalveolar lavage cells, morphological analyses with electron microscopy, and flow cytometry-based analyses of surface markers and a phagocytic capacity assay in macrophages. AM number in the TG mice was significantly decreased compared with wild-type (WT) mice. Morphologically, the high electron density area in the nucleus increased, the shape of pseudopods on the AMs was altered, and actin filament was less localized in the pseudopods of AMs of TG mice, compared with WT mice. The expression of surface markers, F4/80 and CD11b, on peritoneal macrophages in TG mice was reduced compared with WT mice, while those on AMs remained unchanged. Phagocytic capacity was decreased in AMs from TG mice, compared with WT mice. In conclusion, MafB regulates the phenotype of macrophages with respect to the number of alveolar macrophages, the nuclear compartment, cellular shape, surface marker expression, and phagocytic function. MSR-DN MafB TG mice may present a useful model to clarify the precise role of MafB in macrophages. PMID:24040127

  4. The Effects of Acute Blood Loss for Diagnostic Bloodwork and Fluid Replacement in Clinically Ill Mice

    PubMed Central

    Marx, James O; Jensen, JanLee A; Seelye, Stacie; Walton, Raquel M; Hankenson, F Claire

    2015-01-01

    Despite the great value of diagnostic bloodwork for identifying disease in animals, the volume of blood required for these analyses limits its use in laboratory mice, particularly when they are clinically ill. We sought to determine the effects of acute blood loss (ABL) following blood collection for diagnostic bloodwork in healthy mice compared with streptozotocin-induced diabetic and dextran sulfate sodium (DSS)-treated dehydrated mice. ABL caused several mild changes in the control mice, with significant decreases in body weight, temperature, and activity in both experimental groups; increased dehydration and azotemia in the DSS-treated mice; and a significant drop in the blood pressure of the diabetic mice. To determine whether these negative outcomes could be ameliorated, we treated mice with intraperitoneal lactated Ringers solution either immediately after or 30 min before ABL. Notably, preABL administration of fluids helped prevent the worsening of the dehydration and azotemia in the DSS-treated mice and the changes in blood pressure in the diabetic mice. However, fluid administration provided no benefit in control of blood pressure when administered after ABL in the diabetic mice. Furthermore, fluid therapy did not prevent ABL-induced drops in body weight and activity. Although one mouse not receiving fluid therapy became moribund at the 24-h time point, no animals died during the 24-h study. This investigation demonstrates that blood for diagnostic bloodwork can be collected safely from clinically ill mice and that preemptive fluid therapy mitigates some of the negative changes associated with this blood loss. PMID:26141445

  5. Chronic Toxoplasma gondii in Nurr1-null heterozygous mice exacerbates elevated open field activity.

    PubMed

    Eells, Jeffrey B; Varela-Stokes, Andrea; Guo-Ross, Shirley X; Kummari, Evangel; Smith, Holly M; Cox, Erin; Lindsay, David S

    2015-01-01

    Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population) and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%), genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/-) mice and wild-type (+/+) mice were evaluate using an emergence test, activity in an open field and with a novel object, response to bobcat urine and prepulse inhibition of the acoustic startle response (PPI) prior to and 6 weeks after infection with T. gondii. In the emergence test, T. gondii infection significantly decreased the amount of time spent in the cylinder. Toxoplasma gondii infection significantly elevated open field activity in both +/+ and +/- mice but this increase was significantly exacerbated in +/- mice. T. gondii infection reduced PPI in male +/- mice but this was not statistically significant. Aversion to bobcat urine was abolished by T. gondii infection in +/+ mice. In female +/- mice, aversion to bobcat urine remained after T. gondii infection while the male +/- mice showed no aversion to bobcat urine. Antibody titers of infected mice were a critical variable associated with changes in open field activity, such that an inverted U shaped relationship existed between antibody titers and the percent change in open field activity with a significant increase in activity at low and medium antibody titers but no effect at high antibody titers. These data demonstrate that the Nurr1 +/- genotype predisposes mice to T. gondii-induced alterations in behaviors that involve dopamine neurotransmission and are associated with symptoms of schizophrenia. We propose that these alterations in murine behavior were due to further exacerbation of the altered dopamine neurotransmission in Nurr1 +/- mice. PMID:25855987

  6. Mice Deficient in Proglucagon-Derived Peptides Exhibit Glucose Intolerance on a High-Fat Diet but Are Resistant to Obesity.

    PubMed

    Takagi, Yusuke; Kinoshita, Keita; Ozaki, Nobuaki; Seino, Yusuke; Murata, Yoshiharu; Oshida, Yoshiharu; Hayashi, Yoshitaka

    2015-01-01

    Homozygous glucagon-GFP knock-in mice (Gcggfp/gfp) lack proglucagon derived-peptides including glucagon and GLP-1, and are normoglycemic. We have previously shown that Gcggfp/gfp show improved glucose tolerance with enhanced insulin secretion. Here, we studied glucose and energy metabolism in Gcggfp/gfp mice fed a high-fat diet (HFD). Male Gcggfp/gfp and Gcggfp/+ mice were fed either a normal chow diet (NCD) or an HFD for 15-20 weeks. Regardless of the genotype, mice on an HFD showed glucose intolerance, and Gcggfp/gfp mice on HFD exhibited impaired insulin secretion whereas Gcggfp/+ mice on HFD exhibited increased insulin secretion. A compensatory increase in ?-cell mass was observed in Gcggfp/+mice on HFD, but not in Gcggfp/gfp mice on the same diet. Weight gain was significantly lower in Gcggfp/gfp mice than in Gcggfp/+mice. Oxygen consumption was enhanced in Gcggfp/gfp mice compared to Gcggfp/+ mice on an HFD. HFD feeding significantly increased uncoupling protein 1 mRNA expression in brown adipose and inguinal white adipose tissues of Gcggfp/gfp mice, but not of Gcggfp/+mice. Treatment with the glucagon-like peptide-1 receptor agonist liraglutide (200 mg/kg) improved glucose tolerance in Gcggfp/gfp mice and insulin content in Gcggfp/gfp and Gcggfp/+ mice was similar after liraglutide treatment. Our findings demonstrate that Gcggfp/gfp mice develop diabetes upon HFD-feeding in the absence of proglucagon-derived peptides, although they are resistant to diet-induced obesity. PMID:26378455

  7. Demonstrating Allotropic Modifications of Sulfur.

    ERIC Educational Resources Information Center

    McCarty, Jillian L.; Dragojlovic, Veljko

    2002-01-01

    Shows how a common demonstration that consists of slowly heating sulfur powder in a test tube to illustrate sulfur's allotropic modifications can convince students of conclusions about the moon Io which they often find surprising. Describes the demonstration in full. (Author/MM)

  8. A Demonstration of Acid Rain

    ERIC Educational Resources Information Center

    Fong, Man Wai

    2004-01-01

    A demonstration showing acid rain formation is described. Oxides of sulfur and nitrogen that result from the burning of fossil fuels are the major pollutants of acid rain. In this demonstration, SO[subscript 2] gas is produced by the burning of matches. An acid-base indicator will show that the dissolved gas turns an aqueous solution acidic.

  9. Understanding Statistics Using Computer Demonstrations

    ERIC Educational Resources Information Center

    Dunn, Peter K.

    2004-01-01

    This paper discusses programs that clarify some statistical ideas often discussed yet poorly understood by students. The programs adopt the approach of demonstrating what is happening, rather than using the computer to do the work for the students (and hide the understanding). The programs demonstrate normal probability plots, overfitting of…

  10. A Demonstration of Sample Segregation

    ERIC Educational Resources Information Center

    Fritz, Mark D.; Brumbach, Stephen B.; Hartman, JudithAnn R.

    2005-01-01

    The demonstration of sample segregation, which is simple, and visually compelling illustrates the importance of sample handling for students studying analytical chemistry and environmental chemistry. The mixture used in this demonstration has two components, which have big particle size, and different colors, which makes the segregation graphic.

  11. Optics Demonstrations Using Cylindrical Lenses

    ERIC Educational Resources Information Center

    Ivanov, Dragia; Nikolov, Stefan

    2015-01-01

    In this paper we consider the main properties of cylindrical lenses and propose several demonstrational experiments that can be performed with them. Specifically we use simple glasses full of water to demonstrate some basic geometrical optics principles and phenomena. We also present some less standard experiments that can be performed with such…

  12. Interactive Poster and Demonstration Sessions

    E-print Network

    ACL-05 Interactive Poster and Demonstration Sessions Proceedings 26 June 2005 University Poster and Demonstration session took place on Sunday, June 26, 2005 in Ann Arbor Michigan, on the first work (Interactive Posters) or previously published but subsequently improved existing systems

  13. SCHROTH INTERPRETIVE TRAIL DEMONSTRATION PRAIRIE

    E-print Network

    Chen, Deming

    SCHROTH INTERPRETIVE TRAIL MUSIC BARN DEMONSTRATION PRAIRIE FORMER SITE OF THE LOST GARDEN PIONEER and upland forests, a meadow and a 30-acre demonstration prairie » 14 miles of interpretive hiking trails Institute of Architects'List of 150 Great Places in Illinois. #12;FU DOG GARDEN (SCULPTURES) HOUSE

  14. The "Mushroom Cloud" Demonstration Revisited

    ERIC Educational Resources Information Center

    Panzarasa, Guido; Sparnacci, Katia

    2013-01-01

    A revisitation of the classical "mushroom cloud" demonstration is described. Instead of aniline and benzoyl peroxide, the proposed reaction involves household chemicals such as alpha-pinene (turpentine oil) and trichloroisocyanuric acid ("Trichlor") giving an impressive demonstration of oxidation and combustion reactions that…

  15. 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.

  16. A Comprehensive General Chemistry Demonstration

    ERIC Educational Resources Information Center

    Sweeder, Ryan D.; Jeffery, Kathleen A.

    2013-01-01

    This article describes the use of a comprehensive demonstration suitable for a high school or first-year undergraduate introductory chemistry class. The demonstration involves placing a burning candle in a container adjacent to a beaker containing a basic solution with indicator. After adding a lid, the candle will extinguish and the produced…

  17. 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,…

  18. Development of Severe Pathology in Immunized Pregnant Mice Challenged with Lethal Malaria Parasites

    PubMed Central

    Mineo, Shoichiro; Niikura, Mamoru; Inoue, Shin-Ichi; Kuroda, Masahiko

    2013-01-01

    Pregnant women are highly susceptible to malaria infection because of their low immunity and are at increased risk of maternal illness or death, in addition to spontaneous abortion, stillbirth, premature delivery, and low birth weight. However, the detailed pathogenesis of maternal malaria remains unclear. In this study, we evaluated a mouse model that shows similar severe pathological features of pregnant women during Plasmodium falciparum infection and investigated the pathogenesis of maternal malaria. Pregnant mice immunized by infection with an attenuated parasite, Plasmodium berghei XAT, were more susceptible to virulent P. berghei NK65 challenge/infection than were nonpregnant mice and showed high levels of parasitemia and a poor pregnancy outcome associated with placental pathology, such as accumulation of parasitized red blood cells, in the late phase of pregnancy. Notably, the pregnant immune mice challenged/infected with P. berghei NK65 developed liver injury associated with microvesicular fatty infiltration in late pregnancy. The pathological features were similar to acute fatty liver of pregnancy. Higher levels of gamma interferon and nitric oxide (NO) were found in plasma from pregnant immune mice infected with P. berghei NK65 than in plasma from nonpregnant mice. These findings suggest that development of liver injury and placental pathology in pregnant immune mice challenged/infected with P. berghei NK65 is accompanied by enhanced production of proinflammatory cytokines. PMID:23897619

  19. Preservation of cochlear function in Fabp3 (H-Fabp) knockout mice.

    PubMed

    Suzuki, Jun; Oshima, Takeshi; Yoshida, Naohiro; Kimura, Ryuichi; Takata, Yusuke; Owada, Yuji; Kobayashi, Toshimitsu; Katori, Yukio; Osumi, Noriko

    2014-01-01

    Fatty acid-binding protein 3 (Fabp3) is an intracellular lipid trafficking protein that mediates energy metabolism and long-chain fatty acid-related signaling. Fabp3 is expressed in the spiral ganglion neurons and supporting cells of the organ of Corti. However, it is unclear what role Fabp3 plays in the cochlea. Here, we demonstrated that the ABR thresholds of young and aged Fabp3 knockout mice were unchanged compared with those of wild-type mice. Compared with the wild-type mice, the adult mutant mice demonstrated no differences in their vulnerability to acoustic overexposure. These results suggest that Fabp3 deficiency alone does not adversely affect hearing function. PMID:24560810

  20. The development of diet-induced obesity and associated metabolic impairments in Dj-1 deficient mice.

    PubMed

    Seyfarth, Katrin; Poschmann, Gereon; Rozman, Jan; Fromme, Tobias; Rink, Nadine; Hofmann, Andreas; Wurst, Wolfgang; Stühler, Kai; Klingenspor, Martin

    2015-01-01

    DJ-1 constitutes a ubiquitously expressed, oxidative stress-responsive protein with multiple functions. DJ-1 emerged as a candidate from our previous proteome analysis investigating alterations in the hypothalamus in three mouse strains differing in their susceptibility to diet-induced obesity (DIO). Validation studies demonstrated a high-fat diet (HFD)-induced shift in the DJ-1 isoform pattern in the hypothalamus and several other tissues of mice. Others found HFD-induced alterations in DJ-1 protein abundance in adipose tissue and pancreatic islets in wild-type rodents. Here, we investigated the gene-diet interaction by challenging Dj-1(-/-) mice with a HFD. We demonstrate that the development of diet-induced obesity (DIO) Dj-1(-/-) mice is according to wild-type mice with the exception of transient higher gains in fat mass at the expense of lean mass after 14 weeks of feeding. PMID:25448609

  1. Treatment of trypanosome-infected mice with exogenous interferon, interferon inducers, or antibody to interferon

    NASA Technical Reports Server (NTRS)

    Degee, Antonie L. W.; Mansfield, John M.; Sonnenfeld, Gerald

    1986-01-01

    Earlier studies have demonstrated that mice resistant to Trypanosoma brucei rhodesiense (the B10.BR/SgSnJ strain) produces, upon infection by this parasite, two peaks of serum interferon (IFN), while the susceptible mice (C3HeB/FeJ) produces no IFN. In the present study, survival times were compared for B10.BR/SgSnJ, C3HeB/FeJ, and CBA/J (an intermediately resistant strain) mice that were injected, prior to infection with the parasite, with either of the following three preparations (1) IFN-gamma, (2) an antibody to IFN-gamma and (3) polyriboinosinic-polyribocytidylic acid (to induce IFN-alpha/beta). No effect on the survival times of mice by any of these preparations could be demonstrated, contrary to some previous reports.

  2. INDUCTION OF CYP1A1 AD CYP1B1 AND FORMATION OF DNA ADDUCTS IN C57BL/6, BALB/C, AND F1 MICE FOLLOWING IN UTERO EXPOSURE TO 3-METHYLCHOLANTHRENE

    EPA Science Inventory

    Fetal mice are more sensitive to chemical carcinogens than are adults. Previous studies from our laboratory demonstrated differences in the mutational spectrum induced in the Ki-ras gene from lung tumors isolated from [D2 x B6D2F1]F2 mice and Balb/c mice treated in utero with 3?m...

  3. Gene and stress history interplay in emergence of PTSD-like features.

    PubMed

    Chakraborty, Nabarun; Meyerhoff, James; Gautam, Aarti; Muhie, Seid; Jibitu, Meskerem; De Lima, Thereza C M; Hammamieh, Rasha; Jett, Marti

    2015-10-01

    Systematically distinguishing genetic liability from other contributing factors is critical for designing a preventive strategy for post-traumatic stress disorder (PTSD). To address this issue, we investigated a murine model exposing C57BL/6j, DBA/2j and BALB/cj mice to repeated stress via exposure to conspecific aggressors (Agg-E). Naďve mice from each strain were subjected to the proximity of aggressor (Agg) mice for 6h using a 'cage-within-a-cage' paradigm, which was repeated for 5 or 10 days with intermittent and unpredictable direct contact with Agg mice. During the Agg-E stress, DBA/2j developed a different strategy to evade Agg mice, which potentially contributed to its phenotypic resilience to Agg-E stress. Although Agg mice inflicted C57BL/6j and BALB/cj with equivalent numbers of strikes, BALB/cj displayed a distinct behavioral phenotype with delayed exhibition of a number of PTSD-like features. By contrast, C57BL/6j mice displayed unique vulnerability to Agg-E stress induced myocardopathy, possibly attributable to their particular susceptibility to hypoxia. A group of genes (Bdnf, Ngf, Zwint, Cckbr, Slc6a4, Fkbp5) linked to PTSD and synaptic plasticity were significantly altered in C57BL/6j and BALB/cj Agg-E mice. Contributions of Agg-E stress history and genotypic heterogeneity emerged as the key mediators of PTSD-like features. Linking genetic components to specific phenotypic and pathological features could have potential clinical implications. PMID:26025510

  4. Genetic feature selection for gait recognition

    NASA Astrophysics Data System (ADS)

    Tafazzoli, Faezeh; Bebis, George; Louis, Sushil; Hussain, Muhammad

    2015-01-01

    Many research studies have demonstrated that gait can serve as a useful biometric modality for human identification at a distance. Traditional gait recognition systems, however, have mostly been evaluated without explicitly considering the most relevant gait features, which might have compromised performance. We investigate the problem of selecting a subset of the most relevant gait features for improving gait recognition performance. This is achieved by discarding redundant and irrelevant gait features while preserving the most informative ones. Motivated by our previous work on feature subset selection using genetic algorithms (GAs), we propose using GAs to select an optimal subset of gait features. First, features are extracted using kernel principal component analysis (KPCA) on spatiotemporal projections of gait silhouettes. Then, GA is applied to select a subset of eigenvectors in KPCA space that best represents a subject's identity. Each gait pattern is then represented by projecting it only on the eigenvectors selected by the GA. To evaluate the effectiveness of the selected features, we have experimented with two different classifiers: k nearest-neighbor and Naďve Bayes classifier. We report considerable gait recognition performance improvements on the Georgia Tech and CASIA databases.

  5. Hierarchical feature selection for erythema severity estimation

    NASA Astrophysics Data System (ADS)

    Wang, Li; Shi, Chenbo; Shu, Chang

    2014-10-01

    At present PASI system of scoring is used for evaluating erythema severity, which can help doctors to diagnose psoriasis [1-3]. The system relies on the subjective judge of doctors, where the accuracy and stability cannot be guaranteed [4]. This paper proposes a stable and precise algorithm for erythema severity estimation. Our contributions are twofold. On one hand, in order to extract the multi-scale redness of erythema, we design the hierarchical feature. Different from traditional methods, we not only utilize the color statistical features, but also divide the detect window into small window and extract hierarchical features. Further, a feature re-ranking step is introduced, which can guarantee that extracted features are irrelevant to each other. On the other hand, an adaptive boosting classifier is applied for further feature selection. During the step of training, the classifier will seek out the most valuable feature for evaluating erythema severity, due to its strong learning ability. Experimental results demonstrate the high precision and robustness of our algorithm. The accuracy is 80.1% on the dataset which comprise 116 patients' images with various kinds of erythema. Now our system has been applied for erythema medical efficacy evaluation in Union Hosp, China.

  6. Using the Morris Water Maze to Assess Spatial Learning and Memory in Weanling Mice

    PubMed Central

    Barnhart, Christopher D.; Yang, Dongren; Lein, Pamela J.

    2015-01-01

    Mouse models have been indispensable for elucidating normal and pathological processes that influence learning and memory. A widely used method for assessing these cognitive processes in mice is the Morris water maze, a classic test for examining spatial learning and memory. However, Morris water maze studies with mice have principally been performed using adult animals, which preclude studies of critical neurodevelopmental periods when the cellular and molecular substrates of learning and memory are formed. While weanling rats have been successfully trained in the Morris water maze, there have been few attempts to test weanling mice in this behavioral paradigm even though mice offer significant experimental advantages because of the availability of many genetically modified strains. Here, we present experimental evidence that weanling mice can be trained in the Morris water maze beginning on postnatal day 24. Maze-trained weanling mice exhibit significant improvements in spatial learning over the training period and results of the probe trial indicate the development of spatial memory. There were no sex differences in the animals’ performance in these tasks. In addition, molecular biomarkers of synaptic plasticity are upregulated in maze-trained mice at the transcript level. These findings demonstrate that the Morris water maze can be used to assess spatial learning and memory in weanling mice, providing a potentially powerful experimental approach for examining the influence of genes, environmental factors and their interactions on the development of learning and memory. PMID:25886563

  7. Probiotic Use Decreases Intestinal Inflammation and Increases Bone Density in Healthy Male but not Female Mice

    PubMed Central

    MCCABE, LAURA R.; IRWIN, REGINA; SCHAEFER, LAURA; BRITTON, ROBERT A.

    2014-01-01

    Osteoporosis can result from intestinal inflammation, as is seen with inflammatory bowel disease. Probiotics, microorganisms that provide a health benefit to the host when ingested in adequate amounts, can have anti-inflammatory properties and are currently being examined to treat inflammatory bowel disease. Here, we examined if treating healthy male mice with Lactobacillus reuteri ATCC PTA 6475 (a candidate probiotic with anti-TNF? activity) could affect intestinal TNF? levels and enhance bone density. Adult male mice were given L. reuteri 6475 orally by gavage for 3 ×/week for 4 weeks. Examination of jejunal and ileal RNA profiles indicates that L. reuteri suppressed basal TNF? mRNA levels in the jejunum and ileum in male mice, but surprisingly not in female mice. Next, we examined bone responses. Micro-computed tomography demonstrated that L. reuteri 6475 treatment increased male trabecular bone parameters (mineral density, bone volume fraction, trabecular number, and trabecular thickness) in the distal femur metaphyseal region as well as in the lumbar vertebrae. Cortical bone parameters were unaffected. Dynamic and static histomorphometry and serum remodeling parameters indicate that L. reuteri ingestion increases osteoblast serum markers and dynamic measures of bone formation in male mice. In contrast to male mice, L. reuteri had no effect on bone parameters in female mice. Taken together our studies indicate that femoral and vertebral bone formation increases in response to oral probiotic use, leading to increased trabecular bone volume in male mice. PMID:23389860

  8. Pregnancy Represses Induction of Efflux Transporters in Livers of Type I Diabetic Mice

    PubMed Central

    Aleksunes, Lauren M.; Xu, Jialin; Lin, Eugenia; Wen, Xia; Goedken, Michael J.; Slitt, Angela L.

    2013-01-01

    Purpose The purpose of this study was to determine whether down-regulation of transcription factor signaling during pregnancy disrupts the induction of efflux transporters in type I diabetic mice. Methods Type I diabetes was induced in female C57BL/6 mice with multiple low dose intraperitoneal injections of streptozotocin (STZ) at least 2 weeks prior to mating with normoglycemic male mice. On gestation day 14, livers were collected from vehicle- and STZ-treated non-pregnant and pregnant mice for quantification of efflux transporter and transcription factor signaling. Results STZ treatment up-regulated expression of Mrp1–5, Mdr1, Abcg5, Abcg8, Bcrp, and Bsep mRNA and/or protein in the livers of non-pregnant mice. Interestingly, little to no change in transporter expression was observed in STZ-treated mice that became pregnant. Enhanced PPAR?, Nrf2, and FXR transcription factor signaling, as quantified by nuclear binding and target gene regulation, was also observed in non-pregnant mice treated with STZ. Similar to efflux transporter expression, activation of these transcriptional pathways was diminished by pregnancy in STZ-treated mice. Conclusions This study demonstrates the opposing regulation of hepatobiliary efflux transporters in response to diabetes and pregnancy and points to PPAR?, Nrf2, and FXR as candidate pathways underlying the differential expression of transporters. PMID:23319174

  9. Proteomic Alterations in B Lymphocytes of Sensitized Mice in a Model of Chemical-Induced Asthma

    PubMed Central

    De Vooght, Vanessa; Schoofs, Liliane; Nemery, Benoit; Clynen, Elke; Hoet, Peter H. M.

    2015-01-01

    Introduction and Aim The role of B-lymphocytes in chemical-induced asthma is largely unknown. Recent work demonstrated that transferring B lymphocytes from toluene diisocyanate (TDI)-sensitized mice into naďve mice, B cell KO mice and SCID mice, triggered an asthma-like response in these mice after a subsequent TDI-challenge. We applied two-dimensional difference gel electrophoresis (2D-DIGE) to describe the “sensitized signature” of B lymphocytes comparing TDI-sensitized mice with control mice. Results Sixteen proteins were identified that were significantly up- or down-regulated in B lymphocytes of sensitized mice. Particularly differences in the expression of cyclophilin A, cofilin 1 and zinc finger containing CCHC domain protein 11 could be correlated to the function of B lymphocytes as initiators of T lymphocyte independent asthma-like responses. Conclusion This study revealed important alterations in the proteome of sensitized B cells in a mouse model of chemical-induced asthma, which will have an important impact on the B cell function. PMID:26398101

  10. MRI Characterization of Paranodal Junction Failure and Related Spinal Cord Changes in Mice

    PubMed Central

    Takano, Morito; Hikishima, Keigo; Fujiyoshi, Kanehiro; Shibata, Shinsuke; Yasuda, Akimasa; Konomi, Tsunehiko; Hayashi, Akiko; Baba, Hiroko; Honke, Koichi; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya

    2012-01-01

    The paranodal junction is a specialized axon-glia contact zone that is important for normal neuronal activity and behavioral locomotor function in the central nervous system (CNS). Histological examination has been the only method for detecting pathological paranodal junction conditions. Recently, diffusion tensor MRI (DTI) has been used to detect microstructural changes in various CNS diseases. This study was conducted to determine whether MRI and DTI could detect structural changes in the paranodal junctions of the spinal cord in cerebroside sulfotransferase knock-out (CST-KO) mice. Here, we showed that high-resolution MRI and DTI characteristics can reflect paranodal junction failure in CST-KO mice. We found significantly lower T1 times and significantly higher T2 times in the spinal cord MRIs of CST-KO mice as compared to wild-type (WT) mice. Spinal cord DTI showed significantly lower axial diffusivity and significantly higher radial diffusivity in CST-KO mice as compared to WT mice. In contrast, the histological differences in the paranodal junctions of WT and CST-KO mice were so subtle that electron microscopy or immunohistological analyses were necessary to detect them. We also measured gait disturbance in the CST-KO mice, and determined the conduction latency by electrophysiology. These findings demonstrate the potential of using MRI and DTI to evaluate white matter disorders that involve paranodal junction failure. PMID:23300814

  11. Epim?/? mice are partially protected from acute colitis via decreased IL-6 signaling

    PubMed Central

    Shaker, Anisa; Gargus, Matthew; Fink, Julie; Binkley, Jana; Darwech, Isra; Swietlicki, Elzbieta; Levin, Marc S.; Rubin, Deborah C.

    2014-01-01

    Epimorphin (Epim), a member of the syntaxin family of membrane bound, intracellular vesicle docking proteins, is expressed in intestinal myofibroblasts and macrophages. We have previously demonstrated that Epim?/? mice are partially protected from dextran sodium sulfate (DSS)-induced colitis. While IL-6/p-Stat3 signaling has been implicated in the pathogenesis of colitis, the myofibroblast contribution to IL-6 signaling in colitis remains unexplored. Our aim was to investigate the IL-6 pathway in Epim?/? mice in the DSS colitis model. Whole colonic tissue, epithelium, and stroma of WT and congenic Epim?/? mice treated with 5% DSS for 7 days were analyzed for IL-6 and a downstream effector, p-Stat3, by immunostaining and immunoblot. Colonic myofibroblast and peritoneal macrophage IL-6 secretion were evaluated by ELISA. IL-6 and p-Stat3 expression were decreased in Epim?/? vs. WT colon. A relative increase in stromal vs. epithelial p-Stat3 expression was observed in WT mice but not in Epim?/? mice. Epim deletion abrogates IL-6 secretion from colonic myofibroblasts treated with IL-1? and decreases IL-6 secretion from peritoneal macrophages in a sub-set of DSS treated mice. Epim deletion inhibits IL-6 secretion most profoundly from colonic myofibroblasts. Distribution of Stat3 activation is altered in DSS treated Epim?/? mice. Our findings support the notion that myofibroblasts modulate IL-6/p-Stat3 signaling in DSS treated Epim?/? mice. PMID:24731292

  12. Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice.

    PubMed Central

    Lieberman, M W; Wiseman, A L; Shi, Z Z; Carter, B Z; Barrios, R; Ou, C N; Chévez-Barrios, P; Wang, Y; Habib, G M; Goodman, J C; Huang, S L; Lebovitz, R M; Matzuk, M M

    1996-01-01

    gamma-Glutamyl transpeptidase (GGT) is an ectoenzyme that catalyzes the first step in the cleavage of glutathione (GSH) and plays an essential role in the metabolism of GSH and GSH conjugates of carcinogens, toxins, and eicosanoids. To learn more about the role of GGT in metabolism in vivo, we used embryonic stem cell technology to generate GGT-deficient (GGTm1/GGTm1) mice. GGT-deficient mice appear normal at birth but grow slowly and by 6 weeks are about half the weight of wild-type mice. They are sexually immature, develop cataracts, and have coats with a gray cast. Most die between 10 and 18 weeks. Plasma and urine GSH levels in the GGTm1/GGTm1 mice are elevated 6-fold and 2500-fold, respectively, compared with wild-type mice. Tissue GSH levels are markedly reduced in eye, liver, and pancreas. Plasma cyst(e)ine levels in GGTm1/GGTm1 mice are reduced to approximately 20% of wild-type mice. Oral administration of N-acetylcysteine to GGTm1/GGTm1 mice results in normal growth rates and partially restores the normal agouti coat color. These findings demonstrate the importance of GGT and the gamma-glutamyl cycle in cysteine and GSH homeostasis. Images Fig. 1 Fig. 3 PMID:8755578

  13. Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy.

    PubMed

    Titova, Ksenya A; Sergeev, Alexander A; Zamedyanskaya, Alena S; Galahova, Darya O; Kabanov, Alexey S; Morozova, Anastasia A; Bulychev, Leonid E; Sergeev, Artemiy A; Glotova, Tanyana I; Shishkina, Larisa N; Taranov, Oleg S; Omigov, Vladimir V; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

    2015-09-01

    The possibility of using immunocompetent ICR mice and immunodeficient SCID mice as model animals for smallpox to assess antiviral drug efficacy was investigated. Clinical signs of the disease did not appear following intranasal (i.n.) challenge of mice with strain Ind-3a of variola virus (VARV), even when using the highest possible dose of the virus (5.2 log10 p.f.u.). The 50?% infective doses (ID50) of VARV, estimated by the virus presence or absence in the lungs 3 and 4?days post-infection, were 2.7?±?0.4 log10 p.f.u. for ICR mice and 3.5?±?0.7 log10 p.f.u. for SCID mice. After i.n. challenge of ICR and SCID mice with VARV 30 and 50 ID50, respectively, steady reproduction of the virus occurred only in the respiratory tract (lungs and nose). Pathological inflammatory destructive changes were revealed in the respiratory tract and the primary target cells for VARV (macrophages and epithelial cells) in mice, similar to those in humans and cynomolgus macaques. The use of mice to assess antiviral efficacies of NIOCH-14 and ST-246 demonstrated the compliance of results with those described in scientific literature, which opens up the prospect of their use as an animal model for smallpox to develop anti-smallpox drugs intended for humans. PMID:26067292

  14. Altered intestinal epithelium-associated lymphocyte repertoires and function in ApcMin/+ mice.

    PubMed

    Marsh, Lorraine; Coletta, P Louise; Hull, Mark A; Selby, Peter J; Carding, Simon R

    2012-01-01

    ApcMin/+ mice spontaneously develop multiple intestinal adenomas along the length of the small intestine and colon. Currently little is known about the role of the immune system in regulating intestinal tumorigenesis in these animals. This study characterised small intestinal intraepithelial lympho-- cyte (IEL) populations in C56BL/6J ApcMin/+ mice and wild-type (Apc+/+) mice. We also determined the effect that T cells expressing either ?? or ?? encoded T cell receptors (TcR) exert on intestinal tumorigenesis. ApcMin/+ mice had significantly lower numbers of CD3+ IELs compared with Apc+/+ littermates and displayed reduced cytotoxicity against tumour target cells. Further analysis of IEL cytotoxicity revealed differences in the cytotoxic pathways utilised by IELs in ApcMin/+ and Apc+/+ mice with ApcMin/+ IELs displaying an absence of perforin/granzyme-mediated killing and increased levels of Fas-FasL-mediated cytotoxicity compared with wild-type IELs. Analysis of ApcMin/+ mice crossed with ?? T-cell deficient (TcR?-/-) or ?? T-cell deficient (TcR?-/-) mice on the same genetic background revealed decreased tumour multiplicity in the absence of both ?? and ?? T-cells. This study demonstrates that altered T-cell subsets play important roles in promoting tumorigenesis in ApcMin/+ mice and forms the basis for future mechanistic studies. PMID:21879254

  15. Heme oxygenase-1 is a modulator of inflammation and vaso-occlusion in transgenic sickle mice

    PubMed Central

    Belcher, John D.; Mahaseth, Hemachandra; Welch, Thomas E.; Otterbein, Leo E.; Hebbel, Robert P.; Vercellotti, Gregory M.

    2006-01-01

    Transgenic sickle mice expressing ?S hemoglobin have activated vascular endothelium that exhibits enhanced expression of NF-?B and adhesion molecules that promote vascular stasis in sickle, but not in normal, mice in response to hypoxia/reoxygenation. Sickle mice hemolyze rbcs in vivo as demonstrated by increased reticulocyte counts, plasma hemoglobin and bilirubin, and reduced plasma haptoglobin. The heme content is elevated in sickle organs, which promotes vascular inflammation and heme oxygenase-1 expression. Treatment of sickle mice with hemin further increases heme oxygenase-1 expression and inhibits hypoxia/reoxygenation–induced stasis, leukocyte-endothelium interactions, and NF-?B, VCAM-1, and ICAM-1 expression. Heme oxygenase inhibition by tin protoporphyrin exacerbates stasis in sickle mice. Furthermore, treatment of sickle mice with the heme oxygenase enzymatic product carbon monoxide or biliverdin inhibits stasis and NF-?B, VCAM-1, and ICAM-1 expression. Local administration of heme oxygenase-1 adenovirus to subcutaneous skin increases heme oxygenase-1 and inhibits hypoxia/reoxygenation–induced stasis in the skin of sickle mice. Heme oxygenase-1 plays a vital role in the inhibition of vaso-occlusion in transgenic sickle mice. PMID:16485041

  16. Cytotoxic T cells isolated from the central nervous systems of mice infected with Theiler's virus.

    PubMed Central

    Lindsley, M D; Thiemann, R; Rodriguez, M

    1991-01-01

    Intracerebral inoculation of resistant mice (C57BL/10SNJ) with Theiler's murine encephalomyelitis virus (TMEV) results in acute encephalitis followed by subsequent clearance of virus from the central nervous system (CNS). In contrast, infection of susceptible mice (SJL/J) results in virus persistence and chronic immune-mediated demyelination. Both resistance and susceptibility to TMEV-induced disease appear to be immune mediated, since immunosuppression results in enhanced encephalitis in resistant mice but diminished demyelination in susceptible mice. The purpose of these experiments was to determine whether anti-TMEV cytotoxic T lymphocytes (CTLs) are generated during acute and chronic TMEV infection. Nonspecific lectin-dependent cellular cytotoxicity was used initially to detect the cytolytic potential of lymphocytes infiltrating the CNS irrespective of antigen specificity. Using TMEV-infected targets, H-2-restricted TMEV-specific CTLs of the CD8+ phenotype were demonstrated in lymphocytes from the CNS of susceptible and resistant mice, arguing against the hypothesis that the ability to generate CD8+ CTLs mediates resistance. In chronically infected SJL/J mice, TMEV-specific CTL activity was detected in the CNS as late as 226 days postinfection. These experiments demonstrate that virus-specific CTLs are present in the CNS during both acute and chronic TMEV infection. Anti-TMEV CTLs in the CNS of chronically infected SJL/J mice may play a role in demyelination through their ability to lyse TMEV-infected glial cells. PMID:1658365

  17. Tested Demonstrations. A Chemiluminescence Demonstration - Oxalyl Chloride Oxidation.

    ERIC Educational Resources Information Center

    Gilber, George L., Ed.

    1979-01-01

    This inexpensive, effective chemiluminescence demonstration requires minimal preparation. It is based on the oxidation of oxalyl chloride by hydrogen peroxide in the presence of an appropriate fluorescent sensitizer. The reaction mechanism is not completely understood. (BB)

  18. Tested Demonstrations: A Simple Demonstration of Reversible Oxygenation.

    ERIC Educational Resources Information Center

    Kildahl, Nicholas K.

    1983-01-01

    Materials needed, reaction involved, and potential hazards are provided for a demonstration of reversible oxygenation. Also discusses the importance of the reaction in biological systems, focusing on hemoglobin/myoglobin and their function in mammals. (JM)

  19. The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice

    PubMed Central

    Fakharzadeh, Saideh; Sahraian, Mohammad Ali; Hafizi, Maryam; Kalanaky, Somayeh; Masoumi, Zahra; Mahdavi, Mehdi; Kamalian, Nasser; Minagar, Alireza; Nazaran, Mohammad Hassan

    2014-01-01

    Purpose Currently approved therapies for multiple sclerosis (MS) at best only slow down its progression. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In the present study, for the first time we evaluated the therapeutic potential of MSc1 nanocomplex, which was designed based on novel nanochelating technology. Materials and methods MSc1 cell-protection capacity, with and without iron bond, was evaluated against hydrogen peroxide (H2O2)-induced oxidative stress in cultured rat pheochromocytoma-12 cells. The ability of MSc1 to maintain iron bond at pH ranges of 1–7 was evaluated. Nanocomplex toxicity was examined by estimating the intraperitoneal median lethal dose (LD50). Experimental autoimmune encephalomyelitic mice were injected with MSc1 14 days after disease induction, when the clinical symptoms appeared. The clinical score, body weight, and disease-induced mortality were monitored until day 54. In the end, after collecting blood samples for assessing hemoglobin and red blood cell count, the brains and livers of the mice were isolated for hematoxylin and eosin staining and analysis of iron content, respectively. Results The results showed that MSc1 prevented H2O2-induced cell death even after binding with iron, and it preserved its bond with iron constant at pH ranges 1–7. The nanocomplex intraperitoneal LD50 was 1,776.59 mg/kg. MSc1 prompted therapeutic behavior and improved the disabling features of experimental autoimmune encephalomyelitis, which was confirmed by decreased clinical scores versus increased body mass and 100% survival probability. It did not cause any adverse effects on hemoglobin or red blood cell count. Histopathological studies showed no neural loss or lymphocyte infiltration in MSc1-treated mice, while the hepatic iron content was also normal. Conclusion These results demonstrate that MSc1 could be a promising beneficial novel agent and has the capacity to be evaluated in further studies. PMID:25143732

  20. Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XYPOS mice.

    PubMed

    Umemura, Yuria; Miyamoto, Ryosuke; Hashimoto, Rie; Kinoshita, Kyoko; Omotehara, Takuya; Nagahara, Daichi; Hirano, Tetsushi; Kubota, Naoto; Minami, Kiichi; Yanai, Shogo; Masuda, Natsumi; Yuasa, Hideto; Mantani, Youhei; Matsuo, Eiko; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2016-01-01

    Mammalian sexual fate is determined by the presence or absence of sex determining region of the Y chromosome (Sry) in the "bipotential" gonads. Recent studies have demonstrated that both male and female sexual development are induced by distinct and active genetic pathways. Breeding the Y chromosome from Mus m. domesticus poschiavinus (POS) strains into C57BL/6J (B6J) mice (B6J-XYPOS) has been shown to induce sex reversal (75%: bilateral ovary, 25%: true hermaphrodites). However, our B6N-XYPOS mice, which were generated by backcrossing of B6J-XYPOS on an inbred B6N-XX, develop as males (36%: bilateral testis with fertility as well as bilateral ovary (34%), and the remainder develop as true hermaphrodites. Here, we investigated in detail the expressions of essential sex-related genes and histological features in B6N-XYPOS mice from the fetal period to adulthood. The onsets of both Sry and SRY-box 9 (Sox9) expressions as determined spatiotemporally by whole-mount immunohistochemistry in the B6N-XYPOS gonads occurred 2-3 tail somites later than those in B6N-XYB6 gonads, but earlier than those in B6J-XYPOS, respectively. It is possible that such a small difference in timing of the Sry expression underlies testicular development in our B6N-XYPOS. Our study is the first to histologically show the expression and ectopic localization of a female-related gene in the XYPOS testes and a male-related gene in the XYPOS ovaries. The results from these and previous experiments indicate that the interplay between genome variants, epigenetics and developmental gene regulation is crucial for testis development. PMID:26194606